WorldWideScience

Sample records for attenuation ncq models

  1. Investigating the NCQ scaling of elliptic flow at LHC with a multiphase transport model

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Liang [Central China Normal University, Key Laboratory of Quark and Lepton Physics (MOE) and Institute of Particle Physics, Wuhan (China); Central China Normal University, School of Mathematics and Statistics, Wuhan (China); Li, Hui; Shou, Qi-Ye; Yin, Zhong-Bao [Central China Normal University, Key Laboratory of Quark and Lepton Physics (MOE) and Institute of Particle Physics, Wuhan (China); Qin, Hong [Central China Normal University, School of Mathematics and Statistics, Wuhan (China)

    2017-06-15

    The number of constituent quark (NCQ) scaling behavior of elliptic flow has been systematically studied at the LHC energy within the framework of a multiphase transport model (AMPT) in this work. With the variation of the fragmentation parameters, collision centrality and system energy, we find that the initial conditions of parton dynamics are more important than the final state parton cascade process for the existence of NCQ scaling when the hadronic interaction is off in Pb-Pb collisions. By turning on the hadron interaction process, the impacts of hadronic evolution are found to be responsible for a significant violation to the well established scaling structure. Our study suggests that the interpretation of NCQ scaling is not only subject to the hadronization mechanism but also to the initial conditions of parton evolution as well as the hadronic interactions especially for the LHC experiments. (orig.)

  2. Patient perspectives on continuity of care: adaption and preliminary psychometric assessment of a Norwegian version of the Nijmegen Continuity Questionnaire (NCQ-N

    Directory of Open Access Journals (Sweden)

    Øystein Hetlevik

    2017-11-01

    Full Text Available Abstract Background Continuity of care is regarded as a core quality element in healthcare. Continuity can be related to one or more specific caregivers but also applies to collaboration within a team or across boundaries of healthcare. Measuring continuity is important to identify problems and evaluate quality improvement of interventions. This study aimed to assess the feasibility and psychometric properties of a Norwegian version of the Nijmegen Continuity Questionnaire (NCQ. Methods The NCQ was developed in The Netherlands. It measures patients’ experienced continuity of care across multiple care settings and as a multidimensional concept regardless of morbidity. The NCQ comprises 28 items categorised into three subscales; two personal continuity scales, “care giver knows me” and “shows commitment”, asked regarding the patient’s general practitioner (GP and the most important specialist; and one “team/cross boundary continuity” scale, asked regarding primary care, specialised care and cooperation between GP and specialist, with a total of seven factors. The NCQ was translated and adapted to Norwegian (NCQ-N and distributed among patients referred to somatic rehabilitation (N = 984, response rate 34.5%. Confirmatory factor analyses (CFA, Cronbach’s alpha, intra-class correlation (ICC and Bland–Altman plots were used to assess psychometric properties. Results All patients (N = 375 who had responded to all parts of the NCQ-N were included in CFA. The CFA fit indices (CFI 0.941, RMSEA 0.064 (95% CI 0.059–0.070, SRMR 0.041 support a seven-factor structure in the NCQ-N based on the three subscales of the original NCQ. Cronbach’s alpha showed internal consistency (0.84–0.97, and was highest for the team/cross-boundary subscales. The NCQ-N showed overall high reliability with ICC 0.84–91 for personal continuity factors and 0.67–0.91 for team factors, with the lowest score for team continuity within primary care

  3. Precision Model for Microwave Rotary Vane Attenuator

    DEFF Research Database (Denmark)

    Guldbrandsen, Tom

    1979-01-01

    A model for a rotary vane attenuator is developed to describe the attenuator reflection and transmission coefficients in detail. All the parameters of the model can be measured in situ, i.e., without diassembling any part. The tranmission errors caused by internal reflections are calculated from ...

  4. Lg Attenuation Modeling in the Middle East

    Science.gov (United States)

    Pasyanos, M. E.; Matzel, E. M.; Walter, W. R.; Rodgers, A. J.

    2008-12-01

    We present a broadband tomographic model of Lg attenuation in the Middle East derived from source- and site-corrected amplitudes. The study region spans from Turkey through the Arabian Peninsula and Iran to Pakistan, Afghanistan, and northwest India. Absolute amplitude measurements are made on hand-selected and carefully windowed seismograms for tens of stations and thousands of crustal earthquakes resulting in excellent coverage of the region. We have modified the standard attenuation tomography technique to more explicitly define the earthquake source expression in terms of the seismic moment. This facilitates the use of the model to predict the expected amplitudes of new events, an important consideration for earthquake hazard or explosion monitoring applications. We will discuss the updated method and implications of this parameterization. A conjugate gradient method is used to tomographically invert the amplitude dataset of over 8000 paths. We solve for Q variation, as well as site and source terms, for a wide range of frequencies ranging from 0.5 -- 10 Hz. The attenuation results have a strong correlation to tectonics. Shields have low attenuation, while tectonic regions have high attenuation, with the highest attenuation at 1 Hz found in eastern Turkey. The results also compare favorably to other studies in the region made using Lg propagation efficiency, Lg/Pg amplitude ratios and two-station methods. We tomographically invert the amplitude measurements for each frequency independently. In doing so, it appears the frequency-dependence of attenuation is not compatible with the power law representation of Q(f). This research was performed under the auspices of the U.S. Department of Energy by the Lawrence Livermore National Laboratory under contract number DE-AC52-07NA27344. This is LLNL contribution LLNL-ABS-406761.

  5. Overview of recent developments in attenuation models

    International Nuclear Information System (INIS)

    Riera, J.D.

    2001-01-01

    Attenuation equations predict features of the seismic motion, such as the horizontal and vertical peak ground accelerations (PGA), the peak ground velocities (PGV) and the 5% damped spectral acceleration response (SA), in terms of the earthquake magnitude and distance from source to site. Occasionally other factors, like the type of faulting, are considered in the attenuation expressions. An overview of recent developments in this field is presented in the paper, including a discussion of the applicability of various models for short source to site distances. In such a case, i.e. in the neighbourhood of the epicentral region, which is of utmost importance in Nuclear Power Plant applications, the use of two parameters to define the earthquake size is suggested, instead of the single parameter, a magnitude scale. Recent evidence of the importance in such situations of so-called directivity effects, which require a more complete description of the focal mechanism, completes the paper. (author)

  6. Cranking model and attenuation of Coriolis interaction

    International Nuclear Information System (INIS)

    Lyutorovich, N.A.

    1987-01-01

    Description of rotational bands of odd deformed nuclei in the self-consistent Cranking model (SCM) is given. Causes of attenuation of the Coriolis interaction in the nuclei investigated are studied, and account of bound of one-particle degrees of freedom with rotation of the Hartree-Fock-Bogolyubov (HFB) self-consistent method is introduced additionally to SCM for qualitative agreement with experimental data. Merits and shortages of SCM in comparison with the quadruparticle-rotor (QR) model are discussed. All know ways for constructing the Hamiltonian QR model (or analog of such Hamiltonian) on the basis of the microscopic theory are shown to include two more approximations besides others: quasi-particle-rotational interaction leading to pair break is taken into account in the second order of the perturbation theory; some exchange diagrams are neglected among diagrams of the second order according to this interaction. If one makes the same approximations in SCM instead of HFB method, then the dependence of level energies on spin obtained in this case is turned out to be close to the results of the QR model. Besides, the problem on renormalization of matrix elements of quasi-rotational interaction occurs in such nonself-consistent approach as in the QR model. In so far as the similar problem does not occur in SCM, one can make the conclusion that the problem of attenuation of Coriolis interaction involves the approximations given above

  7. Numerical Speadsheet Modeling of Natural Attenuation for Groundwater Contaminant Plumes

    National Research Council Canada - National Science Library

    Twesme, Troy

    1999-01-01

    .... The model was used to evaluate natural attenuation for removal of a trichloroethylene (TCE) plume from a surficial aquifer containing three regions with distinctly different processes for degradation of TCE...

  8. Impact of Scattering Model on Disdrometer Derived Attenuation Scaling

    Science.gov (United States)

    Zemba, Michael; Luini, Lorenzo; Nessel, James; Riva, Carlo (Compiler)

    2016-01-01

    NASA Glenn Research Center (GRC), the Air Force Research Laboratory (AFRL), and the Politecnico di Milano (POLIMI) are currently entering the third year of a joint propagation study in Milan, Italy utilizing the 20 and 40 GHz beacons of the Alphasat TDP5 Aldo Paraboni scientific payload. The Ka- and Q-band beacon receivers were installed at the POLIMI campus in June of 2014 and provide direct measurements of signal attenuation at each frequency. Collocated weather instrumentation provides concurrent measurement of atmospheric conditions at the receiver; included among these weather instruments is a Thies Clima Laser Precipitation Monitor (optical disdrometer) which records droplet size distributions (DSD) and droplet velocity distributions (DVD) during precipitation events. This information can be used to derive the specific attenuation at frequencies of interest and thereby scale measured attenuation data from one frequency to another. Given the ability to both predict the 40 GHz attenuation from the disdrometer and the 20 GHz timeseries as well as to directly measure the 40 GHz attenuation with the beacon receiver, the Milan terminal is uniquely able to assess these scaling techniques and refine the methods used to infer attenuation from disdrometer data.In order to derive specific attenuation from the DSD, the forward scattering coefficient must be computed. In previous work, this has been done using the Mie scattering model, however, this assumes a spherical droplet shape. The primary goal of this analysis is to assess the impact of the scattering model and droplet shape on disdrometer derived attenuation predictions by comparing the use of the Mie scattering model to the use of the T-matrix method, which does not assume a spherical droplet. In particular, this paper will investigate the impact of these two scattering approaches on the error of the resulting predictions as well as on the relationship between prediction error and rain rate.

  9. Context discovery using attenuated Bloom codes: model description and validation

    NARCIS (Netherlands)

    Liu, F.; Heijenk, Geert

    A novel approach to performing context discovery in ad-hoc networks based on the use of attenuated Bloom filters is proposed in this report. In order to investigate the performance of this approach, a model has been developed. This document describes the model and its validation. The model has been

  10. Wave attenuation model for dephasing and measurement of ...

    Indian Academy of Sciences (India)

    An analysis of previous models to simulate inelastic scattering in such systems is presented and a relatively new model based on wave attenuation is introduced. The problem of Aharonov–Bohm (AB) oscillations in conductance of a mesoscopic ring is studied. We show that the conductance is symmetric under flux reversal ...

  11. Outdoor FSO Communications Under Fog: Attenuation Modeling and Performance Evaluation

    KAUST Repository

    Esmail, Maged Abdullah

    2016-07-18

    Fog is considered to be a primary challenge for free space optics (FSO) systems. It may cause attenuation that is up to hundreds of decibels per kilometer. Hence, accurate modeling of fog attenuation will help telecommunication operators to engineer and appropriately manage their networks. In this paper, we examine fog measurement data coming from several locations in Europe and the United States and derive a unified channel attenuation model. Compared with existing attenuation models, our proposed model achieves a minimum of 9 dB, which is lower than the average root-mean-square error (RMSE). Moreover, we have investigated the statistical behavior of the channel and developed a probabilistic model under stochastic fog conditions. Furthermore, we studied the performance of the FSO system addressing various performance metrics, including signal-to-noise ratio (SNR), bit-error rate (BER), and channel capacity. Our results show that in communication environments with frequent fog, FSO is typically a short-range data transmission technology. Therefore, FSO will have its preferred market segment in future wireless fifth-generation/sixth-generation (5G/6G) networks having cell sizes that are lower than a 1-km diameter. Moreover, the results of our modeling and analysis can be applied in determining the switching/thresholding conditions in highly reliable hybrid FSO/radio-frequency (RF) networks.

  12. Seismic Full Waveform Modeling & Imaging in Attenuating Media

    Science.gov (United States)

    Guo, Peng

    Seismic attenuation strongly affects seismic waveforms by amplitude loss and velocity dispersion. Without proper inclusion of Q parameters, errors can be introduced for seismic full waveform modeling and imaging. Three different (Carcione's, Robertsson's, and the generalized Robertsson's) isotropic viscoelastic wave equations based on the generalized standard linear solid (GSLS) are evaluated. The second-order displacement equations are derived, and used to demonstrate that, with the same stress relaxation times, these viscoelastic formulations are equivalent. By introducing separate memory variables for P and S relaxation functions, Robertsson's formulation is generalized to allow different P and S wave stress relaxation times, which improves the physical consistency of the Qp and Qs modelled in the seismograms.The three formulations have comparable computational cost. 3D seismic finite-difference forward modeling is applied to anisotropic viscoelastic media. The viscoelastic T-matrix (a dynamic effective medium theory) relates frequency-dependent anisotropic attenuation and velocity to reservoir properties in fractured HTI media, based on the meso-scale fluid flow attenuation mechanism. The seismic signatures resulting from changing viscoelastic reservoir properties are easily visible. Analysis of 3D viscoelastic seismograms suggests that anisotropic attenuation is a potential tool for reservoir characterization. To compensate the Q effects during reverse-time migration (RTM) in viscoacoustic and viscoelastic media, amplitudes need to be compensated during wave propagation; the propagation velocity of the Q-compensated wavefield needs to be the same as in the attenuating wavefield, to restore the phase information. Both amplitude and phase can be compensated when the velocity dispersion and the amplitude loss are decoupled. For wave equations based on the GSLS, because Q effects are coupled in the memory variables, Q-compensated wavefield propagates faster than

  13. Skull's acoustic attenuation and dispersion modeling on photoacoustic signal

    Science.gov (United States)

    Mohammadi, Leila; Behnam, Hamid; Tavakkoli, Jahan; Nasiriavanaki, Mohammadreza

    2018-02-01

    Despite the promising results of the recent novel transcranial photoacoustic (PA) brain imaging technology, it has been demonstrated that the presence of the skull severely affects the performance of this imaging modality. We theoretically investigate the effects of acoustic heterogeneity induced by skull on the PA signals generated from single particles, with firstly developing a mathematical model for this phenomenon and then explore experimental validation of the results. The model takes into account the frequency dependent attenuation and dispersion effects occur with wave reflection, refraction and mode conversion at the skull surfaces. Numerical simulations based on the developed model are performed for calculating the propagation of photoacoustic waves through the skull. The results show a strong agreement between simulation and ex-vivo study. The findings are as follow: The thickness of the skull is the most PA signal deteriorating factor that affects both its amplitude (attenuation) and phase (distortion). Also we demonstrated that, when the depth of target region is low and it is comparable to the skull thickness, however, the skull-induced distortion becomes increasingly severe and the reconstructed image would be strongly distorted without correcting these effects. It is anticipated that an accurate quantification and modeling of the skull transmission effects would ultimately allow for aberration correction in transcranial PA brain imaging.

  14. Evaluation of attenuating materials: model for the distribution of scattered radiation

    International Nuclear Information System (INIS)

    Costa, Paulo R.

    1996-01-01

    A mathematical model for the behaviour of the distribution of photon scattered by attenuating media is presented. Shielding barriers or attenuating materials used in tests of quality control in radiology are proposed. Comparative results for Lucite are reported

  15. Modeled Radar Attenuation Rate Profile at the Vostok 5G Ice Core Site, Antarctica, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — This data set provides a modeled radar attenuation rate profile, showing the predicted contributions from pure ice and impurities to radar attenuation at the Vostok...

  16. Modeling skull's acoustic attenuation and dispersion on photoacoustic signal

    Science.gov (United States)

    Mohammadi, L.; Behnam, H.; Nasiriavanaki, M. R.

    2017-03-01

    Despite the great promising results of a recent new transcranial photoacoustic brain imaging technology, it has been shown that the presence of the skull severely affects the performance of this imaging modality. In this paper, we investigate the effect of skull on generated photoacoustic signals with a mathematical model. The developed model takes into account the frequency dependence attenuation and acoustic dispersion effects occur with the wave reflection and refraction at the skull surface. Numerical simulations based on the developed model are performed for calculating the propagation of photoacoustic waves through the skull. From the simulation results, it was found that the skull-induced distortion becomes very important and the reconstructed image would be strongly distorted without correcting these effects. In this regard, it is anticipated that an accurate quantification and modeling of the skull transmission effects would ultimately allow for skull aberration correction in transcranial photoacoustic brain imaging.

  17. Program description of FIBRAM (Fiber Optic Radiation Attenuation Model): a radiation attenuation model for optical fibers

    International Nuclear Information System (INIS)

    Ingram, W.J.

    1987-06-01

    The report describes a fiber-optics system model and its computer implementation. This implementation can calculate the bit error ratio (BER) versus time for optical fibers that have been exposed to gamma radiation. The program is designed so that the user may arbitrarily change any or all of the system input variables and produce separate outputs. The primary output of the program is a table of the BER as a function of time. This table may be stored on magnetic media and later incorporated into computer graphic programs. The program was written in FORTRAN 77 for the IBM PC/AT/XT computers. Flow charts and program listings are included in the report

  18. Attenuation of postoperative adhesions using a modeled manual therapy.

    Directory of Open Access Journals (Sweden)

    Geoffrey M Bove

    Full Text Available Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

  19. Attenuation of postoperative adhesions using a modeled manual therapy.

    Science.gov (United States)

    Bove, Geoffrey M; Chapelle, Susan L; Hanlon, Katherine E; Diamond, Michael P; Mokler, David J

    2017-01-01

    Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge. Despite over a century of research, no preventive treatment exists. We hypothesized that postoperative adhesions develop from a lack of movement of the abdominopelvic organs in the immediate postoperative period while rendered immobile by surgery and opiates, and tested whether manual therapy would prevent their development. In a modified rat cecal abrasion model, rats were allocated to receive treatment with manual therapy or not, and their resulting adhesions were quantified. We also characterized macrophage phenotype. In separate experiments we tested the safety of the treatment on a strictureplasty model, and also the efficacy of the treatment following adhesiolysis. We show that the treatment led to reduced frequency and size of cohesive adhesions, but not other types of adhesions, such as those involving intraperitoneal fatty structures. This effect was associated with a delay in the appearance of trophic macrophages. The treatment did not inhibit healing or induce undesirable complications following strictureplasty. Our results support that that maintained movements of damaged structures in the immediate postoperative period has potential to act as an effective preventive for attenuating cohesive postoperative adhesion development. Our findings lay the groundwork for further research, including mechanical and pharmacologic approaches to maintain movements during healing.

  20. Modified polarized geometrical attenuation model for bidirectional reflection distribution function based on random surface microfacet theory.

    Science.gov (United States)

    Liu, Hong; Zhu, Jingping; Wang, Kai

    2015-08-24

    The geometrical attenuation model given by Blinn was widely used in the geometrical optics bidirectional reflectance distribution function (BRDF) models. Blinn's geometrical attenuation model based on symmetrical V-groove assumption and ray scalar theory causes obvious inaccuracies in BRDF curves and negatives the effects of polarization. Aiming at these questions, a modified polarized geometrical attenuation model based on random surface microfacet theory is presented by combining of masking and shadowing effects and polarized effect. The p-polarized, s-polarized and unpolarized geometrical attenuation functions are given in their separate expressions and are validated with experimental data of two samples. It shows that the modified polarized geometrical attenuation function reaches better physical rationality, improves the precision of BRDF model, and widens the applications for different polarization.

  1. Statistical modeling of optical attenuation measurements in continental fog conditions

    Science.gov (United States)

    Khan, Muhammad Saeed; Amin, Muhammad; Awan, Muhammad Saleem; Minhas, Abid Ali; Saleem, Jawad; Khan, Rahimdad

    2017-03-01

    Free-space optics is an innovative technology that uses atmosphere as a propagation medium to provide higher data rates. These links are heavily affected by atmospheric channel mainly because of fog and clouds that act to scatter and even block the modulated beam of light from reaching the receiver end, hence imposing severe attenuation. A comprehensive statistical study of the fog effects and deep physical understanding of the fog phenomena are very important for suggesting improvements (reliability and efficiency) in such communication systems. In this regard, 6-months real-time measured fog attenuation data are considered and statistically investigated. A detailed statistical analysis related to each fog event for that period is presented; the best probability density functions are selected on the basis of Akaike information criterion, while the estimates of unknown parameters are computed by maximum likelihood estimation technique. The results show that most fog attenuation events follow normal mixture distribution and some follow the Weibull distribution.

  2. Attenuation of surface waves due to monsoon rains: A model study for the north Indian Ocean

    Digital Repository Service at National Institute of Oceanography (India)

    Vethamony, P.; Kumar, B.P.; Sarma, Y.V.B.

    The dynamic interaction of intense rain with waves based on momentum exchange is applied to a second generation wave model to predict wave attenuation during monsoon. The scheme takes into account the characteristics of rain and wave parameters...

  3. Anisotropic attenuation in rocks: Theory, modelling and lab measurements

    Czech Academy of Sciences Publication Activity Database

    Vavryčuk, Václav; Svitek, Tomáš; Lokajíček, Tomáš

    2017-01-01

    Roč. 208, č. 3 (2017), s. 1724-1739 ISSN 0956-540X R&D Projects: GA ČR(CZ) GAP210/12/1491; GA ČR(CZ) GC16-19751J; GA MŠk LH13102 Institutional support: RVO:67985530 ; RVO:67985831 Keywords : elasticity and anelasticity * body waves * seismic anisotropy * seismic attenuation Subject RIV: DC - Siesmology, Volcanology, Earth Structure; DB - Geology ; Mineralogy (GLU-S) OBOR OECD: Volcanology; Geology (GLU-S) Impact factor: 2.414, year: 2016

  4. A practical MGA-ARIMA model for forecasting real-time dynamic rain-induced attenuation

    Science.gov (United States)

    Gong, Shuhong; Gao, Yifeng; Shi, Houbao; Zhao, Ge

    2013-05-01

    novel and practical modified genetic algorithm (MGA)-autoregressive integrated moving average (ARIMA) model for forecasting real-time dynamic rain-induced attenuation has been established by combining genetic algorithm ideas with the ARIMA model. It is proved that due to the introduction of MGA into the ARIMA(1,1,7) model, the MGA-ARIMA model has the potential to be conveniently applied in every country or area by creating a parameter database used by the ARIMA(1,1,7) model. The parameter database is given in this paper based on attenuation data measured in Xi'an, China. The methods to create the parameter databases in other countries or areas are offered, too. Based on the experimental results, the MGA-ARIMA model has been proved practical for forecasting dynamic rain-induced attenuation in real time. The novel model given in this paper is significant for developing adaptive fade mitigation technologies at millimeter wave bands.

  5. An empirical model of diagnostic x-ray attenuation under narrow-beam geometry

    International Nuclear Information System (INIS)

    Mathieu, Kelsey B.; Kappadath, S. Cheenu; White, R. Allen; Atkinson, E. Neely; Cody, Dianna D.

    2011-01-01

    Purpose: The purpose of this study was to develop and validate a mathematical model to describe narrow-beam attenuation of kilovoltage x-ray beams for the intended applications of half-value layer (HVL) and quarter-value layer (QVL) estimations, patient organ shielding, and computer modeling. Methods: An empirical model, which uses the Lambert W function and represents a generalized Lambert-Beer law, was developed. To validate this model, transmission of diagnostic energy x-ray beams was measured over a wide range of attenuator thicknesses [0.49-33.03 mm Al on a computed tomography (CT) scanner, 0.09-1.93 mm Al on two mammography systems, and 0.1-0.45 mm Cu and 0.49-14.87 mm Al using general radiography]. Exposure measurements were acquired under narrow-beam geometry using standard methods, including the appropriate ionization chamber, for each radiographic system. Nonlinear regression was used to find the best-fit curve of the proposed Lambert W model to each measured transmission versus attenuator thickness data set. In addition to validating the Lambert W model, we also assessed the performance of two-point Lambert W interpolation compared to traditional methods for estimating the HVL and QVL [i.e., semilogarithmic (exponential) and linear interpolation]. Results: The Lambert W model was validated for modeling attenuation versus attenuator thickness with respect to the data collected in this study (R 2 > 0.99). Furthermore, Lambert W interpolation was more accurate and less sensitive to the choice of interpolation points used to estimate the HVL and/or QVL than the traditional methods of semilogarithmic and linear interpolation. Conclusions: The proposed Lambert W model accurately describes attenuation of both monoenergetic radiation and (kilovoltage) polyenergetic beams (under narrow-beam geometry).

  6. An empirical model of diagnostic x-ray attenuation under narrow-beam geometry.

    Science.gov (United States)

    Mathieu, Kelsey B; Kappadath, S Cheenu; White, R Allen; Atkinson, E Neely; Cody, Dianna D

    2011-08-01

    The purpose of this study was to develop and validate a mathematical model to describe narrow-beam attenuation of kilovoltage x-ray beams for the intended applications of half-value layer (HVL) and quarter-value layer (QVL) estimations, patient organ shielding, and computer modeling. An empirical model, which uses the Lambert W function and represents a generalized Lambert-Beer law, was developed. To validate this model, transmission of diagnostic energy x-ray beams was measured over a wide range of attenuator thicknesses [0.49-33.03 mm Al on a computed tomography (CT) scanner, 0.09-1.93 mm Al on two mammography systems, and 0.1-0.45 mm Cu and 0.49-14.87 mm Al using general radiography]. Exposure measurements were acquired under narrow-beam geometry using standard methods, including the appropriate ionization chamber, for each radiographic system. Nonlinear regression was used to find the best-fit curve of the proposed Lambert W model to each measured transmission versus attenuator thickness data set. In addition to validating the Lambert W model, we also assessed the performance of two-point Lambert W interpolation compared to traditional methods for estimating the HVL and QVL [i.e., semi-logarithmic (exponential) and linear interpolation]. The Lambert W model was validated for modeling attenuation versus attenuator thickness with respect to the data collected in this study (R2 > 0.99). Furthermore, Lambert W interpolation was more accurate and less sensitive to the choice of interpolation points used to estimate the HVL and/or QVL than the traditional methods of semilogarithmic and linear interpolation. The proposed Lambert W model accurately describes attenuation of both monoenergetic radiation and (kilovoltage) polyenergetic beams (under narrow-beam geometry).

  7. Experimental Test of a New Precision Model for Microwave Rotary Vane Attenuators

    DEFF Research Database (Denmark)

    Guldbrandsen, Tom; Guldbrandsen, Birthe; Warner, Frank L.

    1983-01-01

    coefficients have been measured versus angle of rotation by means of a computer-corrected automatic network analyzer and, within the uncertainty, they agree with the model. From the reflection measurements, corrections to the attenuation were calculated using relations derived from the model. The corrections...

  8. Wave attenuation model for dephasing and measurement of ...

    Indian Academy of Sciences (India)

    There are different ways to model dephasing in mesoscopic systems. An interesting method is to attach a voltage probe [3] to the sample as in the inset of figure 1 (Buttiker's model). In this model, an electron captured by a voltage probe is injected back with an uncorrelated phase leading to irreversible loss of phase memory ...

  9. Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model.

    Science.gov (United States)

    Arita, Minetaro; Ami, Yasushi; Wakita, Takaji; Shimizu, Hiroyuki

    2008-02-01

    Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

  10. A simple rain attenuation model for earth-space radio links operating at 10-35 GHz

    Science.gov (United States)

    Stutzman, W. L.; Yon, K. M.

    1986-01-01

    The simple attenuation model has been improved from an earlier version and now includes the effect of wave polarization. The model is for the prediction of rain attenuation statistics on earth-space communication links operating in the 10-35 GHz band. Simple calculations produce attenuation values as a function of average rain rate. These together with rain rate statistics (either measured or predicted) can be used to predict annual rain attenuation statistics. In this paper model predictions are compared to measured data from a data base of 62 experiments performed in the U.S., Europe, and Japan. Comparisons are also made to predictions from other models.

  11. Economic Game Theory to Model the Attenuation of Virulence of an Obligate Intracellular Bacterium.

    Science.gov (United States)

    Tago, Damian; Meyer, Damien F

    2016-01-01

    Diseases induced by obligate intracellular pathogens have a large burden on global human and animal health. Understanding the factors involved in the virulence and fitness of these pathogens contributes to the development of control strategies against these diseases. Based on biological observations, a theoretical model using game theory is proposed to explain how obligate intracellular bacteria interact with their host. The equilibrium in such a game shows that the virulence and fitness of the bacterium is host-triggered and by changing the host's defense system to which the bacterium is confronted, an evolutionary process leads to an attenuated strain. Although, the attenuation procedure has already been conducted in practice in order to develop an attenuated vaccine (e.g., with Ehrlichia ruminantium), there was a lack of understanding of the theoretical basis behind this process. Our work provides a model to better comprehend the existence of different phenotypes and some underlying evolutionary mechanisms for the virulence of obligate intracellular bacteria.

  12. Dose attenuation by a carbon fiber linac couch and modeling with a treatment planning system

    International Nuclear Information System (INIS)

    Sanchez Galiano, P.; Garcia Sancho, J.M.; Crelgo, D.; Pamos, M.; Fernandez, J.; Vivanco, J.

    2010-01-01

    The purpose of this work is to investigate the attenuation caused by a carbon fiber linac treatment couch and the ability of a commercial radiotherapy treatment planning system to simulate it. The attenuation caused by an Exact treatment couch in a Varian Clinac 2100 C/D was characterized in detail. Both 6 MV and 18 MV photon beams were studied. The treatment couch was modeled and incorporated to Elekta XiO treatment planning system. Measured and computed attenuation values were compared. As a result we found that the attenuation caused by this complex treatment couch is strongly dependent on the incidence angle of the beam. The measured attenuation values reach 16% for 6 MV and 10% for 18 MV. The model incorporated to the treatment planning software allows reducing the differences between measured and calculated data below 2.5% and 2.0% for 6 MV and 18 MV respectively. In conclusion, it is strongly recommended accounting for the perturbation caused by this carbon fiber treatment couch when the beam intersects it. The treatment planning system studied can simulate this treatment couch accurately. Clinical implementation of the described method requires a reliable procedure to reproduce the same patient geometry in the treatment delivery and planning. (Author).

  13. Attenuation Model Using the Large-N Array from the Source Physics Experiment

    Science.gov (United States)

    Atterholt, J.; Chen, T.; Snelson, C. M.; Mellors, R. J.

    2017-12-01

    The Source Physics Experiment (SPE) consists of a series of chemical explosions at the Nevada National Security Site. SPE seeks to better characterize the influence of subsurface heterogeneities on seismic wave propagation and energy dissipation from explosions. As a part of this experiment, SPE-5, a 5000 kg TNT equivalent chemical explosion, was detonated in 2016. During the SPE-5 experiment, a Large-N array of 996 geophones (half 3-component and half z-component) was deployed. This array covered an area that includes loosely consolidated alluvium (weak rock) and weathered granite (hard rock), and recorded the SPE-5 explosion as well as 53 weight drops. We use these Large-N recordings to develop an attenuation model of the area to better characterize how geologic structures influence source energy partitioning. We found a clear variation in seismic attenuation for different rock types: high attenuation (low Q) for alluvium and low attenuation (high Q) for granite. The attenuation structure correlates well with local geology, and will be incorporated into the large simulation effort of the SPE program to validate predictive models. (LA-UR-17-26382)

  14. Modeling of Air Attenuation Effects on Gamma Detection at Altitude

    International Nuclear Information System (INIS)

    Detwiler, R. S.

    2002-01-01

    This paper focuses on modeling the detection capabilities of NaI sensor systems at high altitudes for ground sources. The modeling was done with the Monte Carlo N-Transport (MCNP) code developed at Los Alamos National Laboratory. The specific systems modeled were the fixed wing and helicopter aircraft sensor systems, assets of the U. S. Department of Energy's National Nuclear Security Administration Nevada Operations Office (NNSA/NV) Aerial Measuring System (AMS). In previous (2001) modeling, Sodium Iodine (NaI) detector responses were simulated for both point and distributed surface sources as a function of gamma energy and altitude. For point sources, photo-peak efficiencies were calculated for a zero radial distance and an offset equal to the altitude. For distributed sources approximating an infinite plane, gross count efficiencies were calculated and normalized to a uniform surface deposition of 1 (micro)Ci/m 2 . To validate the calculations, benchmark measurements were made for simple source-detector configurations. The 2002 continuation of the modeling presented here includes checking models against available data, and modifications to allow more effective and accurate directional biasing of ground point and distributed sources. Fixed-wing data results will be shown for two point sources as a function of altitude

  15. Seismic attenuation in fractured porous media: insights from a hybrid numerical and analytical model

    International Nuclear Information System (INIS)

    Ekanem, A M; Li, X Y; Chapman, M; Main, I G

    2015-01-01

    Seismic attenuation in fluid-saturated porous rocks can occur by geometric spreading, wave scattering or the internal dissipation of energy, most likely due to the squirt-flow mechanism. In principle, the pattern of seismic attenuation recorded on an array of sensors contains information about the medium, in terms of material heterogeneity and anisotropy, as well as material properties such as porosity, crack density, and pore-fluid composition and mobility. In practice, this inverse problem is challenging. Here we provide some insights into the effects of internal dissipation by analysing synthetic data produced by a hybrid numerical and analytical model for seismic wave propagation in a fractured medium embedded within a layered geological structure. The model is made up of one anisotropic and three isotropic horizontal layers. The anisotropic layer consists of a porous, fluid-saturated material containing vertically aligned inclusions representing a set of fractures. This combination allows squirt-flow to occur between the pores in the matrix and the model fractures. Our results show that the fluid mobility and the associated relaxation time of the fluid-pressure gradient control the frequency range over which attenuation occurs. This induced attenuation increases with incidence angle and azimuth away from the fracture strike-direction. Azimuthal variations in the induced attenuation are elliptical allowing the fracture orientations to be obtained from the axes of the ellipse. These observations hold out the potential of using seismic attenuation as an additional diagnostic in the characterisation of rock formations for a variety of applications including hydrocarbon exploration and production, subsurface storage of CO 2 , and geothermal energy extraction. (paper)

  16. Radiation Background and Attenuation Model Validation and Development

    Energy Technology Data Exchange (ETDEWEB)

    Peplow, Douglas E. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Santiago, Claudio P. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-08-05

    This report describes the initial results of a study being conducted as part of the Urban Search Planning Tool project. The study is comparing the Urban Scene Simulator (USS), a one-dimensional (1D) radiation transport model developed at LLNL, with the three-dimensional (3D) radiation transport model from ORNL using the MCNP, SCALE/ORIGEN and SCALE/MAVRIC simulation codes. In this study, we have analyzed the differences between the two approaches at every step, from source term representation, to estimating flux and detector count rates at a fixed distance from a simple surface (slab), and at points throughout more complex 3D scenes.

  17. Outdoor FSO Communications Under Fog: Attenuation Modeling and Performance Evaluation

    KAUST Repository

    Esmail, Maged Abdullah; Fathallah, Habib; Alouini, Mohamed-Slim

    2016-01-01

    transmission technology. Therefore, FSO will have its preferred market segment in future wireless fifth-generation/sixth-generation (5G/6G) networks having cell sizes that are lower than a 1-km diameter. Moreover, the results of our modeling and analysis can

  18. Attenuation of surface waves in porous media: Shock wave experiments and modelling

    NARCIS (Netherlands)

    Chao, G.E; Smeulders, D.M.J.; Dongen, van M.E.H.

    2005-01-01

    In this project we conduct experimental and numerical investigations on the attenuation mechanisms of surface waves in poroelastic materials. Viscous dissipation effects are modelled in the framework of Biot's theory. The experiments are performed using a shock tube technique. Quantitative agreement

  19. CHROMAT trademark Version 1.1--Soil Chromium Attenuation Evaluation Model

    International Nuclear Information System (INIS)

    Felmy, A.R.; Rai, D.; Zachara, J.M.; Thapa, M.; Gold, M.

    1992-07-01

    This document is the user's manual and technical reference for the Soil Chromium Attenuation Model (CHROMAT trademark), a computer code designed to calculate both the dissolved Cr concentration and the amount of Cr attenuated in soils as a result of the geochemical reactions that occur as Cr-containing leachates migrate through porous soils. The dissolved Cr concentration and the amount of Cr attenuated are calculated using thermodynamic (mechanistic) data for aqueous complexation reactions, adsorption/ desorption reactions, and precipitation/dissolution reactions involving both CR(III) and Cr(VI) species. Use of this mechanistic approach means that CHROMAT trademark requires a minimum amount of site-specific data on leachate and soil characteristics. CHROMAT trademark is distributed in executable form for IBM and IBM-compatible personal computers through a license from the Electric Power Research Institute (EPRI). The user interacts with CHROMAT trademark using menu-driven screen displays. Interactive on-line help options are available. Output from the code can be obtained in tabular or graphic form. This manual describes the development of CHROMAT trademark, including experimental data development in support of the model and model validation studies. The thermodynamic data and computational algorithm are also described. Example problems and results are included

  20. A simple model for the estimation of rain-induced attenuation along earth-space paths at millimeter wavelengths

    Science.gov (United States)

    Stutzman, W. L.; Dishman, W. K.

    1982-01-01

    A simple attenuation model (SAM) is presented for estimating rain-induced attenuation along an earth-space path. The rain model uses an effective spatial rain distribution which is uniform for low rain rates and which has an exponentially shaped horizontal rain profile for high rain rates. When compared to other models, the SAM performed well in the important region of low percentages of time, and had the lowest percent standard deviation of all percent time values tested.

  1. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    International Nuclear Information System (INIS)

    Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

    2014-01-01

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients

  2. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  3. Seismic attenuation relationship with homogeneous and heterogeneous prediction-error variance models

    Science.gov (United States)

    Mu, He-Qing; Xu, Rong-Rong; Yuen, Ka-Veng

    2014-03-01

    Peak ground acceleration (PGA) estimation is an important task in earthquake engineering practice. One of the most well-known models is the Boore-Joyner-Fumal formula, which estimates the PGA using the moment magnitude, the site-to-fault distance and the site foundation properties. In the present study, the complexity for this formula and the homogeneity assumption for the prediction-error variance are investigated and an efficiency-robustness balanced formula is proposed. For this purpose, a reduced-order Monte Carlo simulation algorithm for Bayesian model class selection is presented to obtain the most suitable predictive formula and prediction-error model for the seismic attenuation relationship. In this approach, each model class (a predictive formula with a prediction-error model) is evaluated according to its plausibility given the data. The one with the highest plausibility is robust since it possesses the optimal balance between the data fitting capability and the sensitivity to noise. A database of strong ground motion records in the Tangshan region of China is obtained from the China Earthquake Data Center for the analysis. The optimal predictive formula is proposed based on this database. It is shown that the proposed formula with heterogeneous prediction-error variance is much simpler than the attenuation model suggested by Boore, Joyner and Fumal (1993).

  4. Attenuation of seismic waves and the universal rheological model of the Earth's mantle

    Science.gov (United States)

    Birger, B. I.

    2007-08-01

    Analysis of results of laboratory studies on creep of mantle rocks, data on seismic wave attenuation in the mantle, and rheological micromechanisms shows that the universal, i.e., relevant to all time scales, rheological model of the mantle can be represented as four rheological elements connected in series. These elements account for elasticity, diffusion rheology, high temperature dislocation rheology, and low temperature dislocation rheology. The diffusion rheology element is described in terms of a Newtonian viscous fluid. The high temperature dislocation rheology element is described by the rheological model previously proposed by the author. This model is a combination of a power-law non-Newtonian fluid model for stationary flows and the linear hereditary Andrade model for flows associated with small strains. The low temperature dislocation rheology element is described by the linear hereditary Lomnitz model.

  5. LERC-SLAM - THE NASA LEWIS RESEARCH CENTER SATELLITE LINK ATTENUATION MODEL PROGRAM (IBM PC VERSION)

    Science.gov (United States)

    Manning, R. M.

    1994-01-01

    The frequency and intensity of rain attenuation affecting the communication between a satellite and an earth terminal is an important consideration in planning satellite links. The NASA Lewis Research Center Satellite Link Attenuation Model Program (LeRC-SLAM) provides a static and dynamic statistical assessment of the impact of rain attenuation on a communications link established between an earth terminal and a geosynchronous satellite. The program is designed for use in the specification, design and assessment of satellite links for any terminal location in the continental United States. The basis for LeRC-SLAM is the ACTS Rain Attenuation Prediction Model, which uses a log-normal cumulative probability distribution to describe the random process of rain attenuation on satellite links. The derivation of the statistics for the rainrate process at the specified terminal location relies on long term rainfall records compiled by the U.S. Weather Service during time periods of up to 55 years in length. The theory of extreme value statistics is also utilized. The user provides 1) the longitudinal position of the satellite in geosynchronous orbit, 2) the geographical position of the earth terminal in terms of latitude and longitude, 3) the height above sea level of the terminal site, 4) the yearly average rainfall at the terminal site, and 5) the operating frequency of the communications link (within 1 to 1000 GHz, inclusive). Based on the yearly average rainfall at the terminal location, LeRC-SLAM calculates the relevant rain statistics for the site using an internal data base. The program then generates rain attenuation data for the satellite link. This data includes a description of the static (i.e., yearly) attenuation process, an evaluation of the cumulative probability distribution for attenuation effects, and an evaluation of the probability of fades below selected fade depths. In addition, LeRC-SLAM calculates the elevation and azimuth angles of the terminal

  6. LERC-SLAM - THE NASA LEWIS RESEARCH CENTER SATELLITE LINK ATTENUATION MODEL PROGRAM (MACINTOSH VERSION)

    Science.gov (United States)

    Manning, R. M.

    1994-01-01

    The frequency and intensity of rain attenuation affecting the communication between a satellite and an earth terminal is an important consideration in planning satellite links. The NASA Lewis Research Center Satellite Link Attenuation Model Program (LeRC-SLAM) provides a static and dynamic statistical assessment of the impact of rain attenuation on a communications link established between an earth terminal and a geosynchronous satellite. The program is designed for use in the specification, design and assessment of satellite links for any terminal location in the continental United States. The basis for LeRC-SLAM is the ACTS Rain Attenuation Prediction Model, which uses a log-normal cumulative probability distribution to describe the random process of rain attenuation on satellite links. The derivation of the statistics for the rainrate process at the specified terminal location relies on long term rainfall records compiled by the U.S. Weather Service during time periods of up to 55 years in length. The theory of extreme value statistics is also utilized. The user provides 1) the longitudinal position of the satellite in geosynchronous orbit, 2) the geographical position of the earth terminal in terms of latitude and longitude, 3) the height above sea level of the terminal site, 4) the yearly average rainfall at the terminal site, and 5) the operating frequency of the communications link (within 1 to 1000 GHz, inclusive). Based on the yearly average rainfall at the terminal location, LeRC-SLAM calculates the relevant rain statistics for the site using an internal data base. The program then generates rain attenuation data for the satellite link. This data includes a description of the static (i.e., yearly) attenuation process, an evaluation of the cumulative probability distribution for attenuation effects, and an evaluation of the probability of fades below selected fade depths. In addition, LeRC-SLAM calculates the elevation and azimuth angles of the terminal

  7. Acoustic Velocity and Attenuation in Magnetorhelogical fluids based on an effective density fluid model

    Directory of Open Access Journals (Sweden)

    Shen Min

    2016-01-01

    Full Text Available Magnetrohelogical fluids (MRFs represent a class of smart materials whose rheological properties change in response to the magnetic field, which resulting in the drastic change of the acoustic impedance. This paper presents an acoustic propagation model that approximates a fluid-saturated porous medium as a fluid with a bulk modulus and effective density (EDFM to study the acoustic propagation in the MRF materials under magnetic field. The effective density fluid model derived from the Biot’s theory. Some minor changes to the theory had to be applied, modeling both fluid-like and solid-like state of the MRF material. The attenuation and velocity variation of the MRF are numerical calculated. The calculated results show that for the MRF material the attenuation and velocity predicted with this effective density fluid model are close agreement with the previous predictions by Biot’s theory. We demonstrate that for the MRF material acoustic prediction the effective density fluid model is an accurate alternative to full Biot’s theory and is much simpler to implement.

  8. Cleaning up a salt spill : predictive modelling and monitoring natural attenuation to save remedial costs

    Energy Technology Data Exchange (ETDEWEB)

    Tsang, B.; Shaikh, A.A. [EBA Engineering Consultants Ltd., Calgary, AB (Canada)

    2006-07-01

    Predictive modelling and monitoring natural attenuation to save remedial costs in cleaning up a salt spill were discussed with reference to a site located in central Alberta, as well as a pipeline break in 2002 from a corroded pipe which resulted in a large spill of produced water and oil. Remedial alternatives and an assessment of the site were presented. This included an electromagnetic survey in 2004, groundwater flow regime, soil and groundwater quality data, vegetation survey, and predictive modelling versus observed water quality. Photos and illustrations of the site from the air were provided. A conceptual salt leaching and transport model was proposed as a solution. Model calculation results were also presented. Last, the presentation discussed some important considerations for predictive modeling and next steps for the site. These included continued monitoring, implementation of a restoration plan and engagement of stakeholders such as Alberta Environment and the site landowner. tabs., figs.

  9. Thermoacoustic tomography for an integro-differential wave equation modeling attenuation

    Science.gov (United States)

    Acosta, Sebastián; Palacios, Benjamín

    2018-02-01

    In this article we study the inverse problem of thermoacoustic tomography (TAT) on a medium with attenuation represented by a time-convolution (or memory) term, and whose consideration is motivated by the modeling of ultrasound waves in heterogeneous tissue via fractional derivatives with spatially dependent parameters. Under the assumption of being able to measure data on the whole boundary, we prove uniqueness and stability, and propose a convergent reconstruction method for a class of smooth variable sound speeds. By a suitable modification of the time reversal technique, we obtain a Neumann series reconstruction formula.

  10. Ultrasonic attenuation measurements in neutron-irradiated quartz: a microscopic model for the tunneling states

    International Nuclear Information System (INIS)

    Keppens, V.; Laermans, C.; Coeck, M.

    1996-01-01

    Ultrasonic attenuation measurements are carried out in neutron-irradiated z-cut quartz for three different doses, in a frequency range from 70 to 320 MHz. The data are analyzed using the tunneling model, and the typical TS-parameters are derived. A comparison with the results obtained from similar x-cut samples shows that the coupling of the tunneling states with the longitudinal phonons is direction-dependent. This confirms the anisotropic behaviour of the tunneling states and gives support to the microscopic picture of the TS as a rotation of coupled SiO 4 tetrahedra. (orig.)

  11. A meta-analysis of experimental studies of attenuated Schistosoma mansoni vaccines in the mouse model

    Directory of Open Access Journals (Sweden)

    Mizuho eFukushige

    2015-02-01

    Full Text Available Schistosomiasis is a water-borne, parasitic disease of major public health importance. There has been considerable effort for several decades towards the development of a vaccine against the disease. Numerous mouse experimental studies using attenuated Schistosoma mansoni parasites for vaccination have been published since the 1960s. However, to date, there has been no systematic review or meta-analysis of these data. The aim of this study is to identify measurable experimental conditions that affect the level of protection against re-infection with S. mansoni in mice vaccinated with radiation attenuated cercariae. Following a systematic review, a total of 755 observations were extracted from 105 articles (published 1963-2007 meeting the searching criteria. Random effects meta-regression models were used to identify the influential predictors.Three predictors were found to have statistically significant effects on the level of protection from vaccination: increasing numbers of immunizing parasites had a positive effect on fraction of protection whereas increasing radiation dose and time to challenge infection had negative effects. Models showed that the irradiated cercariae vaccine has the potential to achieve protection as high as 78% with a single dose vaccination. This declines slowly over time but remains high for at least 8 months after the last immunization. These findings provide insights into the optimal delivery of attenuated parasite vaccination and into the nature and development of protective vaccine induced immunity against schistosomiasis which may inform the formulation of human vaccines and the predicted duration of protection and thus frequency of booster vaccines.

  12. Model testing of a 10-kg high explosive blast attenuation maze

    International Nuclear Information System (INIS)

    Bacigalupi, C.M.; Burton, W.A.

    1981-01-01

    The basement area of the proposed High Explosive Applications Facility (HEAF) at the Lawrence Livermore National Laboratory includes 10-kg HE assembly and process cells, and a 10-kg corridor for the transport of up to 10 kg of HE from the receiving dock to the cells and to the experimental firing tanks. Previous model experiments developed a process cell-maze configuration that attenuated the effects of an accidental 10-kg detonation to acceptable levels (maximum of 10 to 11 psi reflected). This document reports 1/8-scale model tests conducted to confirm the maze design and to determine the blast pressures in adjacent areas in the final HEAF building configuration. In addition, pressure/time information was obtained at selected points in the model expansion chamber to provide the architect-engineer with information for structural design

  13. Endothelin receptor antagonist attenuates oxidative stress in a neonatal sepsis piglet model.

    Science.gov (United States)

    Goto, Tatenobu; Hussein, Mohamed Hamed; Kato, Shin; Daoud, Ghada Abdel-Hamid; Kato, Takenori; Sugiura, Takahiro; Kakita, Hiroki; Nobata, Masanori; Kamei, Michi; Mizuno, Haruo; Imai, Masaki; Ito, Tetsuya; Kato, Ineko; Suzuki, Satoshi; Okada, Noriko; Togari, Hajime; Okada, Hidechika

    2012-12-01

    Oxidative stress (oxidant-antioxidant imbalance) plays an important role in the pathophysiology of neonatal sepsis. This study evaluated whether an antisense peptide endothelin receptor antagonist, ETR-P1/fl, could attenuate oxidative stress in a neonatal sepsis model. A total of 18 3-d-old piglets were anesthetized and mechanically ventilated. Six piglets received cecal ligation and perforation (CLP group) for induction of sepsis. Six piglets also received continuous infusion (0.05 mg/kg/h) of ETR-P1/fl 30 min after CLP (ETR-P1/fl group). Six piglets received a sham operation. Serum total hydroperoxide (TH), biological antioxidant potentials (BAPs), oxidative stress index (OSI, calculated as TH/BAP), interleukin (IL)-6, serum glutamic oxaloacetic transaminase (GOT), and creatinine were measured before CLP and at 1, 3, and 6 h after CLP. CLP evoked a state of shock resulting in elevated TH, OSI, and IL-6 levels. ETR-P1/fl administration after CLP resulted in lower serum TH at 1 and 3 h after CLP, OSI at 1 and 3 h after CLP, IL-6 at 1 and 3 h after CLP, and GOT at 3 and 6 h after CLP as compared with the CLP group. ETR-P1/fl treatment significantly attenuated the elevation of serum oxidative stress markers (TH and OSI), IL-6, and GOT in a progressive neonatal sepsis CLP model.

  14. Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a rat model of metabolic syndrome.

    Science.gov (United States)

    Takatsu, Miwa; Nakashima, Chieko; Takahashi, Keiji; Murase, Tamayo; Hattori, Takuya; Ito, Hiromi; Murohara, Toyoaki; Nagata, Kohzo

    2013-11-01

    Calorie restriction (CR) can modulate the features of obesity-related metabolic and cardiovascular diseases. We have recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese rats develop hypertension and manifest left ventricular remodeling and diastolic dysfunction, as well as increased cardiac oxidative stress and inflammation. We have now investigated the effects of CR on cardiac pathophysiology in DS/obese rats. DS/obese rats were fed either normal laboratory chow ad libitum or a calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to 13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean) littermates served as controls. CR reduced body weight in both DS/obese and DS/lean rats, as well as attenuated the development of hypertension in DS/obese rats without affecting blood pressure in DS/lean rats. CR also reduced body fat content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese rats. In addition, it increased serum adiponectin concentration, as well as downregulated the expression of angiotensin-converting enzyme and angiotensin II type 1A receptor genes in the heart of DS/obese rats. Our results thus show that CR attenuated obesity and hypertension, as well as left ventricular remodeling and diastolic dysfunction in DS/obese rats, with these latter effects being associated with reduced cardiac oxidative stress and inflammation.

  15. Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model.

    Science.gov (United States)

    Yumoto, Masato; Nishida, Osamu; Nakamura, Fujio; Katsuya, Hirotada

    2005-01-01

    Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger. We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H2O2). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc). In series 1, treatment with catalase (an H2O2 scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H2O2 may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values. Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.

  16. The attenuation of concentrations model: a new method for assessing mercury mobility in sediments

    Directory of Open Access Journals (Sweden)

    Julio C. Wasserman

    2004-02-01

    Full Text Available In this work we propose a new approach for the determination of the mobility of mercury in sediments based on spatial distribution of concentrations. We chose the Tainheiros Cove, located in the Todos os Santos Bay, Brazil, as the study area, for it has a history of mercury contamination due to a chloro-alkali plant that was active during 12 years. Twenty-six surface sediment samples were collected from the area and mercury concentrations were measured by cold vapour atomic absorption spectrophotometry. A contour map was constructed from the results, indicating that mercury accumulated in a "hot spot" where concentrations reach more than 1 µg g-1. The model is able to estimate mobility of mercury in the sediments based on the distances between iso-concentration contours that determines an attenuation of concentrations factor. Values of attenuation ranged between 0.0729 (East of the hot spot, indicating higher mobility to 0.7727 (North of the hot spot, indicating lower mobility.

  17. Attenuation Factors for B(E2) in the Microscopic Description of Multiphonon States ---A Simple Model Analysis---

    Science.gov (United States)

    Matsuyanagi, K.

    1982-05-01

    With an exactly solvable O(4) model of Piepenbring, Silvestre-Brac and Szymanski, we demonstrate that the attenuation factor for the B(E2) values, derived by the lowest-order approximation of the multiphonon method, takes excellent care of the kinematical anharmonicity effects, if multiphonon states are defined in the intrinsic subspace orthogonal to the pairing rotation. It is also shown that the other attenuation effect characterizing the interacting boson model is not a dominant effect in the model analysed here.

  18. Granulocyte colony stimulating factor attenuates inflammation in a mouse model of amyotrophic lateral sclerosis

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    Giniatullina Raisa

    2011-06-01

    Full Text Available Abstract Background Granulocyte colony stimulating factor (GCSF is protective in animal models of various neurodegenerative diseases. We investigated whether pegfilgrastim, GCSF with sustained action, is protective in a mouse model of amyotrophic lateral sclerosis (ALS. ALS is a fatal neurodegenerative disease with manifestations of upper and lower motoneuron death and muscle atrophy accompanied by inflammation in the CNS and periphery. Methods Human mutant G93A superoxide dismutase (SOD1 ALS mice were treated with pegfilgrastim starting at the presymptomatic stage and continued until the end stage. After long-term pegfilgrastim treatment, the inflammation status was defined in the spinal cord and peripheral tissues including hematopoietic organs and muscle. The effect of GCSF on spinal cord neuron survival and microglia, bone marrow and spleen monocyte activation was assessed in vitro. Results Long-term pegfilgrastim treatment prolonged mutant SOD1 mice survival and attenuated both astro- and microgliosis in the spinal cord. Pegfilgrastim in SOD1 mice modulated the inflammatory cell populations in the bone marrow and spleen and reduced the production of pro-inflammatory cytokine in monocytes and microglia. The mobilization of hematopoietic stem cells into the circulation was restored back to basal level after long-term pegfilgrastim treatment in SOD1 mice while the storage of Ly6C expressing monocytes in the bone marrow and spleen remained elevated. After pegfilgrastim treatment, an increased proportion of these cells in the degenerative muscle was detected at the end stage of ALS. Conclusions GCSF attenuated inflammation in the CNS and the periphery in a mouse model of ALS and thereby delayed the progression of the disease. This mechanism of action targeting inflammation provides a new perspective of the usage of GCSF in the treatment of ALS.

  19. Evaluation of conceptual and numerical models for arsenic mobilization and attenuation during managed aquifer recharge.

    Science.gov (United States)

    Wallis, Ilka; Prommer, Henning; Simmons, Craig T; Post, Vincent; Stuyfzand, Pieter J

    2010-07-01

    Managed Aquifer Recharge (MAR) is promoted as an attractive technique to meet growing water demands. An impediment to MAR applications, where oxygenated water is recharged into anoxic aquifers, is the potential mobilization of trace metals (e.g., arsenic). While conceptual models for arsenic transport under such circumstances exist, they are generally not rigorously evaluated through numerical modeling, especially at field-scale. In this work, geochemical data from an injection experiment in The Netherlands, where the introduction of oxygenated water into an anoxic aquifer mobilized arsenic, was used to develop and evaluate conceptual and numerical models of arsenic release and attenuation under field-scale conditions. Initially, a groundwater flow and nonreactive transport model was developed. Subsequent reactive transport simulations focused on the description of the temporal and spatial evolution of the redox zonation. The calibrated model was then used to study and quantify the transport of arsenic. In the model that best reproduced field observations, the fate of arsenic was simulated by (i) release via codissolution of arsenopyrite, stoichiometrically linked to pyrite oxidation, (ii) kinetically controlled oxidation of dissolved As(III) to As(V), and (iii) As adsorption via surface complexation on neo-precipitated iron oxides.

  20. PREDICTING ATTENUATION OF VIRUSES DURING PERCOLATION IN SOILS: 2. USER'S GUIDE TO THE VIRULO 1.0 COMPUTER MODEL

    Science.gov (United States)

    In the EPA document Predicting Attenuation of Viruses During Percolation in Soils 1. Probabilistic Model the conceptual, theoretical, and mathematical foundations for a predictive screening model were presented. In this current volume we present a User's Guide for the computer mo...

  1. STRATEGIC MODEL FOR ATTENUATING RURAL INEQUITIES IN SOUTH-MUNTENIA REGION

    Directory of Open Access Journals (Sweden)

    CRISTINA BÂLDAN

    2011-01-01

    Full Text Available In carrying out the paper: “Strategic model for attenuating rural inequities in South-Muntenia Region”, I had like primary goals the accomplishment of two kinds of objectives: general objectives and specific objectives. For the general objectives, I followed: developing the approach theoretical mode for combating rural inequities; the development of strategic plans for approaching the rural inequities combat and identifying strategic socio-economic measures dedicated for promoting necessary measures for combating social inequities. And the specific objectives had like goals the SWOT analysis and the development of strategic plans in local profile, based on clusters. The analysis of rural area in South-Muntenia Region has been made at the level of local administrative-territorial units, the smallest territorial level from which is collecting and after the statistic information is published. Utilizing this kind of territorial level is a positive premise for obtaining results with a high accurate degree.

  2. Implementation of viscoelastic mud-induced energy attenuation in the third-generation wave model, SWAN

    Science.gov (United States)

    Beyramzade, Mostafa; Siadatmousavi, Seyed Mostafa

    2018-01-01

    The interaction of waves with fluid mud can dissipate the wave energy significantly over few wavelengths. In this study, the third-generation wave model, SWAN, was advanced to include attenuation of wave energy due to interaction with a viscoelastic fluid mud layer. The performances of implemented viscoelastic models were verified against an analytical solution and viscous formulations for simple one-dimensional propagation cases. Stationary and non-stationary test cases in the Surinam coast and the Atchafalaya Shelf showed that the inclusion of the mud-wave interaction term in the third-generation wave model enhances the model performance in real applications. A high value of mud viscosity (of the order of 0.1 m2/s) was required in both field cases to remedy model overestimation at high frequency ranges of the wave spectrum. The use of frequency-dependent mud viscosity value improved the performance of model, especially in the frequency range of 0.2-0.35 Hz in the wave spectrum. In addition, the mud-wave interaction might affect the high frequency part of the spectrum, and this part of the wave spectrum is also affected by energy transfer from wind to waves, even for the fetch lengths of the order of 10 km. It is shown that exclusion of the wind input term in such cases might result in different values for parameters of mud layer when inverse modeling procedure was employed. Unlike viscous models for wave-mud interaction, the inverse modeling results to a set of mud parameters with the same performance when the viscoelastic model is used. It provides an opportunity to select realistic mud parameters which are in more agreement with in situ measurements.

  3. Selumetinib Attenuates Skeletal Muscle Wasting in Murine Cachexia Model through ERK Inhibition and AKT Activation.

    Science.gov (United States)

    Quan-Jun, Yang; Yan, Huo; Yong-Long, Han; Li-Li, Wan; Jie, Li; Jin-Lu, Huang; Jin, Lu; Peng-Guo, Chen; Run, Gan; Cheng, Guo

    2017-02-01

    Cancer cachexia is a multifactorial syndrome affecting the skeletal muscle. Previous clinical trials showed that treatment with MEK inhibitor selumetinib resulted in skeletal muscle anabolism. However, it is conflicting that MAPK/ERK pathway controls the mass of the skeletal muscle. The current study investigated the therapeutic effect and mechanisms of selumetinib in amelioration of cancer cachexia. The classical cancer cachexia model was established via transplantation of CT26 colon adenocarcinoma cells into BALB/c mice. The effect of selumetinib on body weight, tumor growth, skeletal muscle, food intake, serum proinflammatory cytokines, E3 ligases, and MEK/ERK-related pathways was analyzed. Two independent experiments showed that 30 mg/kg/d selumetinib prevented the loss of body weight in murine cachexia mice. Muscle wasting was attenuated and the expression of E3 ligases, MuRF1 and Fbx32, was inhibited following selumetinib treatment of the gastrocnemius muscle. Furthermore, selumetinib efficiently reduced tumor burden without influencing the cancer cell proliferation, cumulative food intake, and serum cytokines. These results indicated that the role of selumetinib in attenuating muscle wasting was independent of cancer burden. Detailed analysis of the mechanism revealed AKT and mTOR were activated, while ERK, FoxO3a, and GSK3β were inhibited in the selumetinib -treated cachexia group. These indicated that selumetinib effectively prevented skeletal muscle wasting in cancer cachexia model through ERK inhibition and AKT activation in gastrocnemius muscle via cross-inhibition. The study not only elucidated the mechanism of MEK/ERK inhibition in skeletal muscle anabolism, but also validated selumetinib therapy as an effective intervention against cancer cachexia. Mol Cancer Ther; 16(2); 334-43. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Experimental chronic kidney disease attenuates ischemia-reperfusion injury in an ex vivo rat lung model.

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    Chung-Kan Peng

    Full Text Available Lung ischemia reperfusion injury (LIRI is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75% diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR-induced acute lung injury. The clinicopathological parameters of LIRI, including pulmonary edema, lipid peroxidation, histopathological changes, immunohistochemistry changes, chemokine CXCL1, inducible nitric oxide synthase (iNOS, proinflammatory and anti-inflammatory cytokines, heat shock protein expression, and nuclear factor-κB (NF-κB activation were determined. Our results indicated that adenine-fed rats developed CKD as characterized by increased blood urea nitrogen and creatinine levels and the deposition of crystals in the renal tubules and interstitium. IR induced a significant increase in the pulmonary arterial pressure, lung edema, lung injury scores, the expression of CXCL1 mRNA, iNOS level, and protein concentration of the bronchial alveolar lavage fluid (BALF. The tumor necrosis factor-α levels in the BALF and perfusate; the interleukin-10 level in the perfusate; and the malondialdehyde levels in the lung tissue and perfusate were also significantly increased by LIRI. Counterintuitively, adenine-induced CKD significantly attenuated the severity of lung injury induced by IR. CKD rats exhibited increased heat shock protein 70 expression and decreased activation of NF-κB signaling. In conclusion, adenine-induced CKD attenuated LIRI by inhibiting the NF-κB pathway.

  5. Tracer attenuation in groundwater

    Science.gov (United States)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  6. Validation of mathematical models to describe fluid dynamics of a cold riser by gamma ray attenuation

    International Nuclear Information System (INIS)

    Melo, Ana Cristina Bezerra Azedo de

    2004-12-01

    The fluid dynamic behavior of a riser in a cold type FCC model was investigated by means of catalyst concentration distribution measured with gamma attenuation and simulated with a mathematical model. In the riser of the cold model, MEF, 0,032 m in diameter, 2,30 m in length the fluidized bed, whose components are air and FCC catalyst, circulates. The MEF is operated by automatic control and instruments for measuring fluid dynamic variables. An axial catalyst concentration distribution was measured using an Am-241 gamma source and a NaI detector coupled to a multichannel provided with a software for data acquisition and evaluation. The MEF was adapted for a fluid dynamic model validation which describes the flow in the riser, for example, by introducing an injector for controlling the solid flow in circulation. Mathematical models were selected from literature, analyzed and tested to simulate the fluid dynamic of the riser. A methodology for validating fluid dynamic models was studied and implemented. The stages of the work were developed according to the validation methodology, such as data planning experiments, study of the equations which describe the fluidodynamic, computational solvers application and comparison with experimental data. Operational sequences were carried out keeping the MEF conditions for measuring catalyst concentration and simultaneously measuring the fluid dynamic variables, velocity of the components and pressure drop in the riser. Following this, simulated and experimental values were compared and statistical data treatment done, aiming at the required precision to validate the fluid dynamic model. The comparison tests between experimental and simulated data were carried out under validation criteria. The fluid dynamic behavior of the riser was analyzed and the results and the agreement with literature were discussed. The adopt model was validated under the MEF operational conditions, for a 3 to 6 m/s gas velocity in the riser and a slip

  7. A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

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    Joel Bozue

    Full Text Available Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

  8. Attenuation characteristics of monolayer graphene by Pi-and T-networks modeling of multilayer microstrip line

    Institute of Scientific and Technical Information of China (English)

    Pulkit Sharma; Sumit Pratap Singh; Kamlesh Patel

    2017-01-01

    The impedances of Pi-and T-networks are obtained from the measured S-parameters of the multilayer microstrip line by modeling as an attenuator.The changes in impedances have been analyzed for the properties of various superstrates at the microwave ranges.With graphene on glass and graphene on quartz loadings,the impedances have increased and shifted towards lower frequency more in Pi-network than T-network modeling.This shift has become more prominent at higher frequency for the graphene on glass than graphene on quartz.A little increase in attenuation is found for graphene on glass or quartz than bare glass and quartz.The present study can be extended to obtain attenuation characteristic of any thin film by simple experimental method in the microwave frequencies.

  9. Marine Mammal Brucella Reference Strains Are Attenuated in a BALB/c Mouse Model.

    Science.gov (United States)

    Nymo, Ingebjørg H; Arias, Maykel A; Pardo, Julián; Álvarez, María Pilar; Alcaraz, Ana; Godfroid, Jacques; Jiménez de Bagüés, María Pilar

    2016-01-01

    Brucellosis is a zoonosis of worldwide distribution with numerous animal host species. Since the novel isolation of Brucella spp. from marine mammals in 1994 the bacteria have been isolated from various marine mammal hosts. The marine mammal reference strains Brucella pinnipedialis 12890 (harbour seal, Phoca vitulina) and Brucella ceti 12891 (harbour porpoise, Phocoena phocoena) were included in genus Brucella in 2007, however, their pathogenicity in the mouse model is pending. Herein this is evaluated in BALB/c mice with Brucella suis 1330 as a control. Both marine mammal strains were attenuated, however, B. ceti was present at higher levels than B. pinnipedialis in blood, spleen and liver throughout the infection, in addition B. suis and B. ceti were isolated from brains and faeces at times with high levels of bacteraemia. In B. suis-infected mice serum cytokines peaked at day 7. In B. pinnipedialis-infected mice, levels were similar, but peaked predominantly at day 3 and an earlier peak in spleen weight likewise implied an earlier response. The inflammatory response induced pathology in the spleen and liver. In B. ceti-infected mice, most serum cytokine levels were comparable to those in uninfected mice, consistent with a limited inflammatory response, which also was indicated by restricted spleen and liver pathology. Specific immune responses against all three strains were detected in vitro after stimulation of splenocytes from infected mice with the homologous heat-killed brucellae. Antibody responses in vivo were also induced by the three brucellae. The immunological pattern of B. ceti in combination with persistence in organs and limited pathology has heretofore not been described for other brucellae. These two marine mammal wildtype strains show an attenuated pattern in BALB/c mice only previously described for Brucella neotomea.

  10. Marine Mammal Brucella Reference Strains Are Attenuated in a BALB/c Mouse Model.

    Directory of Open Access Journals (Sweden)

    Ingebjørg H Nymo

    Full Text Available Brucellosis is a zoonosis of worldwide distribution with numerous animal host species. Since the novel isolation of Brucella spp. from marine mammals in 1994 the bacteria have been isolated from various marine mammal hosts. The marine mammal reference strains Brucella pinnipedialis 12890 (harbour seal, Phoca vitulina and Brucella ceti 12891 (harbour porpoise, Phocoena phocoena were included in genus Brucella in 2007, however, their pathogenicity in the mouse model is pending. Herein this is evaluated in BALB/c mice with Brucella suis 1330 as a control. Both marine mammal strains were attenuated, however, B. ceti was present at higher levels than B. pinnipedialis in blood, spleen and liver throughout the infection, in addition B. suis and B. ceti were isolated from brains and faeces at times with high levels of bacteraemia. In B. suis-infected mice serum cytokines peaked at day 7. In B. pinnipedialis-infected mice, levels were similar, but peaked predominantly at day 3 and an earlier peak in spleen weight likewise implied an earlier response. The inflammatory response induced pathology in the spleen and liver. In B. ceti-infected mice, most serum cytokine levels were comparable to those in uninfected mice, consistent with a limited inflammatory response, which also was indicated by restricted spleen and liver pathology. Specific immune responses against all three strains were detected in vitro after stimulation of splenocytes from infected mice with the homologous heat-killed brucellae. Antibody responses in vivo were also induced by the three brucellae. The immunological pattern of B. ceti in combination with persistence in organs and limited pathology has heretofore not been described for other brucellae. These two marine mammal wildtype strains show an attenuated pattern in BALB/c mice only previously described for Brucella neotomea.

  11. Modeling of the attenuation of stress waves in concrete based on the Rayleigh damping model using time-reversal and PZT transducers

    Science.gov (United States)

    Tian, Zhen; Huo, Linsheng; Gao, Weihang; Li, Hongnan; Song, Gangbing

    2017-10-01

    Wave-based concrete structural health monitoring has attracted much attention. A stress wave experiences significant attenuation in concrete, however there is a lack of a unified method for predicting the attenuation coefficient of the stress wave. In this paper, a simple and effective absorption attenuation model of stress waves in concrete is developed based on the Rayleigh damping model, which indicates that the absorption attenuation coefficient of stress waves in concrete is directly proportional to the square of the stress wave frequency when the damping ratio is small. In order to verify the theoretical model, related experiments were carried out. During the experiments, a concrete beam was designed in which the d33-model piezoelectric smart aggregates were embedded to detect the propagation of stress waves. It is difficult to distinguish direct stress waves due to the complex propagation paths and the reflection and scattering of stress waves in concrete. Hence, as another innovation of this paper, a new method for computing the absorption attenuation coefficient based on the time-reversal method is developed. Due to the self-adaptive focusing properties of the time-reversal method, the time-reversed stress wave focuses and generates a peak value. The time-reversal method eliminates the adverse effects of multipaths, reflection, and scattering. The absorption attenuation coefficient is computed by analyzing the peak value changes of the time-reversal focused signal. Finally, the experimental results are found to be in good agreement with the theoretical model.

  12. Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model.

    Science.gov (United States)

    Shao, Yi-Ye; Li, Bing; Huang, Yong-Mei; Luo, Qiong; Xie, Yang-Mei; Chen, Ying-Hui

    2017-01-01

    Status epilepticus (SE) results in the generation of reactive oxygen species (ROS), which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE). Thymoquinone (TQ) is a bioactive monomer extracted from black cumin (Nigella sativa) seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway. Electroencephalogram and Racine scale were used to value seizure severity. Passive-avoidance test was used to determine learning and memory function. Moreover, anti-oxidative activity of TQ was observed using Western blot and super oxide dismutase (SOD) activity assay. Latency to SE increased in the TQ-pretreated group compared with rats in the model group, while the total power was significantly lower. Seizure severity measured on the Racine scale was significantly lower in the TQ group compared with the model group. Results of behavioral experiments suggest that TQ may also have a protective effect on learning and memory function. Investigation of the protective mechanism of TQ showed that TQ-pretreatment significantly increased the expression of Nrf2, HO-1 proteins and SOD in the hippocampus. These findings showed that TQ attenuated brain injury induced by SE via an anti-oxidative pathway.

  13. Brazilian red propolis attenuates hypertension and renal damage in 5/6 renal ablation model.

    Directory of Open Access Journals (Sweden)

    Flávio Teles

    Full Text Available The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP, in the 5/6 renal ablation model (Nx. Adult male Wistar rats underwent Nx and were divided into untreated (Nx and RP-treated (Nx+RP groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection.

  14. Pitfalls in urinary stone identification using CT attenuation values: Are we getting the same information on different scanner models?

    Energy Technology Data Exchange (ETDEWEB)

    Grosjean, Romain, E-mail: r.grosjean@chu-nancy.fr [IADI Laboratory, INSERM-U947, Nancy-University, Allée du Morvan, 54500 Vandoeuvre-les-Nancy (France); Daudon, Michel, E-mail: michel.daudon@tnn.aphp.fr [IADI Laboratory, INSERM-U947, Nancy-University, Allée du Morvan, 54500 Vandoeuvre-les-Nancy (France); Chammas, Mario F., E-mail: mariochammas@usp.br [University of Sao Paulo – Division of Urology, Av. Dr. Enéas de Carvalho Aguiar, 255, 7" o Andar – s. 7123, São Paulo (Brazil); Claudon, Michel, E-mail: m.claudon@chu-nancy.fr [IADI Laboratory, INSERM-U947, Nancy-University, Allée du Morvan, 54500 Vandoeuvre-les-Nancy (France); Eschwege, Pascal, E-mail: peschwege@yahoo.com [Department of Urology, Brabois Hospital, University Hospital of Nancy, Allée du Morvan, 54511 Vandoeuvre-les-Nancy (France); Felblinger, Jacques, E-mail: j.felblinger@chu-nancy.fr [IADI Laboratory, INSERM-U947, Nancy-University, Allée du Morvan, 54500 Vandoeuvre-les-Nancy (France); Hubert, Jacques, E-mail: j.hubert@chu-nancy.fr [Department of Urology, Brabois Hospital, University Hospital of Nancy, Allée du Morvan, 54511 Vandoeuvre-les-Nancy (France)

    2013-08-15

    Introduction: Evaluate the capability of different Computed Tomography scanners to determine urinary stone compositions based on CT attenuation values and to evaluate potential differences between each model. Methods: 241 human urinary stones were obtained and their biochemical composition determined. Four different CT scanners (Siemens, Philips, GEMS and Toshiba) were evaluated. Mean CT-attenuation values and the standard deviation were recorded separately and compared with a t-paired test. Results: For all tested CT scanners, when the classification of the various types of stones was arranged according to the mean CT-attenuation values and to the confidence interval, large overlappings between stone types were highlighted. The t-paired test showed that most stone types could not be identified. Some types of stones presented mean CT attenuation values significantly different from one CT scanner to another. At 80 kV, the mean CT attenuation values obtained with the Toshiba Aquilion were significantly different from those obtained with the Siemens Sensation. On the other hand, mean values obtained with the Philips Brilliance were all significantly equal to those obtained with the Siemens Sensation and with the Toshiba Aquilion. At 120 kV mean CT attenuation values of uric acid, cystine and struvite stones obtained with the Philips model are significantly different from those obtained with the Siemens and the Toshiba but equal to those obtained with the GE 64. Conclusions: According to our study, there is a great variability when different brands and models of scanners are compared directly. Furthermore, the CT scan analysis and HU evaluation appears to gather insufficient information in order to characterize and identify the composition of renal stones.

  15. Pitfalls in urinary stone identification using CT attenuation values: Are we getting the same information on different scanner models?

    International Nuclear Information System (INIS)

    Grosjean, Romain; Daudon, Michel; o Andar – s. 7123, São Paulo (Brazil))" data-affiliation=" (University of Sao Paulo – Division of Urology, Av. Dr. Enéas de Carvalho Aguiar, 255, 7o Andar – s. 7123, São Paulo (Brazil))" >Chammas, Mario F.; Claudon, Michel; Eschwege, Pascal; Felblinger, Jacques; Hubert, Jacques

    2013-01-01

    Introduction: Evaluate the capability of different Computed Tomography scanners to determine urinary stone compositions based on CT attenuation values and to evaluate potential differences between each model. Methods: 241 human urinary stones were obtained and their biochemical composition determined. Four different CT scanners (Siemens, Philips, GEMS and Toshiba) were evaluated. Mean CT-attenuation values and the standard deviation were recorded separately and compared with a t-paired test. Results: For all tested CT scanners, when the classification of the various types of stones was arranged according to the mean CT-attenuation values and to the confidence interval, large overlappings between stone types were highlighted. The t-paired test showed that most stone types could not be identified. Some types of stones presented mean CT attenuation values significantly different from one CT scanner to another. At 80 kV, the mean CT attenuation values obtained with the Toshiba Aquilion were significantly different from those obtained with the Siemens Sensation. On the other hand, mean values obtained with the Philips Brilliance were all significantly equal to those obtained with the Siemens Sensation and with the Toshiba Aquilion. At 120 kV mean CT attenuation values of uric acid, cystine and struvite stones obtained with the Philips model are significantly different from those obtained with the Siemens and the Toshiba but equal to those obtained with the GE 64. Conclusions: According to our study, there is a great variability when different brands and models of scanners are compared directly. Furthermore, the CT scan analysis and HU evaluation appears to gather insufficient information in order to characterize and identify the composition of renal stones

  16. Zn/Ga−DFO iron–chelating complex attenuates the inflammatory process in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Haim Bibi

    2014-01-01

    Conclusion: In this mouse model of allergic asthma, Zn/Ga−DFO attenuated allergic airway inflammation. The beneficial effects of treatment were in accord with iron overload abatement in asthmatic lungs by Zn/Ga−DFO. The findings in both cellular and tissue levels supported the existence of a significant anti-inflammatory effect of Zn/Ga−DFO.

  17. Angelica Sinensis attenuates inflammatory reaction in experimental rat models having spinal cord injury.

    Science.gov (United States)

    Xu, Jun; E, Xiao-Qiang; Liu, Hui-Yong; Tian, Jun; Yan, Jing-Long

    2015-01-01

    This study was aimed to evaluate the effect of Angelica Sinensis on experimental rat models in which spinal cord injury was induced by studying different factors. Different factors causing inflammation play a key role in pathophysiology of SCI. Here three groups of rats (n=15, each was used). These included a sham control group where only laminectomy was performed, SCI group where SCI was induced and AS/SCI group where although SCI was induced but Angelica Sinensis was also administered to study its effect and draw a comparison with control. The expression of I-kBα and NF-kB p65 was also studied using western blotting and after recording optical density (OD) values of western blots. MPO activity was used to measure the effect of 20 mg/kg Angelica Sinensis. The levels of proinflammatory cytokines TNF-α, IL-1β and IL-6 were also studied. As compared with SCI group and sham control it was observed that Angelica Sinensis significantly reduced the expression of I-kBα and NF-kB p65, (PSinensis in rat models can attenuate the secondary damage caused by SCI and thus help in controlling the pathology of SCI in rats.

  18. The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Joanna Schwenkgrub

    Full Text Available Since the degeneration of the nigrostriatal dopaminergic pathway in Parkinson's disease (PD is associated with the inflammation process and decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic nucleotide phosphodiesterases (PDEs appears to be a promising therapeutic strategy. We used ibudilast (IBD, a non-selective PDE3,4,10,11 inhibitor, due to the abundant PDE 4 and 10 expression in the striatum. The present study for the first time examined the efficacy of IBD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mouse model of PD.IBD [0, 20, 30, 40, or 50 mg/kg] was injected b.i.d. subcutaneously for nine days to three-month-old male C57Bl/10Tar mice, beginning two days prior to MPTP (60 mg/kg intoxication. High-pressure liquid chromatography, Western blot analysis, and real time RT-PCR methods were applied.Our study demonstrated that chronic administration of IBD attenuated astroglial reactivity and increased glial cell-derived neurotrophic factor (GDNF production in the striatum. Moreover, IBD reduced TNF-α, IL-6, and IL-1β expression.IBD had a well-defined effect on astroglial activation in the mouse model of PD; however, there was no protective effect in the acute phase of injury. Diminished inflammation and an increased level of GDNF may provide a better outcome in the later stages of neurodegeneration.

  19. Astaxanthin attenuates neurotoxicity in a mouse model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    B. Grimmig, L. Daly

    2017-08-01

    Full Text Available Background: Astaxanthin (AXT is a natural carotenoid with diverse biological activities. Although it is best known as a potent antioxidant, recent work suggests additional mechanisms of action that have the potential to oppose the ongoing pathophysiology of Parkinson’s disease (PD. For example, AXT has a putative role in modulating microglial activity and preserving mitochondrial function, thereby implicating this compound as a neuroprotective agent. Both oxidative stress and inflammation are involved in the progression of many neurodegenerative diseases. Therefore, we examined the efficacy for AXT to reduced neurotoxicity in a toxic model of PD in mice. Methods: In this study, we used a 4-week dietary supplementation of algae derived AXT to reduce 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP induced dopaminergic cell death. Results: AXT treated mice were protected against the loss of tyrosine hydroxylase (TH staining in the substantia nigra (SN after MPTP exposure compared to the control diet. This effect of preserved TH immunoreactivity was also observed in the striatum. Furthermore, AXT administration was able to interrupt the neuroinflammatory process known to contribute to neurodegeneration in this model. Conclusions: We demonstrate that AXT neuroprotection was associated with attenuated microglial activation as indicated by reduced immunohistochemical detection of IBA-1 in the SN and striatum of AXT treated mice. Altogether, these studies suggest that AXT has neuroprotective property in the central nervous system against MPTP neurodegeneration.

  20. The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis.

    Science.gov (United States)

    Lindström, Erik; Rizoska, Biljana; Tunblad, Karin; Edenius, Charlotte; Bendele, Alison M; Maul, Don; Larson, Michael; Shah, Neha; Yoder Otto, Valerie; Jerome, Chris; Grabowska, Urszula

    2018-03-09

    MIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of MIV-711 on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), and the prophylactic effects on joint pathology in dogs subjected to partial medial meniscectomy, two surgical models of osteoarthritis (OA). Starting 1 week after surgery, rabbits were dosed daily via oral gavage with either MIV-711 or vehicle (n = 7/group) for 7 weeks. The four treatment groups were: (1) sham + vehicle; (2) ACLT + vehicle; (3) ACLT + MIV-711, 30 µmol/kg and (4) ACLT + MIV-711, 100 µmol/kg. Subchondral bone and articular cartilage structures were assessed by µCT, histomorphometry, and scoring. Dogs subjected to partial medial meniscectomy received either MIV-711 (30 µmol/kg) or vehicle (n = 15/group) via oral gavage once daily, starting 1 day before meniscectomy, for 28 days. Cartilage degradation was assessed at the macroscopic and microscopic levels. The exposures of MIV-711 were assessed in both studies and biomarkers reflecting bone resorption (HP-1 in rabbits, CTX-I in dogs) and cartilage degradation (CTX-II) were measured. In ACLT rabbits, MIV-711 decreased HP-1 levels by up to 72% (p subchondral bone plate and reduced trabecular bone volume in the femur and tibia. These effects were reversed by MIV-711. ACLT resulted in cartilage thickening, which was attenuated by MIV-711. MIV-711 did not affect osteophyte formation or Mankin scores. In dogs, MIV-711 reduced CTX-I and CTX-II levels by 86% (p subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA.

  1. Investigation of attenuation correction in SPECT using textural features, Monte Carlo simulations, and computational anthropomorphic models.

    Science.gov (United States)

    Spirou, Spiridon V; Papadimitroulas, Panagiotis; Liakou, Paraskevi; Georgoulias, Panagiotis; Loudos, George

    2015-09-01

    To present and evaluate a new methodology to investigate the effect of attenuation correction (AC) in single-photon emission computed tomography (SPECT) using textural features analysis, Monte Carlo techniques, and a computational anthropomorphic model. The GATE Monte Carlo toolkit was used to simulate SPECT experiments using the XCAT computational anthropomorphic model, filled with a realistic biodistribution of (99m)Tc-N-DBODC. The simulated gamma camera was the Siemens ECAM Dual-Head, equipped with a parallel hole lead collimator, with an image resolution of 3.54 × 3.54 mm(2). Thirty-six equispaced camera positions, spanning a full 360° arc, were simulated. Projections were calculated after applying a ± 20% energy window or after eliminating all scattered photons. The activity of the radioisotope was reconstructed using the MLEM algorithm. Photon attenuation was accounted for by calculating the radiological pathlength in a perpendicular line from the center of each voxel to the gamma camera. Twenty-two textural features were calculated on each slice, with and without AC, using 16 and 64 gray levels. A mask was used to identify only those pixels that belonged to each organ. Twelve of the 22 features showed almost no dependence on AC, irrespective of the organ involved. In both the heart and the liver, the mean and SD were the features most affected by AC. In the liver, six features were affected by AC only on some slices. Depending on the slice, skewness decreased by 22-34% with AC, kurtosis by 35-50%, long-run emphasis mean by 71-91%, and long-run emphasis range by 62-95%. In contrast, gray-level non-uniformity mean increased by 78-218% compared with the value without AC and run percentage mean by 51-159%. These results were not affected by the number of gray levels (16 vs. 64) or the data used for reconstruction: with the energy window or without scattered photons. The mean and SD were the main features affected by AC. In the heart, no other feature was

  2. Maximizing effectiveness of adaptation action in Pacific Island communities using coastal wave attenuation models

    Science.gov (United States)

    Jung, H.; Carruthers, T.; Allison, M. A.; Weathers, D.; Moss, L.; Timmermans, H.

    2017-12-01

    Pacific Island communities are highly vulnerable to the effects of climate change, specifically accelerating rates of sea level rise, changes to storm intensity and associated rainfall patterns resulting in flooding and shoreline erosion. Nature-based adaptation is being planned not only to reduce the risk from shoreline erosion, but also to support benefits of a healthy ecosystem (e.g., supporting fisheries or coral reefs). In order to assess potential effectiveness of the nature-based actions to dissipate wave energy, two-dimensional X-Beach models were developed to predict the wave attenuation effect of coastal adaptation actions at the pilot sites—the villages of Naselesele and Somosomo on Taveuni island, Fiji. Both sites are experiencing serious shoreline erosion due to sea level rise and storm wave. The water depth (single-beam bathymetry), land elevation (truck-based LiDAR), and vegetation data including stem density and height were collected in both locations in a June 2017 field experiment. Wave height and water velocity were also measured for the model setup and calibration using a series of bottom-mounted instruments deployed in the 0-15 m water depth portions of the study grid. The calibrated model will be used to evaluate a range of possible adaptation actions identified by the community members of Naselesele and Somosomo. Particularly, multiple storm scenario runs with management-relevant shoreline restoration/adaptation options will be implemented to evaluate efficiencies of each adaptation action (e.g., no action, with additional planted trees, with sand mining, with seawalls constructed with natural materials, etc.). These model results will help to better understand how proposed adaption actions may influence future shoreline change and maximize benefits to communities in island nations across the SW Pacific.

  3. Time-domain simulation of constitutive relations for nonlinear acoustics including relaxation for frequency power law attenuation media modeling

    Science.gov (United States)

    Jiménez, Noé; Camarena, Francisco; Redondo, Javier; Sánchez-Morcillo, Víctor; Konofagou, Elisa E.

    2015-10-01

    We report a numerical method for solving the constitutive relations of nonlinear acoustics, where multiple relaxation processes are included in a generalized formulation that allows the time-domain numerical solution by an explicit finite differences scheme. Thus, the proposed physical model overcomes the limitations of the one-way Khokhlov-Zabolotskaya-Kuznetsov (KZK) type models and, due to the Lagrangian density is implicitly included in the calculation, the proposed method also overcomes the limitations of Westervelt equation in complex configurations for medical ultrasound. In order to model frequency power law attenuation and dispersion, such as observed in biological media, the relaxation parameters are fitted to both exact frequency power law attenuation/dispersion media and also empirically measured attenuation of a variety of tissues that does not fit an exact power law. Finally, a computational technique based on artificial relaxation is included to correct the non-negligible numerical dispersion of the finite difference scheme, and, on the other hand, improve stability trough artificial attenuation when shock waves are present. This technique avoids the use of high-order finite-differences schemes leading to fast calculations. The present algorithm is especially suited for practical configuration where spatial discontinuities are present in the domain (e.g. axisymmetric domains or zero normal velocity boundary conditions in general). The accuracy of the method is discussed by comparing the proposed simulation solutions to one dimensional analytical and k-space numerical solutions.

  4. Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model.

    Science.gov (United States)

    Gupta, Amit; Vij, Garima; Sharma, Sameer; Tirkey, Naveen; Rishi, Praveen; Chopra, Kanwaljit

    2009-01-01

    Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels. These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

  5. Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies

    Science.gov (United States)

    Syn, Wing-Kin; Lagaisse, Kimberly; van Hul, Noemi; Heindryckx, Femke; Sowa, Jan-Peter; Peeters, Liesbeth; Van Vlierberghe, Hans; Leclercq, Isabelle A.; Canbay, Ali

    2016-01-01

    Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes and macrophages, peribiliary extracellular matrix (ECM) deposition and ductular reaction (DR). This study aimed to elucidate the relevance of macrophages in the progression of chronic cholangiopathies through macrophage depletion in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group of mice received a single i.p. injection of Clodronate encapsulated liposomes (CLOLipo) at day 7 of a 14 day DDC treatment, while control animals were co-treated with PBSLipo instead. Mice were sacrificed after 7 or respectively 14 days of treatment for immunohistochemical assessment of macrophage recruitment (F4/80), ECM deposition (Sirius Red, Laminin) and DR (CK19). Macrophage depletion during a 14 day DDC treatment resulted in a significant inhibition of ECM deposition. Porto-lobular migration patterns of laminin-rich ECM and ductular structures were significantly attenuated and a progression of DR was effectively inhibited by macrophage depletion. CLOLipo co-treatment resulted in a confined DR to portal regions without amorphous cell clusters. This study suggests that therapeutic options selectively directed towards macrophages might represent a feasible treatment for chronic cholestatic liver diseases. PMID:27618307

  6. Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke.

    Science.gov (United States)

    Liu, Hao; Sun, Xiaowei; Zou, Wei; Leng, Mengtong; Zhang, Beng; Kang, Xiaoyu; He, Tao; Wang, Hui

    2017-06-01

    Hemorrhagic stroke accounts for approximately 15% of all stroke cases, and is associated with high morbidity and mortality. Limited human studies suggested that scalp acupuncture could facilitate functional recovery after cerebral hemorrhage. In the current study, we used an animal model of cerebral hemorrhage to examine the potential effects of scalp acupuncture. Adult male Sprague-Dawley rats received autologous blood (50μL) into the right caudate nucleus on the right side under pentobarbital anesthesia, and then received scalp acupuncture (DU20 through GB7 on the lesion side) or sham acupuncture (1cm to the right side of the acupoints) (n=10 per group). A group of rats receiving autologous blood into the caudate nucleus but no other intervention, as well as a group of rats receiving anesthesia but no blood injection to the brain (n=10 per group) were included as additional controls. Composite neuroscore, corner turn test, forelimb placing test, wire hang task and beam walking were used to evaluate the behavior of rats. Hematoxylin and Eosin (HE) staining was used to observe the histopathological changes. Western blot was used to detect the content of tumor necrosis factor alpha (TNF-α) and nuclear factor-KappaB (NFκB) protein expression. Scalp acupuncture attenuated neurological deficits (phemorrhagic stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. MOBIDIC-U: a watershed-scale model for stormwater attenuation through green infrastructures design

    Science.gov (United States)

    Ercolani, G.; Masseroni, D.; Chiaradia, E. A.; Bischetti, G. B.; Gandolfi, C.; Castelli, F.

    2017-12-01

    Surface water degradation resulting from the effects of urbanization on hydrology, water quality, habitat as well as ecological and environmental compartments represents an issue of primary focus for multiple agencies at the national, regional and local levels. Many management actions are needed throughout urban watersheds to achieve the desired effects on flow mitigation and pollutant reduction, but no single standardized solution can be effective in all locations. In this work, the distributed hydrological model MOBIDIC, already applied for hydrological balance simulations and flood prevention in different Italian regions, is adapted to the urban context (MOBIDIC-U) in order to evaluate alternative plans for stormwater quality management and flow abatement techniques through the adoption of green infrastructures (GIs). In particular the new modules included in MOBIDIC-U allow to (i) automatically define the upstream flow path as well as watershed boundary starting from a selected watershed closure point on the urban drainage network and (ii) obtain suitable graphical outputs for the visualization of flow peak and volume attenuation at the closure point. Moreover, MOBIDIC-U provides a public domain tool capable of evaluating the optimal location, type, and cost of the stormwater management practices needed to meet water quantity and quality goals. Despite the scalability of the model to different urban contexts, the current version of MOBIDIC-U has been developed for the area of the metropolitan city of Milan, Northern Italy. The model is implemented on a GIS platform, which already contains (i) the structure of the urban drainage network of the metropolitan city of Milan; (ii) the database of actual geomorphological and meteorological data for the previous domain (iii) the list of potential GIs, their standard size, installation and maintenance costs. Therefore, MOBIDIC-U provides an easy to use tool to local professionals to design and evaluate urban stormwater

  8. Modeling of 830 nm FSO Link Attenuation in Fog or Wind Turbulence

    Czech Academy of Sciences Publication Activity Database

    Pešek, J.; Fišer, Ondřej; Svoboda, Jaroslav; Schejbal, V.

    2010-01-01

    Roč. 19, č. 2 (2010), s. 237-241 ISSN 1210-2512 R&D Projects: GA ČR GA102/08/0851; GA MŠk OC09027 Institutional research plan: CEZ:AV0Z30420517 Keywords : Free space optics propagation * fog attenuation, * wind turbulence attenuation * turbulent energy Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.503, year: 2010 http://www.radioeng.cz/fulltexts/2010/10_02_237_241.pdf

  9. Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.

    Science.gov (United States)

    Castillo-Courtade, L; Han, S; Lee, S; Mian, F M; Buck, R; Forsythe, P

    2015-09-01

    The prebiotic nature of human milk oligosaccharides (HMOs) and increasing evidence of direct immunomodulatory effects of these sugars suggest that they may have some therapeutic potential in allergy. Here, we assess the effect of two HMOs, 2'-fucosyllactose and 6'-sialyllactose, on symptomatology and immune responses in an ovalbumin-sensitized mouse model of food allergy. The effects of oral treatment with 2'-fucosyllactose and 6'-sialyllactose on anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in sensitized mice were investigated. Mast cell functions in response to oral HMO treatment were also measured in the passive cutaneous anaphylaxis model, and direct effects on IgE-mediated degranulation of mast cells were assessed. Daily oral treatment with 2'-fucosyllactose or 6'-sialyllactose attenuated food allergy symptoms including diarrhea and hypothermia. Treatment with HMOs also suppressed antigen-induced increases in mouse mast cell protease-1 in serum and mast cell numbers in the intestine. These effects were associated with increases in the CD4(+) CD25(+) IL-10(+) cell populations in the Peyer's patches and mesenteric lymph nodes, while 6'-sialyllactose also induced increased IL-10 and decreased TNF production in antigen-stimulated splenocytes. Both 2'-fucosyllactose and 6'-sialyllactose reduced the passive cutaneous anaphylaxis response, but only 6'-sialyllactose directly inhibited mast cell degranulation in vitro, at high concentrations. Our results suggest that 2'-fucosyllactose and 6'-sialyllactose reduce the symptoms of food allergy through induction of IL-10(+) T regulatory cells and indirect stabilization of mast cells. Thus, human milk oligosaccharides may have therapeutic potential in allergic disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Ghrelin Attenuates Retinal Neuronal Autophagy and Apoptosis in an Experimental Rat Glaucoma Model.

    Science.gov (United States)

    Zhu, Ke; Zhang, Meng-Lu; Liu, Shu-Ting; Li, Xue-Yan; Zhong, Shu-Min; Li, Fang; Xu, Ge-Zhi; Wang, Zhongfeng; Miao, Yanying

    2017-12-01

    Ghrelin, a natural ligand for the growth hormone secretagogue receptor type 1a (GHSR-1a), may protect retinal neurons against glaucomatous injury. We therefore characterized the underlying mechanism of the ghrelin/GHSR-1a-mediated neuroprotection with a rat chronic intraocular hypertension (COH) model. The rat COH model was produced by blocking episcleral veins. A combination of immunohistochemistry, Western blot, TUNEL assay, and retrograde labeling of retinal ganglion cells (RGCs) was used. Elevation of intraocular pressure induced a significant increase in ghrelin and GHSR-1a expression in retinal cells, including RGCs and Müller cells. Western blot confirmed that the protein levels of ghrelin exhibited a transient upregulation at week 2 after surgery (G2w), while the GHSR-1a protein levels were maintained at high levels from G2w to G4w. In COH retinas, the ratio of LC3-II/LC-I and beclin1, two autophagy-related proteins, were increased from G1w to G4w, and the cleavage product of caspase3, an apoptotic executioner, was detected from G2w to G4w. Intraperitoneal injection of ghrelin significantly increased the number of surviving RGCs; inhibited the changes of LC3-II/LC-I, beclin1, and the cleavage products of caspase3; and reduced the number of TUNEL-positive cells in COH retinas. Ghrelin treatment also reversed the decreased levels of p-Akt and p-mTOR, upregulated GHSR-1a protein levels, and attenuated glial fibrillary acidic protein levels in COH retinas. All these results suggest that ghrelin may provide neuroprotective effect in COH retinas through activating ghrelin/GHSR-1a system, which was mediated by inhibiting retinal autophagy, ganglion cell apoptosis, and Müller cell gliosis.

  11. Canagliflozin, an SGLT2 inhibitor, attenuates the development of hepatocellular carcinoma in a mouse model of human NASH.

    Science.gov (United States)

    Shiba, Kumiko; Tsuchiya, Kyoichiro; Komiya, Chikara; Miyachi, Yasutaka; Mori, Kentaro; Shimazu, Noriko; Yamaguchi, Shinobu; Ogasawara, Naomi; Katoh, Makoto; Itoh, Michiko; Suganami, Takayoshi; Ogawa, Yoshihiro

    2018-02-05

    Sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. It is unclear whether SGLT2 inhibition could attenuate nonalcoholic steatohepatitis (NASH) and NASH-associated hepatocellular carcinoma. We examined the preventive effects of an SGLT2 inhibitor canagliflozin (CANA) in Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO) mice, a mouse model of human NASH. An eight-week CANA treatment attenuated hepatic steatosis in WD-fed MC4R-KO mice, with increased epididymal fat mass without inflammatory changes. CANA treatment for 20 weeks inhibited the development of hepatic fibrosis in WD-fed MC4R-KO mice. After one year of CANA treatment, the number of liver tumors was significantly reduced in WD-fed MC4R-KO mice. In adipose tissue, CANA suppressed the ratio of oxidative to reduced forms of glutathiones (GSSG/GSH) in WD-fed MC4R-KO mice. Treatment with GSH significantly attenuated the H 2 O 2 -induced upregulation of genes related to NADPH oxidase in 3T3-L1 adipocytes, and that of Il6, Tgfb, and Pdgfb in RAW264.7 cells. This study provides evidence that SGLT2 inhibitors represent the unique class of drugs that can attenuate or delay the onset of NASH and eventually hepatocellular carcinoma, at least partly, through "healthy adipose expansion".

  12. Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.

    Science.gov (United States)

    Cai, Yeping; Zhou, Jiansheng; Webb, Dianne C

    2009-01-01

    Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.

  13. High-frequency percussive ventilation attenuates lung injury in a rabbit model of gastric juice aspiration.

    Science.gov (United States)

    Allardet-Servent, Jérôme; Bregeon, Fabienne; Delpierre, Stéphane; Steinberg, Jean-Guillaume; Payan, Marie-José; Ravailhe, Sylvie; Papazian, Laurent

    2008-01-01

    To test the effects of high-frequency percussive ventilation (HFPV) compared with high-frequency oscillatory ventilation (HFOV) and low-volume conventional mechanical ventilation (LVCMV), on lung injury course in a gastric juice aspiration model. Prospective, randomized, controlled, in-vivo animal study. University animal research laboratory. Forty-three New Zealand rabbits. Lung injury was induced by intratracheal instillation of human gastric juice in order to achieve profound hypoxaemia (PaO2/FIO2ventilated for 4h after randomization in one of the following four groups: HFPV (median pressure 15cmH2O); LVCMV (VT 6mlkg(-1) and PEEP set to reach 15cmH2O plateau pressure); HFOV (mean pressure 15cmH2O); and a high-volume control group HVCMV (VT 12ml kg(-1) and ZEEP). Static respiratory compliance increased after the ventilation period in the HFPV, LVMCV and HFOV groups, in contrast with the HVCMV group. PaO2/FIO2 improved similarly in the HFPV, LVCMV and HFOV groups, and remained lower in the HVCMV group than in the three others. Lung oedema, myeloperoxidase and histological lung injury score were higher in the HVCMV group, but not different among all others. Arterial lactate markedly increased after 4h of ventilation in the HVCMV group, while lower but similar levels were observed in the three other groups. HFPV, like HFOV and protective CMV, improves respiratory mechanics and oxygenation, and attenuates lung damage. The HFPV provides attractive lung protection, but further studies should confirm these results before introducing HFPV into the clinical arena.

  14. Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct-ligated rat model.

    Science.gov (United States)

    Wang, Ya-Yu; Lin, Shih-Yi; Chen, Wen-Ying; Liao, Su-Lan; Wu, Chih-Cheng; Pan, Pin-Ho; Chou, Su-Tze; Chen, Chun-Jung

    2017-05-23

    In traditional Chinese medicine, Glechoma hederacea is frequently prescribed to patients with cholelithiasis, dropsy, abscess, diabetes, inflammation, and jaundice. Polyphenolic compounds are main bioactive components of Glechoma hederacea. This study was aimed to investigate the hepatoprotective potential of hot water extract of Glechoma hederacea against cholestatic liver injury in rats. Cholestatic liver injury was produced by ligating common bile ducts in Sprague-Dawley rats. Saline and hot water extract of Glechoma hederacea were orally administrated using gastric gavages. Liver tissues and bloods were collected and subjected to evaluation using histological, molecular, and biochemical approaches. Using a rat model of cholestasis caused by bile duct ligation (BDL), daily oral administration of Glechoma hederacea hot water extracts showed protective effects against cholestatic liver injury, as evidenced by the improvement of serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Glechoma hederacea extracts alleviated BDL-induced transforming growth factor beta-1 (TGF-β1), connective tissue growth factor, and collagen expression, and the anti-fibrotic effects were accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity. Glechoma hederacea extracts attenuated BDL-induced inflammatory cell infiltration/accumulation, NF-κB and AP-1 activation, and inflammatory cytokine production. Further studies demonstrated an inhibitory effect of Glechoma hederacea extracts on the axis of high mobility group box-1 (HMGB1)/toll-like receptor-4 (TLR4) intracellular signaling pathways. The hepatoprotective, anti-oxidative, anti-inflammatory, and anti-fibrotic effects of Glechoma hederacea extracts seem to be multifactorial. The beneficial effects of daily Glechoma hederacea extracts supplementation were associated with anti-oxidative, anti-inflammatory, and anti-fibrotic potential, as well as down

  15. Progesterone attenuates airway remodeling and glucocorticoid resistance in a murine model of exposing to ozone.

    Science.gov (United States)

    Zhang, Xue; Bao, Wuping; Fei, Xia; Zhang, Yingying; Zhang, Guoqing; Zhou, Xin; Zhang, Min

    2018-04-01

    Airway remodeling is a vital component of chronic obstructive pulmonary disease (COPD). Despite the broad anti-inflammation effects of glucocorticoids, they exhibit relatively little therapeutic benefit in COPD, indicating the accelerating demands of new agents for COPD. We aim to explore the effect of progesterone on airway remodeling in a murine modeling of exposing to ozone and to further examine the potential effect of progesterone on glucocorticoid insensitivity. C57/BL6 mice were exposed to ozone for 12 times over 6 weeks, and were administered with progesterone alone or combined with budesonide (BUD) after each exposure until the 10th week. The peribronchial collagen deposition was measured. The protein levels of MMP8 and MMP9 in bronchoalveolar lavage fluid (BALF) and lungs were assessed. Western blot analysis was used to detect the levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), a-smooth muscle actin (α-SMA), glycogen synthase kinase-3β (GSK-3β). The expression of VEGF and histone deacetylase 2 (HDAC2) in the lung were determined by Immunohistochemical analyses. We observe that progesterone attenuates the peribronchial collagen deposition, as well as the expression of MMP8, MMP9, HIF-1α, VEGF, α-SMA, and GSK-3β in BALF or lung tissues. Progesterone or BUD monotherapy has no effect on HDAC2 production. Progesterone combines with BUD induce dramatically enhanced effects. Thus, these results demonstrate novel roles of progesterone for the pathogenesis and airway remodeling in COPD. Progesterone plus BUD administration exerts more significant inhibition on airway remodeling with dose-independent. Additionally, progesterone may, to some extent, improve the glucocorticoid insensitivity. Copyright © 2018. Published by Elsevier Ltd.

  16. A Unified Statistical Rain-Attenuation Model for Communication Link Fade Predictions and Optimal Stochastic Fade Control Design Using a Location-Dependent Rain-Statistic Database

    Science.gov (United States)

    Manning, Robert M.

    1990-01-01

    A static and dynamic rain-attenuation model is presented which describes the statistics of attenuation on an arbitrarily specified satellite link for any location for which there are long-term rainfall statistics. The model may be used in the design of the optimal stochastic control algorithms to mitigate the effects of attenuation and maintain link reliability. A rain-statistics data base is compiled, which makes it possible to apply the model to any location in the continental U.S. with a resolution of 0-5 degrees in latitude and longitude. The model predictions are compared with experimental observations, showing good agreement.

  17. Modeling wave attenuation by salt marshes in Jamaica Bay, New York, using a new rapid wave model

    Science.gov (United States)

    Marsooli, Reza; Orton, Philip M.; Mellor, George

    2017-07-01

    Using a new rapid-computation wave model, improved and validated in the present study, we quantify the value of salt marshes in Jamaica Bay—a highly urbanized estuary located in New York City—as natural buffers against storm waves. We augment the MDO phase-averaged wave model by incorporating a vegetation-drag-induced energy dissipation term into its wave energy balance equation. We adopt an empirical formula from literature to determine the vegetation drag coefficient as a function of environmental conditions. Model evaluation using data from laboratory-scale experiments show that the improved MDO model accurately captures wave height attenuation due to submerged and emergent vegetation. We apply the validated model to Jamaica Bay to quantify the influence of coastal-scale salt marshes on storm waves. It is found that the impact of marsh islands is largest for storms with lower flood levels, due to wave breaking on the marsh island substrate. However, the role of the actual marsh plants, Spartina alterniflora, grows larger for storms with higher flood levels, when wave breaking does not occur and the vegetative drag becomes the main source of energy dissipation. For the latter case, seasonality of marsh height is important; at its maximum height in early fall, S. alterniflora causes twice the reduction as when it is at a shorter height in early summer. The model results also indicate that the vegetation drag coefficient varies 1 order of magnitude in the study area, and suggest exercising extra caution in using a constant drag coefficient in coastal wetlands.

  18. Modeling of Fog and Smoke Attenuation in Free Space Optical Communications Link Under Controlled Laboratory Conditions

    Czech Academy of Sciences Publication Activity Database

    Ijaz, M.; Ghassemlooy, Z.; Pešek, J.; Fišer, Ondřej; Le Minh, H.; Bentley, E.

    2013-01-01

    Roč. 31, č. 11 (2013), s. 1720-1726 ISSN 0733-8724 R&D Projects: GA ČR(CZ) GAP102/11/1376 Institutional support: RVO:68378289 Keywords : Fog attenuation * free space optics * smoke attenuation * visibility Subject RIV: DG - Athmosphere Sciences, Meteorology Impact factor: 2.862, year: 2013 http://ieeexplore.ieee.org/xpl/login.jsp?tp=&arnumber=6497447&url=http%3A%2F%2Fieeexplore.ieee.org%2Fxpls%2Fabs_all.jsp%3Farnumber%3D6497447

  19. Modelling the attenuation in the ATHENA finite elements code for the ultrasonic testing of austenitic stainless steel welds.

    Science.gov (United States)

    Chassignole, B; Duwig, V; Ploix, M-A; Guy, P; El Guerjouma, R

    2009-12-01

    Multipass welds made in austenitic stainless steel, in the primary circuit of nuclear power plants with pressurized water reactors, are characterized by an anisotropic and heterogeneous structure that disturbs the ultrasonic propagation and makes ultrasonic non-destructive testing difficult. The ATHENA 2D finite element simulation code was developed to help understand the various physical phenomena at play. In this paper, we shall describe the attenuation model implemented in this code to give an account of wave scattering phenomenon through polycrystalline materials. This model is in particular based on the optimization of two tensors that characterize this material on the basis of experimental values of ultrasonic velocities attenuation coefficients. Three experimental configurations, two of which are representative of the industrial welds assessment case, are studied in view of validating the model through comparison with the simulation results. We shall thus provide a quantitative proof that taking into account the attenuation in the ATHENA code dramatically improves the results in terms of the amplitude of the echoes. The association of the code and detailed characterization of a weld's structure constitutes a remarkable breakthrough in the interpretation of the ultrasonic testing on this type of component.

  20. Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma.

    Directory of Open Access Journals (Sweden)

    Kayla G Kinker

    Full Text Available Levels of asymmetric dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase, are increased in lung, sputum, exhaled breath condensate and plasma samples from asthma patients. ADMA is metabolized primarily by dimethylarginine dimethylaminohydrolase 1 (DDAH1 and DDAH2. We determined the effect of DDAH1 overexpression on development of allergic inflammation in a mouse model of asthma. The expression of DDAH1 and DDAH2 in mouse lungs was determined by RT-quantitative PCR (qPCR. ADMA levels in bronchoalveolar lavage fluid (BALF and serum samples were determined by mass spectrometry. Wild type and DDAH1-transgenic mice were intratracheally challenged with PBS or house dust mite (HDM. Airway inflammation was assessed by bronchoalveolar lavage (BAL total and differential cell counts. The levels of IgE and IgG1 in BALF and serum samples were determined by ELISA. Gene expression in lungs was determined by RNA-Seq and RT-qPCR. Our data showed that the expression of DDAH1 and DDAH2 was decreased in the lungs of mice following HDM exposure, which correlated with increased ADMA levels in BALF and serum. Transgenic overexpression of DDAH1 resulted in decreased BAL total cell and eosinophil numbers following HDM exposure. Total IgE levels in BALF and serum were decreased in HDM-exposed DDAH1-transgenic mice compared to HDM-exposed wild type mice. RNA-Seq results showed downregulation of genes in the inducible nitric oxide synthase (iNOS signaling pathway in PBS-treated DDAH1-transgenic mice versus PBS-treated wild type mice and downregulation of genes in IL-13/FOXA2 signaling pathway in HDM-treated DDAH1-transgenic mice versus HDM-treated wild type mice. Our findings suggest that decreased expression of DDAH1 and DDAH2 in the lungs may contribute to allergic asthma and overexpression of DDAH1 attenuates allergen-induced airway inflammation through modulation of Th2 responses.

  1. Verification of photon attenuation characteristics for 3D printer based small animal lung model

    International Nuclear Information System (INIS)

    Lee, Se Ho; Lee, Seung Wook; Han, Su Chul; Park, Seung Woo

    2016-01-01

    Since it is difficult to measure absorbed dose to mice in vivo, replica mice are mostly used as alternative. In this study, realistic mouse phantom was fabricated by using 3D printer (object500 connex3, Stratasys, USA). Elemental inks as material of 3D printer were selected corresponding to mouse tissue. To represent lung, selected material was partially used with air layer. In order to verify material equivalent, super-flex bolus was simply compared to verify photon attenuation characteristics. In the case of lung, Hounsfield unit (HU) of the phantom were compared with a live mouse. In this study, we fabricated mouse phantom by using 3D printer, and practically verified photon attenuation characteristics. The fabricated phantom shows tissue equivalence as well as similar geometry with live mouse. As more and more growing of 3D printer technique, 3D printer based small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study

  2. Verification of photon attenuation characteristics for 3D printer based small animal lung model

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Se Ho; Lee, Seung Wook [Pusan National University, Busan (Korea, Republic of); Han, Su Chul; Park, Seung Woo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-05-15

    Since it is difficult to measure absorbed dose to mice in vivo, replica mice are mostly used as alternative. In this study, realistic mouse phantom was fabricated by using 3D printer (object500 connex3, Stratasys, USA). Elemental inks as material of 3D printer were selected corresponding to mouse tissue. To represent lung, selected material was partially used with air layer. In order to verify material equivalent, super-flex bolus was simply compared to verify photon attenuation characteristics. In the case of lung, Hounsfield unit (HU) of the phantom were compared with a live mouse. In this study, we fabricated mouse phantom by using 3D printer, and practically verified photon attenuation characteristics. The fabricated phantom shows tissue equivalence as well as similar geometry with live mouse. As more and more growing of 3D printer technique, 3D printer based small preclinical animal phantom would increase reliability of verification of absorbed dose in small animal for preclinical study.

  3. Attenuation correction for SPECT

    International Nuclear Information System (INIS)

    Hosoba, Minoru

    1986-01-01

    Attenuation correction is required for the reconstruction of a quantitative SPECT image. A new method for detecting body contours, which are important for the correction of tissue attenuation, is presented. The effect of body contours, detected by the newly developed method, on the reconstructed images was evaluated using various techniques for attenuation correction. The count rates in the specified region of interest in the phantom image by the Radial Post Correction (RPC) method, the Weighted Back Projection (WBP) method, Chang's method were strongly affected by the accuracy of the contours, as compared to those by Sorenson's method. To evaluate the effect of non-uniform attenuators on the cardiac SPECT, computer simulation experiments were performed using two types of models, the uniform attenuator model (UAM) and the non-uniform attenuator model (NUAM). The RPC method showed the lowest relative percent error (%ERROR) in UAM (11 %). However, 20 to 30 percent increase in %ERROR was observed for NUAM reconstructed with the RPC, WBP, and Chang's methods. Introducing an average attenuation coefficient (0.12/cm for Tc-99m and 0.14/cm for Tl-201) in the RPC method decreased %ERROR to the levels for UAM. Finally, a comparison between images, which were obtained by 180 deg and 360 deg scans and reconstructed from the RPC method, showed that the degree of the distortion of the contour of the simulated ventricles in the 180 deg scan was 15 % higher than that in the 360 deg scan. (Namekawa, K.)

  4. Measurement of vascular wall attenuation: Comparison of CT angiography using model-based iterative reconstruction with standard filtered back-projection algorithm CT in vitro

    International Nuclear Information System (INIS)

    Suzuki, Shigeru; Machida, Haruhiko; Tanaka, Isao; Ueno, Eiko

    2012-01-01

    Objectives: To compare the performance of model-based iterative reconstruction (MBIR) with that of standard filtered back projection (FBP) for measuring vascular wall attenuation. Study design: After subjecting 9 vascular models (actual attenuation value of wall, 89 HU) with wall thickness of 0.5, 1.0, or 1.5 mm that we filled with contrast material of 275, 396, or 542 HU to scanning using 64-detector computed tomography (CT), we reconstructed images using MBIR and FBP (Bone, Detail kernels) and measured wall attenuation at the center of the wall for each model. We performed attenuation measurements for each model and additional supportive measurements by a differentiation curve. We analyzed statistics using analyzes of variance with repeated measures. Results: Using the Bone kernel, standard deviation of the measurement exceeded 30 HU in most conditions. In measurements at the wall center, the attenuation values obtained using MBIR were comparable to or significantly closer to the actual wall attenuation than those acquired using Detail kernel. Using differentiation curves, we could measure attenuation for models with walls of 1.0- or 1.5-mm thickness using MBIR but only those of 1.5-mm thickness using Detail kernel. We detected no significant differences among the attenuation values of the vascular walls of either thickness (MBIR, P = 0.1606) or among the 3 densities of intravascular contrast material (MBIR, P = 0.8185; Detail kernel, P = 0.0802). Conclusions: Compared with FBP, MBIR reduces both reconstruction blur and image noise simultaneously, facilitates recognition of vascular wall boundaries, and can improve accuracy in measuring wall attenuation.

  5. Measurement of vascular wall attenuation: comparison of CT angiography using model-based iterative reconstruction with standard filtered back-projection algorithm CT in vitro.

    Science.gov (United States)

    Suzuki, Shigeru; Machida, Haruhiko; Tanaka, Isao; Ueno, Eiko

    2012-11-01

    To compare the performance of model-based iterative reconstruction (MBIR) with that of standard filtered back projection (FBP) for measuring vascular wall attenuation. After subjecting 9 vascular models (actual attenuation value of wall, 89 HU) with wall thickness of 0.5, 1.0, or 1.5 mm that we filled with contrast material of 275, 396, or 542 HU to scanning using 64-detector computed tomography (CT), we reconstructed images using MBIR and FBP (Bone, Detail kernels) and measured wall attenuation at the center of the wall for each model. We performed attenuation measurements for each model and additional supportive measurements by a differentiation curve. We analyzed statistics using analyzes of variance with repeated measures. Using the Bone kernel, standard deviation of the measurement exceeded 30 HU in most conditions. In measurements at the wall center, the attenuation values obtained using MBIR were comparable to or significantly closer to the actual wall attenuation than those acquired using Detail kernel. Using differentiation curves, we could measure attenuation for models with walls of 1.0- or 1.5-mm thickness using MBIR but only those of 1.5-mm thickness using Detail kernel. We detected no significant differences among the attenuation values of the vascular walls of either thickness (MBIR, P=0.1606) or among the 3 densities of intravascular contrast material (MBIR, P=0.8185; Detail kernel, P=0.0802). Compared with FBP, MBIR reduces both reconstruction blur and image noise simultaneously, facilitates recognition of vascular wall boundaries, and can improve accuracy in measuring wall attenuation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Modeling the relative impact of capsular tissue effects on implanted glucose sensor time lag and signal attenuation.

    Science.gov (United States)

    Novak, Matthew T; Yuan, Fan; Reichert, William M

    2010-10-01

    Little is known mechanistically about why implanted glucose sensors lag behind blood glucose levels in both the time to peak sensor response and the magnitude of peak sensor response. A mathematical model of glucose transport from capillaries through surrounding tissue to the sensor surface was constructed to address how different aspects of the tissue affect glucose transport to an implanted sensor. Physiologically relevant values of capsule diffusion coefficient, capsule porosity, cellular glucose consumption, capsule thickness, and subcutaneous vessel density were used as inputs to create simulated sensor traces that mimic experimental instances of time lag and concentration attenuation relative to a given blood glucose profile. Using logarithmic sensitivity analysis, each parameter was analyzed to study the effect of these variables on both lag and attenuation. Results identify capsule thickness as the strongest determinant of sensor time lag, while subcutaneous vessel density and capsule porosity had the largest effects on attenuation of glucose that reaches the sensor surface. These findings provide mechanistic insight for the rational design of sensor modifications that may alleviate the deleterious consequences of tissue effects on implanted sensor performance.

  7. A new parameterization for surface ocean light attenuation in Earth System Models: assessing the impact of light absorption by colored detrital material

    OpenAIRE

    G. E. Kim; M.-A. Pradal; A. Gnanadesikan

    2015-01-01

    Light limitation can affect the distribution of biota and nutrients in the ocean. Light absorption by colored detrital material (CDM) was included in a fully coupled Earth System Model using a new parameterization for shortwave attenuation. Two model runs were conducted, with and without light attenuation by CDM. In a global average sense, greater light limitation associated with CDM increased surface chlorophyll, biomass and nutrients together. These changes can be attribut...

  8. A statistical rain attenuation prediction model with application to the advanced communication technology satellite project. Part 2: Theoretical development of a dynamic model and application to rain fade durations and tolerable control delays for fade countermeasures

    Science.gov (United States)

    Manning, Robert M.

    1987-01-01

    A dynamic rain attenuation prediction model is developed for use in obtaining the temporal characteristics, on time scales of minutes or hours, of satellite communication link availability. Analagous to the associated static rain attenuation model, which yields yearly attenuation predictions, this dynamic model is applicable at any location in the world that is characterized by the static rain attenuation statistics peculiar to the geometry of the satellite link and the rain statistics of the location. Such statistics are calculated by employing the formalism of Part I of this report. In fact, the dynamic model presented here is an extension of the static model and reduces to the static model in the appropriate limit. By assuming that rain attenuation is dynamically described by a first-order stochastic differential equation in time and that this random attenuation process is a Markov process, an expression for the associated transition probability is obtained by solving the related forward Kolmogorov equation. This transition probability is then used to obtain such temporal rain attenuation statistics as attenuation durations and allowable attenuation margins versus control system delay.

  9. Lactobacillus rhamnosus L34 Attenuates Gut Translocation-Induced Bacterial Sepsis in Murine Models of Leaky Gut.

    Science.gov (United States)

    Panpetch, Wimonrat; Chancharoenthana, Wiwat; Bootdee, Kanthika; Nilgate, Sumanee; Finkelman, Malcolm; Tumwasorn, Somying; Leelahavanichkul, Asada

    2018-01-01

    Gastrointestinal (GI) bacterial translocation in sepsis is well known, but the role of Lactobacillus species probiotics is still controversial. We evaluated the therapeutic effects of Lactobacillus rhamnosus L34 in a new sepsis model of oral administration of pathogenic bacteria with GI leakage induced by either an antibiotic cocktail (ATB) and/or dextran sulfate sodium (DSS). GI leakage with ATB, DSS, and DSS plus ATB (DSS+ATB) was demonstrated by fluorescein isothiocyanate (FITC)-dextran translocation to the circulation. The administration of pathogenic bacteria, either Klebsiella pneumoniae or Salmonella enterica serovar Typhimurium, enhanced translocation. Bacteremia was demonstrated within 24 h in 50 to 88% of mice with GI leakage plus the administration of pathogenic bacteria but not with GI leakage induction alone or bacterial gavage alone. Salmonella bacteremia was found in only 16 to 29% and 0% of mice with Salmonella and Klebsiella administrations, respectively. Klebsiella bacteremia was demonstrated in 25 to 33% and 10 to 16% of mice with Klebsiella and Salmonella administrations, respectively. Lactobacillus rhamnosus L34 attenuated GI leakage in these models, as shown by the reductions of FITC-dextran gut translocation, serum interleukin-6 (IL-6) levels, bacteremia, and sepsis mortality. The reduction in the amount of fecal Salmonella bacteria with Lactobacillus treatment was demonstrated. In addition, an anti-inflammatory effect of the conditioned medium from Lactobacillus rhamnosus L34 was also demonstrated by the attenuation of cytokine production in colonic epithelial cells in vitro In conclusion, Lactobacillus rhamnosus L34 attenuated the severity of symptoms in a murine sepsis model induced by GI leakage and the administration of pathogenic bacteria. Copyright © 2017 American Society for Microbiology.

  10. Interval training attenuates the metabolic disturbances in type 1 diabetes rat model.

    Science.gov (United States)

    Rocha, Ricelli Endrigo Ruppel; Coelho, Isabela; Pequito, Daniela Cristina T; Yamagushi, Adriana; Borghetti, Gina; Yamazaki, Ricardo Key; Brito, Gleisson Alisson Pereira de; Machado, Juliano; Kryczyk, Marcelo; Nunes, Everson Araújo; Venera, Graciela; Fernandes, Luiz Claudio

    2013-11-01

    This study investigated the effect of interval training on blood biochemistry and immune parameters in type 1 diabetic rats. Male Wistar rats were divided into four groups: sedentary (SE, n = 15), interval training (IT, n = 17), diabetic sedentary (DSE, n = 17), diabetic interval training (DIT, n = 17). Diabetes was induced by i.v. injection of streptozotocin (60 mg/kg). Swimming Interval Training consisted of 30-s exercise with 30-s rest, for 30 minutes, during 6 weeks, four times a week, with an overload of 15% of body mass. Plasma glucose, lactate, triacylglycerol and total cholesterol concentrations, phagocytic capacity, cationic vesicle content, and superoxide anion and hydrogen peroxide production by blood neutrophils and peritoneal macrophages were evaluated. Proliferation of mesenteric lymphocytes was also estimated. Interval training resulted in attenuation of the resting hyperglycemic state and decreased blood lipids in the DIT group. Diabetes increased the functionality of blood neutrophils and peritoneal macrophages in the DSE group. Interval training increased all functionality parameters of peritoneal macrophages in the IT group. Interval training also led to a twofold increase in the proliferation of mesenteric lymphocytes after 6 weeks of exercise in the DIT group. Low-volume high-intensity physical exercise attenuates hyperglycemia and dislipidemia induced by type 1 diabetes, and induces changes in the functionality of innate and acquired immunity.

  11. Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: observations in an ex vivo model of coronary computed tomography angiography

    International Nuclear Information System (INIS)

    Cademartiri, Filippo; Krestin, Gabriel P.; Mollet, Nico R.; Feyter, Pim J. de; Runza, Giuseppe; Midiri, Massimo; Bruining, Nico; Hamers, Ronald; Somers, Pamela; Knaapen, Michiel; Verheye, Stefan

    2005-01-01

    Assessment of attenuation (measured in Hounsfield units, HU) of human coronary plaques was performed using multislice computed tomography (MSCT) in an ex vivo model. In three ex vivo specimens of left coronary arteries in oil, MSCT was performed after intracoronary injection of four solutions of contrast material (400 mgI/ml iomeprol). The four solutions were diluted as follows: 1/∞, 1/200, 1/80, and 1/20. All scans were performed with the following parameters: slices/collimation 16/0.75 mm, rotation time 375 ms. Each specimen was scored for the presence of atherosclerotic plaques. In each plaque the attenuation was measured in four regions of interest for lumen, plaque (non-calcified thickening of the vessel wall), calcium, and surrounding (oil surrounding the vessel). The results were compared with a one-way analysis of variance test and were correlated with Pearson's test. There were no significant differences in the attenuation of calcium and oil in the four solutions. The mean attenuation in the four solutions for lumen (35±10, 91±7, 246±18, 511±89 HU) and plaque (22±22, 50±26, 107±36, 152±67 HU) was significantly different between each decreasing dilution (p<0.001). The mean attenuation of lumen and plaque of coronary plaques showed high correlation, while the values were significantly different (r=0.73; p<0.001). Intracoronary attenuation modifies significantly the attenuation of plaques assessed with MSCT. (orig.)

  12. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

    Science.gov (United States)

    Li, Chunyi; Mo, Zhihuai; Lei, Junjie; Li, Huiqing; Fu, Ruying; Huang, Yanxia; Luo, Shijian; Zhang, Lei

    2018-06-01

    Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Attrition of schistosomes in an irradiation-attenuated cercarial immunization model of Schistosoma mansoni

    International Nuclear Information System (INIS)

    Stek, M. Jr.; Dean, D.A.; Clark, S.S.

    1981-01-01

    The attrition of Schistosoma mansoni challenge worms was studied in irradiation-attenuated cercaria-immunized mice as a function of site and time. The peak recovery of schistosomula from the lungs of immunized mice was delayed 2 days in comparison with non-immunized controls. The difference between the peak recoveries of control and immunized mice accounted for about half of the final attrition observed at the 7-week adult worm stge. Hepatic-mesenteric vein worm recoveries obtained 10 to 42 days after challenge were reduced in most cases at least as much as the 49-day counts. Somewhat higher reductions were observed at 14 to 28 days than at 49 days, confirming the evidence of delayed migration obtained at the lung phase. These findings, coupled with histologic observations, indicate that at least half of the worm elimination attributable to immunization occurs 8 or more days after the challenge infection

  14. Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2'-O-Methylation Mutant.

    Directory of Open Access Journals (Sweden)

    Bianca Schmid

    2015-12-01

    Full Text Available Dengue virus (DENV is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2'-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2'-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.

  15. Vanillin Attenuated Behavioural Impairments, Neurochemical Deficts, Oxidative Stress and Apoptosis Against Rotenone Induced Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Dhanalakshmi, Chinnasamy; Janakiraman, Udaiyappan; Manivasagam, Thamilarasan; Justin Thenmozhi, Arokiasamy; Essa, Musthafa Mohamed; Kalandar, Ameer; Khan, Mohammed Abdul Sattar; Guillemin, Gilles J

    2016-08-01

    Vanillin (4-hydroxy-3-methoxybenzaldehyde), a pleasant smelling organic aromatic compound, is widely used as a flavoring additive in food, beverage, cosmetic and drug industries. It is reported to cross the blood brain barrier and also displayed antioxidant and neuroprotective activities. We previously reported the neuroprotective effect of vanillin against rotenone induced in in vitro model of PD. The present experiment was aimed to analyze the neuroprotective effect of vanillin on the motor and non-motor deficits, neurochemical variables, oxidative, anti-oxidative indices and the expression of apoptotic markers against rotenone induced rat model of Parkinson's disease (PD). Rotenone treatment exhibited motor and non-motor impairments, neurochemical deficits, oxidative stress and apoptosis, whereas oral administration of vanillin attenuated the above-said indices. However further studies are needed to explore the mitochondrial protective and anti-inflammatory properties of vanillin, as these processes play a vital role in the cause and progression of PD.

  16. Gypenosides attenuate the development of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

    Science.gov (United States)

    Shin, Keon Sung; Zhao, Ting Ting; Park, Keun Hong; Park, Hyun Jin; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

    2015-04-21

    Gypenosides (GPS) and ethanol extract of Gynostemma pentaphyllum (GP-EX) show anxiolytic effects on affective disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD). Long-term administration of L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of severe motor side effects such as L-DOPA-induced-dyskinesia (LID) in PD. The present study investigated the effects of GPS and GP-EX on LID in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Daily administration of L-DOPA (25 mg/kg) in the 6-OHDA-lesioned rat model of PD for 22 days induced expression of LID, which was determined by the body and locomotive AIMs scores and contralateral rotational behaviors. However, co-treatments of GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg) with L-DOPA significantly attenuated the development of LID without compromising the anti-parkinsonian effects of L-DOPA. In addition, the increases in ∆FosB expression and ERK1/2 phosphorylation in 6-OHDA-lesioned rats induced by L-DOPA administration were significantly reduced by co-treatment with GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg). These results suggest that GPS (25 and 50 mg/kg) and GP-EX (50 mg/kg) effectively attenuate the development of LID by modulating the biomarker activities of ∆FosB expression and ERK1/2 phosphorylation in the 6-OHDA-lesioned rat model of PD. GPS and GP-EX will be useful adjuvant therapeutics for LID in PD.

  17. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model.

    Science.gov (United States)

    Carlson, Jolene; O'Donnell, Vivian; Alfano, Marialexia; Velazquez Salinas, Lauro; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Higgs, Stephen; Borca, Manuel V

    2016-10-22

    African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi) showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi). This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN)-γ responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  18. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Directory of Open Access Journals (Sweden)

    Jolene Carlson

    2016-10-01

    Full Text Available African swine fever (ASF is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV. There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN-γ responses, or specific cytokine profiles and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  19. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    Science.gov (United States)

    Suchal, Kapil; Malik, Salma; Gamad, Nanda; Malhotra, Rajiv Kumar; Goyal, Sameer N.; Chaudhary, Uma; Bhatia, Jagriti; Ojha, Shreesh; Arya, Dharamvir Singh

    2016-01-01

    Kaempferol (KMP), a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR) model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p.) was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB), inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3), TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2). In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway. PMID:27087891

  20. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Kapil Suchal

    2016-01-01

    Full Text Available Kaempferol (KMP, a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p. was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB, inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3, TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2. In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.

  1. Lycopene attenuates Aβ1-42 secretion and its toxicity in human cell and Caenorhabditis elegans models of Alzheimer disease.

    Science.gov (United States)

    Chen, Wei; Mao, Liuqun; Xing, Huanhuan; Xu, Lei; Fu, Xiang; Huang, Liyingzi; Huang, Dongling; Pu, Zhijun; Li, Qinghua

    2015-11-03

    Growing evidence suggests concentration of lycopene was reduced in plasma of patients with Alzheimer disease (AD). Lycopene, a member of the carotenoid family, has been identified as an antioxidant to attenuate oxidative damage and has neuroprotective role in several AD models. However, whether lycopene is involved in the pathogenesis of AD and molecular underpinnings are elusive. In this study, we found that lycopene can significantly delay paralysis in the Aβ1-42-transgenic Caenorhabditis elegans strain GMC101. Lycopene treatment reduced Aβ1-42 secretion in SH-SY5Y cells overexpressing the Swedish mutant form of human β-amyloid precursor protein (APPsw). Next, we found lycopene can down-regulate expression level of β-amyloid precursor protein(APP) in APPsw cells. Moreover, lycopene treatment can not change endogenous reactive oxygen species level and apoptosis in APPsw cells. However, lycopene treatment protected against H2O2-induced oxidative stress and copper-induced damage in APPsw cells. Collectively, our data support that elevated lycopene contributes to the lower pathogenesis of AD. Our findings suggest that increasing lycopene in neurons may be a novel approach to attenuate onset and development of AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

    Directory of Open Access Journals (Sweden)

    Raimundo M. G. del Moral

    2013-01-01

    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  3. Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.

    Science.gov (United States)

    Boonloh, Kampeebhorn; Lee, Eun Soo; Kim, Hong Min; Kwon, Mi Hye; Kim, You Mi; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Thawornchinsombut, Supawan; Lee, Eun Young; Kukongviriyapan, Veerapol; Chung, Choon Hee

    2018-03-01

    Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-β, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.

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

    Science.gov (United States)

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

    2014-04-01

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

  5. Kaempferol attenuates acute lung injury in caecal ligation and puncture model of sepsis in mice.

    Science.gov (United States)

    Rabha, Dipankar Jyoti; Singh, Thakur Uttam; Rungsung, Soya; Kumar, Tarun; Parida, Subhashree; Lingaraju, Madhu Cholenahalli; Paul, Avishek; Sahoo, Monalisa; Kumar, Dinesh

    2018-03-01

    Kaempferol is a flavonoid and important part of the diet. Kaempferol has shown antioxidant, antiinflammatory and antidiabetic activities in various studies. However, protective potential of kaempferol in acute lung injury induced by sepsis and its mechanism remains unclear. The present study was undertaken to evaluate the effect of kaempferol in sepsis-induced acute lung injury in mice and its possible mechanism of action. Acute lung injury was induced by CLP surgery in mice. Kaempferol (100 mg/kg bw) was administered orally one hour before caecal ligation and puncture surgery in mice. Mice were divided into four groups sham, KEM+sham, sepsis (CLP), and KEM+sepsis. Assessment of lung injury was done by estimation of protein content in lung tissue, lung edema, proinflammatory cytokines in plasma and lung tissue, oxidative stress, antioxidant enzymes, nitrite production, and histopathology. Kaempferol pretreated mice showed significant (P Kaempferol pretreatment showed reduction in cytokines IL-6, IL-1β, and TNF-α in plasma as well as in lung tissue in comparison with septic mice without pretreatment. Pretreatment with kaempferol did not show any reduction in MDA level in comparison with septic mice. Antioxidant enzymes SOD and catalase and nonenzymatic antioxidant GSH activities were also increased with kaempferol pretreatment in septic mice. Further, kaempferol pretreatment reduced the lung tissue nitrite level (P Kaempferol pretreatment did not decrease bacterial load in septic mice. Mice pretreated with kaempferol followed by sepsis showed lesser infiltration of cells and more arranged alveolar structure in histopathological analysis. The study suggests that kaempferol showed attenuation in sepsis-induced acute lung injury in mice through suppression of oxidative stress, iNOS, and ICAM-1 pathways.

  6. Osthole attenuates hepatic injury in a rodent model of trauma-hemorrhage.

    Science.gov (United States)

    Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

    2013-01-01

    Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway.

  7. Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

    DEFF Research Database (Denmark)

    Brouwers, Olaf; Niessen, Petra M G; Miyata, Toshio

    2014-01-01

    AIMS/HYPOTHESIS: In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed...... the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. METHODS: Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection...... podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation...

  8. The CNTF-derived peptide mimetic Cintrofin attenuates spatial-learning deficits in a rat post-status epilepticus model

    DEFF Research Database (Denmark)

    Russmann, Vera; Seeger, Natalie; Zellinger, Christina

    2013-01-01

    Ciliary neurotrophic growth factor is considered a potential therapeutic agent for central nervous system diseases. We report first in vivo data of the ciliary neurotrophic growth factor peptide mimetic Cintrofin in a rat post-status epilepticus model. Cintrofin prevented long-term alterations...... in the number of doublecortin-positive neuronal progenitor cells and attenuated the persistence of basal dendrites. In contrast, Cintrofin did neither affect acute status epilepticus-associated alterations in hippocampal cell proliferation and neurogenesis nor reveal any relevant effect on seizure activity....... Whereas status epilepticus caused a significant disturbance in spatial learning in reversed peptide-treated rats, the performance of Cintrofin-treated rats did not differ from controls. The study confirms that Cintrofin comprises an active sequence mimicking effects of its parent molecule. While the data...

  9. Spiral model of the Galaxy from observations of the interstellar light attenuation

    International Nuclear Information System (INIS)

    Urasin, L.A.

    1987-01-01

    The model of two arms spiral structure of the Galaxy is made from the observations of space distribution of the interstellar dust matter. This model is the logarithmic spiral with characteristic angle (pith) 6.5 deg

  10. How a joint interpretation of seismic scattering, velocity, and attenuation models explains the nature of the Campi Flegrei (Italy).

    Science.gov (United States)

    Calo, M.; Tramelli, A.

    2017-12-01

    Seismic P and S velocity models (and their ratio Vp/Vs) help illuminating the geometrical structure of the bodies and give insight on the presence of water, molten or gas saturated regions. Seismic attenuation represents the anelastic behavior of the medium. Due to its dependence on temperature, fluid contents and cracks presence, this parameter is also largely used to characterize the structures of volcanoes and geothermal areas. Scattering attenuation is related, in the upper crust, to the amount, size and organization of the fractures giving complementary information on the state of the medium.Therefore a joint interpretation of these models provides an exhaustive view of the elastic parameters in volcanic regions. Campi Flegrei is an active Caldera marked by strong vertical deformations of the ground called bradyseisms and several models have been proposed to describe the nature and the geometry of the bodies responsible of the bradyseisms. Here we show Vp, Vp/Vs, Qp and scattering models carried out by applying an enhanced seismic tomography method that combines de double difference approach (Zhang and Thurber, 2003) and the Weigthed Average Method (Calò et al., 2009, Calò et al., 2011, 2013). The data used are the earthquakes recorded during the largest bradyseism crisis of the 80's. Our method allowed to image structures with linear dimension of 0.5-1.2km, resulting in an improvement of the resolving power at least two times of the other published models (e.g. Priolo et al., 2012). The joint interpretation of seismic models allowed to discern small anomalous bodies at shallow depth (0.5-2.0 km) marked by relatively low Vp, high Vp/Vs ratio and low Qp values associated with the presence of shallow geothermal water saturated reservoir from regions with low Vp, low Vp/Vs and low Qp related to the gas saturated part of the reservoir. At deeper depth (2-3.5 km) bodies with high Vp and Vp/Vs and low Qp are associated with magmatic intrusions. The Scattering

  11. Water Extract of Dolichos lablab Attenuates Hepatic Lipid Accumulation in a Cellular Nonalcoholic Fatty Liver Disease Model.

    Science.gov (United States)

    Im, A-Rang; Kim, Yun Hee; Lee, Hye Won; Song, Kwang Hoon

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rising in prevalence worldwide. Therapeutic strategies for patients with NAFLD are limited by a lack of effective drugs. In this report, we show that Dolichos lablab water extract (DLL-Ex) protects against free fatty acid (FFA)-induced lipid accumulation and attenuates expression of genes involved in lipid droplet accumulation in cellular NAFLD models. The hepatoprotective effects and underlying mechanism of DLL-Ex were assessed using an in vitro cellular model in which NAFLD was simulated by inducing excessive FFA influx into hepatocytes. HepG2 cells were treated with DLL-Ex and FFAs for 24 h, after which intracellular lipid content was observed by using Nile Red and Oil Red O staining. Quantitative real-time polymerase chain reaction was used to measure expression levels of genes related to FFA-mediated cellular energy depletion. Western blotting was used to measure protein levels of phosphorylated c-Jun N-terminal kinase, AMP-activated protein kinase alpha (AMPKα), and peroxisome proliferator-activated receptor γ coactivator 1 alpha. In HepG2 cells, DLL-Ex inhibited expression of CD36, which regulates fatty acid uptake, as well as BODIPY-labeled fatty acid uptake. Additionally, DLL-Ex significantly attenuated FFA-mediated cellular energy depletion and mitochondrial membrane depolarization. Furthermore, DLL-Ex enhanced phosphorylation of AMPK, indicating that AMPK is a critical regulator of DLL-Ex-mediated inhibition of hepatic lipid accumulation, possibly through its antioxidative effect. These results demonstrate that DLL-Ex exerts potent anti-NAFLD activity, suggesting that it could be a potential adjuvant treatment for patients with NAFLD.

  12. Berberine attenuates CCN2-induced IL-1β expression and prevents cartilage degradation in a rat model of osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Shan-Chi [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Lee, Hsiang-Ping [Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan (China); Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan (China); Hung, Chun-Yin [Department of Orthopaedic Surgery, China Medical University Beigang Hospital, Yun-Lin County, Taiwan (China); Tsai, Chun-Hao [Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan (China); Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan (China); Li, Te-Mao [School of Chinese Medicine, China Medical University, Taichung, Taiwan (China); Tang, Chih-Hsin, E-mail: chtang@mail.cmu.edu.tw [Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan (China); Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan (China); Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan (China)

    2015-11-15

    Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator that is abundantly expressed in osteoarthritis (OA). Interleukin-1β (IL-1β) plays a pivotal role in OA pathogenesis. Berberine exhibits an anti-inflammatory effect, but the mechanisms by which it modulates CCN2-induced IL-1β expression in OA synovial fibroblasts (OASFs) remain unknown. We showed that CCN2-induced IL-1β expression is mediated by the activation of α{sub v}β{sub 3}/α{sub v}β{sub 5} integrin-dependent reactive oxygen species (ROS) generation, and subsequent activation of apoptosis signal-regulating kinase 1 (ASK1), p38/JNK, and nuclear factor-κB (NF-κB) signaling pathways. This IL-1β expression in OASFs is attenuated by N-acetylcysteine (NAC), inhibitors of ASK1, p38, or JNK, or treatment with berberine. Furthermore, berberine also reverses cartilage damage in an experimental model of collagenase-induced OA (CIOA). We observed that CCN2 increased IL-1β expression via α{sub v}β{sub 3}/α{sub v}β{sub 5} integrins, ROS, and ASK1, p38/JNK, and NF-κB signaling pathways. Berberine was found to inhibit these signaling components in OASFs in vitro and prevent cartilage degradation in vivo. We suggest a novel therapeutic strategy of using berberine for managing OA. - Highlights: • CCN2 induce IL-1β production via αvβ3/αvβ5 integrin, ROS, ASK1, p38/JNK, and NF-κB. • Berberine attenuates CCN2-induced IL-1β expression in vitro and in OA rat model. • Berberine as natural drug of choice for anti-inflammatory effect to ameliorates OA.

  13. Rivaroxaban attenuates thrombosis by targeting the NF-κB signaling pathway in a rat model of deep venous thrombus.

    Science.gov (United States)

    Ma, Junhao; Li, Xinxi; Wang, Yang; Yang, Zhenwei; Luo, Jun

    2017-12-01

    Anticoagulant therapy is commonly used for the prevention and treatment of patients with deep venous thrombus. Evidence has shown that rivaroxaban is a potential oral anticoagulant drug for the acute treatment of venous thromboembolism. However, the rivaroxaban-mediated molecular mechanism involved in the progression of deep venous thrombosis has not been investigated. In the present study, we investigated the efficacy of rivaroxaban and the underlying signaling pathways in the prevention and treatment of rats with deep venous thrombosis. A rat model with deep vein thrombus formation was established and received treatment with rivaroxaban or PBS as control. The thrombin-activatable fibrinolysis inhibitor (TAFI) and plasminogen activator inhibitor-1 (PAI-1) were analyzed both in vitro and in vivo. The progression of thrombosis and stroke was evaluated after treatment with rivaroxaban or PBS. Nuclear factor-κB (NF-κB) signaling pathway in venous endothelial cells and in the rat model of deep venous thrombus was assessed. The therapeutic effects of rivaroxaban were evaluated as determined by changes in deep venous thrombosis in the rat model. Our results showed that rivaroxaban markedly inhibited TAFI and PAI-1 expression levels, neutrophils, tissue factor, neutrophil extracellular traps (NETs), myeloperoxidase and macrophages in venous endothelial cells and in the rat model of deep venous thrombus. Expression levels of ADP, PAIs, von Willebrand factor (vWF) and thromboxane were downregulated in vein endothelial cells and in serum from the experimental rats. Importantly, the incidences of inferior vena cava filter thrombus were protected by rivaroxaban during heparin-induced thrombolysis deep venous thrombosis in the rat model. We observed that activity of the NF-κB signaling pathway was inhibited by rivaroxaban in vein endothelial cells both in vitro and in vivo. Notably, immunohistology indicated that rivaroxaban attenuated deep venous thrombosis and the

  14. Reactive transport modeling of processes controlling the distribution and natural attenuation of phenolic compounds in a deep sandstone aquifer

    Science.gov (United States)

    Mayer, K. U.; Benner, S. G.; Frind, E. O.; Thornton, S. F.; Lerner, D. N.

    2001-12-01

    Reactive solute transport modeling was utilized to evaluate the potential for natural attenuation of a contaminant plume containing phenolic compounds at a chemical producer in the West Midlands, UK. The reactive transport simulations consider microbially mediated biodegradation of the phenolic compounds (phenols, cresols, and xylenols) by multiple electron acceptors. Inorganic reactions including hydrolysis, aqueous complexation, dissolution of primary minerals, formation of secondary mineral phases, and ion exchange are considered. One-dimensional (1D) and three-dimensional (3D) simulations were conducted. Mass balance calculations indicate that biodegradation in the saturated zone has degraded approximately 1-5% of the organic contaminant plume over a time period of 47 years. Simulations indicate that denitrification is the most significant degradation process, accounting for approximately 50% of the organic contaminant removal, followed by sulfate reduction and fermentation reactions, each contributing 15-20%. Aerobic respiration accounts for less than 10% of the observed contaminant removal in the saturated zone. Although concentrations of Fe(III) and Mn(IV) mineral phases are high in the aquifer sediment, reductive dissolution is limited, producing only 5% of the observed mass loss. Mass balance calculations suggest that no more than 20-25% of the observed total inorganic carbon (TIC) was generated from biodegradation reactions in the saturated zone. Simulations indicate that aerobic biodegradation in the unsaturated zone, before the contaminant entered the aquifer, may have produced the majority of the TIC observed in the plume. Because long-term degradation is limited to processes within the saturated zone, use of observed TIC concentrations to predict the future natural attenuation may overestimate contaminant degradation by a factor of 4-5.

  15. A blueberry-enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress.

    Directory of Open Access Journals (Sweden)

    Carrie M Elks

    Full Text Available To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB have among the highest antioxidant capacities of fruits and vegetables.Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w or an isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved glomerular filtration rate, and decreased renovascular resistance. As measured by electron paramagnetic resonance spectroscopy, significant decreases in total reactive oxygen species (ROS, peroxynitrite, and superoxide production rates were observed in kidney tissues in rats on long-term dietary treatment, consistent with reduced pathology and improved function. Additionally, measures of antioxidant status improved; specifically, renal glutathione and catalase activities increased markedly. Contrasted to these observations indicating reduced OS in the BB group after long-term feeding, similar measurements made in rats fed the same diet for only 2 days yielded evidence of increased OS; specifically, significant increases in total ROS, peroxynitrite, and superoxide production rates in all tissues (kidney, brain, and liver assayed in BB-fed rats. These results were evidence of "hormesis" during brief exposure, which dissipated with time as indicated by enhanced levels of catalase in heart and liver of BB group.Long-term feeding of BB-enriched diet lowered blood pressure, preserved renal hemodynamics, and improved redox status in kidneys of hypertensive rats and concomitantly demonstrated the potential to delay or attenuate development

  16. Extraction procedure compared to attenuation model to assess heavy metals mobility in sediments from Sepetiba Bay, Rio de Janeiro

    International Nuclear Information System (INIS)

    Ribeiro, Andreza Portella

    2006-01-01

    , for Zn, and as level 1, for Cd, Cu, Pb and Ni, according to the CONAMA 344/04 act. A geostatistical approach is presented, the attenuation of concentrations model, which aims to estimate metal mobility in sediments. The proposed model showed the highest attenuation values for Zn, Cd, Cu and Pb in the northeastern region, indicating that the mobility of these metals is low in this region, suggesting low availability, which is in good agreement with the results obtained by the SIGMA[SEM]/[AVS] model. These results indicate good possibilities of applying this model in metal contamination studies in estuarine ecosystems. (author)

  17. Tomography of atomic number and density of materials using dual-energy imaging and the Alvarez and Macovski attenuation model

    Energy Technology Data Exchange (ETDEWEB)

    Paziresh, M.; Kingston, A. M., E-mail: andrew.kingston@anu.edu.au; Latham, S. J.; Fullagar, W. K.; Myers, G. M. [Department of Applied Mathematics, Research School of physics and Engineering, The Australian National University, Canberra 2601 (Australia)

    2016-06-07

    Dual-energy computed tomography and the Alvarez and Macovski [Phys. Med. Biol. 21, 733 (1976)] transmitted intensity (AMTI) model were used in this study to estimate the maps of density (ρ) and atomic number (Z) of mineralogical samples. In this method, the attenuation coefficients are represented [Alvarez and Macovski, Phys. Med. Biol. 21, 733 (1976)] in the form of the two most important interactions of X-rays with atoms that is, photoelectric absorption (PE) and Compton scattering (CS). This enables material discrimination as PE and CS are, respectively, dependent on the atomic number (Z) and density (ρ) of materials [Alvarez and Macovski, Phys. Med. Biol. 21, 733 (1976)]. Dual-energy imaging is able to identify sample materials even if the materials have similar attenuation coefficients at single-energy spectrum. We use the full model rather than applying one of several applied simplified forms [Alvarez and Macovski, Phys. Med. Biol. 21, 733 (1976); Siddiqui et al., SPE Annual Technical Conference and Exhibition (Society of Petroleum Engineers, 2004); Derzhi, U.S. patent application 13/527,660 (2012); Heismann et al., J. Appl. Phys. 94, 2073–2079 (2003); Park and Kim, J. Korean Phys. Soc. 59, 2709 (2011); Abudurexiti et al., Radiol. Phys. Technol. 3, 127–135 (2010); and Kaewkhao et al., J. Quant. Spectrosc. Radiat. Transfer 109, 1260–1265 (2008)]. This paper describes the tomographic reconstruction of ρ and Z maps of mineralogical samples using the AMTI model. The full model requires precise knowledge of the X-ray energy spectra and calibration of PE and CS constants and exponents of atomic number and energy that were estimated based on fits to simulations and calibration measurements. The estimated ρ and Z images of the samples used in this paper yield average relative errors of 2.62% and 1.19% and maximum relative errors of 2.64% and 7.85%, respectively. Furthermore, we demonstrate that the method accounts for the beam hardening effect in density (

  18. Attenuation of TRPV1 and TRPV4 Expression and Function in Mouse Inflammatory Pain Models Using Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Wei-Hsin Chen

    2012-01-01

    Full Text Available Although pain is a major human affliction, our understanding of pain mechanisms is limited. TRPV1 (transient receptor potential vanilloid subtype 1 and TRPV4 are two crucial receptors involved in inflammatory pain, but their roles in EA- (electroacupuncture- mediated analgesia are unknown. We injected mice with carrageenan (carra or a complete Freund’s adjuvant (CFA to model inflammatory pain and investigated the analgesic effect of EA using animal behavior tests, immunostaining, Western blotting, and a whole-cell recording technique. The inflammatory pain model mice developed both mechanical and thermal hyperalgesia. Notably, EA at the ST36 acupoint reversed these phenomena, indicating its curative effect in inflammatory pain. The protein levels of TRPV1 and TRPV4 in DRG (dorsal root ganglion neurons were both increased at day 4 after the initiation of inflammatory pain and were attenuated by EA, as demonstrated by immunostaining and Western blot analysis. We verified DRG electrophysiological properties to confirm that EA ameliorated peripheral nerve hyperexcitation. Our results indicated that the AP (action potential threshold, rise time, and fall time, and the percentage and amplitude of TRPV1 and TRPV4 were altered by EA, indicating that EA has an antinociceptive role in inflammatory pain. Our results demonstrate a novel role for EA in regulating TRPV1 and TRPV4 protein expression and nerve excitation in mouse inflammatory pain models.

  19. The asymmetry in attenuation experiments and the Glashow-Salam-Weinberg model with extended Higgs sector

    International Nuclear Information System (INIS)

    Santangelo, E.M.

    1983-01-01

    The asymmetry seen in beam-dump experiments done in CERN, between ν sub(e)/ν sup(-) sub(e) and ν sub(μ)/ν sup(-) sub(μ), is discussed using the Glashow-Salam-Weinberg model with extended Higgs sector. (L.C.) [pt

  20. Modelling of Wave Attenuation Induced by Multi-Purpose Floating Structures

    DEFF Research Database (Denmark)

    Stratigaki, Vasiliki; Troch, Peter; Stallard, Tim

    2014-01-01

    , polychromatic, long- and short-crested irregular waves), WEC response and modification of the wave field have been measured to provide data for the understanding of WEC farm interactions and for the evaluation of farm interaction numerical models. A first extensive wave farm database is established...

  1. Evaluation of Conceptual and Numerical Models for Arsenic Mobilization and Attenuation during Managed Aquifer Recharge

    NARCIS (Netherlands)

    Post, V.E.A.; Prommer, H.; Wallis, I.; Simmons, C.T.; Stuijfzand, P.J.

    2010-01-01

    Managed Aquifer Recharge (MAR) is promoted as an attractive technique to meet growing water demands. An impediment to MAR applications, where oxygenated water is recharged into anoxic aquifers, is the potential mobilization of trace metals (e.g., arsenic). While conceptual models for arsenic

  2. Comparison of iodinated contrast media for the assessment of atherosclerotic plaque attenuation values by CT coronary angiography: Observations in an ex vivo model

    NARCIS (Netherlands)

    L. la Grutta (Ludovico); M. Galia (Massimo); G. Gentile; G. Lo Re (G.); E. Grassedonio (Emanuele); F. Coppolino; E. Maffei (Erica); E. Maresi (E.); A. Lo Casto (A.); F. Cademartiri (Filippo); M. Midiri (Massimo)

    2013-01-01

    textabstractObjective: To compare the influence of different iodinated contrast media with several dilutions on plaque attenuation in an ex vivo coronary model studied by multislice CT coronary angiography. Methods: In six ex vivo left anterior descending coronary arteries immersed in oil, CT

  3. Purpurogallin, a Natural Phenol, Attenuates High-Mobility Group Box 1 in Subarachnoid Hemorrhage Induced Vasospasm in a Rat Model

    Directory of Open Access Journals (Sweden)

    Chih-Zen Chang

    2014-01-01

    Full Text Available High-mobility group box 1 (HMGB1 was shown to be an important extracellular mediator involved in vascular inflammation of animals following subarachnoid hemorrhage (SAH. This study is of interest to examine the efficacy of purpurogallin, a natural phenol, on the alternation of cytokines and HMGB1 in a SAH model. A rodent double hemorrhage SAH model was employed. Basilar arteries (BAs were harvested to examine HMGB1 mRNA and protein expression (Western blot. CSF samples were to examine IL-1β, IL-6, IL-8, and TNF-α (rt-PCR. Deformed endothelial wall, tortuous elastic lamina, and necrotic smooth muscle were observed in the vessels of SAH groups but were absent in the purpurogallin group. IL-1β, IL-6, and TNF-α in the SAH only and SAH plus vehicle groups were significantly elevated (P<0.01. Purpurgallin dose-dependently reduced HMGB1 protein expression. Likewise, high dose purpurogallin reduced TNF-α and HMGB1 mRNA levels. In conclusion, purpurogallin exerts its neuroinflammation effect through the dual effect of inhibiting IL-6 and TNF-α mRNA expression and reducing HMGB1 protein and mRNA expression. This study supports purpurogallin could attenuate both proinflammatory cytokines and late-onset inflammasome in SAH induced vasospasm.

  4. Preventive Treatment with Ketamine Attenuates the Ischaemia-Reperfusion Response in a Chronic Postischaemia Pain Model

    Directory of Open Access Journals (Sweden)

    Suryamin Liman

    2015-01-01

    Full Text Available Ischemia and inflammation may be pathophysiological mechanisms of complex regional pain syndrome (CRPS. Ketamine has proposed anti-inflammatory effects and has been used for treating CRPS. This study aimed to evaluate anti-inflammatory and analgesic effects of ketamine after ischaemia-reperfusion injury in a chronic postischaemia pain (CPIP model of CRPS-I. Using this model, ischemia was induced in the hindlimbs of male Sprague-Dawley rats. Ketamine, methylprednisolone, or saline was administered immediately after reperfusion. Physical effects, (oedema, temperature, and mechanical and cold allodynia in the bilateral hindpaws, were assessed from 48 hours after reperfusion. Fewer (56% rats in the ketamine group developed CPIP at the 48th hour after reperfusion (nonsignificant. Ketamine treated rats showed a significantly lower temperature in the ischaemic hindpaw compared to saline (P<0.01 and methylprednisolone (P<0.05 groups. Mechanical and cold allodynia were significantly lower in the ischaemic side in the ketamine group (P<0.05. Proinflammatory cytokines TNF-α and IL-2 were significantly lower at the 48th hour after reperfusion in ketamine and methylprednisolone groups, compared to saline (all P<0.05. In conclusion, immediate administration of ketamine after an ischaemia-reperfusion injury can alleviate pain and inflammation in the CPIP model and has potential to treat postischaemic pain.

  5. Thymoquinone attenuates brain injury via an antioxidative pathway in a status epilepticus rat model

    Directory of Open Access Journals (Sweden)

    Shao Yi-ye

    2017-03-01

    Full Text Available Status epilepticus (SE results in the generation of reactive oxygen species (ROS, which contribute to seizure-induced brain injury. It is well known that oxidative stress plays a pivotal role in status epilepticus (SE. Thymoquinone (TQ is a bioactive monomer extracted from black cumin (Nigella sativa seed oil that has anti-inflammatory, anti-cancer, and antioxidant activity in various diseases. This study evaluated the protective effects of TQ on brain injury in a lithium-pilocarpine rat model of SE and investigated the underlying mechanism related to antioxidative pathway.

  6. Program description of FIBRAM: a radiation attenuation model for optical fibers

    International Nuclear Information System (INIS)

    Ingram, W.J.

    1987-06-01

    The report describes a fiber optics system model and its computer implementation. This implementation can calculate the bit error ratio (BER) versus time for optical fibers that have been exposed to gamma radiation. The program is designed so that the user may arbitrarily change any or all of the system input variables and produce separate output calculations. The primary output of the program is a table of the BER as a function of time. This table may be stored on magnetic media and later incorporated into computer graphics programs

  7. Physical modeling and analysis of P-wave attenuation anisotropy in transversely isotropic media

    Digital Repository Service at National Institute of Oceanography (India)

    Zhu, Y.; Tsvankin, I.; Dewangan, P.; Van Wijk, K.

    here H20849Figures 1 and 2aH20850 was to verify the accuracy of the parameter-esti- mation results obtained by Dewangan et al. H208492006H20850. The P-wave source H20849a flat-faced, cylindrical, piezoelectric-contact transducerH20850 was fixed... are assumed to be constant. Receivers 10.8 cm 60 cm Source 70? symmetry axis Figure 1. Physical model of a TI layer with the symmetry axis tilted at 70? H20849from Dewangan et al., 2006H20850. The transmitted wavefield is excited by an ultrasonic contact...

  8. Gain attenuation of gated framing camera

    International Nuclear Information System (INIS)

    Xiao Shali; Liu Shenye; Cao Zhurong; Li Hang; Zhang Haiying; Yuan Zheng; Wang Liwei

    2009-01-01

    The theoretic model of framing camera's gain attenuation is analyzed. The exponential attenuation curve of the gain along the pulse propagation time is simulated. An experiment to measure the coefficient of gain attenuation based on the gain attenuation theory is designed. Experiment result shows that the gain follows an exponential attenuation rule with a quotient of 0.0249 nm -1 , the attenuation coefficient of the pulse is 0.00356 mm -1 . The loss of the pulse propagation along the MCP stripline is the leading reason of gain attenuation. But in the figure of a single stripline, the gain dose not follow the rule of exponential attenuation completely, instead, there is a gain increase at the stripline bottom. That is caused by the reflection of the pulse. The reflectance is about 24.2%. Combining the experiment and theory, which design of the stripline MCP can improved the gain attenuation. (authors)

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

    Directory of Open Access Journals (Sweden)

    Nur Salme Suhana Shamshuddin

    2018-01-01

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

  10. SU-F-BRE-10: Methods to Simulate and Measure the Attenuation for Modeling a Couch Top with Rails for FFF Treatment Delivery On the Varian Edge Linac

    International Nuclear Information System (INIS)

    Gulam, M; Gardner, S; Zhao, B; Snyder, K; Song, K; Li, H; Gordon, J; Wen, N; Chetty, I; Kearns, W

    2014-01-01

    Purpose: To measure attenuation for modelling of the KVue Couchtop for 6X and 10X FFF SRS/SBRT treatment Methods: Treatment planning simulation studies were done using 6X FFF beams to estimate the dosimetric impact of KVue couchtops (including the Q-Fix IGRT [carbon fiber] and Calypso [nonconductive Kevlar material]) with a structure model obtained from a research workstation (Eclipse, advanced planning interface (API) v13). Prior to installation on the Varian Edge linac, the couchtop along with (Kevlar) rails were CT scanned with the rails at various positions. An additional scan with the couchtop 15cm above the CT table top was obtained with 20cm solid water to facilitate precised/indexed data acquisition. Measurements for attenuation were obtained for field sizes of 2, 4 and 10 cm 2 at 42 gantry angles including 6 pairs of opposing fields and other angles for oblique delivery where the beams traversed the couchtop and or rails. The delivery was fully automated with xml scripts running in developer mode. The results were then used to determine an accurate structure model for AAA (Eclipse v11) planning of IMRT and RapidArc delivery. Results: The planning simulation relative dose attenuation for oblique entry was not significantly different than the Exact IGRT or BrainLab iBeam couch except that the rails added 6% additional attenuation. The relative attenuation measurements for PA, PA (rails: inner position), oblique, oblique (rails: outer position), oblique (rails: inner position) were: −2.0%, −2.5%, −15.6%, −2.5%, −5.0% for 6X FFF and −1.4%, −1.5%, −12.2%, − 2.5%, −5.0% for 10X FFF with slight decrease in attenuation versus field size. A Couch structure model (with HU values) was developed. Calculation compared to measurement showed good agreement except for oblique (rails: outer position) where differences approached a magnitude of 6%. Conclusion: A model of the couch structures has been developed accounting for attenuation for FFF beams

  11. Modeling the photochemical attenuation of down-the-drain chemicals during river transport by stochastic methods and field measurements of pharmaceuticals and personal care products.

    Science.gov (United States)

    Hanamoto, Seiya; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki

    2013-01-01

    Existing stochastic models for predicting concentrations of down-the-drain chemicals in aquatic environments do not account for the diurnal variation of direct photolysis by sunlight, despite its being an important factor in natural attenuation. To overcome this limitation, we developed a stochastic model incorporating temporal variations in direct photolysis. To verify the model, we measured 57 pharmaceuticals and personal care products (PPCPs) in a 7.6-km stretch of an urban river, and determined their physical and biological properties in laboratory experiments. During transport along the river, 8 PPCPs, including ketoprofen and azithromycin, were attenuated by >20%, mainly owing to direct photolysis and adsorption to sediments. The photolabile PPCPs attenuated significantly in the daytime but persisted in the nighttime. The observations were similar to the values predicted by the photolysis model for the photolabile PPCPs (i.e., ketoprofen, diclofenac and furosemide) but not by the existing model. The stochastic model developed in this study was suggested to be a novel and useful stochastic model for evaluating direct photolysis of down-the-drain chemicals, which occurs during the river transport.

  12. Modeling relaxation length and density of acacia mangium wood using gamma - ray attenuation technique

    International Nuclear Information System (INIS)

    Tamer A Tabet; Fauziah Abdul Aziz

    2009-01-01

    Wood density measurement is related to the several factors that influence wood quality. In this paper, density, relaxation length and half-thickness value of eight ages, 3, 5, 7, 10, 11, 13 and 15 year-old of Acacia mangium wood were determined using gamma radiation from 137 Cs source. Results show that Acacia mangium tree of age 3 year has the highest relaxation length of 83.33 cm and least density of 0.43 gcm -3 , while the tree of age 15 year has the least Relaxation length of 28.56 cm and highest density of 0.76 gcm -3 . Results also show that the 3 year-old Acacia mangium wood has the highest half thickness value of 57.75 cm and 15 year-old tree has the least half thickness value of 19.85 cm. Two mathematical models have been developed for the prediction of density, variation with relaxation length and half-thickness value of different age of tree. A good agreement (greater than 85% in most cases) was observed between the measured values and predicted ones. Very good linear correlation was found between measured density and the age of tree (R2 = 0.824), and between estimated density and Acacia mangium tree age (R2 = 0.952). (Author)

  13. Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

    Science.gov (United States)

    Jin, Li; Piao, Zhe Hao; Sun, Simei; Liu, Bin; Ryu, Yuhee; Choi, Sin Young; Kim, Gwi Ran; Kim, Hyung-Seok; Kee, Hae Jin; Jeong, Myung Ho

    2017-12-01

    Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Fluvoxamine stimulates oligodendrogenesis of cultured neural stem cells and attenuates inflammation and demyelination in an animal model of multiple sclerosis.

    Science.gov (United States)

    Ghareghani, Majid; Zibara, Kazem; Sadeghi, Heibatollah; Dokoohaki, Shima; Sadeghi, Hossein; Aryanpour, Roya; Ghanbari, Amir

    2017-07-07

    Multiple Sclerosis (MS) require medications controlling severity of the pathology and depression, affecting more than half of the patients. In this study, the effect of antidepressant drug fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in vitro and in vivo. Nanomolar concentrations of fluvoxamine significantly increased cell viability and proliferation of neural stem cells (NSCs) through increasing mRNA expression of Notch1, Hes1 and Ki-67, and protein levels of NICD. Also, physiological concentrations of fluvoxamine were optimal for NSC differentiation toward oligodendrocytes, astrocytes and neurons. In addition, fluvoxamine attenuated experimental autoimmune encephalomyelitis (EAE) severity, a rat MS model, by significantly decreasing its clinical scores. Moreover, fluvoxamine treated EAE rats showed a decrease in IFN-γ serum levels and an increase in IL-4, pro- and anti-inflammatory cytokines respectively, compared to untreated EAE rats. Furthermore, immune cell infiltration and demyelination plaque significantly decreased in spinal cords of fluvoxamine-treated rats, which was accompanied by an increase in protein expression of MBP and GFAP positive cells and a decrease in lactate serum levels, a new biomarker of MS progression. In summary, besides its antidepressant activity, fluvoxamine stimulates proliferation and differentiation of NSCs particularly toward oligodendrocytes, a producer of CNS myelin.

  15. Attenuation of chondrogenic transformation in vascular smooth muscle by dietary quercetin in the MGP-deficient mouse model.

    Directory of Open Access Journals (Sweden)

    Kelly E Beazley

    Full Text Available Cartilaginous metaplasia of vascular smooth muscle (VSM is characteristic for arterial calcification in diabetes and uremia and in the background of genetic alterations in matrix Gla protein (MGP. A better understanding of the molecular details of this process is critical for the development of novel therapeutic approaches to VSM transformation and arterial calcification.This study aimed to identify the effects of bioflavonoid quercetin on chondrogenic transformation and calcification of VSM in the MGP-null mouse model and upon TGF-β3 stimulation in vitro, and to characterize the associated alterations in cell signaling.Molecular analysis revealed activation of β-catenin signaling in cartilaginous metaplasia in Mgp-/- aortae in vivo and during chondrogenic transformation of VSMCs in vitro. Quercetin intercepted chondrogenic transformation of VSM and blocked activation of β-catenin both in vivo and in vitro. Although dietary quercetin drastically attenuated calcifying cartilaginous metaplasia in Mgp-/- animals, approximately one-half of total vascular calcium mineral remained as depositions along elastic lamellae.Quercetin is potent in preventing VSM chondrogenic transformation caused by diverse stimuli. Combined with the demonstrated efficiency of dietary quercetin in preventing ectopic chondrogenesis in the MGP-null vasculature, these findings indicate a potentially broad therapeutic applicability of this safe for human consumption bioflavonoid in the therapy of cardiovascular conditions linked to cartilaginous metaplasia of VSM. Elastocalcinosis is a major component of MGP-null vascular disease and is controlled by a mechanism different from chondrogenic transformation of VSM and not sensitive to quercetin.

  16. Naringin attenuates granule cell dispersion in the dentate gyrus in a mouse model of temporal lobe epilepsy.

    Science.gov (United States)

    Jang, Hannah; Jeong, Kyoung Hoon; Kim, Sang Ryong

    2016-07-01

    Morphological abnormalities of the dentate gyrus (DG) are an important phenotype in the hippocampus of patients with temporal lobe epilepsy. We recently reported that naringin, a bioflavonoid in grapefruit and citrus fruits, exerts beneficial effects in the kainic acid (KA) mouse model of epilepsy. We found that naringin treatment reduced seizure activities and decreased autophagic stress and neuroinflammation in the hippocampus following in vivo lesion with KA. However, it remains unclear whether naringin may also attenuate seizure-induced morphological changes in the DG, collectively known as granule cell dispersion (GCD). To clarify whether naringin treatment reduces GCD, we evaluated the effects of intraperitoneal injection of naringin on GCD and activation of mammalian target of rapamycin complex 1 (mTORC1), an important regulator of GCD, following intrahippocampal injection of KA. Our results showed that naringin treatment significantly reduced KA-induced GCD and mTORC1 activation, which was confirmed by assessing the phosphorylated form of the mTORC1 substrate, 4E-BP1, in the hippocampus. These results suggest that naringin treatment may help prevent epilepsy-induced hippocampal injury by inhibiting mTORC1 activation and thereby reducing GCD in the hippocampus in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Ablating ErbB4 in PV neurons attenuates synaptic and cognitive deficits in an animal model of Alzheimer's disease.

    Science.gov (United States)

    Zhang, Heng; Zhang, Ling; Zhou, Dongming; He, Xiao; Wang, Dongpi; Pan, Hongyu; Zhang, Xiaoqin; Mei, Yufei; Qian, Qi; Zheng, Tingting; Jones, Frank E; Sun, Binggui

    2017-10-01

    Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Influence of convolution filtering on coronary plaque attenuation values: observations in an ex vivo model of multislice computed tomography coronary angiography

    International Nuclear Information System (INIS)

    Cademartiri, Filippo; Palumbo, Alessandro; La Grutta, Ludovico; Runza, Giuseppe; Maffei, Erica; Mollet, Nico R.; Hamers, Ronald; Bruining, Nico; Bartolotta, Tommaso V.; Midiri, Massimo; Somers, Pamela; Knaapen, Michiel; Verheye, Stefan

    2007-01-01

    Attenuation variability (measured in Hounsfield Units, HU) of human coronary plaques using multislice computed tomography (MSCT) was evaluated in an ex vivo model with increasing convolution kernels. MSCT was performed in seven ex vivo left coronary arteries sunk into oil followingthe instillation of saline (1/∞) and a 1/50 solution of contrast material (400 mgI/ml iomeprol). Scan parameters were: slices/collimation, 16/0.75 mm; rotation time, 375 ms. Four convolution kernels were used: b30f-smooth, b36f-medium smooth, b46f-medium and b60f-sharp. An experienced radiologist scored for the presence of plaques and measured the attenuation in lumen, calcified and noncalcified plaques and the surrounding oil. The results were compared by the ANOVA test and correlated with Pearson's test. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. The mean attenuation values were significantly different between the four filters (p < 0.0001) in each structure with both solutions. After clustering for the filter, all of the noncalcified plaque values (20.8 ± 39.1, 14.2 ± 35.8, 14.0 ± 32.0, 3.2 ± 32.4 HU with saline; 74.7 ± 66.6, 68.2 ± 63.3, 66.3 ± 66.5, 48.5 ± 60.0 HU in contrast solution) were significantly different, with the exception of the pair b36f-b46f, for which a moderate-high correlation was generally found. Improved SNRs and CNRs were achieved by b30f and b46f. The use of different convolution filters significantly modified the attenuation values, while sharper filtering increased the calcified plaque attenuation and reduced the noncalcified plaque attenuation. (orig.)

  19. Puerarin Attenuates Ovalbumin-Induced Lung Inflammation and Hemostatic Unbalance in Rat Asthma Model

    Directory of Open Access Journals (Sweden)

    Feng Dong

    2014-01-01

    Full Text Available Aim. We aimed to investigate and evaluate the preventive activity of puerarin on the ovalbumin-induced asthma rat model. Materials and Methods. Male Wistar rats were sensitized intraperitoneally on days 0, 7, and 14 and challenged to ovalbumin intratracheally on day 21. Groups of sensitized rats were treated randomly either with placebo, puerarin, dexamethasone, or puerarin combined with dexamethasone, from days 15 to 20. Inflammatory markers, including cell counts in bronchoalveolar lavage fluid (BALF, inflammatory cytokines, histopathology, and coagulation parameters, such as coagulation tests and the activity of coagulation factors, were analyzed. Results. Puerarin significantly inhibited the recruitment of inflammatory cells in BALF and lung tissue. At the same time, the release of IL-4, IL-10, and IFN-γ in serum and the expression of mRNAs in lung tissue homogenate were changed by puerarin. Administration of puerarin also effectively rectified the coagulation disorder in asthmatic rats, such as prothrombin time (PT (P<0.01, thrombin time (TT (P<0.05, fibrinogen (FIB (P<0.01,the activity of factor II (FII (P<0.01, the activity of factor V (FV (P<0.05, the activity of factor VII (FVII (P<0.05, the activity of factor X (FX (P<0.05, the activity of factor VIII (FVIII (P<0.01, the activity of factor IX (FIX (P<0.05, and the activity of factor XII (FXII (P<0.05. Conclusions. Our results provide a clue that puerarin was useful for the preventive of allergic airway disease in rodents.

  20. Gallic Acid Attenuates Postoperative Intra-Abdominal Adhesion by Inhibiting Inflammatory Reaction in a Rat Model

    Science.gov (United States)

    Wei, Guangbing; Wu, Yunhua; Gao, Qi; Shen, Cong; Chen, Zilu; Wang, Kang; Yu, Junhui

    2018-01-01

    Background Intra-abdominal adhesion is one of the most common complications after abdominal surgery. The efficacy of current treatments for intra-abdominal adhesion is unsatisfactory. In this study, we investigated the effect of gallic acid on the prevention and treatment of intra-abdominal adhesions after abdominal surgery using an intra-abdominal adhesion rat model. Material/Methods The experimental rats were randomly divided into the sham operation group, the control group, the chitosan group, and 3 gallic acid groups of different concentrations. All rats except those in the sham operation group received cecal abrasion to induce adhesion. From the first postoperative day, the rats in the gallic acid groups were administered different concentrations of gallic acid in a 2-ml gavage daily. All rats were sacrificed on postoperative day 7, and the degree of intra-abdominal adhesion was evaluated by the naked eye. The amount of collagen deposited between the injured peritoneal tissues was assessed by Sirius red staining. Serum levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and transforming growth factor-β (TGF-β) were measured by ELISA. Western blot was used to detect the level of NF-κB phosphorylation in the injured peritoneal or adhesion tissues of the rats. Results Compared with the control group, the scores of intra-abdominal adhesions in the rats treated with larger doses of gallic acid were significantly decreased, and the degree of inflammation and fibrosis was also significantly decreased. Gallic acid significantly reduced IL-6, TNF-α, and TGF-β1 serum levels. NF-κB phosphorylation in the higher gallic acid groups was significantly reduced. Conclusions Gallic acid inhibits the formation of postoperative intra-abdominal adhesions in rats by inhibiting the inflammatory reaction and fibrogenesis. Gallic acid is a promising drug for preventing intra-abdominal adhesions. PMID:29429982

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

    Science.gov (United States)

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

    2017-08-30

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

  2. Irrigation model of bleached Kraft mill wastewater through volcanic soil as a pollutants attenuation process.

    Science.gov (United States)

    Navia, R; Inostroza, X; Diez, M C; Lorber, K E

    2006-05-01

    An irrigation process through volcanic soil columns was evaluated for bleached Kraft mill effluent pollutants retention. The system was designed to remove color and phenolic compounds and a simple kinetic model for determining the global mass transfer coefficient and the adsorption rate constant was used. The results clearly indicate that the global mass transfer coefficient values (K(c)a) and the adsorption rate constants are higher for the irrigation processes onto acidified soil. This means that the pretreatment of washing the volcanic soil with an acid solution has a positive effect on the adsorption rate for both pollutant groups. The enhanced adsorption capacity is partially explained by the activation of the metal oxides present in the soil matrix during the acid washing process. Increasing the flow rate from 1.5 to 2.5 ml/min yielded higher (K(c)a) values and adsorption rate constants for both pollutant groups. For instance, regarding color adsorption onto acidified soil, there is an increment of 43% in the (K(c)a) value for the experiment with a flow rate of 2.5 ml/min. Increasing the porosity of the column from 0.55 to 0.59, yielded a decrease in the (K(c)a) values for color and phenolic compounds adsorption processes. Onto natural soil for example, these decreases reached 21% and 24%, respectively. Therefore, the (K(c)a) value is dependent on both the liquid-phase velocity (external resistance) and the soil fraction in the column (internal resistance); making forced convection and diffusion to be the main transport mechanisms involved in the adsorption process. Analyzing the adsorption rate constants (K(c)a)/m, phenolic compounds and color adsorption rates onto acidified soil of 2.25 x 10(-6) and 2.62 x 10(-6) l/mg min were achieved for experiment 1. These adsorption rates are comparable with other adsorption systems and adsorbent materials.

  3. Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation.

    Science.gov (United States)

    Zhao, Zhanzhong; Tang, Xiangfang; Zhao, Xinghui; Zhang, Minhong; Zhang, Weijian; Hou, Shaohua; Yuan, Weifeng; Zhang, Hongfu; Shi, Lijun; Jia, Hong; Liang, Lin; Lai, Zhi; Gao, Junfeng; Zhang, Keyu; Fu, Ling; Chen, Wei

    2014-07-01

    Tylvalosin, a new broad-spectrum, third-generation macrolides, may exert a variety of pharmacological activities. Here, we report on its anti-oxidative and anti-inflammatory activity in RAW 264.7 macrophages and mouse treated with lipopolysaccharide (LPS) as well as piglet challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Tylvalosin treatment markedly decreased IL-8, IL-6, IL-1β, PGE2, TNF-α and NO levels in vitro and in vivo. LPS and PRRSV-induced reactive oxygen species (ROS) production, and the lipid peroxidation in mice lung tissues reduced after tylvalosin treatments. In mouse acute lung injury model induced by LPS, tylvalosin administration significantly attenuated tissues injury, and reduced the inflammatory cells recruitment and activation. The evaluated phospholipase A2 (PLA2) activity and the increased expressions of cPLA2-IVA, p-cPLA2-IVA and sPLA2-IVE were lowered by tylvalosin. Consistent with the mouse results, tylvalosin pretreatment attenuated piglet lung scores with improved growth performance and normal rectal temperature in piglet model induced by PRRSV. Furthermore, tylvalosin attenuated the IκBα phosphorylation and degradation, and blocked the NF-κB p65 translocation. These results indicate that in addition to its direct antimicrobial effect, tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury through suppression of NF-κB activation. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Field-scale model for the natural attenuation of uranium at the Hanford 300 area using high performance computing

    Energy Technology Data Exchange (ETDEWEB)

    Lichtner, Peter C [Los Alamos National Laboratory; Hammond, Glenn E [PNNL

    2009-01-01

    Three-dimensional reactive flow and transport simulations are carried out to better understand the persistence of uranium [U(VI)] at the Hanford 300 Area bordering the Columbia River. The massively parallel code PFLOTRAN developed under a DOE SciDAC-2 project is employed in the simulations. The calculations were carried out on 4096 processor cores on ORNL's Jaguar XT4 & 5 Cray supercomputers with run times on the order of 6 hours, equivalent to several years if performed on a single processor with sufficient memory. A new conceptual model is presented for understanding present-day and future attenuation rates of U(VI) at the 300 Area site. Unique to the conceptual model is the recognition of three distinct phases in the evolution of the site corresponding to: (I) initial emplacement of waste; (II) present-day conditions of slow leaching of U(VI) from the Hanford sediments; and (III) the complete removal of non-labile U(VI) from the source region. This work focuses on Phase II. Both labile and non-labile forms of U(VI) are included in the model as sorbed and mineralized forms of U(VI), respectively. The non-labile form plays an important role in providing a long-term source of U(VI) as it slowly leaches out of the Hanford sediment. Rapid fluctuations in the Columbia River stage on hourly, weekly and seasonal time scales are found to' playa major role in determining the migration behavior of U(VI). The calculations demonstrate that U(VI) is released into the Columbia River at a highly fluctuating rate in a ratchet-like behavior with nonzero U(VI) flux occurring only during flow from contaminated sediment into the river. The cumulative flux, however, is found to increase approximately linearly with time. The flow rate and U(VI) flux into the Columbia River predicted by the model is highly sensitive to the value used in the conductance boundary condition at the river-sediment interface. By fitting the conductance to the measured piezometric head at well 399

  5. Combined SEM/AVS and attenuation of concentration models for the assessment of bioavailability and mobility of metals in sediments of Sepetiba Bay (SE Brazil).

    Science.gov (United States)

    Ribeiro, Andreza Portella; Figueiredo, Ana Maria Graciano; dos Santos, José Osman; Dantas, Elizabeth; Cotrim, Marycel Elena Barboza; Figueira, Rubens Cesar Lopes; Silva Filho, Emmanoel V; Wasserman, Julio Cesar

    2013-03-15

    This study proposes a new methodology to study contamination, bioavailability and mobility of metals (Cd, Cu, Ni, Pb, and Zn) using chemical and geostatistics approaches in marine sediments of Sepetiba Bay (SE Brazil). The chemical model of SEM (simultaneously extracted metals)/AVS (acid volatile sulfides) ratio uses a technique of cold acid extraction of metals to evaluate their bioavailability, and the geostatistical model of attenuation of concentrations estimates the mobility of metals. By coupling the two it was observed that Sepetiba Port, the urban area of Sepetiba and the riverine discharges may constitute potential sources of metals to Sepetiba Bay. The metals are concentrated in the NE area of the bay, where they tend to have their lowest mobility, as shown by the attenuation model, and are not bioavailable, as they tend to associate with sulfide and organic matter originated in the mangrove forests of nearby Guaratiba area. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Frondanol, a Nutraceutical Extract from Cucumaria frondosa, Attenuates Colonic Inflammation in a DSS-Induced Colitis Model in Mice

    Directory of Open Access Journals (Sweden)

    Sandeep B. Subramanya

    2018-04-01

    Full Text Available Frondanol is a nutraceutical lipid extract of the intestine of the edible Atlantic sea cucumber, Cucumaria frondosa, with potent anti-inflammatory effects. In the current study, we investigated Frondanol as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J were given 3% dextran sodium sulfate (DSS in drinking water for 7 days to induce colitis. The colitis group received oral Frondanol (100 mg/kg body weight/per day by gavage and were compared with a control group and the DSS group. Disease activity index (DAI and colon histology were scored for macroscopic and microscopic changes. Colonic tissue length, myeloperoxidase (MPO concentration, neutrophil and macrophage marker mRNA, pro-inflammatory cytokine proteins, and their respective mRNAs were measured using ELISA and real-time RT-PCR. The tissue content of leukotriene B4 (LTB4 was also measured using ELISA. Frondanol significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue MPO concentrations, neutrophil and macrophage mRNA expression (F4/80 and MIP-2, and pro-inflammatory cytokine content (IL-1β, IL-6 and TNF-α both at the protein and mRNA level were significantly reduced by Frondanol. The increase in content of the pro-inflammatory mediator leukotriene B4 (LTB4 induced by DSS was also significantly inhibited by Frondanol. It was thus found that Frondanol supplementation attenuates colon inflammation through its potent anti-inflammatory activity.

  7. Modeling Microalgal Biosediment Formation Based on Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Monitoring.

    Science.gov (United States)

    Ogburn, Zachary L; Vogt, Frank

    2018-03-01

    With increasing amounts of anthropogenic pollutants being released into ecosystems, it becomes ever more important to understand their fate and interactions with living organisms. Microalgae play an important ecological role as they are ubiquitous in marine environments and sequester inorganic pollutants which they transform into organic biomass. Of particular interest in this study is their role as a sink for atmospheric CO 2 , a greenhouse gas, and nitrate, one cause of harmful algal blooms. Novel chemometric hard-modeling methodologies have been developed for interpreting phytoplankton's chemical and physiological adaptations to changes in their growing environment. These methodologies will facilitate investigations of environmental impacts of anthropogenic pollutants on chemical and physiological properties of marine microalgae (here: Nannochloropsis oculata). It has been demonstrated that attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can gain insights into both and this study only focuses on the latter. From time-series of spectra, the rate of microalgal biomass settling on top of a horizontal ATR element is derived which reflects several of phytoplankton's physiological parameters such as growth rate, cell concentrations, cell size, and buoyancy. In order to assess environmental impacts on such parameters, microalgae cultures were grown under 25 different chemical scenarios covering 200-600 ppm atmospheric CO 2 and 0.35-0.75 mM dissolved NO 3 - . After recording time-series of ATR FT-IR spectra, a multivariate curve resolution-alternating least squares (MCR-ALS) algorithm extracted spectroscopic and time profiles from each data set. From the time profiles, it was found that in the considered concentration ranges only NO 3 - has an impact on the cells' physiological properties. In particular, the cultures' growth rate has been influenced by the ambient chemical conditions. Thus, the presented spectroscopic

  8. Inhibiting CXCL12 blocks fibrocyte migration and differentiation and attenuates bronchiolitis obliterans in a murine heterotopic tracheal transplant model.

    Science.gov (United States)

    Harris, David A; Zhao, Yunge; LaPar, Damien J; Emaminia, Abbas; Steidle, John F; Stoler, Mark; Linden, Joel; Kron, Irving L; Lau, Christine L

    2013-03-01

    Fibrocytes are integral in the development of fibroproliferative disease after lung transplantation. Undifferentiated fibrocytes (CD45+anti-collagen 1+CXCR4+) preferentially traffic by way of the CXCR4/CXCL12 axis and differentiate into smooth muscle actin-producing (CD45+CXCR4+α-smooth muscle actin+) cells. We postulated that an antibody directed against CXCL12 would attenuate fibrocyte migration and fibro-obliteration of heterotopic tracheal transplant allografts. A total alloantigenic mismatch murine heterotopic tracheal transplant model of obliterative bronchiolitis was used. The mice were treated with either goat-anti-human CXCL12 F(ab')(2) or goat IgG F(ab')(2). Buffy coat, bone marrow, and trachea allografts were collected and analyzed using flow cytometry. Tracheal luminal obliteration was assessed using hematoxylin-eosin and Direct Red 80 collagen stain. Compared with the controls, the anti-CXCL12-treated mice showed a significant decrease in tracheal allograft fibrocyte populations at 7 and 21 days after transplantation. Bone marrow and buffy coat aspirates showed the same trend at 7 days. In the anti-CXCL12-treated mice, there was a 35% decrease in luminal obliteration at 21 days (65% vs 100% obliterated; interquartile range, 38% vs 10%; P = .010) and decreased luminal collagen deposition at 21 and 28 days after transplantation (P = .042 and P = .012, respectively). Understanding the role of fibrocytes in airway fibrosis after lung transplantation could lead to a paradigm shift in treatment strategy. Anti-CXCL12 antibody afforded protection against infiltrating fibrocytes and reduced the deterioration of the tracheal allografts. Thus, the CXCR4/CXCL12 axis is a novel target for the treatment of fibro-obliteration after lung transplantation, and the quantification of fibrocyte populations could provide clinicians with a biomarker of fibrosis, allowing individualized drug therapy. Copyright © 2013 The American Association for Thoracic Surgery. Published

  9. Exogenous galanin attenuates spatial memory impairment and decreases hippocampal β-amyloid levels in rat model of Alzheimer's disease.

    Science.gov (United States)

    Li, Lei; Yu, Liling; Kong, Qingxia

    2013-11-01

    One of the major pathological characteristics of Alzheimer's disease (AD) is the presence of enhanced deposits of beta-amyloid peptide (Aβ). The neuropeptide galanin (GAL) and its receptors are overexpressed in degenerating brain regions in AD. The functional consequences of galaninergic systems plasticity in AD are unclear. The objective of the present study was to investigate whether exogenous galanin could attenuate spatial memory impairment and hippocampal Aβ aggregation in rat model of AD. The effects of Aβ, galanin, galanin receptor 1 agonist M617 and galanin receptor 2 agonist AR-M1896 on spatial memory were tested by Morris water maze. The effects of Aβ, galanin, M617 and AR-M1896 on hippocampal Aβ protein expression were evaluated by western blot assay. The expression of galanin, galanin receptors 1 and 2 in rats' hippocampus were detected by real time PCR and western blot assay. The results showed that (1) Galanin administration was effective in improving the spatial memory and decreasing hippocampal Aβ levels after intracerebroventricular injection of Aβ; (2) AR-M1896 rather than M617 could imitate these effects of galanin; (3) GAL and GALR2 mRNA and protein levels increased significantly in hippocampus after Aβ administration, while GALR1 mRNA and protein levels did not change; (4) GAL, AR-M1896 and M617 administration did not show significant effect on GAL, GalR1 and GalR2 mRNA and protein levels in hippocampus after Aβ administration. These results implied that galanin receptor 2, but not receptor 1 was involved in the protective effects against spatial memory impairment and hippocampal Aβ aggregation.

  10. Maximum likelihood estimation of the attenuated ultrasound pulse

    DEFF Research Database (Denmark)

    Rasmussen, Klaus Bolding

    1994-01-01

    The attenuated ultrasound pulse is divided into two parts: a stationary basic pulse and a nonstationary attenuation pulse. A standard ARMA model is used for the basic pulse, and a nonstandard ARMA model is derived for the attenuation pulse. The maximum likelihood estimator of the attenuated...

  11. Uranium ISR Mine Closure — General Concepts and Model-Based Simulation of Natural Attenuation for South-Australian Mine Sites

    Energy Technology Data Exchange (ETDEWEB)

    Jeuken, B.; Märten, H.; Woods, P., E-mail: horst.maerten@heathgate.com.au [Heathgate Resources Pty. Ltd. (Heathgate), Adelaide (Australia); Kalka, H.; Nicolai, J. [Umwelt- und Ingenieurtechnik GmbH Dresden (UIT), Dresden (Germany)

    2014-05-15

    Heathgate has demonstrated the effect of natural attenuation (NA) in post in-situ recovery (ISR) aquifer regions during the operation of the Beverley mine since 2001. Enhanced natural attenuation (ENA) has been considered as the key component of the mine closure concept for the new Beverley Four Mile (BFM) project, complemented by an extensive monitoring program. Data from batch and column tests for BFM core samples was used to calibrate a reactive transport model, whose application in conjunction with the hydrological modelling of the BFM aquifer has shown that NA will result in the restoration of the aquifer in time. ENA within a staged mine development program under the site-specific circumstances is discussed. (author)

  12. Reducing C-terminal-truncated alpha-synuclein by immunotherapy attenuates neurodegeneration and propagation in Parkinson's disease-like models.

    Science.gov (United States)

    Games, Dora; Valera, Elvira; Spencer, Brian; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Patrick, Christina; Ubhi, Kiren; Nuber, Silke; Sacayon, Patricia; Zago, Wagner; Seubert, Peter; Barbour, Robin; Schenk, Dale; Masliah, Eliezer

    2014-07-09

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are common neurodegenerative disorders of the aging population, characterized by progressive and abnormal accumulation of α-synuclein (α-syn). Recent studies have shown that C-terminus (CT) truncation and propagation of α-syn play a role in the pathogenesis of PD/DLB. Therefore, we explored the effect of passive immunization against the CT of α-syn in the mThy1-α-syn transgenic (tg) mouse model, which resembles the striato-nigral and motor deficits of PD. Mice were immunized with the new monoclonal antibodies 1H7, 5C1, or 5D12, all directed against the CT of α-syn. CT α-syn antibodies attenuated synaptic and axonal pathology, reduced the accumulation of CT-truncated α-syn (CT-α-syn) in axons, rescued the loss of tyrosine hydroxylase fibers in striatum, and improved motor and memory deficits. Among them, 1H7 and 5C1 were most effective at decreasing levels of CT-α-syn and higher-molecular-weight aggregates. Furthermore, in vitro studies showed that preincubation of recombinant α-syn with 1H7 and 5C1 prevented CT cleavage of α-syn. In a cell-based system, CT antibodies reduced cell-to-cell propagation of full-length α-syn, but not of the CT-α-syn that lacked the 118-126 aa recognition site needed for antibody binding. Furthermore, the results obtained after lentiviral expression of α-syn suggest that antibodies might be blocking the extracellular truncation of α-syn by calpain-1. Together, these results demonstrate that antibodies against the CT of α-syn reduce levels of CT-truncated fragments of the protein and its propagation, thus ameliorating PD-like pathology and improving behavioral and motor functions in a mouse model of this disease. Copyright © 2014 the authors 0270-6474/14/349441-14$15.00/0.

  13. Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

    Directory of Open Access Journals (Sweden)

    Menk M

    2018-05-01

    expressions in the lungs, whereas the expressions of IL-1, IL-10, and IL-4 remained unchanged. During the 240-min observation period, AT2 receptor stimulation did not improve pulmonary gas exchange or lung edema. Conclusion: In this rodent model of acute lung injury after repeated pulmonary lavage, AT2 receptor stimulation attenuates pulmonary inflammation but does not improve gas exchange. Keywords: AT2 receptor, lung failure, ARDS, acute lung injury, Compound 21 (C21

  14. Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model.

    Science.gov (United States)

    Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

    2012-01-01

    The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of

  15. MicroRNA-155 Deficiency Attenuates Liver Steatosis and Fibrosis without Reducing Inflammation in a Mouse Model of Steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Timea Csak

    Full Text Available MicroRNAs (miRs regulate hepatic steatosis, inflammation and fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. We hypothesized that deficiency of miR-155, a master regulator of inflammation, attenuates steatohepatitis and fibrosis.Wild type (WT and miR-155-deficient (KO mice were fed methionine-choline-deficient (MCD or -supplemented (MCS control diet for 5 weeks. Liver injury, inflammation, steatosis and fibrosis were assessed.MCD diet resulted in steatohepatitis and increased miR-155 expression in total liver, hepatocytes and Kupffer cells. Steatosis and expression of genes involved in fatty acid metabolism were attenuated in miR-155 KO mice after MCD feeding. In contrast, miR-155 deficiency failed to attenuate inflammatory cell infiltration, nuclear factor κ beta (NF-κB activation and enhanced the expression of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα and monocyte chemoattractant protein-1 (MCP1 in MCD diet-fed mice. We found a significant attenuation of apoptosis (cleaved caspase-3 and reduction in collagen and α smooth muscle actin (αSMA levels in miR-155 KO mice compared to WTs on MCD diet. In addition, we found attenuation of platelet derived growth factor (PDGF, a pro-fibrotic cytokine; SMAD family member 3 (Smad3, a protein involved in transforming growth factor-β (TGFβ signal transduction and vimentin, a mesenchymal marker and indirect indicator of epithelial-to-mesenchymal transition (EMT in miR-155 KO mice. Nuclear binding of CCAAT enhancer binding protein β (C/EBPβ a miR-155 target involved in EMT was significantly increased in miR-155 KO compared to WT mice.Our novel data demonstrate that miR-155 deficiency can reduce steatosis and fibrosis without decreasing inflammation in steatohepatitis.

  16. An attempt to model the relationship between MMI attenuation and engineering ground-motion parameters using artificial neural networks and genetic algorithms

    Directory of Open Access Journals (Sweden)

    G-A. Tselentis

    2010-12-01

    Full Text Available Complex application domains involve difficult pattern classification problems. This paper introduces a model of MMI attenuation and its dependence on engineering ground motion parameters based on artificial neural networks (ANNs and genetic algorithms (GAs. The ultimate goal of this investigation is to evaluate the target-region applicability of ground-motion attenuation relations developed for a host region based on training an ANN using the seismic patterns of the host region. This ANN learning is based on supervised learning using existing data from past earthquakes. The combination of these two learning procedures (that is, GA and ANN allows us to introduce a new method for pattern recognition in the context of seismological applications. The performance of this new GA-ANN regression method has been evaluated using a Greek seismological database with satisfactory results.

  17. Inhibition of Src kinase activity attenuates amyloid associated microgliosis in a murine model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Dhawan Gunjan

    2012-07-01

    Full Text Available Abstract Background Microglial activation is an important histologic characteristic of the pathology of Alzheimer’s disease (AD. One hypothesis is that amyloid beta (Aβ peptide serves as a specific stimulus for tyrosine kinase-based microglial activation leading to pro-inflammatory changes that contribute to disease. Therefore, inhibiting Aβ stimulation of microglia may prove to be an important therapeutic strategy for AD. Methods Primary murine microglia cultures and the murine microglia cell line, BV2, were used for stimulation with fibrillar Aβ1-42. The non-receptor tyrosine kinase inhibitor, dasatinib, was used to treat the cells to determine whether Src family kinase activity was required for the Aβ stimulated signaling response and subsequent increase in TNFα secretion using Western blot analysis and enzyme-linked immunosorbent assay (ELISA, respectively. A histologic longitudinal analysis was performed using an AD transgenic mouse model, APP/PS1, to determine an age at which microglial protein tyrosine kinase levels increased in order to administer dasatinib via mini osmotic pump diffusion. Effects of dasatinib administration on microglial and astroglial activation, protein phosphotyrosine levels, active Src kinase levels, Aβ plaque deposition, and spatial working memory were assessed via immunohistochemistry, Western blot, and T maze analysis. Results Aβ fibrils stimulated primary murine microglia via a tyrosine kinase pathway involving Src kinase that was attenuated by dasatinib. Dasatinib administration to APP/PS1 mice decreased protein phosphotyrosine, active Src, reactive microglia, and TNFα levels in the hippocampus and temporal cortex. The drug had no effect on GFAP levels, Aβ plaque load, or the related tyrosine kinase, Lyn. These anti-inflammatory changes correlated with improved performance on the T maze test in dasatinib infused animals compared to control animals. Conclusions These data suggest that amyloid

  18. Inhibition of p53 attenuates steatosis and liver injury in a mouse model of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Derdak, Zoltan; Villegas, Kristine A; Harb, Ragheb; Wu, Annie M; Sousa, Aryanna; Wands, Jack R

    2013-04-01

    p53 and its transcriptional target miRNA34a have been implicated in the pathogenesis of fatty liver. We tested the efficacy of a p53 inhibitor, pifithrin-α p-nitro (PFT) in attenuating steatosis, associated oxidative stress and apoptosis in a murine model of non-alcoholic fatty liver disease (NAFLD). C57BL/6 mice were fed a high-fat (HFD) or control diet for 8 weeks; PFT or DMSO (vehicle) was administered three times per week. Markers of oxidative stress and apoptosis as well as mediators of hepatic fatty acid metabolism were assessed by immunohistochemistry, Western blot, real-time PCR, and biochemical assays. PFT administration suppressed HFD-induced weight gain, ALT elevation, steatosis, oxidative stress, and apoptosis. PFT treatment blunted the HFD-induced upregulation of miRNA34a and increased SIRT1 expression. In the livers of HFD-fed, PFT-treated mice, activation of the SIRT1/PGC1α/PPARα axis increased the expression of malonyl-CoA decarboxylase (MLYCD), an enzyme responsible for malonyl-CoA (mCoA) degradation. Additionally, the SIRT1/LKB1/AMPK pathway (upstream activator of MLYCD) was promoted by PFT. Thus, induction of these two pathways by PFT diminished the hepatic mCoA content by enhancing MLYCD expression and function. Since mCoA inhibits carnitine palmitoyltransferase 1 (CPT1), the decrease of hepatic mCoA in the PFT-treated, HFD-fed mice increased CPT1 activity, favored fatty acid oxidation, and decreased steatosis. Additionally, we demonstrated that PFT abrogated steatosis and promoted MLYCD expression in palmitoleic acid-treated human HepaRG cells. The p53 inhibitor PFT diminished hepatic triglyceride accumulation and lipotoxicity in mice fed a HFD, by depleting mCoA and favoring the β-oxidation of fatty acids. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Quantum system under the actions of two counteracting baths: A model for the attenuation-amplification interplay

    International Nuclear Information System (INIS)

    Lorenzen, F.; Moussa, M. H. Y.; Ponte, M. A. de; Almeida, N. G. de

    2009-01-01

    We analyze the dynamical behavior of a quantum system under the actions of two counteracting baths: the inevitable energy draining reservoir and, in opposition, exciting the system, an engineered Glauber's amplifier. We follow the system dynamics towards equilibrium to map its distinctive behavior arising from the interplay of attenuation and amplification. Such a mapping, with the corresponding parameter regimes, is achieved by calculating the evolution of both the excitation and the Glauber-Sudarshan P function. Techniques to compute the decoherence and the fidelity of quantum states under the action of both counteracting baths, based on the Wigner function rather than the density matrix, are also presented. They enable us to analyze the similarity of the evolved state vector of the system with respect to the original one, for all regimes of parameters. Applications of this attenuation-amplification interplay are discussed.

  20. A simple model of ultrasound propagation in a cavitating liquid. Part I: Theory, nonlinear attenuation and traveling wave generation.

    Science.gov (United States)

    Louisnard, O

    2012-01-01

    The bubbles involved in sonochemistry and other applications of cavitation oscillate inertially. A correct estimation of the wave attenuation in such bubbly media requires a realistic estimation of the power dissipated by the oscillation of each bubble, by thermal diffusion in the gas and viscous friction in the liquid. Both quantities and calculated numerically for a single inertial bubble driven at 20 kHz, and are found to be several orders of magnitude larger than the linear prediction. Viscous dissipation is found to be the predominant cause of energy loss for bubbles small enough. Then, the classical nonlinear Caflish equations describing the propagation of acoustic waves in a bubbly liquid are recast and simplified conveniently. The main harmonic part of the sound field is found to fulfill a nonlinear Helmholtz equation, where the imaginary part of the squared wave number is directly correlated with the energy lost by a single bubble. For low acoustic driving, linear theory is recovered, but for larger drivings, namely above the Blake threshold, the attenuation coefficient is found to be more than 3 orders of magnitude larger then the linear prediction. A huge attenuation of the wave is thus expected in regions where inertial bubbles are present, which is confirmed by numerical simulations of the nonlinear Helmholtz equation in a 1D standing wave configuration. The expected strong attenuation is not only observed but furthermore, the examination of the phase between the pressure field and its gradient clearly demonstrates that a traveling wave appears in the medium. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Estimating Rain Attenuation In Satellite Communication Links

    Science.gov (United States)

    Manning, R. M.

    1991-01-01

    Attenuation computed with help of statistical model and meteorological data. NASA Lewis Research Center Satellite Link Attenuation Model (SLAM) program QuickBASIC computer program evaluating static and dynamic statistical assessment of impact of rain attenuation on communication link established between Earth terminal and geosynchronous satellite. Application in specification, design, and assessment of satellite communication links for any terminal location in continental United States. Written in Microsoft QuickBASIC.

  2. Joint Inflammation and Early Degeneration Induced by High-Force Reaching Are Attenuated by Ibuprofen in an Animal Model of Work-Related Musculoskeletal Disorder

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Driban

    2011-01-01

    Full Text Available We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT- mediated dUTP-biotin nick end-labeling (TUNEL increased in wrist articular cartilages; superficial structural changes (e.g., pannus and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation, and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration.

  3. Partial Portal Vein Arterialization Attenuates Acute Bile Duct Injury Induced by Hepatic Dearterialization in a Rat Model.

    Science.gov (United States)

    Jiang, Jun; Wei, Jishu; Wu, Junli; Gao, Wentao; Li, Qiang; Jiang, Kuirong; Miao, Yi

    2016-01-01

    Hepatic infarcts or abscesses occur after hepatic artery interruption. We explored the mechanisms of hepatic deprivation-induced acute liver injury and determine whether partial portal vein arterialization attenuated this injury in rats. Male Sprague-Dawley rats underwent either complete hepatic arterial deprivation or partial portal vein arterialization, or both. Hepatic ischemia was evaluated using biochemical analysis, light microscopy, and transmission electron microscopy. Hepatic ATP levels, the expression of hypoxia- and inflammation-associated genes and proteins, and the expression of bile transporter genes were assessed. Complete dearterialization of the liver induced acute liver injury, as evidenced by the histological changes, significantly increased serum biochemical markers, decreased ATP content, increased expression of hypoxia- and inflammation-associated genes and proteins, and decreased expression of bile transporter genes. These detrimental changes were extenuated but not fully reversed by partial portal vein arterialization, which also attenuated ductular reaction and fibrosis in completely dearterialized rat livers. Collectively, complete hepatic deprivation causes severe liver injury, including bile infarcts and biloma formation. Partial portal vein arterialization seems to protect against acute ischemia-hypoxia-induced liver injury.

  4. Curcumin attenuates the expression of NMDAR-NR1 in Chronic Constructive Injury model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Xiangdi Yu

    2015-03-01

    Full Text Available Objective: Neuropathic pain is a prevalent desease that greatly impairs the patients’ quality of life. A lack of the understanding of its aetiology, inadequate relief, and development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptic effect of curcumin and its effect on expression of N-methyl-D-aspartate (NMDA receptor in spinal dorsal horn and dorsal root ganglion in chronic constriction injury (CCI mode of neuropathic pain of rats. Methods: Paw withdrawal mechanical threshold (PWMT and paw withdrawal thermal latency (PWTL of rats were measured on 2th pre-operative and 1, 3, 5, 7, 10, 14 post-operative days, and the expression of NMDAR NR-1 in spinal dorsal horn and DRG was measured by Immunohistochemical staining and western-blot. Results: CCI rats exhibited significant hyperalgesia after operation as compared with control rats. Chronic treatment with curcumin 100mg/kg/day for 14days starting from the 1 th day after CCI operation significantly attenuated PWMT and PWTL. Curcumin also inhibited the expression of NMDAR NR-1 in spinal dorsal horn and DRG. Conclusion: These results indicate an antinociceptive activity of curcumin possibly through its inhibitory action on expression of NMDAR NR-1 in spinal dorsal horn and DRG and point towards its potential to attenuate neuropathic pain.

  5. Disodium cromoglycate may act as a novel adjuvant for UV-attenuated Toxoplasma gondii vaccine in mouse model.

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    Li, Xi; Wu, Yifan; Huang, Shiguang; Lu, Fangli

    2018-06-01

    We have proven the beneficial effects during acute Toxoplasma gondii infection when mast cells were inhibited by disodium cromoglycate (DSCG). Here we investigated the adjuvant effect of DSCG on the protective efficacy of UV-attenuated T. gondii (UV-Tg) vaccine. Mice were infected with 10 2 Tg alone or infected with 10 2 Tg plus DSCG (Tg + DSCG), immunized with 10 5 UV-Tg and challenged with 10 2 Tg (UV-Tg + Tg) or immunized with 10 5 UV-Tg plus DSCG and challenged with 10 2 Tg (UV-Tg + DSCG + Tg). Compared to Tg group, Tg + DSCG, UV-Tg + Tg, and UV-Tg + DSCG + Tg showed significantly prolonged survival times, decreased parasite burdens, reduced liver histopathologies, and increased levels of Th1 and Th2 cytokines and IL-17 in the livers and spleens by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Compared to UV-Tg + Tg, UV-Tg + DSCG + Tg had significantly longer survival time, lower tissue parasite burden and histopathological score, and higher levels of Th1 and Th2 cytokines and IL-17 in the livers or spleens. Our data suggest that DSCG may play an adjuvant role in the immunization induced by UV-attenuated T. gondii in mice, by promoting cellular immune response against T. gondii challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Partial Portal Vein Arterialization Attenuates Acute Bile Duct Injury Induced by Hepatic Dearterialization in a Rat Model

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    Jun Jiang

    2016-01-01

    Full Text Available Hepatic infarcts or abscesses occur after hepatic artery interruption. We explored the mechanisms of hepatic deprivation-induced acute liver injury and determine whether partial portal vein arterialization attenuated this injury in rats. Male Sprague-Dawley rats underwent either complete hepatic arterial deprivation or partial portal vein arterialization, or both. Hepatic ischemia was evaluated using biochemical analysis, light microscopy, and transmission electron microscopy. Hepatic ATP levels, the expression of hypoxia- and inflammation-associated genes and proteins, and the expression of bile transporter genes were assessed. Complete dearterialization of the liver induced acute liver injury, as evidenced by the histological changes, significantly increased serum biochemical markers, decreased ATP content, increased expression of hypoxia- and inflammation-associated genes and proteins, and decreased expression of bile transporter genes. These detrimental changes were extenuated but not fully reversed by partial portal vein arterialization, which also attenuated ductular reaction and fibrosis in completely dearterialized rat livers. Collectively, complete hepatic deprivation causes severe liver injury, including bile infarcts and biloma formation. Partial portal vein arterialization seems to protect against acute ischemia-hypoxia-induced liver injury.

  7. Curcumin attenuates the scurfy-induced immune disorder, a model of IPEX syndrome, with inhibiting Th1/Th2/Th17 responses in mice.

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    Lee, Gihyun; Chung, Hwan-Suck; Lee, Kyeseok; Lee, Hyeonhoon; Kim, Minhwan; Bae, Hyunsu

    2017-09-15

    Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is a lethal autoimmune disease caused by mutations in the Foxp3 gene scurfin (scurfy). Immunosuppressive therapy for IPEX patients has been generally ineffective and has caused severe side effects, however curcumin has shown immune regulation properties for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases without side effects. The aim of this study was to investigate whether curcumin would attenuate symptoms of IPEX in mouse model and would prolong its survival period. C57BL/6 mice were separated into scurfy or wild-type litter mate groups by genotyping, and each group subsequently was separated into 2 subgroups that were fed a 1% curcumin containing or normal diet from the last day of breast-feeding. After weaning, pups were fed either a 1% curcumin containing or normal diet until all scurfy mice die for survival data. To elucidate immune cell proportions in spleen and lymph nodes, cells were analyzed by flowcytometry. Cellular cytokine production was accessed to investigate the effects of curcumin in T cell differentiation in vitro. Scurfy mice fed a 1% curcumin diet survived 4.0-fold longer compared to scurfy (92.5 days) mice fed a normal diet (23 days). A curcumin diet decreased all of the Th1/Th2/Th17 cell populations and attenuated diverse symptoms such as splenomegaly in scurfy mice. In vitro experiments showed that curcumin treatment directly decreased the Th1/Th2/Th17 cytokine production of IFN-γ, IL-4, and IL-17A in CD4 + T cells. Curcumin diet attenuated the scurfy-induced immune disorder, a model of IPEX syndrome, by inhibiting Th1/Th2/Th17 responses in mice. These results have implications for improving clinical therapy for patients with IPEX and other T cell related autoimmune diseases. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Structurally designed attenuated subunit vaccines for S. aureus LukS-PV and LukF-PV confer protection in a mouse bacteremia model.

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    Hatice Karauzum

    Full Text Available Previous efforts towards S. aureus vaccine development have largely focused on cell surface antigens to induce opsonophagocytic killing aimed at providing sterile immunity, a concept successfully applied to other Gram-positive pathogens such as Streptococcus pneumoniae. However, these approaches have largely failed, possibly in part due to the remarkable diversity of the staphylococcal virulence factors such as secreted immunosuppressive and tissue destructive toxins. S. aureus produces several pore-forming toxins including the single subunit alpha hemolysin as well as bicomponent leukotoxins such as Panton-Valentine leukocidin (PVL, gamma hemolysins (Hlg, and LukED. Here we report the generation of highly attenuated mutants of PVL subunits LukS-PV and LukF-PV that were rationally designed, based on an octameric structural model of the toxin, to be deficient in oligomerization. The attenuated subunit vaccines were highly immunogenic and showed significant protection in a mouse model of S. aureus USA300 sepsis. Protection against sepsis was also demonstrated by passive transfer of rabbit immunoglobulin raised against LukS-PV. Antibodies to LukS-PV inhibited the homologous oligomerization of LukS-PV with LukF-PV as well heterologous oligomerization with HlgB. Importantly, immune sera from mice vaccinated with the LukS mutant not only inhibited the PMN lytic activity produced by the PVL-positive USA300 but also blocked PMN lysis induced by supernatants of PVL-negative strains suggesting a broad protective activity towards other bicomponent toxins. These findings strongly support the novel concept of an anti-virulence, toxin-based vaccine intended for prevention of clinical S. aureus invasive disease, rather than achieving sterile immunity. Such a multivalent vaccine may include attenuated leukotoxins, alpha hemolysin, and superantigens.

  9. Combinational deletion of three membrane protein-encoding genes highly attenuates yersinia pestis while retaining immunogenicity in a mouse model of pneumonic plague.

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    Tiner, Bethany L; Sha, Jian; Kirtley, Michelle L; Erova, Tatiana E; Popov, Vsevolod L; Baze, Wallace B; van Lier, Christina J; Ponnusamy, Duraisamy; Andersson, Jourdan A; Motin, Vladimir L; Chauhan, Sadhana; Chopra, Ashok K

    2015-04-01

    Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and Δlpp ΔmsbB double mutants. While the Δail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the Δlpp Δail double mutant and the Δlpp ΔmsbB Δail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD50) equivalent to 6,800 LD50s of WT CO92. The mutant-infected animals developed balanced TH1- and TH2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD50s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the Δlpp ΔmsbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a

  10. Mesenchymal Stem Cells (MSCs) Attenuate Cutaneous Sclerodermatous Graft-Versus-Host Disease (Scl-GVHD) through Inhibition of Immune Cell Infiltration in a Mouse Model.

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    Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Min, Chang-Ki

    2017-09-01

    Human chronic graft-versus-host disease (GVHD) shares clinical characteristics with a murine sclerodermatous GVHD model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of sclerodermatous GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of chronic GVHD. The clinical and pathological severity of cutaneous sclerodermatous GVHD was significantly attenuated in MSC-treated recipients relative to sclerodermatous GVHD control subjects. After MSC treatment, skin collagen production was significantly reduced, with consistent down-regulation of Tgfb expression. Effects of MSCs on molecular markers implicated in persistent transforming growth factor-β signaling and fibrosis, such as PTEN, phosphorylated Smad-2/3, and matrix metalloproteinase-1, were observed in skin tissue. MSCs neither migrate to the skin nor affect the in vivo expansion of immune effector cells, but they inhibited the infiltration of immune effector cells into skin via down-regulation of CCR4 and CCR8 expression on CD4 + T cells and CCR1 on CD11b + monocyte/macrophages. MSCs diminished expression of chemokines such as CCL1, CCL3, CCL8, CCL17, and CCL22 in skin. MSCs were also dependent on stimulated splenocytes to suppress fibroblast proliferation. Our findings indicate that MSCs attenuate the cutaneous sclerodermatous GVHD by selectively blocking immune cell migration and down-regulating chemokines and chemokine receptors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Sentence Recognition Prediction for Hearing-impaired Listeners in Stationary and Fluctuation Noise With FADE: Empowering the Attenuation and Distortion Concept by Plomp With a Quantitative Processing Model.

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    Kollmeier, Birger; Schädler, Marc René; Warzybok, Anna; Meyer, Bernd T; Brand, Thomas

    2016-09-07

    To characterize the individual patient's hearing impairment as obtained with the matrix sentence recognition test, a simulation Framework for Auditory Discrimination Experiments (FADE) is extended here using the Attenuation and Distortion (A+D) approach by Plomp as a blueprint for setting the individual processing parameters. FADE has been shown to predict the outcome of both speech recognition tests and psychoacoustic experiments based on simulations using an automatic speech recognition system requiring only few assumptions. It builds on the closed-set matrix sentence recognition test which is advantageous for testing individual speech recognition in a way comparable across languages. Individual predictions of speech recognition thresholds in stationary and in fluctuating noise were derived using the audiogram and an estimate of the internal level uncertainty for modeling the individual Plomp curves fitted to the data with the Attenuation (A-) and Distortion (D-) parameters of the Plomp approach. The "typical" audiogram shapes from Bisgaard et al with or without a "typical" level uncertainty and the individual data were used for individual predictions. As a result, the individualization of the level uncertainty was found to be more important than the exact shape of the individual audiogram to accurately model the outcome of the German Matrix test in stationary or fluctuating noise for listeners with hearing impairment. The prediction accuracy of the individualized approach also outperforms the (modified) Speech Intelligibility Index approach which is based on the individual threshold data only. © The Author(s) 2016.

  12. Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD).

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    Ni, Xunjun; Wang, Haiyan

    2016-01-01

    Silymarin, which derived from the milk thistle plant (silybum marianum), has been used for centuries as a natural remedy for diseases of the liver and biliary tract. Considering the therapeutic potential to liver disease, we tested efficacy of silymarin on hepatic steatosis with a high fat diet (HFD)-induced mouse model of non-alcoholic fatty liver disease (NAFLD), and investigated possible effects on lipid metabolic pathways. In our study, silymarin could attenuate the hepatic steatosis, which was proved by both Oil Red O staining and hepatic triglyceride (TG) level determination. Furthermore, compared with INT-747, a potent and selective FXR agonist, silymarin could preserve plasmatic high-density lipoprotein cholesterol (HDL-C) to a higher level and low-density lipoprotein cholesterol (LDL-C) to a lower level, which benefited more to the circulation system. Through real-time PCR analysis, we clarified a vital protective role of silymarin in mRNA regulation of genes involved in lipid metabolism and oxidative stress. It was also shown that silymarin had no effects on body weight, food intake, and liver transaminase. Taken together, silymarin could attenuate hepatic steatosis in a mouse model of NAFLD through regulation of lipid metabolism and oxidative stress, and benefit to the circulation system. All these findings shed new light on NAFLD treatment.

  13. A statistical rain attenuation prediction model with application to the advanced communication technology satellite project. 1: Theoretical development and application to yearly predictions for selected cities in the United States

    Science.gov (United States)

    Manning, Robert M.

    1986-01-01

    A rain attenuation prediction model is described for use in calculating satellite communication link availability for any specific location in the world that is characterized by an extended record of rainfall. Such a formalism is necessary for the accurate assessment of such availability predictions in the case of the small user-terminal concept of the Advanced Communication Technology Satellite (ACTS) Project. The model employs the theory of extreme value statistics to generate the necessary statistical rainrate parameters from rain data in the form compiled by the National Weather Service. These location dependent rain statistics are then applied to a rain attenuation model to obtain a yearly prediction of the occurrence of attenuation on any satellite link at that location. The predictions of this model are compared to those of the Crane Two-Component Rain Model and some empirical data and found to be very good. The model is then used to calculate rain attenuation statistics at 59 locations in the United States (including Alaska and Hawaii) for the 20 GHz downlinks and 30 GHz uplinks of the proposed ACTS system. The flexibility of this modeling formalism is such that it allows a complete and unified treatment of the temporal aspects of rain attenuation that leads to the design of an optimum stochastic power control algorithm, the purpose of which is to efficiently counter such rain fades on a satellite link.

  14. Oridonin Attenuates Synaptic Loss and Cognitive Deficits in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease.

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    Sulei Wang

    Full Text Available Synaptic loss induced by beta-amyloid (Aβ plays a critical role in the pathophysiology of Alzheimer's disease (AD, but the mechanisms underlying this process remain unknown. In this study, we found that oridonin (Ori rescued synaptic loss induced by Aβ1-42 in vivo and in vitro and attenuated the alterations in dendritic structure and spine density observed in the hippocampus of AD mice. In addition, Ori increased the expression of PSD-95 and synaptophysin and promoted mitochondrial activity in the synaptosomes of AD mice. Ori also activated the BDNF/TrkB/CREB signaling pathway in the hippocampus of AD mice. Furthermore, in the Morris water maze test, Ori reduced latency and searching distance and increased the number of platform crosses in AD mice. These data suggest that Ori might prevent synaptic loss and improve behavioral symptoms in Aβ1-42-induced AD mice.

  15. Tranexamic Acid Attenuates The Loss of Lung Barrier Function in a Rat Model of Polytrauma And Hemorrhage With Resuscitation.

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    Wu, Xiaowu; Dubick, Michael A; Schwacha, Martin G; Cap, Andrew P; Darlington, Daniel N

    2017-04-01

    Severe trauma, hemorrhage, and resuscitation can lead to a trauma-related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage, and resuscitation. Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle, and right femur fracture), then bled 40% of their blood volume. One hour after completion of polytrauma and hemorrhage, resuscitation was begun with fresh whole blood (FWB) or FWB with prior bolus administration of TXA (10 mg/kg in 0.2 mL). Polytrauma, hemorrhage, and resuscitation with FWB led to an elevation in lung water content that was significantly reduced with TXA administration. Polytrauma and hemorrhage led to rise in the number of neutrophils/monocytes and platelets in the lungs, and a rise in myeloperoxidase (MPO), neutrophil elastase and complement C5a content. While resuscitation with FWB significantly reduced the cellular infiltrate and MPO, FWB/TXA further reduced the levels of neutrophil/monocytes, neutrophil elastase, and complement C5a. Polytrauma and hemorrhage led to rise in lung plasmin activity that was significantly reduced with either FWB or FWB/TXA resuscitation. Severe trauma and hemorrhage leads to increases in lung water content, and immune cell, platelets, MPO, elastase, and C5a content in lung tissue, all markers of inflammation and acute lung injury. The addition of TXA to FWB resuscitation markedly attenuated the rise in these parameters suggesting its utility in treating acute lung injury.

  16. Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease.

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    Hany H Arab

    Full Text Available Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD via its proinflammatory features. Telmisartan (TLM is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o. attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI, colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α, prostaglandin E2 (PGE2 and myeloperoxidase (MPO activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10. TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB p65 and mRNA of cyclo-oxygenase-2 (COX-2 and inducible nitric oxide synthase (iNOS proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO besides boosting glutathione (GSH, total anti-oxidant capacity (TAC and the activities of superoxide dismutase (SOD and glutathione peroxidase (GPx. With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis.

  17. Resistant starch and exercise independently attenuate weight regain on a high fat diet in a rat model of obesity

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    Johnson Ginger C

    2011-07-01

    Full Text Available Abstract Background Long-term weight reduction remains elusive for many obese individuals. Resistant starch (RS and exercise may be useful for weight maintenance. The effects of RS, with or without exercise, on weight regain was examined during relapse to obesity on a high carbohydrate, high fat (HC/HF diet. Methods Obesity-prone rats were fed ad libitum for 16 weeks then weight reduced on a low fat diet to induce a 17% body weight loss (weight reduced rats. Weight reduced rats were maintained on an energy-restricted low fat diet for 18 weeks, with or without a daily bout of treadmill exercise. Rats were then allowed free access to HC/HF diet containing low (0.3% or high (5.9% levels of RS. Weight regain, energy balance, body composition, adipocyte cellularity, and fuel utilization were monitored as rats relapsed to obesity and surpassed their original, obese weight. Results Both RS and exercise independently attenuated weight regain by reducing the energy gap between the drive to eat and suppressed energy requirements. Exercise attenuated the deposition of lean mass during relapse, whereas its combination with RS sustained lean mass accrual as body weight returned. Early in relapse, RS lowered insulin levels and reduced the deposition of fat in subcutaneous adipose tissue. Exercise cessation at five weeks of relapse led to increased weight gain, body fat, subcutaneous adipocytes, and decreased lean mass; all detrimental consequences to overall metabolic health. Conclusions These data are the first to show the complimentary effects of dietary RS and regular exercise in countering the metabolic drive to regain weight following weight loss and suggest that exercise cessation, in the context of relapse on a HC/HF diet, may have dire metabolic consequences.

  18. Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling.

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    Rajesh Kumar

    Full Text Available Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄, an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂ levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP-9 as well as modulating transforming growth factor (TGF-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.

  19. Development of digital phantoms based on a finite element model to simulate low-attenuation areas in CT imaging for pulmonary emphysema quantification.

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    Diciotti, Stefano; Nobis, Alessandro; Ciulli, Stefano; Landini, Nicholas; Mascalchi, Mario; Sverzellati, Nicola; Innocenti, Bernardo

    2017-09-01

    To develop an innovative finite element (FE) model of lung parenchyma which simulates pulmonary emphysema on CT imaging. The model is aimed to generate a set of digital phantoms of low-attenuation areas (LAA) images with different grades of emphysema severity. Four individual parameter configurations simulating different grades of emphysema severity were utilized to generate 40 FE models using ten randomizations for each setting. We compared two measures of emphysema severity (relative area (RA) and the exponent D of the cumulative distribution function of LAA clusters size) between the simulated LAA images and those computed directly on the models output (considered as reference). The LAA images obtained from our model output can simulate CT-LAA images in subjects with different grades of emphysema severity. Both RA and D computed on simulated LAA images were underestimated as compared to those calculated on the models output, suggesting that measurements in CT imaging may not be accurate in the assessment of real emphysema extent. Our model is able to mimic the cluster size distribution of LAA on CT imaging of subjects with pulmonary emphysema. The model could be useful to generate standard test images and to design physical phantoms of LAA images for the assessment of the accuracy of indexes for the radiologic quantitation of emphysema.

  20. Attenuation in Melting Layer of Precipitation

    NARCIS (Netherlands)

    Klaassen, W.

    1988-01-01

    A model of the melting layer is employed on radar measurements to simulate the attenuation of radio waves at 12, 20 and 30GHz. The attenuation in the melting layer is simulated to be slightly larger than that of rain with the same path length and precipitation intensity. The result appears to depend

  1. Perineural pretreatment of bee venom attenuated the development of allodynia in the spinal nerve ligation injured neuropathic pain model; an experimental study.

    Science.gov (United States)

    Koh, Won Uk; Choi, Seong Soo; Lee, Jong Hyuk; Lee, So Hee; Lee, Sun Kyung; Lee, Yoon Kyung; Leem, Jeong Gil; Song, Jun Gol; Shin, Jin Woo

    2014-11-04

    Diluted bee venom (BV) is known to have anti-nociceptive and anti-inflammatory effects. We therefore assessed whether perineural bee venom pretreatment could attenuate the development of neuropathic pain in the spinal nerve ligation injured animal model. Neuropathic pain was surgically induced in 30 male Sprague Dawley rats by ligation of the L5 and L6 spinal nerves, with 10 rats each treated with saline and 0.05 and 0.1 mg BV. Behavioral testing for mechanical, cold, and thermal allodynia was conducted on postoperative days 3 to 29. Three rats in each group and 9 sham operated rats were sacrificed on day 9, and the expression of transient receptor potential vanilloid type 1 (TRPV1), ankyrin type 1 (TRPA1), and melastatin type 8 (TRPM8) receptors in the ipsilateral L5 dorsal root ganglion was analyzed. The perineural administration of BV to the spinal nerves attenuated the development of mechanical, thermal, and cold allodynia, and the BV pretreatment reduced the expression of TRPV1, TRPA1, TRPM8 and c - Fos in the ipsilateral dorsal root ganglion. The current study demonstrates that the perineural pretreatment with diluted bee venom before the induction of spinal nerve ligation significantly suppresses the development of neuropathic pain. Furthermore, this bee venom induced suppression was strongly related with the involvement of transient receptor potential family members.

  2. Macroseismic intensity attenuation in Iran

    Science.gov (United States)

    Yaghmaei-Sabegh, Saman

    2018-01-01

    Macroseismic intensity data plays an important role in the process of seismic hazard analysis as well in developing of reliable earthquake loss models. This paper presents a physical-based model to predict macroseismic intensity attenuation based on 560 intensity data obtained in Iran in the time period 1975-2013. The geometric spreading and energy absorption of seismic waves have been considered in the proposed model. The proposed easy to implement relation describes the intensity simply as a function of moment magnitude, source to site distance and focal depth. The prediction capability of the proposed model is assessed by means of residuals analysis. Prediction results have been compared with those of other intensity prediction models for Italy, Turkey, Iran and central Asia. The results indicate the higher attenuation rate for the study area in distances less than 70km.

  3. Modeling and Forecasting of Depletion of Additives in Car Engine Oils Using Attenuated Total Reflectance Fast Transform Infrared Spectroscopy

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    Ronald Nguele

    2014-11-01

    Full Text Available On average, additives make up to 7% of a typical lubricant base. Commonly, they are blended with lube oils to enhance specific features thereby improving their qualities. Ultimately, additives participate in the performance of car engine oils. Using an analytical tool, attenuated total reflectance fast transform infrared spectroscopy, various grades of car engine oils, at different mileages, were analyzed. Sulfate oxidation and wear were found to trigger chemical processes which, in the long run, cause lubricant degradation while carbonyl oxidation was observed to occur only at a slow rate. Based upon data obtained from infrared spectra and using a curve fitting technique, mathematical equations predicting the theoretical rates of chemical change due to the aforementioned processes were examined. Additive depletions were found to obey exponential regression rather than polynomial. Moreover, breakpoint (breakpoint is used here to denote the initiation of deterioration of additives and critical mileage (critical mileage defines the distance at which the lubricant is chemically unusable of both samples were determined.

  4. Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome.

    Science.gov (United States)

    Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D

    2016-10-01

    Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aortic wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1(mgR/mgR) mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1(mgR/mgR) tissues, whereas the media layer of MFS aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, MFS mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

  5. In vivo pretreatment of Eudrilus eugeniae powder attenuates β-adrenoceptor toxicity mediated by isoproterenol in rat model

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    Jaganathan Anitha

    2016-08-01

    Full Text Available The present study was designed to discover the potential cardioprotective function of earthworm powder (EWP extracted from Eudrilus eugeniae on isoproterenol (ISO-induced myocardial infarction in male Wistar rats. The rats were divided into four groups, with six rats in each group. Certain rats were pretreated with EWP (200 mg/kg bwt (Group III, and a myocardial infarction was then induced by subcutaneous injection of ISO (85 mg/kg bwt (Group II. Oral pretreatment of 200 mg/kg bwt of EWP for 28 days significantly (p > 0.05 improved the blood profile levels, including (a the lipid profile of total cholesterol (TC, free fatty acids (FFA, and triglycerides (TG; (b low-density lipoprotein (LDL, very low-density lipoprotein (VLDL, high-density lipoprotein (HDL, and protein; and (c A/G ratio, glucose and uric acid levels. The electrophoretic pattern of elevated lactose dehydrogenase (LDH levels was recovered by EWP treatment as evidenced by comparison with ISO-induced rats with cardiac damage. The above results indicate that EWP (200 mg/kg bwt provides a cardioprotective effect by attenuating the blood profile, lipid profile, biochemical levels, and LDH patterns in rats that experienced an ISO-induced myocardial infarction.

  6. Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer's disease by fermented soybean nanonutraceutical.

    Science.gov (United States)

    Bhatt, Prakash Chandra; Pathak, Shruti; Kumar, Vikas; Panda, Bibhu Prasad

    2018-02-01

    The present study was performed to evaluate the efficacy of nanonutraceuticals (NN) for attenuation of neurobehavioral and neurochemical abnormalities in Alzheimer's disease. Solid-state fermentation of soybean with Bacillus subtilis was performed to produce different metabolites (nattokinase, daidzin, genistin and glycitin and menaquinone-7). Intoxication of rats with colchicine caused impairment in learning and memory which was demonstrated in neurobehavioral paradigms (Morris water maze and passive avoidance) linked with decreased activity of acetylcholinesterase (AChE). NN treatment led to a significant increase in TLT in the retention trials as compared to acquisition trial TLT suggesting an improved learning and memory in rats. Further, treatment of NN caused an increase in the activity of AChE (42%), accompanied with a reduced activity of glutathione (42%), superoxide dismutase (43%) and catalase (41%). It also decreased the level of lipid peroxidation (28%) and protein carbonyl contents (30%) in hippocampus as compared to those treated with colchicine alone, suggesting a possible neuroprotective efficacy of NN. Interestingly, in silico studies also demonstrated an effective amyloid-β and BACE-1 inhibition activity. These findings clearly indicated that NN reversed colchicine-induced behavioral and neurochemical alterations through potent antioxidant activity and could possibly impart beneficial effects in cognitive defects associated with Alzheimer's disease.

  7. Repetitive Hyperbaric Oxygenation Attenuates Reactive Astrogliosis and Suppresses Expression of Inflammatory Mediators in the Rat Model of Brain Injury

    Directory of Open Access Journals (Sweden)

    Irena Lavrnja

    2015-01-01

    Full Text Available The exact mechanisms by which treatment with hyperbaric oxygen (HBOT exerts its beneficial effects on recovery after brain injury are still unrevealed. Therefore, in this study we investigated the influence of repetitive HBOT on the reactive astrogliosis and expression of mediators of inflammation after cortical stab injury (CSI. CSI was performed on male Wistar rats, divided into control, sham, and lesioned groups with appropriate HBO. The HBOT protocol was as follows: 10 minutes of slow compression, 2.5 atmospheres absolute (ATA for 60 minutes, and 10 minutes of slow decompression, once a day for 10 consecutive days. Data obtained using real-time polymerase chain reaction, Western blot, and immunohistochemical and immunofluorescence analyses revealed that repetitive HBOT applied after the CSI attenuates reactive astrogliosis and glial scarring, and reduces expression of GFAP (glial fibrillary acidic protein, vimentin, and ICAM-1 (intercellular adhesion molecule-1 both at gene and tissue levels. In addition, HBOT prevents expression of CD40 and its ligand CD40L on microglia, neutrophils, cortical neurons, and reactive astrocytes. Accordingly, repetitive HBOT, by prevention of glial scarring and limiting of expression of inflammatory mediators, supports formation of more permissive environment for repair and regeneration.

  8. A new parameterization for surface ocean light attenuation in Earth System Models: assessing the impact of light absorption by colored detrital material

    Science.gov (United States)

    Kim, G. E.; Pradal, M.-A.; Gnanadesikan, A.

    2015-03-01

    Light limitation can affect the distribution of biota and nutrients in the ocean. Light absorption by colored detrital material (CDM) was included in a fully coupled Earth System Model using a new parameterization for shortwave attenuation. Two model runs were conducted, with and without light attenuation by CDM. In a global average sense, greater light limitation associated with CDM increased surface chlorophyll, biomass and nutrients together. These changes can be attributed to the movement of biological productivity higher up the water column, which increased surface chlorophyll and biomass while simultaneously decreasing total biomass. Meanwhile, the reduction in biomass resulted in greater nutrient availability throughout the water column. Similar results were found on a regional scale in an analysis of the oceans by biome. In coastal regions, surface chlorophyll increased by 35% while total integrated phytoplankton biomass diminished by 18%. The largest relative increases in modeled surface chlorophyll and biomass in the open ocean were found in the equatorial biomes, while largest decreases in depth-integrated biomass and chlorophyll were found in the subpolar and polar biomes. This mismatch of surface and subsurface trends and their regional dependence was analyzed by comparing the competing factors of diminished light availability and increased nutrient availability on phytoplankton growth in the upper 200 m. Overall, increases in surface biomass were expected to accompany greater nutrient uptake and therefore diminish surface nutrients, but changes in light limitation decoupled trends between these two variables. Understanding changes in biological productivity requires both surface and depth-resolved information. Surface trends may be minimal or of the opposite sign to depth-integrated amounts, depending on the vertical structure of phytoplankton abundance.

  9. Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Yannic C. Bartsch

    2018-06-01

    Full Text Available Pro- and anti-inflammatory effector functions of IgG antibodies (Abs depend on their subclass and Fc glycosylation pattern. Accumulation of non-galactosylated (agalactosylated; G0 IgG Abs in the serum of rheumatoid arthritis and systemic lupus erythematosus (SLE patients reflects severity of the diseases. In contrast, sialylated IgG Abs are responsible for anti-inflammatory effects of the intravenous immunoglobulin (pooled human serum IgG from healthy donors, administered in high doses (2 g/kg to treat autoimmune patients. However, whether low amounts of sialylated autoantigen-reactive IgG Abs can also inhibit autoimmune diseases is hardly investigated. Here, we explore whether sialylated autoantigen-reactive IgG Abs can inhibit autoimmune pathology in different mouse models. We found that sialylated IgG auto-Abs fail to induce inflammation and lupus nephritis in a B cell receptor (BCR transgenic lupus model, but instead are associated with lower frequencies of pathogenic Th1, Th17 and B cell responses. In accordance, the transfer of small amounts of immune complexes containing sialylated IgG Abs was sufficient to attenuate the development of nephritis. We further showed that administration of sialylated collagen type II (Col II-specific IgG Abs attenuated the disease symptoms in a model of Col II-induced arthritis and reduced pathogenic Th17 cell and autoantigen-specific IgG Ab responses. We conclude that sialylated autoantigen-specific IgG Abs may represent a promising tool for treating pathogenic T and B cell immune responses in autoimmune diseases.

  10. Pharmacologic antagonism of dopamine receptor D3 attenuates neurodegeneration and motor impairment in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Elgueta, Daniela; Aymerich, María S; Contreras, Francisco; Montoya, Andro; Celorrio, Marta; Rojo-Bustamante, Estefanía; Riquelme, Eduardo; González, Hugo; Vásquez, Mónica; Franco, Rafael; Pacheco, Rodrigo

    2017-02-01

    Neuroinflammation involves the activation of glial cells, which is associated to the progression of neurodegeneration in Parkinson's disease. Recently, we and other researchers demonstrated that dopamine receptor D3 (D3R)-deficient mice are completely refractory to neuroinflammation and consequent neurodegeneration associated to the acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study we examined the therapeutic potential and underlying mechanism of a D3R-selective antagonist, PG01037, in mice intoxicated with a chronic regime of administration of MPTP and probenecid (MPTPp). Biodistribution analysis indicated that intraperitoneally administered PG01037 crosses the blood-brain barrier and reaches the highest concentration in the brain 40 min after the injection. Furthermore, the drug was preferentially distributed to the brain in comparison to the plasma. Treatment of MPTPp-intoxicated mice with PG01037 (30 mg/kg, administrated twice a week for five weeks) attenuated the loss of dopaminergic neurons in the substantia nigra pars compacta, as evaluated by stereological analysis, and the loss of striatal dopaminergic terminals, as determined by densitometric analyses of tyrosine hydroxylase and dopamine transporter immunoreactivities. Accordingly, the treatment resulted in significant improvement of motor performance of injured animals. Interestingly, the therapeutic dose of PG01037 exacerbated astrogliosis and resulted in increased ramification density of microglial cells in the striatum of MPTPp-intoxicated mice. Further analyses suggested that D3R expressed in astrocytes favours a beneficial astrogliosis with anti-inflammatory consequences on microglia. Our findings indicate that D3R-antagonism exerts a therapeutic effect in parkinsonian animals by reducing the loss of dopaminergic neurons in the nigrostriatal pathway, alleviating motor impairments and modifying the pro-inflammatory phenotype of glial cells. Copyright

  11. Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model

    Science.gov (United States)

    Liu, Wei; Jiang, Hong-li; Cai, Lin-li; Yan, Min; Dong, Shou-jin; Mao, Bing

    2016-01-01

    Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1β, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/β, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1β, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/β, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner. PMID:27366191

  12. The set valued unified model of dispersion and attenuation for wave propagation in dielectric (and anelastic media

    Directory of Open Access Journals (Sweden)

    M. Caputo

    1998-06-01

    Full Text Available Since the dispersion and attenuation properties of dielectric and anelastic media, in the frequency domain, are expressed by similar formulae, as shown experimentally by Cole and Cole (1941 and Bagley and Torvik (1983, 1986 respectively, we note that the same properties may be represented in the time domain by means of an equation of the same form; this is obtained by introducing derivatives of fractional order into the system functions of the media. The Laplace Transforms (LT of such system functions contain fractional powers of the imaginary frequency and are, therefore, multivalued functions defined in the Riemann Sheets (RS of the function. We determine the response of the medium (dielectric o anelastic to a generic signal summing the time domain representation due to the branches of the solutions in the RSs of the LT. It is found that, if the initial conditions are equal in all the RSs, the solution is a sum of two exponentials with complex exponents, if the initial conditions are different in some of the RSs, then a transient for each of those RSs is added to the exponentials. In all cases a monochromatic wave is split into a set of waves with the same frequency and slightly different wavelengths which interfere and disperse. As a consequence a monochromatic electromagnetic wave with frequency around 1 MHz in water has a relevant dispersion and beats generating a tunnel effect. In the atmosphere of the Earth the dispersion of a monochromatic wave with frequency around 1 GHz, like those used in tracking artificial satellites, has a negligible effect on the accuracy of the determination of the position of the satellites and the positioning of the bench marks on the Earth. We also find the split eigenfunctions of the free modes of infinite plates and shells made of dielectric and anelastic media.

  13. Simulation of Cloud-aerosol Lidar with Orthogonal Polarization (CALIOP Attenuated Backscatter Profiles Using the Global Model of Aerosol Processes (GLOMAP

    Directory of Open Access Journals (Sweden)

    Young Stuart

    2016-01-01

    Full Text Available To permit the calculation of the radiative effects of atmospheric aerosols, we have linked our aerosol-chemical transport model (CTMGLOMAP to a new radiation module (UKCARADAER. In order to help assess and improve the accuracy of the radiation code, in particular the height dependence of the predicted scattering, we have developed a module that simulates attenuated backscatter (ABS profiles that would be measured by the satellite-borne Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP if it were to sample an atmosphere with the same aerosol loading as predicted by the CTM. Initial results of our comparisons of the predicted ABS profiles with actual CALIOP data are encouraging but some differences are noted, particularly in marine boundary layers where the scattering is currently under-predicted and in dust layers where it is often over-predicted. The sources of these differences are being investigated.

  14. SU-E-T-378: Evaluation of An Analytical Model for the Inter-Seed Attenuation Effect in 103-Pd Multi-Seed Implant Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Safigholi, H; Soliman, A; Song, W [Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, U of T, Toronto, Ontario (Canada); Meigooni, A Soleimani [Comprehensive Cancer Center of Nevada, Las Vegas, Nevada (United States); Han, D [Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, U of T, Toronto, Ontario (Canada); University of California, San Diego, La Jolla, CA (United States)

    2015-06-15

    Purpose: Brachytherapy treatment planning systems based on TG-43 protocol calculate the dose in water and neglects the heterogeneity effect of seeds in multi-seed implant brachytherapy. In this research, the accuracy of a novel analytical model that we propose for the inter-seed attenuation effect (ISA) for 103-Pd seed model is evaluated. Methods: In the analytical model, dose perturbation due to the ISA effect for each seed in an LDR multi-seed implant for 103-Pd is calculated by assuming that the seed of interest is active and the other surrounding seeds are inactive. The cumulative dosimetric effect of all seeds is then summed using the superposition principle. The model is based on pre Monte Carlo (MC) simulated 3D kernels of the dose perturbations caused by the ISA effect. The cumulative ISA effect due to multiple surrounding seeds is obtained by a simple multiplication of the individual ISA effect by each seed, the effect of which is determined by the distance from the seed of interest. This novel algorithm is then compared with full MC water-based simulations (FMCW). Results: The results show that the dose perturbation model we propose is in excellent agreement with the FMCW values for a case with three seeds separated by 1 cm. The average difference of the model and the FMCW simulations was less than 8%±2%. Conclusion: Using the proposed novel analytical ISA effect model, one could expedite the corrections due to the ISA dose perturbation effects during permanent seed 103-Pd brachytherapy planning with minimal increase in time since the model is based on multiplications and superposition. This model can be applied, in principle, to any other brachytherapy seeds. Further work is necessary to validate this model on a more complicated geometry as well.

  15. Selective Cathepsin S Inhibition with MIV-247 Attenuates Mechanical Allodynia and Enhances the Antiallodynic Effects of Gabapentin and Pregabalin in a Mouse Model of Neuropathic Pain.

    Science.gov (United States)

    Hewitt, Ellen; Pitcher, Thomas; Rizoska, Biljana; Tunblad, Karin; Henderson, Ian; Sahlberg, Britt-Louise; Grabowska, Urszula; Classon, Björn; Edenius, Charlotte; Malcangio, Marzia; Lindström, Erik

    2016-09-01

    Cathepsin S inhibitors attenuate mechanical allodynia in preclinical neuropathic pain models. The current study evaluated the effects when combining the selective cathepsin S inhibitor MIV-247 with gabapentin or pregabalin in a mouse model of neuropathic pain. Mice were rendered neuropathic by partial sciatic nerve ligation. MIV-247, gabapentin, or pregabalin were administered alone or in combination via oral gavage. Mechanical allodynia was assessed using von Frey hairs. Neurobehavioral side effects were evaluated by assessing beam walking. MIV-247, gabapentin, and pregabalin concentrations in various tissues were measured. Oral administration of MIV-247 (100-200 µmol/kg) dose-dependently attenuated mechanical allodynia by up to approximately 50% reversal when given as a single dose or when given twice daily for 5 days. No behavioral deficits were observed at any dose of MIV-247 tested. Gabapentin (58-350 µmol/kg) and pregabalin (63-377 µmol/kg) also inhibited mechanical allodynia with virtually complete reversal at the highest doses tested. The minimum effective dose of MIV-247 (100 µmol/kg) in combination with the minimum effective dose of pregabalin (75 µmol/kg) or gabapentin (146 µmol/kg) resulted in enhanced antiallodynic efficacy without augmenting side effects. A subeffective dose of MIV-247 (50 µmol/kg) in combination with a subeffective dose of pregabalin (38 µmol/kg) or gabapentin (73 µmol/kg) also resulted in substantial efficacy. Plasma levels of MIV-247, gabapentin, and pregabalin were similar when given in combination as to when given alone. Cathepsin S inhibition with MIV-247 exerts significant antiallodynic efficacy alone, and also enhances the effect of gabapentin and pregabalin without increasing side effects or inducing pharmacokinetic interactions. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Stimulation of ganglionated plexus attenuates cardiac neural remodeling and heart failure progression in a canine model of acute heart failure post-myocardial infarction.

    Science.gov (United States)

    Luo, Da; Hu, Huihui; Qin, Zhiliang; Liu, Shan; Yu, Xiaomei; Ma, Ruisong; He, Wenbo; Xie, Jing; Lu, Zhibing; He, Bo; Jiang, Hong

    2017-12-01

    Heart failure (HF) is associated with autonomic dysfunction. Vagus nerve stimulation has been shown to improve cardiac function both in HF patients and animal models of HF. The purpose of this present study is to investigate the effects of ganglionated plexus stimulation (GPS) on HF progression and autonomic remodeling in a canine model of acute HF post-myocardial infarction. Eighteen adult mongrel male dogs were randomized into the control (n=8) and GPS (n=10) groups. All dogs underwent left anterior descending artery ligation followed by 6-hour high-rate (180-220bpm) ventricular pacing to induce acute HF. Transthoracic 2-dimensional echocardiography was performed at different time points. The plasma levels of norepinephrine, B-type natriuretic peptide (BNP) and Ang-II were measured using ELISA kits. C-fos and nerve growth factor (NGF) proteins expressed in the left stellate ganglion as well as GAP43 and TH proteins expressed in the peri-infarct zone were measured using western blot. After 6h of GPS, the left ventricular end-diastolic volume, end-systolic volume and ejection fraction showed no significant differences between the 2 groups, but the interventricular septal thickness at end-systole in the GPS group was significantly higher than that in the control group. The plasma levels of norepinephrine, BNP, Ang-II were increased 1h after myocardial infarction while the increase was attenuated by GPS. The expression of c-fos and NGF proteins in the left stellate ganglion as well as GAP43 and TH proteins in cardiac peri-infarct zone in GPS group were significantly lower than that in control group. GPS inhibits cardiac sympathetic remodeling and attenuates HF progression in canines with acute HF induced by myocardial infarction and ventricular pacing. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Attenuation of UVR-induced vitamin D3 synthesis in a mouse model deleted for keratinocyte lathosterol 5-desaturase.

    Science.gov (United States)

    Makarova, Anastasia M; Pasta, Saloni; Watson, Gordon; Shackleton, Cedric; Epstein, Ervin H

    2017-07-01

    The lower risk of some internal cancers at lower latitudes has been linked to greater sun exposure and consequent higher levels of ultraviolet radiation (UVR)-produced vitamin D 3 (D 3 ). To separate the experimental effects of sunlight and of all forms of D 3 , a mouse in which UVR does not produce D 3 would be useful. To this end we have generated mice carrying a modified allele of sterol C5-desaturase (Sc5d), the gene encoding the enzyme that converts lathosterol to 7-dehydrocholesterol (7-DHC), such that Sc5d expression can be inactivated using the Cre/lox site-specific recombination system. By crossing to mice with tissue-specific expression of Cre or CreER 2 (Cre/estrogen receptor), we generated two lines of transgenic mice. One line has constitutive keratinocyte-specific inactivation of Sc5d (Sc5d k14KO ). The other line (Sc5d k14KOi ) has tamoxifen-inducible keratinocyte-specific inactivation of Sc5d. Mice deleted for keratinocyte Sc5d lose the ability to increase circulating D 3 following UVR exposure of the skin. Thus, unlike in control mice, acute UVR exposure did not affect circulating D 3 level in inducible Sc5d k14KOi mice. Keratinocyte-specific inactivation of Sc5d was proven by sterol measurement in hair - in control animals lathosterol and cholesta-7,24-dien-3β-ol, the target molecules of SC5D in the sterol biosynthetic pathways, together constituted a mean of 10% of total sterols; in the conditional knockout mice these sterols constituted a mean of 56% of total sterols. The constitutive knockout mice had an even greater increase, with lathosterol and cholesta-7,24-dien-3β-ol accounting for 80% of total sterols. In conclusion, the dominant presence of the 7-DHC precursors in hair of conditional animals and the lack of increased circulating D 3 following exposure to UVR reflect attenuated production of the D 3 photochemical precursor 7-DHC and, consequently, of D 3 itself. These animals provide a useful new tool for investigating the role of D 3

  18. Construction and Experimental Implementation of a Model-Based Inverse Filter to Attenuate Hysteresis in Ferroelectric Transducers

    National Research Council Canada - National Science Library

    Hatch, Andrew G; Smith, Ralph C; De, Tathagata; Salapaka, Murti V

    2005-01-01

    .... In this paper, we illustrate the construction of inverse filters, based on homogenized energy models, which can be used to approximately linearize the piezoceramic transducer behavior for linear...

  19. Application of the Polynomial-Based Least Squares and Total Least Squares Models for the Attenuated Total Reflection Fourier Transform Infrared Spectra of Binary Mixtures of Hydroxyl Compounds.

    Science.gov (United States)

    Shan, Peng; Peng, Silong; Zhao, Yuhui; Tang, Liang

    2016-03-01

    An analysis of binary mixtures of hydroxyl compound by Attenuated Total Reflection Fourier transform infrared spectroscopy (ATR FT-IR) and classical least squares (CLS) yield large model error due to the presence of unmodeled components such as H-bonded components. To accommodate these spectral variations, polynomial-based least squares (LSP) and polynomial-based total least squares (TLSP) are proposed to capture the nonlinear absorbance-concentration relationship. LSP is based on assuming that only absorbance noise exists; while TLSP takes both absorbance noise and concentration noise into consideration. In addition, based on different solving strategy, two optimization algorithms (limited-memory Broyden-Fletcher-Goldfarb-Shanno (LBFGS) algorithm and Levenberg-Marquardt (LM) algorithm) are combined with TLSP and then two different TLSP versions (termed as TLSP-LBFGS and TLSP-LM) are formed. The optimum order of each nonlinear model is determined by cross-validation. Comparison and analyses of the four models are made from two aspects: absorbance prediction and concentration prediction. The results for water-ethanol solution and ethanol-ethyl lactate solution show that LSP, TLSP-LBFGS, and TLSP-LM can, for both absorbance prediction and concentration prediction, obtain smaller root mean square error of prediction than CLS. Additionally, they can also greatly enhance the accuracy of estimated pure component spectra. However, from the view of concentration prediction, the Wilcoxon signed rank test shows that there is no statistically significant difference between each nonlinear model and CLS. © The Author(s) 2016.

  20. Evaluation of Prehospital Blood Products to Attenuate Acute Coagulopathy of Trauma in a Model of Severe Injury and Shock in Anesthetized Pigs.

    Science.gov (United States)

    Watts, Sarah; Nordmann, Giles; Brohi, Karim; Midwinter, Mark; Woolley, Tom; Gwyther, Robert; Wilson, Callie; Poon, Henrietta; Kirkman, Emrys

    2015-08-01

    Acute trauma coagulopathy (ATC) is seen in 30% to 40% of severely injured casualties. Early use of blood products attenuates ATC, but the timing for optimal effect is unknown. Emergent clinical practice has started prehospital deployment of blood products (combined packed red blood cells and fresh frozen plasma [PRBCs:FFP], and alternatively PRBCs alone), but this is associated with significant logistical burden and some clinical risk. It is therefore imperative to establish whether prehospital use of blood products is likely to confer benefit. This study compared the potential impact of prehospital resuscitation with (PRBCs:FFP 1:1 ratio) versus PRBCs alone versus 0.9% saline (standard of care) in a model of severe injury. Twenty-four terminally anesthetised Large White pigs received controlled soft tissue injury and controlled hemorrhage (35% blood volume) followed by a 30-min shock phase. The animals were allocated randomly to one of three treatment groups during a 60-min prehospital evacuation phase: hypotensive resuscitation (target systolic arterial pressure 80 mmHg) using either 0.9% saline (group 1, n = 9), PRBCs:FFP (group 2, n = 9), or PRBCs alone (group 3, n = 6). Following this phase, an in-hospital phase involving resuscitation to a normotensive target (110 mmHg systolic arterial blood pressure) using PRBCs:FFP was performed in all groups. There was no mortality in any group. A coagulopathy developed in group 1 (significant increase in clot initiation and dynamics shown by TEG [thromboelastography] R and K times) that persisted for 60 to 90 min into the in-hospital phase. The coagulopathy was significantly attenuated in groups 2 and 3 (P = 0.025 R time and P = 0.035 K time), which were not significantly different from each other. Finally, the volumes of resuscitation fluid required was significantly greater in group 1 compared with groups 2 and 3 (P = 0.0067) (2.8 ± 0.3 vs. 1.9 ± 0.2 and 1.8 ± 0.3 L, respectively). This difference was principally

  1. Coupling of Realistic Rate Estimates with Genomics for Assessing Contaminant Attenuation and Long-Term Plume Containment - Task 4: Modeling - Final Report

    International Nuclear Information System (INIS)

    Robert C. Starr

    2005-01-01

    seven plumes at 24 DOE facilities were screened, and 14 plumes were selected for detailed examination. In the plumes selected for further study, spatial changes in the concentration of a conservative co-contaminant were used to compensate for the effects of mixing and temporal changes in TCE release from the contaminant source. Decline in TCE concentration along a flow path in excess of the co contaminant concentration decline was attributed to cometabolic degradation. This study indicated that TCE was degraded in 9 of the 14 plumes examined, with first order degradation half-lives ranging from about 1 to 12 years. TCE degradation in about two-thirds of the plumes examined suggests that cometabolism of TCE in aerobic groundwater is a common occurrence, in contrast to the conventional wisdom that TCE is recalcitrant in aerobic groundwater. The degradation half-life values calculated in this study are short enough that natural attenuation may be a viable remedy in many aerobic plumes. Computer modeling of groundwater flow and contaminant transport and degradation is frequently used to predict the evolution of groundwater plumes, and for evaluating natural attenuation and other remedial alternatives. An important aspect of a computer model is the mathematical approach for describing degradation kinetics. A common approach is to assume that degradation occurs as a first-order process. First order kinetics are easily incorporated into transport models and require only a single value (a degradation half-life) to describe reaction kinetics. The use of first order kinetics is justified in many cases because more elaborate kinetic equations often closely approximate first order kinetics under typical field conditions. A previous modeling study successfully simulated the INL TCE plume using first order degradation kinetics. TCE cometabolism is the result of TCE reacting with microbial enzymes that were produced for other purposes, such as oxidizing a growth substrate to obtain

  2. Ultrasound fields in an attenuating medium

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Gandhi,, D; O'Brien,, W.D., Jr.

    1993-01-01

    of the rectangles and sums all contributions to arrive at the spatial impulse response for the aperture and field point. This approach makes it possible to model all transducer apertures, and the program can readily calculate the emitted, pulse-echo and continuous wave field. Attenuation is included by splitting...... it into a frequency dependent part and frequency independent part. The latter results in an attenuation factor that is multiplied onto the responses from the individual elements, and the frequency dependent part is handled by attenuating the basic one-dimensional pulse. The influence on ultrasound fields from......Ultrasound fields propagating in tissue will undergo changes in shape not only due to diffraction, but also due to the frequency dependent attenuation. Linear fields can be fairly well predicted for a non-attenuating medium like water by using the Tupholme-Stepanishen method for calculating...

  3. Dose attenuation by a carbon fiber linac couch and modeling with a treatment planning system; Medida de la atenuacion producida por la mesa de tratamiento de un acelerador lineal y su modelado en un sistema de planificacion

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez Galiano, P.; Garcia Sancho, J.M.; Crelgo, D.; Pamos, M.; Fernandez, J.; Vivanco, J.

    2010-07-01

    The purpose of this work is to investigate the attenuation caused by a carbon fiber linac treatment couch and the ability of a commercial radiotherapy treatment planning system to simulate it. The attenuation caused by an Exact{copyright} treatment couch in a Varian{copyright} Clinac{copyright} 2100 C/D was characterized in detail. Both 6 MV and 18 MV photon beams were studied. The treatment couch was modeled and incorporated to Elekta{copyright} XiO{copyright} treatment planning system. Measured and computed attenuation values were compared. As a result we found that the attenuation caused by this complex treatment couch is strongly dependent on the incidence angle of the beam. The measured attenuation values reach 16% for 6 MV and 10% for 18 MV. The model incorporated to the treatment planning software allows reducing the differences between measured and calculated data below 2.5% and 2.0% for 6 MV and 18 MV respectively. In conclusion, it is strongly recommended accounting for the perturbation caused by this carbon fiber treatment couch when the beam intersects it. The treatment planning system studied can simulate this treatment couch accurately. Clinical implementation of the described method requires a reliable procedure to reproduce the same patient geometry in the treatment delivery and planning. (Author).

  4. Deletion of Braun lipoprotein and plasminogen-activating protease-encoding genes attenuates Yersinia pestis in mouse models of bubonic and pneumonic plague.

    Science.gov (United States)

    van Lier, Christina J; Sha, Jian; Kirtley, Michelle L; Cao, Anthony; Tiner, Bethany L; Erova, Tatiana E; Cong, Yingzi; Kozlova, Elena V; Popov, Vsevolod L; Baze, Wallace B; Chopra, Ashok K

    2014-06-01

    Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4(+) and CD8(+) T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection.

  5. Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

    Directory of Open Access Journals (Sweden)

    Smeding Lonneke

    2012-03-01

    Full Text Available Abstract Background Injurious mechanical ventilation (MV may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis. Methods Normal rats and intraperitoneal (i.p. lipopolysaccharide (LPS-treated rats were ventilated with low (6 ml/kg and high (19 ml/kg tidal volumes (Vt under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP, central venous pressure (CVP, cardiac output (CO and pulmonary plateau pressure (Pplat were measured. Ex vivo myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM-1 and edema were measured to evaluate endothelial inflammation and leakage. Results MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function ex vivo but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters ex vivo. Conclusion MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.

  6. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    International Nuclear Information System (INIS)

    Jeong, Young-Il; Kim, Seung Hyun; Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja; Park, Jin Wook; Park, Yeong-Min; Lee, Sang Eun

    2011-01-01

    Highlights: → Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. → Induction of CD4 + CD25 + Foxp3 + T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. → C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4 + CD25 + Foxp3 + regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical relationship between the allergic immune

  7. Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin

    International Nuclear Information System (INIS)

    Xiong, Wei; Liu, Liang; Wang, Wen-Quan; Tang, Zhao-You; Ren, Zheng-Gang; Qiu, Shuang-Jian; Sun, Hui-Chuan; Wang, Lu; Liu, Bin-Bin; Li, Qi-Song; Zhang, Wei; Zhu, Xiao-Dong

    2010-01-01

    The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC

  8. Mucosal immunization with live attenuated Francisella novicida U112ΔiglB protects against pulmonary F. tularensis SCHU S4 in the Fischer 344 rat model.

    Directory of Open Access Journals (Sweden)

    Aimee L Signarovitz

    Full Text Available The need for an efficacious vaccine against Francisella tularensis is a consequence of its low infectious dose and high mortality rate if left untreated. This study sought to characterize a live attenuated subspecies novicida-based vaccine strain (U112ΔiglB in an established second rodent model of pulmonary tularemia, namely the Fischer 344 rat using two distinct routes of vaccination (intratracheal [i.t.] and oral. Attenuation was verified by comparing replication of U112ΔiglB with wild type parental strain U112 in F344 primary alveolar macrophages. U112ΔiglB exhibited an LD(50>10(7 CFU compared to the wild type (LD(50 = 5 × 10(6 CFU i.t.. Immunization with 10(7 CFU U112ΔiglB by i.t. and oral routes induced antigen-specific IFN-γ and potent humoral responses both systemically (IgG2a>IgG1 in serum and at the site of mucosal vaccination (respiratory/intestinal compartment. Importantly, vaccination with U112ΔiglB by either i.t. or oral routes provided equivalent levels of protection (50% survival in F344 rats against a subsequent pulmonary challenge with ~25 LD(50 (1.25 × 10(4 CFU of the highly human virulent strain SCHU S4. Collectively, these results provide further evidence on the utility of a mucosal vaccination platform with a defined subsp. novicida U112ΔiglB vaccine strain in conferring protective immunity against pulmonary tularemia.

  9. Minocycline through attenuation of oxidative stress and inflammatory response reduces the neuropathic pain in a rat model of chronic constriction injury

    Directory of Open Access Journals (Sweden)

    Abolfazl Abbaszadeh

    2018-02-01

    Full Text Available Objective(s: Several lines of evidence showed that minocycline possesses antioxidant and anti-inflammatory properties. This study aimed to demonstrate the effects of minocycline in rats subjected to chronic constriction injury (CCI. Materials and Methods: In this study four groups (n = 6–8 of rats were used as follows: Sham, CCI, CCI + minocycline (MIN 10 mg/Kg (IP and CCI + MIN 30 mg/Kg (IP. On days 3, 7, 14, and 21 post-surgery hot-plate, acetone, and von Frey tests were carried out. Finally, Motor Nerve Conduction Velocity Evaluation (MNCV assessment was performed and spinal cords were harvested in order to measure tissue concentrations of TNF_α, IL-1β, Glutathione peroxidase (GPx, Superoxide dismutase (SOD and Malondialdehyde (MDA. Extent of perineural inflammation and damage around the sciatic nerve was histopathologically evaluated. Results: Our results demonstrated that CCI significantly caused hyperalgesia and allodynia twenty-one days after CCI. MIN attenuated heat hyperalgesia, cold and mechanical allodynia and MNCV in animals. MIN also decreased the levels of TNF_α and IL-1β. Antioxidative enzymes (SOD, MDA, and GPx were restored following MIN treatment. Our findings showed that MIN decreased perineural inflammation around the sciatic nerve. According to the results, the neuropathic pain reduced in the CCI hyperalgesia model using 30 mg/kg of minocycline. Conclusion: It is suggested that antinociceptive effects of minocycline might be mediated through the inhibition of inflammatory response and attenuation of oxidative stress.

  10. Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

    Science.gov (United States)

    Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2017-11-01

    Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel Walls; M.T. Taner; Gary Mavko; Jack Dvorkin

    2002-01-01

    In Section 1 of this first report we will describe the work we are doing to collect and analyze rock physics data for the purpose of modeling seismic attenuation from other measurable quantities such as porosity, water saturation, clay content and net stress. This work and other empirical methods to be presented later, will form the basis for ''Q pseudo-well modeling'' that is a key part of this project. In Section 2 of this report, we will show the fundamentals of a new method to extract Q, dispersion, and attenuation from field seismic data. The method is called Gabor-Morlet time-frequency decomposition. This technique has a number of advantages including greater stability and better time resolution than spectral ratio methods.

  12. Infection in a rat model reactivates attenuated virulence after long-term axenic culture of Acanthamoeba spp

    Directory of Open Access Journals (Sweden)

    Carolina De Marco Verissimo

    2013-11-01

    Full Text Available Prolonged culturing of many microorganisms leads to the loss of virulence and a reduction of their infective capacity. However, little is known about the changes in the pathogenic strains of Acanthamoeba after long culture periods. Our study evaluated the effect of prolonged culturing on the invasiveness of different isolates of Acanthamoeba in an in vivo rat model. ATCC strains of Acanthamoeba, isolates from the environment and clinical cases were evaluated. The in vivo model was effective in establishing the infection and differentiating the pathogenicity of the isolates and re-isolates. The amoebae cultured in the laboratory for long periods were less virulent than those that were recently isolated, confirming the importance of passing Acanthamoeba strains in animal models.

  13. A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model

    Directory of Open Access Journals (Sweden)

    McNamara Laurie K

    2007-09-01

    Full Text Available Abstract Background An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiology that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer's disease (AD. This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery molecular target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ and other disease-relevant stressors. However, the vast majority of small molecule drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small molecules capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurologic outcomes. Methods A novel synthetic small molecule based on a molecular scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model. Results A novel, CNS-penetrant, non-toxic, orally bioavailable, small molecule inhibitor of p38α MAPK (MW01-2-069A-SRM was developed. Oral administration of the compound at a low dose (2.5 mg/kg resulted in attenuation of

  14. Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis

    Science.gov (United States)

    XU, WEI; HUANG, MINGQING; ZHANG, YUQIN; LI, HUANG; ZHENG, HAIYIN; YU, LISHUANG; CHU, KEDAN; LIN, YU; CHEN, LIDIAN

    2016-01-01

    Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)-6, IL-8, tumor necrosis factor-α and nuclear factor-κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription-polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE-treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action. PMID:27035125

  15. A biogeochemical transport model to simulate the attenuation of chlorinated hydrocarbon contaminant fluxes across the groundwater-surface water interface

    DEFF Research Database (Denmark)

    Malaguerra, Flavio; Binning, Philip John; Albrechtsen, Hans-Jørgen

    2009-01-01

    and biogeochemical transformation model of the discharge of a TCE plume into a stream, and to determine which parameters most strongly affect pollutant discharge concentrations. Here biological kinetics and the interaction with the soil matrix are implemented in PHREEQC. The ability of PHREEQC to deal with a large...

  16. Landing gear noise attenuation

    Science.gov (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  17. A porcine ex vivo lung perfusion model with maximal argon exposure to attenuate ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    An Martens

    2017-01-01

    Full Text Available Argon (Ar is a noble gas with known organoprotective effects in rodents and in vitro models. In a previous study we failed to find a postconditioning effect of Ar during ex vivo lung perfusion (EVLP on warm-ischemic injury in a porcine model. In this study, we further investigated a prolonged exposure to Ar to decrease cold ischemia-reperfusion injury after lung transplantation in a porcine model with EVLP assessment. Domestic pigs (n = 6/group were pre-conditioned for 6 hours with 21% O 2 and 79% N 2 (CONTR or 79% Ar (ARG. Subsequently, lungs were cold flushed and stored inflated on ice for 18 hours inflated with the same gas mixtures. Next, lungs were perfused for 4 hours on EVLP (acellular while ventilated with 12% O 2 and 88% N 2 (CONTR group or 88% Ar (ARG group. The perfusate was saturated with the same gas mixture but with the addition of CO 2 to an end-tidal CO 2 of 35-45 mmHg. The saturated perfusate was drained and lungs were perfused with whole blood for an additional 2 hours on EVLP. Evaluation at the end of EVLP did not show significant effects on physiologic parameters by prolonged exposure to Ar. Also wet-to-dry weight ratio did not improve in the ARG group. Although in other organ systems protective effects of Ar have been shown, we did not detect beneficial effects of a high concentration of Ar on cold pulmonary ischemia-reperfusion injury in a porcine lung model after prolonged exposure to Ar in this porcine model with EVLP assessment.

  18. A statistical rain attenuation prediction model with application to the advanced communication technology satellite project. 3: A stochastic rain fade control algorithm for satellite link power via non linear Markow filtering theory

    Science.gov (United States)

    Manning, Robert M.

    1991-01-01

    The dynamic and composite nature of propagation impairments that are incurred on Earth-space communications links at frequencies in and above 30/20 GHz Ka band, i.e., rain attenuation, cloud and/or clear air scintillation, etc., combined with the need to counter such degradations after the small link margins have been exceeded, necessitate the use of dynamic statistical identification and prediction processing of the fading signal in order to optimally estimate and predict the levels of each of the deleterious attenuation components. Such requirements are being met in NASA's Advanced Communications Technology Satellite (ACTS) Project by the implementation of optimal processing schemes derived through the use of the Rain Attenuation Prediction Model and nonlinear Markov filtering theory.

  19. The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

    Science.gov (United States)

    Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

    2015-01-01

    We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Yanling Zhang

    Full Text Available Pharmacological inhibition of the proximal tubular sodium-glucose linked cotransporter-2 (SGLT2 leads to glycosuria in both diabetic and non-diabetic settings. As a consequence of their ability to modulate tubuloglomerular feedback, SGLT2 inhibitors, like agents that block the renin-angiotensin system, reduce intraglomerular pressure and single nephron GFR, potentially affording renoprotection. To examine this further we administered the SGLT2 inhibitor, dapagliflozin, to 5/6 (subtotally nephrectomised rats, a model of progressive chronic kidney disease (CKD that like CKD in humans is characterised by single nephron hyperfiltration and intraglomerular hypertension and where angiotensin converting enzyme inhibitors and angiotensin receptor blockers are demonstrably beneficial. When compared with untreated rats, both sham surgery and 5/6 nephrectomised rats that had received dapagliflozin experienced substantial glycosuria. Nephrectomised rats developed hypertension, heavy proteinuria and declining GFR that was unaffected by the administration of dapagliflozin. Similarly, SGLT2 inhibition did not attenuate the extent of glomerulosclerosis, tubulointerstitial fibrosis or overexpression of the profibrotic cytokine, transforming growth factor-ß1 mRNA in the kidneys of 5/6 nephrectomised rats. While not precluding beneficial effects in the diabetic setting, these findings indicate that SGLT2 inhibition does not have renoprotective effects in this classical model of progressive non-diabetic CKD.

  1. Early post-stressor intervention with minocycline, a second-generation tetracycline, attenuates post-traumatic stress response in an animal model of PTSD.

    Science.gov (United States)

    Levkovitz, Yechiel; Fenchel, Daphna; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

    2015-01-01

    We assessed the effects of minocycline, a tetracycline with anti-inflammatory, anti-apoptotic and neuroprotective capacities, in an animal model of post-traumatic stress disorder (PTSD). Rats were exposed to psychogenic stress and treated 1h later with minocycline or saline. Behavioral measures included the elevated plus-maze (EPM) and acoustic startle response (ASR) 7 days post stress-exposure. One day after behavioral testing, animals were exposed to a trauma cue and freezing response was assessed. Local levels of cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the hippocampus, frontal cortex (FC) and hypothalamus were then examined. Minocycline attenuated anxious-like behaviors in stress-exposed rats. In addition, decreased levels of cytokines were measured in exposed rats treated with minocycline compared to their counterparts treated with saline. This study suggests a potential use of minocycline in preventing physiological and behavioral alternations resulting from acute exposure to psychological stress. As this is the first study to report beneficial outcomes for minocycline treatment in an animal model of PTSD, further investigations of the use of minocycline in stress-related conditions with emphasis on PTSD is needed. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  2. Morus alba L. Stem Extract Attenuates Pain and Articular Cartilage Damage in the Anterior Cruciate Ligament Transection-Induced Rat Model of Osteoarthritis.

    Science.gov (United States)

    Khunakornvichaya, Arada; Lekmeechai, Sujinna; Pham, Phi Phuong; Himakoun, Wanwisa; Pitaksuteepong, Tasana; Morales, Noppawan Phumala; Hemstapat, Warinkarn

    2016-01-01

    This study was designed to investigate the anti-nociceptive effect of Morus alba stem extract as well as its cartilage protective effect in the anterior cruciate ligament transection (ACLT)-induced rat model of osteoarthritis (OA). The anti-nociceptive effect of this plant extract was determined by measuring hind limb weight bearing, while the severity of cartilage damage to the knee joints was evaluated using the modified Mankin grading system. Oral administration of M. alba stem extract (56 and 560 mg/kg) significantly attenuated joint pain as indicated by a significant (p alba stem extract at 56 and 560 mg/kg when compared to those of the vehicle-treated OA-induced group. In addition, a significant improvement in the Mankin score was also observed in rats treated with 560 mg/kg M. alba stem extract, which was in agreement with its pain-relieving effect. The results showed that M. alba stem extract exhibited an anti-nociceptive effect as well as cartilage protection in the ACLT-induced rat model of OA, supporting its potential use as a therapeutic treatment for OA. © 2016 S. Karger AG, Basel.

  3. Targeting Interleukin-13 with Tralokinumab Attenuates Lung Fibrosis and Epithelial Damage in a Humanized SCID Idiopathic Pulmonary Fibrosis Model

    Science.gov (United States)

    Zhang, Huilan; Oak, Sameer R.; Coelho, Ana Lucia; Herath, Athula; Flaherty, Kevin R.; Lee, Joyce; Bell, Matt; Knight, Darryl A.; Martinez, Fernando J.; Sleeman, Matthew A.; Herzog, Erica L.; Hogaboam, Cory M.

    2014-01-01

    The aberrant fibrotic and repair responses in the lung are major hallmarks of idiopathic pulmonary fibrosis (IPF). Numerous antifibrotic strategies have been used in the clinic with limited success, raising the possibility that an effective therapeutic strategy in this disease must inhibit fibrosis and promote appropriate lung repair mechanisms. IL-13 represents an attractive target in IPF, but its disease association and mechanism of action remains unknown. In the present study, an overexpression of IL-13 and IL-13 pathway markers was associated with IPF, particularly a rapidly progressive form of this disease. Targeting IL-13 in a humanized experimental model of pulmonary fibrosis using tralokinumab (CAT354) was found to therapeutically block aberrant lung remodeling in this model. However, targeting IL-13 was also found to promote lung repair and to restore epithelial integrity. Thus, targeting IL-13 inhibits fibrotic processes and enhances repair processes in the lung. PMID:24325475

  4. A model of gender prejudice, power, and discrimination: How hierarchy-enhancing factors predominate over hierarchy-attenuating factors

    OpenAIRE

    Kleinlogel, E. P.; Dietz, J.

    2015-01-01

    Gender inequalities remain an issue in our society and particularly in the workplace. Several factors can explain this gender difference in top-level managerial positions such as career ambitions but also biases against women. In our chapter, we propose a model explaining why gender inequalities and particularly discrimination against women is still present in our societies despite social norms and existing legislation on gender equality. To this purpose, we review research on discrimination ...

  5. Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains.

    Science.gov (United States)

    Kostyalik, Diána; Vas, Szilvia; Kátai, Zita; Kitka, Tamás; Gyertyán, István; Bagdy, Gyorgy; Tóthfalusi, László

    2014-11-19

    Shortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet. Chronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis. Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5-9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD. In conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence

  6. Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model.

    Science.gov (United States)

    Omachi, Kohei; Miyakita, Rui; Fukuda, Ryosuke; Kai, Yukari; Suico, Mary Ann; Yokota, Tsubasa; Kamura, Misato; Shuto, Tsuyoshi; Kai, Hirofumi

    2017-12-01

    Alport syndrome (AS) is a hereditary kidney disease caused by mutation of type IV collagen. Loss of collagen network induces collapse of glomerular basement membrane (GBM) structure. The previous studies showed that upregulation of some tyrosine kinase receptors signaling accompanied GBM disorder in AS mouse model. EGFR signaling is one of the well-known receptor kinase signaling that is involved in glomerular diseases. However, whether EGFR signaling is relevant to AS progression is still uninvestigated. Here, we determined the involvement of EGFR in AS and the effect of suppressing EGFR signaling by erlotinib treatment on AS progression. Phosphorylated EGFR expression was investigated by Western blotting analysis and immunostaining of kidney tissues of Col4a5 mutant mice (a mouse model of X-linked AS). To check the effect of blocking EGFR signaling in AS, we administered erlotinib to AS mice once a day (10 mg/kg/day) orally for 18 weeks. Renal function parameters (proteinuria, serum creatinine, and BUN) and renal histology were assessed, and the gene expressions of inflammatory cytokines were analyzed in renal tissues. Phosphorylated EGFR expression was upregulated in AS mice kidney tissues. Erlotinib slightly reduced the urinary protein and suppressed the expression of renal injury markers (Lcn2, Lysozyme) and inflammatory cytokines (Il-6, Il-1β and KC). Erlotinib did not improve renal pathology, such as glomerular sclerosis and fibrosis. These findings suggest that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model.

  7. Attenuated ventricular β-adrenergic response and reduced repolarization reserve in a rabbit model of chronic heart failure

    DEFF Research Database (Denmark)

    Nissen, Jakob Dahl; Thomsen, Morten Bækgaard; Bentzen, Bo Hjorth

    2012-01-01

    Animal models of pacing-induced heart failure (HF) are often associated with high acute mortality secondary to high pacing frequencies. The present study therefore exploits lower-frequency left ventricular pacing (300 beats per minute) in rabbits for 11 weeks to produce chronic HF with low acute...... mortality but profound structural, functional, and electrical remodeling and compare with nonpaced controls. Pacing increased heart weight/body weight ratio and decreased left ventricular fractional shortening in tachypaced only. Electrocardiogram recordings during sinus rhythm revealed QTc prolongation...... in paced animals. Ventricular arrhythmias or sudden death was not observed. Isoproterenol increased heart rate similarly in both groups but showed a blunted QT-shortening effect in tachypaced rabbits compared with controls. Langendorff experiments revealed significant monophasic action potential duration...

  8. Dexamethasone attenuates VEGF expression and inflammation but not barrier dysfunction in a murine model of ventilator-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Maria A Hegeman

    Full Text Available BACKGROUND: Ventilator-induced lung injury (VILI is characterized by vascular leakage and inflammatory responses eventually leading to pulmonary dysfunction. Vascular endothelial growth factor (VEGF has been proposed to be involved in the pathogenesis of VILI. This study examines the inhibitory effect of dexamethasone on VEGF expression, inflammation and alveolar-capillary barrier dysfunction in an established murine model of VILI. METHODS: Healthy male C57Bl/6 mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with an inspiratory pressure of 10 cmH2O ("lower" tidal volumes of ∼7.5 ml/kg; LVT or 18 cmH2O ("higher" tidal volumes of ∼15 ml/kg; HVT. Dexamethasone was intravenously administered at the initiation of HVT-ventilation. Non-ventilated mice served as controls. Study endpoints included VEGF and inflammatory mediator expression in lung tissue, neutrophil and protein levels in bronchoalveolar lavage fluid, PaO2 to FiO2 ratios and lung wet to dry ratios. RESULTS: Particularly HVT-ventilation led to alveolar-capillary barrier dysfunction as reflected by reduced PaO2 to FiO2 ratios, elevated alveolar protein levels and increased lung wet to dry ratios. Moreover, VILI was associated with enhanced VEGF production, inflammatory mediator expression and neutrophil infiltration. Dexamethasone treatment inhibited VEGF and pro-inflammatory response in lungs of HVT-ventilated mice, without improving alveolar-capillary permeability, gas exchange and pulmonary edema formation. CONCLUSIONS: Dexamethasone treatment completely abolishes ventilator-induced VEGF expression and inflammation. However, dexamethasone does not protect against alveolar-capillary barrier dysfunction in an established murine model of VILI.

  9. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model

    International Nuclear Information System (INIS)

    Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao; Karpe, Pinakin Arun; Malek, Vajir; Patel, Deep; Tikoo, Kulbhushan

    2016-01-01

    Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2 weeks. 48 h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocyte count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. - Highlights: • Diminazene aceturate (DIZE), an ACE2 activator prevents ovalbumin-induced asthma. • DIZE acted by upregulating ACE2, downregulating ACE1, MAPKs, markers of inflammation, apoptosis. • DIZE reduced airway inflammation, fibrosis, right ventricular hypertrophy and

  10. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model

    Energy Technology Data Exchange (ETDEWEB)

    Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao; Karpe, Pinakin Arun; Malek, Vajir; Patel, Deep; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com

    2016-09-01

    Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2 weeks. 48 h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocyte count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. - Highlights: • Diminazene aceturate (DIZE), an ACE2 activator prevents ovalbumin-induced asthma. • DIZE acted by upregulating ACE2, downregulating ACE1, MAPKs, markers of inflammation, apoptosis. • DIZE reduced airway inflammation, fibrosis, right ventricular hypertrophy and

  11. P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yan Deng

    2015-01-01

    Conclusions: The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

  12. Icariin Attenuates Synaptic and Cognitive Deficits in an Aβ1–42-Induced Rat Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Chenxia Sheng

    2017-01-01

    Full Text Available Icariin (ICA, a prenylated flavanol glycoside present in abundant quantities in Epimedium sagittatum, has shown promise in the treatment and prevention of Alzheimer’s disease. Damage to synaptic plasticity induced by amyloid-beta-mediated neurotoxicity is considered a main pathological mechanism driving the learning and memory deficits present in patients with Alzheimer’s disease. This study investigated the neuroprotective effects of icariin in an Aβ1–42-induced rat model of Alzheimer’s disease. Our results showed that Aβ1–42 injection induced loss of learning and memory behaviour in the Morris water maze, which could be reversed with intragastric administration of ICA. Furthermore, ICA reversed decreases in PSD-95, BDNF, pTrkB, pAkt, and pCREB expressions and prevented deterioration of synaptic interface structure. These findings indicate that ICA may improve synaptic plasticity through the BDNF/TrkB/Akt pathway and provide further evidence for its clinical application to improve learning and memory in patients with Alzheimer’s disease.

  13. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young-Il [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Kim, Seung Hyun [Div. of AIDS, National Institute of Health, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Ju, Jung Won; Cho, Shin Hyeong; Lee, Won Ja [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of); Park, Jin Wook; Park, Yeong-Min [Dept. of Microbiology and Immunology, College of Medicine, Pusan National University, Yang-San (Korea, Republic of); Lee, Sang Eun, E-mail: ondalgl@cdc.go.kr [Div. of Malaria and Parasitic Diseases, Korea Centers for Disease Control and Prevention, Osong (Korea, Republic of)

    2011-04-22

    Highlights: {yields} Treatment with Clonorchis sinensis-derived total protein attenuates OVA-induced airway inflammation and AHR to methacholine. {yields} Induction of CD4{sup +}CD25{sup +}Foxp3{sup +} T cells and IL-10 along with suppression of splenocyte proliferation by C. sinensis-derived total protein. {yields} C. sinensis-derived total protein interferes with the expression of co-stimulatory molecules in DCs. -- Abstract: Asthma is characterized by Th2-mediated inflammation, resulting in airway hyperresponsiveness (AHR) through airway remodeling. Recent epidemiological and experimental reports have suggested an inverse relationship between the development of allergy and helminth infections. Infection by Clonorchis sinensis, a liver fluke that resides in the bile duct of humans, is endemic predominantly in Asia including Korea and China. Using a murine model for asthma, we investigated the effects of C. sinensis-derived total protein (Cs-TP) on allergen-induced airway inflammation and the mechanism underlying the protective effects of Cs-TP administration on asthma. Treatment with Cs-TP attenuated OVA-induced airway inflammation and methacholine-induced AHR, as well as eosinophilia development, lymphocyte infiltration into the lung, and goblet cell metaplasia. This protective effect of Cs-TP is associated with markedly reduced OVA-specific IgE and Th1/Th2 cytokine production. Moreover, Cs-TP increased the number of CD4{sup +}CD25{sup +}Foxp3{sup +} regulatory T (Treg) cells as well as their suppressive activity. In fact, proliferation of OVA-restimulated splenocytes was suppressed significantly. Cs-TP also inhibited the expression of such co-stimulatory molecules as CD80, CD86, and CD40 in LPS- or OVA-stimulated dendritic cells (DCs), suggesting that Cs-TP could interfere with the capacity of airway DCs to prime naive T cells. These data demonstrate the capacity of C. sinensis to ameliorate allergic asthma and broaden our understanding of the paradoxical

  14. Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model

    Directory of Open Access Journals (Sweden)

    Jingwei Zhou

    2017-01-01

    Full Text Available A derivative formula, DGBX, which is composed of three herbs (Radix astragali, Radix Angelicae sinensis, and Coptis chinensis Franch, is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT (Radix astragali and Radix Angelicae sinensis. We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs due to the aberrant immune response in a mouse model of aplastic anemia (AA. Cyclosporine (CsA, an immunosuppressor, was used as the positive control. Our results indicated that DGBX could downregulate the production of IFNγ in bone marrow cells by interfering with the binding between SLAM and SAP and the expressions of Fyn and T-bet. This herbal formula can also inhibit the activation of Fas-mediated apoptosis, interferon regulatory factor-1-induced JAK/Stat, and eukaryotic initiation factor 2 signaling pathways and thereby induce proliferation and attenuate apoptosis of HSCs. In conclusion, DGBX can relieve the immune-mediated destruction of HSCs, repair hematopoietic failure, and recover the hematopoietic function of HSCs in hematogenesis. Therefore, DGBX can be used in traditional medicine against AA as a complementary and alternative immunosuppressive therapeutic formula.

  15. Possible role of oxidative stress and immunological activation in mouse model of chronic fatigue syndrome and its attenuation by olive extract.

    Science.gov (United States)

    Gupta, Amit; Vij, Garima; Chopra, Kanwaljit

    2010-09-14

    Various putative theories involved in the development of chronic fatigue syndrome revolve around the role of stress, infection and oxidative stress. Scientific evidence highlighting the protective role of nutritional supplements in chronic fatigue syndrome is lacking. Based on these assumptions, the present study was designed to evaluate the effect of olive extract in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigen were used as immunogens. The assessment of chronic fatigue syndrome was based on immobility period during chronic water-immersion stress test for 10 min daily. The stress-induced hyperalgesia was measured by tail withdrawal latency. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and oxidative stress on the 19th day. Serum tumor necrosis factor-alpha (TNF-α) levels were also markedly increased with LPS or BA challenge. Concurrent treatment with olive extract resulted in a significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as serum TNF-α levels. The results of the present study strongly indicate the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome and highlight the valuable role of olive extract in combating chronic fatigue syndrome. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam

    Directory of Open Access Journals (Sweden)

    Min Jae Kim

    2018-01-01

    Full Text Available Aim. Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. Methods. Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4 was performed following ischemic injury. Results. Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg, while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1 expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. Conclusions. These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

  17. Oral immunization using HgbA in a recombinant chancroid vaccine delivered by attenuated Salmonella typhimurium SL3261 in the temperature-dependent rabbit model.

    Science.gov (United States)

    Breau, Cathy; Cameron, D William; Desjardins, Marc; Lee, B Craig

    2012-01-31

    Chancroid, a sexually transmitted genital ulcer disease caused by the Gram-negative bacterium Haemophilus ducreyi, facilitates the acquisition and transmission of HIV. An effective vaccine against chancroid has not been developed. In this preliminary study, the gene encoding the H. ducreyi outer membrane hemoglobin receptor HgbA was cloned into the plasmid pTETnir15. The recombinant construct was introduced into the attenuated Salmonella typhimurium SL3261 strain and stable expression was induced in vitro under anaerobic conditions. The vaccine strain was delivered into the temperature-dependent rabbit model of chancroid by intragastric immunization as a single dose, or as three doses administered at two-weekly intervals. No specific antibody to HgbA was elicited after either dose schedule. Although the plasmid vector survived in vivo passage for up to 15 days following single oral challenge, HgbA expression was restricted to plasmid isolates recovered one day after immunization. Rabbits inoculated with the 3-dose booster regimen achieved no protective immunity from homologous challenge. These results emphasize that refinements in plasmid design to enhance a durable heterologous protein expression are necessary for the development of a live oral vaccine against chancroid. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

    Science.gov (United States)

    Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

    2016-01-01

    Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

    International Nuclear Information System (INIS)

    Lambertucci, Flavia; Motiño, Omar; Villar, Silvina; Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A; Martín-Sanz, Paloma; Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar; Ronco, María Teresa

    2017-01-01

    Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice

  20. Pan-Influenza A Protection by Prime-Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model.

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime-boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro , CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo . Heterologous combination of prime (H1)-boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a "truly" universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising results

  1. Pan-Influenza A Protection by Prime–Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime–boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro, CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo. Heterologous combination of prime (H1)–boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a “truly” universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising

  2. Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Lambertucci, Flavia [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Motiño, Omar [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Villar, Silvina [Instituto de Inmunología, Facultad de Ciencias Médicas, UNR, Suipacha 531, 2000 Rosario (Argentina); Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Martín-Sanz, Paloma [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid (Spain); Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Ronco, María Teresa, E-mail: ronco@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina)

    2017-01-15

    Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice.

  3. Inhibition of p38 MAPK attenuates renal atrophy and fibrosis in a murine renal artery stenosis model.

    Science.gov (United States)

    Wang, Diping; Warner, Gina M; Yin, Ping; Knudsen, Bruce E; Cheng, Jingfei; Butters, Kim A; Lien, Karen R; Gray, Catherine E; Garovic, Vesna D; Lerman, Lilach O; Textor, Stephen C; Nath, Karl A; Simari, Robert D; Grande, Joseph P

    2013-04-01

    Renal artery stenosis (RAS) is an important cause of chronic renal dysfunction. Recent studies have underscored a critical role for CCL2 (MCP-1)-mediated inflammation in the progression of chronic renal damage in RAS and other chronic renal diseases. In vitro studies have implicated p38 MAPK as a critical intermediate for the production of CCL2. However, a potential role of p38 signaling in the development and progression of chronic renal disease in RAS has not been previously defined. We sought to test the hypothesis that inhibition of p38 MAPK ameliorates chronic renal injury in mice with RAS. We established a murine RAS model by placing a cuff on the right renal artery and treated mice with the p38 inhibitor SB203580 or vehicle for 2 wk. In mice treated with vehicle, the cuffed kidney developed interstitial fibrosis, tubular atrophy, and interstitial inflammation. In mice treated with SB203580, the RAS-induced renal atrophy was reduced (70% vs. 39%, P < 0.05). SB203580 also reduced interstitial inflammation and extracellular matrix deposition but had no effect on the development of hypertension. SB203580 partially blocked the induction of CCL2, CCL7 (MCP-3), CC chemokine receptor 2 (CCR2), and collagen 4 mRNA expression in the cuffed kidneys. In vitro, blockade of p38 hindered both TNF-α and TGF-β-induced CCL2 upregulation. Based on these observations, we conclude that p38 MAPK plays a critical role in the induction of CCL2/CCL7/CCR2 system and the development of interstitial inflammation in RAS.

  4. Olive phenolics as c-Met inhibitors: (--Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

    Directory of Open Access Journals (Sweden)

    Mohamed R Akl

    Full Text Available Dysregulation of the Hepatocyte growth factor (HGF/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT, angiogenesis, invasion, and metastasis. (--Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (--oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer. Results showed that (--oleocanthal inhibits the growth of human breast cancer cell lines MDA-MB-231, MCF-7 and BT-474 while similar treatment doses were found to have no effect on normal human MCF10A cell growth. In addition, (--oleocanthal treatment caused a dose-dependent inhibition of HGF-induced cell migration, invasion and G1/S cell cycle progression in breast cancer cell lines. Moreover, (--oleocanthal treatment effects were found to be mediated via inhibition of HGF-induced c-Met activation and its downstream mitogenic signaling pathways. This growth inhibitory effect is associated with blockade of EMT and reduction in cellular motility. Further results from in vivo studies showed that (--oleocanthal treatment suppressed tumor cell growth in an orthotopic model of breast cancer in athymic nude mice. Collectively, the findings of this study suggest that (--oleocanthal is a promising dietary supplement lead with potential for therapeutic use to control malignancies with aberrant c-Met activity.

  5. Attenuation of pyrite oxidation with a fly ash pre-barrier: Reactive transport modelling of column experiments

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Lopez, R.; Cama, J.; Nieto, J.M.; Ayora, C.; Saaltink, M.W. [University of Huelva, Huelva (Spain). Dept. of Geology

    2009-09-15

    Conventional permeable reactive barriers (PRBs) for passive treatment of groundwater contaminated by acid mine drainage (AMD) use limestone as reactive material that neutralizes water acidity. However, the limestone-alkalinity potential ceases as inevitable precipitation of secondary metal-phases on grain surfaces occurs, limiting its efficiency. In the present study, fly ash derived from coal combustion is investigated as an alternative alkalinity generating material for the passive treatment of AMD using solution-saturated column experiments. Unlike conventional systems, the utilization of fly ash in a pre-barrier to intercept the non-polluted recharge water before this water reacts with pyrite-rich wastes is proposed. Chemical variation in the columns was interpreted with the reactive transport code RETRASO. In parallel, kinetics of fly ash dissolution at alkaline pH were studied using flow-through experiments and incorporated into the model. In a saturated column filled solely with pyritic sludge-quartz sand (1: 10), oxidation took place at acidic conditions (pH 3.7). According to SO{sub 4}{sup 2-} release and pH, pyrite dissolution occurred favourably in the solution-saturated porous medium until dissolved O{sub 2} was totally consumed. In a second saturated column, pyrite oxidation took place at alkaline conditions (pH 10.45) as acidity was neutralized by fly ash dissolution in a previous level. At this pH Fe release from pyrite dissolution was immediately depleted as Fe-oxy(hydroxide) phases that precipitated on the pyrite grains, forming Fe-coatings (microencapsulation). With time, pyrite microencapsulation inhibited oxidation in practically 97% of the pyritic sludge. Rapid pyrite-surface passivation decreased its reactivity, preventing AMD production in the relatively short term.

  6. Yougui Pills Attenuate Cartilage Degeneration via Activation of TGF-β/Smad Signaling in Chondrocyte of Osteoarthritic Mouse Model.

    Science.gov (United States)

    Zhang, Lei; Wang, Ping-Er; Ying, Jun; Jin, Xing; Luo, Cheng; Xu, Taotao; Xu, Shibing; Dong, Rui; Xiao, Luwei; Tong, Peijian; Jin, Hongting

    2017-01-01

    Yougui pills (YGPs) have been used for centuries in the treatment of Chinese patients with Kidney-Yang Deficiency Syndrome. Despite the fact that the efficiency of YGPs on treating osteoarthritis has been verified in clinic, the underlying mechanisms are not totally understood. The present study observes the therapeutic role of YGPs and mechanisms underlying its chondroprotective action in osteoarthritic cartilage. To evaluate the chondroprotective effects of YGPs, we examined the impact of orally administered YGPs in a model of destabilization of the medial meniscus (DMM). Male C57BL/6J mice were provided a daily treatment of YGPs and a DMM surgery was performed on the right knee. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histomorphometry, OARSI scoring, micro-CT and immunohistochemistry for COL-2, MMP-13 and pSMAD-2. We also performed the relative experiments mentioned above in mice with Tgfbr2 conditional knockout ( TGF-βRII Col2ER mice) in articular cartilage. To evaluate the safety of YGPs, hematology was determined in each group. Amelioration of cartilage degradation was observed in the YGPs group, with increases in cartilage area and thickness, proteoglycan matrix, and decreases in OARSI score at 12 weeks post surgery. In addition, reduced BV/TV and Tb. Th, and elevated Tb. Sp were observed in DMM-induced mice followed by YGPs treatment. Moreover, the preservation of cartilage correlated with reduced MMP-13, and elevated COL-2 and pSMAD-2 protein expressional levels were also revealed in DMM-induced mice treated with YGPs. Similarly, TGF-βRII Col2ER mice exhibited significant OA-like phenotype. However, no significant difference in cartilage structure was observed in TGF-βRII Col2ER mice after YGPs treatment. Interestingly, no obvious adverse effects were observed in mice from each group based on the hematologic analyses. These findings suggested that YGPs could inhibit cartilage degradation through enhancing TGF

  7. Novel fused oxazepino-indoles (FOIs) attenuate liver carcinogenesis via IL-6/JAK2/STAT3 signaling blockade as evidenced through data-based mathematical modeling.

    Science.gov (United States)

    Singh, Ashok K; Bhadauria, Archana Singh; Kumar, Umesh; Raj, Vinit; Maurya, Vimal; Kumar, Dinesh; Maity, Biswanath; Prakash, Anand; De, Arnab; Samanta, Amalesh; Saha, Sudipta

    2018-05-15

    To potentiate the well-documented tumor protecting ability of paullones, literatures demand for rational modifications in paullone ring structure and exploration of a precise mechanism underlying their antitumor effects. Thus, recently we synthesized novel paullone-like scaffold, 5H-benzo [2, 3][1,4]oxazepino[5,6-b]indoles, where compounds 13a and 14a attenuated the growth of liver cancer specific Hep-G2 cells in vitro and formed stable binding complex with IL-6. Henceforth, we hypothesized that this action is probably due to the blockade of IL-6 mediated JAK2/STAT3 signaling cascade. A preclinical study was conducted using NDEA-induced HCC rat model by oral administration of FOIs at 10 mg/kg dose for 15 days. The molecular insights were confirmed through ELISA, qRT-PCR, western blot analyses. The study was further confirmed by data-based mathematical modeling using the quantitative data obtained from western blot analysis. 1 H NMR based metabolomics study was also performed to unveil metabolite discriminations among various studied groups. We identified that the HCC condition was produced due to the IL-6 induced activation of JAK2 and STAT3 which, in turn, was due to enhanced phosphorylation of JAK2 and STAT3. The treatment with FOIs led to the significant blockade of the IL-6 mediated JAK2/STAT3 signaling pathway. Besides, FOIs showed their potential ability in restoring perturbed metabolites linked to HCC. In particular, the anticancer efficacy of compound 13a was comparable or somewhat better than marketed chemotherapeutics, 5-flurouracil. These findings altogether opened up possibilities of developing fused oxazepino-indoles (FOIs) as new candidate molecule for plausible alternative of paullones to treat liver cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Modelling the fate of six common pharmaceuticals in a small stream: quantification of attenuation and retention in different stream-specific environments

    Science.gov (United States)

    Riml, Joakim; Wörman, Anders; Kunkel, Uwe; Radke, Michael

    2013-04-01

    Detection of pharmaceutical residues in streaming waters is common in urbanized areas. Although the occurrence and source of these micropollutants is known, their behavior in these aquatic ecosystems is still only partly understood. Specifically, quantitative information of biogeochemical processes in stream-specific environments where predominant reactions occur is often missing. In an attempt to address this knowledge gap, we performed simultaneous tracer tests in Säva Brook, Sweden, with bezafibrate, clofibric acid, diclofenac, ibuprofen, metoprolol and naproxen, as well as with the more inert solutes uranine and Rhodamine WT. The breakthrough curves at five successive sampling stations along a 16 km long stream reach were evaluated using a coupled physical-biogeochemical model framework containing surface water transport together with a representation of transient storage in slow/immobile zones of the stream. The multi-tracer experiment opens for decoupling of hydrological and biogeochemical contribution to the fate, and by linking impact and sensitivity analyses to relative significance of model parameters the most important processes for each contaminant were elucidated. Specifically for Säva Brook, the proposed methodology revealed that the pharmaceutical-contaminated stream water remained in the storage zones for times corresponding to 5-25% of the flow time of the stream. Furthermore, the results indicate a great variability in terms of predominant biogeochemical processes between the different contaminants. Rapid reactions occurring in the transient storage zone attenuated both ibuprofen and clofibric acid, and we conclude that a major degradation pathway for these contaminants was biodegradation in the hyporheic zone. In contrast, bezafibrate, metoprolol, and naproxen were mainly affected by sorption both in the storage zone and the main channel, while diclofenac displayed negligible effects of biogeochemical reactions.

  9. Punica granatum L. Juice Attenuates Experimental Cerebral Vasospasm in the Rabbit Subarachnoid Hemorrhage Model: A Basilar Artery Morphometric Study and Apoptosis.

    Science.gov (United States)

    Guvenc, Yahya; Demirci, Adnan; Billur, Deniz; Aydin, Sevim; Ozeren, Ersin; Bayram, Pinar; Dilli, Alper; Gokce, Emre Cemal; Yaman, Onur; Celik, Haydar; Karatay, Mete; Alagoz, Fatih; Kaptanoglu, Erkan

    2017-03-01

    Background This study investigated the effect of Punica granatum L. (pomegranate) juice on the rabbit basilar artery in an experimental subarachnoid hemorrhage (SAH) model. Methods  Eighteen adult male New Zealand white rabbits were randomly divided into three groups: a control group ( n  = 6), SAH group ( n  = 6), and SAH + treatment group ( n  = 6). Basilar artery diameter was measured with magnetic resonance angiography (MRA) in all groups at the beginning of the study. Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 30 ml/kg pomegranate juice via gastric gavage for 4 days after the SAH. The SAH group and SAH + treatment group underwent cerebral MRA after 72 hours. After a neurologic score assessment, all the animals were killed. The wall thickness and lumen area of the basilar artery were measured histometrically in all groups, and the apoptotic cell percentage in the artery was identified. The mean diameter of the basilar artery during MRA was measured. Results  Pomegranate improved neurologic functions compared with the SAH group ( p   0.05). The apoptotic cell rate in the SAH + treatment group was significantly lower than in the SAH group ( p   0.05). Discussion  Pomegranate was shown to have a vasospasm- attenuating effect on the basilar artery in the rabbit SAH model for the first time in our study. Georg Thieme Verlag KG Stuttgart · New York.

  10. Statistical analysis of accurate prediction of local atmospheric optical attenuation with a new model according to weather together with beam wandering compensation system: a season-wise experimental investigation

    Science.gov (United States)

    Arockia Bazil Raj, A.; Padmavathi, S.

    2016-07-01

    Atmospheric parameters strongly affect the performance of Free Space Optical Communication (FSOC) system when the optical wave is propagating through the inhomogeneous turbulent medium. Developing a model to get an accurate prediction of optical attenuation according to meteorological parameters becomes significant to understand the behaviour of FSOC channel during different seasons. A dedicated free space optical link experimental set-up is developed for the range of 0.5 km at an altitude of 15.25 m. The diurnal profile of received power and corresponding meteorological parameters are continuously measured using the developed optoelectronic assembly and weather station, respectively, and stored in a data logging computer. Measured meteorological parameters (as input factors) and optical attenuation (as response factor) of size [177147 × 4] are used for linear regression analysis and to design the mathematical model that is more suitable to predict the atmospheric optical attenuation at our test field. A model that exhibits the R2 value of 98.76% and average percentage deviation of 1.59% is considered for practical implementation. The prediction accuracy of the proposed model is investigated along with the comparative results obtained from some of the existing models in terms of Root Mean Square Error (RMSE) during different local seasons in one-year period. The average RMSE value of 0.043-dB/km is obtained in the longer range dynamic of meteorological parameters variations.

  11. Radiofrequency attenuator and method

    Science.gov (United States)

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  12. Attenuation coefficients of soils

    International Nuclear Information System (INIS)

    Martini, E.; Naziry, M.J.

    1989-01-01

    As a prerequisite to the interpretation of gamma-spectrometric in situ measurements of activity concentrations of soil radionuclides the attenuation of 60 to 1332 keV gamma radiation by soil samples varying in water content and density has been investigated. A useful empirical equation could be set up to describe the dependence of the mass attenuation coefficient upon photon energy for soil with a mean water content of 10%, with the results comparing well with data in the literature. The mean density of soil in the GDR was estimated at 1.6 g/cm 3 . This value was used to derive the linear attenuation coefficients, their range of variation being 10%. 7 figs., 5 tabs. (author)

  13. MCNP-X Monte Carlo Code Application for Mass Attenuation Coefficients of Concrete at Different Energies by Modeling 3 × 3 Inch NaI(Tl Detector and Comparison with XCOM and Monte Carlo Data

    Directory of Open Access Journals (Sweden)

    Huseyin Ozan Tekin

    2016-01-01

    Full Text Available Gamma-ray measurements in various research fields require efficient detectors. One of these research fields is mass attenuation coefficients of different materials. Apart from experimental studies, the Monte Carlo (MC method has become one of the most popular tools in detector studies. An NaI(Tl detector has been modeled, and, for a validation study of the modeled NaI(Tl detector, the absolute efficiency of 3 × 3 inch cylindrical NaI(Tl detector has been calculated by using the general purpose Monte Carlo code MCNP-X (version 2.4.0 and compared with previous studies in literature in the range of 661–2620 keV. In the present work, the applicability of MCNP-X Monte Carlo code for mass attenuation of concrete sample material as building material at photon energies 59.5 keV, 80 keV, 356 keV, 661.6 keV, 1173.2 keV, and 1332.5 keV has been tested by using validated NaI(Tl detector. The mass attenuation coefficients of concrete sample have been calculated. The calculated results agreed well with experimental and some other theoretical results. The results specify that this process can be followed to determine the data on the attenuation of gamma-rays with other required energies in other materials or in new complex materials. It can be concluded that data from Monte Carlo is a strong tool not only for efficiency studies but also for mass attenuation coefficients calculations.

  14. Computer-controlled attenuator.

    Science.gov (United States)

    Mitov, D; Grozev, Z

    1991-01-01

    Various possibilities for applying electronic computer-controlled attenuators for the automation of physiological experiments are considered. A detailed description is given of the design of a 4-channel computer-controlled attenuator, in two of the channels of which the output signal can change by a linear step, in the other two channels--by a logarithmic step. This, together with the existence of additional programmable timers, allows to automate a wide range of studies in different spheres of physiology and psychophysics, including vision and hearing.

  15. Assessment of Public Health and Economic Impact of Intranasal Live-Attenuated Influenza Vaccination of Children in France Using a Dynamic Transmission Model.

    Science.gov (United States)

    Gerlier, L; Lamotte, M; Grenèche, S; Lenne, X; Carrat, F; Weil-Olivier, C; Damm, O; Schwehm, M; Eichner, M

    2017-04-01

    We estimated the epidemiological and economic impact of extending the French influenza vaccination programme from at-risk/elderly (≥65 years) only to healthy children (2-17 years). A deterministic, age-structured, dynamic transmission model was used to simulate the transmission of influenza in the French population, using the current vaccination coverage with trivalent inactivated vaccine (TIV) in at-risk/elderly individuals (current strategy) or gradually extending the vaccination to healthy children (aged 2-17 years) with intranasal, quadrivalent live-attenuated influenza vaccine (QLAIV) from current uptake up to 50% (evaluated strategy). Epidemiological, medical resource use and cost data were taken from international literature and country-specific information. The model was calibrated to the observed numbers of influenza-like illness visits/year. The 10-year number of symptomatic cases of confirmed influenza and direct medical costs ('all-payer') were calculated for the 0-17- (direct and indirect effects) and ≥18-year-old (indirect effect). The incremental cost-effectiveness ratio (ICER) was calculated for the total population, using a 4% discount rate/year. Assuming 2.3 million visits/year and 1960 deaths/year, the model calibration yielded an all-year average basic reproduction number (R 0 ) of 1.27. In the population aged 0-17 years, QLAIV prevented 865,000 influenza cases/year (58.4%), preventing 10-year direct medical expenses of €374 million. In those aged ≥18 years with unchanged TIV coverage, 1.2 million cases/year were averted (27.6%) via indirect effects (additionally prevented expenses, €457 million). On average, 613 influenza-related deaths were averted annually overall. The ICER was €18,001/life-year gained. The evaluated strategy had a 98% probability of being cost-effective at a €31,000/life-year gained threshold. The model demonstrated strong direct and indirect benefits of protecting healthy children against influenza with

  16. Turmeric (Curcuma longa) attenuates food allergy symptoms by regulating type 1/type 2 helper T cells (Th1/Th2) balance in a mouse model of food allergy.

    Science.gov (United States)

    Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Choi, Dae Woon; Kwon, Da-Ae; Bae, Min-Jung; Sung, Ki-Seung; Shon, Dong-Hwa

    2015-12-04

    Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies. Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA. Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice. Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Modulation of sphingosine 1-phosphate (S1P) attenuates spatial learning and memory impairments in the valproic acid rat model of autism.

    Science.gov (United States)

    Wu, Hongmei; Zhang, Quanzhi; Gao, Jingquan; Sun, Caihong; Wang, Jia; Xia, Wei; Cao, Yonggang; Hao, Yanqiu; Wu, Lijie

    2018-03-01

    Autism spectrum disorders (ASD) are a set of pervasive neurodevelopmental disorders that manifest in early childhood, and it is growing up to be a major cause of disability in children. However, the etiology and treatment of ASD are not well understood. In our previous study, we found that serum levels of sphingosine 1-phosphate (S1P) were increased significantly in children with autism, indicating that S1P levels may be involved in ASD. The objective of this study was to identify a link between increased levels of S1P and neurobehavioral changes in autism. We utilized a valproic acid (VPA) -induced rat model of autism to evaluate the levels of S1P and the expression of sphingosine kinase (SphK), a key enzyme for S1P production, in serum and hippocampal tissue. Furthermore, we assessed cognitive functional changes and histopathological and neurochemical alterations in VPA-exposed rats after SphK blockade to explore the possible link between increased levels of S1P and neurobehavioral changes in autism. We found that SphK2 and S1P are upregulated in hippocampal tissue from VPA-exposed rats, while pharmacological inhibition of SphK reduced S1P levels, attenuated spatial learning and memory impairments, increased the expression of phosphorylated CaMKII and CREB and autophagy-related proteins, inhibited cytochrome c release, decreased the expression of apoptosis related proteins, and protected against neuronal loss in the hippocampus. We have demonstrated that an increased level of SphK2/S1P is involved in the spatial learning and memory impairments of autism, and this signaling pathway represents a novel therapeutic target and direction for future studies.

  18. Vitamin A deficiency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobiotic piglet model.

    Directory of Open Access Journals (Sweden)

    Kuldeep S Chattha

    Full Text Available Rotaviruses (RV are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12 and 2-3 fold lower anti-inflammatory (IL10 cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented pigs had significantly higher serum IL12 (PID2 and IFNγ (PID6 compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more

  19. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Directory of Open Access Journals (Sweden)

    James A Cotton

    Full Text Available Giardia duodenalis (syn. G. intestinalis, G. lamblia is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time

  20. Natural attenuation of herbicides

    DEFF Research Database (Denmark)

    Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

    2002-01-01

    A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth gover....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

  1. Measured attenuation correction methods

    International Nuclear Information System (INIS)

    Ostertag, H.; Kuebler, W.K.; Doll, J.; Lorenz, W.J.

    1989-01-01

    Accurate attenuation correction is a prerequisite for the determination of exact local radioactivity concentrations in positron emission tomography. Attenuation correction factors range from 4-5 in brain studies to 50-100 in whole body measurements. This report gives an overview of the different methods of determining the attenuation correction factors by transmission measurements using an external positron emitting source. The long-lived generator nuclide 68 Ge/ 68 Ga is commonly used for this purpose. The additional patient dose from the transmission source is usually a small fraction of the dose due to the subsequent emission measurement. Ring-shaped transmission sources as well as rotating point or line sources are employed in modern positron tomographs. By masking a rotating line or point source, random and scattered events in the transmission scans can be effectively suppressed. The problems of measured attenuation correction are discussed: Transmission/emission mismatch, random and scattered event contamination, counting statistics, transmission/emission scatter compensation, transmission scan after administration of activity to the patient. By using a double masking technique simultaneous emission and transmission scans become feasible. (orig.)

  2. Neuroprotective effect of novel cognitive enhancer noopept on AD-related cellular model involves the attenuation of apoptosis and tau hyperphosphorylation.

    Science.gov (United States)

    Ostrovskaya, Rita U; Vakhitova, Yulia V; Kuzmina, Uliyana Sh; Salimgareeva, Milyausha Kh; Zainullina, Liana F; Gudasheva, Tatiana A; Vakhitov, Vener A; Seredenin, Sergey B

    2014-08-06

    Noopept (N-phenyl-acetyl-L-prolylglycine ethyl ester) was constructed as a dipeptide analog of the standard cognition enhancer, piracetam. Our previous experiments have demonstrated the cognition restoring effect of noopept in several animal models of Alzheimer disease (AD). Noopept was also shown to prevent ionic disbalance, excitotoxicity, free radicals and pro-inflammatory cytokines accumulation, and neurotrophine deficit typical for different kinds of brain damages, including AD. In this study, we investigated the neuroprotective action of noopept on cellular model of AD, Aβ 25-35-induced toxicity in PC12 cells and revealed the underlying mechanisms. The neuroprotective effect of noopept (added to the medium at 10 μM concentration, 72 hours before Аβ 25-35) was studied on Аβ 25-35-induced injury (5 μM for 24 h) in PC12 cells. The ability of drug to protect the impairments of cell viability, calcium homeostasis, ROS level, mitochondrial function, tau phosphorylation and neurite outgrowth caused by Аβ 25-35 were evaluated. Following the exposure of PC12 cells to Аβ 25-35 an increase of the level of ROS, intracellular calcium, and tau phosphorylation at Ser396 were observed; these changes were accompanied by a decrease in cell viability and an increase of apoptosis. Noopept treatment before the amyloid-beta exposure improved PC12 cells viability, reduced the number of early and late apoptotic cells, the levels of intracellular reactive oxygen species and calcium and enhanced the mitochondrial membrane potential. In addition, pretreatment of PC12 cell with noopept significantly attenuated tau hyperphosphorylation at Ser396 and ameliorated the alterations of neurite outgrowth evoked by Аβ25-35. Taken together, these data provide evidence that novel cognitive enhancer noopept protects PC12 cell against deleterious actions of Aβ through inhibiting the oxidative damage and calcium overload as well as suppressing the mitochondrial apoptotic pathway

  3. Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis.

    Science.gov (United States)

    Rose, Johnie; Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

    2009-09-25

    To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life

  4. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  5. Photon attenuation by intensifying screens

    International Nuclear Information System (INIS)

    Holje, G.

    1983-01-01

    The photon attenuation by intensifying screens of different chemical composition has been determined. The attenuation of photons between 20 keV and 120 keV was measured by use of a multi-channel analyzer and a broad bremsstrahlung distribution. The attenuation by the intensifying screens was hereby determined simultaneously at many different monoenergetic photon energies. Experimentally determined attenuations were found to agree well with attenuation calculated from mass attenuation coefficients. The attenuation by the screens was also determined at various bremsstrahlung distributions, simulating those occurring behind the patient in various diagnostic X-ray examinations. The high attenuation in some of the intensifying screens form the basis for an analysis of the construction of asymmetric screen pairs. Single screen systems are suggested as a favourable alternative to thick screen pair systems. (Author)

  6. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel Walls; M.T. Taner; Naum Derzhi; Gary Mavko; Jack Dvorkin

    2003-12-01

    We have developed and tested technology for a new type of direct hydrocarbon detection. The method uses inelastic rock properties to greatly enhance the sensitivity of surface seismic methods to the presence of oil and gas saturation. These methods include use of energy absorption, dispersion, and attenuation (Q) along with traditional seismic attributes like velocity, impedance, and AVO. Our approach is to combine three elements: (1) a synthesis of the latest rock physics understanding of how rock inelasticity is related to rock type, pore fluid types, and pore microstructure, (2) synthetic seismic modeling that will help identify the relative contributions of scattering and intrinsic inelasticity to apparent Q attributes, and (3) robust algorithms that extract relative wave attenuation attributes from seismic data. This project provides: (1) Additional petrophysical insight from acquired data; (2) Increased understanding of rock and fluid properties; (3) New techniques to measure reservoir properties that are not currently available; and (4) Provide tools to more accurately describe the reservoir and predict oil location and volumes. These methodologies will improve the industry's ability to predict and quantify oil and gas saturation distribution, and to apply this information through geologic models to enhance reservoir simulation. We have applied for two separate patents relating to work that was completed as part of this project.

  7. Bulk viscosity and ultrasonic attenuation in liquid metals

    International Nuclear Information System (INIS)

    Awasthi, O.N.; Murthy, B.V.S.

    1984-11-01

    Ultrasonic attenuation in simple liquid metals has been investigated using the thermodynamic theory of relaxation processes incorporating the concept of a two state model for the liquid near the melting point. Agreement of the results with the experimental values of the ultrasonic attenuation and bulk viscosity indicates that this might be an appropriate approach to explain the excess attenuation of ultrasonic waves in liquid metals. (author)

  8. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

    Science.gov (United States)

    Flasche, Stefan; Jit, Mark; Rodríguez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J; Perkins, T Alex; Cummings, Derek A T; Dorigatti, Ilaria; Laydon, Daniel J; España, Guido; Kelso, Joel; Longini, Ira; Lourenco, Jose; Pearson, Carl A B; Reiner, Robert C; Mier-Y-Terán-Romero, Luis; Vannice, Kirsten; Ferguson, Neil

    2016-11-01

    Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in

  9. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia: A Model Comparison Study.

    Directory of Open Access Journals (Sweden)

    Stefan Flasche

    2016-11-01

    Full Text Available Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9. These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%, the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34% and in high-transmission settings (SP9 ≥ 70% by 13%-25% (all simulations: 10%- 34%. These endemicity levels are representative of the

  10. Enhanced Attenuation: Chlorinated Organics

    Science.gov (United States)

    2008-04-01

    attenuation capacity of the aquifer downgradient from the source (e.g., permeable reactive barriers or phytoremediation ) Selection of EA remedies should be...prevalence and/or mobility of nitrate and sulfate compounds and/or metals such as iron, manganese, chromium, copper, and arsenic . Furthermore, in...ranging from very aggressive source destruction and removal methods to less energy-intensive methods, such as phytoremediation . In many cases, it

  11. Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson's disease.

    Science.gov (United States)

    Gotsbacher, Michael P; Telfer, Thomas J; Witting, Paul K; Double, Kay L; Finkelstein, David I; Codd, Rachel

    2017-07-19

    Parkinson's disease (PD) is a neurodegenerative disorder characterised by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region of the brain and formation of α-synuclein-containing intracellular inclusions. Excess intraneuronal iron in the SNpc increases reactive oxygen species (ROS), which identifies removing iron as a possible therapeutic strategy. Desferrioxamine B (DFOB, 1) is an iron chelator produced by bacteria. Its high Fe(iii) affinity, water solubility and low chronic toxicity is useful in removing iron accumulated in plasma from patients with transfusion-dependent blood disorders. Here, lipophilic analogues of DFOB with increased potential to cross the blood-brain barrier (BBB) have been prepared by conjugating ancillary compounds onto the amine terminus. The ancillary compounds included the antioxidants rac-6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (rac-trolox, rac-TLX (a truncated vitamin E variant)), R-TLX, S-TLX, methylated derivatives of 3-(6-hydroxy-2-methylchroman-2-yl)propionic acid (α-CEHC, γ-CEHC, δ-CEHC), or 4-(5-hydroxy-3-methyl-1H-pyrazol-1-yl)benzoic acid (carboxylic acid derivative of edaravone, EDA). Compounds 2-8 could have dual function in attenuating ROS by chelating Fe(iii) and via the antioxidant ancillary group. A conjugate between DFOB and an ancillary unit without antioxidant properties (3,5-dimethyladamantane-1-carboxylic acid (AdA dMe )) was included (9). Compounds 2-9 were more lipophilic (log P -0.05 to 3.39) than DFOB (log P -2.62) and showed an average plasma protein binding 6 times greater than DFOB. The ABTS˙ + radical assay indicated 2-8 had antioxidant activity ascribable to the ancillary fragment. Administration of 2 and 9 in the mouse model of PD using the neurotoxin prodrug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which recapitulates elevated iron of human PD, resulted in significant neuronal protection (p compounds for PD.

  12. Control algorithms for dynamic attenuators

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Scott S., E-mail: sshsieh@stanford.edu [Department of Radiology, Stanford University, Stanford, California 94305 and Department of Electrical Engineering, Stanford University, Stanford, California 94305 (United States); Pelc, Norbert J. [Department of Radiology, Stanford University, Stanford California 94305 and Department of Bioengineering, Stanford University, Stanford, California 94305 (United States)

    2014-06-15

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  13. Control algorithms for dynamic attenuators

    International Nuclear Information System (INIS)

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-01-01

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  14. Control algorithms for dynamic attenuators.

    Science.gov (United States)

    Hsieh, Scott S; Pelc, Norbert J

    2014-06-01

    The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not require a priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current modulation) without

  15. An attenuated projector-backprojector for iterative SPECT reconstruction

    International Nuclear Information System (INIS)

    Gullberg, G.T.; Pelc, N.J.; Huesman, R.H.; Budinger, T.F.; Malko, J.A.

    1985-01-01

    A new ray-driven projector-backprojector which can easily be adapted for hardware implementation is described and simulated in software. The projector-backprojector discretely models the attenuated Radon transform of a source distributed within an attenuating medium as line integrals of discrete pixels, obtained using the standard sampling technique of averaging the emission source or attenuation distribution over small square regions. Attenuation factors are calculated for each pixel during the projection and backprojection operations instead of using precalculated values. The calculation of the factors requires a specification of the attenuation distribution, estimated either from an assumed constant distribution and an approximate body outline or from transmission measurements. The distribution of attenuation coefficients is stored in memory for efficient access during the projection and backprojection operations. The reconstruction of the source distribution is obtained by using a conjugate gradient or SIRT type iterative algorithm which requires one projection and one backprojection operation for each iteration. (author)

  16. Heat-accelerated radioinactivation of attenuated poliovirus

    International Nuclear Information System (INIS)

    Dugan, V.L.; Trujillo, R.

    1975-01-01

    Attenuated poliovirus is inactivated in a synergistic manner when exposed simultaneously to heat and ionizing radiation. The synergistic response is observed in both the thermally labile and stable forms of the virus. A three-term kinetic model may be used to describe the inactivation response of the virus in a thermal and/or ionizing radiation environment. (orig.) [de

  17. Microwave attenuation with composite of copper microwires

    International Nuclear Information System (INIS)

    Gorriti, A.G.; Marin, P.; Cortina, D.; Hernando, A.

    2010-01-01

    It is shown that copper microwires composite media attenuates microwave reflection of metallic surfaces. We show how the distance to the metallic surface, as well as the length and volume fraction of microwires, determine the frequency of maximum absorption and the return loss level. Furthermore, we were able to fit the experimental results with a theoretical model based on Maxwell-Garnett mixing formula.

  18. Microwave attenuation with composite of copper microwires

    Energy Technology Data Exchange (ETDEWEB)

    Gorriti, A.G.; Marin, P. [Instituto de Magnetismo Aplicado, (UCM-ADIF-CSIC) and Departamento de Fisica de Materiales (UCM). P.O. Box 155, Las Rozas, Madrid 28230 (Spain); Cortina, D. [Micromag S.L., Las Rozas, Madrid 28230 (Spain); Hernando, A., E-mail: antonio.hernando@adif.e [Instituto de Magnetismo Aplicado, (UCM-ADIF-CSIC) and Departamento de Fisica de Materiales (UCM). P.O. Box 155, Las Rozas, Madrid 28230 (Spain); Micromag S.L., Las Rozas, Madrid 28230 (Spain)

    2010-05-15

    It is shown that copper microwires composite media attenuates microwave reflection of metallic surfaces. We show how the distance to the metallic surface, as well as the length and volume fraction of microwires, determine the frequency of maximum absorption and the return loss level. Furthermore, we were able to fit the experimental results with a theoretical model based on Maxwell-Garnett mixing formula.

  19. The attenuation of the periodic table

    International Nuclear Information System (INIS)

    Cook, N.D.

    1990-01-01

    Unique among models of nuclear structure, the face-centered-cubic (FCC) lattice model predicts the attenuation of the periodic table at Z < 110 and the impossibility of superheavy nuclei. The total binding energies of superheavy nuclei in the FCC model (109 < Z < 127) were calculated on the basis of parameters obtained from a least-squares best-fit for 914 nuclei (Z < 99). No indication of increased stability is found for any of the transuranic elements

  20. Statistical problems with weather-radar images, II: Attenuation detection

    International Nuclear Information System (INIS)

    Fernandez-Duran, Juan-Jose; Upton, Graham

    2003-01-01

    A procedure based on the combination of a Bayesian changepoint model and ordinary least squares is used to identify and quantify regions where a radar signal has been attenuated (i.e.diminished) as a consequence of intervening weather. A graphical polar display is introduced that illustrates the location and importance of the attenuation

  1. Lattice Boltzmann simulations of attenuation-driven acoustic streaming

    International Nuclear Information System (INIS)

    Haydock, David; Yeomans, J M

    2003-01-01

    We show that lattice Boltzmann simulations can be used to model the attenuation-driven acoustic streaming produced by a travelling wave. Comparisons are made to analytical results and to the streaming pattern produced by an imposed body force approximating the Reynolds stresses. We predict the streaming patterns around a porous material in an attenuating acoustic field

  2. Growth Hormone-Releaser Diet Attenuates Cognitive Dysfunction in Klotho Mutant Mice via Insulin-Like Growth Factor-1 Receptor Activation in a Genetic Aging Model

    Directory of Open Access Journals (Sweden)

    Seok Joo Park

    2014-09-01

    Full Text Available BackgroundIt has been recognized that a defect in klotho gene expression accelerates the degeneration of multiple age-sensitive traits. Accumulating evidence indicates that aging is associated with declines in cognitive function and the activity of growth hormone (GH/insulin-like growth factor-1 (IGF-1.MethodsIn this study, we examined whether a GH-releaser diet could be effective in protecting against cognitive impairment in klotho mutant mice.ResultsThe GH-releaser diet significantly induced the expression of IGF-1 and IGF-1 receptors in the hippocampus of klotho mutant mice. Klotho mutant mice showed significant memory impairments as compared with wild-type mice. In addition, the klotho mutation significantly decreased the expression of cell survival/antiapoptotic factors, including phospho-Akt (p-Akt/phospho-glycogen synthase kinase3β (p-GSK3β, phospho-extracellular signal-related kinase (p-ERK, and Bcl-2, but significantly increased those of cell death/proapoptotic factors, such as phospho-c-jun N-terminal kinase (p-JNK, Bax, and cleaved caspase-3 in the hippocampus. Treatment with GH-releaser diet significantly attenuated both decreases in the expression of cell survival/antiapoptotic factors and increases in the expression of cell death/proapoptotic factors in the hippocampus of klotho mutant mice. In addition, klotho mutation-induced oxidative stress was significantly attenuated by the GH-releaser diet. Consequently, a GH-releaser diet significantly improved memory function in the klotho mutant mice. GH-releaser diet-mediated actions were significantly reversed by JB-1, an IGF-1 receptor antagonist.ConclusionThe results suggest that a GH-releaser diet attenuates oxidative stress, proapoptotic changes and consequent dysfunction in klotho mutant mice by promoting IGF-1 expression and IGF-1 receptor activation.

  3. Ground motion attenuation during M 7.1 Darfield and M 6.2 Christchurch, New Zealand, earthquakes and performance of global Ppedictive models

    Science.gov (United States)

    Segou, Margaret; Kalkan, Erol

    2011-01-01

    fault with M 6.2, followed by a second event (M 6.9), releasing the largest portion of the energy on the right-lateral Greendale fault. The third sub-event (M 5.7) is due to a reverse fault with a right-lateral component (Holden et al. 2011). The Christchurch earthquake occurred on an oblique thrust fault. The comparison of spectral acceleration values at stations near Christchurch reveals that the second event produced much larger amplitudes of shaking than the Darfield event due to its proximity to the epicenter. Both events resulted in noticeably large amplitudes of the vertical motion, often exceeding horizontal motion in the near-fault area. The vertical motions, showing asymmetric acceleration traces and pulses, reached 1.26 g during the Darfield earthquake and 2.2 g during the Christchurch event. These events were recorded by more than 100 strong motion stations operated by the Institute of Geological and Nuclear Sciences (http://www.geonet.org.nz/). Using the processed data from these stations, peak ground acceleration (PGA) and 5%-damped spectral acceleration values at 0.3, 1, and 3 s are used for performance evaluation of the global ground motion predictive equations (GMPEs). The selected GMPEs are the Next Generation Attenuation (NGA) models of Abrahamson and Silva (2008), Boore and Atkinson (2008), Campbell and Bozorgnia (2008), and Chiou and Youngs (2008). The Graizer and Kalkan (2007, 2009) model, which is based on the NGA project database, is also included. These GMPEs are abbreviated respectively as AS08, BA08, CB08, CY08, and GK07. Because they have been used widely for seismic hazard analysis for crustal earthquakes, their performance assessment becomes a critical issue especially for immediate response and recovery planning after major events. The occurrence of aftershocks similar to the Christchurch event will most probably control seismic hazard in the broader area, as confirmed by the recent M 6.0 event on June 13, 2011.

  4. Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of chronic heart failure is associated with attenuation of time-of-day dependence of heart rate and autonomic adaptation, and reduced cardiac chaos.

    Science.gov (United States)

    Zhu, Yujie; Hanafy, Mohamed A; Killingsworth, Cheryl R; Walcott, Gregory P; Young, Martin E; Pogwizd, Steven M

    2014-01-01

    Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2), correlation dimension (CD), and Shannon entropy (SE)) at baseline, as well as 240 days (240 d) and 720 days (720 d) following CHF induction. LV fractional shortening was decreased at both 240 d and 720 d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240 d & 720 d). Morning rise in the ratio of low frequency to high frequency (LF/HF) HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias.

  5. Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of chronic heart failure is associated with attenuation of time-of-day dependence of heart rate and autonomic adaptation, and reduced cardiac chaos.

    Directory of Open Access Journals (Sweden)

    Yujie Zhu

    Full Text Available Patients with chronic heart failure (CHF exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT, traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2, correlation dimension (CD, and Shannon entropy (SE at baseline, as well as 240 days (240 d and 720 days (720 d following CHF induction. LV fractional shortening was decreased at both 240 d and 720 d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240 d & 720 d. Morning rise in the ratio of low frequency to high frequency (LF/HF HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias.

  6. Empirical Relations for Optical Attenuation Prediction from Liquid Water Content of Fog

    Directory of Open Access Journals (Sweden)

    M. S. Khan

    2012-09-01

    Full Text Available Simultaneous measurements of the liquid water content (LWC and optical attenuation have been analyzed to predict optical attenuation caused by fog particles. Attenuation has been measured at two different wavelengths, 830 nm and 1550 nm, across co-located links. Five months measured data have been processed to assess power-law empirical models, which estimate optical attenuation from the LWC. The proposed models are compared with other published models and are demonstrated to perform sufficiently well to predict optical attenuation if the LWC values are available.

  7. Ultrasonic attenuation in superconducting zinc

    International Nuclear Information System (INIS)

    Auluck, S.

    1978-01-01

    The differences in the Zn ultrasonic attenuation data of different workers are analyzed. The superconducting energy gaps deduced from our analysis of the ultrasonic-attenuation data of Cleavelin and Marshall are consistent with the gaps deduced from the knowledge of the Fermi surface and the electron-phonon mass enhancement factor

  8. Glycomacropeptide, a low-phenylalanine protein isolated from cheese whey, supports growth and attenuates metabolic stress in the murine model of phenylketonuria

    Science.gov (United States)

    Solverson, Patrick; Murali, Sangita G.; Brinkman, Adam S.; Nelson, David W.; Clayton, Murray K.; Yen, Chi-Liang Eric

    2012-01-01

    Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pahenu2 (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3–23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3–15% increase in energy expenditure, as reflected in oxygen consumption, and a 3–30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO2 produced/O2 consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice. PMID:22297302

  9. Early-stage attenuation of phase-amplitude coupling in the hippocampus and medial prefrontal cortex in a transgenic rat model of Alzheimer's disease.

    Science.gov (United States)

    Bazzigaluppi, Paolo; Beckett, Tina L; Koletar, Margaret M; Lai, Aaron Y; Joo, Illsung L; Brown, Mary E; Carlen, Peter L; McLaurin, JoAnne; Stefanovic, Bojana

    2018-03-01

    Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of gamma-aminobutyric acid-ergic signaling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABA A ) receptor subunits α1 , α5, and δ, and glutamic acid decarboxylases (GAD65 and GAD67). Concomitant to amyloid deposition and tau hyperphosphorylation, low-gamma band power was strongly attenuated in the HPC and mPFC of TgF344-AD rats in comparison to those in non-transgenic littermates. In addition, the phase-amplitude coupling of the neuronal networks in both areas was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude in TgF344-AD animals. Finally, the gamma coherence between HPC and mPFC was attenuated as well. These results demonstrate significant neuronal network dysfunction at an early stage of AD-like pathology. This network dysfunction precedes the onset of cognitive deficits and is likely driven by Aβ and tau pathologies. This article is part of the Special Issue "Vascular Dementia". © 2017 Her Majesty the Queen in Right of Canada Journal of Neurochemistry © 2017 International Society for Neurochemistry.

  10. ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

    Science.gov (United States)

    Miyazaki, Shingo; Diwan, Ashish D; Kato, Kenji; Cheng, Kevin; Bae, Won C; Sun, Yang; Yamada, Junichi; Muehleman, Carol; Lenz, Mary E; Inoue, Nozomu; Sah, Robert L; Kawakami, Mamoru; Masuda, Koichi

    2018-04-01

    To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

  11. Mapping Pn amplitude spreading and attenuation in Asia

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Xiaoning [Los Alamos National Laboratory; Phillips, William S [Los Alamos National Laboratory; Stead, Richard J [Los Alamos National Laboratory

    2010-12-06

    Pn travels most of its path in the mantle lid. Mapping the lateral variation of Pn amplitude attenuation sheds light on material properties and dynamics of the uppermost region of the mantle. Pn amplitude variation depends on the wavefront geometric spreading as well as material attenuation. We investigated Pn geometric spreading, which is much more complex than a traditionally assumed power-law spreading model, using both synthetic and observed amplitude data collected in Asia. We derived a new Pn spreading model based on the formulation that was proposed previously to account for the spherical shape of the Earth (Yang et. al., BSSA, 2007). New parameters derived for the spreading model provide much better correction for Pn amplitudes in terms of residual behavior. Because we used observed Pn amplitudes to construct the model, the model incorporates not only the effect of the Earth's spherical shape, but also the effect of potential upper-mantle velocity gradients in the region. Using the new spreading model, we corrected Pn amplitudes measured at 1, 2, 4 and 6 Hz and conducted attenuation tomography. The resulting Pn attenuation model correlates well with the regional geology. We see high attenuation in regions such as northern Tibetan Plateau and the western Pacific subduction zone, and low attenuation for stable blocks such as Sichuan and Tarim basins.

  12. Indoor signal attenuation assessment via fuzzy logic

    Directory of Open Access Journals (Sweden)

    Alexandre de Assis Mota

    2011-09-01

    Full Text Available This work focuses on the analysis of signal´s attenuation in indoor environments using a fuzzy logic approach based on the Shadowing Signal Propagation Model (SSPM. The SSPM allows the characterization of the attenuation caused by the environment through the ? parameter present in this model. In addition to this, the Fuzzy Logic provides a form of approximate reasoning that allows the treatment of problems with incomplete, vague and imprecise information. Also, it offers a simple way to obtain a possible solution for a problem using the heuristic knowledge about a particular situation. The results show that the methodology produced satisfactory results, close to the ones yielded by experimental methods.

  13. Transport and attenuation of radiations

    CERN Document Server

    Nimal, J C

    2003-01-01

    This article treats of the calculation methods used for the dimensioning of the protections against radiations. The method consists in determining for a given point the flux of particles coming from a source at a given time. A strong attenuation (of about some few mu Sv.h sup - sup 1) is in general expected between the source and the areas accessible to the personnel or the public. The calculation has to take into account a huge number of radiation-matter interactions and to solve the integral-differential transport equation which links the particles flux to the source. Several methods exist from the simplified physical model with numerical developments to the more or less precise resolution of the transport equation. These methods allows also the calculation of the uncertainties of equivalent dose rates, heat sources, structure damages using the data covariances (efficient cross-sections, modeling, etc..): 1 - transport equation; 2 - Monte-Carlo method; 3 - semi-numerical methods S sub N; 4 - methods based o...

  14. P3 amplitude attenuation secondary to increases in target-to-target interval (TTI) during spatial serial order recall: Implications for EEG models of working memory function.

    Science.gov (United States)

    Hochberger, William C; Axelrod, Jenna L; Sarapas, Casey; Shankman, Stewart A; Hill, S Kristian

    2018-06-08

    Research suggests that increasing delays in stimulus read-out can trigger declines in serial order recall accuracy due to increases in cognitive demand imposed by the delay; however, the exact neural mechanisms associated with this decline are unclear. Changes in neural resource allocation present as the ideal target and can easily be monitored by examining changes in the amplitude of an ERP component known as the P3. Changes in P3 amplitude secondary to exogenous pacing of stimulus read-out via increased target-to-target intervals (TTI) during recall could reflect decreased neural resource allocation due to increased cognitive demand. This shift in resource allocation could result in working memory storage decay and the declines in serial order accuracy described by prior research. In order to examine this potential effect, participants were administered a spatial serial order processing task, with the recall series consisting of a series of correct ("match") or incorrect ("non-match" or "oddball") stimuli. Moreover, the recall series included either a brief (500ms) or extended (2000ms) delay between stimuli. Results were significant for the presence of a P3 response to non-match stimuli for both experimental conditions, and attenuation of P3 amplitude secondary to the increase in target-to-target interval (TTI). These findings suggest that extending the delay between target recognition could increase cognitive demand and trigger a decrease in neural resource allocation that results in a decay of working memory stores.

  15. High-Methionine Diet Attenuates Severity of Arthritis and Modulates IGF-I Related Gene Expressions in an Adjuvant Arthritis Rats Model

    Directory of Open Access Journals (Sweden)

    Mingxin Li

    2016-01-01

    Full Text Available Rheumatoid arthritis, a synthesized form of adjuvant arthritis exhibited throughout many animal species, inhibits liver function and circulation of IGF-I and contributes to the degradation of skeletal muscle mass. One of the primary goals of the present study is determining whether a high-Methionine (high-Met diet is capable of reducing the adverse effects of arthritis, namely, loss of body mass. Following adjuvant injection, forty arthritic rats were randomly assigned to either a control group with a basal diet or a high-Met group with the same basal diet + 0.5% Methionine. After 14 days all rats were terminated. The high-Met group exhibited an increase in body weight and food intake in comparison with the control group (P<0.05. High-Met diet debilitated arthritis-induced surges in the gastrocnemius in both atrogin-1 and the MuRF1 expressions; however, it was observed to have little to no effect on atrogin-1 and MuRF1 gene expression in soleus. At the same time, high-Met diet rats experienced a rise in IGF-I, with lowering of IGFBP-3 gene expression in the gastrocnemius and the soleus. These data suggest that arthritis severity can be partly attenuated by high-Met diet.

  16. Curcumin attenuates beta-amyloid-induced neuroinflammation via activation of peroxisome proliferator-activated receptor-gamma function in a rat model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Zun-Jing Liu

    2016-08-01

    Full Text Available Neuroinflammation is known to have a pivotal role in the pathogenesis of Alzheimer’s disease (AD, and curcumin has been reported to have therapeutical effects on AD because of its anti-inflammatory effects. Curcumin is not only a potent PPARγ agonist, but also has neuroprotective effects on cerebral ischemic injury. However, whether PPARγ activated by curcumin is responsible for the anti-neuroinflammation and neuroprotection on AD remains unclear, and needs to be further investigated. Here, using both APP/PS1 transgenic mice and beta-amyloid-induced neuroinflammation in mixed neuronal/glial cultures, we showed that curcumin significantly alleviated spatial memory deficits in APP/PS1 mice and promoted cholinergic neuronal function in vivo and in vitro. Curcumin also reduced the activation of microglia and astrocytes, as well as cytokine production and inhibited nuclear factor kappa B (NF-κB signaling pathway, suggesting the beneficial effects of curcumin on AD are attributable to the suppression of neuroinflammation. Attenuation of these beneficial effects occurred when co-administrated with PPARγ antagonist GW9662 or silence of PPARγ gene expression, indicating that PPARγ might be involved in anti-inflammatory effects. Circular dichroism and co-immunoprecipitation analysis showed that curcumin directly bound to PPARγ and increased the transcriptional activity and protein levels of PPARγ. Taking together, these data suggested that PPARγ might be a potential target of curcumin, acting to alleviate neuroinflammation and improve neuronal function in AD.

  17. MicroRNA-24 Attenuates Neointimal Hyperplasia in the Diabetic Rat Carotid Artery Injury Model by Inhibiting Wnt4 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Jian Yang

    2016-05-01

    Full Text Available The long-term stimulation of hyperglycemia greatly increases the incidence of vascular restenosis (RS after angioplasty. Neointimal hyperplasia after vascular injury is the pathological cause of RS, but its mechanism has not been elucidated. MicroRNA-24 (miR-24 has low expression in the injured carotid arteries of diabetic rats. However, the role of miR-24 in the vascular system is unknown. In this study, we explore whether over-expression of miR-24 could attenuate neointimal formation in streptozotocin (STZ-induced diabetic rats. Adenovirus (Ad-miR-24-GFP was used to deliver the miR-24 gene to injured carotid arteries in diabetic rats. The level of neointimal hyperplasia was examined by hematoxylin-eosin (HE staining. Vascular smooth muscle cell (VSMC proliferation in the neointima was evaluated by immunostaining for proliferating cell nuclear antigen (PCNA. The mRNA levels of miR-24, PCNA, wingless-type MMTV integration site family member 4 (Wnt4, disheveled-1 (Dvl-1, β-catenin and cell cycle-associated molecules (Cyclin D1, p21 were determined by Quantitative Real-Time PCR (qRT-PCR. PCNA, Wnt4, Dvl-1, β-catenin, Cyclin D1 and p21 protein levels were measured by Western blotting analysis. STZ administration decreased plasma insulin and increased fasting blood glucose in Sprague-Dawley (SD rats. The expression of miR-24 was decreased in the carotid artery after a balloon injury in diabetic rats, and adenoviral transfection (Ad-miR-24-GFP increased the expression of miR-24. Over-expression of miR-24 suppressed VSMC proliferation and neointimal hyperplasia in diabetic rats at 14 days. Furthermore, compared with Sham group, the mRNA and protein levels of PCNA, Wnt4, Dvl-1, β-catenin, and Cyclin D1 were strikingly up-regulated in the carotid arteries of diabetic rats after a balloon injury. Interestingly, up-regulation of miR-24 significantly reduced the mRNA and protein levels of these above molecules. In contrast, the change trend in p21 m

  18. The oral, live attenuated enterotoxigenic Escherichia coli vaccine ACE527 reduces the incidence and severity of diarrhea in a human challenge model of diarrheal disease.

    Science.gov (United States)

    Darsley, Michael J; Chakraborty, Subhra; DeNearing, Barbara; Sack, David A; Feller, Andrea; Buchwaldt, Charlotte; Bourgeois, A Louis; Walker, Richard; Harro, Clayton D

    2012-12-01

    An oral, live attenuated, three-strain recombinant bacterial vaccine, ACE527, was demonstrated to generate strong immune responses to colonization factor and toxin antigens of enterotoxigenic Escherichia coli (ETEC) in human volunteers. The vaccine was safe and well tolerated at doses of up to 10(11) CFU, administered in each of two doses given 21 days apart. These observations have now been extended in a phase 2b study with a total of 70 subjects. Fifty-six of these subjects were challenged 28 days after the second dose of vaccine with the highly virulent ETEC strain H10407 to obtain preliminary indicators of efficacy against disease and to support further development of the vaccine for both travelers and infants in countries where ETEC is endemic. The vaccine had a significant impact on intestinal colonization by the challenge strain, as measured by quantitative fecal culture 2 days after challenge, demonstrating the induction of a functional immune response to the CFA/I antigen. The incidence and severity of diarrhea were also reduced in vaccinees as measured by a number of secondary and ad hoc endpoints, although the 27% reduction seen in the primary endpoint, moderate to severe diarrhea, was not statistically significant. Together, these observations support the hypothesis that the ACE527 vaccine has a dual mode of action, targeting both colonization factors and the heat-labile enterotoxin (LT), and suggest that it should be further developed for more advanced trials to evaluate its impact on the burden of ETEC disease in field settings.

  19. Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

    Energy Technology Data Exchange (ETDEWEB)

    Kalayarasan, Srinivasan, E-mail: kalaivasanbio@gmail.com; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam, E-mail: sudhandiran@yahoo.com

    2013-09-01

    Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells.

  20. Suppression of Pax2 attenuates allodynia and hyperalgesia through ET-1-ETAR-NFAT5 signaling in a rat model of neuropathic pain.

    Science.gov (United States)

    Tai, Lydia Wai; Pan, Zhiqiang; Sun, Liting; Li, Haobo; Gu, Pan; Wong, Stanley Sau Ching; Chung, Sookja K; Cheung, Chi Wai

    2018-05-27

    Endothelin-1 (ET-1) and its receptors (ETAR/ETBR) emerge to be a key signaling axis in neuropathic pain processing and are recognized as new therapeutic targets. Yet, little is known on the functional regulation of ET-1 axis during neuropathic pain. Bioinformatics analysis indicated that paired box gene 2 (Pax2) or nuclear factor of activated T-cells 5 (NFAT5), two transcription factors involved in the modulation of neurotransmission, may regulate ET-1. Therefore, we hypothesized that ET-1 axis may be regulated by Pax2 or NFAT5 in the development of neuropathic pain. After partial sciatic nerve ligation (pSNL), rats displayed allodynia and hyperalgesia, which was associated with increased mRNA and protein expressions of spinal Pax2, NFAT5, and mRNA levels of ET-1 and ETAR, but not ETBR. Knockdown of Pax2 or NFAT5 with siRNA, or inhibition of ETAR with BQ-123 attenuated pSNL-induced pain-like behaviors. At molecular level, Pax2 siRNA, but not NFAT5 siRNA, downregulated ET-1 and ETAR, while ETAR inhibitor reduced NFAT5, indicating Pax2 in the upstream of ET-1 axis with NFAT5 in the downstream. Further, suppression of Pax2 (inhibiting ET-1) or impairment of ET-1 signaling (inhibition of ETAR and/or decrease of NFAT5) deactivated mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, supporting the significance of functional regulation of ET-1 axis in neuropathic pain signaling. These findings demonstrate that Pax2 targeting ET-1-ETAR-NFAT5 is a novel regulatory mechanism underlying neuropathic pain. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Diallylsulfide attenuates excessive collagen production and apoptosis in a rat model of bleomycin induced pulmonary fibrosis through the involvement of protease activated receptor-2

    International Nuclear Information System (INIS)

    Kalayarasan, Srinivasan; Sriram, Narayanan; Soumyakrishnan, Syamala; Sudhandiran, Ganapasam

    2013-01-01

    Pulmonary fibrosis (PF) can be a devastating lung disease. It is primarily caused by inflammation leading to severe damage of the alveolar epithelial cells. The pathophysiology of PF is not yet been clearly defined, but studying lung parenchymal injury by involving reactive oxygen species (ROS) through the activation of protease activated receptor-2 (PAR-2) may provide promising results. PAR-2 is a G-protein coupled receptor is known to play an important role in the development of PF. In this study, we investigated the inhibitory role of diallylsulfide (DAS) against ROS mediated activation of PAR-2 and collagen production accompanied by epithelial cell apoptosis. Bleomycin induced ROS levels may prompt to induce the expression of PAR-2 as well as extracellular matrix proteins (ECM), such as MMP 2 and 9, collagen specific proteins HSP-47, α-SMA, and cytokines IL-6, and IL-8RA. Importantly DAS treatment effectively decreased the expression of all these proteins. The inhibitory effect of DAS on profibrotic molecules is mediated by blocking the ROS level. To identify apoptotic signaling as a mediator of PF induction, we performed apoptotic protein expression, DNA fragmentation analysis and ultrastructural details of the lung tissue were performed. DAS treatment restored all these changes to near normalcy. In conclusion, treatment of PF bearing rats with DAS results in amelioration of the ROS production, PAR-2 activation, ECM production, collagen synthesis and alveolar epithelial cell apoptosis during bleomycin induction. We attained the first evidence that treatment of DAS decreases the ROS levels and may provide a potential therapeutic effect attenuating bleomycin induced PF. - Highlights: • DAS inhibits PAR-2 activity; bleomycin stimulates PAR-2 activity. • Increase in PAR-2 activity is correlated with pulmonary fibrosis • DAS reduces pro-inflammatory activity linked to facilitating pulmonary fibrosis. • DAS inhibits apoptosis of alveolar epithelial cells

  2. Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation.

    Science.gov (United States)

    Hu, Xianwen; Wang, Jingxian; Zhang, Li; Zhang, Qiquan; Duan, Xiaowen; Zhang, Ye

    2018-06-02

    Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS. Copyright © 2018. Published by Elsevier B.V.

  3. A Point Mutation in the Rhesus Rotavirus VP4 Protein Generated through a Rotavirus Reverse Genetics System Attenuates Biliary Atresia in the Murine Model.

    Science.gov (United States)

    Mohanty, Sujit K; Donnelly, Bryan; Dupree, Phylicia; Lobeck, Inna; Mowery, Sarah; Meller, Jaroslaw; McNeal, Monica; Tiao, Greg

    2017-08-01

    Rotavirus infection is one of the most common causes of diarrheal illness in humans. In neonatal mice, rhesus rotavirus (RRV) can induce biliary atresia (BA), a disease resulting in inflammatory obstruction of the extrahepatic biliary tract and intrahepatic bile ducts. We previously showed that the amino acid arginine (R) within the sequence SRL (amino acids 445 to 447) in the RRV VP4 protein is required for viral binding and entry into biliary epithelial cells. To determine if this single amino acid (R) influences the pathogenicity of the virus, we generated a recombinant virus with a single amino acid mutation at this site through a reverse genetics system. We demonstrated that the RRV mutant (RRV VP4-R446G ) produced less symptomatology and replicated to lower titers both in vivo and in vitro than those seen with wild-type RRV, with reduced binding in cholangiocytes. Our results demonstrate that a single amino acid change in the RRV VP4 gene influences cholangiocyte tropism and reduces pathogenicity in mice. IMPORTANCE Rotavirus is the leading cause of diarrhea in humans. Rhesus rotavirus (RRV) can also lead to biliary atresia (a neonatal human disease) in mice. We developed a reverse genetics system to create a mutant of RRV (RRV VP4-R446G ) with a single amino acid change in the VP4 protein compared to that of wild-type RRV. In vitro , the mutant virus had reduced binding and infectivity in cholangiocytes. In vivo , it produced fewer symptoms and lower mortality in neonatal mice, resulting in an attenuated form of biliary atresia. Copyright © 2017 American Society for Microbiology.

  4. α-Asarone Attenuates Cognitive Deficit in a Pilocarpine-Induced Status Epilepticus Rat Model via a Decrease in the Nuclear Factor-κB Activation and Reduction in Microglia Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Hui-juan Liu

    2017-12-01

    Full Text Available BackgroundTemporal lobe epilepsy (TLE is one of the most drug-resistant types of epilepsy with about 80% of TLE patients falling into this category. Increasing evidence suggests that neuroinflammation, which has a critical role in the epileptogenesis of TLE, is associated with microglial activation. Therefore, agents that act toward the alleviation in microglial activation and the attenuation of neuroinflammation are promising candidates to treat TLE. α-Asarone is a major active ingredient of the Acori Graminei Rhizoma used in Traditional Chinese Medicine, which has been used to improve various disease conditions including stroke and convulsions. In addition, an increasing number of studies suggested that α-asarone can attenuate microglia-mediated neuroinflammation. Thus, we hypothesized that α-asarone is a promising neuroprotective agent for the treatment of the TLE.MethodsThe present study evaluated the therapeutic effects of α-asarone on microglia-mediated neuroinflammation and neuroprotection in vitro and in vivo, using an untreated control group, a status epilepticus (SE-induced group, and an SE-induced α-asarone pretreated group. A pilocarpine-induced rat model of TLE was established to investigate the neuroprotective effects of α-asarone in vivo. For the in vitro study, lipopolysaccharide (LPS-stimulated primary cultured microglial cells were used.ResultsThe results indicated that the brain microglial activation in the rats of the SE rat model led to important learning and memory deficit. Preventive treatment with α-asarone restrained microglial activation and reduced learning and memory deficit. In the in vitro studies, α-asarone significantly suppressed proinflammatory cytokine production in primary cultured microglial cells and attenuated the LPS-stimulated neuroinflammatory responses. Our mechanistic study revealed that α-asarone inhibited inflammatory processes by regulation the transcription levels of kappa-B, by blocking

  5. Propofol Attenuates Airway Inflammation in a Mast Cell-Dependent Mouse Model of Allergic Asthma by Inhibiting the Toll-like Receptor 4/Reactive Oxygen Species/Nuclear Factor κB Signaling Pathway.

    Science.gov (United States)

    Li, Hong-Yi; Meng, Jing-Xia; Liu, Zhen; Liu, Xiao-Wen; Huang, Yu-Guang; Zhao, Jing

    2018-06-01

    Propofol, an intravenous anesthetic agent widely used in clinical practice, is the preferred anesthetic for asthmatic patients. This study was designed to determine the protective effect and underlying mechanisms of propofol on airway inflammation in a mast cell-dependent mouse model of allergic asthma. Mice were sensitized by ovalbumin (OVA) without alum and challenged with OVA three times. Propofol was given intraperitoneally 0.5 h prior to OVA challenge. The inflammatory cell count and production of cytokines in the bronchoalveolar lavage fluid (BALF) were detected. The changes of lung histology and key molecules of the toll-like receptor 4 (TLR4)/reactive oxygen species (ROS)/NF-κB signaling pathway were also measured. The results showed that propofol significantly decreased the number of eosinophils and the levels of IL-4, IL-5, IL-6, IL-13, and TNF-α in BALF. Furthermore, propofol significantly attenuated airway inflammation, as characterized by fewer infiltrating inflammatory cells and decreased mucus production and goblet cell hyperplasia. Meanwhile, the expression of TLR4, and its downstream signaling adaptor molecules--myeloid differentiation factor 88 (MyD88) and NF-κB, were inhibited by propofol. The hydrogen peroxide and methane dicarboxylic aldehyde levels were decreased by propofol, and the superoxide dismutase activity was increased in propofol treatment group. These findings indicate that propofol may attenuate airway inflammation by inhibiting the TLR4/MyD88/ROS/NF-κB signaling pathway in a mast cell-dependent mouse model of allergic asthma.

  6. An acoustic eikonal equation for attenuating orthorhombic media

    KAUST Repository

    Hao, Qi

    2017-04-06

    Attenuating orthorhombic models are often used to describe the azimuthal variation of the seismic wave velocity and amplitude in finely layered hydrocarbon reservoirs with vertical fractures. In addition to the P-wave related medium parameters, shear wave parameters are also present in the complex eikonal equation needed to describe the P-wave complex-valued traveltime in an attenuating orthorhombic medium, which increases the complexity of using the P-wave traveltime to invert for the medium parameters in practice. Here, we use the acoustic assumption to derive an acoustic eikonal equation that approximately governs the complex-valued traveltime of P-waves in an attenuating orthorhombic medium. For a homogeneous attenuating orthorhombic media, we solve the eikonal equation using a combination of the perturbation method and Shanks transform. For a horizontal attenuating orthorhombic layer, both the real and imaginary part of the complex-valued reflection traveltime have nonhyperbolic behaviors in terms of the source-receiver offset. Similar to the roles of normal moveout (NMO) velocity and anellipticity, the attenuation NMO velocity and the attenuation anellipticity characterize the variation of the imaginary part of the complex-valued reflection traveltime around zero source-receiver offset.

  7. MR constrained simultaneous reconstruction of activity and attenuation maps in brain TOF-PET/MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Mehranian, Abolfazl; Zaidi, Habib [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland)

    2014-07-29

    The maximum likelihood estimation of attenuation and activity (MLAA) algorithm has been proposed to jointly estimate activity and attenuation from emission data only. Salomon et al employed the MLAA to estimate activity and attenuation from time-of-flight PET data with spatial MR prior information on attenuation. Recently, we proposed a novel algorithm to impose both spatial and statistical constraints on attenuation estimation within the MLAA algorithm using Dixon MR images and a constrained Gaussian mixture model (GMM). In this study, we compare the proposed algorithm with MLAA and MLAA-Salomon in brain TOF-PET/MR imaging.

  8. MR constrained simultaneous reconstruction of activity and attenuation maps in brain TOF-PET/MR imaging

    International Nuclear Information System (INIS)

    Mehranian, Abolfazl; Zaidi, Habib

    2014-01-01

    The maximum likelihood estimation of attenuation and activity (MLAA) algorithm has been proposed to jointly estimate activity and attenuation from emission data only. Salomon et al employed the MLAA to estimate activity and attenuation from time-of-flight PET data with spatial MR prior information on attenuation. Recently, we proposed a novel algorithm to impose both spatial and statistical constraints on attenuation estimation within the MLAA algorithm using Dixon MR images and a constrained Gaussian mixture model (GMM). In this study, we compare the proposed algorithm with MLAA and MLAA_Salomon in brain TOF-PET/MR imaging.

  9. Kupffer cell depletion attenuates leptin-mediated methoxamine-stimulated portal perfusion pressure and thromboxane A2 release in a rodent model of NASH-cirrhosis.

    Science.gov (United States)

    Yang, Ying-Ying; Huang, Yi-Tsau; Tsai, Tung-Hu; Hou, Ming-Chih; Lee, Fa-Yauh; Lee, Shou-Dong; Lin, Han-Chieh

    2012-12-01

    Cirrhotic portal hypertension is characterized by increased hepatic oxidative stress, AA (arachidonic acid)-derived TXA(2) (thromboxane A(2)) release and exaggerated hepatic response to the α-adrenergic agonist MTX (methoxamine). Besides promoting hepatic fibrosis, the role of hyperleptinaemia in the modulation of vascular response in NASH (non-alcoholic steatohepatitis) rat livers remains unknown. The aim of the present study was to explore the possible links between hyperleptinaemia and the disarrangement in the hepatic microcirculation. NASH-cirrhosis with hyperleptinaemia was induced in lean rats by feeding with an HF/MCD (high-fat/methionine-choline-deficient) diet. Portal haemodynamics, various substances, protein and mRNA expression and PUFA (polyunsaturated fatty acid) composition were measured. Finally, the effects of leptin pre-infusion on TXA(2) release and concentration-PPP (portal perfusion pressure) curves in response to MTX were evaluated by simultaneously pre-treatment with the Kupffer cell inactivators GdCl(3) (gadolinium chloride) or EC (encapsulated clodronate), the TXS (TXA(2) synthase) inhibitor furegrelate, the TP receptor (TXA(2) receptor) antagonist SQ29548 and the dual TXS/TP receptor antagonist BM567. In HF/MCD+leptin-lean rats, cirrhosis-induced PPP and MTX hyper-responsiveness were associated with increased hepatic TXA(2) production, TBARS (thiobarbituric acid-reacting substances) levels and the AA (arachidonic acid)/n-3 PUFA ratio, and up-regulation of hepatic leptin, FAS (fatty acid synthase), NADPH oxidase subunits, TXS, TP receptor, TGFβ(1) (transforming growth factor β(1)) proteins and mRNAs. Pre-infusion of leptin significantly enhanced MTX-stimulated PPP elevation and TXA(2) release, which were attenuated by GdCl(3) and EC pre-treatment. Concomitantly pre-incubation with BM567, but not furegrelate or SQ29548, significantly abolished the leptin-enhanced MTX-stimulated increase in PPP in NASH-cirrhotic rats. Hyperleptinaemia

  10. P2X7 Receptor Antagonism Attenuates the Intermittent Hypoxia-induced Spatial Deficits in a Murine Model of Sleep Apnea Via Inhibiting Neuroinflammation and Oxidative Stress.

    Science.gov (United States)

    Deng, Yan; Guo, Xue-Ling; Yuan, Xiao; Shang, Jin; Zhu, Die; Liu, Hui-Guo

    2015-08-20

    The mechanism of the neural injury caused by chronic intermittent hypoxia (CIH) that characterizes obstructive sleep apnea syndrome (OSAS) is not clearly known. The purpose of this study was to investigate whether P2X7 receptor (P2X7R) is responsible for the CIH-induced neural injury and the possible pathway it involves. Eight-week-old male C57BL/6 mice were used. For each exposure time point, eight mice divided in room air (RA) and IH group were assigned to the study of P2X7R expression. Whereas in the 21 days-Brilliant Blue G (BBG, a selective P2X7R antagonist) study, 48 mice were randomly divided into CIH group, BBG-treated CIH group, RA group and BBG-treated RA group. The hippocampus P2X7R expression was determined by Western blotting and real-time polymerase chain reaction (PCR). The spatial learning was analyzed by Morris water maze. The nuclear factor kappa B (NFκB) and NADPH oxidase 2 (NOX2) expressions were analyzed by Western blotting. The expressions of tumor necrosis factor α, interleukin 1β (IL-β), IL-18, and IL-6 were measured by real-time PCR. The malondialdehyde and superoxide dismutase levels were detected by colorimetric method. Cell damage was evaluated by Hematoxylin and Eosin staining and Terminal Transferase dUTP Nick-end Labeling method. The P2X7R mRNA was elevated and sustained after 3-day IH exposure and the P2X7R protein was elevated and sustained after 7-day IH exposure. In the BBG study, the CIH mice showed severer neuronal cell damage and poorer performance in the behavior test. The increased NFκB and NOX2 expressions along with the inflammation injury and oxidative stress were also observed in the CIH group. BBG alleviated CIH-induced neural injury and consequent functional deficits. The P2X7R antagonism attenuates the CIH-induced neuroinflammation, oxidative stress, and spatial deficits, demonstrating that the P2X7R is an important therapeutic target in the cognition deficits accompanied OSAS.

  11. Lithium attenuates cannabinoid-induced dependence in the animal model: involvement of phosphorylated ERK1/2 and GSK-3β signaling pathways.

    Directory of Open Access Journals (Sweden)

    Hamid Reza Rahimi

    2014-09-01

    Full Text Available Cannabis is one of the most banned drugs in the world. Cannabinoid-induced dependence or withdrawal signs are indicated by the result of complex molecular mechanisms including upstream protein kinases (PKs, such as an extracellular signal regulated kinase1/2 (ERK1/2 and downstream glycogen synthase kinase-3β (GSK-3β, which lead to neuronal plasticity. In this study, we examined the protective effect of lithium (Li as a potent ERK1/2 and GSK-3β modulator to prevent the development of dependence on cannabinoids. For this purpose, rats were treated twice daily with increasing doses of WIN 55,212-2 (WIN, 2-8 mg/kg, intraperitoneally (i.p., for five consecutive days. AM251 (AM, 2 mg/kg, a cannabinoid antagonist, was injected i.p to induce manifestations of abstinence in rat dependency on WIN, and the subsequent withdrawal signs were recorded. To evaluate the preventive effect of Li, the rats were pre-treated with Li (10 mg/kg, i.p. twice daily, 30 minutes before every injection of WIN. SL327, as an ERK1/2 inhibitor, was also injected (SL, 50 mg/kg, i.p. 30 minutes before the last doses of WIN in separate groups. The p-ERK1/2, total ERK1/2, p-GSK-3β and total GSK-3β expressions were determined with Western blot method after 60 minutes, prior to the Li, WIN or AM injections. Li and SL pre-treatment attenuated the global withdrawal signs in regarding their modulation effect on the up-regulation of p-ERK1/2 cascade enhanced by AM injection. Furthermore, the p-GSK-3β expression was up-regulated with SL and Li pre-treatment against AM injection, without alteration on the total contents of ERK1/2 and GSK-3β level. Therefore, p-ERK1/2 and p-GSK-3β pathways are involved in the cannabinoid-induced dependence. However, no crosstalk was indicated between these two pathways. In conclusion, Li neuroprotectionwith regard to cannabinoid abstinence may occur through the regulation of the p-ERK1/2 cascade inconsequent of p-GSK-3β signaling pathways in rats.

  12. Validation of mathematical models to describe fluid dynamics of a cold riser by gamma ray attenuation; Validacao de modelos matematicos para descrever a fluidodinamica de um riser utilizando atenuacao gama

    Energy Technology Data Exchange (ETDEWEB)

    Melo, Ana Cristina Bezerra Azedo de

    2004-12-15

    The fluid dynamic behavior of a riser in a cold type FCC model was investigated by means of catalyst concentration distribution measured with gamma attenuation and simulated with a mathematical model. In the riser of the cold model, MEF, 0,032 m in diameter, 2,30 m in length the fluidized bed, whose components are air and FCC catalyst, circulates. The MEF is operated by automatic control and instruments for measuring fluid dynamic variables. An axial catalyst concentration distribution was measured using an Am-241 gamma source and a NaI detector coupled to a multichannel provided with a software for data acquisition and evaluation. The MEF was adapted for a fluid dynamic model validation which describes the flow in the riser, for example, by introducing an injector for controlling the solid flow in circulation. Mathematical models were selected from literature, analyzed and tested to simulate the fluid dynamic of the riser. A methodology for validating fluid dynamic models was studied and implemented. The stages of the work were developed according to the validation methodology, such as data planning experiments, study of the equations which describe the fluidodynamic, computational solvers application and comparison with experimental data. Operational sequences were carried out keeping the MEF conditions for measuring catalyst concentration and simultaneously measuring the fluid dynamic variables, velocity of the components and pressure drop in the riser. Following this, simulated and experimental values were compared and statistical data treatment done, aiming at the required precision to validate the fluid dynamic model. The comparison tests between experimental and simulated data were carried out under validation criteria. The fluid dynamic behavior of the riser was analyzed and the results and the agreement with literature were discussed. The adopt model was validated under the MEF operational conditions, for a 3 to 6 m/s gas velocity in the riser and a slip

  13. Attenuation in Superconducting Circular Waveguides

    Directory of Open Access Journals (Sweden)

    K. H. Yeap

    2016-09-01

    Full Text Available We present an analysis on wave propagation in superconducting circular waveguides. In order to account for the presence of quasiparticles in the intragap states of a superconductor, we employ the characteristic equation derived from the extended Mattis-Bardeen theory to compute the values of the complex conductivity. To calculate the attenuation in a circular waveguide, the tangential fields at the boundary of the wall are first matched with the electrical properties (which includes the complex conductivity of the wall material. The matching of fields with the electrical properties results in a set of transcendental equations which is able to accurately describe the propagation constant of the fields. Our results show that although the attenuation in the superconducting waveguide above cutoff (but below the gap frequency is finite, it is considerably lower than that in a normal waveguide. Above the gap frequency, however, the attenuation in the superconducting waveguide increases sharply. The attenuation eventually surpasses that in a normal waveguide. As frequency increases above the gap frequency, Cooper pairs break into quasiparticles. Hence, we attribute the sharp rise in attenuation to the increase in random collision of the quasiparticles with the lattice structure.

  14. The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury.

    Science.gov (United States)

    Rathinasabapathy, Anandharajan; Horowitz, Alana; Horton, Kelsey; Kumar, Ashok; Gladson, Santhi; Unger, Thomas; Martinez, Diana; Bedse, Gaurav; West, James; Raizada, Mohan K; Steckelings, Ulrike M; Sumners, Colin; Katovich, Michael J; Shenoy, Vinayak

    2018-01-01

    Idiopathic Pulmonary Fibrosis (IPF) is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH) is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT 2 ) receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21), a selective AT 2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg) to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip) either immediately (prevention protocol, BCP) or after 3 days (treatment protocol, BCT) of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition), and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT 2 receptor by C21 attenuates

  15. The Selective Angiotensin II Type 2 Receptor Agonist, Compound 21, Attenuates the Progression of Lung Fibrosis and Pulmonary Hypertension in an Experimental Model of Bleomycin-Induced Lung Injury

    Directory of Open Access Journals (Sweden)

    Anandharajan Rathinasabapathy

    2018-03-01

    Full Text Available Idiopathic Pulmonary Fibrosis (IPF is a chronic lung disease characterized by scar formation and respiratory insufficiency, which progressively leads to death. Pulmonary hypertension (PH is a common complication of IPF that negatively impacts clinical outcomes, and has been classified as Group III PH. Despite scientific advances, the dismal prognosis of IPF and associated PH remains unchanged, necessitating the search for novel therapeutic strategies. Accumulating evidence suggests that stimulation of the angiotensin II type 2 (AT2 receptor confers protection against a host of diseases. In this study, we investigated the therapeutic potential of Compound 21 (C21, a selective AT2 receptor agonist in the bleomycin model of lung injury. A single intra-tracheal administration of bleomycin (2.5 mg/kg to 8-week old male Sprague Dawley rats resulted in lung fibrosis and PH. Two experimental protocols were followed: C21 was administered (0.03 mg/kg/day, ip either immediately (prevention protocol, BCP or after 3 days (treatment protocol, BCT of bleomycin-instillation. Echocardiography, hemodynamic, and Fulton's index assessments were performed after 2 weeks of bleomycin-instillation. Lung tissue was processed for gene expression, hydroxyproline content (a marker of collagen deposition, and histological analysis. C21 treatment prevented as well as attenuated the progression of lung fibrosis, and accompanying PH. The beneficial effects of C21 were associated with decreased infiltration of macrophages in the lungs, reduced lung inflammation and diminished pulmonary collagen accumulation. Further, C21 treatment also improved pulmonary pressure, reduced muscularization of the pulmonary vessels and normalized cardiac function in both the experimental protocols. However, there were no major differences in any of the outcomes measured from the two experimental protocols. Collectively, our findings indicate that stimulation of the AT2 receptor by C21 attenuates

  16. Practical method of breast attenuation correction for cardiac SPECT

    International Nuclear Information System (INIS)

    Oliveira, Anderson de; Nogueira, Tindyua; Gutterres, Ricardo Fraga; Megueriam, Berdj Aram; Santos, Goncalo Rodrigues dos

    2007-01-01

    The breast attenuation effects on SPECT (Single Photon Emission Tomography) myocardium perfusion procedures have been lately scope of continuous inquiry. The requested attenuation correction factors are usually achieved by transmission analysis, making up the exposure of a standard external source to the SPECT, as a routine step. However, its high cost makes this methodology not fully available to the most of nuclear medicines services in Brazil and abroad. To overcome the problem, a new trend is presented in this work, implementing computational models to balance the breast attenuation effects on the left ventricle anterior wall, during myocardium perfusion scintigraphy procedures with SPECT. A neural network was put on in order to provide the attenuation correction indexes, based upon the following patients individual biotypes features: mass, age, height, chest and breast thicknesses, heart size, as well as the imparted activity intake levels. (author)

  17. Practical method of breast attenuation correction for cardiac SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Anderson de; Nogueira, Tindyua; Gutterres, Ricardo Fraga [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil). Coordenacao Geral de Instalacoes Medicas e Industriais (CGMI)]. E-mails: anderson@cnen.gov.br; tnogueira@cnen.gov.br; rguterre@cnen.gov.br; Megueriam, Berdj Aram [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil)]. E-mail: megueriam@hotmail.com; Santos, Goncalo Rodrigues dos [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: goncalo@cnen.gov.br

    2007-07-01

    The breast attenuation effects on SPECT (Single Photon Emission Tomography) myocardium perfusion procedures have been lately scope of continuous inquiry. The requested attenuation correction factors are usually achieved by transmission analysis, making up the exposure of a standard external source to the SPECT, as a routine step. However, its high cost makes this methodology not fully available to the most of nuclear medicines services in Brazil and abroad. To overcome the problem, a new trend is presented in this work, implementing computational models to balance the breast attenuation effects on the left ventricle anterior wall, during myocardium perfusion scintigraphy procedures with SPECT. A neural network was put on in order to provide the attenuation correction indexes, based upon the following patients individual biotypes features: mass, age, height, chest and breast thicknesses, heart size, as well as the imparted activity intake levels. (author)

  18. MRI-guided attenuation correction in whole-body PET/MR. Assessment of the effect of bone attenuation

    International Nuclear Information System (INIS)

    Akbarzadeh, A.; Ay, M.R.; Ahmadian, A.; Riahi Alam, N.; Zaidi, H.

    2013-01-01

    Hybrid positron emission tomography (PET)/MRI presents many advantages in comparison with its counterpart PET/CT in terms of improved soft-tissue contrast, decrease in radiation exposure, and truly simultaneous and multi-parametric imaging capabilities. However, the lack of well-established methodology for MR-based attenuation correction is hampering further development and wider acceptance of this technology. We assess the impact of ignoring bone attenuation and using different tissue classes for generation of the attenuation map on the accuracy of attenuation correction of PET data. This work was performed using simulation studies based on the XCAT phantom and clinical input data. For the latter, PET and CT images of patients were used as input for the analytic simulation model using realistic activity distributions where CT-based attenuation correction was utilized as reference for comparison. For both phantom and clinical studies, the reference attenuation map was classified into various numbers of tissue classes to produce three (air, soft tissue and lung), four (air, lungs, soft tissue and cortical bones) and five (air, lungs, soft tissue, cortical bones and spongeous bones) class attenuation maps. The phantom studies demonstrated that ignoring bone increases the relative error by up to 6.8% in the body and up to 31.0% for bony regions. Likewise, the simulated clinical studies showed that the mean relative error reached 15% for lesions located in the body and 30.7% for lesions located in bones, when neglecting bones. These results demonstrate an underestimation of about 30% of tracer uptake when neglecting bone, which in turn imposes substantial loss of quantitative accuracy for PET images produced by hybrid PET/MRI systems. Considering bones in the attenuation map will considerably improve the accuracy of MR-guided attenuation correction in hybrid PET/MR to enable quantitative PET imaging on hybrid PET/MR technologies. (author)

  19. Earth-Space Link Attenuation Estimation via Ground Radar Kdp

    Science.gov (United States)

    Bolen, Steven M.; Benjamin, Andrew L.; Chandrasekar, V.

    2003-01-01

    A method of predicting attenuation on microwave Earth/spacecraft communication links, over wide areas and under various atmospheric conditions, has been developed. In the area around the ground station locations, a nearly horizontally aimed polarimetric S-band ground radar measures the specific differential phase (Kdp) along the Earth-space path. The specific attenuation along a path of interest is then computed by use of a theoretical model of the relationship between the measured S-band specific differential phase and the specific attenuation at the frequency to be used on the communication link. The model includes effects of rain, wet ice, and other forms of precipitation. The attenuation on the path of interest is then computed by integrating the specific attenuation over the length of the path. This method can be used to determine statistics of signal degradation on Earth/spacecraft communication links. It can also be used to obtain real-time estimates of attenuation along multiple Earth/spacecraft links that are parts of a communication network operating within the radar coverage area, thereby enabling better management of the network through appropriate dynamic routing along the best combination of links.

  20. A promising hybrid approach to SPECT attenuation correction

    International Nuclear Information System (INIS)

    Lewis, N.H.; Faber, T.L.; Corbett, J.R.; Stokely, E.M.

    1984-01-01

    Most methods for attenuation compensation in SPECT either rely on the assumption of uniform attenuation, or use slow iteration to achieve accuracy. However, hybrid methods that combine iteration with simple multiplicative correction can accommodate nonuniform attenuation, and such methods converge faster than other iterative techniques. The authors evaluated two such methods, which differ in use of a damping factor to control convergence. Both uniform and nonuniform attenuation were modeled, using simulated and phantom data for a rotating gamma camera. For simulations done with 360 0 data and the correct attenuation map, activity levels were reconstructed to within 5% of the correct values after one iteration. Using 180 0 data, reconstructed levels in regions representing lesion and background were within 5% of the correct values in three iterations; however, further iterations were needed to eliminate the characteristic streak artifacts. The damping factor had little effect on 360 0 reconstruction, but was needed for convergence with 180 0 data. For both cold- and hot-lesion models, image contrast was better from the hybrid methods than from the simpler geometric-mean corrector. Results from the hybrid methods were comparable to those obtained using the conjugate-gradient iterative method, but required 50-100% less reconstruction time. The relative speed of the hybrid methods, and their accuracy in reconstructing photon activity in the presence of nonuniform attenuation, make them promising tools for quantitative SPECT reconstruction

  1. The LCLS Gas Attenuator Revisited

    International Nuclear Information System (INIS)

    Ryutov, D

    2005-01-01

    In the report ''X-ray attenuation cell'' [1] a preliminary analysis of the gas attenuator for the Linac Coherent Light Source (LCLS) was presented. This analysis was carried out for extremely stringent set of specifications. In particular, a very large diameter for the unobstructed beam was set (1 cm) to accommodate the spontaneous radiation; the attenuator was supposed to cover the whole range of energies of the coherent radiation, from 800 eV to 8000 eV; the maximum attenuation was set at the level of 10 4 ; the use of solid attenuators was not allowed, as well as the use of rotating shutters. The need to reach a sufficient absorption at the high-energy end of the spectrum predetermined the choice of Xe as the working gas (in order to have a reasonable absorption at a not-too-high pressure). A sophisticated differential pumping system that included a Penning-type ion pump was suggested in order to minimize the gas leak into the undulator/accelerator part of the facility. A high cost of xenon meant also that an efficient (and expensive) gas-recovery system would have to be installed. The main parameter that determined the high cost and the complexity of the system was a large radius of the orifice. The present viewpoint allows for much smaller size of the orifice, r 0 = 1.5 mm. (1) The use of solid attenuators is also allowed (R.M. Bionta, private communication). It is, therefore, worthwhile to reconsider various parameters of the gas attenuator for these much less stringent conditions. This brief study should be considered as a physics input for the engineering design. As a working gas we consider now the argon, which, on the one hand, provides a reasonable absorption lengths and, on the other hand, is inexpensive enough to be exhausted into the atmosphere (no recovery). The absorption properties of argon are illustrated by Fig.1 where the attenuation factor A is shown for various beam energies, based on Ref. [2]. The other relevant parameters for argon are

  2. Josephson tunnel junction microwave attenuator

    DEFF Research Database (Denmark)

    Koshelets, V. P.; Shitov, S. V.; Shchukin, A. V.

    1993-01-01

    A new element for superconducting electronic circuitry-a variable attenuator-has been proposed, designed, and successfully tested. The principle of operation is based on the change in the microwave impedance of a superconductor-insulator-superconductor (SIS) Josephson tunnel junction when dc biased...... at different points in the current-voltage characteristic. Both numerical calculations based on the Tien-Gordon theory and 70-GHz microwave experiments have confirmed the wide dynamic range (more than 15-dB attenuation for one stage) and the low insertion loss in the ''open'' state. The performance of a fully...

  3. Continental Fog Attenuation Empirical Relationship from Measured Visibility Data

    Directory of Open Access Journals (Sweden)

    F. Nadeem

    2010-12-01

    Full Text Available Free Space Optics (FSO has the great potential for future communication applications. However, weather influenced reduced availability had been the main cause for its restricted growth. Among different weather influences fog plays the major role. A new model generalized for all FSO wavelengths, has been proposed for the prediction of continental fog attenuation using visibility data. The performance of the proposed model has been compared with well known models for measured attenuation data of Continental fog. The comparison has been performed in terms of Root Mean Square Error (RMSE.

  4. Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis.

    Science.gov (United States)

    Xu, Wei; Huang, Mingqing; Zhang, Yuqin; Li, Huang; Zheng, Haiyin; Yu, Lishuang; Chu, Kedan; Lin, Yu; Chen, Lidian

    2016-05-01

    Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor‑α and nuclear factor‑κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription‑polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE‑treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action.

  5. Restoration of Dopamine Release Deficits during Object Recognition Memory Acquisition Attenuates Cognitive Impairment in a Triple Transgenic Mice Model of Alzheimer's Disease

    Science.gov (United States)

    Guzman-Ramos, Kioko; Moreno-Castilla, Perla; Castro-Cruz, Monica; McGaugh, James L.; Martinez-Coria, Hilda; LaFerla, Frank M.; Bermudez-Rattoni, Federico

    2012-01-01

    Previous findings indicate that the acquisition and consolidation of recognition memory involves dopaminergic activity. Although dopamine deregulation has been observed in Alzheimer's disease (AD) patients, the dysfunction of this neurotransmitter has not been investigated in animal models of AD. The aim of this study was to assess, by in vivo…

  6. Scatter and attenuation correction in SPECT

    International Nuclear Information System (INIS)

    Ljungberg, Michael

    2004-01-01

    The adsorbed dose is related to the activity uptake in the organ and its temporal distribution. Measured count rate with scintillation cameras is related to activity through the system sensitivity, cps/MBq. By accounting for physical processes and imaging limitations we can measure the activity at different time points. Correction for physical factor, such as attenuation and scatter is required for accurate quantitation. Both planar and SPECT imaging can be used to estimate activities for radiopharmaceutical dosimetry. Planar methods have been the most widely used but is a 2D technique. With accurate modelling for imagine in iterative reconstruction, SPECT methods will prove to be more accurate

  7. The Sound Attenuation Coefficient Optimization in Case of a Three Parameter Impedance Model for a Rectangular 3D Straight Lined Duct of Finite Dimensions

    Directory of Open Access Journals (Sweden)

    Stefan BALINT

    2015-09-01

    Full Text Available A method for the minimization of the ratio of the sound pressure level at the exit to that at the entrance is presented for a rectangular 3D straight lined duct carrying a uniform gas flow. The duct dimensions, the incident sound wave as well as the frequency of the sound wave propagation are assumed to be known. It is assumed also that the liner impedance model is the mass-spring–damper model. The idea is to compute the considered ratio for a large number of combinations of the values of the inertance, resistance and stiffness of the liner and, by fitting the obtained data, to establish a formula for the dependence of the ratio in discussion on these three parameters of the liner. Using the obtained formula, the minimum value of the ratio, as well as the values of the inertance, resistance and stiffness, for which the minimum is obtained, are found.

  8. Transient attenuation in optical fibers

    International Nuclear Information System (INIS)

    Hopkins, A.A.; Kelly, R.E.; Looney, L.D.; Lyons, P.B.

    1984-01-01

    Low and high energy pulsed electron beams were used to generate radiation-induced transient attenuation in high-OH, Suprasil core, PCS fibers, demonstrating the energy dependence of the radiation damage and recovery mechanisms. A radiation resistant low-OH fiber was studied and its performance contrasted to that of high-OH materials. Several fibers with differing core compositions were also studied

  9. A Generalized Correction for Attenuation.

    Science.gov (United States)

    Petersen, Anne C.; Bock, R. Darrell

    Use of the usual bivariate correction for attenuation with more than two variables presents two statistical problems. This pairwise method may produce a covariance matrix which is not at least positive semi-definite, and the bivariate procedure does not consider the possible influences of correlated errors among the variables. The method described…

  10. Compact plasmonic variable optical attenuator

    DEFF Research Database (Denmark)

    Leosson, Kristjan; Rosenzveig, Tiberiu; Hermannsson, Pétur Gordon

    2008-01-01

    We demonstrate plasmonic nanowire-based thermo-optic variable optical attenuators operating in the 1525-1625 nm wavelength range. The devices have a footprint as low as 1 mm, extinction ratio exceeding 40 dB, driving voltage below 3 V, and full modulation bandwidth of 1 kHz. The polarization...

  11. Attenuation of Vrancea events revisited

    International Nuclear Information System (INIS)

    Radulian, M.; Popa, M.; Grecu, B.; Panza, G.F.

    2003-11-01

    New aspects of the frequency-dependent attenuation of the seismic waves traveling from Vrancea subcrustal sources toward NW (Transylvanian Basin) and SE (Romanian Plain) are evidenced by the recent experimental data made available by the CALIXTO'99 tomography experiment. The observations validate the previous theoretical computations performed for the assessment, by means of a deterministic approach, of the seismic hazard in Romania. They reveal an essential aspect of the seismic ground motion attenuation, that has important implications on the probabilistic assessment of seismic hazard from Vrancea intermediate-depth earthquakes. The attenuation toward NW is shown to be a much stronger frequency-dependent effect than the attenuation toward SE and the seismic hazard computed by the deterministic approach fits satisfactorily well the observed ground motion distribution in the low-frequency band (< 1 Hz). The apparent contradiction with the historically-based intensity maps arises mainly from a systematic difference in the vulnerability (buildings eigenperiod) of the buildings in the intra- and extra-Carpathians regions. (author)

  12. Wave attenuation across a tidal marsh in San Francisco Bay

    Science.gov (United States)

    Foster-Martinez, Madeline R.; Lacy, Jessica; Ferner, Matthew C.; Variano, Evan A.

    2018-01-01

    Wave attenuation is a central process in the mechanics of a healthy salt marsh. Understanding how wave attenuation varies with vegetation and hydrodynamic conditions informs models of other marsh processes that are a function of wave energy (e.g. sediment transport) and allows for the incorporation of marshes into coastal protection plans. Here, we examine the evolution of wave height across a tidal salt marsh in San Francisco Bay. Instruments were deployed along a cross-shore transect, starting on the mudflat and crossing through zones dominated by Spartina foliosa and Salicornia pacifica. This dataset is the first to quantify wave attenuation for these vegetation species, which are abundant in the intertidal zone of California estuaries. Measurements were collected in the summer and winter to assess seasonal variation in wave attenuation. Calculated drag coefficients of S. foliosa and S. pacifica were similar, indicating equal amounts of vegetation would lead to similar energy dissipation; however, S. pacifica has much greater biomass close to the bed (<20 cm) and retains biomass throughout the year, and therefore, it causes more total attenuation. S. foliosa dies back in the winter, and waves often grow across this section of the marsh. For both vegetation types, attenuation was greatest for low water depths, when the vegetation was emergent. For both seasons, attenuation rates across S. pacifica were the highest and were greater than published attenuation rates across similar (Spartina alterniflora) salt marshes for the comparable depths. These results can inform designs for marsh restorations and management plans in San Francisco Bay and other estuaries containing these species.

  13. Electron attenuation in free, neutral ethane clusters.

    Science.gov (United States)

    Winkler, M; Myrseth, V; Harnes, J; Børve, K J

    2014-10-28

    The electron effective attenuation length (EAL) in free, neutral ethane clusters has been determined at 40 eV kinetic energy by combining carbon 1s x-ray photoelectron spectroscopy and theoretical lineshape modeling. More specifically, theory is employed to form model spectra on a grid in cluster size (N) and EAL (λ), allowing N and λ to be determined by optimizing the goodness-of-fit χ(2)(N, λ) between model and observed spectra. Experimentally, the clusters were produced in an adiabatic-expansion setup using helium as the driving gas, spanning a range of 100-600 molecules in mean cluster size. The effective attenuation length was determined to be 8.4 ± 1.9 Å, in good agreement with an independent estimate of 10 Å formed on the basis of molecular electron-scattering data and Monte Carlo simulations. The aggregation state of the clusters as well as the cluster temperature and its importance to the derived EAL value are discussed in some depth.

  14. Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as an Analytical Method to Investigate the Secondary Structure of a Model Protein Embedded in Solid Lipid Matrices.

    Science.gov (United States)

    Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene; Medlicott, Natalie J

    2018-02-01

    Protein drugs may encounter conformational perturbations during the formulation processing of lipid-based solid dosage forms. In aqueous protein solutions, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can investigate these conformational changes following the subtraction of spectral interference of solvent with protein amide I bands. However, in solid dosage forms, the possible spectral contribution of lipid carriers to protein amide I band may be an obstacle to determine conformational alterations. The objective of this study was to develop an ATR FT-IR spectroscopic method for the analysis of protein secondary structure embedded in solid lipid matrices. Bovine serum albumin (BSA) was chosen as a model protein, while Precirol AT05 (glycerol palmitostearate, melting point 58 ℃) was employed as the model lipid matrix. Bovine serum albumin was incorporated into lipid using physical mixing, melting and mixing, or wet granulation mixing methods. Attenuated total reflection FT-IR spectroscopy and size exclusion chromatography (SEC) were performed for the analysis of BSA secondary structure and its dissolution in aqueous media, respectively. The results showed significant interference of Precirol ATO5 with BSA amide I band which was subtracted up to 90% w/w lipid content to analyze BSA secondary structure. In addition, ATR FT-IR spectroscopy also detected thermally denatured BSA solid alone and in the presence of lipid matrix indicating its suitability for the detection of denatured protein solids in lipid matrices. Despite being in the solid state, conformational changes occurred to BSA upon incorporation into solid lipid matrices. However, the extent of these conformational alterations was found to be dependent on the mixing method employed as indicated by area overlap calculations. For instance, the melting and mixing method imparted negligible effect on BSA secondary structure, whereas the wet granulation mixing method promoted

  15. Genetic ablation of Bcl-x attenuates invasiveness without affecting apoptosis or tumor growth in a mouse model of pancreatic neuroendocrine cancer.

    Directory of Open Access Journals (Sweden)

    Jeffrey H Hager

    Full Text Available Tumor cell death is modulated by an intrinsic cell death pathway controlled by the pro- and anti-apoptotic members of the Bcl-2 family. Up-regulation of anti-apoptotic Bcl-2 family members has been shown to suppress cell death in pre-clinical models of human cancer and is implicated in human tumor progression. Previous gain-of-function studies in the RIP1-Tag2 model of pancreatic islet carcinogenesis, involving uniform or focal/temporal over-expression of Bcl-x(L, demonstrated accelerated tumor formation and growth. To specifically assess the role of endogenous Bcl-x in regulating apoptosis and tumor progression in this model, we engineered a pancreatic beta-cell-specific knockout of both alleles of Bcl-x using the Cre-LoxP system of homologous recombination. Surprisingly, there was no appreciable effect on tumor cell apoptosis rates or on tumor growth in the Bcl-x knockout mice. Other anti-apoptotic Bcl-2 family members were expressed but not substantively altered at the mRNA level in the Bcl-x-null tumors, suggestive of redundancy without compensatory transcriptional up-regulation. Interestingly, the incidence of invasive carcinomas was reduced, and tumor cells lacking Bcl-x were impaired in invasion in a two-chamber trans-well assay under conditions mimicking hypoxia. Thus, while the function of Bcl-x in suppressing apoptosis and thereby promoting tumor growth is evidently redundant, genetic ablation implicates Bcl-x in selectively facilitating invasion, consistent with a recent report documenting a pro-invasive capability of Bcl-x(L upon exogenous over-expression.

  16. Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model.

    Science.gov (United States)

    Kim, So Mi; Hwang, In Koo; Yoo, Dae Young; Eum, Won Sik; Kim, Dae Won; Shin, Min Jea; Ahn, Eun Hee; Jo, Hyo Sang; Ryu, Eun Ji; Yong, Ji In; Cho, Sung-Woo; Kwon, Oh-Shin; Lee, Keun Wook; Cho, Yoon Shin; Han, Kyu Hyung; Park, Jinseu; Choi, Soo Young

    2015-06-01

    Oxidative stress-induced reactive oxygen species (ROS) are responsible for various neuronal diseases. Antioxidant 1 (Atox1) regulates copper homoeostasis and promotes cellular antioxidant defence against toxins generated by ROS. The roles of Atox1 protein in ischaemia, however, remain unclear. In this study, we generated a protein transduction domain fused Tat-Atox1 and examined the roles of Tat-Atox1 in oxidative stress-induced hippocampal HT-22 cell death and an ischaemic injury animal model. Tat-Atox1 effectively transduced into HT-22 cells and it protected cells against the effects of hydrogen peroxide (H2O2)-induced toxicity including increasing of ROS levels and DNA fragmentation. At the same time, Tat-Atox1 regulated cellular survival signalling such as p53, Bad/Bcl-2, Akt and mitogen-activate protein kinases (MAPKs). In the animal ischaemia model, transduced Tat-Atox1 protected against neuronal cell death in the hippocampal CA1 region. In addition, Tat-Atox1 significantly decreased the activation of astrocytes and microglia as well as lipid peroxidation in the CA1 region after ischaemic insult. Taken together, these results indicate that transduced Tat-Atox1 protects against oxidative stress-induced HT-22 cell death and against neuronal damage in animal ischaemia model. Therefore, we suggest that Tat-Atox1 has potential as a therapeutic agent for the treatment of oxidative stress-induced ischaemic damage. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  17. Combination tones along the basilar membrane in a 3D finite element model of the cochlea with acoustic boundary layer attenuation

    Science.gov (United States)

    Böhnke, Frank; Scheunemann, Christian; Semmelbauer, Sebastian

    2018-05-01

    The propagation of traveling waves along the basilar membrane is studied in a 3D finite element model of the cochlea using single and two-tone stimulation. The advantage over former approaches is the consideration of viscous-thermal boundary layer damping which makes the usual but physically unjustified assumption of Rayleigh damping obsolete. The energy loss by viscous boundary layer damping is 70 dB lower than the actually assumed power generation by outer hair cells. The space-time course with two-tone stimulation shows the traveling waves and the periodicity of the beat frequency f2 - f1.

  18. Edaravone attenuates hippocampal damage in an infant mouse model of pneumococcal meningitis by reducing HMGB1 and iNOS expression via the Nrf2/HO-1 pathway.

    Science.gov (United States)

    Li, Zheng; Ma, Qian-Qian; Yan, Yan; Xu, Feng-Dan; Zhang, Xiao-Ying; Zhou, Wei-Qin; Feng, Zhi-Chun

    2016-09-01

    Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger that has shown potent antioxidant, anti-inflammatory and neuroprotective effects in variety of disease models. In this study, we investigated whether edaravone produced neuroprotective actions in an infant mouse model of pneumococcal meningitis. C57BL/6 mice were infected on postnatal d 11 by intracisternal injection of a certain inoculum of Streptococcus pneumoniae. The mice received intracisternal injection of 10 μL of saline containing edaravone (3 mg/kg) once a day for 7 d. The severity of pneumococcal meningitis was assessed with a clinical score. In mice with severe meningitis, the survival rate from the time of infection to d 8 after infection was analyzed using Kaplan-Meier curves. In mice with mild meningitis, the CSF inflammation and cytokine levels in the hippocampus were analyzed d 7 after infection, and the clinical neurological deficit score was evaluated using a neurological scoring system d 14 after infection. The nuclear factor (erythroid-derived 2)-like 2 knockout (Nrf2 KO) mice and heme oxygenase-1 knockout (HO-1 KO) mice were used to confirm the involvement of Nrf2/HO-1 pathway in the neuroprotective actions of edaravone. In mice with severe meningitis, edaravone treatment significantly increased the survival rate (76.4%) compared with the meningitis model group (32.2%). In mice with mild meningitis, edaravone treatment significantly decreased the number of leukocytes and TNF- levels in CSF, as well as the neuronal apoptosis and protein levels of HMGB1 and iNOS in the hippocampus, but did not affect the high levels of IL-10 and IL-6 in the hippocampus. Moreover, edaravone treatment significantly improved the neurological function of mice with mild meningitis. In Nrf2 KO or HO-1 KO mice with the meningitis, edaravone treatment was no longer effective in improving the survival rate of the mice with severe meningitis (20.2% and 53.6%, respectively), nor it affected the

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

    Science.gov (United States)

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

    2018-01-01

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

  20. Contaminant Attenuation and Transport Characterization of 200-UP-1 Operable Unit Sediment Samples

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Brady D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Szecsody, James E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Qafoku, Nikolla [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McElroy, Erin M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Baum, Steven R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Snyder, Michelle MV [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Lawter, Amanda R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Resch, Charles T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Gartman, Brandy N. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zhong, Lirong [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Saunders, Danielle L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Williams, Benjamin D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Horner, Jacob A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Leavy, Ian I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Christiansen, Beren B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Clayton, Ray E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Johnson, Kayla C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2017-09-27

    Contaminants disposed of at the land surface migrate through the vadose zone, forming plumes in groundwater. Processes that occur in the groundwater can attenuate contaminant concentrations during transport through the aquifer. For this reason, quantifying contaminant attenuation and contaminant transport processes in the aquifer, in support of the conceptual site model (CSM) and fate and transport modeling, are important for assessing the need for, and type of, remediation in the groundwater, including monitored natural attenuation (MNA). The framework to characterize attenuation and transport processes provided in U.S. Environmental Protection Agency (EPA) guidance documents was used to guide the laboratory effort reported herein.

  1. Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression.

    Science.gov (United States)

    Xiang, Wei; Tian, Canhui; Peng, Shunli; Zhou, Liang; Pan, Suyue; Deng, Zhen

    2017-11-04

    The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Jin Choi

    Full Text Available Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF, the levels of total immunoglobulin (Ig E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13 and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

  3. Simvastatin Attenuates the Oxidative Stress, Endothelial Thrombogenicity and the Inducibility of Atrial Fibrillation in a Rat Model of Ischemic Heart Failure

    Directory of Open Access Journals (Sweden)

    Kyoung-Im Cho

    2014-08-01

    Full Text Available Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF, and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI-induced heart failure (HF rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group and underwent echocardiography, AF induction studies and left atrial (LA fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX, sarcoplasmic reticulum calcium ATPase (SERCA, endothelial nitric oxide synthase (eNOS and induced nitric oxide synthase (iNOS were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham, which were significantly reduced by simvastatin (p < 0.05 vs. MI. The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.

  4. Intranasal PRGF-Endoret enhances neuronal survival and attenuates NF-κB-dependent inflammation process in a mouse model of Parkinson's disease.

    Science.gov (United States)

    Anitua, Eduardo; Pascual, Consuelo; Pérez-Gonzalez, Rocio; Orive, Gorka; Carro, Eva

    2015-04-10

    Parkinson's disease is a common neurodegenerative disorder of unknown pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Oxidative stress, microglial activation and inflammatory responses seem to contribute to the pathogenesis. Recent data showed that growth factors mediate neuroprotection in rodent models of Parkinson's disease, modulating pro-inflammatory processes. Based on our recent studies showing that plasma rich in growth factors (PRGF-Endoret) mediates neuroprotection as inflammatory moderator in Alzheimer's disease, in the present study we examined the effects of plasma rich in growth factors (PRGF-Endoret) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse as a translational therapeutic approach for Parkinson's disease. We found substantial neuroprotection by PRGF-Endoret in our model of Parkinson's disease, which resulted in diminished inflammatory responses and improved motor performance. Additionally, these effects were associated with robust reduction in nuclear transcription factor-κB (NF-κB) activation, and nitric oxide (NO), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) expression in the substantia nigra. We propose that PRGF-Endoret can prevent dopaminergic degeneration via an NF-κB-dependent signaling process. As the clinical safety profile of PRGF-Endoret is already established, these data suggest that PRGF-Endoret provides a novel neuroprotective strategy for Parkinson's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. An anti-interleukin-2 receptor drug attenuates T- helper 1 lymphocytes-mediated inflammation in an acute model of endotoxin-induced uveitis.

    Directory of Open Access Journals (Sweden)

    Salvador Mérida

    Full Text Available The aim of the present study was to evaluate the anti-inflammatory efficacy of Daclizumab, an anti-interleukin-2 receptor drug, in an experimental uveitis model upon a subcutaneous injection of lipopolysaccharide into Lewis rats, a valuable model for ocular acute inflammatory processes. The integrity of the blood-aqueous barrier was assessed 24 h after endotoxin-induced uveitis by evaluating two parameters: cell count and protein concentration in aqueous humors. The histopathology of all the ocular structures (cornea, lens, sclera, choroid, retina, uvea, and anterior and posterior chambers was also considered. Enzyme-linked immunosorbent assays of the aqueous humor samples were performed to quantify the levels of the different chemokine and cytokine proteins. Similarly, a biochemical analysis of oxidative stress-related markers was also assessed. The inflammation observed in the anterior chamber of the eyes when Daclizumab was administered with endotoxin was largely prevented since the aqueous humor protein concentration substantially lowered concomitantly with a significant reduction in the uveal and vitreous histopathological grading. Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon-γ, also significantly reduced with related anti-oxidant systems recovery. Daclizumab treatment in endotoxin-induced uveitis reduced Th1 lymphocytes-related cytokines, such as Interleukin-2 and Interferon gamma, by about 60-70% and presented a preventive role in endotoxin-induced oxidative stress. This antioxidant protective effect of Daclizumab may be related to several of the observed Daclizumab effects in our study, including IL-6 cytokine regulatory properties and a substantial concomitant drop in INFγ. Concurrently, Daclizumab treatment triggered a significant reduction in both the uveal histopathological grading and protein concentration in aqueous humors, but not in cellular infiltration.

  6. Modelling and attenuation feasibility of the aeroelastic response of active helicopter rotor systems during the engagement/disengagement phase of maritime operation

    Science.gov (United States)

    Khouli, F.

    An aeroelastic phenomenon, known as blade sailing, encountered during maritime operation of helicopters is identified as being a factor that limits the tactical flexibility of helicopter operation in some sea conditions. The hazards associated with this phenomenon and its complexity, owing to the number of factors contributing to its occurrence, led previous investigators to conclude that advanced and validated simulation tools are best suited to investigate it. A research gap is identified in terms of scaled experimental investigation of this phenomenon and practical engineering solutions to alleviate its negative impact on maritime helicopter operation. The feasibility of a proposed strategy to alleviate it required addressing a gap in modelling thin-walled composite active beams/rotor blades. The modelling is performed by extending a mathematically-consistent and asymptotic reduction strategy of the 3-D elastic problem to account for embedded active materials. The derived active cross-sectional theory is validated using 2-D finite element results for closed and open cross-sections. The geometrically-exact intrinsic formulation of active maritime rotor systems is demonstrated to yield compact and symbolic governing equations. The intrinsic feature is shown to allow a classical and proven solution scheme to be successfully applied to obtain time history solutions. A Froude-scaled experimental rotor was designed, built, and tested in a scaled ship airwake environment and representative ship motion. Based on experimental and simulations data, conclusions are drawn regarding the influence of the maritime operation environment and the rotor operation parameters on the blade sailing phenomenon. The experimental data is also used to successfully validate the developed simulation tools. The feasibility of an open-loop control strategy based on the integral active twist concept to counter blade sailing is established in a Mach-scaled maritime operation environment

  7. Inferring global upper-mantle shear attenuation structure by waveform tomography using the spectral element method

    Science.gov (United States)

    Karaoǧlu, Haydar; Romanowicz, Barbara

    2018-06-01

    We present a global upper-mantle shear wave attenuation model that is built through a hybrid full-waveform inversion algorithm applied to long-period waveforms, using the spectral element method for wavefield computations. Our inversion strategy is based on an iterative approach that involves the inversion for successive updates in the attenuation parameter (δ Q^{-1}_μ) and elastic parameters (isotropic velocity VS, and radial anisotropy parameter ξ) through a Gauss-Newton-type optimization scheme that employs envelope- and waveform-type misfit functionals for the two steps, respectively. We also include source and receiver terms in the inversion steps for attenuation structure. We conducted a total of eight iterations (six for attenuation and two for elastic structure), and one inversion for updates to source parameters. The starting model included the elastic part of the relatively high-resolution 3-D whole mantle seismic velocity model, SEMUCB-WM1, which served to account for elastic focusing effects. The data set is a subset of the three-component surface waveform data set, filtered between 400 and 60 s, that contributed to the construction of the whole-mantle tomographic model SEMUCB-WM1. We applied strict selection criteria to this data set for the attenuation iteration steps, and investigated the effect of attenuation crustal structure on the retrieved mantle attenuation structure. While a constant 1-D Qμ model with a constant value of 165 throughout the upper mantle was used as starting model for attenuation inversion, we were able to recover, in depth extent and strength, the high-attenuation zone present in the depth range 80-200 km. The final 3-D model, SEMUCB-UMQ, shows strong correlation with tectonic features down to 200-250 km depth, with low attenuation beneath the cratons, stable parts of continents and regions of old oceanic crust, and high attenuation along mid-ocean ridges and backarcs. Below 250 km, we observe strong attenuation in the

  8. Fish oil feeding attenuates neuroinflammatory gene expression without concomitant changes in brain eicosanoids and docosanoids in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Hopperton, Kathryn E; Trépanier, Marc-Olivier; James, Nicholas C E; Chouinard-Watkins, Raphaël; Bazinet, Richard P

    2018-03-01

    Neuroinflammation is a recognized hallmark of Alzheimer's disease, along with accumulation of amyloid-β plaques, neurofibrillary tangles and synaptic loss. n-3 polyunsaturated fatty acids (PUFA) and molecules derived from them, including eicosapentaenoic acid-derived eicosanoids and docosahexaenoic acid-derived docosanoids, are known to have both anti-inflammatory and pro-resolving properties, while human observational data links consumption of these fatty acids to a decreased risk of Alzheimer's disease. Few studies have examined the neuroinflammation-modulating effects of n-3 PUFA feeding in an Alzheimer's disease-related model, and none have investigated whether these effects are mediated by changes in brain eicosanoids and docosanoids. Here, we use both a fat-1 transgenic mouse and a fish oil feeding model to study the impact of increasing tissue n-3 PUFA on neuroinflammation and the production of pro-inflammatory and pro-resolving lipid mediators. Fat-1 mice, transgenic animals that can convert n-6 to n-3 PUFA, and their wildtype littermates were fed diets containing either fish oil (high n-3 PUFA) or safflower oil (negligible n-3 PUFA) from weaning to 12 weeks. Animals then underwent intracerebroventricular infusion of either amyloid-β 1-40 or a control peptide. Hippocampi were collected from non-surgery and surgery animals 10 days after infusion. Microarray was used to measure enrichment of inflammation-associated gene categories and expression of genes involved in the synthesis of lipid mediators. Results were validated by real-time PCR in a separate cohort of animals. Lipid mediators were measured via liquid chromatography tandem mass spectrometry. Fat-1 and wildtype mice fed fish oil had higher total hippocampal DHA than wildtype mice fed the safflower oil diet. The safflower-fed mice, but not the fat-1 or fish oil-fed mice, had significantly increased expression in gene ontology categories associated with inflammation in response to amyloid

  9. Oxidative stress evoked damages leading to attenuated memory and inhibition of NMDAR–CaMKII–ERK/CREB signalling on consumption of aspartame in rat model

    Directory of Open Access Journals (Sweden)

    Ashok Iyaswamy

    2018-04-01

    Full Text Available Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposes to investigate whether long term (90 days aspartame (40 mg/kg b.wt administration could induce oxidative stress and alter the memory in Wistar strain male albino rats. To mimic the human methanol metabolism, methotrexate (MTX-treated rats were included as a model to study the effects of aspartame. Wistar strain albino rats were administered with aspartame (40 mg/kg b.wt orally and studied along with controls and MTX-treated controls. Aspartame interfered in the body weight and corticosterone levels in the rats. A marked increase in the mRNA and protein expression of neuronal nitric oxide synthase (nNOS and induced nitric oxide synthase (iNOS which resulted in the increased nitric oxide radical's level indicating that aspartame is a stressor. These reactive nitrogen species could be responsible for the altered cell membrane integrity and even cause death of neurons by necrosis or apoptosis. The animals showed a marked decrease in learning, spatial working and spatial recognition memory deficit in the Morris water maze and Y-maze performance task which could have resulted due to reduced hippocampal acetylcholine esterase (AChE activity. The animal brain homogenate also revealed the decrease in the phosphorylation of NMDAR1–CaMKII–ERK/CREB signalling pathway, which well documents the inhibition of phosphorylation leads to the excitotoxicity of the neurons and memory decline. This effect may be due to methanol which may also activate the NOS levels, microglia and astrocytes, inducing neurodegeneration in brain. Neuronal shrinkage of hippocampal layer due to degeneration of pyramidal cells revealed the abnormal neuronal morphology of pyramidal cell layers in the aspartame treated animals. These findings demonstrate that aspartame metabolites could be a contributing factor for the

  10. miR-494 up-regulates the PI3K/Akt pathway via targetting PTEN and attenuates hepatic ischemia/reperfusion injury in a rat model.

    Science.gov (United States)

    Su, Song; Luo, De; Liu, Xiangdong; Liu, Jiang; Peng, Fangyi; Fang, Cheng; Li, Bo

    2017-10-31

    A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir- miR-494 or agomir-NC (negative control) for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI + agomir- miR-494 , and HIRI + agomir-NC were compared. The effect of miR-494 was also assessed in an H 2 O 2 -induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or miR-494 mimics, followed by 6-h H 2 O 2 treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Further, the miR-494 target gene was identified by luciferase reporter assay, and verified both in vitro and in vivo experiments. The activity of AKT pathway was further analyzed in vivo by Western blot. HIRI + agomir- miR-494 rats exhibited significantly higher miR-494 expression, lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and glutamate dehydrogenase (GLDH) level, lower hepatic MDA, TOA, and OSI, alleviated hepatic necrosis, reduced hepatocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI + agomir-NC rats ( P <0.05 or 0.01). After H 2 O 2 treatment, AML-12 cells transfected with miR-494 mimics had significantly higher proliferation and lower apoptosis rate compared with mimics NC group ( P <0.01). PTEN was identified as an miR-494 target gene. PTEN expression was significantly down-regulated in AML12 cells transfected with miR-494 mimics, and was up-regulated by treatment of miR-494 inhibitor ( P <0.01). Moreover, HIRI + agomir- miR-494 rats exhibited significantly lower PTEN expression, and higher p-AKT, p-mTOR, and p-p70S6K levels compared with HIRI + agomir-NC rats. Therefore, miR-494 protected rats against hepatic ischemia/reperfusion (I/R) injury through down-regulating its downstream target gene PTEN , leading to the activation of PI3K/AKT signaling pathway. © 2017 The Author(s).

  11. Role of standardized grape polyphenol preparation as a novel treatment to improve synaptic plasticity through attenuation of features of metabolic syndrome in a mouse model.

    Science.gov (United States)

    Wang, Jun; Tang, Cheuk; Ferruzzi, Mario G; Gong, Bing; Song, Brian J; Janle, Elsa M; Chen, Tzu-Ying; Cooper, Bruce; Varghese, Merina; Cheng, Alice; Freire, Daniel; Bilski, Amanda; Roman, Jessica; Nguyen, Tuyen; Ho, Lap; Talcott, Stephen T; Simon, James E; Wu, Qingli; Pasinetti, Giulio M

    2013-12-01

    Metabolic syndrome has become an epidemic and poses tremendous burden on the health system. People with metabolic syndrome are more likely to experience cognitive decline. As obesity and sedentary lifestyles become more common, the development of early prevention strategies is critical. In this study, we explore the potential beneficial effects of a combinatory polyphenol preparation composed of grape seed extract, Concord purple grape juice extract, and resveratrol, referred to as standardized grape polyphenol preparation (SGP), on peripheral as well as brain dysfunction induced by metabolic syndrome. We found dietary fat content had minimal effect on absorption of metabolites of major polyphenols derived from SGP. Using a diet-induced animal model of metabolic syndrome (DIM), we found that brain functional connectivity and synaptic plasticity are compromised in the DIM mice. Treatment with SGP not only prevented peripheral metabolic abnormality but also improved brain synaptic plasticity. Our study demonstrated that SGP, comprised of multiple bioavailable and bioactive components targeting a wide range of metabolic syndrome related pathological features, provides greater global protection against peripheral and central nervous system dysfunctions and can be potentially developed as a novel prevention/treatment for improving brain connectivity and synaptic plasticity important for learning and memory. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease.

    Science.gov (United States)

    Chao, Yin Xia; He, Bei Ping; Tay, Samuel Sam Wah

    2009-11-30

    Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.

  13. S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson’s Disease Models

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    Chang-Ki Oh

    2017-11-01

    Full Text Available Mutations in PARK6 (PINK1 and PARK2 (Parkin are linked to rare familial cases of Parkinson’s disease (PD. Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1. Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity. SNO-PINK1 decreases Parkin translocation to mitochondrial membranes, disrupting mitophagy in cell lines and human-iPSC-derived neurons. We find levels of SNO-PINK1 in brains of α-synuclein transgenic PD mice similar to those in cell-based models, indicating the pathophysiological relevance of our findings. Importantly, SNO-PINK1-mediated deficits in mitophagy contribute to neuronal cell death. These results reveal a direct molecular link between nitrosative stress, SNO-PINK1 formation, and mitophagic dysfunction that contributes to the pathogenesis of PD.

  14. Repetitive Treatment with Diluted Bee Venom Attenuates the Induction of Below-Level Neuropathic Pain Behaviors in a Rat Spinal Cord Injury Model.

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    Kang, Suk-Yun; Roh, Dae-Hyun; Choi, Jung-Wan; Ryu, Yeonhee; Lee, Jang-Hern

    2015-07-10

    The administration of diluted bee venom (DBV) into an acupuncture point has been utilized traditionally in Eastern medicine to treat chronic pain. We demonstrated previously that DBV has a potent anti-nociceptive efficacy in several rodent pain models. The present study was designed to examine the potential anti-nociceptive effect of repetitive DBV treatment in the development of below-level neuropathic pain in spinal cord injury (SCI) rats. DBV was applied into the Joksamli acupoint during the induction and maintenance phase following thoracic 13 (T13) spinal hemisection. We examined the effect of repetitive DBV stimulation on SCI-induced bilateral pain behaviors, glia expression and motor function recovery. Repetitive DBV stimulation during the induction period, but not the maintenance, suppressed pain behavior in the ipsilateral hind paw. Moreover, SCI-induced increase in spinal glia expression was also suppressed by repetitive DBV treatment in the ipsilateral dorsal spinal cord. Finally, DBV injection facilitated motor function recovery as indicated by the Basso-Beattie-Bresnahan rating score. These results indicate that the repetitive application of DBV during the induction phase not only decreased neuropathic pain behavior and glia expression, but also enhanced locomotor functional recovery after SCI. This study suggests that DBV acupuncture can be a potential clinical therapy for SCI management.

  15. Natural attenuation in a surface water channel and a coastal aquifer by monitoring presence and removal of indicator bacteria, pathogens and antibiotic resistance gene: model development

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    Masciopinto, Costantino; Visino, Fabrizio; Luprano, Maria Laura; Levantesi, Caterina; Tandoi, Valter

    2015-04-01

    The spreading of microbial contamination into the environment, represents a very relevant problem, which leads to an increasing health concern. For this reason, it is important to identify and characterize the extent of natural depuration in water environmental particularly for reducing the presence of faecal contamination indicator bacteria, pathogens and antibiotic resistance genes (ARG). In this study, the presence of the above reported microbial parameters was analyzed in a surface water channel and in a coastal aquifer in southern Italy (Ostuni) southern Italy, both affected by Ostuni municipal treatment plant effluents and by local run-off. Several samples were collected from surface water, flowing in channels, and from wells in our study area. In particular, the water samples were analyzed to detect 7 fecal contamination indicators (E. coli, total coliforms, Clostridium p. spores, somatic coliphages, Enterococci and heterotrophic bacteria), Salmonella spp and the presence of ARGs. The water samples were also tested for chemical constituents. Finally a mathematical model has been developed in order to simulate pathogen migration pathways in the fractured groundwater and corresponding possible mitigation of pathogens in pumping wells.

  16. Receptor for advanced glycation end products involved in lung ischemia reperfusion injury in cardiopulmonary bypass attenuated by controlled oxygen reperfusion in a canine model.

    Science.gov (United States)

    Rong, Jian; Ye, Sheng; Liang, Meng-ya; Chen, Guang-xian; Liu, Hai; Zhang, Jin-Xin; Wu, Zhong-kai

    2013-01-01

    Controlled oxygen reperfusion could protect the lung against ischemia-reperfusion injury in cardiopulmonary bypass (CPB) by downregulating high mobility group box 1 (HMGB1), a high affinity receptor of HMGB1. This study investigated the effect of controlled oxygen reperfusion on receptor for advanced glycation end products (RAGE) expression and its downstream effects on lung ischemia-reperfusion injury. Fourteen canines received CPB with 60 minutes of aortic clamping and cardioplegic arrest followed by 90 minutes of reperfusion. Animals were randomized to receive 80% FiO2 during the entire procedure (control group) or to a test group receiving a controlled oxygen reperfusion protocol. Pathologic changes in lung tissues, RAGE expression, serum interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated. The lung pathologic scores after 25 and 90 minutes of reperfusion were significantly lower in the test group compared with the control group (p RAGE expression, TNF-α, and IL-6 were downregulated by controlled oxygen treatment (p RAGE might be involved in the lung ischemia-reperfusion injury in canine model of CPB, which was downregulated by controlled oxygen reperfusion.

  17. The Role of Hippocampal Estradiol Receptor-α in a Perimenopausal Affective Disorders-Like Rat Model and Attenuating of Anxiety by Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Xun Wang

    2016-01-01

    Full Text Available Hormone replacement therapy is the principal treatment for perimenopausal affective disorders which can cause severe side effects. The present study compared the effects of electroacupuncture (EA and estradiol treatment on perimenopausal affective disorders at the behavioral and cellular levels. In this randomized experimental in vivo study, adult female rats were divided into intact, ovariectomy, chronic unpredictable stress (CUS, and ovariectomy and CUS combination groups. After week 6, all groups were subdivided to three subgroups of control, EA, and estradiol treatment. The behavioral parameters in the open field and the elevated plus maze tests were assessed before and after treatments. Alterations of serum steroid hormones and changes of estradiol receptor-α (ER-α immunofluorescence neurons in the hippocampus sections were evaluated. EA treatment caused more antianxiety effects than estradiol treatment in CUS group (P<0.05. Notably, estradiol and EA treatments had better significant behavioral effects when the models were not estrogen-deficient. Importantly, within each group, compared to the control group, the numbers of ER-α-positive neurons were significantly larger in EA subgroups. Therefore, EA had antianxiety effects on perimenopausal affective disorders caused by CUS but not by estrogen deficiency and upregulation of hippocampus ER-α neurons may contribute to its mechanism of action.

  18. Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.

    Science.gov (United States)

    Chen, Rebecca; Mian, Michelle; Fu, Martin; Zhao, Jing Ying; Yang, Liang; Li, Yefu; Xu, Lin

    2015-11-01

    Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. PET/MRI for Oncologic Brain Imaging: A Comparison of Standard MR-Based Attenuation Corrections with a Model-Based Approach for the Siemens mMR PET/MR System.

    Science.gov (United States)

    Rausch, Ivo; Rischka, Lucas; Ladefoged, Claes N; Furtner, Julia; Fenchel, Matthias; Hahn, Andreas; Lanzenberger, Rupert; Mayerhoefer, Marius E; Traub-Weidinger, Tatjana; Beyer, Thomas

    2017-09-01

    The aim of this study was to compare attenuation-correction (AC) approaches for PET/MRI in clinical neurooncology. Methods: Forty-nine PET/MRI brain scans were included: brain tumor studies using 18 F-fluoro-ethyl-tyrosine ( 18 F-FET) ( n = 31) and 68 Ga-DOTANOC ( n = 7) and studies of healthy subjects using 18 F-FDG ( n = 11). For each subject, MR-based AC maps (MR-AC) were acquired using the standard DIXON- and ultrashort echo time (UTE)-based approaches. A third MR-AC was calculated using a model-based, postprocessing approach to account for bone attenuation values (BD, noncommercial prototype software by Siemens Healthcare). As a reference, AC maps were derived from patient-specific CT images (CTref). PET data were reconstructed using standard settings after AC with all 4 AC methods. We report changes in diagnosis for all brain tumor patients and the following relative differences values (RDs [%]), with regards to AC-CTref: for 18 F-FET (A)-SUVs as well as volumes of interest (VOIs) defined by a 70% threshold of all segmented lesions and lesion-to-background ratios; for 68 Ga-DOTANOC (B)-SUVs as well as VOIs defined by a 50% threshold for all lesions and the pituitary gland; and for 18 F-FDG (C)-RD of SUVs of the whole brain and 10 anatomic regions segmented on MR images. Results: For brain tumor imaging (A and B), the standard PET-based diagnosis was not affected by any of the 3 MR-AC methods. For A, the average RDs of SUV mean were -10%, -4%, and -3% and of the VOIs 1%, 2%, and 7% for DIXON, UTE, and BD, respectively. Lesion-to-background ratios for all MR-AC methods were similar to that of CTref. For B, average RDs of SUV mean were -11%, -11%, and -3% and of the VOIs 1%, -4%, and -3%, respectively. In the case of 18 F-FDG PET/MRI (C), RDs for the whole brain were -11%, -8%, and -5% for DIXON, UTE, and BD, respectively. Conclusion: The diagnostic reading of PET/MR patients with brain tumors did not change with the chosen AC method. Quantitative accuracy of

  20. α7 Nicotinic acetylcholine receptor-mediated anti-inflammatory effect in a chronic migraine rat model via the attenuation of glial cell activation

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    Liu Q

    2018-06-01

    Full Text Available Qing Liu,1 Chaoyang Liu,1 Li Jiang,1 Maolin Li,1 Ting Long,1 Wei He,1 Guangcheng Qin,2 Lixue Chen,2 Jiying Zhou1 1Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China; 2Laboratory Research Center, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China Background: Evidence suggests that the activation of α7 nicotinic acetylcholine receptor (α7nAChR can greatly decrease the neuroinflammation response. Neuroinflammation plays a pivotal role in the pathogenesis of chronic migraine (CM. Clinical observations also show that nicotine gum induces analgesic effects in migraine patients. However, whether α7nAChR is involved in CM is unclear.Objective: To investigate the role of α7nAChR in CM and provide a new therapeutic target for CM.Materials and methods: Thirty-six male Sprague–Dawley rats were distributed randomly into control, CM, PNU-282987, and α-bungarotoxin groups (n=9 rats in each group. The CM model was established by the recurrent daily administration of inflammatory soup on the dura over the course of 1 week. The hind paw threshold and facial allodynia were assessed by the von Frey test. The expression levels of α7nAChR, tumor necrosis factor-alpha, and interleukin-1 beta were analyzed by Western blot and real-time fluorescence quantitative polymerase chain reaction. The location of α7nAChR in the hippocampus was quantified by immunofluorescence, as well as the microglial and astrocyte alterations. Changes in the calcitonin gene-related peptide and the phosphorylated JNK protein among different groups were measured by Western blot.Results: We found that the expression of α7nAChR was reduced after repeated inflammatory soup administration. The increased expression of tumor necrosis factor-alpha, interleukin-1 beta, and calcitonin gene-related peptide in CM group were significantly decreased by PNU-282987 and aggravated by α-bungarotoxin. Moreover, PNU-282987

  1. Cannabinoid CB1 /CB2 receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia.

    Science.gov (United States)

    Scherma, Maria; Satta, Valentina; Collu, Roberto; Boi, Maria Francesca; Usai, Paolo; Fratta, Walter; Fadda, Paola

    2017-08-01

    Anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients. The activity-based anorexia (ABA) rodent model mimics the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether cannabinoid agonists can effectively modify anorexic-like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle. Our data show that subchronic treatment with both the natural CB 1 /CB 2 receptor agonist Δ 9 -tetrahydrocannabinol and the synthetic CB 1 /CB 2 receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by an increase in leptin signalling and a decrease in plasma levels of corticosterone. Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance. © 2017 The British Pharmacological Society.

  2. Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Botanas, Chrislean Jun; Lee, Hyelim; de la Peña, June Bryan; Dela Peña, Irene Joy; Woo, Taeseon; Kim, Hee Jin; Han, Doug Hyun; Kim, Bung-Nyun; Cheong, Jae Hoon

    2016-03-01

    Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-kappaB activation.

    Science.gov (United States)

    Tan, Hong-wei; Xing, Shan-shan; Bi, Xiu-ping; Li, Li; Gong, Hui-ping; Zhong, Ming; Zhang, Yun; Zhang, Wei

    2008-09-01

    Metabolic syndrome is associated with an increased incidence of atherosclerosis. Clinical studies have shown that calcium channel blockers (CCB) inhibit the progression of atherosclerosis. However, the underlying mechanism is unclear. We investigated the inhibitory effect of felodipine on adhesion molecular expression and macrophage infiltration in the aorta of high fructose-fed rats (FFR). Male Wistar rats were given 10% fructose in drinking water. After 32 weeks of high fructose feeding, they were treated with felodipine (5 mg x kg(-1) x d(-1)) for 6 weeks. The control rats were given a normal diet and water. The aortic expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the infiltration of macrophages were measured by real-time RT-PCR and/or immunohistochemistry. NF-kappaB activity was measured by electrophoretic mobility shift assay (EMSA). After 32 weeks of high fructose feeding, FFR displayed increased body weight, systolic blood pressure (SBP), serum insulin, and triglycerides when compared with the control rats. The aortic expressions of ICAM-1 and VCAM-1 were significantly increased in FFR than in the control rats and accompanied by the increased activity of NF-kappaB. FFR also showed significantly increased CD68- positive macrophages in the aortic wall. After treatment with felodipine, SBP, serum insulin, and the homeostasis model assessment decreased significantly. In addition to reducing ICAM-1 and VCAM-1, felodipine decreased macrophages in the aortic wall. EMSA revealed that felodipine inhibited NF-kappaB activation in FFR. Felodipine inhibited vessel wall inflammation. The inhibition of NF-kappaB may be involved in the modulation of vascular inflammatory response by CCB in metabolic syndrome.

  4. Intravenous Glutamine Administration Modulates TNF-α/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model.

    Science.gov (United States)

    Santos, Andressa Cristina Antunes; Correia, Carolina Argondizo; de Oliveira, Dalila Cunha; Nogueira-Pedro, Amanda; Borelli, Primavera; Fock, Ricardo Ambrosio

    2016-12-01

    Protein malnutrition (PM) is a major public health problem in developing countries, affecting the inflammatory response and increasing susceptibility to opportunistic infections. For this reason, an adequate nutritional intervention can improve the quality of life of patients. Glutamine (GLN) is a nonessential amino acid, but can be considered "conditionally essential" for macrophage function in stress situations, in which it plays a role in the improvement of the inflammatory response. Concerning this issue, in the current study, it was of interest to evaluate some biological aspects of peritoneal cells from a protein malnutrition (PM) mouse model challenged with lipopolysaccharide (LPS) and treated intravenously with GLN. Two-month-old male Balb/c mice were subjected to a low-protein diet (2 % protein) and stimulated intravenously with LPS 1 h prior to the injection of 0.75 mg/kg GLN. Malnourished animals showed a reduced number of total peritoneal cells. Malnourished animals stimulated with LPS or LPS plus GLN did not show differences in peritoneal cell counts; however, the control group showed increased cellularity after LPS stimulus, which was reversed after GLN injection. Further, in the animals from both groups stimulated with LPS, GLN decreased the circulating levels of TNF-α and the levels of TNF-α produced by peritoneal cells; additionally, GLN decreased the IL-10 circulating levels in the malnourished animals stimulated with LPS. In addition, peritoneal cells of the control and malnourished groups stimulated with LPS showed a negative modulation of the NFkB signaling pathway after GLN injection. In conclusion, this study shows that GLN has the capacity to reduce TNF-α synthesis as well as to act as a negative regulator of NFkB phosphorylation, leading to a positive outcome in the control of TNF-α production.

  5. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

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    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd., Suite 2114, Bethesda, MD 20892 (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

    2013-01-15

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  6. A Focused Salivary Gland Infection with attenuated MCMV: An Animal Model with Prevention of Pathology Associated with Systemic MCMV Infection1, 2

    Science.gov (United States)

    Pilgrim, Mark J.; Kasman, Laura; Grewal, Jasvir; Bruorton, Mary E.; Werner, Phil; London, Lucille; London, Steven D.

    2010-01-01

    While the salivary gland has been recognized as an important effector site of the common mucosal immune system, a useful model for studying anti-viral salivary gland immune responses in vivo and for exploring the role of the salivary gland within the common mucosal system has been lacking. Murine cytomegalovirus (MCMV) is a beta-herpesvirus that displays a strong tropism for the salivary gland and produces significant morbidity in susceptible mice when introduced by intraperitoneal (i.p.) inoculation. This study tested the hypothesis that MCMV morbidity and pathology could be reduced by injecting the virus directly the submandibular salivary gland (intraglandular (i.g.)), using either in vivo derived MCMV or the less virulent, tissue culture-derived MCMV (tcMCMV). Peak salivary gland viral titers were completely unaffected by infection route (i.p vs. i.g.) after inoculation with either MCMV or tcMCMV. However, i.g. tcMCMV inoculation reduced viremia in all systemic tissues tested compared to i.p. inoculation. Further, systemic organ pathology observed in the liver and spleen after i.p. inoculation with either MCMV or tcMCMV was completely eliminated by i.g. inoculation with tcMCMV. Cellular infiltrates in the salivary glands, after i.p. or i.g. inoculation were composed of both B and T cells, indicating the potential for a local immune response to occur in the salivary gland. These results demonstrate that a focused MCMV infection of the salivary gland without systemic organ pathology is possible using i.g. delivery of tcMCMV. PMID:17320076

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

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    Ken Murakami

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

  8. Final Project Report - Coupled Biogeochemical Process Evaluation for Conceptualizing Trichloriethylene Co-Metabolism: Co-Metabolic Enzyme Activity Probes and Modeling Co-Metabolism and Attenuation

    Energy Technology Data Exchange (ETDEWEB)

    Starr, Robert C; Orr, Brennon R; Lee, M Hope; Delwiche, Mark

    2010-02-26

    Trichloroethene (TCE) (also known as trichloroethylene) is a common contaminant in groundwater. TCE is regulated in drinking water at a concentration of 5 µg/L, and a small mass of TCE has the potential to contaminant large volumes of water. The physical and chemical characteristics of TCE allow it to migrate quickly in most subsurface environments, and thus large plumes of contaminated groundwater can form from a single release. The migration and persistence of TCE in groundwater can be limited by biodegradation. TCE can be biodegraded via different processes under either anaerobic or aerobic conditions. Anaerobic biodegradation is widely recognized, but aerobic degradation is less well recognized. Under aerobic conditions, TCE can be oxidized to non hazardous conditions via cometabolic pathways. This study applied enzyme activity probes to demonstrate that cometabolic degradation of TCE occurs in aerobic groundwater at several locations, used laboratory microcosm studies to determine aerobic degradation rates, and extrapolated lab-measured rates to in situ rates based on concentrations of microorganisms with active enzymes involved in cometabolic TCE degradation. Microcosms were constructed using basalt chips that were inoculated with microorganisms to groundwater at the Idaho National Laboratory Test Area North TCE plume by filling a set of Flow-Through In Situ Reactors (FTISRs) with chips and placing the FTISRs into the open interval of a well for several months. A parametric study was performed to evaluate predicted degradation rates and concentration trends using a competitive inhibition kinetic model, which accounts for competition for enzyme active sites by both a growth substrate and a cometabolic substrate. The competitive inhibition kinetic expression was programmed for use in the RT3D reactive transport package. Simulations of TCE plume evolution using both competitive inhibition kinetics and first order decay were performed.

  9. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    International Nuclear Information System (INIS)

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C.; Ballestas, Mary E.; Kopelovich, Levy; Elmets, Craig A.; Athar, Mohammad

    2013-01-01

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation with large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.

  10. Ultrasonic attenuation of CdSe at low temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, B.J., E-mail: braulio@ula.v [Centro de Estudios de Semiconductores, Departamento de Fisica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of); Calderon, E.; Bracho, D.B. [Centro de Estudios de Semiconductores, Departamento de Fisica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of); Perez, J.F. [Laboratorio de Instrumentacion Cientifica, Facultad de Ciencias, Universidad de Los Andes Apartado de Correos No.1, La Hechicera, Merida 5251 (Venezuela, Bolivarian Republic of)

    2010-08-01

    The ultrasonic attenuation of a single crystal of CdSe has been investigated over the temperature range from 1.2 to 300 K at frequencies of 10, 30 and 90 MHz. We report here the temperature dependence of the attenuation in the range 1.2-30 K for piezoactive and non-piezoactive acoustic waves. A temperature-induced relaxation for two piezoactive waves, which scale with frequency towards higher temperatures, was found. A modified Hutson and White model with a new parameter {gamma} is proposed to explain the relaxation maxima of our data and others in the literature. In this model the parameter {gamma}, which seems to be closely related to the compensation, takes into account the impurities-sound wave piezoelectric coupling. By inverting the proposed expression for the sound attenuation to obtain the electrical conductivity from the relaxation, it is found that impurity conductivity of the hopping type is the dominant conduction process at low temperatures.

  11. Ultrasonic attenuation of CdSe at low temperatures

    International Nuclear Information System (INIS)

    Fernandez, B.J.; Calderon, E.; Bracho, D.B.; Perez, J.F.

    2010-01-01

    The ultrasonic attenuation of a single crystal of CdSe has been investigated over the temperature range from 1.2 to 300 K at frequencies of 10, 30 and 90 MHz. We report here the temperature dependence of the attenuation in the range 1.2-30 K for piezoactive and non-piezoactive acoustic waves. A temperature-induced relaxation for two piezoactive waves, which scale with frequency towards higher temperatures, was found. A modified Hutson and White model with a new parameter γ is proposed to explain the relaxation maxima of our data and others in the literature. In this model the parameter γ, which seems to be closely related to the compensation, takes into account the impurities-sound wave piezoelectric coupling. By inverting the proposed expression for the sound attenuation to obtain the electrical conductivity from the relaxation, it is found that impurity conductivity of the hopping type is the dominant conduction process at low temperatures.

  12. ENHANCEMENTS TO NATURAL ATTENUATION: SELECTED CASE STUDIES

    Energy Technology Data Exchange (ETDEWEB)

    Vangelas, K; W. H. Albright, W; E. S. Becvar, E; C. H. Benson, C; T. O. Early, T; E. Hood, E; P. M. Jardine, P; M. Lorah, M; E. Majche, E; D. Major, D; W. J. Waugh, W; G. Wein, G; O. R. West, O

    2007-05-15

    In 2003 the US Department of Energy (DOE) embarked on a project to explore an innovative approach to remediation of subsurface contaminant plumes that focused on introducing mechanisms for augmenting natural attenuation to achieve site closure. Termed enhanced attenuation (EA), this approach has drawn its inspiration from the concept of monitored natural attenuation (MNA).

  13. Oxidative stress evoked damages leading to attenuated memory and inhibition of NMDAR-CaMKII-ERK/CREB signalling on consumption of aspartame in rat model.

    Science.gov (United States)

    Iyaswamy, Ashok; Kammella, Ananth Kumar; Thavasimuthu, Citarasu; Wankupar, Wankhar; Dapkupar, Wankhar; Shanmugam, Sambantham; Rajan, Ravindran; Rathinasamy, Sheeladevi

    2018-04-01

    Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposes to investigate whether long term (90 days) aspartame (40 mg/kg b.wt) administration could induce oxidative stress and alter the memory in Wistar strain male albino rats. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included as a model to study the effects of aspartame. Wistar strain albino rats were administered with aspartame (40 mg/kg b.wt) orally and studied along with controls and MTX-treated controls. Aspartame interfered in the body weight and corticosterone levels in the rats. A marked increase in the mRNA and protein expression of neuronal nitric oxide synthase (nNOS) and induced nitric oxide synthase (iNOS) which resulted in the increased nitric oxide radical's level indicating that aspartame is a stressor. These reactive nitrogen species could be responsible for the altered cell membrane integrity and even cause death of neurons by necrosis or apoptosis. The animals showed a marked decrease in learning, spatial working and spatial recognition memory deficit in the Morris water maze and Y-maze performance task which could have resulted due to reduced hippocampal acetylcholine esterase (AChE) activity. The animal brain homogenate also revealed the decrease in the phosphorylation of NMDAR1-CaMKII-ERK/CREB signalling pathway, which well documents the inhibition of phosphorylation leads to the excitotoxicity of the neurons and memory decline. This effect may be due to methanol which may also activate the NOS levels, microglia and astrocytes, inducing neurodegeneration in brain. Neuronal shrinkage of hippocampal layer due to degeneration of pyramidal cells revealed the abnormal neuronal morphology of pyramidal cell layers in the aspartame treated animals. These findings demonstrate that aspartame metabolites could be a contributing factor for the development of oxidative

  14. Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model.

    Directory of Open Access Journals (Sweden)

    Jing Luo

    Full Text Available The quorum sensing (QS circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin, rhamnolipid, motilities and exotoxin A regulated by QS in Pseudomonas aeruginosa. Moreover, the expression levels of QS-regulatory genes, including lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin treatment, resulting in significant decreases in the QS signaling molecules 3-oxo-C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to alter gene and protein expression. In vivo experiments indicated that baicalin treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans. Greater worm survival in the baicalin-treated group manifested as an increase in the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of mice infected with Pseudomonas aeruginosa compared with the control group. Moreover, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological and histological analyses revealed

  15. Intra-Articular Injection of Cross-Linked Hyaluronic Acid-Dexamethasone Hydrogel Attenuates Osteoarthritis: An Experimental Study in a Rat Model of Osteoarthritis.

    Science.gov (United States)

    Zhang, Zhiwei; Wei, Xiaochun; Gao, Jizong; Zhao, Yu; Zhao, Yamin; Guo, Li; Chen, Chongwei; Duan, Zhiqing; Li, Pengcui; Wei, Lei

    2016-04-15

    Cross-linked hyaluronic acid hydrogel (cHA gel) and dexamethasone (Dex) have been used to treat knee osteoarthritis (OA) in clinical practice owing to their chondroprotective and anti-inflammatory effects, respectively. The aim of the present study was to compare the treatment effects of the cHA gel pre-mixed with/without Dex in a surgery-induced osteoarthritis model in rats. Anterior cruciate ligament transection (ACLT) surgery was performed on the right knee of rats to induce OA. Male 2-month-old Sprague-Dawley rats were randomly divided into five groups (n = 10/per group): (1) ACLT + saline; (2) ACLT + cHA gel; (3) ACLT + cHA-Dex (0.2 mg/mL) gel; (4) ACLT + cHA-Dex (0.5 mg/mL) gel; (5) Sham + saline. Intra-joint injections were performed four weeks after ACLT in the right knee. All animals were euthanized at 12 weeks post-surgery. Cartilage damage and changes in the synovial membrane were assessed by micro X-ray, Indian ink articular surface staining, Safranin-O/Fast Green staining, immunohistochemistry, hematoxylin and eosin staining of the synovial membrane, and quantitative reverse transcription-polymerase chain reaction for changes in gene expression. Micro X-ray revealed that the knee joint treated with the cHA-Dex gel was wider than those treated with cHA gel alone or saline. The cHA-Dex gel group had less Indian ink staining (indicator of cartilage fibrillation) than the cHA gel or saline injection groups. Safranin-O/Fast Green staining indicated that increased proteoglycan staining and less cartilage damage were found in the cHA-Dex gel group compared with the cHA gel or saline injection groups. Quantification of histology findings from saline, cHA gel, cHA-Dex (0.2 mg/mL) gel, cHA-Dex (0.5 mg/mL) gel, and sham groups were 5.84 ± 0.29, 4.50 ± 0.87, 3.00 ± 1.00, 2.00 ± 0.48, and 0.30 ± 0.58 (p < 0.05), respectively. A strong staining of type II collagen was found in both the cHA-Dex gel groups compared with saline group or cHA alone group. Similar

  16. Intra-Articular Injection of Cross-Linked Hyaluronic Acid-Dexamethasone Hydrogel Attenuates Osteoarthritis: An Experimental Study in a Rat Model of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zhiwei Zhang

    2016-04-01

    Full Text Available Cross-linked hyaluronic acid hydrogel (cHA gel and dexamethasone (Dex have been used to treat knee osteoarthritis (OA in clinical practice owing to their chondroprotective and anti-inflammatory effects, respectively. The aim of the present study was to compare the treatment effects of the cHA gel pre-mixed with/without Dex in a surgery-induced osteoarthritis model in rats. Anterior cruciate ligament transection (ACLT surgery was performed on the right knee of rats to induce OA. Male 2-month-old Sprague-Dawley rats were randomly divided into five groups (n = 10/per group: (1 ACLT + saline; (2 ACLT + cHA gel; (3 ACLT + cHA-Dex (0.2 mg/mL gel; (4 ACLT + cHA-Dex (0.5 mg/mL gel; (5 Sham + saline. Intra-joint injections were performed four weeks after ACLT in the right knee. All animals were euthanized at 12 weeks post-surgery. Cartilage damage and changes in the synovial membrane were assessed by micro X-ray, Indian ink articular surface staining, Safranin-O/Fast Green staining, immunohistochemistry, hematoxylin and eosin staining of the synovial membrane, and quantitative reverse transcription-polymerase chain reaction for changes in gene expression. Micro X-ray revealed that the knee joint treated with the cHA-Dex gel was wider than those treated with cHA gel alone or saline. The cHA-Dex gel group had less Indian ink staining (indicator of cartilage fibrillation than the cHA gel or saline injection groups. Safranin-O/Fast Green staining indicated that increased proteoglycan staining and less cartilage damage were found in the cHA-Dex gel group compared with the cHA gel or saline injection groups. Quantification of histology findings from saline, cHA gel, cHA-Dex (0.2 mg/mL gel, cHA-Dex (0.5 mg/mL gel, and sham groups were 5.84 ± 0.29, 4.50 ± 0.87, 3.00 ± 1.00, 2.00 ± 0.48, and 0.30 ± 0.58 (p < 0.05, respectively. A strong staining of type II collagen was found in both the cHA-Dex gel groups compared with saline group or cHA alone group

  17. Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

    NARCIS (Netherlands)

    Wu, C.; Gratama van Andel, H.A.; Laverman, P.; Boerman, O.C.; Beekman, F.J.

    2013-01-01

    Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well

  18. The Study of Rain Specific Attenuation for the Prediction of Satellite Propagation in Malaysia

    Science.gov (United States)

    Mandeep, J. S.; Ng, Y. Y.; Abdullah, H.; Abdullah, M.

    2010-06-01

    Specific attenuation is the fundamental quantity in the calculation of rain attenuation for terrestrial path and slant paths representing as rain attenuation per unit distance (dB/km). Specific attenuation is an important element in developing the predicted rain attenuation model. This paper deals with the empirical determination of the power law coefficients which allow calculating the specific attenuation in dB/km from the knowledge of the rain rate in mm/h. The main purpose of the paper is to obtain the coefficients of k and α of power law relationship between specific attenuation. Three years (from 1st January 2006 until 31st December 2008) rain gauge and beacon data taken from USM, Nibong Tebal have been used to do the empirical procedure analysis of rain specific attenuation. The data presented are semi-empirical in nature. A year-to-year variation of the coefficients has been indicated and the empirical measured data was compared with ITU-R provided regression coefficient. The result indicated that the USM empirical measured data was significantly vary from ITU-R predicted value. Hence, ITU-R recommendation for regression coefficients of rain specific attenuation is not suitable for predicting rain attenuation at Malaysia.

  19. Mechanisms of geometrical seismic attenuation

    Directory of Open Access Journals (Sweden)

    Igor B. Morozov

    2011-07-01

    Full Text Available In several recent reports, we have explained the frequency dependence of the apparent seismic quality-factor (Q observed in many studies according to the effects of geometrical attenuation, which was defined as the zero-frequency limit of the temporal attenuation coefficient. In particular, geometrical attenuation was found to be positive for most waves traveling within the lithosphere. Here, we present three theoretical models that illustrate the origin of this geometrical attenuation, and we investigate the causes of its preferential positive values. In addition, we discuss the physical basis and limitations of both the conventional and new attenuation models. For waves in media with slowly varying properties, geometrical attenuation is caused by variations in the wavefront curvature, which can be both positive (for defocusing and negative (for focusing. In media with velocity/density contrasts, incoherent reflectivity leads to geometrical-attenuation coefficients which are proportional to the mean squared reflectivity and are always positive. For «coherent» reflectivity, the geometrical attenuation is approximately zero, and the attenuation process can be described according to the concept of «scattering Q». However, the true meaning of this parameter is in describing the mean reflectivity within the medium, and not that of the traditional resonator quality factor known in mechanics. The general conclusion from these models is that non-zero and often positive levels of geometrical attenuation are common in realistic, heterogeneous media, both observationally and theoretically. When transformed into the conventional Q-factor form, this positive geometrical attenuation leads to Q values that quickly increase with frequency. These predictions show that the positive frequency-dependent Q observed in many datasets might represent artifacts of the transformations of the attenuation coefficients into Q.

  1. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    International Nuclear Information System (INIS)

    Cai, Yujun; Li, Jian-Dong; Yan, Chen

    2013-01-01

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis

  2. Boundary layer attenuation in turbulent sodium flows

    International Nuclear Information System (INIS)

    Tenchine, D.

    1994-01-01

    Temperature fluctuations are produced in the sodium coolant of Liquid Metal Reactors when flows at different temperatures are mixing. That occurs in various areas of the reactor plant, in the primary and the secondary circuits. This paper deals with secondary circuit pipings, specifically the Superphenix steam generator outlet. The possibility of thermal striping in this area is studied because of the mixing of a main 'hot' flow surrounded by a smaller 'cold' flow in the vertical pipe located below the steam generator. This work was developed in the frame of a collaboration between CEA, EDF and FRAMATOME. The purpose of our study is to measure temperature fluctuations in the fluid and on the structures, on a sodium reduced scale model of the outlet region of the steam generator. We want to evidence the boundary layer attenuation by comparing wall and fluid measurements. From these experimental data, we shall propose a methodology to predict the boundary layer attenuation and the temperature fluctuations at the surface of the structure, for pipe flow configurations

  3. Vinpocetine attenuates lipid accumulation and atherosclerosis formation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Yujun [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States); Li, Jian-Dong [Center for Inflammation, Immunity and Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Yan, Chen, E-mail: Chen_Yan@urmc.rochester.edu [Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, 601 Elmwood Ave, Rochester, NY 14642 (United States)

    2013-05-10

    Highlights: •Vinpocetine attenuates hyperlipidemia-induced atherosclerosis in a mouse model. •Vinpocetine antagonizes ox-LDL uptake and accumulation in macrophages. •Vinpocetine blocks the induction of ox-LDL receptor LOX-1 in vitro and in vivo. -- Abstract: Atherosclerosis, the major cause of myocardial infarction and stroke, is a chronic arterial disease characterized by lipid deposition and inflammation in the vessel wall. Cholesterol, in low-density lipoprotein (LDL), plays a critical role in the pathogenesis of atherosclerosis. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. Recent study indicated that vinpocetine is a potent anti-inflammatory agent. However, its role in the pathogenesis of atherosclerosis remains unexplored. In the present study, we show that vinpocetine significantly reduced atherosclerotic lesion formation in ApoE knockout mice fed with a high-fat diet. In cultured murine macrophage RAW264.7 cells, vinpocetine markedly attenuated oxidized LDL (ox-LDL) uptake and foam cell formation. Moreover, vinpocetine greatly blocked the induction of ox-LDL receptor 1 (LOX-1) in cultured macrophages as well as in the LOX-1 level in atherosclerotic lesions. Taken together, our data reveal a novel role of vinpocetine in reduction of pathogenesis of atherosclerosis, at least partially through suppressing LOX-1 signaling pathway. Given the excellent safety profile of vinpocetine, this study suggests vinpocetine may be a therapeutic candidate for treating atherosclerosis.

  4. Factors influencing seismic wave attenuation in the lithosphere in continental rift zones

    Directory of Open Access Journals (Sweden)

    А. А. Dobrynina

    2017-01-01

    Full Text Available Attenuation of seismic waves in the crust and the upper mantle has been studied in three global rift systems: the Baikal rift system (Eurasia, the North Tanzanian divergence zone (Africa and the Basin and Range Province (North America. Using the records of direct and coda waves of regional earthquakes, the single scattering theory [Aki, Chouet, 1975], the hybrid model from [Zeng, 1991] and the approach described in [Wennerberg, 1993], we estimated the seismic quality factor (QC, frequency parameter (n, attenuation coefficient (δ, and total attenuation (QT. In addition, we evaluated the contributions of two components into total attenuation: intrinsic attenuation (Qi, and scattering attenuation (Qsc. Values of QC are strongly dependent on the frequency within the range of 0.2–16 Hz, as well as on the length of the coda processing window. The observed increase of QC with larger lengths of the coda processing window can be interpreted as a decrease in attenuation with increasing depth. Having compared the depth variations in the attenuation coefficient (δ and the frequency (n with the velocity structures of the studied regions, we conclude that seismic wave attenuation changes at the velocity boundaries in the medium. Moreover, the comparison results show that the estimated variations in the attenuation parameters with increasing depth are considerably dependent on utilized velocity models of the medium. Lateral variations in attenuation of seismic waves correlate with the geological and geophysical characteristics of the regions, and attenuation is primarily dependent on the regional seismic activity and regional heat flow. The geological inhomogeneities of the medium and the age of crust consolidation are secondary factors. Our estimations of intrinsic attenuation (Qi and scattering attenuation (Qsc show that in all the three studied regions, intrinsic attenuation is the major contributor to total attenuation. Our study shows that the

  5. Ultrasonic attenuation measurements and 'glassy' behaviour of neutron irradiated quartz

    International Nuclear Information System (INIS)

    Laermans, C.; Esteves, V.; Vanelstraete, A.

    1986-01-01

    The ultrasonic attenuation of longitudinal acoustic waves in slightly disordered crystalline quartz has been measured over a temperature range from 1.3 to 300 K, using the pulse-echo technique. Neutron irradiation is demonstrated to increase the ultrasonic attenuation at low temperatures indicating the presence of two-level tunneling systems similar to those of glasses. The present low-temperature acoustic results agree with a frequency independence and a T 3 behaviour for the relaxation process predicted by the two-level tunneling TLS-model where the regime ωT 1 >> 1 holds. (author)

  6. Ixeris dentata (Thunb) Nakai attenuates cognitive impairment in ...

    African Journals Online (AJOL)

    Ixeris dentata (Thunb) Nakai attenuates cognitive impairment in MPTP-treated mouse model of Parkinson's disease. ... Conclusion: IDE exhibits good protection against MPTP-induced behavioral deficits via potential antioxidant defense mechanisms. Therefore, IDE could potentially be developed as a therapeutic approach ...

  7. Determination of Dimensionless Attenuation Coefficient in Shaped Resonators

    Science.gov (United States)

    Daniels, C.; Steinetz, B.; Finkbeiner, J.; Raman, G.; Li, X.

    2003-01-01

    The value of dimensionless attenuation coefficient is an important factor when numerically predicting high-amplitude acoustic waves in shaped resonators. Both the magnitude of the pressure waveform and the quality factor rely heavily on this dimensionless parameter. Previous authors have stated the values used, but have not completely explained their methods. This work fully describes the methodology used to determine this important parameter. Over a range of frequencies encompassing the fundamental resonance, the pressure waves were experimentally measured at each end of the shaped resonators. At the corresponding dimensionless acceleration, the numerical code modeled the acoustic waveforms generated in the resonator using various dimensionless attenuation coefficients. The dimensionless attenuation coefficient that most closely matched the pressure amplitudes and quality factors of the experimental and numerical results was determined to be the value to be used in subsequent studies.

  8. Iterative methods for photoacoustic tomography in attenuating acoustic media

    Science.gov (United States)

    Haltmeier, Markus; Kowar, Richard; Nguyen, Linh V.

    2017-11-01

    The development of efficient and accurate reconstruction methods is an important aspect of tomographic imaging. In this article, we address this issue for photoacoustic tomography. To this aim, we use models for acoustic wave propagation accounting for frequency dependent attenuation according to a wide class of attenuation laws that may include memory. We formulate the inverse problem of photoacoustic tomography in attenuating medium as an ill-posed operator equation in a Hilbert space framework that is tackled by iterative regularization methods. Our approach comes with a clear convergence analysis. For that purpose we derive explicit expressions for the adjoint problem that can efficiently be implemented. In contrast to time reversal, the employed adjoint wave equation is again damping and, thus has a stable solution. This stability property can be clearly seen in our numerical results. Moreover, the presented numerical results clearly demonstrate the efficiency and accuracy of the derived iterative reconstruction algorithms in various situations including the limited view case.

  9. Attenuation of cold stress-induced exacerbation of cardiac and adipose tissue pathology and metabolic disorders in a rat model of metabolic syndrome by the glucocorticoid receptor antagonist RU486.

    Science.gov (United States)

    Nagasawa, K; Matsuura, N; Takeshita, Y; Ito, S; Sano, Y; Yamada, Y; Uchinaka, A; Murohara, T; Nagata, K

    2016-04-25

    Chronic stress affects the central nervous system as well as endocrine, metabolic and immune systems. However, the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We recently characterized DahlS.Z-Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We have now investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology as well as on metabolic parameters in this model. DS/obese rats were exposed to cold stress (immersion in ice-cold water to a depth of 1-2 cm for 2 h per day) with or without subcutaneous injection of the GR antagonist RU486 (2 mg kg(-1)day(-1)) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+)) littermates served as a control. Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction in DS/obese rats in a manner sensitive to RU486 treatment. Cold stress with or without RU486 did not affect body weight or fat mass. In contrast, cold stress further increased cardiac oxidative stress as well as macrophage infiltration and proinflammatory gene expression in LV and visceral fat tissue, with all of these effects being attenuated by RU486. Cold stress also further increased GR and 11β-hydroxysteroid dehydrogenase type 1 mRNA and protein abundance in LV and visceral adipose tissue, and these effects were again inhibited by RU486. In addition, RU486 ameliorated the stress-induced aggravation of dyslipidemia, glucose intolerance and insulin resistance in DS/obese rats. Our results implicate GR signaling in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as of abnormal glucose and lipid metabolism in a rat model of MetS.

  10. Chlorine signal attenuation in concrete.

    Science.gov (United States)

    Naqvi, A A; Maslehuddin, M; Ur-Rehman, Khateeb; Al-Amoudi, O S B

    2015-11-01

    The intensity of prompt gamma-ray was measured at various depths from chlorine-contaminated silica fume (SF) concrete slab concrete specimens using portable neutron generator-based prompt gamma-ray setup. The intensity of 6.11MeV chloride gamma-rays was measured from the chloride contaminated slab at distance of 15.25, 20.25, 25.25, 30.25 and 35.25cm from neutron target in a SF cement concrete slab specimens. Due to attenuation of thermal neutron flux and emitted gamma-ray intensity in SF cement concrete at various depths, the measured intensity of chlorine gamma-rays decreases non-linearly with increasing depth in concrete. A good agreement was noted between the experimental results and the results of Monte Carlo simulation. This study has provided useful experimental data for evaluating the chloride contamination in the SF concrete utilizing gamma-ray attenuation method. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Attenuation and Dispersion in Earth's Materials

    Science.gov (United States)

    Gueguen, Y.

    2012-04-01

    One of the last challenges of Pr. Luigi Burlini has been to set up an experimental apparatus that would measure elastic wave attenuation under high pressure conditions. This project has since been developed by his colleagues and students at ETH. As a tribute to Luigi Burlini, this presentation aims at recalling why such measurements are important , how challenging such a project is, and what the main issues ahead are. Most of our knowledge about either crustal layers (seismic exploration) or deeper layers (seismology) results from data related to elastic wave propagation inside the Earth. The large amount of available data as well as the huge capability of computers are such that descriptions in terms of isotropic homogeneous layers appear to be very crude today. Anisotropic, heterogeneous models are reported at various scales. In addition, accounting for wave attenuation (the Q factor) is potentially of great interest. The Q factor is highly sensitive to processes that involve some departure from perfect elasticity. Its knowledge may provide information on possible fluid content, temperature, etc. This is because various processes may dissipate energy (and thus lower Q value) as a result of fluid flow, solid flow, etc., depending on the precise P-T conditions at depth. This points immediately to the theoretical challenge of Q investigations: there are many possible ways for a rock to not behave as a perfect elastic body. To model these various mechanisms and identify in which conditions they can take place is a first major challenge. The second challenge is on the experimental ground. What is looked for is to get low frequencies (f close to seismic frequencies) Q data on crustal (or mantle) rocks at high pressure P-high temperature T. Experiments in such highT-high P-low f conditions are extremely difficult to perform. Only in Canberra (I. Jackson) and now in Zurich such conditions have been achieved. Attenuation and dispersion (frequency dependence) of elastic

  12. Glutathione attenuates uranyl toxicity in Lactococcus lactis

    Energy Technology Data Exchange (ETDEWEB)

    Fahmy, Karim; Oertel, Jana [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Biophysics; Obeid, M. [Technische Univ. Dresden (Germany); Solioz, M. [Bern Univ. (Switzerland)

    2017-06-01

    We investigated the role of intracellular glutathione (GSH), which in a large number of taxa plays a role in the protection against the toxicity of heavy metals. Anaerobically grown Lactococcus lactis containing an inducible GSH synthesis pathway was used as a model organism allowing the study of GSH-dependent uranyl detoxification without interference from additional reactive oxygen species. Microcalorimetric measurements of the metabolic heat showed that intracellular GSH attenuates the toxicity of uranium at a concentration in the range of 10-150 μM. Isothermal titration calorimetry revealed the endothermic binding of U(VI) to the carboxyl group(s) of GSH. The data indicate that the primary detoxifying mechanism is the intracellular sequestration of carboxyl-coordinated U(VI) into an insoluble complex with GSH.

  13. Glutathione attenuates uranyl toxicity in Lactococcus lactis

    International Nuclear Information System (INIS)

    Fahmy, Karim; Oertel, Jana; Solioz, M.

    2017-01-01

    We investigated the role of intracellular glutathione (GSH), which in a large number of taxa plays a role in the protection against the toxicity of heavy metals. Anaerobically grown Lactococcus lactis containing an inducible GSH synthesis pathway was used as a model organism allowing the study of GSH-dependent uranyl detoxification without interference from additional reactive oxygen species. Microcalorimetric measurements of the metabolic heat showed that intracellular GSH attenuates the toxicity of uranium at a concentration in the range of 10-150 μM. Isothermal titration calorimetry revealed the endothermic binding of U(VI) to the carboxyl group(s) of GSH. The data indicate that the primary detoxifying mechanism is the intracellular sequestration of carboxyl-coordinated U(VI) into an insoluble complex with GSH.

  14. Shock wave attenuation in a micro-channel

    Science.gov (United States)

    Giordano, J.; Perrier, P.; Meister, L.; Brouillette, M.

    2018-05-01

    This work presents optical measurements of shock wave attenuation in a glass micro-channel. This transparent facility, with a cross section ranging from 1 mm× 150 μm to 1 mm× 500 μm, allowed for the use of high-speed schlieren videography to visualize the propagation of a shock wave within the entire micro-channel and to quantify velocity attenuation of the wave due to wall effects. In this paper, we present the experimental technique and the relevant data treatment we have used to increase the sensitivity of shock wave detection. Then, we compared our experimental results for different channel widths, lengths, and shock wave velocities with the analytical model for shock attenuation proposed by Russell (J Fluid Mech 27(2):305-314, 1967), which assumes laminar flow, and by Mirels (Attenuation in a shock tube due to unsteady-boundary-layer action, NACA Report 1333, 1957) for turbulent flow. We found that these models are inadequate to predict the observed data, owing to the presence of fully developed flow which violates the basic assumption of these models. The data are also compared with the empirical shock attenuation models proposed by Zeitoun (Phys Fluids 27(1):011701, 2015) and Deshpande and Puranik (Shock Waves 26(4):465-475, 2016), where better agreement is observed. Finally, we presented experimental data for the flow field behind the shock wave from measurements of the Mach wave angle which shows globally decreasing flow Mach numbers due to viscous wall effects.

  15. Active acoustic leak detection for LMFBR steam generator. Sound attenuation due to bubbles

    International Nuclear Information System (INIS)

    Kumagai, Hiromichi; Sakuma, Toshio

    1995-01-01

    In the steam generators (SG) of LMFBR, it is necessary to detect the leakage of water from tubes of heat exchangers as soon as it occurs. The active acoustic detection method has drawn general interest owing to its short response time and reduction of the influence of background noise. In this paper, the application of the active acoustic detection method for SG is proposed, and sound attenuation by bubbles is investigated experimentally. Furthermore, using the SG sector model, sound field characteristics and sound attenuation characteristics due to injection of bubbles are studied. It is clarified that the sound attenuation depends upon bubble size as well as void fraction, that the distance attenuation of sound in the SG model containing heat transfer tubes is 6dB for each two-fold increase of distance, and that emitted sound attenuates immediately upon injection of bubbles. (author)

  16. Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-βl and Smad2/3 pathways in high-fat diet-induced obesity rat model.

    Science.gov (United States)

    Hong, Seul-Ki; Choo, Eun-Ho; Ihm, Sang-Hyun; Chang, Kiyuk; Seung, Ki-Bae

    2017-11-01

    Obesity-induced myocardial fibrosis may lead to diastolic dysfunction and ultimately heart failure. Activation of the transforming growth factor (TGF)-βl and its downstream Smad2/3 pathways may play a pivotal role in the pathogenesis of obesity-induced myocardial fibrosis, and the antidiabetic dipeptidyl peptidase 4 inhibitors (DPP4i) might affect these pathways. We investigated whether DPP4i reduces myocardial fibrosis by inhibiting the TGF-β1 and Smad2/3 pathways in the myocardium of a diet-induced obesity (DIO) rat model. Eight-week-old male spontaneously hypertensive rats (SHRs) were fed either a normal fat diet (chow) or a high-fat diet (HFD) and then the HFD-fed SHRs were randomized to either the DPP4i (MK-0626) or control (distilled water) groups for 12weeks. At 20weeks old, all the rats underwent hemodynamic and metabolic studies and Doppler echocardiography. Compared with the normal fat diet (chow)-fed SHRs, the HFD-fed SHRs developed a more intense degree of hyperglycemia and dyslipidemia and showed a constellation of left ventricular (LV) diastolic dysfunction, and exacerbated myocardial fibrosis, as well as activation of the TGF-β1 and Smad2/3 pathways. DPP4i significantly improved the metabolic and hemodynamic parameters. The echocardiogram showed that DPP4i improved the LV diastolic dysfunction (early to late ventricular filling velocity [E/A] ratio, 1.49±0.21 vs. 1.77±0.09, p<0.05). Furthermore, DPP4i significantly reduced myocardial fibrosis and collagen production by the myocardium and suppressed TGF-β1 and phosphorylation of Smad2/3 in the heart. In addition, DPP4i decreased TGF-β1-induced collagen production and TGF-β1-mediated phosphorylation and nuclear translocation of Smad2/3 in rat cardiac fibroblasts. In conclusion, DPP4 inhibition attenuated myocardial fibrosis and improved LV diastolic dysfunction in a DIO rat model by modulating the TGF-β1 and Smad2/3 pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Calculation Of Pneumatic Attenuation In Pressure Sensors

    Science.gov (United States)

    Whitmore, Stephen A.

    1991-01-01

    Errors caused by attenuation of air-pressure waves in narrow tubes calculated by method based on fundamental equations of flow. Changes in ambient pressure transmitted along narrow tube to sensor. Attenuation of high-frequency components of pressure wave calculated from wave equation derived from Navier-Stokes equations of viscous flow in tube. Developed to understand and compensate for frictional attenuation in narrow tubes used to connect aircraft pressure sensors with pressure taps on affected surfaces.

  18. Prediction of spectral acceleration response ordinates based on PGA attenuation

    Science.gov (United States)

    Graizer, V.; Kalkan, E.

    2009-01-01

    Developed herein is a new peak ground acceleration (PGA)-based predictive model for 5% damped pseudospectral acceleration (SA) ordinates of free-field horizontal component of ground motion from shallow-crustal earthquakes. The predictive model of ground motion spectral shape (i.e., normalized spectrum) is generated as a continuous function of few parameters. The proposed model eliminates the classical exhausted matrix of estimator coefficients, and provides significant ease in its implementation. It is structured on the Next Generation Attenuation (NGA) database with a number of additions from recent Californian events including 2003 San Simeon and 2004 Parkfield earthquakes. A unique feature of the model is its new functional form explicitly integrating PGA as a scaling factor. The spectral shape model is parameterized within an approximation function using moment magnitude, closest distance to the fault (fault distance) and VS30 (average shear-wave velocity in the upper 30 m) as independent variables. Mean values of its estimator coefficients were computed by fitting an approximation function to spectral shape of each record using robust nonlinear optimization. Proposed spectral shape model is independent of the PGA attenuation, allowing utilization of various PGA attenuation relations to estimate the response spectrum of earthquake recordings.

  19. Occurrence and in-stream attenuation of wastewater-derived pharmaceuticals in Iberian rivers.

    Science.gov (United States)

    Acuña, Vicenç; von Schiller, Daniel; García-Galán, Maria Jesús; Rodríguez-Mozaz, Sara; Corominas, Lluís; Petrovic, Mira; Poch, Manel; Barceló, Damià; Sabater, Sergi

    2015-01-15

    A multitude of pharmaceuticals enter surface waters via discharges of wastewater treatment plants (WWTPs), and many raise environmental and health concerns. Chemical fate models predict their concentrations using estimates of mass loading, dilution and in-stream attenuation. However, current comprehension of the attenuation rates remains a limiting factor for predictive models. We assessed in-stream attenuation of 75 pharmaceuticals in 4 river segments, aiming to characterize in-stream attenuation variability among different pharmaceutical compounds, as well as among river segments differing in environmental conditions. Our study revealed that in-stream attenuation was highly variable among pharmaceuticals and river segments and that none of the considered pharmaceutical physicochemical and molecular properties proved to be relevant in determining the mean attenuation rates. Instead, the octanol-water partition coefficient (Kow) influenced the variability of rates among river segments, likely due to its effect on sorption to sediments and suspended particles, and therefore influencing the balance between the different attenuation mechanisms (biotransformation, photolysis, sorption, and volatilization). The magnitude of the measured attenuation rates urges scientists to consider them as important as dilution when aiming to predict concentrations in freshwater ecosystems. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Cement-based materials' characterization using ultrasonic attenuation

    Science.gov (United States)

    Punurai, Wonsiri

    The quantitative nondestructive evaluation (NDE) of cement-based materials is a critical area of research that is leading to advances in the health monitoring and condition assessment of the civil infrastructure. Ultrasonic NDE has been implemented with varying levels of success to characterize cement-based materials with complex microstructure and damage. A major issue with the application of ultrasonic techniques to characterize cement-based materials is their inherent inhomogeneity at multiple length scales. Ultrasonic waves propagating in these materials exhibit a high degree of attenuation losses, making quantitative interpretations difficult. Physically, these attenuation losses are a combination of internal friction in a viscoelastic material (ultrasonic absorption), and the scattering losses due to the material heterogeneity. The objective of this research is to use ultrasonic attenuation to characterize the microstructure of heterogeneous cement-based materials. The study considers a real, but simplified cement-based material, cement paste---a common bonding matrix of all cement-based composites. Cement paste consists of Portland cement and water but does not include aggregates. First, this research presents the findings of a theoretical study that uses a set of existing acoustics models to quantify the scattered ultrasonic wavefield from a known distribution of entrained air voids. These attenuation results are then coupled with experimental measurements to develop an inversion procedure that directly predicts the size and volume fraction of entrained air voids in a cement paste specimen. Optical studies verify the accuracy of the proposed inversion scheme. These results demonstrate the effectiveness of using attenuation to measure the average size, volume fraction of entrained air voids and the existence of additional larger entrapped air voids in hardened cement paste. Finally, coherent and diffuse ultrasonic waves are used to develop a direct

  1. Effects of methods of attenuation correction on source parameter determination

    Science.gov (United States)

    Sonley, Eleanor; Abercrombie, Rachel E.

    We quantify the effects of using different approaches to model individual earthquake spectra. Applying different approaches can introduce significant variability in the calculated source parameters, even when applied to the same data. To compare large and small earthquake source parameters, the results of multiple studies need to be combined to extend the magnitude range, but the variability introduced by the different approaches hampers the outcome. When studies are combined, there is large uncertainty and large scatter and some systematic differences have been neglected. We model individual earthquake spectra from repeating earthquakes (M˜2) at Parkfield, CA, recorded by a borehole network. We focus on the effects of trade-offs between attenuation (Q) and corner frequency in spectral fitting and the effect of the model shape at the corner frequency on radiated energy. The trade-off between attenuation and corner frequency can increase radiated energy by up to 400% and seismic moment by up to 100%.

  2. Photostimulated attenuation of hypersound in superlattice

    International Nuclear Information System (INIS)

    Mensah, S.Y.; Allotey, F.K.; Adjepong, S.K.

    1992-10-01

    Photostimulated attenuation of hypersound in semiconductor superlattice has been investigated. It is shown that the attenuation coefficient depends on the phonon wave vector q in an oscillatory manner and that from this oscillation the band width Δ of superlattice can be found. (author). 14 refs, 1 fig

  3. Seismic wave attenuation and velocity dispersion in UAE carbonates

    Science.gov (United States)

    Ogunsami, Abdulwaheed Remi

    Interpreting the seismic property of fluids in hydrocarbon reservoirs at low frequency scale has been a cherished goal of petroleum geophysics research for decades. Lately, there has been tremendous interest in understanding attenuation as a result of fluid flow in porous media. Although interesting, the emerging experimental and theoretical information still remain ambiguous and are practically not utilized for reasons not too obscure. Attenuation is frequency dependent and hard to measure in the laboratory at low frequency. This thesis describes and reports the results of an experimental study of low frequency attenuation and velocity dispersion on a selected carbonate reservoir samples in the United Arab Emirates (UAE). For the low frequency measurements, stress-strain method was used to measure the moduli from which the velocity is derived. Attenuation was measured as the phase difference between the applied stress and the strain. For the ultrasonic component, the pulse propagation method was employed. To study the fluid effect especially at reservoir in situ conditions, the measurements were made dry and saturated with liquid butane and brine at differential pressures of up to 5000 psi with pore pressure held constant at 500 psi. Similarly to what has been documented in the literatures for sandstone, attenuation of the bulk compressibility mode dominates the losses in these dry and somewhat partially saturated carbonate samples with butane and brine. Overall, the observed attenuation cannot be simply said to be frequency dependent within this low seismic band. While attenuation seems to be practically constant in the low frequency band for sample 3H, such conclusion cannot be made for sample 7H. For the velocities, significant dispersion is observed and Gassmann generally fails to match the measured velocities. Only the squirt model fairly fits the velocities, but not at all pressures. Although the observed dispersion is larger than Biot's prediction, the fact

  4. A live-attenuated chimeric PCV2 vaccine based on subtype 2b is transmitted to contact pigs but is not upregulated by concurrent infection with PPV and PRRSV and is efficacious in a triple challenge co-infection model

    Science.gov (United States)

    The objective of this study was to determine the safety and efficacy of a new live-attenuated chimeric PCV1/2b vaccine. Forty-six, 21-day-old, PCV2-naïve pigs were randomly assigned to one of six groups (Negative controls, positive controls, Vac-0, Vac-0-PCV2, Contact-PCV2, Vac-28-PCV2). All pigs we...

  5. The coriolis attenuation problem in the perturbed i13/2 neutronbands

    Directory of Open Access Journals (Sweden)

    T. Engeland

    1983-01-01

    Full Text Available The Coriolis attenuation problem in the particle-rotor model is shown to be related to the BCS approximation. A model including the full recoil effect of one- and two-body terms, and with an exact diagonalization of the pairing force, is applied on four nuclei in the rare earth region known to have strongly Coriolis-perturbed i13/2 rotational bands. In all nuclei, the old Coriolis attenuation problem has been removed.

  6. Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

    Directory of Open Access Journals (Sweden)

    Balamurugan Periaswamy

    Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

  7. Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas

    International Nuclear Information System (INIS)

    Veld, Joyce; Vossen, Josephina A.; Torriani, Martin; Bredella, Miriam A.; De Amorim Bernstein, Karen; Halpern, Elkan F.

    2016-01-01

    To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. (orig.)

  8. Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Veld, Joyce; Vossen, Josephina A.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); De Amorim Bernstein, Karen [Massachusetts General Hospital and Harvard Medical School, Department of Radiation Oncology, Francis H Burr Proton Therapy Center, Boston, MA (United States); Halpern, Elkan F. [Massachusetts General Hospital and Harvard Medical School, Institute of Technology Assessment, Boston, MA (United States)

    2016-12-15

    To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. (orig.)

  9. An ice-sheet-wide framework for englacial attenuation from ice-penetrating radar data

    Science.gov (United States)

    Jordan, T. M.; Bamber, J. L.; Williams, C. N.; Paden, J. D.; Siegert, M. J.; Huybrechts, P.; Gagliardini, O.; Gillet-Chaulet, F.

    2016-07-01

    Radar inference of the bulk properties of glacier beds, most notably identifying basal melting, is, in general, derived from the basal reflection coefficient. On the scale of an ice sheet, unambiguous determination of basal reflection is primarily limited by uncertainty in the englacial attenuation of the radio wave, which is an Arrhenius function of temperature. Existing bed-returned power algorithms for deriving attenuation assume that the attenuation rate is regionally constant, which is not feasible at an ice-sheet-wide scale. Here we introduce a new semi-empirical framework for deriving englacial attenuation, and, to demonstrate its efficacy, we apply it to the Greenland Ice Sheet. A central feature is the use of a prior Arrhenius temperature model to estimate the spatial variation in englacial attenuation as a first guess input for the radar algorithm. We demonstrate regions of solution convergence for two input temperature fields and for independently analysed field campaigns. The coverage achieved is a trade-off with uncertainty and we propose that the algorithm can be "tuned" for discrimination of basal melt (attenuation loss uncertainty ˜ 5 dB). This is supported by our physically realistic ( ˜ 20 dB) range for the basal reflection coefficient. Finally, we show that the attenuation solution can be used to predict the temperature bias of thermomechanical ice sheet models and is in agreement with known model temperature biases at the Dye 3 ice core.

  10. Beta attenuation transmission system (BATS)

    Energy Technology Data Exchange (ETDEWEB)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm/sup 2/, of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A /sup 90/Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (..mu..P) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined.

  11. Plasmodium falciparum: attenuation by irradiation

    International Nuclear Information System (INIS)

    Waki, S.; Yonome, I.; Suzuki, M.

    1983-01-01

    The effect of irradiation on the in vitro growth of Plasmodium falciparum was investigated. The cultured malarial parasites at selected stages of development were exposed to gamma rays and the sensitivity of each stage was determined. The stages most sensitive to irradiation were the ring forms and the early trophozoites; late trophozoites were relatively insensitive. The greatest resistance was shown when parasites were irradiated at a time of transition from the late trophozoite and schizont stages to young ring forms. The characteristics of radiosensitive variation in the parasite cycle resembled that of mammalian cells. Growth curves of parasites exposed to doses of irradiation upto 150 gray had the same slope as nonirradiated controls but parasites which were exposed to 200 gray exhibited a growth curve which was less steep than that for parasites in other groups. Less than 10 organisms survived from the 10(6) parasites exposed to this high dose of irradiation; the possibility exists of obtaining radiation-attenuated P. falciparum

  12. Beta attenuation transmission system (BATS)

    International Nuclear Information System (INIS)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm 2 , of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A 90 Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (μP) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined

  13. Attenuation characteristics of gypsum wallboard

    International Nuclear Information System (INIS)

    Christensen, Ralph C.; Sayeg, Joseph

    1978-01-01

    Increased cost of lead is promoting enhanced usage of common building materials for shielding in diagnostic medical and dental facilities where only a few half value layers (HVLs) are needed. We have measured attenuation of x-rays in gypsum wallboard as a function of kVp, filtration, and wallboard thickness. Our findings, obtained using a Victoreen 555 with an 0.1 DAS probe in poor geometry, are in agreement with the sparse data in the literature (Gross and McCullough (1977), Radiology 122: 825. Moos et al. (1961), Oral Surgery, Oral Medicine, and Oral Pathology 14: 569) but extend to thicker wall configurations and different kVp and filtration parameters. We conclude that gypsum wallboard as sole shielding material should be used with great caution. These findings are of value in maximizing the benefit/cost ratio for diagnostic shielding, and strengthen the conviction that, where used for shielding purposes, common building materials must be installed carefully and HVL-depth dependence considered thoroughly. (author)

  14. Viscothermal Coupling Effects on Sound Attenuation in Concentrated Colloidal Dispersions.

    Science.gov (United States)

    Han, Wei

    1995-11-01

    This thesis describes a Unified Coupled Phase Continuum (UCPC) model to analyze sound propagation through aerosols, emulsions and suspensions in terms of frequency dependent attenuation coefficient and sound speed. Expressions for the viscous and thermal coupling coefficients explicitly account for the effects of particle size, shape factor, orientation as well as concentration and the sound frequency. The UCPC model also takes into account the intrinsic acoustic absorption within the fluid medium due to its viscosity and heat conductivity. The effective complex wave number as a function of frequency is derived. A frequency- and concentration-dependent complex Nusselt number for the interfacial thermal coupling coefficient is derived using an approximate similarity between the 'viscous skin drag' and 'heat conduction flux' associated with the discontinuous suspended phase, on the basis of a cell model. The theoretical predictions of attenuation spectra provide satisfactory agreement with reported experimental data on two concentrated suspensions (polystyrene latex and kaolin pigment), two concentrated emulsions (toluene -in-water, n-hexadecane-in-water), and two aerosols (oleic acid droplets-in-nitrogen, alumina-in-air), covering a wide range of relative magnitudes (from 10^ {-3} to 10^{3}) of thermal versus viscous contributions, for dispersed phase volume fractions as high as 50%. The relative differences between the additive result of separate viscous and thermal loss estimates and combined viscothermal absorption results are also presented. Effects of particle shape on viscous attenuation of sound in concentrated suspensions of non-spherical clay particles are studied. Attenuation spectra for 18 frequencies from 3 to 100 MHz are measured and analyzed for eleven kaolin clay slurries with solid concentrations ranging from 0.6% to 35% (w/w). A modified viscous drag coefficient that considers frequency, concentration, particle size, shape and orientation of

  15. A simulation of the optical attenuation of TPB coated light-guide detectors

    International Nuclear Information System (INIS)

    Jones, B J P

    2013-01-01

    This note is provided as a supplementary section to accompany the paper [1] which has been included in these proceedings. It describes some simple simulations which were performed in order to understand the attenuation behaviors of acrylic light-guides operated in air and argon, which were characterized in [2]. Whilst these simulations are only at the level of sophistication of a toy model, they illustrate interesting non-exponential light attenuation effects and the differences between operating light-guide based detectors in argon and air environments. We investigate the effects of surface absorption, surface roughness and wavelength dependence, and use a model tuned on the light-guide attenuation curve measured in air to make a prediction of the light-guide attenuation curve in argon. This curve is compared with data from a liquid argon test stand, and an improvement over a simple exponential model is observed

  16. Attenuation and velocity dispersion in the exploration seismic frequency band

    Science.gov (United States)

    Sun, Langqiu

    In an anelastic medium, seismic waves are distorted by attenuation and velocity dispersion, which depend on petrophysical properties of reservoir rocks. The effective attenuation and velocity dispersion is a combination of intrinsic attenuation and apparent attenuation due to scattering, transmission response, and data acquisition system. Velocity dispersion is usually neglected in seismic data processing partly because of insufficient observations in the exploration seismic frequency band. This thesis investigates the methods of measuring velocity dispersion in the exploration seismic frequency band and interprets the velocity dispersion data in terms of petrophysical properties. Broadband, uncorrelated vibrator data are suitable for measuring velocity dispersion in the exploration seismic frequency band, and a broad bandwidth optimizes the observability of velocity dispersion. Four methods of measuring velocity dispersion in uncorrelated vibrator VSP data are investigated, which are the sliding window crosscorrelation (SWCC) method, the instantaneous phase method, the spectral decomposition method, and the cross spectrum method. Among them, the SWCC method is a new method and has satisfactory robustness, accuracy, and efficiency. Using the SWCC method, velocity dispersion is measured in the uncorrelated vibrator VSP data from three areas with different geological settings, i.e., Mallik gas hydrate zone, McArthur River uranium mines, and Outokumpu crystalline rocks. The observed velocity dispersion is fitted to a straight line with respect to log frequency for a constant (frequency-independent) Q value. This provides an alternative method for calculating Q. A constant Q value does not directly link to petrophysical properties. A modeling study is implemented for the Mallik and McArthur River data to interpret the velocity dispersion observations in terms of petrophysical properties. The detailed multi-parameter petrophysical reservoir models are built according to

  17. Light attenuation in estuarine mangrove lakes

    Science.gov (United States)

    Frankovich, Thomas A.; Rudnick, David T.; Fourqurean, James W.

    2017-01-01

    Submerged aquatic vegetation (SAV) cover has declined in brackish lakes in the southern Everglades characterized by low water transparencies, emphasizing the need to evaluate the suitability of the aquatic medium for SAV growth and to identify the light attenuating components that contribute most to light attenuation. Underwater attenuation of downwards irradiance of photosynthetically active radiation (PAR) was determined over a three year period at 42 sites in shallow (freshwater flow into these areas may dilute CDOM concentrations and improve the salinity and light climate for SAV communities.

  18. Seismic attenuation system for a nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Liszkai, Tamas; Cadell, Seth

    2018-01-30

    A system for attenuating seismic forces includes a reactor pressure vessel containing nuclear fuel and a containment vessel that houses the reactor pressure vessel. Both the reactor pressure vessel and the containment vessel include a bottom head. Additionally, the system includes a base support to contact a support surface on which the containment vessel is positioned in a substantially vertical orientation. An attenuation device is located between the bottom head of the reactor pressure vessel and the bottom head of the containment vessel. Seismic forces that travel from the base support to the reactor pressure vessel via the containment vessel are attenuated by the attenuation device in a direction that is substantially lateral to the vertical orientation of the containment vessel.

  19. Dexmedetomidine in premedication to attenuate the acute ...

    African Journals Online (AJOL)

    Background: The choice of anaesthetic agent for electroconvulsive therapy (ECT) depends on seizure duration, haemodynamic ... and infarction. To attenuate this acute ... scheduled for ECT, physical status ASA I and II, age between 18 and.

  20. Attenuation measurements in solutions of some carbohydrates

    International Nuclear Information System (INIS)

    Gagandeep; Singh, K.; Lark, B.S.; Sahota, H.S.

    2000-01-01

    The linear attenuation coefficients in aqueous solutions of three carbohydrates, glucose (C 6 H 12 O 6 ), maltose monohydrate (C 12 H 22 O 11 ·H 2 O), and sucrose (C 12 H 22 O 11 ), were determined at 81, 356, 511, 662, 1,173, and 1,332 keV by the gamma-ray transmission method in a good geometry setup. From the precisely measured densities of these solutions, mass attenuation coefficients were then obtained that varied systematically with the corresponding changes in the concentrations (g/cm 3 ) of these solutions. The experimental results were used in terms of effective atomic numbers and electron densities. A comparison between experimental and theoretical values of attenuation coefficients has proven that the study has a potential application for the determination of attenuation coefficients of solid solutes from their solutions without obtaining them in pure crystalline form

  1. Attenuation Measurements in Solutions of Some Carbohydrates

    International Nuclear Information System (INIS)

    Gagandeep; Singh, Kulwant; Lark, B.S.; Sahota, H.S.

    2000-01-01

    The linear attenuation coefficients in aqueous solutions of three carbohydrates, glucose (C 6 H 12 O 6 ), maltose monohydrate (C 12 H 22 O 11 .H 2 O), and sucrose (C 12 H 22 O 11 ), were determined at 81, 356, 511, 662, 1173, and 1332 keV by the gamma-ray transmission method in a good geometry setup. From the precisely measured densities of these solutions, mass attenuation coefficients were then obtained that varied systematically with the corresponding changes in the concentrations (g/cm 3 ) of these solutions. The experimental results were used in terms of effective atomic numbers and electron densities. A comparison between experimental and theoretical values of attenuation coefficients has proven that the study has a potential application for the determination of attenuation coefficients of solid solutes from their solutions without obtaining them in pure crystalline form

  2. Radiation-attenuated vaccine for lungworm disease

    International Nuclear Information System (INIS)

    Singh, C.M.

    1977-01-01

    The work done at the Indian Veternary Research Institute, Izatnagar, on the development of a vaccine for lungworm diseases is reported. Research work done includes: (1) studies on the epidemiology and the incidence of the lungworm infections, (ii) studies on the radiation-attenuated lungworm Dictyocaulus filaria vaccine, (iii) studies on other parasites using ionizing radiation, (iv) incidence of lungworm infection in sheep in Jammu and Kashmir State, (v) suitable dose of gamma radiation for attenuation, (vi) laboratory studies with radiation-attenuated D. filaria vaccine, (vii) serology of D. filaria infection, (viii) field trials with the radiation-attenuated vaccine, (ix) immune response of previously exposed lambs to vaccination, (x) comparative susceptibility of sheep and goats to infection with D. filaria, (xi) quantitative studies of D. filaria in lambs and (xii) production and supply of lungworm vaccine. (A.K.)

  3. Backscatter and attenuation characterization of ventricular myocardium

    Science.gov (United States)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  4. Endogenous cueing attenuates object substitution masking.

    Science.gov (United States)

    Germeys, Filip; Pomianowska, I; De Graef, P; Zaenen, P; Verfaillie, K

    2010-07-01

    Object substitution masking (OSM) is a form of visual masking in which a briefly presented target surrounded by four small dots is masked by the continuing presence of the four dots after target offset. A major parameter in the prediction of OSM is the time required for attention to be directed to the target following its onset. Object substitution theory (Di Lollo et al. in J Exp Psychol Gen 129:481-507, 2000) predicts that the sooner attention can be focused at the target's location, the less masking will ensue. However, recently Luiga and Bachmann (Psychol Res 71:634-640, 2007) presented evidence that precueing of attention to the target location prior to target-plus-mask onset by means of a central (endogenous) arrow cue does not reduce OSM. When attention was cued exogenously, OSM was attenuated. Based on these results, Luiga and Bachmann argued that object substitution theory should be adapted by differentiating the ways of directing attention to the target location. The goal of the present study was to further examine the dissociation between the effects of endogenous and exogenous precueing on OSM. Contrary to Luiga and Bachmann, our results show that prior shifts of attention to the target location initiated by both exogenous and endogenous cues reduce OSM as predicted by object substitution theory and its computational model CMOS.

  5. Silibinin attenuates allergic airway inflammation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: ghyan@ybu.edu.cn [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  6. Silibinin attenuates allergic airway inflammation in mice

    International Nuclear Information System (INIS)

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-01-01

    Highlights: ► Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. ► Silibinin reduces the levels of various cytokines into the lung of allergic mice. ► Silibinin prevents the development of airway hyperresponsiveness in allergic mice. ► Silibinin suppresses NF-κB transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-κB) pathway. Because NF-κB activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-κB activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-κB activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  7. Transient hepatic attenuation differences in neonates

    International Nuclear Information System (INIS)

    Towbin, Alexander J.; Fleck, Robert; Ying, Jun

    2009-01-01

    A transient hepatic attenuation difference (THAD) is a hepatic perfusion anomaly seen on contrast-enhanced CT scans caused by an alteration in the dual blood supply of the liver. Although THADs have been described in adolescents and adults, they have not previously been described in neonates. We describe the appearance and evaluate the frequency of THADs in neonates ≤1 month of age compared to other infants younger than 2 years. A retrospective study was performed looking at all CT angiograms from 2000 to 2007 in infants <2 years of age. The incidence of THADs was compared among four age groups. Significance was determined using a logistic regression model. The study included 128 CT angiograms. A THAD was seen in 9/26 infants <1 month of age, in 3/50 infants 1 to 6 months of age, in 1/23 infants 6 months to 1 year of age, and in 1/29 infants 1 to 2 years of age. A THAD was found significantly more frequently in infants <1 month of age than in the older age groups (P<0.05). THADs are benign entities that can be seen normally in the neonatal age group. When the characteristic appearance is seen on CT, no further imaging is needed. (orig.)

  8. Statins attenuate polymethylmethacrylate-mediated monocyte activation.

    LENUS (Irish Health Repository)

    Laing, Alan J

    2012-02-03

    BACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte\\/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

  9. Obesity attenuates gender differences in cardiovascular mortality.

    Science.gov (United States)

    Song, Xin; Tabák, Adam G; Zethelius, Björn; Yudkin, John S; Söderberg, Stefan; Laatikainen, Tiina; Stehouwer, Coen D A; Dankner, Rachel; Jousilahti, Pekka; Onat, Altan; Nilsson, Peter M; Satman, Ilhan; Vaccaro, Olga; Tuomilehto, Jaakko; Qiao, Qing

    2014-10-19

    To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender. Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale. Men had higher CVD mortality than women in all four BMI categories (obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals. Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.

  10. Effect of duct shape, Mach number, and lining construction on measured suppressor attenuation and comparison with theory

    Science.gov (United States)

    Olsen, W. A.; Krejsa, E. A.; Coats, J. W.

    1972-01