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Sample records for extended lead target

  1. Studies on neutron production in the interaction of 7.4 GeV protons with extended lead target

    CERN Document Server

    Hashemi-Nezhad, S R; Ochs, M; Wan, J S; Schmidt, T; Langrock, E J; Vater, P; Adam, J; Bamblevskij, V P; Bradnova, V; Gelovani, L K; Kalinnikov, V K; Krivopustov, M I; Kulakov, B A; Sosnin, A N; Perelygin, V P; Pronskikh, V S; Stegailov, V I; Tsoupko-Sitnikov, V M; Modolo, G; Odoj, R; Phlippen, P W; Adloff, J C; Debeauvais, M; Zamani-Valassiadou, M; Dwivedi, K K; Wilson, B

    1999-01-01

    A cylindrical lead target of diameter 8 cm and length 20 cm was irradiated with 7.4 GeV protons along the axis of the cylinder. The lead target was surrounded with a paraffin layer of thickness 6 cm to moderate the neutrons produced in p + Pb reactions. The spatial distribution of the slow and fast neutrons on different surfaces of the moderator were determined using LR 115 2B detectors (through sup 1 sup 0 B(n,alpha) sup 7 Li reactions) and CR39 detectors (through proton recoils) respectively. Such results can be valuable in the studies and design of Accelerator Driven Subcritical Nuclear Reactors and Nuclear Waste Incinerators.

  2. Does string theory lead to extended inflation?

    Science.gov (United States)

    Campbell, Bruce A.; Linde, Andrei; Olive, Keith A.

    1991-05-01

    We consider the relationship between string theory and currently proposed models of extended inflation. In doing so, we discuss the conformal actions in string theory and in Jordan-Brans-Dicke gravity. We show explicitly the equivalence of pictures in which either gauge or gravitational couplings are changing with time. We demonstrate that the existence of the dilation in string theory does not naturally lead to extended inflation as currently discussed. We also discuss the resolution of the graceful exit problem of old inflation in Einstein gravity using either power-law inflation, or exponential inflation with a changing bubble formation rate. On leave of absence from School of Physics and Astronomy, University of Minnesota, Minneapolis, MN 55455, USA.

  3. Affinity Propagation Clustering of Measurements for Multiple Extended Target Tracking

    OpenAIRE

    Tao Zhang; Renbiao Wu

    2015-01-01

    More measurements are generated by the target per observation interval, when the target is detected by a high resolution sensor, or there are more measurement sources on the target surface. Such a target is referred to as an extended target. The probability hypothesis density filter is considered an efficient method for tracking multiple extended targets. However, the crucial problem of how to accurately and effectively partition the measurements of multiple extended targets remains unsolved....

  4. Extended Target Shape Estimation by Fitting B-Spline Curve

    Directory of Open Access Journals (Sweden)

    Jin-long Yang

    2014-01-01

    Full Text Available Taking into account the difficulty of shape estimation for the extended targets, a novel algorithm is proposed by fitting the B-spline curve. For the single extended target tracking, the multiple frame statistic technique is introduced to construct the pseudomeasurement sets and the control points are selected to form the B-spline curve. Then the shapes of the extended targets are extracted under the Bayes framework. Furthermore, the proposed shape estimation algorithm is modified suitably and combined with the probability hypothesis density (PHD filter for multiple extended target tracking. Simulations show that the proposed algorithm has a good performance for shape estimate of any extended targets.

  5. Affinity Propagation Clustering of Measurements for Multiple Extended Target Tracking

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-09-01

    Full Text Available More measurements are generated by the target per observation interval, when the target is detected by a high resolution sensor, or there are more measurement sources on the target surface. Such a target is referred to as an extended target. The probability hypothesis density filter is considered an efficient method for tracking multiple extended targets. However, the crucial problem of how to accurately and effectively partition the measurements of multiple extended targets remains unsolved. In this paper, affinity propagation clustering is introduced into measurement partitioning for extended target tracking, and the elliptical gating technique is used to remove the clutter measurements, which makes the affinity propagation clustering capable of partitioning the measurement in a densely cluttered environment with high accuracy. The Gaussian mixture probability hypothesis density filter is implemented for multiple extended target tracking. Numerical results are presented to demonstrate the performance of the proposed algorithm, which provides improved performance, while obviously reducing the computational complexity.

  6. Affinity Propagation Clustering of Measurements for Multiple Extended Target Tracking.

    Science.gov (United States)

    Zhang, Tao; Wu, Renbiao

    2015-09-08

    More measurements are generated by the target per observation interval, when the target is detected by a high resolution sensor, or there are more measurement sources on the target surface. Such a target is referred to as an extended target. The probability hypothesis density filter is considered an efficient method for tracking multiple extended targets. However, the crucial problem of how to accurately and effectively partition the measurements of multiple extended targets remains unsolved. In this paper, affinity propagation clustering is introduced into measurement partitioning for extended target tracking, and the elliptical gating technique is used to remove the clutter measurements, which makes the affinity propagation clustering capable of partitioning the measurement in a densely cluttered environment with high accuracy. The Gaussian mixture probability hypothesis density filter is implemented for multiple extended target tracking. Numerical results are presented to demonstrate the performance of the proposed algorithm, which provides improved performance, while obviously reducing the computational complexity.

  7. Affinity Propagation Clustering of Measurements for Multiple Extended Target Tracking

    National Research Council Canada - National Science Library

    Zhang, Tao; Wu, Renbiao

    2015-01-01

    .... In this paper, affinity propagation clustering is introduced into measurement partitioning for extended target tracking, and the elliptical gating technique is used to remove the clutter measurements...

  8. Extended emitter target tracking using GM-PHD filter.

    Directory of Open Access Journals (Sweden)

    Youqing Zhu

    Full Text Available If equipped with several radar emitters, a target will produce more than one measurement per time step and is denoted as an extended target. However, due to the requirement of all possible measurement set partitions, the exact probability hypothesis density filter for extended target tracking is computationally intractable. To reduce the computational burden, a fast partitioning algorithm based on hierarchy clustering is proposed in this paper. It combines the two most similar cells to obtain new partitions step by step. The pseudo-likelihoods in the Gaussian-mixture probability hypothesis density filter can then be computed iteratively. Furthermore, considering the additional measurement information from the emitter target, the signal feature is also used in partitioning the measurement set to improve the tracking performance. The simulation results show that the proposed method can perform better with lower computational complexity in scenarios with different clutter densities.

  9. Novel Fractional Order Calculus Extended PN for Maneuvering Targets

    Directory of Open Access Journals (Sweden)

    Jikun Ye

    2017-01-01

    Full Text Available Based on the theory of fractional order calculus (FOC, a novel extended proportional guidance (EPN law for intercepting the maneuvering target is proposed. In the first part, considering the memory function and filter characteristic of FOC, the novel extended PN guidance algorithm is developed based on the conventional PN after introducing the properties and operation rules of FOC. Further, with the help of FOC theory, the average load and ballistics characteristics of proposed guidance law are analyzed. Then, using the small offset kinematic model, the robustness of the new guidance law against autopilot parameters is studied theoretically by analyzing the sensitivity of the closed loop guidance system. At last, representative numerical results show that the designed guidance law obtains a better performance than the traditional PN for maneuvering target.

  10. Resistor array performance errors associated with extended targets

    Science.gov (United States)

    Sisko, R. Bryan; Marlow, Steven A.; Huber, August J.; Thompson, Rhoe A.

    2006-05-01

    In recent hardware-in-the-loop tests conducted in a cryogenic chamber, a dual band sensor observed radiometric anomalies for extended targets. In order to understand the radiometric errors associated with the infrared projection arrays, systematic measurements were performed at both cryogenic and ambient temperatures. Air Force Research Laboratory (AFRL) engineers have previously investigated an artifact observed in these arrays called "busbar robbing," but these observations were of square blocks of emitters and did not characterize radiometric accuracy of extended targets in a dynamic engagement scenario. It was discovered that when numerous emitters in a contiguous pattern are turned on, rather than scattered over the array, the "busbar robbing" effect causes the actual emitter outputs to be different from what you measure if you drive them to the same level with fewer pixels. When the emitters that are driven have some "aspect ratio" or elongated shape, then the effect is dependent on how this pattern is aligned with the emitter axes. The results of these experiments address the radiometric error that can be expected from the resistor array projectors for end game scenarios when a target becomes extended at both ambient and cryogenic temperatures.

  11. The Advanced Linked Extended Reconnaissance & Targeting Technology Demonstration project

    Science.gov (United States)

    Edwards, Mark

    2008-04-01

    The Advanced Linked Extended Reconnaissance & Targeting (ALERT) Technology Demonstration (TD) project is addressing many operational needs of the future Canadian Army's Surveillance and Reconnaissance forces. Using the surveillance system of the Coyote reconnaissance vehicle as an experimental platform, the ALERT TD project aims to significantly enhance situational awareness by fusing multi-sensor and tactical data, developing automated processes, and integrating beyond line-of-sight sensing. The project is exploiting important advances made in computer processing capability, displays technology, digital communications, and sensor technology since the design of the original surveillance system. As the major research area within the project, concepts are discussed for displaying and fusing multi-sensor and tactical data within an Enhanced Operator Control Station (EOCS). The sensor data can originate from the Coyote's own visible-band and IR cameras, laser rangefinder, and ground-surveillance radar, as well as from beyond line-of-sight systems such as mini-UAVs and unattended ground sensors. Video-rate image processing has been developed to assist the operator to detect poorly visible targets. As a second major area of research, automatic target cueing capabilities have been added to the system. These include scene change detection, automatic target detection and aided target recognition algorithms processing both IR and visible-band images to draw the operator's attention to possible targets. The merits of incorporating scene change detection algorithms are also discussed. In the area of multi-sensor data fusion, up to Joint Defence Labs level 2 has been demonstrated. The human factors engineering aspects of the user interface in this complex environment are presented, drawing upon multiple user group sessions with military surveillance system operators. The paper concludes with Lessons Learned from the project. The ALERT system has been used in a number of C4ISR

  12. Tracking of maneuvering non-ellipsoidal extended target with varying number of sub-objects

    Science.gov (United States)

    Hu, Qi; Ji, Hongbing; Zhang, Yongquan

    2018-01-01

    A target that generates multiple measurements at each time step is called the extended target and an ellipse can be used to approximate its extension. When the spatial distributions of measurements can reflect its true shape, in this situation the extended target is called a non-ellipsoidal extended target and its complicated extended state cannot be accurately approximated by single ellipse. In view of this, the non-ellipsoidal extended target tracking (NETT) filter was proposed, which uses multiple ellipses (called sub-objects) to approximate the extended state. However, the existing NETT filters are limited to the framework that the number of sub-objects remains still, which does not match the actual tracking situations. When the attitude of the target changes, the view from the sensor on the target may change, then the shape of the non-ellipsoidal extended target varies as well as the reasonable number of sub-objects needed for approximation. To solve this problem, we propose a varying number of sub-objects for non-ellipsoidal extended target tracking gamma Gaussian inverse Wishart (VN-NETT-GGIW) filter. The proposed filter estimates the kinematic, extension and measurement-rate states of each sub-object as well as the number of sub-objects. The simulation results show that the proposed filter can be used for the target changing attitude situation and is more close to the practice application.

  13. From drug target to leads--sketching a physicochemical pathway for lead molecule design in silico.

    Science.gov (United States)

    Shaikh, S A; Jain, T; Sandhu, G; Latha, N; Jayaram, B

    2007-01-01

    The discovery of new pharmaceuticals via computer modeling is one of the key challenges in modern medicine. The advent of global networks of genomic, proteomic and metabolomic endeavors is ushering in an increasing number of novel and clinically important targets for screening. Computational methods are anticipated to play a pivotal role in exploiting the structural and functional information to understand specific molecular recognition events of the target macromolecule with candidate hits leading ultimately to the design of improved leads for the target. In this review, we sketch a system independent, comprehensive physicochemical pathway for lead molecule design focusing on the emerging in silico trends and techniques. We survey strategies for the generation of candidate molecules, docking them with the target and ranking them based on binding affinities. We present a molecular level treatment for distinguishing affinity from specificity of a ligand for a given target. We also discuss the significant aspects of drug absorption, distribution, metabolism, excretion and toxicity (ADMET) and highlight improved protocols required for higher quality and throughput of in silico methods employed at early stages of discovery. We present a realization of the various stages in the pathway proposed with select examples from the literature and from our own research to demonstrate the way in which an iterative process of computer design and validation can aid in developing potent leads. The review thus summarizes recent advances and presents a viewpoint on improvements envisioned in the years to come for automated computer aided lead molecule discovery.

  14. Lead (Pb) hohlraum: target for inertial fusion energy.

    Science.gov (United States)

    Ross, J S; Amendt, P; Atherton, L J; Dunne, M; Glenzer, S H; Lindl, J D; Meeker, D; Moses, E I; Nikroo, A; Wallace, R

    2013-01-01

    Recent progress towards demonstrating inertial confinement fusion (ICF) ignition at the National Ignition Facility (NIF) has sparked wide interest in Laser Inertial Fusion Energy (LIFE) for carbon-free large-scale power generation. A LIFE-based fleet of power plants promises clean energy generation with no greenhouse gas emissions and a virtually limitless, widely available thermonuclear fuel source. For the LIFE concept to be viable, target costs must be minimized while the target material efficiency or x-ray albedo is optimized. Current ICF targets on the NIF utilize a gold or depleted uranium cylindrical radiation cavity (hohlraum) with a plastic capsule at the center that contains the deuterium and tritium fuel. Here we show a direct comparison of gold and lead hohlraums in efficiently ablating deuterium-filled plastic capsules with soft x rays. We report on lead hohlraum performance that is indistinguishable from gold, yet costing only a small fraction.

  15. Activation analysis of targets and lead in a lead slowing down spectrometer system

    Directory of Open Access Journals (Sweden)

    Yongdeok Lee

    2018-02-01

    Full Text Available A neutron generation system was developed to induce fissile fission in a lead slowing down spectrometer (LSDS system. The source neutron is one of the key factors for LSDS system work. The LSDS was developed to quantify the isotopic contents of fissile materials in spent nuclear fuel and recycled fuel. The source neutron is produced at a multilayered target by the (e,γ(γ,n reaction and slowed down at the lead medium. Activation analysis of the target materials is necessary to estimate the lifetime, durability, and safety of the target system. The CINDER90 code was used for the activation analysis, and it can involve three-dimensional geometry, position dependent neutron flux, and multigroup cross-section libraries. Several sensitivity calculations for a metal target with different geometries, materials, and coolants were done to achieve a high neutron generation rate and a low activation characteristic. Based on the results of the activation analysis, tantalum was chosen as a target material due to its better activation characteristics, and helium gas was suggested as a coolant. In addition, activation in a lead medium was performed. After a distance of 55 cm from the lead surface to the neutron incidence, the neutron intensity dramatically decreased; this result indicates very low activation.

  16. Extending dynamic segmentation with lead generation : A latent class Markov analysis of financial product portfolios

    NARCIS (Netherlands)

    Paas, L.J.; Bijmolt, T.H.A.; Vermunt, J.K.

    2004-01-01

    A recent development in marketing research concerns the incorporation of dynamics in consumer segmentation.This paper extends the latent class Markov model, a suitable technique for conducting dynamic segmentation, in order to facilitate lead generation.We demonstrate the application of the latent

  17. Radar correlated imaging for extended target by the combination of negative exponential restraint and total variation

    Science.gov (United States)

    Qian, Tingting; Wang, Lianlian; Lu, Guanghua

    2017-07-01

    Radar correlated imaging (RCI) introduces the optical correlated imaging technology to traditional microwave imaging, which has raised widespread concern recently. Conventional RCI methods neglect the structural information of complex extended target, which makes the quality of recovery result not really perfect, thus a novel combination of negative exponential restraint and total variation (NER-TV) algorithm for extended target imaging is proposed in this paper. The sparsity is measured by a sequential order one negative exponential function, then the 2D total variation technique is introduced to design a novel optimization problem for extended target imaging. And the proven alternating direction method of multipliers is applied to solve the new problem. Experimental results show that the proposed algorithm could realize high resolution imaging efficiently for extended target.

  18. A fast ellipse extended target PHD filter using box-particle implementation

    Science.gov (United States)

    Zhang, Yongquan; Ji, Hongbing; Hu, Qi

    2018-01-01

    This paper presents a box-particle implementation of the ellipse extended target probability hypothesis density (ET-PHD) filter, called the ellipse extended target box particle PHD (EET-BP-PHD) filter, where the extended targets are described as a Poisson model developed by Gilholm et al. and the term ;box; is here equivalent to the term ;interval; used in interval analysis. The proposed EET-BP-PHD filter is capable of dynamically tracking multiple ellipse extended targets and estimating the target states and the number of targets, in the presence of clutter measurements, false alarms and missed detections. To derive the PHD recursion of the EET-BP-PHD filter, a suitable measurement likelihood is defined for a given partitioning cell, and the main implementation steps are presented along with the necessary box approximations and manipulations. The limitations and capabilities of the proposed EET-BP-PHD filter are illustrated by simulation examples. The simulation results show that a box-particle implementation of the ET-PHD filter can avoid the high number of particles and reduce computational burden, compared to a particle implementation of that for extended target tracking.

  19. Do more health insurance options lead to higher wages? Evidence from states extending dependent coverage.

    Science.gov (United States)

    Dillender, Marcus

    2014-07-01

    Little is known about how health insurance affects labor market decisions for young adults. This is despite the fact that expanding coverage for people in their early 20s is an important component of the Affordable Care Act. This paper studies how having an outside source of health insurance affects wages by using variation in health insurance access that comes from states extending dependent coverage to young adults. Using American Community Survey and Census data, I find evidence that extending health insurance to young adults raises their wages. The increases in wages can be explained by increases in human capital and the increased flexibility in the labor market that comes from people no longer having to rely on their own employers for health insurance. The estimates from this paper suggest the Affordable Care Act will lead to wage increases for young adults. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Affinity Propagation Based Measurement Partition Algorithm for Multiple Extended Target Tracking

    Directory of Open Access Journals (Sweden)

    Yang Jin-long

    2015-08-01

    Full Text Available It is difficult to accurately and rapidly partition measurement sets of multiple extended targets in cluttered environment. Hence the affinity propagation method is introduced and a novel measurement partition algorithm is proposed. First, the measurement set is preprocessed by using density analysis to remove clutters from the measurements. Second, the number and location of the extended targets is determined via competition among the measurements. Finally, state estimates are obtained by using the probability hypothesis density filter. Simulations show that the proposed algorithm offers good performance in measurement partitioning of extended target tracking with clutter disturbance. Compared with the distance partition and K-means++ methods, the proposed method effectively minimizes the computation time and retrieves the number of targets iteratively.

  1. Polonium problem in lead-bismuth flow target

    Energy Technology Data Exchange (ETDEWEB)

    Pankratov, D.V.; Yefimov, E.I.; Bugreev, M.I. [State Scientific Centre of Russian Federation-Institute of Physics and Power Engineering, Obninsk (Russian Federation)

    1996-06-01

    Alpha-active polonium nuclides Po198 - Po210 are formed in a lead-bismuth target as results of reactions Bi{sup 209}(n,{gamma})Bi{sup 210} {yields} Po{sup 210}, Bi{sup 209}(p,xn)Po{sup 210} {yields} Po{sup 210 {minus} x} (x = 1-12), Pb{sup 208}({alpha},xn) {yields} Po{sup 210 {minus} x + 2} (x = 2-14). The most important nuclides are Po-210 (T{sub {1/2}}=138.4 day), Po-209 (T{sub {1/2}}=102 years) and Po-208 (T{sub {1/2}}=2.9 years). Polonium activity of the circuit for SINQ - conditions is about 15,000 Ci after 1-year operation. Polonium radiation hazard is connected with its output from the coolant and formation of aerosol and surface alpha-activity after the circuit break-down for repair works or in accidents. One of the important issues of polonium removal system creation is containing and storing polonium removed. Its storage in solidified alkaline is not expedient because of secondary neutron formation as a result of ({alpha},n) - reaction on oxygen and sodium nucleus. The estimations carried out demonstrated that by polonium concentration {approx} 100 Ci/l neutron current on the container surface can reach {approx} 10{sup 4}n/(cm{sup 2}s). Concentration and storage of polonium in solidified lead-bisumth seems the most convenient. The calculations demonstrated that in a 100 l container 50,000 Ci of polonium can be stored (as much as 3 times more than 1-year polonium product in SINQ-conditions) under temperature in the container less than melting point of lead bismuth (the wall temperature is about 100{degrees}C).

  2. Structural characteristics of the shock-induced boundary layer separation extended to the leading edge

    Science.gov (United States)

    Tao, Y.; Liu, W. D.; Fan, X. Q.; Zhao, Y. L.

    2017-07-01

    For a better understanding of the local unstart of supersonic/hypersonic inlet, a series of experiments has been conducted to investigate the shock-induced boundary layer separation extended to the leading edge. Using the nanoparticle-based planar laser scattering, we recorded the fine structures of these interactions under different conditions and paid more attention to their structural characteristics. According to their features, these interactions could be divided into four types. Specifically, Type A wave pattern is similar to the classic shock wave/turbulent boundary layer interaction, and Type B wave configuration consists of an overall Mach reflection above the large scale separation bubble. Due to the gradual decrease in the size of the separation bubble, the separation bubble was replaced by several vortices (Type C wave pattern). Besides, for Type D wave configuration which exists in the local unstart inlet, there appears to be some flow spillage around the leading edge.

  3. Track-Before-Detect Algorithm for Weak Extended Target Based on Particle Filter under Clutter Environment

    Directory of Open Access Journals (Sweden)

    Wu Sunyong

    2017-06-01

    Full Text Available The Track-Before-Detect (TBD algorithm based on the particle filter is proposed for weak extended target detection and tracking in low signal to clutter noise radio. The rod-shaped object is analyzed by dividing the cell on range and azimuth under the Weibull clutter. On the basis of a point target, the likelihood function and particle weights can be obtained by the target spread function. In the TBD algorithm, the binary target variable and the target shape parameters is added to the state vector and the scattering points in the sample collection is given based on the particle filter, which can detect and estimate the target state and the shape parameters under the clutter environment. Simulation results show that the stability of the algorithm is very good.

  4. Eliminating Childhood Lead Poisoning: A Federal Strategy Targeting Lead Paint Hazards.

    Science.gov (United States)

    2000

    Noting that lead poisoning is a preventable disease, this report details a coordinated federal program to eliminate childhood lead poisoning in the United States. The report describes how lead poisoning harms children, how pervasive lead poisoning is, and how lead paint hazards in housing could be eliminated in 10 years. Following information on…

  5. Time-reversal optical tomography: detecting and locating extended targets in a turbid medium

    Science.gov (United States)

    Wu, Binlin; Cai, W.; Xu, M.; Gayen, S. K.

    2012-03-01

    Time Reversal Optical Tomography (TROT) is developed to locate extended target(s) in a highly scattering turbid medium, and estimate their optical strength and size. The approach uses Diffusion Approximation of Radiative Transfer Equation for light propagation along with Time Reversal (TR) Multiple Signal Classification (MUSIC) scheme for signal and noise subspaces for assessment of target location. A MUSIC pseudo spectrum is calculated using the eigenvectors of the TR matrix T, whose poles provide target locations. Based on the pseudo spectrum contours, retrieval of target size is modeled as an optimization problem, using a "local contour" method. The eigenvalues of T are related to optical strengths of targets. The efficacy of TROT to obtain location, size, and optical strength of one absorptive target, one scattering target, and two absorptive targets, all for different noise levels was tested using simulated data. Target locations were always accurately determined. Error in optical strength estimates was small even at 20% noise level. Target size and shape were more sensitive to noise. Results from simulated data demonstrate high potential for application of TROT in practical biomedical imaging applications.

  6. Radar Constant-Modulus Waveform Design with Prior Information of the Extended Target and Clutter.

    Science.gov (United States)

    Yue, Wenzhen; Zhang, Yan; Liu, Yimin; Xie, Jingwen

    2016-06-17

    Radar waveform design is of great importance for radar system performances and has drawn considerable attention recently. Constant modulus is an important waveform design consideration, both from the point of view of hardware realization and to allow for full utilization of the transmitter's power. In this paper, we consider the problem of constant-modulus waveform design for extended target detection with prior information about the extended target and clutter. At first, we propose an arbitrary-phase unimodular waveform design method via joint transmitter-receiver optimization. We exploit a semi-definite relaxation technique to transform an intractable non-convex problem into a convex problem, which can then be efficiently solved. Furthermore, quadrature phase shift keying waveform is designed, which is easier to implement than arbitrary-phase waveforms. Numerical results demonstrate the effectiveness of the proposed methods.

  7. Radar Constant-Modulus Waveform Design with Prior Information of the Extended Target and Clutter

    Directory of Open Access Journals (Sweden)

    Wenzhen Yue

    2016-06-01

    Full Text Available Radar waveform design is of great importance for radar system performances and has drawn considerable attention recently. Constant modulus is an important waveform design consideration, both from the point of view of hardware realization and to allow for full utilization of the transmitter’s power. In this paper, we consider the problem of constant-modulus waveform design for extended target detection with prior information about the extended target and clutter. At first, we propose an arbitrary-phase unimodular waveform design method via joint transmitter-receiver optimization. We exploit a semi-definite relaxation technique to transform an intractable non-convex problem into a convex problem, which can then be efficiently solved. Furthermore, quadrature phase shift keying waveform is designed, which is easier to implement than arbitrary-phase waveforms. Numerical results demonstrate the effectiveness of the proposed methods.

  8. Capture reactions at astrophysically relevant energies: extended gas target experiments and GEANT simulations

    CERN Document Server

    Kölle, V; Braitmayer, S E; Mohr, P J; Wilmes, S; Staudt, G; Hammer, J W; Jäger, M; Knee, H; Kunz, R; Mayer, A

    1999-01-01

    Several resonances of the capture reaction sup 2 sup 0 Ne(alpha, gamma) sup 2 sup 4 Mg were measured using an extended windowless gas target system. Detailed GEANT simulations were performed to derive the strength and the total width of the resonances from the measured yield curve. The crucial experimental parameters, which are mainly the density profile in the gas target and the efficiency of the gamma-ray detector, were analyzed by a comparison between the measured data and the corresponding simulation calculations. The excellent agreement between the experimental data and the simulations gives detailed insight into these parameters. (author)

  9. Factors leading to inflation targeting : The impact of adoption

    NARCIS (Netherlands)

    Samarina, Anna; Sturm, Jan-Egbert

    2013-01-01

    This paper examines how the analysis of inflation targeting (IT) adoption is affected by allowing for a structural change after adoption, using panel probit models for 60 countries over the period 1985-2008. Our findings suggest that there is a structural change after IT adoption. Including the

  10. Factors leading to inflation targeting - the impact of adoption

    NARCIS (Netherlands)

    Samarina, Anna; Sturm, Jan-Egbert

    2013-01-01

    This paper examines how the analysis of inflation targeting (IT) adoption is affected by the choice of the analyzed period. We test whether country characteristics influence the decision to apply IT differently before and after its adoption, using panel probit models for 60 countries over the period

  11. Ultrasound imaging of extended targets using a windowed time-reversal MUSIC method

    Science.gov (United States)

    Labyed, Yassin; Huang, Lianjie

    2012-03-01

    Time-reversal with Multiple Signal Classification (TR-MUSIC) is an ultrasound imaging algorithm for detecting small targets embedded in a medium. This technique can produce images with subwavelength resolution when the targets are pointlike, and when the number of targets is fewer than the number of transducer elements used to image the medium. In this experimental study, we evaluate the performance of the TR-MUSIC algorithm when the interrogated medium contains extended targets that cannot be considered as point scatterers. We construct tissue-mimicking phantoms embedded with distributed glass spheres. We show that the quality of the phantom images obtained using the TR-MUSIC algorithm decreases with increasing sphere size. However, significant improvement is achieved when the image plane is divided into sub-regions, where each sub-region is imaged separately. The windowed TR-MUSIC algorithm accurately locates the spheres (extended targets), but the images do not provide quantitative information about the shape and reflectivity of the spheres.

  12. Cyanobacterial Cyclopeptides as Lead Compounds to Novel Targeted Cancer Drugs

    Science.gov (United States)

    Sainis, Ioannis; Fokas, Demosthenes; Vareli, Katerina; Tzakos, Andreas G.; Kounnis, Valentinos; Briasoulis, Evangelos

    2010-01-01

    Cyanobacterial cyclopeptides, including microcystins and nodularins, are considered a health hazard to humans due to the possible toxic effects of high consumption. From a pharmacological standpoint, microcystins are stable hydrophilic cyclic heptapeptides with a potential to cause cellular damage following uptake via organic anion-transporting polypeptides (OATP). Their intracellular biological effects involve inhibition of catalytic subunits of protein phosphatase 1 (PP1) and PP2, glutathione depletion and generation of reactive oxygen species (ROS). Interestingly, certain OATPs are prominently expressed in cancers as compared to normal tissues, qualifying MC as potential candidates for cancer drug development. In the era of targeted cancer therapy, cyanotoxins comprise a rich source of natural cytotoxic compounds with a potential to target cancers expressing specific uptake transporters. Moreover, their structure offers opportunities for combinatorial engineering to enhance the therapeutic index and resolve organ-specific toxicity issues. In this article, we revisit cyanobacterial cyclopeptides as potential novel targets for anticancer drugs by summarizing existing biomedical evidence, presenting structure-activity data and discussing developmental perspectives. PMID:20411119

  13. Cyanobacterial Cyclopeptides as Lead Compounds to Novel Targeted Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Evangelos Briasoulis

    2010-03-01

    Full Text Available Cyanobacterial cyclopeptides, including microcystins and nodularins, are considered a health hazard to humans due to the possible toxic effects of high consumption. From a pharmacological standpoint, microcystins are stable hydrophilic cyclic heptapeptides with a potential to cause cellular damage following uptake via organic anion-transporting polypeptides (OATP. Their intracellular biological effects involve inhibition of catalytic subunits of protein phosphatase 1 (PP1 and PP2, glutathione depletion and generation of reactive oxygen species (ROS. Interestingly, certain OATPs are prominently expressed in cancers as compared to normal tissues, qualifying MC as potential candidates for cancer drug development. In the era of targeted cancer therapy, cyanotoxins comprise a rich source of natural cytotoxic compounds with a potential to target cancers expressing specific uptake transporters. Moreover, their structure offers opportunities for combinatorial engineering to enhance the therapeutic index and resolve organ-specific toxicity issues. In this article, we revisit cyanobacterial cyclopeptides as potential novel targets for anticancer drugs by summarizing existing biomedical evidence, presenting structure-activity data and discussing developmental perspectives.

  14. Influence of Different Moderator Materials on Characteristics of Neutron Fluxes Generated under Irradiation of Lead Target with Proton Beams

    CERN Document Server

    Sosnin, A N; Polanski, A; Petrochenkov, S A; Golovatyuk, V M; Krivopustov, M I; Bamblevski, V P; Westmeier, W; Odoj, R; Brandt, R; Robotham, H; Hashemi-Nezhad, S R; Zamani-Valassiadou, M

    2002-01-01

    Neutron fields generated in extended heavy (Z\\geq 82) targets under irradiation with proton beams at energies in the range of 1 GeV are investigated. Influence of different moderators on the spectra and multiplicities of neutrons escaping the surface of the assembly consisting of a lead target (\\varnothing 8 cm\\times 20 cm or \\varnothing 8cm\\times 50 cm) screened by variable thickness of polyethylene or graphite, respectively, was compared in the present work. It is shown that the effectiveness of graphite as a material used in such assemblies to moderate spallation neutrons down to thermal energies is significantly lower than that of paraffin.

  15. Estimation of peak heat flux onto the targets for CFETR with extended divertor leg

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chuanjia; Chen, Bin [School of Nuclear Science and Technology, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China); Xing, Zhe [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Wu, Haosheng [School of Nuclear Science and Technology, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China); Mao, Shifeng, E-mail: sfmao@ustc.edu.cn [School of Nuclear Science and Technology, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China); Luo, Zhengping; Peng, Xuebing [Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Ye, Minyou [School of Nuclear Science and Technology, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China); Institute of Plasma Physics, Chinese Academy of Sciences, Hefei, Anhui 230031 (China)

    2016-11-01

    Highlights: • A hypothetical geometry is assumed to extend the outer divertor leg in CFETR. • Density scan SOLPS simulation is done to study the peak heat flux onto target. • Attached–detached regime transition in out divertor occurs at lower puffing rate. • Unexpected delay of attached–detached regime transition occurs in inner divertor. - Abstract: China Fusion Engineering Test Reactor (CFETR) is now in conceptual design phase. CFETR is proposed as a good complement to ITER for demonstrating of fusion energy. Divertor is a crucial component which faces the plasmas and handles huge heat power for CFETR and future fusion reactor. To explore an effective way for heat exhaust, various methods to reduce the heat flux to divertor target should be considered for CFETR. In this work, the effect of extended out divertor leg on the peak heat flux is studied. The magnetic configuration of the long leg divertor is obtained by EFIT and Tokamak Simulation Code (TSC), while a hypothetical geometry is assumed to extend the out divertor leg as long as possible inside vacuum vessel. A SOLPS simulation is performed to study peak heat flux of the long leg divertor for CFETR. D{sub 2} gas puffing is used and increasing of the puffing rate means increase of plasma density. Both peak heat flux onto inner and outer targets are below 10 MW/m{sup 2} is achieved. A comparison between the peak heat flux between long leg and conventional divertor shows that an attached–detached regime transition of out divertor occurs at lower gas puffing gas puffing rate for long leg divertor. While for the inner divertor, even the configuration is almost the same, the situation is opposite.

  16. The SDSS-IV extended Baryon Oscillation Spectroscopic Survey: final emission line galaxy target selection

    Science.gov (United States)

    Raichoor, A.; Comparat, J.; Delubac, T.; Kneib, J.-P.; Yèche, Ch; Dawson, K. S.; Percival, W. J.; Dey, A.; Lang, D.; Schlegel, D. J.; Gorgoni, C.; Bautista, J.; Brownstein, J. R.; Mariappan, V.; Seo, H.-J.; Tinker, J. L.; Ross, A. J.; Wang, Y.; Zhao, G.-B.; Moustakas, J.; Palanque-Delabrouille, N.; Jullo, E.; Newmann, J. A.; Prada, F.; Zhu, G. B.

    2017-11-01

    We describe the algorithm used to select the emission line galaxy (ELG) sample at z ˜ 0.85 for the extended Baryon Oscillation Spectroscopic Survey of the Sloan Digital Sky Survey IV, using photometric data from the DECam Legacy Survey. Our selection is based on a selection box in the g - r versus r - z colour-colour space and a cut on the g-band magnitude, to favour galaxies in the desired redshift range with strong [O II] emission. It provides a target density of 200 deg-2 on the North Galactic Cap and of 240 deg-2 on the South Galactic Cap (SGC), where we use a larger selection box because of deeper imaging. We demonstrate that this selection passes the extended Baryon Oscillation Spectroscopic Survey requirements in terms of homogeneity. About 50 000 ELGs have been observed since the observations have started in 2016, September. These roughly match the expected redshift distribution, though the measured efficiency is slightly lower than expected. The efficiency can be increased by enlarging the redshift range and with incoming pipeline improvement. The cosmological forecast based on these first data predict σ _{D_V}/D_V = 0.023, in agreement with previous forecasts. Lastly, we present the stellar population properties of the ELG SGC sample. Once observations are completed, this sample will be suited to provide a cosmological analysis at z ˜ 0.85, and will pave the way for the next decade of massive spectroscopic cosmological surveys, which heavily rely on ELGs. The target catalogue over the SGC will be released along with DR14.

  17. Flowing lead spallation target design for use in an ADTT experimental facility located at LAMPF

    Science.gov (United States)

    Beard, C. A.; Bracht, R. R.; Buksa, J. J.; Chaves, W.; DeVolder, B. G.; O'Brien, H.; Park, J. J.; Parker, R. B.; Pillai, C.; Potter, R. C.; Reid, R. S.; Trujillo, D. A.; Vela, O. A.; Venneri, F.; Weinacht, D. J.; Wender, S. A.; Wilson, W. B.; Woloshun, K. A.

    1995-09-01

    A conceptual design has been initiated for a flowing lead spallation target for use in an ADTT experimental facility located at LAMPF. The lead is contained using Nb-1Zr as the structural material. This material was selected based on its favorable material properties as well as its compatibility with the flowing lead. Heat deposited in the lead and the Nb-1Zr container by the 800-MeV, 1-mA beam is removed by the flowing lead and transferred to helium via a conventional heat exchanger. The neutronic, thermal hydraulic, and stress characteristics of the system have been determined. In addition, a module to control the thaw and freeze of the lead has been developed and incorporated into the target system design. The entire primary target system (spallation target, thaw/freeze system, and intermediate heat exchanger) has been designed to be built as a contained module to allow easy insertion into an experimental ADTT blanket assembly and to provide multiple levels of containment for the lead. For the 800-MeV LAMPF beam, the target delivers a source of approximately 18 neutrons/proton. A total of 540 kW are deposited in the target. The lead temperature ranges from 400 to 500 C. The peak structural heating occurs at the beam interface, and the target is designed to maximize cooling at this point. An innovative thin-window structure has been incorporated that allows direct, convective cooling of the window by the inlet flowing lead. Safe and reliable operation of the target has been maximized through simple, robust engineering.

  18. Rational design of chemical genetic probes of RNA function and lead therapeutics targeting repeating transcripts.

    Science.gov (United States)

    Disney, Matthew D

    2013-12-01

    RNA is an important yet vastly underexploited target for small molecule chemical probes or lead therapeutics. Small molecules have been used successfully to modulate the function of the bacterial ribosome, viral RNAs and riboswitches. These RNAs are either highly expressed or can be targeted using substrate mimicry, a mainstay in the design of enzyme inhibitors. However, most cellular RNAs are neither highly expressed nor have a lead small molecule inhibitor, a significant challenge for drug discovery efforts. Herein, I describe the design of small molecules targeting expanded repeating transcripts that cause myotonic muscular dystrophy (DM). These test cases illustrate the challenges of designing small molecules that target RNA and the advantages of targeting repeating transcripts. Lastly, I discuss how small molecules might be more advantageous than oligonucleotides for targeting RNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. PASylation of Murine Leptin Leads to Extended Plasma Half-Life and Enhanced in Vivo Efficacy.

    Science.gov (United States)

    Morath, Volker; Bolze, Florian; Schlapschy, Martin; Schneider, Sarah; Sedlmayer, Ferdinand; Seyfarth, Katrin; Klingenspor, Martin; Skerra, Arne

    2015-05-04

    Leptin plays a central role in the control of energy homeostasis and appetite and, thus, has attracted attention for therapeutic approaches in spite of its limited pharmacological activity owing to the very short circulation in the body. To improve drug delivery and prolong plasma half-life, we have fused murine leptin with Pro/Ala/Ser (PAS) polypeptides of up to 600 residues, which adopt random coil conformation with expanded hydrodynamic volume in solution and, consequently, retard kidney filtration in a similar manner as polyethylene glycol (PEG). Relative to unmodified leptin, size exclusion chromatography and dynamic light scattering revealed an approximately 21-fold increase in apparent size and a much larger molecular diameter of around 18 nm for PAS(600)-leptin. High receptor-binding activity for all PASylated leptin versions was confirmed in BIAcore measurements and cell-based dual-luciferase assays. Pharmacokinetic studies in mice revealed a much extended plasma half-life after ip injection, from 26 min for the unmodified leptin to 19.6 h for the PAS(600) fusion. In vivo activity was investigated after single ip injection of equimolar doses of each leptin version. Strongly increased and prolonged hypothalamic STAT3 phosphorylation was detected for PAS(600)-leptin. Also, a reduction in daily food intake by up to 60% as well as loss in body weight of >10% lasting for >5 days was observed, whereas unmodified leptin was merely effective for 1 day. Notably, application of a PASylated superactive mouse leptin antagonist (SMLA) led to the opposite effects. Thus, PASylated leptin not only provides a promising reagent to study its physiological role in vivo but also may offer a superior drug candidate for clinical therapy.

  20. Geometric-model-free tracking of extended targets using 3D lidar measurements

    Science.gov (United States)

    Steinemann, Philipp; Klappstein, Jens; Dickmann, Juergen; von Hundelshausen, Felix; Wünsche, Hans-Joachim

    2012-06-01

    Tracking of extended targets in high definition, 360-degree 3D-LIDAR (Light Detection and Ranging) measurements is a challenging task and a current research topic. It is a key component in robotic applications, and is relevant to path planning and collision avoidance. This paper proposes a new method without a geometric model to simultaneously track and accumulate 3D-LIDAR measurements of an object. The method itself is based on a particle filter and uses an object-related local 3D grid for each object. No geometric object hypothesis is needed. Accumulation allows coping with occlusions. The prediction step of the particle filter is governed by a motion model consisting of a deterministic and a probabilistic part. Since this paper is focused on tracking ground vehicles, a bicycle model is used for the deterministic part. The probabilistic part depends on the current state of each particle. A function for calculating the current probability density function for state transition is developed. It is derived in detail and based on a database consisting of vehicle dynamics measurements over several hundreds of kilometers. The adaptive probability density function narrows down the gating area for measurement data association. The second part of the proposed method addresses weighting the particles with a cost function. Different 3D-griddependent cost functions are presented and evaluated. Evaluations with real 3D-LIDAR measurements show the performance of the proposed method. The results are also compared to ground truth data.

  1. The fate of nontargeted endocardial leads during the extraction of one or more targeted leads in pediatrics and congenital heart disease.

    Science.gov (United States)

    McCanta, Anthony C; Tanel, Ronn E; Gralla, Jane; Runciman, David Martin; Collins, Kathryn K

    2014-01-01

    Extraction of targeted endocardial leads can lead to inadvertent damage or dislodgement of nontargeted leads, though the frequency of this has not been reported in pediatrics and congenital heart disease (CHD). This is a retrospective review of lead extraction procedures from 2002 to 2010 from two pediatric and CHD centers evaluating unplanned interventions on nontargeted leads during the extraction of one or more targeted leads. Nontargeted leads were present in the 22 lead extraction procedures performed on 20 patients with median age 15 years (interquartile range, 11.5-18.5 years): 11 (55%) with structurally normal hearts and nine (45%) with CHD. Twenty of 23 targeted leads (86%) were extracted with complete success. Of the 22 nontargeted leads, including 17 atrial leads and five ventricular leads, seven (32%) required further intervention including: five extracted due to damage, dislodgement, or change in device location; one abandoned due to damage; and one dislodged requiring a second procedure for repositioning. The remaining 15 nontargeted leads (68%) were unharmed. Nontargeted leads requiring further intervention had a shorter lead duration in situ (median 2 years, interquartile range 0.5-3.5 years) than unharmed nontargeted leads (median 6.6 years, interquartile range 4.1-9.1 years; P = 0.01). Age at extraction, CHD, implantable cardioverter defibrillator leads, atrial lead position, or primary extraction modality did not predict further intervention for nontargeted leads. Major complications occurred in one procedure (4.5%) with no deaths. In pediatrics and CHD, nontargeted leads are frequently damaged or dislodged during the extraction of targeted leads. The risk of lead damage or dislodgement has implications for procedural planning and counseling for patients and families of pediatric and CHD patients requiring lead extraction. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

  2. 40 CFR 745.226 - Certification of individuals and firms engaged in lead-based paint activities: target housing and...

    Science.gov (United States)

    2010-07-01

    ... engaged in lead-based paint activities: target housing and child-occupied facilities. 745.226 Section 745... LEAD-BASED PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.226 Certification of individuals and firms engaged in lead-based paint activities: target housing...

  3. Heating of heat-conducting targets by laser pulses with a high-intensity leading spike

    Science.gov (United States)

    Ageev, V. P.; Burdin, S. G.; Konov, V. I.; Uglov, S. A.; Chapliev, N. I.

    1983-04-01

    The results of an analysis of the solution of a one-dimensional heat conduction equation are used to study the specific features of the thermal effects of laser pulses with a leading spike on a target. Simple criteria are obtained for establishing the ability of a pulse to cause a given increase in the target surface temperature during the leading edge of a spike and also during the tail of the laser pulse. A study is made of the influence of the inhomogeneity of the distribution of surface heat sources on the realization of processes characterized by a threshold in respect of the temperature of the irradiated surface. The results obtained are compared with the experimental delay time in the process of initiation of an air breakdown plasma by interaction of CO2 laser pulses with a metal target.

  4. Fabrication of self-supporting targets of lead (206,208Pb) using evaporation technique

    Science.gov (United States)

    Goyal, Savi; Abhilash, S. R.; Kabiraj, D.; Kalkal, Sunil; Mandal, S.

    2015-03-01

    The self-supporting 206,208Pb enriched isotopic targets of thicknesses varying from 500 μg/cm2 to 800 μg/cm2 have been prepared in the high vacuum environment at the target laboratory of Inter University Accelerator Centre (IUAC), by using the resistive heating method. The limited amount of the target material, selection of the parting agent, highly oxidizing tendency of the Pb in the atmosphere and the separation of the lead film from the glass slides were the few major challenges faced in the fabrication of the targets. A limited amount of isotopic material (100 mg) was utilized for the preparation of more than 20 thick self-supporting targets of 206Pb and 208Pb isotopes. Several attempts were made to overcome the difficulty of finding a suitable parting agent to avoid direct contact of water with the target material are discussed, along with the methods adopted for the fabrication of the targets. Further Energy Dispersive X-ray (EDX) analysis was performed to check the elemental purity of the foils. These targets have been successfully used for several nuclear physics experiments using the neutron detector setup known as National Array of Neutron Detectors (NAND) at IUAC, New Delhi.

  5. Fabrication of self-supporting targets of lead ({sup 206,208}Pb) using evaporation technique

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Savi, E-mail: savi.november@gmail.com [Department of Physics & Astrophysics, University of Delhi, Delhi 110007 (India); Abhilash, S.R.; Kabiraj, D. [Inter University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India); Kalkal, Sunil; Mandal, S. [Department of Physics & Astrophysics, University of Delhi, Delhi 110007 (India)

    2015-03-21

    The self-supporting {sup 206,208}Pb enriched isotopic targets of thicknesses varying from 500 μg/cm{sup 2} to 800 μg/cm{sup 2} have been prepared in the high vacuum environment at the target laboratory of Inter University Accelerator Centre (IUAC), by using the resistive heating method. The limited amount of the target material, selection of the parting agent, highly oxidizing tendency of the Pb in the atmosphere and the separation of the lead film from the glass slides were the few major challenges faced in the fabrication of the targets. A limited amount of isotopic material (100 mg) was utilized for the preparation of more than 20 thick self-supporting targets of {sup 206}Pb and {sup 208}Pb isotopes. Several attempts were made to overcome the difficulty of finding a suitable parting agent to avoid direct contact of water with the target material are discussed, along with the methods adopted for the fabrication of the targets. Further Energy Dispersive X-ray (EDX) analysis was performed to check the elemental purity of the foils. These targets have been successfully used for several nuclear physics experiments using the neutron detector setup known as National Array of Neutron Detectors (NAND) at IUAC, New Delhi.

  6. Lead

    Science.gov (United States)

    ... is serious about making sure companies that break the law are held accountable In the past year, EPA ... the health effects of lead in drinking water The law mandates no-lead products for drinking water after ...

  7. 40 CFR 745.227 - Work practice standards for conducting lead-based paint activities: target housing and child...

    Science.gov (United States)

    2010-07-01

    ... lead-based paint activities: target housing and child-occupied facilities. 745.227 Section 745.227... PAINT POISONING PREVENTION IN CERTAIN RESIDENTIAL STRUCTURES Lead-Based Paint Activities § 745.227 Work practice standards for conducting lead-based paint activities: target housing and child-occupied facilities...

  8. Momentum measurement by the Multiple Coulomb Scattering method in the OPERA lead emulsion target

    CERN Document Server

    Agafonova, N.; Altinok, O.; Anokhina, A.; Aoki, S.; Ariga, A.; Ariga, T.; Autiero, D.; Badertscher, A.; Bagulya, A.; Ben Dhahbi, A.; Bertolin, A.; Besnier, M.; Bozza, C.; Brugiere, T.; Brugnera, R.; Brunet, F.; Brunetti, G.; Buontempo, S.; Cazes, A.; Chaussard, L.; Chernyavskiy, M.; Chiarella, V.; Chukanov, A.; D'Ambrosio, N.; Dal Corso, F.; De Lellis, G.; del Amo Sanchez, P.; Declais, Y.; De Serio, M.; Di Capua, F.; Di Crescenzo, A.; Di Ferdinando, D.; Di Marco, N.; Dmitrievski, S.; Dracos, M.; Duchesneau, D.; Dusini, S.; Dzhatdoev, T.; Ebert, J.; Egorov, O.; Enikeev, R.; Ereditato, A.; Esposito, L.S.; Favier, J.; Ferber, T.; Fini, R.A.; Frekers, D.; Fukuda, T.; Garfagnini, A.; Giacomelli, G.; Giorgini, M.; Gollnitz, C.; Goldberg, J.; Golubkov, D.; Goncharova, L.; Gornushkin, Y.; Grella, G.; Grianti, F.; Guler, A.M.; Gustavino, C.; Hagner, C.; Hamada, K.; Hara, T.; Hierholzer, M.; Hollnagel, A.; Hoshino, K.; Ieva, M.; Ishida, H.; Jakovcic, K.; Jollet, C.; Juget, F.; Kamiscioglu, M.; Kazuyama, K.; Kim, S.H.; Kimura, M.; Kitagawa, N.; Klicek, B.; Knuesel, J.; Kodama, K.; Komatsu, M.; Kose, U.; Kreslo, I.; Kubota, H.; Lazzaro, C.; Lenkeit, J.; Lippi, I.; Ljubicic, A.; Longhin, A.; Loverre, P.; Lutter, G.; Malgin, A.; Mandrioli, G.; Manai, K.; Marteau, J.; Matsuo, T.; Matveev, V.; Mauri, N.; Medinaceli, E.; Meisel, F.; Meregaglia, A.; Migliozzi, P.; Mikado, S.; Miyamoto, S.; Monacelli, P.; Morishima, K.; Moser, U.; Muciaccia, M.T.; Naganawa, N.; Naka, T.; Nakamura, M.; Nakano, T.; Naumov, D.; Nikitina, V.; Niwa, K.; Nonoyama, Y.; Ogawa, S.; Okateva, N.; Olshevskiy, A.; Paniccia, M.; Paoloni, A.; Park, B.D.; Park, I.G.; Pastore, A.; Patrizii, L.; Pennacchio, E.; Pessard, H.; Pretzl, K.; Pilipenko, V.; Pistillo, C.; Polukhina, N.; Pozzato, M.; Pupilli, F.; Rescigno, R.; Roganova, T.; Rokujo, H.; Romano, G.; Rosa, G.; Rostovtseva, I.; Rubbia, A.; Russo, A.; Ryasny, V.; Ryazhskaya, O.; Sato, O.; Sato, Y.; Schembri, A.; Schmidt-Parzefall, W.; Schroeder, H.; Scotto Lavina, L.; Sheshukov, A.; Shibuya, H.; Shoziyoev, G.; Simone, S.; Sioli, M.; Sirignano, C.; Sirri, G.; Song, J.S.; Spinetti, M.; Stanco, L.; Starkov, N.; Stipcevic, M.; Strauss, T.; Strolin, P.; Takahashi, S.; Tenti, M.; Terranova, F.; Tezuka, I.; Tioukov, V.; Tolun, P.; Trabelsi, A.; Tran, T.; Tufanli, S.; Vilain, P.; Vladimirov, M.; Votano, L.; Vuilleumier, J.L.; Wilquet, G.; Wonsak, B.; Yakushev, V.; Yoon, C.S.; Yoshioka, T.; Yoshida, J.; Zaitsev, Y.; Zemskova, S.; Zghiche, A.; Zimmermann, R.

    2012-01-01

    A new method of momentum measurement of charged particles through Multiple Coulomb Scattering (MCS) in the OPERA lead emulsion target is presented. It is based on precise measurements of track angular deviations performed thanks to the very high resolution of nuclear emulsions. The algorithm has been tested with Monte Carlo (MC) pions. The results are found to describe within the expected uncertainties the data obtained from test beams. We also report a comparison of muon momenta evaluated through MCS in the OPERA lead emulsion target with those determined by the electronic detectors for neutrino charged current interaction events. The two independent measurements agree within the experimental uncertainties, and the results validate the algorithm developed for the emulsion detector of OPERA.

  9. Quantitative resistance can lead to evolutionary changes in traits not targeted by the resistance QTLs

    Science.gov (United States)

    Van den Berg, Femke; Lannou, Christian; Gilligan, Christopher A; van de Bosch, Frank

    2014-01-01

    This paper addresses the general concern in plant pathology that the introduction of quantitative resistance in the landscape can lead to increased pathogenicity. Hereto, we study the hypothetical case of a quantitative trait loci (QTL) acting on pathogen spore production per unit lesion area. To regain its original fitness, the pathogen can break the QTL, restoring its spore production capacity leading to an increased spore production per lesion. Or alternatively, it can increase its lesion size, also leading to an increased spore production per lesion. A data analysis shows that spore production per lesion (affected by the resistance QTL) and lesion size (not targeted by the QTL) are positively correlated traits, suggesting that a change in magnitude of a trait not targeted by the QTL (lesion size) might indirectly affect the targeted trait (spore production per lesion). Secondly, we model the effect of pathogen adaptation towards increased lesion size and analyse its consequences for spore production per lesion. The model calculations show that when the pathogen is unable to overcome the resistance associated QTL, it may compensate for its reduced fitness by indirect selection for increased pathogenicity on both the resistant and susceptible cultivar, but whereby the QTLs remain effective. PMID:24665339

  10. Lead

    Science.gov (United States)

    ... Test Safety Alert: Learn about CDC Recommendations Second Informational Call (CDC-RFA-17-1701PPHF17), April 5, 2017, ... CLPPP CAP Healthy Homes Assessment Tools Lead Health Literacy Initiative Refugee Tool Kit Resources Healthy Homes and ...

  11. Docking Studies in Target Proteins Involved in Antibacterial Action Mechanisms: Extending the Knowledge on Standard Antibiotics to Antimicrobial Mushroom Compounds

    Directory of Open Access Journals (Sweden)

    Maria José Alves

    2014-01-01

    Full Text Available In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a, alanine racemase (Alr, d-alanyl-d-alanine synthetase (Ddl, isoleucyl-tRNA sinthetase (IARS, DNA gyrase subunit B, topoisomerase IV (TopoIV, dihydropteroate synthetase (DHPS and dihydrofolate reductase (DHFR using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets.

  12. Docking studies in target proteins involved in antibacterial action mechanisms: extending the knowledge on standard antibiotics to antimicrobial mushroom compounds.

    Science.gov (United States)

    Alves, Maria José; Froufe, Hugo J C; Costa, Ana F T; Santos, Anabela F; Oliveira, Liliana G; Osório, Sara R M; Abreu, Rui M V; Pintado, Manuela; Ferreira, Isabel C F R

    2014-01-29

    In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a), alanine racemase (Alr), d-alanyl-d-alanine synthetase (Ddl), isoleucyl-tRNA sinthetase (IARS), DNA gyrase subunit B, topoisomerase IV (TopoIV), dihydropteroate synthetase (DHPS) and dihydrofolate reductase (DHFR) using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins) the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets.

  13. Evaluation of some features for extended target extraction in polarimetric and non-polarimetric radar

    NARCIS (Netherlands)

    Van Genderen, P.; Kovalenko, V.

    2009-01-01

    Detection in most surveillance radars is based on the condition of point targets against a more or less homogeneous background. Currently, the resolution of many new types of radar is increasing, at least in the range dimension. Therefore many objects can no longer be considered as points. Also as a

  14. Extended model of raw data signals for space-time adaptive processing and moving target indicators

    NARCIS (Netherlands)

    Lidický, L.; Hoogeboom, P.

    2006-01-01

    This paper presents a multi-channel synthetic aperture radar (SAR) signal model. Its purpose is to study nonstationary raw SAR signals in moving target indication (MTI) systems. This is opposed to the traditional approach in which only stationary (harmonic) signals are considered. The principal

  15. Investigation of Lead Target Nuclei Used on Accelerator-Driven Systems for Tritium Production

    Science.gov (United States)

    Tel, E.; Aydin, A.

    2012-02-01

    High-current proton accelerators are being researched at Los Alamos National Laboratory and other laboratories for accelerator production of tritium, transmuting long-lived radioactive waste into shorter-lived products, converting excess plutonium, and producing energy. These technologies make use of spallation neutrons produced in ( p,xn) and ( n,xn) nuclear reactions on high-Z targets. Through ( p,xn) and ( n,xn) nuclear reactions, neutrons are produced and are moderated by heavy water. These moderated neutrons are subsequently captured on 3He to produce tritium via the ( n,p) reaction. Tritium self-sufficiency must be maintained for a commercial fusion power plant. Rubbia succeeded in a proposal of a full scale demonstration plant of the Energy Amplifier. This plant is to be known the accelerator-driven system (ADS). The ADS can be used for production of neutrons in spallation neutron source and they can act as an intense neutron source in accelerator-driven subcritical reactors, capable of incinerating nuclear waste and of producing energy. Thorium and Uranium are nuclear fuels and Lead, Bismuth, Tungsten are the target nuclei in these reactor systems. The spallation targets can be Pb, Bi, W, etc. isotopes and these target material can be liquid or solid. Naturally Lead includes the 204Pb (%1.42), 206Pb (%24.1), 207Pb (%22.1) and 208Pb (%52.3) isotopes. The design of ADS systems and also a fusion-fission hybrid reactor systems require the knowledge of a wide range of better data. In this study, by using Hartree-Fock method with an effective nucleon-nucleon Skyrme interactions rms nuclear charge radii, rms nuclear mass radii, rms nuclear proton, neutron radii and neutron skin thickness were calculated for the 204, 206, 208Pb isotopes . The calculated results have been compared with those of the compiled experimental and theoretical values of other studies.

  16. Extended methods using thick-targets for nuclear reaction data of radioactive isotopes

    Science.gov (United States)

    Ebata, Shuichiro; Aikawa, Masayuki; Imai, Shotaro

    2017-09-01

    The nuclear transmutation is a technology to dispose of radioactive wastes. However, we do not have enough basic data for its developments, such as thick-target yields (TTY) and the interaction cross sections for radioactive material. We suggest two methods to estimate the TTY using inverse kinematics and to obtain the excitation function of the interaction cross sections which is named the thick-target transmission (T3) method. We deduce the energy-dependent conversion relation between the TTYs of the original system and its inverse kinematics, which can be replaced to a constant coefficient in the high energy region. Furthermore we show the usefulness of the T3 method to investigate the excitation function of the 12C + 27Al reaction in the simulation.

  17. Next-to leading order analysis of target mass corrections to structure functions and asymmetries

    Energy Technology Data Exchange (ETDEWEB)

    L. T. Brady, A. Accardi, T. J. Hobbs, W. Melnitchouk

    2011-10-01

    We perform a comprehensive analysis of target mass corrections (TMCs) to spin-averaged structure functions and asymmetries at next-to-leading order. Several different prescriptions for TMCs are considered, including the operator product expansion, and various approximations to it, collinear factorization, and xi-scaling. We assess the impact of each of these on a number of observables, such as the neutron to proton F{sub 2} structure function ratio, and parity-violating electron scattering asymmetries for protons and deuterons which are sensitive to gamma-Z interference effects. The corrections from higher order radiative and nuclear effects on the parity-violating deuteron asymmetry are also quantified.

  18. Extended protection capabilities of an immature dendritic-cell targeting malaria sporozoite vaccine.

    Science.gov (United States)

    Luo, Kun; Zavala, Fidel; Gordy, James; Zhang, Hong; Markham, Richard B

    2017-04-25

    Mouse studies evaluating candidate malaria vaccines have typically examined protective efficacy over the relatively short time frames of several weeks after the final of multiple immunizations. The current study examines the protective ability in a mouse model system of a novel protein vaccine construct in which the adjuvant polyinosinic polycytidilic acid (poly(I:C)) is used in combination with a vaccine in which the immature dendritic cell targeting chemokine, macrophage inflammatory protein 3 alpha (MIP3α), is fused to the circumsporozoite protein (CSP) of Plasmodium falciparum (P. falciparum). Two vaccinations, three weeks apart, elicited extraordinarily high, MIP3α-dependent antibody responses. MIP3α was able to target the vaccine to the CCR6 receptor found predominantly on immature dendritic cells and significantly enhanced the cellular influx at the vaccination site. At three and 23 weeks after the final of two immunizations, mice were challenged by intravenous injection of 5×10 3 transgenic Plasmodium berghei sporozoites expressing P. falciparum CSP, a challenge dose approximately one order of magnitude greater than that which is encountered after mosquito bite in the clinical setting. A ninety-seven percent reduction in liver sporozoite load was observed at both time points, 23 weeks being the last time point tested. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Fragile X and autism: Intertwined at the molecular level leading to targeted treatments

    Directory of Open Access Journals (Sweden)

    Hagerman Randi

    2010-09-01

    Full Text Available Abstract Fragile X syndrome (FXS is caused by an expanded CGG repeat (> 200 repeats in the 5' untranslated portion of the fragile mental retardation 1 gene (FMR1, leading to deficiency or absence of the FMR1 protein (FMRP. FMRP is an RNA carrier protein that controls the translation of several other genes that regulate synaptic development and plasticity. Autism occurs in approximately 30% of FXS cases, and pervasive developmental disorder, not otherwise specified (PDD-NOS occurs in an additional 30% of cases. Premutation repeat expansions (55 to 200 CGG repeats may also give rise to autism spectrum disorders (ASD, including both autism and PDD-NOS, through a different molecular mechanism that involves a direct toxic effect of the expanded CGG repeat FMR1 mRNA. RNA toxicity can also lead to aging effects including tremor, ataxia and cognitive decline, termed fragile X-associated tremor ataxia syndrome (FXTAS, in premutation carriers in late life. In studies of mice bearing premutation expansions, there is evidence of early postnatal neuronal cell toxicity, presenting as reduced cell longevity, decreased dendritic arborization and altered synaptic morphology. There is also evidence of mitochondrial dysfunction in premutation carriers. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in autism without fragile X mutations. Research regarding dysregulation of neurotransmitter systems in FXS, including the metabotropic glutamate receptor (mGluR1/5 pathway and γ aminobutyric acid (GABAA pathways, have led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism.

  20. A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target.

    Science.gov (United States)

    Debnath, Anjan; Parsonage, Derek; Andrade, Rosa M; He, Chen; Cobo, Eduardo R; Hirata, Ken; Chen, Steven; García-Rivera, Guillermina; Orozco, Esther; Martínez, Máximo B; Gunatilleke, Shamila S; Barrios, Amy M; Arkin, Michelle R; Poole, Leslie B; McKerrow, James H; Reed, Sharon L

    2012-06-01

    Entamoeba histolytica, a protozoan intestinal parasite, is the causative agent of human amebiasis. Amebiasis is the fourth leading cause of death and the third leading cause of morbidity due to protozoan infections worldwide(1), resulting in ~70,000 deaths annually. E. histolytica has been listed by the National Institutes of Health as a category B priority biodefense pathogen in the United States. Treatment relies on metronidazole(2), which has adverse effects(3), and potential resistance of E. histolytica to the drug is an increasing concern(4,5). To facilitate drug screening for this anaerobic protozoan, we developed and validated an automated, high-throughput screen (HTS). This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as active against E. histolytica in culture. Auranofin was ten times more potent against E. histolytica than metronidazole. Transcriptional profiling and thioredoxin reductase assays suggested that auranofin targets the E. histolytica thioredoxin reductase, preventing the reduction of thioredoxin and enhancing sensitivity of trophozoites to reactive oxygen-mediated killing. In a mouse model of amebic colitis and a hamster model of amebic liver abscess, oral auranofin markedly decreased the number of parasites, the detrimental host inflammatory response and hepatic damage. This new use of auranofin represents a promising therapy for amebiasis, and the drug has been granted orphan-drug status from the FDA.

  1. Low cost power lead extended pre-compliance conducted EMI measurement setup and diagnostics with compact LISN

    CSIR Research Space (South Africa)

    Grobler, Inus

    2013-06-01

    Full Text Available An extended pre-compliance measurement setup has been created in the development laboratory to measure and diagnose conducted EMI up to tOO MHz without the use of a spectrum analyser. A dual compact Line Impedance Stabilisation Network (LISN) had...

  2. Extending supplementary feeding for children younger than 5 years with moderate acute malnutrition leads to lower relapse rates

    Science.gov (United States)

    Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. Rural Malawian children 6 to 59 months old with MAM, defin...

  3. Extending multi-tenant architectures: a database model for a multi-target support in SaaS applications

    Science.gov (United States)

    Rico, Antonio; Noguera, Manuel; Garrido, José Luis; Benghazi, Kawtar; Barjis, Joseph

    2016-05-01

    Multi-tenant architectures (MTAs) are considered a cornerstone in the success of Software as a Service as a new application distribution formula. Multi-tenancy allows multiple customers (i.e. tenants) to be consolidated into the same operational system. This way, tenants run and share the same application instance as well as costs, which are significantly reduced. Functional needs vary from one tenant to another; either companies from different sectors run different types of applications or, although deploying the same functionality, they do differ in the extent of their complexity. In any case, MTA leaves one major concern regarding the companies' data, their privacy and security, which requires special attention to the data layer. In this article, we propose an extended data model that enhances traditional MTAs in respect of this concern. This extension - called multi-target - allows MT applications to host, manage and serve multiple functionalities within the same multi-tenant (MT) environment. The practical deployment of this approach will allow SaaS vendors to target multiple markets or address different levels of functional complexity and yet commercialise just one single MT application. The applicability of the approach is demonstrated via a case study of a real multi-tenancy multi-target (MT2) implementation, called Globalgest.

  4. Insights into Integrated Lead Generation and Target Identification in Malaria and Tuberculosis Drug Discovery.

    Science.gov (United States)

    Okombo, John; Chibale, Kelly

    2017-07-18

    New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery. This Account recaps the existing challenges facing antimalarial and antituberculosis drug discovery, including limitations associated with experimental animal models as well as biological complexities intrinsic to the causative pathogens. We enlist various highlights from a body of work within our research group aimed at identifying and characterizing new chemical leads, and navigating these challenges to contribute toward the global drug discovery and development pipeline in malaria and tuberculosis. We describe a catalogue of in-house efforts toward deriving safe and efficacious preclinical drug development candidates via cell-based medicinal chemistry optimization of phenotypic whole-cell medium and high throughput screening hits sourced from various small molecule chemical libraries. We also provide an appraisal of target-based screening, as invoked in our laboratory for mechanistic evaluation of the hits generated, with particular focus on the enzymes within the de novo pyrimidine biosynthetic and hemoglobin degradation pathways, the latter constituting a heme detoxification process and an associated cysteine

  5. Extending flood forecasting lead time in a large watershed by coupling WRF QPF with a distributed hydrological model

    Science.gov (United States)

    Li, Ji; Chen, Yangbo; Wang, Huanyu; Qin, Jianming; Li, Jie; Chiao, Sen

    2017-03-01

    Long lead time flood forecasting is very important for large watershed flood mitigation as it provides more time for flood warning and emergency responses. The latest numerical weather forecast model could provide 1-15-day quantitative precipitation forecasting products in grid format, and by coupling this product with a distributed hydrological model could produce long lead time watershed flood forecasting products. This paper studied the feasibility of coupling the Liuxihe model with the Weather Research and Forecasting quantitative precipitation forecast (WRF QPF) for large watershed flood forecasting in southern China. The QPF of WRF products has three lead times, including 24, 48 and 72 h, with the grid resolution being 20 km  × 20 km. The Liuxihe model is set up with freely downloaded terrain property; the model parameters were previously optimized with rain gauge observed precipitation, and re-optimized with the WRF QPF. Results show that the WRF QPF has bias with the rain gauge precipitation, and a post-processing method is proposed to post-process the WRF QPF products, which improves the flood forecasting capability. With model parameter re-optimization, the model's performance improves also. This suggests that the model parameters be optimized with QPF, not the rain gauge precipitation. With the increasing of lead time, the accuracy of the WRF QPF decreases, as does the flood forecasting capability. Flood forecasting products produced by coupling the Liuxihe model with the WRF QPF provide a good reference for large watershed flood warning due to its long lead time and rational results.

  6. Targeting Extracellular Cyclophilin A Reduces Neuroinflammation and Extends Survival in a Mouse Model of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Pasetto, Laura; Pozzi, Silvia; Castelnovo, Mariachiara; Basso, Manuela; Estevez, Alvaro G; Fumagalli, Stefano; De Simoni, Maria Grazia; Castellaneta, Valeria; Bigini, Paolo; Restelli, Elena; Chiesa, Roberto; Trojsi, Francesca; Monsurrò, Maria Rosaria; Callea, Leonardo; Malešević, Miroslav; Fischer, Gunter; Freschi, Mattia; Tortarolo, Massimo; Bendotti, Caterina; Bonetto, Valentina

    2017-02-08

    Neuroinflammation is a major hallmark of amyotrophic lateral sclerosis (ALS), which is currently untreatable. Several anti-inflammatory compounds have been evaluated in patients and in animal models of ALS, but have been proven disappointing in part because effective targets have not yet been identified. Cyclophilin A, also known as peptidylprolyl cis-/trans-isomerase A (PPIA), as a foldase is beneficial intracellularly, but extracellularly has detrimental functions. We found that extracellular PPIA is a mediator of neuroinflammation in ALS. It is a major inducer of matrix metalloproteinase 9 and is selectively toxic for motor neurons. High levels of PPIA were found in the CSF of SOD1G93A mice and rats and sporadic ALS patients, suggesting that our findings may be relevant for familial and sporadic cases. A specific inhibitor of extracellular PPIA, MM218, given at symptom onset, rescued motor neurons and extended survival in the SOD1G93A mouse model of familial ALS by 11 d. The treatment resulted in the polarization of glia toward a prohealing phenotype associated with reduced NF-κB activation, proinflammatory markers, endoplasmic reticulum stress, and insoluble phosphorylated TDP-43. Our results indicates that extracellular PPIA is a promising druggable target for ALS and support further studies to develop a therapy to arrest or slow the progression of the disease in patients.SIGNIFICANCE STATEMENT We provide evidence that extracellular cyclophilin A, also known as peptidylprolyl cis-/trans-isomerase A (PPIA), is a mediator of the neuroinflammatory reaction in amyotrophic lateral sclerosis (ALS) and is toxic for motor neurons. Supporting this, a specific extracellular PPIA inhibitor reduced neuroinflammation, rescued motor neurons, and extended survival in the SOD1G93A mouse model of familial ALS. Our findings suggest selective pharmacological inhibition of extracellular PPIA as a novel therapeutic strategy, not only for SOD1-linked ALS, but possibly also for

  7. Heteroleptic Copper Photosensitizers: Why an Extended π-System Does Not Automatically Lead to Enhanced Hydrogen Production.

    Science.gov (United States)

    Heberle, Martin; Tschierlei, Stefanie; Rockstroh, Nils; Ringenberg, Mark; Frey, Wolfgang; Junge, Henrik; Beller, Matthias; Lochbrunner, Stefan; Karnahl, Michael

    2017-01-05

    A series of heteroleptic copper(I) photosensitizers of the type [(P^P)Cu(N^N)] + with an extended π-system in the backbone of the diimine ligand has been prepared. The structures of all complexes are completely characterized by NMR spectroscopy, mass spectrometry, and X-ray crystallography. These novel photosensitizers were assessed with respect to the photocatalytic reduction of protons in the presence of triethylamine and [Fe 3 (CO) 12 ]. Although the solid-state structures and computational results show no significant impact of the π-extension on the structural properties, decreased activities were observed. To explain this drop, a combination of electrochemical and photophysical measurements including time-resolved emission as well as transient absorption spectroscopy in the femto- to nanosecond time regime was used. Consequently, shortened excited state lifetimes caused by the rapid depopulation of the excited states located at the diimine ligand are identified as a major reason for the low photocatalytic performance. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Improvement of a puromycin-linker to extend the selection target varieties in cDNA display method.

    Science.gov (United States)

    Ueno, Shingo; Kimura, Shinnosuke; Ichiki, Takanori; Nemoto, Naoto

    2012-12-31

    cDNA display using a puromycin-linker to covalently bridge a protein and its coding cDNA is a stable and efficient in vitro protein selection method. The optimal design of the often-used puromycin-linker is vital for effective selection. In this report, an improved puromycin-linker containing deoxyinosine bases as cleavage sites, which are recognized by endonuclease V, was introduced to extend the variety of the selection targets to molecules such as RNA. The introduction of this linker enables efficient in vitro protein selection without contamination from RNase T1, which is used for the conventional linker containing ribonucleotide G bases. In addition, mRNA-protein fusion efficiency was found to not depend on the length of the flexible poly (ethylene glycol) (PEG) region of the linker. These findings will allow practical and easy-to-use in vitro protein selection by cDNA display. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Linker-extended native cyanovirin-N facilitates PEGylation and potently inhibits HIV-1 by targeting the glycan ligand.

    Directory of Open Access Journals (Sweden)

    Jia Chen

    Full Text Available Cyanovirin-N (CVN potently inhibits human immunodeficiency virus type 1 (HIV-1 infection, but both cytotoxicity and immunogenicity have hindered the translation of this protein into a viable therapeutic. A molecular docking analysis suggested that up to 12 residues were involved in the interaction of the reverse parallel CVN dimer with the oligosaccharide targets, among which Leu-1 was the most prominent hot spot residue. This finding provided a possible explanation for the lack of anti-HIV-1 activity observed with N-terminal PEGylated CVN. Therefore, linker-CVN (LCVN was designed as a CVN derivative with a flexible and hydrophilic linker (Gly4Ser3 at the N-terminus. The N-terminal α-amine of LCVN was PEGylated to create 10 K PEG-aldehyde (ALD-LCVN. LCVN and 10 K PEG-ALD-LCVN retained the specificity and affinity of CVN for high mannose N-glycans. Moreover, LCVN exhibited significant anti-HIV-1 activity with attenuated cytotoxicity in the HaCaT keratinocyte cell line and MT-4 T lymphocyte cell lines. 10 K PEG-ALD-LCVN also efficiently inactivated HIV-1 with remarkably decreased cytotoxicity and pronounced cell-to-cell fusion inhibitory activity in vitro. The linker-extended CVN and the mono-PEGylated derivative were determined to be promising candidates for the development of an anti-HIV-1 agent. This derivatization approach provided a model for the PEGylation of biologic candidates without introducing point mutations.

  10. Extending supplementary feeding for children younger than 5 years with moderate acute malnutrition leads to lower relapse rates.

    Science.gov (United States)

    Trehan, Indi; Banerjee, Somalee; Murray, Ellen; Ryan, Kelsey N; Thakwalakwa, Chrissie; Maleta, Kenneth M; Manary, Mark J

    2015-04-01

    Children with moderate acute malnutrition (MAM) have a high rate of relapse and death in the year following recovery. In this pilot study, we evaluate the long-term benefits of an extended course of nutritional therapy for children with MAM. Rural Malawian children 6 to 59 months old with MAM, defined as a weight-for-height z score (WHZ) between -2 and -3, were provided supplementary feeding for a fixed duration of 12 weeks. The children were then studied for 12 months to assess long-term nutritional status, and compared with children initially treated only until they first reached WHZ > -2. Compared with children treated until they reached WHZ > -2, children treated for 12 weeks were more likely to remain well nourished (71% vs 63%, P = 0.0015) and maintain more normal anthropometric indices during 12 months of follow-up; there was also a trend towards lower rates of severe acute malnutrition (7% vs 10%, P = 0.067) and death (2% vs 4%, P = 0.082). Regression modeling showed that mid-upper arm circumference and WHZ at the end of supplementary feeding were the most important factors in predicting which children remained well nourished (P children with MAM may not be as important as their anthropometry in terms of remaining well nourished after initial recovery. The presently accepted recovery criteria of WHZ of -2 may be insufficient for ensuring long-term nutritional health; consideration should be given to setting higher recovery criteria.

  11. Non-virally engineered human adipose mesenchymal stem cells produce BMP4, target brain tumors, and extend survival.

    Science.gov (United States)

    Mangraviti, Antonella; Tzeng, Stephany Y; Gullotti, David; Kozielski, Kristen L; Kim, Jennifer E; Seng, Michael; Abbadi, Sara; Schiapparelli, Paula; Sarabia-Estrada, Rachel; Vescovi, Angelo; Brem, Henry; Olivi, Alessandro; Tyler, Betty; Green, Jordan J; Quinones-Hinojosa, Alfredo

    2016-09-01

    There is a need for enabling non-viral nanobiotechnology to allow safe and effective gene therapy and cell therapy, which can be utilized to treat devastating diseases such as brain cancer. Human adipose-derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and represent a promising delivery vehicle for targeted brain tumor therapy. In this study, we demonstrate that non-viral, biodegradable polymeric nanoparticles (NPs) can be used to engineer hAMSCs with higher efficacy (75% of cells) than leading commercially available reagents and high cell viability. To accomplish this, we engineered a poly(beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with significantly higher efficacy than Lipofectamine™ 2000. We then assessed the ability of NP-engineered hAMSCs to deliver bone morphogenetic protein 4 (BMP4), which has been shown to have a novel therapeutic effect by targeting human brain tumor initiating cells (BTIC), a source of cancer recurrence, in a human primary malignant glioma model. We demonstrated that hAMSCs genetically engineered with polymeric nanoparticles containing BMP4 plasmid DNA (BMP4/NP-hAMSCs) secrete BMP4 growth factor while maintaining their multipotency and preserving their migration and invasion capacities. We also showed that this approach can overcome a central challenge for brain therapeutics, overcoming the blood brain barrier, by demonstrating that NP-engineered hAMSCs can migrate to the brain and penetrate the brain tumor after both intranasal and systemic intravenous administration. Critically, athymic rats bearing human primary BTIC-derived tumors and treated intranasally with BMP4/NP-hAMSCs showed significantly improved survival compared to those treated with control GFP/NP-hAMCSs. This study demonstrates that synthetic polymeric nanoparticles are a safe and effective approach for stem cell-based cancer-targeting therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. A role for fragment-based drug design in developing novel lead compounds for central nervous system targets

    Directory of Open Access Journals (Sweden)

    Michael J. Wasko

    2015-09-01

    Full Text Available Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment-based drug design, an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for growing the lead candidate. Current efforts in virtual fragment-based drug design within central nervous system (CNS targets are reviewed, as is a recent rule-based optimization strategy in which new molecules are generated within a 3D receptor binding pocket using the fragment as a scaffold. This process places special emphasis on creating synthesizable molecules but also exposes computational questions worth addressing. Fragment-based methods provide a viable, relatively low-cost alternative for therapeutic lead discovery and optimization that can be applied to CNS targets to augment current design strategies.

  13. 75 FR 51808 - Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied...

    Science.gov (United States)

    2010-08-23

    ...-9] Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied... for renovation, repair and painting programs in accordance with section 402(c)(3) of TSCA, 15 U.S.C... CFR 745.324(d)(2), to administer and enforce requirements for a renovation, repair and painting...

  14. 75 FR 13127 - Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied...

    Science.gov (United States)

    2010-03-18

    ... AGENCY Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied... for a renovation, repair and painting program in accordance with section 402(c)(3) of TSCA, 15 U.S.C... administer and enforce requirements for a renovation, repair and painting program in accordance with section...

  15. 76 FR 12106 - Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied...

    Science.gov (United States)

    2011-03-04

    ... AGENCY Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied..., repair and painting program in accordance with section 402(c)(3) of TSCA. This notice also announces that... a renovation, repair and painting program in accordance with section 402(c)(3) of TSCA. This notice...

  16. ARTICLES: Heating of heat-conducting targets by laser pulses with a high-intensity leading spike

    Science.gov (United States)

    Ageev, Vladimir P.; Burdin, S. G.; Konov, Vitalii I.; Uglov, S. A.; Chapliev, N. I.

    1983-04-01

    The results of an analysis of the solution of a one-dimensional heat conduction equation are used to study the specific features of the thermal effects of laser pulses with a leading spike on a target. Simple criteria are obtained for establishing the ability of a pulse to cause a given increase in the target surface temperature during the leading edge of a spike and also during the tail of the laser pulse. A study is made of the influence of the inhomogeneity of the distribution of surface heat sources on the realization of processes characterized by a threshold in respect of the temperature of the irradiated surface. The results obtained are compared with the experimental delay time in the process of initiation of an air breakdown plasma by interaction of CO2 laser pulses with a metal target.

  17. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    Directory of Open Access Journals (Sweden)

    David Toomey

    Full Text Available BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i homologous to previously crystallized proteins or (ii targets of known drugs, but are (iii not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under 'change-of-application' patents.

  18. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    LENUS (Irish Health Repository)

    Toomey, David

    2009-01-01

    BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins\\/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and\\/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY\\/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS\\/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under \\'change-of-application\\' patents.

  19. Lead discovery and chemical biology approaches targeting the ubiquitin proteasome system.

    Science.gov (United States)

    Akinjiyan, Favour A; Carbonneau, Seth; Ross, Nathan T

    2017-10-15

    Protein degradation is critical for proteostasis, and the addition of polyubiquitin chains to a substrate is necessary for its recognition by the 26S proteasome. Therapeutic intervention in the ubiquitin proteasome system has implications ranging from cancer to neurodegeneration. Novel screening methods and chemical biology tools for targeting E1-activating, E2-conjugating and deubiquitinating enzymes will be discussed in this review. Approaches for targeting E3 ligase-substrate interactions as well as the proteasome will also be covered, with a focus on recently described approaches. Copyright © 2017. Published by Elsevier Ltd.

  20. Measurement of gas and volatile elements production rates in molten lead bismuth target

    CERN Document Server

    Andersson, M

    2004-01-01

    Production rates of gas and volatile elements produced following spallation raction of 1.4 GeV protons on a liquid LBE target have been measured. The experiment was performed at the ISOLDE facility at CERN. These data are of great interest for the developments of targets for accelerator driven systems such as MEGAPIE. Calculations were performed using the Monte Carlo code FLUKA coupled with an evolution code such as ORIHET3. Preliminary results show good comparison with MC data for Hg and for noble gases. For other elements such as I results indicate that only a fraction of the produced isotopes are released.

  1. Dual-acting of Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B

    2017-01-01

    Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as selective multitarget chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mtdrugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. How genetic testing can lead to targeted management of XIAP deficiency-related inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; LaCasse, Eric Charles

    2017-01-01

    X-linked lymphoproliferative disease type 2 (XLP-2, OMIM 300635) is a primary immunodeficiency caused by the loss of X chromosome-linked inhibitor of apoptosis (XIAP), the X-linked inhibitor of apoptosis gene at Xq25. XLP-2 individuals are susceptible to several specific and potentially fatal inf......, and expedite specific targeted therapy.Genet Med advance online publication 14 July 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.82....

  3. Peripheral Attentional Targets under Covert Attention Lead to Paradoxically Enhanced Alpha Desynchronization in Neurofibromatosis Type 1.

    Directory of Open Access Journals (Sweden)

    Gilberto Silva

    Full Text Available The limited capacity of the human brain to process the full extent of visual information reaching the visual cortex requires the recruitment of mechanisms of information selection through attention. Neurofibromatosis type-1 (NF1 is a neurodevelopmental disease often exhibiting attentional deficits and learning disabilities, and is considered to model similar impairments common in other neurodevelopmental disorders such as autism. In a previous study, we found that patients with NF1 are more prone to miss targets under overt attention conditions. This finding was interpreted as a result of increased occipito-parietal alpha oscillations. In the present study, we used electroencephalography (EEG to study alpha power modulations and the performance of patients with NF1 in a covert attention task. Covert attention was required in order to perceive changes (target offset of a peripherally presented stimulus. Interestingly, alpha oscillations were found to undergo greater desynchronization under this task in the NF1 group compared with control subjects. A similar pattern of desynchronization was found for beta frequencies while no changes in gamma oscillations could be identified. These results are consistent with the notion that different attentional states and task demands generate different patterns of abnormal modulation of alpha oscillatory processes in NF1. Under covert attention conditions and while target offset was reported with relatively high accuracy (over 90% correct responses, excessive desynchronization was found. These findings suggest an abnormal modulation of oscillatory activity and attentional processes in NF1. Given the known role of alpha in modulating attention, we suggest that alpha patterns can show both abnormal increases and decreases that are task and performance dependent, in a way that enhanced alpha desynchronization may reflect a compensatory mechanism to keep performance at normal levels. These results suggest that

  4. Peripheral Attentional Targets under Covert Attention Lead to Paradoxically Enhanced Alpha Desynchronization in Neurofibromatosis Type 1.

    Science.gov (United States)

    Silva, Gilberto; Ribeiro, Maria J; Costa, Gabriel N; Violante, Inês; Ramos, Fabiana; Saraiva, Jorge; Castelo-Branco, Miguel

    2016-01-01

    The limited capacity of the human brain to process the full extent of visual information reaching the visual cortex requires the recruitment of mechanisms of information selection through attention. Neurofibromatosis type-1 (NF1) is a neurodevelopmental disease often exhibiting attentional deficits and learning disabilities, and is considered to model similar impairments common in other neurodevelopmental disorders such as autism. In a previous study, we found that patients with NF1 are more prone to miss targets under overt attention conditions. This finding was interpreted as a result of increased occipito-parietal alpha oscillations. In the present study, we used electroencephalography (EEG) to study alpha power modulations and the performance of patients with NF1 in a covert attention task. Covert attention was required in order to perceive changes (target offset) of a peripherally presented stimulus. Interestingly, alpha oscillations were found to undergo greater desynchronization under this task in the NF1 group compared with control subjects. A similar pattern of desynchronization was found for beta frequencies while no changes in gamma oscillations could be identified. These results are consistent with the notion that different attentional states and task demands generate different patterns of abnormal modulation of alpha oscillatory processes in NF1. Under covert attention conditions and while target offset was reported with relatively high accuracy (over 90% correct responses), excessive desynchronization was found. These findings suggest an abnormal modulation of oscillatory activity and attentional processes in NF1. Given the known role of alpha in modulating attention, we suggest that alpha patterns can show both abnormal increases and decreases that are task and performance dependent, in a way that enhanced alpha desynchronization may reflect a compensatory mechanism to keep performance at normal levels. These results suggest that dysregulation of

  5. Halo excitations in fragmentation of sup 6 He at 240 MeV/u on carbon and lead targets

    CERN Document Server

    Aleksandrov, D V; Axelsson, L; Baumann, T; García-Borge, M J; Chulkov, L V; Cub, J; Dostal, W; Eberlein, B; Elze, T W; Emling, H; Geissel, H; Goldberg, V Z; Grünschloss, A; Hellström, M; Holeczek, J; Holzmann, R; Jonson, B; Kratz, J V; Kraus, G; Kulessa, R; Leifels, Y; Leistenschneider, A; Leth, T; Markenroth, K G; Meister, M; Mukha, I; Münzenberg, G; Nickel, F; Nilsson, T; Nyman, G H; Petersen, B; Pfützner, M; Pribora, V N; Richter, A; Riisager, K; Scheidenberger, C; Schrieder, G; Schwab, W; Simon, H; Smedberg, M H; Stroth, J; Surowiec, A; Tengblad, O; Zhukov, M V

    2000-01-01

    Dissociation of a 240 MeV/u beam of sup 6 He, incident on carbon and lead targets, has been studied in kinematically complete experiments to investigate low-lying excitation modes in the halo nucleus sup 6 He. It is shown that alignment effects characterize the inelastic scattering and allow an unambiguous assignment of the spin of a narrow resonance observed in the excitation energy spectrum. The differential cross sections for the sup 6 He inelastic scattering on carbon and lead targets were deduced from the measured momenta of the two neutrons and the alpha-particle. An analysis of these distributions shows that quadrupole and, possibly, monopole excitations characterize the hadronic interaction, while the dipole mode is dominating in Coulomb dissociation. Neither theoretically predicted new resonance states in sup 6 He nor nuclear excitation of a dipole mode were found. Direct evidence has been obtained for strong suppression of Coulomb post-acceleration in direct Coulomb breakup in a lead target.

  6. Interactions of 160 GeV/Nucleon $^{207}$Pb Nuclei in Emulsion Chambers with Copper and Lead Targets

    CERN Multimedia

    2002-01-01

    % EMU13 \\\\ \\\\ Nuclear emulsions will be used as targets and trackers to investigate the interactions of $^{207}$Pb nuclei in emulsion, copper and lead targets; specifically (i) the pseudorapidity distributions of charged particles including analysis of particle fluctuations in pseudorapidity and azimuthal angle distributions, (ii) the transverse momentum distribution of $\\alpha$ fragments from the projectile nucleus. \\\\ \\\\Several emulsion chambers with different geometry and targets will be exposed to the $^{207}$Pb beam. Each chamber will be irradiated with the beam of low density $^{207}$Pb ions (several hundred per cm$^2$). Interactions with small impact parameter, characterized by high multiplicity and disruption of the projectile nucleus will be found with high efficiency. Measurements in the emulsion will include the number and emission angles of charged particles produced and the emission angles of $\\alpha$ fragments from the projectile nucleus.

  7. Measurement of Gas and Volatile Elements Production Cross Section in a Molten Lead-Bismuth Target

    CERN Multimedia

    2002-01-01

    MEGAPIE is a project for a 1 MW liquid PbBi spallation source, to be built at the SINQ facility at the Paul Scherrer Institut, which will be an important step in the roadmap towards the demonstration of the ADS concept and high power molten metal targets in general. In the design and construction of such a challenging project it is extremely important to evaluate the amount and type of gas and volatile elements which will be produced, for a reliable and safe operation of the experiment. Both stable (H, $^{4}$He and other noble gases) and radioactive isotopes are of interest. Currently, different design options are under consideration to deal with the gas produced during operation. \\\\ For a correct estimation of the production cross sections, a measurement with a liquid PbBi target and a proton beam of energy close to the one of MEGAPIE (575 MeV) is necessary. We would like to use the ISOLDE facility, which offers the unique opportunity via its mass spectrometric analysis of the elements present in the gas pha...

  8. Targeting insulin-like growth factor 1 leads to amelioration of inflammatory demyelinating disease.

    Directory of Open Access Journals (Sweden)

    Matthew F Cusick

    Full Text Available In patients with multiple sclerosis (MS and in mice with experimental autoimmune encephalomyelitis (EAE, proliferating autoreactive T cells play an important role in the pathogenesis of the disease. Due to the importance of these myelin-specific T cells, these cells have been therapeutic targets in a variety of treatments. Previously we found that Lenaldekar (LDK, a novel small molecule, could inhibit exacerbations in a preclinical model of MS when given at the start of an EAE exacerbation. In those studies, we found that LDK could inhibit human T cell recall responses and murine myelin responses in vitro. In these new studies, we found that LDK could inhibit myelin specific T cell responses through the insulin-like growth factor-1 receptor (IGF-1R pathway. Alteration of this pathway led to marked reduction in T cell proliferation and expansion. Blocking this pathway could account for the observed decreases in clinical signs and inflammatory demyelinating disease, which was accompanied by axonal preservation. Our data indicate that IGF-1R could be a potential target for new therapies for the treatment of autoimmune diseases where autoreactive T cell expansion is a requisite for disease.

  9. Targeting insulin-like growth factor 1 leads to amelioration of inflammatory demyelinating disease.

    Science.gov (United States)

    Cusick, Matthew F; Libbey, Jane E; Trede, Nikolaus S; Fujinami, Robert S

    2014-01-01

    In patients with multiple sclerosis (MS) and in mice with experimental autoimmune encephalomyelitis (EAE), proliferating autoreactive T cells play an important role in the pathogenesis of the disease. Due to the importance of these myelin-specific T cells, these cells have been therapeutic targets in a variety of treatments. Previously we found that Lenaldekar (LDK), a novel small molecule, could inhibit exacerbations in a preclinical model of MS when given at the start of an EAE exacerbation. In those studies, we found that LDK could inhibit human T cell recall responses and murine myelin responses in vitro. In these new studies, we found that LDK could inhibit myelin specific T cell responses through the insulin-like growth factor-1 receptor (IGF-1R) pathway. Alteration of this pathway led to marked reduction in T cell proliferation and expansion. Blocking this pathway could account for the observed decreases in clinical signs and inflammatory demyelinating disease, which was accompanied by axonal preservation. Our data indicate that IGF-1R could be a potential target for new therapies for the treatment of autoimmune diseases where autoreactive T cell expansion is a requisite for disease.

  10. BBB penetration-targeting physicochemical lead selection: Ecdysteroids as chemo-sensitizers against CNS tumors.

    Science.gov (United States)

    Müller, Judit; Martins, Ana; Csábi, József; Fenyvesi, Ferenc; Könczöl, Árpád; Hunyadi, Attila; Balogh, György T

    2017-01-01

    The anticancer potential of ecdysteroids, especially their chemo-sensitizing activity has recently gained a substantial scientific interest. A comprehensive physicochemical profiling was performed for a set of natural or semi-synthetic ecdysteroids (N=37) to identify a lead compound against central nervous system (CNS) tumors. Calculated properties, such as lipophilicity (clogP), topological polar surface area (TPSA), brain-to-plasma ratio (clogBB) along with the measured blood-brain barrier specific in vitro permeability (logPe) were evaluated in parallel. Compounds with the highest CNS-availability predicted (clogBB>0.0 and logPe>-6.0) showed moderate to high lipophilicity (clogP=3.89-5.25), relatively low TPSA (94.45Å2), and shared a common apolar 2,3- and 20,22-diacetonide motif (25, 30-33). These ecdysteroids were selected for testing their capacity to sensitize SH-SY5Y neuroblastoma cells to vincristine. All of the five tested compounds exerted a remarkably strong, dose dependent chemo-sensitizing activity: at 2.5-10.0μM ecdysteroids increased the cytotoxic activity of vincristine one to three orders of magnitude in (e.g., from IC50=39.5±2.9nM to as low as 0.056±0.03nM). Moreover, analysis of the combination index (CI) revealed outstanding synergism between ecdysteroids and vincristine (CI50=0.072-0.444). Thus, based on drug-likeness, physchem character and in vitro CNS activity, compound 25 was proposed as a lead for further in vivo studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Neonicotinoids target distinct nicotinic acetylcholine receptors and neurons, leading to differential risks to bumblebees

    Science.gov (United States)

    Moffat, Christopher; Buckland, Stephen T.; Samson, Andrew J.; McArthur, Robin; Chamosa Pino, Victor; Bollan, Karen A.; Huang, Jeffrey T.-J.; Connolly, Christopher N.

    2016-04-01

    There is growing concern over the risk to bee populations from neonicotinoid insecticides and the long-term consequences of reduced numbers of insect pollinators to essential ecosystem services and food security. Our knowledge of the risk of neonicotinoids to bees is based on studies of imidacloprid and thiamethoxam and these findings are extrapolated to clothianidin based on its higher potency at nicotinic acetylcholine receptors. This study addresses the specificity and consequences of all three neonicotinoids to determine their relative risk to bumblebees at field-relevant levels (2.5 ppb). We find compound-specific effects at all levels (individual cells, bees and whole colonies in semi-field conditions). Imidacloprid and clothianidin display distinct, overlapping, abilities to stimulate Kenyon cells, indicating the potential to differentially influence bumblebee behavior. Bee immobility was induced only by imidacloprid, and an increased vulnerability to clothianidin toxicity only occurred following chronic exposure to clothianidin or thiamethoxam. At the whole colony level, only thiamethoxam altered the sex ratio (more males present) and only clothianidin increased queen production. Finally, both imidacloprid and thiamethoxam caused deficits in colony strength, while no detrimental effects of clothianidin were observed. Given these findings, neonicotinoid risk needs to be considered independently for each compound and target species.

  12. ISSUES IN ACHIEVING TARGETED FUNDING FOR LEADING SCIENTISTS AND SCIENTIFIC COMMUNITIES USING INDEXES OF PUBLICATION ACTIVITY

    Directory of Open Access Journals (Sweden)

    N. G. Kurakova

    2015-01-01

    Full Text Available In order to increase the competitiveness of the Russian scientific-technological complex in the global environment, it is planned to increase competition through State funding, spent on research and development. This will allow the focus of investment resources on the most perspective ideas and projects of the most efficient scientists, communities and organisations. The article suggests that we will witness the widening of competitive forms of funding against the simultaneous and gradual cuts in the share of financing through State contracts.One of the key criteria for evaluating the competency of team leaders and research applicants for State funding are measuring those who have «achieved high scientific results in concrete field of science», as a scientometric indicator, characterising their publication activity and citation rating.The article provides evidence showing that evaluation of individual scientists and whole scientific communities based on their publication activity indicators and impact is limited and challenges the ability for targeted funding and transparency in the selection process for executive projects.

  13. K-targeted metabolomic analysis extends chemical subtraction to DESIGNER extracts: selective depletion of extracts of hops (Humulus lupulus).

    Science.gov (United States)

    Ramos Alvarenga, René F; Friesen, J Brent; Nikolić, Dejan; Simmler, Charlotte; Napolitano, José G; van Breemen, Richard; Lankin, David C; McAlpine, James B; Pauli, Guido F; Chen, Shao-Nong

    2014-12-26

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid-liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DESIGNER extract = total extract ± target compound(s). Expanding the scope of the recently reported depletion of extracts by immunoaffinity or solid phase liquid chromatography, the present approach allows a more flexible, single- or multi-targeted removal of constituents from complex extracts such as botanicals. Chemical subtraction enables both chemical and biological characterization, including detection of synergism/antagonism by both the subtracted targets and the remaining metabolite mixture, as well as definition of the residual complexity of all fractions. The feasibility of the DESIGNER concept is shown by K-targeted subtraction of four bioactive prenylated phenols, isoxanthohumol (1), 8-prenylnaringenin (2), 6-prenylnaringenin (3), and xanthohumol (4), from a standardized hops (Humulus lupulus L.) extract using specific solvent systems. Conversely, adding K-targeted isolates allows enrichment of the original extract and hence provides an augmented DESIGNER material. Multiple countercurrent separation steps were used to purify each of the four compounds, and four DESIGNER extracts with varying depletions were prepared. The DESIGNER approach innovates the characterization of chemically complex extracts through integration of enabling technologies such as countercurrent separation, K-by-bioactivity, the residual complexity concepts, as well as quantitative analysis by (1)H NMR, LC-MS, and HiFSA-based NMR fingerprinting.

  14. 10-Hydroxy-2-decenoic Acid, the Major Lipid Component of Royal Jelly, Extends the Lifespan of Caenorhabditis elegans through Dietary Restriction and Target of Rapamycin Signaling

    Directory of Open Access Journals (Sweden)

    Yoko Honda

    2015-01-01

    Full Text Available Royal jelly (RJ produced by honeybees has been reported to possess diverse health-beneficial properties and has been implicated to have a function in longevity across diverse species as well as honeybees. 10-Hydroxy-2-decenoic acid (10-HDA, the major lipid component of RJ produced by honeybees, was previously shown to increase the lifespan of Caenorhabditis elegans. The objective of this study is to elucidate signaling pathways that are involved in the lifespan extension by 10-HDA. 10-HDA further extended the lifespan of the daf-2 mutants, which exhibit long lifespan through reducing insulin-like signaling (ILS, indicating that 10-HDA extended lifespan independently of ILS. On the other hand, 10-HDA did not extend the lifespan of the eat-2 mutants, which show long lifespan through dietary restriction caused by a food-intake defect. This finding indicates that 10-HDA extends lifespan through dietary restriction signaling. We further found that 10-HDA did not extend the lifespan of the long-lived mutants in daf-15, which encodes Raptor, a target of rapamycin (TOR components, indicating that 10-HDA shared some longevity control mechanisms with TOR signaling. Additionally, 10-HDA was found to confer tolerance against thermal and oxidative stress. 10-HDA increases longevity not through ILS but through dietary restriction and TOR signaling in C. elegans.

  15. The Effect of Beam Intensity on Temperature Distribution in ADS Windowless Lead-Bismuth Eutectic Spallation Target

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2014-01-01

    Full Text Available The spallation target is the component coupling the accelerator and the reactor and is regarded as the “heart” of the accelerator driven system (ADS. Heavy liquid metal lead-bismuth eutectic (LBE is served as core coolant and spallation material to carry away heat deposition of spallation reaction and produce high flux neutron. So it is very important to study the heat transfer process in the target. In this paper, the steady-state flow pattern has been numerically obtained and taken as the input for the nuclear physics calculation, and then the distribution of the extreme large power density of the heat load is imported back to the computational fluid dynamics as the source term in the energy equation. Through the coupling, the transient and steady-state temperature distribution in the windowless spallation target is obtained and analyzed based on the flow process and heat transfer. Comparison of the temperature distribution with the different beam intensity shows that its shape is the same as broken wing of the butterfly. Nevertheless, the maximum temperature as well as the temperature gradient is different. The results play an important role and can be applied to the further design and optimization of the ADS windowless spallation target.

  16. Identification and Functional Analysis of MicroRNAs and Their Targets in Platanus acerifolia under Lead (Pb Stress

    Directory of Open Access Journals (Sweden)

    Yuanlong Wang

    2015-03-01

    Full Text Available MicroRNAs (miRNAs play important regulatory roles in development and stress responses in plants. Lead (Pb is a non-essential element that is highly toxic to living organisms. Platanus acerifolia is grown as a street tree in cities throughout temperate regions for its importance in improving the urban ecological environment. MiRNAs that respond to abiotic stresses have been identified in plants; however, until now, the influence of Pb stress on P. acerifolia miRNAs has not been reported. To identify miRNAs and predict their target genes under Pb stress, two small RNA and two degradome libraries were constructed from Pb-treated and Pb-free leaves of P. acerifolia seedlings. After sequencing, 55 known miRNAs and 129 novel miRNAs were obtained, and 104 target genes for the miRNAs were identified by degradome sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to predict the functions of the targets. The expressions of eight differentially expressed miRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR. This is the first report about P. acerifolia miRNAs and their target genes under Pb stress. This study has provided data for further research into molecular mechanisms involved in resistance of P. acerifolia to Pb stress.

  17. Spallation Neutron Spectrum on a Massive Lead/Paraffin Target Irradiated with 1 GeV Protons

    CERN Document Server

    Adam, J; Barashenkov, V S; Brandt, R; Golovatiouk, V M; Kalinnikov, V G; Katovsky, K; Krivopustov, M I; Kumar, V; Kumawat, H; Odoj, R; Pronskikh, V S; Solnyshkin, A A; Stegailov, V I; Tsoupko-Sitnikov, V M; Westmeier, W

    2004-01-01

    The spectra of gamma-ray emitted by decaying residual nuclei, produced by spallation neutrons with (n, xn), (n,xnyp), (n,p), (n,gamma) reactions in activation threshold detectors - namely, ^{209}Bi, ^{197}Au, ^{59}Co, ^{115}In, ^{232}Th, were measured in the Laboratory of Nuclear Problems (LNP), JINR, Dubna, Russia. Spallation neutrons were generated by bombarding a 20 cm long cylindrical lead target, 8 cm in diameter, surrounded by a 6 cm thick layer of paraffin moderator, with a 1 GeV proton beam from the Nuclotron accelerator. Reaction rates and spallation neutron spectrum were measured and compared with CASCADE code calculations.

  18. Lab-on-a-plate: extending the functionality of MALDI-MS and LDI-MS targets.

    Science.gov (United States)

    Urban, Pawel L; Amantonico, Andrea; Zenobi, Renato

    2011-01-01

    We review the literature that describes how (matrix-assisted) laser desorption/ionization (MA)LDI target plates can be used not only as sample supports, but beyond that: as functional parts of analytical protocols that incorporate detection by MALDI-MS or matrix-free LDI-MS. Numerous steps of analytical procedures can be performed directly on the (MA)LDI target plates prior to the ionization of analytes in the ion source of a mass spectrometer. These include homogenization, preconcentration, amplification, purification, extraction, digestion, derivatization, synthesis, separation, detection with complementary techniques, data storage, or other steps. Therefore, we consider it helpful to define the "lab-on-a-plate" as a format for carrying out extensive sample treatment as well as bioassays directly on (MA)LDI target plates. This review introduces the lab-on-plate approach and illustrates it with the aid of relevant examples from the scientific and patent literature. Copyright © 2011 Wiley Periodicals, Inc.

  19. Target acquisition modeling over the exact optical path: extending the EOSTAR TDA with the TOD sensor performance model

    Science.gov (United States)

    Dijk, J.; Bijl, P.; Oppeneer, M.; ten Hove, R. J. M.; van Iersel, M.

    2017-10-01

    The Electro-Optical Signal Transmission and Ranging (EOSTAR) model is an image-based Tactical Decision Aid (TDA) for thermal imaging systems (MWIR/LWIR) developed for a sea environment with an extensive atmosphere model. The Triangle Orientation Discrimination (TOD) Target Acquisition model calculates the sensor and signal processing effects on a set of input triangle test pattern images, judges their orientation using humans or a Human Visual System (HVS) model and derives the system image quality and operational field performance from the correctness of the responses. Combination of the TOD model and EOSTAR, basically provides the possibility to model Target Acquisition (TA) performance over the exact path from scene to observer. In this method ship representative TOD test patterns are placed at the position of the real target, subsequently the combined effects of the environment (atmosphere, background, etc.), sensor and signal processing on the image are calculated using EOSTAR and finally the results are judged by humans. The thresholds are converted into Detection-Recognition-Identification (DRI) ranges of the real target. In experiments is shown that combination of the TOD model and the EOSTAR model is indeed possible. The resulting images look natural and provide insight in the possibilities of combining the two models. The TOD observation task can be done well by humans, and the measured TOD is consistent with analytical TOD predictions for the same camera that was modeled in the ECOMOS project.

  20. Target acquisition modeling over the exact optical path: Extending the EOSTAR TDA with the TOD sensor performance model

    NARCIS (Netherlands)

    Dijk, J.; Bijl, P.; Oppeneer, M.; Hove, R.J.M. ten; Iersel, M. van

    2017-01-01

    The Electro-Optical Signal Transmission and Ranging (EOSTAR) model is an image-based Tactical Decision Aid (TDA) for thermal imaging systems (MWIR/LWIR) developed for a sea environment with an extensive atmosphere model. The Triangle Orientation Discrimination (TOD) Target Acquisition model

  1. Technically Extended MultiParameter Optimization (TEMPO): An Advanced Robust Scoring Scheme To Calculate Central Nervous System Druggability and Monitor Lead Optimization.

    Science.gov (United States)

    Ghose, Arup K; Ott, Gregory R; Hudkins, Robert L

    2017-01-18

    At the discovery stage, it is important to understand the drug design concepts for a CNS drug compared to those for a non-CNS drug. Previously, we published on ideal CNS drug property space and defined in detail the physicochemical property distribution of CNS versus non-CNS oral drugs, the application of radar charting (a graphical representation of multiple physicochemical properties used during CNS lead optimization), and a recursive partition classification tree to differentiate between CNS- and non-CNS drugs. The objective of the present study was to further understand the differentiation of physicochemical properties between CNS and non-CNS oral drugs by the development and application of a new CNS scoring scheme: Technically Extended MultiParameter Optimization (TEMPO). In this multiparameter method, we identified eight key physicochemical properties critical for accurately assessing CNS druggability: (1) number of basic amines, (2) carbon-heteroatom (non-carbon, non-hydrogen) ratio, (3) number of aromatic rings, (4) number of chains, (5) number of rotatable bonds, (6) number of H-acceptors, (7) computed octanol/water partition coefficient (AlogP), and (8) number of nonconjugated C atoms in nonaromatic rings. Significant features of the CNS-TEMPO penalty score are the extension of the multiparameter approach to generate an accurate weight factor for each physicochemical property, the use of limits on both sides of the computed property space range during the penalty calculation, and the classification of CNS and non-CNS drug scores. CNS-TEMPO significantly outperformed CNS-MPO and the Schrödinger QikProp CNS parameter (QP_CNS) in evaluating CNS drugs and has been extensively applied in support of CNS lead optimization programs.

  2. Low- and high-order harmonic generation in the extended plasmas produced by laser ablation of zinc and manganese targets

    Energy Technology Data Exchange (ETDEWEB)

    Ganeev, R. A., E-mail: rashid-ganeev@mail.ru [Ophthalmology and Advanced Laser Medical Center, Saitama Medical University, Saitama 350-0495 (Japan); Physical Department, Voronezh State University, Voronezh 394006 (Russian Federation); Baba, M.; Suzuki, M.; Yoneya, S.; Kuroda, H. [Ophthalmology and Advanced Laser Medical Center, Saitama Medical University, Saitama 350-0495 (Japan)

    2014-12-28

    The systematic studies of the harmonic generation of ultrashort laser pulses in the 5-mm-long Zn and Mn plasmas (i.e., application of nanosecond, picosecond, and femtosecond pulses for ablation, comparison of harmonic generation from atomic, ionic, and cluster-contained species of plasma, variation of plasma length, two-color pump of plasmas, etc.) are presented. The conversion efficiency of the 11th–19th harmonics generated in the Zn plasma was ∼5 × 10{sup −5}. The role of the ionic resonances of Zn near the 9th and 10th harmonics on the enhancement of harmonics is discussed. The enhancement of harmonics was also analyzed using the two-color pump of extended plasmas, which showed similar intensities of the odd and even harmonics along the whole range of generation. The harmonics up to the 107th order were demonstrated in the case of manganese plasma. The comparison of harmonic generation in the 5-mm-long and commonly used short (≤0.5 mm) plasma plumes showed the advanced properties of extended media.

  3. Internal Ribosome Entry Site-Based Bicistronic In Situ Reporter Assays for Discovery of Transcription-Targeted Lead Compounds.

    Science.gov (United States)

    Lang, Liwei; Ding, Han-Fei; Chen, Xiaoguang; Sun, Shi-Yong; Liu, Gang; Yan, Chunhong

    2015-07-23

    Although transgene-based reporter gene assays have been used to discover small molecules targeting expression of cancer-driving genes, the success is limited due to the fact that reporter gene expression regulated by incomplete cis-acting elements and foreign epigenetic environments does not faithfully reproduce chemical responses of endogenous genes. Here, we present an internal ribosome entry site-based strategy for bicistronically co-expressing reporter genes with an endogenous gene in the native gene locus, yielding an in situ reporter assay closely mimicking endogenous gene expression without disintegrating its function. This strategy combines the CRISPR-Cas9-mediated genome-editing tool with the recombinase-mediated cassette-exchange technology, and allows for rapid development of orthogonal assays for excluding false hits generated from primary screens. We validated this strategy by developing a screening platform for identifying compounds targeting oncogenic eIF4E, and demonstrated that the novel reporter assays are powerful in searching for transcription-targeted lead compounds with high confidence. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Ewald: an extended wide-angle Laue diffractometer for the second target station of the Spallation Neutron Source.

    Science.gov (United States)

    Coates, Leighton; Robertson, Lee

    2017-08-01

    Visualizing hydrogen atoms in biological materials is one of the biggest remaining challenges in biophysical analysis. While X-ray techniques have unrivaled capacity for high-throughput structure determination, neutron diffraction is uniquely sensitive to hydrogen atom positions in crystals of biological materials and can provide a more complete picture of the atomic and electronic structures of biological macromolecules. This information can be essential in providing predictive understanding and engineering control of key biological processes, for example, in catalysis, ligand binding and light harvesting, and to guide bioengineering of enzymes and drug design. One very common and large capability gap for all neutron atomic resolution single-crystal diffractometers is the weak flux of available neutron beams, which results in limited signal-to-noise ratios giving a requirement for sample volumes of at least 0.1 mm3. The ability to operate on crystals an order of magnitude smaller (0.01 mm3) will open up new and more complex systems to studies with neutrons which will help in our understanding of enzyme mechanisms and enable us to improve drugs against multi resistant bacteria. With this is mind, an extended wide-angle Laue diffractometer, 'Ewald', has been designed, which can collect data using crystal volumes below 0.01 mm3.

  5. Single lead atrial vs. dual chamber pacing in sick sinus syndrome: extended register-based follow-up in the DANPACE trial.

    Science.gov (United States)

    Brandt, Niels H; Kirkfeldt, Rikke Esberg; Nielsen, Jens Cosedis; Mortensen, Leif Spange; Jensen, Gunnar Vagn Hagemann; Johansen, Jens Brock; Haugan, Ketil

    2017-12-01

    The DANPACE trial randomized patients with sick sinus syndrome (SSS) to single lead atrial (AAIR) or dual chamber (DDDR) pacemaker (PM). After 5 years follow-up, no difference in overall survival, stroke or heart failure (HF) was observed, whereas risk of atrial fibrillation (AF) and PM reoperation were increased in the AAIR group. The present study aimed to investigate very long term risk of death, AF hospitalization, stroke, HF and rate of change in pacing mode using national register-based data. The study population consisted of all 1384 patients included at Danish PM centres in the DANPACE trial randomized to AAIR (n = 696) or DDDR (n = 688). Long-term follow-up data was obtained from Danish national registers. Analysis was intention-to-treat. results: During mean follow-up of 8.9 years, 413 patients (59.3%) died in the AAIR-group compared to 367 (53.3%) in the DDDR-group (adjusted hazard ratio 1.03; 95% confidence interval 0.90-1.19; P = 0.65). We observed no difference in risk of AF hospitalization, stroke or HF. During extended follow-up, annual rate of pacing mode change to DDDR in the AAIR group was 4.5%, and higher than the 2.3% observed during trial conduct. This register-based long-term follow-up study indicates that there is no difference in mortality among patients with SSS randomized to AAIR or DDDR pacing, even with very long follow-up. Nor is there any difference in risk of AF hospitalization, stroke or HF. The higher rate of pacing mode-change to DDDR in the AAIR group suggests a different management of patients with an AAIR PM after the DANPACE trial.

  6. Particle distributions, entering the vacuum tube, from an 80 x 80 x 60 cm3 lead target.

    CERN Document Server

    Borcea, C; Kadi, Y; Lacoste, V; Vlachoudis, V; CERN. Geneva. SPS and LEP Division

    2000-01-01

    The neutron Time of Flight (n_TOF) facility at CERN is a source of neutrons produced by spallation of 20 GeV/c protons onto a solid lead target. The outstanding characteristics of this facility (very high intensity, 200m flight path, wide spectral function) make it an extremely useful tool that provides the necessary data for the design and understanding of Accelerator Driven Systems. Simulating geometries like the n_TOF tunnel, with a long flight path, and with the imposed background conditions, is a very difficult and time consuming task. To accomplish it, several software packages have been assembled using specially written interfaces. This report, describes the simulations performed, for the collection of data of the particles entering the neutron tube, necessary for the subsequent parametrization of their distributions.

  7. Post-irradiation analysis of an ISOLDE lead-bismuth target: Stable and long-lived noble gas nuclides

    Energy Technology Data Exchange (ETDEWEB)

    Leya, I., E-mail: Ingo.Leya@space.unibe.ch [University of Bern, Space Science and Planetology, Bern (Switzerland); Grimberg, A. [University of Bern, Space Science and Planetology, Bern (Switzerland); Isotope Geochemistry, ETH Zürich, Zürich (Switzerland); David, J.-C. [CEA/Saclay, Irfu/SPhN, 91191 Gif-sur-Yvette, Cedex (France); Schumann, D.; Neuhausen, J. [Paul Scherrer Institut, Villigen (Switzerland); Zanini, L. [Paul Scherrer Institut, Villigen (Switzerland); European Spallation Source ESS AB, P.O. Box 117, SE-22100 Lund (Sweden); Noah, E. [University of Geneva, Département de Physique Nucléaire et Corpusculaire, Geneve (Switzerland)

    2016-07-15

    We measured the isotopic concentrations of long-lived and stable He, Ne, Ar, Kr, and Xe isotopes in a sample from a lead-bismuth eutectic target irradiated with 1.0 and 1.4 GeV protons. Our data indicate for most noble gases nearly complete release with retention fractions in the range of percent or less. Higher retention fractions result from the decay of long-lived radioactive progenitors from groups 1, 2, or 7 of the periodic table. From the data we can calculate a retention fraction for {sup 3}H of 2–3%. For alkaline metals we find retention fractions of about 10%, 30%, and 50% for Na, Rb, and Cs, respectively. For the alkaline earth metal Ba we found complete retention. Finally, the measured Kr and Xe concentrations indicate that there was some release of the halogens Br and I during and/or after the irradiation.

  8. Spatial distribution of neutrons in paraffin moderator surrounding a lead target irradiated with protons at intermediate energies

    CERN Document Server

    Adam, J; Bradnova, V

    2002-01-01

    The distribution of neutrons emitted during the irradiation with 0.65, 1.0 and 1.5 GeV protons from a lead target (O / = 8 cm, l = 20 cm) and moderated by a surrounding paraffin moderator of 6 cm thick was studied with a radiochemical sensor along the beam axis on top of the moderator. Small sup 1 sup 3 sup 9 La-sensors of approximately 1 g were used to measure essentially the thermal neutron fluence at different depths near the surface: i.e., on top of the moderator, in 10 mm deep holes and in 20 mm deep holes. The reaction sup 1 sup 3 sup 9 La(n, gamma) sup 1 sup 4 sup 0 La (tau sub 1 sub / sub 2 = 40.27 h) was studied using standard procedures of gamma spectroscopy and data analysis. The neutron induced activity of sup 1 sup 4 sup 0 La increases strongly with the depth of the hole inside the moderator, its activity distribution along the beam direction on top of the moderator has its maximum about 10 cm downstream the entrance of the protons into the lead and the induced activity increases about linearity ...

  9. Targeting bed nucleus of the stria terminalis for severe obsessive-compulsive disorder: more unexpected lead placement in obsessive-compulsive disorder than in surgery for movement disorders.

    Science.gov (United States)

    Nuttin, Bart; Gielen, Frans; van Kuyck, Kris; Wu, Hemmings; Luyten, Laura; Welkenhuysen, Marleen; Brionne, Thomas C; Gabriëls, Loes

    2013-01-01

    In preparation for a multicenter study, a protocol was written on how to perform surgical targeting of the bed nucleus of the stria terminalis, based on the lead implantation experience in patients with treatment-refractory obsessive-compulsive disorder (OCD) at the Universitaire Ziekenhuizen Leuven (UZ Leuven). When analyzing the postoperative images, we were struck by the fact that the difference between the postoperative position of the leads and the planned position seemed larger than expected. The precision of targeting in four patients with severe OCD who received bilateral model 3391 leads (Medtronic) was compared with the precision of targeting in the last seven patients who underwent surgery at UZ Leuven for movement disorders (four with Parkinson disease and three with essential tremor; all received bilateral leads). Because the leads implanted in six of the seven patients with movement disorders were model 3387 leads (Medtronic), targeting precision was also analyzed in four patients with OCD in whom model 3387 leads were implanted in the same target as the other patients with OCD. In the patients with OCD, every implanted lead deviated at least 1.3 mm from its intended position in at least one of three directions (lateral, anteroposterior, and depth), whereas in the patients with movement disorders, the maximal deviation of any of all implanted leads was 1.3 mm. The deviations in lead placement were comparable in patients with OCD who received a model 3387 implant and patients who received a model 3391 implant. In the patients with OCD, all leads were implanted more posteriorly than planned. The cause of the posterior deviation could not be determined with certainty. The most likely cause was an increased mechanical resistance of the brain tissue along the trajectory when following the targeting protocol compared with the trajectories classically used for subthalamic nucleus or ventral intermediate nucleus of the thalamus stimulation. Copyright © 2013

  10. 2,5-Dimethyl-Celecoxib Extends Drosophila Life Span via a Mechanism That Requires Insulin and Target of Rapamycin Signaling.

    Science.gov (United States)

    Wu, Qi; Lian, Ting; Fan, Xiaolan; Song, Chaochun; Gaur, Uma; Mao, Xueping; Yang, Deying; Piper, Matthew D W; Yang, Mingyao

    2017-10-01

    The search for antiaging drugs is a key component of gerontology research. A few drugs with positive effects on life span in model organisms have been found. Here, we report that 2,5-dimethyl-celecoxib, a derivative of the anti-inflammatory drug celecoxib, can extend Drosophila life span and delay aging by a mechanism involving insulin signaling and target of rapamycin signaling. Importantly, its positive effects were apparent when the treatment window was restricted to the beginning of life or the later half. 2,5-Dimethyl-celecoxib-induced longevity was also associated with improvements in physical activity, intestinal integrity, and increased autophagy. In addition, 2,5-dimethyl-celecoxib exhibited protective effects against several kinds of stress such as starvation and heat. The generally positive effects of 2,5-dimethyl-celecoxib on both health and life span, combined with its mode of action via evolutionarily conserved signaling pathways, indicate that it has the potential to become an effective antiaging drug. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Biophysical Analysis of the N-Terminal Domain from the Human Protein Phosphatase 1 Nuclear Targeting Subunit PNUTS Suggests an Extended Transcription Factor TFIIS-Like Fold.

    Science.gov (United States)

    Zacharchenko, Thomas; Barsukov, Igor; Rigden, Daniel J; Bennett, Daimark; Mayans, Olga

    2016-10-01

    Human protein phosphatase 1 nuclear targeting subunit (PNUTS) plays critical roles in DNA repair, cell growth and survival. The N-terminal domain of PNUTS mediates interactions with Tox4 and the phosphatase and tensin homolog PTEN, which are essential for the roles of this protein. To study this N-terminal domain, we have established its recombinant overproduction in E. coli utilizing NusA fusion. Upon removal of the tag, the remaining PNUTS sample is soluble and highly pure. We have characterized the domain using circular dichroism and nuclear magnetic resonance and analyzed its sequence using bioinformatics. All data agree in suggesting that the PNUTS N-terminal segment adopts a compact, globular fold rich in α-helical content, where the folded fraction is substantially larger than the previously annotated fold. We conclude that this domain adopts a single fold, likely being an extended form of the transcription factor S-II leucine/tryptophan conserved-motif. Thermal denaturation yielded a melting temperature of ~49.5 °C, confirming the stability of the fold. These findings pave the way for the molecular characterization of functional interactions mediated by the N-terminal region of PNUTS.

  12. More target features in visual working memory leads to poorer search guidance: Evidence from contralateral delay activity

    Science.gov (United States)

    Schmidt, Joseph; MacNamara, Annmarie; Proudfit, Greg Hajcak; Zelinsky, Gregory J.

    2014-01-01

    The visual-search literature has assumed that the top-down target representation used to guide search resides in visual working memory (VWM). We directly tested this assumption using contralateral delay activity (CDA) to estimate the VWM load imposed by the target representation. In Experiment 1, observers previewed four photorealistic objects and were cued to remember the two objects appearing to the left or right of central fixation; Experiment 2 was identical except that observers previewed two photorealistic objects and were cued to remember one. CDA was measured during a delay following preview offset but before onset of a four-object search array. One of the targets was always present, and observers were asked to make an eye movement to it and press a button. We found lower magnitude CDA on trials when the initial search saccade was directed to the target (strong guidance) compared to when it was not (weak guidance). This difference also tended to be larger shortly before search-display onset and was largely unaffected by VWM item-capacity limits or number of previews. Moreover, the difference between mean strong- and weak-guidance CDA was proportional to the increase in search time between mean strong-and weak-guidance trials (as measured by time-to-target and reaction-time difference scores). Contrary to most search models, our data suggest that trials resulting in the maintenance of more target features results in poor search guidance to a target. We interpret these counterintuitive findings as evidence for strong search guidance using a small set of highly discriminative target features that remain after pruning from a larger set of features, with the load imposed on VWM varying with this feature-consolidation process. PMID:24599946

  13. Gills are an initial target of zinc oxide nanoparticles in oysters Crassostrea gigas, leading to mitochondrial disruption and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Trevisan, Rafael; Delapedra, Gabriel; Mello, Danielle F.; Arl, Miriam [Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil); Schmidt, Éder C. [Department of Cell Biology, Embryology and Genetic, Federal University of Santa Catarina, 88049-900 Florianópolis, SC (Brazil); Meder, Fabian; Monopoli, Marco [Centre for Bionano Interactions, University College Dublin, Dublin (Ireland); Cargnin-Ferreira, Eduardo [Federal Institute of Santa Catarina, Campus Garopaba, Laboratory of Histological Markers, 88495-000 Garopaba, SC (Brazil); Bouzon, Zenilda L. [Department of Cell Biology, Embryology and Genetic, Federal University of Santa Catarina, 88049-900 Florianópolis, SC (Brazil); Fisher, Andrew S. [School of Geography, Earth and Environmental Sciences, University of Plymouth, PL4 8AA Plymouth (United Kingdom); Sheehan, David [Department of Biochemistry, University College Cork, Cork (Ireland); Dafre, Alcir L., E-mail: alcir.dafre@ufsc.br [Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, SC (Brazil)

    2014-08-15

    hemocyte count). At 24 h post exposure, decreased (−29%) glutathione reductase (GR) activity was observed in gills, but other biochemical responses were observed only after 48 h of exposure: lower GR activity (−28%) and levels of protein thiols (−21%), increased index of lipid peroxidation (+49%) and GPx activity (+26%). In accordance with ultrastructural changes and zinc load, digestive gland showed delayed biochemical responses. Except for a decreased GR activity (−47%) at 48 h post exposure, the biochemical alterations seen in gills were not present in digestive gland. The results indicate that gills are able to incorporate zinc prior (24 h) to digestive gland (48 h), leading to earlier mitochondrial disruption and oxidative stress. Our data suggest that gills are the initial target of ZnONP and that mitochondria are organelles particularly susceptible to ZnONP in C. gigas.

  14. A Role for Fragment-Based Drug Design in Developing Novel Lead Compounds for Central Nervous System Targets

    National Research Council Canada - National Science Library

    Wasko, Michael J; Pellegrene, Kendy A; Madura, Jeffry D; Surratt, Christopher K

    2015-01-01

    .... A variant of VS is fragment-based drug design (FBDD), an emerging in silico lead discovery method that introduces low-molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model...

  15. Orally administered colistin leads to colistin-resistant intestinal flora and fails to prevent faecal colonisation with extended-spectrum β-lactamase-producing enterobacteria in hospitalised newborns.

    Science.gov (United States)

    Strenger, Volker; Gschliesser, Tanja; Grisold, Andrea; Zarfel, Gernot; Feierl, Gebhard; Masoud, Lilian; Hoenigl, Martin; Resch, Bernhard; Müller, Wilhelm; Urlesberger, Berndt

    2011-01-01

    Colonisation and infection with extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is an emerging problem. The aim of this study was to investigate whether colistin, which is reported to be effective against multiresistant enterobacteria, prevents ESBL-E colonisation in neonates. For prophylaxis of necrotising enterocolitis, oral gentamicin (15 mg/kg/day) is routinely used in all neonates hospitalised at the Neonatal Intensive Care Unit of University Hospital Graz (Austria). During the study period from May 2005 to September 2007, three ESBL-E outbreaks (total duration 18 months) occurred. During these outbreaks, gentamicin was immediately replaced by oral colistin (8 mg/kg/day) in all hospitalised neonates. All neonates colonised with ESBL-E during the study period were retrospectively analysed with regard to the influence of colistin on ESBL-E colonisation. Genetic relatedness of isolates was assessed by repetitive sequence-based polymerase chain reaction (rep-PCR). During the study period, 30 (4.5%) of 667 neonates were colonised with ESBL-E. Twelve of twenty-one patients colonised with Klebsiella pneumoniae (ESBL-Kp) and one of nine patients colonised with Klebsiella oxytoca (ESBL-Ko) had received oral colistin at time of colonisation with ESBL-E. Amongst ESBL-Kp, the rate of colistin resistance was significantly higher in the colistin group (P=0.0075). Four different clones of ESBL-Kp and three different clones of ESBL-Ko were isolated, indicating the occurrence of patient-to-patient transmission. Colistin-resistant as well as colistin-susceptible isolates were detected within the same clones, indicating induction of resistance. At the dosage used, oral colistin did not prevent colonisation with ESBL-E and appeared to select colistin-resistant strains or to induce colistin resistance. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  16. Screen Anti-influenza Lead Compounds That Target the PAC Subunit of H5N1 Viral RNA Polymerase

    Science.gov (United States)

    Xiang, Junfeng; Li, Qian; Liang, Huanhuan; Tang, Yalin; Liu, Yingfang

    2012-01-01

    The avian influenza (H5N1) viral RNA polymerase protein PAC was used as a target to screen nine chlorogenic acid derivatives for their polymerase inhibitor activity. Among them, seven compounds were PAC ligands, and four inhibited influenza RNA polymerase activity. These results aid in the design of anti-influenza agents based on caffeoylquinic acid. PMID:22936968

  17. Downregulation of chloroplast-targeted beta-amylase leads to a starch-excess phenotype in leaves

    DEFF Research Database (Denmark)

    Scheidig, A.; Fröhlich, A.; Schulze, S.

    2002-01-01

    A functional screen in Escherichia coli was established to identify potato genes coding for proteins involved in transitory starch degradation. One clone isolated had a sequence very similar to a recently described chloroplast-targeted 5-amylase of Arabidopsis. Expression of the gene in E. coli s...

  18. IRES-based Bicistronic in-situ Reporter Assays for Discovery of Transcription-targeted Lead Compounds

    OpenAIRE

    Lang, Liwei; Ding, Han-Fei; Chen, Xiaoguang; Sun, Shi-Yong; Liu, Gang; Yan, Chunhong

    2015-01-01

    Although transgene-based reporter gene assays have been used to discover small molecules targeting expression of cancer-driving genes, the success is limited due to the fact that reporter gene expression regulated by incomplete cis-acting elements and foreign epigenetic environments does not faithfully reproduce chemical responses of endogenous genes. Here we present an IRES-based strategy for bicistronically co-expressing reporter genes with an endogenous gene in the native gene locus, yield...

  19. Volatile elements production rates in a 1.4 Gev proton-irradiated molten lead-bismuth target

    CERN Document Server

    Zanini, L; Everaerts, P; Fallot, M; Franberg, H; Gröschel, F; Jost, C; Kirchner, T; Kojima, Y; Köster, U; Lebenhaft, J; Manfrina, E; Pitcher, E J; Ravn, H L; Tall, Y; Wagner, W; Wohlmuther, M

    2005-01-01

    Production rates of volatile elements following spallation reaction of 1.4 GeV protons on a liquid Pb/Bi target have been measured. The experiment was performed at the ISOLDE facility at CERN. These data are of interest for the developments of targets for accelerator driven systems such as MEGAPIE. Additional data have been taken on a liquid Pb target. Calculations were performed using the FLUKA and MCNPX Monte Carlo codes coupled with the evolution codes ORIHET3 and FISPACT using different options for the intra-nuclear cascades and evaporation models. Preliminary results from the data analysis show good comparison with calculations for Hg and for noble gases. For other elements such as I it is apparent that only a fraction of the produced isotopes is released. The agreement with the experimental data varies depending on the model combination used. The best results are obtained using MCNPX with the INCL4/ABLA models and with FLUKA. Discrepancies are found for some isotopes produced by fission using the MCNPX ...

  20. Disclosing the Parameters Leading to High Productivity of Retroviral Producer Cells Lines: Evaluating Random Versus Targeted Integration.

    Science.gov (United States)

    Bandeira, Vanessa S; Tomás, Hélio A; Alici, Evren; Carrondo, Manuel J T; Coroadinha, Ana S

    2017-04-01

    Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T and natural killer cells to be used in immune cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GaLV-pseudotyped gammaretroviral vector productivity in stable producer cells, using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination). The retroviral vector contains a thymidine kinase suicide gene fused with a ouabain-resistant Na + ,K + -ATPase gene, a potential safer and faster marker. The establishment of retroviral vector producer cells is traditionally performed by randomly integrating the retroviral vector expression cassette codifying the transgene. More recently, recombinase-mediated cassette exchange methodologies have been introduced to achieve targeted integration. Herein we compared random and targeted integration of the retroviral vector transgene construct. Two retroviral producer cell lines, 293 OuaS and 293 FlexOuaS, were generated by random and targeted integration, respectively, producing high titers (on the order of 10 7 infectious particles·ml -1 ). Results showed that the retroviral vector transgene cassette is the key retroviral vector component determining the viral titers notwithstanding, single-copy integration is sufficient to provide high titers. The expression levels of the three retroviral constructs (gag-pol, GaLV env, and retroviral vector transgene) were analyzed. Although gag-pol and GaLV env gene expression levels should surpass a minimal threshold, we found that relatively modest expression levels of these two expression cassettes are required. Their levels of

  1. Herbal Lead as Ideal Bioactive Compounds Against Probable Drug Targets of Ebola Virus in Comparison with Known Chemical Analogue: A Computational Drug Discovery Perspective.

    Science.gov (United States)

    Setlur, Anagha S; Naik, Sujay Y; Skariyachan, Sinosh

    2017-06-01

    Ebola is a deadly virus that has recently emerged as an enormous public health concern which causes dangerous illness with high fatality rates of 90 %. The virus is not receptive to known antivirals, and hence, there is a promising need to identify novel inhibitors to combat the disease. The present study deals with identification of potential herbal leads that probably subdue the activity of four major drug targets of Ebola virus such as VP24, VP30, VP35 and VP40 by computer-aided virtual screening. The selection of receptors was performed based on their functional roles in the disease. The drug likeliness and ADMET parameters of 150 herbal ligands were computationally predicted. Those molecules that qualified these parameters were preferred for docking studies with the protein targets. An existing chemical antiviral drug, BCX4430 was also docked and its theoretical binding energy was scrutinized. The docking studies suggested that herbal ligand Limonin demonstrated high binding properties with VP24 and VP35 (binding energy -9.7 kcal/mol). Similarly, curcumin exhibited good binding with VP30 (binding energy -9.6 kcal/mol). Further, Mahanine displayed superior interaction with VP40 (binding energy -7.7 kcal/mol). These herbal leads demonstrated better binding potential than the known chemical analogue in the computational studies. This study serves to bestow paramount information for further experimental studies concerning the utility of herbal ligands as probable lead molecules against Ebola viral targets.

  2. Extended Emotions

    OpenAIRE

    Krueger, Joel; Szanto, Thomas

    2016-01-01

    Until recently, philosophers and psychologists conceived of emotions as brain- and body-bound affairs. But researchers have started to challenge this internalist and individualist orthodoxy. A rapidly growing body of work suggests that some emotions incorporate external resources and thus extend beyond the neurophysiological confines of organisms; some even argue that emotions can be socially extended and shared by multiple agents. Call this the extended emotions thesis (ExE). In this article...

  3. Development of pyridine dicoumarols as potent anti HIV-1 leads, targeting HIV-1 associated topoisomeraseIIβ kinase.

    Science.gov (United States)

    Kammari, Kurumurthy; Devaraya, Kiran; Bommakanti, Akhila; Kondapi, Anand K

    2017-09-01

    A structural study of a series of pyridine dicoumarol derivatives with potential activity against a novel Topoisomerase IIβ kinase which was identified in the HIV-1 viral lysate, compounds were designed and synthesized based on a 3D-QSAR study. Based on QSAR model we have designed and synthesized a series of pyridine dicoumarol derivatives and characterized by spectral studies, all the molecules are biologically evaluated by kinase assay, cytotoxicity assay, ELISA and PCR method. We demonstrated the achievement of water soluble disodium pyridine dicoumarate derivatives showing high anti-HIV-1 activity (IC50 HIV-1-associated topoisomerase IIβ kinase inhibitors for clinical application against AIDS. A new class of anti-HIV-1 lead compounds have been designed and tested. Further studies would result in development of  novel and potential drugs.

  4. Monte carlo simulations of the n_TOF lead spallation target with the Geant4 toolkit: A benchmark study

    Directory of Open Access Journals (Sweden)

    Lerendegui-Marco J.

    2017-01-01

    Full Text Available Monte Carlo (MC simulations are an essential tool to determine fundamental features of a neutron beam, such as the neutron flux or the γ-ray background, that sometimes can not be measured or at least not in every position or energy range. Until recently, the most widely used MC codes in this field had been MCNPX and FLUKA. However, the Geant4 toolkit has also become a competitive code for the transport of neutrons after the development of the native Geant4 format for neutron data libraries, G4NDL. In this context, we present the Geant4 simulations of the neutron spallation target of the n_TOF facility at CERN, done with version 10.1.1 of the toolkit. The first goal was the validation of the intra-nuclear cascade models implemented in the code using, as benchmark, the characteristics of the neutron beam measured at the first experimental area (EAR1, especially the neutron flux and energy distribution, and the time distribution of neutrons of equal kinetic energy, the so-called Resolution Function. The second goal was the development of a Monte Carlo tool aimed to provide useful calculations for both the analysis and planning of the upcoming measurements at the new experimental area (EAR2 of the facility.

  5. IL2-caspase3 chimeric protein controls lymphocyte reactivity by targeted apoptosis, leading to amelioration of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Irony-Tur-Sinai, Michal; Lichtenstein, Michal; Brenner, Talma; Lorberboum-Galski, Haya

    2009-09-01

    IL2-caspase3 chimeric protein was designed to target and kill cells expressing the high affinity IL-2 receptor. Its effects on lymphocyte reactivity and on experimental autoimmune encephalomyelitis (EAE), a T-cell mediated disease, were tested in this study. Our data show that IL2-caspase3 promoted cell specific apoptosis both in vitro and in vivo. Cell lines preferentially expressing the IL-2R alpha chain and encephalitogenic lymphocytes derived from EAE-induced mice were highly sensitive to the chimeras' activity. This was demonstrated by increased DNA fragmentation and annexin labeling together with reduced specific T-cell proliferation in response to IL2-casepase3 treatment. Furthermore, IL2-caspase3 treatment of EAE-induced mice caused a significant delay in disease onset together with a reduction in disease burden. The efficacy of IL2-caspase3 treatment was dependent on the time at which treatment begun, with the chimera ameliorating EAE only when administered at maximal activation of peripheral lymphocytes. According to our findings we suggest that the chimeric protein IL2-caspase3 may provide a novel approach for the treatment of a variety of autoimmune disorders, such as multiple sclerosis, as well as for other pathological conditions that involve uncontrolled expansion of activated T cells.

  6. Small Molecules from Nature Targeting G-Protein Coupled Cannabinoid Receptors: Potential Leads for Drug Discovery and Development

    Directory of Open Access Journals (Sweden)

    Charu Sharma

    2015-01-01

    Full Text Available The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB1 and CB2 which have been explored as potential therapeutic targets for drug discovery and development. Currently, there are numerous cannabinoid based synthetic drugs used in clinical practice like the popular ones such as nabilone, dronabinol, and Δ9-tetrahydrocannabinol mediates its action through CB1/CB2 receptors. However, these synthetic based Cannabis derived compounds are known to exert adverse psychiatric effect and have also been exploited for drug abuse. This encourages us to find out an alternative and safe drug with the least psychiatric adverse effects. In recent years, many phytocannabinoids have been isolated from plants other than Cannabis. Several studies have shown that these phytocannabinoids show affinity, potency, selectivity, and efficacy towards cannabinoid receptors and inhibit endocannabinoid metabolizing enzymes, thus reducing hyperactivity of endocannabinoid systems. Also, these naturally derived molecules possess the least adverse effects opposed to the synthetically derived cannabinoids. Therefore, the plant based cannabinoid molecules proved to be promising and emerging therapeutic alternative. The present review provides an overview of therapeutic potential of ligands and plants modulating cannabinoid receptors that may be of interest to pharmaceutical industry in search of new and safer drug discovery and development for future therapeutics.

  7. Defective resection at DNA double-strand breaks leads to de novo telomere formation and enhances gene targeting.

    Directory of Open Access Journals (Sweden)

    Woo-Hyun Chung

    2010-05-01

    Full Text Available The formation of single-stranded DNA (ssDNA at double-strand break (DSB ends is essential in repair by homologous recombination and is mediated by DNA helicases and nucleases. Here we estimated the length of ssDNA generated during DSB repair and analyzed the consequences of elimination of processive resection pathways mediated by Sgs1 helicase and Exo1 nuclease on DSB repair fidelity. In wild-type cells during allelic gene conversion, an average of 2-4 kb of ssDNA accumulates at each side of the break. Longer ssDNA is formed during ectopic recombination or break-induced replication (BIR, reflecting much slower repair kinetics. This relatively extensive resection may help determine sequences involved in homology search and prevent recombination within short DNA repeats next to the break. In sgs1Delta exo1Delta mutants that form only very short ssDNA, allelic gene conversion decreases 5-fold and DSBs are repaired by BIR or de novo telomere formation resulting in loss of heterozygosity. The absence of the telomerase inhibitor, PIF1, increases de novo telomere pathway usage to about 50%. Accumulation of Cdc13, a protein recruiting telomerase, at the break site increases in sgs1Delta exo1Delta, and the requirement of the Ku complex for new telomere formation is partially bypassed. In contrast to this decreased and alternative DSB repair, the efficiency and accuracy of gene targeting increases dramatically in sgs1Delta exo1Delta cells, suggesting that transformed DNA is very stable in these mutants. Altogether these data establish a new role for processive resection in the fidelity of DSB repair.

  8. On moving targets and magic bullets: Can the UK lead the way with responsible data linkage for health research?

    Science.gov (United States)

    Laurie, G; Ainsworth, J; Cunningham, J; Dobbs, C; Jones, K H; Kalra, D; Lea, N C; Sethi, N

    2015-11-01

    To provide an overview of essential elements of good governance of data linkage for health-related research, to consider lessons learned so far and to examine key factors currently impeding the delivery of good governance in this area. Given the considerable hurdles which must be overcome and the changing landscape of health research and data linkage, a principled, proportionate, risk-based approach to governance is advocated. In light of the considerable value of data linkage to health and well-being, the United Kingdom aspires to design and deliver good governance in health-related research. A string of projects have been asking: what does good governance look like in data linkage for health research? It is argued here that considerable progress can and must be made in order to develop the UK's contribution to future health and wealth economies, particularly in light of mis-start initiatives such as care.data in NHS England. Discussion centres around lessons learned from previous successful health research initiatives, identifying those governance mechanisms which are essential to achieving good governance. This article suggests that a crucial element in any step-increase of research capability will be the adoption of adaptive governance models. These must recognise a range of approaches to delivering safe and effective data linkage, while remaining responsive to public and research user expectations and needs as these shift and change with time and experience. The targets are multiple and constantly moving. There is not--nor should we seek--a single magic bullet in delivering good governance in health research. Copyright © 2015. Published by Elsevier Ireland Ltd.

  9. Investigation of Space and Energy Distributions of Neutrons Generated in Lead Target and Uranium Blanket of the Electronuclear System "Energy plus Transmutation" under Irradiation with Protons at 1.5 GeV

    CERN Document Server

    Zhuk, I V; Krivopustov, M I; Sosnin, A N; Chultem, D; Vestmaer, V; Tumendelger, T; Zaveryukha, O S; Pavlyuk, A B

    2002-01-01

    The work contains the results of space-energy distributions of neutrons in U/Pb assembly, consisting of extended lead target and the model of natural uranium blanket irradiated with relativistic protons at 1.5 GeV. The research is carried out in the framework of a series of experiments using the model of subcritical heterogeneous electronuclear system at the Laboratory of High Energies, JINR, Dubna ("Investigation of Physical Aspects of Electronuclear Method of Energy Production and Transmutation of Radioactive Waste Using Beams from JINR Synchrophasotron/Nuclotron" - project "Energy plus Transmutation"). The results of measurements and calculations of ^{235}U, ^{238}U and ^{232}Th fission rate distributions as well as threshold spectral indexes {\\bar\\sigma_f^{^{232}Th}}/{\\bar\\sigma_f^{^{235}U}} and {\\bar\\sigma_f^{^{238}U}}/{\\bar\\sigma_f^{^{235}U}} along the radius of the target and model uranium blanket are presented. The results of measurements and calculations of ^{234}U, ^{236}U and ^{237}Np fission rate ...

  10. Measurements of spallation neutrons from a thick lead target bombarded with 0.5 and 1.5 GeV protons

    Energy Technology Data Exchange (ETDEWEB)

    Meigo, Shin-ichiro; Takada, Hiroshi; Chiba, Satoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment] [and others

    1997-03-01

    Double differential neutron spectra from a thick lead target bombarded with 0.5 and 1.5 GeV protons have been measured with the time-of-flight technique. In order to obtain the neutron spectra without the effect of the flight time fluctuation by neutron scattering in the target, an unfolding technique has also been employed in the low energy region below 3 MeV. The measured data have been compared with the calculated results of NMTC/JAERI-MCNP-4A code system. It has been found that the code system gives about 50 % lower neutron yield than the experimental ones in the energy region between 20 and 80 MeV for both incident energies. The disagreements, however, have been improved well by taking account of the inmedium nucleon-nucleon scattering cross sections in the NMTC/JAERI code. (author)

  11. Targeted expression of redesigned and codon optimised synthetic gene leads to recrystallisation inhibition and reduced electrolyte leakage in spring wheat at sub-zero temperatures.

    Science.gov (United States)

    Khanna, Harjeet K; Daggard, Grant E

    2006-12-01

    Antifreeze proteins (AFPs) adsorb to ice crystals and inhibit their growth, leading to non-colligative freezing point depression. Crops like spring wheat, that are highly susceptible to frost damage, can potentially be made frost tolerant by expressing AFPs in the cytoplasm and apoplast where ice recrystallisation leads to cellular damage. The protein sequence for HPLC-6 alpha-helical antifreeze protein from winter flounder was rationally redesigned after removing the prosequences in the native protein. Wheat nuclear gene preferred amino acid codons were used to synthesize a recombinant antifreeze gene, rAFPI. Antifreeze protein was targeted to the apoplast using a Murine leader peptide sequence from the mAb24 light chain or retained in the endoplasmic reticulum using C-terminus KDEL sequence. The coding sequences were placed downstream of the rice Actin promoter and Actin-1 intron and upstream of the nopaline synthase terminator in the plant expression vectors. Transgenic wheat lines were generated through micro projectile bombardment of immature embryos of spring wheat cultivar Seri 82. Levels of antifreeze protein in the transgenic lines without any targeting peptide were low (0.06-0.07%). The apoplast-targeted protein reached a level of 1.61% of total soluble protein, 90% of which was present in the apoplast. ER-retained protein accumulated in the cells at levels up to 0.65% of total soluble proteins. Transgenic wheat line T-8 with apoplast-targeted antifreeze protein exhibited the highest levels of antifreeze activity and provided significant freezing protection even at temperatures as low as -7 degrees C.

  12. K-Targeted Metabolomic Analysis Extends Chemical Subtraction to DESIGNER Extracts: Selective Depletion of Extracts of Hops (Humulus lupulus)⊥

    Science.gov (United States)

    2015-01-01

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid–liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DESIGNER extract = total extract ± target compound(s). Expanding the scope of the recently reported depletion of extracts by immunoaffinity or solid phase liquid chromatography, the present approach allows a more flexible, single- or multi-targeted removal of constituents from complex extracts such as botanicals. Chemical subtraction enables both chemical and biological characterization, including detection of synergism/antagonism by both the subtracted targets and the remaining metabolite mixture, as well as definition of the residual complexity of all fractions. The feasibility of the DESIGNER concept is shown by K-targeted subtraction of four bioactive prenylated phenols, isoxanthohumol (1), 8-prenylnaringenin (2), 6-prenylnaringenin (3), and xanthohumol (4), from a standardized hops (Humulus lupulus L.) extract using specific solvent systems. Conversely, adding K-targeted isolates allows enrichment of the original extract and hence provides an augmented DESIGNER material. Multiple countercurrent separation steps were used to purify each of the four compounds, and four DESIGNER extracts with varying depletions were prepared. The DESIGNER approach innovates the characterization of chemically complex extracts through integration of enabling technologies such as countercurrent separation, K-by-bioactivity, the residual complexity concepts, as well as quantitative analysis by 1H NMR, LC-MS, and HiFSA-based NMR fingerprinting. PMID:25437744

  13. Left Ventricular Lead Placement Targeted at the Latest Activated Site Guided by Electrophysiological Mapping in Coronary Sinus Branches Improves Response to Cardiac Resynchronization Therapy.

    Science.gov (United States)

    Liang, Yanchun; Yu, Haibo; Zhou, Weiwei; Xu, Guoqing; Sun, Y I; Liu, Rong; Wang, Zulu; Han, Yaling

    2015-12-01

    Electrophysiological mapping (EPM) in coronary sinus (CS) branches is feasible for guiding LV lead placement to the optimal, latest activated site at cardiac resynchronization therapy (CRT) procedures. However, whether this procedure optimizes the response to CRT has not been demonstrated. This study was to evaluate effects of targeting LV lead at the latest activated site guided by EPM during CRT. Seventy-six consecutive patients with advanced heart failure who were referred for CRT were divided into mapping (MG) and control groups (CG). In MG, the LV lead, also used as a mapping bipolar electrode, was placed at the latest activated site determined by EPM in CS branches. In CG, conventional CRT procedure was performed. Patients were followed for 6 months after CRT. Baseline characteristics were comparable between the 2 groups. In MG (n = 29), EPM was successfully performed in 85 of 91 CS branches during CRT. A LV lead was successfully placed at the latest activated site guided by EPM in 27 (93.1%) patients. Compared with CG (n = 47), MG had a significantly higher rate (86.2% vs. 63.8%, P = 0.039) of response (>15% reduction in LV end-systolic volume) to CRT, a higher percentage of patients with clinical improvement of ≥2 NYHA functional classes (72.4% vs. 44.7%, P = 0.032), and a shorter QRS duration (P = 0.004). LV lead placed at the latest activated site guided by EPM resulted in a significantly greater CRT response, and a shorter QRS duration. © 2015 Wiley Periodicals, Inc.

  14. Extended Emotions

    DEFF Research Database (Denmark)

    Krueger, Joel; Szanto, Thomas

    2016-01-01

    beyond the neurophysiological confines of organisms; some even argue that emotions can be socially extended and shared by multiple agents. Call this the extended emotions thesis (ExE). In this article, we consider different ways of understanding ExE in philosophy, psychology, and the cognitive sciences....... First, we outline the background of the debate and discuss different argumentative strategies for ExE. In particular, we distinguish ExE from cognate but more moderate claims about the embodied and situated nature of cognition and emotion (Section 1). We then dwell upon two dimensions of ExE: emotions......Until recently, philosophers and psychologists conceived of emotions as brain- and body-bound affairs. But researchers have started to challenge this internalist and individualist orthodoxy. A rapidly growing body of work suggests that some emotions incorporate external resources and thus extend...

  15. Extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1993-01-01

    Physicists firmly believe that the differential equations of nature should be hyperbolic so as to exclude action at a distance; yet the equations of irreversible thermodynamics - those of Navier-Stokes and Fourier - are parabolic. This incompatibility between the expectation of physicists and the classical laws of thermodynamics has prompted the formulation of extended thermodynamics. After describing the motifs and early evolution of this new branch of irreversible thermodynamics, the authors apply the theory to mon-atomic gases, mixtures of gases, relativistic gases, and "gases" of phonons and photons. The discussion brings into perspective the various phenomena called second sound, such as heat propagation, propagation of shear stress and concentration, and the second sound in liquid helium. The formal mathematical structure of extended thermodynamics is exposed and the theory is shown to be fully compatible with the kinetic theory of gases. The study closes with the testing of extended thermodynamics thro...

  16. Lead Discovery of Type II BRAF V600E Inhibitors Targeting the Structurally Validated DFG-Out Conformation Based upon Selected Fragments

    Directory of Open Access Journals (Sweden)

    Qingwen Zhang

    2016-07-01

    Full Text Available The success of the first approved kinase inhibitor imatinib has spurred great interest in the development of type II inhibitors targeting the inactive DFG-out conformation, wherein the Phe of the DFG motif at the start of the activation loop points into the ATP binding site. Nevertheless, kinase inhibitors launched so far are heavily biased toward type I inhibitors targeting the active DFG-in conformation, wherein the Phe of the DFG motif flips by approximately 180° relative to the inactive conformation, resulting in Phe and Asp swapping their positions. Data recently obtained with structurally validated type II inhibitors supported the conclusion that type II inhibitors are more selective than type I inhibitors. In our type II BRAF V600E inhibitor lead discovery effort, we identified phenylaminopyrimidine (PAP and unsymmetrically disubstituted urea as two fragments that are frequently presented in FDA-approved protein kinase inhibitors. We therefore defined PAP and unsymmetrically disubstituted urea as privileged fragments for kinase drug discovery. A pharmacophore for type II inhibitors, 4-phenylaminopyrimidine urea (4-PAPU, was assembled based upon these privileged fragments. Lead compound SI-046 with BRAF V600E inhibitory activity comparable to the template compound sorafenib was in turn obtained through preliminary structure–activity relationship (SAR study. Molecular docking suggested that SI-046 is a bona fide type II kinase inhibitor binding to the structurally validated “classical DFG-out” conformation of BRAF V600E. Our privileged fragments-based approach was shown to efficiently deliver a bona fide type II kinase inhibitor lead. In essence, the theme of this article is to showcase the strategy and rationale of our approach.

  17. Comparison of inert supports in laser desorption/ionization mass spectrometry of peptides: pencil lead, porous silica gel, DIOS-chip and NALDI target.

    Science.gov (United States)

    Shenar, Nawar; Cantel, Sonia; Martinez, Jean; Enjalbal, Christine

    2009-08-01

    In the search for alternative inert surfaces replacing silicon chips in Desorption/Ionization On porous Silicon (DIOS)-like mass spectrometry analyses, nanostructured silicon-based NALDI chips were evaluated in Laser Desorption/Ionization (LDI) of peptides. Comparisons were made using commercially available DIOS chips (MassPREP-DIOS-target), amorphous carbon powder from lead pencil and porous silica gel used for chromatographic purposes as reference supports. A set of synthetic model peptides presenting variable amino acid sequences of various lengths was analyzed under all conditions. The LDI responses of the four 'matrix-free' techniques were compared, especially in terms of peptide detection sensitivity and overall experiment robustness. Copyright (c) 2009 John Wiley & Sons, Ltd.

  18. Rational extended thermodynamics

    CERN Document Server

    Müller, Ingo

    1998-01-01

    Ordinary thermodynamics provides reliable results when the thermodynamic fields are smooth, in the sense that there are no steep gradients and no rapid changes. In fluids and gases this is the domain of the equations of Navier-Stokes and Fourier. Extended thermodynamics becomes relevant for rapidly varying and strongly inhomogeneous processes. Thus the propagation of high­ frequency waves, and the shape of shock waves, and the regression of small-scale fluctuation are governed by extended thermodynamics. The field equations of ordinary thermodynamics are parabolic while extended thermodynamics is governed by hyperbolic systems. The main ingredients of extended thermodynamics are • field equations of balance type, • constitutive quantities depending on the present local state and • entropy as a concave function of the state variables. This set of assumptions leads to first order quasi-linear symmetric hyperbolic systems of field equations; it guarantees the well-posedness of initial value problems and f...

  19. New orally active DNA minor groove binding small molecule CT-1 acts against breast cancer by targeting tumor DNA damage leading to p53-dependent apoptosis.

    Science.gov (United States)

    Saini, Karan Singh; Hamidullah; Ashraf, Raghib; Mandalapu, Dhanaraju; Das, Sharmistha; Siddiqui, Mohd Quadir; Dwivedi, Sonam; Sarkar, Jayanta; Sharma, Vishnu Lal; Konwar, Rituraj

    2017-04-01

    Targeting tumor DNA damage and p53 pathway is a clinically established strategy in the development of cancer chemotherapeutics. Majority of anti-cancer drugs are delivered through parenteral route for reasons like severe toxicity, lack of stability, and poor enteral absorption. Current DNA targeting drugs in clinical like anthracycline suffers from major drawbacks like cardiotoxicity. Here, we report identification of a new orally active small molecule curcumin-triazole conjugate (CT-1) with significant anti-breast cancer activity in vitro and in vivo. CT-1 selectively and significantly inhibits viability of breast cancer cell lines; retards cells cycle progression at S phase and induce mitochondrial-mediated cell apoptosis. CT-1 selectively binds to minor groove of DNA and induces DNA damage leading to increase in p53 along with decrease in its ubiquitination. Inhibition of p53 with pharmacological inhibitor as well as siRNA revealed the necessity of p53 in CT-1-mediated anti-cancer effects in breast cancer cells. Studies using several other intact p53 and deficient p53 cancer cell lines further confirmed necessity of p53 in CT-1-mediated anti-cancer response. Pharmacological inhibition of pan-caspase showed CT-1 induces caspase-dependent cell death in breast cancer cells. Most interestingly, oral administration of CT-1 induces significant inhibition of tumor growth in LA-7 syngeneic orthotropic rat mammary tumor model. CT-1 treated mammary tumor shows enhancement in DNA damage, p53 upregulation, and apoptosis. Collectively, CT-1 exhibits potent anti-cancer effect both in vitro and in vivo and could serve as a safe orally active lead for anti-cancer drug development. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. HSV-1 targets lymphatic vessels in the eye and draining lymph node of mice leading to edema in the absence of a functional type I interferon response.

    Science.gov (United States)

    Bryant-Hudson, Katie M; Chucair-Elliott, Ana J; Conrady, Christopher D; Cohen, Alex; Zheng, Min; Carr, Daniel J J

    2013-10-01

    Herpes simplex virus type-1 (HSV-1) induces new lymphatic vessel growth (lymphangiogenesis) in the cornea via expression of vascular endothelial growth factor by virally infected epithelial cells. Here, we extend this observation to demonstrate the selective targeting of corneal lymphatics by HSV-1 in the absence of functional type I interferon (IFN) pathway. Specifically, we examined the impact of HSV-1 replication on angiogenesis using type I IFN receptor deficient (CD118(-/-)) mice. HSV-1-induced lymphatic and blood vessel growth into the cornea proper was time-dependent in immunocompetent animals. In contrast, there was an initial robust growth of lymphatic vessels into the cornea of HSV-1-infected CD118(-/-)mice, but such vessels disappeared by day 5 postinfection. The loss was selective as blood vessel integrity remained intact. Magnetic resonance imaging and confocal microscopy analysis of the draining lymph nodes of CD118(-/-) mice revealed extensive edema and loss of lymphatics compared with wild-type mice. In addition to a loss of lymphatic vessels in CD118(-/-) mice, HSV-1 infection resulted in epithelial thinning associated with geographic lesions and edema within the cornea, which is consistent with a loss of lymphatic vasculature. These results underscore the key role functional type I IFN pathway plays in the maintenance of structural integrity within the cornea in addition to the anti-viral characteristics often ascribed to the type I IFN cytokine family. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  1. date extended

    Indian Academy of Sciences (India)

    C A L AN DER OF EVENTS. Date of issue of bid document : 2016 September 21. Extended Due date and Time for Receipt of Tender : Up to 2016 October 17, Time 13:00 Hrs. Date and Time of opening of bid : 2016 October 17, Time 15:00 Hrs. Cost of Bid Document : Rs. 100/- only (Non-refundable). Earnest Money Deposit ...

  2. Extending Puppet

    CERN Document Server

    Franceschi, Alessandro

    2014-01-01

    This book is a clear, detailed and practical guide to learn about designing and deploying you puppet architecture, with informative examples to highlight and explain concepts in a focused manner. This book is designed for users who already have good experience with Puppet, and will surprise experienced users with innovative topics that explore how to design, implement, adapt, and deploy a Puppet architecture. The key to extending Puppet is the development of types and providers, for which you must be familiar with Ruby.

  3. Oncogenic ras-driven cancer cell vesiculation leads to emission of double-stranded DNA capable of interacting with target cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Tae Hoon; Chennakrishnaiah, Shilpa [Montreal Children’s Hospital, Research Institute of McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Audemard, Eric [McGill University and Genome Quebec Innovation Centre, Montreal, Quebec (Canada); Montermini, Laura; Meehan, Brian [Montreal Children’s Hospital, Research Institute of McGill University Health Centre, McGill University, Montreal, Quebec (Canada); Rak, Janusz, E-mail: janusz.rak@mcgill.ca [Montreal Children’s Hospital, Research Institute of McGill University Health Centre, McGill University, Montreal, Quebec (Canada)

    2014-08-22

    Highlights: • Oncogenic H-ras stimulates emission of extracellular vesicles containing double-stranded DNA. • Vesicle-associated extracellular DNA contains mutant N-ras sequences. • Vesicles mediate intercellular transfer of mutant H-ras DNA to normal fibroblasts where it remains for several weeks. • Fibroblasts exposed to vesicles containing H-ras DNA exhibit increased proliferation. - Abstract: Cell free DNA is often regarded as a source of genetic cancer biomarkers, but the related mechanisms of DNA release, composition and biological activity remain unclear. Here we show that rat epithelial cell transformation by the human H-ras oncogene leads to an increase in production of small, exosomal-like extracellular vesicles by viable cancer cells. These EVs contain chromatin-associated double-stranded DNA fragments covering the entire host genome, including full-length H-ras. Oncogenic N-ras and SV40LT sequences were also found in EVs emitted from spontaneous mouse brain tumor cells. Disruption of acidic sphingomyelinase and the p53/Rb pathway did not block emission of EV-related oncogenic DNA. Exposure of non-transformed RAT-1 cells to EVs containing mutant H-ras DNA led to the uptake and retention of this material for an extended (30 days) but transient period of time, and stimulated cell proliferation. Thus, our study suggests that H-ras-mediated transformation stimulates vesicular emission of this histone-bound oncogene, which may interact with non-transformed cells.

  4. Ginger components as new leads for the design and development of novel multi-targeted anti-Alzheimer’s drugs: a computational investigation

    Directory of Open Access Journals (Sweden)

    Azam F

    2014-10-01

    Full Text Available Faizul Azam,1,2 Abdualrahman M Amer,1 Abdullah R Abulifa,1 Mustafa M Elzwawi1 1Faculty of Pharmacy, Misurata University, Misurata, Libya; 2Department of Pharmaceutical Chemistry, Nims Institute of Pharmacy, Nims University, Jaipur, Rajasthan, India Abstract: Ginger (Zingiber officinale, despite being a common dietary adjunct that contributes to the taste and flavor of foods, is well known to contain a number of potentially bioactive phytochemicals having valuable medicinal properties. Although recent studies have emphasized their benefits in Alzheimer’s disease, limited information is available on the possible mechanism by which it renders anti-Alzheimer activity. Therefore, the present study seeks to employ molecular docking studies to investigate the binding interactions between active ginger components and various anti-Alzheimer drug targets. Lamarckian genetic algorithm methodology was employed for docking of 12 ligands with 13 different target proteins using AutoDock 4.2 program. Docking protocol was validated by re-docking of all native co-crystallized ligands into their original binding cavities exhibiting a strong correlation coefficient value (r2=0.931 between experimentally reported and docking predicted activities. This value suggests that the approach could be a promising computational tool to aid optimization of lead compounds obtained from ginger. Analysis of binding energy, predicted inhibition constant, and hydrophobic/hydrophilic interactions of ligands with target receptors revealed acetylcholinesterase as most promising, while c-Jun N-terminal kinase was recognized as the least favorable anti-Alzheimer’s drug target. Common structural requirements include hydrogen bond donor/acceptor area, hydrophobic domain, carbon spacer, and distal hydrophobic domain flanked by hydrogen bond donor/acceptor moieties. In addition, drug-likeness score and molecular properties responsible for a good pharmacokinetic profile were calculated

  5. Ecotoxicology: Lead

    Science.gov (United States)

    Scheuhammer, A.M.; Beyer, W.N.; Schmitt, C.J.; Jorgensen, Sven Erik; Fath, Brian D.

    2008-01-01

    Lead (Pb) is a naturally occurring metallic element; trace concentrations are found in all environmental media and in all living things. However, certain human activities, especially base metal mining and smelting; combustion of leaded gasoline; the use of Pb in hunting, target shooting, and recreational angling; the use of Pb-based paints; and the uncontrolled disposal of Pb-containing products such as old vehicle batteries and electronic devices have resulted in increased environmental levels of Pb, and have created risks for Pb exposure and toxicity in invertebrates, fish, and wildlife in some ecosystems.

  6. Synergistic and targeted therapy with a procaspase-3 activator and temozolomide extends survival in glioma rodent models and is feasible for the treatment of canine malignant glioma patients.

    Science.gov (United States)

    Joshi, Avadhut D; Botham, Rachel C; Schlein, Lisa J; Roth, Howard S; Mangraviti, Antonella; Borodovsky, Alexandra; Tyler, Betty; Joslyn, Steve; Looper, Jayme S; Podell, Michael; Fan, Timothy M; Hergenrother, Paul J; Riggins, Gregory J

    2017-10-06

    Glioblastoma is a deadly brain cancer with a median survival time of ∼15 months. Ionizing radiation plus the DNA alkylator temozolomide (TMZ) is the current standard therapy. PAC-1, a procaspase-3 activating small molecule, is blood-brain barrier penetrant and has previously demonstrated ability to synergize with diverse pro-apoptotic chemotherapeutics. We studied if PAC-1 could enhance the activity of TMZ, and whether addition of PAC-1 to standard treatment would be feasible in spontaneous canine malignant gliomas. Using cell lines and online gene expression data, we identified procaspase-3 as a potential molecular target for most glioblastomas. We investigated PAC-1 as a single agent and in combination with TMZ against glioma cells in culture and in orthotopic rodent models of glioma. Three dogs with spontaneous gliomas were treated with an analogous human glioblastoma treatment protocol, with concurrent PAC-1. Procaspase-3 is expressed in gliomas, with higher gene expression correlating with increased tumor grade and decreased prognosis. PAC-1 is cytotoxic to glioma cells in culture and active in orthotopic rodent glioma models. PAC-1 added to TMZ treatments in cell culture increases apoptotic death, and the combination significantly increases survival in orthotopic glioma models. Addition of PAC-1 to TMZ and radiation was well-tolerated in 3 out of 3 pet dogs with spontaneous glioma, and partial to complete tumor reductions were observed. Procaspase-3 is a clinically relevant target for treatment of glioblastoma. Synergistic activity of PAC-1/TMZ in rodent models and the demonstration of feasibility of the combined regime in canine patients suggest potential for PAC-1 in the treatment of glioblastoma.

  7. Tacrine, Trolox and Tryptoline as Lead Compounds for the Design and Synthesis of Multi-target Agents for Alzheimer's Disease Therapy.

    Science.gov (United States)

    Teponnou, Gerard A K; Joubert, Jacques; Malan, Sarel F

    2017-01-01

    The versatile biological activities of tacrine, trolox and β-carboline derivatives make them promising lead structures for the development of multifunctional Alzheimer's disease (AD) agents. Based on the topology of the active site of cholinesterases and other target proteins involved in the pathogenesis of AD, we have designed and synthesized tacrine-trolox and tacrine-tryptoline hybrids with various linker chain lengths. The hybrids containing the trolox moiety (8a-8d) showed moderate to high TcAChE inhibition (IC50: 17.37 - 2200 nM), eqBuChE inhibition (IC50: 3.16 - 128.82 nM) and free radical scavenging activities (IC50: 11.48 - 49.23 µM). The hybrids with longer linker chain lengths in general showed better ChE inhibitory activity. As expected, free radical scavenging activities were not significantly affected by varying linker chain lengths. The hybrid compound containing the tryptoline moiety linked with a 7 carbon spacer to tacrine (14) displayed the best AChE and BuChE inhibitory activity (IC50 = 17.37 and 3.16 nM). Docking experiments exhibited that compounds 8d and 14 were able to bind to both the CAS and PAS of TcAChE and eqBuChE, suggesting that they will be able to inhibit ChE induced Aβ aggregation. Novel multi-target agents that exhibit good ChE inhibition (8d and 14) and anti-oxidant (8d) activity were identified as suitable candidates for further investigation.

  8. Cathepsin B is a New Drug Target for Traumatic Brain Injury Therapeutics: Evidence for E64d as a Promising Lead Drug Candidate

    Directory of Open Access Journals (Sweden)

    Gregory eHook

    2015-09-01

    Full Text Available There currently is no therapeutic drug treatment for traumatic brain injury (TBI despite decades of experimental clinical trials. This may be because the mechanistic pathways for improving TBI outcomes have yet to be identified and exploited. As such, there remains a need to seek out new molecular targets and their drug candidates to find new treatments for TBI. This review presents supporting evidence for cathepsin B, a cysteine protease, as a potentially important drug target for TBI. Cathepsin B expression is greatly up-regulated in TBI animal models, as well as in trauma patients. Importantly, knockout of the cathepsin B gene in TBI mice results in substantial improvements of TBI-caused deficits in behavior, pathology, and biomarkers, as well as improvements in related injury models. During the process of TBI-induced injury, cathepsin B likely escapes the lysosome, its normal subcellular location, into the cytoplasm or extracellular matrix (ECM where its unleashed proteolytic power causes destruction via necrotic, apoptotic, autophagic, and activated glia-induced cell death, together with ECM breakdown and inflammation. Significantly, chemical inhibitors of cathepsin B are effective for improving deficits in TBI and related injuries including ischemia, cerebral bleeding, cerebral aneurysm, edema, pain, infection, nephritis, epilepsy, rheumatoid arthritis, pancreatitis, Huntington’s disease, and Alzheimer’s disease. The inhibitor E64d shows prominent efficacy for amelioration of TBI-caused deficits in preclinical models. In clinical trials, E64d has been shown to be safe based on its toxicological profile and, thus, illustrates the compound as an excellent candidate for drug development. These data support the overall conclusion that drug development of cathepsin B inhibitors, with E64d or a novel analog as a lead drug candidate, should be accelerated to improve the outcomes of TBI and related injuries.

  9. SIGNIFICANCE OF TARGETED EXOME SEQUENCING AND METHODS OF DATA ANALYSIS IN THE DIAGNOSIS OF GENETIC DISORDERS LEADING TO THE DEVELOPMENT OF EPILEPTIC ENCEPHALOPATHY

    Directory of Open Access Journals (Sweden)

    Tatyana Victorovna Kozhanova

    2017-08-01

    Full Text Available Epilepsy is the most common serious neurological disorder, and there is a genetic basis in almost 50% of people with epilepsy. The diagnosis of genetic epilepsies makes to estimate reasons of seizures in the patient. Last decade has shown tremendous growth in gene sequencing technologies, which have made genetic tests available. The aim is to show significance of targeted exome sequencing and methods of data analysis in the diagnosis of hereditary syndromes leading to the development of epileptic encephalopathy. We examined 27 patients with с early EE (resistant to antiepileptic drugs, psychomotor and speech development delay in the psycho-neurological department. Targeted exome sequencing was performed for patients without a previously identified molecular diagnosis using 454 Sequencing GS Junior sequencer (Roche and IlluminaNextSeq 500 platform. As a result of the analysis, specific epilepsy genetic variants were diagnosed in 27 patients. The greatest number of cases was due to mutations in the SCN1A gene (7/27. The structure of mutations for other genes (mutations with a minor allele frequency of less than 0,5% are presented: ALDH7A1 (n=1, CACNA1C (n=1, CDKL5 (n=1, CNTNAP2 (n=2, DLGAP2 (n=2, DOCK7 (n=2, GRIN2B (n=2, HCN1 (n=1, NRXN1 (n=3, PCDH19 (n=1, RNASEH2B (n=2, SLC2A1 (n=1, UBE3A (n=1. The use of the exome sequencing in the genetic practice allows to significantly improve the effectiveness of medical genetic counseling, as it made possible to diagnose certain variants of genetically heterogeneous groups of diseases with similar of clinical manifestations.

  10. Extending Experiences

    DEFF Research Database (Denmark)

    A computer game's player is experiencing not only the game as a designer-made artefact, but also a multitude of social and cultural practices and contexts of both computer game play and everyday life. As a truly multidisciplinary anthology, Extending Experiences sheds new light on the mesh...... of possibilities and influences the player engages with. Part one, Experiential Structures of Play, considers some of the key concepts commonly used to address the experience of a computer game player. The second part, Bordering Play, discusses conceptual and practical overlaps of games and everyday life...... and the impacts of setting up, crossing and breaking the boundaries of game and non-game. Part three, Interfaces of Play, looks at games as technological and historical artefacts and commodities. The fourth part, Beyond Design, introduces new models for the practical and theoretical dimensions of game design....

  11. Feasibility studies for quarkonium production at a fixed-target experiment using the LHC proton and lead beams (AFTER@LHC)

    CERN Document Server

    Massacrier, L; Fleuret, F; Hadjidakis, C; Kikola, D; Lansberg, J P; Shao, H -S

    2015-01-01

    Used in the fixed-target mode, the multi-TeV LHC proton and lead beams allow for studies of heavy-flavour hadroproduction with unprecedented precision at backward rapidities - far negative Feyman-x - using conventional detection techniques. At the nominal LHC energies, quarkonia can be studies in detail in p+p, p+d and p+A collisions at sqrt(s_NN) ~ 115 GeV as well as in Pb+p and Pb+A collisions at sqrt(s_NN) ~ 72 GeV with luminosities roughly equivalent to that of the collider mode, i.e. up to 20 fb-1 yr-1 in p+p and p+d collisions, up to 0.6 fb-1 yr-1 in p+A collisions and up to 10 nb-1 yr-1 in Pb+A collisions. In this paper, we assess the feasibility of such studies by performing fast simulations using the performance of a LHCb-like detector.

  12. Mitochondria are the main source and one of the targets of Pb (lead)-induced oxidative stress in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Sousa, Cátia A; Soares, Eduardo V

    2014-06-01

    The yeast Saccharomyces cerevisiae is a useful model organism for studying lead (Pb) toxicity. Yeast cells of a laboratory S. cerevisiae strain (WT strain) were incubated with Pb concentrations up to 1,000 μmol/l for 3 h. Cells exposed to Pb lost proliferation capacity without damage to the cell membrane, and they accumulated intracellular superoxide anion (O2 (.-)) and hydrogen peroxide (H2O2). The involvement of the mitochondrial electron transport chain (ETC) in the generation of reactive oxygen species (ROS) induced by Pb was evaluated. For this purpose, an isogenic derivative ρ(0) strain, lacking mitochondrial DNA, was used. The ρ(0) strain, without respiratory competence, displayed a lower intracellular ROS accumulation and a higher resistance to Pb compared to the WT strain. The kinetic study of ROS generation in yeast cells exposed to Pb showed that the production of O2 (.-) precedes the accumulation of H2O2, which is compatible with the leakage of electrons from the mitochondrial ETC. Yeast cells exposed to Pb displayed mutations at the mitochondrial DNA level. This is most likely a consequence of oxidative stress. In conclusion, mitochondria are an important source of Pb-induced ROS and, simultaneously, one of the targets of its toxicity.

  13. Large-angle production of charged pions by 3 GeV/c - 12.9 GeV/c protons on beryllium, aluminium and lead targets

    CERN Document Server

    Catanesi, M.G.; Edgecock, R.; Ellis, Malcolm; Soler, F.J.P.; Gossling, C.; Bunyatov, S.; Krasnoperov, A.; Popov, B.; Serdiouk, V.; Tereschenko, V.; Di Capua, E.; Vidal-Sitjes, G.; Artamonov, A.; Giani, S.; Gilardoni, S.; Gorbunov, P.; Grant, A.; Grossheim, A.; Ivanchenko, V.; Kayis-Topaksu, A.; Panman, J.; Papadopoulos, I.; Tcherniaev, E.; Tsukerman, I.; Veenhof, R.; Wiebusch, C.; Zucchelli, P.; Blondel, A.; Borghi, S.; Morone, M.C.; Prior, G.; Schroeter, R.; Meurer, C.; Gastaldi, U.; Mills, G.B.; Graulich, J.S.; Gregoire, G.; Bonesini, M.; Ferri, F.; Kirsanov, M.; Bagulya, A.; Grichine, V.; Polukhina, N.; Palladino, V.; Coney, L.; Schmitz, D.; Barr, G.; De Santo, A.; Bobisut, F.; Gibin, D.; Guglielmi, A.; Mezzetto, M.; Dumarchez, J.; Dore, U.; Orestano, D.; Pastore, F.; Tonazzo, A.; Tortora, L.; Booth, C.; Howlett, L.; Bogomilov, M.; Chizhov, M.; Kolev, D.; Tsenov, R.; Piperov, Stefan; Temnikov, P.; Apollonio, M.; Chimenti, P.; Giannini, G.; Burguet-Castell, J.; Cervera-Villanueva, A.; Gomez-Cadenas, J.J.; Martin-Albo, J.; Novella, P.; Sorel, M.; CERN. Geneva

    2008-01-01

    Measurements of the double-differential $\\pi^{\\pm}$ production cross-section in the range of momentum $100 \\MeVc \\leq p < 800 \\MeVc$ and angle $0.35 \\rad \\leq \\theta < 2.15 \\rad$ in proton--beryllium, proton--aluminium and proton--lead collisions are presented. The data were taken with the HARP detector in the T9 beam line of the CERN PS. The pions were produced by proton beams in a momentum range from 3 \\GeVc to 12.9 \\GeVc hitting a target with a thickness of 5% of a nuclear interaction length. The tracking and identification of the produced particles was performed using a small-radius cylindrical time projection chamber (TPC) placed inside a solenoidal magnet. Incident particles were identified by an elaborate system of beam detectors. Results are obtained for the double-differential cross-sections at six incident proton beam momenta (3 \\GeVc, 5 \\GeVc, 8 \\GeVc, 8.9 \\GeVc (Be only), 12 \\GeVc and 12.9 \\GeVc (Al only)) and compared to previously available data.

  14. π-Extended Tetrathiafulvalenes

    DEFF Research Database (Denmark)

    Petersen, Johannes Fabritius

    This Ph.D.-thesis focuses on the synthesis and properties of various redox-active ¼-extended tetrathiafulvalenes. One class of molecules are so-called H-cruciform shaped molecules. In these molecules the formation of a central stilbene double bond is elucidated. Here it was found that the formation...... of the stilbene bond originates from preformation of a 1,3-dioxa-2-phospholane, formed by reaction between P(OEt)3 present under the reaction conditions and two aldehydes. Under the reaction conditions this 1,3-dioxa-2-phospholane can then be converted to the stilbene. These mechanistic studies lead...

  15. CRISPR-Cas9 Targeted Mutagenesis Leads to Simultaneous Modification of Different Homoeologous Gene Copies in Polyploid Oilseed Rape (Brassica napus).

    Science.gov (United States)

    Braatz, Janina; Harloff, Hans-Joachim; Mascher, Martin; Stein, Nils; Himmelbach, Axel; Jung, Christian

    2017-06-01

    In polyploid species, altering a trait by random mutagenesis is highly inefficient due to gene redundancy. We have stably transformed tetraploid oilseed rape (Brassica napus) with a CRISPR-Cas9 construct targeting two ALCATRAZ (ALC) homoeologs. ALC is involved in valve margin development and, thus, contributes to seed shattering from mature fruits. Knocking out ALC would increase shatter resistance to avoid seed loss during mechanical harvest. We obtained a transgenic T1 plant with four alc mutant alleles by the use of a single target sequence. All mutations were stably inherited to the T2 progeny. The T2 generation was devoid of any wild-type alleles, proving that the underlying T1 was a nonchimeric double heterozygote. T-DNA and ALC loci were not linked, as indicated by random segregation in the T2 generation. Hence, we could select double mutants lacking the T-DNA already in the first offspring generation. However, whole-genome sequencing data revealed at least five independent insertions of vector backbone sequences. We did not detect any off-target effects in two genome regions homologous to the target sequence. The simultaneous alteration of multiple homoeologs by CRISPR-Cas9 mutagenesis without any background mutations will offer new opportunities for using mutant genotypes in rapeseed breeding. © 2017 American Society of Plant Biologists. All Rights Reserved.

  16. Market Diffusion of Extended Cycle Hormonal Contraceptives

    Directory of Open Access Journals (Sweden)

    Megen Leeds Schumacher, Pharm.D.

    2012-01-01

    Full Text Available Background: Extended cycle hormonal contraceptives (e.g. Seasonale, Seasonique when introduced in 2003 were considered a very novel approach to contraception. The idea of manipulating the menstrual cycle so that women would experience just four menstruations a year was radical and was assumed to be responsible for the slow acceptance rate among the general public.Objective: This report analyzes two different aspects of the acceptance of this unique idea in the population. The first was the level of usage of extended cycle hormonal contraceptives in the general population, which was measured by a review of sales figures over time in the United States. The second was an examination of market diffusion as it relates to consumer perceptions regarding the characteristics of these products.Methods: To determine the degree of usage of extended cycle hormonal contraceptives the yearly sales, in terms of units sold, were compared with that of other leading methods of hormonal contraception. Along with the data, survey answers were obtained from 65 women who volunteered to participate in the study. Participants were selected randomly to represent the target population to assess the level of awareness about the benefits, risks, and any other concerns regarding the use of extended cycle hormonal contraceptives.Results: The yearly sales data of units sold showed a definitive increase in the sales of extended cycle hormonal contraceptives since their release on the market. The survey results showed an overwhelming awareness in the study population about the extended regimen. However, only about half of the women in the survey group were aware of its benefits. The main concern reported was the perceived significant side effect profile.Conclusion: Though awareness about the extended cycle hormonal contraception regimen was widespread, the survey population was not well informed about the advantages and the disadvantages regarding the degree of severity of side

  17. Targeting Tryptophan Decarboxylase to Selected Subcellular Compartments of Tobacco Plants Affects Enzyme Stability and in Vivo Function and Leads to a Lesion-Mimic Phenotype1

    Science.gov (United States)

    Di Fiore, Stefano; Li, Qiurong; Leech, Mark James; Schuster, Flora; Emans, Neil; Fischer, Rainer; Schillberg, Stefan

    2002-01-01

    Tryptophan decarboxylase (TDC) is a cytosolic enzyme that catalyzes an early step of the terpenoid indole alkaloid biosynthetic pathway by decarboxylation of l-tryptophan to produce the protoalkaloid tryptamine. In the present study, recombinant TDC was targeted to the chloroplast, cytosol, and endoplasmic reticulum (ER) of tobacco (Nicotiana tabacum) plants to evaluate the effects of subcellular compartmentation on the accumulation of functional enzyme and its corresponding enzymatic product. TDC accumulation and in vivo function was significantly affected by the subcellular localization. Immunoblot analysis demonstrated that chloroplast-targeted TDC had improved accumulation and/or stability when compared with the cytosolic enzyme. Because ER-targeted TDC was not detectable by immunoblot analysis and tryptamine levels found in transient expression studies and in transgenic plants were low, it was concluded that the recombinant TDC was most likely unstable if ER retained. Targeting TDC to the chloroplast stroma resulted in the highest accumulation level of tryptamine so far reported in the literature for studies on heterologous TDC expression in tobacco. However, plants accumulating high levels of functional TDC in the chloroplast developed a lesion-mimic phenotype that was probably triggered by the relatively high accumulation of tryptamine in this compartment. We demonstrate that subcellular targeting may provide a useful strategy for enhancing accumulation and/or stability of enzymes involved in secondary metabolism and to divert metabolic flux toward desired end products. However, metabolic engineering of plants is a very demanding task because unexpected, and possibly unwanted, effects may be observed on plant metabolism and/or phenotype. PMID:12114570

  18. Lead Test

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Lead Send Us Your Feedback Choose Topic At a ... Related Content View Sources Also Known As Blood Lead Test Blood Lead Level BLL Formal Name Lead, ...

  19. Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development.

    Science.gov (United States)

    Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G; Graham, Mark J; Berliner, Judith A; Lusis, Aldons J; Cai, Lei; Temel, Ryan E; Rateri, Debra L; Lee, Sangderk

    2017-01-01

    The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting.

  20. Sub-chronic inhalation of lead oxide nanoparticles revealed their broad distribution and tissue-specific subcellular localization in target organs

    Czech Academy of Sciences Publication Activity Database

    Dumková, J.; Smutná, Tereza; Vrlíková, Lucie; Le Coustumer, P.; Večeřa, Zbyněk; Dočekal, Bohumil; Mikuška, Pavel; Čapka, Lukáš; Fictum, P.; Hampl, A.; Buchtová, Marcela

    2017-01-01

    Roč. 14, č. 1 (2017), č. článku 55. ISSN 1743-8977 R&D Projects: GA ČR(CZ) GAP503/11/2315; GA ČR(CZ) GBP503/12/G147 Institutional support: RVO:67985904 ; RVO:68081715 Keywords : nanoparticles * lead oxide * electron microscopy * toxicity * inhalation Subject RIV: EA - Cell Biology; CB - Analytical Chemistry, Separation (UIACH-O) Impact factor: 8.577, year: 2016

  1. Extending the Schizosaccharomyces pombe molecular genetic toolbox.

    Directory of Open Access Journals (Sweden)

    Dorota Fennessy

    Full Text Available Targeted alteration of the genome lies at the heart of the exploitation of S. pombe as a model system. The rate of analysis is often determined by the efficiency with which a target locus can be manipulated. For most loci this is not a problem, however for some loci, such as fin1+, rates of gene targeting below 5% can limit the scope and scale of manipulations that are feasible within a reasonable time frame. We now describe a simple modification of transformation procedure for directing integration of genomic sequences that leads to a 5-fold increase in the transformation efficiency when antibiotic based dominant selection markers are used. We also show that removal of the pku70+ and pku80+ genes, which encode DNA end binding proteins required for the non-homologous end joining DNA repair pathway, increases the efficiency of gene targeting at fin1+ to around 75-80% (a 16-fold increase. We describe how a natMX6/rpl42+ cassette can be used for positive and negative selection for integration at a targeted locus. To facilitate the evaluation of the impact of a series of mutations on the function of a gene of interest we have generated three vector series that rely upon different selectable markers to direct the expression of tagged/untagged molecules from distinct genomic integration sites. pINTL and pINTK vectors use ura4+ selection to direct disruptive integration of leu1+ and lys1+ respectively, while pINTH vectors exploit nourseothricin resistance to detect the targeted disruption of a hygromycin B resistance conferring hphMX6 cassette that has been integrated on chromosome III. Finally, we have generated a series of multi-copy expression vectors that use resistance to nourseothricin or kanamycin/G418 to select for propagation in prototrophic hosts. Collectively these protocol modifications and vectors extend the versatility of this key model system.

  2. Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS.

    Science.gov (United States)

    Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F; Bauer, Peter O; Chew, Jeannie; Yang, Wang-Yong; Fostvedt, Erik; Jansen-West, Karen; Belzil, Veronique V; Desaro, Pamela; Johnston, Amelia; Overstreet, Karen; Oh, Seok-Yoon; Todd, Peter K; Berry, James D; Cudkowicz, Merit E; Boeve, Bradley F; Dickson, Dennis; Floeter, Mary Kay; Traynor, Bryan J; Morelli, Claudia; Ratti, Antonia; Silani, Vincenzo; Rademakers, Rosa; Brown, Robert H; Rothstein, Jeffrey D; Boylan, Kevin B; Petrucelli, Leonard; Disney, Matthew D

    2014-09-03

    A repeat expansion in C9ORF72 causes frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). RNA of the expanded repeat (r(GGGGCC)exp) forms nuclear foci or undergoes repeat-associated non-ATG (RAN) translation, producing "c9RAN proteins." Since neutralizing r(GGGGCC)exp could inhibit these potentially toxic events, we sought to identify small-molecule binders of r(GGGGCC)exp. Chemical and enzymatic probing of r(GGGGCC)8 indicate that it adopts a hairpin structure in equilibrium with a quadruplex structure. Using this model, bioactive small molecules targeting r(GGGGCC)exp were designed and found to significantly inhibit RAN translation and foci formation in cultured cells expressing r(GGGGCC)66 and neurons transdifferentiated from fibroblasts of repeat expansion carriers. Finally, we show that poly(GP) c9RAN proteins are specifically detected in c9ALS patient cerebrospinal fluid. Our findings highlight r(GGGGCC)exp-binding small molecules as a possible c9FTD/ALS therapeutic and suggest that c9RAN proteins could potentially serve as a pharmacodynamic biomarker to assess efficacy of therapies that target r(GGGGCC)exp. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  4. Lead optimization of N-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: discovery of PKI-402.

    Science.gov (United States)

    Dehnhardt, Christoph M; Venkatesan, Aranapakam M; Delos Santos, Efren; Chen, Zecheng; Santos, Osvaldo; Ayral-Kaloustian, Semiramis; Brooijmans, Natasja; Mallon, Robert; Hollander, Irwin; Feldberg, Larry; Lucas, Judy; Chaudhary, Inder; Yu, Ker; Gibbons, Jay; Abraham, Robert; Mansour, Tarek S

    2010-01-28

    Herein we describe the identification and lead optimization of triazolopyrimidines as a novel class of potent dual PI3K/mTOR inhibitors, resulting in the discovery of 3 (PKI-402). Compound 3 exhibits good physical properties and PK parameters, low nanomolar potency against PI3Kalpha and mTOR, and excellent inhibition of cell proliferation in several human cancer cell lines. Furthermore, in vitro and in vivo biomarker studies demonstrated the ability of 3 to shut down the PI3K/Akt pathway and induce apoptosis in cancer cells. In addition, 3 showed excellent in vivo efficacy in various human cancer xenografts, validating suppression of PI3K/mTOR signaling as a potential anticancer therapy.

  5. Silicone chain extender

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a silicone chain extender, more particularly a chain extender for silicone polymers and copolymers, to a chain extended silicone polymer or copolymer and to a functionalized chain extended silicone polymer or copolymer, to a method for the preparation thereof...

  6. A human polymorphism affects NEDD4L subcellular targeting by leading to two isoforms that contain or lack a C2 domain.

    Science.gov (United States)

    Garrone, Nicholas F; Blazer-Yost, Bonnie L; Weiss, Robert B; Lalouel, Jean-Marc; Rohrwasser, Andreas

    2009-04-13

    Ubiquitination serves multiple cellular functions, including proteasomal degradation and the control of stability, function, and intracellular localization of a wide variety of proteins. NEDD4L is a member of the HECT class of E3 ubiquitin ligases. A defining feature of NEDD4L protein isoforms is the presence or absence of an amino-terminal C2 domain, a class of subcellular, calcium-dependent targeting domains. We previously identified a common variant in human NEDD4L that generates isoforms that contain or lack a C2 domain. To address the potential functional significance of the NEDD4L common variant on NEDD4L subcellular localization, NEDD4L isoforms that either contained or lacked a C2 domain were tagged with enhanced green fluorescent protein, transfected into Xenopus laevis kidney epithelial cells, and imaged by performing confocal microscopy on live cells. We report that the presence or absence of this C2 domain exerts differential effects on the subcellular distribution of NEDD4L, the ability of C2 containing and lacking NEDD4L isoforms to mobilize in response to a calcium stimulus, and the intracellular transport of subunits of the NEDD4L substrate, ENaC. Furthermore, the ability of the C2-containing isoform to influence beta-ENaC mobilization from intracellular pools involves the NEDD4L active site for ubiquitination. We propose a model to account for the potential impact of this common genetic variant on protein function at the cellular level. NEDD4L isoforms that contain or lack a C2 domain target different intracellular locations. Additionally, whereas the C2-containing NEDD4L isoform is capable of shuttling between the plasma membrane and intracellular compartments in response to calcium stimulus the C2-lacking isoform can not. The C2-containing isoform differentially affects the mobilization of ENaC subunits from intracellular pools and this trafficking step requires NEDD4L ubiquitin ligase activity. This observation suggests a new mechanism for the

  7. A human polymorphism affects NEDD4L subcellular targeting by leading to two isoforms that contain or lack a C2 domain

    Directory of Open Access Journals (Sweden)

    Lalouel Jean-Marc

    2009-04-01

    Full Text Available Abstract Background Ubiquitination serves multiple cellular functions, including proteasomal degradation and the control of stability, function, and intracellular localization of a wide variety of proteins. NEDD4L is a member of the HECT class of E3 ubiquitin ligases. A defining feature of NEDD4L protein isoforms is the presence or absence of an amino-terminal C2 domain, a class of subcellular, calcium-dependent targeting domains. We previously identified a common variant in human NEDD4L that generates isoforms that contain or lack a C2 domain. Results To address the potential functional significance of the NEDD4L common variant on NEDD4L subcellular localization, NEDD4L isoforms that either contained or lacked a C2 domain were tagged with enhanced green fluorescent protein, transfected into Xenopus laevis kidney epithelial cells, and imaged by performing confocal microscopy on live cells. We report that the presence or absence of this C2 domain exerts differential effects on the subcellular distribution of NEDD4L, the ability of C2 containing and lacking NEDD4L isoforms to mobilize in response to a calcium stimulus, and the intracellular transport of subunits of the NEDD4L substrate, ENaC. Furthermore, the ability of the C2-containing isoform to influence β-ENaC mobilization from intracellular pools involves the NEDD4L active site for ubiquitination. We propose a model to account for the potential impact of this common genetic variant on protein function at the cellular level. Conclusion NEDD4L isoforms that contain or lack a C2 domain target different intracellular locations. Additionally, whereas the C2-containing NEDD4L isoform is capable of shuttling between the plasma membrane and intracellular compartments in response to calcium stimulus the C2-lacking isoform can not. The C2-containing isoform differentially affects the mobilization of ENaC subunits from intracellular pools and this trafficking step requires NEDD4L ubiquitin ligase

  8. MicroRNA miR-29c down-regulation leading to de-repression of its target DNA methyltransferase 3a promotes ischemic brain damage.

    Directory of Open Access Journals (Sweden)

    Gopal Pandi

    Full Text Available Recent studies showed that stroke extensively alters cerebral microRNA (miRNA expression profiles and several miRNAs play a role in mediating ischemic pathophysiology. We currently evaluated the significance of miR-29c, a highly expressed miRNA in rodent brain that was significantly down-regulated after focal ischemia in adult rats as well as after oxygen-glucose deprivation in PC12 cells. Bioinformatics indicated that DNA methyltransferase 3a (DNMT3a is a major target of miR-29c and co-transfection with premiR-29c prevented DNMT3a 3'UTR vector expression. In PC12 cells, treatment with premiR-29c prevented OGD-induced cell death (by 58 ± 6%; p<0.05. Furthermore, treatment with antagomiR-29c resulted in a 46 ± 5% cell death in PC12 cells. When rats were treated with premiR-29c and subjected to transient focal ischemia, post-ischemic miR-29c levels were restored and the infarct volume decreased significantly (by 34 ± 6%; p<0.05 compared to control premiR treated group. DNMT3a siRNA treatment also significantly curtailed the post-OGD cell death in PC12 cells (by 54 ± 6%; p<0.05 and decreased the post-ischemic infarct volume in rats (by 30 ± 5%; p<0.05 compared to respective control siRNA treated groups. The miR-29c gene promoter showed specific binding sites for the transcription factor REST and the miR-29c promoter vector expression was curtailed when cotransfected with a REST expressing plasmid. Furthermore, treatment with REST siRNA prevented the post-ischemic miR-29c down-regulation and DNMT3a induction in PC12 cells and curtailed ischemic cell death (by 64 ± 9%; p<0.05 compared to control siRNA treatment. These studies suggest that miR-29c is a pro-survival miRNA and its down-regulation is a promoter of ischemic brain damage by acting through its target DNMT3a. Furthermore, REST is an upstream transcriptional controller of miR-29c and curtailing REST induction prevents miR-29c down-regulation and ischemic neuronal death.

  9. Lead Structures for Applications in Photodynamic Therapy. 6. Temoporfin Anti-Inflammatory Conjugates to Target the Tumor Microenvironment for In Vitro PDT.

    Directory of Open Access Journals (Sweden)

    Luke Rogers

    Full Text Available Due to the ongoing development of clinical photodynamic therapy (PDT, the search continues for optimized photosensitizers that can overcome some of the side effects associated with this type of treatment modality. The main protagonists being: post-treatment photosensitivity, due to only limited cellular selectivity and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory agents within the tumor microenvironment. A photosensitizer that could overcome one or both of these drawbacks would be highly attractive to those engaged in clinical PDT. Certain non-steroidal anti-inflammatory drugs (NSAIDs when used in combination with PDT have shown to increase the cytotoxicity of the treatment modality by targeting the tumor microenvironment. Temoporfin (m-THPC, the gold standard chlorin-based photosensitizer (PS since its discovery in the 1980's, has successfully been conjugated to non-steroidal anti-inflammatory compounds, in an attempt to address the issue of post-treatment tumor regrowth. Using a modified Steglich esterification reaction, a library of "iPorphyrins" was successfully synthesized and evaluated for their PDT efficacy.

  10. HAMS: High-Affinity Mass Spectrometry Screening. A High-Throughput Screening Method for Identifying the Tightest-Binding Lead Compounds for Target Proteins with No False Positive Identifications

    Science.gov (United States)

    Imaduwage, Kasun P.; Go, Eden P.; Zhu, Zhikai; Desaire, Heather

    2016-11-01

    A major challenge in drug discovery is the identification of high affinity lead compounds that bind a particular target protein; these leads are typically identified by high throughput screens. Mass spectrometry has become a detection method of choice in drug screening assays because the target and the ligand need not be modified. Label-free assays are advantageous because they can be developed more rapidly than assays requiring labels, and they eliminate the risk of the label interfering with the binding event. However, in commonly used MS-based screening methods, detection of false positives is a major challenge. Here, we describe a detection strategy designed to eliminate false positives. In this approach, the protein and the ligands are incubated together, and the non-binders are separated for detection. Hits (protein binders) are not detectable by MS after incubation with the protein, but readily identifiable by MS when the target protein is not present in the incubation media. The assay was demonstrated using three different proteins and hundreds of non-inhibitors; no false positive hits were identified in any experiment. The assay can be tuned to select for ligands of a particular binding affinity by varying the quantity of protein used and the immobilization method. As examples, the method selectively detected inhibitors that have Ki values of 0.2 μM, 50 pM, and 700 pM. These findings demonstrate that the approach described here compares favorably with traditional MS-based screening methods.

  11. Dual NAMPT and BTK Targeting Leads to Synergistic Killing of Waldenström Macroglobulinemia Cells Regardless of MYD88 and CXCR4 Somatic Mutation Status.

    Science.gov (United States)

    Cea, Michele; Cagnetta, Antonia; Acharya, Chirag; Acharya, Prakrati; Tai, Yu-Tzu; Yang, Cao; Lovera, Davide; Soncini, Debora; Miglino, Maurizio; Fraternali-Orcioni, Giulio; Mastracci, Luca; Nencioni, Alessio; Montecucco, Fabrizio; Monacelli, Fiammetta; Ballestrero, Alberto; Hideshima, Teru; Chauhan, Dharminder; Gobbi, Marco; Lemoli, Roberto M; Munshi, Nikhil; Treon, Steven P; Anderson, Kenneth C

    2016-12-15

    Nicotinamide phosphoribosyltransferase (Nampt) regulates intracellular NAD+ pool and is highly expressed in a number of malignancies. FK866, a selective inhibitor of Nampt, depletes intracellular NAD+ levels, thereby blocking cellular metabolism and triggering sensitization to other drugs and cell death. Here we characterized the antitumor effects of Nampt inhibition in Waldenström macroglobulinemia. We investigated Nampt role in MW cells using both mRNA and protein expression analyses. We have also used loss-of-function approaches to investigate the growth and survival effects of Nampt on MW cells and further tested the anti-MW activity of dual Nampt and BTK inhibition in vitro and in vivo RESULTS: We found that Waldenström macroglobulinemia cells exhibit high levels of Nampt compared with normal B cells. Loss of function studies suggested a potential oncogenic role of Nampt in Waldenström macroglobulinemia cells, and BTK-inhibitor ibrutinib and FK866 resulted in a significant and synergistic anti-Waldenström macroglobulinemia cell death, regardless of MYD88 and CXCR4 mutational status. Cell death was associated with: (i) activation of caspase-3, PARP and downregulation of Mcl-1, (ii) enhanced intracellular ATP and NAD+ depletion, (iii) inhibition of NF-κB signaling, and (iv) inhibition of multiple prosurvival signaling pathways. In a murine xenograft Waldenström macroglobulinemia model, low-dose combination FK866 and ibrutinib is well tolerated, significantly inhibits tumor growth, and prolongs host survival. Our results show intracellular NAD+ level as crucial for proliferation and survival of Waldenström macroglobulinemia cells, and provides the mechanistic preclinical rationale for targeting Nampt, either alone or with Ibrutinib, to overcome drug resistance and improve patient outcome in Waldenström macroglobulinemia. Clin Cancer Res; 22(24); 6099-109. ©2016 AACR. ©2016 American Association for Cancer Research.

  12. Diversity in the architecture of ATLs, a family of plant ubiquitin-ligases, leads to recognition and targeting of substrates in different cellular environments.

    Science.gov (United States)

    Aguilar-Hernández, Victor; Aguilar-Henonin, Laura; Guzmán, Plinio

    2011-01-01

    Ubiquitin-ligases or E3s are components of the ubiquitin proteasome system (UPS) that coordinate the transfer of ubiquitin to the target protein. A major class of ubiquitin-ligases consists of RING-finger domain proteins that include the substrate recognition sequences in the same polypeptide; these are known as single-subunit RING finger E3s. We are studying a particular family of RING finger E3s, named ATL, that contain a transmembrane domain and the RING-H2 finger domain; none of the member of the family contains any other previously described domain. Although the study of a few members in A. thaliana and O. sativa has been reported, the role of this family in the life cycle of a plant is still vague. To provide tools to advance on the functional analysis of this family we have undertaken a phylogenetic analysis of ATLs in twenty-four plant genomes. ATLs were found in all the 24 plant species analyzed, in numbers ranging from 20-28 in two basal species to 162 in soybean. Analysis of ATLs arrayed in tandem indicates that sets of genes are expanding in a species-specific manner. To get insights into the domain architecture of ATLs we generated 75 pHMM LOGOs from 1815 ATLs, and unraveled potential protein-protein interaction regions by means of yeast two-hybrid assays. Several ATLs were found to interact with DSK2a/ubiquilin through a region at the amino-terminal end, suggesting that this is a widespread interaction that may assist in the mode of action of ATLs; the region was traced to a distinct sequence LOGO. Our analysis provides significant observations on the evolution and expansion of the ATL family in addition to information on the domain structure of this class of ubiquitin-ligases that may be involved in plant adaptation to environmental stress.

  13. Diversity in the architecture of ATLs, a family of plant ubiquitin-ligases, leads to recognition and targeting of substrates in different cellular environments.

    Directory of Open Access Journals (Sweden)

    Victor Aguilar-Hernández

    Full Text Available Ubiquitin-ligases or E3s are components of the ubiquitin proteasome system (UPS that coordinate the transfer of ubiquitin to the target protein. A major class of ubiquitin-ligases consists of RING-finger domain proteins that include the substrate recognition sequences in the same polypeptide; these are known as single-subunit RING finger E3s. We are studying a particular family of RING finger E3s, named ATL, that contain a transmembrane domain and the RING-H2 finger domain; none of the member of the family contains any other previously described domain. Although the study of a few members in A. thaliana and O. sativa has been reported, the role of this family in the life cycle of a plant is still vague. To provide tools to advance on the functional analysis of this family we have undertaken a phylogenetic analysis of ATLs in twenty-four plant genomes. ATLs were found in all the 24 plant species analyzed, in numbers ranging from 20-28 in two basal species to 162 in soybean. Analysis of ATLs arrayed in tandem indicates that sets of genes are expanding in a species-specific manner. To get insights into the domain architecture of ATLs we generated 75 pHMM LOGOs from 1815 ATLs, and unraveled potential protein-protein interaction regions by means of yeast two-hybrid assays. Several ATLs were found to interact with DSK2a/ubiquilin through a region at the amino-terminal end, suggesting that this is a widespread interaction that may assist in the mode of action of ATLs; the region was traced to a distinct sequence LOGO. Our analysis provides significant observations on the evolution and expansion of the ATL family in addition to information on the domain structure of this class of ubiquitin-ligases that may be involved in plant adaptation to environmental stress.

  14. Dual NAMPT and BTK Targeting Leads to Synergistic Killing of Waldenstrom's Macroglobulinemia Cells Regardless of MYD88 and CXCR4 Somatic Mutations Status

    Science.gov (United States)

    Cea, Michele; Cagnetta, Antonia; Acharya, Chirag; Acharya, Prakrati; Tai, Yu-Tzu; Yang, Guang; Lovera, Davide; Soncini, Debora; Miglino, Maurizio; Fraternali-Orcioni, Giulio; Mastracci, Luca; Nencioni, Alessio; Montecucco, Fabrizio; Ballestrero, Alberto; Hideshima, Teru; Chauhan, Dharminder; Gobbi, Marco; Lemoli, Roberto M.; Munshi, Nikhil; Treon, Steven P.; Anderson, Kenneth C.

    2018-01-01

    Purpose Nicotinamide phosphoribosyltransferase (Nampt) regulates intracellular NAD+ pool and is highly expressed in a number of malignancies. FK866, a selective inhibitor of Nampt, depletes intracellular NAD+ levels, thereby blocking cellular metabolism and triggering sensitization to other drugs and cell death. Here we characterized the anti-tumor effects of Nampt inhibition in Waldenström Macroglobulinemia (WM). Experimental Design We investigated Nampt role in MW cells using both mRNA and protein expression analyses. We have also used loss-of-function approaches to investigate the growth and survival effects of Nampt on MW cells and further tested the anti-MW activity of dual Nampt and BTK inhibition in vitro and in vivo. Results We found that WM cells exhibit high levels of Nampt compared with normal B cells. Loss of function studies suggested a potential oncogenic role of Nampt in WM cells, and BTK-inhibitor ibrutinib and FK866 resulted in a significant and synergistic anti-WM cell death, regardless of MYD88 and CXCR4 mutational status. Cell death was associated with: 1) activation of caspase-3, PARP and down-regulation of Mcl-1; 2) enhanced intracellular ATP and NAD+ depletion; 3) inhibition of NF-kappa B signaling; and 4) inhibition of multiple pro-survival signaling pathways. In a murine xenograft WM model, low-dose combination FK866 and Ibrutinib is well tolerated, significantly inhibits tumor growth, and prolongs host survival. Conclusions our results show intracellular NAD+ level as crucial for proliferation and survival of WM cells, and provides the mechanistic preclinical rationale for targeting Nampt, either alone or with Ibrutinib, to overcome drug resistance and improve patient outcome in WM. PMID:27287071

  15. Exclusion Bounds for Extended Anyons

    Science.gov (United States)

    Larson, Simon; Lundholm, Douglas

    2017-08-01

    We introduce a rigorous approach to the many-body spectral theory of extended anyons, that is quantum particles confined to two dimensions that interact via attached magnetic fluxes of finite extent. Our main results are many-body magnetic Hardy inequalities and local exclusion principles for these particles, leading to estimates for the ground-state energy of the anyon gas over the full range of the parameters. This brings out further non-trivial aspects in the dependence on the anyonic statistics parameter, and also gives improvements in the ideal (non-extended) case.

  16. Mammalian Target of Rapamycin Inhibition in Trypanosoma cruzi-Infected Macrophages Leads to an Intracellular Profile That Is Detrimental for Infection

    Directory of Open Access Journals (Sweden)

    Jorge David Rojas Márquez

    2018-02-01

    Full Text Available The causative agent of Chagas’ disease, Trypanosoma cruzi, affects approximately 10 million people living mainly in Latin America, with macrophages being one of the first cellular actors confronting the invasion during T. cruzi infection and their function depending on their proper activation and polarization into distinct M1 and M2 subtypes. Macrophage polarization is thought to be regulated not only by cytokines and growth factors but also by environmental signals. The metabolic checkpoint kinase mammalian target of rapamycin (mTOR-mediated sensing of environmental and metabolic cues influences macrophage polarization in a complex and as of yet incompletely understood manner. Here, we studied the role of the mTOR pathway in macrophages during T. cruzi infection. We demonstrated that the parasite activated mTOR, which was beneficial for its replication since inhibition of mTOR in macrophages by different inhibitors decreased parasite replication. Moreover, in rapamycin pretreated and infected macrophages, we observed a decreased arginase activity and expression, reduced IL-10 and increased interleukin-12 production, compared to control infected macrophages treated with DMSO. Surprisingly, we also found a reduced iNOS activity and expression in these macrophages. Therefore, we investigated possible alternative mechanisms involved in controlling parasite replication in rapamycin pretreated and infected macrophages. Although, cytoplasmic ROS and the enzyme indoleamine 2, 3-dioxygenase (IDO were not involved, we observed a significant increase in IL-6, TNF-α, and IL-1β production. Taking into account that IL-1β is produced by activation of the cytoplasmic receptor NLRP3, which is one of the main components of the inflammasome, we evaluated NLRP3 expression during mTOR inhibition and T. cruzi infection. We observed that rapamycin-pretreated and infected macrophages showed a significant increase in NLRP3 expression and produced higher levels of

  17. Lead poisoning

    Science.gov (United States)

    ... or dust from lead-based paint. Toys and furniture painted before 1976. Painted toys and decorations made ... by decades of car exhaust or years of house paint scrapings. Lead is more common in soil ...

  18. Lead Poisoning

    Science.gov (United States)

    ... a hard, durable surface. In 1977, federal regulations banned lead from paint for general use. But homes ... OTHERS: Lead has recently been found in some plastic mini-blinds and vertical blinds which were made ...

  19. Relational Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    This first chapter presents the exploratory and curious approach to leading as relational processes – an approach that pervades the entire book. We explore leading from a perspective that emphasises the unpredictable challenges and triviality of everyday life, which we consider an interesting......, relevant and realistic way to examine leading. The chapter brings up a number of concepts and contexts as formulated by researchers within the field, and in this way seeks to construct a first understanding of relational leading....

  20. Extended icosahedral structures

    CERN Document Server

    Jaric, Marko V

    1989-01-01

    Extended Icosahedral Structures discusses the concepts about crystal structures with extended icosahedral symmetry. This book is organized into six chapters that focus on actual modeling of extended icosahedral crystal structures. This text first presents a tiling approach to the modeling of icosahedral quasiperiodic crystals. It then describes the models for icosahedral alloys based on random connections between icosahedral units, with particular emphasis on diffraction properties. Other chapters examine the glassy structures with only icosahedral orientational order and the extent of tra

  1. Heterologous human/rat HER2-specific exosome-targeted T cell vaccine stimulates potent humoral and CTL responses leading to enhanced circumvention of HER2 tolerance in double transgenic HLA-A2/HER2 mice.

    Science.gov (United States)

    Xie, Yufeng; Wu, Jie; Xu, Aizhang; Ahmeqd, Shahid; Sami, Amer; Chibbar, Rajni; Freywald, Andrew; Zheng, Changyu; Xiang, Jim

    2018-03-07

    DNA vaccines composed of heterologous human HER2 and rat neu sequences induce stronger antibody response and protective antitumor immunity than either HER2 or neu DNA vaccines in transgenic mice. We previously developed HER2-specific exosome-targeted T-cell vaccine HER2-T EXO capable of stimulating HER2-specific CD8 + T-cell responses, but only leading to partial protective immunity in double-transgenic HLA-A2/HER2 mice with self-immune tolerance to HER2. Here, we constructed an adenoviral vector AdV HuRt expressing HuRt fusion protein composed of NH 2 -HER2 1-407 (Hu) and COOH-neu 408-690 (Rt) fragments, and developed a heterologous human/rat HER2-specific exosome-targeted T-cell vaccine HuRt-T EXO using polyclonal CD4 + T-cells uptaking exosomes released by AdV HuRt -transfected dendritic cells. We found that the HuRt-T EXO vaccine stimulates enhanced CD4 + T-cell responses leading to increased induction of HER2-specific antibody (∼70 µg/ml) compared to that (∼40 µg/ml) triggered by the homologous HER2-T EXO vaccine. By using PE-H-2K d /HER2 23-71 tetramer, we determined that HuRt-T EXO stimulates stronger HER2-specific CD8 + T-cell responses eradicating 90% of HER2-specific target cells, while HER2-T EXO -induced CD8 + T-cell responses only eliminating 53% targets. Furthermore, HuRt-T EXO , but not HER2-T EXO vaccination, is capable of suppressing early stage-established HER2-expressing 4T1 HER2 breast cancer in its lung metastasis or subcutaneous form in BALB/c mice, and of completely protecting transgenic HLA-A2/HER2 mice from growth of HLA-A2/HER2-expressing BL6-10 A2/HER2 melanoma. HuRt-T EXO -stimulated HER2-specific CD8 + T-cells not only are cytolytic to trastuzumab-resistant HLA-A2/HER2-expressing BT474/A2 breast tumor cells in vitro but also eradicates pre-established BT474/A2 tumors in athymic nude mice. Therefore, our novel heterologous human/rat HER2-specific T-cell vaccine HuRt-T EXO, circumventing HER2 tolerance, may provide a new

  2. Lead Toxicity

    Science.gov (United States)

    ... blue-gray metal that is mined from the earth’s crust. • Lead has been used for many industrial ... including the kidneys, heart, and reproductive system, • Pregnant women should know that the developing fetus is very ...

  3. Lead Poisoning

    Science.gov (United States)

    ... has also been associated with juvenile delinquency and criminal behavior. In adults, lead can increase blood pressure ... and-forth manner, but rather from left to right (or vise-versa), or from the top of ...

  4. Lead Test

    Science.gov (United States)

    ... poison you. Most lead is present as an inorganic compound and does not move well through the ... D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 474. Wu, A. (© ...

  5. Grape seed extract targets mitochondrial electron transport chain complex III and induces oxidative and metabolic stress leading to cytoprotective autophagy and apoptotic death in human head and neck cancer cells.

    Science.gov (United States)

    Shrotriya, Sangeeta; Deep, Gagan; Lopert, Pamela; Patel, Manisha; Agarwal, Rajesh; Agarwal, Chapla

    2015-12-01

    Head and neck squamous cell carcinoma (HNSCC) is a major killer worldwide and innovative measures are urgently warranted to lower the morbidity and mortality caused by this malignancy. Aberrant redox and metabolic status in HNSCC cells offer a unique opportunity to specifically target cancer cells. Therefore, we investigated the efficacy of grape seed extract (GSE) to target the redox and bioenergetic alterations in HNSCC cells. GSE treatment decreased the mitochondrial electron transport chain complex III activity, increased the mitochondrial superoxide levels and depleted the levels of cellular antioxidant (glutathione), thus resulting in the loss of mitochondrial membrane potential in human HNSCC Detroit 562 and FaDu cells. Polyethylene glycol-SOD addition reversed the GSE-mediated apoptosis without restoring complex III activity. Along with redox changes, GSE inhibited the extracellular acidification rate (representing glycolysis) and oxygen consumption rate (indicating oxidative phosphorylation) leading to metabolic stress in HNSCC cells. Molecular studies revealed that GSE activated AMP-activated protein kinase (AMPK), and suppressed Akt/mTOR/4E-BP1/S6K signaling in both Detroit 562 and FaDu cells. Interestingly, GSE increased the autophagic load specifically in FaDu cells, and autophagy inhibition significantly augmented the apoptosis in these cells. Consistent with in vitro results, in vivo analyses also showed that GSE feeding in nude mice activated AMPK and induced-autophagy in FaDu xenograft tumor tissues. Overall, these findings are innovative as we for the first time showed that GSE targets ETC complex III and induces oxidative and metabolic stress, thereby, causing autophagy and apoptotic death in HNSCC cells. © 2014 Wiley Periodicals, Inc.

  6. Extended family medicine training

    Science.gov (United States)

    Slade, Steve; Ross, Shelley; Lawrence, Kathrine; Archibald, Douglas; Mackay, Maria Palacios; Oandasan, Ivy F.

    2016-01-01

    Abstract Objective To examine trends in family medicine training at a time when substantial pedagogic change is under way, focusing on factors that relate to extended family medicine training. Design Aggregate-level secondary data analysis based on the Canadian Post-MD Education Registry. Setting Canada. Participants All Canadian citizens and permanent residents who were registered in postgraduate family medicine training programs within Canadian faculties of medicine from 1995 to 2013. Main outcome measures Number and proportion of family medicine residents exiting 2-year and extended (third-year and above) family medicine training programs, as well as the types and numbers of extended training programs offered in 2015. Results The proportion of family medicine trainees pursuing extended training almost doubled during the study period, going from 10.9% in 1995 to 21.1% in 2013. Men and Canadian medical graduates were more likely to take extended family medicine training. Among the 5 most recent family medicine exit cohorts (from 2009 to 2013), 25.9% of men completed extended training programs compared with 18.3% of women, and 23.1% of Canadian medical graduates completed extended training compared with 13.6% of international medical graduates. Family medicine programs vary substantially with respect to the proportion of their trainees who undertake extended training, ranging from a low of 12.3% to a high of 35.1% among trainees exiting from 2011 to 2013. Conclusion New initiatives, such as the Triple C Competency-based Curriculum, CanMEDS–Family Medicine, and Certificates of Added Competence, have emerged as part of family medicine education and credentialing. In acknowledgment of the potential effect of these initiatives, it is important that future research examine how pedagogic change and, in particular, extended training shapes the care family physicians offer their patients. As part of that research it will be important to measure the breadth and uptake of

  7. Measurements of gas and volatile element production rates from an irradiated molten lead and lead-bismuth spallation target with proton beams of 1 and 1.4 GeV; Mesures de taux de production d'elements gazeux et volatiles lors de reactions induites par des protons de 1 et 1,4 GeV sur des cibles epaisses de plomb et plomb-bismuth liquides

    Energy Technology Data Exchange (ETDEWEB)

    Tall, Y

    2008-03-15

    The integrated project EUROTRANS (European Research Programme for the Transmutation of High Level Nuclear Waste in an Accelerator Driven System) of the 6. EURATOM Framework Programme aims to demonstrate the transmutation of radioactive waste in ADS (Accelerator Driven Sub-critical system). It will carry out a first advanced design of an experimental facility to demonstrate the technical feasibility of transmutation, and will produce a conceptual design of an industrial facility dedicated to transmutation. An ADS consists of three fundamental elements: the accelerator of protons, the sub-critical core and the spallation target. SUBATECH (physique Sub-Atomique et des Technologies associees) laboratory is involved to the study of the chosen liquid lead-bismuth as a spallation ADS target. The irradiation of liquid lead-bismuth target with energetic proton beam generates in addition to neutrons, volatile and radioactive residues. In order to determine experimentally the production rates of gas and volatile elements following a spallation reaction in a lead-bismuth target, the experiment IS419 was performed at the ISOLDE facility at CERN (Centre Europeen de la Recherche Nucleaire). This experiment constitutes the frame of the thesis whose main objective is to assess and study the production and release rates of many gas and volatile element from the irradiated lead-bismuth target with an energetic proton beam. The obtained data are compared to Monte Carlo simulation code (MCNPX) results in order to test the intranuclear cascade model of Bertini and of Cugnon, and the evaporation options of Dresner and Schmidt. (author)

  8. Leading men

    DEFF Research Database (Denmark)

    Bekker-Nielsen, Tønnes

    2016-01-01

    Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also disting...

  9. Extended defects in Germanium

    CERN Document Server

    Osgood, R M

    2008-01-01

    Intends to provide a fundamental understanding of the extended-defect formation during Ge materials and device processing, providing ways to distinguish harmful from less detrimental defects and should point out ways for defect engineering and control.

  10. Who Leads China's Leading Universities?

    Science.gov (United States)

    Huang, Futao

    2017-01-01

    This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

  11. Extended producer responsibility for consumer waste: the gap between economic theory and implementation.

    Science.gov (United States)

    Dubois, Maarten

    2012-09-01

    Although economic theory supports the use of extended producer responsibility (EPR) to stimulate prevention and recycling of waste, EPR systems implemented in Europe are often criticized as a result of weak incentives for prevention and green product design. Using a stylized economic model, this article evaluates the efficiency of European EPR systems. The model reveals that the introduction of static collection targets creates a gap between theory and implementation. Static targets lead to inefficient market outcomes and weak incentives for prevention and green product design. The minimum collection targets should be complemented with a tax on producers for the non-collected waste fraction. Because such a tax internalizes the cost of waste disposal, more efficient price signals will lead to better incentives for waste management in a complex and dynamic market.

  12. An extended day program

    Directory of Open Access Journals (Sweden)

    Ševkušić-Mandić Slavica G.

    2002-01-01

    Full Text Available The paper presents the results of a pilot project evaluation, carried out as an action investigation whose aim was to provide a better quality extended day for primary school students. The project included the training of teachers involved in extended day program, designing of special activities performed by teachers with children once a week as well as changes and equipping of premises where children stay. The aims of the program were conception and performance of activities in a less formal way than during regular instructional days, linking of learning at school and acquired knowledge to everyday experiences, and work on contents contributing to the development of child's interests and creativity. The program was accomplished in a Belgrade primary school during the 2001/2002 academic year, comprising students of 1st and 2nd grades (N=77. The effects of the program were monitored throughout the academic year (observation and teachers' reports on accomplished workshops and at the end of the academic year (teachers and students' opinions of the program, academic achievement and creativity of students attending the extended day program compared with students not attending it. Findings about positive effects of the program on students' broadening of interests and willingness to express themselves creatively, indicate unequivocally that there is a need for developing special extended day programs. The extended day program is an opportunity for school to exert greater educational influence that has yet to be tapped.

  13. Extended spider cognition.

    Science.gov (United States)

    Japyassú, Hilton F; Laland, Kevin N

    2017-05-01

    There is a tension between the conception of cognition as a central nervous system (CNS) process and a view of cognition as extending towards the body or the contiguous environment. The centralised conception requires large or complex nervous systems to cope with complex environments. Conversely, the extended conception involves the outsourcing of information processing to the body or environment, thus making fewer demands on the processing power of the CNS. The evolution of extended cognition should be particularly favoured among small, generalist predators such as spiders, and here, we review the literature to evaluate the fit of empirical data with these contrasting models of cognition. Spiders do not seem to be cognitively limited, displaying a large diversity of learning processes, from habituation to contextual learning, including a sense of numerosity. To tease apart the central from the extended cognition, we apply the mutual manipulability criterion, testing the existence of reciprocal causal links between the putative elements of the system. We conclude that the web threads and configurations are integral parts of the cognitive systems. The extension of cognition to the web helps to explain some puzzling features of spider behaviour and seems to promote evolvability within the group, enhancing innovation through cognitive connectivity to variable habitat features. Graded changes in relative brain size could also be explained by outsourcing information processing to environmental features. More generally, niche-constructed structures emerge as prime candidates for extending animal cognition, generating the selective pressures that help to shape the evolving cognitive system.

  14. Extending quantum mechanics entails extending special relativity

    Science.gov (United States)

    Aravinda, S.; Srikanth, R.

    2016-05-01

    The complementarity between signaling and randomness in any communicated resource that can simulate singlet statistics is generalized by relaxing the assumption of free will in the choice of measurement settings. We show how to construct an ontological extension for quantum mechanics (QMs) through the oblivious embedding of a sound simulation protocol in a Newtonian spacetime. Minkowski or other intermediate spacetimes are ruled out as the locus of the embedding by virtue of hidden influence inequalities. The complementarity transferred from a simulation to the extension unifies a number of results about quantum non-locality, and implies that special relativity has a different significance for the ontological model and for the operational theory it reproduces. Only the latter, being experimentally accessible, is required to be Lorentz covariant. There may be certain Lorentz non-covariant elements at the ontological level, but they will be inaccessible at the operational level in a valid extension. Certain arguments against the extendability of QM, due to Conway and Kochen (2009) and Colbeck and Renner (2012), are attributed to their assumption that the spacetime at the ontological level has Minkowski causal structure.

  15. Poster Session- Extended Abstracts

    Science.gov (United States)

    Jack D. Alexander III; Jean Findley; Brenda K. Kury; Jan L. Beyers; Douglas S. Cram; Terrell T. Baker; Jon C. Boren; Carl Edminster; Sue A. Ferguson; Steven McKay; David Nagel; Trent Piepho; Miriam Rorig; Casey Anderson; Jeanne Hoadley; Paulette L. Ford; Mark C. Andersen; Ed L. Fredrickson; Joe Truett; Gary W. Roemer; Brenda K. Kury; Jennifer Vollmer; Christine L. May; Danny C. Lee; James P. Menakis; Robert E. Keane; Zhi-Liang Zhu; Carol Miller; Brett Davis; Katharine Gray; Ken Mix; William P. Kuvlesky Jr.; D. Lynn Drawe; Marcia G. Narog; Roger D. Ottmar; Robert E. Vihnanek; Clinton S. Wright; Timothy E. Paysen; Burton K. Pendleton; Rosemary L. Pendleton; Carleton S. White; John Rogan; Doug Stow; Janet Franklin; Jennifer Miller; Lisa Levien; Chris Fischer; Emma Underwood; Robert Klinger; Peggy Moore; Clinton S. Wright

    2008-01-01

    Titles found within Poster Session-Extended Abstracts include:Assessment of emergency fire rehabilitation of four fires from the 2000 fire season on the Vale, Oregon, BLM district: review of the density sampling materials and methods: p. 329 Growth of regreen, seeded for erosion control, in the...

  16. Extending Critical Performativity

    DEFF Research Database (Denmark)

    Spicer, André; Alvesson, Mats; Kärreman, Dan

    2016-01-01

    In this article we extend the debate about critical performativity. We begin by outlining the basic tenets of critical performativity and how this has been applied in the study of management and organization. We then address recent critiques of critical performance. We note these arguments suffer...

  17. Parameterization of extended systems

    DEFF Research Database (Denmark)

    Niemann, Hans Henrik

    2006-01-01

    The YJBK parameterization (of all stabilizing controllers) is extended to handle systems with additional sensors and/or actuators. It is shown that the closed loop transfer function is still an affine function in the YJBK parameters in the nominal case. Further, some closed-loop stability results...

  18. Diagrammar in an extended theory of gravity

    Science.gov (United States)

    Dunbar, David C.; Godwin, John H.; Jehu, Guy R.; Perkins, Warren B.

    2017-08-01

    We show how the S-matrix of an extended theory of gravity defined by its three-point amplitudes can be constructed by demanding factorisation. The resultant S-matrix has tree amplitudes obeying the same soft singularity theorems as Einstein gravity including the sub-sub-leading terms.

  19. Venus: No Breaks from an Extended Childhood

    Science.gov (United States)

    Moore, W. B.; Kankanamge, D. G. J.

    2017-05-01

    High surface temperatures lead to lower heat flow and lower stress as planets transition out of the heat-pipe mode into subsolidus convection. This causes Venus to miss the window for plate tectonics due to an extended heat-pipe childhood.

  20. Extended Irreversible Thermodynamics

    CERN Document Server

    Jou, David

    2010-01-01

    This is the 4th edition of the highly acclaimed monograph on Extended Irreversible Thermodynamics, a theory that goes beyond the classical theory of irreversible processes. In contrast to the classical approach, the basic variables describing the system are complemented by non-equilibrium quantities. The claims made for extended thermodynamics are confirmed by the kinetic theory of gases and statistical mechanics. The book covers a wide spectrum of applications, and also contains a thorough discussion of the foundations and the scope of the current theories on non-equilibrium thermodynamics. For this new edition, the authors critically revised existing material while taking into account the most recent developments in fast moving fields such as heat transport in micro- and nanosystems or fast solidification fronts in materials sciences. Several fundamental chapters have been revisited emphasizing physics and applications over mathematical derivations. Also, fundamental questions on the definition of non-equil...

  1. Start-Stop Moment Optimization of Range Extender and Control Strategy Design for Extended -Range Electric Vehicle

    Science.gov (United States)

    Zhao, Jing-bo; Han, Bing-yuan; Bei, Shao-yi

    2017-10-01

    Range extender is the core component of E-REV, its start-stop control determines the operation modes of vehicle. This paper based on a certain type of E-REV, researched constant power control strategy of range extender in extended-range model, to target range as constraint condition, combined with different driving cycle conditions, by correcting battery SOC for range extender start-stop moment, optimized the control strategy of range extender, and established the vehicle and range extender start-stop control simulation model. Selected NEDC and UDDS conditions simulation results show that: under certain target mileage, the range extender running time reduced by 37.2% and 28.2% in the NEDC condition, and running time UDDS conditions were reduced by 40.6% and 33.5% in the UDDS condition, reached the purpose of meeting the vehicle mileage and reducing consumption and emission.

  2. The Fly Printer - Extended

    DEFF Research Database (Denmark)

    Beloff, Laura; Klaus, Malena

    2016-01-01

    Artist talk / Work-in-progress What is the purpose of a machine or an artifact, like the Fly Printer, that is dislocated, that produces images that have no meaning, no instrumentality, that depict nothing in the world? The biological and the cultural are reunited in this apparatus as a possibilit...... the results. The extended version of the Fly Printer containing the technological perception and DNNs is a collaboration between Laura Beloff and Malene Theres Klaus...

  3. The dialogically extended mind

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Gangopadhyay, Nivedita; Tylén, Kristian

    2014-01-01

    , we argue that language enhances our cognitive capabilities in a much more radical way: The skilful engagement of public material symbols facilitates evolutionarily unprecedented modes of collective perception, action and reasoning (interpersonal synergies) creating dialogically extended minds. We...... relate our approach to other ideas about collective minds and review a number of empirical studies to identify the mechanisms enabling the constitution of interpersonal cognitive systems....

  4. Extended Theories of Gravitation

    Directory of Open Access Journals (Sweden)

    Fatibene Lorenzo

    2013-09-01

    Full Text Available Within the framework of extended theories of gravitation we shall discuss physical equivalences among different formalisms and classical tests. As suggested by the Ehlers-Pirani-Schild framework, the conformal invariance will be preserved and its effect on observational protocols discussed. Accordingly, we shall review standard tests showing how Palatini f(R-theories naturally passes solar system tests. Observation protocols will be discussed in this wider framework.

  5. Extended uncertainty from first principles

    Energy Technology Data Exchange (ETDEWEB)

    Costa Filho, Raimundo N., E-mail: rai@fisica.ufc.br [Departamento de Física, Universidade Federal do Ceará, Caixa Postal 6030, Campus do Pici, 60455-760 Fortaleza, Ceará (Brazil); Braga, João P.M., E-mail: philipe@fisica.ufc.br [Instituto de Ciências Exatas e da Natureza-ICEN, Universidade da Integração Internacional da Lusofonia Afro-Brasileira-UNILAB, Campus dos Palmares, 62785-000 Acarape, Ceará (Brazil); Lira, Jorge H.S., E-mail: jorge.lira@mat.ufc.br [Departamento de Matemática, Universidade Federal do Ceará, Caixa Postal 6030, Campus do Pici, 60455-760 Fortaleza, Ceará (Brazil); Andrade, José S., E-mail: soares@fisica.ufc.br [Departamento de Física, Universidade Federal do Ceará, Caixa Postal 6030, Campus do Pici, 60455-760 Fortaleza, Ceará (Brazil)

    2016-04-10

    A translation operator acting in a space with a diagonal metric is introduced to describe the motion of a particle in a quantum system. We show that the momentum operator and, as a consequence, the uncertainty relation now depend on the metric. It is also shown that, for any metric expanded up to second order, this formalism naturally leads to an extended uncertainty principle (EUP) with a minimum momentum dispersion. The Ehrenfest theorem is modified to include an additional term related to a tidal force arriving from the space curvature introduced by the metric. For one-dimensional systems, we show how to map a harmonic potential to an effective potential in Euclidean space using different metrics.

  6. Topics in Extended Dynamical Systems

    Science.gov (United States)

    Bhagavatula, Ravi S.

    This thesis consists of three chapters. Each chapter is self-contained and is devoted to the investigation of a particular topic in extended dynamical systems. In the first chapter, an approach based on Langevin equations is implemented to understand the non-Gaussian nature of the probability distribution function (PDF) of local diffusive variables in extended dynamical systems, e.g., a passive scalar advected by turbulent velocity fluctuations. Two mechanisms are proposed for the origin of non-Gaussian tails: One relies on the nature of temporal correlations of the fluctuations that couple additively to the diffusive field, leading to exponential and stretched exponential tails in the PDF; the other depends on multiplicative coupling between the diffusive field and the fluctuations, producing algebraic tails in the PDF. The mechanisms are illustrated using models for a passive scalar and also a current driven Josephson junction array. This study indicates that shapes of local PDFs in turbulent states are non-universal and crucially depend on local couplings and time scales. The second chapter establishes the existence of a class of locally conserving chaotic (deterministic) systems that exhibit Generic Scale Invariance--algebraic decay of spatial and temporal correlations without tuning parameters. This study also reveals the similarity between noise and chaos in extended systems as far as long-wavelength and long -time behavior is concerned. Specifically, a two dimensional coupled-map lattice model with a conserved density is numerically shown to exhibit, in agreement with heuristic arguments, algebraic decay of spatio-temporal correlations in chaotic states with simple predictable exponents. The third chapter investigates scaling behavior of earthquakes in seismic zone models in which an earthquake is modeled by a quasi-static description that ignores short -time dynamics during an earthquake. The models incorporate the essential feature of long-ranged stress

  7. Extended spider cognition

    OpenAIRE

    Japyassú, Hilton F.; Laland, Kevin Neville

    2017-01-01

    HFJ received a visiting professor fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - Brazil) (PDE PDE232691/2014-2). Research supported in part by a Grant from the John Templeton Foundation to KNL. There is a tension between the conception of cognition as a central nervous system (CNS) process, and a view of cognition as extending towards the body or the contiguous environment. The centralised conception requires large or complex nervous systems to cope w...

  8. THE EXTENDED VIRGO CLUSTER CATALOG

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suk; Rey, Soo-Chang; Lee, Youngdae; Chung, Jiwon; Pak, Mina; Yi, Wonhyeong; Lee, Woong [Department of Astronomy and Space Science, Chungnam National University, 99 Daehak-ro, Daejeon 305-764 (Korea, Republic of); Jerjen, Helmut [Research School of Astronomy and Astrophysics, The Australian National University, Cotter Road, Weston, ACT 2611 (Australia); Lisker, Thorsten [Astronomisches Rechen-Institut, Zentrum für Astronomie der Universität Heidelberg (ZAH), Mönchhofstraße 12-14, D-69120 Heidelberg (Germany); Sung, Eon-Chang [Korea Astronomy and Space Science institute, 776 Daedeokdae-ro, Daejeon 305-348 (Korea, Republic of)

    2015-01-01

    We present a new catalog of galaxies in the wider region of the Virgo cluster, based on the Sloan Digital Sky Survey (SDSS) Data Release 7. The Extended Virgo Cluster Catalog (EVCC) covers an area of 725 deg{sup 2} or 60.1 Mpc{sup 2}. It is 5.2 times larger than the footprint of the classical Virgo Cluster Catalog (VCC) and reaches out to 3.5 times the virial radius of the Virgo cluster. We selected 1324 spectroscopically targeted galaxies with radial velocities less than 3000 km s{sup –1}. In addition, 265 galaxies that have been overlooked in the SDSS spectroscopic survey but have available redshifts in the NASA Extragalactic Database are also included. Our selection process secured a total of 1589 galaxies, 676 of which are not included in the VCC. The certain and possible cluster members are defined by means of redshift comparison with a cluster infall model. We employed two independent and complementary galaxy classification schemes: the traditional morphological classification based on the visual inspection of optical images and a characterization of galaxies from their spectroscopic features. SDSS u, g, r, i, and z passband photometry of all EVCC galaxies was performed using Source Extractor. We compare the EVCC galaxies with the VCC in terms of morphology, spatial distribution, and luminosity function. The EVCC defines a comprehensive galaxy sample covering a wider range in galaxy density that is significantly different from the inner region of the Virgo cluster. It will be the foundation for forthcoming galaxy evolution studies in the extended Virgo cluster region, complementing ongoing and planned Virgo cluster surveys at various wavelengths.

  9. Extending juvenility in grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kaeppler, Shawn; de Leon Gatti, Natalia; Foerster, Jillian

    2017-04-11

    The present invention relates to compositions and methods for modulating the juvenile to adult developmental growth transition in plants, such as grasses (e.g. maize). In particular, the invention provides methods for enhancing agronomic properties in plants by modulating expression of GRMZM2G362718, GRMZM2G096016, or homologs thereof. Modulation of expression of one or more additional genes which affect juvenile to adult developmental growth transition such as Glossy15 or Cg1, in conjunction with such modulation of expression is also contemplated. Nucleic acid constructs for down-regulation of GRMZM2G362718 and/or GRMZM2G096016 are also contemplated, as are transgenic plants and products produced there from, that demonstrate altered, such as extended juvenile growth, and display associated phenotypes such as enhanced yield, improved digestibility, and increased disease resistance. Plants described herein may be used, for example, as improved forage or feed crops or in biofuel production.

  10. Extended Poisson Exponential Distribution

    Directory of Open Access Journals (Sweden)

    Anum Fatima

    2015-09-01

    Full Text Available A new mixture of Modified Exponential (ME and Poisson distribution has been introduced in this paper. Taking the Maximum of Modified Exponential random variable when the sample size follows a zero truncated Poisson distribution we have derived the new distribution, named as Extended Poisson Exponential distribution. This distribution possesses increasing and decreasing failure rates. The Poisson-Exponential, Modified Exponential and Exponential distributions are special cases of this distribution. We have also investigated some mathematical properties of the distribution along with Information entropies and Order statistics of the distribution. The estimation of parameters has been obtained using the Maximum Likelihood Estimation procedure. Finally we have illustrated a real data application of our distribution.

  11. Extending rational maps

    Science.gov (United States)

    Martin, Gaven J.

    We investigate when a rational endomorphism of the Riemann sphere overline{C} extends to a mapping of the upper half-space {H3 which is rational with respect to some measurable conformal structure. Such an extension has the property that it and all its iterates have uniformly bounded distortion. Such maps are called uniformly quasiregular. We show that, in the space of rational mappings of degree d , such an extension is possible in the structurally stable component where there is a single (attracting) component of the Fatou set and the Julia set is a Cantor set. We show that generally outside of this set no such extension is possible. In particular, polynomials can never admit such an extension.

  12. Reduced Extended MHD

    Science.gov (United States)

    Morrison, P. J.; Abdelhamid, H. M.; Grasso, D.; Hazeltine, R. D.; Lingam, M.; Tassi, E.

    2015-11-01

    Over the years various reduced fluid models have been obtained for modeling plasmas, with the goal of capturing important physics while maintaining computability. Such models have included the physics contained in various generalizations of Ohm's law, including Hall drift and electron inertia. In a recent publication it was shown that full 3D extended MHD is a Hamiltonian system by finding its noncanonical Poisson bracket. Subsequently, this bracket was shown to be derivable from that for Hall MHD by a series of remarkable transformations, which greatly simplifies the proof of the Jacobi identity and allows one to immediately obtain generalizations of the helicity and cross helicity. In this poster we use this structure to obtain exact reduced fluid models with the effects of full two-fluid theory. Results of numerical computations of collisionless reconnection using an exact reduced 4-field model will be presented and analytical comparisons of mode structure of previous reduced models will be made.

  13. Down-Regulation of miR-129-5p and the let-7 Family in Neuroendocrine Tumors and Metastases Leads to Up-Regulation of Their Targets Egr1, G3bp1, Hmga2 and Bach1

    DEFF Research Database (Denmark)

    Dossing, Kristina B. V.; Binderup, Tina; Kaczkowski, Bogumil

    2014-01-01

    by miR-129-5p. let-7 overexpression inhibited growth of carcinoid cell lines, and let-7 inhibition increased protein content of the transcription factor BACH1 and its targets MMP1 and HMGA2, all known to promote bone metastases. Immunohistochemistry analysis revealed that let-7 targets are highly...... and an intestinal carcinoid cell line. Analysis of mRNA expression changes identified EGR1 and G3BP1 as miR-129-5p targets. They were validated by luciferase assay and western blotting, and found robustly expressed in NETs by immunohistochemistry. Knockdown of EGR1 and G3BP1 mimicked the growth inhibition induced...... expressed in NETs and metastases. We found down-regulation of miR-129-5p and the let-7 family, and identified new neuroendocrine specific targets for these miRNAs, which contributes to the growth and metastatic potential of these tumors....

  14. Remarkable connections between extended magnetohydrodynamics models

    Energy Technology Data Exchange (ETDEWEB)

    Lingam, M., E-mail: manasvi@physics.utexas.edu; Morrison, P. J., E-mail: morrison@physics.utexas.edu; Miloshevich, G., E-mail: gmilosh@physics.utexas.edu [Department of Physics and Institute for Fusion Studies, The University of Texas at Austin, Austin, Texas 78712 (United States)

    2015-07-15

    Through the use of suitable variable transformations, the commonality of all extended magnetohydrodynamics (MHD) models is established. Remarkable correspondences between the Poisson brackets of inertialess Hall MHD and inertial MHD (which has electron inertia, but not the Hall drift) and extended MHD (which has both effects) are established. The helicities (two in all) for each of these models are obtained through these correspondences. The commonality of all the extended MHD models is traced to the existence of two Lie-dragged 2-forms, which are closely associated with the canonical momenta of the two underlying species. The Lie-dragging of these 2-forms by suitable velocities also leads to the correct equations of motion. The Hall MHD Poisson bracket is analyzed in detail, the Jacobi identity is verified through a detailed proof, and this proof ensures the Jacobi identity for the Poisson brackets of all the models.

  15. Use of integrin-linked kinase to extend function of encapsulated pancreatic tissue

    Energy Technology Data Exchange (ETDEWEB)

    Blanchette, James O [Department of Chemical Engineering, University of South Carolina, Columbia, SC (United States); Langer, Steven J; Leinwand, Leslie L [Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO (United States); Sahai, Suchit; Topiwala, Pritesh S [Biomedical Engineering Program, University of South Carolina, Columbia, SC (United States); Anseth, Kristi S, E-mail: blanchej@cec.sc.ed [Howard Hughes Medical Institute, Boulder, CO (United States)

    2010-12-15

    We have studied the impact of overexpression of an intracellular signaling protein, integrin-linked kinase (ILK), on the survival and function of encapsulated islet tissue used for the treatment of type 1 diabetes. The dimensions of the encapsulated tissue can impact the stresses placed on the tissue and ILK overexpression shows the ability to extend function of dissociated cells as well as intact islets. These results suggest that lost cell-extracellular matrix interactions in cell encapsulation systems can lead to decreased insulin secretion and ILK signaling is a target to overcome this phenomenon. (communication)

  16. Extended Mixed Vector Equilibrium Problems

    Directory of Open Access Journals (Sweden)

    Mijanur Rahaman

    2014-01-01

    Full Text Available We study extended mixed vector equilibrium problems, namely, extended weak mixed vector equilibrium problem and extended strong mixed vector equilibrium problem in Hausdorff topological vector spaces. Using generalized KKM-Fan theorem (Ben-El-Mechaiekh et al.; 2005, some existence results for both problems are proved in noncompact domain.

  17. Drug Extends Lives of Patients with Advanced Prostate Cancer: Studies

    Science.gov (United States)

    ... Extends Lives of Patients With Advanced Prostate Cancer: Studies Findings could 'change clinical practice overnight,' leading oncologist ... when added to standard androgen deprivation therapy, both studies found. Abiraterone also appeared to more than double ...

  18. Research Advances: DNA Computing Targets West Nile Virus, Other Deadly Diseases, and Tic-Tac-Toe; Marijuana Component May Offer Hope for Alzheimer's Disease Treatment; New Wound Dressing May Lead to Maggot Therapy--Without the Maggots

    Science.gov (United States)

    King, Angela G.

    2007-01-01

    This article presents three reports of research advances. The first report describes a deoxyribonucleic acid (DNA)-based computer that could lead to faster, more accurate tests for diagnosing West Nile Virus and bird flu. Representing the first "medium-scale integrated molecular circuit," it is the most powerful computing device of its type to…

  19. MCMC with strings and branes: The suburban algorithm (Extended Version)

    Science.gov (United States)

    Heckman, Jonathan J.; Bernstein, Jeffrey G.; Vigoda, Ben

    2017-08-01

    Motivated by the physics of strings and branes, we develop a class of Markov chain Monte Carlo (MCMC) algorithms involving extended objects. Starting from a collection of parallel Metropolis-Hastings (MH) samplers, we place them on an auxiliary grid, and couple them together via nearest neighbor interactions. This leads to a class of “suburban samplers” (i.e. spread out Metropolis). Coupling the samplers in this way modifies the mixing rate and speed of convergence for the Markov chain, and can in many cases allow a sampler to more easily overcome free energy barriers in a target distribution. We test these general theoretical considerations by performing several numerical experiments. For suburban samplers with a fluctuating grid topology, performance is strongly correlated with the average number of neighbors. Increasing the average number of neighbors above zero initially leads to an increase in performance, though there is a critical connectivity with effective dimension deff ˜ 1, above which “groupthink” takes over, and the performance of the sampler declines.

  20. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  1. ECG monitoring leads and special leads.

    Science.gov (United States)

    Francis, Johnson

    ECG monitoring is common place in the hospital and even pre-hospital setting. The need for different types of lead systems in different settings has been emphasised. Simple three electrode bipolar recording is ubiquitous for monitoring. This can be used to record modified bipolar chest leads as well. Using five leads gives the option of getting a chest lead in addition to bipolar limb leads, enhancing detection of ischemia during procedures. Lead stability is important when the movement of the subject is maximum as in exercise testing. Mason-Likar modification with limb leads shifted to the torso is popular for exercise testing, though the diagnostic value of the ECG is altered. Lund system with leads on proximal part of limbs have both stability and fair diagnostic value. EASI lead system permits derivation of 12 leads from just five electrodes. Lewis lead and the newly devised modified limb lead system are useful in enhancing detection of atrial activity. Fontaine lead has been designed to improve visualization of Epsilon wave in arrhythmogenic right ventricular dysplasia. Copyright © 2016 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

  2. Learn about Lead

    Science.gov (United States)

    ... Protection Agency Search Search Lead Contact Us Share Learn about Lead General Lead Information Read more about ... water, soil, consumer products, food, and occupational settings. Learn more about sources of lead exposure: At home ...

  3. Lead Poisoning Prevention Tips

    Science.gov (United States)

    ... or removed safely. How are children exposed to lead? Lead-based paint and lead contaminated dust are ... What can be done to prevent exposure to lead? It is important to determine the construction year ...

  4. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  5. Extending cosmology: the metric approach

    OpenAIRE

    Mendoza, S.

    2012-01-01

    Comment: 2012, Extending Cosmology: The Metric Approach, Open Questions in Cosmology; Review article for an Intech "Open questions in cosmology" book chapter (19 pages, 3 figures). Available from: http://www.intechopen.com/books/open-questions-in-cosmology/extending-cosmology-the-metric-approach

  6. On core stability and extendability

    OpenAIRE

    Shellshear, Evan

    2011-01-01

    This paper investigates conditions under which the core of a TU cooperative game is stable. In particular the author extends the idea of extendability to find new conditions under which the core is stable. It is also shown that these new conditions are not necessary for core stability.

  7. Extended Active Disturbance Rejection Controller

    Science.gov (United States)

    Gao, Zhiqiang (Inventor); Tian, Gang (Inventor)

    2016-01-01

    Multiple designs, systems, methods and processes for controlling a system or plant using an extended active disturbance rejection control (ADRC) based controller are presented. The extended ADRC controller accepts sensor information from the plant. The sensor information is used in conjunction with an extended state observer in combination with a predictor that estimates and predicts the current state of the plant and a co-joined estimate of the system disturbances and system dynamics. The extended state observer estimates and predictions are used in conjunction with a control law that generates an input to the system based in part on the extended state observer estimates and predictions as well as a desired trajectory for the plant to follow.

  8. Leptin and the OB-receptor as anti-obesity target: recent in silico advances in the comprehension of the protein-protein interaction and rational drug design of anti- obesity lead compounds.

    Science.gov (United States)

    Tutone, Marco; Lauria, Antonino; Almerico, Anna Maria

    2014-01-01

    The OB-receptor or leptin receptor (LR) is crucial for energy homeostasis and regulation of food uptake. Leptin is a 16 kDa hormone that is mainly secreted by fat cells into the bloodstream. Under normal circumstances, circulating leptin levels are proportionate to the fat body mass. Sensing of elevated leptin levels by the hypothalamic neuro-circuitry activates a negative feedback loop resulting in reduced food intake and increased energy expenditure. Decreased leptin concentrations lead to opposite effects. Therefore, rational design of leptin agonists/antagonists could be an appealing challenge in the battle against obesity. The Leptin/LR interactions have been studied in several works by means of different molecular modelling approaches, spreading from homology modelling to manual docking. No small molecules have ever been proposed as agonists of the Ob receptor but researchers' efforts focused only on leptin-related synthetic peptides as receptor antagonists and on peptidomimetics. In this review we try to track a timeline of obtained in silico information to clarify the mechanism of interaction between leptin and its receptor, together to summarize the more recent efforts to propose new drugs usable in anti-obesity therapy. Final considerations could be useful starting points for the rational drug design of new lead compounds.

  9. Down regulation of Peroxiredoxin-3 in 3T3-L1 adipocytes leads to oxidation of Rictor in the mammalian-target of rapamycin complex 2 (mTORC2).

    Science.gov (United States)

    Olson, Dalay H; Burrill, Joel S; Kuzmicic, Jovan; Hahn, Wendy S; Park, Ji-Man; Kim, Do-Hyung; Bernlohr, David A

    2017-11-25

    Mitochondrially-derived oxidative stress has been implicated in the development of obesity-induced insulin resistance and is correlated with down regulation of Peroxiredoxin-3 (Prdx3). Prdx3 knockout mice exhibit whole-body insulin resistance, while Prdx3 transgenic animals remain insulin sensitive when placed on a high fat diet. To define the molecular events linking mitochondrial oxidative stress to insulin action, Prdx3 was silenced in 3T3-L1 adipocytes (Prdx3 KD) and the resultant cells evaluated for mitochondrial function, endoplasmic reticulum stress (ER stress), mitochondrial unfolded protein response (mtUPR) and insulin signaling. Prdx3 KD cells exhibit a two-fold increase in H2O2, reduced insulin-stimulated glucose transport and attenuated S473 phosphorylation of the mTORC2 substrate, Akt. Importantly, the decrease in glucose uptake can be rescued by pre-treatment with the antioxidant N-acetyl-cysteine (NAC). The changes in insulin sensitivity occur independently from activation of the ER stress or mtUPR pathways. Analysis of mTORC2, the complex responsible for phosphorylating Akt at S473, reveals increased cysteine oxidation of Rictor in Prdx3 KD cells that can be rescued with NAC. Taken together, these data suggest mitochondrial dysfunction in adipocytes may attenuate insulin signaling via oxidation of the mammalian-target of rapamycin complex 2 (mTORC2). Copyright © 2017. Published by Elsevier Inc.

  10. Accounting for glint in target tracking

    Science.gov (United States)

    Tanner, Gwen L.

    1998-09-01

    Glint is a major error source for radar tracking at short ranges. It occurs because a target is not a single reflector, but is a collection of reflectors. The returns from these multiple sources may interfere, leading to apparent shifts in the target position. Glint is non- Gaussian and correlated in nature, and may even have infinite variance. Previous work on glint includes the use of the score method to reduce the effect of large errors, and the use of filters which account for the correlation. Only limited work has been done using multiple model techniques. The importance of glint in missile applications justifies further work in the area. The work presented here investigated several multiple hypothesis techniques which seemed particularly suited to this problem. One approach was to approximate the error distribution with a Gaussian mixture. This generates a multiple hypothesis filter, where each hypothesis uses a simple extended Kalman filter. This was extended to take account of the correlation structure of the glint. These methods were tested against a fairly realistic representation of glint which provided a stressing test for the filters.

  11. Lead and the Romans

    Science.gov (United States)

    Reddy, Aravind; Braun, Charles L.

    2010-01-01

    Lead poisoning has been a problem since early history and continues into modern times. An appealing characteristic of lead is that many lead salts are sweet. In the absence of cane and beet sugars, early Romans used "sugar of lead" (lead acetate) to sweeten desserts, fruits, and sour wine. People most at risk would have been those who…

  12. Topological defects in extended inflation

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, E.J. (Department of Physics, University of Sussex, Brighton BN1 9QH (United Kingdom)); Kolb, E.W. (NASA/Fermilab Astrophysics Center, Fermi National Accelerator Laboratory, Batavia, IL (USA) Department of Astronomy and Astrophysics, Enrico Fermi Institute, The University of Chicago, Chicago, IL (USA)); Liddle, A.R. (Astronomy Centre, Department of Physics, University of Sussex, Brighton (United Kingdom))

    1990-10-15

    We consider the production of topological defects, especially cosmic strings, in extended-inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of the bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings.

  13. Topological defects in extended inflation

    Energy Technology Data Exchange (ETDEWEB)

    Copeland, E.J. (Sussex Univ., Brighton (UK). Dept. of Physics); Kolb, E.W. (Fermi National Accelerator Lab., Batavia, IL (USA) Chicago Univ., IL (USA). Enrico Fermi Inst.); Liddle, A.R. (Sussex Univ., Brighton (UK). Astronomy Centre)

    1990-04-01

    We consider the production of topological defects, especially cosmic strings, in extended inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings. 18 refs.

  14. Extended lactation in dairy cows

    DEFF Research Database (Denmark)

    Sorensen, Annette; Muir, D. Donald; Knight, Christopher Harold

    2008-01-01

    of the lactation, protein and fat percentages increasing and lactose percentage decreasing, irrespective of treatment. The quality of the milk for processing into cheese, fermented products, heat-treated products and cream liqueurs was assessed by calculation of casein number (casein protein as a proportion...... interventions, the results lend support to the economic arguments in favour of extended lactation cycles. The likely welfare benefits of extended lactation are also discussed....

  15. Extender for securing a closure

    Science.gov (United States)

    Thomas, II, Patrick A.

    2012-10-02

    An apparatus for securing a closure such as door or a window that opens and closes by movement relative to a fixed structure such as a wall or a floor. Many embodiments provide a device for relocating a padlock from its normal location where it secures a fastener (such as a hasp) to a location for the padlock that is more accessible for locking and unlocking the padlock. Typically an extender is provided, where the extender has a hook at a first end that is disposed through the eye of the staple of the hasp, and at an opposing second end the extender has an annulus, such as a hole in the extender or a loop or ring affixed to the extender. The shackle of the padlock may be disposed through the annulus and may be disposed through the eye of a second staple to secure the door or window in a closed or open position. Some embodiments employ a rigid sheath to enclose at least a portion of the extender. Typically the rigid sheath has an open state where the hook is exposed outside the sheath and a closed state where the hook is disposed within the sheath.

  16. The influence of lead length on the fractures associated with leading corners and sidings

    CSIR Research Space (South Africa)

    Turner, PA

    1989-02-01

    Full Text Available leading and lagging panels was found generally to extend further into the lagging panel with increasing lead length. Curves fitted to the data seem to be asymptotic to a limiting fracture extent of about 15 to 20 m. More information is needed on the siding...

  17. Lead (Pb) Air Pollution

    Science.gov (United States)

    ... Environmental Protection Agency Search Search Lead (Pb) Air Pollution Contact Us Share As a result of EPA's ... protect aquatic and terrestrial ecosystems. Lead (Pb) Air Pollution Basic Information How does lead get in the ...

  18. Targeted disruption of the JAK2/STAT3 pathway in combination with systemic administration of paclitaxel inhibits the priming of ovarian cancer stem-like cells leading to a reduced tumor burden

    Directory of Open Access Journals (Sweden)

    Khalid eAbubaker

    2014-04-01

    Full Text Available Chemotherapy resistance associated with recurrent disease is the major cause of poor survival of ovarian cancer patients. We have recently demonstrated activation of the JAK2/STAT3 pathway and the enhancement of a cancer stem cell (CSC-like phenotype in ovarian cancer cells treated in vitro with chemotherapeutic agents. To elucidate further these mechanisms in vivo, we used a two tiered paclitaxel treatment approach in nude mice inoculated with ovarian cancer cells. In the first approach, we demonstrate that a single intraperitoneal administration of paclitaxel in mice 7 days after subcutaneous transplantation of the HEY ovarian cancer cell line resulted in a significant increase in the expression of CA125, Oct4 and CD117 in mice xenografts compared to control mice xenografts which did not receive paclitaxel. In the second approach, mice were administered once weekly with paclitaxel and/or a daily dose of the JAK2 specific inhibitor, CYT387, over four weeks. Mice receiving paclitaxel only demonstrated a significant decrease in tumor volume compared to control mice. At the molecular level, mouse tumors remaining after paclitaxel administration showed a significant increase in the expression of Oct4 and CD117 coinciding with a significant activation of the JAK2/STAT3 pathway compared to control tumors. The addition of CYT387 with paclitaxel resulted in the suppression of JAK2/STAT3 activation and abrogation of Oct4 and CD117 expression in mouse xenografts. This coincided with significantly smaller tumors in mice administered CYT387 in addition to paclitaxel, compared to the control group and the group of mice receiving paclitaxel only. These data suggest that the systemic administration of paclitaxel enhances Oct4 and CD117 associated CSC-like marker expression in surviving cancer cells in vivo, which can be suppressed by the addition of the JAK2 specific inhibitor CYT387, leading to a significantly smaller tumor burden. These novel findings have

  19. Pricing Extendible Options Using the Fast Fourier Transform

    Directory of Open Access Journals (Sweden)

    Siti Nur Iqmal Ibrahim

    2014-01-01

    Full Text Available This paper applies the fast Fourier transform (FFT approach, within the Black-Scholes framework, to the valuation of options whose time to maturity can be extended to a future date (extendible options. We determine the valuation of the extendible options as sums of expectations of indicator functions, leading to a semianalytic expression for the value of the options over a range of strikes. Compared to Monte Carlo simulation, numerical examples demonstrate that the FFT is both computationally more efficient and higher in accuracy.

  20. Tilt anisoplanatism in extended turbulence propagation

    Science.gov (United States)

    Magee, Eric P.; Whiteley, Matthew R.; Das, Shashikala T.; Welsh, Byron M.

    2003-04-01

    The use of high-energy laser (HEL) weapon systems in tactical air-to-ground target engagements offers great promise for revolutionizing the USAF's war-fighting capabilities. Laser directed-energy systems will enable ultra-precision strike with minimal collateral damage and significant stand-off range for the aerial platform. The tactical directed energy application differs in many crucial ways from the conventional approach used in missile defense. Tactical missions occur at much lower altitudes and involve look-down to low-contrast ground targets instead of a high-contrast boosting missile. At these lower altitudes, the strength of atmospheric turbulence is greatly enhanced. Although the target slant ranges are much shorter, tactical missions may still involve moderate values of the Rytov number (0.1-0.5), and small isoplanatic angles compared to the diffraction angle. With increased density of air in the propagation path, and the potential for slow-moving or stationary ground targets, HEL-induced thermal blooming will certainly be a concern. In order to minimize the errors induced by tracking through thermal blooming, offset aimpoint tracking can be used. However, this will result in significant tilt anisoplanatism, thus degrading beam stabilization on target. In this paper we investigate the effects of extended turbulence on tracking (or tilt) anisoplanatism using theory and wave optics simulations. The simulations show good agreement with geometric optics predictions at angles larger than about 5 micro-radians (asymptotic regime) while at smaller angles the agreement is poor. We present a theoretical basis for this observation.

  1. Cryogenic current leads

    Energy Technology Data Exchange (ETDEWEB)

    Zizek, F.

    1982-01-01

    Theoretical, technical and design questions are examined of cryogenic current leads for SP of magnetic systems. Simplified mathematical models are presented for the current leads. To illustrate modeling, the calculation is made of the real current leads for 500 A and three variants of current leads for 1500 A for the enterprise ''Shkoda.''

  2. Viability of bull semen extended with commercial semen extender ...

    African Journals Online (AJOL)

    Andrea Raseona

    Abstract. The aim of this study was to evaluate the viability of bull spermatozoa diluted with commercial semen extender and two culture media stored at controlled room temperature (24 °C) for 72 hours. Two Nguni bulls were used for semen collection with the aid of an electro-ejaculator. After macroscopic evaluation ...

  3. Extended cognition in science communication.

    Science.gov (United States)

    Ludwig, David

    2014-11-01

    The aim of this article is to propose a methodological externalism that takes knowledge about science to be partly constituted by the environment. My starting point is the debate about extended cognition in contemporary philosophy and cognitive science. Externalists claim that human cognition extends beyond the brain and can be partly constituted by external devices. First, I show that most studies of public knowledge about science are based on an internalist framework that excludes the environment we usually utilize to make sense of science and does not allow the possibility of extended knowledge. In a second step, I argue that science communication studies should adopt a methodological externalism and accept that knowledge about science can be partly realized by external information resources such as Wikipedia. © The Author(s) 2013.

  4. Extended memory management under RTOS

    Science.gov (United States)

    Plummer, M.

    1981-01-01

    A technique for extended memory management in ROLM 1666 computers using FORTRAN is presented. A general software system is described for which the technique can be ideally applied. The memory manager interface with the system is described. The protocols by which the manager is invoked are presented, as well as the methods used by the manager.

  5. Extended time-interval analysis

    DEFF Research Database (Denmark)

    Fynbo, Hans Otto Uldall; Riisager, Karsten

    2014-01-01

    Several extensions of the halflife analysis method recently suggested by Horvat and Hardy are put forward. Goodness-of-fit testing is included, and the method is extended to cases where more information is available for each decay event which allows applications also for e.g. γ decay data. The re...

  6. Extended duration orbiter (EDO) insignia

    Science.gov (United States)

    1990-01-01

    Extended duration orbiter (EDO) insignia incorporates a space shuttle orbiter with payload bay doors (PLBDs) open and a spacelab module inside. Trailing the orbiter are the initials EDO. The EDO-modified Columbia, Orbiter Vehicle (OV) 102, will be flown for the first EDO mission, STS-50.

  7. Extended Duration Orbiter Medical Project

    Science.gov (United States)

    Leach, C. S.; Pool, S. L.; Sawin, C. F.; Nicogossian, A. E.

    1990-01-01

    The Extended Duration Orbiter (EDO) program addresses a need for more time to perform experiments and other tasks during Space Shuttle missions. As a part of this program, the Extended Duration Orbiter Medical Project (EDOMP) has been instituted to obtain information about physiologic effects of extending mission duration and the effectiveness of countermeasures against factors that might compromise crew health, safety, or performance on extended-duration missions. Only those investigations that address and characterize operational problems, develop countermeasures, or evaluate the effectiveness of countermeasures will be pursued. The EDOMP investigations will include flight-associated Detailed Supplementary Objectives as well as ground-based studies simulating the influence of microgravity. Investigator teams have been formed in the following areas: biomedical physiology, cardiovascular and fluid/electrolyte physiology, environmental health, muscle and exercise physiology, and neurophysiology. Major operational questions must be answered in each of these areas, and investigations have been designed to answer them. The EDO program will proceed only after countermeasures have been shown to be effective in preventing or mitigating the adverse changes they have been designed to attenuate. The program is underway and will continue on each Shuttle flight as the manifest builds toward a 16-day orbital flight.

  8. Applying and extending Oracle Spatial

    CERN Document Server

    Simon Gerard Greener, Siva Ravada

    2013-01-01

    This book is an advanced practical guide to applying and extending Oracle Spatial.This book is for existing users of Oracle and Oracle Spatial who have, at a minimum, basic operational experience of using Oracle or an equivalent database. Advanced skills are not required.

  9. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  10. Effect of lead pollution on fitness and its dependence on ...

    Indian Academy of Sciences (India)

    Lead is one of the most present contaminants in the environment, and different species respond differently to this type of pollution. If combined with genomic stress, lead may act ... The progeny were reared on a standard medium and a medium with 200 g/mL of lead acetate. Development time was significantly extended to ...

  11. The Extended Relativity Theory in Clifford Spaces

    CERN Document Server

    Castro, C

    2004-01-01

    A brief review of some of the most important features of the Extended Relativity theory in Clifford-spaces ( $C$-spaces) is presented whose " point" coordinates are noncommuting Clifford-valued quantities and which incoporate the lines, areas, volumes, .... degrees of freedom associated with the collective particle, string, membrane, ... dynamics of the $p$-loop histories (closed p-branes) living in target $D$-dimensional spacetime backgrounds. $C$-space Relativity naturally incoporates the ideas of an invariant length (Planck scale), maximal acceleration, noncommuting coordinates, supersymmetry, holography, superluminal propagation, higher derivative gravity with torsion and variable dimensions/signatures that allows to study the dynamics of all (closed ) p-branes, for all values of $ p $, in a unified footing. It resolves the ordering ambiguities in QFT and the problem of time in Cosmology. A discussion of the maximal-acceleration Relativity principle in phase-spaces follows along with the study of the inva...

  12. The Extended Relativity Theory in Clifford Spaces

    CERN Document Server

    Castro, C

    2004-01-01

    A brief review of some of the most important features of the Extended Relativity theory in Clifford-spaces ($C$-spaces) is presented whose " point" coordinates are noncommuting Clifford-valued quantities and which incorporate the lines, areas, volumes,.... degrees of freedom associated with the collective particle, string, membrane,... dynamics of $p$-loops (closed p-branes) living in target $D$-dimensional spacetime backgrounds. $C$-space Relativity naturally incorporates the ideas of an invariant length (Planck scale), maximal acceleration, noncommuting coordinates, supersymmetry, holography, higher derivative gravity with torsion and variable dimensions/signatures that allows to study the dynamics of all (closed) p-branes, for all values of $ p $, on a unified footing. It resolves the ordering ambiguities in QFT and the problem of time in Cosmology. A discussion of the maximal-acceleration Relativity principle in phase-spaces follows along with the study of the invariance group of symmetry transformations ...

  13. Lead content of foodstuffs.

    Science.gov (United States)

    Mitchell, D G; Aldous, K M

    1974-05-01

    The lead content of a number of foodstuffs, particularly baby fruit juices and milk, is reported. Samples were analyzed in quadruplicate by using an automated Delves cup atomic absorption procedure. A large proportion of the products examined contained significant amounts of lead. Of 256 metal can examined, the contents of 62% contained a lead level of 100 mug/l. or more, 37% contained 200 mug/l. or more and 12% contained 400 mug/l. lead or more. Of products in glass and aluminum containers, only 1% had lead levels in excess of 200 mug/l. Lead levels of contents also correlate with the seam length/volume ratio of the leaded seam can. A survey of bulk milk showed a mean lead level of 40 mug/l. for 270 samples; for canned evaporated milk the mean level was 202 mug/l. These data indicate a potential health hazard.

  14. Lead and tap water

    Science.gov (United States)

    Water contaminated with lead ... The Environmental Protection Agency (EPA) monitors drinking water in the United States. It requires water suppliers to produce annual water quality reports. These reports include information about lead amounts, and they ...

  15. NA49: lead-lead collision

    CERN Multimedia

    1996-01-01

    This is an image of an actual lead ion collision taken from tracking detectors on the NA49 experiment, part of the heavy ion project at CERN. These collisions produce a very complicated array of hadrons as the heavy ions break up. It is hoped that one of these collisions will eventually create a new state of matter known as quark-gluon plasma.

  16. Continuum balances from extended Hamiltonian dynamics.

    Science.gov (United States)

    Giusteri, Giulio G; Podio-Guidugli, Paolo; Fried, Eliot

    2017-06-14

    The classical procedure devised by Irving and Kirkwood in 1950 and completed slightly later by Noll produces counterparts of the basic balance laws of standard continuum mechanics starting from an ordinary Hamiltonian description of the dynamics of a system of material points. Post-1980 molecular dynamics simulations of the time evolution of such systems use extended Hamiltonians such as those introduced by Andersen, Nosé, and Parrinello and Rahman. The additional terms present in these extensions affect the statistical properties of the system so as to capture certain target phenomenologies that would otherwise be beyond reach. We here propose a physically consistent application of the Irving-Kirkwood-Noll procedure to the extended Hamiltonian systems of material points. Our procedure produces balance equations at the continuum level featuring non-standard terms because the presence of auxiliary degrees of freedom gives rise to additional fluxes and sources that influence the thermodynamic and transport properties of the continuum model. Being aware of the additional contributions may prove crucial when designing multiscale computational schemes in which information is exchanged between the atomistic and continuum levels.

  17. Infection Rates of Electrical Leads Used for Percutaneous Neurostimulation of the Peripheral Nervous System.

    Science.gov (United States)

    Ilfeld, Brian M; Gabriel, Rodney A; Saulino, Michael F; Chae, John; Peckham, P Hunter; Grant, Stuart A; Gilmore, Christopher A; Donohue, Michael C; deBock, Matthew G; Wongsarnpigoon, Amorn; Boggs, Joseph W

    2017-07-01

    Percutaneous neurostimulation of the peripheral nervous system involves the insertion of a wire "lead" through an introducing needle to target a nerve/plexus or a motor point within a muscle. Electrical current may then be passed from an external generator through the skin via the lead for various therapeutic goals, including providing analgesia. With extended use of percutaneous leads sometimes greater than a month, infection is a concern. It was hypothesized that the infection rate of leads with a coiled design is lower than for leads with a noncoiled cylindrical design. The literature was retrospectively reviewed for clinical studies of percutaneous neurostimulation of the peripheral nervous system of greater than 2 days that included explicit information on adverse events. The primary endpoint was the number of infections per 1,000 indwelling days. Forty-three studies were identified that met inclusion criteria involving coiled (n = 21) and noncoiled (n = 25) leads (3 studies involved both). The risk of infection with noncoiled leads was estimated to be 25 times greater than with coiled leads (95% confidence interval [CI] 2 to 407, P = 0.006). The infection rates were estimated to be 0.03 (95% CI 0.01 to 0.13) infections per 1,000 indwelling days for coiled leads and 0.83 (95% CI 0.16 to 4.33) infections per 1,000 indwelling days for noncoiled leads (P = 0.006). Percutaneous leads used for neurostimulation of the peripheral nervous system have a much lower risk of infection with a coiled design compared with noncoiled leads: approximately 1 infection for every 30,000 vs. 1,200 indwelling days, respectively. © 2016 The Authors. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.

  18. Lead Poisoning (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Lead Poisoning KidsHealth > For Parents > Lead Poisoning Print A ... Family en español La intoxicación por plomo About Lead Poisoning If you have young kids, it's important ...

  19. Lead Poisoning in Childhood.

    Science.gov (United States)

    Pueschel, Siegfried M., Ed.; Linakis, James G., Ed.; Anderson, Angela C., Ed.

    The magnitude of childhood lead poisoning has been inexplicably neglected by modern medicine and by legislators. However, since the 1970s, increased attention has been focused on lead poisoning, and advances have been made in several areas, including understanding of the neurodevelopmental and behavioral ramifications of lead poisoning, and…

  20. Lead poisoning: An overview

    Science.gov (United States)

    Gendel, Neil

    1993-01-01

    A problem that should be of great concern to all of us is the lead poisoning of children. First, I would like to present a short overview concerning the reasons everyone should care about lead poisoning, then discuss the history of lead poisoning, what is happening today across the country, and the future.

  1. Lead Poisoning in Children.

    Science.gov (United States)

    Drummond, A. H., Jr.

    1981-01-01

    Early symptoms of lead poisoning in children are often overlooked. Lead poisoning has its greatest effects on the brain and nervous system. The obvious long-term solution to the lead poisoning problem is removal of harmful forms of the metal from the environment. (JN)

  2. Cyanobacterial Cyclopeptides as Lead Compounds to Novel Targeted Cancer Drugs

    OpenAIRE

    Sainis, Ioannis; Fokas, Demosthenes; Vareli, Katerina; Tzakos, Andreas G.; Kounnis, Valentinos; Briasoulis, Evangelos

    2010-01-01

    Cyanobacterial cyclopeptides, including microcystins and nodularins, are considered a health hazard to humans due to the possible toxic effects of high consumption. From a pharmacological standpoint, microcystins are stable hydrophilic cyclic heptapeptides with a potential to cause cellular damage following uptake via organic anion-transporting polypeptides (OATP). Their intracellular biological effects involve inhibition of catalytic subunits of protein phosphatase 1 (PP1) and PP2, glutathio...

  3. Standard Hip Ventrodorsal Leg Extended View In The Diagnosis Of ...

    African Journals Online (AJOL)

    Canine hip dysplasia (CHD) is hereditary developmental condition that involves a lack of conformity between the femoral head and acetabulum. It invariably leads to osteoarthritis. We hereby review the standard hip ventrodorsal leg extended view to be adopted by our Tanzanian veterinarians. Diagnostic radiography is the ...

  4. Emotional Arousal of Beginning Physics Teachers during Extended Experimental Investigations

    Science.gov (United States)

    Ritchie, Stephen M.; Tobin, Kenneth; Sandhu, Maryam; Sandhu, Satwant; Henderson, Senka; Roth, Wolff-Michael

    2013-01-01

    Teachers often have difficulty implementing inquiry-based activities, leading to the arousal of negative emotions. In this multicase study of beginning physics teachers in Australia, we were interested in the extent to which their expectations were realized and how their classroom experiences while implementing extended experimental investigations…

  5. Analytical Results Connecting Stellar Structure Parameters and Extended Reaction Rates

    Directory of Open Access Journals (Sweden)

    Hans J. Haubold

    2014-01-01

    Full Text Available Possible modification in the velocity distribution in the nonresonant reaction rates leads to an extended reaction rate probability integral. The closed form representation for these thermonuclear functions is used to obtain the stellar luminosity and neutrino emission rates. The composite parameter that determines the standard nuclear reaction rate through the Maxwell-Boltzmann energy distribution is extended to * by the extended reaction rates through a more general distribution than the Maxwell-Boltzmann distribution. The new distribution is obtained by the pathway model introduced by Mathai (2005. Simple analytic models considered by various authors are utilized for evaluating stellar luminosity and neutrino emission rates and are obtained in generalized special functions such as Meijer's G-function and Fox's H-function. The standard and extended nonresonant thermonuclear functions are compared by plotting them. Behaviour of the new energy distribution, which is more general than the Maxwell-Boltzmann, is also studied.

  6. Evaluate extended surface exchangers carefully

    Energy Technology Data Exchange (ETDEWEB)

    Ganapathy, V. (ABCO Industries, Inc., Abilene, TX (US))

    1990-10-01

    Various types of fins, such as circumferential, rectangular, pegs and rods are used in heat transfer equipment. Fins can be used inside as well as on the outside of tubes. However, to illustrate the basic facts of heat transfer and how one should evaluate fins, these discussions pertain to circumferential solid or serrated fins used widely in the energy equipment industry. Extended surfaces have the advantage of reducing the size and weight of heat transfer equipment. In addition they can result in lower gas pressure drop, thus reducing the operating costs. This article compares the performance of an evaporator for a heat recovery steam generator (HRSG) using bare and finned tubes. The fact this article brings out is that extended surfaces should be evaluated and purchased based on performance and not based on surface area alone.

  7. Extended Supersymmetries in One Dimension

    Directory of Open Access Journals (Sweden)

    F. Toppan

    2008-01-01

    Full Text Available This work covers part of the material presented at the Advanced Summer School in Prague. It is mostly devoted to the structural properties of Extended Supersymmetries in One Dimension. Several results are presented on the classification of linear, irreducible representations realized on a finite number of time-dependent fields. The connections between supersymmetry transformations, Clifford algebras and division algebras are discussed. A manifestly supersymmetric framework for constructing invariants without using the notion of superfields is presented. A few examples of one-dimensional, N-extended, off-shell invariant sigma models are computed. The relation between supersymmetry transformations and graph theory is outlined. The notion of the fusion algebra of irreps tensor products is presented. The relevance of one-dimensional Supersymmetric Quantum Mechanics as a way to extract information on higher dimensional supersymmetric field theories is discussed. 

  8. Extending a browser C++ simulator

    OpenAIRE

    Segarra Roca, Albert

    2017-01-01

    Getting started in computer programming involves using a number of tools such as editors, compilers, debuggers, and terminals. Learning how to use them can be challenging for programming begginers, and installing them may be demanding for certain organizations such as high schools. C– is a project that aims to bridge this gap by providing an educational C++ development environment that runs in a web browser. The goal of this thesis is to extend and improve the current implement...

  9. Locating and extending livelihoods research

    DEFF Research Database (Denmark)

    Prowse, Martin

    2008-01-01

    Much poverty and development research is not explicit about its methodology or philosophical foundations. Based on the extended case method of Burawoy and the epistemological standpoint of critical realism, this paper discusses a methodological approach for reflexive inductive livelihoods research...... that overcomes the unproductive social science dualism of positivism and social constructivism. The approach is linked to a conceptual framework and a menu of research methods that can be sequenced and iterated in light of research questions....

  10. Evolving extended naive Bayes classifiers

    OpenAIRE

    Klawonn, Frank; Angelov, Plamen

    2006-01-01

    Naive Bayes classifiers are a very simple, but often effective tool for classification problems, although they are based on independence assumptions that do not hold in most cases. Extended naive Bayes classifiers also rely on independence assumptions, but break them down to artificial subclasses, in this way becoming more powerful than ordinary naive Bayes classifiers. Since the involved computations for Bayes classifiers are basically generalised mean value calculations, they easily render ...

  11. Lead encephalopathy in adults

    Directory of Open Access Journals (Sweden)

    Janapareddy Vijaya Bhaskara Rao

    2014-01-01

    Full Text Available Lead poisoning is a common occupational health hazard in developing countries. We report the varied clinical presentation, diagnostic and management issues in two adult patients with lead encephalopathy. Both patients worked in a battery manufacturing unit. Both patients presented with seizures and one patient also complained of abdominal colic and vomiting. Both were anemic and a lead line was present. Blood lead level in both the patients was greater than 25 µg/dl. Magnetic resonance imaging of brain revealed bilateral symmetric involvement of the thalamus, lentiform nucleus in both patients and also the external capsules, sub-cortical white matter in one patient. All these changes, seen as hyperintensities in T2-weighted images suggested demyelination. They were advised avoidance of further exposure to lead and were treated with anti-epileptics; one patient also received D-penicillamine. They improved well on follow-up. Lead encephalopathy is an uncommon but important manifestation of lead toxicity in adults.

  12. Lead in the environment

    Science.gov (United States)

    Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Anthropogenic uses of lead have probably altered its availability and environmental distribution more than any other toxic element. Consequently, lead concentrations in many living organisms may be approaching thresholds of toxicity for the adverse effects of lead. Such thresholds are difficult to define, as they vary with the chemical and physical form of lead, exposure regime, other elements present and also vary both within and between species. The technological capability to accurately quantify low lead concentrations has increased over the last decade, and physiological and behavioral effects have been measured in wildlife with tissue lead concentrations below those previously considered safe for humans.s.236 Consequently. lead criteria for the protection of wildlife and human health are frequently under review, and 'thresholds' of lead toxicity are being reconsidered. Proposed lead criteria for the protection of natural resources have been reviewed by Eisler. Uptake of lead by plants is limited by its generally low availability in soils and sediments, and toxicity may be limited by storage mechanisms and its apparently limited translocation within most plants. Lead does not generally accumulate within the foliar parts of plants, which limits its transfer to higher trophic levels. Although lead may concentrate in plant and animal tissues, no evidence of biomagnification exists. Acid deposition onto surface waters and soils with low buffering capacity may influence the availability of lead for uptake by plants and animals, and this may merit investigation at susceptible sites. The biological significance of chronic low-level lead exposure to wildlife is sometimes difficult to quantify. Animals living in urban environments or near point sources of lead emission are inevitably subject to greater exposure to lead and enhanced risk of lead poisoning. Increasingly strict controls on lead emissions in many countries have reduced exposure to lead from some sources

  13. Applying SPAM to the extended MWA

    Science.gov (United States)

    Hurley-Walker, N.; Intema, H.

    2017-01-01

    The extended baselines of the MWA move the instrument into a more difficult calibration and imaging regime, where the more widely-separated antennas are more likely to view the sky through different ionospheric conditions, leading to differential refractive effects over the array. Current extrapolations by Trott, Jordan, and Hurley-Walker imply that the diffractive scale will remain larger than the longest baseline for 50-70% of observations, but these are extrapolations only. Other instruments have performed observations with baselines longer than the diffractive scale, and used software techniques to mitigate the ionospheric distortions. One such survey is the Tata Institute of Fundamental Research Giant Metrewave Radio Telescope Sky Survey (TGSS) at 150 MHz. Intema et al. (2016) used the Source Peeling & Atmospheric Modeling (SPAM) software to produce a catalogue of over 600,000 sources from data that had previously been slow and difficult to process. This proposal is for a short series of observations to test the usage of the SPAM software on the extended MWA, and to find the optimal observing parameters for its use. If successful, this could assist other groups in effectively utilising the long baselines.

  14. ALICE: Simulated lead-lead collision

    CERN Document Server

    2003-01-01

    This track is an example of simulated data modelled for the ALICE detector on the Large Hadron Collider (LHC) at CERN, which will begin taking data in 2008. ALICE will focus on the study of collisions between nuclei of lead, a heavy element that produces many different particles when collided. It is hoped that these collisions will produce a new state of matter known as the quark-gluon plasma, which existed billionths of a second after the Big Bang.

  15. Organic Lead Toxicology

    Directory of Open Access Journals (Sweden)

    Jiří Patočka

    2008-01-01

    Full Text Available Lead is one of the oldest known and most widely studied occupational and environmental poison. Despite intensive study, there is still debate about the toxic effects of lead, both from low-level exposure in the general population owing to environmental pollution and historic use of lead in paint and plumbing and from exposure in the occupational setting. Significant position have organic lead compounds used more than 60 years as antiknock additives in gasoline. Chemical and toxicological characteristics of main tetraalkyl leads used as gasoline additives are discussed in this article. The majority of industries historically associated with high lead exposure have made dramatic advances in their control of occupational exposure. However, cases of unacceptably high exposure and even of frank lead poisoning are still seen, predominantly in the demolition and tank cleaning industries. Nevertheless, in most industries blood lead levels have declined below levels at which signs or symptoms are seen and the current focus of attention is on the subclinical effects of exposure. The significance of some of these effects for the overt health of the workers is often the subject of debate. Inevitably there is pressure to reduce lead exposure in the general population and in working environments, because current studies show that no level of lead exposure appears to be a ‘safe’ and even the current ‘low’ levels of exposure, especially in children, are associated with neurodevelopmental deficits.

  16. Drowning: a leading killer!

    Directory of Open Access Journals (Sweden)

    Nuno Domingos Garrido

    2016-10-01

    Full Text Available Drowning kills at least 372,000 people worldwide every year and is the 3rd leading cause of unintentional death, accounting for 7% of all deaths stemming from accidents (WHO, 2014. Conceptually, “drowning” is a complex and multi-faceted phenomenon, characterized as a chain of events (Bierens, 2006. Drowning is defined as the process of experiencing respiratory impairment from immersion or submersion in liquid. Research on drowning as a phenomenon presents several difficulties - most of all, that global data concerning the number of occurrences are not accurate. Nevertheless, detailed analysis of the registered incidents allows the identification of risk factors of drowning. An in-depth analysis of the risk factors is the basis for the creation of targeted and effective strategies to prevent drowning. Due to variability of situations which could lead to a drowning episode, experts suggest the adoption of a multi-layer prevention model, rather than opting for isolated measures, since no single measure can prevent all deaths and injuries caused by submersion. Among the preventive measures we would like to emphasize instruction in swimming and water safety. So, what does "knowing how to swim" really mean? Some authors define mastery of this competence as swimming a given distance, while others put the emphasis on how this/any given distance is swum (Stallman, Junge, & Blixt, 2008. It has long been realized that there is no contradiction between learning those competencies which make a person less susceptible to drowning and those competencies which prepare the path towards higher levels of performance and competition. Aquatic movement researchers and practitioners and drowning prevention researchers and practitioners, share in the responsibility for drowning prevention though they are often unaware of it. The question “What should be taught to children?” is too infrequently asked. There remains great variation in what is taught and programs

  17. Multi-lead heat sink

    Science.gov (United States)

    Roose, Lars D.

    1984-01-01

    The disclosure relates to a heat sink used to protect integrated circuits from the heat resulting from soldering them to circuit boards. A tubular housing contains a slidable member which engages somewhat inwardly extending connecting rods, each of which is rotatably attached at one end to the bottom of the housing. The other end of each rod is fastened to an expandable coil spring loop. As the member is pushed downward in the housing, its bottom edge engages and forces outward the connecting rods, thereby expanding the spring so that it will fit over an integrated circuit. After the device is in place, the member is slid upward and the spring contracts about the leads of the integrated circuit. Soldering is now conducted and the spring absorbs excess heat therefrom to protect the integrated circuit. The placement steps are repeated in reverse order to remove the heat sink for use again.

  18. Richtmyer - Meshkov instability in a spherical target with density variation

    CERN Document Server

    Mandal, Labakanta; Banerjee, Rahul; Khan, Manoranjan; Gupta, M R

    2011-01-01

    The motion of unstable fluid interface due to Richtmyer - Meshkov (RM) instability incorporating with density variation has been studied in a spherical target using Lagrangian formulation. During the compression in Inertial Confinement Fusion (ICF)process, the density of deuterium - tritium (DT) fuel increases 1000 times greater than the density of gaseous DT fuel within the core of spherical target. We have extended the feature of density variation [PRA,84-Mikaelian & Lindl] in spherical geometry.Due to convergent shock impingement, the perturbed interface will be nonspherical which leads to the density variation in both radial as well as in polar angle. We have shown that the interface of perturbed surface decreases with time to reach a minimum and then kick back to gradual increase. As the perturbed radius decreases, the density increases and reaches a maxima corresponding to a minima of perturbed radius. This is the practical situation of density characteristics during implosion of ICF. The numerical ...

  19. Lead-Free Piezoelectrics

    CERN Document Server

    Nahm, Sahn

    2012-01-01

    Ecological restrictions in many parts of the world are demanding the elimination of Pb from all consumer items. At this moment in the piezoelectric ceramics industry, there is no issue of more importance than the transition to lead-free materials. The goal of Lead-Free Piezoelectrics is to provide a comprehensive overview of the fundamentals and developments in the field of lead-free materials and products to leading researchers in the world. The text presents chapters on demonstrated applications of the lead-free materials, which will allow readers to conceptualize the present possibilities and will be useful for both students and professionals conducting research on ferroelectrics, piezoelectrics, smart materials, lead-free materials, and a variety of applications including sensors, actuators, ultrasonic transducers and energy harvesters.

  20. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  1. Lead and the skin

    Energy Technology Data Exchange (ETDEWEB)

    Allen, B.R.; Moore, M.R.; Hunter, J.A.A.

    1975-01-01

    The increasing use of lead will continue to give rise to problems of toxicity. Protective measures have resulted in florid lead poisoning becoming rare. Attention has recently turned to the possibility of prolonged exposure to low doses of lead causing morbidity in the absence of the classical clinical features of poisoning. Lead is absorbed mostly through the lungs and gastrointestinal tract. Some is also absorbed through the skin but with inorganic compounds the amount is small. Shortly after the most widely used compound, tetraethyl lead, was first manufactured, cases of toxicity began to occur. Manufacture was forbidden until plant design produced greater safety. Significant absorption can occur through the skin. The hazard to those handling leaded gasoline in a normal manner is probably small, mainly because 95 percent of a dose applied to the open skin surface evaporates. Hair has been used as a biopsy material to assess lead exposure. The biological effects of lead poisoning are discussed, including the synergistic effects of lead and agents provoking porphyria.

  2. An ISOLDE target unit

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    A good dozen different targets are available for ISOLDE, made of different materials and equipped with different kinds of ion-sources, according to the needs of the experiments. Each separator (GPS: general purpose; HRS: high resolution) has its own target. Because of the high radiation levels, robots effect the target changes, about 80 times per year. In the standard unit shown in picture _01, the target is the cylindrical object in the front. It contains uranium-carbide kept at a temperature of 2200 deg C, necessary for the isotopes to be able to escape. At either end, one sees the heater current leads, carrying 700 A. The Booster beam, some 3E13 protons per pulse, enters the target from left. The evaporated isotope atoms enter a hot-plasma ion source (the black object behind the target). The whole unit sits at 60 kV potential (pulsed in synchronism with the arrival of the Booster beam) which accelerates the ions (away from the viewer) towards one of the 2 separators.

  3. Departies: conceptualizing extended youth parties

    DEFF Research Database (Denmark)

    Fjær, Eivind Grip; Tutenges, Sébastien

    2017-01-01

    -taking behaviors, such as drug use and violence. Here, we scrutinize the research on extended youth parties to identify general changes that young people undergo at these events. We call these celebrations departies, because they center on the organization and facilitation of momentary departures from...... immoral; (4) stylistically, by altering their stylistic expressions through dress, demeanor, and consumption; and (5) experientially, because the parties generate mood and mind alterations. These are overlapping and intertwined elements, the combination of which amounts to a distinct type of youth party...

  4. Measurement Challenges at Low Blood Lead Levels.

    Science.gov (United States)

    Caldwell, Kathleen L; Cheng, Po-Yung; Jarrett, Jeffery M; Makhmudov, Amir; Vance, Kathryn; Ward, Cynthia D; Jones, Robert L; Mortensen, Mary E

    2017-08-01

    In 2012, the Centers for Disease Control and Prevention (CDC) adopted its Advisory Committee on Childhood Lead Poisoning Prevention recommendation to use a population-based reference value to identify children and environments associated with lead hazards. The current reference value of 5 μg/dL is calculated as the 97.5th percentile of the distribution of blood lead levels (BLLs) in children 1 to 5 years old from 2007 to 2010 NHANES data. We calculated and updated selected percentiles, including the 97.5th percentile, by using NHANES 2011 to 2014 blood lead data and examined demographic characteristics of children whose blood lead was ≥90th percentile value. The 97.5th percentile BLL of 3.48 µg/dL highlighted analytical laboratory and clinical interpretation challenges of blood lead measurements ≤5 μg/dL. Review of 5 years of results for target blood lead values Lead and Multi-Element Proficiency quality assurance program showed 40% unable to quantify and reported a nondetectable result at a target blood lead value of 1.48 µg/dL, compared with 5.5% at a target BLL of 4.60 µg/dL. We describe actions taken at the CDC's Environmental Health Laboratory in the National Center for Environmental Health, which measures blood lead for NHANES, to improve analytical accuracy and precision and to reduce external lead contamination during blood collection and analysis. Copyright © 2017 by the American Academy of Pediatrics.

  5. Historical View on Lead: Guidelines and Regulations.

    Science.gov (United States)

    Pohl, Hana R; Ingber, Susan Z; Abadin, Henry G

    2017-04-10

    Lead has been used in many commodities for centuries. As a result, human exposure has occurred through the production and use of these lead-containing products. For example, leaded gasoline, lead-based paint, and lead solder/pipes in water distribution systems have been important in terms of exposure potential to the general population. Worker exposures occur in various industrial activities such as lead smelting and refining, battery manufacturing, steel welding or cutting operations, printing, and construction. Some industrial locations have also been a source of exposure to the surrounding communities. While the toxicity of relatively high lead exposures has been recognized for centuries, modern scientific studies have shown adverse health effects at very low doses, particularly in the developing nervous system of fetuses and children. This chapter reflects on historical and current views on lead toxicity. It also addresses the development and evolution of exposure prevention policies. As discussed here, these lead policies target a variety of potential exposure routes and sources. The changes reflect our better understanding of lead toxicity. The chapter provides lead-related guidelines and regulations currently valid in the U. S. and in many countries around the world. The reader will learn about the significant progress that has been made through regulations and guidelines to reduce exposure and prevent lead toxicity.

  6. EFFECT OF LEAD ACETATE

    African Journals Online (AJOL)

    MICROSOFT

    The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

  7. Leading Acquisition Reform

    Science.gov (United States)

    2011-03-22

    Army and Undersecretary of Defense for Acquisition, for a reduction of the Excalibur and Accelerated Precision Mortar initiative rounds.25...Can’t Dance? Leading a Great Enterprise Through Dramatic Change, (New York: HarperCollins Publishers, 2003), 235. 13 John P. Kotter , Leading Change

  8. Developmental immunotoxicology of lead.

    Science.gov (United States)

    Dietert, Rodney R; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-07-15

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered.

  9. Lead - nutritional considerations

    Science.gov (United States)

    ... lead soldered cans goes into effect. If imported wine containers have a lead foil wrapper, wipe the rim and neck of the bottle with a towel moistened with lemon juice, vinegar, or wine before using. DO NOT store wine, spirits, or ...

  10. Lead toxicity: Current concerns

    Energy Technology Data Exchange (ETDEWEB)

    Goyer, R.A. (Univ. of Western Ontario, London (Canada))

    1993-04-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium-mediated control of vascular smooth muscle contraction and on the renin-angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. 97 refs.

  11. The Extended Relativity Theory in Clifford Spaces

    Directory of Open Access Journals (Sweden)

    Castro C.

    2005-04-01

    Full Text Available An introduction to some of the most important features of the Extended Relativity theory in Clifford-spaces (C-spaces is presented whose “point” coordinates are non-commuting Clifford-valued quantities which incorporate lines, areas, volumes, hyper-volumes. . . degrees of freedom associated with the collective particle, string, membrane, p-brane. . . dynamics of p-loops (closed p-branes in target D-dimensional spacetime backgrounds. C-space Relativity naturally incorporates the ideas of an invariant length (Planck scale, maximal acceleration, non-commuting coordinates, supersymmetry, holography, higher derivative gravity with torsion and variable dimensions/signatures. It permits to study the dynamics of all (closed p-branes, for all values of p, on a unified footing. It resolves the ordering ambiguities in QFT, the problem of time in Cosmology and admits superluminal propagation (tachyons without violations of causality. A discussion of the maximal-acceleration Relativity principle in phase-spaces follows and the study of the invariance group of symmetry transformations in phase-space allows to show why Planck areas are invariant under acceleration-boosts transformations. This invariance feature suggests that a maximal-string tension principle may be operating in Nature. We continue by pointing out how the relativity of signatures of the underlying n-dimensional spacetime results from taking different n-dimensional slices through C-space. The conformal group in spacetime emerges as a natural subgroup of the Clifford group and Relativity in C-spaces involves natural scale changes in the sizes of physical objects without the introduction of forces nor Weyl’s gauge field of dilations. We finalize by constructing the generalization of Maxwell theory of Electrodynamics of point charges to a theory in C-spaces that involves extended charges coupled to antisymmetric tensor fields of arbitrary rank. In the concluding remarks we outline briefly

  12. Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis

    Directory of Open Access Journals (Sweden)

    Jolly Emmitt R

    2005-11-01

    Full Text Available Abstract Background A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis. Results Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria. Conclusion We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.

  13. Maritime Load Dependent Lead Times - An Analysis

    DEFF Research Database (Denmark)

    Pahl, Julia

    2017-01-01

    steps and increased container lead times. Proposed solutions to fight congestion range from extend-ing port capacities to process optimization of parts of the maritime supply chain. The potential that lies in information sharing and integrated planning using IT has received some attention, but mainly...... on the operational level concerning timely information sharing. Collaborative planning approaches for the maritime supply chain are scarce. The production industry already implemented planning and in-formation concepts. Problems related to the maritime supply chain have great similarities with those encountered...... in production. Inspired by supply chain planning systems, we analyze the current state of (collaborative) planning in the maritime transport chain with focus on containers. Regarding the problem of congestion, we particularly emphasize on load dependent lead times (LDLT) which are well studied in production....

  14. Center for Extended Magnetohydrodynamics Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, Jesus [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2017-02-14

    This researcher participated in the DOE-funded Center for Extended Magnetohydrodynamics Modeling (CEMM), a multi-institutional collaboration led by the Princeton Plasma Physics Laboratory with Dr. Stephen Jardin as the overall Principal Investigator. This project developed advanced simulation tools to study the non-linear macroscopic dynamics of magnetically confined plasmas. The collaborative effort focused on the development of two large numerical simulation codes, M3D-C1 and NIMROD, and their application to a wide variety of problems. Dr. Ramos was responsible for theoretical aspects of the project, deriving consistent sets of model equations applicable to weakly collisional plasmas and devising test problems for verification of the numerical codes. This activity was funded for twelve years.

  15. Hamiltonian dynamics of extended objects

    Energy Technology Data Exchange (ETDEWEB)

    Capovilla, R [Departamento de FIsica, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo Postal 14-740, 07000 Mexico, DF (Mexico); Guven, J [School of Theoretical Physics, Dublin Institute for Advanced Studies, 10 Burlington Road, Dublin 4 (Ireland); Rojas, E [Instituto de Ciencias Nucleares, Universidad Nacional Autonoma de Mexico, Apdo Postal 70-543, 04510 Mexico, DF (Mexico)

    2004-12-07

    We consider relativistic extended objects described by a reparametrization-invariant local action that depends on the extrinsic curvature of the worldvolume swept out by the object as it evolves. We provide a Hamiltonian formulation of the dynamics of such higher derivative models which is motivated by the ADM formulation of general relativity. The canonical momenta are identified by looking at boundary behaviour under small deformations of the action; the relationship between the momentum conjugate to the embedding functions and the conserved momentum density is established. The canonical Hamiltonian is constructed explicitly; the constraints on the phase space, both primary and secondary, are identified and the role they play in the theory is described. The multipliers implementing the primary constraints are identified in terms of the ADM lapse and shift variables and Hamilton's equations are shown to be consistent with the Euler-Lagrange equations.

  16. Extended mission life support systems

    Science.gov (United States)

    Quattrone, P. D.

    1985-01-01

    Extended manned space missions which include interplanetary missions require regenerative life support systems. Manned mission life support considerations are placed in perspective and previous manned space life support system technology, activities and accomplishments in current supporting research and technology (SR&T) programs are reviewed. The life support subsystem/system technologies required for an enhanced duration orbiter (EDO) and a space operations center (SOC), regenerative life support functions and technology required for manned interplanetary flight vehicles, and future development requirements are outlined. The Space Shuttle Orbiters (space transportation system) is space cabin atmosphere is maintained at Earth ambient pressure of 14.7 psia (20% O2 and 80% N2). The early Shuttle flights will be seven-day flights, and the life support system flight hardware will still utilize expendables.

  17. Extended Fundamental Model of Resonance

    Science.gov (United States)

    Breiter, Sławomir

    2003-03-01

    Fundamental models are the simplest, one degree of freedom Hamiltonians that serve as a tool to understand the qualitative effects of various resonances. A new, extended fundamental model (EFM) is proposed in order to improve the classical, Andoyer type, second fundamental model (SFM). The EFM Hamiltonian differs from the SFM by the addition of a term with the third power of momentum; it depends on two free parameters. The new model is studied for the case of a first-order resonance, where up to five critical points can be present. Similarly, to the respective SFM, it admits only the saddle-node bifurcations of critical points, but its advantage lies in the capability of generating the separatrix bifurcations, known also as saddle connections. The reduction of parameters for the EFM has been performed in a way that allows the use of the model in the case of the so-called abnormal resonance.

  18. Learning Extended Finite State Machines

    Science.gov (United States)

    Cassel, Sofia; Howar, Falk; Jonsson, Bengt; Steffen, Bernhard

    2014-01-01

    We present an active learning algorithm for inferring extended finite state machines (EFSM)s, combining data flow and control behavior. Key to our learning technique is a novel learning model based on so-called tree queries. The learning algorithm uses the tree queries to infer symbolic data constraints on parameters, e.g., sequence numbers, time stamps, identifiers, or even simple arithmetic. We describe sufficient conditions for the properties that the symbolic constraints provided by a tree query in general must have to be usable in our learning model. We have evaluated our algorithm in a black-box scenario, where tree queries are realized through (black-box) testing. Our case studies include connection establishment in TCP and a priority queue from the Java Class Library.

  19. Catalytic distillation extends its reach

    Energy Technology Data Exchange (ETDEWEB)

    Rock, K.; McGuirk, T. [Catalytic Distillation Technologies, Houston, TX (United States); Gildert, G.R. [Catalytic Distillation Technologies, Pasadena, TX (United States)

    1997-07-01

    Since the early 1980s, catalytic distillation processes have been selected by more than a hundred operators for various applications. Since such a unit performs both reaction and distillation simultaneously, a combined column can replace a separate, fixed-bed reactor and distillation column, thereby eliminating equipment and reducing capital costs. And, compared to the conventional approach, catalytic distillation may also improve other factors, such as reactant conversion, selectivity, mass transfer, operating pressure, oligomer formation and catalyst fouling. The constant washing of the catalyst by liquid flowing down the column and the distillation of high-boiling foulants results in extended catalyst life. Four selective hydrogenation applications of catalytic distillation are discussed: Butadiene selective hydrogenation combined within an MTBE unit; Pentadiene selective hydrogenation; C{sub 4} acetylene conversion; and Benzene saturation.

  20. Oral hydromorphone extended-release.

    Science.gov (United States)

    Guay, David R P

    2010-12-01

    To review the chemistry, pharmacodynamics, pharmacokinetics, efficacy, tolerability, dosing, and role of the Osmotic-controlled Release Oral delivery System (OROS) hydromorphone extended-release (ER) tablets. A MEDLINE/PUBMED search (1986-August 2010) was conducted to identify studies in the English language, with additional references being obtained from their bibliographies. All studies of hydromorphone ER were reviewed. This is the second long-acting hydromorphone formulation to receive approval by the Food and Drug Administration (a twice-daily formulation was approved in September 2004, but was subsequently withdrawn in July 2005). Hydromorphone is a semi-synthetic mu-opioid receptor agonist structurally similar to morphine, hydrocodone, and oxymorphone. OROS ER technology allows once-daily dosing. Clinical trials have focused on the convertibility of (an) other opioid(s) to hydromorphone ER in chronic malignant and nonmalignant pain. This product displays the expected opioid side effects, being comparable to oxycodone controlled-release. Coadministration with ethanol does not produce the degree of "dose-dumping" seen with the former hydromorphone twice-daily product or oxymorphone ER. Hydromorphone ER is indicated for the management of moderate-to-severe pain in opioidtolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period of time. Dosage adjustment is recommended in patients with moderate hepatic impairment (Child-Pugh class B) and moderate renal impairment (creatinine clearance of 30-60 mL/min). Hydromorphone ER is the newest oral opioid to enter a crowded marketplace now totaling 15 different Schedule 2 opioids (including tapentadol), and tramadol, available in oral, parenteral, rectal, transdermal, transmucosal, and intranasal formulations. It does not appear to have any unique assets or liabilities and should be considered as one of many oral opioids available for the management of persistent pain of moderate

  1. Lead User Innovation

    DEFF Research Database (Denmark)

    Brem, Alexander; Larsen, Henry

    2015-01-01

    User innovation and especially the integration of lead users is a key topic in the innovation management literature of recent years. This paper contributes by providing a rare perspective into what easily could be seen as innovation failure, shown from two perspectives. We show how a lack of shared...... imagination hampers participation and kills innovation between interdependent stakeholders at the threshold between invention and innovation in practice. We present a first case in the fun-sport industry where an external lead user and diverse firm representatives in different functions fail to create......, deliver and capture the value of an innovatively new device together. From the perspective of the lead user, we show antecedents and effects of social interaction between organizational actors and the lead user on the development of social capital, especially trust and shared imagination. The second case...

  2. Vision-Based Position Estimation Utilizing an Extended Kalman Filter

    Science.gov (United States)

    2016-12-01

    GPS jammers are available for as little as $50 [1]. Even malfunctioning equipment can lead to a drone losing its position and thus aborting the...the UAV loses GPS but must maintain a relative position to the target. The drone uses the algorithm to accomplish this task. The exemplary scenario...passive measurements without using GPS . The algorithm receives an image from the drone . It locates the target in the image and outputs an angle. The

  3. Magnesium Diboride Current Leads

    Science.gov (United States)

    Panek, John

    2010-01-01

    A recently discovered superconductor, magnesium diboride (MgB2), can be used to fabricate conducting leads used in cryogenic applications. Dis covered to be superconducting in 2001, MgB2 has the advantage of remaining superconducting at higher temperatures than the previously used material, NbTi. The purpose of these leads is to provide 2 A of electricity to motors located in a 1.3 K environment. The providing environment is a relatively warm 17 K. Requirements for these leads are to survive temperature fluctuations in the 5 K and 11 K heat sinks, and not conduct excessive heat into the 1.3 K environment. Test data showed that each lead in the assembly could conduct 5 A at 4 K, which, when scaled to 17 K, still provided more than the required 2 A. The lead assembly consists of 12 steelclad MgB2 wires, a tensioned Kevlar support, a thermal heat sink interface at 4 K, and base plates. The wires are soldered to heavy copper leads at the 17 K end, and to thin copper-clad NbTi leads at the 1.3 K end. The leads were designed, fabricated, and tested at the Forschungszentrum Karlsruhe - Institut foer Technische Physik before inclusion in Goddard's XRS (X-Ray Spectrometer) instrument onboard the Astro-E2 spacecraft. A key factor is that MgB2 remains superconducting up to 30 K, which means that it does not introduce joule heating as a resistive wire would. Because the required temperature ranges are 1.3-17 K, this provides a large margin of safety. Previous designs lost superconductivity at around 8 K. The disadvantage to MgB2 is that it is a brittle ceramic, and making thin wires from it is challenging. The solution was to encase the leads in thin steel tubes for strength. Previous designs were so brittle as to risk instrument survival. MgB2 leads can be used in any cryogenic application where small currents need to be conducted at below 30 K. Because previous designs would superconduct only at up to 8 K, this new design would be ideal for the 8-30 K range.

  4. Building and testing models with extended Higgs sectors

    Science.gov (United States)

    Ivanov, Igor P.

    2017-07-01

    Models with non-minimal Higgs sectors represent a mainstream direction in theoretical exploration of physics opportunities beyond the Standard Model. Extended scalar sectors help alleviate difficulties of the Standard Model and lead to a rich spectrum of characteristic collider signatures and astroparticle consequences. In this review, we introduce the reader to the world of extended Higgs sectors. Not pretending to exhaustively cover the entire body of literature, we walk through a selection of the most popular examples: the two- and multi-Higgs-doublet models, as well as singlet and triplet extensions. We will show how one typically builds models with extended Higgs sectors, describe the main goals and the challenges which arise on the way, and mention some methods to overcome them. We will also describe how such models can be tested, what are the key observables one focuses on, and illustrate the general strategy with a subjective selection of results.

  5. Proceedings of the workshop on nonlinear MHD and extended MHD

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    Nonlinear MHD simulations have proven their value in interpreting experimental results over the years. As magnetic fusion experiments reach higher performance regimes, more sophisticated experimental diagnostics coupled with ever expanding computer capabilities have increased both the need for and the feasibility of nonlinear global simulations using models more realistic than regular ideal and resistive MHD. Such extended-MHD nonlinear simulations have already begun to produce useful results. These studies are expected to lead to ever more comprehensive simulation models in the future and to play a vital role in fully understanding fusion plasmas. Topics include the following: (1) current state of nonlinear MHD and extended-MHD simulations; (2) comparisons to experimental data; (3) discussions between experimentalists and theorists; (4) /equations for extended-MHD models, kinetic-based closures; and (5) paths toward more comprehensive simulation models, etc. Selected papers have been indexed separately for inclusion in the Energy Science and Technology Database.

  6. Methanol as a gasoline extender: a critique.

    Science.gov (United States)

    Wigg, E E

    1974-11-29

    The tests conducted with the three vehicles at different emission control levels suggest that, in the area of fuel economy and emissions, potential benefits with methanol blends are related to carburetion and are only significant in the case of the rich-operating cars built before emission control standards were imposed. Theoretical considerations related to methanol's leaning effect on carburetion support this conclusion. Potential advantages for methanol in these areas are therefore continuously diminishing as the older cars leave the roads. At present, these older cars use only about one-fourth of the totalc motor gasoline consumed and, before methanol could be used on a large scale, this fraction would be much smaller. The use of methanol in gasoline would almost certainly create severe product quality problems. Water contamination could lead to phase separation in the distribution system and possibly in the car tank as well, and this would require additional investment in fuel handling and blending equipment. Excess fuel volatility in hot weather may also have adverse effects on car performance if the methanol blends include typical concentrations of butanes and pentanes. Removal of these light hydrocarbon components would detract from methanol's role as a gasoline extender and if current fuel volatility specifications were maintained, its use could lead to a net loss in the total available energy for use in motor fuels. Car performance problems associated with excessively lean operation would also be expected in the case of a significant proportion of late-model cars which are adjusted to operate on lean fuel-air mixtures. If methanol does become available in large quantities, these factors suggest that it would be more practical to use it for purposes other than those related to the extending of motor gasoline, such as for gas turbines used for electric power generation. In this case, the "pure" methanol would act as a cleanburning fuel, having none of the

  7. antimicrobial susceptibility pattern of extended spectrum

    African Journals Online (AJOL)

    JAMILU

    ABSTRACT. The emergence of resistant strains of urogenital extended spectrum beta-lactamase producing ... antimicrobial susceptibility test using CLSI recommended, WHO modified Kirby Bauer disc diffusion method. ... Keywords: Extended Spectrum Beta-lactamases, Prevalence, Gram-negative urogenital isolates,.

  8. Positive mass theorem in extended supergravities

    Directory of Open Access Journals (Sweden)

    Masato Nozawa

    2014-10-01

    Full Text Available Following the Witten–Nester formalism, we present a useful prescription using Weyl spinors towards the positivity of mass. As a generalization of arXiv:1310.1663, we show that some “positivity conditions” must be imposed upon the gauge connections appearing in the supercovariant derivative acting on spinors. A complete classification of the connection fulfilling the positivity conditions is given. It turns out that these positivity conditions are indeed satisfied for a number of extended supergravity theories. It is shown that the positivity property holds for the Einstein-complex scalar system, provided that the target space is Hodge–Kähler and the potential is expressed in terms of the superpotential. In the Einstein–Maxwell-dilaton theory with a dilaton potential, the dilaton coupling function and the superpotential are fixed by the positive mass property. We also explore the N=8 gauged supergravity and demonstrate that the positivity of the mass holds independently of the gaugings and the deformation parameters.

  9. 42 CFR 488.310 - Extended survey.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Extended survey. 488.310 Section 488.310 Public...) STANDARDS AND CERTIFICATION SURVEY, CERTIFICATION, AND ENFORCEMENT PROCEDURES Survey and Certification of Long-Term Care Facilities § 488.310 Extended survey. (a) Purpose of survey. The purpose of an extended...

  10. Extended empirical likelihood for estimating equations

    OpenAIRE

    Min Tsao; Fan Wu

    2014-01-01

    We derive an extended empirical likelihood for parameters defined by estimating equations which generalizes the original empirical likelihood to the full parameter space. Under mild conditions, the extended empirical likelihood has all the asymptotic properties of the original empirical likelihood. The first-order extended empirical likelihood is easy to use and substantially more accurate than the original empirical likelihood.

  11. A quantum extended Kalman filter

    Science.gov (United States)

    Emzir, Muhammad F.; Woolley, Matthew J.; Petersen, Ian R.

    2017-06-01

    In quantum physics, a stochastic master equation (SME) estimates the state (density operator) of a quantum system in the Schrödinger picture based on a record of measurements made on the system. In the Heisenberg picture, the SME is a quantum filter. For a linear quantum system subject to linear measurements and Gaussian noise, the dynamics may be described by quantum stochastic differential equations (QSDEs), also known as quantum Langevin equations, and the quantum filter reduces to a so-called quantum Kalman filter. In this article, we introduce a quantum extended Kalman filter (quantum EKF), which applies a commutative approximation and a time-varying linearization to systems of nonlinear QSDEs. We will show that there are conditions under which a filter similar to a classical EKF can be implemented for quantum systems. The boundedness of estimation errors and the filtering problem with ‘state-dependent’ covariances for process and measurement noises are also discussed. We demonstrate the effectiveness of the quantum EKF by applying it to systems that involve multiple modes, nonlinear Hamiltonians, and simultaneous jump-diffusive measurements.

  12. Extended attention span training system

    Science.gov (United States)

    Pope, Alan T.; Bogart, Edward H.

    1991-01-01

    Attention Deficit Disorder (ADD) is a behavioral disorder characterized by the inability to sustain attention long enough to perform activities such as schoolwork or organized play. Treatments for this disorder include medication and brainwave biofeedback training. Brainwave biofeedback training systems feed back information to the trainee showing him how well he is producing the brainwave pattern that indicates attention. The Extended Attention Span Training (EAST) system takes the concept a step further by making a video game more difficult as the player's brainwaves indicate that attention is waning. The trainee can succeed at the game only by maintaining an adequate level of attention. The EAST system is a modification of a biocybernetic system that is currently being used to assess the extent to which automated flight management systems maintain pilot engagement. This biocybernetic system is a product of a program aimed at developing methods to evaluate automated flight deck designs for compatibility with human capabilities. The EAST technology can make a contribution in the fields of medical neuropsychology and neurology, where the emphasis is on cautious, conservative treatment of youngsters with attention disorders.

  13. The motivation behind extended suicide

    Directory of Open Access Journals (Sweden)

    Roman Kuruc

    2014-12-01

    Full Text Available The investigation of motivation of suicidal behaviour in cases of so-called extended suicide is of great importance from a forensic-psychological viewpoint. The initiator of such action is often a person suffering from endogenous depression. The motives behind successful suicide are generally not known. This paper aims to demonstrate the motives behind the successful suicide, less frequent in our conditions, of two family members – a father and a son. The case has been thoroughly analysed by morphological methods with the help of additional laboratory tests. At the centre was a suicide letter which was hidden in a very unusual way and which was elucidated only thanks to autopsy of both persons. The manner of realisation – hanging – was among the most frequent in the region and in the state too. The men were not under the influence of any toxic substances. The motivation behind the suicide was an escape from hard living conditions.

  14. Extended high frequency audiometry in users of personal listening devices.

    Science.gov (United States)

    Kumar, Poornima; Upadhyay, Prabhakar; Kumar, Ashok; Kumar, Sunil; Singh, Gautam Bir

    Noise exposure leads to high frequency hearing loss. Use of Personal Listening Devices may lead to decline in high frequency hearing sensitivity because of prolonged exposure to these devices at high volume. This study explores the changes in hearing thresholds by Extended High Frequency audiometry in users of personal listening devices. A descriptive, hospital based observational study was performed with total 100 subjects in age group of 15-30years. Subjects were divided in two groups consisting of 30 subjects (Group A) with no history of Personal Listening Devices use and (Group B) having 70 subjects with history of use of Personal Listening Devices. Conventional pure tone audiometry with extended high frequency audiometry was performed in all the subjects. Significant differences in hearing thresholds of Personal Listening Device users were seen at high frequencies (3kHz, 4kHz and 6kHz) and extended high frequencies (9kHz, 10kHz, 11kHz, 13kHz, 14kHz, 15kHz and 16kHz) with p value 5years usage at high volume. Thus, it can be reasonably concluded that extended high frequencies can be used for early detection of NIHL in PLD users. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Participatory adaptive management leads to environmental learning outcomes extending beyond the sphere of science

    Science.gov (United States)

    Fujitani, Marie; McFall, Andrew; Randler, Christoph; Arlinghaus, Robert

    2017-01-01

    Resolving uncertainties in managed social-ecological systems requires adaptive experimentation at whole-ecosystem levels. However, whether participatory adaptive management fosters ecological understanding among stakeholders beyond the sphere of science is unknown. We experimentally involved members of German angling clubs (n = 181 in workshops, n = 2483 in total) engaged in self-governance of freshwater fisheries resources in a large-scale ecological experiment of active adaptive management of fish stocking, which constitutes a controversial management practice for biodiversity and ecosystem functioning when conducted inappropriately. The collaborative ecological experiments spanned several years and manipulated fish densities in 24 lakes with two species. In parallel, we experimentally compared changes in ecological knowledge and antecedents of proenvironmental behavior in stakeholders and managers who were members of a participatory adaptive management treatment group, with those receiving only a standard lecture, relative to placebo controls. Using a within-subjects pretest-posttest control design, changes in ecological knowledge, environmental beliefs, attitudes, norms, and behavioral intentions were evaluated. Participants in adaptive management retained more knowledge of ecological topics after a period of 8 months compared to those receiving a standard lecture, both relative to controls. Involvement in adaptive management was also the only treatment that altered personal norms and beliefs related to stocking. Critically, only the stakeholders who participated in adaptive management reduced their behavioral intentions to engage in fish stocking in the future. Adaptive management is essential for robust ecological knowledge, and we show that involving stakeholders in adaptive management experiments is a powerful tool to enhance ecological literacy and build environmental capacity to move toward sustainability. PMID:28630904

  16. Participatory adaptive management leads to environmental learning outcomes extending beyond the sphere of science.

    Science.gov (United States)

    Fujitani, Marie; McFall, Andrew; Randler, Christoph; Arlinghaus, Robert

    2017-06-01

    Resolving uncertainties in managed social-ecological systems requires adaptive experimentation at whole-ecosystem levels. However, whether participatory adaptive management fosters ecological understanding among stakeholders beyond the sphere of science is unknown. We experimentally involved members of German angling clubs ( n = 181 in workshops, n = 2483 in total) engaged in self-governance of freshwater fisheries resources in a large-scale ecological experiment of active adaptive management of fish stocking, which constitutes a controversial management practice for biodiversity and ecosystem functioning when conducted inappropriately. The collaborative ecological experiments spanned several years and manipulated fish densities in 24 lakes with two species. In parallel, we experimentally compared changes in ecological knowledge and antecedents of proenvironmental behavior in stakeholders and managers who were members of a participatory adaptive management treatment group, with those receiving only a standard lecture, relative to placebo controls. Using a within-subjects pretest-posttest control design, changes in ecological knowledge, environmental beliefs, attitudes, norms, and behavioral intentions were evaluated. Participants in adaptive management retained more knowledge of ecological topics after a period of 8 months compared to those receiving a standard lecture, both relative to controls. Involvement in adaptive management was also the only treatment that altered personal norms and beliefs related to stocking. Critically, only the stakeholders who participated in adaptive management reduced their behavioral intentions to engage in fish stocking in the future. Adaptive management is essential for robust ecological knowledge, and we show that involving stakeholders in adaptive management experiments is a powerful tool to enhance ecological literacy and build environmental capacity to move toward sustainability.

  17. Extending Newtonian Dynamics to Include Stochastic Processes

    Science.gov (United States)

    Zak, Michail

    2009-01-01

    A paper presents further results of continuing research reported in several previous NASA Tech Briefs articles, the two most recent being Stochastic Representations of Chaos Using Terminal Attractors (NPO-41519), [Vol. 30, No. 5 (May 2006), page 57] and Physical Principle for Generation of Randomness (NPO-43822) [Vol. 33, No. 5 (May 2009), page 56]. This research focuses upon a mathematical formalism for describing post-instability motions of a dynamical system characterized by exponential divergences of trajectories leading to chaos (including turbulence as a form of chaos). The formalism involves fictitious control forces that couple the equations of motion of the system with a Liouville equation that describes the evolution of the probability density of errors in initial conditions. These stabilizing forces create a powerful terminal attractor in probability space that corresponds to occurrence of a target trajectory with probability one. The effect in configuration space (ordinary three-dimensional space as commonly perceived) is to suppress exponential divergences of neighboring trajectories without affecting the target trajectory. As a result, the post-instability motion is represented by a set of functions describing the evolution of such statistical quantities as expectations and higher moments, and this representation is stable.

  18. Broadband absorption through extended resonance modes in random metamaterials

    Energy Technology Data Exchange (ETDEWEB)

    Hao, J.; Niemiec, R.; Lheurette, É.; Lippens, D. [Institut d' Électronique de Microélectronique et Nanotechnologies, IEMN-UMR CNRS 8520, Université de Lille 1, Avenue Poincaré, BP 60069, 59652 Villeneuve d' Ascq Cedex (France); Burgnies, L. [Institut d' Électronique de Microélectronique et Nanotechnologies, IEMN-UMR CNRS 8520, Université de Lille 1, Avenue Poincaré, BP 60069, 59652 Villeneuve d' Ascq Cedex (France); Université du Littoral Côte d' Opale, Rue Ferdinand Buisson, CS 80699, 62228 Calais cedex (France)

    2016-05-21

    The properties of disordered metamaterial absorbers are analyzed on the basis of numerical simulations and experimental characterizations. A broadening of the absorption spectrum is clearly evidenced. This effect is the consequence of both the coupling between nearby resonators leading to the occurrence of extended magnetic resonance modes and the interconnection of elementary particles yielding the definition of resonating clusters. The angular robustness of the absorbing structure under oblique incidence is also demonstrated for a wide domain of angles.

  19. Extended Thomas-Fermi expansion from nuclear linear response

    Energy Technology Data Exchange (ETDEWEB)

    Navarro, J. [IFIC, Centre Mixt CSIC, Universitat de Valencia, Avda Dr Moliner 50, E-46.100 Burjassot (Spain); Vinas, X. [Departamento Estructura i Constituents de la Materia, Facultat de Fisica, Universitat de Barcelona, Diagonal 645, E-08028 Barcelona (Spain)

    1996-09-01

    The coefficients of the successive h/2{pi}{sup 2} orders of the extended Thomas-Fermi expansion of the kinetic energy density are obtained to the leading order in the density inhomogeneities. This is done by comparing the corresponding static polarizability with the exact value in two cases: a non-interacting nuclear infinite system and symmetric nuclear matter with a Skyrme interaction. (author)

  20. Lead toxicity in plants

    OpenAIRE

    Sharma, Pallavi; Dubey, Rama Shanker

    2005-01-01

    Contamination of soils by heavy metals is of widespread occurrence as a result of human, agricultural and industrial activities. Among heavy metals, lead is a potential pollutant that readily accumulates in soils and sediments. Although lead is not an essential element for plants, it gets easily absorbed and accumulated in different plant parts. Uptake of Pb in plants is regulated by pH, particle size and cation exchange capacity of the soils as well as by root exudation and other physico-che...

  1. A novel flow battery: A lead acid battery based on an electrolyte with soluble lead(II). Part IX: Electrode and electrolyte conditioning with hydrogen peroxide

    Science.gov (United States)

    Collins, John; Li, Xiaohong; Pletcher, Derek; Tangirala, Ravichandra; Stratton-Campbell, Duncan; Walsh, Frank C.; Zhang, Caiping

    Extended cycling of a soluble lead acid battery can lead to problems due to an imbalance in the coulombic efficiency leading to deposits of Pb and PbO2 on the electrodes. Periodic addition of hydrogen peroxide to the electrolyte of the soluble lead acid flow battery largely overcomes several operational problems seen during extended cycling, using a 10 cm × 10 cm parallel plate flow cell. It is shown that this treatment greatly extends the number of cycles that can be achieved with a reasonable energy-, voltage-, and charge efficiency of 54-66%, 71%, and 77-91%.

  2. Leading through Conflict

    Science.gov (United States)

    Gerzon, Mark

    2006-01-01

    This article talks about leading significant learning opportunities through conflict of ideas in a school system. Catalyzing school change can turn emotional differences of opinion into learning opportunities. Leaders who want to deal effectively with these challenging, often tense situations need to be more than good managers. They need to be…

  3. Turning lead into gold

    DEFF Research Database (Denmark)

    Jensen, Steffen Moltrup Ernø

    For years the field of entrepreneurship has been blinded by the alchemical promise of turning lead into gold, of finding the ones most likely to become the next Branson, Zuckerberg or Gates. The promise has been created in the midst of political and scientific agendas where certain individuals...

  4. Relational Perspectives on Leading

    DEFF Research Database (Denmark)

    Relational Perspectives on Leading discusses leadership from a relational and social constructionism perspective as practiced on an everyday basis between people. The book pursues a fast growing, practice-based approach - particularly within the Anglo-Saxon parts of the world - to organization...

  5. Relational Perspectives on Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    Relational Perspectives on Leading discusses leadership from a relational and social constructionism perspective as practiced on an everyday basis between people. The book pursues a fast growing, practice-based approach - particularly within the Anglo-Saxon parts of the world - to organization...

  6. Measurement of double differential cross sections for light charged particles production in neutron induced reaction at 62.7 MeV on lead target; Mesures des sections efficaces doublement differentielles de production de particules chargees legeres lors de reactions induites par neutrons de 62.7 MeV sur cible de plomb

    Energy Technology Data Exchange (ETDEWEB)

    Kerveno, M

    2000-09-27

    In order to develop new options for nuclear waste management, studies are carrying out on the perfecting of hybrid systems (sub-critical reactor driven by accelerator). This thesis work takes place more precisely in the framework of nuclear data linked to hybrid systems development. Increasing the upper limit energy value (from 20 to 150 MeV) of data bases supposes that theoretical codes could have sufficient predictive power in this energy range. Thus it's necessary to measure new cross sections to constrain these codes. The experiment, performed at Louvain-la-Neuve Cyclotron, aims to determine the double differential cross sections for light charged particles production in neutron induced reactions at 62.7 MeV on natural lead target. The detection device consists of 6 NE102-CsI telescopes. Time of flight measurements are used to reconstruct the neutron energy spectra. The general framework (hybrid systems and associated nuclear data problematic) in which this work takes place is presented in a first part. The experimental set up used for our measurements is described in a second part. The three following parts are dedicated to the data analysis and double differential cross sections extraction. The particle discrimination, the energy calibration of detectors as the different corrections applied to the experimental spectra are related in details. And finally a comparative study between our experimental results and some theoretical predictions is presented. (author)

  7. Microenvironmental targets in sarcoma

    Directory of Open Access Journals (Sweden)

    Monika eEhnman

    2015-11-01

    Full Text Available Sarcomas are rare malignant tumors affecting all age groups. They are typically classified according to their resemblance to corresponding normal tissue. Their heterogeneous features, for example in terms of disease-driving genetic aberrations and body location, complicate both disease classification and development of novel treatment regimens. Many years of failure of improved patient outcome in clinical trials has lead to the conclusion that novel targeted therapies are likely needed in combination with current multimodality regimens. Sarcomas have not, in contrast to the common carcinomas, been the subject for larger systematic studies on how tumor behavior relates to characteristics of the tumor microenvironment. There is consequently an urgent need for identifying suitable molecular targets, not only in tumor cells, but also in the tumor microenvironment. This review discusses preclinical and clinical data about potential molecular targets in sarcomas. Studies on targeted therapies involving the tumor microenvironment are prioritized. A greater understanding of the biological context is expected to facilitate more successful design of future clinical trials in sarcoma.

  8. HEPS4Power - Extended-range Hydrometeorological Ensemble Predictions for Improved Hydropower Operations and Revenues

    Science.gov (United States)

    Bogner, Konrad; Monhart, Samuel; Liniger, Mark; Spririg, Christoph; Jordan, Fred; Zappa, Massimiliano

    2015-04-01

    In recent years large progresses have been achieved in the operational prediction of floods and hydrological drought with up to ten days lead time. Both the public and the private sectors are currently using probabilistic runoff forecast in order to monitoring water resources and take actions when critical conditions are to be expected. The use of extended-range predictions with lead times exceeding 10 days is not yet established. The hydropower sector in particular might have large benefits from using hydro meteorological forecasts for the next 15 to 60 days in order to optimize the operations and the revenues from their watersheds, dams, captions, turbines and pumps. The new Swiss Competence Centers in Energy Research (SCCER) targets at boosting research related to energy issues in Switzerland. The objective of HEPS4POWER is to demonstrate that operational extended-range hydro meteorological forecasts have the potential to become very valuable tools for fine tuning the production of energy from hydropower systems. The project team covers a specific system-oriented value chain starting from the collection and forecast of meteorological data (MeteoSwiss), leading to the operational application of state-of-the-art hydrological models (WSL) and terminating with the experience in data presentation and power production forecasts for end-users (e-dric.ch). The first task of the HEPS4POWER will be the downscaling and post-processing of ensemble extended-range meteorological forecasts (EPS). The goal is to provide well-tailored forecasts of probabilistic nature that should be reliable in statistical and localized at catchment or even station level. The hydrology related task will consist in feeding the post-processed meteorological forecasts into a HEPS using a multi-model approach by implementing models with different complexity. Also in the case of the hydrological ensemble predictions, post-processing techniques need to be tested in order to improve the quality of the

  9. Low density lipoproteins mediated nanoplatforms for cancer targeting

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant, E-mail: prashant_pharmacy04@rediffmail.com; Jain, Narendra K., E-mail: jnarendr@yahoo.co.in [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-09-15

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature's method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL-drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier.

  10. Low density lipoproteins mediated nanoplatforms for cancer targeting

    Science.gov (United States)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant; Jain, Narendra K.

    2013-09-01

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature's method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL-drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier.

  11. Creating targeted initial populations for genetic product searches in heterogeneous markets

    Science.gov (United States)

    Foster, Garrett; Turner, Callaway; Ferguson, Scott; Donndelinger, Joseph

    2014-12-01

    Genetic searches often use randomly generated initial populations to maximize diversity and enable a thorough sampling of the design space. While many of these initial configurations perform poorly, the trade-off between population diversity and solution quality is typically acceptable for small-scale problems. Navigating complex design spaces, however, often requires computationally intelligent approaches that improve solution quality. This article draws on research advances in market-based product design and heuristic optimization to strategically construct 'targeted' initial populations. Targeted initial designs are created using respondent-level part-worths estimated from discrete choice models. These designs are then integrated into a traditional genetic search. Two case study problems of differing complexity are presented to illustrate the benefits of this approach. In both problems, targeted populations lead to computational savings and product configurations with improved market share of preferences. Future research efforts to tailor this approach and extend it towards multiple objectives are also discussed.

  12. The Matrix Element Method at Next-to-Leading Order

    OpenAIRE

    Campbell, John M.; Giele, Walter T.; Williams, Ciaran

    2012-01-01

    This paper presents an extension of the matrix element method to next-to-leading order in perturbation theory. To accomplish this we have developed a method to calculate next-to-leading order weights on an event-by-event basis. This allows for the definition of next-to-leading order likelihoods in exactly the same fashion as at leading order, thus extending the matrix element method to next-to-leading order. A welcome by-product of the method is the straightforward and efficient generation of...

  13. Managing, Leading, and Bossing

    Science.gov (United States)

    2011-08-01

    Defense AT&L: July–August 2011 76 Managing , Leading, and Bossing Stan Emelander Boss Manager Leader Emelander is a project manager in the Army’s...and management . He is level II certified in program management and level I in systems engineering. Leaders fascinate us. From the smallest shop to...me about your boss” will work. Another great question is, “What’s the difference between a leader and a manager ?” Early in my career, I thought there

  14. Lead tungstate scintillation material

    CERN Document Server

    Annenkov, A N; Lecoq, P

    2002-01-01

    In this paper we summarize the results of a research programme on lead-tungstate (PWO) crystals performed by the CMS Collaboration at CERN, as well as by other groups who promoted the progress of the PWO scintillation crystal technology. Crystal properties, mass production technology, scintillation mechanism, origin of colouring, defects in crystal and radiation induced phenomena, light yield improvement and results of beam tests are described. (96 refs).

  15. Problem of lead in petrol: The effect of triethyl lead

    Energy Technology Data Exchange (ETDEWEB)

    Roederer, G.

    1985-10-01

    Triethyl lead is a highly toxic derivate of the anti-knock agent tetraethyl lead. Contrary to anorganic lead compounds triethyl lead causes serious disorders in the central nervous system of poisoned mammals leading to dramatic mental changes. Triethyl lead destroys microtubuli in the cells of plants and animals. It is assumed that the neurotoxic effect of triethyl lead is caused by its interacting with the microtubuli of the nerves (neurotubuli) and their subsequent destruction.

  16. A Trial of Extending Hemodialysis Hours and Quality of Life.

    Science.gov (United States)

    Jardine, Meg J; Zuo, Li; Gray, Nicholas A; de Zoysa, Janak R; Chan, Christopher T; Gallagher, Martin P; Monaghan, Helen; Grieve, Stuart M; Puranik, Rajesh; Lin, Hongli; Eris, Josette M; Zhang, Ling; Xu, Jinsheng; Howard, Kirsten; Lo, Serigne; Cass, Alan; Perkovic, Vlado

    2017-06-01

    The relationship between increased hemodialysis hours and patient outcomes remains unclear. We randomized (1:1) 200 adult recipients of standard maintenance hemodialysis from in-center and home-based hemodialysis programs to extended weekly (≥24 hours) or standard (target 12-15 hours, maximum 18 hours) hemodialysis hours for 12 months. The primary outcome was change in quality of life from baseline assessed by the EuroQol 5 dimension instrument (3 level) (EQ-5D). Secondary outcomes included medication usage, clinical laboratory values, vascular access events, and change in left ventricular mass index. At 12 months, median weekly hemodialysis hours were 24.0 (interquartile range, 23.6-24.0) and 12.0 (interquartile range, 12.0-16.0) in the extended and standard groups, respectively. Change in EQ-5D score at study end did not differ between groups (mean difference, 0.04 [95% confidence interval, -0.03 to 0.11]; P=0.29). Extended hours were associated with lower phosphate and potassium levels and higher hemoglobin levels. Blood pressure (BP) did not differ between groups at study end. Extended hours were associated with fewer BP-lowering agents and phosphate-binding medications, but were not associated with erythropoietin dosing. In a substudy with 95 patients, we detected no difference between groups in left ventricular mass index (mean difference, -6.0 [95% confidence interval, -14.8 to 2.7] g/m2; P=0.18). Five deaths occurred in the extended group and two in the standard group (P=0.44); two participants in each group withdrew consent. Similar numbers of patients experienced vascular access events in the two groups. Thus, extending weekly hemodialysis hours did not alter overall EQ-5D quality of life score, but was associated with improvement in some laboratory parameters and reductions in medication burden. (Clinicaltrials.gov identifier: NCT00649298). Copyright © 2017 by the American Society of Nephrology.

  17. Nurses' extended work hours: Patient, nurse and organizational outcomes.

    Science.gov (United States)

    Kunaviktikul, W; Wichaikhum, O; Nantsupawat, A; Nantsupawat, R; Chontawan, R; Klunklin, A; Roongruangsri, S; Nantachaipan, P; Supamanee, T; Chitpakdee, B; Akkadechanunt, T; Sirakamon, S

    2015-09-01

    Nursing shortages have been associated with increased nurse workloads that may result in work errors, thus impacting patient, nurse and organizational outcomes. To examine for the first time in Thailand nurses' extended work hours (working more than 40 h per week) and its relationship to patient, nurse and organizational outcomes. Using multistage sampling, 1524 registered nurses working in 90 hospitals across Thailand completed demographic forms: the Nurses' Extended Work Hours Form; the Patient, Nurse, Organizational Outcomes Form; the Organizational Productivity Questionnaire and the Maslach Burnout Inventory. The data were analysed using descriptive statistics, Spearman's rank correlation and logistic regression. The average extended work hour of respondents was 18.82 h per week. About 80% worked two consecutive shifts. The extended work hours had a positive correlation with patient outcomes, such as patient identification errors, pressure ulcers, communication errors and patient complaints and with nurse outcomes of emotional exhaustion and depersonalization. Furthermore, we found a negative correlation between extended work hours and job satisfaction as a whole, intent to stay and organizational productivity. Nurses who had extended work hours of >16 h per week were significantly more likely to perceive all four adverse patient outcomes than participants working an extended ≤8 h per week. Patient outcomes were measured by respondents' self-reports. This may not always reflect the real occurrence of adverse events. Associations between extended work hours and outcomes for patients, nurses and the organization were found. The findings demonstrate that working two shifts (16 h) more than the regular work hours lead to negative outcomes for patients, nurses and the organization. Our findings add to increasing international evidence that nurses' poor working conditions result in negative outcomes for professionals, patients and health systems

  18. Extended empirical likelihood for general estimating equations

    OpenAIRE

    Tsao, Min; Wu, Fan

    2013-01-01

    We derive an extended empirical likelihood for parameters defined by estimating equations which generalizes the original empirical likelihood for such parameters to the full parameter space. Under mild conditions, the extended empirical likelihood has all asymptotic properties of the original empirical likelihood. Its contours retain the data-driven shape of the latter. It can also attain the second order accuracy. The first order extended empirical likelihood is easy-to-use yet it is substan...

  19. An algebraic approach to symmetric extended formulations

    OpenAIRE

    Braun, Gábor; Pokutta, Sebastian

    2012-01-01

    Extended formulations are an important tool to obtain small (even compact) formulations of polytopes by representing them as projections of higher dimensional ones. It is an important question whether a polytope admits a small extended formulation, i.e., one involving only a polynomial number of inequalities in its dimension. For the case of symmetric extended formulations (i.e., preserving the symmetries of the polytope) Yannakakis established a powerful technique to derive lower bounds and ...

  20. Does Extended Pre Quit Bupropion Aid in Extinguishing Smoking Behavior?

    Science.gov (United States)

    Hawk, Larry W; Ashare, Rebecca L; Rhodes, Jessica D; Oliver, Jason A; Cummings, Kenneth Michael; Mahoney, Martin C

    2015-11-01

    Understanding the mechanisms by which bupropion promotes smoking cessation may lead to more effective treatment. To the extent that reduced smoking reinforcement is one such mechanism, a longer duration of pre quit bupropion treatment should promote extinction of smoking behavior. We evaluated whether 4 weeks of pre quit bupropion (extended run-in) results in greater pre quit reductions in smoking rate and cotinine and, secondarily, greater short-term abstinence, than standard 1 week of pre quit bupropion (standard run-in). Adult smokers (n = 95; 48 females) were randomized to a standard run-in group (n = 48; 3-week placebo, then 1-week bupropion pre quit) or an extended run-in group (4-week pre quit bupropion; n = 47). Both groups received group behavioral counseling and 7 weeks of post quit bupropion. Smoking rate (and craving, withdrawal, and subjective effects) was collected daily during the pre quit period; biochemical data (cotinine and carbon monoxide) were collected at study visits. During the pre quit period, the extended run-in group exhibited a greater decrease in smoking rate, compared to the standard run-in group, interaction p = .03. Cigarette craving and salivary cotinine followed a similar pattern, though the latter was evident only among women. Biochemically verified 4-week continuous abstinence rates were higher in the extended run-in group (53%) than the standard run-in group (31%), p = .033. The extended use of bupropion prior to a quit attempt reduces smoking behavior during the pre quit period and improved short-term abstinence rates. The data are consistent with an extinction-of-reinforcement model and support further investigation of extended run-in bupropion therapy for smoking cessation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Echo structures and Target Strength modelling for a synthetic submarine

    NARCIS (Netherlands)

    Schippers, P.; Beerens, S.P.

    2007-01-01

    Since the early nineties, performance modelling of active sonars has been developed at TNO in the ALMOST model, including propagation and sonar processing, based on point targets of given Target Strength. Recently, the modelling was extended with a computation module for target echo structure,

  2. lead glass brick

    CERN Multimedia

    When you look through the glass at a picture behind, the picture appears raised up because light is slowed down in the dense glass. It is this density (4.06 gcm-3) that makes lead glass attractive to physicists. The refractive index of the glass is 1.708 at 400nm (violet light), meaning that light travels in the glass at about 58% its normal speed. At CERN, the OPAL detector uses some 12000 blocks of glass like this to measure particle energies.

  3. Leading change: 2--planning.

    Science.gov (United States)

    Kerridge, Joanna

    National initiatives have outlined the importance of involving frontline staff in service improvement, and the ability to influence and manage change has been identified as an essential skill for delivering new models of care. Nurses often have to take the lead in managing change in clinical practice. The second in a three-part series is designed to help nurses at all levels develop the knowledge and skills to function as change agents within their organisations. This article focuses on planning the change and dealing with resistance.

  4. The theory of expanded, extended, and enhanced opportunities for youth physical activity promotion.

    Science.gov (United States)

    Beets, Michael W; Okely, Anthony; Weaver, R Glenn; Webster, Collin; Lubans, David; Brusseau, Tim; Carson, Russ; Cliff, Dylan P

    2016-11-16

    Physical activity interventions targeting children and adolescents (≤18 years) often focus on complex intra- and inter-personal behavioral constructs, social-ecological frameworks, or some combination of both. Recently published meta-analytical reviews and large-scale randomized controlled trials have demonstrated that these intervention approaches have largely produced minimal or no improvements in young people's physical activity levels. In this paper, we propose that the main reason for previous studies' limited effects is that fundamental mechanisms that lead to change in youth physical activity have often been overlooked or misunderstood. Evidence from observational and experimental studies is presented to support the development of a new theory positing that the primary mechanisms of change in many youth physical activity interventions are approaches that fall into one of the following three categories: (a) the expansion of opportunities for youth to be active by the inclusion of a new occasion to be active, (b) the extension of an existing physical activity opportunity by increasing the amount of time allocated for that opportunity, and/or (c) the enhancement of existing physical activity opportunities through strategies designed to increase physical activity above routine practice. Their application and considerations for intervention design and interpretation are presented. The utility of these mechanisms, referred to as the Theory of Expanded, Extended, and Enhanced Opportunities (TEO), is demonstrated in their parsimony, logical appeal, support with empirical evidence, and the direct and immediate application to numerous settings and contexts. The TEO offers a new way to understand youth physical activity behaviors and provides a common taxonomy by which interventionists can identify appropriate targets for interventions across different settings and contexts. We believe the formalization of the TEO concepts will propel them to the forefront in the

  5. Response matrix of an extended Bonner sphere system

    CERN Document Server

    Vylet, V

    2002-01-01

    We have developed a system of Bonner spheres designed for use around high-energy accelerators. The upper energy limit of the system was extended using a lead radiator, which acts as an energy converter via the (n,xn) reaction. In addition, we use sup 1 sup 1 C activation as an additional component integrated into the system and the spectra unfolding process. In the first version of the system, the lead radiator was present in only one sphere with diameter of 30.48 cm. The object of the present work was to investigate the geometry of the lead radiator and its use in moderators of several different sizes. As a result, we have developed a modular design and calculated the response matrix of the new system.

  6. Extending Abdominal Aortic Aneurysm Detection to Older Age Groups

    DEFF Research Database (Denmark)

    Makrygiannis, Georgios; Labalue, Philippe; Erpicum, Marie

    2016-01-01

    . Current screening policies (e.g., men aged 65-74 years), however, do not account for aging and increased life expectancy of Western populations. This study investigated AAA detection by extending the target population to older age groups (75-85 years). METHODS: AAA screening was conducted in the County......-74 age group but rose to 7.3% in the age-extended group (75-85 years). Further in addition to age, height, current smoking, history of coronary artery disease, hypercholesterolemia, peripheral artery disease of the lower limbs, and varicose veins were significantly associated with the presence of AAA....... CONCLUSIONS: These preliminary findings, based on a representative sample of the elderly population of the Liège region, support the idea that current AAA screening policies should be updated to cover an increasingly aging population. The presence of varicose veins as a potential risk factor for AAA should...

  7. Achieving Plant CRISPR Targeting that Limits Off-Target Effects

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Wolt

    2016-11-01

    Full Text Available The CRISPR-Cas9 system (clustered regularly interspaced short palindromic repeats with associated Cas9 protein has been used to generate targeted changes for direct modification of endogenous genes in an increasing number of plant species; but development of plant genome editing has not yet fully considered potential off-target mismatches that may lead to unintended changes within the genome. Assessing the specificity of CRISPR-Cas9 for increasing editing efficiency as well as the potential for unanticipated downstream effects from off-target mutations is an important regulatory consideration for agricultural applications. Increasing genome-editing specificity entails developing improved design methods that better predict the prevalence of off-target mutations as a function of genome composition and design of the engineered ribonucleoprotein (RNP. Early results from CRISPR-Cas9 genome editing in plant systems indicate that the incidence of off-target mutation frequencies is quite low; however, by analyzing CRISPR-edited plant lines and improving both computational tools and reagent design, it may be possible to further decrease unanticipated effects at potential mismatch sites within the genome. This will provide assurance that CRISPR-Cas9 reagents can be designed and targeted with a high degree of specificity. Improved and experimentally validated design tools for discriminating target and potential off-target positions that incorporate consideration of the designed nuclease fidelity and selectivity will help to increase confidence for regulatory decision making for genome-edited plants.

  8. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  9. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could ...

  10. Optimal base-stock policy for the inventory system with periodic review, backorders and sequential lead times

    DEFF Research Database (Denmark)

    Johansen, Søren Glud; Thorstenson, Anders

    2008-01-01

    We extend well-known formulae for the optimal base stock of the inventory system with continuous review and constant lead time to the case with periodic review and stochastic, sequential lead times. Our extension uses the notion of the 'extended lead time'. The derived performance measures...

  11. Extended Hubbard models for ultracold atoms in optical lattices

    Energy Technology Data Exchange (ETDEWEB)

    Juergensen, Ole

    2015-06-05

    In this thesis, the phase diagrams and dynamics of various extended Hubbard models for ultracold atoms in optical lattices are studied. Hubbard models are the primary description for many interacting particles in periodic potentials with the paramount example of the electrons in solids. The very same models describe the behavior of ultracold quantum gases trapped in the periodic potentials generated by interfering beams of laser light. These optical lattices provide an unprecedented access to the fundamentals of the many-particle physics that govern the properties of solid-state materials. They can be used to simulate solid-state systems and validate the approximations and simplifications made in theoretical models. This thesis revisits the numerous approximations underlying the standard Hubbard models with special regard to optical lattice experiments. The incorporation of the interaction between particles on adjacent lattice sites leads to extended Hubbard models. Offsite interactions have a strong influence on the phase boundaries and can give rise to novel correlated quantum phases. The extended models are studied with the numerical methods of exact diagonalization and time evolution, a cluster Gutzwiller approximation, as well as with the strong-coupling expansion approach. In total, this thesis demonstrates the high relevance of beyond-Hubbard processes for ultracold atoms in optical lattices. Extended Hubbard models can be employed to tackle unexplained problems of solid-state physics as well as enter previously inaccessible regimes.

  12. Time-Extended Policies in Mult-Agent Reinforcement Learning

    Science.gov (United States)

    Tumer, Kagan; Agogino, Adrian K.

    2004-01-01

    Reinforcement learning methods perform well in many domains where a single agent needs to take a sequence of actions to perform a task. These methods use sequences of single-time-step rewards to create a policy that tries to maximize a time-extended utility, which is a (possibly discounted) sum of these rewards. In this paper we build on our previous work showing how these methods can be extended to a multi-agent environment where each agent creates its own policy that works towards maximizing a time-extended global utility over all agents actions. We show improved methods for creating time-extended utilities for the agents that are both "aligned" with the global utility and "learnable." We then show how to crate single-time-step rewards while avoiding the pi fall of having rewards aligned with the global reward leading to utilities not aligned with the global utility. Finally, we apply these reward functions to the multi-agent Gridworld problem. We explicitly quantify a utility's learnability and alignment, and show that reinforcement learning agents using the prescribed reward functions successfully tradeoff learnability and alignment. As a result they outperform both global (e.g., team games ) and local (e.g., "perfectly learnable" ) reinforcement learning solutions by as much as an order of magnitude.

  13. ADD, LD and Extended Information Processing.

    Science.gov (United States)

    Stolzenberg, J. B.; Cherkes-Julkowski, M.

    This study examines executive function and its relationship to attention dysfunction and working memory. It attempts to document the manifestations of executive function problems in school-related extended processing tasks, such as verbal problem-solving in math and reading of extended passages. Subjects (in grades 1-12) included 49 children with…

  14. Extended, Embodied Cognition and Second Language Acquisition

    Science.gov (United States)

    Atkinson, Dwight

    2010-01-01

    A "cognitivist" approach to cognition has traditionally dominated second language acquisition (SLA) studies. In this article, I examine two alternative approaches--"extended cognition" and "embodied cognition"--for how they might help us conceptualize SLA. More specifically, I present: (i) summaries of extended and embodied cognition, followed by…

  15. Who Gets to Lead the Multinational Team?

    DEFF Research Database (Denmark)

    Paunova, Minna

    2017-01-01

    of their core self-evaluations. A study of over 230 individuals from 46 nationalities working in 36 self-managing teams generally supports the expected main and moderation effects. Individual core self-evaluations enhance an otherwise weak effect of English proficiency, but compensate for low levels of national......This article examines the emergence of informal leadership in multinational teams. Building on and extending status characteristics theory, the article proposes and tests a model that describes how global inequalities reproduce in multinational teams, and accounts for who gets to lead these teams...

  16. Alzheimer's Disease: Another Target for Heparin Therapy

    Directory of Open Access Journals (Sweden)

    Luigi Bergamaschini

    2009-01-01

    Full Text Available Alzheimer's disease (AD is the leading cause of dementia and cognitive decline in the elderly. Brain tissue changes indicate that the two main proteins involved in AD are amyloid-β(A-β, which is associated with the formation of senile amyloid plaques, and tau, which is associated with the formation of neurofibrillary tangles. Although a central role for A-β in the pathogenesis of AD is indisputable, considerable evidence indicates that A-β production is not the sole culprit in AD pathology. AD is also accompanied by an inflammatory response that contributes to irreversible changes in neuronal viability and brain function, and accumulating evidence supports the pivotal role of complement and contact systems in its pathogenesis and progression. The complexity of AD pathology provides numerous potential targets for therapeutic interventions. Compounds that interact directly with A-β protein or interfere with its production and/or aggregation can reduce the inflammatory and neurotoxic effects of A-β, and heparin, a glycosaminoglycan mixture currently used in the prophylaxis and treatment of thrombosis, might be a candidate, as recent research has been extended to consider its nonanticoagulant properties, including its modulation of various proteases and anti-inflammatory activity.

  17. The leading joint hypothesis for spatial reaching arm motions.

    Science.gov (United States)

    Ambike, Satyajit; Schmiedeler, James P

    2013-02-01

    The leading joint hypothesis (LJH), developed for planar arm reaching, proposes that the interaction torques experienced by the proximal joint are low compared to the corresponding muscle torques. The human central nervous system could potentially ignore these interaction torques at the proximal (leading) joint with little effect on the wrist trajectory, simplifying joint-level control. This paper investigates the extension of the LJH to spatial reaching. In spatial motion, a number of terms in the governing equation (Euler's angular momentum balance) that vanish for planar movements are non-trivial, so their contributions to the joint torque must be classified as net, interaction or muscle torque. This paper applies definitions from the literature to these torque components to establish a general classification for all terms in Euler's equation. This classification is equally applicable to planar and spatial motion. Additionally, a rationale for excluding gravity torques from the torque analysis is provided. Subjects performed point-to-point reaching movements between targets whose locations ensured that the wrist paths lay in various portions of the arm's spatial workspace. Movement kinematics were recorded using electromagnetic sensors located on the subject's arm segments and thorax. The arm was modeled as a three-link kinematic chain with idealized spherical and revolute joints at the shoulder and elbow. Joint torque components were computed using inverse dynamics. Most movements were 'shoulder-led' in that the interaction torque impulse was significantly lower than the muscle torque impulse for the shoulder, but not the elbow. For the few elbow-led movements, the interaction impulse at the elbow was low, while that at the shoulder was high, and these typically involved large elbow and small shoulder displacements. These results support the LJH and extend it to spatial reaching motion.

  18. Strontium doping of bone graft extender

    Science.gov (United States)

    2011-01-01

    Background and purpose Allografts are often used during revision hip replacement surgery for stabilization of the implant. Resorption of the allograft may exceed new bone formation, and instability of the prosthesis can develop. We investigated whether strontium could regulate the imbalance of fast resorption of allograft and slower formation of new bone, because it is both an anabolic and an anticatabolic agent. Method Strontium was added to the implant interface environment by doping a hydroxyapatite bone graft extender. 10 dogs each received 2 experimental titanium implants. The implants were inserted within a 2.7-mm concentric gap in cancellous bone. The gap was filled with 50% (v/v) allograft mixed with 50% bone graft extender. The extender either had 5% strontium doping (SrHA) or was undoped (HA). After 4 weeks, osseointegration and mechanical fixation were evaluated by histomorphometry and by push-out test. Results SrHA bone graft extender induced a 1.2-fold increase in volume of new bone, a 1.2-fold increase in allograft remaining in the gap, and a 1.4-fold increase in surface area of the bone graft extender material in contact with new bone compared to HA bone graft extender. All these increases were statistically significant. SrHA bone graft extender did not significantly improve ongrowth of bone onto the implants or improve any of the mechanical push-out parameters compared to HA bone graft extender. Interpretation Doping of the HA bone graft extender with 5% strontium increased gap healing, preserved more of the allograft in the gap, and increased the ongrowth of bone onto the bone graft extender material, but did not improve mechanical fixation. PMID:21895497

  19. Extended physics as a theoretical framework for systems biology?

    Science.gov (United States)

    Miquel, Paul-Antoine

    2011-08-01

    In this essay we examine whether a theoretical and conceptual framework for systems biology could be built from the Bailly and Longo (2008, 2009) proposal. These authors aim to understand life as a coherent critical structure, and propose to develop an extended physical approach of evolution, as a diffusion of biomass in a space of complexity. Their attempt leads to a simple mathematical reconstruction of Gould's assumption (1989) concerning the bacterial world as a "left wall of least complexity" that we will examine. Extended physical systems are characterized by their constructive properties. Time is acting and new properties emerge by their history that can open the list of their initial properties. This conceptual and theoretical framework is nothing more than a philosophical assumption, but as such it provides a new and exciting approach concerning the evolution of life, and the transition between physics and biology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Lead and lead-based alloys as waste matrix materials

    Energy Technology Data Exchange (ETDEWEB)

    Arustamov, A.E.; Ojovan, M.I.; Kachalov, M.B.

    1999-07-01

    Metals and alloys with relatively low melting temperatures such as lead and lead-based alloys are considered in Russia as prospective matrices for encapsulation of spent nuclear fuel in containers in preparation for final disposal in underground repositories. Now lead and lead-based alloys are being used for conditioning spent sealed radioactive sources at radioactive waste disposal facilities.

  1. MEET ISOLDE - Target Production

    CERN Multimedia

    2017-01-01

    MEET ISOLDE - Target Production. Everything at ISOLDE starts with a target and the target production team realise on more then 50 years of experience to build and develop new targets for ISOLDE’s wide physics program.

  2. HAIR LEAD CONCENTRATION IN NAKHLAK LEAD MINERS VERSUS CONTROL GROUP

    Directory of Open Access Journals (Sweden)

    N IZADI

    2002-03-01

    Full Text Available Introduction. Lead poisoning is a major problem in environmental health. Exposure can occur via air, soil, food and water. Occupational exposure is the most common source of lead poisoning in adults. Lead miners are exposed to an additional source of poisoning in long term. Hair analysis may be used to evaluate chronic lead toxicity. This study compare the hair lead concentration in Nakhlak lead miners and Mohammadieh people who live 130 km far from the lead mine. Methods. Hair samples from 24 Nakhlak lead miners and 26 adult men of Mohammadieh village were gathered, washed by detergent and distilled water and dissolved by wet digestion. Lead concentrations of the samples were measured by flame atomic absorption spectroscopy. Results. There was a significant difference between hair lead concentration of Nakhlak lead miners and Mohammadieh people (P < 0.001. The mean of lead concentrations were 52.43±27.7 µg/g (mean ± SD and 17.32±3.43 µg/g hair of the lead mine workers and the Mohammadieh people, respectively. There was also a significant regression between the number of exposure years and the lead concentration of hair in Nakhlak lead miners (P < 0.001, r=0.8. Discussion. Presence of lead compounds in work environment especially in the air may be an important factor for the difference between hair lead concentration of Nakhlak lead miners and Mohammadieh people. However, the hair lead concentration in Mohammadieh people is also reasonably high. It means that these people are also exposed to lead through the other sources e.g. food, soil, water and air.

  3. Human lead metabolism: Chronic exposure, bone lead and physiological models

    Science.gov (United States)

    Fleming, David Eric Berkeley

    Exposure to lead is associated with a variety of detrimental health effects. After ingestion or inhalation, lead may be taken up from the bloodstream and retained by bone tissue. X-ray fluorescence was used to make in vivo measurements of bone lead concentration at the tibia and calcaneus for 367 active and 14 retired lead smelter workers. Blood lead levels following a labour disruption were used in conjunction with bone lead readings to examine the endogenous release of lead from bone. Relations between bone lead and a cumulative blood lead index differed depending on time of hiring. This suggests that the transfer of lead from blood to bone has changed over time, possibly as a result of varying exposure conditions. A common polymorphism in the δ-aminolevulinate dehydratase (ALAD) enzyme may influence the distribution of lead in humans. Blood lead levels were higher for smelter workers expressing the more rare ALAD2 allele. Bone lead concentrations, however, were not significantly different. This implies that a smaller proportion of lead in blood is distributed to tissue for individuals expressing the ALAD2 allele. The O'Flaherty physiological model of lead metabolism was modified slightly and tested with input from the personal exposure histories of smelter workers. The model results were consistent with observation in tern of endogenous exposure to lead and accumulation of lead in cortical bone. Modelling the calcaneus as a trabecular bone site did not reproduce observed trends. variations in lead metabolism between different trabecular sites may therefore be significant. The model does not incorporate a genetic component, and its output did not reflect observed differences in this respect. This result provides further support for the influence of the ALAD polymorphism on lead metabolism. Experimental trials with a digital spectrometer revealed superior energy resolution and count throughput relative to the conventional X-ray fluorescence system. The associated

  4. The matrix element method at next-to-leading order

    Science.gov (United States)

    Campbell, John M.; Giele, Walter T.; Williams, Ciaran

    2012-11-01

    This paper presents an extension of the matrix element method to next-to-leading order in perturbation theory, for electro-weak final states. To accomplish this we have developed a method to calculate next-to-leading order weights on an event-by-event basis. This allows for the definition of next-to-leading order likelihoods in exactly the same fashion as at leading order, thus extending the matrix element method to next-to-leading order. A welcome by-product of the method is the straightforward and efficient generation of unweighted next-to-leading order events. As examples of the application of our next-to-leading order matrix element method we consider the measurement of the mass of the Z boson and also the search for the Higgs boson in the four lepton channel.

  5. Extended cycle hormonal contraception in adolescents.

    Science.gov (United States)

    Sucato, Gina S; Gerschultz, Kelly L

    2005-10-01

    There is increasing interest in the use of extended cycles of hormonal contraception to manage menstrual cycle-related complaints in adolescents and to accommodate the menstrual preferences of patients using hormonal contraception. This review summarizes recent findings related to the use of extended cycles and highlights their relevance to adolescents. Many adolescents would prefer to menstruate less frequently. Among health care providers who prescribe hormonal contraceptives, the majority believe suppressing withdrawal bleeding is well tolerated and prescribe extended cycling regimens to their patients. Shortening or eliminating the hormone-free interval results in greater ovarian suppression and thus may increase contraceptive efficacy. Studies in adult women have not identified changes in metabolic parameters beyond what would be expected from traditional cyclic use. New endometrial biopsy data have found no pathologic changes; most women using an extended cycle had atrophic endometriums. Extended cycling is frequently associated with breakthrough bleeding. In some women, this can be managed with a brief hormone-free interval. Recent findings demonstrate high levels of interest in extended cycling among adolescents and providers, and continue to add to the growing body of literature supporting the safety and improved contraceptive efficacy of extended regimens. Further research is warranted to focus on issues including cancer, thrombotic disease and fertility, and should enroll a sufficient adolescent sample.

  6. Charge identification in CR-39 nuclear track detector using relativistic lead ion fragmentation

    CERN Document Server

    Manzoor, S; Rana, M A; Shahzad, M I; Sher, G; Sajid, M; Khan, H A; Giacomelli, G; Giorgini, M; Mandrioli, G; Patrizii, L; Popa, V; Serra, P; Togo, V

    2000-01-01

    Three stacks of plastic CR-39 Nuclear Track Detectors (NTD) were exposed to 158 A GeV /sup 207/Pb ions at the CERN-SPS beam facility. The main purpose of this experiment was the calibration of the CR-39 for the search of atmospheric magnetic monopoles. Different targets (Al, Cu and Pb) were used to produce a large spectrum of charge ions for the purpose of calibration as well as the study of ultrarelativistic lead ion fragmentation. The exposure of each stack was performed at normal incidence with a fluence of about 1500 ion/cm /sup 2/. The total number of lead ions in each spill was about 7.8*10 /sup 4/ and there were eight spills incident on each stack. For the stack with the Cu target, the lengths of etched cones on one face of the CR-39 were measured. From this measurement procedure, a new calibration curve has been generated for the extended charge region 63or=2, and a large dynamical range in counting rates of up to 10/sup 9/ s/sup -1/ due to single particle or current readout, respectively. (2 refs).

  7. Modeling the Extended Warranty: A Managerial Focus

    OpenAIRE

    Myung, Noah; Eger, Robert J.

    2015-01-01

    We provide a model of an extended warranty. To maximize profit, a producer always wants to sell with some type of warranty as opposed to selling with no warranty. The extended warranty is more likely to be provided as the consumer becomes more patient, as the producer becomes impatient, or if the likelihood of product failure does not increase too much in the extended period. We show that there is a separating equilibrium in which the high quality producers sell with warranties and the low qu...

  8. Extended Hamiltonian approach to continuous tempering.

    Science.gov (United States)

    Gobbo, Gianpaolo; Leimkuhler, Benedict J

    2015-06-01

    We introduce an enhanced sampling simulation technique based on continuous tempering, i.e., on continuously varying the temperature of the system under investigation. Our approach is mathematically straightforward, being based on an extended Hamiltonian formulation in which an auxiliary degree of freedom, determining the effective temperature, is coupled to the physical system. The physical system and its temperature evolve continuously in time according to the equations of motion derived from the extended Hamiltonian. Due to the Hamiltonian structure, it is easy to show that a particular subset of the configurations of the extended system is distributed according to the canonical ensemble for the physical system at the correct physical temperature.

  9. Leading Your Leaders

    Science.gov (United States)

    Hale, Wayne N.

    2008-01-01

    life is good. More often when an unbelievably difficult test fails, we are left with a very long discussion of why and what was wrong in the design or execution of the test. Make sure that the test is well defined. Even then, it is important to explain to your leaders what inherent accuracy (or error) the test conditions or equipment have and what the assumptions or initial conditions were for the test. Test results without a good understanding of the test's accuracy or the pedigree of the test assumptions are worth very little. Finally, there is flight test data. Always limited, never at the edge of the envelope, it still shows how the real hardware works in a combined environment. Flight experience is dangerous because it typically doesn't show how close to the edge of the cliff the equipment is operating, but it does demonstrate how the hardware really works. A flight test is the ultimate test, again taken with the knowledge that it is probably not the extreme but something more like the middle of the environmental and systems performance. Good understanding of a problem and its solution always relies on a combination of all these methods. Be sure to lead your leaders by using all the tools you have at your disposal. At the end of the day, decisions in space flight always come down to a risk trade. Our business is not remotely safe, not in the sense that the public, the media, or our legislators use the term. Everything we do has a risk, cost, schedule, or performance trade-off. For your leaders to make an appropriate decision, you need to educate them, lead them, talk with them, and engage them in the discussion until full understanding takes place. It's your job. *

  10. An extended lattice model accounting for traffic jerk

    Science.gov (United States)

    Redhu, Poonam; Siwach, Vikash

    2018-02-01

    In this paper, a flux difference lattice hydrodynamics model is extended by considering the traffic jerk effect which comes due to vehicular motion of non-motor automobiles. The effect of traffic jerk has been examined through linear stability analysis and shown that it can significantly enlarge the unstable region on the phase diagram. To describe the phase transition of traffic flow, mKdV equation near the critical point is derived through nonlinear stability analysis. The theoretical findings have been verified using numerical simulation which confirms that the jerk parameter plays an important role in stabilizing the traffic jam efficiently in sensing the flux difference of leading sites.

  11. Extended quasiparticle approximation for relativistic electrons in plasmas

    Directory of Open Access Journals (Sweden)

    V.G.Morozov

    2006-01-01

    Full Text Available Starting with Dyson equations for the path-ordered Green's function, it is shown that the correlation functions for relativistic electrons (positrons in a weakly coupled non-equilibrium plasmas can be decomposed into sharply peaked quasiparticle parts and off-shell parts in a rather general form. To leading order in the electromagnetic coupling constant, this decomposition yields the extended quasiparticle approximation for the correlation functions, which can be used for the first principle calculation of the radiation scattering rates in QED plasmas.

  12. TRACTION-EXTENDED THERAPY OF PATIENTS WITH LUMBAR DEGENERATIVE DISEASE

    OpenAIRE

    V. A. Zhirnov; D. P. Krest'yanov; A. K. Vasil'kin

    2013-01-01

    Based on the survey of 148 patients with an lumbar degenerative disease, there have been studied immediate and medium-term results of the comprehensive conservative treatment of the patients with and without application of traction exposure on the spine. It was found out that the traction of the spine leads to a quicker and more durable relief of symptoms in comparison with the control groups where traction therapy wasn't carried out. Application of the traction-extended therapy in three plan...

  13. The Symmetry behind Extended Flavour Democracy and Large Leptonic Mixing

    CERN Document Server

    Silva-Marcos, Joaquim I

    2002-01-01

    We show that there is a minimal discrete symmetry which leads to the extended flavour democracy scenario constraining the Dirac neutrino, the charged lepton and the Majorana neutrino mass term ($M_R$) to be all proportional to the democratic matrix, with all elements equal. In particular, this discrete symmetry forbids other large contributions to $M_R$, such as a term proportional to the unit matrix, which would normally be allowed by a $S_{3L}\\times S_{3R}$ permutation symmetry. This feature is crucial in order to obtain large leptonic mixing, without violating 't Hooft's, naturalness principle.

  14. Leading clever people.

    Science.gov (United States)

    Goffee, Rob; Jones, Gareth

    2007-03-01

    In an economy driven by ideas and intellectual know-how, top executives recognize the importance of employing smart, highly creative people. But if clever people have one defining characteristic, it's that they do not want to be led. So what is a leader to do? The authors conducted more than 100 interviews with leaders and their clever people at major organizations such as PricewaterhouseCoopers, Cisco Systems, Novartis, the BBC, and Roche. What they learned is that the psychological relationships effective leaders have with their clever people are very different from the ones they have with traditional followers. Those relationships can be shaped by seven characteristics that clever people share: They know their worth--and they know you have to employ them if you want their tacit skills. They are organizationally savvy and will seek the company context in which their interests are most generously funded. They ignore corporate hierarchy; although intellectual status is important to them, you can't lure them with promotions. They expect instant access to top management, and if they don't get it, they may think the organization doesn't take their work seriously. They are plugged into highly developed knowledge networks, which both increases their value and makes them more of a flight risk. They have a low boredom threshold, so you have to keep them challenged and committed. They won't thank you--even when you're leading them well. The trick is to act like a benevolent guardian: to grant them the respect and recognition they demand, protect them from organizational rules and politics, and give them room to pursue private efforts and even to fail. The payoff will be a flourishing crop of creative minds that will enrich your whole organization.

  15. Gas Production in the MEGAPIE Spallation Target

    OpenAIRE

    Thiollière, Nicolas; Zanini, Luca; David, Jean-Christophe; Eikenberg, Jost; Guertin, Arnaud; Konobeyev, Alexander Yu.; Lemaire, Sébastien; Panebianco, Stefano

    2011-01-01

    International audience; The MEGAwatt PIlot Experiment (MEGAPIE) project was started in 2000 to design, build, and operate a liquid lead-bismuth eutectic (LBE) spallation neutron target at the power level of 1 MW. The target was irradiated for 4 months in 2006 at the Paul Scherrer Institute in Switzerland. Gas samples wereextracted in various phases of operation and analyzed by g spectroscopy, leading to the determination of the main radioactive isotopes released from the LBE. Comparison with ...

  16. Targeting Killing of Breast Tumor Stem Cells

    National Research Council Canada - National Science Library

    Chen, Si-Yi

    2005-01-01

    .... Toward the goal, we have prepared HA molecules from human umbilical cord hyaluronic acid by hydrolysed by Bee venom. However, we have encountered the technical difficulty to produce CD44-targeted liposomes that are incorporated with HA molecules. Due to the technical problems, this proposed study has been extended for additional one year.

  17. Targeted Killing of Breast Tumor Stem Cells

    National Research Council Canada - National Science Library

    Chen, Si-Yi

    2004-01-01

    .... Toward the goal, we have prepared HA molecules from human umbilical cord hyaluronic acid by hydrolysed by Bee venom. However, we have encountered the technical difficulty to produce CD44-targeted liposomes that are incorporated with HA molecules. Due to the technical problems, this proposed study has been extended for additional one year.

  18. Generalized Laplace Transforms and Extended Heaviside Calculus

    Science.gov (United States)

    Deakin, Michael A. B.

    2008-01-01

    An extended Heaviside calculus proposed by Peraire in a recent paper is similar to a generalization of the Laplace transform proposed by the present author. This similarity will be illustrated by analysis of an example supplied by Peraire.

  19. Extended Adjuvant Therapy for Breast Cancer

    Science.gov (United States)

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  20. PREVALENCE OF EXTENDED SPECTRUM β-LACTAMASES ...

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. Confirmed variants of enterobacteriaceae isolated from 143 patients that attended Murtala. Mohammed Specialist Hospital Kano, were screened for extended spectrum β-lactamases (ESBLs) production using Clinical Laboratory Standards Institute (CLSI) breakpoint. Suspected ESBLs producers were ...

  1. Cooperative tumour cell membrane targeted phototherapy

    Science.gov (United States)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  2. Some Aspects of Extended Kinetic Equation

    Directory of Open Access Journals (Sweden)

    Dilip Kumar

    2015-09-01

    Full Text Available Motivated by the pathway model of Mathai introduced in 2005 [Linear Algebra and Its Applications, 396, 317–328] we extend the standard kinetic equations. Connection of the extended kinetic equation with fractional calculus operator is established. The solution of the general form of the fractional kinetic equation is obtained through Laplace transform. The results for the standard kinetic equation are obtained as the limiting case.

  3. Musical Manipulations and the Emotionally Extended Mind

    Directory of Open Access Journals (Sweden)

    Joel Krueger

    2015-05-01

    Full Text Available I respond to Kersten's criticism in his article "Music and Cognitive Extension" of my approach to the musically extended emotional mind in Krueger (2014. I specify how we manipulate—and in so doing, integrate with—music when, as active listeners, we become part of a musically extended cognitive system. I also indicate how Kersten's account might be enriched by paying closer attention to the way that music functions as an environmental artifact for emotion regulation.

  4. Extended Dislocations in Plastically Deformed Metallic Nanoparticles

    OpenAIRE

    Bin Zheng; Yi-Nong Wang; Min Qi; Huiling Du

    2016-01-01

    In the present study, the sawtooth nature of compressive loading of metallic nanoparticles is observed using a molecular dynamics simulation. The atomic structure evolution confirmed that extended dislocations are the main defects split into two asynchronous partial disloca‐ tions, along with stored and released fault energy. This is considered the essence of sawtooth loading. The size of the nanoparticles relative to the equilibrium width of the extended dislocation is discussed to explain t...

  5. Extended Dislocations in Plastically Deformed Metallic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Bin Zheng

    2016-05-01

    Full Text Available In the present study, the sawtooth nature of compressive loading of metallic nanoparticles is observed using a molecular dynamics simulation. The atomic structure evolution confirmed that extended dislocations are the main defects split into two asynchronous partial disloca‐ tions, along with stored and released fault energy. This is considered the essence of sawtooth loading. The size of the nanoparticles relative to the equilibrium width of the extended dislocation is discussed to explain the simulation results.

  6. Amelioration of lead-induced hepatotoxicity by Allium sativum ...

    African Journals Online (AJOL)

    2010-01-07

    Jan 7, 2010 ... tobacco smoke. Lead can disrupt biological systems by altering the molecular interactions, cell signaling, and ultimately cellular function. The toxic effect of lead nitrate is well documented in mammals, ... through the respiratory and gastrointestinal systems. Liver is a frequent target for many toxicants (2).

  7. LIFE Target Fabrication Research Plan Sept 2008

    Energy Technology Data Exchange (ETDEWEB)

    Miles, R; Biener, J; Kucheyev, S; Montesanti, R; Satcher, J; Spadaccini, C; Rose, K; Wang, M; Hamza, A; Alexander, N; Brown, L; Hund, J; Petzoldt, R; Sweet, W; Goodin, D

    2008-11-10

    The target-system for the baseline LIFE fast-ignition target was analyzed to establish a preliminary estimate for the costs and complexities involved in demonstrating the technologies needed to build a prototype LIFE plant. The baseline fast-ignition target upon which this analysis was developed is shown in Figure 1.0-1 below. The LIFE target-system incorporates requirements for low-cost, high throughput manufacture, high-speed, high accuracy injection of the target into the chamber, production of sufficient energy from implosion and recovery and recycle of the imploded target material residue. None of these functions has been demonstrated to date. Existing target fabrication techniques which lead to current 'hot spot' target costs of {approx}$100,000 per target and at a production rate of 2/day are unacceptable for the LIFE program. Fabrication techniques normally used for low-cost, low accuracy consumer products such as toys must be adapted to the high-accuracy LIFE target. This will be challenge. A research program resulting is the demonstration of the target-cycle technologies needed for a prototype LIFE reactor is expected to cost {approx}$51M over the course of 5 years. The effort will result in targets which will cost an estimated $0.23/target at a rep-rate of 20 Hz or about 1.73M targets/day.

  8. Extended Access List untuk Mengendalikan Trafik Jaringan

    Directory of Open Access Journals (Sweden)

    Hari Antoni Musril

    2016-12-01

    Full Text Available Keamana jaringan komputer saat ini menjadi hal penting untuk diterapkan. Banyak organisasi yang telah menjadikan teknologi informasi sebagai bahagian penting dalam menunjang aktivitasnya. Akses pengguna yang tidak dibatasi menjadi ancaman bagi sebuah organisasi, karena banyak data dan informasi penting yang tersebar dalam perangkat jaringan komputer di organisasi tersebut dapat disusupi oleh pihak yang tidak berwenang. Salah satu usaha yang dapat dilakukan adalah dengan menerapkan extended access list yang merupakan salah satu bagian dari metode access control list. Extended access list dapat menyaring lalu lintas data suatu jaringan dengan mengontrol apakah paket-paket tersebut dilewatkan atau dihentikan. Extended access list juga dapat menjamin keamanan untuk setiap komputer sehingga jalur komunikasi serta hak akses setiap komputer dapat berjalan dengan baik. Extended access list memungkinkan penyaringan berdasarkan sumber atau alamat tujuan, protokol yang dipilih, port yang digunakan, dan apakah koneksi sudah ditetapkan. Tulisan ini membahas penerapan extended access list dalam jaringan supaya dapat melakukan filter terhadap paket data yang melewati jaringan. Penerapannya menggunakan software Packet Tracer 6.1.1 untuk membuat prototipe jaringan dan mensimulasikannya. Sehingga nanti dapat diterapkan pada jaringan yang sebenarnya. List yang dibangun pada penelitian ini diterapkan untuk protokol antara lain : TCP (WWW, FTP, Telnet, SMTP, POP3, UDP (DNS, dan ICMP (Ping. Hasilnya didapatkan extended access list yang dikonfigurasi pada router dalam topologi penelitian ini mampu melakukan filter terhadap paket yang melewati jaringan. Hasil konfigurasinya sangat spesifik, sehingga penerapan hak akses permit dan deny dapat dilakukan sesuai dengan aturan dan skenario yang dirancang.

  9. Targeted Therapies for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Idoroenyi Amanam

    2018-01-01

    Full Text Available Pancreatic cancer is the third leading cause of cancer related death and by 2030, it will be second only to lung cancer. We have seen tremendous advances in therapies for lung cancer as well as other solid tumors using a molecular targeted approach but our progress in treating pancreatic cancer has been incremental with median overall survival remaining less than one year. There is an urgent need for improved therapies with better efficacy and less toxicity. Small molecule inhibitors, monoclonal antibodies and immune modulatory therapies have been used. Here we review the progress that we have made with these targeted therapies.

  10. The OPERA experiment Target Tracker

    CERN Document Server

    Adam, T; Borer, K.; Campagne, Jean-Eric; Con-Sen, N.; de La Taille, C.; Dick, N.; Dracos, M.; Gaudiot, G.; Goeltzenlichter, T.; Gornushkin, Y.; Grapton, J.-N.; Guyonnet, J.-L.; Hess, M.; Igersheim, R.; Janicsko Csathy, J.; Jollet, C.; Juget, F.; Kocher, H.; Krasnoperov, A.; Krumstein, Z.; Martin-Chassard, G.; Moser, U.; Nozdrin, A.; Olchevski, A.; Porokhovoi, S.; Raux, L.; Sadovski, A.; Schuler, J.; Schutz, H.-U.; Schwab, C.; Smolnikov, A.; Van Beek, G.; Vilain, P.; Walchli, T.; Wilquet, G.; Wurtz, J.

    2007-01-01

    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.

  11. Targeted corneal transplantation.

    Science.gov (United States)

    Jhanji, Vishal; Mehta, Jod S; Sharma, Namrata; Sharma, Bhavana; Vajpayee, Rasik B

    2012-07-01

    Corneal transplantation surgery has moved from an era of conventional penetrating keratoplasty to selective replacement of the diseased corneal layer with complementary healthy donor corneal tissue. Anterior lamellar transplantation surgeries do not involve replacement of corneal endothelium, consequently eliminating the occurrence of endothelial rejection. Similarly, in diseases affecting the corneal endothelium, selective replacement with a lamellar lenticule bearing healthy endothelium provides better outcomes in terms of ocular surface, lesser astigmatism and quick visual recovery. In addition to the advantages of enhanced surgical outcomes, targeted corneal transplantation allows the use of one donor cornea for more than one recipient, thereby offering a viable solution to the problem of paucity of donor corneas. Evolving techniques of corneal transplantation have enabled better utilization of donor corneal tissue. Anterior lamellar as well as endothelial keratoplasty surgeries have become first-choice surgeries in appropriately selected cases. This review briefly discusses some of these novel surgical techniques. A better understanding of targeted corneal transplantation would lead to adaptation of the concept of component corneal surgery. This would further enable the corneal surgeons to circumvent the problem of donor corneal shortage especially in the developing world.

  12. Quantum state targeting

    Science.gov (United States)

    Rudolph, Terry; Spekkens, Robert W.

    2004-11-01

    We introduce a primitive for quantum cryptography that we term “state targeting.” We show that increasing one’s probability of success in this task above a minimum amount implies an unavoidable increase in the probability of a particular kind of failure. This is analogous to the unavoidable disturbance to a quantum state that results from gaining information about its identity, and can be shown to be a purely quantum effect. We solve various optimization problems for state targeting that are useful for the security analysis of two-party cryptographic tasks implemented between remote antagonistic parties. Although we focus on weak coin flipping, the results are significant for other two-party protocols, such as strong coin flipping, partially binding and concealing bit commitment, and bit escrow. Furthermore, the results have significance not only for the traditional notion of security in cryptography, that of restricting a cheater’s ability to bias the outcome of the protocol, but also for a different notion of security that arises only in the quantum context, that of cheat sensitivity. Finally, our analysis leads to some interesting secondary results, namely, a generalization of Uhlmann’s theorem and an operational interpretation of the fidelity between two mixed states.

  13. Extended van Hove singularity and superconducting instability in doped graphene.

    Science.gov (United States)

    McChesney, J L; Bostwick, Aaron; Ohta, Taisuke; Seyller, Thomas; Horn, Karsten; González, J; Rotenberg, Eli

    2010-04-02

    We have investigated the effects of doping on a single layer of graphene using angle-resolved photoemission spectroscopy. We show that many-body interactions severely warp the Fermi surface, leading to an extended van Hove singularity (EVHS) at the graphene M point. The ground state properties of graphene with such an EVHS are calculated, analyzing the competition between a magnetic instability and the tendency towards superconductivity. We find that the latter plays the dominant role as it is enhanced by the strong modulation of the interaction along the Fermi line, leading to an energy scale for the onset of the pairing instability as large as 1 meV when the Fermi energy is sufficiently close to the EVHS.

  14. TRACTION-EXTENDED THERAPY OF PATIENTS WITH LUMBAR DEGENERATIVE DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Zhirnov

    2013-01-01

    Full Text Available Based on the survey of 148 patients with an lumbar degenerative disease, there have been studied immediate and medium-term results of the comprehensive conservative treatment of the patients with and without application of traction exposure on the spine. It was found out that the traction of the spine leads to a quicker and more durable relief of symptoms in comparison with the control groups where traction therapy wasn't carried out. Application of the traction-extended therapy in three planes with a usage of robotized set for dry skeletal traction of a new generation KinetracKNX-7000 is proved to increase the effectiveness of treatment for the patients with stated pathology, fasten regress of the pain syndrome and clinical symptomatology, lead to more durable and lasting remission of the desease, in comparison with the patients that had traction of the spine in one plane only during the treatment.

  15. Targeted therapy for sarcomas

    Directory of Open Access Journals (Sweden)

    Forscher C

    2014-03-01

    Full Text Available Charles Forscher,1 Monica Mita,2 Robert Figlin3 1Sarcoma Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 3Academic Development Program, Samuel Oschin Comprehensive Cancer Institute, and Division of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA Abstract: Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing's sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing's sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. Keywords: sarcoma, targeted agents, tyrosine kinase inhibitors, mTor inhibition

  16. Design of the LBNF Beamline Target Station

    OpenAIRE

    Tariq, S.; Ammigan, K.; Anderson, K.; Buccellato, S. A.; Crowley, C. F.; Hartsell, B. D.; Hurh, P.; Hylen, J.; Kasper, P.; Krafczyk, G. E.; Lee, A.; Lundberg, B.; Marchionni, A; Mokhov, N. V.; Moore, C. D.

    2016-01-01

    The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-fil...

  17. Extending Isobar Model for Kaon Photoproduction up to 16 GeV

    CERN Document Server

    Mart, T

    2003-01-01

    We extend the isobar model for kaon photoproduction to consider higher energy data by combining the model with a Regge approach. The extended model works nicely between threshold and 16 GeV. It is shown that model with crossing symmetric Born terms leads to a better description of experimental data. We use the model to calculate contributions of kaon channels to the Gerasimov-Drell-Hearn sum rule up to 16 GeV.

  18. Light curves from supernova shock breakout through an extended wind

    Energy Technology Data Exchange (ETDEWEB)

    Ginzburg, Sivan; Balberg, Shmuel [Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel)

    2014-01-01

    Recent observations suggest that some supernovae may be the result of an explosion into an optically thick circumstellar material, the product of pre-explosion mass loss (wind) by the progenitor star. This scenario has been studied previously both analytically and numerically. However, many previous studies base their analysis on the diffusion approximation for radiation transfer, which is inappropriate in the optically thin outer layers of the wind. Here we study the deviations from diffusion and calculate light curves more accurately using a Monte Carlo approach to photon transfer. We distinguish between 'compact' winds, for which the diffusion approximation is appropriate, and 'extended' winds, which require a more delicate treatment of the radiation. We show that this effect is more significant than that of the light-travel time difference to a distant observer, which has a secondary influence on the light curves of extended-wind systems. We also comment on the applicability of the widely used flux-limited diffusion approximation in this context: we find that it generally does not reproduce the Monte Carlo results. The flux-limited diffusion approximation leads to results that are not only quantitatively but also qualitatively wrong in the extended-wind regime.

  19. Safety and Health Topics: Lead

    Science.gov (United States)

    ... gray, heavy metal that occurs naturally in the Earth’s crust. Lead was one of the first metals ... even at very low blood lead levels. Pregnant women or those who might become pregnant must avoid ...

  20. [Extended endoscopic endonasal approach to skull base].

    Science.gov (United States)

    López-Arbolay, Omar; González-González, Justo; Rojas-Manresa, Jorge Luis

    2012-11-01

    Different approaches to the skull base have been developed through the sphenoidal sinus. Traditional boundaries of the trans-sphenoidal approach can be extended in antero-posterior and lateral plane. We review our experience with extended endoscopic endonasal approach in 127 cases. We used the extended endoscopic endonasal approach in 127 patients with different lesions of the skull base. This study specifically focuses on: type of lesions, surgical approach, outcome and surgical complications. Extended endoscopic endonasal approach was used in 127 patients with following lesions: 61 invasive adenomas to cavernous sinus, 10 clival chordomas, 21 craniopharyngiomas, 26 meningiomas, 4 cerebrospinal fluid leakages, one meningoencephalocele, 2 malignan lesions and 2 thyroid ophthalmopathy. In tumoral lesions gross total resection was achieved in 82.5%, with better results in craniopharyngiomas 90.5%, followed by invasive adenomas with 85.2%, and meningiomas with 84.6%. The most frequent complications were the insipid (8.6%) diabetes, meningoencefalitis (3.9%) and the hydrocephalic (3.9%). Mortality was 3.9%. The extended endoscopic endonasal approach is a promising minimally invasive alternative for selective cases with skull base lesions. As techniques and technology advance this approach may become the procedure of choice for most lesions and should be considered an option in the management of the patients with these complex pathologies by skull base surgeon. Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  1. Modeling extended lactations of dairy cows.

    Science.gov (United States)

    Vargas, B; Koops, W J; Herrero, M; Van Arendonk, J A

    2000-06-01

    Nine mathematical models were compared for their ability to predict daily milk yields (n = 294,986) in standard 305-d and extended lactations of dairy cows of Costa Rica. Lactations were classified by parity (first and later), lactation length (9 to 10, 11 to 12, 13 to 14, 15 to 16, and 16 to 17 mo), and calving to conception interval (1 to 2, 3 to 4, 5 to 6, 7 to 8, and 9 to 10 mo). Of the nine models, the diphasic model and lactation persistency model resulted in the best goodness of fit as measured by adjusted coefficient of determination, residual standard deviation, and Durbin-Watson coefficient. All other models showed less accuracy and positively correlated residuals. In extended lactations, models were also fitted using only test-day records before 305 d, which resulted in a different ranking. The diphasic model showed the best prediction of milk yield in standard and extended lactations. We concluded that the diphasic model provided accurate estimates of milk yield for standard and extended lactations. Interpretation of parameters deserves further attention because of the large variation observed. As expected, the calving to conception interval was found to have a negative effect on milk yield for cows with a standard lactation length. In extended lactations, these negative effects of pregnancy on milk yield were not observed.

  2. Lead Exposure Hazard Management Guide

    Science.gov (United States)

    1993-12-01

    effects of lead on humans beings have been known for many years. Acute overexposure to lead can kill in a matter of days. Chronic overexposure to lead in...8217--: -7 Thserconnsa*Im will help achive one of dh nationial health objectives specified by Healthy Peple 2000, which is to eliminate exposures that

  3. Effects of lead on the kidney: Roles of high-affinity lead-binding proteins

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, B.A. (Univ. of Maryland, Baltimore (United States)); DuVal, G. (Univ of Maryland Medical School, Baltimore (United States))

    1991-02-01

    Lead-induced nephropathy produces both tubular and interstitial manifestations of cell injury, but the pathophysiology of these lesions is not completely understood. Delineation of the molecular factors underlying renal handling of lead is one of central importance in understanding the mechanisms of renal cell injury from this agent. Recent studies from this laboratory have identified several distinct high-affinity lead-binding proteins (PbBP) from rat kidney and brain that appear to play critical roles in the intracellular bioavailability of lead to several essential cellular processes in these target tissues at low dose levels. These studies have also shown that the real PbBP is selectively localized in only certain nephrons and only specific segments of the renal proximal tubule. The striking nephron and cell-type specificity of the localization reaction could result from physoiological differences in nephron functional activity or selective molecular uptake mechanisms/metabolism differences that act to define target cell populations in the kidney. In addition, other preliminary studies have shown that short-term, high-dose lead exposure produces increased excretion of this protein into the urine with concomitant decreases in renal concentrations.

  4. In vitro 3-D model based on extending time of culture for studying chronological epidermis aging.

    Science.gov (United States)

    Dos Santos, Morgan; Metral, Elodie; Boher, Aurélie; Rousselle, Patricia; Thepot, Amélie; Damour, Odile

    2015-09-01

    Skin aging is a complex phenomenon in which several mechanisms operate simultaneously. Among them, intrinsic aging is a time-dependent process, which leads to gradual skin changes affecting its structure and function such as thinning down of both epidermal and dermal compartments and a flattening and fragility of the dermo-epidermal junction. Today, several approaches have been proposed for the generation of aged skin in vitro, including skin explants from aged donors and three-dimensional skin equivalent treated by aging-inducing chemical compounds or engineered with human cells isolated from aged donors. The aim of this study was to develop and validate a new in vitro model of aging based on skin equivalent demonstrating the same phenotypic changes that were observed in chronological aging. By using prolonged culture as a proxy for cellular aging, we extended to 120 days the culture time of a skin equivalent model based on collagen-glycosaminoglycan-chitosan porous polymer and engineered with human skin cells from photo-protected sites of young donors. Morphological, immunohistological and ultrastructural analysis at different time points of the culture allowed characterizing the phenotypic changes observed in our model in comparison to samples of non photo-exposed normal human skin from different ages. We firstly confirmed that long-term cultured skin equivalents are still morphologically consistent and functionally active even after 120 days of culture. However, similar to in vivo chronological skin aging a significant decrease of the epidermis thickness as well as the number of keratinocyte expressing proliferation marker Ki67 are observed in extended culture time skin equivalent. Epidermal differentiation markers loricrin, filaggrin, involucrin and transglutaminase, also strongly decreased. Ultrastructural analysis of basement membrane showed typical features of aged skin such as duplication of lamina densa and alterations of hemidesmosomes. Moreover, the

  5. The Extended Family and Children's Educational Success

    DEFF Research Database (Denmark)

    Jæger, Mads Meier

    2012-01-01

    characteristics of grandparents and aunts and uncles have few direct effects on educational success, resources in the extended family compensate lacking resources in low-SES families, which in turn promote children’s educational success. The main conclusion is that the total effect of family background......Research on family background and educational success focuses almost exclusively on two generations and on parents and children. This paper argues that the extended family makes up a significant part of the total effect of family background on educational success. Empirical results based...... on the Wisconsin Longitudinal Study show that, net of family factors shared by siblings from the same immediate family, factors shared by first cousins from the same extended family account for a nontrivial part of the total variance in children’s educational success. Results also show that while socioeconomic...

  6. Pharmacogenomics of GPCR Drug Targets

    DEFF Research Database (Denmark)

    Hauser, Alexander Sebastian; Chavali, Sreenivas; Masuho, Ikuo

    2017-01-01

    Natural genetic variation in the human genome is a cause of individual differences in responses to medications and is an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are the targets of 475 (∼34%) Food and Drug Administration (FDA)-approved drugs...... and account for a global sales volume of over 180 billion US dollars annually, the prevalence of genetic variation among GPCRs targeted by drugs is unknown. By analyzing data from 68,496 individuals, we find that GPCRs targeted by drugs show genetic variation within functional regions such as drug......- and effector-binding sites in the human population. We experimentally show that certain variants of μ-opioid and Cholecystokinin-A receptors could lead to altered or adverse drug response. By analyzing UK National Health Service drug prescription and sales data, we suggest that characterizing GPCR variants...

  7. Lead poisoning in an adult: lead mobilization by pregnancy?

    Science.gov (United States)

    Riess, Matthias L; Halm, Josiah K

    2007-08-01

    We report a case of acute lead poisoning in an adult female who had last been exposed to lead 7 years ago. She presented with abdominal pain, knee pain, and neurological symptoms, hypertension, chronic kidney disease, and anemia with basophilic stippling and lead gum lines. Compared to during her recent pregnancy, her lead level had almost tripled in 5 months to 81 mcg/dL. Chelation therapy was initiated and improved the patient's symptoms and lead level significantly. In the absence of any new lead exposure or other reasons for increased bone turnover, this acute lead increase was likely due to skeletal mobilization caused by increased resorption from mineralized tissue during and after her pregnancy. This case report illustrates the seriousness of long-term health effects associated with lead poisoning at a multi-organ level, even years after the initial exposure. Thus, patient care should not be limited to the acute treatment of increased lead levels, but also include prevention of increased mobilization and bone turnover and appropriate patient education. In this context, we review various aspects of lead toxicity, especially during pregnancy and lactation.

  8. A computational framework for modeling targets as complex adaptive systems

    Science.gov (United States)

    Santos, Eugene; Santos, Eunice E.; Korah, John; Murugappan, Vairavan; Subramanian, Suresh

    2017-05-01

    Modeling large military targets is a challenge as they can be complex systems encompassing myriad combinations of human, technological, and social elements that interact, leading to complex behaviors. Moreover, such targets have multiple components and structures, extending across multiple spatial and temporal scales, and are in a state of change, either in response to events in the environment or changes within the system. Complex adaptive system (CAS) theory can help in capturing the dynamism, interactions, and more importantly various emergent behaviors, displayed by the targets. However, a key stumbling block is incorporating information from various intelligence, surveillance and reconnaissance (ISR) sources, while dealing with the inherent uncertainty, incompleteness and time criticality of real world information. To overcome these challenges, we present a probabilistic reasoning network based framework called complex adaptive Bayesian Knowledge Base (caBKB). caBKB is a rigorous, overarching and axiomatic framework that models two key processes, namely information aggregation and information composition. While information aggregation deals with the union, merger and concatenation of information and takes into account issues such as source reliability and information inconsistencies, information composition focuses on combining information components where such components may have well defined operations. Since caBKBs can explicitly model the relationships between information pieces at various scales, it provides unique capabilities such as the ability to de-aggregate and de-compose information for detailed analysis. Using a scenario from the Network Centric Operations (NCO) domain, we will describe how our framework can be used for modeling targets with a focus on methodologies for quantifying NCO performance metrics.

  9. Sum rules in extended RPA theories

    Energy Technology Data Exchange (ETDEWEB)

    Adachi, S.; Lipparini, E.

    1988-11-28

    Different moments m/sub k/ of the excitation strength function are studied in the framework of the second RPA and of the extended RPA in which 2p2h correlations are explicitly introduced into the ground state by using first-order perturbation theory. Formal properties of the equations of motion concerning sum rules are derived and compared with those exhibited by the usual 1p1h RPA. The problem of the separation of the spurious solutions in extended RPA calculations is also discussed.

  10. Extended Interneuronal Network of the Dentate Gyrus

    Directory of Open Access Journals (Sweden)

    Gergely G. Szabo

    2017-08-01

    Full Text Available Local interneurons control principal cells within individual brain areas, but anecdotal observations indicate that interneuronal axons sometimes extend beyond strict anatomical boundaries. Here, we use the case of the dentate gyrus (DG to show that boundary-crossing interneurons with cell bodies in CA3 and CA1 constitute a numerically significant and diverse population that relays patterns of activity generated within the CA regions back to granule cells. These results reveal the existence of a sophisticated retrograde GABAergic circuit that fundamentally extends the canonical interneuronal network.

  11. The extended oloid and its inscribed quadrics

    OpenAIRE

    Bäsel, Uwe; Dirnböck, Hans

    2015-01-01

    The oloid is the convex hull of two circles with equal radius in perpendicular planes so that the center of each circle lies on the other circle. It is part of a developable surface which we call extended oloid. We determine the tangential system of all inscribed quadrics $\\mathcal{Q}_\\lambda$ of the extended oloid $\\mathcal{O}$ where $\\lambda$ is the system parameter. From this result we conclude parameter equations of the touching curve $\\mathcal{C}_\\lambda$ between $\\mathcal{O}$ and $\\math...

  12. Turbo Codes Extended with Outer BCH Code

    DEFF Research Database (Denmark)

    Andersen, Jakob Dahl

    1996-01-01

    The "error floor" observed in several simulations with the turbo codes is verified by calculation of an upper bound to the bit error rate for the ensemble of all interleavers. Also an easy way to calculate the weight enumerator used in this bound is presented. An extended coding scheme is propose...... including an outer BCH code correcting a few bit errors.......The "error floor" observed in several simulations with the turbo codes is verified by calculation of an upper bound to the bit error rate for the ensemble of all interleavers. Also an easy way to calculate the weight enumerator used in this bound is presented. An extended coding scheme is proposed...

  13. Extending Symfony 2 web application framework

    CERN Document Server

    Armand, Sébastien

    2014-01-01

    Symfony is a high performance PHP framework for developing MVC web applications. Symfony1 allowed for ease of use but its shortcoming was the difficulty of extending it. However, this difficulty has now been eradicated by the more powerful and extensible Symfony2. Information on more advanced techniques for extending Symfony can be difficult to find, so you need one resource that contains the advanced features in a way you can understand. This tutorial offers solutions to all your Symfony extension problems. You will get to grips with all the extension points that Symfony, Twig, and Doctrine o

  14. Extending the application of DSAM to atypical stopping media

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.; Samanta, S.; Bhattacharjee, R. [UGC-DAE Consortium for Scientific Research, Kolkata Centre, Kolkata 700098 (India); Raut, R., E-mail: rraut@alpha.iuc.res.in [UGC-DAE Consortium for Scientific Research, Kolkata Centre, Kolkata 700098 (India); Ghugre, S.S. [UGC-DAE Consortium for Scientific Research, Kolkata Centre, Kolkata 700098 (India); Sinha, A.K. [UGC-DAE Consortium for Scientific Research, Indore 452001 (India); Garg, U. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556 (United States); Chakrabarti, R.; Mukhopadhyay, S. [Nuclear Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Dhal, A.; Raju, M. Kumar; Madhavan, N.; Muralithar, S.; Singh, R.P. [Inter University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110067 (India); Suryanarayana, K.; Rao, P.V. Madhusudhana [Department of Nuclear Physics, Andhra University, Visakhapatnam 530003 (India); Palit, R.; Saha, S.; Sethi, J. [Tata Institute of Fundamental Research, Mumbai 400005 (India)

    2017-01-01

    A methodology that manifolds the possibilities of level lifetime measurements using the Doppler Shift Attenuation Method (DSAM), and extends its application beyond the conventional thin-target-on-thick-elemental-backing setups, is presented. This has been achieved primarily through application of the TRIM code to simulate the stopping of the recoils in the target and the backing media. Using the TRIM code, primarily adopted in the domain of materials research, in the context of lifetime analysis require rendition of the simulation results into a representation that appropriately incorporates the nuances of nuclear reaction along with the associated kinematics, besides the transformation from an energy-coordinate representation to a velocity-direction profile as required for lifetime analysis. The present development makes it possible to practice DSAM in atypical experimental scenarios such as those using molecular or multi-layered target and/or backing as the stopping medium. These aberrant cases, that were beyond representation in the customary Doppler shape analysis can, in the light of the present work, be conveniently used in the DSAM based investigations. The new approach has been validated through re-examination of known lifetimes measured both in the conventional as well as in the deviant setups.

  15. Childhood lead poisoning associated with lead dust contamination of family vehicles and child safety seats - Maine, 2008.

    Science.gov (United States)

    2009-08-21

    Persons employed in high-risk lead-related occupations can transport lead dust home from a worksite through clothing, shoes, tools, or vehicles. During 2008, the Maine Childhood Lead Poisoning Prevention Program (MCLPPP) identified 55 new cases of elevated (>or=15 microg/dL) venous blood lead levels (BLLs) among children aged lead poisoning cases in Maine during 2003-2007 had been linked to lead hazards in the child's home, no lead-based paint or dust or water with elevated lead levels were found inside the homes associated with six of the 2008 cases (i.e., five families, including one family with two affected siblings). An expanded environmental investigation determined that these six children were exposed to lead dust in the family vehicles and in child safety seats. The sources of the lead dust were likely household contacts who worked in high-risk lead exposure occupations. Current recommendations for identifying and reducing risk from take-home lead poisoning include 1) ensuring that children with elevated BLLs are identified through targeted blood lead testing, 2) directing prevention activities to at-risk workers and employers, and 3) improving employer safety protocols. State and federal prevention programs also should consider, when appropriate, expanded environmental lead dust testing to include vehicles and child safety seats.

  16. Ecdysone receptor agonism leading to lethal molting ...

    Science.gov (United States)

    Molting is a key biological process in growth, development, reproduction and survival in arthropods. Complex neuroendocrine pathways are involved in the regulation of molting and may potentially become targets of environmental endocrine disrupting compounds (EDCs). For example, several classes of pesticides used in agriculture and aquaculture specifically target key endocrine regulators of the molting process. These chemicals may also pose hazards to non-target species by causing molting defects, thus affecting the health of the ecosystems. The present review summarized the available knowledge on molting-related endocrine regulation and disruption in arthropods (with special focus on insects and crustaceans), in order to identify research gaps and develop a toxicity mechanism-based model for environmental hazard and risk assessment. Based on the review, multiple targets in the molting processes that EDCs can interact with were characterized to inform future studies. An adverse outcome pathway (AOP) describing ecdysone receptor agonism leading to incomplete ecdysis associated mortality was developed according to the OECD guideline and evaluated for weight of evidence using the Evolved Bradford Hill Criteria. This review proposed the first invertebrate endocrine disruption AOP and may serve as a knowledge foundation for future environmental studies and AOP development. Development of high throughput toxicology (HTT) programs (e.g., ToxCast, Tox21) and potential a

  17. Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance

    DEFF Research Database (Denmark)

    Widlund, Anne Lykkegaard; Vang, Ole; Ye, Lan

    2013-01-01

    and compromise the function of mitochondria in cultured muscle cells, implying that defects in bioenergetics might be an unavoidable consequence of targeting mTORC1 in vivo. Therefore, we tested whether rapamycin, at the same doses used to extend lifespan, affects mitochondrial function in skeletal muscle. While...

  18. Determining lead sources in Mexico using the lead isotope ratio

    Directory of Open Access Journals (Sweden)

    Chaudhary-Webb Madhu

    2003-01-01

    Full Text Available OBJECTIVE: Lead poisoning can, in some cases, be traced to a specific route or source of exposure on the basis of the individual's blood lead isotope ratio. To assess the major source of lead exposure among women residing in Mexico City, we compared blood, ceramic, and gasoline lead isotope ratios. MATERIAL AND METHODS: The study population, randomly selected from participants of a large trial, (1/1996-12/1996 comprised of 16 women whose lead levels exceeded 10 µg/dl and who reported using lead-glazed ceramics. Lead isotope ratios were performed on a Perkin Elmer 5000 Inductively Coupled Plasma Mass Spectrometer (ICP-MS interfaced with a Perkin Elmer HGA-600MS Electrothermal Vaporization System (ETV. RESULTS: The isotope ratios (206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb of both the blood specimens and their corresponding ceramic specimens were highly correlated, with r=0.9979, r²=0.9958, r=0.9957, r²=0.9915 and r=0.9945, r²=0.9890 values for the three isotope ratios, respectively, suggesting that the lead exposure most likely resulted from the use of these ceramic. Measurements of lead isotope ratios from leaded gasoline in use at the time of blood sampling, differed from those in blood and ceramics. CONCLUSIONS: Determining lead isotope ratios can be an efficient tool to identify a major source of lead exposure and to support the implementation of public health prevention and control measures.

  19. Early cortical facilitation for emotionally arousing targets during the attentional blink

    Directory of Open Access Journals (Sweden)

    Ihssen Niklas

    2006-07-01

    Full Text Available Abstract Background The present study aimed to investigate the time course of electrocortical facilitation for affectively arousing written words during the so-called 'attentional blink' (AB period in a rapid serial visual presentation (RSVP task. The AB refers to a period of reduced awareness for second-target stimuli following a first target by an interval of about 200–500 ms. Pleasant, neutral, and unpleasant written verbs were used as second targets in an 8.6-Hz RSVP paradigm that contained affectively neutral words as distractors. Replicating and extending behavioral studies, we expected that emotional second targets would be associated with better identification accuracy and greater electrocortical activity, compared with neutral targets. Results The steady-state visual evoked potential was recorded using 129 scalp electrodes. The time-varying energy at the presentation frequency of 8.6 Hz was extracted as a continuous measure of electrocortical activity related to the RSVP stream. Behavioral data showed that at an inter-target interval of 232 ms, the report for emotionally arousing (pleasant and unpleasant words was more accurate than for neutral control words. This result was mirrored by the electrocortical response at posterior sensors, which showed rapid amplitude enhancement (120–270 ms after T2 onset for pleasant and unpleasant targets specifically. Conclusion The present data suggest that identification facilitation for emotionally arousing target words in the AB is related to rapid enhancement of sensory processing. Affectively arousing information is preferentially selected at the level of early perceptual analysis, leading to facilitation at later stages of processing, including consolidation in working memory and visual awareness.

  20. Chronic lead poisoning in horses

    Energy Technology Data Exchange (ETDEWEB)

    Knight, H.D.; Burau, R.G.

    1973-05-01

    Chronic lead poisoning in horses was manifested as anorexia, loss of body weight, muscular weakness, anemia, laryngeal hemiplegia, and, terminally, inhalation pneumonia. Some deaths were sudden and unexplained. The lead content in liver specimens from 10 horses was greater than that considered indicative of lead intoxication; however, the lead content of blood was equivocal. The most conclusive laboratory finding was increased urine lead concentration after chelation therapy. The concentration of lead in a sample of vegetation considered to be representative of what a horse would eat if he was grazing in the area sampled was 325 ppM (oven-dry basis). It was determined that a 450-kg horse grazing grass of this lead content would consume 2.9 Gm of lead daily (6.4 mg/kg of body weight), an amount considered toxic for horses. Leaching lowered the calcium content of the forage but failed to reduce the lead concentration of the plants significantly, thus opening the possibility that winter rains might have influenced the onset of poisoning. Airborne fallout from a nearby lead smelter was proposed as the primary mode of pasture contamination.

  1. Childhood lead poisoning: an overview.

    Science.gov (United States)

    Hon, K L; Fung, C K; Leung, A Kc

    2017-12-01

    Childhood lead poisoning is a major public health concern in many countries. In 2015, the Hong Kong SAR Government and its citizens faced a major public health crisis due to the presence of lead in the drinking water of a number of public housing estates. Fortunately, no child was diagnosed with lead poisoning that required treatment with chelation. Lead is a ubiquitous, naturally occurring material that exists in air, dust, soil, and water. It is also widely present in industrial products including petrol, paints, ceramics, food cans, candies, cosmetics, traditional remedies, batteries, solder, stained glass, crystal vessels, ammunition, ceramic glazes, jewellry, and toys. It can also be found in human milk. There is no safe blood lead level and it may be impossible to completely eliminate lead from any city. Hence routine measurement of blood lead levels is not considered useful. Acute poisoning, especially with encephalopathy, deserves immediate medical treatment in hospital. Chelation therapy is recommended if blood lead level is 45 μg/dL or higher. For blood levels between 20 and 45 μg/dL, treatment is indicated if the child is symptomatic. For blood levels below 20 μg/dL in otherwise asymptomatic children, the principle of treatment is to provide long-term neurodevelopmental follow-up and counselling. In all cases, immediate removal of the source of lead exposure is vital. Even low levels of lead exposure can significantly impair learning, educational attainment, and neurodevelopment.

  2. SENSITIVITY OF EXTENDED-SPECTRUM β - LACTAMASES ...

    African Journals Online (AJOL)

    DR. AMINU

    extract and fractions were tested for antimicrobial activity against confirmed extended spectrum β- lactamases (ESBLs) producing enterobacteriaceae isolates of Escherichia coli, ... oncology and neonatal units (Kohler et al, 1999). Medicinal plants have long been utilized as a source of therapeutic agents worldwide due to ...

  3. Apixaban for Extended Treatment of Venous Thromboembolism

    NARCIS (Netherlands)

    Agnelli, Giancarlo; Buller, Harry R.; Cohen, Alexander; Curto, Madelyn; Gallus, Alexander S.; Johnson, Margot; Porcari, Anthony; Raskob, Gary E.; Weitz, Jeffrey I.; Gallus, Alexander; Raskob, Gary; Weitz, Jeffrey; Prins, Martin; Brandjes, Dees; Kolbach, Dinanda; Limburg, Martinus; Mac Gillavry, Melvin; Otten, Johannes Martinus; Peters, Ron; Roos, Yvo; Segers, Annelise; Slagboom, Ton; Bounameaux, Henry; Hirsh, Jack; Samama, Meyer Michel; Wedel, Hans; Masiukiewicz, Urszula; Pak, Raphael; Sanders, Paul; Sisson, Melanie; Sullivan, Beth; Thompson, John; Auerbach, Jennifer; Cesario, Lynne; Gamero, Miguel; Gordon, Margot; Griffiths, Angela; Noble, Melanie; Ott, Jana; Pennington, Ann; Peffer, Allison; Reinhold, Peggy; Simmons, Melanie; Urwin, Keri; Ceresetto, Jose; McRae, Simon; Pabinger, Ingrid; Pereira, Adamastor Humberto; Spencer, Fred; Gorican, Karel; Husted, Steen Elkiaer; Mottier, Dominique; Harenberg, Job; Pinjala, Ramakrishna; Zeltser, David; Imberti, Davide; Sandset, Morten; Torbicki, Adam; Fijalkowska, Anna; Albino, Jose Pereira; Kirienko, Alexander; Shvarts, Yury; Monreal, Manuel; Jacobson, Barry; Dolan, Gerry; Gudz, Ivan; Ortel, Tom; Spyropoulos, Alex; Torbicki, A.; Fijalkowska, A.; Skupyy, O.; Beryer-Westendorf, J.; de Pellegrin, A.; Prasol, V.; Schellong, S.; Jacobson, B.; Falvo, N.; Abramov, I.; Cizek, V.; Husted, S.; Desai, S.; Gudz, I.; Barillari, G.; Sergeev, O.; Chetter, I.; Inbal, A.; McCollum, C.; Shvalb, P.; Torp-Pedersen, C.; Vasylyuk, S.; Kraemmer Nielsen, H.; Pernod, G.; Schmidt, J.; Bova, C.; Gerasymov, V.; Pabinger-Fasching, I.; Skalicka, L.; Zaichuk, A.; Achkar, A.; Bremmelgaard, A.; Chochola, J.; Gould, T.; Khalafallah, A.; Jakobsen, T.; Rose, P.; Zhukov, B.; Dedek, V.; Mirete Ferrer, J.; Pesant, Y.; Repin, A.; Salem, H.; Solis Morales, L.; Spacek, R.; Cannon, K.; Grzelakowski, P.; Jindal, R.; Pereira, A.; Zidkova, E.; Ambrosio, G.; Cardozo, M.; Dunaj, M.; Gallus, A.; Gavish, D.; Ghanima, W.; Harenberg, J.; Leduc, J. J.; Mismetti, P.; Panico, M.; Porreca, E.; Riera, A.; Bareford, D.; Chong, B.; Dvoryashina, I.; Gómez Cerezo, J.; Kobza, I.; Nielsen, T.; Pendleton, R.; Pullman, J.; Schiffman, G.; Stanbro, M.; Zwettler, U.; Aquilanti, S.; Bratsch, H.; Cohen, K.; Elias, D.; Gan, E.; Holaj, R.; Klinke, W.; Liu, H. S. Y.; Sandset, P. M.; van Nieuwenhuizen, E.; Álvarez-Sala, L. A.; Basson, M.; Braester, A.; Bura-Riviere, A.; Calvo Vargas, C.; Cohen, A.; Correa, J.; Elias, M.; Frost, L.; Imberti, D.; Landolfi, R.; Marschang, P.; Moreira, R.; Mottier, D.; Natarajan, S.; Pottier, P.; Tosetto, A.; Tuxen, C.; Vöhringer, H. F.; Alexander, A.; Barbarash, O.; Fajardo Campos, P.; Graham, M.; Gubka, O.; Hudcovic, M.; Hussein, O.; Jackson, D.; Katelnitskiy, I.; Lawall, H.; Monreal, M.; Palareti, G.; Poggio, R.; Roos, J.; Simonneau, G.; Smith, S. W.; Szopinski, P.; Ortel, T.; Zimlichman, R.; Bridgers, D.; Colan, D.; Czekalski, P.; de Jong, D.; Fortinez, J. T.; Garcia Bragado, F.; Harrington, D.; Izbicki, G.; Kadr, H.; Koslow, A.; Loftus, I.; Marais, H.; Neumeister, A.; Oliven, A.; Palla, A.; Pop, C.; Prandoni, P.; Puskas, A.; Sanchez Llamas, F.; Shotan, A.; Shvarts, Y.; Singh, P.; Tveit, A.; Baker, R.; Borja, V.; Brenner, B.; Brown, H.; Ceresetto, J.; Cha, T. J.; Cohen, Y.; D'Angelo, A.; Dhar, A.; Friis, E.; Hueur, H.; Jiménez Rodríguez Madridejos, R.; Karl, J.; Karrasch, J.; Lishner, M.; Manenti, E.; McRae, S.; Meneveau, N.; Nguyen, D.; Sanchez-Escalante, L.; Santoscoy Ibarra, J.; Sokurenko, G.; Staroverov, I.; Stein, R.; Abdullah, I.; Agnelli, G.; Alcocer Gamba, M.; Balanda, J.; Bruckner, I.; Calabuig Alborch, J.; Caraco, Y.; Comerota, A.; Cromer, M.; de Araujo Filho, J.; de los Rios Ibarra, M.; Diaz-Castañon, J.; Doshi, A.; Ebrahim, I.; Fessel, W. J.; Fletcher, E.; Fourie, N.; Fu, C.; Gutowski, P.; Haddad, G.; Hoffman, U.; Jardula, M.; Kvasnicka, T.; Lewczuk, J.; Leyden, M.; Livneh, A.; Lodigiani, C.; Lovell, C.; Miekus, P.; Paloma, M. J.; Parakh, R.; Raval, M.; Schmidt-Lucke, J.; Shtutin, O.; Soroka, V.; Stevens, D.; Sulik, P.; Tay, J. C.; Vejby-Christensen, H.; Vinereanu, D.; Baghestanian, M.; Bono, J.; Cerana, S.; Freire, A.; Gibson, K.; Giumelli, C.; Iastrebner, C.; Karpenko, A.; Kelly, A.; Lacroix, P.; LaFata, J.; Lobo, S.; Macik, B. G.; Marchena Yglesias, P.; Nishinari, K.; Pinjala, R.; Podczeck-Schweighofer, A.; Raby, K.; Sirpal, S.; Solymoss, S.; Spencer, F.; van Zyl, L.; Vargas Núñez, J. A.; von Bilderling, P.; Warr, T.; Wronski, J.; Wurster, M.; Albino, J. A.; Albuquerque, L.; Averill, F.; Baek, S. H.; Bello, F.; Bergoeing, M.; Blanc, F. X.; Bloomberg, R.; Bolster, D.; Brockmyre, A.; Calimano, C.; Checketts, D.; Cieplinski, W.; Chervu, A.; Collado, F.; Denaro, C.; Gaciong, Z.; Game, M.; Iskander, A.; Kaatz, S.; Kim, D. I.; Koura, F.; Laguna, F.; Lanas Zanetti, F.; Lindhoff-Last, E.; Melaniuk, M.; Meade, A.; Murphy, T.; Ng, H. J.; Páramo Fernández, J. A.; Patil, C.; Piovella, F.; Prisco, D.; Pruszczyk, P.; Reimers, G.; Rivera, E.; Rodriguez-Cintron, W.; Rosenthal, S.; Salbach, P.; Salvador, D.; Schuller, D.; Siragusa, S.; Staniszewski, R.; Torp, R.; Vora, K.; Yip, G.; Alfieri, A.; Belaji, V.; Bhagavan, N.; Carnovali, M.; Cobos Segarra, J.; Di Todaro, F.; Dowell, A.; Corder, C.; Crispin, P.; Cuadrado, J.; Flippo, G.; Fraiz, J.; Guillaumon, A.; Gvora, T.; Hakki, S.; Harris, L.; Ison, R.; Htun, P. T.; Jasani, R.; Kates, M.; Kaminski, L.; Kamerkar, D.; Kirienko, A.; Kroger, K.; LaPerna, L.; Leiva, J.; Luber, J.; McCann, A.; McKenzie, W.; Menna Barreto, S.; Moran, J.; Nikulnikov, P.; Paliwal, Y.; Patel, M.; Pilger, E.; Renwick, W.; Shevela, A.; Starosiliz, D.; Stringam, S.; Spyropoulos, A.; To, R.; Updegrove, J.; van Bellen, B.; Waintrub, M.; White, J.; Yeo, E.; Zangroniz, P.; Zeltser, D.

    2013-01-01

    BACKGROUND Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. METHODS In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with

  4. Extending and embedding the Python interpreter

    NARCIS (Netherlands)

    G. van Rossum (Guido)

    1995-01-01

    textabstractPython is an interpreted, object-oriented programming language. This document describes how to write modules in C or C++ to extend the Python interpreter with new modules. Those modules can define new functions but also new object types and their methods. The document also describes

  5. Observational constraints on extended Chaplygin gas cosmologies

    Indian Academy of Sciences (India)

    We investigate cosmological models with extended Chaplygin gas (ECG) as a candidate for dark energy and determine the equation of state parameters using observed data namely, observed Hubble data, baryon acousticoscillation data and cosmic microwave background shift data. Cosmological models are investigated ...

  6. The Extended Mind Thesis and Mechanistic Explanations

    DEFF Research Database (Denmark)

    Fazekas, Peter

    2013-01-01

    The Extended Mind Thesis (EMT) is traditionally formulated against the bedrock of functionalism, and ongoing debates are typically bogged down with questions concerning the exact relationship between EMT and different versions of functionalism. In this paper, I offer a novel ally for EMT: the new...

  7. Extended working hours: Impacts on workers

    Science.gov (United States)

    D. Mitchell; T. Gallagher

    2010-01-01

    Some logging business owners are trying to manage their equipment assets by increasing the scheduled machine hours. The intent is to maximize the total tons produced by a set of equipment. This practice is referred to as multi-shifting, double-shifting, or extended working hours. One area often overlooked is the impact that working non-traditional hours can have on...

  8. Extended Resin Composite Restorations: Techniques and Procedures

    NARCIS (Netherlands)

    Loomans, B.A.C.; Hilton, T.

    2016-01-01

    This article gives an overview of the state of the art of different restorative treatment procedures and techniques needed for placing extended posterior resin composite restorations. Clinical aspects related to the procedure are discussed and reviewed based on the current literature, such as the

  9. [Combined hormonal contraception in cycles artificially extended].

    Science.gov (United States)

    Bustillos-Alamilla, Edgardo; Zepeda-Zaragoza, J; Hernández-Ruiz, M A; Briones-Landa, Carlos Humberto

    2010-01-01

    To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.

  10. Extending the Instructional Systems Development Methodology.

    Science.gov (United States)

    O'Neill, Colin E.

    1993-01-01

    Describes ways that components of Information Engineering (IE) methodology can be used by training system developers to extend Instructional Systems Development (ISD) methodology. Aspects of IE that are useful in ISD are described, including requirements determination, group facilitation, integrated automated tool support, and prototyping.…

  11. Antibiotic Susceptibility Pattern of Extended Spectrum ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antibiotic susceptibility pattern of various bacterial pathogens including extended spectrum betalactamase (ESBL) producers in Kano, Nigeria. Method: A total of 604 consecutive clinical samples obtained from Aminu Kano Teaching Hospital. (AKTH), Kano between January and July 2010 were ...

  12. Q-Method Extended Kalman Filter

    Science.gov (United States)

    Zanetti, Renato; Ainscough, Thomas; Christian, John; Spanos, Pol D.

    2012-01-01

    A new algorithm is proposed that smoothly integrates non-linear estimation of the attitude quaternion using Davenport s q-method and estimation of non-attitude states through an extended Kalman filter. The new method is compared to a similar existing algorithm showing its similarities and differences. The validity of the proposed approach is confirmed through numerical simulations.

  13. Some Remarks on the Extended Galilean Transformation.

    Science.gov (United States)

    Greenberger, Daniel M.

    1979-01-01

    The extended Galilean transformation carries an inertial frame into a rigid frame with uniform spatial, but arbitrary translational acceleration. Besides being useful in discussing the equivalence principle, this transformation provides a physical interpretation for the theorem in nonrelativistic quantum mechanics, that we cannot coherently…

  14. Extended plate and beam demonstration home

    Science.gov (United States)

    Patricia Gunderson; Vladimir Kochkin; Xiping Wang

    2018-01-01

    An extended plate and beam (EP&B) design was developed at Home Innovation Research Labs (Upper Marlboro, Maryland) in an effort to provide traditional light-frame wall construction details that are compatible with continuous insulating sheathing. This would encourage wide-spread adoption of high-R walls and promote greater energy efficiency in new houses. The...

  15. Modeling survival data extending the cox model

    CERN Document Server

    Therneau, Terry M

    2000-01-01

    Extending the Cox Model is aimed at researchers, practitioners, and graduate students who have some exposure to traditional methods of survival analysis The emphasis is on semiparametric methods based on the proportional hazards model The inclusion of examples with SAS and S-PLUS code will make the book accessible to most working statisticians

  16. Impact of Divorce on the Extended Family.

    Science.gov (United States)

    Fisher, Esther Oshiver, Ed.

    1981-01-01

    Contains 11 articles focusing on psychological, sociological, legal, economic, and clinical aspects of divorce and the extended family. Examines issues including: (1) dynamics of the family kinship system; (2) family life cycle and divorce; (3) kin role in divorce adjustment; and (4) changes in family relationships. (RC)

  17. The inflation sector of extended inflation

    Science.gov (United States)

    Kolb, Edward W.

    1991-01-01

    In extended inflation, the inflationary era is brought to a close by the process of percolation of true vacuum bubbles produced in a first-order phase transition. This paper discusses several effects that might obtain if the universe undergoes an inflationary first-order phase transition.

  18. Extended Learning Time: Research and Resources

    Science.gov (United States)

    Stelow, Shawn; Holland, Jenifer Gager; Jackson, Rebecca

    2012-01-01

    In recent years policymakers have increasingly looked to Extended Learning Time (ELT) as a means of improving student outcomes. As a result, some school districts have increased academic time for students by adding time to the school day or days to the school year. In other communities, schools and community-based organizations have partnered to…

  19. Modelling extended lactations of dairy cows

    NARCIS (Netherlands)

    Vargas, B.; Koops, W.J.; Herrero, M.; Arendonk, van J.A.M.

    2000-01-01

    Nine mathematical models were compared for their ability to predict daily milk yields (n = 294,986) in standard 305-d and extended lactations of dairy cows of Costa Rica. Lactations were classified by parity (first and later), lactation length (9 to 10, 11 to 12, 13 to 14, 15 to 16, and 16 to 17

  20. Incidence and antimicrobial susceptibility pattern of extended ...

    African Journals Online (AJOL)

    During the past few years, extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and other species of Enterobacteriaceae have become a matter of great concern in human and veterinary medicine. Several studies in recent years documented the prevalence and occurrence of ESBLproducing ...

  1. Prevalence of Extended Spectrum Beta Lactamases (ESBL ...

    African Journals Online (AJOL)

    Resistance to broad spectrum β lactams, mediated by extended spectrum beta lactamase (ESβL) is an increasing problem worldwide. Production of these enzymes in clinical infections can result in treatment failure if one of the second or third generation cephalosporins is used. This study investigates the incidence of ESBL ...

  2. Schedule-extended synchronous dataflow graphs

    NARCIS (Netherlands)

    Damavandpeyma, M.; Stuijk, S.; Basten, T.; Geilen, M.; Corporaal, H.

    2013-01-01

    Synchronous dataflow graphs (SDFGs) are used extensively to model streaming applications. An SDFG can be extended with scheduling decisions, allowing SDFG analysis to obtain properties, such as throughput or buffer sizes for the scheduled graphs. Analysis times depend strongly on the size of the

  3. Short Communication: Production of extended spectrum beta ...

    African Journals Online (AJOL)

    Multidrug resistant strains of Klebsiella pneumoniae and Escherichia coli constitute a problem in many hospitals. The antibiotic susceptibility profile and the Production of Extended Spetrum Beta-Lactamase (ESBL) of the strains of Klebsiella pneumoniae and Escherichia coli were assessed by the Kirby-Bauer technique and ...

  4. Remarks on the extended characteristic uncertainty relations

    Energy Technology Data Exchange (ETDEWEB)

    Trifonov, D.A. [Institute for Nuclear Research, Sofia (Bulgaria)

    2001-03-09

    Three remarks concerning the form and the range of validity of the state-extended characteristic uncertainty relations (URs) are presented. A more general definition of the uncertainty matrix for pure and mixed states is suggested. Some new URs are provided. (author). Letter-to-the-editor.

  5. Extending the frontiers of employment regulation:

    African Journals Online (AJOL)

    UWC

    legislation will be needed in changing the complex of political, social and economic factors by which that inequality ..... workers is prevalent.57 While SD7 does not deal with discrimination, the EEA extends comprehensive ..... Employer indifference or resistance (active or passive) remains the single greatest barrier to more ...

  6. Experimental limits on antigravity in extended supergravity

    OpenAIRE

    Bellucci, S.; Faraoni, V.

    1995-01-01

    The available tests of the equivalence principle constrain the mass of the Higgs-like boson appearing in extended supergravity theories. We determine the constraints imposed by the present and future high precision experiments on the antigravity fields arising from $N=2,8$ supergravity.

  7. SENSITIVITY OF EXTENDED-SPECTRUM β - LACTAMASES ...

    African Journals Online (AJOL)

    DR. AMINU

    INTRODUCTION. Extended spectrum β-lactamases (ESBLs) are plasmid mediated enzymes that confer resistance to bacterial pathogens. The enzymes pose threat to current β- .... Brick-red precipitates at the bottom of the test tubes would denote the presence of reducing sugars in accordance with Brain and. Turner (1975).

  8. Horizant: gabapentin enacarbil extended-release tablets

    National Research Council Canada - National Science Library

    2011-01-01

    ... enacarbil extended-release tablets for the treatment of moderate-to-severe RLS in adults. Gabapentin enacarbil is not recommended for patients required to sleep during the daytime and remain awake at night. Efficacy. Gabapentin enacarbil efficacy was established in two 12-week clinical studies in adults diagnosed with RLS using the International Restless ...

  9. The extended arm of health professionals?

    DEFF Research Database (Denmark)

    Norlyk, Annelise; Martinsen, Bente

    2013-01-01

    responsibility for both the patient's well-being and for the patient's compliance with the daily regimen. Relatives were caught in a conflicting double role. They were the extended arm of the health professionals but also the caring, supporting partner. A tension arose between relatives' desire to help...

  10. Observation of TeV gamma ray extended sources with ARGO-YBJ

    Energy Technology Data Exchange (ETDEWEB)

    Vernetto, Silvia, E-mail: vernetto@to.infn.it

    2014-04-01

    More than 80% of TeV galactic gamma ray sources are spatially extended and many of them are still unidentified. The extended emission could be the result of cosmic ray interactions with the ambient medium which provides the target to produce TeV gamma rays. The sensitivity of ground based gamma ray detectors decreases for extended sources; shower detectors, due to their large field of view, are less affected with respect to Cherenkov telescopes. The ARGO-YBJ experiment (Yangbajing Cosmic Ray Laboratory, Tibet, China, 4300 m of altitude) is an air shower detector devoted to gamma ray astronomy at energies above a few hundred GeV, with an integrated sensitivity ranging from 0.24 to ∼1 Crab units, depending on the source declination. In this paper the observation of galactic extended sources with ARGO-YBJ during 5 years is reviewed.

  11. Extending data worth methods to select multiple observations targeting specific hydrological predictions of interest

    Science.gov (United States)

    Vilhelmsen, Troels N.; Ferré, Ty P. A.

    2016-04-01

    Hydrological models are often developed to forecasting future behavior in response due to natural or human induced changes in stresses affecting hydrologic systems. Commonly, these models are conceptualized and calibrated based on existing data/information about the hydrological conditions. However, most hydrologic systems lack sufficient data to constrain models with adequate certainty to support robust decision making. Therefore, a key element of a hydrologic study is the selection of additional data to improve model performance. Given the nature of hydrologic investigations, it is not practical to select data sequentially, i.e. to choose the next observation, collect it, refine the model, and then repeat the process. Rather, for timing and financial reasons, measurement campaigns include multiple wells or sampling points. There is a growing body of literature aimed at defining the expected data worth based on existing models. However, these are almost all limited to identifying single additional observations. In this study, we present a methodology for simultaneously selecting multiple potential new observations based on their expected ability to reduce the uncertainty of the forecasts of interest. This methodology is based on linear estimates of the predictive uncertainty, and it can be used to determine the optimal combinations of measurements (location and number) established to reduce the uncertainty of multiple predictions. The outcome of the analysis is an estimate of the optimal sampling locations; the optimal number of samples; as well as a probability map showing the locations within the investigated area that are most likely to provide useful information about the forecasting of interest.

  12. Lead toxicity in battery workers.

    Science.gov (United States)

    Qasim, Saeeda Fouzia; Baloch, Malka

    2014-11-01

    Lead poisoning is a medical condition caused by increased levels of lead in the body. Routes of exposure include contaminated air, water, soil, food and consumer products. Occupational exposure is the main cause of lead poisoning in the adults. Two cases of occupational lead poisoning in adult battery workers are hereby presented. Both male patients had initial non-specific symptoms of intermittent abdominal pain, fatigue and headache for 6 - 8 years. Later on, they developed psychosis, slurred speech, tremors of hands and initially underwent treatment for Parkinsonism and Wilson's disease because of clinical misdiagnosis. They were diagnosed with lead poisoning later and were treated successfully with lead chelator (CaNa2 EDTA).

  13. Collisional disruptions of rotating targets

    Science.gov (United States)

    Ševeček, Pavel; Broz, Miroslav

    2017-10-01

    Collisions are key processes in the evolution of the Main Asteroid Belt and impact events - i.e. target fragmentation and gravitational reaccumulation - are commonly studied by numerical simulations, namely by SPH and N-body methods. In our work, we extend the previous studies by assuming rotating targets and we study the dependence of resulting size-distributions on the pre-impact rotation of the target. To obtain stable initial conditions, it is also necessary to include the self-gravity already in the fragmentation phase which was previously neglected.To tackle this problem, we developed an SPH code, accelerated by SSE/AVX instruction sets and parallelized. The code solves the standard set of hydrodynamic equations, using the Tillotson equation of state, von Mises criterion for plastic yielding and scalar Grady-Kipp model for fragmentation. We further modified the velocity gradient by a correction tensor (Schäfer et al. 2007) to ensure a first-order conservation of the total angular momentum. As the intact target is a spherical body, its gravity can be approximated by a potential of a homogeneous sphere, making it easy to set up initial conditions. This is however infeasible for later stages of the disruption; to this point, we included the Barnes-Hut algorithm to compute the gravitational accelerations, using a multipole expansion of distant particles up to hexadecapole order.We tested the code carefully, comparing the results to our previous computations obtained with the SPH5 code (Benz and Asphaug 1994). Finally, we ran a set of simulations and we discuss the difference between the synthetic families created by rotating and static targets.

  14. Taking the Lead : Gender, Social Context and Preference to Lead

    NARCIS (Netherlands)

    Hong, A.P.C.I.; Schaafsma, J.; van der Wijst, P.J.

    Previous research has demonstrated that women tend to emerge as leaders less often than men. In the present study, we examined to what extent women's and men's preference to lead is influenced by social context. It was hypothesized that women have a less strong preference to lead than men in a

  15. Undue Lead Absorption and Lead Poisoning in Children: An Overview.

    Science.gov (United States)

    Lin-Fu, J. S.

    The toxic effects of lead, a useful metal ubiquitous in the human environment, have long been known. The occupational hazards of lead poisoning were well established by the early 19th century, but plumbism in children caused by paint ingestion was not reported until the turn of the century. Even in 1924, the child was said to live in a "lead…

  16. Leading Millennials Motivating And Leading Millennial Service Members

    Science.gov (United States)

    2016-02-20

    AIR WAR COLLEGE AIR UNIVERSITY LEADING MILLENNIALS MOTIVATING AND LEADING MILLENNIAL SERVICE MEMBERS by Joanne MacGregor, LTC...young adults ( Millennials ) serving in the U.S. military. These factors may not be readily apparent to Generation X and Y leaders. This paper argues...motivate, and discipline millennial subordinates while maximizing their talents through active and thoughtful professional development. 5

  17. Strategic Military Leaders - Leading Tomorrow

    Science.gov (United States)

    2008-02-29

    St ra te gy R es ea rc h Pr oj ec t STRATEGIC MILITARY LEADERS –LEADING TOMORROW BY COLONEL NG WAI KIT Singapore Army DISTRIBUTION...Strategic Military Leaders - Leading Tomorrow 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Ng Kit 5d. PROJECT...STRATEGIC MILITARY LEADERS – LEADING TOMORROW by Colonel Ng Wai Kit Singapore Army Dr. Leonard Wong Project

  18. Safe Leads and Lead Changes in Competitive Team Sports

    CERN Document Server

    Clauset, A; Redner, S

    2015-01-01

    We investigate the time evolution of lead changes within individual games of competitive team sports. Exploiting ideas from the theory of random walks, the number of lead changes within a single game follows a Gaussian distribution. We show that the probability that the last lead change and the time of the largest lead size are governed by the same arcsine law, a bimodal distribution that diverges at the start and at the end of the game. We also determine the probability that a given lead is "safe" as a function of its size $L$ and game time $t$. Our predictions generally agree with comprehensive data on more than 1.25 million scoring events in roughly 40,000 games across four professional or semi-professional team sports, and are more accurate than popular heuristics currently used in sports analytics.

  19. Safe leads and lead changes in competitive team sports

    Science.gov (United States)

    Clauset, A.; Kogan, M.; Redner, S.

    2015-06-01

    We investigate the time evolution of lead changes within individual games of competitive team sports. Exploiting ideas from the theory of random walks, the number of lead changes within a single game follows a Gaussian distribution. We show that the probability that the last lead change and the time of the largest lead size are governed by the same arcsine law, a bimodal distribution that diverges at the start and at the end of the game. We also determine the probability that a given lead is "safe" as a function of its size L and game time t . Our predictions generally agree with comprehensive data on more than 1.25 million scoring events in roughly 40 000 games across four professional or semiprofessional team sports, and are more accurate than popular heuristics currently used in sports analytics.

  20. Refractoriness of on extended movement to directional change.

    Science.gov (United States)

    Williams, L R

    1971-12-01

    An extended movement was used to compare the memory-drum and single-channel definitions of psychological refractoriness. The basic movement In response to the first signal (S1) was a forward lunge and a concurrent arm swing through a target string. The response to the second signal (S2) was a reversal of the original movement The interstimulus Interval (ISI) ranged from .10 - .70 sec. in .10-sec. steps. The hypothesis that refractoriness of the reversal movement would decrease as ISI shortened was confirmed by the fact that error frequencies decreased significantly and substantially with decreasing IS I. The availability of some residual capacity to deal with S2 during the refractory period was also indicated by an examination of the relationship between RT2 and the interval between S2 and RT1. This departure from the classical single-channel model shows some agreement with the neuromotor-programming theory.

  1. Mast cells: target and source of neuropeptides.

    Science.gov (United States)

    Tore, F; Tuncel, N

    2009-01-01

    Mast cells, originating from bone marrow pluripotential cells are generally populated near to strategic locations of mammalian body. They store a wide variety of biologically active molecules in their granules and also can de novo synthesize an additional spectrum of mediators, depending on their microenvironment, phenotype and status. Mast cells have numerous receptors that can trigger a wide spectrum of cellular responses, some of them which can be preprogrammed against specific pathogens. Mast cells secrete mediators, go under total degranulation, or degranulate only some of the specific granules with required content according to the environmental conditions, pathogens or signaling molecules binding to their receptors. Mast cells are functionally multi faceted cells. A single cell can behave such as an immune cell, an endocrine cell and even as a sensorial neuron. In this context, mast cells can significantly influence inflammation, tissue remodeling, host defense and homeostasis. Specifically the mast cells proximal to nerve fibers, contain, secrete and respond to, several neuropeptides, suggesting many potential functions for mast cells in health and disease. Mast cells are target cells for neuropeptides and, they have distinct profiles of responsiveness to these molecules. This extends the flexibility of neurogenic signaling pathways via reciprocity. Those neuropeptides have direct and indirect effects on mast cells such as inducing or suppression of degranulation, triggering, modulation or amplification of mediator content and release. The exploration of interactions of mast cells and neurons is a promising field of study which may bring treatments to several diseases. Since mast cells seem to form the major link between neurons and inflammation via neuropeptides, mast cell and mast cell mediator connection may lead to a better understanding of the autocrine, paracrine, and neuro-immune-endocrine systems in physiology and physiopathology. Therefore, mast

  2. High temperature superconductor current leads

    Science.gov (United States)

    Hull, John R.; Poeppel, Roger B.

    1995-01-01

    An electrical lead having one end for connection to an apparatus in a cryogenic environment and the other end for connection to an apparatus outside the cryogenic environment. The electrical lead includes a high temperature superconductor wire and an electrically conductive material distributed therein, where the conductive material is present at the one end of the lead at a concentration in the range of from 0 to about 3% by volume, and at the other end of the lead at a concentration of less than about 20% by volume. Various embodiments are shown for groups of high temperature superconductor wires and sheaths.

  3. Lead Poisoning in Wild Birds

    Science.gov (United States)

    Lahner, Lesanna L.; Franson, J. Christian

    2009-01-01

    Lead in its various forms has been used for thousands of years, originally in cooking utensils and glazes and more recently in many industrial and commercial applications. However, lead is a potent, potentially deadly toxin that damages many organs in the body and can affect all animals, including humans. By the mid 1990s, lead had been removed from many products in the United States, such as paint and fuel, but it is still commonly used in ammunition for hunting upland game birds, small mammals, and large game animals, as well as in fishing tackle. Wild birds, such as mourning doves, bald eagles, California condors, and loons, can die from the ingestion of one lead shot, bullet fragment, or sinker. According to a recent study on loon mortality, nearly half of adult loons found sick or dead during the breeding season in New England were diagnosed with confirmed or suspected lead poisoning from ingestion of lead fishing weights. Recent regulations in some states have restricted the use of lead ammunition on certain upland game hunting areas, as well as lead fishing tackle in areas frequented by common loons and trumpeter swans. A variety of alternatives to lead are available for use in hunting, shooting sports, and fishing activities.

  4. D-beta-hydroxybutyrate extends lifespan in C. elegans.

    Science.gov (United States)

    Edwards, Clare; Canfield, John; Copes, Neil; Rehan, Muhammad; Lipps, David; Bradshaw, Patrick C

    2014-08-01

    The ketone body beta-hydroxybutyrate (βHB) is a histone deacetylase (HDAC) inhibitor and has been shown to be protective in many disease models, but its effects on aging are not well studied. Therefore we determined the effect of βHB supplementation on the lifespan ofC. elegans nematodes. βHB supplementation extended mean lifespan by approximately 20%. RNAi knockdown of HDACs hda-2 or hda-3 also increased lifespan and further prevented βHB-mediated lifespan extension. βHB-mediated lifespan extension required the DAF-16/FOXO and SKN-1/Nrf longevity pathways, the sirtuin SIR-2.1, and the AMP kinase subunit AAK-2. βHB did not extend lifespan in a genetic model of dietary restriction indicating that βHB is likely functioning through a similar mechanism. βHB addition also upregulated ΒHB dehydrogenase activity and increased oxygen consumption in the worms. RNAi knockdown of F55E10.6, a short chain dehydrogenase and SKN-1 target gene, prevented the increased lifespan and βHB dehydrogenase activity induced by βHB addition, suggesting that F55E10.6 functions as an inducible βHB dehydrogenase. Furthermore, βHB supplementation increased worm thermotolerance and partially prevented glucose toxicity. It also delayed Alzheimer's amyloid-beta toxicity and decreased Parkinson's alpha-synuclein aggregation. The results indicate that D-βHB extends lifespan through inhibiting HDACs and through the activation of conserved stress response pathways.

  5. Pharmacokinetics and Pharmacodynamics of Extended Infusion Versus Short Infusion Piperacillin-Tazobactam in Critically Ill Patients Undergoing CRRT.

    Science.gov (United States)

    Shotwell, Matthew S; Nesbitt, Ross; Madonia, Phillip N; Gould, Edward R; Connor, Michael J; Salem, Charbel; Aduroja, Olufemi A; Amde, Milen; Groszek, Joseph J; Wei, Peilin; Taylor, Maria E; Tolwani, Ashita J; Fissell, William H

    2016-08-08

    Infection is the most common cause of death in severe AKI, but many patients receiving continuous RRT do not reach target antibiotic concentrations in plasma. Extended infusion of β-lactams is associated with improved target attainment in critically ill patients; thus, we hypothesized that extended infusion piperacillin-tazobactam would improve piperacillin target attainment compared with short infusion in patients receiving continuous RRT. We conducted an institutional review board-approved observational cohort study of piperacillin-tazobactam pharmacokinetics and pharmacodynamics in critically ill patients receiving continuous venovenous hemodialysis and hemodiafiltration at three tertiary care hospitals between 2007 and 2015. Antibiotic concentrations in blood and/or dialysate samples were measured by liquid chromatography, and one- and two-compartment pharmacokinetic models were fitted to the data using nonlinear mixed effects regression. Target attainment for piperacillin was defined as achieving four times the minimum inhibitory concentration of 16 μg/ml for >50% of the dosing cycle. The probabilities of target attainment for a range of doses, frequencies, and infusion durations were estimated using a Monte Carlo simulation method. Target attainment was also examined as a function of patient weight and continuous RRT effluent rate. Sixty-eight participants had data for analysis. Regardless of infusion duration, 6 g/d piperacillin was associated with ≤45% target attainment, whereas 12 g/d was associated with ≥95% target attainment. For 8 and 9 g/d, target attainment ranged between 68% and 85%. The probability of target attainment was lower at higher effluent rates and patient weights. For all doses, frequencies, patient weights, and continuous RRT effluent rates, extended infusion was associated with higher probability of target attainment compared with short infusion. Extended infusions of piperacillin-tazobactam are associated with greater probability

  6. Enhancing Assisted Living Technology with Extended Visual Memory

    Directory of Open Access Journals (Sweden)

    Joo-Hwee Lim

    2011-05-01

    Full Text Available Human vision and memory are powerful cognitive faculties by which we understand the world. However, they are imperfect and further, subject to deterioration with age. We propose a cognitive-inspired computational model, Extended Visual Memory (EVM, within the Computer-Aided Vision (CAV framework, to assist human in vision-related tasks. We exploit wearable sensors such as cameras, GPS and ambient computing facilities to complement a user's vision and memory functions by answering four types of queries central to visual activities, namely, Retrieval, Understanding, Navigation and Search. Learning of EVM relies on both frequency-based and attention-driven mechanisms to store view-based visual fragments (VF, which are abstracted into high-level visual schemas (VS, both in the visual long-term memory. During inference, the visual short-term memory plays a key role in visual similarity computation between input (or its schematic representation and VF, exemplified from VS when necessary. We present an assisted living scenario, termed EViMAL (Extended Visual Memory for Assisted Living, targeted at mild dementia patients to provide novel functions such as hazard-warning, visual reminder, object look-up and event review. We envisage EVM having the potential benefits in alleviating memory loss, improving recall precision and enhancing memory capacity through external support.

  7. Rescue of an extending capsulorrhexis by creating a midway tangential anterior capsular flap: a novel technique in 22 eyes.

    Science.gov (United States)

    Mohammadpour, Mehrdad

    2010-06-01

    To show how an extending capsulorrhexis can be rescued by a midway tangential capsular flap in order to achieve an uneventful phacoemulsification. Consecutive case series. Twenty-two eyes of 22 patients with extending capsulorrhexis treated at the Farabi Eye Hospital, Tehran. First, a tangential capsular opening was created on the border of the presumed continuous curvilinear capsulorrhexis just midway between the beginning of the capsulorrhexis and the edge of the extending capsulorrhexis, to make a tangential flap of the anterior capsule. Second, the centre of this new flap was grasped and pulled centripetally until the edges of the new flap joined the edges of the extending flap to complete the capsulorrhexis. The technique was successfully performed in all cases, leading to an uneventful phacoemulsification. Midway tangential capsular flap is a safe and effective technique to rescue an extending capsulorrhexis and leads to an uneventful phacoemulsification.

  8. Use of an Extended Kalman Filter

    Science.gov (United States)

    1990-09-01

    navigation radars available anywhere in the market. Those belonging to the FURUNO company are the most popular . This radar will be used on the present...Smugglers", Popular Communications, June 1990 4. Kourkoulis, D., Bearings Only Target Tracking-Maneuvering Target, Master’s Thesis, Naval Postgraduate...CA. 93943-5002 3. Jefatura de Educacion 1 Comandancia General de la Armada Av. Wollmer, San Bernardino CP.1011 Caracas, Venezuela. 4. Escuela Superior

  9. Studies on physical characteristics of spallation neutron target

    CERN Document Server

    Wan Jun Sheng; Xia Hai Hong; Zhang Li; Zhang Ying

    2002-01-01

    The spallation target of ADS was studied using DCM/CEM program. The simulation of the lead target of 0.6 m length and 0.2 m in diameter bombarded with 0.1 - 1.6 GeV proton beams was carried out. The neutron spectra, neutron fluence distribution over the lead target, energy deposition and neutron production in the lead target were studied. Some former experimental results can be explained very well with the calculated results. The simulation results agree very well with the former theoretical and experimental results

  10. Resistance to Antibiotics Mediated by Target Alterations

    Science.gov (United States)

    Spratt, Brian G.

    1994-04-01

    The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

  11. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano; David, Jean-Christophe; Leray, Sylvie; Letourneau, Alain; Michel-Sendis, Franco; Stankunas, Gediminas [CEA/IRFU, Gif-sur-Yvette (France); Berg, Klara; Filges, Uwe; Groeschel, Friedrich; Luethy, Markus; Scazzi, Selene; Tobler, Leonhard; Zanini, Luca [PSI, Villigen (Switzerland); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Gif-sur-Yvette (France); Guertin, Arnaud; Thiolliere, Nicolas [SUBATECH, Nantes (France); Konobeyev, Alexander Yu. [FZK/IRS, Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, St. Paul Lez Durance (France); Lemaire, Sebastien [CEA/DAM/DCSA/SCGA, Bruyeres-le-Chatel (France)

    2008-07-01

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). The project is an important step in the road-map towards the demonstration of the Accelerator Driven System (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment. (authors)

  12. Neutronic characterization of the MEGAPIE target

    Energy Technology Data Exchange (ETDEWEB)

    Panebianco, Stefano [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France)], E-mail: Stefano.panebianco@cea.fr; Berg, Klara [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); David, Jean-Christophe [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Eid, Mohamed [CEA/DEN/DM2S/SERMA, Centre de Saclay, F-91194 Gif-sur-Yvette (France); Filges, Uwe; Groeschel, Friedrich [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Guertin, Arnaud [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Konobeyev, Alexander Yu [Forschungszentrum Karlsruhe, IRS, D-76021 Karlsruhe (Germany); Latge, Christian [CEA/DEN/DTN/DIR, Centre de Cadarache, F-13108 Saint-Paul-lez-Durance (France); Lemaire, Sebastien [CEA, DAM Ile de France, F-91297 Bruyeres le Chatel (France); Leray, Sylvie; Letourneau, Alain [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Luethy, Markus [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Michel-Sendis, Franco [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Scazzi, Selene [Paul Scherrer Institut, CH-5232 Villigen (Switzerland); Stankunas, Gediminas [CEA, Irfu, Centre de Saclay, F-91191 Gif-sur-Yvette (France); Thiolliere, Nicolas [SUBATECH, Ecole des Mines, F-44307 Nantes (France); Tobler, Leonhard; Zanini, Luca [Paul Scherrer Institut, CH-5232 Villigen (Switzerland)

    2009-04-15

    The MEGAPIE project aimed to design, build and operate a liquid metal spallation neutron target of about 1 MW beam power in the SINQ facility at the Paul Scherrer Institut (Villigen, Switzerland). This project is an important step in the roadmap towards the demonstration of the accelerator driven system (ADS) concept and high power liquid metal targets in general. Following the design phase, an experimental program was defined to provide a complete characterization of the facility by performing a 'mapping' of the neutron flux at different points, from the center of the target to the beam lines. The neutronic performance of the target was studied using different experimental techniques with the goals of validating the Monte Carlo codes used in the design of the target; additionally, the performance was compared with the solid lead targets used before and after the MEGAPIE experiment.

  13. Lead Exposure: Weighing Down IQ.

    Science.gov (United States)

    Science News, 1979

    1979-01-01

    Researchers at Harvard Medical School and the Children's Hospital Medical Center in Boston have found that children exposed to high but well below identified toxic levels of lead show significantly lower IQ levels and a higher incidence of undesirable classroom behavior than do children with low levels of lead exposure. (Author/BB)

  14. Lead Exposure and Child Behavior.

    Science.gov (United States)

    Sciarillo, William G.; And Others

    1992-01-01

    Provides evidence of detrimental effects of lead exposure on child behavior at levels typical of present-day exposure. Behavior and lead-blood level were examined for 201 African-American children aged 2 through 5 years. A standardized parent report measure and consideration of maternal morale are features of study methodology. (SLD)

  15. Lead poisoning from souvenir earthenware.

    Science.gov (United States)

    Hellström-Lindberg, Eva; Björklund, Andreas; Karlson-Stiber, Christine; Harper, Pauline; Seldén, Anders I

    2006-02-01

    A case of massive lead poisoning from juice contained in a Greek earthenware jug as well as six satellite cases of high lead exposure of similar origin is reported. The intoxicated patient was successfully treated with dimercaptosuccinic acid. Ceramic producers should adhere to the longstanding European legislation.

  16. Lead-free primary explosives

    Science.gov (United States)

    Huynh, My Hang V.

    2010-06-22

    Lead-free primary explosives of the formula (cat).sub.Y[M.sup.II(T).sub.X(H.sub.2O).sub.6-X].sub.Z, where T is 5-nitrotetrazolate, and syntheses thereof are described. Substantially stoichiometric equivalents of the reactants lead to high yields of pure compositions thereby avoiding dangerous purification steps.

  17. Leading change: a concept analysis.

    Science.gov (United States)

    Nelson-Brantley, Heather V; Ford, Debra J

    2017-04-01

    To report an analysis of the concept of leading change. Nurses have been called to lead change to advance the health of individuals, populations, and systems. Conceptual clarity about leading change in the context of nursing and healthcare systems provides an empirical direction for future research and theory development that can advance the science of leadership studies in nursing. Concept analysis. CINAHL, PubMed, PsycINFO, Psychology and Behavioral Sciences Collection, Health Business Elite and Business Source Premier databases were searched using the terms: leading change, transformation, reform, leadership and change. Literature published in English from 2001 - 2015 in the fields of nursing, medicine, organizational studies, business, education, psychology or sociology were included. Walker and Avant's method was used to identify descriptions, antecedents, consequences and empirical referents of the concept. Model, related and contrary cases were developed. Five defining attributes of leading change were identified: (a) individual and collective leadership; (b) operational support; (c) fostering relationships; (d) organizational learning; and (e) balance. Antecedents were external or internal driving forces and organizational readiness. The consequences of leading change included improved organizational performance and outcomes and new organizational culture and values. A theoretical definition and conceptual model of leading change were developed. Future studies that use and test the model may contribute to the refinement of a middle-range theory to advance nursing leadership research and education. From this, empirically derived interventions that prepare and enable nurses to lead change to advance health may be realized. © 2016 John Wiley & Sons Ltd.

  18. Blood Test: Lead (For Parents)

    Science.gov (United States)

    ... Important? Top 10 Homework Tips Raising Confident Kids Blood Test: Lead KidsHealth > For Parents > Blood Test: Lead Print A A A What's in this ... locate a vein Helping Your Child Having a blood test is relatively painless. Still, many children are afraid ...

  19. Proof of the extended Bloch-Messiah theorem in the thermal Hartree-Fock-Bogoliubov theory

    Science.gov (United States)

    Tanabe, K.; Sugawara-Tanabe, K.

    1990-09-01

    It is shown that an application of the thermo field dynamics (TFD) to the thermal Hartree-Fock-Bogoliubov (THFB) theory leads to the extended form of the Bloch-Messiah theorem for the finite temperature formalism. The generalized density matrix defined on the enlarged operator space including tilded into account the thermal fluctuation of fermion number for the system under consideration.

  20. Understanding how Supernova Light Curves are Affected by the Density Profiles of Extended Material

    Science.gov (United States)

    Mühleisen, Marc; Piro, Anthony

    2017-01-01

    The light curve of a supernova can provide important clues about the structure of the exploding progenitor. When extended material is present, shock cooling of this material can lead to a prominent early peak distinct from the main radioactive nickel peak, as seen in some Type IIb supernovae. We explore whether the density profile of the extended material plays a role in shaping these light curves. We perform a series of numerical supernova simulations with a range of extended mass configurations. We find that steeper density profiles for the extended material shrink the width and decrease the luminosity of the early peak of the light curve. We conclude that light curves with a distinct, early peak do not imply a particular structure, but rather may arise from several distinct mass configurations. This places limits on how much can be inferred about the progenitor's structure from its light curve.

  1. Adaptive Waveform Design for Cognitive Radar in Multiple Targets Situations

    Directory of Open Access Journals (Sweden)

    Xiaowen Zhang

    2018-02-01

    Full Text Available In this paper, the problem of cognitive radar (CR waveform optimization design for target detection and estimation in multiple extended targets situations is investigated. This problem is analyzed in signal-dependent interference, as well as additive channel noise for extended targets with unknown target impulse response (TIR. To address this problem, an improved algorithm is employed for target detection by maximizing the detection probability of the received echo on the promise of ensuring the TIR estimation precision. In this algorithm, an additional weight vector is introduced to achieve a trade-off among different targets. Both the estimate of TIR and transmit waveform can be updated at each step based on the previous step. Under the same constraint on waveform energy and bandwidth, the information theoretical approach is also considered. In addition, the relationship between the waveforms that are designed based on the two criteria is discussed. Unlike most existing works that only consider single target with temporally correlated characteristics, waveform design for multiple extended targets is considered in this method. Simulation results demonstrate that compared with linear frequency modulated (LFM signal, waveforms designed based on maximum detection probability and maximum mutual information (MI criteria can make radar echoes contain more multiple-target information and improve radar performance as a result.

  2. Thermodynamic Products in the Extended Phase Space

    CERN Document Server

    Pradhan, Parthapratim

    2016-01-01

    We have examined the thermodynamic properties of spherically symmetric charged-AdS black hole, charged AdS BH surrounded by quintessence and charged AdS BH in $f(R)$ gravity in the extended phase-space. Where the cosmological constant should be treated as thermodynamic pressure and its conjugate parameter as thermodynamic volume. Then they should behave as a analog of Van der Waal like systems. In the extended phase space we have calculated the \\emph{entropy product} and \\emph{thermodynamic volume product} of all horizons. The mass(or enthalpy) independent nature of the said products signals they are "universal" quantities. Various types of pictorial diagram of the specific heat is given. The divergence of the specific heat indicates that the second order phase transition occurs under certain condition.

  3. Optimizing Extender Code for NCSX Analyses

    Energy Technology Data Exchange (ETDEWEB)

    M. Richman, S. Ethier, and N. Pomphrey

    2008-01-22

    Extender is a parallel C++ code for calculating the magnetic field in the vacuum region of a stellarator. The code was optimized for speed and augmented with tools to maintain a specialized NetCDF database. Two parallel algorithms were examined. An even-block work-distribution scheme was comparable in performance to a master-slave scheme. Large speedup factors were achieved by representing the plasma surface with a spline rather than Fourier series. The accuracy of this representation and the resulting calculations relied on the density of the spline mesh. The Fortran 90 module db access was written to make it easy to store Extender output in a manageable database. New or updated data can be added to existing databases. A generalized PBS job script handles the generation of a database from scratch

  4. Junction conditions in extended Teleparallel gravities

    Energy Technology Data Exchange (ETDEWEB)

    De la Cruz-Dombriz, Álvaro [Departamento de Física Teórica I, Ciudad Universitaria, Universidad Complutense de Madrid, E-28040 Madrid (Spain); Dunsby, Peter K.S.; Sáez-Gómez, Diego, E-mail: dombriz@fis.ucm.es, E-mail: peter.dunsby@uct.ac.za, E-mail: diego.saezgomez@uct.ac.za [Astrophysics, Cosmology and Gravity Centre (ACGC), Department of Mathematics and Applied Mathematics, University of Cape Town, Rondebosch 7701, Cape Town (South Africa)

    2014-12-01

    In the context of extended Teleparallel gravity theories, we address the issue of junction conditions required to guarantee the correct matching of different regions of spacetime. In the absence of shells/branes, these conditions turn out to be more restrictive than their counterparts in General Relativity as in other extended theories of gravity. In fact, the general junction conditions on the matching hypersurfaces depend on the underlying theory and a new condition on the induced tetrads in order to avoid delta-like distributions in the field equations. This result imposes strict consequences on the viability of standard solutions such as the Einstein-Straus-like construction. We find that the continuity of the scalar torsion is required in order to recover the usual General Relativity results.

  5. Application of electron closures in extended MHD

    Science.gov (United States)

    Held, Eric; Adair, Brett; Taylor, Trevor

    2017-10-01

    Rigorous closure of the extended MHD equations in plasma fluid codes includes the effects of electron heat conduction along perturbed magnetic fields and contributions of the electron collisional friction and stress to the extended Ohms law. In this work we discuss application of a continuum numerical solution to the Chapman-Enskog-like electron drift kinetic equation using the NIMROD code. The implementation is a tightly-coupled fluid/kinetic system that carefully addresses time-centering in the advance of the fluid variables with their kinetically-computed closures. Comparisons of spatial accuracy, computational efficiency and required velocity space resolution are presented for applications involving growing magnetic islands in cylindrical and toroidal geometry. The reduction in parallel heat conduction due to particle trapping in toroidal geometry is emphasized. Work supported by DOE under Grant Nos. DE-FC02-08ER54973 and DE-FG02-04ER54746.

  6. Extending applicability of bimetric theory: chameleon bigravity

    Science.gov (United States)

    De Felice, Antonio; Mukohyama, Shinji; Uzan, Jean-Philippe

    2018-02-01

    This article extends bimetric formulations of massive gravity to make the mass of the graviton to depend on its environment. This minimal extension offers a novel way to reconcile massive gravity with local tests of general relativity without invoking the Vainshtein mechanism. On cosmological scales, it is argued that the model is stable and that it circumvents the Higuchi bound, hence relaxing the constraints on the parameter space. Moreover, with this extension the strong coupling scale is also environmentally dependent in such a way that it is kept sufficiently higher than the expansion rate all the way up to the very early universe, while the present graviton mass is low enough to be phenomenologically interesting. In this sense the extended bigravity theory serves as a partial UV completion of the standard bigravity theory. This extension is very generic and robust and a simple specific example is described.

  7. Extended range interferometry based on wavefront shaping

    Science.gov (United States)

    Szczupak, M. L.; Salbut, L.

    2007-09-01

    There are many cases when absolute measurements of objects with large height differences or height discontinuity is needed. These measurements can not be covered by classical interferometry since the range of non-ambiguity is limited to half the optical wavelength. Several techniques have been already developed for extending of non-ambiguity range. However most of them is based on multi-wavelength methods which demands expensive light sources and special environment conditions. In this work the new interferometric technique for absolute measurements of large steps discontinuities is proposed. Variable wavefront of the illuminating beam and special procedure for calibration of the measurement volume are used for extending of the measurement range without using multispectral sources. Additionally, calibration of the measurement area simplifies fringe processing and quicken measures. Theoretical analysis of this technique, its numerical simulations and experimental verification are presented and discussed.

  8. Simulation methods with extended stability for stiff biochemical Kinetics

    Directory of Open Access Journals (Sweden)

    Rué Pau

    2010-08-01

    Full Text Available Abstract Background With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (biochemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA. The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes. Conclusions The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (biochemical systems.

  9. Lepton flavor violation in an extended MSSM

    CERN Document Server

    Espinosa-Castañeda, R.; Gómez-Bock, M.; Mondragón, M.

    2016-01-01

    In this work we explore a lepton flavor violation effect induced at one loop for a flavor structure in an extended minimal standard supersymmetric model, considering an ansatz for the trilinear term. In particular we find a finite expression which will show the impact of this phenomena in the $h\\to \\mu \\tau$ decay, produced by a mixing in the trilinear coupling of the soft supersymmetric Lagrangian.

  10. Extended Deterministic Mean-Field Games

    KAUST Repository

    Gomes, Diogo A.

    2016-04-21

    In this paper, we consider mean-field games where the interaction of each player with the mean field takes into account not only the states of the players but also their collective behavior. To do so, we develop a random variable framework that is particularly convenient for these problems. We prove an existence result for extended mean-field games and establish uniqueness conditions. In the last section, we consider the Master Equation and discuss properties of its solutions.

  11. Deterministic automata for extended regular expressions

    Directory of Open Access Journals (Sweden)

    Syzdykov Mirzakhmet

    2017-12-01

    Full Text Available In this work we present the algorithms to produce deterministic finite automaton (DFA for extended operators in regular expressions like intersection, subtraction and complement. The method like “overriding” of the source NFA(NFA not defined with subset construction rules is used. The past work described only the algorithm for AND-operator (or intersection of regular languages; in this paper the construction for the MINUS-operator (and complement is shown.

  12. Interacting Holstein and extended-Holstein bipolarons

    OpenAIRE

    Chakraborty, Monodeep; Tezuka, Masaki; Min, B. I.

    2013-01-01

    Employing the recently developed self-consistent variational basis generation scheme, we have investigated the bipolaron-bipolaron interaction within the purview of Holstein-Hubbard and the extended-Holstein-Hubbard (F2H) model on a discrete one-dimensional lattice. The density-matrix renormalization group (DMRG) method has also been used for the Holstein-Hubbard model. We have shown that there exists no bipolaron-bipolaron attraction in the Holstein-Hubbard model. In contrast, we have obtain...

  13. The renewable tradition (extended play remix

    Directory of Open Access Journals (Sweden)

    Mark Amerika

    2009-12-01

    Full Text Available Drawing from a network of appropriation artists, process philosophers, performance poets, pla(ygiarists, and other remix provocateurs, this experimental artist essay investigates the act of remixologically inhabiting the body language of others and, in the process, devises an aesthetic theory that situates the contemporary artist as a "postproduction medium" whose methodologies further extend avant-garde practice into the 21st century.

  14. Extending DUNE: The dune-xt modules

    OpenAIRE

    Leibner, Tobias; Milk, René; Schindler, Felix

    2016-01-01

    We present our effort to extend and complement the core modules of the Distributed and Unified Numerics Environment DUNE (http://dune-project.org) by a well tested and structured collection of utilities and concepts. We describe key elements of our four modules dune-xt-common, dune-xt-grid, dune-xt-la and dune-xt-functions, which aim at further enabling the programming of generic algorithms within DUNE as well as adding an extra layer of usability and convenience.

  15. FRW Cosmology with the Extended Chaplygin Gas

    Directory of Open Access Journals (Sweden)

    B. Pourhassan

    2014-01-01

    Full Text Available We propose extended Chaplygin gas equation of state for which it recovers barotropic fluid with quadratic equation of state. We use numerical method to investigate the behavior of some cosmological parameters such as scale factor, Hubble expansion parameter, energy density, and deceleration parameter. We also discuss the resulting effective equation of state parameter. Using density perturbations we investigate the stability of the theory.

  16. Socially extended intentions-in-action

    DEFF Research Database (Denmark)

    Blomberg, Olle

    2011-01-01

    . Tollefsen’s account is specifically constructed to account for the joint activities of infants and toddlers who lack the capacity to think of others as planning agents and grasp their plan-like intentions (a capacity required by Michael Bratman’s (1992, 1993, 2009a, 2009b) influential account of joint...... activity). At the end of the paper, I raise some doubts regarding the extent to which infants and toddlers have socially extended intentions-in-action....

  17. Fusion Rules for Extended Current Algebras

    OpenAIRE

    Baver, Ernest; Gepner, Doron

    1996-01-01

    The initial classification of fusion rules have shown that rational conformal field theory is very limited. In this paper we study the fusion rules of extend ed current algebras. Explicit formulas are given for the S matrix and the fusion rules, based on the full splitting of the fixed point fields. We find that in s ome cases sensible fusion rules are obtained, while in others this procedure lea ds to fractional fusion constants.

  18. Biosorption of lead phosphates by lead-tolerant bacteria as a mechanism for lead immobilization.

    Science.gov (United States)

    Rodríguez-Sánchez, Viridiana; Guzmán-Moreno, Jesús; Rodríguez-González, Vicente; Flores-de la Torre, Juan Armando; Ramírez-Santoyo, Rosa María; Vidales-Rodríguez, Luz Elena

    2017-08-01

    The study of metal-tolerant bacteria is important for bioremediation of contaminated environments and development of green technologies for material synthesis due to their potential to transform toxic metal ions into less toxic compounds by mechanisms such as reduction, oxidation and/or sequestration. In this study, we report the isolation of seven lead-tolerant bacteria from a metal-contaminated site at Zacatecas, México. The bacteria were identified as members of the Staphylococcus and Bacillus genera by microscopic, biochemical and 16S rDNA analyses. Minimal inhibitory concentration of these isolates was established between 4.5 and 7.0 mM of Pb(NO3)2 in solid and 1.0-4.0 mM of Pb(NO3)2 in liquid media. A quantitative analysis of the lead associated to bacterial biomass in growing cultures, revealed that the percentage of lead associated to biomass was between 1 and 37% in the PbT isolates. A mechanism of complexation/biosorption of lead ions as inorganic phosphates (lead hydroxyapatite and pyromorphite) in bacterial biomass, was determined by Fourier transform infrared spectroscopy and X-ray diffraction analyses. Thus, the ability of the lead-tolerant isolates to transform lead ions into stable and highly insoluble lead minerals make them potentially useful for immobilization of lead in mining waste.

  19. Experimental model of lead nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Khalil-Manesh, F.; Gonick, H.C. (Cedars-Sinai Medical Center, Los Angeles, CA (United States)); Cohen, A. (UCLA-Harbor General Hospital, Torrance, CA (United States)); Bergamaschi, E.; Mutti, A. (Univ. of Parma (Italy))

    1992-06-01

    Male Sprague-Dawley rats were exposed to high-dose (0.5%) lead acetate for periods ranging from 1 to 9 months; then lead exposure was discontinued, and animals were sacrificed after 12 months. Two additional groups of low-dose (0.01%) and high-dose (0.5%) rats were exposed to lead for 6 months, then lead was discontinued and the rats were treated with three 5-day courses of 0.5% DMSA (dimercaptosuccinic acid) over the next 6 months. Low-dose lead-treated rats showed no significant pathological changes with or without DMSA treatment, but exhibited a significant increase in GFR after DMSA. High-dose lead-treated animals showed no functional or pathological changes when lead exposure was discontinued after 1 month. However, when duration of exposure was 6 or 9 months, GFR was decreased and serum creatinine and urea nitrogen were increased as compared to controls. Tubulointerstitial disease was severe. Administration of DMSA resulted in an improvement in GFR and a decrease in albuminuria, together with a reduction in size and number of nuclear inclusion bodies in proximal tubules. However, tubulointerstitial scarring was only minimally reduced. It may be concluded that, except for brief initial exposure, discontinuation of high-dose lead exposure fails to reverse lead-induced renal damage. Treatment with the chelator, DMSA, improves renal function but has less effect on pathological alterations. As GFR improved after DMSA treatment in both low-dose and high-dose lead-treated rats, irrespective of the degree of pathological alterations, it may be concluded that the DMSA effect is most likely mediated by hemodynamic changes.

  20. Thermodynamic volume and the extended Smarr relation

    Science.gov (United States)

    Hyun, Seungjoon; Jeong, Jaehoon; Park, Sang-A.; Yi, Sang-Heon

    2017-04-01

    We continue to explore the scaling transformation in the reduced action formalism of gravity models. As an extension of our construction, we consider the extended forms of the Smarr relation for various black holes, adopting the cosmological constant as the bulk pressure as in some literatures on black holes. Firstly, by using the quasi-local formalism for charges, we show that, in a general theory of gravity, the volume in the black hole thermodynamics could be defined as the thermodynamic conjugate variable to the bulk pressure in such a way that the first law can be extended consistently. This, so called, thermodynamic volume can be expressed explicitly in terms of the metric and field variables. Then, by using the scaling transformation allowed in the reduced action formulation, we obtain the extended Smarr relation involving the bulk pressure and the thermodynamic volume. In our approach, we do not resort to Euler's homogeneous scaling of charges while incorporating the would-be hairy contribution without any difficulty.