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Sample records for gross-pitaevskii gp equation

  1. Numerical simulation for the Gross-Pitaevskii equation based on the lattice Boltzmann method

    Science.gov (United States)

    Wang, Huimin

    2017-09-01

    A lattice Boltzmann model for the Gross-Pitaevskii equation is proposed in this paper. Some numerical tests for one- and two-dimensional Gross-Pitaevskii equation have been conducted. The waves of the Gross-Pitaevskii equation are simulated. Numerical results show that the lattice Boltzmann method is an effective method for the wave of the Gross-Pitaevskii equation.

  2. Hydrodynamical form for the one-dimensional Gross-Pitaevskii equation

    Directory of Open Access Journals (Sweden)

    Haidar Mohamad

    2014-06-01

    Full Text Available We establish a well-posedness result for the hydrodynamical form (HGP of the one dimensional Gross-Pitaevskii equation (GP via the classical form of this equation. The result established in this way proves that (HGP is locally well-posed since the solution of (GP can vanished at some $t\

  3. Kinetic Thomas-Fermi solutions of the Gross-Pitaevskii equation

    OpenAIRE

    Ölschläger, M.; Wirth, G.; Smith, C. Morais; Hemmerich, A.

    2010-01-01

    Approximate solutions of the Gross-Pitaevskii (GP) equation, obtained upon neglection of the kinetic energy, are well known as Thomas-Fermi solutions. They are characterized by the compensation of the local potential by the collisional energy. In this article we consider exact solutions of the GP-equation with this property and definite values of the kinetic energy, which suggests the term "kinetic Thomas-Fermi" (KTF) solutions. We point out that a large class of light-shift potentials gives ...

  4. Optimal Bilinear Control of Gross--Pitaevskii Equations

    KAUST Repository

    Hintermüller, Michael

    2013-01-01

    A mathematical framework for optimal bilinear control of nonlinear Schrödinger equations of Gross--Pitaevskii type arising in the description of Bose--Einstein condensates is presented. The obtained results generalize earlier efforts found in the literature in several aspects. In particular, the cost induced by the physical workload over the control process is taken into account rather than the often used L^2- or H^1-norms for the cost of the control action. Well-posedness of the problem and existence of an optimal control are proved. In addition, the first order optimality system is rigorously derived. Also a numerical solution method is proposed, which is based on a Newton-type iteration, and used to solve several coherent quantum control problems.

  5. Envelope Periodic Solutions to One-Dimensional Gross-Pitaevskii Equation in Bose-Einstein Condensation

    Institute of Scientific and Technical Information of China (English)

    LIU Shi-Kuo; GAO Bin; FU Zun-Tao; LIU Shi-Da

    2009-01-01

    In this paper, applying the dependent and independent variables transformations as well as the Jacobi elliptic function expansion method, the envelope periodic solutions to one-dimensional Gross-Pitaevskii equation in Bose-Einstein condensates are obtained.

  6. Propagating and annihilating vortex dipoles in the Gross-Pitaevskii equation

    CERN Document Server

    Rorai, Cecilia; Fisher, Michael E

    2013-01-01

    Quantum vortex dynamics in Bose-Einstein condensates or superfluid helium can be informatively described by the Gross-Pitaevskii (GP) equation. Various approximate analytical formulae for a single stationary vortex are recalled and their shortcomings demonstrated. Significantly more accurate two-point [2/2] and [3/3] Pade' approximants for stationary vortex profiles are presented. Two straight, singly quantized, antiparallel vortices, located at a distance d apart, form a vortex dipole, which, in the GP model, can either annihilate or propagate indefinitely as a `solitary wave'. We show, through calculations performed in a periodic domain, that the details and types of behavior displayed by vortex dipoles depend strongly on the initial conditions rather than only on the separation distance (as has been previously claimed). It is found, indeed, that the choice of the initial two-vortex profile (i.e., the modulus of the `effective wave function'), strongly affects the vortex trajectories and the time scale of t...

  7. Long time dynamics near the symmetry breaking bifurcation for nonlinear Schr\\"odinger/Gross-Pitaevskii Equations

    CERN Document Server

    Marzuola, Jeremy L

    2009-01-01

    We consider a class nonlinear Schr\\"odinger / Gross-Pitaevskii equations (NLS/GP) with a focusing (attractive) nonlinear potential and symmetric double well linear potential. NLS/GP plays a central role in the modeling of nonlinear optical and mean-field quantum many-body phenomena. It is known that there is a critical $L^2$ norm (optical power / particle number) at which there is a symmetry breaking bifurcation of the ground state. We study the rich dynamical behavior near the symmetry breaking point. The source of this behavior in the full Hamiltonian PDE is related to the dynamics of a finite-dimensional Hamiltonian reduction. We derive this reduction, analyze a part of its phase space and prove a {\\it shadowing theorem} on the persistence of solutions, with oscillating mass-transport between wells, on very long, but finite, time scales within the full NLS/GP. The infinite time dynamics for NLS/GP are expected to depart, from the finite dimensional reduction, due to resonant coupling of discrete and contin...

  8. Remarks on the Blow-Up Solutions for the Critical Gross-Pitaevskii Equation

    Directory of Open Access Journals (Sweden)

    Xiaoguang Li

    2013-01-01

    Full Text Available This paper is concerned with the blow-up solutions of the critical Gross-Pitaevskii equation, which models the Bose-Einstein condensate. The existence and qualitative properties of the minimal blow-up solutions are obtained.

  9. An Efficient Compact Finite Difference Method for the Solution of the Gross-Pitaevskii Equation

    Directory of Open Access Journals (Sweden)

    Rongpei Zhang

    2015-01-01

    matrices. The CFDM-AIF method is implemented to investigate the ground and first excited state solutions of the Gross-Pitaevskii equation in two-dimensional (2D and three-dimensional (3D Bose-Einstein condensates (BECs. Numerical results are presented to demonstrate the validity, accuracy, and efficiency of the CFDM-AIF method.

  10. Kinetic Thomas-Fermi solutions of the Gross-Pitaevskii equation

    Science.gov (United States)

    Ölschläger, M.; Wirth, G.; Smith, C. Morais; Hemmerich, A.

    2009-04-01

    Approximate solutions of the Gross-Pitaevskii (GP) equation, obtained upon neglection of the kinetic energy, are well known as Thomas-Fermi solutions. They are characterized by the compensation of the local potential by the collisional energy. In this article we consider exact solutions of the GP-equation with this property and definite values of the kinetic energy, which suggests the term "kinetic Thomas-Fermi" (KTF) solutions. Despite their formal simplicity, KTF-solutions can possess complex current density fields with unconventional topology. We point out that a large class of light-shift potentials gives rise to KTF-solutions. As elementary examples, we consider one-dimensional and two-dimensional optical lattice scenarios, obtained by means of the superposition of two, three and four laser beams, and discuss the stability properties of the corresponding KTF-solutions. A general method is proposed to excite two-dimensional KTF-solutions in experiments by means of time-modulated light-shift potentials.

  11. Efficient and accurate methods for solving the time-dependent spin-2 Gross-Pitaevskii equation

    CERN Document Server

    Symes, L M

    2016-01-01

    We develop numerical methods for solving the spin-2 Gross-Pitaevskii equation. The basis of our work is a two-way splitting of this evolution equation that leads to two exactly solvable subsystems. Utilizing second-order and fourth-order composition schemes we realize two fully symplectic integration algorithms, the first such algorithms for evolving spin-2 condensates. We demonstrate the accuracy of these algorithms against other methods on application to an exact continuous wave solution that we derive.

  12. Special solutions of the Riccati equation with applications to the Gross-Pitaevskii nonlinear PDE

    Directory of Open Access Journals (Sweden)

    Anas Al Bastami

    2010-05-01

    Full Text Available A method for finding solutions of the Riccati differential equation $y' = P(x + Q(xy + R(xy^2$ is introduced. Provided that certain relations exist between the coefficient $P(x$, $Q(x$ and $R(x$, the above equation can be solved in closed form. We determine the required relations and find the general solutions to the aforementioned equation. The method is then applied to the Riccati equation arising in the solution of the multidimensional Gross-Pitaevskii equation of Bose-Einstein condensates by the F-expansion and the balance principle techniques.

  13. Riccati generalization of self-similar solutions of nonautonomous Gross-Pitaevskii equation

    Science.gov (United States)

    Panigrahi, P. K.; Gupta, Rama; Goyal, Amit; Kumar, C. N.

    2013-07-01

    We present a systematic analytical approach to construct a family of self-similar waves, related through a free parameter, in quasi one-dimension Gross-Pitaevskii equation with time-varying parameters. This approach enables us to control the dynamics of dark and bright similaritons, and first- and second- order self-similar rogue waves in Bose-Einstein condensate through the modulation of time dependent trapping potential. The analysis is done for the sech2- type time-varying quadratic trapping potential for two different choices of linear potential.

  14. CUDA programs for solving the time-dependent dipolar Gross-Pitaevskii equation in an anisotropic trap

    Science.gov (United States)

    Lončar, Vladimir; Balaž, Antun; Bogojević, Aleksandar; Škrbić, Srdjan; Muruganandam, Paulsamy; Adhikari, Sadhan K.

    2016-03-01

    In this paper we present new versions of previously published numerical programs for solving the dipolar Gross-Pitaevskii (GP) equation including the contact interaction in two and three spatial dimensions in imaginary and in real time, yielding both stationary and non-stationary solutions. New versions of programs were developed using CUDA toolkit and can make use of Nvidia GPU devices. The algorithm used is the same split-step semi-implicit Crank-Nicolson method as in the previous version (Kishor Kumar et al., 2015), which is here implemented as a series of CUDA kernels that compute the solution on the GPU. In addition, the Fast Fourier Transform (FFT) library used in the previous version is replaced by cuFFT library, which works on CUDA-enabled GPUs. We present speedup test results obtained using new versions of programs and demonstrate an average speedup of 12-25, depending on the program and input size.

  15. A finite-element toolbox for the stationary Gross-Pitaevskii equation with rotation

    Science.gov (United States)

    Vergez, Guillaume; Danaila, Ionut; Auliac, Sylvain; Hecht, Frédéric

    2016-12-01

    We present a new numerical system using classical finite elements with mesh adaptivity for computing stationary solutions of the Gross-Pitaevskii equation. The programs are written as a toolbox for FreeFem++ (www.freefem.org), a free finite-element software available for all existing operating systems. This offers the advantage to hide all technical issues related to the implementation of the finite element method, allowing to easily code various numerical algorithms. Two robust and optimized numerical methods were implemented to minimize the Gross-Pitaevskii energy: a steepest descent method based on Sobolev gradients and a minimization algorithm based on the state-of-the-art optimization library Ipopt. For both methods, mesh adaptivity strategies are used to reduce the computational time and increase the local spatial accuracy when vortices are present. Different run cases are made available for 2D and 3D configurations of Bose-Einstein condensates in rotation. An optional graphical user interface is also provided, allowing to easily run predefined cases or with user-defined parameter files. We also provide several post-processing tools (like the identification of quantized vortices) that could help in extracting physical features from the simulations. The toolbox is extremely versatile and can be easily adapted to deal with different physical models.

  16. Evolution of a superfluid vortex filament tangle driven by the Gross-Pitaevskii equation

    CERN Document Server

    Villois, Alberto; Krstulovic, Giorgio

    2016-01-01

    The development and decay of a turbulent vortex tangle driven by the Gross-Pitaevskii equation is studied. Using a recently-developed accurate and robust tracking algorithm, all quantised vortices are extracted from the fields. The Vinen's decay law for the total vortex length with a coefficient that is in quantitative agreement with the values measured in Helium II is observed. The topology of the tangle is then studied showing that linked rings may appear during the decay. The tracking also allows for determining the statistics of small-scales quantities of vortex lines, exhibiting large fluctuations of curvature and torsion. Finally, the temporal evolution of the Kelvin wave spectrum is obtained providing evidence of the development of a weak-wave turbulence cascade.

  17. New exact solutions of nonlinear Gross-Pitaevskii equation with weak bias magnetic and time-dependent laser fields

    Institute of Scientific and Technical Information of China (English)

    Li Hua-Mei

    2005-01-01

    By using the mapping method and an appropriate transformation, we find new exact solutions of nonlinear Gross-Pitaevskii equation with weak bias magnetic and time-dependent laser fields. The solutions obtained in this paper include Jacobian elliptic function solutions, combined Jacobian elliptic function solutions , triangular function solutions, bright and dark solitons, and soliton-like solutions.

  18. Bounds on the tight-binding approximation for the Gross-Pitaevskii equation with a periodic potential

    CERN Document Server

    Pelinovsky, Dmitry

    2007-01-01

    We justify the validity of the discrete nonlinear Schrodinger equation for the tight-binding approximation in the context of the Gross-Pitaevskii equation with a periodic potential. Our construction of the periodic potential and the associated Wannier functions is based on the previous work, while our analysis involving energy estimates and Gronwall's inequality addresses time-dependent localized solutions on large but finite time intervals.

  19. Quenched dynamics of two-dimensional solitons and vortices in the Gross-Pitaevskii equation

    CERN Document Server

    Chen, Qian-Yong; Malomed, Boris A

    2012-01-01

    We consider a two-dimensional (2D) counterpart of the experiment that led to the creation of quasi-1D bright solitons in Bose-Einstein condensates (BECs) [Nature 417, 150--153 (2002)]. We start by identifying the ground state of the 2D Gross-Pitaevskii equation for repulsive interactions, with a harmonic-oscillator (HO) trap, and with or without an optical lattice (OL). Subsequently, we switch the sign of the interaction to induce interatomic attraction and monitor the ensuing dynamics. Regions of the stable self-trapping and catastrophic collapse of 2D fundamental solitons are identified in the parameter plane of the OL strength and BEC norm. The increase of the OL strength expands the persistence domain for the solitons to larger norms. For single-charged solitary vortices, in addition to the survival and collapse regimes, an intermediate one is identified, where the vortex resists the collapse but loses its structure, transforming into a fundamental soliton. The same setting may also be implemented in the ...

  20. CUDA programs for solving the time-dependent dipolar Gross-Pitaevskii equation in an anisotropic trap

    CERN Document Server

    Loncar, Vladimir; Bogojevic, Aleksandar; Skrbic, Srdjan; Muruganandam, Paulsamy; Adhikari, Sadhan K

    2016-01-01

    In this paper we present new versions of previously published numerical programs for solving the dipolar Gross-Pitaevskii (GP) equation including the contact interaction in two and three spatial dimensions in imaginary and in real time, yielding both stationary and non-stationary solutions. New versions of programs were developed using CUDA toolkit and can make use of Nvidia GPU devices. The algorithm used is the same split-step semi-implicit Crank-Nicolson method as in the previous version (R. Kishor Kumar et al., Comput. Phys. Commun. 195, 117 (2015)), which is here implemented as a series of CUDA kernels that compute the solution on the GPU. In addition, the Fast Fourier Transform (FFT) library used in the previous version is replaced by cuFFT library, which works on CUDA-enabled GPUs. We present speedup test results obtained using new versions of programs and demonstrate an average speedup of 12 to 25, depending on the program and input size.

  1. Stationary and Dynamical Solutions of the Gross-Pitaevskii Equation for a Bose-Einstein Condensate in a PT symmetric Double Well

    Directory of Open Access Journals (Sweden)

    Holger Cartarius

    2013-01-01

    Full Text Available We investigate the Gross-Pitaevskii equation for a Bose-Einstein condensate in a PT symmetric double-well potential by means of the time-dependent variational principle and numerically exact solutions. A one-dimensional and a fully three-dimensional setup are used. Stationary states are determined and the propagation of wave function is investigated using the time-dependent Gross-Pitaevskii equation. Due to the nonlinearity of the Gross-Pitaevskii equation the potential dependson the wave function and its solutions decide whether or not the Hamiltonian itself is PT symmetric. Stationary solutions with real energy eigenvalues fulfilling exact PT symmetry are found as well as PT broken eigenstates with complex energies. The latter describe decaying or growing probability amplitudes and are not true stationary solutions of the time-dependent Gross-Pitaevskii equation. However, they still provide qualitative information about the time evolution of the wave functions.

  2. Unidimensional reduction of the 3D Gross-Pitaevskii equation with two- and three-body interactions

    CERN Document Server

    Cardoso, W B; Bazeia, D

    2010-01-01

    We deal with the three-dimensional Gross-Pitaevskii equation, which is used to describe a cloud of dilute bosonic atoms that interact under competing two- and three-body scattering potentials. We study the case where the cloud of atoms is strongly confined in two spatial dimensions, allowing us to build an unidimensional nonlinear equation, controlled by the nonlinearities and the confining potentials that trap the system along the longitudinal coordinate. We focus attention on specific limits, dictated by the cubic and quintic coefficients, and we implement numerical simulations to help us to quantify the validity of the procedure.

  3. Dynamics of Nonlinear Schrodinger / Gross-Pitaevskii Equations; Mass Transfer in Systems with Solitons and Degenerate Neutral Modes

    CERN Document Server

    Gang, Zhou

    2008-01-01

    Nonlinear Schrodinger / Gross-Pitaevskii equations play a central role in the understanding of nonlinear optical and macroscopic quantum systems. The large time dynamics of such systems is governed by interactions of the nonlinear ground state manifold, discrete neutral modes (``excited states'') and dispersive radiation. Systems with symmetry, in spatial dimensions larger than one, typically have degenerate neutral modes. Thus, we study the large time dynamics of systems with degenerate neutral modes. This requires a new normal form (nonlinear matrix Fermi Golden Rule) governing the system's large time asymptotic relaxation to the ground state (soliton) manifold.

  4. C programs for solving the time-dependent Gross-Pitaevskii equation in a fully anisotropic trap

    Science.gov (United States)

    Vudragović, Dušan; Vidanović, Ivana; Balaž, Antun; Muruganandam, Paulsamy; Adhikari, Sadhan K.

    2012-09-01

    We present C programming language versions of earlier published Fortran programs (Muruganandam and Adhikari (2009) [1]) for calculating both stationary and non-stationary solutions of the time-dependent Gross-Pitaevskii (GP) equation. The GP equation describes the properties of dilute Bose-Einstein condensates at ultra-cold temperatures. C versions of programs use the same algorithms as the Fortran ones, involving real- and imaginary-time propagation based on a split-step Crank-Nicolson method. In a one-space-variable form of the GP equation, we consider the one-dimensional, two-dimensional, circularly-symmetric, and the three-dimensional spherically-symmetric harmonic-oscillator traps. In the two-space-variable form, we consider the GP equation in two-dimensional anisotropic and three-dimensional axially-symmetric traps. The fully-anisotropic three-dimensional GP equation is also considered. In addition to these twelve programs, for six algorithms that involve two and three space variables, we have also developed threaded (OpenMP parallelized) programs, which allow numerical simulations to use all available CPU cores on a computer. All 18 programs are optimized and accompanied by makefiles for several popular C compilers. We present typical results for scalability of threaded codes and demonstrate almost linear speedup obtained with the new programs, allowing a decrease in execution times by an order of magnitude on modern multi-core computers. New version program summary Program title: GP-SCL package, consisting of: (i) imagtime1d, (ii) imagtime2d, (iii) imagtime2d-th, (iv) imagtimecir, (v) imagtime3d, (vi) imagtime3d-th, (vii) imagtimeaxial, (viii) imagtimeaxial-th, (ix) imagtimesph, (x) realtime1d, (xi) realtime2d, (xii) realtime2d-th, (xiii) realtimecir, (xiv) realtime3d, (xv) realtime3d-th, (xvi) realtimeaxial, (xvii) realtimeaxial-th, (xviii) realtimesph. Catalogue identifier: AEDU_v2_0. Program Summary URL: http://cpc.cs.qub.ac.uk/summaries/AEDU_v2_0.html

  5. Finite temperature and dissipative corrections to the Gross-Pitaevskii equation from $\\lambda\\Phi^4$ one loop contributions

    CERN Document Server

    Matos, T

    2011-01-01

    Starting with a scalar field in a thermal bath and using the one loop quantum correction potential, we rewrite the Klein-Gordon equation in its thermodynamical representation and study the behavior of this scalar field due to temperature variations in the equations of motion. We find the generalization of a Gross-Pitaevskii like equation for a relativistic Bose gas with finite temperature, the corresponding thermodynamic and viscosity expressions, and an expression for the postulate of the first law of the thermodynamics for this BECs. We also propose that the equations obtained might help to explain at some level the phase transition of a Bose-Einstein Condensate in terms of quantum field theory in a simple way.

  6. Analytical solutions of the coupled Gross-Pitaevskii equations for the three-species Bose-Einstein condensates

    CERN Document Server

    Liu, Y M

    2016-01-01

    The coupled Gross-Pitaevskii equations for the g.s. of the three-species condensates (3-BEC) have been solved analytically under the Thomas-Fermi approximation. Six types of spatial configurations in miscible phase are found. The whole parameter-space has been divided into zones each supports a specific configuration (miscible or immiscible). The borders of the zones are described by analytical formulae. Due to the division, the variation of the spatial configuration against the parameters can be visualized, and the effects of the parameters can be thereby understood. There are regions in the parameter-space where the configuration is highly sensitive to the parameters. These regions are tunable and valuable for the determination of the parameters.

  7. Resolution of the Gross-Pitaevskii equation with the imaginary-time method on a Lagrange mesh.

    Science.gov (United States)

    Baye, D; Sparenberg, J-M

    2010-11-01

    The Lagrange-mesh method is an approximate variational calculation which has the simplicity of a mesh calculation. Combined with the imaginary-time method, it is applied to the iterative resolution of the Gross-Pitaevskii equation. Two variants of a fourth-order factorization of the exponential of the Hamiltonian and two types of mesh (Lagrange-Hermite and Lagrange-sinc) are employed and compared. The accuracy is checked with the help of these comparisons and of the virial theorem. The Lagrange-Hermite mesh provides very accurate results with short computing times for values of the dimensionless parameter of the nonlinear term up to 10⁴. For higher values up to 10⁷, the Lagrange-sinc mesh is more efficient. Examples are given for anisotropic and nonseparable trapping potentials.

  8. Hybrid OpenMP/MPI programs for solving the time-dependent Gross-Pitaevskii equation in a fully anisotropic trap

    Science.gov (United States)

    Satarić, Bogdan; Slavnić, Vladimir; Belić, Aleksandar; Balaž, Antun; Muruganandam, Paulsamy; Adhikari, Sadhan K.

    2016-03-01

    We present hybrid OpenMP/MPI (Open Multi-Processing/Message Passing Interface) parallelized versions of earlier published C programs (Vudragović et al. 2012) for calculating both stationary and non-stationary solutions of the time-dependent Gross-Pitaevskii (GP) equation in three spatial dimensions. The GP equation describes the properties of dilute Bose-Einstein condensates at ultra-cold temperatures. Hybrid versions of programs use the same algorithms as the C ones, involving real- and imaginary-time propagation based on a split-step Crank-Nicolson method, but consider only a fully-anisotropic three-dimensional GP equation, where algorithmic complexity for large grid sizes necessitates parallelization in order to reduce execution time and/or memory requirements per node. Since distributed memory approach is required to address the latter, we combine MPI programming paradigm with existing OpenMP codes, thus creating fully flexible parallelism within a combined distributed/shared memory model, suitable for different modern computer architectures. The two presented C/OpenMP/MPI programs for real- and imaginary-time propagation are optimized and accompanied by a customizable makefile. We present typical scalability results for the provided OpenMP/MPI codes and demonstrate almost linear speedup until inter-process communication time starts to dominate over calculation time per iteration. Such a scalability study is necessary for large grid sizes in order to determine optimal number of MPI nodes and OpenMP threads per node.

  9. Analysis of the Complex Gross-Pitaevskii Equation for the Bose-Einstein Condensation of Exciton-Polaritons

    KAUST Repository

    Núñez, Jesus

    2011-08-01

    Considered as a fundamental step for the development of the atomic laser and quantum computing, as well as the theoretical explanation of super fluidity, the Bose- Einstein condensate (BEC) has emerged as one of the most important topics in modern physics. This project is devoted to the analysis of a condensate based on exciton-polaritons. This BEC is characterized by a high critical temperature of condensation (about 20 K) and non-equilibrium dynamics. A mathematical model called complex Gross- Pitaevskii equation (cGPE) is used to describe its behavior. The steady state solutions of the cGPE are studied and a numerical method based on a collocation method is proposed in order to find these solutions. Once the steady state solutions are found, a linear stability analysis is performed, demonstrating that the steady state solutions become unstable as the pumping spot radius increases. Finally, the manifestations of these instabilities are analyzed by direct simulation of the cGPE, using a second order time-splitting spectral method. As a result, it is possible to see the formation of quantum vortices, which increase in number as the pumping spot radius increases.

  10. OpenMP Fortran and C programs for solving the time-dependent Gross-Pitaevskii equation in an anisotropic trap

    CERN Document Server

    Young-S., Luis E; Muruganandam, Paulsamy; Adhikari, Sadhan K; Balaz, Antun

    2016-01-01

    We present new version of previously published Fortran and C programs for solving the Gross-Pitaevskii equation for a Bose-Einstein condensate with contact interaction in one, two and three spatial dimensions in imaginary and real time, yielding both stationary and non-stationary solutions. To reduce the execution time on multicore processors, new versions of parallelized programs are developed using Open Multi-Processing (OpenMP) interface. The input in the previous versions of programs was the mathematical quantity nonlinearity for dimensionless form of Gross-Pitaevskii equation, whereas in the present programs the inputs are quantities of experimental interest, such as, number of atoms, scattering length, oscillator length for the trap, etc. New output files for some integrated one- and two-dimensional densities of experimental interest are given. We also present speedup test results for the new programs.

  11. Variational Approach to the Orbital Stability of Standing Waves of the Gross-Pitaevskii Equation

    KAUST Repository

    Hadj Selem, Fouad

    2014-08-26

    This paper is concerned with the mathematical analysis of a masssubcritical nonlinear Schrödinger equation arising from fiber optic applications. We show the existence and symmetry of minimizers of the associated constrained variational problem. We also prove the orbital stability of such solutions referred to as standing waves and characterize the associated orbit. In the last section, we illustrate our results with few numerical simulations. © 2014 Springer Basel.

  12. Analytical traveling-wave solutions to a generalized Gross-Pitaevskii equation with some new time and space varying nonlinearity coefficients and external fields

    Science.gov (United States)

    Castro López, R.; Sun, Guo-Hua; Camacho-Nieto, O.; Yáñez-Márquez, C.; Dong, Shi-Hai

    2017-09-01

    We present analytical matter-wave solutions to a generalized Gross-Pitaevskii (GGP) equation with several new time and space varying nonlinearity coefficients and external fields. This is realized by taking a suitable similarity transformation to the GGP equation which makes the original partial differential equation into a stationary and ordinary differential equation. We report a few families of analytical solutions of the GGP equation with several new time and space varying nonlinearity interactions, in which some physically relevant soliton solutions are found. The profile features of the evolution wave functions depend on the different choices of the composite functions ξ.

  13. Numerically exact dynamics of the interacting many-body Schroedinger equation for Bose-Einstein condensates. Comparison to Bose-Hubbard and Gross-Pitaevskii theory

    Energy Technology Data Exchange (ETDEWEB)

    Sakmann, Kaspar

    2010-07-21

    In this thesis, the physics of trapped, interacting Bose-Einstein condensates is analyzed by solving the many-body Schroedinger equation. Particular emphasis is put on coherence, fragmentation and reduced density matrices. First, the ground state of a trapped Bose-Einstein condensate and its correlation functions are obtained. Then the dynamics of a bosonic Josephson junction is investigated by solving the time-dependent many-body Schroedinger equation numerically exactly. These are the first exact results in literature in this context. It is shown that the standard approximations of the field, Gross-Pitaevskii theory and the Bose-Hubbard model fail at weak interaction strength and within their range of expected validity. For stronger interactions the dynamics becomes strongly correlated and a new equilibration phenomenon is discovered. By comparison with exact results it is shown that a symmetry of the Bose- Hubbard model between attractive and repulsive interactions must be considered an artefact of the model. A conceptual innovation of this thesis are time-dependent Wannier functions. Equations of motion for time-dependent Wannier functions are derived from the variational principle. By comparison with exact results it is shown that lattice models can be greatly improved at little computational cost by letting the Wannier functions of a lattice model become time-dependent. (orig.)

  14. Dark and bright solitons for a three-dimensional Gross-Pitaevskii equation with distributed time-dependent coefficients in the Bose-Einstein condensation

    Science.gov (United States)

    Liu, Lei; Tian, Bo; Zhen, Hui-Ling; Wu, Xiao-Yu; Shan, Wen-Rui

    2017-02-01

    Under investigation in this paper is a three-dimensional Gross-Pitaevskii equation with the distributed time-dependent coefficients, which describes the phenomena associated with the three-dimensional Bose-Einstein condensation. Under the constraint α(t) = 2 β(t) , we obtain the bilinear forms, dark and bright N-soliton solutions via the Hirota method and symbolic computation, where t is the scaled time, α(t) and β(t) are the coefficients for the strength of the quadratic potential and diffraction, respectively. Specially, compared with the bright soliton solutions previously reported, we eliminate one constraint and obtain more soliton parameters. We give the existence constraints of the dark and bright N solitons, respectively. Choosing the diffraction and gain/loss coefficients, we observe the growth, decay, periodic oscillation, periodic collapse and revival of the dark and bright solitons. Relationships between the BEC time-dependent coefficients and soliton properties are studied. With the help of the asymptotic and graphic analysis, elastic interactions of the dark and bright two solitons are exhibited.

  15. OpenMP, OpenMP/MPI, and CUDA/MPI C programs for solving the time-dependent dipolar Gross-Pitaevskii equation

    CERN Document Server

    Loncar, Vladimir; Skrbic, Srdjan; Muruganandam, Paulsamy; Adhikari, Sadhan K; Balaz, Antun

    2016-01-01

    We present new versions of the previously published C and CUDA programs for solving the dipolar Gross-Pitaevskii equation in one, two, and three spatial dimensions, which calculate stationary and non-stationary solutions by propagation in imaginary or real time. Presented programs are improved and parallelized versions of previous programs, divided into three packages according to the type of parallelization. First package contains improved and threaded version of sequential C programs using OpenMP. Second package additionally parallelizes three-dimensional variants of the OpenMP programs using MPI, allowing them to be run on distributed-memory systems. Finally, previous three-dimensional CUDA-parallelized programs are further parallelized using MPI, similarly as the OpenMP programs. We also present speedup test results obtained using new versions of programs in comparison with the previous sequential C and parallel CUDA programs. The improvements to the sequential version yield a speedup of 1.1 to 1.9, depen...

  16. OpenMP, OpenMP/MPI, and CUDA/MPI C programs for solving the time-dependent dipolar Gross-Pitaevskii equation

    Science.gov (United States)

    Lončar, Vladimir; Young-S., Luis E.; Škrbić, Srdjan; Muruganandam, Paulsamy; Adhikari, Sadhan K.; Balaž, Antun

    2016-12-01

    We present new versions of the previously published C and CUDA programs for solving the dipolar Gross-Pitaevskii equation in one, two, and three spatial dimensions, which calculate stationary and non-stationary solutions by propagation in imaginary or real time. Presented programs are improved and parallelized versions of previous programs, divided into three packages according to the type of parallelization. First package contains improved and threaded version of sequential C programs using OpenMP. Second package additionally parallelizes three-dimensional variants of the OpenMP programs using MPI, allowing them to be run on distributed-memory systems. Finally, previous three-dimensional CUDA-parallelized programs are further parallelized using MPI, similarly as the OpenMP programs. We also present speedup test results obtained using new versions of programs in comparison with the previous sequential C and parallel CUDA programs. The improvements to the sequential version yield a speedup of 1.1-1.9, depending on the program. OpenMP parallelization yields further speedup of 2-12 on a 16-core workstation, while OpenMP/MPI version demonstrates a speedup of 11.5-16.5 on a computer cluster with 32 nodes used. CUDA/MPI version shows a speedup of 9-10 on a computer cluster with 32 nodes.

  17. An user-friendly software tool for the solution of the time-dependent Schroedinger and Gross-Pitaevskii equations

    Energy Technology Data Exchange (ETDEWEB)

    Serafini, Thomas; Bertoni, Andrea, E-mail: andrea.bertoni@unimore.i [S3 National Research Center, INFM-CNR, 41125 Modena (Italy)

    2009-11-15

    In this work we present TDStool, a general-purpose easy-to-use software tool for the solution of the time-dependent Schroedinger equation in 2D and 3D domains with arbitrary time-dependent potentials. The numerical algorithms adopted in the code, namely Fourier split-step and box-integration methods, are sketched and the main characteristics of the tool are illustrated. As an example, the dynamics of a single electron in systems of two and three coupled quantum dots is obtained. The code is released as an open-source project and has a build-in graphical interface for the visualization of the results.

  18. Dark solitons in a Gross-Pitaevskii equation with a power-law nonlinearity: application to ultracold Fermi gases near the Bose-Einstein condensation regime

    Energy Technology Data Exchange (ETDEWEB)

    Yan, D; Kevrekidis, P G [Department of Mathematics and Statistics, University of Massachusetts, Amherst, MA 01003-4515 (United States); Frantzeskakis, D J, E-mail: kevrekid@math.umass.edu [Department of Physics, University of Athens, Panepistimiopolis, Zografos, Athens 157 84 (Greece)

    2011-10-14

    In this work, we consider a model of a defocusing nonlinear Schroedinger equation with a variable nonlinearity exponent. This is motivated by the study of a superfluid Fermi gas in the Bose-Einstein condensation (BEC)-Bardeen-Cooper-Schrieffer crossover. In particular, we focus on the relevant mean-field model in the regime from BEC to unitarity and especially consider the modification of the nearly black soliton oscillation frequency due to the variation in the nonlinearity exponent in a harmonic trapping potential. The analytical expressions given as a function of the relevant nonlinearity exponent are corroborated by numerical computations and also extended past the BEC limit. (paper)

  19. On the Well-Posedness and Scattering for the Gross-Pitaevskii Hierarchy via Quantum de Finetti

    Science.gov (United States)

    Chen, Thomas; Hainzl, Christian; Pavlović, Nataša; Seiringer, Robert

    2014-07-01

    We prove the existence of scattering states for the defocusing cubic Gross-Pitaevskii (GP) hierarchy in . Moreover, we show that an exponential energy growth condition commonly used in the well-posedness theory of the GP hierarchy is, in a specific sense, necessary. In fact, we prove that without the latter, there exist initial data for the focusing cubic GP hierarchy for which instantaneous blowup occurs.

  20. Large amplitude spatial fluctuations in the boundary region of the Bose-Einstein condensate in the Gross-Pitaevskii regime

    DEFF Research Database (Denmark)

    Tuszynski, J. A.; Middleton, J.; Portet, S.

    2003-01-01

    is found which are characterised by pronounced large-amplitude oscillations close to the boundary of the condensate. The limiting case within this class is a nodeless ground state which is known from recent investigations as an extension of the Thomas-Fermi approximation. We have found the energies......The Gross-Pitaevskii regime of a Bose-Einstein condensate is investigated using a fully non-linear approach. The confining potential first adopted is that of a linear ramp. An infinite class of new analytical solutions of this linear ramp potential approximation to the Gross-Pitaevskii equation...... of the oscillatory states to lie above the ground state energy but recent experimental work, especially on spatially confined superconductors, indicates that such states may be easily occupied and made manifest at finite temperatures. We have also investigated their stability using a Poincare section analysis...

  1. A vortex filament tracking method for the Gross-Pitaevskii model of a superfluid

    Science.gov (United States)

    Villois, Alberto; Krstulovic, Giorgio; Proment, Davide; Salman, Hayder

    2016-10-01

    We present an accurate and robust numerical method to track quantised vortex lines in a superfluid described by the Gross-Pitaevskii equation. By utilising the pseudo-vorticity field of the associated complex scalar order parameter of the superfluid, we are able to track the topological defects of the superfluid and reconstruct the vortex lines which correspond to zeros of the field. Throughout, we assume our field is periodic to allow us to make extensive use of the Fourier representation of the field and its derivatives in order to retain spectral accuracy. We present several case studies to test the precision of the method which include the evaluation of the curvature and torsion of a torus vortex knot, and the measurement of the Kelvin wave spectrum of a vortex line and a vortex ring. The method we present makes no a priori assumptions on the geometry of the vortices and is therefore applicable to a wide range of systems such as a superfluid in a turbulent state that is characterised by many vortex rings coexisting with sound waves. This allows us to track the positions of the vortex filaments in a dense turbulent vortex tangle and extract statistical information about the distribution of the size of the vortex rings and the inter-vortex separations. In principle, the method can be extended to track similar topological defects arising in other physical systems.

  2. Spatial patterns for the three species Gross-Pitaevskii system in the plane

    Directory of Open Access Journals (Sweden)

    Marco Squassina

    2008-05-01

    Full Text Available In this paper we highlight some particular spatial patterns of ground state solutions for the three species Gross-Pitaevskii system in the plane having physical coefficients with particular attention to the cases where the inter-species coefficients become large. The solutions models least energy stationary states of a mixture of three Bose-Einstein condensates.

  3. Bose gas to Bose-Einstein Condensate by the Phase Transition of the Klein-Gordon equation

    CERN Document Server

    Matos, Tonatiuh

    2012-01-01

    We rewrite the complex Klein-Gordon (KG) equation with a mexican-hat scalar field potential in a thermal bath with one loop contribution as a new Gross-Pitaevskii (GP)-like equation. We interpret it as a charged and finite temperature generalization of the GP equation. We find its hydrodynamic version as well and using it, we derive the corresponding thermodynamics. We obtain a generalized first law for a charged Bose-Einstein Condensate (BEC). We translate the breaking of the U(1) local symmetry of the KG field into the new version of the GP equation and demonstrate that this symmetry breaking corresponds to a phase transition of the gas into a BEC, and show the conditions for which this system naturally becomes superfluid and/or superconductor.

  4. Exact eigenfunctions of the linear ramp potential in the Gross-Pitaevskii equation for the Bose-Einstein condensate

    DEFF Research Database (Denmark)

    Tuszynski, J. A.; Middleton, J.; Christiansen, Peter Leth;

    2001-01-01

    transcendent and can be very accurately estimated using elementary functions which are globally non-singular. We analyse the physical characteristics of these condensate wavefunctions whose novel feature is a damped oscillatory profile. The nodeless solution, which corresponds to the lowest energy state...

  5. On the Gross–Pitaevskii equation for trapped dipolar quantum gases

    KAUST Repository

    Carles, Rémi

    2008-09-29

    We study the time-dependent Gross-Pitaevskii equation describing Bose-Einstein condensation of trapped dipolar quantum gases. Existence and uniqueness as well as the possible blow-up of solutions are studied. Moreover, we discuss the problem of dimension reduction for this nonlinear and nonlocal Schrödinger equation. © 2008 IOP Publishing Ltd and London Mathematical Society.

  6. Schroedinger Equation and the Quantization of Celestial Systems

    Directory of Open Access Journals (Sweden)

    Smarandache F.

    2006-04-01

    Full Text Available In the present article, we argue that it is possible to generalize Schroedinger equation to describe quantization of celestial systems. While this hypothesis has been described by some authors, including Nottale, here we argue that such a macroquantization was formed by topological superfluid vortice. We also provide derivation of Schroedinger equation from Gross-Pitaevskii-Ginzburg equation, which supports this superfluid dynamics interpretation.

  7. Hydrodynamic representation of the Klein-Gordon-Einstein equations in the weak field limit

    CERN Document Server

    Suárez, Abril

    2015-01-01

    Using a generalization of the Madelung transformation, we derive the hydrodynamic representation of the Klein-Gordon-Einstein equations in the weak field limit. We consider a complex self-interacting scalar field with an arbitrary potential of the form $V(|\\varphi|^2)$. We compare the results with simplified models in which the gravitational potential is introduced by hand in the Klein-Gordon equation, and assumed to satisfy a (generalized) Poisson equation. Nonrelativistic hydrodynamic equations based on the Schr\\"odinger-Poisson equations or on the Gross-Pitaevskii-Poisson equations are recovered in the limit $c\\rightarrow +\\infty$.

  8. Hydrodynamic representation of the Klein-Gordon-Einstein equations in the weak field limit

    Science.gov (United States)

    Suárez, Abril; Chavanis, Pierre-Henri

    2015-11-01

    Using a generalization of the Madelung transformation, we derive the hydrodynamic representation of the Klein-Gordon-Einstein equations in the weak field limit. We consider a complex self-interacting scalar field with an arbitrary potential of the form V(|ϕ|2). We compare the results with simplified models in which the gravitational potential is introduced by hand in the Klein-Gordon equation, and assumed to satisfy a (generalized) Poisson equation. Nonrelativistic hydrodynamic equations based on the Schrodinger-Poisson equations or on the Gross-Pitaevskii-Poisson equations are recovered in the limit c → +∞.

  9. Dynamics of partial differential equations

    CERN Document Server

    Wayne, C Eugene

    2015-01-01

    This book contains two review articles on the dynamics of partial differential equations that deal with closely related topics but can be read independently. Wayne reviews recent results on the global dynamics of the two-dimensional Navier-Stokes equations. This system exhibits stable vortex solutions: the topic of Wayne's contribution is how solutions that start from arbitrary initial conditions evolve towards stable vortices. Weinstein considers the dynamics of localized states in nonlinear Schrodinger and Gross-Pitaevskii equations that describe many optical and quantum systems. In this contribution, Weinstein reviews recent bifurcations results of solitary waves, their linear and nonlinear stability properties, and results about radiation damping where waves lose energy through radiation.   The articles, written independently, are combined into one volume to showcase the tools of dynamical systems theory at work in explaining qualitative phenomena associated with two classes of partial differential equ...

  10. Exact solutions for generalized variable-coefficients Ginzburg-Landau equation: Application to Bose-Einstein condensates with multi-body interatomic interactions

    Science.gov (United States)

    Kengne, E.; Lakhssassi, A.; Vaillancourt, R.; Liu, Wu-Ming

    2012-12-01

    We present a double-mapping method (D-MM), a natural combination of a similarity with F-expansion methods, for obtaining general solvable nonlinear evolution equations. We focus on variable-coefficients complex Ginzburg-Landau equations (VCCGLE) with multi-body interactions. We show that it is easy by this method to find a large class of exact solutions of Gross-Pitaevskii and Gross-Pitaevskii-Ginzburg equations. We apply the D-MM to investigate the dynamics of Bose-Einstein condensation with two- and three-body interactions. As a surprising result, we obtained that it is very easy to use the built D-MM to obtain a large class of exact solutions of VCCGLE with two-body interactions via a generalized VCCGLE with two- and three-body interactions containing cubic-derivative terms. The results show that the proposed method is direct, concise, elementary, and effective, and can be a very effective and powerful mathematical tool for solving many other nonlinear evolution equations in physics.

  11. Higher-order splitting algorithms for solving the nonlinear Schr\\"odinger equation and their instabilities

    CERN Document Server

    Chin, Siu A

    2007-01-01

    Since the kinetic and the potential energy term of the real time nonlinear Schr\\"odinger equation can each be solved exactly, the entire equation can be solved to any order via splitting algorithms. We verified the fourth-order convergence of some well known algorithms by solving the Gross-Pitaevskii equation numerically. All such splitting algorithms suffer from a latent numerical instability even when the total energy is very well conserved. A detail error analysis reveals that the noise, or elementary excitations of the nonlinear Schr\\"odinger, obeys the Bogoliubov spectrum and the instability is due to the exponential growth of high wave number noises caused by the splitting process. For a continuum wave function, this instability is unavoidable no matter how small the time step. For a discrete wave function, the instability can be avoided only for $\\dt k_{max}^2{<\\atop\\sim}2 \\pi$, where $k_{max}=\\pi/\\Delta x$.

  12. Study of symmetry breaking of charged scalar field: Hydrodynamic version

    CERN Document Server

    Matos, T

    2015-01-01

    We rewrite the Klein-Gordon (KG) equation for a complex scalar field as a new Gross-Pitaevskii (GP)-like equation. The potential of the scalar field is a mexican-hat potential and the field is in a thermal bath with one loop contribution. We interpret the new GP equation as a finite temperature generalization of the GP equation for a charged field. We find its hydrodynamic version as well and using it, we derive the corresponding thermodynamics. We also obtain a generalized first law for a charged Bose-Einstein Condensate (BEC).

  13. Study of symmetry breaking of charged scalar field: Hydrodynamic version

    Science.gov (United States)

    Matos, T.; Rodríguez-Meza, M. A.

    2014-11-01

    We rewrite the Klein-Gordon (KG) equation for a complex scalar field as a new Gross-Pitaevskii (GP)-like equation. The potential of the scalar field is a mexican-hat potential and the field is in a thermal bath with one loop contribution. We interpret the new GP equation as a finite temperature generalization of the GP equation for a charged field. We find its hydrodynamic version as well and using it, we derive the corresponding thermodynamics. We also obtain a generalized first law for a charged Bose-Einstein Condensate (BEC).

  14. A Time-Splitting and Sine Spectral Method for Dynamics of Dipolar Bose-Einstein Condensate

    Directory of Open Access Journals (Sweden)

    Si-Qi Li

    2013-01-01

    Full Text Available A two-component Bose-Einstein condensate (BEC described by two coupled a three-dimension Gross-Pitaevskii (GP equations is considered, where one equation has dipole-dipole interaction while the other one has only the usual s-wave contact interaction, in a cigar trap. The time-splitting and sine spectral method in space is proposed to discretize the time-dependent equations for computing the dynamics of dipolar BEC. The singularity in the dipole-dipole interaction brings significant difficulties both in mathematical analysis and in numerical simulations. Numerical results are given to show the efficiency of this method.

  15. Hydrodynamic representation of the Klein-Gordon-Einstein equations in the weak field limit: General formalism and perturbations analysis

    Science.gov (United States)

    Suárez, Abril; Chavanis, Pierre-Henri

    2015-07-01

    Using a generalization of the Madelung transformation, we derive the hydrodynamic representation of the Klein-Gordon-Einstein equations in the weak field limit. We consider a complex self-interacting scalar field with a λ |φ |4 potential. We study the evolution of the spatially homogeneous background in the fluid representation and derive the linearized equations describing the evolution of small perturbations in a static and in an expanding Universe. We compare the results with simplified models in which the gravitational potential is introduced by hand in the Klein-Gordon equation, and assumed to satisfy a (generalized) Poisson equation. Nonrelativistic hydrodynamic equations based on the Schrödinger-Poisson equations or on the Gross-Pitaevskii-Poisson equations are recovered in the limit c →+∞. We study the evolution of the perturbations in the matter era using the nonrelativistic limit of our formalism. Perturbations whose wavelength is below the Jeans length oscillate in time while perturbations whose wavelength is above the Jeans length grow linearly with the scale factor as in the cold dark matter model. The growth of perturbations in the scalar field model is substantially faster than in the cold dark matter model. When the wavelength of the perturbations approaches the cosmological horizon (Hubble length), a relativistic treatment is mandatory. In that case, we find that relativistic effects attenuate or even prevent the growth of perturbations. This paper exposes the general formalism and provides illustrations in simple cases. Other applications of our formalism will be considered in companion papers.

  16. Effective equations for matter-wave gap solitons in higher-order transversal states.

    Science.gov (United States)

    Mateo, A Muñoz; Delgado, V

    2013-10-01

    We demonstrate that an important class of nonlinear stationary solutions of the three-dimensional (3D) Gross-Pitaevskii equation (GPE) exhibiting nontrivial transversal configurations can be found and characterized in terms of an effective one-dimensional (1D) model. Using a variational approach we derive effective equations of lower dimensionality for BECs in (m,n(r)) transversal states (states featuring a central vortex of charge m as well as n(r) concentric zero-density rings at every z plane) which provides us with a good approximate solution of the original 3D problem. Since the specifics of the transversal dynamics can be absorbed in the renormalization of a couple of parameters, the functional form of the equations obtained is universal. The model proposed finds its principal application in the study of the existence and classification of 3D gap solitons supported by 1D optical lattices, where in addition to providing a good estimate for the 3D wave functions it is able to make very good predictions for the μ(N) curves characterizing the different fundamental families. We have corroborated the validity of our model by comparing its predictions with those from the exact numerical solution of the full 3D GPE.

  17. Exceptional Points for Nonlinear Schroedinger Equations Describing Bose-Einstein Condensates of Ultracold Atomic Gases

    Directory of Open Access Journals (Sweden)

    G. Wunner

    2011-01-01

    Full Text Available The coalescence of two eigenfunctions with the same energy eigenvalue is not possible in Hermitian Hamiltonians. It is, however, a phenomenon well known from non-hermitian quantum mechanics. It can appear, e.g., for resonances in open systems, with complex energy eigenvalues. If two eigenvalues of a quantum mechanical system which depends on two or more parameters pass through such a branch point singularity at a critical set of parameters, the point in the parameter space is called an exceptional point. We will demonstrate that exceptional points occur not only for non-hermitean Hamiltonians but also in the nonlinear Schroedinger equations which describe Bose-Einstein condensates, i.e., the Gross-Pitaevskii equation for condensates with a short-range contact interaction, and with additional long-range interactions. Typically, in these condensates the exceptional points are also found to be bifurcation points in parameter space. For condensates with a gravity-like interaction between the atoms, these findings can be confirmed in an analytical way.

  18. equations

    Directory of Open Access Journals (Sweden)

    Xinzhi Liu

    1998-01-01

    Full Text Available This paper studies a class of high order delay partial differential equations. Employing high order delay differential inequalities, several oscillation criteria are established for such equations subject to two different boundary conditions. Two examples are also given.

  19. stableGP

    Data.gov (United States)

    National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

  20. Dark solitons, dispersive shock waves, and transverse instabilities

    CERN Document Server

    Hoefer, M A

    2011-01-01

    The nature of transverse instabilities to dark solitons and dispersive shock waves for the (2+1)-dimensional defocusing nonlinear Schrodinger equation / Gross-Pitaevskii (NLS / GP) equation is considered. Special attention is given to the small (shallow) amplitude regime, which limits to the Kadomtsev-Petviashvili (KP) equation. We study analytically and numerically the eigenvalues of the linearized NLS / GP equation. The dispersion relation for shallow solitons is obtained asymptotically beyond the KP limit. This yields 1) the maximum growth rate and associated wavenumber of unstable perturbations; and 2) the separatrix between convective and absolute instabilities. The latter result is used to study the transition between convective and absolute instabilities of oblique dispersive shock waves (DSWs). Stationary and nonstationary oblique DSWs are constructed analytically and investigated numerically by direct simulations of the NLS / GP equation. The instability properties of oblique DSWs are found to be dir...

  1. Large amplitude spatial fluctuations in the boundary region of the Bose-Einstein condensate in the Gross-Pitaevskii regime

    DEFF Research Database (Denmark)

    Tuszynski, J. A.; Middleton, J.; Portet, S.

    2003-01-01

    of the oscillatory states to lie above the ground state energy but recent experimental work, especially on spatially confined superconductors, indicates that such states may be easily occupied and made manifest at finite temperatures. We have also investigated their stability using a Poincare section analysis...

  2. Stable dipole solitons and soliton complexes in the nonlinear Schrödinger equation with periodically modulated nonlinearity

    Energy Technology Data Exchange (ETDEWEB)

    Lebedev, M. E., E-mail: gloriouslair@gmail.com, E-mail: galfimov@yahoo.com; Alfimov, G. L., E-mail: gloriouslair@gmail.com, E-mail: galfimov@yahoo.com [National Research University of Electronic Technology MIET, Zelenograd, Moscow 124498 (Russian Federation); Malomed, Boris A., E-mail: malomed@post.tau.ac.il [Department of Physical Electronics, School of Electrical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978 (Israel); Laboratory of Nonlinear-Optical Informatics, ITMO University, St. Petersburg 197101 (Russian Federation)

    2016-07-15

    We develop a general classification of the infinite number of families of solitons and soliton complexes in the one-dimensional Gross-Pitaevskii/nonlinear Schrödinger equation with a nonlinear lattice pseudopotential, i.e., periodically modulated coefficient in front of the cubic term, which takes both positive and negative local values. This model finds direct implementations in atomic Bose-Einstein condensates and nonlinear optics. The most essential finding is the existence of two branches of dipole solitons (DSs), which feature an antisymmetric shape, being essentially squeezed into a single cell of the nonlinear lattice. This soliton species was not previously considered in nonlinear lattices. We demonstrate that one branch of the DS family (namely, which obeys the Vakhitov-Kolokolov criterion) is stable, while unstable DSs spontaneously transform into stable fundamental solitons (FSs). The results are obtained in numerical and approximate analytical forms, the latter based on the variational approximation. Some stable bound states of FSs are found too.

  3. Microsoft Dynamics GP 2013 implementation

    CERN Document Server

    Yudin, Victoria

    2013-01-01

    A step-by-step guide for planning and carrying out your Microsoft Dynamics GP 2013 implementation. Detailed descriptions and illustrations of setup screens and practical examples and advice are included for the Dynamics GP system and core modules.If you are a new or existing Microsoft Dynamics GP consultant or an end user who wants to implement, install, and set up core modules of Dynamics GP 2013, then this book is for you. A basic understanding of business management systems and either Dynamics GP or a similar application is recommended.

  4. Quantum aspects of the GP model. [GP (Gregorash-Papini)

    Energy Technology Data Exchange (ETDEWEB)

    Wood, W.R.

    1992-01-01

    The possibility that the description of Nature provided by the theories of general relativity and quantum mechanics may be made more complete by incorporating the ideas of the causal interpretation of quantum mechanics into a conformally invariant theory in Weyl space is investigated. The unified theory of gravitation and electromagnetism provided by the Gregorash-Papini (GP) model is shown to support both the particle and wave aspects required in the causal interpretation, as well as a nonlinear Klein-Gordon wave equation. The Gauss-Mainardi-Codazzi formalism is developed in Weyl geometry and used to construct a particle model in terms of a spherically symmetry thin shell with a scalar-field-induced surface stress-energy tensor. By breaking the interior Weyl invariance at the microscopic scale, a new means by which Weyl's geometric interpretation of the exterior electromagnetic field may be reconciled with atomic standards of length becomes possible. The properties of the resulting interior anti-de Sitter space may play an important role in accounting for the nonlocal effects that are present in any causal interpretation. The particle, represented by the thin shell, is embedded in the exterior Madelung fluid of the GP model such that de Broglie's guidance principle is satisfied. It is argued that a proper analysis of the guidance mechanism hypothesized in the causal interpretation is possible only in a geometrical formulation. The possibility that the causal theory developed in Weyl space requires a maximal acceleration is investigated. A limiting acceleration arises in other theories when aspects of quantum mechanics are employed. A controversial derivation based on the time-energy uncertainty relation is clarified and two new arguments for a maximal acceleration are presented. The demonstration that the causal theory in Weyl space also requires a maximal acceleration supports the view that it is possible to provide a spacetime description of quantum

  5. Nonlinear Dynamics of Globally Coupled Sine-Gordon Equations

    Science.gov (United States)

    2011-05-01

    studied too, including a triangular configuration of linearly coupled parallel fiber Bragg gratings [15], coupled triplets of Gross-Pitaevskii...B. Dueholm, O. A. Levring, J. Mygind, N. F. Pedersen , O. H. Soerensen, and M. Cirillo, Phys. Rev. Lett. 46, 1299 (1981); E. Joergensen, V. P...Malomed, Phys. Rev. B 37, 9325 (1988); A. V. Ustinov, H. Kohlstedt, M. Cirillo, N. F. Pedersen , G. Hallmanns, and C. Heiden, ibid. B 48, 10614

  6. Uncoupling GP1 and GP2 expression in the Lassa virus glycoprotein complex: implications for GP1 ectodomain shedding

    Directory of Open Access Journals (Sweden)

    Illick Kerry A

    2008-12-01

    Full Text Available Abstract Background Sera from convalescent Lassa fever patients often contains antibodies to Lassa virus (LASV glycoprotein 1 (GP1, and glycoprotein 2 (GP2; Immunization of non-human primates with viral vectors expressing the arenaviral glycoprotein complex (GPC confers full protective immunity against a lethal challenge with LASV. Thus, the development of native or quasi native recombinant LASV GP1 and GP2 as soluble, uncoupled proteins will improve current diagnostics, treatment, and prevention of Lassa fever. To this end, mammalian expression systems were engineered for production and purification of secreted forms of soluble LASV GP1 and GP2 proteins. Results Determinants for mammalian cell expression of secreted uncoupled Lassa virus (LASV glycoprotein 1 (GP1 and glycoprotein 2 (GP2 were established. Soluble GP1 was generated using either the native glycoprotein precursor (GPC signal peptide (SP or human IgG signal sequences (s.s.. GP2 was secreted from cells only when (1 the transmembrane (TM domain was deleted, the intracellular domain (IC was fused to the ectodomain, and the gene was co-expressed with a complete GP1 gene in cis; (2 the TM and IC domains were deleted and GP1 was co-expressed in cis; (3 expression of GP1 was driven by the native GPC SP. These data implicate GP1 as a chaperone for processing and shuttling GP2 to the cell surface. The soluble forms of GP1 and GP2 generated through these studies were secreted as homogeneously glycosylated proteins that contained high mannose glycans. Furthermore, observation of GP1 ectodomain shedding from cells expressing wild type LASV GPC represents a novel aspect of arenaviral glycoprotein expression. Conclusion These results implicate GP1 as a chaperone for the correct processing and shuttling of GP2 to the cell surface, and suggest that native GPC SP plays a role in this process. In the absence of GP1 and GPC SP the GP2 protein may be processed by an alternate pathway that produces

  7. About Time, GP and MMG

    Directory of Open Access Journals (Sweden)

    Elena Bagina

    2016-05-01

    Today the MMG already exists without GP. But today’s MMG is also different from that of 1967 or 1987. Thus, such questions as “What is Methodology?” and “What place does it occupy in the contemporary thinking?” remain urgent.

  8. Dissipative self-gravitating Bose-Einstein condensates with arbitrary nonlinearity as a model of dark matter halos

    CERN Document Server

    Chavanis, Pierre-Henri

    2016-01-01

    We develop a general formalism applying to Newtonian self-gravitating Bose-Einstein condensates. This formalism may find application in the context of dark matter halos. We introduce a generalized Gross-Pitaevskii equation including a source of dissipation (damping) and an arbitrary nonlinearity. Using the Madelung transformation, we derive the hydrodynamic representation of this generalized Gross-Pitaevskii equation and obtain a damped quantum Euler equation involving a friction force proportional and opposite to the velocity and a pressure force associated with an equation of state determined by the nonlinearity present in the generalized Gross-Pitaevskii equation. In the strong friction limit, we obtain a quantum Smoluchowski equation. These equations satisfy an $H$-theorem for a free energy functional constructed with a generalized entropy. We specifically consider the Boltzmann and Tsallis entropies associated with isothermal and polytropic equations of state. We also consider the entropy associated with...

  9. Evolution of Matter Wave Interference of Bose-Condensed Gas in a 1D Optical Lattice

    Institute of Scientific and Technical Information of China (English)

    XU Zhi-Jun; ZHANG Dong-Mei

    2007-01-01

    For a Bose-condensed gas in a combined potential consisting of an axially-symmetric harmonic magnetic trap and one-dimensional (1D) optical lattice, using the mean-field Gross-Pitaevskii (G-P) equation and the propagator method, we obtain the analytical result of the order parameter for matter wave interference at any time. The evolution of the interference pattern under a variation of the relative phase △φ between successive subcondensates trapped on an optical lattices is also studied. For △φ = π, the interference pattern is symmetric with two sharp peaks, which are symmetrically located on a straight line on both sides of a vacant central peak and moving apart from each other. This work is in agreement with available experimental results.

  10. Microsoft Dynamics GP 2013 financial management

    CERN Document Server

    Grieve, Ian

    2013-01-01

    A standard tutorial-based approach covering Microsoft Dynamics GP 2013 and its six financial modules. The book is intended to allow users to improve their system use and workflow by introducing new modules to assist in financial management.This book is for you if you're a Dynamics GP partner, or Dynamics GP user, primarily focused on delivering application optimizations. This book assumes that you have a working knowledge of Microsoft Dynamics GP and have an understanding of the requirements of financial management.

  11. Quantum Aspects of the GP Model.

    Science.gov (United States)

    Wood, William Robert

    In this thesis, the possibility that the description of Nature provided by the theories of general relativity and quantum mechanics may be made more complete by incorporating the ideas of the causal interpretation of quantum mechanics into a conformally invariant theory in Weyl space is investigated. The unified theory of gravitation and electromagnetism provided by the Gregorash-Papini (GP) model is shown to support both the particle and wave aspects required in the causal interpretation, as well as a nonlinear Klein-Gordon wave equation. The Gauss-Mainardi-Codazzi formalism is developed in Weyl geometry and then used to construct a particle model in terms of a spherically symmetric thin shell with a scalar-field-induced surface stress-energy tensor. By breaking the interior Weyl invariance at the microscopic scale, a new means by which Weyl's geometric interpretation of the exterior electromagnetic field may be reconciled with atomic standards of length becomes possible. In addition, the properties of the resulting interior anti-de Sitter space may prove to play an important role in accounting for the nonlocal effects that are necessarily present in any causal interpretation. The particle, which is represented by the thin shell, is embedded in the exterior Madelung fluid of the GP model such that de Broglie's guidance principle is satisfied. It is argued that a proper analysis of the guidance mechanism hypothesized in the causal interpretation is possible only in a geometrical formulation. The possibility that the causal theory that is developed in Weyl space requires a maximal acceleration is also investigated. A limiting acceleration has recently been shown to arise in other theories when aspects of quantum mechanics, such as the uncertainty relations, are employed. A controversial derivation based on the time-energy uncertainty relation is clarified and two new arguments for a maximal acceleration are presented. Finally, the demonstration that the causal

  12. 关于右GP-V-环%On right GP-V-rings

    Institute of Scientific and Technical Information of China (English)

    杨春兰

    2009-01-01

    GP-V-ring(GP-V-module) is studied which is a generalization of P-V-ring (P-V-module),and the characters are searched for.For example,if R is a right GP-V-ring,then for any maximal subideal K of a principal right ideal U=aR,a∈R,there exists a maximal right ideal H of R that H∩anR=K∩anR,for some n∈Z+;Every principal right ideal of a right GP-V-ring is idempotent,any direct summand of a right GP-V-ring is again a right GP-V-ring and so on.Furthermore,the question when a GP-V-ring is Von Neumann regular is discussed in the remainder.%主要研究GP-V-环(GP-V-模),它是P-V-环(P-V-模)的推广.讨论了这一类环的某些性质,例如:设R是GP-V-环,则对主右理想U=aR的任意极大子理想K,存在n∈Z+和R的极大右理想H使得H∩anR=K∩anR;右GP-V-环的每个主右理想都是幂等的;右GP-V-环的直和项仍是右GP-V-环;等等.此外,还讨论了右GP-V-环什么时候是Von Neumann正则环.

  13. On {pi}gp-continuous functions in topological spaces

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Han E-mail: jihpark@pknu.ac.kr; Park, Jin Keun

    2004-05-01

    The concept of {pi}gp-closed sets was introduced by Park [On {pi}gp-closed sets in topological spaces, Indian J. Pure Appl. Math., in press]. The aim of this paper is to consider and characterize {pi}gp-irresolute and {pi}gp-continuous functions via the concept of {pi}gp-closed sets and to relate these concepts to the classes of {pi}GPO-compact spaces and {pi}GP-connected spaces.

  14. High Temperature Superconducting State in Metallic Nanoclusters and Nano-Based Systems

    Science.gov (United States)

    2013-12-01

    the Nonlinear Schrodinger Equation” JETP 112, 469-478 (2011) The nonlinear Schrodinger equation, known in low-temperature physics as Gross...paper we study the Gross-Pitaevskii equation of the theory of superfluidity, i.e. the nonlinear Schrodinger equation of the Ginzburg-Landau type. We

  15. Optimal state discrimination and unstructured search in nonlinear quantum mechanics

    Science.gov (United States)

    Childs, Andrew M.; Young, Joshua

    2016-02-01

    Nonlinear variants of quantum mechanics can solve tasks that are impossible in standard quantum theory, such as perfectly distinguishing nonorthogonal states. Here we derive the optimal protocol for distinguishing two states of a qubit using the Gross-Pitaevskii equation, a model of nonlinear quantum mechanics that arises as an effective description of Bose-Einstein condensates. Using this protocol, we present an algorithm for unstructured search in the Gross-Pitaevskii model, obtaining an exponential improvement over a previous algorithm of Meyer and Wong. This result establishes a limitation on the effectiveness of the Gross-Pitaevskii approximation. More generally, we demonstrate similar behavior under a family of related nonlinearities, giving evidence that the ability to quickly discriminate nonorthogonal states and thereby solve unstructured search is a generic feature of nonlinear quantum mechanics.

  16. GP73 — EDRN Public Portal

    Science.gov (United States)

    The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. GP73 is a type II Golgi transmembrane protein. It processes proteins synthesized in the rough endoplasmic reticulum and assists in the transport of protein cargo through the Golgi apparatus. The expression of the GP73 gene has been observed to be upregulated in response to viral infection. Alternatively spliced transcript variants encoding the same protein have been described for this gene. Kladeny, RD. et al. 2000, found significant up-regulation of GOLPH2 expression in human hepatocyte cells infected with a recombinant adenovirus. EDRN investigator Block, TM et al. 2005, found that GP73 over-expression in serum correlate with liver cancer in woodchucks and humans. Chinnayian's lab reported that GP73 transcript was over-expressed in prostate cancer patients urine sediment (Laxman B. et al. 2008).

  17. Military GP training-the future.

    Science.gov (United States)

    Herod, T P; Johnson, G A

    2013-01-01

    There is clearly a significant step from being a well-supported GP Registrar to being a fully independent GP in the NHS and this is even more apparent for a newly qualified Military GP There are many additional duties and responsibilities placed upon a Military GP that the current training curriculum and exams do not cover and which must be learnt post-CCT, whilst undertaking independent practice for the first time. Having a Military First 5 initiative for support during this time would no doubt be of some use, but having a dedicated period of training to re-militarise newly qualified Military GPs would provide an opportunity to improve and make more efficient the initial transition from training to independent practice. In the long term, incorporating as much as possible of this proposed period of post-CCT Military training into a 4th year of GP training would be the ideal. However, discussions between Surgeon General, the Defence Deanery and the RCGP would be required to define which training elements would be acceptable to be incorporated and there will no doubt be some aspects (e.g. weapons handling) that might be deemed unacceptable by the RCGP, and thus a period of post-CCT Military training may still be a key component of a longer term solution. The options for enhancing Military GP training warrant thorough exploration as they have the potential to provide significant benefit not only for future trainees but also for the military in general.

  18. Touchdown General Primer (GP5+/GP6+ PCR and optimized sample DNA concentration support the sensitive detection of human papillomavirus

    Directory of Open Access Journals (Sweden)

    Simmons-Arnold Linda

    2005-11-01

    approach. Of 26 breast tumors, 5 (19% tested HPV positive by the standard assay and 15/26 (58% using a touchdown protocol. Conclusion Touchdown modification of the GP5+/GP6+ PCR assay enables the detection of HPV undetected under regular assay conditions. The use of standardized DNA quantities in a PCR rather than standard sample volumes containing arbitrary amounts of DNA is supported. A touchdown approach may be beneficial as an analytical test for the re-evaluation of (apparently HPV negative abnormal cervical cytological or histological samples, and for investigating the association of HPV with disease conditions at diverse organ sites. The clinical utility of a touchdown approach for HPV detection requires further investigation as increased assay analytical sensitivity may not necessarily equate with improved clinical sensitivity or specificity.

  19. Numerical simulation of trapped dipolar quantum gases: Collapse studies and vortex dynamics

    KAUST Repository

    Sparber, Christof

    2010-01-01

    We numerically study the three dimensional Gross-Pitaevskii equation for dipolar quantum gases using a time-splitting algorithm. We are mainly concerned with numerical investigations of the possible blow-up of solutions, i.e. collapse of the condensate, and the dynamics of vortices. © American Institute of Mathematical Sciences.

  20. Bifurcation of Vortex Density Current in Trapped Bose Condensates

    Institute of Scientific and Technical Information of China (English)

    XU Tao; ZHANG ShengLi

    2002-01-01

    Vortex density current in the Gross-Pitaevskii theory is studied. It is shown that the inner structure of the topological vortices can be classified by Brouwer degrees and Hopf indices of φ-mapping. The dynamical equations of vortex density current have been given. The bifurcation behavior at the critical points of the current is discussed in detail.

  1. The Theory of Atom Lasers

    OpenAIRE

    Ballagh, R.; Savage, C. M.

    2000-01-01

    We review the current theory of atom lasers. A tutorial treatment of second quantisation and the Gross-Pitaevskii equation is presented, and basic concepts of coherence are outlined. The generic types of atom laser models are surveyed and illustrated by specific examples. We conclude with detailed treatments of the mechanisms of gain and output coupling.

  2. Chaos in a Bose-Einstein condensate

    Institute of Scientific and Technical Information of China (English)

    Wang Zhi-Xia; Ni Zheng-Guo; Cong Fu-Zhong; Liu Xue-Shen; Chen Lei

    2010-01-01

    It is demonstrated that Smale-horseshoe chaos exists in the time evolution of the one-dimensional Bose-Einstein condensate driven by time-periodic harmonic or inverted-harmonic potential.A formally exact solution of the timedependent Gross-Pitaevskii equation is constructed,which describes the matter shock waves with chaotic or periodic amplitudes and phases.

  3. Parametric resonance of capillary waves at the interface between two immiscible Bose-Einstein condensates

    NARCIS (Netherlands)

    Kobyakov, D.; Bychkov, V.; Lundh, E.; Bezett, A.H.; Marklund, M.

    2012-01-01

    We study the parametric resonance of capillary waves on the interface between two immiscible Bose-Einstein condensates pushed towards each other by an oscillating force. Guided by analytical models, we solve numerically the coupled Gross-Pitaevskii equations for a two-component Bose-Einstein condens

  4. Polypharmacy and older people - the GP perspective

    DEFF Research Database (Denmark)

    Vass, M; Hendriksen, C

    2005-01-01

    is recommended at every encounter, and time consuming comprehensive follow-up will be demanded, 'polypharmacy consultations' surely will be built into GP contracts in the future. The authors state that a number of pharmacological regimens for older people are outperformed by non-pharmacological treatment...

  5. Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GP1 Ectodomain Shedding

    Science.gov (United States)

    2008-12-23

    contributors Abstract Background: Sera from convalescent Lassa fever patients often contains antibodies to Lassa virus (LASV) glycoprotein 1 (GP1...uncoupled proteins will improve current diagnostics, treatment, and prevention of Lassa fever . To this end, mammalian expression systems were engineered for...stages of Lassa fever . Published: 23 December 2008 Virology Journal 2008, 5:161 doi:10.1186/1743-422X-5-161 Received: 14 December 2008 Accepted: 23

  6. Cystein 402 of HIV gp 120 is essential for CD4-binding and resistance of gp 120 to intracellular degradation.

    Science.gov (United States)

    Hemming, A; Bolmstedt, A; Flodby, P; Lundberg, L; Gidlund, M; Wigzell, H; Olofsson, S

    1989-01-01

    A DNA fragment encoding the CD4-binding region of human immunodeficiency virus type 1 (HIV) gp 120 was excised from an SV40-based expression vector containing gp 160, and subcloned into phage M13 for site-directed mutagenesis. Mutant vectors were constructed and CV-1 cells were transfected with constructs, where Cys402 was substituted for a serine, and metabolically labelled with [3H]-N-acetylglucosamine (GlcN). Radioimmunoprecipitation with an hyperimmunserum, specific for gp 120/gp 160, and subsequent SDS-polyacrylamide gel electrophoresis demonstrated presence of gp 160, whereas gp 120 was replaced by [3H]-GlcN-labelled material, migrating as a diffuse band corresponding to 80-105k, suggesting increased sensitivity of mutant env gene products to proteolysis after cleavage to gp 120. Wild type gp 120 and gp 160 bound to CD4, whereas neither gp 160 nor gp 120 from mutant-transfected cell lysates did bind to CD4. Altogether the results indicated that Cys402, probably by participating in a disulfide bridge, is essential for (i) the CD4-binding ability of env gene products and for (ii) the physical stability of gp 120.

  7. Endocytic Trafficking of HIV gp120 is Mediated by Dynamin and Plays a Role in gp120 Neurotoxicity.

    Science.gov (United States)

    Wenzel, Erin D; Bachis, Alessia; Avdoshina, Valeria; Taraballi, Francesca; Tasciotti, Ennio; Mocchetti, Italo

    2017-09-01

    Neurons that endocytose the human immunodeficiency virus-1 (HIV) protein gp120 exhibit neurite retraction and activation of caspase-3, suggesting that the endocytic process may be crucial for gp120-mediated neuronal injury. The goal of this study is to demonstrate that internalization and accumulation of gp120 play a role in its neurotoxic effects. In mammalian cells, endocytosis is primarily a dynamin-dependent process. To establish whether gp120 is endocytosed in a dynamin-dependent manner, we used fibroblasts in which deletion of dynamins was induced by tamoxifen. We observed a robust reduction of intracellular gp120 immunoreactivity in tamoxifen-treated cells. To examine whether endocytosis of gp120 is crucial for its neurotoxic effect, we blocked gp120 internalization into primary rat cortical neurons by dynasore, an inhibitor of the dynamin GTP-ase activity. We found that dynasore blocks both gp120 internalization and neurotoxicity. We then utilized gp120-loaded mesoporous silica nanoparticles to deliver gp120 intracellularly. We established that once internalized, gp120 is neurotoxic regardless of chemokine receptor activation. Our data suggest that dynamin-dependent endocytosis of gp120 is critical for its neurotoxicity.

  8. Statistical analysis of highly correlated systems in biology and physics

    Science.gov (United States)

    Martin, Hector Garcia

    In this dissertation, I present my work on the statistical study of highly correlated systems in three fields of science: ecology, microbial ecology and physics. I propose an explanation for how the highly correlated distribution of species individuals, and an abundance distribution commonly observed in ecological systems, give rise to a power law dependence between a given area and the number of unique species it harbors. This is one of the oldest known ecological patterns: the power-law Species Area Rule. As a natural extension of my studies in ecology, I have undertaken both theoretical research and field work in the developing field of microbial ecology. In particular, I participated in a multidisciplinary study of the impact of microbes on the formation of macroscopic calcium carbonate terraces at Yellowstone National Park Hot Springs. I have used ecological techniques to characterize the biodiversity of our study site and developed a new bootstrap method for extracting abundance information from clone libraries. This has singled out the most abundant microorganisms and paved the way for future studies of the possible non-passive role of microorganisms in carbonate precipitation. The third part of my thesis uses statistical techniques to explore the correlations in rotating Bose-Einstein condensates. I have used finite difference techniques to solve the Gross-Pitaevskii equation in order to obtain the structure of a vortex in a lattice. Surprisingly, I have found that, in order to understand this structure, it is necessary to add a correction to the Gross-Pitaevskii equation which introduces a dependence on the particle scattering length. I have also used Path Integral Monte Carlo techniques to explore the limit of rapid rotations, where the Gross-Pitaevskii equation is no longer valid. Interestingly, the Gross-Pitaevskii equation seems to be valid for much higher densities than expected if properly renormalized. I show that, in accord with the prediction of

  9. Main: 1GP4 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1GP4 シロイヌナズナ Arabidopsis Arabidopsis thaliana (L.) Heynh. Leucoanthocyanidin Dioxyg...enase Name=Ldox; Orderedlocusnames=At4g22880; Orfnames=F7h19.60; Arabidopsis Thaliana Molecule: Anthocyanidin... Synthase; Synonym: Leucoanthocyanidin Dioxygenase; Chain: A; Engineered: Yes Oxygenase R.C.Wilmouth, J.J.T...rnbull, R.Welford, I.Clifton, A.Prescott, C.Schofield Structure And Mechanism Of Anthocyanidin Synthase From

  10. Hyperion 5113/GP Infrasound Sensor Evaluation.

    Energy Technology Data Exchange (ETDEWEB)

    Merchant, Bion J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    Sandia National Laboratories has tested and evaluated an infrasound sensor, the 5113/GP manufactured by Hyperion. These infrasound sensors measure pressure output by a methodology developed by the University of Mississippi. The purpose of the infrasound sensor evaluation was to determine a measured sensitivity, transfer function, power, self-noise, dynamic range, and seismic sensitivity. These sensors are being evaluated prior to deployment by the U.S. Air Force.

  11. GP Workbench Manual: Technical Manual, User's Guide, and Software Guide

    Science.gov (United States)

    Oden, Charles P.; Moulton, Craig W.

    2006-01-01

    GP Workbench is an open-source general-purpose geophysical data processing software package written primarily for ground penetrating radar (GPR) data. It also includes support for several USGS prototype electromagnetic instruments such as the VETEM and ALLTEM. The two main programs in the package are GP Workbench and GP Wave Utilities. GP Workbench has routines for filtering, gridding, and migrating GPR data; as well as an inversion routine for characterizing UXO (unexploded ordinance) using ALLTEM data. GP Workbench provides two-dimensional (section view) and three-dimensional (plan view or time slice view) processing for GPR data. GP Workbench can produce high-quality graphics for reports when Surfer 8 or higher (Golden Software) is installed. GP Wave Utilities provides a wide range of processing algorithms for single waveforms, such as filtering, correlation, deconvolution, and calculating GPR waveforms. GP Wave Utilities is used primarily for calibrating radar systems and processing individual traces. Both programs also contain research features related to the calibration of GPR systems and calculating subsurface waveforms. The software is written to run on the Windows operating systems. GP Workbench can import GPR data file formats used by major commercial instrument manufacturers including Sensors and Software, GSSI, and Mala. The GP Workbench native file format is SU (Seismic Unix), and subsequently, files generated by GP Workbench can be read by Seismic Unix as well as many other data processing packages.

  12. Allosteric modulation of the HIV-1 gp120-gp41 association site by adjacent gp120 variable region 1 (V1 N-glycans linked to neutralization sensitivity.

    Directory of Open Access Journals (Sweden)

    Heidi E Drummer

    Full Text Available The HIV-1 gp120-gp41 complex, which mediates viral fusion and cellular entry, undergoes rapid evolution within its external glycan shield to enable escape from neutralizing antibody (NAb. Understanding how conserved protein determinants retain functionality in the context of such evolution is important for their evaluation and exploitation as potential drug and/or vaccine targets. In this study, we examined how the conserved gp120-gp41 association site, formed by the N- and C-terminal segments of gp120 and the disulfide-bonded region (DSR of gp41, adapts to glycan changes that are linked to neutralization sensitivity. To this end, a DSR mutant virus (K601D with defective gp120-association was sequentially passaged in peripheral blood mononuclear cells to select suppressor mutations. We reasoned that the locations of suppressors point to structural elements that are functionally linked to the gp120-gp41 association site. In culture 1, gp120 association and viral replication was restored by loss of the conserved glycan at Asn¹³⁶ in V1 (T138N mutation in conjunction with the L494I substitution in C5 within the association site. In culture 2, replication was restored with deletion of the N¹³⁹INN sequence, which ablates the overlapping Asn¹⁴¹-Asn¹⁴²-Ser-Ser potential N-linked glycosylation sequons in V1, in conjunction with D601N in the DSR. The 136 and 142 glycan mutations appeared to exert their suppressive effects by altering the dependence of gp120-gp41 interactions on the DSR residues, Leu⁵⁹³, Trp⁵⁹⁶ and Lys⁶⁰¹. The 136 and/or 142 glycan mutations increased the sensitivity of HIV-1 pseudovirions to the glycan-dependent NAbs 2G12 and PG16, and also pooled IgG obtained from HIV-1-infected individuals. Thus adjacent V1 glycans allosterically modulate the distal gp120-gp41 association site. We propose that this represents a mechanism for functional adaptation of the gp120-gp41 association site to an evolving glycan

  13. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility

    Energy Technology Data Exchange (ETDEWEB)

    Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E.; Schief, William R.; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D. (UWASH); (NIH); (Tulane); (DFCI)

    2010-04-15

    The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded {beta}-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate - and structurally plastic - layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated {beta}-sandwich and providing for conformational diversity used in immune evasion. A 'layered' gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a {beta}-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

  14. HEAT SHOCK PROTEIN gp96 AND CANCER IMMUNOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    岳培彬; 杨树德; 黄常志

    2002-01-01

    Heat shock protein gp96 is a highly conserved and monomorphic glycoprotein in the endoplasmic reticulum.It functions as molecular chaperone and can associate with a variety of antigenic peptides noncovalently in vivo and in vitro. Recent studies have indicated that gp96 molecules participate in major histocompatibility complex class I - restricted antigen presentation pathway. Immunization of mice with gp96 preparations isolated from cancer cells can elicit a cancer - specific protective T cell immune response that is recallable, which is a prerequisite for gp96 as a therapeutic vaccine against cancers. The immunogenicity of gp96 molecules has been attributed to the antigenic peptides associated with them. These phenomena provide a new pathway for cancer immunotherapy. The mechanism that the gp96 -peptide complex induces specific immune response and the explorations for gp96 - peptide complex as a therapeutic cancer vaccine are reviewed.

  15. Characterization of Immune Responses Induced by Ebola Virus Glycoprotein (GP) and Truncated GP Isoform DNA Vaccines and Protection Against Lethal Ebola Virus Challenge in Mice

    Science.gov (United States)

    Li, Wenfang; Ye, Ling; Carrion, Ricardo; Mohan, Gopi S.; Nunneley, Jerritt; Staples, Hilary; Ticer, Anysha; Patterson, Jean L.; Compans, Richard W.; Yang, Chinglai

    2015-01-01

    In addition to its surface glycoprotein (GP), Ebola virus directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. We recently reported that sGP actively diverts host antibody responses against the epitopes that it shares with GP and thereby allows itself to absorb anti-GP antibodies, a phenomenon we termed “antigenic subversion.” To investigate the effect of antigenic subversion by sGP on protection against virus infection, we compared immune responses induced by different prime-boost immunization regimens with GP and sGP DNA vaccines in mice and their efficacy against lethal Ebola virus challenge. Similar levels of anti-GP antibodies were induced by 2 immunizations with sGP and GP DNA vaccines. However, 2 immunizations with GP but not sGP DNA vaccine fully protected mice from lethal challenge. Boosting with sGP or GP DNA vaccine in mice that had been primed by GP or sGP DNA vaccine augmented the levels of anti-GP antibody responses and further improved protective efficacy against Ebola virus infection. These results show that both the quality and the levels of anti-GP antibody responses affect the efficacy of protection against Ebola virus infection. PMID:25877553

  16. Verification of 'learning credits' by GP appraisers.

    Science.gov (United States)

    Murie, Jill; Wakeling, Judy

    2011-11-01

    The RCGP CPD Learning Credits system aims to enable GPs to demonstrate knowledge and skills relevant to their daily practice. Credits are self-assessed and will form part of the 'evidence' necessary for successful revalidation. At an appraisal, GP appraisers verify the credits in terms of the time spent on the CPD activity and its impact on the GP's practice. The purpose of this study was to examine the extent to which GPs (as appraisees) are able to self-assess their own learning and, as appraisers, verify credits in a standardised way. All 17 GP appraisers in NHS Lanarkshire were invited to participate in a study, which triangulated three sources of evidence on credits: self-rating, peer-assessment and workshop discussion. The resultant data were analysed on an Excel spreadsheet. Outcomes included self-assessed credit value, peer-assessed mean score (range) and free text. Of the 17 appraisers, 15 completed the paperwork and 13 attended the workshop. GPs' self-assessed learning credits were equivalent to peer-assessed score in 5/15 cases, but considered overestimates in 4/15 and underestimates in 6/15 cases. The most extreme variance was for an oncology module, where the variance ranged from 28% to 200% of the self-assessed score. GPs have a variable understanding of how to award themselves learning credits and of how to judge the credits of potential appraisees. Without adequate resources for appraisal training, validated instruments, calibration and reliability, verification of the learning credit system will be flawed by its subjective and arbitrary nature.

  17. Supply and demand in physician markets: a panel data analysis of GP services in Australia.

    Science.gov (United States)

    McRae, Ian; Butler, James R G

    2014-09-01

    To understand the trends in any physician services market it is necessary to understand the nature of both supply and demand, but few studies have jointly examined supply and demand in these markets. This study uses aggregate panel data on general practitioner (GP) services at the Statistical Local Area level in Australia spanning eight years to estimate supply and demand equations for GP services. The structural equations of the model are estimated separately using population-weighted fixed effects panel modelling with the two stage least squares formulation of the generalised method of moments approach (GMM (2SLS)). The estimated price elasticity of demand of [Formula: see text] is comparable with other studies. The direct impact of GP density on demand, while significant, proves almost immaterial in the context of near vertical supply curves. Supply changes are therefore due to shifts in the position of the curves, partly determined by a time trend. The model is validated by comparing post-panel model predictions with actual market outcomes over a period of three years and is found to provide surprisingly accurate projections over a period of significant policy change. The study confirms the need to jointly consider supply and demand in exploring the behaviour of physician services markets.

  18. Prediction of the secondary structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, J E; Lund, O; Nielsen, Jens Ole

    1996-01-01

    Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  19. Prediction of the Secondary Structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, Jan; Lund, Ole; Nielsen, Jens O.

    1996-01-01

    Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  20. GP130 activation induces myeloma and collaborates with MYC

    Science.gov (United States)

    Dechow, Tobias; Steidle, Sabine; Götze, Katharina S.; Rudelius, Martina; Behnke, Kerstin; Pechloff, Konstanze; Kratzat, Susanne; Bullinger, Lars; Fend, Falko; Soberon, Valeria; Mitova, Nadya; Li, Zhoulei; Thaler, Markus; Bauer, Jan; Pietschmann, Elke; Albers, Corinna; Grundler, Rebekka; Schmidt-Supprian, Marc; Ruland, Jürgen; Peschel, Christian; Duyster, Justus; Rose-John, Stefan; Bassermann, Florian; Keller, Ulrich

    2014-01-01

    Multiple myeloma (MM) is a plasma cell neoplasm that results from clonal expansion of an Ig-secreting terminally differentiated B cell. Advanced MM is characterized by tissue damage that involves bone, kidney, and other organs and is typically associated with recurrent genetic abnormalities. IL-6 signaling via the IL-6 signal transducer GP130 has been implicated as an important driver of MM pathogenesis. Here, we demonstrated that ectopic expression of constitutively active GP130 (L-GP130) in a murine retroviral transduction-transplantation model induces rapid MM development of high penetrance. L-GP130–expressing mice recapitulated all of the characteristics of human disease, including monoclonal gammopathy, BM infiltration with lytic bone lesions, and protein deposition in the kidney. Moreover, the disease was easily transplantable and allowed different therapeutic options to be evaluated in vitro and in vivo. Using this model, we determined that GP130 signaling collaborated with MYC to induce MM and was responsible and sufficient for directing the plasma cell phenotype. Accordingly, we identified Myc aberrations in the L-GP130 MM model. Evaluation of human MM samples revealed recurrent activation of STAT3, a downstream target of GP130 signaling. Together, our results indicate that deregulated GP130 activity contributes to MM pathogenesis and that pathways downstream of GP130 activity have potential as therapeutic targets in MM. PMID:25384216

  1. Transport in a capacitive ultracold atomtronic circuit

    Science.gov (United States)

    Edwards, Mark; Eller, Benjamin; Eckel, Steve; Clark, Charles

    A recent NIST experiment studied the transport of a gaseous Bose-Einstein condensate (BEC) confined in an atomtronic ``dumbbell'' circuit. The optically created condensate potential consisted of a tight harmonic potential in the vertical direction confining the BEC to a horizontial plane. The horizontal potential consisted of two cylindrical wells separated by a channel produced by a harmonic oscillator potential transverse to the line joining the wells. The BEC, formed in the ``source'' well, was released to flow toward the ``drain'' well. The evolution of this system was shown to be reproduced by a model electronic circuit consisting of a charged capacitor, C, in series with an inductor, L, and a parallel combination of a resistor, R, and a Josephson junction. We modeled this system with the Gross-Pitaevskii (GP) equation and found good agreement with the data provided that the confining potential is carefully reproduced. The GP simulations show behavior, not detectable in the experiment, that atoms can jump out of the dumbbell area after filling up the drain well. We also present the dependence of R and L on the channel shape. Supported by NSF Grants PHY-1413768 and ARO Atomtronics MURI.

  2. Kinetic Thomas–Fermi solutions of the Gross–Pitaevskii equation

    NARCIS (Netherlands)

    Ölschläger, M.; Wirth, G.; de Morais Smith, C.; Hemmerich, Andreas

    2009-01-01

    Approximate solutions of the Gross–Pitaevskii (GP) equation, obtained upon neglection of the kinetic energy, are well known as Thomas–Fermi solutions. They are characterized by the compensation of the local potential by the collisional energy. In this article we consider exact solutions of the GP-eq

  3. Prediction of the secondary structure of HIV-1 gp120

    DEFF Research Database (Denmark)

    Hansen, J E; Lund, O; Nielsen, Jens Ole

    1996-01-01

    The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

  4. Musculoskeletal (MSK) and Sport and Exercise Medicine (SEM) in General Practice (GP): A Novel GP-based MSK and SEM Clinic for Managing Musculoskeletal symptoms in a GP.

    Science.gov (United States)

    Heron, Neil

    2015-01-01

    Musculoskeletal (MSK) complaints are common within primary care (1) (2) (3) but some General Practitioners (GPs)/family physicians do not feel comfortable managing these symptoms (3), preferring to refer onto hospital specialists or Integrated Clinical Assessment and Treatment Services (ICATs). Long waiting times for hospital outpatient reviews are a major cause of patient inconvenience and complaints (4). We therefore aimed to establish a GP-ran MSK and sport and exercise medicine (SEM) clinic based within a Belfast GP surgery that would contribute to a sustainable improvement in managing these common conditions within primary care as well as reducing waiting times for patients with these conditions to see a specialist. This shift from hospital-based to community-based management is in-keeping with recent policy changes within the UK health-system, including Transforming Your Care within Northern Ireland (NI) (5). The GP-ran MSK and SEM clinic was held monthly within a Belfast GP practice, staffed by one GP with a specialist interest in MSK and SEM conditions and its performance was reviewed over a three month period. Parameters audited included cases seen, orthopaedic and x-ray referral rates and secondary care referrals comparing the GP practice's performance to the same time period in the previous year as well as patient satisfaction questionnaires.

  5. Josephson Dynamics of a Bose-Einstein Condensate Trapped in a Double-Well Potential

    Institute of Scientific and Technical Information of China (English)

    YANG Hong-Wei; ZUO Wei

    2007-01-01

    The Josephson equations for a Bose-Einstein Condensate gas trapped in a double-well potential are derived with the two-mode approximation by the Gross-Pitaevskii equation. The dynamical characteristics of the equations are obtained by the numerical phase diagrams. The nonlinear self-trapping effect appeared in the phase diagrams are emphatically discussed, and the condition EcN>4EJ is presented.

  6. β2GP1, Anti-β2GP1 Antibodies and Platelets: Key Players in the Antiphospholipid Syndrome

    Directory of Open Access Journals (Sweden)

    Yik C. Ho

    2016-05-01

    Full Text Available Anti-beta 2 glycoprotein 1 (anti-β2GP1 antibodies are commonly found in patients with autoimmune diseases such as the antiphospholipid syndrome (APS and systemic lupus erythematosus (SLE. Their presence is highly associated with increased risk of vascular thrombosis and/or recurrent pregnancy-related complications. Although they are a subtype of anti-phospholipid (APL antibody, anti-β2GP1 antibodies form complexes with β2GP1 before binding to different receptors associated with anionic phospholipids on structures such as platelets and endothelial cells. β2GP1 consists of five short consensus repeat termed “sushi” domains. It has three interchangeable conformations with a cryptic epitope at domain 1 within the molecule. Anti-β2GP1 antibodies against this cryptic epitope are referred to as ‘type A’ antibodies, and have been suggested to be more strongly associated with both vascular and obstetric complications. In contrast, ‘type B’ antibodies, directed against other domains of β2GP1, are more likely to be benign antibodies found in asymptomatic patients and healthy individuals. Although the interactions between anti-β2GP1 antibodies, β2GP1, and platelets have been investigated, the actual targeted metabolic pathway(s and/or receptor(s involved remain to be clearly elucidated. This review will discuss the current understanding of the interaction between anti-β2GP1 antibodies and β2GP1, with platelet receptors and associated signalling pathways.

  7. Review: Gp-340/DMBT1 in mucosal innate immunity

    DEFF Research Database (Denmark)

    Madsen, Jens; Mollenhauer, Jan; Holmskov, Uffe

    2010-01-01

    Deleted in Malignant Brain Tumour 1 (DMBT1) is a gene that encodes alternatively spliced proteins involved in mucosal innate immunity. It also encodes a glycoprotein with a molecular mass of 340 kDa, and is referred to as gp-340 (DMBT1(gp340)) and salivary agglutinin (DMBT1(SAG)). DMBT1(gp340...... proteins, including serum and secretory IgA, C1q, lactoferrin, MUC5B and trefoil factor 2 (TFF2), all molecules with involvement in innate immunity and/or wound-healing processes. Recent generation of Dmbt1-deficient mice has provided the research field of DMBT1 with a model that allows research...

  8. ARC Code TI: Block-GP: Scalable Gaussian Process Regression

    Data.gov (United States)

    National Aeronautics and Space Administration — Block GP is a Gaussian Process regression framework for multimodal data, that can be an order of magnitude more scalable than existing state-of-the-art nonlinear...

  9. GP73的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨盛力; 潘晓莉

    2011-01-01

    高尔基体糖蛋白- 73( Golgi Protein 73,GP73)又称Ⅱ型高尔基体膜蛋白(Golgi phosphoprotein 2,GOLPH2)和GOLM1,因其在SDS-PAGE中显示相对分子质量为7.3×104,所以称为GP73[1].近期研究表明,GP73在多种疾病中表达异常,但GP73与肝脏疾病,尤其同肝癌关系密切,有望成为肝癌早期诊断的血清学标志物,且敏感性优于AFP.

  10. Stability of Bright Solitons in Bose-Einstein Condensates

    Institute of Scientific and Technical Information of China (English)

    YU Hui-You; YAN Jia-Ren; XIE Qiong-Tao

    2004-01-01

    We investigate the stability of bright solitons in Bose-Einstein condensates by including a feeding term and a loss one in the Gross-Pitaevskii equation. Based on the direct approach of perturbation theory for the nonlinear Schrodinger equation, we give the explicit dependence of the height and other related quantities of bright solitons on the feeding and loss term. It is found that the three-body recombination loss plays a crucial role in stabilizing bright solitons.

  11. HIV跨膜蛋白gp36和gp41的截短及融合表达%Truncation and Fusion Expression of Tans-membrane Proteins gp36 and gp41 of HIV

    Institute of Scientific and Technical Information of China (English)

    肖健; 朱华松; 尹娟; 孙可芳; 汪超英; 端义坤; 余模松

    2006-01-01

    目的将HIV-1的跨膜蛋白gp41和HIV-2跨膜蛋白gp36进行截短,并在大肠杆菌中进行融合表达.方法用PCR将gp41和gp36的编码基因进行截短,回收的PCR产物纯化后克隆到连接载体pGEM-T上,然后用BamH Ⅰ、EcoR Ⅰ和SalⅠ切下目的基因,并构建到表达载体pGEX-4T-3,导入宿主细胞BL21,用IPTG诱导表达.结果酶切鉴定显示,截短的HIV-1 gp41和HIV-2 gp36跨膜蛋白基因大小与预期的一致,表达产物经SDS-PAGE分析显示在相对分子质量66 000处出现融合表达条带,Western blot分析显示,与相应抗体出现特异性反应.结论已成功对gp41和gp36跨膜蛋白进行截短,并构建表达载体进行表达,为跨膜蛋白的进一步应用研究奠定基础.

  12. Antioxidant protection from HIV-1 gp120-induced neuroglial toxicity

    Directory of Open Access Journals (Sweden)

    Walsh Kimberley A

    2004-05-01

    Full Text Available Abstract Background The pathogenesis of HIV-1 glycoprotein 120 (gp120 associated neuroglial toxicity remains unresolved, but oxidative injury has been widely implicated as a contributing factor. In previous studies, exposure of primary human central nervous system tissue cultures to gp120 led to a simplification of neuronal dendritic elements as well as astrocytic hypertrophy and hyperplasia; neuropathological features of HIV-1-associated dementia. Gp120 and proinflammatory cytokines upregulate inducible nitric oxide synthase (iNOS, an important source of nitric oxide (NO and nitrosative stress. Because ascorbate scavenges reactive nitrogen and oxygen species, we studied the effect of ascorbate supplementation on iNOS expression as well as the neuronal and glial structural changes associated with gp120 exposure. Methods Human CNS cultures were derived from 16–18 week gestation post-mortem fetal brain. Cultures were incubated with 400 μM ascorbate-2-O-phosphate (Asc-p or vehicle for 18 hours then exposed to 1 nM gp120 for 24 hours. The expression of iNOS and neuronal (MAP2 and astrocytic (GFAP structural proteins was examined by immunohistochemistry and immunofluorescence using confocal scanning laser microscopy (CSLM. Results Following gp120 exposure iNOS was markedly upregulated from undetectable levels at baseline. Double label CSLM studies revealed astrocytes to be the prime source of iNOS with rare neurons expressing iNOS. This upregulation was attenuated by the preincubation with Asc-p, which raised the intracellular concentration of ascorbate. Astrocytic hypertrophy and neuronal injury caused by gp120 were also prevented by preincubation with ascorbate. Conclusions Ascorbate supplementation prevents the deleterious upregulation of iNOS and associated neuronal and astrocytic protein expression and structural changes caused by gp120 in human brain cell cultures.

  13. Scalar field as a Bose-Einstein condensate?

    Energy Technology Data Exchange (ETDEWEB)

    Castellanos, Elías; Escamilla-Rivera, Celia [Mesoamerican Centre for Theoretical Physics (ICTP regional headquarters in Central America, the Caribbean and Mexico), Universidad Autónoma de Chiapas, Carretera Zapata Km. 4, Real del Bosque (Terán), 29040, Tuxtla Gutiérrez, Chiapas (Mexico); Macías, Alfredo [Departamento de Física, Universidad Autónoma Metropolitana-Iztapalapa, A.P. 55-534, Mexico D.F. 09340 (Mexico); Núñez, Darío, E-mail: ecastellanos@mctp.mx, E-mail: cescamilla@mctp.mx, E-mail: amac@xanum.uam.mx, E-mail: nunez@nucleares.unam.mx [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C.U., A.P. 70-543, México D.F. 04510 (Mexico)

    2014-11-01

    We discuss the analogy between a classical scalar field with a self-interacting potential, in a curved spacetime described by a quasi-bounded state, and a trapped Bose-Einstein condensate. In this context, we compare the Klein-Gordon equation with the Gross-Pitaevskii equation. Moreover, the introduction of a curved background spacetime endows, in a natural way, an equivalence to the Gross-Pitaevskii equation with an explicit confinement potential. The curvature also induces a position dependent self-interaction parameter. We exploit this analogy by means of the Thomas-Fermi approximation, commonly used to describe the Bose-Einstein condensate, in order to analyze the quasi bound scalar field distribution surrounding a black hole.

  14. EIAV gp45和HIV gp120基因在不同表达系统中表达效果比较%Effect Comparison of EIAV gp45 and HIV gp120 Genes Using Different Expressional Systems

    Institute of Scientific and Technical Information of China (English)

    崔严方; 孙佩龙; 刘新奇

    2011-01-01

    马传染性贫血病毒(EIAV) gp45基因编码跨膜蛋白TM,该蛋白在介导病毒与靶细胞之间的融膜过程中起关键作用.gp120蛋白是人类免疫缺陷病毒(HIV)的外膜糖蛋白,是病毒的主要抗原.通过大肠杆菌原核表达系统和果蝇细胞真核表达系统分别表达gp45及gp120,并对其表达效果进行对比,结果表明:在大肠杆菌表达系统中,gp45可成功表达,而gp120却不能表达.在真核表达系统中,gp120成功表达,而gp45却未能表达.通过对这两种系统表达情况效果的比较,发现gp45在原核系统中表达有利,而gp120在真核系统中表达有优势,表明这些基因的表达具有特异性,本研究指导我们根据特定的基因选用适当的表达系统,以便纯化所需的目的蛋白,同时也为深入研究HIV的包膜蛋白的生物学结构特性及推动相关疫苗的研究奠定基础.%Equine Infectious Anemia Virus (EIAV) gp45 gene codes transmembrane protein TM, which plays a key role in mediating membrane fusion reaction between virus and target cells. Gpl20 protein is the outer membrane glycoprotein of human immunodeficiency virus (HIV) , which is the major antigen of virus. In this paper, gp45 and gpl20 genes were expressed individually in prokaryotic and eukaryotic expression systems in order to contrast the expressional effects. The results showed that in E. Coli gp45 was successfully expressed, but gpl20 was not expressed. In eukaryotic drosophila S2 cells gpl20 expressed, but gp45 did not expressed. By comparison, gp45 expressed advantageously in E coli, but gpl20 expressed dominantly in drosophila S2 cells, which suggested that these genes had expressional specificities. The studies in the paper guide us to choose the proper expression systems according to the specific genes in order to purify target proteins. Meanwhile, this will lay foundation for further studying biology structural characteristics of HIV membrane proteins and the promotion of related

  15. Liposome-mediated cellular delivery of active gp91(phox.

    Directory of Open Access Journals (Sweden)

    Bruno Marques

    Full Text Available BACKGROUND: Gp91(phox is a transmembrane protein and the catalytic core of the NADPH oxidase complex of neutrophils. Lack of this protein causes chronic granulomatous disease (CGD, a rare genetic disorder characterized by severe and recurrent infections due to the incapacity of phagocytes to kill microorganisms. METHODOLOGY: Here we optimize a prokaryotic cell-free expression system to produce integral mammalian membrane proteins. CONCLUSIONS: Using this system, we over-express truncated forms of the gp91(phox protein under soluble form in the presence of detergents or lipids resulting in active proteins with a "native-like" conformation. All the proteins exhibit diaphorase activity in the presence of cytosolic factors (p67(phox, p47(phox, p40(phox and Rac and arachidonic acid. We also produce proteoliposomes containing gp91(phox protein and demonstrate that these proteins exhibit activities similar to their cellular counterpart. The proteoliposomes induce rapid cellular delivery and relocation of recombinant gp91(phox proteins to the plasma membrane. Our data support the concept of cell-free expression technology for producing recombinant proteoliposomes and their use for functional and structural studies or protein therapy by complementing deficient cells in gp91(phox protein.

  16. Educational expectations of GP trainers. A EURACT needs analysis.

    Science.gov (United States)

    Guldal, Dilek; Windak, Adam; Maagaard, Roar; Allen, Justin; Kjaer, Niels K

    2012-12-01

    In this background paper, we discuss the educational needs of family medicine teachers and trainers in the light of a EURACT (European Academy of Teachers in General Practice) project aimed at the development of a European framework for the professional development of general practice (GP) educators. There is evidence that the ideal GP educator would benefit from systematic training in teaching skills. Although international literature indicates that such skills training should be in supervision, feedback, assessment and educational management, it is not clear if these needs vary between trainers who teach general practice in different settings and environments. Needs assessment: Recently EURACT, in collaboration with partners from five EU countries and Turkey, set up a project aimed at the development of a comprehensive 'training the trainers' programme. The project included a baseline survey of perceived educational needs and wants among both novice and expert European GP educators. The survey demonstrated that the educational needs of GP educators did not vary much in the content areas in which training was required throughout Europe but did vary in the level and depth of knowledge needed; this depended on their experience and level of expertise as teachers. Based on the information gathered and experience gained from previous EURACT courses, a Leonardo da Vinci project has developed and launched a comprehensive programme with courses at three levels of participant expertise, to address the personal learning needs of GP educators.

  17. Reconnection of superfluid vortex bundles.

    Science.gov (United States)

    Alamri, Sultan Z; Youd, Anthony J; Barenghi, Carlo F

    2008-11-21

    Using the vortex filament model and the Gross-Pitaevskii nonlinear Schroedinger equation, we show that bundles of quantized vortex lines in He II are structurally robust and can reconnect with each other maintaining their identity. We discuss vortex stretching in superfluid turbulence and show that, during the bundle reconnection process, kelvin waves of large amplitude are generated, in agreement with the finding that helicity is produced by nearly singular vortex interactions in classical Euler flows.

  18. Nonlinear Mixing of Collective Modes in Harmonically Trapped Bose-Einstein Condensates

    OpenAIRE

    Mizoguchi, Takahiro; Watabe, Shohei; Nikuni, Tetsuro

    2016-01-01

    We study nonlinear mixing effects among quadrupole modes and scissors modes in a harmonically trapped Bose-Einstein condensate. Using a perturbative technique in conjunction with a variational approach with a Gaussian trial wave function for the Gross-Pitaevskii equation, we find that mode mixing selectively occurs. Our perturbative approach is useful in gaining qualitative understanding of the recent experiment [Yamazaki et al., J. Phys. Soc. Japan 84, 44001 (2015)], exhibiting a beating phe...

  19. A Proposed Casimir-Like Effect Between Contaminants in Ideal Bose-Einstein Condensates

    OpenAIRE

    2007-01-01

    It is hypothesized that, within Bose-Einstein condensates, contaminants will form a potential that effects the energy state of a condensate. While assuming a system governed by the Gross-Pitaevskii equation, contaminants are modelled as boundary conditions for the wave function of the condensate. It is then found that the energy of the system depends directly upon the distance between contaminants. Energy is minimized as two particles either come together or move apart depending on the nature...

  20. Nonlinear Dynamics in Double Square Well Potential

    CERN Document Server

    Khomeriki, Ramaz; Ruffo, Stefano; Wimberger, Sandro; 10.1007/s11232-007-0096-y

    2009-01-01

    Considering the coherent nonlinear dynamics in double square well potential we find the example of coexistence of Josephson oscillations with a self-trapping regime. This macroscopic bistability is explained by proving analytically the simultaneous existence of symmetric, antisymmetric and asymmetric stationary solutions of the associated Gross-Pitaevskii equation. The effect is illustrated and confirmed by numerical simulations. This property allows to make suggestions on possible experiments using Bose-Einstein condensates in engineered optical lattices or weakly coupled optical waveguide arrays.

  1. Bouncing cosmologies from quantum gravity condensates

    CERN Document Server

    Oriti, Daniele; Wilson-Ewing, Edward

    2016-01-01

    We show how the large-scale cosmological dynamics can be obtained from the hydrodynamics of isotropic group field theory condensate states in the Gross-Pitaevskii approximation. The correct Friedmann equations are recovered in the semi-classical limit for some choices of the parameters in the action for the group field theory, and quantum gravity corrections arise in the high-curvature regime causing a bounce which generically resolves the big-bang and big-crunch singularities.

  2. The Weak-Coupling of Bose-Einstein Condensates

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xiao-Ji; MA Zao-Yuan; CHEN Xu-Zong; WANG Yi-Qiu

    2003-01-01

    The coherent characteristics of four trapped Bose-Einstein condensates (BEC) conjunct one by one in aring shape which is divided by two far off-resonant lasers, are studied. Four coupled Gross-Pitaevskii equations are usedto describe the dynamics of the system. Two kinds of self-trapping effects are discussed in the coupled BECs, and thephase diagrams for different initial conditions and different coupling strengths are discussed. This study can be used todetermine interaction parameters between atoms in BEC.

  3. Local management of the nonlinearity of Bose-Einstein condensates with pinched potentials

    Science.gov (United States)

    Guerreiro, A.; Silva, Nuno A.

    2016-12-01

    We present a proposal for the local control of the nonlinearity in quasi-one-dimensional Bose-Einstein condensates induced by a local pinching of the transverse confining potential. We investigate the scattering of bright matter-wave solitons through a pinched potential using numerical simulations of the full three-dimensional Gross-Pitaevskii equation and the corresponding effective one-dimensional model with spatially varying nonlinearity.

  4. Skyrmion Spin Textures In Polariton Microcavities

    CERN Document Server

    Cilibrizzi, Pasquale; Liew, Tim C H; Hoadi, Hamid; Askitopoulos, Alexis; Brodbeck, Sebastian; Schneider, Christian; Shelykh, Ivan A; Höfling, Sven; Lagoudakis, Pavlos

    2016-01-01

    We study the polarisation dynamics of a spatially expanding polariton condensate under nonresonant linearly polarized optical excitation. The spatially and temporally resolved polariton emission reveals the formation of Skyrmions in the form of a quadruplet polarisation pattern both in the linear and circular Stokes parameters and an octuplet in the diagonal polarisations. A theoretical model based on the Gross-Pitaevskii equation coupled with an exciton reservoir describes the nontrivial spin textures through the optical spin-Hall effect.

  5. Tannin inhibits HIV-1 entry by targeting gp41

    Institute of Scientific and Technical Information of China (English)

    Lin L(U); Shu-wen LIU; Shi-bo JIANG; Shu-guang WU

    2004-01-01

    AIM: To investigate the mechanism by which tannin inhibits HIV-1 entry into target cells. METHODS: The inhibitory activity of tannin on HIV-1 replication and entry was detected by p24 production and HIV-1-mediated cell fusion, respectively. The inhibitory activity on the gp41 six-helix bundle formation was determined by an improved sandwich ELISA. RESULTS: Tannins from different sources showed potent inhibitory activity on HIV-1 replication,HIV-1-mediated cell fusion, and the gp4 six-helix bundle formation. CONCLUSION: Tannin inhibits HIV-1 entry into target cells by interfering with the gp41 six-helix bundle formation, thus blocking HIV-1 fusion with the target cell.

  6. GP140/CDCPI in the Development of Prostate Cancer Metastasis

    Science.gov (United States)

    2013-09-01

    RM: The pluripotency of hair follicle stem cells. Cell Cycle 2006, 5:232–233 54. Hirst CE, Ng ES, Azzola L, Voss AK, Thomas T, Stanley EG, Elefanty...analyze the role of gp140/CDCP1 in prostate cancer metastasis and to determine whether targeting gp140/CDCP1 could serve as a treatment against...KS, Xin H: Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model. Cancer Res 2008, 68

  7. Patient influences on satisfaction and loyalty for GP services.

    Science.gov (United States)

    Rundle-Thiele, Sharyn; Russell-Bennett, Rebekah

    2010-04-01

    Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centered care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

  8. Expression of HIV trans-membrane protein gp41 and pronucleus gp36 and their antigenicity%HIV跨膜蛋白gp41和gp36原核表达及抗原性研究

    Institute of Scientific and Technical Information of China (English)

    袁作为; 帅光泽; 张君; 胡接力; 郑建

    2010-01-01

    目的 构建HIV跨膜蛋白gp41和gp36原核表达载体,诱导表达HIV抗原,为HIV快速诊断和蛋白疫苗研究提供材料基础.方法 用PCR方法对HIV-1包膜蛋白gp41和HIV-2包膜蛋白gp36基因序列进行全长、截短扩增,分别或以融合表达方式克隆入原核表达载体pQE30、pET32a(+)及pGST-MOLUC,重组质粒经异丙基硫代半乳糖苷(isopropyl-β-D-thiogalactopyranoside, IPTG)诱导表达,并经Ni-NAT或谷胱甘肽-Sepharose-4B层析柱亲和纯化HIV跨膜糖蛋白抗原,对获得的纯化抗原进行Western blot检测,利用HIV抗原制备ELISA检测试剂盒,并分析HIV临床样本. 结果 成功构建了HIV包膜蛋白的原核表达载体,利用亲和层析纯化得到了纯度较高的HIV包膜蛋白;Western blot分析结果证实表达纯化的HIV跨膜蛋白gp41(aa.538~718)、gp36(aa.533~764)以及gp41-gp36均能和HIV阳性血清反应;ELISA试剂盒检测临床样本显示,特异性达95%以上,灵敏度达100%.结论 获得了有生物学活性的HIV截短包膜蛋白,并可用于HIV快速检测试剂盒的研发.

  9. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa.

  10. Hill's equation

    CERN Document Server

    Magnus, Wilhelm

    2004-01-01

    The hundreds of applications of Hill's equation in engineering and physics range from mechanics and astronomy to electric circuits, electric conductivity of metals, and the theory of the cyclotron. New applications are continually being discovered and theoretical advances made since Liapounoff established the equation's fundamental importance for stability problems in 1907. Brief but thorough, this volume offers engineers and mathematicians a complete orientation to the subject.""Hill's equation"" connotes the class of homogeneous, linear, second order differential equations with real, period

  11. Delayed collapses of BECs in relation to AdS gravity

    CERN Document Server

    Biasi, Anxo F; Paredes, Angel

    2016-01-01

    We numerically investigate spherically symmetric collapses in the Gross-Pitaevskii equation with attractive nonlinearity in a harmonic potential. Even below threshold for direct collapse, the wave function bounces off from the origin and may eventually become singular after a number of oscillations in the trapping potential. This is reminiscent of the evolution of Einstein gravity sourced by a scalar field in Anti-de Sitter space where collapse corresponds to black hole formation. We carefully examine the long time evolution of the wave function for continuous families of initial states in order to sharpen out this coincidence which may bring new insights in both directions. On one hand, we comment on possible implications for the so-called Bosenova collapses in cold atom Bose-Einstein condensates. On the other hand, Gross-Pitaevskii provides a toy model to study the relevance of either the resonance conditions or the nonlinearity for the problem of Anti-de Sitter instability.

  12. The Role of the Charged Residues of the GP2 Helical Regions in Ebola Entry

    Institute of Scientific and Technical Information of China (English)

    Haiqing Jiang; Jizhen Wang; Balaji Manicassamy; Santhakumar Manicassamy; Michael Caffrey; Lijun Rong

    2009-01-01

    The glycoprotein (GP) of Ebola is the sole structural protein that forms the spikes on the viral envelope. The GP contains two subunits, GP1 and GP2, linked by a disulfide bond, which are responsible for receptor binding and membrane fusion, respectively. In this study, the full length of GP gene of Ebola Zaire species, 2028 base pairs in length, was synthesized using 38 overlapping oligonucleotides by multiple rounds of polymerase chain reaction (PCR). The synthesized GP gene was shown to be efficiently expressed in mammalian cells. Furthermore, an efficient HIV-based pseudotyping system was developed using the synthetic GP gene, providing a safe approach to dissecting the entry mechanism of Ebola viruses. Using this pseudotyping system and mutational analysis, the role of the charged residues in the GP2 helical regions was examined. It was found that substitutions of the most charged residues in the regions did not adversely affect GP expression, processing, or viral incorporation, however, most of the mutations greatly impaired the ability of GP to mediate efficient viral infection. These results demonstrate that these charged residues of GP2 play an important role in GP-mediated Ebola entry into its host cells. We propose that these charged residues are involved in forming the intermediate conformation(s) of GP in membrane fusion and Ebola entry.

  13. Do practice nurse solve future GP capacity problems?

    NARCIS (Netherlands)

    Lamkaddem, M.; Haan, J. de; Bakker, D. de

    2003-01-01

    Background: Task delegation is viewed as an important policy instrument to counter foreseen future shortages in GP capacity in the Netherlands. Therefore, a national programme to introduce practice nurses in general practice was launched in 1998 by the National Association of General Practice. In 20

  14. The HIV Protein gp120 Alters Mitochondrial Dynamics in Neurons

    Science.gov (United States)

    Castellano, Paul; Dedoni, Simona; Palchik, Guillermo; Trejo, Margarita; Adame, Anthony; Rockenstein, Edward; Eugenin, Eliseo; Masliah, Eliezer; Mocchetti, Italo

    2016-01-01

    Neurotoxicity of human immunodeficiency virus-1 (HIV) includes synaptic simplification and neuronal apoptosis. However, the mechanisms of HIV-associated neurotoxicity remain unclear, thus precluding an effective treatment of the neurological complications. The present study was undertaken to characterize novel mechanisms of HIV neurotoxicity that may explain how HIV subjects develop neuronal degeneration. Several neurodegenerative disorders are characterized by mitochondrial dysfunction; therefore, we hypothesized that HIV promotes mitochondrial damage. We first analyzed brains from HIV encephalitis (HIVE) by electron microscopy. Several sections of HIVE subjects contained enlarged and damaged mitochondria compared to brains from HIV subjects with no neurological complications. Similar pathologies were observed in mice overexpressing the HIV protein gp120, suggesting that this viral protein may be responsible for mitochondrial pathology found in HIVE. To gain more information about the cellular mechanisms of gp120 neurotoxicity, we exposed rat cortical neurons to gp120 and we determined cellular oxygen consumption rate, mitochondrial distribution, and trafficking. Our data show that gp120 evokes impairment in mitochondrial function and distribution. These data suggest that one of the mechanisms of HIV neurotoxicity includes altered mitochondrial dynamics in neurons. PMID:26936603

  15. Technology in practice – GP computer use by age.

    Science.gov (United States)

    Henderson, Joan; Pollack, Allan; Gordon, Julie; Miller, Graeme

    2014-12-01

    Since 2005, more than 95% of general practitioners (GPs) have had access to computers in their clinical work. We have analysed the most recent 2 years of BEACH data (April 2012-March 2014) to determine whether GP age affects clinical computer use.

  16. Potable Water Treatment Facility General Permit (PWTF GP) ...

    Science.gov (United States)

    2017-04-10

    The Final PWTF GP establishes permit eligibility conditions, Notice of Intent (NOI) requirements, effluent limitations, standards, prohibitions, and best management practices for facilities that discharge to waters in the Commonwealth of Massachusetts (including both Commonwealth and Indian country lands) and the State of New Hampshire.

  17. The GP retainer scheme: report of a national survey.

    Science.gov (United States)

    Lockyer, Lesley; Young, Pat; Main, Paul Gn; Morison, Jim

    2014-11-01

    The current context of organisational change and new working patterns, together with the high cost of medical training, mean it is of vital importance that the NHS retains its trained workforce. The GP retainer scheme supports doctors who for reasons of personal circumstance are restricted in their ability to compete for employment in medicine, and aims to facilitate the retention of their skills and confidence. This national study evaluates the experiences and views of current and past GP retainers and provides a rigorous assessment of the retainer scheme. It is a mixed method study: an online questionnaire was completed by 318 current and ex-retainers across the UK; follow-up telephone interviews were conducted with 30 respondents. The study finds that the GP retainer scheme is effective in retaining GPs through times of transition and provides evidence to support the continuing funding of the scheme across the UK. The scheme is beneficial for doctors who also have a role in caring for young children and is also highly valued by a minority of GP retainers who are using it to return to work after illness, or to practice in a more limited role, due to chronic illness or disability. This study found variations in the implementation of the educational entitlement which is fundamental to the scheme. A minority of retainers experienced problems with the implementation of the scheme and recommendations are made for improvements.

  18. GP registrar well-being: a cross-sectional survey

    Directory of Open Access Journals (Sweden)

    Schattner Peter

    2010-02-01

    Full Text Available Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS, a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Results Survey response rate of 51% (102/199. Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS and 7% mild to moderately anxious (DASS. Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors; similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. Conclusions This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

  19. Identification and characterization of a broadly cross-reactive HIV-1 human monoclonal antibody that binds to both gp120 and gp41.

    Directory of Open Access Journals (Sweden)

    Mei-Yun Zhang

    Full Text Available Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb, designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env. M43 bound to recombinant gp140 s from various primary isolates, to membrane-associated Envs on transfected cells and HIV-1 infected cells, as well as to recombinant gp120 s and gp41 fusion intermediate structures containing N-trimer structure, but did not bind to denatured recombinant gp140 s and the CD4 binding site (CD4bs mutant, gp120 D368R, suggesting that the m43 epitope is conformational and overlaps the CD4bs on gp120 and the N-trimer structure on gp41. M43 neutralized 34% of the HIV-1 primary isolates from different clades and all the SHIVs tested in assays based on infection of peripheral blood mononuclear cells (PBMCs by replication-competent virus, but was less potent in cell line-based pseudovirus assays. In contrast to CD4, m43 did not induce Env conformational changes upon binding leading to exposure of the coreceptor binding site, enhanced binding of mAbs 2F5 and 4E10 specific for the membrane proximal external region (MPER of gp41 Envs, or increased gp120 shedding. The overall modest neutralization activity of m43 is likely due to the limited binding of m43 to functional Envs which could be increased by antibody engineering if needed. M43 may represent a new class of bnAbs targeting conformational epitopes overlapping structures on both gp120 and gp41. Its novel epitope and possibly new mechanism(s of neutralization could helpdesign improved vaccine immunogens and candidate therapeutics.

  20. Patient and GP characteristics associated with antidepressant treatment in depressed patients: a multilevel analysis.

    NARCIS (Netherlands)

    Dijk, L. van; Volkers, A.; Bakker, D. de

    2007-01-01

    Background: Antidepressants are frequently prescribed drugs in Dutch general practice, but patients differ in the treatment they receive. Both patient and GP characteristics may explain this difference. Objectives: To identify patient and GP characteristics associated with antidepressant treatment i

  1. EigenGP: Sparse Gaussian process models with data-dependent eigenfunctions

    OpenAIRE

    Qi, Yuan; Dai, Bo; Zhu, Yao

    2012-01-01

    Gaussian processes (GPs) provide a nonparametric representation of functions. However, classical GP inference suffers from high computational cost and it is difficult to design nonstationary GP priors in practice. In this paper, we propose a sparse Gaussian process model, EigenGP, based on the Karhunen-Loeve (KL) expansion of a GP prior. We use the Nystrom approximation to obtain data dependent eigenfunctions and select these eigenfunctions by evidence maximization. This selection reduces the...

  2. 恶性肿瘤患者血清GP-DA活性探讨

    Institute of Scientific and Technical Information of China (English)

    孙秀娟

    2010-01-01

    本文测定90例临床恶性肿瘤患者血清GP-DA活力.发现肝癌患者GP-DA活力升高,胃癌GP-DA活力显著减低.肝癌患者血清GP-DA活力与r-GT呈正相关(r=0.7649)、与AFP无相关(r=0.1024).

  3. Integral equations

    CERN Document Server

    Moiseiwitsch, B L

    2005-01-01

    Two distinct but related approaches hold the solutions to many mathematical problems--the forms of expression known as differential and integral equations. The method employed by the integral equation approach specifically includes the boundary conditions, which confers a valuable advantage. In addition, the integral equation approach leads naturally to the solution of the problem--under suitable conditions--in the form of an infinite series.Geared toward upper-level undergraduate students, this text focuses chiefly upon linear integral equations. It begins with a straightforward account, acco

  4. HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.

    Directory of Open Access Journals (Sweden)

    Meimei Shan

    2007-11-01

    Full Text Available The human immunodeficiency virus type 1 (HIV-1 envelope glycoprotein gp120 is a vaccine immunogen that can signal via several cell surface receptors. To investigate whether receptor biology could influence immune responses to gp120, we studied its interaction with human, monocyte-derived dendritic cells (MDDCs in vitro. Gp120 from the HIV-1 strain JR-FL induced IL-10 expression in MDDCs from 62% of donors, via a mannose C-type lectin receptor(s (MCLR. Gp120 from the strain LAI was also an IL-10 inducer, but gp120 from the strain KNH1144 was not. The mannose-binding protein cyanovirin-N, the 2G12 mAb to a mannose-dependent gp120 epitope, and MCLR-specific mAbs inhibited IL-10 expression, as did enzymatic removal of gp120 mannose moieties, whereas inhibitors of signaling via CD4, CCR5, or CXCR4 were ineffective. Gp120-stimulated IL-10 production correlated with DC-SIGN expression on the cells, and involved the ERK signaling pathway. Gp120-treated MDDCs also responded poorly to maturation stimuli by up-regulating activation markers inefficiently and stimulating allogeneic T cell proliferation only weakly. These adverse reactions to gp120 were MCLR-dependent but independent of IL-10 production. Since such mechanisms might suppress immune responses to Env-containing vaccines, demannosylation may be a way to improve the immunogenicity of gp120 or gp140 proteins.

  5. File list: ALL.Dig.20.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Dig.20.AllAg.GP5d hg19 All antigens Digestive tract GP5d SRX360576,SRX360569,SR...2,SRX360583,SRX360573,SRX360572,SRX360586 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Dig.20.AllAg.GP5d.bed ...

  6. File list: ALL.Dig.50.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Dig.50.AllAg.GP5d hg19 All antigens Digestive tract GP5d SRX360576,SRX360569,SR...2,SRX360583,SRX360573,SRX360572,SRX360586 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Dig.50.AllAg.GP5d.bed ...

  7. File list: ALL.Dig.05.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Dig.05.AllAg.GP5d hg19 All antigens Digestive tract GP5d SRX360569,SRX360576,SR...9,SRX360590,SRX360586,SRX360572,SRX360573 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Dig.05.AllAg.GP5d.bed ...

  8. File list: ALL.Dig.10.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Dig.10.AllAg.GP5d hg19 All antigens Digestive tract GP5d SRX360569,SRX360576,SR...0,SRX360583,SRX360573,SRX360572,SRX360586 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Dig.10.AllAg.GP5d.bed ...

  9. Riccati equations

    Directory of Open Access Journals (Sweden)

    Lloyd K. Williams

    1987-01-01

    Full Text Available In this paper we find closed form solutions of some Riccati equations. Attention is restricted to the scalar as opposed to the matrix case. However, the ones considered have important applications to mathematics and the sciences, mostly in the form of the linear second-order ordinary differential equations which are solved herewith.

  10. Equation poems

    Science.gov (United States)

    Prentis, Jeffrey J.

    1996-05-01

    One of the most challenging goals of a physics teacher is to help students see that the equations of physics are connected to each other, and that they logically unfold from a small number of basic ideas. Derivations contain the vital information on this connective structure. In a traditional physics course, there are many problem-solving exercises, but few, if any, derivation exercises. Creating an equation poem is an exercise to help students see the unity of the equations of physics, rather than their diversity. An equation poem is a highly refined and eloquent set of symbolic statements that captures the essence of the derivation of an equation. Such a poetic derivation is uncluttered by the extraneous details that tend to distract a student from understanding the essential physics of the long, formal derivation.

  11. Penetration equations

    Energy Technology Data Exchange (ETDEWEB)

    Young, C.W. [Applied Research Associates, Inc., Albuquerque, NM (United States)

    1997-10-01

    In 1967, Sandia National Laboratories published empirical equations to predict penetration into natural earth materials and concrete. Since that time there have been several small changes to the basic equations, and several more additions to the overall technique for predicting penetration into soil, rock, concrete, ice, and frozen soil. The most recent update to the equations was published in 1988, and since that time there have been changes in the equations to better match the expanding data base, especially in concrete penetration. This is a standalone report documenting the latest version of the Young/Sandia penetration equations and related analytical techniques to predict penetration into natural earth materials and concrete. 11 refs., 6 tabs.

  12. Tryptophan dendrimers that inhibit HIV replication, prevent virus entry and bind to the HIV envelope glycoproteins gp120 and gp41.

    Science.gov (United States)

    Rivero-Buceta, Eva; Doyagüez, Elisa G; Colomer, Ignacio; Quesada, Ernesto; Mathys, Leen; Noppen, Sam; Liekens, Sandra; Camarasa, María-José; Pérez-Pérez, María-Jesús; Balzarini, Jan; San-Félix, Ana

    2015-12-01

    Dendrimers containing from 9 to 18 tryptophan residues at the peryphery have been efficiently synthesized and tested against HIV replication. These compounds inhibit an early step of the replicative cycle of HIV, presumably virus entry into its target cell. Our data suggest that HIV inhibition can be achieved by the preferred interaction of the compounds herein described with glycoproteins gp120 and gp41 of the HIV envelope preventing interaction between HIV and the (co)receptors present on the host cells. The results obtained so far indicate that 9 tryptophan residues on the periphery are sufficient for efficient gp120/gp41 binding and anti-HIV activity.

  13. Expression of external glycoprotein gp105 and transmembrane glycoprotein gp36 of human immunodeficiency virus type 2 in insect cell by Bac-to-Bac system%用细菌/杆状病毒系统在昆虫细胞中表达HIV-2 外膜糖蛋白gp105和跨膜糖蛋白gp36

    Institute of Scientific and Technical Information of China (English)

    张应玖; 金宁一; 金善荣; 王宏伟; 沈家骢

    2001-01-01

    目的 用细菌/杆状病毒(BactoBac)表达系统在昆虫细胞Sf9中表达HIV-2外膜糖蛋白gp105和跨膜糖蛋白gp36,为研制艾滋病疫苗和诊断试剂奠定基础。方法 分别将HIV-2外膜蛋白gp105和跨膜蛋白gp36全基因序列克隆到杆状病毒转座载体pFastBacHTa和pFastBacHTb中多角体启动子下游,构建成重组转座载体pFastBacHTa-gp105和pFastBacHTb-gp36,利用细菌/杆状病毒(BactoBac)表达系统筛选重组杆状病毒,并在昆虫细胞Sf9中表达HIV-2的gp105和gp36。结果 SDS-PAGE分析结果表明,gp105基因表达产物为一66000u糖蛋白,gp36基因则表达一41000u糖蛋白,与天然产物一致。Westernblot结果显示:两者均具有抗原特异性。结论 gp105和gp36在昆虫细胞中得到了高效表达,并均被糖基化;gp105接近天然产物,gp36与天然产物一致。%Objective To develop effective vaccine and diagnostic agents ofAIDS, the external glycoprotein gp105 and transmembrane glycoprotein gp36 of human immunodeficiency virus type 2 were expressed in insect cells Spodoptera frugiperda (Sf9) using baculovirus expression system : Bac-to-Bac system. Methods The recombinant transfer vector pFast Bac HTa-gp105 and pFast Bac HTb-gp36 were constructed by cloning HIV-2 gp105 gene and gp36 gene into the end of polyhedrin promoter of baculovirus transfer vector pFast Bac HTa and pFast Bac HTb respectively. HIV-2 external glycoprotein gp105 and transmembrane glycoprotein gp36 were expressed in insect cells Spodoptera frugiperda (Sf9) by transposing these two foreign genes to shuttle vector bacmid respectively using Bac-to-Bac system. Results The resulting products determined by SDS-PAGE showed that recombinant baculovirusescontaining gp105 gene expressed a 66 kDa glycoprotein, whereas those contai-ning gp36 gene generated a 41 000u glycoprotein, the apparent molecular weight of which is equivalent to that of natural gp36. Western blot indicated that

  14. Educational expectations of GP trainers. A EURACT needs analysis

    DEFF Research Database (Denmark)

    Guldal, D.; Windak, A.; Maagaard, Roar

    2012-01-01

    Introduction: In this background paper, we discuss the educational needs of family medicine teachers and trainers in the light of a EURACT (European Academy of Teachers in General Practice) project aimed at the development of a European framework for the professional development of general practice...... (GP) educators. Background: There is evidence that the ideal GP educator would benefit from systematic training in teaching skills. Although international literature indicates that such skills training should be in supervision, feedback, assessment and educational management, it is not clear...... and depth of knowledge needed; this depended on their experience and level of expertise as teachers. Implications: Based on the information gathered and experience gained from previous EURACT courses, a Leonardo da Vinci project has developed and launched a comprehensive programme with courses at three...

  15. Developing GP monitoring systems guided by a soft systems approach.

    Science.gov (United States)

    Hindle, T

    1995-11-01

    This paper describes a selected aspect of a research project concerned with 'contracts and competition' in the recently reformed National Health Service. The particular feature highlighted in this paper is the central role played by the general practitioners in the health service as principal sources of the demands made on provider units (particularly hospitals) and, hence, critical determinants of volumes and costs in contracting. A practical outcome of the research has been the development of GP monitoring systems to be used by provider units particularly in the context of marketing-led referral expectations. The approach used to highlight areas of potential GP contract management and monitoring improvements has been a development of soft systems methodology.

  16. Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

    Directory of Open Access Journals (Sweden)

    Ryan B Craig

    Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

  17. Impact of Leishmania metalloprotease GP63 on macrophage signaling

    OpenAIRE

    Isnard, Amandine; Shio, Marina T.; Olivier, Martin

    2012-01-01

    The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly infl...

  18. Membrane topology analysis of HIV-1 envelope glycoprotein gp41

    Directory of Open Access Journals (Sweden)

    Xiao Dan

    2010-11-01

    Full Text Available Abstract Background The gp41 subunit of the HIV-1 envelope glycoprotein (Env has been widely regarded as a type I transmembrane protein with a single membrane-spanning domain (MSD. An alternative topology model suggested multiple MSDs. The major discrepancy between the two models is that the cytoplasmic Kennedy sequence in the single MSD model is assigned as the extracellular loop accessible to neutralizing antibodies in the other model. We examined the membrane topology of the gp41 subunit in both prokaryotic and mammalian systems. We attached topological markers to the C-termini of serially truncated gp41. In the prokaryotic system, we utilized a green fluorescent protein (GFP that is only active in the cytoplasm. The tag protein (HaloTag and a membrane-impermeable ligand specific to HaloTag was used in the mammalian system. Results In the absence of membrane fusion, both the prokaryotic and mammalian systems (293FT cells supported the single MSD model. In the presence of membrane fusion in mammalian cells (293CD4 cells, the data obtained seem to support the multiple MSD model. However, the region predicted to be a potential MSD is the highly hydrophilic Kennedy sequence and is least likely to become a MSD based on several algorithms. Further analysis revealed the induction of membrane permeability during membrane fusion, allowing the membrane-impermeable ligand and antibodies to cross the membrane. Therefore, we cannot completely rule out the possible artifacts. Addition of membrane fusion inhibitors or alterations of the MSD sequence decreased the induction of membrane permeability. Conclusions It is likely that a single MSD model for HIV-1 gp41 holds true even in the presence of membrane fusion. The degree of the augmentation of membrane permeability we observed was dependent on the membrane fusion and sequence of the MSD.

  19. Blended learning in CME: the perception of GP trainers.

    Science.gov (United States)

    Te Pas, E; Meinema, J G; Visser, M R M; van Dijk, N

    2016-05-01

    Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

  20. Basket Option Pricing Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.

    2010-08-01

    We introduce a basket option pricing problem arisen in financial mathematics. We discretized the problem based on the alternating direction implicit (ADI) method and parallel cyclic reduction is applied to solve the set of tridiagonal matrices generated by the ADI method. To reduce the computational time of the problem, a general purpose graphics processing units (GP-GPU) environment is considered. Numerical results confirm the convergence and efficiency of the proposed method. © 2010 IEEE.

  1. Blood-Brain Barrier Abnormalities Caused by HIV-1 gp120: Mechanistic and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Louboutin

    2012-01-01

    Full Text Available The blood-brain barrier (BBB is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120 as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP injection] or chronic [using SV(gp120, an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents. Gp120 was directly toxic to brain endothelial cells. Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs. These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae. MMP-2 and MMP-9 were upregulated following gp120-injection. Gp120 reduced laminin and tight junction proteins. Reactive oxygen species (ROS activate MMPs. Injecting gp120 induced lipid peroxidation. Gene transfer of antioxidant enzymes protected against gp120-induced BBB abnormalities. NMDA upregulates the proform of MMP-9. Using the NMDA receptor (NMDAR-1 inhibitor, memantine, we observed partial protection from gp120-induced BBB injury. Thus, (1 HIV-envelope gp120 disrupts the BBB; (2 this occurs via lesions in brain microvessels, MMP activation and degradation of vascular basement membrane and vascular tight junctions; (3 NMDAR-1 activation plays a role in this BBB injury; and (4 antioxidant gene delivery as well as NMDAR-1 antagonists may protect the BBB.

  2. Differential equations

    CERN Document Server

    Tricomi, FG

    2013-01-01

    Based on his extensive experience as an educator, F. G. Tricomi wrote this practical and concise teaching text to offer a clear idea of the problems and methods of the theory of differential equations. The treatment is geared toward advanced undergraduates and graduate students and addresses only questions that can be resolved with rigor and simplicity.Starting with a consideration of the existence and uniqueness theorem, the text advances to the behavior of the characteristics of a first-order equation, boundary problems for second-order linear equations, asymptotic methods, and diff

  3. Indirect ELISA with Recombinant GP5 for Detecting Antibodies to Porcine Reproductive and Respiratory Syndrome Virus

    Institute of Scientific and Technical Information of China (English)

    Yan Chen; Hong Tian; Jian-Hui He; Jin-Yin Wu; You-jun Shang; Xiang-tao Liu

    2011-01-01

    Porcine reproductive and respiratory syndrome is caused by the PRRS virus(PRRSV), which has six structural proteins(GP2, GP3, GP4, GP5, M and N). GP5 and N protein are important targets for serological detection by enzyme-linked immunosorbent assay(ELISA)and other methods. Toward this goal, we developed an indirect ELISA with recombinant GP5 antigens and this method was validated by comparison to the LSI PRRSV-Ab ELISA kit. The results indicated that the optimal concentration of coated recombinant antigen was 0.2 μg/well for a serum dilution of 1:40. The rate of agreement with the LSI PRRSV-Ab kit was 88.7%(266/300). These results support the potential use of recombinant GP5 as an antigen for indirect ELISA to detect PRRSV antibodies in pigs.

  4. Involvement of Leishmania donovani major surface glycoprotein gp63 in promastigote multiplication

    Indian Academy of Sciences (India)

    Sanjeev Pandey; Phuljhuri Chakraborti; Rakhi Sharma; Santu Bandyopadhyay; Dwijen Sarkar; Samit Adhya

    2004-03-01

    The major surface glycoprotein gp63 of the kinetoplastid protozoal parasite Leishmania is implicated as a ligand mediating uptake of the parasite into, and survival within, the host macrophage. By expressing gp63 antisense RNA from an episomal vector in L. donovani promastigotes, gp63-deficient transfectants were obtained. Reduction of the gp63 level resulted in increased generation times, altered cell morphology, accumulation of cells in the G2/M phase of the cell cycle, and increased numbers of binucleate cells with one or two kinetoplasts. Growth was stimulated, and the number of binucleate cells reduced, by addition to the culture of a bacterially expressed fusion protein containing the fibronectin-like SRYD motif and the zinc-binding (metalloprotease) domain of gp63. These observations support an additional role of gp63 in promastigote multiplication; the fibronectin-like properties of gp63 may be important in this process.

  5. Cytotoxicity of HIV-gp41 segments expressed in E.Coli

    Institute of Scientific and Technical Information of China (English)

    YUAN Yuhua; BI Changhao; LI Ju; WANG Xueqian; GENG Yunqi; CHEN Qimin

    2004-01-01

    The failed attempt to express HIV-gp41 in E. coli led to the investigation of HIV-gp41 segments, which is responsible for the toxicity to E. coli cells. A series of deletion mutants containing different regions of gp41 gene were constructed and expressed in E. coli BL21(DE3) strain. After IPTG induction, the high mortality of host bacteria was observed in host bacteria carrying the deletion mutants of gp41 gene except for those transformed with pET-HN2; coordinately, the mRNA transcripts of the gp41 was rapidly decreased; and the release of [3H]uridine increased upon induction. All these data suggested that GP41 protein has a cytotoxic effect on E. coli, and it is the cytotoxicity of the gp41 gene product that contributes to the high mortality when expressed in E. coli.

  6. The consequence of regional gradients of P-gp and CYP3A4 for drug-drug interactions by P-gp inhibitors and the P-gp/CYP3A4 interplay in the human intestine ex vivo.

    Science.gov (United States)

    Li, Ming; de Graaf, Inge A M; van de Steeg, Evita; de Jager, Marina H; Groothuis, Geny M M

    2017-04-01

    Intestinal P-gp and CYP3A4 work coordinately to reduce the intracellular concentration of drugs, and drug-drug interactions (DDIs) based on this interplay are of clinical importance and require pre-clinical investigation. Using precision-cut intestinal slices (PCIS) of human jejunum, ileum and colon, we investigated the P-gp/CYP3A4 interplay and related DDIs with P-gp inhibitors at the different regions of the human intestine with quinidine (Qi), dual substrate of P-gp and CYP3A4, as probe. All the P-gp inhibitors increased the intracellular concentrations of Qi by 2.1-2.6 fold in jejunum, 2.6-3.8 fold in ileum but only 1.2-1.3 fold in colon, in line with the different P-gp expression in these intestinal regions. The selective P-gp inhibitors (CP100356 and PSC833) enhanced 3-hydroxy-quinidine (3OH-Qi) in jejunum and ileum, while dual inhibitors of P-gp and CYP3A4 (verapamil and ketoconazole) decreased the 3OH-Qi production, despite of the increased intracellular Qi concentration, due to inhibition of CYP3A4. The outcome of DDIs based on P-gp/CYP3A4 interplay, shown as remarkable changes in the intracellular concentration of both the parent drug and the metabolite, varied among the intestinal regions, probably due to the different expression of P-gp and CYP3A4, and were different from those found in rat PCIS, which may have important implications for the disposition and toxicity of drugs and their metabolites.

  7. Human α1-antitrypin binds to heat-shock protein gp96 and protects from endogenous gp96-mediated injury in vivo

    Directory of Open Access Journals (Sweden)

    Eli Chaim Lewis

    2013-10-01

    Full Text Available The extracellular form of the abundant heat shock protein, gp96, is involved in human autoimmune pathologies. In patients with type 1 diabetes, circulating gp96 is found to be elevated, and is bound to the acute-phase protein, α1-antitrypsin (AAT. The two molecules also engage intracellularly during the physiological folding of AAT. AAT therapy promotes pancreatic islet survival in both transplantation and autoimmune diabetes models, and several clinical trials are currently examining AAT therapy for individuals with type 1 diabetes. However, its mechanism of action is yet unknown. Here, we examine whether the protective activity of AAT is related to binding of extracellular gp96. Primary mouse islets, macrophages and dendritic cells were added recombinant gp96 in the presence of clinical-grade human AAT (hAAT, GlassiaTM, Kamada Ltd, Israel. Islet function was evaluated by insulin release. The effect of hAAT on IL-1β/IFNγ-induced gp96 cell surface levels was also evaluated. In vivo, skin transplants were performed for examination of robust immune responses, and systemic inflammation was induced by cecal puncture. Endogenous gp96 was inhibited by gp96-inhibitory peptide (gp96i, Compugen Ltd., Israel in an allogeneic islet transplantation model. Our findings indicate that hAAT binds to gp96 and diminishes gp96-induced inflammatory responses; e.g., hAAT-treated gp96-stimulated islets released less pro-inflammatory cytokines (IL-1β by 6.16-fold and TNFα by 2.69-fold and regained gp96-disrupted insulin release. hAAT reduced cell activation during both skin transplantation and systemic inflammation, as well as lowered inducible surface levels of gp96 on immune cells. Finally, inhibition of gp96 significantly improved immediate islet graft function. These results suggest that hAAT is a regulator of gp96-mediated inflammatory responses, an increasingly appreciated endogenous damage response with relevance to human pathologies that are exacerbated

  8. Regulation of the expression of chaperone gp96 in macrophages and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Lutz Wolfram

    Full Text Available The chaperone function of the ER-residing heat shock protein gp96 plays an important role in protein physiology and has additionally important immunological functions due to its peptide-binding capacity. Low amounts of gp96 stimulate immunity; high quantities induce tolerance by mechanisms not fully understood. A lack of gp96 protein in intestinal macrophages (IMACs from Crohn`s disease (CD patients correlates with loss of tolerance against the host gut flora, leading to chronic inflammation. Since gp96 shows dose-dependent direction of immunological reactions, we studied primary IMACs and developed cell models to understand the regulation of gp96 expression. Induction of gp96-expression was higher in in vitro differentiated dendritic cells (i.v.DCs than in in vitro differentiated macrophages (i.v.MACs, whereas monocytes (MOs expressed only low gp96 levels. The highest levels of expression were found in IMACs. Lipopolysaccharide (LPS, muramyl dipeptide (MDP, tumour necrosis factor (TNF, and Interleukin (IL-4 induced gp96-expression, while IL12, IL-17, IL-23 and interferon (IFN-γ were not effective indicating that Th1 and Th17 cells are probably not involved in the induction of gp96. Furthermore, gp96 was able to induce its own expression. The ER-stress inducer tunicamycin increased gp96-expression in a concentration- and time-dependent manner. Both ulcerative colitis (UC and CD patients showed significantly elevated gp96 mRNA levels in intestinal biopsies which correlated positively with the degree of inflammation of the tissue. Since gp96 is highly expressed on the one hand upon stress induction as during inflammation and on the other hand possibly mediating tolerance, these results will help to understand the whether gp96 plays a role in the pathophysiology of inflammatory bowel disease (IBD.

  9. Differential equations

    CERN Document Server

    Barbu, Viorel

    2016-01-01

    This textbook is a comprehensive treatment of ordinary differential equations, concisely presenting basic and essential results in a rigorous manner. Including various examples from physics, mechanics, natural sciences, engineering and automatic theory, Differential Equations is a bridge between the abstract theory of differential equations and applied systems theory. Particular attention is given to the existence and uniqueness of the Cauchy problem, linear differential systems, stability theory and applications to first-order partial differential equations. Upper undergraduate students and researchers in applied mathematics and systems theory with a background in advanced calculus will find this book particularly useful. Supplementary topics are covered in an appendix enabling the book to be completely self-contained.

  10. Uncoupling GP1 and GP2 Expression in the Lassa Virus Glycoprotein Complex: Implications for GPI Ectodomain Shedding

    Science.gov (United States)

    2008-12-23

    contributors Abstract Background: Sera from convalescent Lassa fever patients often contains antibodies to Lassa virus (LASV) glycoprotein 1 (GP1...uncoupled proteins will improve current diagnostics, treatment, and prevention of Lassa fever . To this end, mammalian expression systems were engineered for...stages of Lassa fever . Published: 23 December 2008 Virology Journal 2008, 5:161 doi:10.1186/1743-422X-5-161 Received: 14 December 2008 Accepted: 23

  11. Exposure of undergraduates to authentic GP teaching and subsequent entry to GP training: a quantitative study of UK medical schools.

    Science.gov (United States)

    Alberti, Hugh; Randles, Hannah L; Harding, Alex; McKinley, Robert K

    2017-04-01

    It has been suggested that the quantity of exposure to general practice teaching at medical school is associated with future choice of a career as a GP. To examine the relationship between general practice exposure at medical school and the percentage of each school's graduates appointed to a general practice training programme after foundation training (postgraduate years 1 and 2). A quantitative study of 29 UK medical schools. The UK Foundation Programme Office (UKFPO) destination surveys of 2014 and 2015 were used to determine the percentage of graduates of each UK medical school who were appointed to a GP training programme after foundation year 2. The Spearman rank correlation was used to examine the correlation between these data and the number of sessions spent in placements in general practice at each medical school. A statistically significant association was demonstrated between the quantity of authentic general practice teaching at each medical school and the percentage of its graduates who entered GP training after foundation programme year 2 in both 2014 (correlation coefficient [r] 0.41, P = 0.027) and 2015 (r 0.3, P = 0.044). Authentic general practice teaching here is described as teaching in a practice with patient contact, in contrast to non-clinical sessions such as group tutorials in the medical school. The authors have demonstrated, for the first time in the UK, an association between the quantity of clinical GP teaching at medical school and entry to general practice training. This study suggests that an increased use of, and investment in, undergraduate general practice placements would help to ensure that the UK meets its target of 50% of medical graduates entering general practice. © British Journal of General Practice 2017.

  12. Identification and Characterization of a Broadly Cross-Reactive HIV-1 Human Monoclonal Antibody That Binds to Both gp120 and gp41

    NARCIS (Netherlands)

    Zhang, Mei-Yun; Yuan, Tingting; Li, Jingjing; Borges, Andrew Rosa; Watkins, Jennifer D.; Guenaga, Javier; Yang, Zheng; Wang, Yanping; Wilson, Richard; Li, Yuxing; Polonis, Victoria R.; Pincus, Seth H.; Ruprecht, Ruth M.; Dimitrov, Dimiter S.

    2012-01-01

    Identification of broadly cross-reactive HIV-1-neutralizing antibodies (bnAbs) may assist vaccine immunogen design. Here we report a novel human monoclonal antibody (mAb), designated m43, which co-targets the gp120 and gp41 subunits of the HIV-1 envelope glycoprotein (Env). M43 bound to recombinant

  13. Mini-P-gp and P-gp Co-Expression in Brown Trout Erythrocytes: A Prospective Blood Biomarker of Aquatic Pollution

    Science.gov (United States)

    Valton, Emeline; Amblard, Christian; Desmolles, François; Combourieu, Bruno; Penault-Llorca, Frédérique; Bamdad, Mahchid

    2015-01-01

    In aquatic organisms, such as fish, blood is continually exposed to aquatic contaminants. Multidrug Resistance (MDR) proteins are ubiquitous detoxification membrane pumps, which recognize various xenobiotics. Moreover, their expression is induced by a large class of drugs and pollutants. We have highlighted the co-expression of a mini P-gp of 75 kDa and a P-gp of 140 kDa in the primary culture of brown trout erythrocytes and in the erythrocytes of wild brown trout collected from three rivers in the Auvergne region of France. In vitro experiments showed that benzo[a]pyrene, a highly toxic pollutant model, induced the co-expression of mini-P-gp and P-gp in trout erythrocytes in a dose-dependent manner and relay type response. Similarly, in the erythrocytes of wild brown trout collected from rivers contaminated by a mixture of PAH and other multi-residues of pesticides, mini-P-gp and P-gp were able to modulate their expression, according to the nature of the pollutants. The differential and complementary responses of mini-P-gp and P-gp in trout erythrocytes suggest the existence in blood cells of a real protective network against xenobiotics/drugs. This property could be exploited to develop a blood biomarker of river pollution. PMID:26854141

  14. Existence and mass concentration of 2D attractive Bose-Einstein condensates with periodic potentials

    Science.gov (United States)

    Wang, Qingxuan; Zhao, Dun

    2017-02-01

    In this paper we consider a two-dimensional attractive Bose-Einstein condensate with periodic potential, described by Gross-Pitaevskii (GP) functional. By concentration-compactness lemma we show that minimizers of this functional exist when the interaction strength a satisfies a* 0, and there is no minimizer for a ≥a*. When a approaches a*, using concentration-compactness arguments again we obtain an optimal energy estimate depending on the shape of periodic potential. Moreover, we analyze the mass concentration.

  15. The SPL7013 dendrimer destabilizes the HIV-1 gp120-CD4 complex

    Science.gov (United States)

    Nandy, Bidisha; Saurabh, Suman; Sahoo, Anil Kumar; Dixit, Narendra M.; Maiti, Prabal K.

    2015-11-01

    The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude the CD4 binding site on gp120, suggesting that SPL7013 does not prevent the binding of R5 gp120 to CD4. Using MD simulations to compute binding energies of several docked structures, we find that SPL7013 binding to gp120 significantly weakens the gp120-CD4 complex. Finally, we use steered molecular dynamics (SMD) to study the kinetics of the dissociation of the gp120-CD4 complex in the absence of the dendrimer and with the dendrimer bound in each of the several stable configurations to gp120. We find that SPL7013 significantly lowers the force required to rupture the gp120-CD4 complex and accelerates its dissociation. Taken together, our findings suggest that SPL7013 compromises the stability of the R5 gp120-CD4 complex, potentially preventing the accrual of the requisite number of gp120-CD4 complexes across the virus-cell interface, thereby blocking virus entry.The poly (l-lysine)-based SPL7013 dendrimer with naphthalene disulphonate surface groups blocks the entry of HIV-1 into target cells and is in clinical trials for development as a topical microbicide. Its mechanism of action against R5 HIV-1, the HIV-1 variant implicated in transmission across individuals, remains poorly understood. Using docking and fully atomistic MD simulations, we find that SPL7013 binds tightly to R5 gp120 in the gp120-CD4 complex but weakly to gp120 alone. Further, the binding, although to multiple regions of gp120, does not occlude

  16. Models for the Binary Complex of Bacteriophage T4 Gp59 Helicase Loading Protein. GP32 Single-Stranded DNA-Binding Protein and Ternary Complex with Pseudo-Y Junction DNA

    Energy Technology Data Exchange (ETDEWEB)

    Hinerman, Jennifer M. [Univ. of Toledo, OH (United States); Dignam, J. David [Univ. of Toledo, OH (United States); Mueser, Timothy C. [Univ. of Toledo, OH (United States)

    2012-04-05

    The bacteriophage T4 gp59 helicase assembly protein (gp59) is required for loading of gp41 replicative helicase onto DNA protected by gp32 single-stranded DNA-binding protein. The gp59 protein recognizes branched DNA structures found at replication and recombination sites. Binding of gp32 protein (full-length and deletion constructs) to gp59 protein measured by isothermal titration calorimetry demonstrates that the gp32 protein C-terminal A-domain is essential for protein-protein interaction in the absence of DNA. Sedimentation velocity experiments with gp59 protein and gp32ΔB protein (an N-terminal B-domain deletion) show that these proteins are monomers but form a 1:1 complex with a dissociation constant comparable with that determined by isothermal titration calorimetry. Small angle x-ray scattering (SAXS) studies indicate that the gp59 protein is a prolate monomer, consistent with the crystal structure and hydrodynamic properties determined from sedimentation velocity experiments. SAXS experiments also demonstrate that gp32ΔB protein is a prolate monomer with an elongated A-domain protruding from the core. Moreover, fitting structures of gp59 protein and the gp32 core into the SAXS-derived molecular envelope supports a model for the gp59 protein-gp32ΔB protein complex. Our earlier work demonstrated that gp59 protein attracts full-length gp32 protein to pseudo-Y junctions. A model of the gp59 protein-DNA complex, modified to accommodate new SAXS data for the binary complex together with mutational analysis of gp59 protein, is presented in the accompanying article (Dolezal, D., Jones, C. E., Lai, X., Brister, J. R., Mueser, T. C., Nossal, N. G., and Hinton, D. M. (2012) J. Biol. Chem. 287, 18596–18607).

  17. Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

    Directory of Open Access Journals (Sweden)

    Valeria Feinshtein

    2013-09-01

    Full Text Available Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD, a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp and Breast Cancer Resistance Protein (BCRP expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp for comparison. Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3 and rhodamine123(rh123. Cyclosporine A (CsA served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3 and rh123 was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

  18. NMR observation of HIV-1 gp120 conformational flexibility resulting from V3 truncation.

    Science.gov (United States)

    Moseri, Adi; Schnur, Einat; Noah, Eran; Zherdev, Yuri; Kessler, Naama; Singhal Sinha, Eshu; Abayev, Meital; Naider, Fred; Scherf, Tali; Anglister, Jacob

    2014-07-01

    The envelope spike of HIV-1, which consists of three external gp120 and three transmembrane gp41 glycoproteins, recognizes its target cells by successively binding to its primary CD4 receptor and a coreceptor molecule. Until recently, atomic-resolution structures were available primarily for monomeric HIV-1 gp120, in which the V1, V2 and V3 variable loops were omitted (gp120core ), in complex with soluble CD4 (sCD4). Differences between the structure of HIV gp120core in complex with sCD4 and the structure of unliganded simian immunodeficiency virus gp120core led to the hypothesis that gp120 undergoes a major conformational change upon sCD4 binding. To investigate the conformational flexibility of gp120, we generated two forms of mutated gp120 amenable for NMR studies: one with V1, V2 and V3 omitted ((mut) gp120core ) and the other containing the V3 region [(mut) gp120core (+V3)]. The TROSY-(1)H-(15)N-HSQC spectra of [(2)H, (13)C, (15)N]Arg-labeled and [(2)H, (13)C, (15)N]Ile-labeled unliganded (mut) gp120core showed many fewer crosspeaks than the expected number, and also many fewer crosspeaks in comparison with the labeled (mut) gp120core bound to the CD4-mimic peptide, CD4M33. This finding suggests that in the unliganded form, (mut) gp120core shows considerable flexibility and motions on the millisecond time scale. In contrast, most of the expected crosspeaks were observed for the unliganded (mut) gp120core (+V3), and only a few changes in chemical shift were observed upon CD4M33 binding. These results indicate that (mut) gp120core (+V3) does not show any significant conformational flexibility in its unliganded form and does not undergo any significant conformational change upon CD4M33 binding, underlining the importance of V3 in stabilizing the gp120core conformation. © 2014 FEBS.

  19. Parallelized Local Volatility Estimation Using GP-GPU Hardware Acceleration

    KAUST Repository

    Douglas, Craig C.

    2010-01-01

    We introduce an inverse problem for the local volatility model in option pricing. We solve the problem using the Levenberg-Marquardt algorithm and use the notion of the Fréchet derivative when calculating the Jacobian matrix. We analyze the existence of the Fréchet derivative and its numerical computation. To reduce the computational time of the inverse problem, a GP-GPU environment is considered for parallel computation. Numerical results confirm the validity and efficiency of the proposed method. ©2010 IEEE.

  20. RING finger palmitoylation of the endoplasmic reticulum Gp78 E3 ubiquitin ligase.

    Science.gov (United States)

    Fairbank, Maria; Huang, Kun; El-Husseini, Alaa; Nabi, Ivan R

    2012-07-30

    Gp78 is an E3 ubiquitin ligase within the endoplasmic reticulum-associated degradation pathway. We show that Flag-tagged gp78 undergoes sulfhydryl cysteine palmitoylation (S-palmitoylation) within the RING finger motif, responsible for its ubiquitin ligase activity. Screening of 19 palmitoyl acyl transferases (PATs) identified five that increased gp78 RING finger palmitoylation. Endoplasmic reticulum (ER)-localized Myc-DHHC6 overexpression promoted the peripheral ER distribution of Flag-gp78 while RING finger mutation and the palmitoylation inhibitor 2-bromopalmitate restricted gp78 to the central ER. Palmitoylation of RING finger cysteines therefore regulates gp78 distribution to the peripheral ER. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  1. Characterization of the Lassa virus GP1 ectodomain shedding: implications for improved diagnostic platforms

    Directory of Open Access Journals (Sweden)

    Branco Luis M

    2009-09-01

    Full Text Available Abstract Background There is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of Lassa fever. In this regard, detection of early markers of Lassa virus (LASV infection may improve diagnosis and ultimately successful treatment with antivirals. Characterization of LASV GP1 ectodomain shedding is an important step toward developing sensitive diagnostics to detect circulating levels of this viral glycoprotein in infected patient sera. Results Secretion of GP1 from mammalian cells expressing a native LASV GPC gene was not mediated by proteolytic cleavage, as determined by treatment with a panel of matrix metalloprotease (MMP inhibitors. The shedding of GP1 was also not the result of over-expression of GPC under the control of a strong intron-A containing CMV promoter, as the soluble component could be immunoprecipitated from supernatants of cells expressing low levels of GPC under the control of an intronless promoter. Cells transfected with GPC retained surface membrane-associated expression of GP1 as determined by immunofluorescence assay, in addition to secreting the glycoprotein. Secreted GP1 derived from GPC expression has a higher content of high mannose N-linked glycosylation than sGP1 expressed independently from the GP2 portion of the protein. Neither GP1 isoform contains sialylated N-glycans, O-linked carbohydrate chains, or galactose-β(1-4-N-acetylglucosamine commonly present in complex and hybrid N-glycan structures. Conclusion These results demonstrate the non-proteolytic secretory nature of GP1 shedding during expression of the arenaviral glycoprotein complex. This phenomenon parallels shedding of a secretory glycoprotein component in filovirus replication. The glycosylation pattern of soluble GP1 resulting from expression of GPC was different from that of a soluble GP1 construct (sGP1-RRAA-FLAG, highlighting the intricately orchestrated post

  2. File list: Oth.Dig.05.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.05.AllAg.GP5d hg19 TFs and others Digestive tract GP5d SRX360576,SRX360594,...0,SRX360578,SRX360581,SRX360577,SRX360588,SRX360595,SRX360579,SRX360590 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.05.AllAg.GP5d.bed ...

  3. File list: Oth.Dig.50.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.50.AllAg.GP5d hg19 TFs and others Digestive tract GP5d SRX360576,SRX360580,...8,SRX360581,SRX360577,SRX360588,SRX360595,SRX360579,SRX360590,SRX360582 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.50.AllAg.GP5d.bed ...

  4. File list: Oth.Dig.10.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.10.AllAg.GP5d hg19 TFs and others Digestive tract GP5d SRX360576,SRX360589,...0,SRX360578,SRX360581,SRX360577,SRX360588,SRX360595,SRX360579,SRX360590 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.10.AllAg.GP5d.bed ...

  5. File list: Oth.Dig.20.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Dig.20.AllAg.GP5d hg19 TFs and others Digestive tract GP5d SRX360576,SRX360580,...8,SRX360581,SRX360577,SRX360588,SRX360595,SRX360579,SRX360590,SRX360582 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Dig.20.AllAg.GP5d.bed ...

  6. Antibody responses to the immunodominant Cryptosporidium gp15 antigen and gp15 polymorphisms in a case-control study of cryptosporidiosis in children in Bangladesh.

    Science.gov (United States)

    Allison, Genève M; Rogers, Kathleen A; Borad, Anoli; Ahmed, Sabeena; Karim, Mohammad Mahbubul; Kane, Anne V; Hibberd, Patricia L; Naumova, Elena N; Calderwood, Stephen B; Ryan, Edward T; Khan, Wasif A; Ward, Honorine D

    2011-07-01

    Although Cryptospridium hominis is the dominant Cryptosporidium species infecting humans, immune responses to cognate antigens in C. hominis-infected persons have not been reported. We investigated antibody responses to the immunodominant gp15 antigen from C. hominis and C. parvum, in C. hominis-infected Bangladeshi children less than five years of age with diarrhea (cases) and uninfected children with diarrhea (controls). We also investigated polymorphisms in the C. hominis gp15 sequence from cases. Serum IgG responses to gp15 from both species were significantly greater in cases than controls. In spite of polymorphisms in the gp15 sequence, there was a significant correlation between antibody levels to gp15 from both species, indicating cross-reactivity to conserved epitopes. Cases with acute diarrhea had a significantly greater serum IgA response to gp15 compared with those with persistent diarrhea, suggesting that this response may be associated with protection from prolonged disease. These findings support further investigation of gp15 as a vaccine candidate.

  7. HIV entry inhibitors targeting HIV-1 gp120:research advances%作用于HIV gp120的进入抑制剂研究进展

    Institute of Scientific and Technical Information of China (English)

    刘叔文; 陈之朋; 王玉芹

    2011-01-01

    HIV-1 is an envelope virus. Two glycoprotein subunits, gp120 and gp41, are on the virus membrane and mediate the virus entry. The membrane fusion events leading to HIV entry into the target cell are initiated by the binding of gp120 to CD4 and subsequently to a co-receptor, CXCR4 or CCR5. Then the conformation of gp41 has also changed, resulting in the fusion between the viral and cellular membranes. Many antibodies, proteins, saccharides, peptides and small molecule compounds which bind to gp120 can deter the progress of virus entry. This review discusses recent progress in the development of anti-HIV agents targeting gp120.%HIV-1病毒为包膜病毒,其感染靶细胞的第一步是由HIV包膜蛋白表面亚基gp120与靶细胞上的CD4分子和辅助受体(趋化因子受体CCR5或CXCR4等)结合,导致gp41的构型发生改变,启动病毒包膜与靶细胞膜的融合.与gp120相结合的一些抗体、蛋白、多糖、多肽和小分子化合物,都可能影响HIV-1病毒包膜和靶细胞膜融合的过程,从而起到抗HIV-1病毒的作用.该文对近年来以HIV gp120为靶点的HIV进入抑制剂的研究进展进行综述.

  8. What patients value in their GP and how GPs react to patients' written comments

    DEFF Research Database (Denmark)

    Elverdam, Beth

    Introduction: In EuroPEP patients evaluate their GP. A questionnaire with a few free-text answered questions is used. Aim: To analyse patients' written statements to two free-text answered questions: what do you appreciate with your GP and what could be improved?. Patients' statements were analysed....... If the GP on the other hand, acts incompetently, the patient looses all confidence in him/her. Further, they write on accessibility to the practice, timekeeping and interior decoration and personnel. Analysing the comments of each GP was easy and provided a coherent picture of the patients' experiences...

  9. Reversal of P-gp-mediated multidrug resistance in colon cancer by cinobufagin.

    Science.gov (United States)

    Yuan, Zeting; Shi, Xiaojing; Qiu, Yanyan; Jia, Tingting; Yuan, Xia; Zou, Yu; Liu, Cheng; Yu, Hui; Yuan, Yuxia; He, Xue; Xu, Ke; Yin, Peihao

    2017-03-01

    Cinobufagin (CBF) is isolated from the skin and posterior auricular glands of the Asiatic toad (Bufo gargarizans). This study investigated the reversal effect of CBF on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in colon cancer. The effect of CBF on the cytotoxicity of anticancer drugs in P-gp overexpressing LoVo/ADR, HCT116/L, Cao-2/ADR cells and their parental cells was determined using CCK-8 assay. Apoptosis of anti-cancer drugs and accumulation of doxorubicin (DOX) and Rhodamine 123 (Rho123) in P-gp overexpressing cells were evaluated by flow cytometry. Results indicated that CBF significantly enhanced the sensitivity of P-gp substrate drugs on P-gp overexpressing cells, but had no effect on their parental cells. CBF enhanced the effect of DOX against P-gp-overexpressing LoVo/ADR cell xenografts in nude mice. Moreover, CBF also increased cell apoptosis of chemotherapy agents and intracellular accumulation of DOX and Rho123 in the MDR cells. Further research on the mechanisms revealed non-competitive inhibition of P-gp ATPase activity, but without altering the expression of P-gp. These findings demonstrated that CBF could be further developed into a safe and potent P-gp modulator for combination use with anticancer drugs in cancer chemotherapy.

  10. The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae

    Directory of Open Access Journals (Sweden)

    Lowe Anson W

    2009-07-01

    Full Text Available Abstract Background GP2 is the major membrane protein present in the pancreatic zymogen granule, and is cleaved and released into the pancreatic duct along with exocrine secretions. The function of GP2 is unknown. GP2's amino acid sequence is most similar to that of uromodulin, which is secreted by the kidney. Recent studies have demonstrated uromodulin binding to bacterial Type 1 fimbria. The fimbriae serve as adhesins to host receptors. The present study examines whether GP2 also shares similar binding properties to bacteria with Type 1 fimbria. Commensal and pathogenic bacteria, including E. coli and Salmonella, express type 1 fimbria. Methods An in vitro binding assay was used to assay the binding of recombinant GP2 to defined strains of E. coli that differ in their expression of Type 1 fimbria or its subunit protein, FimH. Studies were also performed to determine whether GP2 binding is dependent on the presence of mannose residues, which is a known determinant for FimH binding. Results GP2 binds E. coli that express Type 1 fimbria. Binding is dependent on GP2 glycosylation, and specifically the presence of mannose residues. Conclusion GP2 binds to Type 1 fimbria, a bacterial adhesin that is commonly expressed by members of the Enterobacteriacae family.

  11. A Betabaculovirus-Encoded gp64 Homolog Codes for a Functional Envelope Fusion Protein

    Science.gov (United States)

    Ardisson-Araújo, Daniel M. P.; Melo, Fernando L.; Clem, Rollie J.; Wolff, José L. C.

    2015-01-01

    The GP64 envelope fusion protein is a hallmark of group I alphabaculoviruses. However, the Diatraea saccharalis granulovirus genome sequence revealed the first betabaculovirus species harboring a gp64 homolog (disa118). In this work, we have shown that this homolog encodes a functional envelope fusion protein and could enable the infection and fusogenic abilities of a gp64-null prototype baculovirus. Therefore, GP64 may complement or may be in the process of replacing F protein activity in this virus lineage. PMID:26537678

  12. What patients value in their GP and how GPs react to patients' written comments

    DEFF Research Database (Denmark)

    Elverdam, Beth

    ' comments. Results: Patients wrote very precise comments. Patients value a GP who has time to listen, makes the patient feel central and makes the patient experience continuity in their relationship. The patients question neither the GP's professional skills nor their possible breach of professional secrecy....... If the GP on the other hand, acts incompetently, the patient looses all confidence in him/her. Further, they write on accessibility to the practice, timekeeping and interior decoration and personnel. Analysing the comments of each GP was easy and provided a coherent picture of the patients' experiences...

  13. Regularity of Rings Whose Every Simple Singular Left R-module is GP-injective

    Institute of Scientific and Technical Information of China (English)

    宋贤梅

    2005-01-01

    In this paper, some new relations between GP-V′-rings and regular rings under certain special conditions have been found. It is proved that R is left self-injective regular with Soc(RR)≠0 if and only if R is a left GP-V′-ring containingan injective maximal left ideal and Soc(RR) 属于 Soc(RR). Moreover, for an MELTring R, it is shown that R is regular if and only if R is a left GP-injective left GP-V′-ring.

  14. Intracellular mannose binding lectin mediates subcellular trafficking of HIV-1 gp120 in neurons.

    Science.gov (United States)

    Teodorof, C; Divakar, S; Soontornniyomkij, B; Achim, C L; Kaul, M; Singh, K K

    2014-09-01

    Human immunodeficiency virus-1 (HIV-1) enters the brain early during infection and leads to severe neuronal damage and central nervous system impairment. HIV-1 envelope glycoprotein 120 (gp120), a neurotoxin, undergoes intracellular trafficking and transport across neurons; however mechanisms of gp120 trafficking in neurons are unclear. Our results show that mannose binding lectin (MBL) that binds to the N-linked mannose residues on gp120, participates in intravesicular packaging of gp120 in neuronal subcellular organelles and also in subcellular trafficking of these vesicles in neuronal cells. Perinuclear MBL:gp120 vesicular complexes were observed and MBL facilitated the subcellular trafficking of gp120 via the endoplasmic reticulum (ER) and Golgi vesicles. The functional carbohydrate recognition domain of MBL was required for perinuclear organization, distribution and subcellular trafficking of MBL:gp120 vesicular complexes. Nocodazole, an agent that depolymerizes the microtubule network, abolished the trafficking of MBL:gp120 vesicles, suggesting that these vesicular complexes were transported along the microtubule network. Live cell imaging confirmed the association of the MBL:gp120 complexes with dynamic subcellular vesicles that underwent trafficking in neuronal soma and along the neurites. Thus, our findings suggest that intracellular MBL mediates subcellular trafficking and transport of viral glycoproteins in a microtubule-dependent mechanism in the neurons.

  15. A study into the effectiveness of unqualified GP assistants.

    Science.gov (United States)

    Philip, Marilyn; Turnbull, Betty

    This article aims to address the potential shortfall in care provision offered by general practitioners (GPs) resulting from pending retirement and the retention and recruitment crisis. An educational module was developed that offered both theory and practise to unqualified general practice assistants. The module content was determined following discussion with local GPs. A small qualitative study of six students was carried out to review efficacy of participants in their new role. Using a grounded theory approach, participant and supervisor views of course content and delivery, role preparation diversity were analysed and compared. Tape-recorded interviews were conducted and analysis carried out employing the constant comparative method. Data were coded and emergent themes categorized. Overall, participants agreed that the module had strengthened their knowledge, added new skills, heightened their job satisfaction, added significant diversity to their role and enhanced their employability potential. Five participants communicated that they were more confident in performing clinical skills and advising health improvement techniques. Supervisors also reported that participants displayed a more competent and professional approach to health care, which was complementary to the role of the GP and practice nurse. Ultimately this allowed both GP and practice nurse to focus on dealing with chronic illness targets, as required in the new directive (Scottish Executive, 2004).

  16. The GP as first responder in a major medical emergency.

    Science.gov (United States)

    Somers, G T; Drinkwater, E J; Torcello, N

    1997-12-01

    While there have been many articles and seminars on the Ash Wednesday bushfire and Port Arthur shooting disasters, the role, responsibility and support structure of general practitioners (GPs) and the effect of the disaster on them, have received little attention. This paper looks at the role of the GP as the first responder in a disaster in rural and semi-rural Australia. Hopefully, a structured involvement, with adequate preparation and recovery, will minimise harm to these respondents. This article was written after a local GP response to disasters had been incorporated into the local Displan of one region. This response was successfully activated by Victorian State Displan during the Dandenong Ranges bushfire disaster of January, 1997. A disaster is said to have occurred when normal community and organisational arrangements are overwhelmed by an event, and extraordinary responses need to be instituted. First responder has become the generic term for those who arrive at the scene during the early phase of the response, that is, before centralised coordination is in place. Displan is the abbreviation for the State Emergency Response Plan. The phases of emergency management consist of: prevention; preparation; response; and recovery.

  17. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

    2015-10-15

    The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml-1. The median IC50 of neutralized viruses was 0.033 μg ml-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

  18. Mode of action for linear peptide inhibitors of HIV-1 gp120 interactions.

    Science.gov (United States)

    Biorn, Alyssa C; Cocklin, Simon; Madani, Navid; Si, Zhihai; Ivanovic, Tijana; Samanen, James; Van Ryk, Donald I; Pantophlet, Ralph; Burton, Dennis R; Freire, Ernesto; Sodroski, Joseph; Chaiken, Irwin M

    2004-02-24

    The linear peptide 12p1 (RINNIPWSEAMM) was previously isolated from a phage display library and was found to inhibit interaction of HIV-1 gp120 with both CD4 and a CCR5 surrogate, mAb 17b [Ferrer, M., and Harrison, S. (1999) J. Virol. 73, 5795-5802]. In this work, we investigated the mechanism that leads to this dual inhibition of gp120 binding. We found that there is a direct interaction of 12p1 with gp120, which occurs with a binding stoichiometry of 1:1. The peptide inhibits binding of monomeric YU2 gp120 to both sCD4 and 17b at IC(50) values of 1.1 and 1.6 microM, respectively. The 12p1 peptide also inhibited the binding of these ligands to trimeric envelope glycoproteins, blocked the binding of gp120 to the native coreceptor CCR5, and specifically inhibited HIV-1 infection of target cells in vitro. Analyses of sCD4 saturation of monomeric gp120 in the presence or absence of a fixed concentration of peptide suggest that 12p1 suppression of CD4 binding to gp120 is due to allosteric inhibitory effects rather than competitive inhibition of CD4 binding. Using a panel of gp120 mutants that exhibit weakened inhibition by 12p1, the putative binding site of the peptide was mapped to a region immediately adjacent to, but distinguishable from, the CD4 binding footprint. In the case of the peptide, the effects of single-12p1 residue substitutions and various peptide truncations indicate that the side chain of Trp7 and other structural elements of 12p1 are critical for gp120 binding or efficient inhibition of binding of a ligand to gp120. Finally, 12p1 was unable to inhibit binding of sCD4 to a gp120 mutant that is believed to resemble the CD4-induced conformation of gp120. These results suggest that 12p1 preferentially binds gp120 prior to engagement of CD4; binding of the peptide to gp120 limits the interaction with ligands (CD4 and CCR5) that are generally crucial for viral entry. More importantly, these results indicate that 12p1 binds to a unique site that may prove

  19. P-gp activity and inhibition in the different regions of human intestine ex vivo.

    Science.gov (United States)

    Li, Ming; de Graaf, Inge A M; de Jager, Marina H; Groothuis, Geny M M

    2017-03-01

    Although intestinal P-glycoprotein (P-gp) has been extensively studied in vitro and in animals, its activity and the consequences of P-gp inhibition for drug disposition and toxicity in humans are still difficult to accurately extrapolate from these studies. Moreover, existing in vitro models do not take into consideration that the intestine is heterogeneous with respect to P-gp expression. Recently, we reported rat precision-cut intestinal slices (PCIS) as a physiological ex vivo model to study the regional gradient of P-gp activity and inhibition. Here we extended the application of PCIS to the human intestine. For this purpose rhodamine 123 (R123) accumulation in the presence or absence of the P-gp inhibitors verapamil, cyclosporine A, quinidine, ketoconazole, PSC833 and CP100356 was measured in PCIS of human duodenum, jejunum, ileum and colon. R123 accumulation in the presence of the P-gp inhibitors appeared to be most enhanced in the ileum compared to the other regions. Moreover, the regional differences in accumulation are in line with published differences in abundance of P-gp. The rank order of the potency of the P-gp inhibitors, reflected by their IC50 , was comparable to that in rat PCIS. However, the increase in accumulation of the P-gp substrate R123 by the inhibitors was larger in human ileum PCIS than in rat PCIS, indicating species difference in P-gp abundance. These data show that human PCIS are an appropriate ex vivo model to study the activity of intestinal P-gp and predict the inhibitory effect of drugs and of transporter-mediated drug-drug interactions in the human intestine. Copyright © 2016 John Wiley & Sons, Ltd.

  20. A multi-system approach assessing the interaction of anticonvulsants with P-gp.

    Directory of Open Access Journals (Sweden)

    David Dickens

    Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

  1. Deletion of the highly conserved N-glycan at Asn260 of HIV-1 gp120 affects folding and lysosomal degradation of gp120, and results in loss of viral infectivity.

    Directory of Open Access Journals (Sweden)

    Leen Mathys

    Full Text Available N-linked glycans covering the surface of the HIV-1 glycoprotein gp120 are of major importance for the correct folding of this glycoprotein. Of the, on average, 24 N-linked glycans present on gp120, the glycan at Asn260 was reported to be essential for the correct expression of gp120 and gp41 in the virus particle and deletion of the N260 glycan in gp120 heavily compromised virus infectivity. We show here that gp160 containing the N260Q mutation reaches the Golgi apparatus during biosynthesis. Using pulse-chase experiments with [35S] methionine/cysteine, we show that oxidative folding was slightly delayed in case of mutant N260Q gp160 and that CD4 binding was markedly compromised compared to wild-type gp160. In the search of compensatory mutations, we found a mutation in the V1/V2 loop of gp120 (S128N that could partially restore the infectivity of mutant N260Q gp120 virus. However, the mutation S128N did not enhance any of the above-mentioned processes so its underlying compensatory mechanism must be a conformational effect that does not affect CD4 binding per se. Finally, we show that mutant N260Q gp160 was cleaved to gp120 and gp41 to a much lower extent than wild-type gp160, and that it was subject of lysosomal degradation to a higher extent than wild-type gp160 showing a prominent role of this process in the breakdown of N260-glycan-deleted gp160, which could not be counteracted by the S128N mutation. Moreover, at least part of the wild-type or mutant gp160 that is normally targeted for lysosomal degradation reached a conformation that enabled CD4 binding.

  2. HIV-1 gp41的酵母表面展示及表达优化%Yeast Surface Display of HIV-1 gp41 and Expression Enhancement

    Institute of Scientific and Technical Information of China (English)

    向柱方; 林影; 叶波; 韩双艳; 赵树进

    2008-01-01

    以His标签检测蛋白的表达,利用酿酒酵母表面展示系统,成功地将HIV-1 gp41片段锚定在酵母表面,并检测到gp41的活性.以pMD18T-gp41为模板,通过PCR技术克隆了gp41基因,将gp41基因通过双酶切连接到载体pICAS-His上,构建了gp41酵母表面展示载体,并将其转化至酿酒酵母(Saccharomyces cerevisiae)MT8-1中.重组菌经培养,利用免疫荧光染色方法进行染色,显微镜观察发现重组酵母细胞表面有绿色荧光,流式细胞仪结果进一步证实gp41正确折叠展示于酵母细胞表面.采用不同浓度的葡萄糖培养基进行表达优化.当葡萄糖浓度为1%时,82.46%的酵母细胞表达了gp41抗原;随着葡萄糖浓度升高,蛋白表达受到抑制.

  3. Integral equations

    CERN Document Server

    Tricomi, Francesco Giacomo

    1957-01-01

    This classic text on integral equations by the late Professor F. G. Tricomi, of the Mathematics Faculty of the University of Turin, Italy, presents an authoritative, well-written treatment of the subject at the graduate or advanced undergraduate level. To render the book accessible to as wide an audience as possible, the author has kept the mathematical knowledge required on the part of the reader to a minimum; a solid foundation in differential and integral calculus, together with some knowledge of the theory of functions is sufficient. The book is divided into four chapters, with two useful

  4. Protection promoted by pGP3 or pGP4 against Chlamydia muridarum is mediated by CD4(+) cells in C57BL/6N mice.

    Science.gov (United States)

    Mosolygó, Tímea; Szabó, Agnes M; Balogh, Emese P; Faludi, Ildikó; Virók, Dezső P; Endrész, Valéria; Samu, Alíz; Krenács, Tibor; Burián, Katalin

    2014-09-08

    Urogenital tract infection with Chlamydia trachomatis is a leading cause of sexually transmitted infections. There is currently no commercially available vaccine against C. trachomatis. The highly conserved plasmid of chlamydiae has been considered to be a virulence factor and the plasmid proteins have important roles in the Chlamydia-specific immune response. This study was designed to evaluate the efficacy of vaccination with plasmid proteins in the prevention of C. muridarum lung infection in a mouse model. C57BL/6N mice were immunised 3 times subcutaneously with recombinant pGP3 or pGP4 and infected with C. muridarum. Immunisation of the mice with recombinant pGP3 or pGP4 protein caused a significantly lower chlamydial burden in the lungs of the infected mice; the lower IFN-γ level indicated a reduced extent of inflammation. In vitro or in vivo neutralisation of C. muridarum with sera obtained from immunised mice did not reduce the number of viable C. muridarum in the lungs of mice. However, adoptive transfer of the CD4(+) spleen cells isolated from the immunised mice resulted in a significantly reduced bacterial burden. Our results indicate that it is not the pGP3- and pGP4-specific antibodies, but the CD4(+) cells that are responsible for the protective effect of the immune response to plasmid proteins.

  5. PASS-GP: Predictive active set selection for Gaussian processes

    DEFF Research Database (Denmark)

    Henao, Ricardo; Winther, Ole

    2010-01-01

    to the active set selection strategy and marginal likelihood optimization on the active set. We make extensive tests on the USPS and MNIST digit classification databases with and without incorporating invariances, demonstrating that we can get state-of-the-art results (e.g.0.86% error on MNIST) with reasonable......We propose a new approximation method for Gaussian process (GP) learning for large data sets that combines inline active set selection with hyperparameter optimization. The predictive probability of the label is used for ranking the data points. We use the leave-one-out predictive probability...... available in GPs to make a common ranking for both active and inactive points, allowing points to be removed again from the active set. This is important for keeping the complexity down and at the same time focusing on points close to the decision boundary. We lend both theoretical and empirical support...

  6. Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.

    Science.gov (United States)

    Tamamis, Phanourios; Floudas, Christodoulos A

    2014-01-01

    The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13-21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics.

  7. Preparation and Characterization of Chitosan/β-GP Membranes for Guided Bone Regeneration

    Institute of Scientific and Technical Information of China (English)

    CUI Jun; JIANG Baoqi; LIANG Jie; SUN Chang; LAN Jing; SUN Xiaoning; HUANG Haiyun; SUN Kangning; XU Xin

    2011-01-01

    Bioabsorbable chitosan/β-glycerol phosphate (CS/β-GP) composite membranes were fabricated through a relatively PH neutral and mild sol-gel process for guided bone regeneration (GBR). Their structural properties, morphology, and tensile strength were investigated. FTIR and XRD analyses indicated that there were chemical bonds between the CS and β-GP. SEM analysis revealed that the CS/β-GP composite membranes had a porous structure both at the surface and in sublayers.Even though the incorporation ofβ-GP in the CS matrix decreased the initial tensile strength of the membrane, the CS/β-GP membranes were still fit for GBR application with their tensile strength of roughly I MPa. The concentration ofβ-GP was proportional to the pore size and thickness but was inversely proportional to the tensile strength of the CS/β-GP membrane. The present findings indicate that, based on its characteristics, the CS/β-GP composite membrane is a potential bioresorbable membrane for use in guided bone regeneration.

  8. Admission and poor performance of trainees in the postgraduate GP training in the Netherlands

    NARCIS (Netherlands)

    Vermeulen, M.I.

    2014-01-01

    Until 2014 the selection for the Dutch postgraduate GP training was conducted locally, on the eight GP departments. The procedure consisted of a letter of application and a semi-structured interview. We investigated to what extend department of choice, candidates’ characteristics and qualities expla

  9. Systemic Functional Linguistic Genre Pedagogy ((SFL GP) in a Tertiary EFL Writing Context in Indonesia

    Science.gov (United States)

    Emilia, Emi; Hamied, Fuad Abdul

    2015-01-01

    This article reports on the results of a study aiming to investigate whether systemic functional linguistic genre pedagogy (SFL GP) can help students develop their writing ability in English and the students' opinions about the teaching program using SFL GP. The study was conducted in one semester with 19 student teachers taking a writing course…

  10. Pharmacological induction of CCL5 in vivo prevents gp120-mediated neuronal injury

    Science.gov (United States)

    Campbell, Lee A.; Avdoshina, Valeriya; Day, Chris; Lim, Seung T.; Mocchetti, Italo

    2015-01-01

    The human immunodeficiency virus (HIV) envelope protein gp120 promotes neuronal injury which is believed to contribute to HIV-associated neurocognitive disorders. Therefore, blocking the neurotoxic effect of gp120 may lead to alternative strategies to reduce the neurotoxic effect of HIV. In vitro, the neurotoxic effect of M-tropic gp120BaL is reduced by the chemokine CCL5, the natural ligand of CCR5 receptors. To determine whether CCL5 reduces the toxic effect of gp120BaL in vivo, animals were intrastriatally injected with lentiviral vectors overexpressing CCL5 prior to an intrastriatal injection of gp120BaL (400 ng). Neuronal injury was determined by silver staining, cleaved caspase-3 and TUNEL. Overexpression of CCL5 decreased gp120-mediated neuronal injury. CCL5 expression can be up-regulated by chronic morphine. Therefore, we examined whether morphine reduces the neurotoxic effect of gp120BaL. Rats stereotaxically injected with gp120BaL into the striatum received saline or chronic morphine for five days (10 mg/kg escalating to 30 mg/kg twice a day). Morphine-treated rats showed a decrease in all markers used to determine neuronal degeneration compared to saline-treated rats. The neuroprotective effect of morphine was significantly attenuated by expressing CCL5 shRNA. Our results suggest that compounds that increase the endogenous production of CCL5 may be used to reduce the pathogenesis of HIV–associated neurocognitive disorders. PMID:25623966

  11. Triage of febrile children at a GP cooperative : determinants of a consultation

    NARCIS (Netherlands)

    Monteny, Miriam; Berger, Marjolein Y.; van der Wouden, Johannes C.; Broekman, Berth J.; Koes, Bart W.

    2008-01-01

    Background Most febrile children contacting a GP cooperative are seen by a GP, although the incidence of serious illness is low. The guidelines for triage might not be suitable in primary care. Aim To investigate the determinants related to the outcome of triage in febrile children. Design of study

  12. 抗HIV-1gp41合成多肽gp41-5单克隆抗体的制备及初步鉴定%Preparation and Identification of Monoclonal Antibodies Against Synthesized Peptides gp41-5 Derived from HIV-1 Envelop gp41 Core Structure

    Institute of Scientific and Technical Information of China (English)

    于澜; 徐志凯; 王海涛; 张芳琳; 白文涛; 司瑞; 胡刚

    2006-01-01

    制备抗HIV-1 gp41合成多肽gp41-5的单克隆抗体(mAb),为筛选抗HⅣ-1多肽及分析gp41的抗原表位提供有用工具.常规动物免疫、细胞融合、克隆化制备抗gp41-5多肽mAb,并用EUSA法对其特异性、抗原识别表位及相对亲和力等做了初步鉴定.获得了4株抗gp41-5多肽的mAb,这4株mAb均特异识别gp41-5多肽,但不与gp41的N36或C34多肽片段反应.得到的4株mAb能特异结合gp41核心结构的空间构象.

  13. Screening and Identification of ssDNA Aptamer for Human GP73

    Directory of Open Access Journals (Sweden)

    Jingchun Du

    2015-01-01

    Full Text Available As one tumor marker of HCC, Golgi Protein 73 (GP73 is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens.

  14. Spectroscopic Classification of ASASSN-16gp as a Type Ia SN

    Science.gov (United States)

    Strader, Jay; Chomiuk, Laura; Prieto, Jose L.

    2016-07-01

    We obtained an optical spectrum of ASASSN-16gp (ATel #9199) on UT July 6.96 with the Goodman Spectrograph on the SOAR telescope. Classification with SNID (Blondin and Tonry 2007, ApJ, 666, 1024) indicates ASASSN-16gp is a normal Type Ia SN observed at 20-30 days after peak.

  15. Stochastic partial differential equations

    CERN Document Server

    Chow, Pao-Liu

    2014-01-01

    Preliminaries Introduction Some Examples Brownian Motions and Martingales Stochastic Integrals Stochastic Differential Equations of Itô Type Lévy Processes and Stochastic IntegralsStochastic Differential Equations of Lévy Type Comments Scalar Equations of First Order Introduction Generalized Itô's Formula Linear Stochastic Equations Quasilinear Equations General Remarks Stochastic Parabolic Equations Introduction Preliminaries Solution of Stochastic Heat EquationLinear Equations with Additive Noise Some Regularity Properties Stochastic Reaction-Diffusion Equations Parabolic Equations with Grad

  16. Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

    Directory of Open Access Journals (Sweden)

    Johansson Ingegerd

    2007-06-01

    Full Text Available Abstract Background Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of Streptococcus mutans (implicated in caries, harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of S. mutans. Methods A case-referent study was performed in 12-year-old Swedish children with high (n = 19 or low (n = 19 caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of S. mutans using the partial least squares (PLS multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms. Results All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively. The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37 and saliva adhesion of S. mutans Ingbritt (VIP = 1.47. The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of S. mutans strains Ingbritt and NG8 and Lactococcus lactis expressing AgI/II adhesins (SpaP or PAc compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins. Conclusion Gp-340 I behaves as a caries

  17. Hybrid Wavelet-Postfix-GP Model for Rainfall Prediction of Anand Region of India

    Directory of Open Access Journals (Sweden)

    Vipul K. Dabhi

    2014-01-01

    Full Text Available An accurate prediction of rainfall is crucial for national economy and management of water resources. The variability of rainfall in both time and space makes the rainfall prediction a challenging task. The present work investigates the applicability of a hybrid wavelet-postfix-GP model for daily rainfall prediction of Anand region using meteorological variables. The wavelet analysis is used as a data preprocessing technique to remove the stochastic (noise component from the original time series of each meteorological variable. The Postfix-GP, a GP variant, and ANN are then employed to develop models for rainfall using newly generated subseries of meteorological variables. The developed models are then used for rainfall prediction. The out-of-sample prediction performance of Postfix-GP and ANN models is compared using statistical measures. The results are comparable and suggest that Postfix-GP could be explored as an alternative tool for rainfall prediction.

  18. EigenGP: Gaussian processes with sparse data-dependent eigenfunctions

    CERN Document Server

    Qi, Yuan; Zhu, Yao

    2012-01-01

    Gaussian processes (GPs) provide a nonparametric representation of functions. Given N training points, the exact GP inference incurs high computational cost. A variety of sparse GP methods have been proposed to speed up GP inference. These methods essentially trade prediction accuracy with computational effciency. In this paper, we address this problem from a new perspective: we define an exact Gaussian process model, EigenGP, whose covariance function has a sparse spectrum adaptive to data. Specifically, we estimate eigenfunctions of covariance function based on training data and use an empirical Bayesian approach to select these eigenfunctions. Thus, unlike the previous Nystrom-based methods, EigenGP defines an exact Gaussian process model with an data-dependent covariance function. To handle nonlinear likelihoods, we develop an efficient expectation propagation inference algorithm, and couple it with an active-set algorithm for evidence maximization. Because the selected eigenfunctions (based on Gaussian ...

  19. Scalar Field as a Bose-Einstein Condensate?

    CERN Document Server

    Castellanos, Elías; Núñez, Darío

    2013-01-01

    We present a flat space analogy between a classical scalar field with a self-interacting potential and a Bose-Einstein condensate (BEC). In particular, we reduce the Klein-Gordon equation, governing the dynamics of the scalar field, to a Gross-Pitaevskii--like equation (GPE), governing the dynamics of BEC's. Moreover, the introduction of a curved background spacetime endows, in a natural way, the resulting GPE-like equation with an explicit confinement potential. Additionally, Thomas-Fermi approximation is applied to the 3-dimensional version of this GPE, in order to calculate some thermodynamical properties of the self-interacting scalar field system.

  20. HIV-1膜蛋白基因gp120和gp41的合成及在毕赤酵母中的表达%Expression of Human Immunodeficiency Virus-1 gp120 and gp41 Gene Synthesized in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    洪国强; 胡波; 李朝霞

    2008-01-01

    目的 合成适合酵母表述的HIV-1 膜蛋白gp120和gp41基因,在半赤酵母中高效表达分泌型重组HIV-1 gp120和sp41抗原.方法 选用酵母偏爱的同义密码子替换野生型gp120和gp41基因的酵母稀有密码子,采取基因搭桥法及聚合酶链反应(PCR),合成HIV-1 8p120和gp41基因,构建分泌型重组质粒并转化半赤酵母菌株GS115,经甲醇诱导表达HIV-1外膜糖蛋白gp120和sp41.结果 DNA测序证实合成的HIV-1 gp120和sp41基因正确克隆到表达载体中;聚丙烯酰胺凝胶电泳及免疫印迹显示gp120和sp41在毕赤酵母中高效分泌表达.结论 gp120和gp41合成基因在毕赤酵母表达系统高效分泌表达.

  1. Kinetic Thomas–Fermi solutions of the Gross–Pitaevskii equation

    NARCIS (Netherlands)

    Ölschläger, M.; Wirth, G.; de Morais Smith, C.; Hemmerich, Andreas

    2009-01-01

    Approximate solutions of the Gross–Pitaevskii (GP) equation, obtained upon neglection of the kinetic energy, are well known as Thomas–Fermi solutions. They are characterized by the compensation of the local potential by the collisional energy. In this article we consider exact solutions of the

  2. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

    Science.gov (United States)

    Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Ndabambi, Nonkululeko; Druz, Aliaksandr; Williamson, Carolyn

    2017-01-01

    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

  3. Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

    Energy Technology Data Exchange (ETDEWEB)

    Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

    2017-01-11

    A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

  4. Study on Genetic Diversity of HIV-1 gp41 Gene Segment%HIV-1 gp41基因片段亚型多样性研究

    Institute of Scientific and Technical Information of China (English)

    刘翌; 杨成勇

    2006-01-01

    [目的]应用HIV-1 env gp41基因分型技术进行出入境HIV感染者HIV-1亚型多样性研究.[方法]采用套式逆转录PCR方法对env gp41和gp120(C2-V3区)进行基因扩增、测序、亚型对比分析,以及应用威斯康星GCG公司软件进行系统树分析和用美国Los Alamos国家实验室的HIV-Blast软件进行序列的亚型鉴定.[结果]对22份样本的gp41和gp120(C2-V3区)的基因亚型进行对比分析,结果表明gp41和gp120(C2-V3区)在亚型上具有一致性.对65例来自中国、非洲、欧洲、美洲和东南亚的出入境HIV-1阳性者进行gp41扩增基因亚型分析,发现有A、B、C、D、F1、G亚型和重组亚型AC、01_AE、02-AG、07_BC、08_BC、06_cpx、18 cpx共计13种亚型,其中重组株占33.8%(22/65).中国籍出入境感染者包括了A、B、C、D、F1、G亚型和重组亚型01_AE、02_AG、07_BC、08_BC在内的10种亚型,其中重组株占25%(7/28).[结论]用gp41替代gp120(C2-V3区)进行HIV-1亚型分析较为理想.出入境人群中HIV感染者感染的HIV毒株几乎包括了全球流行的所有亚型,多种国内少见的亚型已经通过国际旅行者传入国内.

  5. File list: InP.Dig.50.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.50.AllAg.GP5d hg19 Input control Digestive tract GP5d SRX360587,SRX360571,S...RX360585,SRX360573,SRX360572,SRX360586 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.50.AllAg.GP5d.bed ...

  6. File list: InP.Dig.05.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.05.AllAg.GP5d hg19 Input control Digestive tract GP5d SRX360587,SRX360585,S...RX360571,SRX360586,SRX360572,SRX360573 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.05.AllAg.GP5d.bed ...

  7. File list: InP.Dig.20.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.20.AllAg.GP5d hg19 Input control Digestive tract GP5d SRX360587,SRX360571,S...RX360585,SRX360573,SRX360572,SRX360586 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.20.AllAg.GP5d.bed ...

  8. File list: InP.Dig.10.AllAg.GP5d [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Dig.10.AllAg.GP5d hg19 Input control Digestive tract GP5d SRX360587,SRX360585,S...RX360571,SRX360573,SRX360572,SRX360586 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Dig.10.AllAg.GP5d.bed ...

  9. Cloning and sequence analysis of the Antheraea pernyi nucleopolyhedrovirus gp64 gene

    Indian Academy of Sciences (India)

    Wenbing Wang; Shanying Zhu; Liqun Wang; Feng Yu; Weide Shen

    2005-12-01

    Frequent outbreaks of the purulence disease of Chinese oak silkworm are reported in Middle and Northeast China. The disease is produced by the pathogen Antheraea pernyi nucleopolyhedrovirus (AnpeNPV). To obtain molecular information of the virus, the polyhedra of AnpeNPV were purified and characterized. The genomic DNA of AnpeNPV was extracted and digested with HindIII. The genome size of AnpeNPV is estimated at 128 kb. Based on the analysis of DNA fragments digested with HindIII, 23 fragments were bigger than 564 bp. A genomic library was generated using HindIII and the positive clones were sequenced and analysed. The gp64 gene, encoding the baculovirus envelope protein GP64, was found in an insert. The nucleotide sequence analysis indicated that the AnpeNPV gp64 gene consists of a 1530 nucleotide open reading frame (ORF), encoding a protein of 509 amino acids. Of the eight gp64 homologues, the AnpeNPV gp64 ORF shared the most sequence similarity with the gp64 gene of Anticarsia gemmatalis NPV, but not Bombyx mori NPV. The upstream region of the AnpeNPV gp64 ORF encoded the conserved transcriptional elements for early and late stage of the viral infection cycle. These results indicated that AnpeNPV belongs to group I NPV and was far removed in molecular phylogeny from the BmNPV.

  10. Esters of the Marine-Derived Triterpene Sipholenol A Reverse P-GP-Mediated Drug Resistance

    Directory of Open Access Journals (Sweden)

    Yongchao Zhang

    2015-04-01

    Full Text Available Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1. Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines, we identified that the semisynthetic esters sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from [3H]-paclitaxel accumulation and efflux studies suggested that these two triterpenoids were able to increase the intracellular accumulation of paclitaxel by inhibiting its active efflux. In addition, western blot analysis revealed that these two compounds did not alter the expression levels of P-gp when treated up to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp membranes, which suggested that they might be substrates of P-gp. Moreover, in silico molecular docking studies revealed the virtual binding modes of these two compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may represent potential reversal agents for the treatment of multidrug resistant cancers.

  11. Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review.

    Science.gov (United States)

    Le Floch, B; Bastiaens, H; Le Reste, J Y; Lingner, H; Hoffman, R D; Czachowski, S; Assenova, R; Koskela, T H; Klemenc-Ketis, Z; Nabbe, P; Sowinska, A; Montier, T; Peremans, L

    2016-09-13

    Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.

  12. Structural and Functional Studies on the Marburg Virus GP2 Fusion Loop.

    Science.gov (United States)

    Liu, Nina; Tao, Yisong; Brenowitz, Michael D; Girvin, Mark E; Lai, Jonathan R

    2015-10-01

    Marburg virus (MARV) and the ebolaviruses belong to the family Filoviridae (the members of which are filoviruses) that cause severe hemorrhagic fever. Infection requires fusion of the host and viral membranes, a process that occurs in the host cell endosomal compartment and is facilitated by the envelope glycoprotein fusion subunit, GP2. The N-terminal fusion loop (FL) of GP2 is a hydrophobic disulfide-bonded loop that is postulated to insert and disrupt the host endosomal membrane during fusion. Here, we describe the first structural and functional studies of a protein corresponding to the MARV GP2 FL. We found that this protein undergoes a pH-dependent conformational change, as monitored by circular dichroism and nuclear magnetic resonance. Furthermore, we report that, under low pH conditions, the MARV GP2 FL can induce content leakage from liposomes. The general aspects of this pH-dependent structure and lipid-perturbing behavior are consistent with previous reports on Ebola virus GP2 FL. However, nuclear magnetic resonance studies in lipid bicelles and mutational analysis indicate differences in structure exist between MARV and Ebola virus GP2 FL. These results provide new insight into the mechanism of MARV GP2-mediated cell entry.

  13. Atomic force microscopy fishing and mass spectrometry identification of gp120 on immobilized aptamers

    Directory of Open Access Journals (Sweden)

    Ivanov YD

    2014-10-01

    Full Text Available Yuri D Ivanov,1 Natalia S Bukharina,1 Tatyana O Pleshakova,1 Pavel A Frantsuzov,1 Elena Yu Andreeva,1 Anna L Kaysheva,1,2 Victor G Zgoda,1 Alexander A Izotov,1 Tatyana I Pavlova,1 Vadim S Ziborov,1 Sergey P Radko,1 Sergei A Moshkovskii,1 Alexander I Archakov1 1Department of Personalized Medicine, Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences, Moscow, Russia; 2PostgenTech Ltd., Moscow, Russia Abstract: Atomic force microscopy (AFM was applied to carry out direct and label-free detection of gp120 human immunodeficiency virus type 1 envelope glycoprotein as a target protein. This approach was based on the AFM fishing of gp120 from the analyte solution using anti-gp120 aptamers immobilized on the AFM chip to count gp120/aptamer complexes that were formed on the chip surface. The comparison of image contrasts of fished gp120 against the background of immobilized aptamers and anti-gp120 antibodies on the AFM images was conducted. It was shown that an image contrast of the protein/aptamer complexes was two-fold higher than the contrast of the protein/antibody complexes. Mass spectrometry identification provided an additional confirmation of the target protein presence on the AFM chips after biospecific fishing to avoid any artifacts. Keywords: gp120 HIV-1 envelope glycoprotein, aptamer, atomic force microscopy, mass spectrometry

  14. Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions.

    Directory of Open Access Journals (Sweden)

    Victor Buzon

    2010-05-01

    Full Text Available The HIV-1 envelope glycoprotein (Env composed of the receptor binding domain gp120 and the fusion protein subunit gp41 catalyzes virus entry and is a major target for therapeutic intervention and for neutralizing antibodies. Env interactions with cellular receptors trigger refolding of gp41, which induces close apposition of viral and cellular membranes leading to membrane fusion. The energy released during refolding is used to overcome the kinetic barrier and drives the fusion reaction. Here, we report the crystal structure at 2 A resolution of the complete extracellular domain of gp41 lacking the fusion peptide and the cystein-linked loop. Both the fusion peptide proximal region (FPPR and the membrane proximal external region (MPER form helical extensions from the gp41 six-helical bundle core structure. The lack of regular coiled-coil interactions within FPPR and MPER splay this end of the structure apart while positioning the fusion peptide towards the outside of the six-helical bundle and exposing conserved hydrophobic MPER residues. Unexpectedly, the section of the MPER, which is juxtaposed to the transmembrane region (TMR, bends in a 90 degrees-angle sideward positioning three aromatic side chains per monomer for membrane insertion. We calculate that this structural motif might facilitate the generation of membrane curvature on the viral membrane. The presence of FPPR and MPER increases the melting temperature of gp41 significantly in comparison to the core structure of gp41. Thus, our data indicate that the ordered assembly of FPPR and MPER beyond the core contributes energy to the membrane fusion reaction. Furthermore, we provide the first structural evidence that part of MPER will be membrane inserted within trimeric gp41. We propose that this framework has important implications for membrane bending on the viral membrane, which is required for fusion and could provide a platform for epitope and lipid bilayer recognition for broadly

  15. Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

    Directory of Open Access Journals (Sweden)

    Xinghui Li

    Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

  16. Documentation only - no data type tows data collected in the Gulf of Alaska and North Pacific Ocean on the CHARTER/FISHING BOATS cruises GP0108, GP0207-01 and GP0207-02 as part of the NEP project from 2001-07-29 to 2002-08-06 (NODC Accession 0115275)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NODC Accession 0115275 includes tows data collected aboard the CHARTER/FISHING BOATS during cruises GP0108, GP0207-01 and GP0207-02 in the Gulf of Alaska and North...

  17. Lineage-specific differences between human and simian immunodeficiency virus regulation of gp120 trimer association and CD4 binding.

    Science.gov (United States)

    Finzi, Andrés; Pacheco, Beatriz; Xiang, Shi-Hua; Pancera, Marie; Herschhorn, Alon; Wang, Liping; Zeng, Xing; Desormeaux, Anik; Kwong, Peter D; Sodroski, Joseph

    2012-09-01

    Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both viruses, the gp120 N/C termini and the inner domain β-sandwich and layer 2 support the noncovalent association of gp120 with the envelope glycoprotein trimer. Layer 1 of the SIVmac gp120 inner domain contributes more to trimer association than the corresponding region of HIV-1 gp120. On the other hand, layer 1 plays an important role in stabilizing the CD4-bound conformation of HIV-1 but not SIVmac gp120 and thus contributes to HIV-1 binding to CD4. In SIVmac, CD4 binding is instead enhanced by tryptophan 375, which fills the Phe 43 cavity of gp120. Activation of SIVmac by soluble CD4 is dependent on tryptophan 375 and on layer 1 residues that determine a tight association of gp120 with the trimer. Distinct biological requirements for CD4 usage have resulted in lineage-specific differences in the HIV-1 and SIV gp120 structures that modulate trimer association and CD4 binding.

  18. Membrane insertion and assembly of epitope-tagged gp9 at the tip of the M13 phage

    Directory of Open Access Journals (Sweden)

    Kuhn Andreas

    2011-09-01

    Full Text Available Abstract Background Filamentous M13 phage extrude from infected Escherichia coli with a tip structure composed of gp7 and gp9. This tip structure is extended by the assembly of the filament composed of the major coat protein gp8. Finally, gp3 and gp6 terminate the phage structure at the proximal end. Up to now, gp3 has been the primary tool for phage display technology. However, gp7, gp8 and gp9 could also be used for phage display and these phage particles should bind to two different or more surfaces when the modified coat proteins are combined. Therefore, we tested here if the amino-terminal end of gp9 can be modified and whether the modified portion is exposed and detectable on the M13 phage particles. Results The amino-terminal region of gp9 was modified by inserting short sequences that encode antigenic epitopes. We show here that the modified gp9 proteins correctly integrate into the membrane using the membrane insertase YidC exposing the modified epitope into the periplasm. The proteins are then efficiently assembled onto the phage particles. Also extensions up to 36 amino acid residues at the amino-terminal end of gp9 did not interfere with membrane integration and phage assembly. The exposure of the antigenic tags on the phage was visualised with immunogold labelling by electron microscopy and verified by dot blotting with antibodies to the tags. Conclusions Our results suggest that gp9 at the phage tip is suitable for the phage display technology. The modified gp9 can be supplied in trans from a plasmid and fully complements M13 phage with an amber mutation in gene 9. The modified phage tip is very well accessible to antibodies.

  19. Monoclonal Antibodies Recognizing HIV-1 gp41 Could Inhibit Env-Mediated Syncytium Formation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Geng; CHEN Yinghua

    2005-01-01

    Some monoclonal antibodies (mAbs) could inhibit infection by HIV-1. In this study, four mAbs against HIV-1 gp41 were prepared in mice. All four mAbs could bind to the recombinant soluble gp41 and recognize the native envelope glycoprotein gp160 expressed on the HIV-Env+ CHO-WT cell in flow cytometry analysis. Interestingly, the results show that all four mAbs purified by affinity chromatography could inhibit HIV-1 Env-mediated membrane fusion (syncytium formation) by 40%-60% at 10 μg/mL, which implies potential inhibitory activities against HIV-1.

  20. Molecular motions and conformational transition between different conformational states of HIV-1 gp120 envelope glycoprotein

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The HIV-1 gp120 exterior envelope glycoprotein undergoes a series of conformational rearrangements while sequentially interacting with the receptor CD4 and coreceptor CCR5 or CXCR4 on the surface of host cells to initiate virus entry. Both the crystal structures of the HIV-1 gp120 core bound by the CD4 and antigen 17b and the SIV gp120 core prebound by CD4 are known. Despite the wealth of knowledge on these static snapshots of molecular conformations, the details of molecular motions involved in conformational transition that are crucial to intervention remain elusive. We presented comprehensive comparative analyses of the dynamics behaviors of the gp120 in its CD4-complexed, CD4-free and CD4-unliganded states based on the homology models with modeled V3 and V4 loops by means of CONCOORD computer simulation to generate ensembles of feasible protein structures that were subsequently analysed by essential dynamics analyses to identify preferred concerted motions. The revealed collective fluctuations are dominated by complex modes of combinational motions of the rotation/twisting, flexing/closure, and shortness/elongation between or within the inner, outer, and bridging-sheet domains, and these modes are related to the CD4 association and HIV neutralization avoidance. Further essential subspace overlap analyses were performed to quantitatively distinguish the preference for conformational transitions between the three states, revealing that the unliganded gp120 has a greater potential to translate its conformation into the conformational state adopted by the CD4-complexed gp120 than by the CD4-free gp120, whereas the CD4-free gp120 has a greater potential to translate its conformation into the unliganded state than the CD4-complexed gp120 does. These dy-namics data of gp120 in its different conformations are helpful in understanding the relationship be-tween the molecular motion/conformational transition and the function of gp120, and in gp120-structure-based subunit

  1. Cross-over to quasi-condensation: mean-field theories and beyond

    Science.gov (United States)

    Henkel, Carsten; Sauer, Tim-O.; Proukakis, N. P.

    2017-06-01

    We analyze the cross-over of a homogeneous, weakly interacting Bose gas in one dimension from the ideal gas into the dense quasi-condensate phase. We review a number of mean-field theories, perturbative or self-consistent, and provide accurate evaluations of equation of state, density fluctuations, and correlation functions. A smooth crossover is reproduced by classical-field simulations based on the stochastic Gross-Pitaevskii equation and the Yang-Yang solution to the one-dimensional Bose gas.

  2. Phonon-Josephson resonances in atomtronic circuits

    Science.gov (United States)

    Bidasyuk, Y. M.; Prikhodko, O. O.; Weyrauch, M.

    2016-09-01

    We study the resonant excitation of sound modes from Josephson oscillations in Bose-Einstein condensates. From the simulations for various setups using the Gross-Pitaevskii mean-field equations and Josephson equations we observe additional tunneling currents induced by resonant phonons. The proposed experiment may be used for spectroscopy of phonons as well as other low-energy collective excitations in Bose-Einstein condensates. We also argue that the observed effect may mask the observation of Shapiro resonances if not carefully controlled.

  3. Chaotic Josephson effects in two-coupled Bose-Einstein condensates

    Science.gov (United States)

    Fang, Jianshu; Hai, Wenhua; Chong, Guishu; Xie, Qiongtao

    2005-04-01

    We discuss the chaotic Josephson effects in two weakly coupled Bose-Einstein condensates (BECs). The boson Josephson junction (BJJ) dynamics in BECs is governed by the two-mode Gross-Pitaevskii equation. We obtained a perturbed chaotic solution of the BJJ equation by using the direct perturbation technique. Theoretical analysis reveals that the stable oscillating orbits are embedded in the Melnikov chaotic attractors. The corresponding numerical results show that the Poincaré sections in the equivalent phase space (φ,φ˙) sensitively depends on the system parameter and initial conditions. Therefore, we can control the transitions between chaos and order by adjusting these parameters and conditions.

  4. Component separation in harmonically trapped boson-fermion mixtures

    DEFF Research Database (Denmark)

    Nygaard, Nicolai; Mølmer, Klaus

    1999-01-01

    We present a numerical study of mixed boson-fermion systems at zero temperature in isotropic and anise tropic harmonic traps. We investigate the phenomenon of component separation as a function of the strength ut the interparticle interaction. While solving a Gross-Pitaevskii mean-field equation...... for the boson distribution in the trap, we utilize two different methods to extract the density profile of the fermion component; a semiclassical Thomas-Fermi approximation and a quantum-mechanical Slater determinant Schrodinger equation....

  5. Cleaner Production Assessment of Fast Bordeaux GP Base

    Directory of Open Access Journals (Sweden)

    Mausumi Mukhopadhyay

    2011-01-01

    Full Text Available The pilot plant study of cleaner production (CP process of a dyes intermediate, Fast Bordeaux GP Base (2-nitro-p-anisidine, is presented in this work. The existing production process with acetic anhydride as raw material generates highly polluting (high chemical oxygen demand, huge-volume effluent, and thus the treatment is expensive. In the proposed process, raw material acetic anhydride in acetylation step is replaced with acetic acid. The reaction conditions like reaction time (3 h, temperature (120∘C and molar ratio of p-anisidine and acetic acid (1 : 3.58 are optimized in the laboratory scale and implemented in pilot plant. The extent of conversion has been monitored by nitrite value test, and purity of product mixture is measured with thin-layer chromatography (TLC. The acidic wastewater quantity is dramatically reduced by incorporating recycling in washing scheme, and thus water consumption is reduced. Reduction in wastewater generation and reduction/elimination of treatment cost is also observed. Chemical oxygen demand (COD of the effluent stream is reduced by the recovery of by-products sodium acetate and spent acid. The technoeconomical feasibility studies show that the proposed CP options are highly economical and environmental friendly.

  6. Myeloma light chains are ligands for cubilin (gp280).

    Science.gov (United States)

    Batuman, V; Verroust, P J; Navar, G L; Kaysen, J H; Goda, F O; Campbell, W C; Simon, E; Pontillon, F; Lyles, M; Bruno, J; Hammond, T G

    1998-08-01

    Although myeloma light chains are known to undergo receptor-mediated endocytosis in the kidney, the molecular identity of the receptor has not been characterized. We examined the interaction between cubilin (gp280) and four species of light chains isolated from the urine of patients with multiple myeloma. Four lines of evidence identify cubilin, a giant glycoprotein receptor, which is restricted in distribution to endocytic scavenger pathways and which has potent effects on endosomal trafficking, as a potentially physiologically relevant binding site for light chains: 1) light chains coeluted during immunoaffinity purification of cubilin; 2) polyclonal antisera to cubilin but not control sera, displaced human light chain binding from rat renal brush-border membranes; 3) cubilin bound to multiple species of light chains during surface plasmon resonance; 4) anti-cubilin antiserum interfered with light chain endocytosis by visceral yolk sac epithelial cells. However, both binding of light chains to brush-border membranes and endocytosis of light chains by yolk sac epithelial cells were only partially inhibited by anticubilin antibodies, suggesting presence of additional or alternate binding sites for light chains. Excess light chain had a potent inhibitory effect on endosomal fusion in vitro. Binding showed dose and time-dependent saturability with low-affinity, high-capacity equilibrium binding parameters. These data demonstrate that cubilin plays a role in the endocytosis and trafficking of light chains in renal proximal tubule cells.

  7. Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

    Energy Technology Data Exchange (ETDEWEB)

    Bellamy-McIntyre, Anna K. [Macfarlane Burnet Institute for Medical Research and Public Health, Vic. 3004 (Australia); Department of Microbiology, Monash University, Vic. 3168 (Australia); Baer, Severine [Program Infection and Cancer, Abt. F010 and INSERM U701, Deutsches Krebsforschungszentrum, Heidelberg (Germany); Ludlow, Louise [Macfarlane Burnet Institute for Medical Research and Public Health, Vic. 3004 (Australia); Drummer, Heidi E. [Macfarlane Burnet Institute for Medical Research and Public Health, Vic. 3004 (Australia); Department of Microbiology, Monash University, Vic. 3168 (Australia); Department of Microbiology and Immunology, The University of Melbourne, Vic. 3010 (Australia); Poumbourios, Pantelis, E-mail: apoumbourios@burnet.edu.au [Macfarlane Burnet Institute for Medical Research and Public Health, Vic. 3004 (Australia); Department of Microbiology, Monash University, Vic. 3168 (Australia)

    2010-04-16

    The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1{sub QH1549.13} blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.

  8. Numerical simulation code for self-gravitating Bose-Einstein condensates

    Science.gov (United States)

    Madarassy, Enikő J. M.; Toth, Viktor T.

    2013-04-01

    We completed the development of simulation code that is designed to study the behavior of a conjectured dark matter galactic halo that is in the form of a Bose-Einstein Condensate (BEC). The BEC is described by the Gross-Pitaevskii equation, which can be solved numerically using the Crank-Nicholson method. The gravitational potential, in turn, is described by Poisson’s equation, that can be solved using the relaxation method. Our code combines these two methods to study the time evolution of a self-gravitating BEC. The inefficiency of the relaxation method is balanced by the fact that in subsequent time iterations, previously computed values of the gravitational field serve as very good initial estimates. The code is robust (as evidenced by its stability on coarse grids) and efficient enough to simulate the evolution of a system over the course of 109 years using a finer (100×100×100) spatial grid, in less than a day of processor time on a contemporary desktop computer. Catalogue identifier: AEOR_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEOR_v1_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 5248 No. of bytes in distributed program, including test data, etc.: 715402 Distribution format: tar.gz Programming language: C++ or FORTRAN. Computer: PCs or workstations. Operating system: Linux or Windows. Classification: 1.5. Nature of problem: Simulation of a self-gravitating Bose-Einstein condensate by simultaneous solution of the Gross-Pitaevskii and Poisson equations in three dimensions. Solution method: The Gross-Pitaevskii equation is solved numerically using the Crank-Nicholson method; Poisson’s equation is solved using the relaxation method. The time evolution of the system is governed by the Gross-Pitaevskii equation; the solution of Poisson

  9. Recombinant expression and purification of T4 phage Hoc, Soc, gp23, gp24 proteins in native conformations with stability studies.

    Directory of Open Access Journals (Sweden)

    Paulina Miernikiewicz

    Full Text Available Understanding the biological activity of bacteriophage particles is essential for rational design of bacteriophages with defined pharmacokinetic parameters and to identify the mechanisms of immunobiological activities demonstrated for some bacteriophages. This work requires highly purified preparations of the individual phage structural proteins, possessing native conformation that is essential for their reactivity, and free of incompatible biologically active substances such as bacterial lipopolysaccharide (LPS. In this study we describe expression in E. coli and purification of four proteins forming the surface of the bacteriophage T4 head: gp23, gp24, gphoc and gpsoc. We optimized protein expression using a set of chaperones for effective production of soluble proteins in their native conformations. The assistance of chaperones was critical for production of soluble gp23 (chaperone gp31 of T4 phage and of gpsoc (chaperone TF of E. coli. Phage head proteins were purified in native conditions by affinity chromatography and size-exclusion chromatography. Two-step LPS removal allowed immunological purity grade with the average endotoxin activity less than 1 unit per ml of protein preparation. The secondary structure and stability of the proteins were studied using circular dichroism (CD spectrometry, which confirmed that highly purified proteins preserve their native conformations. In increasing concentration of a denaturant (guanidine hydrochloride, protein stability was proved to increase as follows: gpsoc, gp23, gphoc. The denaturation profile of gp24 protein showed independent domain unfolding with the most stable larger domain. The native purified recombinant phage proteins obtained in this work were shown to be suitable for immunological experiments in vivo and in vitro.

  10. Prevalence of Human Papillomavirus Types Among Mexican Women with Intraepithelial Lesions and Cervical Cancer: Detection with MY09/MY011 and GP5+/GP6+ Primer Systems

    Directory of Open Access Journals (Sweden)

    Gloria Fernández-Tilapa

    2007-01-01

    Full Text Available Squamous cervical carcinoma (SCC is the most common cancer found in Mexican women. Human papillomavirus (HPV infection is a prerequisite for this disease. In Mexico little is known about the prevalence of HPV-types and knowledge of the circulating genotypes by region is limited. The aim of this study was to determine the prevalence and genotypes of HPV in biopsies from women with intraepithelial lesions and SCC. A total of 211 cervical biopsies were studied. Histopathological analysis was done and HPV DNA was detected by PCR using MY09/MY11 (MY-PCR and GP5+/GP6+ (GP+PCR primers. Viral type was determined by RFLP’s or sequencing. Tissues were classified as low-grade squamous intraepithelial lesion (LSIL in 123 cases, high-grade squamous intraepithelial lesion (HSL in 40 and SCC in 48. Prevalence of HPV was 55.3% in LSIL, 65% in HSIL and 91.7% in SCC by MY-PCR. These percentages increased to 83, 77.5 and 100%, respectively, when HPV-negative samples were analyzed by GP+PCR. In 138 of 211 samples (65.4%, HPV was detected by MY-PCR and 43 (20.4% were positive by GP+PCR. In 166 (91.7% of 181 infections high risk HPV-types were found. Twelve genotypes were detected (16, 18, 31, 33, 45, 52, 58, 59, 61, 66, 70, 81. Prevalence of HPV 16 in LSIL, HSIL and SCC, were 70.6, 54.8 and 70.8%, respectively and it was the most common type in all cases (67.9%. A significantly higher number of positive samples were detected with MY-PCR and GP+PCR. The high prevalence of HPV infection with high-risk types, especially HPV16, among Mexican women with SIL and SCC, has important implications in the treatment and prophylaxis.

  11. Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

    Energy Technology Data Exchange (ETDEWEB)

    Costantini, Lindsey M. [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Irvin, Susan C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Kennedy, Steven C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Guo, Feng [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Goldstein, Harris; Herold, Betsy C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Snapp, Erik L., E-mail: erik-lee.snapp@einstein.yu.edu [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

    2015-02-15

    The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

  12. Variant size- and glycoforms of the scavenger receptor cysteine-rich protein gp-340 with differential bacterial aggregation

    DEFF Research Database (Denmark)

    Eriksson, Christer; Frängsmyr, Lars; Danielsson Niemi, Liza

    2007-01-01

    Glycoprotein gp-340 aggregates bacteria in saliva as part of innate defence at mucosal surfaces. We have detected size- and glycoforms of gp-340 between human saliva samples (n = 7) and lung gp-340 from a proteinosis patient using antibodies and lectins in Western blots and ELISA measurements...... bands. Purified I to IV proteins all revealed a N-terminal sequence TGGWIP upon Edman degradation. Moreover, purified gp-340 from the seven donors and lung gp-340 shared N-glycans, sialylated Galbeta1-3GalNAc and (poly)lactosamine structures. However, the larger size gp-340 grouping II/III (n = 4....... Western blots of saliva samples, and of gp-340 purified, from the seven donors using a gp-340 specific antibody distinguished four gp-340 size variants, designated I to IV (n = 2,2,2 and 1). While saliva gp-340 variants I to III had single bands of increasing sizes, variant IV and lung gp-340 had double...

  13. Optimization of expression of human immunodeficiency virus type 1 envelope gp41 in E coli%人类免疫缺陷病毒-1包膜糖蛋白gp41的表达及优化

    Institute of Scientific and Technical Information of China (English)

    包丽娜; 白杨; 姚岚; 庄敏; 凌虹

    2016-01-01

    目的 优化HIV-1本地流行株06044 gp41蛋白表达设计,为gp41免疫原的制备提供实验基础.方法 以含HIV-1 06044 gp41基因的质粒为模板,采用聚合酶链反应(PCR)扩增gp41目的基因,分别构建原核表达载体pET26b-gp41T(含546~683 aa片段)及去掉N-端(NHR)和C-端(CHR)七价重复序列中间部分loop区(582~627aa)的pET26b-gp41 T(△L),经测序确认后,转化至大肠杆菌感受态细胞BL21 (DE3)中,IPTG诱导表达.用聚丙烯酰氨凝胶电泳(SDS-PAGE)及Western blot检测并鉴定重组表达蛋白.优化了重组蛋白的诱导表达条件.结果 pET26b-gp41T和pET26b-gp4 1T (△L)重组表达质粒均能表达gp41蛋白,gp41T (△L)蛋白表达量高于gp41T;不同IPTG浓度诱导的蛋白表达量没有区别;用1 mmol/L IPTG诱导后,37℃条件下表达量最高.Western blot结果显示,gp41T (△L)与His抗体结合性能好.结论 实验获得了稳定表达HIV-1 06044 gp41的原核表达载体以及表达条件,为大量制备gp41蛋白免疫原奠定了基础.%Objective To optimize the expression of HIV-1 envelope gp41 in E coli.Methods The HIV-1 06044 gp41 gene encoding 546 ~ 683 aa was amplified by PCR and the prokaryotic expression plasmid pET26b-gp41T was constructed.Meanwhile,plasmid pET26b-gp41T (△L) lacking the loop (582 ~ 627aa) between NHR and CHR of gp41 was also constructed.After identification by sequencing,the plasmids were transformed into E.coli BL21 (DE3) and the protein expression was induced by Isopropyl β-D-1-thiogalactopyrano-side (IPTG) and analyzed by polypropylene acyl ammonia gel electrophoresis (SDS-PAGE) and Western Blot.The protein expression condition was optimized.Results The pET26b-gp41T and pET26b-gp41T (△L) can express specific gp41 protein.Under 1 mmol/L IPTG induction,the gp41T(△L) protein expression quantity was higher than gp41T and the best expression was at 37 ℃.Comparing with gp41T,gp41T (△L) protein showed better affinity to his antibody

  14. Human cytomegalovirus Fcγ binding proteins gp34 and gp68 antagonize Fcγ receptors I, II and III.

    Directory of Open Access Journals (Sweden)

    Eugenia Corrales-Aguilar

    2014-05-01

    Full Text Available Human cytomegalovirus (HCMV establishes lifelong infection with recurrent episodes of virus production and shedding despite the presence of adaptive immunological memory responses including HCMV immune immunoglobulin G (IgG. Very little is known how HCMV evades from humoral and cellular IgG-dependent immune responses, the latter being executed by cells expressing surface receptors for the Fc domain of IgG (FcγRs. Remarkably, HCMV expresses the RL11-encoded gp34 and UL119-118-encoded gp68 type I transmembrane glycoproteins which bind Fcγ with nanomolar affinity. Using a newly developed FcγR activation assay, we tested if the HCMV-encoded Fcγ binding proteins (HCMV FcγRs interfere with individual host FcγRs. In absence of gp34 or/and gp68, HCMV elicited a much stronger activation of FcγRIIIA/CD16, FcγRIIA/CD32A and FcγRI/CD64 by polyclonal HCMV-immune IgG as compared to wildtype HCMV. gp34 and gp68 co-expression culminates in the late phase of HCMV replication coinciding with the emergence of surface HCMV antigens triggering FcγRIII/CD16 responses by polyclonal HCMV-immune IgG. The gp34- and gp68-dependent inhibition of HCMV immune IgG was fully reproduced when testing the activation of primary human NK cells. Their broad antagonistic function towards FcγRIIIA, FcγRIIA and FcγRI activation was also recapitulated in a gain-of-function approach based on humanized monoclonal antibodies (trastuzumab, rituximab and isotypes of different IgG subclasses. Surface immune-precipitation showed that both HCMV-encoded Fcγ binding proteins have the capacity to bind trastuzumab antibody-HER2 antigen complexes demonstrating simultaneous linkage of immune IgG with antigen and the HCMV inhibitors on the plasma membrane. Our studies reveal a novel strategy by which viral FcγRs can compete for immune complexes against various Fc receptors on immune cells, dampening their activation and antiviral immunity.

  15. Lessons from the GP-B Experience for Future Fundamental Physics Missions in Space

    Science.gov (United States)

    Kolodziejczak, Jeffery

    2006-01-01

    Gravity Probe B launched in April 2004 and completed its science data collection in September 2005, with the objective of sub-milliarcsec measurement of two General Relativistic effects on the spin axis orientation of orbiting gyroscopes. Much of the technology required by GP-B has potential application in future missions intended to make precision measurements. The philosophical approach and experiment design principles developed for GP-B are equally adaptable to these mission concepts. This talk will discuss GP-B's experimental approach and the technological and philosophical lessons learned that apply to future experiments in fundamental physics. Measurement of fundamental constants to high precision, probes of short-range forces, searches for equivalence principle violations, and detection of gravitational waves are examples of concepts and missions that will benefit kern GP-B's experience.

  16. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Directory of Open Access Journals (Sweden)

    Ling-ling Shen

    2015-01-01

    Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  17. Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro

    DEFF Research Database (Denmark)

    Niemeier, A; Willnow, T; Dieplinger, H;

    1999-01-01

    Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein of unknown physiological function. The mechanism of Lp(a) atherogenicity as well as its catabolic pathways are only incompletely understood at present. In this report, we show that the low density lipoprotein receptor (LDLR) gene family member...... megalin/glycoprotein (gp) 330 is capable of binding and mediating the cellular uptake and degradation of Lp(a) in vitro. A mouse embryonic yolk sac cell line with native expression of megalin/gp330 but genetically deficient in LDLR-related protein (LRP) and a control cell line carrying a double knockout...... unlabeled Lp(a) and LDL suggested that Lp(a) uptake is mediated at least partially by apolipoprotein B100. Binding and uptake of DiI-Lp(a) resulted in strong signals on megalin/gp330-expressing cells versus background only on control cells. In addition, we show that purified megalin/gp330, immobilized...

  18. Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

    Institute of Scientific and Technical Information of China (English)

    Ling-ling Shen; Li-juan Yang; Ying Xu; Jun Dong; Ming-liang Jiang; Si-si Liu; Min-chun Cai; Zhong-qiu Hong; Li-qing Lin; Yan-yan Xing; Gui-lin Chen; Rui Pan

    2015-01-01

    Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extra-cellular microelectrode recording techniques, this study conifrmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca2+concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

  19. Cloning and Sequence Analysis of the gp41 Gene of Clanis bilineata Nuclear Polyhedrosis Virus

    Institute of Scientific and Technical Information of China (English)

    ZHU Shan-ying; WANG Wen-bing; ZHU Jiang

    2006-01-01

    Clanis bilineata Nucleo Polyhedro Virus (CbNPV) was purified from Clanis bilineata larva. To obtain the molecular information of the virus, the genomic DNA of CbNPV was extracted, and a DNA fragment library of the virus was constructed using shotgun. The positive clones were then sequenced and analyzed. An open-reading frame (ORF) that has high identity with the gp41 gene of most NPVs was found in the library. The gp41 gene of CbNPV is 933 base pair long and encodes a protein of 310 amino acids. The result of the amino acid sequence analysis showed that the CbNPV gp41 has 53-61 and 56-73% identities with Group Ⅰ and Ⅱ NPVs gp41 proteins, respectively. The result indicates that the isolated CbNPV is a novel baculovirus, and the CbNPV shares a much closer relationship with Group Ⅱ NPVs.

  20. Role of the intracellular receptor domain of gp130 (exon 17) in human inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Christoph J. Auernhammer; Thomas Ochsenkühn; Kathrin Zitzmann; Fabian Schnitzler; Julia Seiderer; Peter Lohse; George Vlotides; Dieter Engelhardt; Michael Sackmann; Burkhard G(o)ke

    2005-01-01

    AIM: To study the role of the intracellular receptor domain of gp130 in human inflammatory bowel disease (IBD).METHODS: We amplified and sequenced the complete exon 17 of the human gp130 gene in 146 patients with IBD. According to clinical and histopathological signs,the 146 patients with IBD were classified as having Crohn's disease (n = 73) or ulcerative colitis (n = 63),or as indeterminate status (n = 10).RESULTS: No mutations in exon 17 of the gp130 gene could be detected in any of the 146 patients with IBD examined.CONCLUSION: There is no evidence that mutations in exon 17 of the gp130 gene are involved in the pathogenesis of human IBD.

  1. Characterization of a Novel Neutralizing Monoclonal Antibody Against Ebola Virus GP.

    Science.gov (United States)

    Reynard, Olivier; Volchkov, Viktor E

    2015-10-01

    Ebola virus is the etiological agent of a severe hemorrhagic fever with a high mortality rate. As the only protein exposed on the surface of viral particles, the spike glycoprotein GP is the unique target for neutralizing monoclonal antibodies. In this study, we demonstrate the strong neutralization capacity of the monoclonal antibody #3327 and characterize its activity. GP residues that are required for recognition and neutralization were found to be located both in the internal fusion loop and in the receptor-binding domain. Analysis of Ebola virus entry in the presence of #3327 allows us to hypothesize that this antibody binds to the virus particle before internalization and endosomal processing of GP and likely prevents the final viral fusion step. Importantly, #3327 is able to block entry of virions bearing GP that contain the Q508 escape mutation common to a number of virus-neutralizing antibodies, and therefore provides future perspectives for treatment strategies against Ebola virus infection.

  2. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

    DEFF Research Database (Denmark)

    Holmskov, U; Mollenhauer, J; Madsen, J

    1999-01-01

    Surfactant protein D (SP-D) is an oligomeric C type lectin that promotes phagocytosis by binding to microbial surface carbohydrates. A 340-kDa glycoprotein (gp-340) has been shown to bind SP-D in the presence of calcium but does so independently of carbohydrate recognition. This protein exists both...... transcription-PCR analysis showed that the main sites of synthesis of gp-340 are lung, trachea, salivary gland, small intestine, and stomach. Immunohistochemistry revealed strong staining for gp-340 in alveolar and other tissue macrophages. Immunostaining of the macrophage membrane was either uniform or focal...... intestine and in the ducts of salivary glands. The distribution of gp-340 in macrophages is compatible with a role as an opsonin receptor for SP-D....

  3. Identification of a binding site of the human immunodeficiency virus envelope protein gp120 to neuronal specific tubulin

    Science.gov (United States)

    Avdoshina, Valeria; Taraballi, Francesca; Dedoni, Simona; Corbo, Claudia; Paige, Mikell; Kont, Yasemin Saygideğer; Üren, Aykut; Tasciotti, Ennio; Mocchetti, Italo

    2016-01-01

    Human immunodeficiency virus-1 (HIV) promotes synaptic simplification and neuronal apoptosis, and causes neurological impairments termed HIV-associated neurological disorders (HAND). HIV-associated neurotoxicity may be brought about by acute and chronic mechanisms that still remain to be fully characterized. The HIV envelope glycoprotein gp120 causes neuronal degeneration similar to that observed in HAND subjects. The present study was undertaken to discover novel mechanisms of gp120 neurotoxicity that could explain how the envelope protein promotes neurite pruning. Gp120 has been shown to associate with various intracellular organelles as well as microtubules in neurons. We then analyzed lysates of neurons exposed to gp120 with liquid chromatography mass spectrometry for potential protein interactors. We found that one of the proteins interacting with gp120 is tubulin β-3 (TUBB3), a major component of neuronal microtubules. We then tested the hypothesis that gp120 binds to neuronal microtubules. Using surface plasmon resonance we confirmed that gp120 binds with high affinity to neuronal specific TUBB3. We have also identified the binding site of gp120 to TUBB3. We then designed a small peptide (Helix-A) that displaced gp120 from binding to TUBB3. To determine whether this peptide could prevent gp120-mediated neurotoxicity, we crosslinked Helix-A to mesoporous silica nanoparticles (Helix-A nano) to enhance the intracellular delivery of the peptide. We then tested the neuroprotective property of Helix-A nano against three strains of gp120 in rat cortical neurons. Helix-A nano prevented gp120-mediated neurite simplification as well as neuronal loss. These data propose that gp120 binding to TUBB3 could be another mechanism of gp120 neurotoxicity. PMID:26826352

  4. Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion.

    Science.gov (United States)

    Rodrigues, João Paulo Ferreira; Sant'ana, Guilherme Hideki Takahashi; Juliano, Maria Aparecida; Yoshida, Nobuko

    2017-09-01

    Successful infection by Trypanosoma cruzi, the agent of Chagas' disease, is critically dependent on host cell invasion by metacyclic trypomastigote (MT) forms. Two main metacyclic stage-specific surface molecules, gp82 and gp90, play determinant roles in target cell invasion in vitro and in oral T. cruzi infection in mice. The structure and properties of gp82, which is highly conserved among T. cruzi strains, are well known. Information on gp90 is still rather sparse. Here, we attempted to fill that gap. gp90, purified from poorly invasive G strain MT and expressing gp90 at high levels, inhibited HeLa cell lysosome spreading and the gp82-mediated internalization of a highly invasive CL strain MT expressing low levels of a diverse gp90 molecule. A recombinant protein containing the conserved C-terminal domain of gp90 exhibited the same properties as the native G strain gp90: it counteracted the host cell lysosome spreading induced by recombinant gp82 and exhibited an inhibitory effect on HeLa cell invasion by CL strain MT. Assays to identify the gp90 sequence associated with the property of downregulating MT invasion, using synthetic peptides spanning the gp90 C-terminal domain, revealed the sequence GVLYTADKEW. These data, plus the findings that lysosome spreading was induced upon HeLa cell interaction with CL strain MT, but not with G strain MT, and that in mixed infection CL strain MT internalization was inhibited by G strain MT, suggest that the inhibition of target cell lysosome spreading is the mechanism by which the gp90 molecule exerts its downregulatory role. Copyright © 2017 Rodrigues et al.

  5. Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

    Directory of Open Access Journals (Sweden)

    Peng Sang

    Full Text Available Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

  6. Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.

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    Phanourios Tamamis

    Full Text Available The binding of protein HIV-1 gp120 to coreceptors CCR5 or CXCR4 is a key step of the HIV-1 entry to the host cell, and is predominantly mediated through the V3 loop fragment of HIV-1 gp120. In the present work, we delineate the molecular recognition of chemokine receptor CCR5 by a dual tropic HIV-1 gp120 V3 loop, using a comprehensive set of computational tools predominantly based on molecular dynamics simulations and free energy calculations. We report, what is to our knowledge, the first complete HIV-1 gp120 V3 loop : CCR5 complex structure, which includes the whole V3 loop and the N-terminus of CCR5, and exhibits exceptional agreement with previous experimental findings. The computationally derived structure sheds light into the functional role of HIV-1 gp120 V3 loop and CCR5 residues associated with the HIV-1 coreceptor activity, and provides insights into the HIV-1 coreceptor selectivity and the blocking mechanism of HIV-1 gp120 by maraviroc. By comparing the binding of the specific dual tropic HIV-1 gp120 V3 loop with CCR5 and CXCR4, we observe that the HIV-1 gp120 V3 loop residues 13-21, which include the tip, share nearly identical structural and energetic properties in complex with both coreceptors. This result paves the way for the design of dual CCR5/CXCR4 targeted peptides as novel potential anti-AIDS therapeutics.

  7. Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

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    Langeslag Michiel

    2011-12-01

    Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

  8. Structural dynamics of HIV-1 envelope Gp120 outer domain with V3 loop.

    Directory of Open Access Journals (Sweden)

    Masaru Yokoyama

    Full Text Available BACKGROUND: The net charge of the hypervariable V3 loop on the HIV-1 envelope gp120 outer domain plays a key role in modulating viral phenotype. However, the molecular mechanisms underlying the modulation remain poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: By combining computational and experimental approaches, we examined how V3 net charge could influence the phenotype of the gp120 interaction surface. Molecular dynamics simulations of the identical gp120 outer domain, carrying a V3 loop with net charge of +3 or +7, showed that the V3 change alone could induce global changes in fluctuation and conformation of the loops involved in binding to CD4, coreceptor and antibodies. A neutralization study using the V3 recombinant HIV-1 infectious clones showed that the virus carrying the gp120 with +3 V3, but not with +7 V3, was resistant to neutralization by anti-CD4 binding site monoclonal antibodies. An information entropy study shows that otherwise variable surface of the gp120 outer domain, such as V3 and a region around the CD4 binding loop, are less heterogeneous in the gp120 subpopulation with +3 V3. CONCLUSIONS/SIGNIFICANCE: These results suggest that the HIV-1 gp120 V3 loop acts as an electrostatic modulator that influences the global structure and diversity of the interaction surface of the gp120 outer domain. Our findings will provide a novel structural basis to understand how HIV-1 adjusts relative replication fitness by V3 mutations.

  9. Stabilization of HIV-1 gp120-CD4 Receptor Complex through Targeted Interchain Disulfide Exchange*

    Science.gov (United States)

    Cerutti, Nichole; Mendelow, Barry V.; Napier, Grant B.; Papathanasopoulos, Maria A.; Killick, Mark; Khati, Makobetsa; Stevens, Wendy; Capovilla, Alexio

    2010-01-01

    HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120-CD4 receptor complex, substitution of Ser60 on the CD4 domain 1 α-helix with Cys positions a thiol in proximity of the gp120 V1/V2 loop disulfide (Cys126–Cys196), satisfying the stereochemical and geometric conditions for redox exchange between CD4 Cys60 and gp120 Cys126, and the consequent formation of an interchain disulfide bond. In this study, we provide experimental evidence for this effect by describing the expression, purification, refolding, receptor binding and antiviral activity analysis of a recombinant two-domain CD4 variant containing the S60C mutation (2dCD4-S60C). We show that 2dCD4-S60C binds HIV-1 gp120 with a significantly higher affinity than wild-type protein under conditions that facilitate disulfide exchange and that this translates into a corresponding increase in the efficacy of CD4-mediated viral entry inhibition. We propose that targeted redox exchange between conserved gp120 disulfides and nucleophilic moieties positioned strategically on CD4 (or CD4-like scaffolds) conceptualizes a new strategy in the development of high affinity HIV-1 Env ligands, with important implications for therapy and vaccine development. More generally, this chalcogen substitution approach provides a general means of stabilizing receptor-ligand complexes where the structural and biophysical conditions for disulfide exchange are satisfied. PMID:20538591

  10. Stabilization of HIV-1 gp120-CD4 receptor complex through targeted interchain disulfide exchange.

    Science.gov (United States)

    Cerutti, Nichole; Mendelow, Barry V; Napier, Grant B; Papathanasopoulos, Maria A; Killick, Mark; Khati, Makobetsa; Stevens, Wendy; Capovilla, Alexio

    2010-08-13

    HIV-1 enters cells via interaction between the trimeric envelope (Env) glycoprotein gp120/gp41 and the host cell surface receptor molecule CD4. The requirement of CD4 for viral entry has rationalized the development of recombinant CD4-based proteins as competitive viral attachment inhibitors and immunotherapeutic agents. In this study, we describe a novel recombinant CD4 protein designed to bind gp120 through a targeted disulfide-exchange mechanism. According to structural models of the gp120-CD4 receptor complex, substitution of Ser(60) on the CD4 domain 1 alpha-helix with Cys positions a thiol in proximity of the gp120 V1/V2 loop disulfide (Cys(126)-Cys(196)), satisfying the stereochemical and geometric conditions for redox exchange between CD4 Cys(60) and gp120 Cys(126), and the consequent formation of an interchain disulfide bond. In this study, we provide experimental evidence for this effect by describing the expression, purification, refolding, receptor binding and antiviral activity analysis of a recombinant two-domain CD4 variant containing the S60C mutation (2dCD4-S60C). We show that 2dCD4-S60C binds HIV-1 gp120 with a significantly higher affinity than wild-type protein under conditions that facilitate disulfide exchange and that this translates into a corresponding increase in the efficacy of CD4-mediated viral entry inhibition. We propose that targeted redox exchange between conserved gp120 disulfides and nucleophilic moieties positioned strategically on CD4 (or CD4-like scaffolds) conceptualizes a new strategy in the development of high affinity HIV-1 Env ligands, with important implications for therapy and vaccine development. More generally, this chalcogen substitution approach provides a general means of stabilizing receptor-ligand complexes where the structural and biophysical conditions for disulfide exchange are satisfied.

  11. The association between GP and patient ratings of quality of care at outpatient clinics

    Science.gov (United States)

    Garratt, Andrew; Iversen, Hilde; Ruud, Torleif

    2009-01-01

    Background. GPs and patients are frequently asked to evaluate mental health care, but studies including evaluations from both groups are rare. Objective. To assess the association between GPs' and patients' assessment of mental health outpatient clinic in Norway and identify important health care predictors for patient and GP satisfaction with the clinics. Methods. Two cross-sectional national surveys were carried out: survey of GPs in 2006 and patients in 2007 evaluating outpatient clinics at 69 community mental health centres in Norway. A total of 2009 GPs and 9001 outpatients assessed the clinics by means of a postal questionnaire. Main outcome measures were correlations between GP and patient ratings of the outpatient clinics at the clinic level and health care predictors for patient satisfaction and GP satisfaction with the clinics. Results. Clinic scores for GPs' and patients' assessment of waiting time were moderate to highly correlated (0.65), while clinic scores for GP and patient satisfaction had a lower but significant positive association (0.37). Significant positive correlations between clinic scores for GP and patients ratings were found for 38 of the 48 associations tested. The most important predictors for patient satisfaction with the clinics were interaction with the clinician (beta: 0.23) and being met with politeness and respect at the clinic (beta: 0.19), while the most important predictors for GP satisfaction with the clinics were perceived competence (beta: 0.25), rejection of referrals (beta: −0.17) and waiting time for patients (beta: −0.16). Conclusions. A consistent positive association between GP and patient ratings at the clinic level was identified. Mental health services aiming at improving GP and patient satisfaction should be sensitive to the fact that the two groups prioritize different health care factors. PMID:19584122

  12. The re-emergence of the GP73 and fucosylated liver cancer biomarkers

    Institute of Scientific and Technical Information of China (English)

    Block Timothy

    2014-01-01

    The-study-shows-that-GP73-alone-may-not-be-sufficient-to-achieve-the-discrimination-in-every-popula-tion.-This-is-because-many-other-clinical-factors-may-influence-the-levels-of-the-biomarker.-This-review-attempts-to-identify-some-of-these-clinical-variables,and-helps-provide-a-means-of-using-these-clinical-values,in-combi-nation-with-GP73,to-achieve-the-best-use-of-the-entire-clinical-biomarker-family.

  13. Chitosan Influences the Expression of P-gp and Metabolism of Norfloxacin in Grass Carp.

    Science.gov (United States)

    Hu, Kun; Xie, Xinyan; Zhao, Yi-Ni; Li, Yi; Ruan, Jiming; Li, Hao-Ran; Jin, Tianyi; Yang, Xian-Le

    2015-06-01

    The aim of this study was to investigate the relationship between the administration of chitosan (CTS), expression of permeability glycoprotein (P-gp), and the metabolism of norfloxacin (NOR) in Grass Carp Ctenopharyngodon idella. Fish were administrated with a single dose of either NOR, CTS, 1:5 NOR-CTS or 1:10 NOR-CTS. The P-gp expression was analyzed by immunohistochemistry and real time-PCR. The concentration of NOR was determined using HPLC. The mRNA and protein expression of P-gp in the fish intestine was significantly enhanced following a single dosage of 40 mg/kg NOR, and peak expression occurred at 3 h after drug administration (P < 0.05). A single dosage of both 1:5 NOR-CTS and 1:10 NOR-CTS reduced the intestinal P-gp expression to levels significantly lower than that from NOR alone (P < 0.05), but significantly higher than that from the control (P < 0.05). Interestingly, CTS alone also led to a slight decrease in P-gp expression. In addition, pharmacokinetic assays revealed a marked increase in area under the curve (AUC) of NOR with 1:5 and 1:10 NOR-CTS, by approximately 1.5-fold and threefold, respectively. Finally, the relative bioavailability of NOR after a single oral dosage of 1:5 and 1:10 NOR-CTS was enhanced to 148.02% and 304.98%, respectively. In this study, we demonstrated that the transmembrane glycoprotein P-gp regulates NOR metabolism in the intestine of Grass Carp, suggesting that NOR may be a direct substrate of P-gp. More importantly, we showed that CTS can inhibit P-gp expression in a dose-dependent manner and improve the relative bioavailability of NOR in this species.

  14. Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike

    Science.gov (United States)

    Lee, Jeong Hyun; Leaman, Daniel P.; Kim, Arthur S.; Torrents de La Peña, Alba; Sliepen, Kwinten; Yasmeen, Anila; Derking, Ronald; Ramos, Alejandra; de Taeye, Steven W.; Ozorowski, Gabriel; Klein, Florian; Burton, Dennis R.; Nussenzweig, Michel C.; Poignard, Pascal; Moore, John P.; Klasse, Per Johan; Sanders, Rogier W.; Zwick, Michael B.; Wilson, Ian A.; Ward, Andrew B.

    2015-09-01

    The recent identification of three broadly neutralizing antibodies (bnAbs) against gp120-gp41 interface epitopes has expanded the targetable surface on the HIV-1 envelope glycoprotein (Env) trimer. By using biochemical, biophysical and computational methods, we map the previously unknown trimer epitopes of two related antibodies, 3BC315 and 3BC176. A cryo-EM reconstruction of a soluble Env trimer bound to 3BC315 Fab at 9.3 Å resolution reveals that the antibody binds between two gp41 protomers, and neutralizes the virus by accelerating trimer decay. In contrast, bnAb 35O22 binding to a partially overlapping quaternary epitope at the gp120-gp41 interface does not induce decay. A conserved gp41-proximal glycan at N88 was also shown to play a role in the binding kinetics of 3BC176 and 3BC315. Finally, our data suggest that the dynamic structure of the Env trimer influences exposure of bnAb epitopes.

  15. Small-angle scattering from GP zones in Al–Cu alloy

    Indian Academy of Sciences (India)

    K T Kashyap; Praveennath G Koppad

    2011-12-01

    It is well known that Guinier Preston (GP) zones form in Al–Cu alloys upon solutionizing and artificial aging, which are extensively used in commercial practice. It is well established that GP zones are discshaped precipitates, i.e. disks of clusters of copper atoms in the FCC aluminium matrix. These disks have coherency strain fields in aluminium that give the alloy its high yield strength. The formation of GP zones in the supersaturated aluminium matrix is thought to be heterogeneous nucleation and growth. Some authors have believed that the formation of GP zones is by spinodal decomposition of the supersaturated Al–Cu solid solution. The main objective of the present work is to test whether spinodal decomposition is responsible for the formation of GP zones in Al–Cu alloy. The experimental alloy AA2219 was selected for its high copper content (Al–6%Cu–0.2%Zr). After solutionizing and artificial aging, the aging curve was plotted and smallangle scattering experiments were carried on the powdered samples as a function of time during artificial aging. Small-angle scattering data were analysed, and evidence has been obtained for the occurrence of spinodal decomposition as the mechanism responsible in the early stages of formation of GP zones.

  16. HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

    Directory of Open Access Journals (Sweden)

    Chungen Pan

    2010-02-01

    Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

  17. The murine gammaherpesvirus-68 gp150 acts as an immunogenic decoy to limit virion neutralization.

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    Laurent Gillet

    Full Text Available Herpesviruses maintain long-term infectivity without marked antigenic variation. They must therefore evade neutralization by other means. Immune sera block murine gammaherpesvirus-68 (MHV-68 infection of fibroblasts, but fail to block and even enhance its infection of IgG Fc receptor-bearing cells, suggesting that the antibody response to infection is actually poor at ablating virion infectivity completely. Here we analyzed this effect further by quantitating the glycoprotein-specific antibody response of MHV-68 carrier mice. Gp150 was much the commonest glycoprotein target and played a predominant role in driving Fc receptor-dependent infection: when gp150-specific antibodies were boosted, Fc receptor-dependent infection increased; and when gp150-specific antibodies were removed, Fc receptor-dependent infection was largely lost. Neither gp150-specific monoclonal antibodies nor gp150-specific polyclonal sera gave significant virion neutralization. Gp150 therefore acts as an immunogenic decoy, distorting the MHV-68-specific antibody response to promote Fc receptor-dependent infection and so compromise virion neutralization. This immune evasion mechanism may be common to many non-essential herpesvirus glycoproteins.

  18. Factors influencing the EBM behaviour of GP trainers: a mixed method study.

    Science.gov (United States)

    Te Pas, E; van Dijk, N; Bartelink, M E L; Wieringa-De Waard, M

    2013-01-01

    General practitioner (GP) trainees state that their trainers are not consistent in using evidence-based medicine (EBM) or are even dismissive of it. As trainers are important role models in the Dutch GP training system this could have a large influence on the EBM training of GP trainees. To establish the motivations and barriers of Dutch GP trainers in using EBM. A questionnaire on personal characteristics, knowledge, skills (Berlin, score 0-15) and attitude (McColl, VAS score 0-100), and statements about EBM barriers were presented to 106 GP trainers. Additionally, three focus group sessions with trainers (n = 30) were held. Knowledge and skills were less than half correct (mean 6.1, standard deviation (SD) 2.9); the overall score on attitude was 58.8 (SD 9.4). Factor analysis showed four categories of barriers: EBM competence (mean 3.5 (SD 0.8)), search activities (mean 3.5 (SD 0.8)), motivation (mean 3.8 (SD 0.7)) and time (mean 2.5 (SD 0.9)). After analysis of the focus group sessions, five categories of motivations and barriers predominated: EBM competence, attitude and behaviour, sources, time and logistics. GP trainers experience motivations in EBM; however, these motivations can also be barriers, depending on the trainer's level of knowledge and attitude.

  19. [Cloning and expression of gp37 gene of avian leukosis virus subgroup J].

    Science.gov (United States)

    Wang, Xiao-Wei; Liu, Qing; Xu, Qing-Qing; Cai, Li-Ming; Wang, Zhen-Zhen; Wang, Gui-Hua; Cheng, Zi-Qiang

    2012-03-01

    The transmembrane protein (TM) encoded by gp37 gene plays a critical role when virus fusion with cell membrane occurs. Several highly conserved regions in TM are important targets for antivirus studies. Studies on structure and function of TM will provide basic information for anti-retrovirus, especially for avian leukosis virus. In the study, gp37 gene was amplified by PCR from the Chinese strain ALV-J-WS0701. The gp37 gene was cloned into pMD18-T vector, and was sequenced. Then, pFast-BacHTb-gp37 vector was constructed and expressed by baculovirus expression vector system. The expression product of gp37 gene was analyzed by indirect immunofluorescence assay and Western blot. The results showed that positive green fluorescence was present in sf9 cells infected with recombinant virus and a protein band with a molecular weight of 21kD was present in Western blot. It is concluded that gp37 gene was expressed in sf9 cells infected with recombinant virus successfully.

  20. Student-centred GP ambassadors: Perceptions of experienced clinical tutors in general practice undergraduate training.

    Science.gov (United States)

    Von Below, Bernhard; Haffling, Ann-Christin; Brorsson, Annika; Mattsson, Bengt; Wahlqvist, Mats

    2015-06-01

    To explore experienced general practitioner (GP) tutor perceptions of a skilled GP tutor of medical students. Interview study based on focus groups. Twenty GPs experienced in tutoring medical students at primary health care centres in two Swedish regions were interviewed. Four focus-group interviews were analysed using qualitative content analysis. Twenty GP tutors, median age 50, specifically selected according to age, gender, and location participated in two focus groups in Gothenburg and Malmö, respectively. Meaning units in the texts were extracted, coded and condensed into categories and themes. Three main themes emerged: "Professional as GP and ambassador to general practice", "Committed and student-centred educator", and "Coordinator of the learning environment". Experienced GP tutors describe their skills as a clinical tutor as complex and diversified. A strong professional identity within general practice is vital and GP tutors describe themselves as ambassadors to general practice, essential to the process of recruiting a new generation of general practitioners. Leaders of clinical education and health care planners must understand the complexity in a clinical tutor's assignment and provide adequate support, time, and resources in order to facilitate a sustainable tutorship and a good learning environment, which could also improve the necessary recruitment of future GPs.

  1. Nasal delivery of P-gp substrates to the brain through the nose-brain pathway.

    Science.gov (United States)

    Shingaki, Tomotaka; Hidalgo, Ismael J; Furubayashi, Tomoyuki; Sakane, Toshiyasu; Katsumi, Hidemasa; Yamamoto, Akira; Yamashita, Shinji

    2011-06-01

    The objective of this study was to evaluate in rats the potential utility of the nasal route to enhance central nervous system (CNS) delivery of drugs recognized by P-glycoprotein (P-gp). Well-known P-gp substrates verapamil and talinolol were perfused nasally or infused intravenously, and when plasma concentrations following intravenous infusion and nasal perfusion showed similar profiles. The concentration of verapamil in the brain after nasal perfusion was twice that after intravenous infusion. Although talinolol in the brain and the cerebrospinal fluid after i.v. infusion were below the detection limit, it was detected after nasal perfusion. When rats were treated with cyclosporin A, brain concentrations of verapamil after both administration modes were increased significantly, while those of talinolol were not significantly changed. Since the permeability of talinolol is low, talinolol in the brain which was transported directly from the nasal cavity has little chance of transport by P-gp localized in the apical membrane of cerebral microvessel endothelial cells. The potential for drug delivery utilizing the nose-CNS route was confirmed for P-gp substrates. The advantage of nasal delivery over i.v. delivery of talinolol to the brain was more significant than that of verapamil, suggesting that nasal administration is more useful strategy for the brain delivery of low-permeability P-gp substrates than the use of P-gp inhibitors.

  2. Numerical modeling of exciton-polariton Bose-Einstein condensate in a microcavity

    Science.gov (United States)

    Voronych, Oksana; Buraczewski, Adam; Matuszewski, Michał; Stobińska, Magdalena

    2017-06-01

    within a semiconductor microcavity. It is described by a set of nonlinear differential equations similar in spirit to the Gross-Pitaevskii (GP) equation, but their unique properties do not allow standard GP solving frameworks to be utilized. Finding an accurate and efficient numerical algorithm as well as development of optimized numerical software is necessary for effective theoretical investigation of exciton-polaritons. Solution method: A Runge-Kutta method of 4th order was employed to solve the set of differential equations describing exciton-polariton superfluids. The method was fitted for the exciton-polariton equations and further optimized. The C++ programs utilize OpenMP extensions and vector operations in order to fully utilize the computer hardware. Running time: 6h for 100 ps evolution, depending on the values of parameters

  3. Extracellular Matrix Proteins Mediate HIV-1 gp120 Interactions with α4β7.

    Science.gov (United States)

    Plotnik, David; Guo, Wenjin; Cleveland, Brad; von Haller, Priska; Eng, Jimmy K; Guttman, Miklos; Lee, Kelly K; Arthos, James; Hu, Shiu-Lok

    2017-08-16

    Gut-homing α4β7(high) CD4(+) T lymphocytes have been shown to be preferentially targeted by Human Immunodeficiency Virus-1 (HIV), and are implicated in HIV pathogenesis. Previous studies demonstrated that HIV envelope protein gp120 binds and signals through α4β7, and that this likely contributes to the infection of α4β7(high) T cells and promotes cell-to-cell virus transmission. Structures within the second variable loop (V2) of gp120, including the tripeptide motif LDV/I, are thought to mediate gp120-α4β7 binding. However, lack of α4β7 binding has been reported in gp120 proteins containing LDV/I, and the precise determinants of gp120-α4β7 binding are not fully defined. In this work, we report the novel finding that fibronectins mediate indirect gp120-α4β7 interactions. We show that Chinese Hamster Ovary (CHO) cells used to express recombinant gp120 produced fibronectins and other extracellular matrix proteins that co-purified with gp120. CHO fibronectins were able to mediate the binding of a diverse panel of gp120 proteins to α4β7 in an in vitro cell binding assay. The V2 loop was not required for fibronectin-mediated binding of gp120 to α4β7, nor did V2-specific antibodies block this interaction. Removal of fibronectin through anion exchange chromatography abrogated V2-independent gp120-α4β7 binding. Additionally, we showed a recombinant human fibronectin fragment mediated gp120-α4β7 interactions in a similar manner to CHO fibronectin. These findings provide an explanation for the apparent contradictory observations regarding the gp120-α4β7 interaction and offer new insights into the potential role of fibronectin and other extracellular matrix proteins in HIV-1 biology.IMPORTANCE Immune tissues within the gut are severely damaged by HIV, and this plays an important role in the development of AIDS. Integrin α4β7 plays a major role in the trafficking of lymphocytes, including CD4(+) T cells, into gut lymphoid tissues. Previous reports

  4. Differential role of gp130-dependent STAT and Ras signalling for haematopoiesis following bone-marrow transplantation.

    Directory of Open Access Journals (Sweden)

    Daniela C Kroy

    Full Text Available INTRODUCTION: Bone marrow transplantation (BMT is a complex process regulated by different cytokines and growth factors. The pleiotropic cytokine IL-6 (Interleukin-6 and related cytokines of the same family acting on the common signal transducer gp130 are known to play a key role in bone marrow (BM engraftment. In contrast, the exact signalling events that control IL-6/gp130-driven haematopoietic stem cell development during BMT remain unresolved. METHODS: Conditional gp130 knockout and knockin mice were used to delete gp130 expression (gp130(ΔMx, or to selectively disrupt gp130-dependent Ras (gp130(ΔMxRas or STAT signalling (gp130(ΔMxSTAT in BM cells. BM derived from the respective strains was transplanted into irradiated wildtype hosts and repopulation of various haematopoietic lineages was monitored by flow cytometry. RESULTS: BM derived from gp130 deficient donor mice (gp130(ΔMx displayed a delayed engraftment, as evidenced by reduced total white blood cells (WBC, marked thrombocytopenia and anaemia in the early phase after BMT. Lineage analysis unravelled a restricted development of CD4(+ and CD8(+ T-cells, CD19(+ B-cells and CD11b(+ myeloid cells after transplantation of gp130-deficient BM grafts. To further delineate the two major gp130-induced signalling cascades, Ras-MAPK and STAT1/3-signalling respectively, we used gp130(ΔMxRas and gp130(ΔMxSTAT donor BM. BMT of gp130(ΔMxSTAT cells significantly impaired engraftment of CD4(+, CD8(+, CD19(+ and CD11b(+ cells, whereas gp130(ΔMxRas BM displayed a selective impairment in early thrombopoiesis. Importantly, gp130-STAT1/3 signalling deficiency in BM grafts severely impaired survival of transplanted mice, thus demonstrating a pivotal role for this pathway in BM graft survival and function. CONCLUSION: Our data unravel a vital function of IL-6/gp130-STAT1/3 signals for BM engraftment and haematopoiesis, as well as for host survival after transplantation. STAT1/3 and ras

  5. Differential Role of gp130-Dependent STAT and Ras Signalling for Haematopoiesis Following Bone-Marrow Transplantation

    Science.gov (United States)

    Kroy, Daniela C.; Hebing, Lisa; Sander, Leif E.; Gassler, Nikolaus; Erschfeld, Stephanie; Sackett, Sara; Galm, Oliver; Trautwein, Christian; Streetz, Konrad L.

    2012-01-01

    Introduction Bone marrow transplantation (BMT) is a complex process regulated by different cytokines and growth factors. The pleiotropic cytokine IL-6 (Interleukin-6) and related cytokines of the same family acting on the common signal transducer gp130 are known to play a key role in bone marrow (BM) engraftment. In contrast, the exact signalling events that control IL-6/gp130-driven haematopoietic stem cell development during BMT remain unresolved. Methods Conditional gp130 knockout and knockin mice were used to delete gp130 expression (gp130ΔMx), or to selectively disrupt gp130-dependent Ras (gp130ΔMxRas) or STAT signalling (gp130ΔMxSTAT) in BM cells. BM derived from the respective strains was transplanted into irradiated wildtype hosts and repopulation of various haematopoietic lineages was monitored by flow cytometry. Results BM derived from gp130 deficient donor mice (gp130ΔMx) displayed a delayed engraftment, as evidenced by reduced total white blood cells (WBC), marked thrombocytopenia and anaemia in the early phase after BMT. Lineage analysis unravelled a restricted development of CD4(+) and CD8(+) T-cells, CD19(+) B-cells and CD11b(+) myeloid cells after transplantation of gp130-deficient BM grafts. To further delineate the two major gp130-induced signalling cascades, Ras-MAPK and STAT1/3-signalling respectively, we used gp130ΔMxRas and gp130ΔMxSTAT donor BM. BMT of gp130ΔMxSTAT cells significantly impaired engraftment of CD4(+), CD8(+), CD19(+) and CD11b(+) cells, whereas gp130ΔMxRas BM displayed a selective impairment in early thrombopoiesis. Importantly, gp130-STAT1/3 signalling deficiency in BM grafts severely impaired survival of transplanted mice, thus demonstrating a pivotal role for this pathway in BM graft survival and function. Conclusion Our data unravel a vital function of IL-6/gp130-STAT1/3 signals for BM engraftment and haematopoiesis, as well as for host survival after transplantation. STAT1/3 and ras-dependent pathways thereby exert

  6. HIV-1 gp41 NHR结合性环肽的研究%Study of the cyclic peptide binding to HIV-1 gp41 NHR

    Institute of Scientific and Technical Information of China (English)

    刘北一; 朱平; 姜世勃; 富宁

    2006-01-01

    目的筛选可与HIV-1 gp41 NHR结合的环肽,为研制抗HIV-1早期感染的小分子药物奠定基础.方法采用P+LS方法,用源于gp41 NHR的合成肽N36肽筛选噬菌体环七肽库,ELISA鉴定噬菌体克隆,根据阳性克隆的DNA序列,合成环肽并鉴定其与N36肽结合.结果经3轮筛选、鉴定,得到11个和N36肽结合的噬菌体克隆.DNA测序并推导氨基酸序列,表明这11个克隆展示同一序列CDRHQHKRC.根据此序列合成的环肽NA(Biotin-SACDRHQHKRCGG)经与载体蛋白BSA偶联后,ELISA鉴定表明交联物可特异地与N36肽结合,这种结合可被游离N36肽、以及源于gp41 CHR的肽C34抑制.结论SACDRHQHKRCGG环肽为HIV-1 gp41 NHR结合肽.

  7. Partial Differential Equations

    CERN Document Server

    1988-01-01

    The volume contains a selection of papers presented at the 7th Symposium on differential geometry and differential equations (DD7) held at the Nankai Institute of Mathematics, Tianjin, China, in 1986. Most of the contributions are original research papers on topics including elliptic equations, hyperbolic equations, evolution equations, non-linear equations from differential geometry and mechanics, micro-local analysis.

  8. GpIIb/IIIa+ subpopulation of rat megakaryocyte progenitor cells exhibits high responsiveness to human thrombopoietin.

    Science.gov (United States)

    Kato, T; Horie, K; Hagiwara, T; Maeda, E; Tsumura, H; Ohashi, H; Miyazaki, H

    1996-08-01

    The recently cloned factor thrombopoietin (TPO) has been shown to exhibit megakaryocyte colony-stimulating activity in vitro. In this investigation, to further evaluate the action of TPO on megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]), GpIIb/IIIa+ and GpIIb/IIIa- populations of CFU-MK were prepared from rat bone marrow cells based on their reactivity with P55 antibody, a monoclonal antibody against rat GpIIb/IIIa, and their responsiveness to recombinant human TPO (rhTPO) and recombinant rat interleukin-3 (rrIL-3) was examined using a megakaryocyte colony-forming assay (Meg-CSA). rhTPO supported only megakaryocyte colony growth from both fractions in a dose-dependent fashion. The mean colony size observed with the GpIIb/IIIa+ population was smaller than that seen with the GpIIb/IIIa- population. With the optimal concentration of either rhTPO or rrIL-3, similar numbers of megakaryocyte colonies were formed from the GpIIb/IIIa+ population previously shown to be highly enriched for CFU-MK. In contrast, the maximum number of megakaryocyte colonies from the GpIIb/IIIa- population stimulated by rhTPO was only 24.2% of that achieved with rrIL-3. Morphologic analysis of rhTPO-promoted megakaryocyte colonies from the GpIIb/IIIa+ population showed that the average colony size was smaller but that the mean diameter of individual megakaryocytes was larger than in megakaryocyte colonies promoted with rrIL-3. rhTPO plus rrIL-3, each at suboptimal concentrations, had an additive effect on proliferation of CFU-MK in the GpIIb/IIIa+ fraction, whereas rhTPO plus murine IL-6 or murine granulocyte-macrophage colony-stimulating factor (mG-M-CSF) modestly but significantly reduced megakaryocyte colony growth. These results indicate that TPO preferentially acts on GpIIb/IIIa+ late CFU-MK with lower proliferative capacity and interacts with some other cytokines in CFU-MK development.

  9. Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition.

    Science.gov (United States)

    Dewanjee, Saikat; Dua, Tarun K; Bhattacharjee, Niloy; Das, Anup; Gangopadhyay, Moumita; Khanra, Ritu; Joardar, Swarnalata; Riaz, Muhammad; Feo, Vincenzo De; Zia-Ul-Haq, Muhammad

    2017-05-25

    Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc. Due to its diverse tissue distribution, P-gp is a novel protective barrier to stop the intake of xenobiotics into the human body. Over-expression of P-gp leads to decreased intracellular accretion of many chemotherapeutic agents thus assisting in the development of MDR. Eventually, the effectiveness of these drugs is decreased. P-gp inhibitors act by altering intracellular ATP levels which are the source of energy and/or by affecting membrane contours to increase permeability. However, the use of synthetic inhibitors is known to cause serious toxicities. For this reason, the search for more potent and less toxic P-gp inhibitors of natural origin is underway. The present review aims to recapitulate the research findings on bioactive constituents of natural origin with P-gp inhibition characteristics. Natural bioactive constituents with P-gp modulating effects offer great potential for semi-synthetic modification to produce new scaffolds which could serve as valuable investigative tools to recognize the function of complex ABC transporters apart from evading the systemic toxicities shown by synthetic counterparts. Despite the many published scientific findings encompassing P-gp inhibitors, however, this article stand alones because it provides a vivid picture to the readers

  10. Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

    Directory of Open Access Journals (Sweden)

    Annie Albin Lumen

    Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

  11. Molecular basis for variable expression of merozoite surface antigen gp45 among American isolates of Babesia bigemina.

    Science.gov (United States)

    Fisher, T G; McElwain, T F; Palmer, G H

    2001-06-01

    Immunization with the merozoite surface glycoprotein gp45 induces protection against challenge using the homologous Babesia bigemina strain. However, gp45 B-cell epitopes are highly polymorphic among B. bigemina strains isolated from different geographical locations within North and South America. The molecular basis for this polymorphism was investigated using the JG-29 biological clone of a Mexico strain of B. bigemina and comparison with the Puerto Rico, St. Croix, and Texcoco strains. The molecular size and antibody reactivity of gp45 expressed by the JG-29 clone were identical to those of the parental Mexico strain. gp45 cDNA and the genomic locus encompassing gp45 were cloned and sequenced from JG-29. The locus sequence and Southern blot data were consistent with a single gp45 copy in the JG-29 genome. The JG-29 cDNA expressed the full-length protein recognized by the gp45-specific monoclonal antibody 14/1.3.2. The genomes of the Puerto Rico and St. Croix strains of B. bigemina were shown to lack a closely related gp45-like gene by PCR using multiple primer sets and by Southern blots using both full-length and region-specific gp45 probes. This genomic difference was confirmed using unpassaged isolates from a 1999 disease outbreak in Puerto Rico. In contrast, the Texcoco strain retains a gp45 gene, encoding an open reading frame identical to that of JG-29. However, the Texcoco gp45 gene is not transcribed. These two mechanisms, lack of a closely related gp45-like gene and failure to transcribe gp45, result in generation of antigenic polymorphism among B. bigemina strains, and the latter mechanism is unique compared to prior mechanisms of antigenic polymorphism identified in babesial parasites.

  12. LogGP-U:一种统一的并行计算模型%LogGP-U:unified parallel computational model

    Institute of Scientific and Technical Information of China (English)

    王向前; 王昊; 马宏星; 耿锐

    2015-01-01

    提出一种统一的并行计算模型LogGP-U(Unified LogGP),它是一个基于LogGP的并行计算模型,给出在几种并行程序设计模式下对应的修正形式。使用这个模型既可以准确度量一般情况下并行程序的时间复杂性,也可以度量通信和计算重叠、单边通信等形式下并行程序的时间复杂性。用这个模型分析了cannon矩阵乘在几种编程模式下的理论性能,并在曙光4000A集群上进行验证LogGP-U模型的有效性。%This paper presents a unified model of parallel computational model, LogGP-U. LogGP-U model is based on LogGP model. The corresponding amendment models of several parallel programming patterns are also given. Through this model time complexity for usual parallel programs can be measured accurately as well as for those which employ technique such as overlapping of communication and computation, one-sided communication and so on. The theoretical time complexity of cannon matrix multiplication is analysed, and then the accuracy of the model is verified on Dawning 4000A cluster.

  13. Evaluation of Particle Numbers via Two Root Mean Square Radii in a 2-Species Bose-Einstein Condensate*

    Science.gov (United States)

    He, Yan-Zhang; Liu, Yi-Min; Bao, Cheng-Guang

    2017-08-01

    The coupled Gross-Pitaevskii equations for two-species BEC have been solved analytically under the Thomas-Fermi approximation (TFA). Based on the analytical solution, two formulae are derived to relate the particle numbers NA and NB with the root mean square radii of the two kinds of atoms. Only the case that both kinds of atoms have nonzero distribution at the center of an isotropic trap is considered. In this case the TFA has been found to work nicely. Thus, the two formulae are applicable and are useful for the evaluation of NA and NB .

  14. Evaporative cooling of cold atoms at surfaces

    CERN Document Server

    Märkle, J; Federsel, P; Jetter, B; Günther, A; Fortágh, J; Proukakis, N P; Judd, T E

    2014-01-01

    We theoretically investigate the evaporative cooling of cold rubidium atoms that are brought close to a solid surface. The dynamics of the atom cloud are described by coupling a dissipative Gross-Pitaevskii equation for the condensate with a quantum Boltzmann description of the thermal cloud (the Zaremba-Nikuni-Griffin method). We have also performed experiments to allow for a detailed comparison with this model and find that it can capture the key physics of this system provided the full collisional dynamics of the thermal cloud are included. In addition, we suggest how to optimize surface cooling to obtain the purest and largest condensates.

  15. Acoustic black hole in a stationary hydrodynamic flow of microcavity polaritons.

    Science.gov (United States)

    Nguyen, H S; Gerace, D; Carusotto, I; Sanvitto, D; Galopin, E; Lemaître, A; Sagnes, I; Bloch, J; Amo, A

    2015-01-23

    We report an experimental study of superfluid hydrodynamic effects in a one-dimensional polariton fluid flowing along a laterally patterned semiconductor microcavity and hitting a micron-sized engineered defect. At high excitation power, superfluid propagation effects are observed in the polariton dynamics; in particular, a sharp acoustic horizon is formed at the defect position, separating regions of sub- and supersonic flow. Our experimental findings are quantitatively reproduced by theoretical calculations based on a generalized Gross-Pitaevskii equation. Promising perspectives to observe Hawking radiation via photon correlation measurements are illustrated.

  16. The mathematics of the Bose gas and its condensation

    CERN Document Server

    Lieb, Elliott H; Solovej, Jan Philip; Yngvason, Jakob

    2006-01-01

    This book surveys results about the quantum mechanical many-body problem of the Bose gas that have been obtained by the authors over the last seven years. These topics are relevant to current experiments on ultra-cold gases; they are also mathematically rigorous, using many analytic techniques developed over the years to handle such problems. Some of the topics treated are the ground state energy, the Gross-Pitaevskii equation, Bose-Einstein condensation, superfluidity, one-dimensional gases, and rotating gases. The book also provides a pedagogical entry into the field for graduate students and researchers.

  17. Evolutions of matter-wave bright soliton with spatially modulated nonlinearity

    Institute of Scientific and Technical Information of China (English)

    Yongshan Cheng; Fei Liu

    2009-01-01

    The evolution characteristics of a matter-wave bright soliton are investigated by means of the variational approach in the presence of spatially varying nonlinearity.It is found that the atom density envelope of the soliton is changed as a result of the spatial variation of the s-wave scattering length.The stable soliton can exist in appropriate initial conditions.The movement of the soliton depends on the sign and value of the coefficient of spatially modulated nonlinearity.These theoretical predictions are confirmed by the full numerical simulations of the one-dimensional Gross-Pitaevskii equation.

  18. Evolution of Matter Wave Interference of Bose-Condensed Gas in a 2D Optical Lattice

    Institute of Scientific and Technical Information of China (English)

    XUZhi-Jun; LINGuo-Cheng; XUJun; LIZhen

    2005-01-01

    We investigate the average particle-number distribution of the atoms in the combined potential of 2D optical lattices and 31) harmonic magnetic trap based on the Gross-Pitaevskii equation. After the combined potential is switched of[, and only the optical lattice is switched off, we give the analytical results of the wavefunction of the Bosecondensed gas at any time t by using a propagator method. For both disk-shaped and cigar-shaped Bose-condensed gas,we discuss the evolution process of the central and side peaks of the interference pattern.

  19. Collapse of triaxial bright solitons in atomic Bose-Einstein condensates

    Science.gov (United States)

    Mazzarella, G.; Salasnich, L.

    2009-12-01

    We study triaxial bright solitons made of attractive Bose-condensed atoms characterized by the absence of confinement in the longitudinal axial direction but trapped by an anisotropic harmonic potential in the transverse plane. By numerically solving the three-dimensional Gross-Pitaevskii equation we investigate the effect of the transverse trap anisotropy on the critical interaction strength above which there is the collapse of the condensate. The comparison with previous predictions [A. Gammal, L. Tomio, T. Frederico, Phys. Rev. A 66 (2002) 043619] shows significant differences for large anisotropies.

  20. Low Energy Excitations of a Bose-Einstein Condensate: A Time-Dependent Variational Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Garcia, V.M.; Michinel, H.; Cirac, J.; Lewenstein, M.; Zoller, P. [Departamento de Matematicas, Escuela Tecnica Superior de Ingenieros Industriales, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain)]|[Departamento de Fisica Aplicada, E. U. Optica e Optometria, Universidade de Santiago de Compostela, 15706 Santiago de Compostela (Spain)]|[Departamento de Fisica Aplicada, Facultad de CC. Quimicas, Universidad de Castilla-La Mancha, 13071 Ciudad Real (Spain)]|[Comissariat a l`Energie Atomique, DSM/DRECAM/SPAM, Centre d`Etudes de Saclay, 91191 Gif-sur-Yvette (France)]|[Institute for Theoretical Physics, University of Innsbruck, A-6020 Innsbruck (Austria)

    1996-12-01

    We solve the time-dependent Gross-Pitaevskii equation by a variational ansatz to calculate the excitation spectrum of a Bose-Einstein condensate in a trap. The trial wave function is a Gaussian which allows an essentially analytical treatment of the problem. Our results reproduce numerical calculations over the whole range from small to large particle numbers, and agree exactly with the Stringari results in the strong interaction limit. Excellent agreement is obtained with the recent JILA experiment and predictions for the negative scattering length case are also made. {copyright} {ital 1996 The American Physical Society.}

  1. Nonlinear transport of Bose-Einstein condensates in a double barrier potential

    Institute of Scientific and Technical Information of China (English)

    Fang Jian-Shu

    2008-01-01

    The stable nonlinear transport of the Bose-Einstein condensates through a double barrier potential in a waveguide is studied.By using the direct perturbation method we have obtained a perturbed solution of Gross-Pitaevskii equation.Theoretical analysis reveals that this perturbed solution is a stable periodic solution,which shows that the transport of Bose-Einstein condensed atoms in this system is a stable nonlinear transport.The corresponding numerical results are in good agreement with the theoretical analytical results.

  2. Stability Diagrams of a Bose-Einstein Condensate in a Periodic Array of Quantum Wells

    Institute of Scientific and Technical Information of China (English)

    XUE Rui; LIANG Zhao-Xin; LI Wei-Dong

    2009-01-01

    With the help of a set of exact closed-form solutions to the stationary Gross-Pitaevskii equation, we compre-hensively investigate Landau and dynamical instabilities of a Bose-Einstein condensate in a periodic array of quantum wells. In the tight-binding limit, the analytical expressions for both Landau and dynamical instabilities are obtained in terms of the compressibility and effective mass of the BEC system. Then the stability phase diagrams are shown to be similar to the one in the case of the sinusoidal optical lattice.

  3. Dynamics of Bright/Dark Solitons in Bose-Einstein Condensates with Time-Dependent Scattering Length and External Potential

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ai-Xia; XUE Ju-Kui

    2008-01-01

    We present an analytical study on the dynamics of bright and dark solitons in Bose-Einstein condensates with time-varying atomic scattering length in a time-varying external parabolic potential.A set of exact soliton solutions of the one-dimensional Gross-Pitaevskii equation are obtained,including fundamental bright solitons,higher-order bright solitons,and dark solitons.The results show that the soliton's parameters(amplitude,width,and period)can be changed in a controllable manner by changing the scattering length and external potential.This may be helpful to design experiments.

  4. Dynamical density fluctuations of superfluids near the critical velocity.

    Science.gov (United States)

    Kato, Yusuke; Watabe, Shohei

    2010-07-16

    We propose a stability criterion of superfluids in condensed Bose-Einstein systems, which incorporates the spectral function or the autocorrelation function of the local density. Within the Gross-Pitaevskii-Bogoliubov theory, we demonstrate the validity of our criterion for the soliton-emission instability, with use of explicit forms of zero modes of the Bogoliubov equation and a dynamical scaling near the saddle-node bifurcation. We also show that the criterion is applicable to the Landau phonon instability and the Landau roton instability within the single-mode approximation.

  5. Radial action-phase quantization in Bose-Einstein condensates

    Energy Technology Data Exchange (ETDEWEB)

    Reinisch, Gilbert [Departement Cassiopee, Observatoire de la Cote d' Azur, BP 4229, 06304-Nice cedex 4 (France)], E-mail: gilbert@oca.eu

    2008-02-04

    The 2D radial stationary nonlinear Schroedinger equation yields a new action-phase quantization of energy, in contrast with the linear case where the energy levels are degenerated with respect to the Ermakov constant. Characteristic values of radial energy quantization are given in the Gross-Pitaevskii mean-field description for the main vortex-nucleation experiments performed in rotating Bose-Einstein condensates. Finally, the link with Einstein's conjecture about non-quantizability of quasiperiodic orbits on a 2D torus is pointed out.

  6. Dynamics of bubbles in a two-component Bose-Einstein condensate

    Science.gov (United States)

    Sasaki, Kazuki; Suzuki, Naoya; Saito, Hiroki

    2011-03-01

    The dynamics of a phase-separated two-component Bose-Einstein condensate are investigated, in which a bubble of one component moves through the other component. Numerical simulations of the Gross-Pitaevskii equation reveal a variety of dynamics associated with the creation of quantized vortices. In two dimensions, a circular bubble deforms into an ellipse and splits into fragments with vortices, which undergo the Magnus effect. The Bénard-von Kármán vortex street is also generated. In three dimensions, a spherical bubble deforms into toruses with vortex rings. When two rings are formed, they exhibit leapfrogging dynamics.

  7. Phase diagram of microcavity polariton condensates with a harmonic potential trap

    Science.gov (United States)

    Chen, Ting-Wei; Wei, Ming-Dar; Cheng, Szu-Cheng; Hsieh, Wen-Feng

    2014-01-01

    We theoretically explore the phase transition in inhomogeneous exciton-polariton condensates with variable pumping conditions. Through Bogoliubov excitations to the radial-symmetric solutions of complex Gross-Pitaevskii equation, we determine not only the bifurcation of stable and unstable modes by the sign of fluid compressibility but also two distinct stable modes which are characterized by the elementary excitations and the stability of singly quantized vortex. One state is the quasi-condensate BKT phase with Goldstone flat dispersion; the other state is the localized-BEC phase which exhibits linear-type dispersion and has an excitation energy gap at zero momentum.

  8. Controllable Persistent Atom Current of Bose-Einstein Condensates in an Optical Lattice Ring

    Institute of Scientific and Technical Information of China (English)

    ZHENG Gong-Ping; LIANG Jiu-Qing

    2005-01-01

    In this paper the macroscopic quantum state of Bose-Einstein condensates in optical lattices is studied by solving the periodic Gross-Pitaevskii equation in one-dimensional geometry. It is shown that an exact solution seen to be a travelling wave of excited macroscopic quantum states resultes in a persistent atom current, which can be controlled by adjusting of the barrier height of the optical periodic potential. A critical condition to generate the travelling wave is demonstrated and we moreover propose a practical experiment to realize the persistent atom current in a toroidal atom waveguide.

  9. Depletion of superfluidity in a disordered non-equilibrium quantum condensate

    Energy Technology Data Exchange (ETDEWEB)

    Janot, Alexander; Rosenow, Bernd [Institut fuer Theoretische Physik, Universitaet Leipzig, 04009 Leipzig (Germany); Hyart, Timo [Institute of Physics, Leiden University, Niels Bohrweg 2, 2333 CA Leiden (Netherlands); Eastham, Paul [School of Physics, Trinity College, Dublin 2 (Ireland)

    2013-07-01

    Observations of quantum coherence in driven systems, e.g. polariton condensates, have strongly stimulated experimental as well as theoretical efforts during the last decade. We analyze the superfluid stiffness of a non-equilibrium quantum-condensate in a disordered environment taking gain and loss of particles into account. To this end a modified effective Gross-Pitaevskii equation is employed. We find that the disorder-driven depletion of superfluidity is strongly enhanced due to the gain-loss mechanism. It turns out that the condensate remains stiff at finite length scales only.

  10. Mechanism of stimulated Hawking radiation in a laboratory Bose-Einstein condensate

    CERN Document Server

    Wang, Yi-Hsieh; Edwards, Mark; Clark, Charles W

    2016-01-01

    We model a sonic black hole analog in a quasi one-dimensional Bose-Einstein condensate, using a Gross-Pitaevskii equation matching the configuration of a recent experiment by Steinhauer. The model agrees well with the experimental observations, with no adjustable parameters, demonstrating their hydrodynamic nature. With enhanced but experimentally feasible parameters we establish by spectral analysis that a growing bow wave is generated at the inner (white hole) horizon, stimulating the emission of Hawking radiation. The black hole laser effect plays no role.

  11. Helicity conservation under quantum reconnection of vortex rings

    CERN Document Server

    Zuccher, Simone

    2016-01-01

    Here we show that under quantum reconnection, simulated by using the three-dimensional Gross- Pitaevskii equation, self-helicity of a system of two interacting vortex rings remains conserved. By resolving the fine structure of the vortex cores, we demonstrate that total length of the vortex system reaches a maximum at the reconnection time, while both writhe helicity and twist helicity remain separately unchanged throughout the process. Self-helicity is computed by two independent methods, and topological information is based on the extraction and analysis of geometric quantities such as writhe, total torsion and intrinsic twist of the reconnecting vortex rings.

  12. Revisiting the NMR structure of the ultrafast downhill folding protein gpW from bacteriophage λ.

    Directory of Open Access Journals (Sweden)

    Lorenzo Sborgi

    Full Text Available GpW is a 68-residue protein from bacteriophage λ that participates in virus head morphogenesis. Previous NMR studies revealed a novel α+β fold for this protein. Recent experiments have shown that gpW folds in microseconds by crossing a marginal free energy barrier (i.e., downhill folding. These features make gpW a highly desirable target for further experimental and computational folding studies. As a step in that direction, we have re-determined the high-resolution structure of gpW by multidimensional NMR on a construct that eliminates the purification tags and unstructured C-terminal tail present in the prior study. In contrast to the previous work, we have obtained a full manual assignment and calculated the structure using only unambiguous distance restraints. This new structure confirms the α+β topology, but reveals important differences in tertiary packing. Namely, the two α-helices are rotated along their main axis to form a leucine zipper. The β-hairpin is orthogonal to the helical interface rather than parallel, displaying most tertiary contacts through strand 1. There also are differences in secondary structure: longer and less curved helices and a hairpin that now shows the typical right-hand twist. Molecular dynamics simulations starting from both gpW structures, and calculations with CS-Rosetta, all converge to our gpW structure. This confirms that the original structure has strange tertiary packing and strained secondary structure. A comparison of NMR datasets suggests that the problems were mainly caused by incomplete chemical shift assignments, mistakes in NOE assignment and the inclusion of ambiguous distance restraints during the automated procedure used in the original study. The new gpW corrects these problems, providing the appropriate structural reference for future work. Furthermore, our results are a cautionary tale against the inclusion of ambiguous experimental information in the determination of protein

  13. Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate

    DEFF Research Database (Denmark)

    Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume

    2013-01-01

    broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity.......Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies...... with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV...

  14. Antibodies to several conformation-dependent epitopes of gp120/gp41 inhibit CCR-5-dependent cell-to-cell fusion mediated by the native envelope glycoprotein of a primary macrophage-tropic HIV-1 isolate

    OpenAIRE

    Verrier, Florence C.; Charneau, Pierre; Altmeyer, Ralf; Laurent, Stephanie; Borman, Andrew M.; Girard, Marc

    1997-01-01

    The β-chemokine receptor CCR-5 is essential for the efficient entry of primary macrophage-tropic HIV-1 isolates into CD4+ target cells. To study CCR-5-dependent cell-to-cell fusion, we have developed an assay system based on the infection of CD4+ CCR-5+ HeLa cells with a Semliki Forest virus recombinant expressing the gp120/gp41 envelope (Env) from a primary clade B HIV-1 isolate (BX08), or from a laboratory T cell line-adapted strain (LAI). In this system, gp120/gp41 of the “nonsyncytium-ind...

  15. The truncated form of glycoprotein gp2 of equine herpesvirus 1 (EHV-1) vaccine strain KyA is not functionally equivalent to full-length gp2 encoded by EHV-1 wild-type strain RacL11.

    Science.gov (United States)

    von Einem, Jens; Wellington, Janet; Whalley, J Millar; Osterrieder, Kerstin; O'Callaghan, Dennis J; Osterrieder, Nikolaus

    2004-03-01

    Most equine herpesvirus 1 (EHV-1) strains, including the naturally occurring virulent RacL11 isolate, encode a large glycoprotein, gp2 (250 kDa), which is expressed from gene 71. Besides other alterations in the viral genome, the avirulent strain KyA harbors an in-frame deletion of 1,242 nucleotides in gene 71. To examine the contributions of gp2 variation to virus growth and virulence, mutant RacL11 and KyA viruses expressing full-length or truncated gp2 were generated. Western blot analyses demonstrated expression of a 250-kDa gp2 in cells infected with RacL11 virus or a mutant KyA virus harboring full-length gene 71, whereas a 75- to 80-kDa gp2 was detected in cells infected with KyA or mutant RacL11 virus expressing KyA gp2. The RacL11 gp2 precursor of 250 kDa in size and its truncated KyA counterpart of 80 kDa, as well as the 42-kDa carboxy-terminal gp2 subunit, were incorporated into virus particles. Absence of gp2 in RacL11 resulted in a 6-fold reduction of extracellular virus titers and a 13% reduction of plaque diameters, whereas gp2-negative KyA exhibited a 55% reduction in plaque diameter and a 51-fold decrease in extracellular virus titers. The massive growth defects of gp2-negative KyA could be restored by reinsertion of the truncated but not the full-length gp2 gene. The virulence of the generated gp2 mutant viruses was compared to the virulence of KyA and RacL11 in a murine infection model. RacL11 lacking gp2 was apathogenic for BALB/c mice, and insertion of the truncated KyA gp2 gene into RacL11 was unable to restore virulence. Similarly, replacement in the KyA genome of the truncated with the full-length RacL11 gene 71 did not result in the generation of virulent virus. From the results we conclude that full-length and truncated EHV-1 gp2 are not functionally equivalent and cannot compensate for the action of their homologues in allogeneic virus backgrounds.

  16. Obesidad, inflamación e insulino-resistencia: papel de los ligandos del receptor gp 130 Obesity, inflammation and insulin resistance: role of gp 130 receptor ligands

    Directory of Open Access Journals (Sweden)

    B. Marcos-Gómez

    2008-08-01

    Full Text Available La obesidad puede ser considerada como una patología inflamatoria crónica de bajo grado, caracterizada por una elevación de los niveles plasmáticos de citoquinas proinflamatorias como el factor de necrosis tumoral alfa (TNF-alfa, y proteínas reactantes de fase aguda como la proteína C reactiva. En este contexto, algunas de las citoquinas de la familia de interleuquina (IL-6 han sido también implicadas en el proceso inflamatorio asociado a obesidad y enfermedades relacionadas. Además de IL-6, pertenecen a esta familia citoquinas como IL-11, ciliary neurotrophic factor (CNTF, cardiotrophin-1 (CT-1, cardiotrophin- like cytokine (CLC, leukemia inhibitory factor (LIF y oncostatin M (OsM. Todas ellas ejercen sus acciones biológicas mediante la interacción con un complejo receptor del que forma parte una molécula glicoproteica transductora de la señal denominada glicoproteína 130 (gp130, por lo que también se denominan citoquinas gp130. Sin embargo, su papel en obesidad y sus complicaciones es controvertido; así, mientras que algunas han sido implicadas en el desarrollo de obesidad y enfermedades relacionadas como enfermedad hepática, insulino-resistencia y patología cardiovascular, otros estudios han llevado a proponer a los ligandos del receptor gp130 como potenciales agentes terapéuticos para el tratamiento de la obesidad y sus patologías asociadas. De hecho, el tratamiento con CNTF ha demostrado ser efectivo en la reducción del peso corporal, promoviendo la inhibición de la ingesta, la activación del gasto energético y la sensibilidad a la insulina. En esta revisión se analiza el potencial terapéutico de algunas de las citoquinas ligando del receptor gp130 en procesos de obesidad y enfermedades relacionadas.Obesity can be considered as a low grade inflammatory disease, characterized by increased plasma levels of proinflammatory cytokines such as tumoral necrosis factor-alpha (TNF-alpha, and acute phase reactant proteins

  17. Quasilinear equations with source terms on Carnot groups

    CERN Document Server

    Phuc, Nguyen Cong

    2012-01-01

    In this paper we give necessary and sufficient conditions for the existence of solutions to quasilinear equations of Lane--Emden type with measure data on a Carnot group $\\mathbb G$ of arbitrary step. The quasilinear part involves operators of the $p$-Laplacian type $\\Delta_{\\mathbb G,\\,p}\\,$, $1equations with source terms which has been known only for equations involving the sub-Laplacian ($p=2$) on the Heisenberg group.

  18. Expression of glycoprotein gp43 in stage-specific forms and during dimorphic differentiation of Paracoccidioides brasiliensis.

    Science.gov (United States)

    Mattar-Filho, R; Azevedo, M O; Pereira, M; Jesuino, R S; Salem-Izacc, S M; Brito, W A; Gesztesi, J L; Soares, R B; Felipe, M S; Soares, C M

    1997-01-01

    Expression of the 43 kDa glycoprotein (gp43) was analysed in several Paracoccidioides brasiliensis isolates. Using one- and two-dimensional analysis of crude cellular extracts, it was shown that protein expression in yeast and mycelium was dependent on the isolate analysed. In two strains, in both yeast and mycelium cells. gp43 was present, whereas expression was restricted to the yeast phase of two other strains. The clinical implications of this phase-specific gp43 expression are uncertain.

  19. Envelope deglycosylation enhances antigenicity of HIV-1 gp41 epitopes for both broad neutralizing antibodies and their unmutated ancestor antibodies.

    Directory of Open Access Journals (Sweden)

    Ben-Jiang Ma

    2011-09-01

    Full Text Available The HIV-1 gp41 envelope (Env membrane proximal external region (MPER is an important vaccine target that in rare subjects can elicit neutralizing antibodies. One mechanism proposed for rarity of MPER neutralizing antibody generation is lack of reverted unmutated ancestor (putative naive B cell receptor antibody reactivity with HIV-1 envelope. We have studied the effect of partial deglycosylation under non-denaturing (native conditions on gp140 Env antigenicity for MPER neutralizing antibodies and their reverted unmutated ancestor antibodies. We found that native deglycosylation of clade B JRFL gp140 as well as group M consensus gp140 Env CON-S selectively increased the reactivity of Env with the broad neutralizing human mAbs, 2F5 and 4E10. Whereas fully glycosylated gp140 Env either did not bind (JRFL, or weakly bound (CON-S, 2F5 and 4E10 reverted unmutated ancestors, natively deglycosylated JRFL and CON-S gp140 Envs did bind well to these putative mimics of naive B cell receptors. These data predict that partially deglycoslated Env would bind better than fully glycosylated Env to gp41-specific naïve B cells with improved immunogenicity. In this regard, immunization of rhesus macaques demonstrated enhanced immunogenicity of the 2F5 MPER epitope on deglyosylated JRFL gp140 compared to glycosylated JRFL gp140. Thus, the lack of 2F5 and 4E10 reverted unmutated ancestor binding to gp140 Env may not always be due to lack of unmutated ancestor antibody reactivity with gp41 peptide epitopes, but rather, may be due to glycan interference of binding of unmutated ancestor antibodies of broad neutralizing mAb to Env gp41.

  20. Protective effects of curcumin against human immunodeficiency virus 1 gp120 V3 loop-induced neuronal injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zheng Gong; Yanyan Xing; Jun Dong; Lijuan Yang; Hongmei Tang; Rui Pan; Sai Xie; Luyan Guo; Junbin Wang; Qinyin Deng; Guoyin Xiong

    2012-01-01

    Curcumin improves the learning and memory deficits in rats induced by the gp120 V3 loop. The present study cultured rat hippocampal neurons with 1 nM gp120 V3 loop and 1 μM curcumin for 24 hours. The results showed that curcumin inhibited the gp120 V3 loop-induced mitochondrial membrane potential decrease, reduced the mRNA expression of the pro-apoptotic gene caspase-3, and attenuated hippocampal neuronal injury.

  1. Roles of glycans in interactions between gp120 and HIV broadly neutralizing antibodies.

    Science.gov (United States)

    Qi, Yifei; Jo, Sunhwan; Im, Wonpil

    2016-03-01

    Many novel broadly neutralizing antibodies against human immunodeficiency virus (HIV) have been identified during the past decade, providing promising templates for the development of an effective HIV-1 vaccine. Structural studies reveal that the epitopes of some of these antibodies involve one or more crucial glycans, without which the binding is completely abolished. In this study, we have investigated the critical roles of glycans in interactions between HIV-1 gp120 and two broadly neutralizing antibodies PG9 (targeting V1/V2) and PGT128 (targeting V3) that are able to neutralize more than 70% of HIV-1 isolates. We have performed molecular dynamics simulations of a number of systems including antibody-gp120 complex with and without glycans, antibody, gp120 with and without glycans, and glycan-only systems. The simulation results show that the complex structures are stabilized by the glycans, and the multivalent interactions between the antibody and gp120 promote cooperativities to further enhance the binding. In the free gp120, the glycans increase the flexibility of the V1/V2 and V3 loops, which likely increases the entropy cost of the antibody recognition. However, the antibodies are able to bind the flexible interface by recognizing the preexisting glycan conformation, and penetrating the glycan shield with flexible complementarity determining region loops that sample the bound conformations occasionally.

  2. Endotoxemia enhances expression of the signaling receptor (GP130) on protein and molecular level.

    Science.gov (United States)

    Marsik, Claudia; Halama, Thomas; Cardona, Francesco; Schlifke, Irene; Mittermayer, Friedrich; Jilma, Bernd

    2005-03-01

    Interleukin 6 (IL-6) performs a prominent role during sepsis. To examine the molecular regulation of IL-6, IL-6 receptor, and signaling receptor gp130 during endotoxemia, nine healthy young volunteers received a bolus injection of lipopolysaccharide (LPS) on day 1 and saline on day 2 in a double blind, randomized, placebo-controlled trial. LPS enhanced IL-6 release 300-fold. IL-6 mRNA expression was not significantly altered in blood samples at any time after LPS infusion in vivo, while incubation of whole blood with 50 pg/ml LPS up-regulated IL-6 mRNA levels 8000- to 50,000-fold in vitro. LPS infusion increased synthesis of gp130 mRNA 5.5-fold compared to baseline at 4 h (P < 0.05), while no significant change was observed in the placebo period (P = 0.001 between groups). LPS increased the percentage of gp130 positive neutrophils gp130 700% over baseline at 8 h (P < 0.01 versus baseline and placebo). IL-6 receptor levels were not significantly altered by low-grade endotoxemia. In conclusion, endotoxemia up-regulates gp130 expression in vivo and in vitro. Quantification of IL-6 mRNA expression in circulating leukocytes is unlikely a suitable marker for monitoring of endotoxemia.

  3. HIV-1 gp120 envelope glycoprotein determinants for cytokine burst in human monocytes

    Science.gov (United States)

    Coutu, Mathieu; Prévost, Jérémie; Brassard, Nathalie; Peres, Adam; Stegen, Camille; Madrenas, Joaquín; Kaufmann, Daniel E.; Finzi, Andrés

    2017-01-01

    The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear. Enhanced chemokine receptor binding and subsequent clustering receptors may lead to cytokine production. By using a comprehensive panel of gp120 mutants, here we show that CD4 binding is mandatory for cytokine outburst in monocytes. Our data suggest that targeting monocytes in HIV-infected patients might decrease systemic inflammation and the potential tissue injury associated with the production of inflammatory cytokines. Understanding how gp120 mediates a cytokine burst in monocytes might help develop new approaches to improve the chronic inflammation that persists in these patients despite effective suppression of viremia by antiretroviral therapy. PMID:28346521

  4. Uterine deletion of Gp130 or Stat3 shows implantation failure with increased estrogenic responses.

    Science.gov (United States)

    Sun, Xiaofei; Bartos, Amanda; Whitsett, Jeffrey A; Dey, Sudhansu K

    2013-09-01

    Leukemia inhibitory factor (LIF), a downstream target of estrogen, is essential for implantation in mice. LIF function is thought to be mediated by its binding to LIF receptor (LIFR) and recruitment of coreceptor GP130 (glycoprotein 130), and this receptor complex then activates signal transducer and activator of transcription (STAT)1/3. However, the importance of LIFR and GP130 acting via STAT3 in implantation remains uncertain, because constitutive inactivation of Lifr, Gp130, or Stat3 shows embryonic lethality in mice. To address this issue, we generated mice with conditional deletion of uterine Gp130 or Stat3 and show that both GP130 and STAT3 are critical for uterine receptivity and implantation. Implantation failure in these deleted mice is associated with higher uterine estrogenic responses prior to the time of implantation. These heightened estrogenic responses are not due to changes in ovarian hormone levels or expression of their nuclear receptors. In the deleted mice, estrogen-responsive gene, Lactoferrin (Ltf), and Mucin 1 protein, were up-regulated in the uterus. In addition, progesterone-responsive genes, Hoxa10 and Indian hedgehog (Ihh), were markedly down-regulated in STAT3-inactivated uteri. These changes in uteri of deleted mice were reflected by the failure of differentiation of the luminal epithelium, which is essential for blastocyst attachment.

  5. Giardiasis in North West England: faecal specimen requesting rates by GP practice.

    Science.gov (United States)

    Reeve, N F; Fanshawe, T R; Lamden, K; Diggle, P J; Cheesbrough, J; Keegan, T J

    2015-06-01

    Many cases of giardiasis in the UK are undiagnosed and among other things, diagnosis is dependent upon the readiness of GPs to request a specimen. The aim of this study is to assess the rate of specimens requested per GP practice in Central Lancashire, to examine the differences between GP practices and to estimate the pattern of unexplained spatial variation in the practice rate of specimens after adjustment for deprivation. To achieve this, we fitted a set of binomial and Poisson regression models, with random effects for GP practice. Our analysis suggests that there were differences in the rate of specimens by GP practices (P < 0·001) for a single year, but no difference in the proportion of positive tests per specimen submitted or in the rate of positive specimens per practice population. There was a difference in the cumulative rate of positive specimens per practice population over a 9-year period (P < 0·001). Neither the specimen rate per practice for a single year nor the cumulative rate of positive specimens over multiple years demonstrated significant spatial correlation. Hence, spatial variation in the incidence of giardiasis is unlikely to be confounded by variation in GP rate of specimens.

  6. Gp120 on HIV-1 Virions Lacks O-Linked Carbohydrate.

    Directory of Open Access Journals (Sweden)

    Elizabeth Stansell

    Full Text Available As HIV-1-encoded envelope protein traverses the secretory pathway, it may be modified with N- and O-linked carbohydrate. When the gp120s of HIV-1 NL4-3, HIV-1 YU2, HIV-1 Bal, HIV-1 JRFL, and HIV-1 JRCSF were expressed as secreted proteins, the threonine at consensus position 499 was found to be O-glycosylated. For SIVmac239, the corresponding threonine was also glycosylated when gp120 was recombinantly expressed. Similarly-positioned, highly-conserved threonines in the influenza A virus H1N1 HA1 and H5N1 HA1 envelope proteins were also found to carry O-glycans when expressed as secreted proteins. In all cases, the threonines were modified predominantly with disialylated core 1 glycans, together with related core 1 and core 2 structures. Secreted HIV-1 gp140 was modified to a lesser extent with mainly monosialylated core 1 O-glycans, suggesting that the ectodomain of the gp41 transmembrane component may limit the accessibility of Thr499 to glycosyltransferases. In striking contrast to these findings, gp120 on purified virions of HIV-1 Bal and SIV CP-MAC lacked any detectable O-glycosylation of the C-terminal threonine. Our results indicate the absence of O-linked carbohydrates on Thr499 as it exists on the surface of virions and suggest caution in the interpretation of analyses of post-translational modifications that utilize recombinant forms of envelope protein.

  7. Role of a Putative gp41 Dimerization Domain in Human Immunodeficiency Virus Type 1 Membrane Fusion

    Energy Technology Data Exchange (ETDEWEB)

    Liu, J.; Deng, Y; Li, Q; Dey, A; Moore, J; Lu, M

    2010-01-01

    The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell entails a series of conformational changes in the gp41 transmembrane glycoprotein that mediates the fusion of the viral and target cell membranes. A trimer-of-hairpins structure formed by the association of two heptad repeat (HR) regions of the gp41 ectodomain has been implicated in a late step of the fusion pathway. Earlier native and intermediate states of the protein are postulated to mediate the antiviral activity of the fusion inhibitor enfuvirtide and of broadly neutralizing monoclonal antibodies (NAbs), but the details of these structures remain unknown. Here, we report the identification and crystal structure of a dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil with two distinct C-terminal {alpha}-helical overhangs. This dimer structure is conferred largely by interactions within a central core that corresponds to the sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential intermediate conformation of gp41. These results should enhance our understanding of the molecular basis of the gp41 fusogenic structural transitions and thereby guide rational, structure-based efforts to design new fusion inhibitors and vaccine candidates intended to induce broadly neutralizing antibodies.

  8. Introducing peer observation of teaching to GP teachers: a questionnaire study.

    Science.gov (United States)

    Adshead, Lesley; White, Patrick T; Stephenson, Anne

    2006-03-01

    In medical education programmes which rely on clinical teachers spread across diverse sites, the application of peer observation of teaching offers the potential of both supporting teachers and maintaining quality. This paper reports on a questionnaire survey carried out with general practitioner (GP) teachers of medical undergraduate students from King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals. The aim of the study was to determine GP teachers' views on a proposed programme of peer observation of their teaching. The majority of GP teachers identified benefits of the proposed scheme with 69% saying it would help improve the education of future doctors. However, despite seeing the benefits, less than half wished to take part in the programme. Two thirds cited time and paperwork as major disincentives to taking part and 62% said that they felt it would make them feel under scrutiny. No associations were found between measures of workload and willingness to take part. This suggests that a fundamental fear of scrutiny and criticism may be the main hurdle to be overcome in implementing the scheme. Imposing peer observation on GP teachers in the form proposed could create suspicion and distance between the university department and practice-based GP teachers and may even result in a loss of teachers. The introduction of peer observation is more likely to be successful if GPs' apprehensions are addressed. Using peer observation to strengthen the process of quality assurance may undermine its role in the support and development of clinical teachers.

  9. [Clothing make the doctor--patients have more confidence in a smartly dressed GP].

    Science.gov (United States)

    Kocks, Janwillem W H; Lisman-van Leeuwen, Yvonne; Berkelmans, P G J Ine

    2010-01-01

    To investigate the influence of the general practitioner's style of clothing on the patient's level of confidence in that doctor; is vanity a functional attribute for the GP? Experimental comparative study. 4 photographic models representing 4 types of GP, namely the older male, younger male, older female and younger female GP, were each photographed dressed in 4 different styles of clothing (business wear, formal, semi-formal and casual). These photos were shown to evaluators with the question 'How much confidence do you have in this doctor?' The level of confidence was allocated a score on a numerical scale from 0 (no confidence) to 10 (complete confidence). There were 2 groups of evaluators: patients aged ≥ 65 years and professionals attending a symposium. The clothing style had a significant impact on the level of confidence in the older and younger male doctor and in the younger female doctor. The assessment by elderly patients (n = 116) differed significantly from the assessment by professionals (n = 59). The professionals had a far more pronounced opinion on style of clothing than the patients did. Business wear and formal clothing generally inspired more confidence than casual clothing. A GP's style of clothing affects the patient's initial level of confidence in that doctor. Vanity therefore seems to be a functional attribute for the GP.

  10. Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the diagest 3-GP motivation study

    Directory of Open Access Journals (Sweden)

    Berkhout Christophe

    2012-06-01

    Full Text Available Abstract Background Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs’ attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. Methods We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs’ level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Results Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152 of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. Conclusions When a hospital-led study

  11. Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

    Directory of Open Access Journals (Sweden)

    Meritxell Granell

    2017-06-01

    Full Text Available Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127 punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238, while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein.

  12. Physico-chemical Properties and Bioactivities of a Glycoconjugate LbGp5B from Lycium barbarum L.

    Institute of Scientific and Technical Information of China (English)

    PENG,Xue-Mei(彭雪梅); PENG,Xue-Mei; QI,Chun-Hui(齐春会); QI,Chun-Hui; TIAN,Geng-Yuan (田庚元); TIAN,Geng-Yuan; ZHANG,Yong-Xiang(张永详); ZHANG,Yong-Xiang

    2001-01-01

    A glycoconjugatedesignated as LbGp5B was isolated from the fruit of Lyciun barbarum L. and purified to homogeneity by gel filtration .LbGp5B is composed of rhamnose (Rha), arabinose (Ara), galactose (Gal), glucose (Glc), galacturonic acid (GalA) and seveateen amino acids. The molecular weight of LbGp5B was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and by matrix-asisted laser desorption/ionization (MALDI) time of fight (T OF) mass spectrometry (MS). The preliminary experiments showed that LbGp5B promoted splenocyte proliferation in mice and inhihited the peroxidation of low density lipoprotein (LDL).

  13. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability

    Science.gov (United States)

    Kong, Leopold; He, Linling; de Val, Natalia; Vora, Nemil; Morris, Charles D.; Azadnia, Parisa; Sok, Devin; Zhou, Bin; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Zhu, Jiang

    2016-06-01

    The trimeric HIV-1 envelope glycoprotein (Env) is critical for host immune recognition and neutralization. Despite advances in trimer design, the roots of Env trimer metastability remain elusive. Here we investigate the contribution of two Env regions to metastability. First, we computationally redesign a largely disordered bend in heptad region 1 (HR1) of SOSIP trimers that connects the long, central HR1 helix to the fusion peptide, substantially improving the yield of soluble, well-folded trimers. Structural and antigenic analyses of two distinct HR1 redesigns confirm that redesigned Env closely mimics the native, prefusion trimer with a more stable gp41. Next, we replace the cleavage site between gp120 and gp41 with various linkers in the context of an HR1 redesign. Electron microscopy reveals a potential fusion intermediate state for uncleaved trimers containing short but not long linkers. Together, these results outline a general approach for stabilization of Env trimers from diverse HIV-1 strains.

  14. Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors

    DEFF Research Database (Denmark)

    Ameri, Jacqueline; Borup, Rehannah; Prawiro, Christy

    2017-01-01

    cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2) as a specific cell surface marker for isolating pancreatic endoderm cells (PECs) from differentiated hESCs and human fetal pancreas. Isolated GP2+ PECs efficiently differentiated into glucose responsive insulin......-producing cells in vitro. We found that in vitro PEC proliferation declines due to enhanced expression of the cyclin-dependent kinase (CDK) inhibitors CDKN1A and CDKN2A. However, we identified a time window when reducing CDKN1A or CDKN2A expression increased proliferation and yield of GP2+ PECs. Altogether, our...... results contribute tools and concepts toward the isolation and use of PECs as a source for the safe production of hPSC-derived β cells....

  15. LEDS GP Success Story: Fostering Coordinated LEDS Support in Kenya (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2014-03-01

    The LEDS Global Partnership (LEDS GP) strives to advance climate-resilient, low-emission development through catalyzing collaboration, information exchange, and action on the ground. The Government of Kenya is a key LEDS GP member and offers an inspiring example of how LEDS GP is having an impact globally. The 2012 LEDS Collaboration in Action workshop in London provided an interactive space for members to share experiences on cross-ministerial LEDS leadership and to learn about concrete development impacts of LEDS around the world. Inspired by these stories, the Kenya's Ministry of State for Planning, National Development and Vision 2030 (MPND) began to collaborate closely with the Ministry of Environment and Mineral Resources to create strong links between climate change action and development in the country, culminating in the integration of Kenya's National Climate Change Action Plan and the country's Medium Term Development Plan.

  16. Doctors telling stories: the place of anecdote in GP registrar training.

    Science.gov (United States)

    Alderson, T St J; Bateman, H

    2002-11-01

    Observational studies within a hospital setting confirm the widespread use of anecdotes in hospital-based medical education and hypothesize a number of reasons for this. Whilst anecdotes may be used effectively in teaching there can be dangers in their inappropriate use. There is no information on the level and nature of the use of anecdotes within medical education in the community. The authors undertook a questionnaire study that asked GP trainers about how they used anecdote in their GP registrar teaching. The results suggested that GP trainers use anecdotes frequently in their registrar teaching, recognize the use of anecdotes described in the literature and have little concern that anecdotes might mislead. The authors discuss how anecdotes may be used to help build registrars' illness scripts, and to develop ways of thinking and working congruent with the existing professional community.

  17. P-gp Protein Expression and Transport Activity in Rodent Seizure Models and Human Epilepsy.

    Science.gov (United States)

    Hartz, Anika M S; Pekcec, Anton; Soldner, Emma L B; Zhong, Yu; Schlichtiger, Juli; Bauer, Bjoern

    2017-03-02

    A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to antiseizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of antiseizure drugs, and thus, contribute to antiseizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier. Exposing isolated rat brain capillaries to glutamate ex vivo upregulated P-gp expression to levels that were similar to those in capillaries isolated from rats that had status epilepticus or chronic epilepsy. Moreover, the fold-increase in P-gp protein expression seen in animal models is consistent with the fold-increase in P-gp observed in human brain capillaries isolated from patients with epilepsy compared to age-matched control individuals. Overall, the in vivo/ex vivo approach presented here allows detailed analysis of the mechanisms underlying seizure-induced changes of P-gp expression and transport activity at the blood-brain barrier. This approach can be extended to other blood-brain barrier proteins that might contribute to drug-resistant epilepsy or other CNS disorders as well.

  18. Influences on GP coping and resilience: a qualitative study in primary care.

    Science.gov (United States)

    Cheshire, Anna; Ridge, Damien; Hughes, John; Peters, David; Panagioti, Maria; Simon, Chantal; Lewith, George

    2017-06-01

    'Neoliberal' work policies, austerity, NHS restructuring, and increased GP consultation rates provide the backdrop against increasing reports of GP burnout and an impending shortage of GPs. To explore GPs' experiences of workplace challenges and stresses, and their coping strategies, particularly focusing on understanding the impact of recent NHS workplace change. Study design was qualitative, with data collected from two focus groups and seven one-to-one telephone interviews. Focus groups and one-to-one telephone interviews explored the experiences of GPs currently practising in England, recruited through convenience sampling. Data were collected using a semi-structured interview approach and analysed using thematic analysis. There were 22 GP participants recruited: focus groups (n = 15) and interviews (n = 7). Interviewees understood GPs to be under intense and historically unprecedented pressures, which were tied to the contexts in which they work, with important moral implications for 'good' doctoring. Many reported that being a full-time GP was too stressful: work-related stress led to mood changes, sleep disruption, increases in anxiety, and tensions with loved ones. Some had subsequently sought ways to downsize their clinical workload. Workplace change resulted in little time for the things that helped GP resilience: a good work-life balance and better contact with colleagues. Although some GPs were coping better than others, GPs acknowledged that there was only so much an individual GP could do to manage their stress, given the external work issues they faced. GPs experience their emotional lives and stresses as being meaningfully shaped by NHS factors. To support GPs to provide effective care, resilience building should move beyond the individual to include systemic work issues. © British Journal of General Practice 2017.

  19. Liposomes containing recombinant gp85 protein vaccine against ALV-J in chickens.

    Science.gov (United States)

    Zhang, Limei; Cai, Dongjie; Zhao, Xiaona; Cheng, Ziqiang; Guo, Huijun; Qi, Chunhua; Liu, Jianzhu; Xu, Ruixue; Zhao, Peng; Cui, Zhizhong

    2014-05-01

    To study the potential of liposome vaccines in the clinical prevention of ALV-J, the effect of recombinant gp85 protein of subgroup J avian leukosis virus (ALV-J) entrapped by liposomes in chickens against ALV-J infection was investigated in this paper. A recombinant plasmid (PET28a-gp85) containing the PET28a vector and gp85 gene was constructed and then expressed in Rosetta (DE3) cells with 0.5mM IPTG to produce recombinant gp85 proteins that could be entrapped by liposomes through reverse-phase evaporation. The chickens were inoculated intramuscularly either once or twice with the liposomes or with Freund's adjuvant emulsion containing recombinant gp85 protein. Sixty chickens were raised to one week old for the first inoculation and to three weeks old for the second inoculation. Chickens raised to five weeks old were challenged with a 10(2.4) 50% tissue culture infective dose (TCID50) of ALV-J. Blood samples were collected from each chicken at weekly intervals for serum antibody and viremia analyses. Changes in serum antibodies showed that positive serum antibodies (S/P value >0.6) could be induced in all groups regardless of the frequency of inoculation but improved significantly in the twice-inoculated groups. As well, high levels of antibodies emerged earlier in the Freund's adjuvant groups but persisted longer in the liposome groups. Detection of viremia indicated that the liposomes provide better protection against ALV-J than Freund's adjuvant emulsion and that this protection is directly influenced by serum antibody levels. Overall, this study reveals the potential of liposome vaccines containing recombinant gp85 protein in the clinical prevention of ALV-J.

  20. Structural Characterization of HIV gp41 with the Membrane-proximal External Region

    Energy Technology Data Exchange (ETDEWEB)

    Shi, W.; Bohon, J; Han, D; Habte, H; Qin, Y; Cho, M; Chance, M

    2010-01-01

    Human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein (gp120/gp41) plays a critical role in virus infection and pathogenesis. Three of the six monoclonal antibodies considered to have broadly neutralizing activities (2F5, 4E10, and Z13e1) bind to the membrane-proximal external region (MPER) of gp41. This makes the MPER a desirable template for developing immunogens that can elicit antibodies with properties similar to these monoclonal antibodies, with a long term goal of developing antigens that could serve as novel HIV vaccines. In order to provide a structural basis for rational antigen design, an MPER construct, HR1-54Q, was generated for x-ray crystallographic and x-ray footprinting studies to provide both high resolution atomic coordinates and verification of the solution state of the antigen, respectively. The crystal structure of HR1-54Q reveals a trimeric, coiled-coil six-helical bundle, which probably represents a postfusion form of gp41. The MPER portion extends from HR2 in continuation of a slightly bent long helix and is relatively flexible. The structures observed for the 2F5 and 4E10 epitopes agree well with existing structural data, and enzyme-linked immunosorbent assays indicate that the antigen binds well to antibodies that recognize the above epitopes. Hydroxyl radical-mediated protein footprinting of the antigen in solution reveals specifically protected and accessible regions consistent with the predictions based on the trimeric structure from the crystallographic data. Overall, the HR1-54Q antigen, as characterized by crystallography and footprinting, represents a postfusion, trimeric form of HIV gp41, and its structure provides a rational basis for gp41 antigen design suitable for HIV vaccine development.

  1. Conservation and antigenicity of N-terminal sequences of GP185 from different Plasmodium falciparum isolates.

    Science.gov (United States)

    Howard, R F; Ardeshir, F; Reese, R T

    1986-01-01

    Complementary DNA (cDNA) clones for GP185, a major antigenically diverse glycoprotein of Plasmodium falciparum, were isolated from a cDNA library of the Honduras I/CDC (Honduras I) isolate, and 1052 bp were sequenced. The expression of cDNA fragments in Escherichia coli using the vector pCQV2 allowed verification of the reading frame. This GP185 cDNA sequence, like the cDNA sequence for a homologous gene of the K1 isolate [Hall et al., Nature 311 (1984) 379-382], codes for a polypeptide which is truncated due to multiple, in-frame stop codons. This polypeptide corresponds to the N-terminal 15% of the proposed coding region of the GP185 gene [Holder et al., Nature 317 (1985) 270-273]. Comparison of the nucleotide sequences for the GP185 gene of Honduras I and five other isolates indicated that there are two areas of conserved DNA sequence, one of 310 bp (beginning 181 bp upstream from the proposed initiation codon) and the other of greater than or equal to 360 bp (located entirely within the coding region), separated by a region encoding isolate-specific tandem amino acid repeats. Rat antiserum was raised to a fusion protein derived from the conserved regions and the intervening repeat region of this Honduras I protein. This antiserum bound GP185 on immunoblots of the homologous Honduras I isolate and the heterologous K1 isolate, which has different tandem repeats. Serum from owl monkeys and humans previously infected with P. falciparum reacted with the fusion protein on immunoblots demonstrating that determinants in the N-terminal 15% of GP185 were immunogenic in infected individuals and suggesting that some of these sites are conserved among isolates.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Kinetic energy equations for the average-passage equation system

    Science.gov (United States)

    Johnson, Richard W.; Adamczyk, John J.

    1989-01-01

    Important kinetic energy equations derived from the average-passage equation sets are documented, with a view to their interrelationships. These kinetic equations may be used for closing the average-passage equations. The turbulent kinetic energy transport equation used is formed by subtracting the mean kinetic energy equation from the averaged total instantaneous kinetic energy equation. The aperiodic kinetic energy equation, averaged steady kinetic energy equation, averaged unsteady kinetic energy equation, and periodic kinetic energy equation, are also treated.

  3. Kinetic energy equations for the average-passage equation system

    Science.gov (United States)

    Johnson, Richard W.; Adamczyk, John J.

    1989-01-01

    Important kinetic energy equations derived from the average-passage equation sets are documented, with a view to their interrelationships. These kinetic equations may be used for closing the average-passage equations. The turbulent kinetic energy transport equation used is formed by subtracting the mean kinetic energy equation from the averaged total instantaneous kinetic energy equation. The aperiodic kinetic energy equation, averaged steady kinetic energy equation, averaged unsteady kinetic energy equation, and periodic kinetic energy equation, are also treated.

  4. HLA-C increases HIV-1 infectivity and is associated with gp120

    Directory of Open Access Journals (Sweden)

    Beretta Alberto

    2008-08-01

    Full Text Available Abstract Background A recently identified genetic polymorphism located in the 5' region of the HLA-C gene is associated with individual variations in HIV-1 viral load and with differences in HLA-C expression levels. HLA-C has the potential to restrict HIV-1 by presenting epitopes to cytotoxic T cells but it is also a potent inhibitor of NK cells. In addition, HLA-C molecules incorporated within the HIV-1 envelope have been shown to bind to the envelope glycoprotein gp120 and enhance viral infectivity. We investigated this last property in cell fusion assays where the expression of HLA-C was silenced by small interfering RNA sequences. Syncytia formation was analyzed by co-cultivating cell lines expressing HIV-1 gp120/gp41 from different laboratory and primary isolates with target cells expressing different HIV-1 co-receptors. Virus infectivity was analyzed using pseudoviruses. Molecular complexes generated during cell fusion (fusion complexes were purified and analyzed for their HLA-C content. Results HLA-C positive cells co-expressing HIV-1 gp120/gp41 fused more rapidly and produced larger syncytia than HLA-C negative cells. Transient transfection of gp120/gp41 from different primary isolates in HLA-C positive cells resulted in a significant cell fusion increase. Fusion efficiency was reduced in HLA-C silenced cells compared to non-silenced cells when co-cultivated with different target cell lines expressing HIV-1 co-receptors. Similarly, pseudoviruses produced from HLA-C silenced cells were significantly less infectious. HLA-C was co-purified with gp120 from cells before and after fusion and was associated with the fusion complex. Conclusion Virionic HLA-C molecules associate to Env and increase the infectivity of both R5 and X4 viruses. Genetic polymorphisms associated to variations in HLA-C expression levels may therefore influence the individual viral set point not only by means of a regulation of the virus-specific immune response but also

  5. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Institute of Scientific and Technical Information of China (English)

    Beuy Joob; Viroj Wiwanitkit

    2014-01-01

    The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present. Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus. The in-depth analysis of the viral protein to find the binding site, active pocket is needed. Here, the authors analyzed the envelope glycoprotein GP2 from Ebola virus. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus was done. According to this assessment, 7 active pockets with varied druggability could be identified.

  6. Identification of active pocket and protein druggability within envelope glycoprotein GP2 from Ebola virus

    Institute of Scientific and Technical Information of China (English)

    Beuy; Joob; Viroj; Wiwanitkit

    2014-01-01

    The drug searching for combating the present outbreak of Ebola virus infection is the urgent activity at present.Finding the new effective drug at present must base on the molecular analysis of the pathogenic virus.The in-depth analysis of the viral protein to find the binding site,active pocket is needed.Here,the authors analyzed the envelope glycoprotein GP2 from Ebola virus.Identification of active pocket and protein draggability within envelope glycoprotein GP2 from Ebola virus was done.According to this assessment,7 active pockets with varied draggability could be identified.

  7. GP Cellulose将增加Georgia厂的绒毛浆产量

    Institute of Scientific and Technical Information of China (English)

    苏传胜

    2006-01-01

    GP Cellulose目前已成为Koch Industries完全拥有的子公司。GP Cellulose不久将对其制浆部进行一次大的投资,此次投资将使位于佐治亚州的Brunswick绒毛浆厂的生产能力达到预期的95.3万t/a,比其目前的74.9万t/a增加27%。

  8. Why are some patients in treatment for advanced cancer reluctant to consult their GP?

    DEFF Research Database (Denmark)

    Åbom, Birgit; Pfeiffer, Per

    2009-01-01

    ' possibility of staying at home and dying at home. This study, however, shows that due to some patients' barriers special attention is needed to guarantee the switch over from the cancer treatment centre to home-based end-of-life care. This is increasingly important as cancer patients to a still larger extent......-treatment-related matters. However, as the disease progressed they also described how they perceived unmet psychosocial needs. After ending chemotherapy, re-establishment of the contact between patient and GP was in this study dependent on a proactive attitude by the GP. CONCLUSION: GPs are important for cancer patients...

  9. Fate of the surface protein gp70 during entry of retrovirus into mouse fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, K.B.

    1985-04-15

    The kinetics of the viral surface protein gp70 and the viral core proteins p30 and p15C were followed during retrovirus entry into mouse fibroblasts. All three proteins were internalized, but whereas essentially all the gp70 was degraded, approximately one-third of the core proteins remained stable in the cells. These diverging routes of the different proteins are in agreement with the proposed route, that retrovirus enters the cells by endocytosis followed by a membrane fusion between the virus membrane and the vesicle membrane.

  10. Interference with phage lambda development by the small subunit of the phage 21 terminase, gp1.

    OpenAIRE

    1991-01-01

    Bacteriophage lambda development is blocked in cells carrying a plasmid that expresses the terminase genes of phage 21. The interference is caused by the small subunit of phage 21 terminase, gp1. Mutants of lambda able to form plaques in the presence of gp1 include sti mutants. One such mutation, sti30, is an A. T-to-G.C transition mutation at base pair 184 on the lambda chromosome. The sti30 mutation extends the length of the ribosome-binding sequence of the Nul gene that is complementary to...

  11. What is a good general practitioner (GP)? The development and evaluation of a multi-source feedback instrument for GP appraisal.

    Science.gov (United States)

    Shepherd, Annabel; Lough, Murray

    2010-05-01

    Although multi-source feedback (MSF) has been used in primary healthcare, the development of an MSF instrument specific to this setting in the UK has not been previously described. The aims of this study were to develop and evaluate an MSF instrument for GPs in Scotland taking part in appraisal. The members of ten primary healthcare teams in the west of Scotland were asked to provide comments in answer to the question, 'What is a good GP?'. The data were reduced and coded by two researchers and questions were devised. Following content validity testing the MSF process was evaluated with volunteers using face-to-face interviews and a postal survey. Thirty-seven statements covering the six domains of communication skills, professional values, clinical care, working with colleagues, personality issues and duties and responsibilities were accepted as relevant by ten primary healthcare teams using a standard of 80 percent agreement. The evaluation found the MSF process to be feasible and acceptable and participants provided some evidence of educational impact. An MSF instrument for GPs has been developed based on the concept of 'the good GP' as described by the primary healthcare team. The evaluation of the resultant MSF process illustrates the potential of MSF, when delivered in the supportive environment of GP appraisal, to provide feedback which has the possibility of improving working relationships between GPs and their colleagues.

  12. Truncation and expression of HIV-1 trans-membrane protein gp41%HIV-1跨膜蛋白gp41的截短及表达

    Institute of Scientific and Technical Information of China (English)

    端义坤; 张涛; 余模松

    2003-01-01

    将HIV-1跨膜蛋白gp41进行截短,在大肠杆菌中进行表达并纯化.PCR扩增gp41的部分编码基因,回收的PCR产物纯化后克隆到连接载体pGEM-T上,然后用EcoR I和Sa1 I切下目的基因,并构建到表达载体pGEX-4T3上,导入宿主细胞BL21(DE3),用IPTG诱导表达,表达产物用亲和层析进行纯化并作相应鉴定.截短的HIV-1跨膜蛋白gp41能直接在大肠杆菌内进行表达,利用亲和层析能方便地将目的蛋白进行纯化,为跨膜蛋白的进一步应用打下基础.

  13. Solving Nonlinear Wave Equations by Elliptic Equation

    Institute of Scientific and Technical Information of China (English)

    FU Zun-Tao; LIU Shi-Da; LIU Shi-Kuo

    2003-01-01

    The elliptic equation is taken as a transformation and applied to solve nonlinear wave equations. It is shown that this method is more powerful to give more kinds of solutions, such as rational solutions, solitary wave solutions,periodic wave solutions and so on, so it can be taken as a generalized method.

  14. The membrane-spanning domain of gp41 plays a critical role in intracellular trafficking of the HIV envelope protein

    Directory of Open Access Journals (Sweden)

    Kondo Naoyuki

    2010-11-01

    Full Text Available Abstract Background The sequences of membrane-spanning domains (MSDs on the gp41 subunit are highly conserved among many isolates of HIV-1. The GXXXG motif, a potential helix-helix interaction motif, and an arginine residue (rare in hydrophobic MSDs are especially well conserved. These two conserved elements are expected to locate on the opposite sides of the MSD, if the MSD takes a α-helical secondary structure. A scanning alanine-insertion mutagenesis was performed to elucidate the structure-function relationship of gp41 MSD. Results A circular dichroism analysis of a synthetic gp41 MSD peptide determined that the secondary structure of the gp41 MSD was α-helical. We then performed a scanning alanine-insertion mutagenesis of the entire gp41 MSD, progressively shifting the relative positions of MSD segments around the helix axis. Altering the position of Gly694, the last residue of the GXXXG motif, relative to Arg696 (the number indicates the position of the amino acid residues in HXB2 Env around the axis resulted in defective fusion. These mutants showed impaired processing of the gp160 precursor into gp120 and gp41. Furthermore, these Env mutants manifested inefficient intracellular transport in the endoplasmic reticulum and Golgi regions. Indeed, a transplantation of the gp41 MSD portion into the transmembrane domain of another membrane protein, Tac, altered its intracellular distribution. Our data suggest that the intact MSD α-helix is critical in the intracellular trafficking of HIV-1 Env. Conclusions The relative position between the highly conserved GXXXG motif and an arginine residue around the gp41 MSD α-helix is critical for intracellular trafficking of HIV-1 Env. The gp41 MSD region not only modulates membrane fusion but also controls biosynthesis of HIV-1 Env.

  15. Ileal Inflammation May Trigger the Development of GP2-Specific Pancreatic Autoantibodies in Patients with Crohn’s Disease

    Directory of Open Access Journals (Sweden)

    Polychronis Pavlidis

    2012-01-01

    Full Text Available Why zymogen glycoprotein 2 (GP2, the Crohn’s disease (CD-specific pancreatic autoantigen, is the major target of humoral autoimmunity in inflammatory bowel diseases (IBD is uknown. Recent evidence demonstrates that GP2 is also present on the apical surface of microfold (M intestinal cells. As the colon lacks GP2-rich M cells, we assumed that patients with colonic CD are seronegative for anti-GP2. Anti-GP2 antibodies were tested in 225 CDs, including 45 patients with colonic location (L2, 45 with terminal ileum (L1 and 135 with ileocolonic involvement; 225 patients with ulcerative colitis (UC were also tested. Anti-GP2 reactivity was detected in 59 (26.2% CDs and 15 (6.7% UCs (P<0.001. Only 5 CDs with L2 had anti-GP2 antibodies, compared to 54/180 (30.0%, P=0.0128 of the CDs with L1 and L3. Anti-GP2 antibody positive CD patients had higher ASCA titres compared to seronegative cases. Amongst the 128 CD patients with previous surgical intervention, 45 (35.0% were anti-GP2 antibody positive compared to 14/97 (14.0% without surgical (P<0.001. Our data support the assumption that ileal inflammation is required for the development of anti-GP2 antibodies in CD, and suggest that the intestine rather than the pancreatic juice is the antigenic source required for the initiation of anti-GP2 antibodies.

  16. Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment.

    Science.gov (United States)

    Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

    2008-09-30

    Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS.

  17. THE NUMERICAL STABILITY OF THE BLOCK θ-METHODS FOR DELAY DIFFERENTIAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper focuses on the numerical stability of the block θ-methods adapted to differential equations with a dday argument. For the block θ-methods, an interpolation procedure is introduced which leads to the mumerical processes that satisfy an important asymptotic stability condition related to the class of test problems y' (t)=ay(t)+by(t-r) with a,b∈C, Re(a)<- |b| and τ>0. We prove that the block θ-method is GP-stable if and only if the method is A-stable for ordinary differential equations. Furthermore, it is proved that the P-and GP-stability are equivalent for the block θ-method.

  18. Vaccination of Plasmid DNA Encoding Somatostatin Gene Fused with GP5 Gene of Porcine Reproductive and Respiratory Syndrome Virus Induces Anti-GP5 Antibodies and Promotes Growth Performance in Immunized Pigs

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Somatostatin (SS) is a hormone that inhibits the secretion of growth hormone. Immunization against SS can promote the growth of animals. This paper described the effects of DNA immunization on the growth and antibody response in mice and pigs immunized with a plasmid DNA encoding SS fused with GP5 of porcine reproductive and respiratory syndrome virus (PRRSV). A fragment of 180 bp encoding partial SS gene was amplified by PCR from the genomic DNA of peripheral blood mononuclear cells of pigs, and cloned as a fusion gene with PRRSV GP5 in plasmid pISGRTK3. Three times of immunization with the resulting plasmid pISG-SS/GP5 induced anti-GP5 antibodies in BALB/c mice and pigs, as demonstrated by GP5-specific ELISA and immunoblotting. Compared with pigs immunized with empty vector pISGRTK3, the growth performance of pigs immunized with pISG-SS/GP5 was increased by 11.1% on the 13th week after the last vaccination. The results indicated the plasmid DNA encoding SS and PRRSV GP5 fusion gene elicited anti-GP5 antibodies and improved the growth performance of immunized pigs.

  19. 人免疫缺陷病毒跨膜蛋白gp41在大肠杆菌中的表达%EXPRESSION OF HIV TRANS-MEMBRANEANTIGEN.(gp41).GENE IN ESCHERICHIA COLI

    Institute of Scientific and Technical Information of China (English)

    陈晨; 刘坤; 王金忠; 马明; 耿运琪; 陈启民; 朱效科; 夏建晖

    2001-01-01

    为研究廉价的HIV血清学诊断系统,实现检测试剂国产化,用原核pET系统表达HIV跨膜蛋白gp41.研究发现,全长及缺失C端1/3的gp41在E.coli中均不能有效表达.仅保留N端1/3的gp41(包含gp41主要抗原决定簇,594~613氨基酸)有一定量的表达;通过金属螯合层析,产物得到部分纯化;Western blot显示产物有很好的反应原性.推测gp41在E.coli中较低表达量可能与mRNA的二级结构有关.

  20. Introduction to differential equations

    CERN Document Server

    Taylor, Michael E

    2011-01-01

    The mathematical formulations of problems in physics, economics, biology, and other sciences are usually embodied in differential equations. The analysis of the resulting equations then provides new insight into the original problems. This book describes the tools for performing that analysis. The first chapter treats single differential equations, emphasizing linear and nonlinear first order equations, linear second order equations, and a class of nonlinear second order equations arising from Newton's laws. The first order linear theory starts with a self-contained presentation of the exponen

  1. The Modified Magnetohydrodynamical Equations

    Institute of Scientific and Technical Information of China (English)

    EvangelosChaliasos

    2003-01-01

    After finding the really self-consistent electromagnetic equations for a plasma, we proceed in a similar fashion to find how the magnetohydrodynamical equations have to be modified accordingly. Substantially this is done by replacing the "Lorentz" force equation by the correct (in our case) force equation. Formally we have to use the vector potential instead of the magnetic field intensity. The appearance of the formulae presented is the one of classical vector analysis. We thus find a set of eight equations in eight unknowns, as previously known concerning the traditional MHD equations.

  2. Genetic Structure and Expression of the Surface Glycoprotein GP82, the Main Adhesin of Trypanosoma cruzi Metacyclic Trypomastigotes

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Ceridorio Correa

    2013-01-01

    Full Text Available T. cruzi improves the likelihood of invading or adapting to the host through its capacity to present a large repertoire of surface molecules. The metacyclic stage-specific surface glycoprotein GP82 has been implicated in host cell invasion. GP82 is encoded by multiple genes from the trans-sialidase superfamily. GP82 shows a modular organization, with some variation of N-terminal region flanking a conserved central core where the binding sites to the mammalian cell and gastric mucin are located. The function of GP82 as adhesin in host cell invasion process could expose the protein to an intense conservative and selective pressure. GP82 is a GPI-anchored surface protein, synthesized as a 70 kDa precursor devoid of N-linked sugars. GPI-minus variants accumulate in the ER indicating that GPI anchor acts as a forward transport signal for progressing along the secretory pathway as suggested for T. cruzi mucins. It has been demonstrated that the expression of GP82 is constitutive and may be regulated at post-transcriptional level, for instance, at translational level and/or mRNA stabilization. GP82 mRNAs are mobilized to polysomes and consequently translated, but only in metacyclic trypomastigotes. Analysis of transgenic parasites indicates that the mechanism regulating GP82 expression involves multiple elements in the 3′UTR.

  3. C-11-verapamil to Assess P-gp Function in Human Brain During Aging, Depression and Neurodegenerative Disease

    NARCIS (Netherlands)

    Bartels, A. L.; de Klerk, O. L.; Kortekaas, R.; de Vries, J. J.; Leenders, K. L.

    2010-01-01

    P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a wide range of substrates from the brain. This is important for maintaining loco-regional homeostasis and for protecting the brain against blood-borne toxic substances. Altered P-gp function seems

  4. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...on through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. Authors Lee C, Liu QH, Tomkowicz B, Yi

  5. Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

    2016-04-15

    Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

  6. Structural and mechanistic basis for the inhibition of Escherichia coli RNA polymerase by T7 Gp2.

    Science.gov (United States)

    James, Ellen; Liu, Minhao; Sheppard, Carol; Mekler, Vladimir; Cámara, Beatriz; Liu, Bing; Simpson, Pete; Cota, Ernesto; Severinov, Konstantin; Matthews, Steve; Wigneshweraraj, Sivaramesh

    2012-09-14

    The T7 phage-encoded small protein Gp2 is a non-DNA-binding transcription factor that interacts with the jaw domain of the Escherichia coli (Ec) RNA polymerase (RNAp) β' subunit and inhibits transcriptionally proficient promoter-complex (RPo) formation. Here, we describe the high-resolution solution structure of the Gp2-Ec β' jaw domain complex and show that Gp2 and DNA compete for binding to the β' jaw domain. We reveal that efficient inhibition of RPo formation by Gp2 requires the amino-terminal σ(70) domain region 1.1 (R1.1), and that Gp2 antagonizes the obligatory movement of R1.1 during RPo formation. We demonstrate that Gp2 inhibits RPo formation not just by steric occlusion of the RNAp-DNA interaction but also through long-range antagonistic effects on RNAp-promoter interactions around the RNAp active center that likely occur due to repositioning of R1.1 by Gp2. The inhibition of Ec RNAp by Gp2 thus defines a previously uncharacterized mechanism by which bacterial transcription is regulated by a viral factor. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp.

    Science.gov (United States)

    Zhou, Yan; Zhang, Guoqiang; Rao, Zhi; Yang, Yang; Zhou, Qian; Qin, Hongyan; Wei, Yuhui; Wu, Xin'an

    2015-07-01

    Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood-brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX - SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX - SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and -22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX - SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX+ empty SLN) and VLX solution with Verapamil (VLX + Ver), respectively. Furthermore, the protein mass of P-gp in VLX - SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.

  8. Genetic vaccination against the melanocyte lineage-specific antigen gp100 induces cytotoxic T lymphocyte-mediated tumor protection.

    Science.gov (United States)

    Schreurs, M W; de Boer, A J; Figdor, C G; Adema, G J

    1998-06-15

    Melanocyte lineage-specific antigens, such as gp100, have been shown to induce both cellular and humoral immune responses against melanoma. Therefore, these antigens are potential targets for specific antimelanoma immunotherapy. A novel approach to induce both cellular and humoral immunity is genetic vaccination, the injection of antigen-encoding naked plasmid DNA. In a mouse model, we investigated whether genetic vaccination against the human gp100 antigen results in specific antitumor immunity. The results demonstrate that vaccinated mice were protected against a lethal challenge with syngeneic B16 melanoma-expressing human gp100, but not control-transfected B16. Both cytotoxic T cells and IgG specific for human gp100 could be detected in human gp100-vaccinated mice. However, only adoptive transfer of spleen-derived lymphocytes, not of the serum, isolated from protected mice was able to transfer antitumor immunity to nonvaccinated recipients, indicating that CTLs are the predominant effector cells. CTI, lines generated from human gp100-vaccinated mice specifically recognized human gp100. Interestingly, one of the CTL lines cross-reacted between human and mouse gp100, indicating the recognition of a conserved epitope. However, these CTLs did not appear to be involved in the observed tumor protection. Collectively, our results indicate that genetic vaccination can result in a potent antitumor response in vivo and constitutes a potential immunotherapeutic strategy to fight cancer.

  9. Autographa californica multiple nucleopolyhedrovirus GP64 protein: Analysis of domain I and V amino acid interactions and membrane fusion activity

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Qianlong [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Blissard, Gary W. [Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, United State (United States); Liu, Tong-Xian [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Li, Zhaofei, E-mail: zhaofeili73@outlook.com [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China)

    2016-01-15

    The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, but no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.

  10. A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition

    NARCIS (Netherlands)

    Hulsik, D.L.; Liu, Y.Y.; Strokappe, N.M.; Battella, S.; el Khattabi, M.; Bonvin, A.M.J.J.; Verrips, C.T.; Rutten, L.

    2013-01-01

    The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposo

  11. Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

    Science.gov (United States)

    Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

    2016-12-13

    In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms.

  12. Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance.

    Science.gov (United States)

    Muz, Barbara; Kusdono, Hubert D; Azab, Feda; de la Puente, Pilar; Federico, Cinzia; Fiala, Mark; Vij, Ravi; Salama, Noha N; Azab, Abdel Kareem

    2017-12-01

    Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression. We found that in MM patients P-gp expression positively correlated with the hypoxic marker, HIF-1α. Hypoxia increased P-gp protein expression and its efflux capabilities in MM cells in vitro using flow cytometry. We reported herein that hypoxia-mediated resistance to carfilzomib and bortezomib in MM cells is due to P-gp activity and was reversed by tariquidar, a P-gp inhibitor. These results suggest combining proteasome inhibitors with P-gp inhibition for future clinical studies.

  13. Rat precision-cut intestinal slices to study P-gp activity and the potency of its inhibitors ex vivo

    NARCIS (Netherlands)

    Li, Ming; de Graaf, Inge A M; de Jager, Marina H; Groothuis, Geny M M

    2015-01-01

    Rat Precision-Cut Intestinal Slices (PCIS) were evaluated as ex vivo model to study the regional gradient of P-gp activity, and to investigate whether the rank order of inhibitory potency of P-gp inhibitors can be correctly reproduced in this model with more accurate IC50 values than with current in

  14. Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

    Science.gov (United States)

    d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

    2015-04-16

    ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. HIV-1gp120 induces neuronal apoptosis through enhancement of 4-aminopyridine-senstive outward K+ currents.

    Directory of Open Access Journals (Sweden)

    Lina Chen

    Full Text Available Human immunodeficiency virus type 1 (HIV-1-associated dementia (HAD usually occurs late in the course of HIV-1 infection and the mechanisms underlying HAD pathogenesis are not well understood. Accumulating evidence indicates that neuronal voltage-gated potassium (Kv channels play an important role in memory processes and acquired neuronal channelopathies in HAD. To examine whether Kv channels are involved in HIV-1-associated neuronal injury, we studied the effects of HIV-1 glycoprotein 120 (gp120 on outward K+ currents in rat cortical neuronal cultures using whole-cell patch techniques. Exposure of cortical neurons to gp120 produced a dose-dependent enhancement of A-type transient outward K+ currents (IA. The gp120-induced increase of IA was attenuated by T140, a specific antagonist for chemokine receptor CXCR4, suggesting gp120 enhancement of neuronal IA via CXCR4. Pretreatment of neuronal cultures with a protein kinase C (PKC inhibitor, GF109203X, inhibited the gp120-induced increase of IA. Biological significance of gp120 enhancement of IA was demonstrated by experimental results showing that gp120-induced neuronal apoptosis, as detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay and caspase-3 staining, was attenuated by either an IA blocker 4-aminopyridine or a specific CXCR4 antagonist T140. Taken together, these results suggest that gp120 may induce caspase-3 dependent neuronal apoptosis by enhancing IA via CXCR4-PKC signaling.

  16. Memory B cell antibodies to HIV-1 gp140 cloned from individuals infected with clade A and B viruses.

    Directory of Open Access Journals (Sweden)

    Hugo Mouquet

    Full Text Available Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is a crucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important as these antibodies may target conserved epitopes on the HIV envelope gp160 protein. To this end we have used a clade B YU-2 gp140 trimeric antigen and single-cell antibody cloning methods to obtain 189 new anti-gp140 antibodies representing 51 independent B cell clones from the IgG memory B cells of 3 patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing a diverse antibody response to HIV gp140 envelope protein, characterized by differentially expanded B-cell clones producing highly hypermutated antibodies with heterogenous gp140-specificity and neutralizing activity. In addition to their high-affinity binding to the HIV spike, the vast majority of the new anti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VRC01 or PG9, two clonally-related antibodies isolated from a clade A HIV-1 infected donor, directed against the gp120 variable loop 3, rank in the top 5% of the neutralizers identified in our large collection of 185 unique gp140-specific antibodies in terms of breadth and potency.

  17. Radioimmunodetection of lung cancer using radioactive antibody against a glycoprotein (GP 68) found in developing mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Shuji; Ishido, Miki; Kubodera, Akiko; Kubota, Kazuhiko (Science Univ. of Tokyo (Japan)); Awaya, Akira; Hashimoto, Yoshihide; Fukui, Hideo; Muramatsu, Hisako; Muramatsu, Takashi

    1991-12-01

    The in vivo localization of a polyclonal antibody (GP68 PoAb) against a glycoprotein, which was found in developing mouse brain, was studied in murine tumor model. The biodistribution of {sup 125}I-GP68 PoAb 3 days postinjection into the mice bearing eight different kinds of solid tumor represented a high uptake ratio by metastatic lung cancer, mammary tumor such as MMT 060562 and adenocarcinoma 755, and melanoma B-16. In immunoscintigraphic studies, adenocarcinoma 755 and metastatic lung cancer were successfully visualized with {sup 131}I-GP68 PoAb at 3 days postinjection. The strongly positive images of these tumors with {sup 131}I-GP68 PoAb were accorded well with the data on tissue distribution of this antibody. These results suggest that GP68 PoAb may be applicable to the detection of the mammary and/or metastatic lung cancer. (author).

  18. Sublingual vein parameters, AFP, AFP-L3, and GP73 in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Zhao, J; Guo, L-Y; Yang, J-M; Jia, J-W

    2015-06-26

    This study evaluated the diagnostic value of alpha-fetoprotein (AFP), AFP heterogeneity 3 (AFP-L3), Golgi protein 73 (GP73), and sublingual vein parameters in hepatocellular carcinoma (HCC). Levels of serum AFP, AFP-L3, GP73, and sublingual vein scores were measured in 34 patients with chronic hepatitis, 65 patients with post-hepatitis B cirrhosis, 71 patients with HCC, and 6 healthy controls. Logistic regression analysis was used to explore potential correlations. Sublingual vein grades in patients with HCC were higher than those in the other three groups; sublingual vein scores were also different between groups; combined diagnosis using AFP, GP73, and sublingual vein grade was superior to the individual parameters alone or when only two were used in different combinations. Thus, sublingual vein grade can be considered as an independent risk factor for diagnosis of HCC. Furthermore, combined detection with AFP, GP73, and sublingual vein grade is simple, inexpensive, and effective. It may therefore be suitable for screening high-risk populations for early diagnosis of HCC.

  19. Sequence and phylogenetic analysis of the gp200 protein of Ehrlichia canis from dogs in Taiwan.

    Science.gov (United States)

    Huang, Chia-Chia; Hsieh, Yu-Chen; Tsang, Chau-Loong; Chung, Yang-Tsung

    2010-12-01

    Ehrlichia (E.) canis is a Gram-negative obligate intracellular bacterium responsible for canine monocytic ehrlichiosis. Currently, the genetic diversity of E. canis strains worldwide is poorly defined. In the present study, sequence analysis of the nearly full-length 16S rDNA (1,620 bp) and the complete coding region (4,269 bp) of the gp200 gene, which encodes the largest major immunoreactive protein in E. canis, from 17 Taiwanese samples was conducted. The resultant 16S rDNA sequences were found to be identical to each other and have very high homology (99.4~100%) with previously reported E. canis sequences. Additionally, phylogenetic analysis of gp200 demonstrated that the E. canis Taiwanese genotype was genetically distinct from other reported isolates obtained from the United States, Brazil, and Israel, and that it formed a separate clade. Remarkable variations unique to the Taiwanese genotype were found throughout the deduced amino acid sequence of gp200, including 15 substitutions occurring in two of five known species-specific epitopes. The gp200 amino acid sequences of the Taiwanese genotype bore 94.4~94.6 identities with those of the isolates from the United States and Brazil, and 93.7% homology with that of the Israeli isolate. Taken together, these results suggest that the Taiwanese genotype represents a novel strain of E. canis that has not yet been characterized.

  20. Computational Design of Hypothetical New Peptides Based on a Cyclotide Scaffold as HIV gp120 Inhibitor.

    Science.gov (United States)

    Sangphukieo, Apiwat; Nawae, Wanapinun; Laomettachit, Teeraphan; Supasitthimethee, Umaporn; Ruengjitchatchawalya, Marasri

    2015-01-01

    Cyclotides are a family of triple disulfide cyclic peptides with exceptional resistance to thermal/chemical denaturation and enzymatic degradation. Several cyclotides have been shown to possess anti-HIV activity, including kalata B1 (KB1). However, the use of cyclotides as anti-HIV therapies remains limited due to the high toxicity in normal cells. Therefore, grafting anti-HIV epitopes onto a cyclotide might be a promising approach for reducing toxicity and simultaneously improving anti-HIV activity. Viral envelope glycoprotein gp120 is required for entry of HIV into CD4+ T cells. However, due to a high degree of variability and physical shielding, the design of drugs targeting gp120 remains challenging. We created a computational protocol in which molecular modeling techniques were combined with a genetic algorithm (GA) to automate the design of new cyclotides with improved binding to HIV gp120. We found that the group of modified cyclotides has better binding scores (23.1%) compared to the KB1. By using molecular dynamic (MD) simulation as a post filter for the final candidates, we identified two novel cyclotides, GA763 and GA190, which exhibited better interaction energies (36.6% and 22.8%, respectively) when binding to gp120 compared to KB1. This computational design represents an alternative tool for modifying peptides, including cyclotides and other stable peptides, as therapeutic agents before the synthesis process.

  1. Medication management strategy for older people with polypharmacy: the GP's perspective.

    NARCIS (Netherlands)

    Sinnige, J.; Korevaar, J.C.; Lieshout, J. van; Westert, G.P.; Schellevis, F.G.; Braspenning, J.C.C.

    2016-01-01

    Background & Aim: for older patients with polypharmacy medication management is a process of careful deliberation that needs periodic adjustment based on treatment effects and changing conditions. The aim of this study is to gain insight into the GP's medication management strategy for patients with

  2. Degradation of 1,2-Dibromoethane by Mycobacterium sp. Strain GP1

    NARCIS (Netherlands)

    Poelarends, Gerrit J.; Hylckama Vlieg, Johan E.T. van; Marchesi, Julian R.; Freitas dos Santos, Luisa M.; Janssen, Dick B.

    1999-01-01

    The newly isolated bacterial strain GP1 can utilize 1,2-dibromoethane as the sole carbon and energy source. On the basis of 16S rRNA gene sequence analysis, the organism was identified as a member of the subgroup which contains the fast-growing mycobacteria, The first step in 1,2-dibromoethane metab

  3. 77 FR 66830 - LNG Development Company, LLC and Oregon Pipeline Company; Northwest Pipeline GP; Notice of...

    Science.gov (United States)

    2012-11-07

    ... Energy Regulatory Commission LNG Development Company, LLC and Oregon Pipeline Company; Northwest Pipeline GP; Notice of Extension of Comment Period for the Oregon LNG Export and Washington Expansion Projects This notice announces the extension of the public scoping process and comment period for the Oregon...

  4. Overweight and obesitas: effect on GP consultation and the use of medication.

    NARCIS (Netherlands)

    Dijk, L. van; Otters, H.; Schuit, J.

    2004-01-01

    Background: Most research on health consequences of obesitas examined differences in occurrences of specific health problems such as diabetes mellitus and coronary heart disease and related use of care, rather than investigating differences in the use of care in general, such as rate GP consultation

  5. Relationship between sealing ability of Activ GP and Gutta Flow and methods of calcium hydroxide removal

    Directory of Open Access Journals (Sweden)

    Vineeta Nikhil

    2012-01-01

    Full Text Available Aim: To evaluate the effect of method of calcium hydroxide intracanal dressing removal, on sealing ability of Gutta Flow and Activ GP. Materials and Methods: Seventy extracted mandibular premolars were sectioned at CEJ and canals were prepared with profile 4% rotary file till #40. Canals were filled with calcium hydroxide, coronally sealed with Cavit G and stored at 37°C. After 7 days, samples were divided on the basis of calcium hydroxide removal method (Master apical file, Navi Tip FX, and F File and obturating material (Activ GP and Gutta Flow. Three coats of nail polish were applied except 2 mm around apical foramen and samples were immersed in India ink dye, sectioned, and observed under stereomicroscope for microleakage. Results: The results were statistically analyzed with one way ANOVA-F with Tukey HSD test with the null hypothesis set as 5%. Conclusions: The seal of the canal system was adversely impacted by residual calcium hydroxide when Activ GP and Gutta Flow were used as obturating material and the sealing ability of Activ GP and Gutta Flow was better when MAF was used for removal of calcium hydroxide than F file or Navi tip FX.

  6. Molecular characterization of HIV-1 subtype C gp-120 regions potentially involved in virus adaptive mechanisms.

    Directory of Open Access Journals (Sweden)

    Alessandra Cenci

    Full Text Available The role of variable regions of HIV-1 gp120 in immune escape of HIV has been investigated. However, there is scant information on how conserved gp120 regions contribute to virus escaping. Here we have studied how molecular sequence characteristics of conserved C3, C4 and V3 regions of clade C HIV-1 gp120 that are involved in HIV entry and are target of the immune response, are modulated during the disease course. We found an increase of "shifting" putative N-glycosylation sites (PNGSs in the α2 helix (in C3 and in C4 and an increase of sites under positive selection pressure in the α2 helix during the chronic stage of disease. These sites are close to CD4 and to co-receptor binding sites. We also found a negative correlation between electric charges of C3 and V4 during the late stage of disease counteracted by a positive correlation of electric charges of α2 helix and V5 during the same stage. These data allow us to hypothesize possible mechanisms of virus escape involving constant and variable regions of gp120. In particular, new mutations, including new PNGSs occurring near the CD4 and CCR5 binding sites could potentially affect receptor binding affinity and shield the virus from the immune response.

  7. Study of coherence strain of GP II zones in an aged aluminum composite

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez-Rivera, J.L., E-mail: jose.hernandez@cimav.edu.mx [Centro de Investigacion en Materiales Avanzados (CIMAV), Laboratorio Nacional de Nanotecnologia, Miguel de Cervantes 120, C.P. 31109, Chihuahua (Mexico); Stuttgart Center for Electron Microscopy, Max Planck Institute for Intelligent Systems (formerly Max Planck Institute for Metals Research), Heisenbergstrase 3, 70569 Stuttgart (Germany); Rivera, J.J. Cruz [Facultad de Ingenieria-Instituto de Metalurgia, Universidad Autonoma de San Luis Potosi, Sierra Leona 550, Lomas 2a seccion, C.P. 78210, San Luis Potosi (Mexico); Koch, C.T. [Department of Physics, Ulm University, 86069 Ulm (Germany); Stuttgart Center for Electron Microscopy, Max Planck Institute for Intelligent Systems (formerly Max Planck Institute for Metals Research), Heisenbergstrase 3, 70569 Stuttgart (Germany); Oezdoel, V.B. [Stuttgart Center for Electron Microscopy, Max Planck Institute for Intelligent Systems (formerly Max Planck Institute for Metals Research), Heisenbergstrase 3, 70569 Stuttgart (Germany); Martinez-Sanchez, R. [Centro de Investigacion en Materiales Avanzados (CIMAV), Laboratorio Nacional de Nanotecnologia, Miguel de Cervantes 120, C.P. 31109, Chihuahua (Mexico)

    2012-09-25

    Highlights: Black-Right-Pointing-Pointer Precipitation sequence was changed in 2024 Al alloy. Black-Right-Pointing-Pointer Image artifacts ought to the mask size and shape increased the real strain value. Black-Right-Pointing-Pointer The strain distribution around experimental GP area was non uniform and more complex than reference. Black-Right-Pointing-Pointer The origin of this strain distribution are related to mechanisms by which GP precipitates lose coherence. - Abstract: Strain mapping using the geometric phase analysis (GPA) technique was applied to Al-GP II (Guinier-Preston) nanoscale precipitates, using both high resolution transmission electron microscopy (HRTEM) micrographs as well as the exit wave function (EWF) obtained by focal series reconstruction. The experimental strain results were compared with strain maps obtained from an atomic model which consisted of an Al supercell containing a GP II precipitate. It was built as a reference from literature data. The experimental results demonstrate a complex strain distribution and larger fluctuations than the reference strain maps. These differences were found to be partly a consequence of image artifacts produced by the technique as well as complex microstructural events which were present at the development stage studied.

  8. Extending an Afrikaans pronunciation dictionary using Dutch resources and P2P/GP2P

    CSIR Research Space (South Africa)

    Loots, L

    2010-11-01

    Full Text Available . This is compared to the more common approach of extending the Afrikaans dictionary by means of graphemeto-phoneme (G2P) conversion. The results indicate that the Afrikaans pronunciations obtained by P2P and GP2P from the Dutch dictionary are more accurate than...

  9. Computational Design of Hypothetical New Peptides Based on a Cyclotide Scaffold as HIV gp120 Inhibitor.

    Directory of Open Access Journals (Sweden)

    Apiwat Sangphukieo

    Full Text Available Cyclotides are a family of triple disulfide cyclic peptides with exceptional resistance to thermal/chemical denaturation and enzymatic degradation. Several cyclotides have been shown to possess anti-HIV activity, including kalata B1 (KB1. However, the use of cyclotides as anti-HIV therapies remains limited due to the high toxicity in normal cells. Therefore, grafting anti-HIV epitopes onto a cyclotide might be a promising approach for reducing toxicity and simultaneously improving anti-HIV activity. Viral envelope glycoprotein gp120 is required for entry of HIV into CD4+ T cells. However, due to a high degree of variability and physical shielding, the design of drugs targeting gp120 remains challenging. We created a computational protocol in which molecular modeling techniques were combined with a genetic algorithm (GA to automate the design of new cyclotides with improved binding to HIV gp120. We found that the group of modified cyclotides has better binding scores (23.1% compared to the KB1. By using molecular dynamic (MD simulation as a post filter for the final candidates, we identified two novel cyclotides, GA763 and GA190, which exhibited better interaction energies (36.6% and 22.8%, respectively when binding to gp120 compared to KB1. This computational design represents an alternative tool for modifying peptides, including cyclotides and other stable peptides, as therapeutic agents before the synthesis process.

  10. GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

    NARCIS (Netherlands)

    Jong-Potjer, L.C. de; Elsinga, J.; Cessie, S. le; Pal-de Bruin, K.M. van der; Knuistingh Neven, A.; Buitendijk, S.E.; Assendelft, W.J.J.

    2006-01-01

    Background: Preconception counselling (PCC) can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. Methods: Randomised trial of usual care versus

  11. 78 FR 20316 - Final Issuance of General NPDES Permits (GP) for Small Suction Dredges in Idaho

    Science.gov (United States)

    2013-04-04

    ... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Final Issuance of General NPDES Permits (GP) for Small Suction Dredges in Idaho AGENCY... placer mining operations in Idaho for small suction dredges (intake nozzle size of 5 inches in diameter...

  12. Antibiotics in Dutch general practice: nationwide electronic GP database and national reimbursement rates.

    NARCIS (Netherlands)

    Akkerman, A.E.; Kuyvenhoven, M.M.; Verheij, T.J.M.; Dijk, L. van

    2008-01-01

    PURPOSE: In order to assess whether different databases generate information which can be reliable compared with each other, this study aimed to assess to which degree prescribing rates for systemic antibiotics from a nationwide electronic general practitioner (GP) database correspond with national

  13. Superantigen activates the gp130 receptor on adipocytes resulting in altered adipocyte metabolism.

    Science.gov (United States)

    Banke, Elin; Rödström, Karin; Ekelund, Mikael; Dalla-Riva, Jonathan; Lagerstedt, Jens O; Nilsson, Staffan; Degerman, Eva; Lindkvist-Petersson, Karin; Nilson, Bo

    2014-06-01

    The bacteria Staphylococcus aureus is part of the normal bacterial flora and produces a repertoire of enterotoxins which can cause food poisoning and toxic shock and might contribute to the pathogenesis of inflammatory diseases. These enterotoxins directly cross-link the T cell receptor with MHC class II, activating large amounts of T cells and are therefore called superantigens. It was recently discovered that the superantigen SEA binds to the cytokine receptor gp130. As obesity and type 2 diabetes are highly associated with inflammation of the adipose tissue and gp130 has been shown to play an important role in adipocytes, we wanted to investigate the effect of SEA on adipocyte signaling and function. Binding of SEA to gp130 was examined using surface plasmon resonance in a cell free system. Effects of SEA on adipocyte signaling, insulin sensitivity and function were studied using western blotting and biological assays for lipolysis, lipogenesis and glucose uptake. We demonstrate that SEA binds to gp130 with a medium affinity. Furthermore, SEA induces phosphorylation of a key downstream target, STAT3, in adipocytes. SEA also inhibits insulin-induced activation of PKB and PKB downstream signaling which was associated with reduced basal and insulin induced glucose uptake, reduced lipogenesis as well as reduced ability of insulin to inhibit lipolysis. SEA inhibits insulin signaling as well as insulin biological responses in adipocytes supporting that bacterial infection might contribute to the development of insulin resistance and type 2 diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. SYSTEMIC FUNCTIONAL LINGUISTIC GENRE PEDAGOGY (SFL GP IN A TERTIARY EFL WRITING CONTEXT IN INDONESIA

    Directory of Open Access Journals (Sweden)

    Emi Emilia

    2015-07-01

    Full Text Available This article reports on the results of a study aiming to investigate whether systemic functional linguistic genre pedagogy (SFL GP can help students develop their writing ability in English and the students’ opinions about the teaching program using SFL GP. The study was conducted in one semester with 19 student teachers taking a writing course on argumentative texts, in the English Department at a state university in West Java, Indonesia. The texts in focus were Exposition, Discussion and Response to Literary Works, but in the interests of space, the article will centre around Exposition. The study used a qualitative case study research design with data collected from participant observations for 16 meetings, analysis of students’ texts collected over the program, and questionnaires distributed at the conclusion of the program. The results indicate that despite some aspects that still need improvement, SFL GP can generally help students develop their writing ability. Observation data show students’ writing skill improvement supported by students’ texts which depicts good control of the schematic structure and linguistic features of the texts in focus. Finally, questionnaire data reveal students’ consciousness of improved writing skill and positive responses to each activity in the program. Based on the results of the study, it is recommended that SFL GP be implemented in other contexts in Indonesia and other countries.

  15. Working as a locum GP: their professional role in organizational context.

    NARCIS (Netherlands)

    Batenburg, R.; Hassel, D. van; Velden, L. van der

    2012-01-01

    Context: The workforce of General Practitioners (GPs) in the Netherlands is closely monitored and planned to ensure their pivotal role in primary care and the Dutch health care system. While the majority of GPs have their own practice or are employed by other GP practices or health community centres

  16. How Do Gut Feelings Feature in Tutorial Dialogues on Diagnostic Reasoning in GP Traineeship?

    Science.gov (United States)

    Stolper, C. F.; Van de Wiel, M. W. J.; Hendriks, R. H. M.; Van Royen, P.; Van Bokhoven, M. A.; Van der Weijden, T.; Dinant, G. J.

    2015-01-01

    Diagnostic reasoning is considered to be based on the interaction between analytical and non-analytical cognitive processes. Gut feelings, a specific form of non-analytical reasoning, play a substantial role in diagnostic reasoning by general practitioners (GPs) and may activate analytical reasoning. In GP traineeships in the Netherlands, trainees…

  17. The assessment of genetic risk of breast cancer : a set of GP guidelines

    NARCIS (Netherlands)

    de Bock, GH; Vlieland, TPMV; Hageman, GCHA; Oosterwijk, JC; Springer, MP; Kievit, J

    Background. Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to

  18. Supergene Gp-9 is associated polyandry and male reproductive success in fire ants

    Science.gov (United States)

    Supergenes are groups of loci inherited together to facilitate the co-segregation of adaptive variation. We demonstrate that facultative polyandry and male reproductive success have a simple genetic basis in the fire ant Solenopsis invicta and depend solely on male genotype within the Gp-9 supergene...

  19. Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C. (Harvard-Med); (NIMR)

    2010-07-13

    HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

  20. Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells

    DEFF Research Database (Denmark)

    Stavru, Fabrizia; Nautrup-Pedersen, Gitte; Cordes, Volker C

    2006-01-01

    So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several...

  1. Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

    DEFF Research Database (Denmark)

    Holmskov, U; Mollenhauer, J; Madsen, J

    1999-01-01

    in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine...

  2. Approaches for Identification of HIV-1 Entry Inhibitors Targeting gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Asim K. Debnath

    2013-01-01

    Full Text Available The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon, was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD, it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs.

  3. 杜仲抗HIV gp41活性部位的研究

    Institute of Scientific and Technical Information of China (English)

    吕琳; 徐伟; 孙燕荣; 刘叔文; 饶进军; 吴曙光

    2008-01-01

    目的:研究杜仲活性成分对HIV gp41六股螺旋束的抑制作用,为寻求新的抗HIV病毒进入抑制剂提供实验依据.方法:杜仲萃取物配制成1 mg/ml的样品液,用高效液相色谱法检测样品对HIV gp41六股螺旋束结构形成的抑制作用,并采用酚试剂法检测样品中鞣酸含量.结果:杜仲提取物浓度1 mg/ml可有效降低gp41峰高,1 mg/ml的样品中含鞣酸10μg/ml.结论:杜仲可抑制HIV gp41六股螺旋束的形成,其有效成分可能不包括鞣酸.

  4. 基于gp41的HIV亚单位疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    邵继平; 姜世勃; 刘叔文

    2011-01-01

    艾滋病疫苗是当今时代最具挑战性的科学难题之一,现有的以诱导体液免疫为目的的HIV-1抗原均难以诱导产生有效的、持续的广谱中和抗体.近年来,一些具有广谱中和活性的HIV单克隆抗体(mAb)的发现及其相应抗原表位的阐明,给以诱导HIV体液免疫的疫苗研究带来了新的希望.相比于gp120,HⅣgp41的序列更为保守,糖基化位点更少,更适合作为疫苗的抗原.本文综述了靶向gp41的广谱中和抗体及其抗原表位,并阐述了对目前国际上基于gp41的HⅣ亚单位疫苗设计思路及进展.

  5. The use of GP electronic medical records for international comparisons on prescription.

    NARCIS (Netherlands)

    Verheij, R.; Dijk, L. van; Pringle, M.; Elliott, C.; Fleming, D.M.

    2007-01-01

    Aims: Much international research on prescription does not take into account the associated diagnoses. Subsequently, large scale international comparisons on what is prescribed for which disease are relatively rare. Routinely collected GP electronic medical records, whose use is well established in

  6. Medication management strategy for older people with polypharmacy: the GP's perspective.

    NARCIS (Netherlands)

    Sinnige, J.; Korevaar, J.C.; Lieshout, J. van; Westert, G.P.; Schellevis, F.G.; Braspenning, J.C.C.

    2016-01-01

    Background & Aim: for older patients with polypharmacy medication management is a process of careful deliberation that needs periodic adjustment based on treatment effects and changing conditions. The aim of this study is to gain insight into the GP's medication management strategy for patients with

  7. Cryptosporidium parvum GP60 subtypes in dairy cattle from Buenos Aires, Argentina

    Science.gov (United States)

    Cryptosporidium parvum from 73 dairy calves less than two months old from Buenos Aires province (Argentina) were molecularly characterized using sequence analysis of the GP60 gene. Seventy five sequences were obtained, and seven different subtypes were identified, all belonging to the IIa subtype f...

  8. Speeding up IA mechanically-steered multistatic radar scheduling with GP-GPUs

    CSIR Research Space (South Africa)

    Focke, RW

    2016-07-01

    Full Text Available In this paper, the authors investigate speeding up the execution time of Interval Algebra (IA) mechanically-steered multistatic and multisite radar scheduling using a general-purpose graphical processing unit (GP-GPU). Multistatic/multisite radar...

  9. Epidemiology and resistance patterns in urinary pathogens from long-term care facilities and GP populations.

    LENUS (Irish Health Repository)

    Brabazon, E D

    2012-06-01

    Urinary tract infections (UTIs) are a major source of antimicrobial prescribing in the clinical setting and a potential reservoir for the emergence of resistant organisms. Although studies have been published on resistance rates for urinary pathogens from both hospital and general practitioner (GP) settings, there is little information from Long-Term Care Facilities (LTCFs) in Ireland. This study aimed to document the epidemiology and resistance rates in urinary isolates, in the LTCF and GP setting, from samples submitted to a typical microbiology laboratory. In 2010, there were 963 urinary isolates from LTCFs and 1,169 urinary isolates from GPs, identified from patients 65 years and over, with cytology suggestive of infection. E. coil was the most common causative organism identified. There were significantly higher levels of resistance to ampicillin, co-amoxiclav, ciprofloxacin, nitrofurantoin, trimethoprim, and piperacillin\\/tazobactam in the LTCF population compared to the GP population (e.g. for E. coli, 86%-v-69%; 30%-v- 21%; 58%-v-26%, 10%-v-3%, 68%-v-48%, 10%-v- 4% respectively). Isolates with resistance mechanisms to beta-lactams, were identified in both populations. Results presented in this paper demonstrate significant differences between resistance rates in LTCF and GP populations which suggest that there are implications for empiric antimicrobial prescribing for UTIs in the LTCF setting.

  10. The use of GP electronic medical records for international comparisons on prescription.

    NARCIS (Netherlands)

    Verheij, R.; Dijk, L. van; Pringle, M.; Elliott, C.; Fleming, D.M.

    2007-01-01

    Aims: Much international research on prescription does not take into account the associated diagnoses. Subsequently, large scale international comparisons on what is prescribed for which disease are relatively rare. Routinely collected GP electronic medical records, whose use is well established in

  11. On the Raychaudhuri equation

    Indian Academy of Sciences (India)

    George F R Ellis

    2007-07-01

    The Raychaudhuri equation is central to the understanding of gravitational attraction in astrophysics and cosmology, and in particular underlies the famous singularity theorems of general relativity theory. This paper reviews the derivation of the equation, and its significance in cosmology.

  12. Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHU Chen

    2014-10-01

    Full Text Available ObjectiveTo explore the early diagnostic values of serum alpha-fetoprotein (AFP, gamma-glutamyltransferase Ⅱ (GGTⅡ, and Golgi protein 73 (GP73 in patients with primary hepatocellular carcinoma (PHC. MethodsThe serum specimens of 100 patients with liver diseases (50 cases of hepatitis and liver cirrhosis and 50 cases of PHC and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic (ROC curves of single or combined test results were made, and the areas under the ROC curves (AUCs were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. ResultsThe level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups (F=16.224, P<0.05, but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group (P>0.05. Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group (F=193.128, F=20.231, P<0.05 for both. When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94.6% and the sensitivity was 98.8%. ConclusionThe GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

  13. Glycoform and net charge heterogeneity in gp120 immunogens used in HIV vaccine trials.

    Directory of Open Access Journals (Sweden)

    Bin Yu

    Full Text Available BACKGROUND: The RV144 clinical trial showed for the first time that vaccination could provide modest but significant protection from HIV-1 infection. To understand the protective response, and to improve upon the vaccine's efficacy, it is important to define the structure of the immunogens used in the prime/boost regimen. Here we examined the heterogeneity in net charge, attributable to glycoform variation, of the gp120 immunogens contained in the AIDSVAX B/E vaccine. METHODOLOGY/PRINCIPAL FINDINGS: Isoelectric focusing and glycosidase digestion were used to assess variation in net charge of the gp120s contained in the AIDSVAX B/E vaccine used in the RV144 trial. We observed 16 variants of MN-rgp120 and 24 variants of A244-rgp120. Glycoform variation in gp120 produced in Chinese hamster ovary cells was compared to glycoform variation in gp120 produced in the 293F human embryonic kidney cell line, often used for neutralization assays. We found that gp120 variants produced in CHO cells were distinctly more acidic than gp120 variants produced in 293 cells. The effect of glycoform heterogeneity on antigenicity was assessed using monoclonal antibodies. The broadly neutralizing PG9 MAb bound to A244-rgp120, but not to MN-rgp120, whether produced in CHO or in 293. However, PG9 was able to bind with high affinity to MN-rgp120 and A244-rgp120 produced in 293 cells deficient in N-acetylglucosaminyltransferase I. CONCLUSIONS/SIGNIFICANCE: MN- and A244-rgp120 used in the RV144 trial exhibited extensive heterogeneity in net charge due to variation in sialic acid-containing glycoforms. These differences were cell line-dependent, affected the antigenicity of recombinant envelope proteins, and may affect assays used to measure neutralization. These studies, together with recent reports documenting broadly neutralizing antibodies directed against carbohydrate epitopes of gp120, suggest that glycoform variation is a key variable to be considered in the production

  14. Glycoform and Net Charge Heterogeneity in gp120 Immunogens Used in HIV Vaccine Trials

    Science.gov (United States)

    Yu, Bin; Morales, Javier F.; O'Rourke, Sara M.; Tatsuno, Gwen P.; Berman, Phillip W.

    2012-01-01

    Background The RV144 clinical trial showed for the first time that vaccination could provide modest but significant protection from HIV-1 infection. To understand the protective response, and to improve upon the vaccine's efficacy, it is important to define the structure of the immunogens used in the prime/boost regimen. Here we examined the heterogeneity in net charge, attributable to glycoform variation, of the gp120 immunogens contained in the AIDSVAX B/E vaccine. Methodology/Principal Findings Isoelectric focusing and glycosidase digestion were used to assess variation in net charge of the gp120s contained in the AIDSVAX B/E vaccine used in the RV144 trial. We observed 16 variants of MN-rgp120 and 24 variants of A244-rgp120. Glycoform variation in gp120 produced in Chinese hamster ovary cells was compared to glycoform variation in gp120 produced in the 293F human embryonic kidney cell line, often used for neutralization assays. We found that gp120 variants produced in CHO cells were distinctly more acidic than gp120 variants produced in 293 cells. The effect of glycoform heterogeneity on antigenicity was assessed using monoclonal antibodies. The broadly neutralizing PG9 MAb bound to A244-rgp120, but not to MN-rgp120, whether produced in CHO or in 293. However, PG9 was able to bind with high affinity to MN-rgp120 and A244-rgp120 produced in 293 cells deficient in N-acetylglucosaminyltransferase I. Conclusions/Significance MN- and A244-rgp120 used in the RV144 trial exhibited extensive heterogeneity in net charge due to variation in sialic acid-containing glycoforms. These differences were cell line-dependent, affected the antigenicity of recombinant envelope proteins, and may affect assays used to measure neutralization. These studies, together with recent reports documenting broadly neutralizing antibodies directed against carbohydrate epitopes of gp120, suggest that glycoform variation is a key variable to be considered in the production and evaluation of

  15. The death of a patient: a model for reflection in GP training

    Directory of Open Access Journals (Sweden)

    Schuling Jan

    2011-03-01

    Full Text Available Abstract Background The Dutch government has chosen a policy of strengthening palliative care in order to enable patients to die at home according to their preference. In order to facilitate this care by GPs, we wanted to know how to support them in their training. Therefore we examined the ways in which the death of a patient influences the doctor both at a professional and at a personal level. Methods Based on a qualitative study, we developed a model for reflection for GP trainees on the meaning of the death of patients and its influence on the GP. The qualitative study was done in 2007 and is based on open in-depth interviews and a focus group. We recruited 18 participants who were highly professional GPs and experienced in talking about the death of patients. We invited GPs from a list of experienced GPs, who in addition are also second-opinion GPs for euthanasia (SCEN-physicians and from a pool of GP trainers, our intention being to include GPs holding a variety of world views. Interviews were audio-taped and transcribed verbatim. A grounded theory approach was used to analyze the results. Themes were first identified independently by three researchers, then after discussion these three sets were rearranged to one list of themes and their mutual relation were determined. A model for the interaction of the GP at professional and at a personal level was formulated. Results Forty three themes emerged from the interviews and focus group. These themes fell into three groups: professional values and experiences, personal values and experiences, and the opinions of the GPs as to what constitutes a good death. We constructed a model of the doctor-patient relationship on the basis of these findings. This model enables GP trainees identifying the unique character of the doctor-patient relationship as well as its reciprocity when the two were confronted by the patient's impending death. Conclusions In dealing with the approaching death of a patient

  16. Critical review and hydrologic application of threshold detection methods for the generalized Pareto (GP) distribution

    Science.gov (United States)

    Mamalakis, Antonios; Langousis, Andreas; Deidda, Roberto

    2016-04-01

    Estimation of extreme rainfall from data constitutes one of the most important issues in statistical hydrology, as it is associated with the design of hydraulic structures and flood water management. To that extent, based on asymptotic arguments from Extreme Excess (EE) theory, several studies have focused on developing new, or improving existing methods to fit a generalized Pareto (GP) distribution model to rainfall excesses above a properly selected threshold u. The latter is generally determined using various approaches, such as non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data, graphical methods where one studies the dependence of GP distribution parameters (or related metrics) on the threshold level u, and Goodness of Fit (GoF) metrics that, for a certain level of significance, locate the lowest threshold u that a GP distribution model is applicable. In this work, we review representative methods for GP threshold detection, discuss fundamental differences in their theoretical bases, and apply them to 1714 daily rainfall records from the NOAA-NCDC open-access database, with more than 110 years of data. We find that non-parametric methods that are intended to locate the changing point between extreme and non-extreme regions of the data are generally not reliable, while methods that are based on asymptotic properties of the upper distribution tail lead to unrealistically high threshold and shape parameter estimates. The latter is justified by theoretical arguments, and it is especially the case in rainfall applications, where the shape parameter of the GP distribution is low; i.e. on the order of 0.1 ÷ 0.2. Better performance is demonstrated by graphical methods and GoF metrics that rely on pre-asymptotic properties of the GP distribution. For daily rainfall, we find that GP threshold estimates range between 2÷12 mm/d with a mean value of 6.5 mm/d, while the existence of quantization in the

  17. Beginning partial differential equations

    CERN Document Server

    O'Neil, Peter V

    2014-01-01

    A broad introduction to PDEs with an emphasis on specialized topics and applications occurring in a variety of fields Featuring a thoroughly revised presentation of topics, Beginning Partial Differential Equations, Third Edition provides a challenging, yet accessible,combination of techniques, applications, and introductory theory on the subjectof partial differential equations. The new edition offers nonstandard coverageon material including Burger's equation, the telegraph equation, damped wavemotion, and the use of characteristics to solve nonhomogeneous problems. The Third Edition is or

  18. Renormalizing Partial Differential Equations

    OpenAIRE

    Bricmont, J.; Kupiainen, A.

    1994-01-01

    In this review paper, we explain how to apply Renormalization Group ideas to the analysis of the long-time asymptotics of solutions of partial differential equations. We illustrate the method on several examples of nonlinear parabolic equations. We discuss many applications, including the stability of profiles and fronts in the Ginzburg-Landau equation, anomalous scaling laws in reaction-diffusion equations, and the shape of a solution near a blow-up point.

  19. Ordinary differential equations

    CERN Document Server

    Greenberg, Michael D

    2014-01-01

    Features a balance between theory, proofs, and examples and provides applications across diverse fields of study Ordinary Differential Equations presents a thorough discussion of first-order differential equations and progresses to equations of higher order. The book transitions smoothly from first-order to higher-order equations, allowing readers to develop a complete understanding of the related theory. Featuring diverse and interesting applications from engineering, bioengineering, ecology, and biology, the book anticipates potential difficulties in understanding the various solution steps

  20. Worrying about wasting GP time as a barrier to help-seeking: a community-based, qualitative study

    Science.gov (United States)

    Cromme, Susanne K; Whitaker, Katriina L; Winstanley, Kelly; Renzi, Cristina; Smith, Claire Friedemann; Wardle, Jane

    2016-01-01

    Background Worrying about wasting GP time is frequently cited as a barrier to help-seeking for cancer symptoms. Aim To explore the circumstances under which individuals feel that they are wasting GP time. Design and setting Community-based, qualitative interview studies that took place in London, the South East and the North West of England. Method Interviewees (n = 62) were recruited from a sample (n = 2042) of adults aged ≥50 years, who completed a ‘health survey’ that included a list of cancer ‘alarm’ symptoms. Individuals who reported symptoms at baseline that were still present at the 3-month follow-up (n = 271), and who had also consented to be contacted (n = 215), constituted the pool of people invited for interview. Analyses focused on accounts of worrying about wasting GP time. Results Participants were worried about wasting GP time when time constraints were visible, while dismissive interactions with their GP induced a worry of unnecessary help-seeking. Many felt that symptoms that were not persistent, worsening, or life-threatening did not warrant GP attention. Additionally, patients considered it time-wasting when they perceived attention from nurses or pharmacists to be sufficient, or when appointment structures (for example, ‘one issue per visit’) were not adhered to. Close relationships with GPs eased worries about time-wasting, while some patients saw GPs as fulfilling a service financed by taxpayers. Conclusion Worrying about wasting GP time is a complex barrier to help-seeking. GP time and resource scarcity, symptom gravity, appointment etiquette, and previous GP interactions contribute to increasing worries. Friendly GP relationships, economic reasoning, and a focus on the GP’s responsibilities as a medical professional reduce this worry. PMID:27215569

  1. Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Zhu; Cheng-Lin Li; Zhen-Wei Lang; George F Gao; Po Tien

    2004-01-01

    AIM: Gp96, also known as Grp94, is a member of heat shock protein (HSP) family and binds repertoires of peptides thereof eliciting peptide-specific T cell immune responses.It predominantly locates inside the endoplasmic reticulum (ER) with some cell surface expression in certain cancerous cells. Previous studies have shown that gp96 expression level was up-regulated in tumor cells, including hepatocellular carcinoma (HCC). However, relationship between the extent of gp96 expression and disease progression especially HBV-induced chronic infection, cirrhosis and hepatocellular carcinoma, has not been addressed before. As primary HCC can be induced and progressed from chronic hepatitis B virus (HBV) infection and HBV-induced cirrhosis, we designed an immunohistochemical experiment to test the correlation between gp96 expression level and HBV-induced disease progression, from chronic HBV infection, cirrhosis to HCC.METHODS: We chose liver samples from different patients of hepatitis B virus induced diseases, including chronic hepatitis B (77 patients), cirrhosis (27 patients) and primary HCC (30 patients), to test the expression level of gp96 in different affected groups. Formalin-fixed, and paraffinembedded liver tissues taken from these patients were immuno-stained by using an anti-gp96 monoclonal antibody for the expression level of gp96 protein in the sections. In addition, Western blotting of whole cell lysates derived from established human embryonic liver cell lines and several human HCC cell lines (Huh7, HepG2, SSMC-7721) was compared with the expression of gp96.RESULTS: We found that the extent of elevated gp96expression was significantly correlated with the disease progression, and was the highest in HCC patients, lowest in chronic HBV infection and was that of the cirrhosis in the middle.CONCLUSION: Increased expression of gp96 might be used as a diagnostic or prognostic bio-marker for the HBV infection and HBV-induced diseases.

  2. Use of Two-Body Correlated Basis Functions with van der Waals Interaction to Study the Shape-Independent Approximation for a Large Number of Trapped Interacting Bosons

    Science.gov (United States)

    Lekala, M. L.; Chakrabarti, B.; Das, T. K.; Rampho, G. J.; Sofianos, S. A.; Adam, R. M.; Haldar, S. K.

    2017-01-01

    We study the ground-state and the low-lying excitations of a trapped Bose gas in an isotropic harmonic potential for very small (˜ 3) to very large (˜ 10^7 ) particle numbers. We use the two-body correlated basis functions and the shape-dependent van der Waals interaction in our many-body calculations. We present an exhaustive study of the effect of inter-atomic correlations and the accuracy of the mean-field equations considering a wide range of particle numbers. We calculate the ground-state energy and the one-body density for different values of the van der Waals parameter C6 . We compare our results with those of the modified Gross-Pitaevskii results, the correlated Hartree hypernetted-chain equations (which also utilize the two-body correlated basis functions), as well as of the diffusion Monte Carlo for hard sphere interactions. We observe the effect of the attractive tail of the van der Waals potential in the calculations of the one-body density over the truly repulsive zero-range potential as used in the Gross-Pitaevskii equation and discuss the finite-size effects. We also present the low-lying collective excitations which are well described by a hydrodynamic model in the large particle limit.

  3. STABILITY OF BOSE-EINSTEIN CONDENSATES IN A PT-SYMMETRIC DOUBLE-δ POTENTIAL CLOSE TO BRANCH POINTS

    Directory of Open Access Journals (Sweden)

    Andreas Löhle

    2014-04-01

    Full Text Available A Bose-Einstein condensate trapped in a double-well potential, where atoms are incoupled to one side and extracted from the other, can in the mean-field limit be described by the nonlinear Gross-Pitaevskii equation (GPE with a PT symmetric external potential. If the strength of the in- and outcoupling is increased two PT broken states bifurcate from the PT symmetric ground state. At this bifurcation point a stability change of the ground state is expected. However, it is observed that this stability change does not occur exactly at the bifurcation but at a slightly different strength of the in-/outcoupling effect. We investigate a Bose-Einstein condensate in a PT symmetric double-δ potential and calculate the stationary states. The ground state’s stability is analysed by means of the Bogoliubov-de Gennes equations and it is shown that the difference in the strength of the in-/outcoupling between the bifurcation and the stability change can be completely explained by the norm-dependency of the nonlinear term in the Gross-Pitaevskii equation.

  4. Matched comparison of GP and consultant rating of electronic discharge summaries.

    Science.gov (United States)

    Stainkey, Lesley; Pain, Tilley; McNichol, Margaret; Hack, John; Roberts, Lynden

    2010-01-01

    Queensland Health is implementing a state-wide system to electronically generate and distribute discharge summaries. Previously, general practitioners (GPs) have indicated that the quality of the discharge summary does not support clinical handover. While the electronic system will address some issues (e.g. legibility and timeliness), the quality of the discharge summary content is predominantly independent of method of generation. As discharge summaries are usually generated by interns, we proposed that improvement in the quality of the summary may be achieved through education. This project aimed to compare the perceptions of hospital-based consultant educators and recipient GPs regarding discharge summary content and quality. The discharge summary and audit tool were sent to the recipient GP (n=134) and a hospital consultant (n=14) for satisfaction rating, using a 5- point Likert scale for questions relating to diagnosis, the listing of clinical management, medication, pathology, investigations, and recommendations to GP. Sampling was performed by selecting up to 10 discharge summaries completed by each first-year intern (n=36) in 2009, during the second, third and fourth rotations at the Townsville Hospital until a total of 403 was reached. Matched responses were compared using the Kappa statistic. The response rate was 93% (n=375) and 63% (n=254) for consultants and GPs respectively. Results from this study demonstrated that GPs were more satisfied with discharge summaries than were consultants. An anomaly occurred in three questions where, despite the majority of GPs rating satisfied or very satisfied, a small but proportionally greater number of GPs were very dissatisfied when compared with consultants. Poor or fair agreement between GPs and consultants was demonstrated in medications, pathology results, investigations and recommendations to GP, with GPs rating higher satisfaction in all questions. Lower consultant satisfaction ratings compared with GP

  5. Complete dissociation of the HIV-1 gp41 ectodomain and membrane proximal regions upon phospholipid binding

    Energy Technology Data Exchange (ETDEWEB)

    Roche, Julien; Louis, John M.; Aniana, Annie [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States); Ghirlando, Rodolfo [National Institutes of Health, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (United States); Bax, Ad, E-mail: bax@nih.gov [National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Chemical Physics (United States)

    2015-04-15

    The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. Strong lipid affinity of the ectodomain suggests that its heptad repeat regions play an active role in destabilizing membranes by directly binding to the lipid bilayers and thereby lowering the free-energy barrier for membrane fusion. In such a model, immediately following the shedding of gp120, the N-heptad and C-heptad helices dissociate and melt into the host cell and viral membranes, respectively, pulling the destabilized membranes into juxtaposition, ready for fusion. Post-fusion, reaching the final 6-helix bundle (6HB) conformation then involves competition between intermolecular interactions needed for formation of the symmetric 6HB trimer and the membrane affinity of gp41’s ectodomain, including its membrane-proximal regions. Our solution NMR study of the structural and dynamic properties of three constructs containing the ectodomain of gp41 with and without its membrane-proximal regions suggests that these segments do not form inter-helical interactions until the very late steps of the fusion process. Interactions between the polar termini of the heptad regions, which are not associating with the lipid surface, therefore may constitute the main driving force initiating formation of the final post-fusion states. The absence of significant intermolecular ectodomain interactions in the presence of dodecyl phosphocholine highlights the importance of trimerization of gp41’s transmembrane helix to prevent complete dissociation of the trimer during the course of fusion.

  6. Diagnostic value of serum GP73 and AFP in hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Shao-hui TANG

    2013-09-01

    Full Text Available Objective To evaluate the diagnostic value of serum Golgi protein 73 (GP73 and alpha fetoprotein (AFP in patients with hepatocellular carcinoma (HCC. Methods The Cochrane Central Register of Controlled Trials, PubMed, EMBase, Web of Science, Nature, Science, Springer link, Chinese Journal Full-Text Database (CNKI, Database for Chinese Technical Periodical (VIP, Wanfang Digital Journal Full-text Database (before October 2012 were retrieved to collect relevant literature in which the diagnostic value of serum GP73 and AFP in patients with HCC was evaluated. The statistical information and scientific quality were assessed and classified. The data were analyzed using Meta-Disc 1.4 software. The diagnostic value of serum GP73 and AFP in HCC was evaluated by the statistical indicators as pooled sensitivity, pooled specificity, pooled likelihood ratio and summary receiver operating characteristic curve (ROC curve. Results Eighteen articles were collected and 5279 cases were included in the study (2075 HCC and 3204 NHCC patients. After heterogeneity test, the data were analyzed by random-effect model. The results showed that, the pooled sensitivity, specificity of the serum GP73 and AFP were 0.78(0.76-0.79 and 0.55(0.53-0.57, 0.84(0.83-0.86 and 0.80(0.78-0.81, respectively. The pooled positive likelihood ratio and negative likelihood ratio was 5.60(4.05-7.74 and 2.92(2.04-4.17, 0.28(0.24-0.32 and 0.58(0.51-0.67, respectively. The ROC area under the curve (AUC was 0.8849 and 0.6827, and Z test showed that the difference was statistically significant (P<0.01. Conclusion The serum GP73 has a higher sensitivity and specificity than AFP in the diagnosis of HCC, and it can be regarded as one of the valuable reference tests in patients with HCC.

  7. Structure of the Bacteriophage [phi]KZ Lytic Transglycosylase gp144

    Energy Technology Data Exchange (ETDEWEB)

    Fokine, Andrei; Miroshnikov, Konstantin A.; Shneider, Mikhail M.; Mesyanzhinov, Vadim V.; Rossmann, Michael G. (SOIBC); (Purdue)

    2008-04-02

    Lytic transglycosylases are enzymes that act on the peptidoglycan of bacterial cell walls. They cleave the glycosidic linkage between N-acetylmuramoyl and N-acetylglucosaminyl residues with the concomitant formation of a 1,6-anhydromuramoyl product. The x-ray structure of the lytic transglycosylase gp144 from the Pseudomonas bacteriophage {phi}KZ has been determined to 2.5-{angstrom} resolution. This protein is probably employed by the bacteriophage in the late stage of the virus reproduction cycle to destroy the bacterial cell wall to release the phage progeny. {phi}KZ gp144 is a 260-residue {alpha}-helical protein composed of a 70-residue N-terminal cell wall-binding domain and a C-terminal catalytic domain. The fold of the N-terminal domain is similar to the peptidoglycan-binding domain from Streptomyces albus G d-Ala-d-Ala carboxypeptidase and to the N-terminal prodomain of human metalloproteinases that act on extracellular matrices. The C-terminal catalytic domain of gp144 has a structural similarity to the catalytic domain of the transglycosylase Slt70 from Escherichia coli and to lysozymes. The gp144 catalytic domain has an elongated groove that can bind at least five sugar residues at sites A-E. As in other lysozymes, the peptidoglycan cleavage (catalyzed by Glu{sup 115} in gp144) occurs between sugar-binding subsites D and E. The x-ray structure of the {phi}KZ transglycosylase complexed with the chitotetraose (N-acetylglucosamine){sub 4} has been determined to 2.6-{angstrom} resolution. The N-acetylglucosamine residues of the chitotetraose bind in sites A-D.

  8. Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

    Directory of Open Access Journals (Sweden)

    Cátia Teixeira

    Full Text Available HIV-1 gp41 facilitates the viral fusion through a conformational switch involving the association of three C-terminal helices along the conserved hydrophobic grooves of three N-terminal helices coiled-coil. The control of these structural rearrangements is thought to be central to HIV-1 entry and, therefore, different strategies of intervention are being developed. Herewith, we describe a procedure to simulate the folding of an HIV-1 gp41 simplified model. This procedure is based on the construction of plausible conformational pathways, which describe protein transition between non-fusogenic and fusogenic conformations. The calculation of the paths started with 100 molecular dynamics simulations of the non-fusogenic conformation, which were found to converge to different intermediate states. Those presenting defined criteria were selected for separate targeted molecular dynamics simulations, subjected to a force constant imposing a movement towards the gp41 fusogenic conformation. Despite significant diversity, a preferred sequence of events emerged when the simulations were analyzed in terms of the formation, breakage and evolution of the contacts. We pointed out 29 residues as the most relevant for the movement of gp41; also, 2696 possible interactions were reduced to only 48 major interactions, which reveals the efficiency of the method. The analysis of the evolution of the main interactions lead to the detection of four main behaviors for those contacts: stable, increasing, decreasing and repulsive interactions. Altogether, these results suggest a specific small cavity of the HIV-1 gp41 hydrophobic groove as the preferred target to small molecules.

  9. Initial cos cleavage of bacteriophage lambda concatemers requires proheads and gpFI in vivo.

    Science.gov (United States)

    Sippy, Jean; Feiss, Michael

    2004-04-01

    The development of bacteriophage lambda and double-stranded DNA viruses in general involves the convergence of two separate pathways: DNA replication and head assembly. Clearly, packaging will proceed only if an empty capsid shell, the prohead, is present to receive the DNA, but genetic evidence suggests that proheads play another role in the packaging process. For example, lambda phages with an amber mutation in any head gene or in FI, the gene encoding the accessory packaging protein gpFI, are able to produce normal amounts of DNA concatemers but they are not cut, or matured, into unit length chromosomes for packaging. Similar observations have been made for herpes simplex 1 virus. In the case of lambda, a negative model proposes that in the amber phages, unassembled capsid components are inhibitory to maturation, and a positive model suggests that assembled proheads are required for cutting. We tested the negative model by using a deletion mutant devoid of all prohead genes and FI in an in vivo cos cleavage assay; in this deleted phage, the cohesive ends were not cut. When lambda proheads and gpFI were provided in vivo via a second prophage, cutting was restored, and gpFI was required, results that support the positive model. Phage 21 is a sister phage of lambda, and although its capsid proteins share approximately 60% residue identity with lambda's, phage 21 proheads did not restore cutting, even when provided with the accessory protein gpFI. Models for the role of proheads and gpFI in cos cutting are discussed.

  10. The Modified Magnetohydrodynamical Equations

    Institute of Scientific and Technical Information of China (English)

    Evangelos Chaliasos

    2003-01-01

    After finding the really self-consistent electromagnetic equations for a plasma, we proceed in a similarfashion to find how the magnetohydrodynamical equations have to be modified accordingly. Substantially this is doneby replacing the "Lorentz" force equation by the correct (in our case) force equation. Formally we have to use the vectorpotential instead of the magnetic field intensity. The appearance of the formulae presented is the one of classical vectoranalysis. We thus find a set of eight equations in eight unknowns, as previously known concerning the traditional MHDequations.

  11. Singular stochastic differential equations

    CERN Document Server

    Cherny, Alexander S

    2005-01-01

    The authors introduce, in this research monograph on stochastic differential equations, a class of points termed isolated singular points. Stochastic differential equations possessing such points (called singular stochastic differential equations here) arise often in theory and in applications. However, known conditions for the existence and uniqueness of a solution typically fail for such equations. The book concentrates on the study of the existence, the uniqueness, and, what is most important, on the qualitative behaviour of solutions of singular stochastic differential equations. This is done by providing a qualitative classification of isolated singular points, into 48 possible types.

  12. Fractional Differential Equations

    Directory of Open Access Journals (Sweden)

    Jianping Zhao

    2012-01-01

    Full Text Available An extended fractional subequation method is proposed for solving fractional differential equations by introducing a new general ansätz and Bäcklund transformation of the fractional Riccati equation with known solutions. Being concise and straightforward, this method is applied to the space-time fractional coupled Burgers’ equations and coupled MKdV equations. As a result, many exact solutions are obtained. It is shown that the considered method provides a very effective, convenient, and powerful mathematical tool for solving fractional differential equations.

  13. The application of P-gp inhibiting phospholipids as novel oral bioavailability enhancers - An in vitro and in vivo comparison.

    Science.gov (United States)

    Weinheimer, Manuel; Fricker, Gert; Burhenne, Jürgen; Mylius, Patricia; Schubert, Rolf

    2017-10-15

    The efflux transporter P-glycoprotein (P-gp) significantly modulates drug transport across the intestinal mucosa, strongly reducing the systemic absorption of various active pharmaceutical ingredients. P-gp inhibitors could serve as helpful tools to enhance the oral bioavailability of those substances. As a membrane-associated protein P-gp is surrounded and influenced by phospholipids. Some synthetic phospholipids have been found to strongly reduce P-gp's activity. In this study two representative phospholipids, 1,2-dioctanoyl-sn-glycero-3-phosphocholine (8:0 PC) and 1,2-didecanoyl-sn-glycero-3-phosphocholine (10:0 PC), were compared with Tween® 80 and Cremophor® EL, both commonly used surfactants with P-gp inhibitory properties. Their influence on the cellular transport of the P-gp substrate rhodamine 123 (RH123) was examined using Caco-2 cell layers. In addition, fluorescence anisotropy measurements were performed in order to investigate their effect on membrane fluidity. Finally, we compared the phospholipids with Tween® 80 and the competitive P-gp inhibitor verapamil in an in vivo study, testing their effects on the oral bioavailability of the P-gp substrate drug ritonavir. Both phospholipids not only led to the strongest absorption of RH123, but a permeability enhancing effect was detected in addition to the P-gp inhibition. Their effects on membrane fluidity were not consistent with their P-gp inhibiting effects, and therefore suggested a more complex mode of action. Both phospholipids significantly increased the area under the ritonavir plasma level curve (AUC) within 150min by more than tenfold, but were inferior to Tween® 80, which showed superior solubilizing effects. Finally, these phospholipids represent a novel substance class showing a high permeabilization potential for P-gp substrates. Because of their physiological structure and intestinal degradability, good tolerability without systemic absorption is expected. Formulating P-gp substrates with

  14. 采用TDC-GP1的激光测距系统设计%The Design of Laser Ranging System with TDC-GP1

    Institute of Scientific and Technical Information of China (English)

    童敏明; 张徵

    2006-01-01

    在激光测距系统中,时标是影响测距系统精确度的关键因素.文章利用ACAM的高精度时间间隔测量芯片TDC-GP1、自触发脉冲激光飞行时间测量方法设计了一种结构简单、测量精度高的脉冲激光测距系统.

  15. Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

    Science.gov (United States)

    Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

    2016-10-01

    Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

  16. 每个非奇异单左R-模均为GP-内射的环的正则性%Regularity of Rings Whose Every Simple Singular Left R-module is GP-injective

    Institute of Scientific and Technical Information of China (English)

    宋贤梅

    2005-01-01

    In this paper, some new relations between GP-V′-rings and regular rings under certain special conditions have been found. It is proved that R is left selfinjective regular with Soc(RR) ≠ 0 if and only if R is a left GP-V′-ring containing an injective maximal left ideal and Soc(RR) (∈) Soc(RR). Moreover, for an MELT ring R, it is shown that R is regular if and only if R is a left GP-injective left GPV′-ring.

  17. Mulberroside A suppresses PXR-mediated transactivation and gene expression of P-gp in LS174T cells.

    Science.gov (United States)

    Li, Yuhua; Huang, Ling; Sun, Jiahong; Wei, Xiaohua; Wen, Jinhua; Zhong, Guoping; Huang, Min; Bi, Huichang

    2016-12-05

    Mulberroside A (Mul A) is the main bioactive constituents of Sangbaipi, which is officially listed in the Chinese Pharmacopoeia. The pregnane X receptor (PXR) has been recognized as the critical mediator of human P-glycoprotein (P-gp) gene transactivation. In this study, the effect of Mul A on PXR-mediated transactivation and gene expression of P-gp was investigated. It was found that Mul A significantly suppressed PXR-mediated P-gp luciferase activity induced by rifampicin (Rif). Furthermore, Rif induced an elevation of P-gp expression and transport activity, which was apparently suppressed by Mul A. However, Mul A did not suppress the P-gp luciferase activity, P-gp expression, and function in the absence of Rif. These findings suggest that Mul A suppresses PXR-mediated transactivation and P-gp expression induced by Rif. This should be taken into consideration to predict any potential herb-drug interactions when Mul A or Sangbaipi are co-administered with Rif or other PXR agonist drugs.

  18. Potent antitumor effect elicited by gp96-peptide complexes pulsed by dendritic cell on mice of H22 liver cancer

    Institute of Scientific and Technical Information of China (English)

    YANG Wei; CAO Chun-xia; CHU Yong-lie; LIU Qing-guang; YU Liang; PAN Cheng-en

    2006-01-01

    Objective: To improve DC-based tumor vaccination, we studied whether dendritic cells (DCs) which cocultured with H22 liver cancer cells-derived heat shock protein (HSP) glycoprotein 96(gp96) affect the T cell-activating potential in vitro and the induction of tumor immunity in vivo. Methods: Maturation of murine bone marrow-derived DC was induced by GM-CSF plus IL-4, which mimiced the immunostimulatory effect of DC. Cocultured DC and gp96-peptide complexes were used to vaccine H22liver cancer cells of mice. Using murine models we compared the immunogenecity of DC modified by gp96-peptides complexes derived from murine liver cancer cells alone or inactive tumor cells. To verify the specificity of the vaccine, in vitro assays were executed. Serum cytokine levels were quantified to explore the supposed pathway of DC modified by gp96 peptide complexes and its effect on antitumor immune response.Results: DC modified by gp96-peptide complexes can activate spleen lymphocyte and the latter can specifically kill H22 cells but not Ehrilich ascites carcinoma cells. Modified DC can induce potent tumor-antigenspecific immune response, augment the proliferation of Th1 cells, and inhibit tumor growth. Conclusion:In this study, we have developed a novel DC-mediated tumor vaccine by combing the gp96 antigenic peptides complexes and inducing immune response against specific tumor cells. gp96 can be identified as a potent DC activator.

  19. The complex co-translational processing of glycoprotein GP5 of type 1 porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Thaa, Bastian; Kaufer, Susanne; Neumann, Sara A; Peibst, Bernadett; Nauwynck, Hans; Krause, Eberhard; Veit, Michael

    2017-08-12

    GP5 and M, the major membrane proteins of porcine reproductive and respiratory syndrome virus (PRRSV), are the driving force for virus budding and a target for antibodies. We studied co-translational processing of GP5 from an European PRRSV-1 strain. Using mass spectrometry, we show that in virus particles of a Lelystad variant, the signal peptide of GP5 was absent due to cleavage between glycine-34 and asparagine-35. This cleavage site removes an epitope for a neutralizing monoclonal antibody, but leaves intact another epitope recognized by neutralizing pig sera. Upon ectopic expression of this GP5 in cells, signal peptide cleavage was however inefficient. Complete cleavage occurred when cysteine-24 was changed to proline or an unused glycosylation site involving asparagine-35 was mutated. Insertion of proline at position 24 also caused carbohydrate attachment to asparagine-35. Glycosylation sites introduced downstream of residue 35 were used, but did not inhibit signal peptide processing. Co-expression of the M protein rescued this processing defect in GP5, suggesting a novel function of M towards GP5. We speculate that a complex interplay of the co-translational modifications of GP5 affect the N-terminal structure of the mature proteins and hence its antigenicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Single-molecule analysis of human immunodeficiency virus type 1 gp120-receptor interactions in living cells.

    Science.gov (United States)

    Chang, Melissa I; Panorchan, Porntula; Dobrowsky, Terrence M; Tseng, Yiider; Wirtz, Denis

    2005-12-01

    A quantitative description of the binding interactions between human immunodeficiency virus (HIV) type 1 envelope glycoproteins and their host cell surface receptors remains incomplete. Here, we introduce a single-molecule analysis that directly probes the binding interactions between an individual viral subunit gp120 and a single receptor CD4 and/or chemokine coreceptor CCR5 in living cells. This analysis differentiates single-molecule binding from multimolecule avidity and shows that, while the presence of CD4 is required for gp120 binding to CCR5, the force required to rupture a single gp120-coreceptor bond is significantly higher and its lifetime is much longer than those of a single gp120-receptor bond. The lifetimes of these bonds are themselves shorter than those of the P-selectin/PSGL-1 bond involved in leukocyte attachment to the endothelium bonds during an inflammation response. These results suggest an amended model of HIV entry in which, immediately after the association of gp120 to its receptor, gp120 seeks its coreceptor to rapidly form a new bond. This "bond transfer" occurs only if CCR5 is in close proximity to CD4 and CD4 is still attached to gp120. The analysis presented here may serve as a general framework to study mechanisms of receptor-mediated interactions between viral envelope proteins and host cell receptors at the single-molecule level in living cells.

  1. Serum Gp96 is a chaperone of complement-C3 during graft-versus-host disease

    Science.gov (United States)

    Seignez, Antoine; Joly, Anne-Laure; Chaumonnot, Killian; Hazoumé, Adonis; Sanka, Michel; Boudesco, Christophe; Hammann, Arlette; Seigneuric, Renaud; Jégo, Gaetan; Ducoroy, Patrick; Delarue, Patrice; Senet, Patrick; Castilla-Llorente, Cristina; Solary, Eric; Durey, Marie-Agnès; Rubio, Marie-Thérèse; Hermine, Olivier; Kohli, Evelyne

    2017-01-01

    Better identification of severe acute graft-versus-host disease (GvHD) may improve the outcome of this life-threatening complication of allogeneic hematopoietic stem cell transplantation. GvHD induces tissue damage and the release of damage-associated molecular pattern (DAMP) molecules. Here, we analyzed GvHD patients (n = 39) to show that serum heat shock protein glycoprotein 96 (Gp96) could be such a DAMP molecule. We demonstrate that serum Gp96 increases in gastrointestinal GvHD patients and its level correlates with disease severity. An increase in Gp96 serum level was also observed in a mouse model of acute GvHD. This model was used to identify complement C3 as a main partner of Gp96 in the serum. Our biolayer interferometry, yeast two-hybrid and in silico modeling data allowed us to determine that Gp96 binds to a complement C3 fragment encompassing amino acids 749–954, a functional complement C3 hot spot important for binding of different regulators. Accordingly, in vitro experiments with purified proteins demonstrate that Gp96 downregulates several complement C3 functions. Finally, experimental induction of GvHD in complement C3–deficient mice confirms the link between Gp96 and complement C3 in the serum and with the severity of the disease. PMID:28352659

  2. A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics.

    Science.gov (United States)

    Saaby, Lasse; Brodin, Birger

    2017-09-01

    Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate kinetic parameters, such as Km and Vmax, for carrier-mediated transport, whereas half-maximal inhibitor concentration (IC50) and the disassociation constant for an inhibitor/P-gp complex (Ki) have been determined to estimate P-gp inhibition. This review addresses in vitro methods commonly used to study P-gp transport kinetics and aims at providing a critical evaluation of the application of steady-state Michaelis-Menten analysis of kinetic parameters for substrate/P-gp interactions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Induction of neutralizing antibodies by varicella-zoster virus gpII glycoprotein expressed from recombinant vaccinia virus.

    Science.gov (United States)

    Massaer, M; Haumont, M; Place, M; Bollen, A; Jacobs, P

    1993-03-01

    The gpII glycoprotein of varicella-zoster virus (VZV) was produced in CV1 cells via vaccinia virus recombinants. Two different DNA constructs were expressed: the first one encodes the complete gpII protein (gpII s+a+) and the second a truncated species lacking the membrane anchorage domain (gpII s+a-). To achieve expression both coding sequences had to be engineered at the 5' end by substituting the unusually short (24 bp) natural signal sequence by a more conventional one encoding 29 amino acids. Recombinant gpII proteins were detected in vaccinia virus-infected cells by ELISA and immunoprecipitation. Both forms of recombinant gpII proteins were produced as glycosylated single-chain molecules of respectively 110K and 90K. Upon reduction these were only partially converted into subunits. A rabbit infected with the vaccinia virus recombinant expressing the complete gpII produced antibodies which recognized VZV antigens and neutralized VZV infectivity in vitro, independent of complement.

  4. HIV-1包膜蛋白gp41优势抗原的构建及可溶性表达%Construction and Prokaryotic Expression of Soluble HIV-1 gp41 Dominant Epitopes

    Institute of Scientific and Technical Information of China (English)

    杜刚; 江蒙蒙; 尹林; 王宏萍; 周晓明

    2011-01-01

    目的:筛选1型人免疫缺陷病毒(HIV-1)中国流行株中包膜蛋白gp41的优势抗原片段,构建具有区域流行代表性的HIV-1 gp41重组抗原,为改进现有HIV-1初筛试剂盒中使用的同类抗原奠定基础.方法:利用免疫斑点杂交和生物信息学方法,从收集自重庆、广州、上海的区域代表性150份HIV-1感染者血清标本中筛选gp41抗原性强的候选样本,利用RT-PCR及巢式PCR方法扩增包含重要抗原表位决定蔟的gp41基因片段,与原核表达载体pQE30连接,转化大肠杆菌M15构建gp41重组抗原表达菌株,表达后经亲和层析纯化、SDS-PAGE和Western印迹鉴定.结果:兔源HRP标记的gp41多抗能识别标本中gp41抗原性差异,得到候选样本,扩增包含gp41主要抗原表位片段;构建了包含gp41抗原表达簇的重组原核表达质粒,表达、纯化后经His标签抗体Western印迹鉴定为阳性.结论:高纯度的重组优势gp41抗原的构建和鉴定,为进一步改进现有HIV初筛诊断奠定了基础.%Objective: To prepare the major antigen fragment of gp41 of HIV-1 based on main epidemic strains in China and to construct representative gp41 recombinant antigen of HIV-1 for further improving the efficacy of current HIV screening test. Methods: Combined with viral load of each sample, dot blot and bioinfomatic analysis were to identify two candidate samples from 150 HIV-1 postive serums collected from Chongqing, Guangzhou and Shanghai. Subsequently, RT-PCR and nested PCR were performed to synthesize gp41 epitope-specific sequences, then the cloned fragments containing dominant gp41 epitopes cotransformed with the backbone vector pQE30 into E.coil M15 was performed to obtain recombinant gp41 expression strain. Results: Rabbit HRP-labelled anti-gp41 polyclonal antibody could recognize the different gp41 intensity in 150 samples, from which the result led to the successful selection of two candidate samples. Then we constructed the recombinant

  5. Enhancing exposure of HIV-1 neutralization epitopes through mutations in gp41.

    Directory of Open Access Journals (Sweden)

    Catherine A Blish

    2008-01-01

    Full Text Available BACKGROUND: The generation of broadly neutralizing antibodies is a priority in the design of vaccines against HIV-1. Unfortunately, most antibodies to HIV-1 are narrow in their specificity, and a basic understanding of how to develop antibodies with broad neutralizing activity is needed. Designing methods to target antibodies to conserved HIV-1 epitopes may allow for the generation of broadly neutralizing antibodies and aid the global fight against AIDS by providing new approaches to block HIV-1 infection. Using a naturally occurring HIV-1 Envelope (Env variant as a template, we sought to identify features of Env that would enhance exposure of conserved HIV-1 epitopes. METHODS AND FINDINGS: Within a cohort study of high-risk women in Mombasa, Kenya, we previously identified a subtype A HIV-1 Env variant in one participant that was unusually sensitive to neutralization. Using site-directed mutagenesis, the unusual neutralization sensitivity of this variant was mapped to two amino acid mutations within conserved sites in the transmembrane subunit (gp41 of the HIV-1 Env protein. These two mutations, when introduced into a neutralization-resistant variant from the same participant, resulted in 3- to >360-fold enhanced neutralization by monoclonal antibodies specific for conserved regions of both gp41 and the Env surface subunit, gp120, >780-fold enhanced neutralization by soluble CD4, and >35-fold enhanced neutralization by the antibodies found within a pool of plasmas from unrelated individuals. Enhanced neutralization sensitivity was not explained by differences in Env infectivity, Env concentration, Env shedding, or apparent differences in fusion kinetics. Furthermore, introduction of these mutations into unrelated viral Env sequences, including those from both another subtype A variant and a subtype B variant, resulted in enhanced neutralization susceptibility to gp41- and gp120-specific antibodies, and to plasma antibodies. This enhanced

  6. An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques.

    Science.gov (United States)

    Schwartz, Jennifer A; Prado, Ilia; Misamore, Johnathan; Weiss, Deborah; Francis, Jesse; Pal, Ranajit; Huaman, Maria; Cristillo, Anthony; Lewis, George K; Gallo, Robert C; DeVico, Anthony L; Fouts, Timothy R

    2016-07-01

    A promising concept for human immunodeficiency virus (HIV) vaccines focuses immunity on the highly conserved transition state structures and epitopes that appear when the HIV glycoprotein gp120 binds to its receptor, CD4. We are developing chimeric antigens (full-length single chain, or FLSC) in which gp120 and CD4 sequences are flexibly linked to allow stable intrachain complex formation between the two moieties (A. DeVico et al., Proc Natl Acad Sci U S A 104:17477-17482, 2007, doi:10.1073/pnas.0707399104; T. R. Fouts et al., J Virol 74:11427-11436, 2000, doi:10.1128/JVI.74.24.11427-11436.2000). Proof of concept studies with nonhuman primates show that FLSC elicited heterologous protection against simian-human immunodeficiency virus (SHIV)/simian immunodeficiency virus (SIV) (T. R. Fouts et al., Proc Natl Acad Sci U S A 112:E992-E999, 2016, doi:10.1073/pnas.1423669112), which correlated with antibodies against transition state gp120 epitopes. Nevertheless, advancement of any vaccine that comprises gp120-CD4 complexes must consider whether the CD4 component breaks tolerance and becomes immunogenic in the autologous host. To address this, we performed an immunotoxicology study with cynomolgus macaques vaccinated with either FLSC or a rhesus variant of FLSC containing macaque CD4 sequences (rhFLSC). Enzyme-linked immunosorbent assay (ELISA) binding titers, primary CD3(+) T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4(+) T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures

  7. The Crystal Structure of Bacteriophage HK97 gp6: Defining a Large Family of Head-Tail Connector Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Cardarelli, Lia; Lam, Robert; Tuite, Ashleigh; Baker, Lindsay A; Sadowski, Paul D; Radford, Devon R; Rubinstein, John L; Battaile, Kevin P; Chirgadze, Nickolay; Maxwell, Karen L; Davidson, Alan R [UHN; (Toronto); (HWMRI)

    2011-11-23

    The final step in the morphogenesis of long-tailed double-stranded DNA bacteriophages is the joining of the DNA-filled head to the tail. The connector is a specialized structure of the head that serves as the interface for tail attachment and the point of egress for DNA from the head during infection. Here, we report the determination of a 2.1 Å crystal structure of gp6 of bacteriophage HK97. Through structural comparisons, functional studies, and bioinformatic analysis, gp6 has been determined to be a component of the connector of phage HK97 that is evolutionarily related to gp15, a well-characterized connector component of bacteriophage SPP1. Whereas the structure of gp15 was solved in a monomeric form, gp6 crystallized as an oligomeric ring with the dimensions expected for a connector protein. Although this ring is composed of 13 subunits, which does not match the symmetry of the connector within the phage, sequence conservation and modeling of this structure into the cryo-electron microscopy density of the SPP1 connector indicate that this oligomeric structure represents the arrangement of gp6 subunits within the mature phage particle. Through sequence searches and genomic position analysis, we determined that gp6 is a member of a large family of connector proteins that are present in long-tailed phages. We have also identified gp7 of HK97 as a homologue of gp16 of phage SPP1, which is the second component of the connector of this phage. These proteins are members of another large protein family involved in connector assembly.

  8. High Overtone Quasinormal Modes of Analog Black Holes and the Small Scale Structure of the Background Fluid

    CERN Document Server

    Daghigh, Ramin G

    2014-01-01

    The goal of this paper is to build a foundation for, and explore the possibility of, using high overtone quasinormal modes of analog black holes to probe the small scale (microscopic) structure of a background fluid in which an analog black hole is formed. This may provide a tool to study the small scale structure of some interesting quantum systems such as Bose-Einstein condensates. In order to build this foundation, we first look into the hydrodynamic case where we calculate the high overtone quasinormal mode frequencies of a 3+1 dimensional canonical non-rotating acoustic black hole. The leading order calculations have been done earlier in the literature. Here, we obtain the first order correction. We then analyze the high overtone quasinormal modes of acoustic black holes in a Bose-Einstein condensate using the linearized Gross-Pitaevskii equation. We point out that at the high overtone quasinormal mode limit, the only term that is important in the linearized Gross-Pitaevskii equation is the quantum poten...

  9. Numerical studies of superfluids and superconductors

    CERN Document Server

    Winiecki, T

    2001-01-01

    superconducting wire subject to an external magnetic field. We observe the motion of flux lines, and hence dissipation, due to the Lorentz force. We measure the V - I curve which is analogous to the drag force in a superfluid. With the introduction of impurities, flux lines become pinned which gives rise to an increased critical current. In this thesis we demonstrate the power of the Gross-Pitaevskii and the time-dependent Ginzburg-Landau equations by numerically solving them for various fundamental problems related to superfluidity and superconductivity. We start by studying the motion of a massive object through a quantum fluid modelled by the Gross-Pitaevskii equation. Below a critical velocity, the object does not exchange momentum or energy with the fluid. This is a manifestation of its superfluid nature. We discuss the effect of applying a constant force to the object and show that for small forces a vortex ring is created to which the object becomes attached. For a larger force the object detaches from...

  10. Fusion proteins of HIV-1 envelope glycoprotein gp120 with CD4-induced antibodies showed enhanced binding to CD4 and CD4 binding site antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weizao, E-mail: chenw3@mail.nih.gov [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Feng, Yang [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Wang, Yanping [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); The Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Zhu, Zhongyu; Dimitrov, Dimiter S. [Protein Interactions Group, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Some recombinant HIV-1 gp120s do not preserve their conformations on gp140s. Black-Right-Pointing-Pointer We hypothesize that CD4i antibodies could induce conformational changes in gp120. Black-Right-Pointing-Pointer CD4i antibodies enhance binding of CD4 and CD4bs antibodies to gp120. Black-Right-Pointing-Pointer CD4i antibody-gp120 fusion proteins could have potential as vaccine immunogens. -- Abstract: Development of successful AIDS vaccine immunogens continues to be a major challenge. One of the mechanisms by which HIV-1 evades antibody-mediated neutralizing responses is the remarkable conformational flexibility of its envelope glycoprotein (Env) gp120. Some recombinant gp120s do not preserve their conformations on gp140s and functional viral spikes, and exhibit decreased recognition by CD4 and neutralizing antibodies. CD4 binding induces conformational changes in gp120 leading to exposure of the coreceptor-binding site (CoRbs). In this study, we test our hypothesis that CD4-induced (CD4i) antibodies, which target the CoRbs, could also induce conformational changes in gp120 leading to better exposed conserved neutralizing antibody epitopes including the CD4-binding site (CD4bs). We found that a mixture of CD4i antibodies with gp120 only weakly enhanced CD4 binding. However, such interactions in single-chain fusion proteins resulted in gp120 conformations which bound to CD4 and CD4bs antibodies better than the original or mutagenically stabilized gp120s. Moreover, the two molecules in the fusion proteins synergized with each other in neutralizing HIV-1. Therefore, fusion proteins of gp120 with CD4i antibodies could have potential as components of HIV-1 vaccines and inhibitors of HIV-1 entry, and could be used as reagents to explore the conformational flexibility of gp120 and mechanisms of entry and immune evasion.

  11. Design of Laser Range Finder Based on TDC_GP21%基于TDC_GP21的激光测距仪设计

    Institute of Scientific and Technical Information of China (English)

    纪晓轮; 蒋钱; 陈江伟; 张旭野

    2015-01-01

    为提高激光测距仪测距精度,采用ACAM公司的时间数字转换芯片TDC_GP21,设计了高精度的时间间隔测量模块,采用数据拟合算法对测距系统进行了标定,并用多项测距算术平均值的方法提高系统测距精度.测量结果表明系统电路简单、精度较高、成本更低、具有量产可行性.%In order to improve the ranging accuracy of laser range finder,we used the time digital converter chip TDC_GP21 of ACAM,designing a high precision time interval measurement module,using data fitting algorithm to calibrate the ranging system,and the average value of multiple ranging arithmetic is used to improve the accuracy of the system.The measurement results show that the circuit is simple,the precision is high,the cost is lower,and it has the feasibility of mass production.

  12. Association of enhanced HIV-1 neutralization by a single Y681H substitution in gp41 with increased gp120-CD4 interaction and macrophage infectivity.

    Directory of Open Access Journals (Sweden)

    Rajesh Ringe

    Full Text Available HIV-1 variants that show unusual sensitivity to autologous antibodies due to presence of critical neutralization signatures would likely contribute towards rational envelope based HIV-1 vaccine design. In the present study, we found that presence of a naturally occurring H681 in gp41 membrane proximal external region (MPER of a clade C envelope (Env obtained from a recently infected Indian patient conferred increased sensitivity to autologous and heterologous plasma antibodies. Furthermore, Env-pseudotyped viruses expressing H681 showed increased sensitivity to soluble CD4, b12 and 4E10 monoclonal antibodies both in related and unrelated Envs and was corroborated with increased Env susceptibility and binding to cellular CD4 as well as with prolonged exposure of MPER epitopes. The increased gp120-CD4 interaction was further associated with relative exposure of CD4-induced epitopes and macrophage infectivity. In summary, our data indicate that Y681H substitution exposes neutralizing epitopes in CD4bs and MPER towards comprehensive interference in HIV-1 entry.

  13. Differential equations for dummies

    CERN Document Server

    Holzner, Steven

    2008-01-01

    The fun and easy way to understand and solve complex equations Many of the fundamental laws of physics, chemistry, biology, and economics can be formulated as differential equations. This plain-English guide explores the many applications of this mathematical tool and shows how differential equations can help us understand the world around us. Differential Equations For Dummies is the perfect companion for a college differential equations course and is an ideal supplemental resource for other calculus classes as well as science and engineering courses. It offers step-by-step techniques, practical tips, numerous exercises, and clear, concise examples to help readers improve their differential equation-solving skills and boost their test scores.

  14. Nonlinear Dirac Equations

    Directory of Open Access Journals (Sweden)

    Wei Khim Ng

    2009-02-01

    Full Text Available We construct nonlinear extensions of Dirac's relativistic electron equation that preserve its other desirable properties such as locality, separability, conservation of probability and Poincaré invariance. We determine the constraints that the nonlinear term must obey and classify the resultant non-polynomial nonlinearities in a double expansion in the degree of nonlinearity and number of derivatives. We give explicit examples of such nonlinear equations, studying their discrete symmetries and other properties. Motivated by some previously suggested applications we then consider nonlinear terms that simultaneously violate Lorentz covariance and again study various explicit examples. We contrast our equations and construction procedure with others in the literature and also show that our equations are not gauge equivalent to the linear Dirac equation. Finally we outline various physical applications for these equations.

  15. Partial differential equations

    CERN Document Server

    Evans, Lawrence C

    2010-01-01

    This text gives a comprehensive survey of modern techniques in the theoretical study of partial differential equations (PDEs) with particular emphasis on nonlinear equations. The exposition is divided into three parts: representation formulas for solutions; theory for linear partial differential equations; and theory for nonlinear partial differential equations. Included are complete treatments of the method of characteristics; energy methods within Sobolev spaces; regularity for second-order elliptic, parabolic, and hyperbolic equations; maximum principles; the multidimensional calculus of variations; viscosity solutions of Hamilton-Jacobi equations; shock waves and entropy criteria for conservation laws; and, much more.The author summarizes the relevant mathematics required to understand current research in PDEs, especially nonlinear PDEs. While he has reworked and simplified much of the classical theory (particularly the method of characteristics), he primarily emphasizes the modern interplay between funct...

  16. Fractional Chemotaxis Diffusion Equations

    CERN Document Server

    Langlands, T A M

    2010-01-01

    We introduce mesoscopic and macroscopic model equations of chemotaxis with anomalous subdiffusion for modelling chemically directed transport of biological organisms in changing chemical environments with diffusion hindered by traps or macro-molecular crowding. The mesoscopic models are formulated using Continuous Time Random Walk master equations and the macroscopic models are formulated with fractional order differential equations. Different models are proposed depending on the timing of the chemotactic forcing. Generalizations of the models to include linear reaction dynamics are also derived. Finally a Monte Carlo method for simulating anomalous subdiffusion with chemotaxis is introduced and simulation results are compared with numerical solutions of the model equations. The model equations developed here could be used to replace Keller-Segel type equations in biological systems with transport hindered by traps, macro-molecular crowding or other obstacles.

  17. Drift-Diffusion Equation

    Directory of Open Access Journals (Sweden)

    K. Banoo

    1998-01-01

    equation in the discrete momentum space. This is shown to be similar to the conventional drift-diffusion equation except that it is a more rigorous solution to the Boltzmann equation because the current and carrier densities are resolved into M×1 vectors, where M is the number of modes in the discrete momentum space. The mobility and diffusion coefficient become M×M matrices which connect the M momentum space modes. This approach is demonstrated by simulating electron transport in bulk silicon.

  18. Developmental Partial Differential Equations

    OpenAIRE

    Duteil, Nastassia Pouradier; Rossi, Francesco; Boscain, Ugo; Piccoli, Benedetto

    2015-01-01

    In this paper, we introduce the concept of Developmental Partial Differential Equation (DPDE), which consists of a Partial Differential Equation (PDE) on a time-varying manifold with complete coupling between the PDE and the manifold's evolution. In other words, the manifold's evolution depends on the solution to the PDE, and vice versa the differential operator of the PDE depends on the manifold's geometry. DPDE is used to study a diffusion equation with source on a growing surface whose gro...

  19. Differential equations I essentials

    CERN Document Server

    REA, Editors of

    2012-01-01

    REA's Essentials provide quick and easy access to critical information in a variety of different fields, ranging from the most basic to the most advanced. As its name implies, these concise, comprehensive study guides summarize the essentials of the field covered. Essentials are helpful when preparing for exams, doing homework and will remain a lasting reference source for students, teachers, and professionals. Differential Equations I covers first- and second-order equations, series solutions, higher-order linear equations, and the Laplace transform.

  20. Ordinary differential equations

    CERN Document Server

    Pontryagin, Lev Semenovich

    1962-01-01

    Ordinary Differential Equations presents the study of the system of ordinary differential equations and its applications to engineering. The book is designed to serve as a first course in differential equations. Importance is given to the linear equation with constant coefficients; stability theory; use of matrices and linear algebra; and the introduction to the Lyapunov theory. Engineering problems such as the Watt regulator for a steam engine and the vacuum-tube circuit are also presented. Engineers, mathematicians, and engineering students will find the book invaluable.

  1. gpICA: A Novel Nonlinear ICA Algorithm Using Geometric Linearization

    Directory of Open Access Journals (Sweden)

    Nguyen Thang Viet

    2007-01-01

    Full Text Available A new geometric approach for nonlinear independent component analysis (ICA is presented in this paper. Nonlinear environment is modeled by the popular post nonlinear (PNL scheme. To eliminate the nonlinearity in the observed signals, a novel linearizing method named as geometric post nonlinear ICA (gpICA is introduced. Thereafter, a basic linear ICA is applied on these linearized signals to estimate the unknown sources. The proposed method is motivated by the fact that in a multidimensional space, a nonlinear mixture is represented by a nonlinear surface while a linear mixture is represented by a plane, a special form of the surface. Therefore, by geometrically transforming the surface representing a nonlinear mixture into a plane, the mixture can be linearized. Through simulations on different data sets, superior performance of gpICA algorithm has been shown with respect to other algorithms.

  2. Bayesian Smoothing with Gaussian Processes Using Fourier Basis Functions in the spectralGP Package

    Directory of Open Access Journals (Sweden)

    Christopher J. Paciorek

    2007-04-01

    Full Text Available The spectral representation of stationary Gaussian processes via the Fourier basis provides a computationally efficient specification of spatial surfaces and nonparametric regression functions for use in various statistical models. I describe the representation in detail and introduce the spectralGP package in R for computations. Because of the large number of basis coefficients, some form of shrinkage is necessary; I focus on a natural Bayesian approach via a particular parameterized prior structure that approximates stationary Gaussian processes on a regular grid. I review several models from the literature for data that do not lie on a grid, suggest a simple model modification, and provide example code demonstrating MCMC sampling using the spectralGP package. I describe reasons that mixing can be slow in certain situations and provide some suggestions for MCMC techniques to improve mixing, also with example code, and some general recommendations grounded in experience.

  3. gpICA: A Novel Nonlinear ICA Algorithm Using Geometric Linearization

    Science.gov (United States)

    Nguyen, Thang Viet; Patra, Jagdish Chandra; Emmanuel, Sabu

    2006-12-01

    A new geometric approach for nonlinear independent component analysis (ICA) is presented in this paper. Nonlinear environment is modeled by the popular post nonlinear (PNL) scheme. To eliminate the nonlinearity in the observed signals, a novel linearizing method named as geometric post nonlinear ICA (gpICA) is introduced. Thereafter, a basic linear ICA is applied on these linearized signals to estimate the unknown sources. The proposed method is motivated by the fact that in a multidimensional space, a nonlinear mixture is represented by a nonlinear surface while a linear mixture is represented by a plane, a special form of the surface. Therefore, by geometrically transforming the surface representing a nonlinear mixture into a plane, the mixture can be linearized. Through simulations on different data sets, superior performance of gpICA algorithm has been shown with respect to other algorithms.

  4. P-gp/ABCB1 exerts differential impacts on brain and fetal exposure to norbuprenorphine.

    Science.gov (United States)

    Liao, Michael Z; Gao, Chunying; Shireman, Laura M; Phillips, Brian; Risler, Linda J; Neradugomma, Naveen K; Choudhari, Prachi; Prasad, Bhagwat; Shen, Danny D; Mao, Qingcheng

    2017-01-19

    Norbuprenorphine is the major active metabolite of buprenorphine which is commonly used to treat opiate addiction during pregnancy. Norbuprenorphine produces marked respiratory depression and was 10 times more potent than buprenorphine. Therefore, it is important to understand the mechanism that controls fetal exposure to norbuprenorphine, as exposure to this compound may pose a significant risk to the developing fetus. P-gp/ABCB1 and BCRP/ABCG2 are two major efflux transporters regulating tissue distribution of drugs. Previous studies have shown that norbuprenorphine, but not buprenorphine, is a P-gp substrate. In this study, we systematically examined and compared the roles of P-gp and BCRP in determining maternal brain and fetal distribution of norbuprenorphine using transporter knockout mouse models. We administered 1mg/kg norbuprenorphine by retro-orbital injection to pregnant FVB wild-type, Abcb1a(-/-)/1b(-/-), and Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice on gestation day 15. The fetal AUC of norbuprenorphine was ∼64% of the maternal plasma AUC in wild-type mice, suggesting substantial fetal exposure to norbuprenorphine. The maternal plasma AUCs of norbuprenorphine in Abcb1a(-/-)/1b(-/-) and Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice were ∼2 times greater than that in wild-type mice. Fetal AUCs in Abcb1a(-/-)/1b(-/-) and Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice were also increased compared to wild-type mice; however, the fetal-to-maternal plasma AUC ratio remained relatively unchanged by the knockout of Abcb1a/1b or Abcb1a/1b/Abcg2. In contrast, the maternal brain-to-maternal plasma AUC ratio in Abcb1a(-/-)/1b(-/-) or Abcb1a(-/-)/1b(-/-)/Abcg2(-/-) mice was increased ∼30-fold compared to wild-type mice. Protein quantification by LC-MS/MS proteomics revealed significantly higher amounts of P-gp protein in the wild-type mice brain than that in the placenta. These results indicate that fetal exposure to norbuprenorphine is substantial and that P-gp has a minor impact on

  5. 乳酸菌GP100抑制霉菌和酵母菌的应用研究%Application study on Lactic acid bacteria GP100 to inhibit mold and yeast

    Institute of Scientific and Technical Information of China (English)

    马霞; 韩迪; 陶纯长; 赵霞; 方曙光

    2011-01-01

    通过双层平板培养法.研究证明了乳酸菌GP100对霉菌M1有不完全抑制作用和对霉菌M2、M3和M4有完全抑制作用;并通过酸奶样品数据统计法.研究证明了乳酸菌GP100对酵母茵污染率可降低43.9%.%This study indicates that Lactic add bacteria GP100 has effects of partial inhibition against mold M1 and complete inhibition against molds M2, M3, and M4 by double plate culture method. Statistics analysis of yogurt samples shows that GP100 reduced the yeast pollution rate under atmospheric temperature by 43,9%.

  6. Structural conformation of prokaryotic plasmid expressing the gp41 of HIV-1 SF2 strain%HIV-1 SF2株env基因(gp41)的克隆构建及其原核表达

    Institute of Scientific and Technical Information of China (English)

    董梅; 鲁晓青; 陈向伟; 王斌

    2001-01-01

    目的克隆并在大肠杆菌中表达HIV gp41.方法应用PCR技术,纯化HIV-1 SF2株外膜蛋白env基因(gp41),并重组入原核高效表达载体pBV220,在大肠杆菌HB101中进行表达.结果 SDS-PAGE电泳结果表明,在44 000处有一条蛋白表达带.Western blot证明,44 000蛋白带可与HIV-1阳性血清发生特异性反应.结论该重组表达gp41的融合蛋白,可为HIV-1 gp41.

  7. NHERF1 regulates gp120-induced internalization and signaling by CCR5, and HIV-1 production.

    Science.gov (United States)

    Kuang, Yi-Qun; Pang, Wei; Zheng, Yong-Tang; Dupré, Denis J

    2012-02-01

    The scaffolding protein Na(+) /H(+) exchanger regulator factor 1 (NHERF1) plays an important role in the trafficking of G protein-coupled receptors. We previously demonstrated that NHERF1 is involved in chemokine receptor CCR5 homodimer internalization and signal transduction. Given the importance of CCR5 internalization during HIV-1 infection, we evaluated NHERF1's contribution in HIV-1 infection. We challenged human osteosarcoma cells coexpressing CD4 and CCR5 cells expressing either NHERF1 fragment domains or WT NHERF1 with an HIV-1 strain to examine the effects of NHERF1 on HIV-1 entry and replication. WT NHERF1 potentiates HIV-1 envelope gp120-induced CCR5 internalization, and promotes the replication of HIV-1. In order to better understand how NHERF1 affects signal transduction, different domains of NHERF1 were overexpressed in cells to analyze their effect on the different signaling pathways. Here, we show that NHERF1 can associate with CCR5, and promote activation of the gp120-induced MAPK/ERK, focal adhesion kinase and RhoA (Ras homolog gene family member A) signaling pathways. NHERF1 overexpression also increases HIV-1 host cell migration triggered by gp120 via focal adhesion kinase (FAK) signaling. Finally, NHERF1 enhanced actin filament rearrangement in host cells, an important step in post-entry HIV-1 replication events. While postsynaptic density 95/disk-large/zonula occludens 2 (PDZ2) appears to be the major contributor in those events, other domains also participate in the regulation of gp120-induced signaling pathways. Altogether, our results suggest a very important role of the scaffold NHERF1 in the regulation of HIV-1 entry and replication.

  8. Construction and Identification of Recombinant Fowlpox Virus Expressing GP5/GP3 of Pig Reproduction and Respiration Syndrome Virus(PRRSV) and Swine IL-18%表达PRRSV GP5、GP3和猪IL-18的重组鸡痘病毒的构建及鉴定

    Institute of Scientific and Technical Information of China (English)

    沈国顺; 金宁一; 秦晓光; 庄天中; 尹荣兰; 马鸣潇

    2006-01-01

    目的 研制安全有效的预防猪繁殖与呼吸综合征病毒(PRRSV)重组鸡痘病毒活载体疫苗.方法 将PRRSV长春株的GP5和GP3基因插入到含有猪IL-18基因的鸡痘病毒转移载体pUTAL复合启动子下游,构建重组鸡痘病毒转移载体pUTAL-IL-18-GP5-GP3.将该重组质粒与鸡痘病毒(FPV)282-E4株共转染鸡胚成纤维细胞(CEF),进行同源重组.通过3次BrdU加压筛选,经PCR、RT-PCR和IFA方法鉴定重组病毒.结果 从重组鸡痘病毒基因组和总RNA中扩增出340 bp的目的基因片段,感染重组病毒的CEF细胞与特异性荧光抗体发生阳性反应,表明目的基因在重组鸡痘病毒中得到表达.结论 已成功构建1株重组鸡痘病毒,并可正确表达PRRSV ORF5/ORF3基因.

  9. Divergence of the TRP36 protein (gp36) in Ehrlichia canis strains found in Brazil.

    Science.gov (United States)

    Aguiar, Daniel M; Melo, Andreia L T

    2015-03-01

    The molecular characterization of 16S rRNA gene and immunoreactive proteins of Ehrlichia canis usually provide little information about the overall diversity of this organism. On the other hand, distinct sequences of the Tandem Repeat Protein 36 (TRP36/gp36) gene of E. canis have been reported, indicating substantial degree of diversity. The present letter aims to update and discuss the molecular divergence of the TRP36 protein between strains of E. canis isolated in different countries including Brazil.

  10. Absence of Metalloprotease GP63 Alters the Protein Content of Leishmania Exosomes

    OpenAIRE

    Kasra Hassani; Marina Tiemi Shio; Caroline Martel; Denis Faubert; Martin Olivier

    2014-01-01

    Protozoan parasites of Leishmania genus are able to successfully infect their host macrophage due to multiple virulence strategies that result in its deactivation. Recent studies suggest Leishmania GP63 to be a critical virulence factor in modulation of many macrophage molecules, including protein tyrosine phosphatases (PTPs) and transcription factors (TFs). Additionally, we and others recently reported that Leishmania-released exosomes can participate in pathogenesis. Exosomes are 40-100 nm ...

  11. Selected Thermophysical Properties of 2,2 Dimethylcyclopentyl Methylphosphonofluoridate (GP) and 2,2 Dimethylcyclopentanol (DMCP)

    Science.gov (United States)

    2016-09-01

    current GP vapor pressure data, measured using complementary methods, provides confidence in the data presented herein. The two DSC values that have...melting temperature. In the present case, the vapor pressure at the melting point has been assigned a value of P = 290 Pa, which was determined...generated using complementary techniques in our work provides confidence in the accuracy of the vapor pressure data presented in this report

  12. Making sense of change: patients' views of diabetes and GP-led integrated diabetes care.

    Science.gov (United States)

    Burridge, Letitia H; Foster, Michele M; Donald, Maria; Zhang, Jianzhen; Russell, Anthony W; Jackson, Claire L

    2016-02-01

    Health system reform is directed towards better management of diabetes. However, change can be difficult, and patients' perspectives are a key aspect of implementing change. This study investigated patients' perceptions and experiences of type 2 diabetes (T2DM), self-care and engagement with GP-led integrated diabetes care. Qualitative interviews were conducted with purposively selected patients with T2DM following their initial medical appointment in the new model of care. Normalization process theory was used to orientate the thematic analysis, to explain the work of implementing change. Two specialist GP-based complex diabetes services in primary care in Brisbane, Australia. Intervention group patients (n = 30) in a randomized controlled trial to evaluate a model of GP-led integrated care for complex T2DM. Participants' experiences and perceptions of diabetes management and a GP-led model of care. Three themes were identified: sensibility of change, 'diabetic life' and diabetes care alliance. The imperative of change made sense, but some participants experienced dissonance between this rational view and their lived reality. Diabetes invaded life, revealing incongruities between participants' values and living with diabetes. They appreciated a flexible and personalized approach to care. Participants responded to advice in ways that seemed rational within the complexities of their life context. Their diabetes partnerships with health professionals coupled providers' biomedical expertise with patients' contextual expertise. Learning to manage relationships with various health professionals adds to patients' diabetes-related work. Providers need to adopt a flexible, interactive approach and foster trust, to enable better diabetes care. © 2015 John Wiley & Sons Ltd.

  13. Patient safety skills in primary care: a national survey of GP educators

    OpenAIRE

    Ahmed, Maria; Arora, Sonal; McKay, John; Long, Susannah; Vincent, Charles; Kelly, Moya; Sevdalis, Nick; Bowie, Paul

    2014-01-01

    Background Clinicians have a vital role in promoting patient safety that goes beyond their technical competence. The qualities and attributes of the safe hospital doctor have been explored but similar work within primary care is lacking. Exploring the skills and attributes of a safe GP may help to inform the development of training programmes to promote patient safety within primary care. This study aimed to determine the views of General Practice Educational Supervisors (GPES) regarding the ...

  14. Designing a Soluble Near Full-Length HIV-1 GP41 Trimer

    Science.gov (United States)

    2012-11-26

    stabilized in a prehairpin-like structure, as evident from binding of a HR2 peptide to exposed HR1 grooves, lack of binding to hexa -helical bundle...the HR1 helices. The hexa -helical bundle thus formed brings the host and viral membranes in close proximity facilitating membrane fusion and...crystal structure of the hexa - helical bundle intermediate (see Fig. 1B and Fig. 3A), the core of fusion-active gp41, has been determined (33), very

  15. A study of role expansion: a new GP role in cardiology care

    Science.gov (United States)

    2014-01-01

    Background The National Health Service is reconfiguring health care services in order to meet the increasing challenge of providing care for people with long-term conditions and to reduce the demand on specialised outpatient hospital services by enhancing primary care. A review of cardiology referrals to specialised care and the literature on referral management inspired the development of a new GP role in Cardiology. This new extended role was developed to enable GPs to diagnose and manage patients with mild to moderate heart failure or atrial fibrillation and to use a range of diagnostics effectively in primary care. This entailed GPs participating in a four-session short course with on-going clinical supervision. The new role was piloted in a small number of GP practices in one county in England for four months. This study explores the impact of piloting the Extended Cardiology role on the GP’s role, patients’ experience, service delivery and quality. Methods A mixed methods approach was employed including semi-structured interviews with GPs, a patient experience survey, a quality review of case notes, and analysis on activity and referral data. Results The participating GPs perceived the extended GP role as a professional development opportunity that had the potential to reduce healthcare utilisation and costs, through a reduction in referrals, whilst meeting the patient’s wishes for the provision of care closer to home. Patient experience of the new GP service was positive. The standard of clinical practice was judged acceptable. There was a fall in referrals during the study period. Conclusion This new role in cardiology was broadly welcomed as a model of care by the participating GPs and by patients, because of the potential to improve the quality of care for patients in primary care and reduce costs. As this was a pilot study further development and continuing evaluation of the model is recommended. PMID:24885826

  16. Guanine-06 methylation reduces the reactivity of d(GpG) towards platinum complexes.

    Science.gov (United States)

    Struik, A F; Zuiderwijk, C T; van Boom, J H; Elding, L I; Reedijk, J

    1991-12-01

    6-methylated guanine dinucleotides were used to study the influence of hydrogen bonding on the specific binding of the antitumor drug cDDP, cis-PtCl2(NH3)2, to DNA. In this interaction, the guanine-06 site appears to be important in explaining the preference for a pGpG-N7(1),N7(2) chelate, which results from H-bridge formation with the ammine ligand of cDDP. Guanine-06 methylated dinucleotides and the nonmodified dinucleotides were reacted with [Pt(dien)Cl]+, cis-PtCl2(NH3)2, and cis-[Pt(NH3)2(H2O)2]2+ and the reaction products were characterized by 1H NMR using pH titrations. Methylation at guanine-06 clearly reduces the preference for the guanine. In competition experiments monitored by NMR and experiments using UV spectrophotometry a decreasing reactivity towards [Pt(dien)(H2O)]2+ and cis-[Pt(NH3)2(H2O)2]2+ was found, in the order of d(GpG) greater than d(GomepG) greater than d(GpGome) greater than d(GomepGome). The difference in reactivity between 5' guanine methylation and 3' guanine methylation is ascribed to differences in the H-bond formation with the backbone phosphate. The resulting reduced stacking of the bases in both modified dinucleotides, compared to the bases in d(GpG), results in a preference for the 3' guanine over 5'.

  17. Conformational alterations in the CD4 binding cavity of HIV-1 gp120 influencing gp120-CD4 interactions and fusogenicity of HIV-1 envelopes derived from brain and other tissues

    Directory of Open Access Journals (Sweden)

    Ramsland Paul A

    2011-06-01

    Full Text Available Abstract Background CD4-binding site (CD4bs alterations in gp120 contribute to HIV-1 envelope (Env mediated fusogenicity and the ability of gp120 to utilize low levels of cell-surface CD4. In a recent study, we constructed three-dimensional models of gp120 to illustrate CD4bs conformations associated with enhanced fusogenicity and enhanced CD4-usage of a modestly-sized panel of blood-derived HIV-1 Envs (n = 16. These conformations were characterized by a wider aperture of the CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop. Here, we sought to provide further validation of the utility of these models for understanding mechanisms that influence Env function, by characterizing the structure-function relationships of a larger panel of Envs derived from brain and other tissues (n = 81. Findings Three-dimensional models of gp120 were generated by our recently validated homology modelling protocol. Analysis of predicted CD4bs structures showed correlations between the aperture width of the CD4bs cavity and ability of the Envs to mediate cell-cell fusion, scavenge low-levels of cell-surface CD4, bind directly to soluble CD4, and bind to the Env mAb IgG1b12 whose epitope overlaps the gp120 CD4bs. These structural alterations in the CD4bs cavity were associated with repositioning of the V5 loop. Conclusions Using a large, independent panel of Envs, we can confirm the utility of three-dimensional gp120 structural models for illustrating CD4bs alterations that can affect Env function. Furthermore, we now provide new evidence that these CD4bs alterations augment the ability of gp120 to interact with CD4 by increasing the exposure of the CD4bs.

  18. Enabling tomorrow's doctors to address obesity in a GP consultation: an action research project.

    Science.gov (United States)

    Leedham-Green, Kathleen E; Pound, Rebecca; Wylie, Ann

    2016-11-01

    Obesity is a leading risk factor for morbidity and mortality, however, guidelines for prevention and management are relatively recently established. Little is known about what needs to be in place to put these into practice. This research provides an insight into how senior medical students consult with obese patients in general practice, the range of their learning needs, and the impact of various educational strategies that aim to bring their practice closer to current evidence-based guidelines. It centres on a series of compulsory but formative reflective case studies written by final year students at one large medical school on their GP rotation as they consult independently with obese patients with 'next room' GP tutor support. Analysis of these case studies was used to inform a three-year educational action research project. By systematically identifying and addressing learning needs, including barriers and enablers to best practice, we have demonstrated how senior medical students, and their GP tutors, can acquire the role legitimacy and role competency required for effective practice.

  19. HIV gp120 induces, NF-kappaB dependent, HIV replication that requires procaspase 8.

    Directory of Open Access Journals (Sweden)

    Gary D Bren

    Full Text Available BACKGROUND: HIV envelope glycoprotein gp120 causes cellular activation resulting in anergy, apoptosis, proinflammatory cytokine production, and through an unknown mechanism, enhanced HIV replication. METHODOLOGY/PRINCIPAL FINDINGS: We describe that the signals which promote apoptosis are also responsible for the enhanced HIV replication. Specifically, we demonstrate that the caspase 8 cleavage fragment Caspase8p43, activates p50/p65 Nuclear Factor kappaB (NF-kappaB, in a manner which is inhibited by dominant negative IkappaBalpha. This caspase 8 dependent NF-kappaB activation occurs following stimulation with gp120, TNF, or CD3/CD28 crosslinking, but these treatments do not activate NF-kappaB in cells deficient in caspase 8. The Casp8p43 cleavage fragment also transactivates the HIV LTR through NF-kappaB, and the absence of caspase 8 following HIV infection greatly inhibits HIV replication. CONCLUSION/SIGNIFICANCE: Gp120 induced caspase 8 dependent NF-kappaB activation is a novel pathway of HIV replication which increases understanding of the biology of T-cell death, as well as having implications for understanding treatment and prevention of HIV infection.

  20. Sequence Variation in the Gp120 region of SHIV-CN97001 during in vivo Passage

    Institute of Scientific and Technical Information of China (English)

    Qiang LIU; Gui-bo YANG; Yue MA; Chen-li QIU; Jie-jie DAI; Hui XING; Yi-ming SHAO

    2008-01-01

    SHIV-CN97001 played an important role in assessing the immune effect and strategy of the AIDS vaccine which included genes of the predominant prevalent HIV-1 strain in China. In this study, SHIV-CN97001 was in vivo passaged serially to construct pathogenic SHIV-CN97001/rhesus macaques model. To identify variation in the gp120 region of SHIV-CN97001 during passage, the fragments of gp120 gene were amplified by RT-PCR from the plasma of SHIV-CN97001 infected animals at the peak viral load time point and the gene distances (divergence, diversity) were calculated using DISTANCE. The analysis revealed that the genetic distances of SHIV-CN97001 in the third passage animals were the highest during in vivo passage. It had a relationship between viral divergence from the founder strain and viral replication ability. The nucleic acid sequence of the V3 region was highly conservative. All of the SHIV-CN97001 strains had V3 loop central motif (GPGQ) and were predicted to be using CCR5 co-receptor on the basis of the critical amino acids within V3 loop. These results show that there was no significant increase in the genetic distance during serial passage, and SHIV-CN97001 gp120 gene evolved toward ancestral states upon transmission to a new host. This could partly explain why there was no pathogenic viral strain obtained during in vivo passage.

  1. Gold manno-glyconanoparticles for intervening in HIV gp120 carbohydrate-mediated processes.

    Science.gov (United States)

    Di Gianvincenzo, Paolo; Chiodo, Fabrizio; Marradi, Marco; Penadés, Soledad

    2012-01-01

    After nearly three decades since the discovery of human immunodeficiency virus (HIV) (1983), no effective vaccine or microbicide is available, and the virus continues to infect millions of people worldwide each year. HIV antiretroviral drugs reduce the death rate and improve the quality of life in infected patients, but they are not able to completely remove HIV from the body. The glycoprotein gp120, part of the envelope glycoprotein (Env) of HIV, is responsible for virus entry and infection of host cells. High-mannose type glycans that decorate gp120 are involved in different carbohydrate-mediated HIV binding. We have demonstrated that oligomannoside-coated gold nanoparticles (manno-GNPs) are able to interfere with HIV high-mannose glycan-mediated processes. In this chapter, we describe the methods for the preparation and characterization of manno-GNPs and the experiments performed by means of SPR and STD-NMR techniques to evaluate the ability of manno-GNPs to inhibit 2G12 antibody binding to gp120. The antibody 2G12-mediated HIV neutralization and the lectin DC-SIGN-mediated HIV trans-infection in cellular systems are also described.

  2. Patients' perceptions of GP non-verbal communication: a qualitative study.

    Science.gov (United States)

    Marcinowicz, Ludmila; Konstantynowicz, Jerzy; Godlewski, Cezary

    2010-02-01

    During doctor-patient interactions, many messages are transmitted without words, through non-verbal communication. To elucidate the types of non-verbal behaviours perceived by patients interacting with family GPs and to determine which cues are perceived most frequently. In-depth interviews with patients of family GPs. Nine family practices in different regions of Poland. At each practice site, interviews were performed with four patients who were scheduled consecutively to see their family doctor. Twenty-four of 36 studied patients spontaneously perceived non-verbal behaviours of the family GP during patient-doctor encounters. They reported a total of 48 non-verbal cues. The most frequent features were tone of voice, eye contact, and facial expressions. Less frequent were examination room characteristics, touch, interpersonal distance, GP clothing, gestures, and posture. Non-verbal communication is an important factor by which patients spontaneously describe and evaluate their interactions with a GP. Family GPs should be trained to better understand and monitor their own non-verbal behaviours towards patients.

  3. Epitope mapping of a monoclonal antibody against the Gp85 of avian leukosis virus subgroup J.

    Science.gov (United States)

    Sun, Miao; Yu, Duo; Mo, Hongfei; Cao, Hong; Chen, Chen; Chen, Fuyong

    2012-06-01

    Avian leukosis virus subgroup J poses a great threat to the poultry industry in China. To reduce the economic losses, a quick method for detection of ALV-J antigen is required for diagnosis and identification of the congenitally transmitting hens. In this study, we report the production and evaluation of one monoclonal antibody (MAb) suitable for achieving these goals. The gp85 gene of avian leukosis virus subgroup J CAUHM01 China isolates was subcloned into the expression vectors pGEX-6p-1 and pET28a and successfully expressed in E. coli. After immunizing BALB/c mice with recombinant His-Jgp85 protein, splenic cells from immunized mice were fused with SP2/0 myeloma cells to produce hybridomas. We isolated and characterized one ALV-J gp85-specific MAb by determining its titer, affinity and IgG subclass. In addition, we performed epitope mapping and determined the epitope for the MAb 1E3 to be 81-92 aa of ALV-J gp85 protein (LPWDPQELDILG). Bioinformatics analysis and IFA studies revealed that this epitope is conserved among all ALV-J isolates and that this antibody could serve as a useful reagent for ALV-J detection and diagnosis.

  4. Positive evolution of the glycoprotein (GP) gene is related to transmission of the Ebola virus.

    Science.gov (United States)

    Jing, Y X; Wang, L N; Wu, X M; Song, C X

    2016-03-28

    Ebola hemorrhagic fever is a fatal disease caused by the negative-strand RNA of the Ebola virus. A high-intensity outbreak of this fever was reported in West Africa last year; however, there is currently no definitive treatment strategy available for this disease. In this study, we analyzed the molecular evolutionary history and attempted to determine the positive selection sites in the Ebola genes using multiple-genomic sequences of the various Ebola virus subtypes, in order to gain greater clarity into the evolution of the virus and its various subtypes. Only the glycoprotein (GP) gene was positively selected among the 8 Ebola genes, with the other genes remaining in the purification stage. The positive selection sites in the GP gene were identified by a random-site model; these sites were found to be located in the mucin-like region, which is associated with transmembrane protein binding. Additionally, different branches of the phylogenetic tree displayed different positive sites, which in turn was responsible for differences in the cell adhesion ability of the virus. In conclusion, the pattern of positive sites in the GP gene is associated with the epidemiology and prevalence of Ebola in different areas.

  5. CTL responses to Leishmania mexicana gp63-cDNA vaccine in a murine model.

    Science.gov (United States)

    Ali, S A; Rezvan, H; McArdle, S E; Khodadadi, A; Asteal, F A; Rees, R C

    2009-07-01

    Immunity to Leishmania is believed to be strongly dependent upon the activation of Th1 immune responses, although the exact role of cytotoxic T lymphocytes (CTLs) has not yet been determined. The aims of this study were to establish a suitable cytotoxicity assay to measure CTL activity and to compare immunity induced by Leishmania mexicana gp63 cDNA via i.m. injection and gene gun immunization in the BALB/c mouse model. The CTL activity was evaluated by short-term (51)Cr-release cytotoxicity assays against CT26 tumour cells transfected with L. mexicana gp63 cDNA and dendritic cells (DCs) loaded with soluble Leishmania antigen (SLA) as targets. The results clearly demonstrated that higher protection to L. mexicana infection was induced by gene gun DNA-immunization vs. i.m. injection. Cytotoxic T lymphocyte activity of splenocytes was observed in mice immunized either with L. mexicana gp63 cDNA or SLA and long-lived CTL activity was observed in immunized and/or re-challenged mice but not naïve mice infected with the parasite.

  6. Penyutradaraan Teater Bangsawan Dengan Naskah Melayu Peterakna Episode Peri Bunian Karya G.P. Ade Dharmawi

    Directory of Open Access Journals (Sweden)

    Asri Nofriani

    2013-11-01

    Full Text Available Tujuan penyutradaraan ini adalah menghadirkan unsur-unsur atau elemen-elemen pertunjukan Teater Bangsawan Muda dan Teater Bangsawan Tua sehingga tercipta pertunjukan Teater Bangsawan masa kini. Sejarah dan perkembangan teater bangsawan di Riau memiliki hubungan yang erat dengan teater di semenanjung Malaya. Para peneliti mengkategorikan drama Melayu Bangsawan sebagai drama tradisional. Tulisan berikut membahas drama Peterakna episode Peri Bunian karya GP Ade Dharmawi. Karya yang penulis buat ini menggunakan idiompola teater bangsawan. Peterakna adalah takhta kerajaan Melayu kuno. Peri Bunian merupakan episode yangmenggabungkan dua alam manusia, natural dan supranatural Orang Bunian.Kata kunci: Teater bangsawan, peterakna, orang bunian, teater RiauABSTRACTThe Directing of Bangsawan Theater Using Malay Script Peterakna Episode Peri Bunian Created By G.P. Ade Dharmawi. The aim of this directing is presenting the performance elements of young Bangsawan Theater and old Bangsawan Theater so that the performance of modern Bangsawan Theater can be created. The researchers have categorized Malay drama Bangsawan Theatre as a traditional drama. This article discusses about the show of Peterakna, Episode Peri Bunian created by G.P. Ade Dharmawi which has adopted and used the idiomatic pattern of Bangsawan Theater. Peterakna is the throne of the ancient Malay kingdom. In addition, Peri Bunian is an episode that combines two men’s world, the natural and supranatural of Bunian people.Keywords: Teater bangsawan, Peterakna, Peri Bunian, Riau theatre.

  7. The Ambiguous Effect of GP Competition: The Case of Hospital Admissions.

    Science.gov (United States)

    Islam, M Kamrul; Kjerstad, Egil

    2016-10-14

    In the theoretical literature on general practitioner (GP) behaviour, one prediction is that intensified competition induces GPs to provide more services resulting in fewer hospital admissions. This potential substitution effect has drawn political attention in countries looking for measures to reduce the growth in demand for hospital care. However, intensified competition may induce GPs to secure hospital admissions a signal to attract new patients and to keep the already enlisted ones satisfied, resulting in higher admission rates at hospitals. Using both static and dynamic panel data models, we aim to enhance the understanding of whether such relations are causal. Results based on ordinary least square (OLS) models indicate that aggregate inpatient admissions are negatively associated with intensified competition both in the full sample and for the sub-sample patients aged 45 to 69, while outpatient admissions are positively associated. Fixed-effect estimations do not confirm these results though. However, estimations of dynamic models show significant negative (positive) effects of GP competition on aggregate inpatient (outpatient) admissions in the full sample and negative effects on aggregate inpatient admissions and emergency admissions for the sub-sample. Thus, intensified GP competition may reduce inpatient hospital admissions by inducing GPs to provide more services, whereas, the alternative hypothesis seems valid for outpatient admissions. © 2016 The Authors. Health Economics Published by John Wiley & Sons, Ltd.

  8. Long term GP opinions and involvement after a consultation-liaison intervention for mental health problems

    Directory of Open Access Journals (Sweden)

    Passerieux Christine

    2008-07-01

    Full Text Available Abstract Background Shared Mental Health care between Psychiatry and Primary care has been developed to improve the care of common mental health problems but has not hitherto been adequately evaluated. The present study evaluated a consultation-liaison intervention with two objectives: to explore long-term GP opinions (relating to impact on their management and on patient medical outcome and to determine the secondary referral rate, after a sufficient time lapse following the intervention to reflect a "real-world" primary care setting. Methods All the 139 collaborating GPs (response rate: 84.9% were invited two years after the intervention to complete a retrospective telephone survey for each patient (181 patients; response rate: 69.6%. Results 91.2% of GPs evaluated effects as positive for primary care management (mainly as support and 58.9% noted positive effects for patient medical outcome. Two years post-intervention, management was shared care for 79.7% of patients (the GP as the psychiatric care provider and care by a psychiatrist for 20.3% patients. Secondary referral occurred finally in 44.2% of cases. Conclusion The intervention supported GP partners in their management of patients with common mental health problems. Further studies are required on the appropriateness of the care provider.

  9. Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability.

    Directory of Open Access Journals (Sweden)

    Xuefeng Zhang

    2012-01-01

    Full Text Available Dissemination of HIV in the host involves transit of the virus and virus-infected cells across the lymphatic endothelium. HIV may alter lymphatic endothelial permeability to foster dissemination, but the mechanism is largely unexplored. Using a primary human lymphatic endothelial cell model, we found that HIV-1 envelope protein gp120 induced lymphatic hyperpermeability by disturbing the normal function of Robo4, a novel regulator of endothelial permeability. HIV-1 gp120 induced fibronectin expression and integrin α₅β₁ phosphorylation, which led to the complexing of these three proteins, and their subsequent interaction with Robo4 through its fibronectin type III repeats. Moreover, pretreatment with an active N-terminus fragment of Slit2, a Robo4 agonist, protected lymphatic endothelial cells from HIV-1 gp120-induced hyperpermeability by inhibiting c-Src kinase activation. Our results indicate that targeting Slit2/Robo4 signaling may protect the integrity of the lymphatic barrier and limit the dissemination of HIV in the host.

  10. [Eukaryotic Expression and Immunogenic Research of Recombination Ebola Virus Membrane Protein Gp-Fc].

    Science.gov (United States)

    Zhang, Xiaoguang; Yang, Ren; Wang, Jiao; Wang, Xuan; Hou, Mieling; An, Lina; Zhu, Ying; Cao, Yuxi; Zeng, Yi

    2016-01-01

    We used 293 cells to express the recombinant membrane protein of the Ebola virus. Then, the immunogenicity of the recombinant protein was studied by immunized BALB/c mice. According to the codon use frequency of humans, the gene encoding the extracellular domain of the Ebola virus membrane protein was optimized, synthesized, and inserted into the eukaryotic expression plasmid pXG-Fc to construct the human IgG Fc and Ebola GP fusion protein expression plasmid pXG-modGP-Fc. To achieve expression, the fusion protein expression vector was transfected into high-density 293 cells using transient transfection technology. The recombinant protein was purified by protein A affinity chromatography. BALB/c mice were immunized with the purified fusion protein, and serum antibody titers evaluated by an indirect enzyme-linked immunosorbent assay (ELISA). Purification and analyses of the protein revealed that the eukaryotic expression vector could express the recombinant protein GP-Fc effectively, and that the recombinant protein in the supernatant of the cell culture was present as a dimer. After immunization with the purified recombinant protein, a high titer of antigen-specific IgG could be detected in the serum of immunized mice by indirect ELISA, showing that the recombinant protein had good immunogenicity. These data suggest that we obtained a recombinant protein with good immunogenicity. Our study is the basis for development of a vaccine against the Ebola virus and for screening of monoclonal antibodies.

  11. Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2+ Human Pancreatic Progenitors

    Directory of Open Access Journals (Sweden)

    Jacqueline Ameri

    2017-04-01

    Full Text Available Stem cell-based therapy for type 1 diabetes would benefit from implementation of a cell purification step at the pancreatic endoderm stage. This would increase the safety of the final cell product, allow the establishment of an intermediate-stage stem cell bank, and provide a means for upscaling β cell manufacturing. Comparative gene expression analysis revealed glycoprotein 2 (GP2 as a specific cell surface marker for isolating pancreatic endoderm cells (PECs from differentiated hESCs and human fetal pancreas. Isolated GP2+ PECs efficiently differentiated into glucose responsive insulin-producing cells in vitro. We found that in vitro PEC proliferation declines due to enhanced expression of the cyclin-dependent kinase (CDK inhibitors CDKN1A and CDKN2A. However, we identified a time window when reducing CDKN1A or CDKN2A expression increased proliferation and yield of GP2+ PECs. Altogether, our results contribute tools and concepts toward the isolation and use of PECs as a source for the safe production of hPSC-derived β cells.

  12. 基于GP2Y0A02距离测量的仿真与辅助设计%Simulation and Design of Distance Measurement Based on GP2Y0A02

    Institute of Scientific and Technical Information of China (English)

    李建新

    2014-01-01

    To realize the non-contact distance measurement, the distance optical test system based on GP2Y0A02 is designed us-ing multiple simulation and design software. The voltage value of GP2Y0A02 is measured in PROTEUS, and the fitting curve of GP2Y0A02 voltage and distance is established using multiple linear regressions in Matlab;finally distance is measured by the fitting curve with procedure. The test results show that satisfied measurement accuracy can be attained using appropriate data processing methods for the nonlinear position measurement.%为了实现非接触距离测量,利用多个仿真与设计软件设计了采用GP2Y0A02模块的距离光学测试系统。在PROTEUS中测量GP2Y0A02电压值,并在Matlab中采用多元线性回归建立GP2Y0A02电压与距离的拟合曲线,最后在开发的测量程序中利用拟合曲线求解得到距离量。测试结果表明,对于非线性位置测量采用适当数据处理方法能得到满意的测量精度。

  13. The structural and functional researches of HIV-1 gp41 NC six-helix-bundle%HIV-1gp41NC六螺旋的结构与功能研究

    Institute of Scientific and Technical Information of China (English)

    朱赟; 陈应华

    2010-01-01

    AIDS是严重危害人类健康的疾病,而HIV是导致这种疾病的病毒.gp41六螺旋在介导HIV-1病毒与靶细胞间的膜融合过程中起着重要作用.因此,对于gp41结合蛋白的研究有助于深入了解gp41在HIV-1感染整个过程中扮演的角色,解释gp41对靶细胞的调控机制,为寻找新的抗艾滋病药物靶点以及艾滋病抑制剂的设计提供有益的思路.作者的实验室相继发现了一批与gp41六螺旋结构相互作用的蛋白质,进而对HIV-1 gp41六螺旋介导的膜融合过程和HIV-1感染机理有了更深入的了解.

  14. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication

    DEFF Research Database (Denmark)

    Meschi, Joseph; Crouch, Erika C; Skolnik, Paul;

    2005-01-01

    The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL......) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate...... defence against HIV. A chimeric protein containing the N-terminal and collagen domains of SP-D linked to the neck and carbohydrate-recognition domains of MBL (called SP-D/MBL(neck+CRD)) had greater ability to bind to gp120 and inhibit virus replication than either SP-D or MBL. The enhanced binding of SP...

  15. Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus.

    Science.gov (United States)

    Lee, Andrew M; Cruite, Justin; Welch, Megan J; Sullivan, Brian; Oldstone, Michael B A

    2013-08-01

    Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8(+) T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13.

  16. Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

    DEFF Research Database (Denmark)

    Kemp, M; Hey, A S; Bendtzen, K

    1994-01-01

    The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... self-healing cutaneous leishmaniasis. The T-cell clones expressed CD4, and the alpha chain of the T-cell antigen receptor. GP63 reactive T-cell clones activated by antigen or by immobilized anti-CD3 antibody released relative large amounts of interferon-gamma and no or little interleukin-4, thereby...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...

  17. The Wouthuysen equation

    NARCIS (Netherlands)

    Hazewinkel, M.

    1995-01-01

    Dedication: I dedicate this paper to Prof. P.C. Baayen, at the occasion of his retirement on 20 December 1994. The beautiful equation which forms the subject matter of this paper was invented by Wouthuysen after he retired. The four complex variable Wouthuysen equation arises from an original space-

  18. Functional Cantor equation

    Science.gov (United States)

    Shabat, A. B.

    2016-12-01

    We consider the class of entire functions of exponential type in relation to the scattering theory for the Schrödinger equation with a finite potential that is a finite Borel measure. These functions have a special self-similarity and satisfy q-difference functional equations. We study their asymptotic behavior and the distribution of zeros.

  19. Dissipative Boussinesq equations

    CERN Document Server

    Dutykh, D; Dias, Fr\\'{e}d\\'{e}ric; Dutykh, Denys

    2007-01-01

    The classical theory of water waves is based on the theory of inviscid flows. However it is important to include viscous effects in some applications. Two models are proposed to add dissipative effects in the context of the Boussinesq equations, which include the effects of weak dispersion and nonlinearity in a shallow water framework. The dissipative Boussinesq equations are then integrated numerically.

  20. Navier-Stokes equation

    Directory of Open Access Journals (Sweden)

    Hannelore Breckner

    2000-01-01

    Full Text Available We consider a stochastic equation of Navier-Stokes type containing a noise part given by a stochastic integral with respect to a Wiener process. The purpose of this paper is to approximate the solution of this nonlinear equation by the Galerkin method. We prove the convergence in mean square.