A conjugate gradient method for solving the non-LTE line radiation transfer problem

NASA Astrophysics Data System (ADS)

Paletou, F.; Anterrieu, E.

2009-12-01

This study concerns the fast and accurate solution of the line radiation transfer problem, under non-LTE conditions. We propose and evaluate an alternative iterative scheme to the classical ALI-Jacobi method, and to the more recently proposed Gauss-Seidel and successive over-relaxation (GS/SOR) schemes. Our study is indeed based on applying a preconditioned bi-conjugate gradient method (BiCG-P). Standard tests, in 1D plane parallel geometry and in the frame of the two-level atom model with monochromatic scattering are discussed. Rates of convergence between the previously mentioned iterative schemes are compared, as are their respective timing properties. The smoothing capability of the BiCG-P method is also demonstrated.

Three-dimensional forward modeling of DC resistivity using the aggregation-based algebraic multigrid method

NASA Astrophysics Data System (ADS)

Chen, Hui; Deng, Ju-Zhi; Yin, Min; Yin, Chang-Chun; Tang, Wen-Wu

2017-03-01

To speed up three-dimensional (3D) DC resistivity modeling, we present a new multigrid method, the aggregation-based algebraic multigrid method (AGMG). We first discretize the differential equation of the secondary potential field with mixed boundary conditions by using a seven-point finite-difference method to obtain a large sparse system of linear equations. Then, we introduce the theory behind the pairwise aggregation algorithms for AGMG and use the conjugate-gradient method with the V-cycle AGMG preconditioner (AGMG-CG) to solve the linear equations. We use typical geoelectrical models to test the proposed AGMG-CG method and compare the results with analytical solutions and the 3DDCXH algorithm for 3D DC modeling (3DDCXH). In addition, we apply the AGMG-CG method to different grid sizes and geoelectrical models and compare it to different iterative methods, such as ILU-BICGSTAB, ILU-GCR, and SSOR-CG. The AGMG-CG method yields nearly linearly decreasing errors, whereas the number of iterations increases slowly with increasing grid size. The AGMG-CG method is precise and converges fast, and thus can improve the computational efficiency in forward modeling of three-dimensional DC resistivity.

A modified three-term PRP conjugate gradient algorithm for optimization models.

PubMed

Wu, Yanlin

2017-01-01

The nonlinear conjugate gradient (CG) algorithm is a very effective method for optimization, especially for large-scale problems, because of its low memory requirement and simplicity. Zhang et al. (IMA J. Numer. Anal. 26:629-649, 2006) firstly propose a three-term CG algorithm based on the well known Polak-Ribière-Polyak (PRP) formula for unconstrained optimization, where their method has the sufficient descent property without any line search technique. They proved the global convergence of the Armijo line search but this fails for the Wolfe line search technique. Inspired by their method, we will make a further study and give a modified three-term PRP CG algorithm. The presented method possesses the following features: (1) The sufficient descent property also holds without any line search technique; (2) the trust region property of the search direction is automatically satisfied; (3) the steplengh is bounded from below; (4) the global convergence will be established under the Wolfe line search. Numerical results show that the new algorithm is more effective than that of the normal method.

GPU computing with Kaczmarz’s and other iterative algorithms for linear systems

PubMed Central

Elble, Joseph M.; Sahinidis, Nikolaos V.; Vouzis, Panagiotis

2009-01-01

The graphics processing unit (GPU) is used to solve large linear systems derived from partial differential equations. The differential equations studied are strongly convection-dominated, of various sizes, and common to many fields, including computational fluid dynamics, heat transfer, and structural mechanics. The paper presents comparisons between GPU and CPU implementations of several well-known iterative methods, including Kaczmarz’s, Cimmino’s, component averaging, conjugate gradient normal residual (CGNR), symmetric successive overrelaxation-preconditioned conjugate gradient, and conjugate-gradient-accelerated component-averaged row projections (CARP-CG). Computations are preformed with dense as well as general banded systems. The results demonstrate that our GPU implementation outperforms CPU implementations of these algorithms, as well as previously studied parallel implementations on Linux clusters and shared memory systems. While the CGNR method had begun to fall out of favor for solving such problems, for the problems studied in this paper, the CGNR method implemented on the GPU performed better than the other methods, including a cluster implementation of the CARP-CG method. PMID:20526446

Moving force identification based on modified preconditioned conjugate gradient method

NASA Astrophysics Data System (ADS)

Chen, Zhen; Chan, Tommy H. T.; Nguyen, Andy

2018-06-01

This paper develops a modified preconditioned conjugate gradient (M-PCG) method for moving force identification (MFI) by improving the conjugate gradient (CG) and preconditioned conjugate gradient (PCG) methods with a modified Gram-Schmidt algorithm. The method aims to obtain more accurate and more efficient identification results from the responses of bridge deck caused by vehicles passing by, which are known to be sensitive to ill-posed problems that exist in the inverse problem. A simply supported beam model with biaxial time-varying forces is used to generate numerical simulations with various analysis scenarios to assess the effectiveness of the method. Evaluation results show that regularization matrix L and number of iterations j are very important influence factors to identification accuracy and noise immunity of M-PCG. Compared with the conventional counterpart SVD embedded in the time domain method (TDM) and the standard form of CG, the M-PCG with proper regularization matrix has many advantages such as better adaptability and more robust to ill-posed problems. More importantly, it is shown that the average optimal numbers of iterations of M-PCG can be reduced by more than 70% compared with PCG and this apparently makes M-PCG a preferred choice for field MFI applications.

A BiCGStab2 variant of the IDR(s) method for solving linear equations

NASA Astrophysics Data System (ADS)

Abe, Kuniyoshi; Sleijpen, Gerard L. G.

2012-09-01

The hybrid Bi-Conjugate Gradient (Bi-CG) methods, such as the BiCG STABilized (BiCGSTAB), BiCGstab(l), BiCGStab2 and BiCG×MR2 methods are well-known solvers for solving a linear equation with a nonsymmetric matrix. The Induced Dimension Reduction (IDR)(s) method has recently been proposed, and it has been reported that IDR(s) is often more effective than the hybrid BiCG methods. IDR(s) combining the stabilization polynomial of BiCGstab(l) has been designed to improve the convergence of the original IDR(s) method. We therefore propose IDR(s) combining the stabilization polynomial of BiCGStab2. Numerical experiments show that our proposed variant of IDR(s) is more effective than the original IDR(s) and BiCGStab2 methods.

Conjugate-gradient preconditioning methods for shift-variant PET image reconstruction.

PubMed

Fessler, J A; Booth, S D

1999-01-01

Gradient-based iterative methods often converge slowly for tomographic image reconstruction and image restoration problems, but can be accelerated by suitable preconditioners. Diagonal preconditioners offer some improvement in convergence rate, but do not incorporate the structure of the Hessian matrices in imaging problems. Circulant preconditioners can provide remarkable acceleration for inverse problems that are approximately shift-invariant, i.e., for those with approximately block-Toeplitz or block-circulant Hessians. However, in applications with nonuniform noise variance, such as arises from Poisson statistics in emission tomography and in quantum-limited optical imaging, the Hessian of the weighted least-squares objective function is quite shift-variant, and circulant preconditioners perform poorly. Additional shift-variance is caused by edge-preserving regularization methods based on nonquadratic penalty functions. This paper describes new preconditioners that approximate more accurately the Hessian matrices of shift-variant imaging problems. Compared to diagonal or circulant preconditioning, the new preconditioners lead to significantly faster convergence rates for the unconstrained conjugate-gradient (CG) iteration. We also propose a new efficient method for the line-search step required by CG methods. Applications to positron emission tomography (PET) illustrate the method.

Fast Quantitative Susceptibility Mapping with L1-Regularization and Automatic Parameter Selection

PubMed Central

Bilgic, Berkin; Fan, Audrey P.; Polimeni, Jonathan R.; Cauley, Stephen F.; Bianciardi, Marta; Adalsteinsson, Elfar; Wald, Lawrence L.; Setsompop, Kawin

2014-01-01

Purpose To enable fast reconstruction of quantitative susceptibility maps with Total Variation penalty and automatic regularization parameter selection. Methods ℓ1-regularized susceptibility mapping is accelerated by variable-splitting, which allows closed-form evaluation of each iteration of the algorithm by soft thresholding and FFTs. This fast algorithm also renders automatic regularization parameter estimation practical. A weighting mask derived from the magnitude signal can be incorporated to allow edge-aware regularization. Results Compared to the nonlinear Conjugate Gradient (CG) solver, the proposed method offers 20× speed-up in reconstruction time. A complete pipeline including Laplacian phase unwrapping, background phase removal with SHARP filtering and ℓ1-regularized dipole inversion at 0.6 mm isotropic resolution is completed in 1.2 minutes using Matlab on a standard workstation compared to 22 minutes using the Conjugate Gradient solver. This fast reconstruction allows estimation of regularization parameters with the L-curve method in 13 minutes, which would have taken 4 hours with the CG algorithm. Proposed method also permits magnitude-weighted regularization, which prevents smoothing across edges identified on the magnitude signal. This more complicated optimization problem is solved 5× faster than the nonlinear CG approach. Utility of the proposed method is also demonstrated in functional BOLD susceptibility mapping, where processing of the massive time-series dataset would otherwise be prohibitive with the CG solver. Conclusion Online reconstruction of regularized susceptibility maps may become feasible with the proposed dipole inversion. PMID:24259479

A constrained-gradient method to control divergence errors in numerical MHD

NASA Astrophysics Data System (ADS)

Hopkins, Philip F.

2016-10-01

In numerical magnetohydrodynamics (MHD), a major challenge is maintaining nabla \\cdot {B}=0. Constrained transport (CT) schemes achieve this but have been restricted to specific methods. For more general (meshless, moving-mesh, ALE) methods, `divergence-cleaning' schemes reduce the nabla \\cdot {B} errors; however they can still be significant and can lead to systematic errors which converge away slowly. We propose a new constrained gradient (CG) scheme which augments these with a projection step, and can be applied to any numerical scheme with a reconstruction. This iteratively approximates the least-squares minimizing, globally divergence-free reconstruction of the fluid. Unlike `locally divergence free' methods, this actually minimizes the numerically unstable nabla \\cdot {B} terms, without affecting the convergence order of the method. We implement this in the mesh-free code GIZMO and compare various test problems. Compared to cleaning schemes, our CG method reduces the maximum nabla \\cdot {B} errors by ˜1-3 orders of magnitude (˜2-5 dex below typical errors if no nabla \\cdot {B} cleaning is used). By preventing large nabla \\cdot {B} at discontinuities, this eliminates systematic errors at jumps. Our CG results are comparable to CT methods; for practical purposes, the nabla \\cdot {B} errors are eliminated. The cost is modest, ˜30 per cent of the hydro algorithm, and the CG correction can be implemented in a range of numerical MHD methods. While for many problems, we find Dedner-type cleaning schemes are sufficient for good results, we identify a range of problems where using only Powell or `8-wave' cleaning can produce order-of-magnitude errors.

Performance comparison of a new hybrid conjugate gradient method under exact and inexact line searches

NASA Astrophysics Data System (ADS)

Ghani, N. H. A.; Mohamed, N. S.; Zull, N.; Shoid, S.; Rivaie, M.; Mamat, M.

2017-09-01

Conjugate gradient (CG) method is one of iterative techniques prominently used in solving unconstrained optimization problems due to its simplicity, low memory storage, and good convergence analysis. This paper presents a new hybrid conjugate gradient method, named NRM1 method. The method is analyzed under the exact and inexact line searches in given conditions. Theoretically, proofs show that the NRM1 method satisfies the sufficient descent condition with both line searches. The computational result indicates that NRM1 method is capable in solving the standard unconstrained optimization problems used. On the other hand, the NRM1 method performs better under inexact line search compared with exact line search.

Myocardial perfusion magnetic resonance imaging using sliding-window conjugate-gradient HYPR methods in canine with stenotic coronary arteries.

PubMed

Ge, Lan; Kino, Aya; Lee, Daniel; Dharmakumar, Rohan; Carr, James C; Li, Debiao

2010-01-01

First-pass perfusion magnetic resonance imaging (MRI) is a promising technique for detecting ischemic heart disease. However, the diagnostic value of the method is limited by the low spatial coverage, resolution, signal-to-noise ratio (SNR), and cardiac motion-related image artifacts. A combination of sliding window and conjugate-gradient HighlY constrained back-PRojection reconstruction (SW-CG-HYPR) method has been proposed in healthy volunteer studies to reduce the acquisition window for each slice while maintaining the temporal resolution of 1 frame per heartbeat in myocardial perfusion MRI. This method allows for improved spatial coverage, resolution, and SNR. In this study, we use a controlled animal model to test whether the myocardial territory supplied by a stenotic coronary artery can be detected accurately by SW-CG-HYPR perfusion method under pharmacological stress. Results from 6 mongrel dogs (15-25 kg) studies demonstrate the feasibility of SW-CG-HYPR to detect regional perfusion defects. Using this method, the acquisition time per cardiac cycle was reduced by a factor of 4, and the spatial coverage was increased from 2 to 3 slices to 6 slices as compared with the conventional techniques including both turbo-Fast Low Angle Short (FLASH) and echoplanar imaging (EPI). The SNR of the healthy myocardium at peak enhancement with SW-CG-HYPR (12.68 ± 2.46) is significantly higher (P < 0.01) than the turbo-FLASH (8.65 ± 1.93) and EPI (5.48 ± 1.24). The spatial resolution of SW-CG-HYPR images is 1.2 × 1.2 × 8.0 mm, which is better than the turbo-FLASH (1.8 × 1.8 × 8.0 mm) and EPI (2.0 × 1.8 × 8.0 mm). Sliding-window CG-HYPR is a promising technique for myocardial perfusion MRI. This technique provides higher image quality with respect to significantly improved SNR and spatial resolution of the myocardial perfusion images, which might improve myocardial perfusion imaging in a clinical setting.

Adjustment technique without explicit formation of normal equations /conjugate gradient method/

NASA Technical Reports Server (NTRS)

Saxena, N. K.

1974-01-01

For a simultaneous adjustment of a large geodetic triangulation system, a semiiterative technique is modified and used successfully. In this semiiterative technique, known as the conjugate gradient (CG) method, original observation equations are used, and thus the explicit formation of normal equations is avoided, 'huge' computer storage space being saved in the case of triangulation systems. This method is suitable even for very poorly conditioned systems where solution is obtained only after more iterations. A detailed study of the CG method for its application to large geodetic triangulation systems was done that also considered constraint equations with observation equations. It was programmed and tested on systems as small as two unknowns and three equations up to those as large as 804 unknowns and 1397 equations. When real data (573 unknowns, 965 equations) from a 1858-km-long triangulation system were used, a solution vector accurate to four decimal places was obtained in 2.96 min after 1171 iterations (i.e., 2.0 times the number of unknowns).

A combined finite element-boundary integral formulation for solution of two-dimensional scattering problems via CGFFT. [Conjugate Gradient Fast Fourier Transformation

NASA Technical Reports Server (NTRS)

Collins, Jeffery D.; Volakis, John L.; Jin, Jian-Ming

1990-01-01

A new technique is presented for computing the scattering by 2-D structures of arbitrary composition. The proposed solution approach combines the usual finite element method with the boundary-integral equation to formulate a discrete system. This is subsequently solved via the conjugate gradient (CG) algorithm. A particular characteristic of the method is the use of rectangular boundaries to enclose the scatterer. Several of the resulting boundary integrals are therefore convolutions and may be evaluated via the fast Fourier transform (FFT) in the implementation of the CG algorithm. The solution approach offers the principal advantage of having O(N) memory demand and employs a 1-D FFT versus a 2-D FFT as required with a traditional implementation of the CGFFT algorithm. The speed of the proposed solution method is compared with that of the traditional CGFFT algorithm, and results for rectangular bodies are given and shown to be in excellent agreement with the moment method.

Gonadotropin stimulation of cyclic adenosine monophosphate and testosterone production without detectable high-affinity binding sites in purified Leydig cells from rat testis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Browne, E.S.; Bhalla, V.K.

1991-02-01

Rat testicular interstitial cells were separated by three different gradient-density procedures and, with each, two biochemically and morphologically distinct cell fractions were isolated. The lighter density cells in fraction-I bound iodine 125-labeled human chorionic gonadotropin (hCG) with high-affinity (apparent equilibrium dissociation constant, Kd, approximately 10{sup {minus} 10} M) without producing either cyclic adenosine monophosphate or testosterone in response to hormone action. The heavier-density cells displayed morphologic features typical of Leydig cells and produced cyclic adenosine monophosphate and testosterone in the presence of hCG without detectable {sup 125}I-labeled hCG high-affinity binding. These cell fractions were further characterized by studies using deglycosylatedmore » hCG, a known antagonist to hCG action. Cell concentration-dependent studies with purified Leydig cells revealed that maximal testosterone production was achieved when lower cell concentrations (0.5 x 10(6) cells/250 microliters) were used for in vitro hCG stimulation assays. Under these conditions, the {sup 125}I-labeled hCG binding was barely detectable (2.24 fmol; 2,698 sites/cell). Furthermore, these studies revealed that the hCG-specific binding in Leydig cells is overestimated by the classic method for nonspecific binding correction using excess unlabeled hormone. An alternate method is presented.« less

Two-step reconstruction method using global optimization and conjugate gradient for ultrasound-guided diffuse optical tomography.

PubMed

Tavakoli, Behnoosh; Zhu, Quing

2013-01-01

Ultrasound-guided diffuse optical tomography (DOT) is a promising method for characterizing malignant and benign lesions in the female breast. We introduce a new two-step algorithm for DOT inversion in which the optical parameters are estimated with the global optimization method, genetic algorithm. The estimation result is applied as an initial guess to the conjugate gradient (CG) optimization method to obtain the absorption and scattering distributions simultaneously. Simulations and phantom experiments have shown that the maximum absorption and reduced scattering coefficients are reconstructed with less than 10% and 25% errors, respectively. This is in contrast with the CG method alone, which generates about 20% error for the absorption coefficient and does not accurately recover the scattering distribution. A new measure of scattering contrast has been introduced to characterize benign and malignant breast lesions. The results of 16 clinical cases reconstructed with the two-step method demonstrates that, on average, the absorption coefficient and scattering contrast of malignant lesions are about 1.8 and 3.32 times higher than the benign cases, respectively.

Layout optimization with algebraic multigrid methods

NASA Technical Reports Server (NTRS)

Regler, Hans; Ruede, Ulrich

1993-01-01

Finding the optimal position for the individual cells (also called functional modules) on the chip surface is an important and difficult step in the design of integrated circuits. This paper deals with the problem of relative placement, that is the minimization of a quadratic functional with a large, sparse, positive definite system matrix. The basic optimization problem must be augmented by constraints to inhibit solutions where cells overlap. Besides classical iterative methods, based on conjugate gradients (CG), we show that algebraic multigrid methods (AMG) provide an interesting alternative. For moderately sized examples with about 10000 cells, AMG is already competitive with CG and is expected to be superior for larger problems. Besides the classical 'multiplicative' AMG algorithm where the levels are visited sequentially, we propose an 'additive' variant of AMG where levels may be treated in parallel and that is suitable as a preconditioner in the CG algorithm.

Multigrid accelerated simulations for Twisted Mass fermions

NASA Astrophysics Data System (ADS)

Bacchio, Simone; Alexandrou, Constantia; Finkerath, Jacob

2018-03-01

Simulations at physical quark masses are affected by the critical slowing down of the solvers. Multigrid preconditioning has proved to deal effectively with this problem. Multigrid accelerated simulations at the physical value of the pion mass are being performed to generate Nf = 2 and Nf = 2 + 1 + 1 gauge ensembles using twisted mass fermions. The adaptive aggregation-based domain decomposition multigrid solver, referred to as DD-αAMG method, is employed for these simulations. Our simulation strategy consists of an hybrid approach of different solvers, involving the Conjugate Gradient (CG), multi-mass-shift CG and DD-αAMG solvers. We present an analysis of the multigrid performance during the simulations discussing the stability of the method. This significant speeds up the Hybrid Monte Carlo simulation by more than a factor 4 at physical pion mass compared to the usage of the CG solver.

Myocardial perfusion MRI with sliding-window conjugate-gradient HYPR.

PubMed

Ge, Lan; Kino, Aya; Griswold, Mark; Mistretta, Charles; Carr, James C; Li, Debiao

2009-10-01

First-pass perfusion MRI is a promising technique for detecting ischemic heart disease. However, the diagnostic value of the method is limited by the low spatial coverage, resolution, signal-to-noise ratio (SNR), and cardiac motion-related image artifacts. In this study we investigated the feasibility of using a method that combines sliding window and CG-HYPR methods (SW-CG-HYPR) to reduce the acquisition window for each slice while maintaining the temporal resolution of one frame per heartbeat in myocardial perfusion MRI. This method allows an increased number of slices, reduced motion artifacts, and preserves the relatively high SNR and spatial resolution of the "composite images." Results from eight volunteers demonstrate the feasibility of SW-CG-HYPR for accelerated myocardial perfusion imaging with accurate signal intensity changes of left ventricle blood pool and myocardium. Using this method the acquisition time per cardiac cycle was reduced by a factor of 4 and the number of slices was increased from 3 to 8 as compared to the conventional technique. The SNR of the myocardium at peak enhancement with SW-CG-HYPR (13.83 +/- 2.60) was significantly higher (P < 0.05) than the conventional turbo-FLASH protocol (8.40 +/- 1.62). Also, the spatial resolution of the myocardial perfection images was significantly improved. SW-CG-HYPR is a promising technique for myocardial perfusion MRI. (c) 2009 Wiley-Liss, Inc.

Speed and convergence properties of gradient algorithms for optimization of IMRT.

PubMed

Zhang, Xiaodong; Liu, Helen; Wang, Xiaochun; Dong, Lei; Wu, Qiuwen; Mohan, Radhe

2004-05-01

Gradient algorithms are the most commonly employed search methods in the routine optimization of IMRT plans. It is well known that local minima can exist for dose-volume-based and biology-based objective functions. The purpose of this paper is to compare the relative speed of different gradient algorithms, to investigate the strategies for accelerating the optimization process, to assess the validity of these strategies, and to study the convergence properties of these algorithms for dose-volume and biological objective functions. With these aims in mind, we implemented Newton's, conjugate gradient (CG), and the steepest decent (SD) algorithms for dose-volume- and EUD-based objective functions. Our implementation of Newton's algorithm approximates the second derivative matrix (Hessian) by its diagonal. The standard SD algorithm and the CG algorithm with "line minimization" were also implemented. In addition, we investigated the use of a variation of the CG algorithm, called the "scaled conjugate gradient" (SCG) algorithm. To accelerate the optimization process, we investigated the validity of the use of a "hybrid optimization" strategy, in which approximations to calculated dose distributions are used during most of the iterations. Published studies have indicated that getting trapped in local minima is not a significant problem. To investigate this issue further, we first obtained, by trial and error, and starting with uniform intensity distributions, the parameters of the dose-volume- or EUD-based objective functions which produced IMRT plans that satisfied the clinical requirements. Using the resulting optimized intensity distributions as the initial guess, we investigated the possibility of getting trapped in a local minimum. For most of the results presented, we used a lung cancer case. To illustrate the generality of our methods, the results for a prostate case are also presented. For both dose-volume and EUD based objective functions, Newton's method far outperforms other algorithms in terms of speed. The SCG algorithm, which avoids expensive "line minimization," can speed up the standard CG algorithm by at least a factor of 2. For the same initial conditions, all algorithms converge essentially to the same plan. However, we demonstrate that for any of the algorithms studied, starting with previously optimized intensity distributions as the initial guess but for different objective function parameters, the solution frequently gets trapped in local minima. We found that the initial intensity distribution obtained from IMRT optimization utilizing objective function parameters, which favor a specific anatomic structure, would lead to a local minimum corresponding to that structure. Our results indicate that from among the gradient algorithms tested, Newton's method appears to be the fastest by far. Different gradient algorithms have the same convergence properties for dose-volume- and EUD-based objective functions. The hybrid dose calculation strategy is valid and can significantly accelerate the optimization process. The degree of acceleration achieved depends on the type of optimization problem being addressed (e.g., IMRT optimization, intensity modulated beam configuration optimization, or objective function parameter optimization). Under special conditions, gradient algorithms will get trapped in local minima, and reoptimization, starting with the results of previous optimization, will lead to solutions that are generally not significantly different from the local minimum.

On the electromagnetic scattering from infinite rectangular grids with finite conductivity

NASA Technical Reports Server (NTRS)

Christodoulou, C. G.; Kauffman, J. F.

1986-01-01

A variety of methods can be used in constructing solutions to the problem of mesh scattering. However, each of these methods has certain drawbacks. The present paper is concerned with a new technique which is valid for all spacings. The new method involved, called the fast Fourier transform-conjugate gradient method (FFT-CGM), represents an iterative technique which employs the conjugate gradient method to improve upon each iterate, utilizing the fast Fourier transform. The FFT-CGM method provides a new accurate model which can be extended and applied to the more difficult problems of woven mesh surfaces. The formulation of the FFT-conjugate gradient method for aperture fields and current densities for a planar periodic structure is considered along with singular operators, the formulation of the FFT-CG method for thin wires with finite conductivity, and reflection coefficients.

Parallel Conjugate Gradient: Effects of Ordering Strategies, Programming Paradigms, and Architectural Platforms

NASA Technical Reports Server (NTRS)

Oliker, Leonid; Heber, Gerd; Biswas, Rupak

2000-01-01

The Conjugate Gradient (CG) algorithm is perhaps the best-known iterative technique to solve sparse linear systems that are symmetric and positive definite. A sparse matrix-vector multiply (SPMV) usually accounts for most of the floating-point operations within a CG iteration. In this paper, we investigate the effects of various ordering and partitioning strategies on the performance of parallel CG and SPMV using different programming paradigms and architectures. Results show that for this class of applications, ordering significantly improves overall performance, that cache reuse may be more important than reducing communication, and that it is possible to achieve message passing performance using shared memory constructs through careful data ordering and distribution. However, a multi-threaded implementation of CG on the Tera MTA does not require special ordering or partitioning to obtain high efficiency and scalability.

Age- and gender-related regional variations of human brain cortical thickness, complexity, and gradient in the third decade.

PubMed

Creze, Maud; Versheure, Leslie; Besson, Pierre; Sauvage, Chloe; Leclerc, Xavier; Jissendi-Tchofo, Patrice

2014-06-01

Brain functional and cytoarchitectural maturation continue until adulthood, but little is known about the evolution of the regional pattern of cortical thickness (CT), complexity (CC), and intensity or gradient (CG) in young adults. We attempted to detect global and regional age- and gender-related variations of brain CT, CC, and CG, in 28 healthy young adults (19-33 years) using a three-dimensional T1 -weighted magnetic resonance imaging sequence and surface-based methods. Whole brain interindividual variations of CT and CG were similar to that in the literature. As a new finding, age- and gender-related variations significantly affected brain complexity (P < 0.01) on posterior cingulate and middle temporal cortices (age), and the fronto-orbital cortex (gender), all in the right hemisphere. Regions of interest analyses showed age and gender significant interaction (P < 0.05) on the temporopolar, inferior, and middle temporal-entorrhinal cortices bilaterally, as well as left inferior parietal. In addition, we found significant inverse correlations between CT and CC and between CT and CG over the whole brain and markedly in precentral and occipital areas. Our findings differ in details from previous reports and may correlate with late brain maturation and learning plasticity in young adults' brain in the third decade. Copyright © 2013 Wiley Periodicals, Inc.

Preserving Symmetry in Preconditioned Krylov Subspace Methods

NASA Technical Reports Server (NTRS)

Chan, Tony F.; Chow, E.; Saad, Y.; Yeung, M. C.

1996-01-01

We consider the problem of solving a linear system Ax = b when A is nearly symmetric and when the system is preconditioned by a symmetric positive definite matrix M. In the symmetric case, one can recover symmetry by using M-inner products in the conjugate gradient (CG) algorithm. This idea can also be used in the nonsymmetric case, and near symmetry can be preserved similarly. Like CG, the new algorithms are mathematically equivalent to split preconditioning, but do not require M to be factored. Better robustness in a specific sense can also be observed. When combined with truncated versions of iterative methods, tests show that this is more effective than the common practice of forfeiting near-symmetry altogether.

Exploring chemical reaction mechanisms through harmonic Fourier beads path optimization.

PubMed

Khavrutskii, Ilja V; Smith, Jason B; Wallqvist, Anders

2013-10-28

Here, we apply the harmonic Fourier beads (HFB) path optimization method to study chemical reactions involving covalent bond breaking and forming on quantum mechanical (QM) and hybrid QM∕molecular mechanical (QM∕MM) potential energy surfaces. To improve efficiency of the path optimization on such computationally demanding potentials, we combined HFB with conjugate gradient (CG) optimization. The combined CG-HFB method was used to study two biologically relevant reactions, namely, L- to D-alanine amino acid inversion and alcohol acylation by amides. The optimized paths revealed several unexpected reaction steps in the gas phase. For example, on the B3LYP∕6-31G(d,p) potential, we found that alanine inversion proceeded via previously unknown intermediates, 2-iminopropane-1,1-diol and 3-amino-3-methyloxiran-2-ol. The CG-HFB method accurately located transition states, aiding in the interpretation of complex reaction mechanisms. Thus, on the B3LYP∕6-31G(d,p) potential, the gas phase activation barriers for the inversion and acylation reactions were 50.5 and 39.9 kcal∕mol, respectively. These barriers determine the spontaneous loss of amino acid chirality and cleavage of peptide bonds in proteins. We conclude that the combined CG-HFB method further advances QM and QM∕MM studies of reaction mechanisms.

A fast pulse design for parallel excitation with gridding conjugate gradient.

PubMed

Feng, Shuo; Ji, Jim

2013-01-01

Parallel excitation (pTx) is recognized as a crucial technique in high field MRI to address the transmit field inhomogeneity problem. However, it can be time consuming to design pTx pulses which is not desirable. In this work, we propose a pulse design with gridding conjugate gradient (CG) based on the small-tip-angle approximation. The two major time consuming matrix-vector multiplications are substituted by two operators which involves with FFT and gridding only. Simulation results have shown that the proposed method is 3 times faster than conventional method and the memory cost is reduced by 1000 times.

Sensitive method for the quantitative determination of proguanil and its metabolites in rat blood and plasma by liquid chromatography-mass spectrometry.

PubMed

Leveque, Nathalie L; Charman, William N; Chiu, Francis C K

2006-01-18

A sensitive, simple and fast liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the determination of proguanil (PG) and its metabolites, cycloguanil (CG) and 1-(4-chlorophenyl)biguanide (4CPB), was developed and validated over a concentration range of 1-2000 ng/mL using only 50 microL of blood or plasma. After a simple solvent precipitation procedure, the supernatant was analysed directly by HPLC-MS/MS. Separation was achieved using an ethyl-linked phenyl reverse phase column with polar endcapping with an acetonitrile-water-formic acid gradient. Mass spectrometry was performed using a triple quadrupole mass spectrometer operating in positive electrospray ionization mode. The elution of PG (254.07-->169.99), CG (252.12-->195.02) and 4CPB (212.06-->153.06) was monitored using selected reaction monitoring. The three compounds and the internal standard (chloroproguanil) were well separated by HPLC and no interfering peaks were detected at the usual concentrations found in blood and plasma. The limit of quantification of PG and CG was 1 ng/mL and 5 ng/mL for 4CPB in rat blood and plasma. The extraction efficiency of PG, CG and 4CPB from rat blood and plasma was higher than 73%. The intra- and inter-assay variability of PG, CG and 4CPB were within 12% and the accuracy within +/-5%. This new assay offers higher sensitivity and a much shorter run time over earlier methods.

PSO-Assisted Development of New Transferable Coarse-Grained Water Models.

PubMed

Bejagam, Karteek K; Singh, Samrendra; An, Yaxin; Berry, Carter; Deshmukh, Sanket A

2018-02-15

We have employed two-to-one mapping scheme to develop three coarse-grained (CG) water models, namely, 1-, 2-, and 3-site CG models. Here, for the first time, particle swarm optimization (PSO) and gradient descent methods were coupled to optimize the force-field parameters of the CG models to reproduce the density, self-diffusion coefficient, and dielectric constant of real water at 300 K. The CG MD simulations of these new models conducted with various timesteps, for different system sizes, and at a range of different temperatures are able to predict the density, self-diffusion coefficient, dielectric constant, surface tension, heat of vaporization, hydration free energy, and isothermal compressibility of real water with excellent accuracy. The 1-site model is ∼3 and ∼4.5 times computationally more efficient than 2- and 3-site models, respectively. To utilize the speed of 1-site model and electrostatic interactions offered by 2- and 3-site models, CG MD simulations of 1:1 combination of 1- and 2-/3-site models were performed at 300 K. These mixture simulations could also predict the properties of real water with good accuracy. Two new CG models of benzene, consisting of beads with and without partial charges, were developed. All three water models showed good capacity to solvate these benzene models.

First Impressions of a Scintrex CG-6 Portable Gravimeter in an Extensive Field Campaign

NASA Astrophysics Data System (ADS)

van Westrum, D.; Kanney, J.

2017-12-01

First Impressions of a Scintrex CG-6 Portable Gravimeter in an Extensive Field Campaign AGU Fall Meeting 2017 Derek van Westrum and Jeff Kanney NOAA's National Geodetic Survey conducted its third and final Geoid Slope Validation Survey (GSVS) this past summer in the rugged mountains of southern Colorado. In addition to leveling, long period GPS, and defelction of vertical observations, absolute gravity and vertical gravity gradients were measured at 235 bench marks (approximately 1.5 km spacing) along US-160 between Durango and Walsenburg, Colorado. In previous surveys (Texas-2011 and Iowa-2014), an A10 absolute gravimeter was used to measure graivty at approximately 10-15% of the bench marks. The remaining marks were determined by using LaCoste & Romberg relative gravimeters. The same relative instruments were also used to measure two-tier (linear) vertical gravity gradients at the A10 sites. In the current work - becuase of the rapidly changing terrain in the Rocky Mountains - it was decided to employ the A10 at all 235 bench marks, and acquire three-tier (quadratic) gradients at every bench mark using the new Scintrex CG-6 Autograv relative gravimeter. Using these results, we will provide a real worldsummary of the CG-6's behavior by examining noise levels, repeatability, and acquisition rates. In addition, the coincident A10 absolute data set allows us to evaluate the CG-6's accuracy, and allows us to simulate and discuss various relative gravity survey designs.

Bauschinger Effect and Back Stress in Gradient Cu-Ge Alloy

NASA Astrophysics Data System (ADS)

Hu, Xianzhi; Jin, Shenbao; Zhou, Hao; Yin, Zhe; Yang, Jian; Gong, Yulan; Zhu, Yuntian; Sha, Gang; Zhu, Xinkun

2017-09-01

Using surface mechanical attrition treatment (SMAT), a gradient structure composed of two gradient structure (GS) layers and a coarse grain (CG) layer was generated from a Cu-5.7 wt pct Ge alloy, significantly improving the yield strength of the sample. Unloading-reloading tests showed an unusual Bauschinger effect in these GS samples. The back stresses caused by the accumulated geometrically necessary dislocations (GNDs) on the GS/CG border increased with increasing strain. As found by electron backscatter diffraction (EBSD), the GNDs are mainly distributed in the gradient structured layer, and the density of the GNDs increase with increasing SMAT time. The effect of the back stress increased with increasing SMAT processing time due to the increase in the strain gradient. The pronounced Bauschinger effect in a GS sample can improve the resistance to forward plastic flow and finally contributes to the high strength of GS samples.

Determination of the second virial coefficient of bovine serum albumin under varying pH and ionic strength by composition-gradient multi-angle static light scattering.

PubMed

Ma, Yingfang; Acosta, Diana M; Whitney, Jon R; Podgornik, Rudolf; Steinmetz, Nicole F; French, Roger H; Parsegian, V Adrian

2015-01-01

Composition-gradient multi-angle static light scattering (CG-MALS) is an emerging technique for the determination of intermolecular interactions via the second virial coefficient B22. With CG-MALS, detailed studies of the second virial coefficient can be carried out more accurately and effectively than with traditional methods. In addition, automated mixing, delivery and measurement enable high speed, continuous, fluctuation-free sample delivery and accurate results. Using CG-MALS we measure the second virial coefficient of bovine serum albumin (BSA) in aqueous solutions at various values of pH and ionic strength of a univalent salt (NaCl). The systematic variation of the second virial coefficient as a function of pH and NaCl strength reveals the net charge change and the isoelectric point of BSA under different solution conditions. The magnitude of the second virial coefficient decreases to 1.13 x 10(-5) ml*mol/g(2) near the isoelectric point of pH 4.6 and 25 mM NaCl. These results illuminate the role of fundamental long-range electrostatic and van der Waals forces in protein-protein interactions, specifically their dependence on pH and ionic strength.

Validating a Coarse-Grained Potential Energy Function through Protein Loop Modelling

PubMed Central

MacDonald, James T.; Kelley, Lawrence A.; Freemont, Paul S.

2013-01-01

Coarse-grained (CG) methods for sampling protein conformational space have the potential to increase computational efficiency by reducing the degrees of freedom. The gain in computational efficiency of CG methods often comes at the expense of non-protein like local conformational features. This could cause problems when transitioning to full atom models in a hierarchical framework. Here, a CG potential energy function was validated by applying it to the problem of loop prediction. A novel method to sample the conformational space of backbone atoms was benchmarked using a standard test set consisting of 351 distinct loops. This method used a sequence-independent CG potential energy function representing the protein using -carbon positions only and sampling conformations with a Monte Carlo simulated annealing based protocol. Backbone atoms were added using a method previously described and then gradient minimised in the Rosetta force field. Despite the CG potential energy function being sequence-independent, the method performed similarly to methods that explicitly use either fragments of known protein backbones with similar sequences or residue-specific /-maps to restrict the search space. The method was also able to predict with sub-Angstrom accuracy two out of seven loops from recently solved crystal structures of proteins with low sequence and structure similarity to previously deposited structures in the PDB. The ability to sample realistic loop conformations directly from a potential energy function enables the incorporation of additional geometric restraints and the use of more advanced sampling methods in a way that is not possible to do easily with fragment replacement methods and also enable multi-scale simulations for protein design and protein structure prediction. These restraints could be derived from experimental data or could be design restraints in the case of computational protein design. C++ source code is available for download from http://www.sbg.bio.ic.ac.uk/phyre2/PD2/. PMID:23824634

Transport synthetic acceleration with opposing reflecting boundary conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zika, M.R.; Adams, M.L.

2000-02-01

The transport synthetic acceleration (TSA) scheme is extended to problems with opposing reflecting boundary conditions. This synthetic method employs a simplified transport operator as its low-order approximation. A procedure is developed that allows the use of the conjugate gradient (CG) method to solve the resulting low-order system of equations. Several well-known transport iteration algorithms are cast in a linear algebraic form to show their equivalence to standard iterative techniques. Source iteration in the presence of opposing reflecting boundary conditions is shown to be equivalent to a (poorly) preconditioned stationary Richardson iteration, with the preconditioner defined by the method of iteratingmore » on the incident fluxes on the reflecting boundaries. The TSA method (and any synthetic method) amounts to a further preconditioning of the Richardson iteration. The presence of opposing reflecting boundary conditions requires special consideration when developing a procedure to realize the CG method for the proposed system of equations. The CG iteration may be applied only to symmetric positive definite matrices; this condition requires the algebraic elimination of the boundary angular corrections from the low-order equations. As a consequence of this elimination, evaluating the action of the resulting matrix on an arbitrary vector involves two transport sweeps and a transmission iteration. Results of applying the acceleration scheme to a simple test problem are presented.« less

On the inversion of geodetic integrals defined over the sphere using 1-D FFT

NASA Astrophysics Data System (ADS)

García, R. V.; Alejo, C. A.

2005-08-01

An iterative method is presented which performs inversion of integrals defined over the sphere. The method is based on one-dimensional fast Fourier transform (1-D FFT) inversion and is implemented with the projected Landweber technique, which is used to solve constrained least-squares problems reducing the associated 1-D cyclic-convolution error. The results obtained are as precise as the direct matrix inversion approach, but with better computational efficiency. A case study uses the inversion of Hotine’s integral to obtain gravity disturbances from geoid undulations. Numerical convergence is also analyzed and comparisons with respect to the direct matrix inversion method using conjugate gradient (CG) iteration are presented. Like the CG method, the number of iterations needed to get the optimum (i.e., small) error decreases as the measurement noise increases. Nevertheless, for discrete data given over a whole parallel band, the method can be applied directly without implementing the projected Landweber method, since no cyclic convolution error exists.

An optimization-based approach for solving a time-harmonic multiphysical wave problem with higher-order schemes

NASA Astrophysics Data System (ADS)

Mönkölä, Sanna

2013-06-01

This study considers developing numerical solution techniques for the computer simulations of time-harmonic fluid-structure interaction between acoustic and elastic waves. The focus is on the efficiency of an iterative solution method based on a controllability approach and spectral elements. We concentrate on the model, in which the acoustic waves in the fluid domain are modeled by using the velocity potential and the elastic waves in the structure domain are modeled by using displacement. Traditionally, the complex-valued time-harmonic equations are used for solving the time-harmonic problems. Instead of that, we focus on finding periodic solutions without solving the time-harmonic problems directly. The time-dependent equations can be simulated with respect to time until a time-harmonic solution is reached, but the approach suffers from poor convergence. To overcome this challenge, we follow the approach first suggested and developed for the acoustic wave equations by Bristeau, Glowinski, and Périaux. Thus, we accelerate the convergence rate by employing a controllability method. The problem is formulated as a least-squares optimization problem, which is solved with the conjugate gradient (CG) algorithm. Computation of the gradient of the functional is done directly for the discretized problem. A graph-based multigrid method is used for preconditioning the CG algorithm.

3-D Magnetotelluric Forward Modeling And Inversion Incorporating Topography By Using Vector Finite-Element Method Combined With Divergence Corrections Based On The Magnetic Field (VFEH++)

NASA Astrophysics Data System (ADS)

Shi, X.; Utada, H.; Jiaying, W.

2009-12-01

The vector finite-element method combined with divergence corrections based on the magnetic field H, referred to as VFEH++ method, is developed to simulate the magnetotelluric (MT) responses of 3-D conductivity models. The advantages of the new VFEH++ method are the use of edge-elements to eliminate the vector parasites and the divergence corrections to explicitly guarantee the divergence-free conditions in the whole modeling domain. 3-D MT topographic responses are modeling using the new VFEH++ method, and are compared with those calculated by other numerical methods. The results show that MT responses can be modeled highly accurate using the VFEH+ +method. The VFEH++ algorithm is also employed for the 3-D MT data inversion incorporating topography. The 3-D MT inverse problem is formulated as a minimization problem of the regularized misfit function. In order to avoid the huge memory requirement and very long time for computing the Jacobian sensitivity matrix for Gauss-Newton method, we employ the conjugate gradient (CG) approach to solve the inversion equation. In each iteration of CG algorithm, the cost computation is the product of the Jacobian sensitivity matrix with a model vector x or its transpose with a data vector y, which can be transformed into two pseudo-forwarding modeling. This avoids the full explicitly Jacobian matrix calculation and storage which leads to considerable savings in the memory required by the inversion program in PC computer. The performance of CG algorithm will be illustrated by several typical 3-D models with horizontal earth surface and topographic surfaces. The results show that the VFEH++ and CG algorithms can be effectively employed to 3-D MT field data inversion.

Evaluation and comparison of diffusion MR methods for measuring apparent transcytolemmal water exchange rate constant

NASA Astrophysics Data System (ADS)

Tian, Xin; Li, Hua; Jiang, Xiaoyu; Xie, Jingping; Gore, John C.; Xu, Junzhong

2017-02-01

Two diffusion-based approaches, CG (constant gradient) and FEXI (filtered exchange imaging) methods, have been previously proposed for measuring transcytolemmal water exchange rate constant kin, but their accuracy and feasibility have not been comprehensively evaluated and compared. In this work, both computer simulations and cell experiments in vitro were performed to evaluate these two methods. Simulations were done with different cell diameters (5, 10, 20 μm), a broad range of kin values (0.02-30 s-1) and different SNR's, and simulated kin's were directly compared with the ground truth values. Human leukemia K562 cells were cultured and treated with saponin to selectively change cell transmembrane permeability. The agreement between measured kin's of both methods was also evaluated. The results suggest that, without noise, the CG method provides reasonably accurate estimation of kin especially when it is smaller than 10 s-1, which is in the typical physiological range of many biological tissues. However, although the FEXI method overestimates kin even with corrections for the effects of extracellular water fraction, it provides reasonable estimates with practical SNR's and more importantly, the fitted apparent exchange rate AXR showed approximately linear dependence on the ground truth kin. In conclusion, either CG or FEXI method provides a sensitive means to characterize the variations in transcytolemmal water exchange rate constant kin, although the accuracy and specificity is usually compromised. The non-imaging CG method provides more accurate estimation of kin, but limited to large volume-of-interest. Although the accuracy of FEXI is compromised with extracellular volume fraction, it is capable of spatially mapping kin in practice.

Influence of structural features of carrageenan on the formation of polyelectrolyte complexes with chitosan.

PubMed

Volod'ko, A V; Davydova, V N; Glazunov, V P; Likhatskaya, G N; Yermak, I M

2016-03-01

The polyelectrolyte complexes (PEC) of carrageenans (CG)-κ-, κ/β-, λ-and x-CG with chitosan were obtained. The formation of PEC was detected by Fourier-transform infrared (FTIR) spectroscopy and by centrifugation in a Percoll gradient. The influence of the structural peculiarities of CG on its interaction with chitosan was studied. The results of centrifugation showed that x-CG with a high degree of sulphation (SD) was completely bound to chitosan, unlike low SD κ-CG and κ/β-CG. Binding constant values showed there was a high affinity of CG for chitosan. CG with flexible macromolecule conformation and high SD exhibited the greatest binding affinity for chitosan. The full-atomic 3D-structures of the PEC κ-CG: chitosan in solution have been obtained by the experiments in silico for the first time. The amino groups of chitosan make the largest contribution to the energy of the complex formation by means of hydrogen and ionic bonds. The most probable complexes have stoichiometries of 1:1 and 1:1.5. Copyright © 2015 Elsevier B.V. All rights reserved.

A combined finite element and boundary integral formulation for solution via CGFFT of 2-dimensional scattering problems

NASA Technical Reports Server (NTRS)

Collins, Jeffery D.; Volakis, John L.

1989-01-01

A new technique is presented for computing the scattering by 2-D structures of arbitrary composition. The proposed solution approach combines the usual finite element method with the boundary integral equation to formulate a discrete system. This is subsequently solved via the conjugate gradient (CG) algorithm. A particular characteristic of the method is the use of rectangular boundaries to enclose the scatterer. Several of the resulting boundary integrals are therefore convolutions and may be evaluated via the fast Fourier transform (FFT) in the implementation of the CG algorithm. The solution approach offers the principle advantage of having O(N) memory demand and employs a 1-D FFT versus a 2-D FFT as required with a traditional implementation of the CGFFT algorithm. The speed of the proposed solution method is compared with that of the traditional CGFFT algorithm, and results for rectangular bodies are given and shown to be in excellent agreement with the moment method.

A 3D finite-difference BiCG iterative solver with the Fourier-Jacobi preconditioner for the anisotropic EIT/EEG forward problem.

PubMed

Turovets, Sergei; Volkov, Vasily; Zherdetsky, Aleksej; Prakonina, Alena; Malony, Allen D

2014-01-01

The Electrical Impedance Tomography (EIT) and electroencephalography (EEG) forward problems in anisotropic inhomogeneous media like the human head belongs to the class of the three-dimensional boundary value problems for elliptic equations with mixed derivatives. We introduce and explore the performance of several new promising numerical techniques, which seem to be more suitable for solving these problems. The proposed numerical schemes combine the fictitious domain approach together with the finite-difference method and the optimally preconditioned Conjugate Gradient- (CG-) type iterative method for treatment of the discrete model. The numerical scheme includes the standard operations of summation and multiplication of sparse matrices and vector, as well as FFT, making it easy to implement and eligible for the effective parallel implementation. Some typical use cases for the EIT/EEG problems are considered demonstrating high efficiency of the proposed numerical technique.

Inelastic scattering with Chebyshev polynomials and preconditioned conjugate gradient minimization.

PubMed

Temel, Burcin; Mills, Greg; Metiu, Horia

2008-03-27

We describe and test an implementation, using a basis set of Chebyshev polynomials, of a variational method for solving scattering problems in quantum mechanics. This minimum error method (MEM) determines the wave function Psi by minimizing the least-squares error in the function (H Psi - E Psi), where E is the desired scattering energy. We compare the MEM to an alternative, the Kohn variational principle (KVP), by solving the Secrest-Johnson model of two-dimensional inelastic scattering, which has been studied previously using the KVP and for which other numerical solutions are available. We use a conjugate gradient (CG) method to minimize the error, and by preconditioning the CG search, we are able to greatly reduce the number of iterations necessary; the method is thus faster and more stable than a matrix inversion, as is required in the KVP. Also, we avoid errors due to scattering off of the boundaries, which presents substantial problems for other methods, by matching the wave function in the interaction region to the correct asymptotic states at the specified energy; the use of Chebyshev polynomials allows this boundary condition to be implemented accurately. The use of Chebyshev polynomials allows for a rapid and accurate evaluation of the kinetic energy. This basis set is as efficient as plane waves but does not impose an artificial periodicity on the system. There are problems in surface science and molecular electronics which cannot be solved if periodicity is imposed, and the Chebyshev basis set is a good alternative in such situations.

Reducing computational costs in large scale 3D EIT by using a sparse Jacobian matrix with block-wise CGLS reconstruction.

PubMed

Yang, C L; Wei, H Y; Adler, A; Soleimani, M

2013-06-01

Electrical impedance tomography (EIT) is a fast and cost-effective technique to provide a tomographic conductivity image of a subject from boundary current-voltage data. This paper proposes a time and memory efficient method for solving a large scale 3D EIT inverse problem using a parallel conjugate gradient (CG) algorithm. The 3D EIT system with a large number of measurement data can produce a large size of Jacobian matrix; this could cause difficulties in computer storage and the inversion process. One of challenges in 3D EIT is to decrease the reconstruction time and memory usage, at the same time retaining the image quality. Firstly, a sparse matrix reduction technique is proposed using thresholding to set very small values of the Jacobian matrix to zero. By adjusting the Jacobian matrix into a sparse format, the element with zeros would be eliminated, which results in a saving of memory requirement. Secondly, a block-wise CG method for parallel reconstruction has been developed. The proposed method has been tested using simulated data as well as experimental test samples. Sparse Jacobian with a block-wise CG enables the large scale EIT problem to be solved efficiently. Image quality measures are presented to quantify the effect of sparse matrix reduction in reconstruction results.

Measuring ammonia concentrations and emissions from agricultural land and liquid surfaces: a review.

PubMed

Shah, Sanjay B; Westerman, Philip W; Arogo, Jactone

2006-07-01

Aerial ammonia concentrations (Cg) are measured using acid scrubbers, filter packs, denuders, or optical methods. Using Cg and wind speed or airflow rate, ammonia emission rate or flux can be directly estimated using enclosures or micrometeorological methods. Using nitrogen (N) recovery is not recommended, mainly because the different gaseous N components cannot be separated. Although low cost and replicable, chambers modify environmental conditions and are suitable only for comparing treatments. Wind tunnels do not modify environmental conditions as much as chambers, but they may not be appropriate for determining ammonia fluxes; however, they can be used to compare emissions and test models. Larger wind tunnels that also simulate natural wind profiles may be more useful for comparing treatments than micrometeorological methods because the latter require larger plots and are, thus, difficult to replicate. For determining absolute ammonia flux, the micrometeorological methods are the most suitable because they are nonintrusive. For use with micrometeorological methods, both the passive denuders and optical methods give comparable accuracies, although the latter give real-time Cg but at a higher cost. The passive denuder is wind weighted and also costs less than forced-air Cg measurement methods, but it requires calibration. When ammonia contamination during sample preparation and handling is a concern and separating the gas-phase ammonia and aerosol ammonium is not required, the scrubber is preferred over the passive denuder. The photothermal interferometer, because of its low detection limit and robustness, may hold potential for use in agriculture, but it requires evaluation. With its simpler theoretical basis and fewer restrictions, the integrated horizontal flux (IHF) method is preferable over other micrometeorological methods, particularly for lagoons, where berms and land-lagoon boundaries modify wind flow and flux gradients. With uniform wind flow, the ZINST method requiring measurement at one predetermined height may perform comparably to the IHF method but at a lower cost.

Reconstruction of electrical impedance tomography (EIT) images based on the expectation maximum (EM) method.

PubMed

Wang, Qi; Wang, Huaxiang; Cui, Ziqiang; Yang, Chengyi

2012-11-01

Electrical impedance tomography (EIT) calculates the internal conductivity distribution within a body using electrical contact measurements. The image reconstruction for EIT is an inverse problem, which is both non-linear and ill-posed. The traditional regularization method cannot avoid introducing negative values in the solution. The negativity of the solution produces artifacts in reconstructed images in presence of noise. A statistical method, namely, the expectation maximization (EM) method, is used to solve the inverse problem for EIT in this paper. The mathematical model of EIT is transformed to the non-negatively constrained likelihood minimization problem. The solution is obtained by the gradient projection-reduced Newton (GPRN) iteration method. This paper also discusses the strategies of choosing parameters. Simulation and experimental results indicate that the reconstructed images with higher quality can be obtained by the EM method, compared with the traditional Tikhonov and conjugate gradient (CG) methods, even with non-negative processing. Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.

Hybrid Quantum Mechanics/Molecular Mechanics/Coarse Grained Modeling: A Triple-Resolution Approach for Biomolecular Systems.

PubMed

Sokkar, Pandian; Boulanger, Eliot; Thiel, Walter; Sanchez-Garcia, Elsa

2015-04-14

We present a hybrid quantum mechanics/molecular mechanics/coarse-grained (QM/MM/CG) multiresolution approach for solvated biomolecular systems. The chemically important active-site region is treated at the QM level. The biomolecular environment is described by an atomistic MM force field, and the solvent is modeled with the CG Martini force field using standard or polarizable (pol-CG) water. Interactions within the QM, MM, and CG regions, and between the QM and MM regions, are treated in the usual manner, whereas the CG-MM and CG-QM interactions are evaluated using the virtual sites approach. The accuracy and efficiency of our implementation is tested for two enzymes, chorismate mutase (CM) and p-hydroxybenzoate hydroxylase (PHBH). In CM, the QM/MM/CG potential energy scans along the reaction coordinate yield reaction energies that are too large, both for the standard and polarizable Martini CG water models, which can be attributed to adverse effects of using large CG water beads. The inclusion of an atomistic MM water layer (10 Å for uncharged CG water and 5 Å for polarizable CG water) around the QM region improves the energy profiles compared to the reference QM/MM calculations. In analogous QM/MM/CG calculations on PHBH, the use of the pol-CG description for the outer water does not affect the stabilization of the highly charged FADHOOH-pOHB transition state compared to the fully atomistic QM/MM calculations. Detailed performance analysis in a glycine-water model system indicates that computation times for QM energy and gradient evaluations at the density functional level are typically reduced by 40-70% for QM/MM/CG relative to fully atomistic QM/MM calculations.

Quantifying the Energy Efficiency of Object Recognition and Optical Flow

DTIC Science & Technology

2014-03-28

other linear solvers, such as conjugate- gradient (CG), preconditioned conjugate-gradient (PCG), and red-black Gauss Seidel (RB). We have also... Seidel , and conjugate gradient solvers. We are interested in the energy it takes to get a given solution quality. In Figure 6, we plot the quality of...in terms of Joules. Conversely, our implementation of red-black Gauss Seidel proves to be very inefficient when we consider Joules instead of just

Mapping the Conjugate Gradient Algorithm onto High Performance Heterogeneous Computers

DTIC Science & Technology

2014-05-01

Matrix Storage Formats According to J . Dongarra (Dongerra 2000), the efficiency of most iterative methods, such as CG, can be attributed to the...valh = aij) ⇒ (colh = j ). The ptr integer vector is of length n + 1 and contains the index in val where each matrix row starts. For example, the...first nonzero element of matrix rowm is found at index ptrm of val. By convention, ptrn+1 ≡ nz + 1. Notice that (aij) ⇒ (ptri ≤ j < ptri+1) for all i. An

High-Resolution Multi-Shot Spiral Diffusion Tensor Imaging with Inherent Correction of Motion-Induced Phase Errors

PubMed Central

Truong, Trong-Kha; Guidon, Arnaud

2014-01-01

Purpose To develop and compare three novel reconstruction methods designed to inherently correct for motion-induced phase errors in multi-shot spiral diffusion tensor imaging (DTI) without requiring a variable-density spiral trajectory or a navigator echo. Theory and Methods The first method simply averages magnitude images reconstructed with sensitivity encoding (SENSE) from each shot, whereas the second and third methods rely on SENSE to estimate the motion-induced phase error for each shot, and subsequently use either a direct phase subtraction or an iterative conjugate gradient (CG) algorithm, respectively, to correct for the resulting artifacts. Numerical simulations and in vivo experiments on healthy volunteers were performed to assess the performance of these methods. Results The first two methods suffer from a low signal-to-noise ratio (SNR) or from residual artifacts in the reconstructed diffusion-weighted images and fractional anisotropy maps. In contrast, the third method provides high-quality, high-resolution DTI results, revealing fine anatomical details such as a radial diffusion anisotropy in cortical gray matter. Conclusion The proposed SENSE+CG method can inherently and effectively correct for phase errors, signal loss, and aliasing artifacts caused by both rigid and nonrigid motion in multi-shot spiral DTI, without increasing the scan time or reducing the SNR. PMID:23450457

Multilinear approach to the precipitation-lightning relationship: a case study of summer local electrical storms in the northern part of Spain during 2002-2009 period

NASA Astrophysics Data System (ADS)

Herrero, I.; Ezcurra, A.; Areitio, J.; Diaz-Argandoña, J.; Ibarra-Berastegi, G.; Saenz, J.

2013-11-01

Storms developed under local instability conditions are studied in the Spanish Basque region with the aim of establishing precipitation-lightning relationships. Those situations may produce, in some cases, flash flood. Data used correspond to daily rain depth (mm) and the number of CG flashes in the area. Rain and lightning are found to be weakly correlated on a daily basis, a fact that seems related to the existence of opposite gradients in their geographical distribution. Rain anomalies, defined as the difference between observed and estimated rain depth based on CG flashes, are analysed by PCA method. Results show a first EOF explaining 50% of the variability that linearly relates the rain anomalies observed each day and that confirms their spatial structure. Based on those results, a multilinear expression has been developed to estimate the rain accumulated daily in the network based on the CG flashes registered in the area. Moreover, accumulates and maximum values of rain are found to be strongly correlated, therefore making the multilinear expression a useful tool to estimate maximum precipitation during those kind of storms.

Myocardial perfusion magnetic resonance imaging using sliding-window conjugate-gradient highly constrained back-projection reconstruction for detection of coronary artery disease.

PubMed

Ma, Heng; Yang, Jun; Liu, Jing; Ge, Lan; An, Jing; Tang, Qing; Li, Han; Zhang, Yu; Chen, David; Wang, Yong; Liu, Jiabin; Liang, Zhigang; Lin, Kai; Jin, Lixin; Bi, Xiaoming; Li, Kuncheng; Li, Debiao

2012-04-15

Myocardial perfusion magnetic resonance imaging (MRI) with sliding-window conjugate-gradient highly constrained back-projection reconstruction (SW-CG-HYPR) allows whole left ventricular coverage, improved temporal and spatial resolution and signal/noise ratio, and reduced cardiac motion-related image artifacts. The accuracy of this technique for detecting coronary artery disease (CAD) has not been determined in a large number of patients. We prospectively evaluated the diagnostic performance of myocardial perfusion MRI with SW-CG-HYPR in patients with suspected CAD. A total of 50 consecutive patients who were scheduled for coronary angiography with suspected CAD underwent myocardial perfusion MRI with SW-CG-HYPR at 3.0 T. The perfusion defects were interpreted qualitatively by 2 blinded observers and were correlated with x-ray angiographic stenoses ≥50%. The prevalence of CAD was 56%. In the per-patient analysis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of SW-CG-HYPR was 96% (95% confidence interval 82% to 100%), 82% (95% confidence interval 60% to 95%), 87% (95% confidence interval 70% to 96%), 95% (95% confidence interval 74% to100%), and 90% (95% confidence interval 82% to 98%), respectively. In the per-vessel analysis, the corresponding values were 98% (95% confidence interval 91% to 100%), 89% (95% confidence interval 80% to 94%), 86% (95% confidence interval 76% to 93%), 99% (95% confidence interval 93% to 100%), and 93% (95% confidence interval 89% to 97%), respectively. In conclusion, myocardial perfusion MRI using SW-CG-HYPR allows whole left ventricular coverage and high resolution and has high diagnostic accuracy in patients with suspected CAD. Copyright © 2012 Elsevier Inc. All rights reserved.

Direct reconstruction of cardiac PET kinetic parametric images using a preconditioned conjugate gradient approach

PubMed Central

Rakvongthai, Yothin; Ouyang, Jinsong; Guerin, Bastien; Li, Quanzheng; Alpert, Nathaniel M.; El Fakhri, Georges

2013-01-01

Purpose: Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach. Methods: Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame. The authors reconstructed the parametric images directly from the sinograms by optimizing a cost function, which included the Poisson log-likelihood and a spatial regularization terms, using the preconditioned conjugate gradient (PCG) algorithm with the proposed preconditioner. The proposed preconditioner is a diagonal matrix whose diagonal entries are the ratio of the parameter and the sensitivity of the radioactivity associated with parameter. The authors compared the reconstructed parametric images using the direct approach with those reconstructed using the conventional indirect approach. Results: At the same bias, the direct approach yielded significant relative reduction in standard deviation by 12%–29% and 32%–70% for 50 × 106 and 10 × 106 detected coincidences counts, respectively. Also, the PCG method effectively reached a constant value after only 10 iterations (with numerical convergence achieved after 40–50 iterations), while more than 500 iterations were needed for CG. Conclusions: The authors have developed a novel approach based on the PCG algorithm to directly reconstruct cardiac PET parametric images from sinograms, and yield better estimation of kinetic parameters than the conventional indirect approach, i.e., curve fitting of reconstructed images. The PCG method increases the convergence rate of reconstruction significantly as compared to the conventional CG method. PMID:24089922

Performance Comparison of Systematic Methods for Rigorous Definition of Coarse-Grained Sites of Large Biomolecules.

PubMed

Zhang, Yuwei; Cao, Zexing; Zhang, John Zenghui; Xia, Fei

2017-02-27

Construction of coarse-grained (CG) models for large biomolecules used for multiscale simulations demands a rigorous definition of CG sites for them. Several coarse-graining methods such as the simulated annealing and steepest descent (SASD) based on the essential dynamics coarse-graining (ED-CG) or the stepwise local iterative optimization (SLIO) based on the fluctuation maximization coarse-graining (FM-CG), were developed to do it. However, the practical applications of these methods such as SASD based on ED-CG are subject to limitations because they are too expensive. In this work, we extend the applicability of ED-CG by combining it with the SLIO algorithm. A comprehensive comparison of optimized results and accuracy of various algorithms based on ED-CG show that SLIO is the fastest as well as the most accurate algorithm among them. ED-CG combined with SLIO could give converged results as the number of CG sites increases, which demonstrates that it is another efficient method for coarse-graining large biomolecules. The construction of CG sites for Ras protein by using MD fluctuations demonstrates that the CG sites derived from FM-CG can reflect the fluctuation properties of secondary structures in Ras accurately.

Addendum to `numerical modeling of an enhanced very early time electromagnetic (VETEM) prototype system'

USGS Publications Warehouse

Cui, T.J.; Chew, W.C.; Aydiner, A.A.; Wright, D.L.; Smith, D.V.; Abraham, J.D.

2000-01-01

Two numerical models to simulate an enhanced very early time electromagnetic (VETEM) prototype system that is used for buried-object detection and environmental problems are presented. In the first model, the transmitting and receiving loop antennas accurately analyzed using the method of moments (MoM), and then conjugate gradient (CG) methods with the fast Fourier transform (FFT) are utilized to investigate the scattering from buried conducting plates. In the second model, two magnetic dipoles are used to replace the transmitter and receiver. Both the theory and formulation are correct and the simulation results for the primary magnetic field and the reflected magnetic field are accurate.

Hierarchical Coarse-Graining Via a Generalized Yvon-Born Green Framework: Many-Body Correlations, Mappings, and Structural Accuracy

NASA Astrophysics Data System (ADS)

Rudzinski, Joseph F.

Atomically-detailed molecular dynamics simulations have emerged as one of the most powerful theoretic tools for studying complex, condensed-phase systems. Despite their ability to provide incredible molecular insight, these simulations are insufficient for investigating complex biological processes, e.g., protein folding or molecular aggregation, on relevant length and time scales. The increasing scope and sophistication of atomically-detailed models has motivated the development of "hierarchical" approaches, which parameterize a low resolution, coarse-grained (CG) model based on simulations of an atomically-detailed model. The utility of hierarchical CG models depends on their ability to accurately incorporate the correct physics of the underlying model. One approach for ensuring this "consistency" between the models is to parameterize the CG model to reproduce the structural ensemble generated by the high resolution model. The many-body potential of mean force is the proper CG energy function for reproducing all structural distributions of the atomically-detailed model, at the CG level of resolution. However, this CG potential is a configuration-dependent free energy function that is generally too complicated to represent or simulate. The multiscale coarse-graining (MS-CG) method employs a generalized Yvon-Born-Green (g-YBG) relation to directly determine a variationally optimal approximation to the many-body potential of mean force. The MS-CG/g-YBG method provides a convenient and transparent framework for investigating the equilibrium structure of the system, at the CG level of resolution. In this work, we investigate the fundamental limitations and approximations of the MS-CG/g-YBG method. Throughout the work, we propose several theoretic constructs to directly relate the MS-CG/g-YBG method to other popular structure-based CG approaches. We investigate the physical interpretation of the MS-CG/g-YBG correlation matrix, the quantity responsible for disentangling the various contributions to the average force on a CG site. We then employ an iterative extension of the MS-CG/g-YBG method that improves the accuracy of a particular set of low order correlation functions relative to the original MS-CG/g-YBG model. We demonstrate that this method provides a powerful framework for identifying the precise source of error in an MS-CG/g-YBG model. We then propose a method for identifying an optimal CG representation, prior to the development of the CG model. We employ these techniques together to demonstrate that in the cases where the MS-CG/g-YBG method fails to determine an accurate model, a fundamental problem likely exists with the chosen CG representation or interaction set. Additionally, we explicitly demonstrate that while the iterative model successfully improves the accuracy of the low order structure, it does so by distorting the higher order structural correlations relative to the underlying model. Finally, we apply these methods to investigate the utility of the MS-CG/g- YBG method for developing models for systems with complex intramolecular structure. Overall, our results demonstrate the power of the g-YBG framework for developing accurate CG models and for investigating the driving forces of equilibrium structures for complex condensed-phase systems. This work also explicitly motivates future development of bottom-up CG methods and highlights some outstanding problems in the field. iii.

The granulocytes are the main immunocompetent hemocytes in Crassostrea gigas.

PubMed

Wang, Weilin; Li, Meijia; Wang, Lingling; Chen, Hao; Liu, Zhaoqun; Jia, Zhihao; Qiu, Limei; Song, Linsheng

2017-02-01

Hemocytes comprise diverse cell types with morphological and functional heterogeneity and play indispensable roles in immunological homeostasis of invertebrates. The morphological classification of different hemocytes in mollusk has been studied since the 1970's, yet the involvement of the different sub-populations in immune functions is far from clear. In the present study, three types of hemocytes were morphologically identified and separated as agranulocytes, semi-granulocytes and granulocytes by flow cytometry and Percoll ® density gradient centrifugation. The granulocytes were characterized functionally as the main phagocytic and encapsulating population, while semi-granulocytes and agranulocytes exhibited low or no such capacities, respectively. Meanwhile, the lysosome activity and the productions of ROS and NO were all mainly concentrated in granulocytes under both normal and immune-activated situations. Further, the mRNA transcripts of some immune related genes, including CgTLR, CgClathrin, CgATPeV, CgLysozyme, CgDefensin and CgIL-17, were mainly expressed in granulocytes, lower in semi-granulocytes and agranulocytes. These results collectively suggested that the granulocytes were the main immunocompetent hemocytes in oyster C. gigas, and a differentiation relationship among these three sub-population hemocytes was inferred based on the gradual changes in morphological, functional and molecular features. Copyright © 2016 Elsevier Ltd. All rights reserved.

CPDES3: A preconditioned conjugate gradient solver for linear asymmetric matrix equations arising from coupled partial differential equations in three dimensions

NASA Astrophysics Data System (ADS)

Anderson, D. V.; Koniges, A. E.; Shumaker, D. E.

1988-11-01

Many physical problems require the solution of coupled partial differential equations on three-dimensional domains. When the time scales of interest dictate an implicit discretization of the equations a rather complicated global matrix system needs solution. The exact form of the matrix depends on the choice of spatial grids and on the finite element or finite difference approximations employed. CPDES3 allows each spatial operator to have 7, 15, 19, or 27 point stencils and allows for general couplings between all of the component PDE's and it automatically generates the matrix structures needed to perform the algorithm. The resulting sparse matrix equation is solved by either the preconditioned conjugate gradient (CG) method or by the preconditioned biconjugate gradient (BCG) algorithm. An arbitrary number of component equations are permitted only limited by available memory. In the sub-band representation used, we generate an algorithm that is written compactly in terms of indirect induces which is vectorizable on some of the newer scientific computers.

CPDES2: A preconditioned conjugate gradient solver for linear asymmetric matrix equations arising from coupled partial differential equations in two dimensions

NASA Astrophysics Data System (ADS)

Anderson, D. V.; Koniges, A. E.; Shumaker, D. E.

1988-11-01

Many physical problems require the solution of coupled partial differential equations on two-dimensional domains. When the time scales of interest dictate an implicit discretization of the equations a rather complicated global matrix system needs solution. The exact form of the matrix depends on the choice of spatial grids and on the finite element or finite difference approximations employed. CPDES2 allows each spatial operator to have 5 or 9 point stencils and allows for general couplings between all of the component PDE's and it automatically generates the matrix structures needed to perform the algorithm. The resulting sparse matrix equation is solved by either the preconditioned conjugate gradient (CG) method or by the preconditioned biconjugate gradient (BCG) algorithm. An arbitrary number of component equations are permitted only limited by available memory. In the sub-band representation used, we generate an algorithm that is written compactly in terms of indirect indices which is vectorizable on some of the newer scientific computers.

Direct reconstruction of cardiac PET kinetic parametric images using a preconditioned conjugate gradient approach.

PubMed

Rakvongthai, Yothin; Ouyang, Jinsong; Guerin, Bastien; Li, Quanzheng; Alpert, Nathaniel M; El Fakhri, Georges

2013-10-01

Our research goal is to develop an algorithm to reconstruct cardiac positron emission tomography (PET) kinetic parametric images directly from sinograms and compare its performance with the conventional indirect approach. Time activity curves of a NCAT phantom were computed according to a one-tissue compartmental kinetic model with realistic kinetic parameters. The sinograms at each time frame were simulated using the activity distribution for the time frame. The authors reconstructed the parametric images directly from the sinograms by optimizing a cost function, which included the Poisson log-likelihood and a spatial regularization terms, using the preconditioned conjugate gradient (PCG) algorithm with the proposed preconditioner. The proposed preconditioner is a diagonal matrix whose diagonal entries are the ratio of the parameter and the sensitivity of the radioactivity associated with parameter. The authors compared the reconstructed parametric images using the direct approach with those reconstructed using the conventional indirect approach. At the same bias, the direct approach yielded significant relative reduction in standard deviation by 12%-29% and 32%-70% for 50 × 10(6) and 10 × 10(6) detected coincidences counts, respectively. Also, the PCG method effectively reached a constant value after only 10 iterations (with numerical convergence achieved after 40-50 iterations), while more than 500 iterations were needed for CG. The authors have developed a novel approach based on the PCG algorithm to directly reconstruct cardiac PET parametric images from sinograms, and yield better estimation of kinetic parameters than the conventional indirect approach, i.e., curve fitting of reconstructed images. The PCG method increases the convergence rate of reconstruction significantly as compared to the conventional CG method.

Acceleration of Linear Finite-Difference Poisson-Boltzmann Methods on Graphics Processing Units.

PubMed

Qi, Ruxi; Botello-Smith, Wesley M; Luo, Ray

2017-07-11

Electrostatic interactions play crucial roles in biophysical processes such as protein folding and molecular recognition. Poisson-Boltzmann equation (PBE)-based models have emerged as widely used in modeling these important processes. Though great efforts have been put into developing efficient PBE numerical models, challenges still remain due to the high dimensionality of typical biomolecular systems. In this study, we implemented and analyzed commonly used linear PBE solvers for the ever-improving graphics processing units (GPU) for biomolecular simulations, including both standard and preconditioned conjugate gradient (CG) solvers with several alternative preconditioners. Our implementation utilizes the standard Nvidia CUDA libraries cuSPARSE, cuBLAS, and CUSP. Extensive tests show that good numerical accuracy can be achieved given that the single precision is often used for numerical applications on GPU platforms. The optimal GPU performance was observed with the Jacobi-preconditioned CG solver, with a significant speedup over standard CG solver on CPU in our diversified test cases. Our analysis further shows that different matrix storage formats also considerably affect the efficiency of different linear PBE solvers on GPU, with the diagonal format best suited for our standard finite-difference linear systems. Further efficiency may be possible with matrix-free operations and integrated grid stencil setup specifically tailored for the banded matrices in PBE-specific linear systems.

Calibration of colour gradient bias in shear measurement using HST/CANDELS data

NASA Astrophysics Data System (ADS)

Er, X.; Hoekstra, H.; Schrabback, T.; Cardone, V. F.; Scaramella, R.; Maoli, R.; Vicinanza, M.; Gillis, B.; Rhodes, J.

2018-06-01

Accurate shape measurements are essential to infer cosmological parameters from large area weak gravitational lensing studies. The compact diffraction-limited point spread function (PSF) in space-based observations is greatly beneficial, but its chromaticity for a broad-band observation can lead to new subtle effects that could hitherto be ignored: the PSF of a galaxy is no longer uniquely defined and spatial variations in the colours of galaxies result in biases in the inferred lensing signal. Taking Euclid as a reference, we show that this colour gradient bias (CG bias) can be quantified with high accuracy using available multicolour Hubble Space Telescope (HST) data. In particular we study how noise in the HST observations might impact such measurements and find this to be negligible. We determine the CG bias using HST observations in the F606W and F814W filters and observe a correlation with the colour, in line with expectations, whereas the dependence with redshift is weak. The biases for individual galaxies are generally well below 1 per cent, which may be reduced further using morphological information from the Euclid data. Our results demonstrate that CG bias should not be ignored, but it is possible to determine its amplitude with sufficient precision, so that it will not significantly bias the weak lensing measurements using Euclid data.

Hydrodynamic properties of the gonadotropin receptor from a murine Leydig tumor cell line are altered by desensitization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rebois, R.V.; Bradley, R.M.; Titlow, C.C.

1987-10-06

The murine Leydig tumor cell line 1 (MLTC-1) contains gonadotropin receptors (GR) that are coupled to adenylate cyclase through the stimulatory guanine nucleotide binding protein (G/sub s/). The binding of human choriogonadotropin (hGC) causes MLTC-1 cells to accumulate cAMP. With time, the ability of MLTC-1 cells to respond to hCG is attenuated by a process called desensitization. The hydrodynamic properties of GR from control and desensitized MLTC-1 cells were studied. Sucrose density gradient sedimentation in H/sub 2/O and D/sub 2/O and gel filtration chromatography were used to estimate the Stokes radius (a), partial specific volume (v/sub c/), sedimentation coefficient (s/submore » 20,w/), and molecular weight (M/sub r/) of the detergent-solubilized hormone-receptor complex (hCG-GR). (/sup 125/I)hCG was bound to MLTC-1 cells under conditions that allow (37/sup 0/C) or prevent (0/sup 0/C) desensitization, and hCG-GR was solubilized in Triton X-100. In the absence of desensitization, control hCG-GR had a M/sub r/ of 213,000, whereas desensitized hCG-GR had a M/sub r/ of 158,000. Deglycosylated hCG (DG-HCG) is an antagonist that binds to GR with high affinity but fails to stimulate adenylate cyclase or cause desensitization. (/sup 125/I)DG-hCG was bound to MLTC-1 cells and DG-hCG-GR solubilized in Triton X-100. The hydrodynamic properties of DG-hCG-GR were the same as that for control hCG-GR. There was no evidence for the association of adenylate cyclase or G/sub s/ with GR in Triton X-100 solubilized preparations. When hCG was cross-linked to GR and solubilized with sodium dodecyl sulfate (SDS), the M/sub r/ was found to be 116,000, which was similar to that determined by SDS-polyacrylamide gel electrophoresis and less than that of the Triton X-100 solubilized control hCG-GR.« less

Immunoextraction-Tandem Mass Spectrometry Method for Measuring Intact Human Chorionic Gonadotropin, Free β-Subunit, and β-Subunit Core Fragment in Urine

PubMed Central

Woldemariam, Getachew A.; Butch, Anthony W.

2015-01-01

BACKGROUND Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles. Because of the potential for abuse, hCG is banned (males only) in most sports and has been placed on the World Anti-Doping Agency list of prohibited substances. Intact hCG, free β-subunit (hCGβ), and β-subunit core fragment (hCGβcf) are the major variants or isoforms in urine. Immunoassays are used by antidoping laboratories to measure urinary hCG. Cross-reactivity with isoforms differs among immunoassays, resulting in widely varying results. We developed a sequential im-munoextraction method with LC-MS/MS detection for quantification of intact hCG, hCGβ, and hCGβcf in urine. METHODS hCG isoforms were immunoextracted with antibody-conjugated magnetic beads and digested with trypsin, and hCGβ and hCGβcf unique peptides were quantified by LC-MS/MS with the corresponding heavy peptides as internal standard. hCG isoform concentrations were determined in urine after administration of hCG, and the intact hCG results were compared to immunoassay results. RESULTS The method was linear to 20 IU/L. Total imprecision was 6.6%-13.7% (CV), recovery ranged from 91% to 109%, and the limit of quantification was 0.2 IU/L. Intact hCG predominated in the urine after administration of 2 hCG formulations. The window of detection ranged from 6 to 9 days. Mean immunoassay results were 12.4-15.5 IU/L higher than LC-MS/MS results. CONCLUSIONS The performance characteristics of the method are acceptable for measuring hCG isoforms, and the method can quantify intact hCG and hCGβ separately. The limit of quantification will allow LC-MS/MS hCG reference intervals to be established in nondoping male athletes for improved doping control. PMID:24899693

Wetting boundary condition for the color-gradient lattice Boltzmann method: Validation with analytical and experimental data

NASA Astrophysics Data System (ADS)

Akai, Takashi; Bijeljic, Branko; Blunt, Martin J.

2018-06-01

In the color gradient lattice Boltzmann model (CG-LBM), a fictitious-density wetting boundary condition has been widely used because of its ease of implementation. However, as we show, this may lead to inaccurate results in some cases. In this paper, a new scheme for the wetting boundary condition is proposed which can handle complicated 3D geometries. The validity of our method for static problems is demonstrated by comparing the simulated results to analytical solutions in 2D and 3D geometries with curved boundaries. Then, capillary rise simulations are performed to study dynamic problems where the three-phase contact line moves. The results are compared to experimental results in the literature (Heshmati and Piri, 2014). If a constant contact angle is assumed, the simulations agree with the analytical solution based on the Lucas-Washburn equation. However, to match the experiments, we need to implement a dynamic contact angle that varies with the flow rate.

Quantum theory of multiscale coarse-graining.

PubMed

Han, Yining; Jin, Jaehyeok; Wagner, Jacob W; Voth, Gregory A

2018-03-14

Coarse-grained (CG) models serve as a powerful tool to simulate molecular systems at much longer temporal and spatial scales. Previously, CG models and methods have been built upon classical statistical mechanics. The present paper develops a theory and numerical methodology for coarse-graining in quantum statistical mechanics, by generalizing the multiscale coarse-graining (MS-CG) method to quantum Boltzmann statistics. A rigorous derivation of the sufficient thermodynamic consistency condition is first presented via imaginary time Feynman path integrals. It identifies the optimal choice of CG action functional and effective quantum CG (qCG) force field to generate a quantum MS-CG (qMS-CG) description of the equilibrium system that is consistent with the quantum fine-grained model projected onto the CG variables. A variational principle then provides a class of algorithms for optimally approximating the qMS-CG force fields. Specifically, a variational method based on force matching, which was also adopted in the classical MS-CG theory, is generalized to quantum Boltzmann statistics. The qMS-CG numerical algorithms and practical issues in implementing this variational minimization procedure are also discussed. Then, two numerical examples are presented to demonstrate the method. Finally, as an alternative strategy, a quasi-classical approximation for the thermal density matrix expressed in the CG variables is derived. This approach provides an interesting physical picture for coarse-graining in quantum Boltzmann statistical mechanics in which the consistency with the quantum particle delocalization is obviously manifest, and it opens up an avenue for using path integral centroid-based effective classical force fields in a coarse-graining methodology.

Self-calibrated Multiple-echo Acquisition with Radial Trajectories using the Conjugate Gradient Method (SMART-CG)

PubMed Central

Jung, Youngkyoo; Samsonov, Alexey A; Bydder, Mark; Block, Walter F.

2011-01-01

Purpose To remove phase inconsistencies between multiple echoes, an algorithm using a radial acquisition to provide inherent phase and magnitude information for self correction was developed. The information also allows simultaneous support for parallel imaging for multiple coil acquisitions. Materials and Methods Without a separate field map acquisition, a phase estimate from each echo in multiple echo train was generated. When using a multiple channel coil, magnitude and phase estimates from each echo provide in-vivo coil sensitivities. An algorithm based on the conjugate gradient method uses these estimates to simultaneously remove phase inconsistencies between echoes, and in the case of multiple coil acquisition, simultaneously provides parallel imaging benefits. The algorithm is demonstrated on single channel, multiple channel, and undersampled data. Results Substantial image quality improvements were demonstrated. Signal dropouts were completely removed and undersampling artifacts were well suppressed. Conclusion The suggested algorithm is able to remove phase cancellation and undersampling artifacts simultaneously and to improve image quality of multiecho radial imaging, the important technique for fast 3D MRI data acquisition. PMID:21448967

Anomalous Lightning Behavior During the 26-27 August 2007 Northern Great Plains Severe Weather Event

NASA Astrophysics Data System (ADS)

Logan, Timothy

2018-02-01

Positive polarity lightning strokes can be useful indicators of thunderstorm behavior. A combination of National Lightning Detection Network and Next Generation Radar retrievals is used to analyze the anomalous positive cloud-to-ground (CG) lightning behavior of a rare, late summer severe weather event that occurred on 26-27 August 2007 in the Northern Great Plains region of the United States and southern Canada. Seven discrete supercells (SC1-SC7) exhibiting frequent and intense lightning were responsible for numerous reports of severe weather (e.g., severe hail and 16 tornadoes) including catastrophic damage to the town of Northwood, North Dakota, caused by SC2. Biomass burning smoke from wildfires in Idaho and Montana was present prior to convective initiation. A positive CG lightning stroke rate of nearly 30 strokes per minute was observed 10 min before the EF4 tornado struck Northwood. SC2 was also responsible for all the reports of tornadoes exceeding an EF2 rating. The strongest peak currents (>200 kA) were observed in SC1-SC4 with SC2 having a maximum value of 280 kA. SC2 dominated the statistics of the line of supercells accounting for 27% of all CG lightning strokes. Positive CG lightning accounted for over 40% of all CG lightning strokes in SC4-SC7 on average, and the maximum exceeded 90% in SC6 and SC7. Increasing positive CG lightning dominance was correlated with an increasing northward gradient of smoke aerosol loading in addition to severe weather being reported before the maximum in positive CG lighting stroke rate (SC5 and SC6). This suggests that a complex combination of synoptic forcing and aerosol perturbation likely led to the observed anomalous positive CG lightning behavior in the supercells.

Effects of Ordering Strategies and Programming Paradigms on Sparse Matrix Computations

NASA Technical Reports Server (NTRS)

Oliker, Leonid; Li, Xiaoye; Husbands, Parry; Biswas, Rupak; Biegel, Bryan (Technical Monitor)

2002-01-01

The Conjugate Gradient (CG) algorithm is perhaps the best-known iterative technique to solve sparse linear systems that are symmetric and positive definite. For systems that are ill-conditioned, it is often necessary to use a preconditioning technique. In this paper, we investigate the effects of various ordering and partitioning strategies on the performance of parallel CG and ILU(O) preconditioned CG (PCG) using different programming paradigms and architectures. Results show that for this class of applications: ordering significantly improves overall performance on both distributed and distributed shared-memory systems, that cache reuse may be more important than reducing communication, that it is possible to achieve message-passing performance using shared-memory constructs through careful data ordering and distribution, and that a hybrid MPI+OpenMP paradigm increases programming complexity with little performance gains. A implementation of CG on the Cray MTA does not require special ordering or partitioning to obtain high efficiency and scalability, giving it a distinct advantage for adaptive applications; however, it shows limited scalability for PCG due to a lack of thread level parallelism.

Probabilistic image modeling with an extended chain graph for human activity recognition and image segmentation.

PubMed

Zhang, Lei; Zeng, Zhi; Ji, Qiang

2011-09-01

Chain graph (CG) is a hybrid probabilistic graphical model (PGM) capable of modeling heterogeneous relationships among random variables. So far, however, its application in image and video analysis is very limited due to lack of principled learning and inference methods for a CG of general topology. To overcome this limitation, we introduce methods to extend the conventional chain-like CG model to CG model with more general topology and the associated methods for learning and inference in such a general CG model. Specifically, we propose techniques to systematically construct a generally structured CG, to parameterize this model, to derive its joint probability distribution, to perform joint parameter learning, and to perform probabilistic inference in this model. To demonstrate the utility of such an extended CG, we apply it to two challenging image and video analysis problems: human activity recognition and image segmentation. The experimental results show improved performance of the extended CG model over the conventional directed or undirected PGMs. This study demonstrates the promise of the extended CG for effective modeling and inference of complex real-world problems.

The multiscale coarse-graining method. II. Numerical implementation for coarse-grained molecular models

PubMed Central

Noid, W. G.; Liu, Pu; Wang, Yanting; Chu, Jhih-Wei; Ayton, Gary S.; Izvekov, Sergei; Andersen, Hans C.; Voth, Gregory A.

2008-01-01

The multiscale coarse-graining (MS-CG) method [S. Izvekov and G. A. Voth, J. Phys. Chem. B 109, 2469 (2005);J. Chem. Phys. 123, 134105 (2005)] employs a variational principle to determine an interaction potential for a CG model from simulations of an atomically detailed model of the same system. The companion paper proved that, if no restrictions regarding the form of the CG interaction potential are introduced and if the equilibrium distribution of the atomistic model has been adequately sampled, then the MS-CG variational principle determines the exact many-body potential of mean force (PMF) governing the equilibrium distribution of CG sites generated by the atomistic model. In practice, though, CG force fields are not completely flexible, but only include particular types of interactions between CG sites, e.g., nonbonded forces between pairs of sites. If the CG force field depends linearly on the force field parameters, then the vector valued functions that relate the CG forces to these parameters determine a set of basis vectors that span a vector subspace of CG force fields. The companion paper introduced a distance metric for the vector space of CG force fields and proved that the MS-CG variational principle determines the CG force force field that is within that vector subspace and that is closest to the force field determined by the many-body PMF. The present paper applies the MS-CG variational principle for parametrizing molecular CG force fields and derives a linear least squares problem for the parameter set determining the optimal approximation to this many-body PMF. Linear systems of equations for these CG force field parameters are derived and analyzed in terms of equilibrium structural correlation functions. Numerical calculations for a one-site CG model of methanol and a molecular CG model of the EMIM+∕NO3− ionic liquid are provided to illustrate the method. PMID:18601325

USA hCG reference service, 10-year report.

PubMed

Cole, Laurence A; Laidler, Laura L; Muller, Carolyn Y

2010-08-01

The USA hCG Reference Service has been dealing with cases of persistent low levels of hCG and gestational trophoblastic diseases for 10years. Here we present the complete experience. Total hCG in serum and urine was measured using the Siemen's Immulite 1000 assay. Hyperglycosylated hCG, nicked hCG, free ss-subunit and ss-core fragment were measured using microtiterplate assays with antibodies B152, B151, FBT11 and B210, respectively. The USA hCG Reference Service has identified 83 cases of false-positive hCG, 71 cases of aggressive gestational trophoblastic disease (GTD), 52 cases of minimally invasive GTD, 168 cases of quiescent GTD and 22 cases of placenta site trophoblastic tumor (PSTT). In addition, 103 cases of pituitary hCG have been identified, 60 cases of nontrophoblastic tumor, 4 cases of inherited hCG and 2 cases of Munchausen's syndrome. This is 565 cases total. Multiple new methods are described and tested for diagnosing all of these disorders. The USA hCG Reference Service experience shows new methods for detecting multiple hCG-related disorders and recommends new approaches for detecting these hCG-related disorders. 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effects of Conjugate Gradient Methods and Step-Length Formulas on the Multiscale Full Waveform Inversion in Time Domain: Numerical Experiments

NASA Astrophysics Data System (ADS)

Liu, Youshan; Teng, Jiwen; Xu, Tao; Badal, José; Liu, Qinya; Zhou, Bing

2017-05-01

We carry out full waveform inversion (FWI) in time domain based on an alternative frequency-band selection strategy that allows us to implement the method with success. This strategy aims at decomposing the seismic data within partially overlapped frequency intervals by carrying out a concatenated treatment of the wavelet to largely avoid redundant frequency information to adapt to wavelength or wavenumber coverage. A pertinent numerical test proves the effectiveness of this strategy. Based on this strategy, we comparatively analyze the effects of update parameters for the nonlinear conjugate gradient (CG) method and step-length formulas on the multiscale FWI through several numerical tests. The investigations of up to eight versions of the nonlinear CG method with and without Gaussian white noise make clear that the HS (Hestenes and Stiefel in J Res Natl Bur Stand Sect 5:409-436, 1952), CD (Fletcher in Practical methods of optimization vol. 1: unconstrained optimization, Wiley, New York, 1987), and PRP (Polak and Ribière in Revue Francaise Informat Recherche Opertionelle, 3e Année 16:35-43, 1969; Polyak in USSR Comput Math Math Phys 9:94-112, 1969) versions are more efficient among the eight versions, while the DY (Dai and Yuan in SIAM J Optim 10:177-182, 1999) version always yields inaccurate result, because it overestimates the deeper parts of the model. The application of FWI algorithms using distinct step-length formulas, such as the direct method ( Direct), the parabolic search method ( Search), and the two-point quadratic interpolation method ( Interp), proves that the Interp is more efficient for noise-free data, while the Direct is more efficient for Gaussian white noise data. In contrast, the Search is less efficient because of its slow convergence. In general, the three step-length formulas are robust or partly insensitive to Gaussian white noise and the complexity of the model. When the initial velocity model deviates far from the real model or the data are contaminated by noise, the objective function values of the Direct and Interp are oscillating at the beginning of the inversion, whereas that of the Search decreases consistently.

Transport synthetic acceleration for long-characteristics assembly-level transport problems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zika, M.R.; Adams, M.L.

2000-02-01

The authors apply the transport synthetic acceleration (TSA) scheme to the long-characteristics spatial discretization for the two-dimensional assembly-level transport problem. This synthetic method employs a simplified transport operator as its low-order approximation. Thus, in the acceleration step, the authors take advantage of features of the long-characteristics discretization that make it particularly well suited to assembly-level transport problems. The main contribution is to address difficulties unique to the long-characteristics discretization and produce a computationally efficient acceleration scheme. The combination of the long-characteristics discretization, opposing reflecting boundary conditions (which are present in assembly-level transport problems), and TSA presents several challenges. The authorsmore » devise methods for overcoming each of them in a computationally efficient way. Since the boundary angular data exist on different grids in the high- and low-order problems, they define restriction and prolongation operations specific to the method of long characteristics to map between the two grids. They implement the conjugate gradient (CG) method in the presence of opposing reflection boundary conditions to solve the TSA low-order equations. The CG iteration may be applied only to symmetric positive definite (SPD) matrices; they prove that the long-characteristics discretization yields an SPD matrix. They present results of the acceleration scheme on a simple test problem, a typical pressurized water reactor assembly, and a typical boiling water reactor assembly.« less

An overview of NSPCG: A nonsymmetric preconditioned conjugate gradient package

NASA Astrophysics Data System (ADS)

Oppe, Thomas C.; Joubert, Wayne D.; Kincaid, David R.

1989-05-01

The most recent research-oriented software package developed as part of the ITPACK Project is called "NSPCG" since it contains many nonsymmetric preconditioned conjugate gradient procedures. It is designed to solve large sparse systems of linear algebraic equations by a variety of different iterative methods. One of the main purposes for the development of the package is to provide a common modular structure for research on iterative methods for nonsymmetric matrices. Another purpose for the development of the package is to investigate the suitability of several iterative methods for vector computers. Since the vectorizability of an iterative method depends greatly on the matrix structure, NSPCG allows great flexibility in the operator representation. The coefficient matrix can be passed in one of several different matrix data storage schemes. These sparse data formats allow matrices with a wide range of structures from highly structured ones such as those with all nonzeros along a relatively small number of diagonals to completely unstructured sparse matrices. Alternatively, the package allows the user to call the accelerators directly with user-supplied routines for performing certain matrix operations. In this case, one can use the data format from an application program and not be required to copy the matrix into one of the package formats. This is particularly advantageous when memory space is limited. Some of the basic preconditioners that are available are point methods such as Jacobi, Incomplete LU Decomposition and Symmetric Successive Overrelaxation as well as block and multicolor preconditioners. The user can select from a large collection of accelerators such as Conjugate Gradient (CG), Chebyshev (SI, for semi-iterative), Generalized Minimal Residual (GMRES), Biconjugate Gradient Squared (BCGS) and many others. The package is modular so that almost any accelerator can be used with almost any preconditioner.

Systematic methods for defining coarse-grained maps in large biomolecules.

PubMed

Zhang, Zhiyong

2015-01-01

Large biomolecules are involved in many important biological processes. It would be difficult to use large-scale atomistic molecular dynamics (MD) simulations to study the functional motions of these systems because of the computational expense. Therefore various coarse-grained (CG) approaches have attracted rapidly growing interest, which enable simulations of large biomolecules over longer effective timescales than all-atom MD simulations. The first issue in CG modeling is to construct CG maps from atomic structures. In this chapter, we review the recent development of a novel and systematic method for constructing CG representations of arbitrarily complex biomolecules, in order to preserve large-scale and functionally relevant essential dynamics (ED) at the CG level. In this ED-CG scheme, the essential dynamics can be characterized by principal component analysis (PCA) on a structural ensemble, or elastic network model (ENM) of a single atomic structure. Validation and applications of the method cover various biological systems, such as multi-domain proteins, protein complexes, and even biomolecular machines. The results demonstrate that the ED-CG method may serve as a very useful tool for identifying functional dynamics of large biomolecules at the CG level.

A modified conjugate gradient method based on the Tikhonov system for computerized tomography (CT).

PubMed

Wang, Qi; Wang, Huaxiang

2011-04-01

During the past few decades, computerized tomography (CT) was widely used for non-destructive testing (NDT) and non-destructive examination (NDE) in the industrial area because of its characteristics of non-invasiveness and visibility. Recently, CT technology has been applied to multi-phase flow measurement. Using the principle of radiation attenuation measurements along different directions through the investigated object with a special reconstruction algorithm, cross-sectional information of the scanned object can be worked out. It is a typical inverse problem and has always been a challenge for its nonlinearity and ill-conditions. The Tikhonov regulation method is widely used for similar ill-posed problems. However, the conventional Tikhonov method does not provide reconstructions with qualities good enough, the relative errors between the reconstructed images and the real distribution should be further reduced. In this paper, a modified conjugate gradient (CG) method is applied to a Tikhonov system (MCGT method) for reconstructing CT images. The computational load is dominated by the number of independent measurements m, and a preconditioner is imported to lower the condition number of the Tikhonov system. Both simulation and experiment results indicate that the proposed method can reduce the computational time and improve the quality of image reconstruction. Copyright © 2010 ISA. Published by Elsevier Ltd. All rights reserved.

Self-calibrated multiple-echo acquisition with radial trajectories using the conjugate gradient method (SMART-CG).

PubMed

Jung, Youngkyoo; Samsonov, Alexey A; Bydder, Mark; Block, Walter F

2011-04-01

To remove phase inconsistencies between multiple echoes, an algorithm using a radial acquisition to provide inherent phase and magnitude information for self correction was developed. The information also allows simultaneous support for parallel imaging for multiple coil acquisitions. Without a separate field map acquisition, a phase estimate from each echo in multiple echo train was generated. When using a multiple channel coil, magnitude and phase estimates from each echo provide in vivo coil sensitivities. An algorithm based on the conjugate gradient method uses these estimates to simultaneously remove phase inconsistencies between echoes, and in the case of multiple coil acquisition, simultaneously provides parallel imaging benefits. The algorithm is demonstrated on single channel, multiple channel, and undersampled data. Substantial image quality improvements were demonstrated. Signal dropouts were completely removed and undersampling artifacts were well suppressed. The suggested algorithm is able to remove phase cancellation and undersampling artifacts simultaneously and to improve image quality of multiecho radial imaging, the important technique for fast three-dimensional MRI data acquisition. Copyright © 2011 Wiley-Liss, Inc.

Accurate optimization of amino acid form factors for computing small-angle X-ray scattering intensity of atomistic protein structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tong, Dudu; Yang, Sichun; Lu, Lanyuan

2016-06-20

Structure modellingviasmall-angle X-ray scattering (SAXS) data generally requires intensive computations of scattering intensity from any given biomolecular structure, where the accurate evaluation of SAXS profiles using coarse-grained (CG) methods is vital to improve computational efficiency. To date, most CG SAXS computing methods have been based on a single-bead-per-residue approximation but have neglected structural correlations between amino acids. To improve the accuracy of scattering calculations, accurate CG form factors of amino acids are now derived using a rigorous optimization strategy, termed electron-density matching (EDM), to best fit electron-density distributions of protein structures. This EDM method is compared with and tested againstmore » other CG SAXS computing methods, and the resulting CG SAXS profiles from EDM agree better with all-atom theoretical SAXS data. By including the protein hydration shell represented by explicit CG water molecules and the correction of protein excluded volume, the developed CG form factors also reproduce the selected experimental SAXS profiles with very small deviations. Taken together, these EDM-derived CG form factors present an accurate and efficient computational approach for SAXS computing, especially when higher molecular details (represented by theqrange of the SAXS data) become necessary for effective structure modelling.« less

Grazed Riparian Management and Stream Channel Response in Southeastern Minnesota (USA) Streams

NASA Astrophysics Data System (ADS)

Magner, Joseph A.; Vondracek, Bruce; Brooks, Kenneth N.

2008-09-01

The U.S. Department of Agriculture-Natural Resources Conservation Service has recommended domestic cattle grazing exclusion from riparian corridors for decades. This recommendation was based on a belief that domestic cattle grazing would typically destroy stream bank vegetation and in-channel habitat. Continuous grazing (CG) has caused adverse environmental damage, but along cohesive-sediment stream banks of disturbed catchments in southeastern Minnesota, short-duration grazing (SDG), a rotational grazing system, may offer a better riparian management practice than CG. Over 30 physical and biological metrics were gathered at 26 sites to evaluate differences between SDG, CG, and nongrazed sites (NG). Ordinations produced with nonmetric multidimensional scaling (NMS) indicated a gradient with a benthic macroinvertebrate index of biotic integrity (IBI) and riparian site management; low IBI scores associated with CG sites and higher IBI scores associated with NG sites. Nongrazed sites were associated with reduced soil compaction and higher bank stability, as measured by the Pfankuch stability index; whereas CG sites were associated with increased soil compaction and lower bank stability, SDG sites were intermediate. Bedrock geology influenced NMS results: sites with carbonate derived cobble were associated with more stable channels and higher IBI scores. Though current riparian grazing practices in southeastern Minnesota present pollution problems, short duration grazing could reduce sediment pollution if managed in an environmentally sustainable fashion that considers stream channel response.

Grazed riparian management and stream channel response in southeastern Minnesota (USA) streams

USGS Publications Warehouse

Magner, J.A.; Vondracek, B.; Brooks, K.N.

2008-01-01

The U.S. Department of Agriculture-Natural Resources Conservation Service has recommended domestic cattle grazing exclusion from riparian corridors for decades. This recommendation was based on a belief that domestic cattle grazing would typically destroy stream bank vegetation and in-channel habitat. Continuous grazing (CG) has caused adverse environmental damage, but along cohesive-sediment stream banks of disturbed catchments in southeastern Minnesota, short-duration grazing (SDG), a rotational grazing system, may offer a better riparian management practice than CG. Over 30 physical and biological metrics were gathered at 26 sites to evaluate differences between SDG, CG, and nongrazed sites (NG). Ordinations produced with nonmetric multidimensional scaling (NMS) indicated a gradient with a benthic macroinvertebrate index of biotic integrity (IBI) and riparian site management; low IBI scores associated with CG sites and higher IBI scores associated with NG sites. Nongrazed sites were associated with reduced soil compaction and higher bank stability, as measured by the Pfankuch stability index; whereas CG sites were associated with increased soil compaction and lower bank stability, SDG sites were intermediate. Bedrock geology influenced NMS results: sites with carbonate derived cobble were associated with more stable channels and higher IBI scores. Though current riparian grazing practices in southeastern Minnesota present pollution problems, short duration grazing could reduce sediment pollution if managed in an environmentally sustainable fashion that considers stream channel response. ?? 2008 Springer Science+Business Media, LLC.

Comparative Evaluations of Randomly Selected Four Point-of-Care Glucometer Devices in Addis Ababa, Ethiopia.

PubMed

Wolde, Mistire; Tarekegn, Getahun; Kebede, Tedla

2018-05-01

Point-of-care glucometer (PoCG) devices play a significant role in self-monitoring of the blood sugar level, particularly in the follow-up of high blood sugar therapeutic response. The aim of this study was to evaluate blood glucose test results performed with four randomly selected glucometers on diabetes and control subjects versus standard wet chemistry (hexokinase) methods in Addis Ababa, Ethiopia. A prospective cross-sectional study was conducted on randomly selected 200 study participants (100 participants with diabetes and 100 healthy controls). Four randomly selected PoCG devices (CareSens N, DIAVUE Prudential, On Call Extra, i-QARE DS-W) were evaluated against hexokinase method and ISO 15197:2003 and ISO 15197:2013 standards. The minimum and maximum blood sugar values were recorded by CareSens N (21 mg/dl) and hexokinase method (498.8 mg/dl), respectively. The mean sugar values of all PoCG devices except On Call Extra showed significant differences compared with the reference hexokinase method. Meanwhile, all four PoCG devices had strong positive relationship (>80%) with the reference method (hexokinase). On the other hand, none of the four PoCG devices fulfilled the minimum accuracy measurement set by ISO 15197:2003 and ISO 15197:2013 standards. In addition, the linear regression analysis revealed that all four selected PoCG overestimated the glucose concentrations. The overall evaluation of the selected four PoCG measurements were poorly correlated with standard reference method. Therefore, before introducing PoCG devices to the market, there should be a standardized evaluation platform for validation. Further similar large-scale studies on other PoCG devices also need to be undertaken.

Development of DPD coarse-grained models: From bulk to interfacial properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Solano Canchaya, José G.; Dequidt, Alain, E-mail: alain.dequidt@univ-bpclermont.fr; Goujon, Florent

2016-08-07

A new Bayesian method was recently introduced for developing coarse-grain (CG) force fields for molecular dynamics. The CG models designed for dissipative particle dynamics (DPD) are optimized based on trajectory matching. Here we extend this method to improve transferability across thermodynamic conditions. We demonstrate the capability of the method by developing a CG model of n-pentane from constant-NPT atomistic simulations of bulk liquid phases and we apply the CG-DPD model to the calculation of the surface tension of the liquid-vapor interface over a large range of temperatures. The coexisting densities, vapor pressures, and surface tensions calculated with different CG andmore » atomistic models are compared to experiments. Depending on the database used for the development of the potentials, it is possible to build a CG model which performs very well in the reproduction of the surface tension on the orthobaric curve.« less

Collocation and Galerkin Time-Stepping Methods

NASA Technical Reports Server (NTRS)

Huynh, H. T.

2011-01-01

We study the numerical solutions of ordinary differential equations by one-step methods where the solution at tn is known and that at t(sub n+1) is to be calculated. The approaches employed are collocation, continuous Galerkin (CG) and discontinuous Galerkin (DG). Relations among these three approaches are established. A quadrature formula using s evaluation points is employed for the Galerkin formulations. We show that with such a quadrature, the CG method is identical to the collocation method using quadrature points as collocation points. Furthermore, if the quadrature formula is the right Radau one (including t(sub n+1)), then the DG and CG methods also become identical, and they reduce to the Radau IIA collocation method. In addition, we present a generalization of DG that yields a method identical to CG and collocation with arbitrary collocation points. Thus, the collocation, CG, and generalized DG methods are equivalent, and the latter two methods can be formulated using the differential instead of integral equation. Finally, all schemes discussed can be cast as s-stage implicit Runge-Kutta methods.

Effect of Changing the Center of Gravity on Human Performance in Simulated Lunar Gravity

NASA Technical Reports Server (NTRS)

Chappell, Steven P.; Norcross, Jason R.; Gernhardt, Michael L.

2010-01-01

The presentation slides include: Moving Past Apollo, Testing in Analog Environments, NEEMO/NBL CG (center of gravity) Studies, Center of Gravity Test Design and Methods, CG Suited Locations and Results, CG Individual Considerations, CG Shirt-Sleeve Locations and Results.

Blockwise conjugate gradient methods for image reconstruction in volumetric CT.

PubMed

Qiu, W; Titley-Peloquin, D; Soleimani, M

2012-11-01

Cone beam computed tomography (CBCT) enables volumetric image reconstruction from 2D projection data and plays an important role in image guided radiation therapy (IGRT). Filtered back projection is still the most frequently used algorithm in applications. The algorithm discretizes the scanning process (forward projection) into a system of linear equations, which must then be solved to recover images from measured projection data. The conjugate gradients (CG) algorithm and its variants can be used to solve (possibly regularized) linear systems of equations Ax=b and linear least squares problems minx∥b-Ax∥2, especially when the matrix A is very large and sparse. Their applications can be found in a general CT context, but in tomography problems (e.g. CBCT reconstruction) they have not widely been used. Hence, CBCT reconstruction using the CG-type algorithm LSQR was implemented and studied in this paper. In CBCT reconstruction, the main computational challenge is that the matrix A usually is very large, and storing it in full requires an amount of memory well beyond the reach of commodity computers. Because of these memory capacity constraints, only a small fraction of the weighting matrix A is typically used, leading to a poor reconstruction. In this paper, to overcome this difficulty, the matrix A is partitioned and stored blockwise, and blockwise matrix-vector multiplications are implemented within LSQR. This implementation allows us to use the full weighting matrix A for CBCT reconstruction without further enhancing computer standards. Tikhonov regularization can also be implemented in this fashion, and can produce significant improvement in the reconstructed images. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Development and evaluation of an automatically adjusting coarse-grained force field for a β-O-4 type lignin from atomistic simulations

NASA Astrophysics Data System (ADS)

Li, Wenzhuo; Zhao, Yingying; Huang, Shuaiyu; Zhang, Song; Zhang, Lin

2017-01-01

This goal of this work was to develop a coarse-grained (CG) model of a β-O-4 type lignin polymer, because of the time consuming process required to achieve equilibrium for its atomistic model. The automatic adjustment method was used to develop the lignin CG model, which enables easy discrimination between chemically-varied polymers. In the process of building the lignin CG model, a sum of n Gaussian functions was obtained by an approximation of the corresponding atomistic potentials derived from a simple Boltzmann inversion of the distributions of the structural parameters. This allowed the establishment of the potential functions of the CG bond stretching and angular bending. To obtain the potential function of the CG dihedral angle, an algorithm similar to a Fourier progression form was employed together with a nonlinear curve-fitting method. The numerical potentials of the nonbonded portion of the lignin CG model were obtained using a potential inversion iterative method derived from the corresponding atomistic nonbonded distributions. The study results showed that the proposed CG model of lignin agreed well with its atomistic model in terms of the distributions of bond lengths, bending angles, dihedral angles and nonbonded distances between the CG beads. The lignin CG model also reproduced the static and dynamic properties of the atomistic model. The results of the comparative evaluation of the two models suggested that the designed lignin CG model was efficient and reliable.

Screening method to evaluate point-of-care human chorionic gonadotropin (hCG) devices for susceptibility to the hook effect by hCG β core fragment: evaluation of 11 devices.

PubMed

Nerenz, Robert D; Song, Haowei; Gronowski, Ann M

2014-04-01

The predominant hCG variant in urine, hCG β core fragment (hCGβcf), has been demonstrated to cause false-negative results in qualitative point-of-care (POC) hCG devices. This is a major concern for healthcare professionals using POC pregnancy tests. We developed a screening method to evaluate qualitative POC hCG devices for their susceptibility to inhibition by hCGβcf. Using this method, we evaluated the performance of 11 commonly used devices. A wide range of purified hCG and hCGβcf concentrations were mixed and tested on 2 POC devices. By use of those results, a screening method was defined and 9 additional POC devices were evaluated. Two solutions containing (a) 500 pmol/L (171 IU/L) intact hCG with 0 pmol/L hCGβcf and (b) 500 pmol/L intact hCG with 500 000 pmol/L hCGβcf were used to screen all POC devices. The OSOM and Cen-Med Elite devices were found to be most susceptible to false-negative results due to hCGβcf. The BC Icon 20 and the Alere were the least susceptible. The remaining 7 were moderately affected. Devices that gave the strongest signal with hCGβcf alone were those that were least likely to show a hook effect. The screening method put forth here can be used by device users and manufacturers to evaluate POC devices for inhibition by hCGβcf. Of 11 devices evaluated, only 2 have been identified that exhibit minimal to no susceptibility to hCGβcf.

A quasi-Newton algorithm for large-scale nonlinear equations.

PubMed

Huang, Linghua

2017-01-01

In this paper, the algorithm for large-scale nonlinear equations is designed by the following steps: (i) a conjugate gradient (CG) algorithm is designed as a sub-algorithm to obtain the initial points of the main algorithm, where the sub-algorithm's initial point does not have any restrictions; (ii) a quasi-Newton algorithm with the initial points given by sub-algorithm is defined as main algorithm, where a new nonmonotone line search technique is presented to get the step length [Formula: see text]. The given nonmonotone line search technique can avoid computing the Jacobian matrix. The global convergence and the [Formula: see text]-order convergent rate of the main algorithm are established under suitable conditions. Numerical results show that the proposed method is competitive with a similar method for large-scale problems.

Efficient construction of unified continuous and discontinuous Galerkin formulations for the 3D Euler equations

NASA Astrophysics Data System (ADS)

Abdi, Daniel S.; Giraldo, Francis X.

2016-09-01

A unified approach for the numerical solution of the 3D hyperbolic Euler equations using high order methods, namely continuous Galerkin (CG) and discontinuous Galerkin (DG) methods, is presented. First, we examine how classical CG that uses a global storage scheme can be constructed within the DG framework using constraint imposition techniques commonly used in the finite element literature. Then, we implement and test a simplified version in the Non-hydrostatic Unified Model of the Atmosphere (NUMA) for the case of explicit time integration and a diagonal mass matrix. Constructing CG within the DG framework allows CG to benefit from the desirable properties of DG such as, easier hp-refinement, better stability etc. Moreover, this representation allows for regional mixing of CG and DG depending on the flow regime in an area. The different flavors of CG and DG in the unified implementation are then tested for accuracy and performance using a suite of benchmark problems representative of cloud-resolving scale, meso-scale and global-scale atmospheric dynamics. The value of our unified approach is that we are able to show how to carry both CG and DG methods within the same code and also offer a simple recipe for modifying an existing CG code to DG and vice versa.

Constructing Optimal Coarse-Grained Sites of Huge Biomolecules by Fluctuation Maximization.

PubMed

Li, Min; Zhang, John Zenghui; Xia, Fei

2016-04-12

Coarse-grained (CG) models are valuable tools for the study of functions of large biomolecules on large length and time scales. The definition of CG representations for huge biomolecules is always a formidable challenge. In this work, we propose a new method called fluctuation maximization coarse-graining (FM-CG) to construct the CG sites of biomolecules. The defined residual in FM-CG converges to a maximal value as the number of CG sites increases, allowing an optimal CG model to be rigorously defined on the basis of the maximum. More importantly, we developed a robust algorithm called stepwise local iterative optimization (SLIO) to accelerate the process of coarse-graining large biomolecules. By means of the efficient SLIO algorithm, the computational cost of coarse-graining large biomolecules is reduced to within the time scale of seconds, which is far lower than that of conventional simulated annealing. The coarse-graining of two huge systems, chaperonin GroEL and lengsin, indicates that our new methods can coarse-grain huge biomolecular systems with up to 10,000 residues within the time scale of minutes. The further parametrization of CG sites derived from FM-CG allows us to construct the corresponding CG models for studies of the functions of huge biomolecular systems.

Efficient Inversion of Mult-frequency and Multi-Source Electromagnetic Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gary D. Egbert

2007-03-22

The project covered by this report focused on development of efficient but robust non-linear inversion algorithms for electromagnetic induction data, in particular for data collected with multiple receivers, and multiple transmitters, a situation extremely common in eophysical EM subsurface imaging methods. A key observation is that for such multi-transmitter problems each step in commonly used linearized iterative limited memory search schemes such as conjugate gradients (CG) requires solution of forward and adjoint EM problems for each of the N frequencies or sources, essentially generating data sensitivities for an N dimensional data-subspace. These multiple sensitivities allow a good approximation to themore » full Jacobian of the data mapping to be built up in many fewer search steps than would be required by application of textbook optimization methods, which take no account of the multiplicity of forward problems that must be solved for each search step. We have applied this idea to a develop a hybrid inversion scheme that combines features of the iterative limited memory type methods with a Newton-type approach using a partial calculation of the Jacobian. Initial tests on 2D problems show that the new approach produces results essentially identical to a Newton type Occam minimum structure inversion, while running more rapidly than an iterative (fixed regularization parameter) CG style inversion. Memory requirements, while greater than for something like CG, are modest enough that even in 3D the scheme should allow 3D inverse problems to be solved on a common desktop PC, at least for modest (~ 100 sites, 15-20 frequencies) data sets. A secondary focus of the research has been development of a modular system for EM inversion, using an object oriented approach. This system has proven useful for more rapid prototyping of inversion algorithms, in particular allowing initial development and testing to be conducted with two-dimensional example problems, before approaching more computationally cumbersome three-dimensional problems.« less

Development of a High-Resolution Multi-Locus Microsatellite Typing Method for Colletotrichum gloeosporioides.

PubMed

Mehta, Nikita; Hagen, Ferry; Aamir, Sadaf; Singh, Sanjay K; Baghela, Abhishek

2017-12-01

Colletotrichum gloeosporioides is an economically important fungal pathogen causing substantial yield losses indifferent host plants. To understand the genetic diversity and molecular epidemiology of this fungus, we have developed a novel, high-resolution multi-locus microsatellite typing (MLMT) method. Bioinformatic analysis of C. gloeosporioides unannotated genome sequence yielded eight potential microsatellite loci, of which five, CG1 (GT) n , CG2 (GT1) n , CG3 (TC) n , CG4 (CT) n , and CG5 (CT1) n were selected for further study based on their universal amplification potential, reproducibility, and repeat number polymorphism. The selected microsatellites were used to analyze 31 strains of C. gloeosporioides isolated from 20 different host plants from India. All microsatellite loci were found to be polymorphic, and the approximate fragment sizes of microsatellite loci CG1, CG2, CG3, CG4, and CG5 were in ranges of 213-241, 197-227, 231-265, 209-275, and 132-188, respectively. Among the 31 isolates, 55 different genotypes were identified. The Simpson's index of diversity (D) values for the individual locus ranged from 0.79 to 0.92, with the D value of all combined five microsatellite loci being 0.99. Microsatellite data analysis revealed that isolates from Ocimum sanctum , Capsicum annuum (chili pepper), and Mangifera indica (mango) formed distinct clusters, therefore exhibited some level of correlation between certain genotypes and host. The developed MLMT method would be a powerful tool for studying the genetic diversity and any possible genotype-host correlation in C. gloeosporioides .

General aviation accidents related to exceedance of airplane weight/center of gravity limits.

PubMed

Boyd, Douglas D

2016-06-01

Obesity, affects a third of the US population and its corollary occupant weight adversely impacts safe flight operations. Increased aircraft weight results in longer takeoff/landing distances, degraded climb gradients and airframe failure may occur in turbulence. In this study, the rate, temporal changes, and lethality of accidents in piston-powered, general aviation aircraft related to exceeding the maximum aircraft weight/center of gravity (CG) limits were determined. Nation-wide person body mass were from the National Health and Nutrition Examination Survey. The NTSB database was used to identify accidents related to operation of aircraft outside of their weight/CG envelope. Statistical analyses employed T-tests, proportion tests and a Poisson distribution. While the average body mass climbed steadily (p<0.001) between 1999 and 2014 the rate of accidents related to exceedance of the weight/CG limits did not change (p=0.072). However, 57% were fatal, higher (p<0.001) than the 21% for mishaps attributed to other causes/factors. The majority (77%) of accidents were due to an overloaded aircraft operating within its CG limits. As to the phase of flight, accidents during takeoff and those occurring enroute carried the lowest (50%) and highest (85%) proportion of fatal accidents respectively. While the rate of general aviation accidents related to operating an aircraft outside of its weight/CG envelope has not increased over the past 15 years, these types of accidents carry a high risk of fatality. Airmen should be educated as to such risks and to dispel the notion held by some that flights may be safely conducted with an overloaded aircraft within its CG limits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Numerical Solution of the Gyrokinetic Poisson Equation in TEMPEST

NASA Astrophysics Data System (ADS)

Dorr, Milo; Cohen, Bruce; Cohen, Ronald; Dimits, Andris; Hittinger, Jeffrey; Kerbel, Gary; Nevins, William; Rognlien, Thomas; Umansky, Maxim; Xiong, Andrew; Xu, Xueqiao

2006-10-01

The gyrokinetic Poisson (GKP) model in the TEMPEST continuum gyrokinetic edge plasma code yields the electrostatic potential due to the charge density of electrons and an arbitrary number of ion species including the effects of gyroaveraging in the limit kρ1. The TEMPEST equations are integrated as a differential algebraic system involving a nonlinear system solve via Newton-Krylov iteration. The GKP preconditioner block is inverted using a multigrid preconditioned conjugate gradient (CG) algorithm. Electrons are treated as kinetic or adiabatic. The Boltzmann relation in the adiabatic option employs flux surface averaging to maintain neutrality within field lines and is solved self-consistently with the GKP equation. A decomposition procedure circumvents the near singularity of the GKP Jacobian block that otherwise degrades CG convergence.

Multiscale Modeling at Nanointerfaces: Polymer Thin Film Materials Discovery via Thermomechanically Consistent Coarse Graining

NASA Astrophysics Data System (ADS)

Hsu, David D.

Due to high nanointerfacial area to volume ratio, the properties of "nanoconfined" polymer thin films, blends, and composites become highly altered compared to their bulk homopolymer analogues. Understanding the structure-property mechanisms underlying this effect is an active area of research. However, despite extensive work, a fundamental framework for predicting the local and system-averaged thermomechanical properties as a function of configuration and polymer species has yet to be established. Towards bridging this gap, here, we present a novel, systematic coarse-graining (CG) method which is able to capture quantitatively, the thermomechanical properties of real polymer systems in bulk and in nanoconfined geometries. This method, which we call thermomechanically consistent coarse-graining (TCCG), is a two-bead-per-monomer CG hybrid approach through which bonded interactions are optimized to match the atomistic structure via the Iterative Boltzmann Inversion method (IBI), and nonbonded interactions are tuned to macroscopic targets through parametric studies. We validate the TCCG method by systematically developing coarse-grain models for a group of five specialized methacrylate-based polymers including poly(methyl methacrylate) (PMMA). Good correlation with bulk all-atom (AA) simulations and experiments is found for the temperature-dependent glass transition temperature (Tg) Flory-Fox scaling relationships, self-diffusion coefficients of liquid monomers, and modulus of elasticity. We apply this TCCG method also to bulk polystyrene (PS) using a comparable coarse-grain CG bead mapping strategy. The model demonstrates chain stiffness commensurate with experiments, and we utilize a density-correction term to improve the transferability of the elastic modulus over a 500 K range. Additionally, PS and PMMA models capture the unexplained, characteristically dissimilar scaling of Tg with the thickness of free-standing films as seen in experiments. Using vibrational density of states (VDOS) analysis, we discover that increasing backbone to sidechain mass ratio in CG models increases the amplitude of sidechain fluctuations associated with flexibility, and suppresses the free-surface Tg-nanoconfinement effect. This uncovers that intrinsic mass distribution and sidechain flexibility differences in the PS and PMMA chemical structure are central to explaining the dissimilarities in their free surface response. PS and PMMA models are subsequently combined in the supported bilayer film configuration to explore the local Tg-nanoconfinement effect associated with different interface types at nanometer resolution. We find that Tg gradients in the interphase regions where chain mobility deviates from the bulk are independent of the film thickness above a critical thickness and add by the principle of superposition below the critical thickness to good approximation. The analytical expressions describing the interphase regions and their interactions demonstrate geometric universality and can be used to derive accurate local and global Tg estimations for complex nanophase blends and nanocomposite configurations. Our studies ascertain the significance of molecular characteristics on nanoconfinement, and highlight the ability for chemistry-specific CG models to explore and predict thermomechanical property modification accompanying interfacial nanoconfinement.

Solubilization, partial purification, and properties of omega-conotoxin receptors associated with voltage-dependent calcium channels from rat brain synaptosomes.

PubMed

Rosenberg, R L; Isaacson, J S; Tsien, R W

1989-01-01

These experiments provide a starting point for biochemical characterization of Ca channels from neuronal membranes, using omega-CgTX as a specific marker. The purification of the omega-CgTX receptors is far from complete. Each of the purification steps described results in only a two- to fivefold enrichment of the receptor proteins, and is accompanied by a loss of receptor concentration and stability, so the maximal specific activity achieved by a combination of these steps falls several orders of magnitude short of that of a large, homogeneous, active protein. Nevertheless, these studies have yielded important information about the omega-CgTX receptor. The Stokes' radius, determined from gel exclusion chromatography, is approximately 87 A, and the sedimentation coefficient, determined from sucrose gradient sedimentation, is approximately 19 S. These values are similar to those found for the DHP receptors solubilized in digitonin. We have also found that at least some of the omega-CgTX receptors have complex carbohydrate moieties that are recognized by WGA, together with evidence of heterogeneity of receptor glycosylation. Additionally, we have been able to use the solubilized, partially purified receptors in cross-linking experiments to tentatively identify the molecular weights of the omega-CgTX targets from rat brain. A large peptide of approximately 300 kDa, similar to that identified in photoaffinity studies, is very clearly labeled by the chemical incorporation of [125I]omega-CgTX into partially purified receptor preparations, but some ambiguity remains because of the faint labeling of peptides in the 120-170-kDa range. The approximately 300-kDa peptide is much larger than any single peptide component of DHP receptors from skeletal muscle, and it may be related to a molecular combination of the 170-kDa and 135-kDa subunits of the DHP receptor. Because [125I]omega-CgTX presumably labels both N- and L-type neuronal Ca channels, both channel types will probably be found in the purified preparations. Thus, at some time, it will be necessary to separate DHP-sensitive L-type channels from preparations of L- and N-type channels identified by omega-CgTX binding.

Detection of buried targets using a new enhanced very early time electromagnetic (VETEM) prototype system

USGS Publications Warehouse

Cui, T.J.; Chew, W.C.; Aydiner, A.A.; Wright, D.L.; Smith, D.V.

2001-01-01

In this paper, numerical simulations of a new enhanced very early time electromagnetic (VETEM) prototype system are presented, where a horizontal transmitting loop and two horizontal receiving loops are used to detect buried targets, in which three loops share the same axis and the transmitter is located at the center of receivers. In the new VETEM system, the difference of signals from two receivers is taken to eliminate strong direct-signals from the transmitter and background clutter and furthermore to obtain a better SNR for buried targets. Because strong coupling exists between the transmitter and receivers, accurate analysis of the three-loop antenna system is required, for which a loop-tree basis function method has been utilized to overcome the low-frequency breakdown problem. In the analysis of scattering problem from buried targets, a conjugate gradient (CG) method with fast Fourier transform (FFT) is applied to solve the electric field integral equation. However, the convergence of such CG-FFT algorithm is extremely slow at very low frequencies. In order to increase the convergence rate, a frequency-hopping approach has been used. Finally, the primary, coupling, reflected, and scattered magnetic fields are evaluated at receiving loops to calculate the output electric current. Numerous simulation results are given to interpret the new VETEM system. Comparing with other single-transmitter-receiver systems, the new VETEM has better SNR and ability to reduce the clutter.

Distributed Memory Parallel Computing with SEAWAT

NASA Astrophysics Data System (ADS)

Verkaik, J.; Huizer, S.; van Engelen, J.; Oude Essink, G.; Ram, R.; Vuik, K.

2017-12-01

Fresh groundwater reserves in coastal aquifers are threatened by sea-level rise, extreme weather conditions, increasing urbanization and associated groundwater extraction rates. To counteract these threats, accurate high-resolution numerical models are required to optimize the management of these precious reserves. The major model drawbacks are long run times and large memory requirements, limiting the predictive power of these models. Distributed memory parallel computing is an efficient technique for reducing run times and memory requirements, where the problem is divided over multiple processor cores. A new Parallel Krylov Solver (PKS) for SEAWAT is presented. PKS has recently been applied to MODFLOW and includes Conjugate Gradient (CG) and Biconjugate Gradient Stabilized (BiCGSTAB) linear accelerators. Both accelerators are preconditioned by an overlapping additive Schwarz preconditioner in a way that: a) subdomains are partitioned using Recursive Coordinate Bisection (RCB) load balancing, b) each subdomain uses local memory only and communicates with other subdomains by Message Passing Interface (MPI) within the linear accelerator, c) it is fully integrated in SEAWAT. Within SEAWAT, the PKS-CG solver replaces the Preconditioned Conjugate Gradient (PCG) solver for solving the variable-density groundwater flow equation and the PKS-BiCGSTAB solver replaces the Generalized Conjugate Gradient (GCG) solver for solving the advection-diffusion equation. PKS supports the third-order Total Variation Diminishing (TVD) scheme for computing advection. Benchmarks were performed on the Dutch national supercomputer (https://userinfo.surfsara.nl/systems/cartesius) using up to 128 cores, for a synthetic 3D Henry model (100 million cells) and the real-life Sand Engine model ( 10 million cells). The Sand Engine model was used to investigate the potential effect of the long-term morphological evolution of a large sand replenishment and climate change on fresh groundwater resources. Speed-ups up to 40 were obtained with the new PKS solver.

A new algorithm for construction of coarse-grained sites of large biomolecules.

PubMed

Li, Min; Zhang, John Z H; Xia, Fei

2016-04-05

The development of coarse-grained (CG) models for large biomolecules remains a challenge in multiscale simulations, including a rigorous definition of CG representations for them. In this work, we proposed a new stepwise optimization imposed with the boundary-constraint (SOBC) algorithm to construct the CG sites of large biomolecules, based on the s cheme of essential dynamics CG. By means of SOBC, we can rigorously derive the CG representations of biomolecules with less computational cost. The SOBC is particularly efficient for the CG definition of large systems with thousands of residues. The resulted CG sites can be parameterized as a CG model using the normal mode analysis based fluctuation matching method. Through normal mode analysis, the obtained modes of CG model can accurately reflect the functionally related slow motions of biomolecules. The SOBC algorithm can be used for the construction of CG sites of large biomolecules such as F-actin and for the study of mechanical properties of biomaterials. © 2015 Wiley Periodicals, Inc.

Pregnancy testing with hCG--future prospects.

PubMed

Berger, Peter; Sturgeon, Catharine

2014-12-01

Pregnancy tests for human chorionic gonadotrophin (hCG) are used widely in hospital and home settings. Assays measuring hCG also have uses in prenatal screening and oncology. The output from three recent international workshops provides a framework for reliable measurement of hCG. Requirements for future hCG assays include use of clear descriptive nomenclature, informed selection of antibodies of well-defined epitope specificities, and design of robust methods. Tests will be precisely characterized and calibrated in SI units using six International Reference Reagents (IRR) for hCG and variants, and the Fifth International Standard for hCG 07/364, making it possible to report clinical results in molar units. These measures will help to increase patient safety by reducing the risk of erroneous or misleading hCG results. Copyright © 2014 Elsevier Ltd. All rights reserved.

Senior Managers’ Viewpoints Toward Challenges of Implementing Clinical Governance: A National Study in Iran

PubMed Central

Ravaghi, Hamid; Heidarpour, Peigham; Mohseni, Maryam; Rafiei, Sima

2013-01-01

Background: Quality improvement should be assigned as the main mission for healthcare providers. Clinical Governance (CG) is used not only as a strategy focusing on responding to public and government’s intolerance of poor healthcare standards, but also it is implemented for quality improvement in a number of countries. This study aims to identify the key contributing factors in the implementation process of CG from the viewpoints of senior managers in curative deputies of Medical Universities in Iran. Methods: A quantitative method was applied via a questionnaire distributed to 43 senior managers in curative deputies of Iran Universities of Medical Sciences. Data were analyzed using SPSS. Results: Analysis revealed that a number of items were important in the successful implementation of CG from the senior managers’ viewpoints. These items included: knowledge and attitude toward CG, supportive culture, effective communication, teamwork, organizational commitment, and the support given by top managers. Medical staff engagement in CG implementation process, presence of an official position for CG officers, adequate resources, and legal challenges were also regarded as important factors in the implementation process. Conclusion: Knowledge about CG, organizational culture, managerial support, ability to communicate goals and strategies, and the presence of effective structures to support CG, were all related to senior managers’ attitude toward CG and ultimately affected the success of quality improvement activities. PMID:24596887

Pixel-based OPC optimization based on conjugate gradients.

PubMed

Ma, Xu; Arce, Gonzalo R

2011-01-31

Optical proximity correction (OPC) methods are resolution enhancement techniques (RET) used extensively in the semiconductor industry to improve the resolution and pattern fidelity of optical lithography. In pixel-based OPC (PBOPC), the mask is divided into small pixels, each of which is modified during the optimization process. Two critical issues in PBOPC are the required computational complexity of the optimization process, and the manufacturability of the optimized mask. Most current OPC optimization methods apply the steepest descent (SD) algorithm to improve image fidelity augmented by regularization penalties to reduce the complexity of the mask. Although simple to implement, the SD algorithm converges slowly. The existing regularization penalties, however, fall short in meeting the mask rule check (MRC) requirements often used in semiconductor manufacturing. This paper focuses on developing OPC optimization algorithms based on the conjugate gradient (CG) method which exhibits much faster convergence than the SD algorithm. The imaging formation process is represented by the Fourier series expansion model which approximates the partially coherent system as a sum of coherent systems. In order to obtain more desirable manufacturability properties of the mask pattern, a MRC penalty is proposed to enlarge the linear size of the sub-resolution assistant features (SRAFs), as well as the distances between the SRAFs and the main body of the mask. Finally, a projection method is developed to further reduce the complexity of the optimized mask pattern.

Comparison of some new pretreatment methods for second generation bioethanol production from wheat straw and water hyacinth.

PubMed

Guragain, Yadhu Nath; De Coninck, Joelle; Husson, Florence; Durand, Alain; Rakshit, Sudip Kumar

2011-03-01

Pretreatment of lignocellulosic residues like water hyacinth (WH) and wheat straw (WS) using crude glycerol (CG) and ionic liquids (IL) pretreatment was evaluated and compared with conventional dilute acid pretreatment (DAT) in terms of enzymatic hydrolysis yield and fermentation yield of pretreated samples. In the case of WS, 1-butyl-3-methylimidazolium acetate pretreatment was found to be the best method. The hydrolysis yields of glucose and total reducing sugars were 2.1 and 3.3 times respectively higher by IL pretreatment than DAT, while it was 1.4 and 1.9 times respectively higher with CG pretreatment. For WH sample, CG pretreatment was as effective as DAT and more effective than IL pretreatment regarding hydrolysis yield. The fermentation inhibition was not noticeable with both types of pretreatment methods and feedstocks. Besides, CG pretreatment was found as effective as pure glycerol pretreatment for both feedstocks. This opens up an attractive economic route for the utilization of CG. Copyright © 2010 Elsevier Ltd. All rights reserved.

Simultaneous travel time tomography for updating both velocity and reflector geometry in triangular/tetrahedral cell model

NASA Astrophysics Data System (ADS)

Bai, Chao-ying; He, Lei-yu; Li, Xing-wang; Sun, Jia-yu

2018-05-01

To conduct forward and simultaneous inversion in a complex geological model, including an irregular topography (or irregular reflector or velocity anomaly), we in this paper combined our previous multiphase arrival tracking method (referred as triangular shortest-path method, TSPM) in triangular (2D) or tetrahedral (3D) cell model and a linearized inversion solver (referred to as damped minimum norms and constrained least squares problem solved using the conjugate gradient method, DMNCLS-CG) to formulate a simultaneous travel time inversion method for updating both velocity and reflector geometry by using multiphase arrival times. In the triangular/tetrahedral cells, we deduced the partial derivative of velocity variation with respective to the depth change of reflector. The numerical simulation results show that the computational accuracy can be tuned to a high precision in forward modeling and the irregular velocity anomaly and reflector geometry can be accurately captured in the simultaneous inversion, because the triangular/tetrahedral cell can be easily used to stitch the irregular topography or subsurface interface.

Simultaneous travel time tomography for updating both velocity and reflector geometry in triangular/tetrahedral cell model

NASA Astrophysics Data System (ADS)

Bai, Chao-ying; He, Lei-yu; Li, Xing-wang; Sun, Jia-yu

2017-12-01

To conduct forward and simultaneous inversion in a complex geological model, including an irregular topography (or irregular reflector or velocity anomaly), we in this paper combined our previous multiphase arrival tracking method (referred as triangular shortest-path method, TSPM) in triangular (2D) or tetrahedral (3D) cell model and a linearized inversion solver (referred to as damped minimum norms and constrained least squares problem solved using the conjugate gradient method, DMNCLS-CG) to formulate a simultaneous travel time inversion method for updating both velocity and reflector geometry by using multiphase arrival times. In the triangular/tetrahedral cells, we deduced the partial derivative of velocity variation with respective to the depth change of reflector. The numerical simulation results show that the computational accuracy can be tuned to a high precision in forward modeling and the irregular velocity anomaly and reflector geometry can be accurately captured in the simultaneous inversion, because the triangular/tetrahedral cell can be easily used to stitch the irregular topography or subsurface interface.

Inverse Coarse-Graining: A New Tool for Molecular Design

DTIC Science & Technology

2010-12-16

simulations. When compared with the more general multiscale coarse-graining (MS-CG) method, the EF-CG method retains the transferable part of the CG...Y.; Yan, T.; Voth, G. A., A Multiscale coarse-graining study of liquid/vacuum interface of room-temperature ionic liquids with alkyl substituents of...Energetic Room Temperature Ionic Liquid 1-Hydroxyethyl-4Amino-1, 2, 4-Triazolium Nitrate (HEATN). J. Phys. Chem. B 2008, 112, 3121-3131. 6. Liu, P

A majorized Newton-CG augmented Lagrangian-based finite element method for 3D restoration of geological models

NASA Astrophysics Data System (ADS)

Tang, Peipei; Wang, Chengjing; Dai, Xiaoxia

2016-04-01

In this paper, we propose a majorized Newton-CG augmented Lagrangian-based finite element method for 3D elastic frictionless contact problems. In this scheme, we discretize the restoration problem via the finite element method and reformulate it to a constrained optimization problem. Then we apply the majorized Newton-CG augmented Lagrangian method to solve the optimization problem, which is very suitable for the ill-conditioned case. Numerical results demonstrate that the proposed method is a very efficient algorithm for various large-scale 3D restorations of geological models, especially for the restoration of geological models with complicated faults.

[Risk-benefit analysis of a hCG-500 kcal reducing diet (cura romana) in females].

PubMed

Rabe, T; Richter, S; Kiesel, L; Runnebaum, B

1987-05-01

The British physician A.T.W. Simeons described in 1954 a new method for dieting. He combined a reduction diet (500 kcal per day) with daily injections of the pregnancy hormone human chorionic gonadotropin (hCG) (125 IU i.m.). According to Simeons the patient should not lose more weight during a 4-to-6 weeks' diet than without hCG, but the injections should facilitate to maintain the diet and to lose body weight at specific parts of the body (e.g. hip, belly, thigh). After the first publication various studies conducted with male and female patients analysed the efficacy of the "Cura romana". 10 of these studies showed positive and another 10 studies negative results with regard to hCG-related weight reduction. Two of these studies with positive results were double-blind studies (hCG vs. placebo). Most of them were reports on therapeutical experiences and were not controlled studies. According to these reports the body proportions normalized and the feeling of hunger was tolerable. Four out of 10 studies with negative results were controlled studies (hCG vs. control without hCG), whereas 6 were double-blind studies. These studies showed a significant weight reduction during dieting, but no differences between treatment groups in respect of body weight, body proportions and feeling of hunger. One of them is the only German study conducted by Rabe et al. in 1981 in which 82 randomised premenopausal volunteers had been dieting either with hCG or without hCG injections. In recent publications describing mostly well-documented double-blind studies authors largely reject hCG administration in dieting. Supporters of the hCG diet must prove the efficacy of this method in controlled studies according to the German Drug Law. Until then the opinion of the German steroid toxicology panel is still valid, that hCG is ineffective in dieting and should not be used (Bolt 1982 a, 1982 b).

The impact of losing a child on the clinical presentation of complicated grief

PubMed Central

Zetumer, Samuel; Young, Ilanit; Shear, M. Katherine; Skritskaya, Natalia; Lebowitz, Barry; Simon, Naomi; Reynolds, Charles; Mauro, Christine; Zisook, Sidney

2014-01-01

Background It is unclear whether bereaved parents with Complicated Grief (CG) struggle with their grief differently than others with CG. This study addressed this question by comparing CG severity, CG-related symptoms, thoughts and behaviors, and comorbid psychiatric diagnoses of bereaved parents with CG to the diagnoses and symptoms of others with CG. Methods Baseline data from 345 participants enrolled in the Healing Emotions After Loss (HEAL) study, a multi-site CG treatment study, were used to compare parents with CG (n = 75) to others with CG (n = 275). Data from the parent group was then used to compare parents with CG who had lost a younger child (n = 24) to parents with CG who had lost an older child (n = 34). Demographic and loss-related data were also gathered and used to control for confounders between groups. Results Parents with CG demonstrated slightly higher levels of CG (p = .025), caregiver self-blame (p = .007), and suicidality (p = .025) than non-parents with CG. Parents who had lost younger children were more likely to have had a wish to be dead since the loss than parents who had lost older children (p = .041). Limitations All data were gathered from a treatment research study, limiting the of these results. No corrections were made for multiple comparisons. The comparison of parents who lost younger children to parents who lost older children was limited by a small sample size. Conclusions Even in the context of CG, the relationship to the deceased may have a bearing on the degree and severity of grief symptoms and associated features. Bereaved parents with CG reported more intense CG, self-blame, and suicidality than other bereaved groups with CG, though this finding requires confirmation. The heightened levels of suicidal ideation experienced by parents with CG, especially after losing a younger child, suggest the value of routinely screening for suicidal thoughts and behaviors in this group. PMID:25217759

High-dose hook effect in six automated human chorionic gonadotrophin assays.

PubMed

Al-Mahdili, Huda A; Jones, Graham R D

2010-07-01

The high-dose hook effect is a well-known phenomenon of two-site immunoassays including those for human chorionic gonadotrophin (hCG). We investigated the occurrence of a high-dose hook effect in six routinely available hCG assays using a sample with a total hCG concentration of approximately 3,600,000 IU/L. Dilutions of a sample with high hCG concentration were analysed using six common methods: Advia Centaur, Immulite 2000, Dimension RxL, Unicel DxI 800, Roche E170 and Abbott Architect. The measured concentrations and corresponding assay signals were obtained for each method. Performance was compared with manufacturer claims. Four of the tested platforms demonstrated a clear high-dose hook effect, while the other methods showed no hook effect at the highest level tested. Our results indicate that the hook effect may occur in some hCG assays, although the risk of reporting falsely low results was in most cases at higher concentrations than those indicated in manufacturers' product information. Assay design plays a major role in its occurrence. Laboratories should be aware of the assay limitations in this regard.

Aztec user`s guide. Version 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutchinson, S.A.; Shadid, J.N.; Tuminaro, R.S.

1995-10-01

Aztec is an iterative library that greatly simplifies the parallelization process when solving the linear systems of equations Ax = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. Aztec is intended as a software tool for users who want to avoid cumbersome parallel programming details but who have large sparse linear systems which require an efficiently utilized parallel processing system. A collection of data transformation tools are provided that allow for easy creation of distributed sparsemore » unstructured matrices for parallel solution. Once the distributed matrix is created, computation can be performed on any of the parallel machines running Aztec: nCUBE 2, IBM SP2 and Intel Paragon, MPI platforms as well as standard serial and vector platforms. Aztec includes a number of Krylov iterative methods such as conjugate gradient (CG), generalized minimum residual (GMRES) and stabilized biconjugate gradient (BICGSTAB) to solve systems of equations. These Krylov methods are used in conjunction with various preconditioners such as polynomial or domain decomposition methods using LU or incomplete LU factorizations within subdomains. Although the matrix A can be general, the package has been designed for matrices arising from the approximation of partial differential equations (PDEs). In particular, the Aztec package is oriented toward systems arising from PDE applications.« less

Human chorionic gonadotropin (hCG) in the secretome of cultured embryos: hyperglycosylated hCG and hCG-free beta subunit are potential markers for infertility management and treatment.

PubMed

Butler, Stephen A; Luttoo, Jameel; Freire, Maísa O T; Abban, Thomas K; Borrelli, Paola T A; Iles, Ray K

2013-09-01

Human chorionic gonadotropin (hCG) is produced by trophoblast cells throughout pregnancy, and gene expression studies have indicated that hCG-beta subunit (hCGβ) expression is active at the 2 blastomere stage. Here, we investigated the qualitative hCG output of developing embryos in culture and hCG isoforms expressed in the secretome as a novel sensitive method for detecting hCG. Culture media was collected from the culture plates of 118 embryos in culture (including controls and embryos at different stages of culture) from 16 patients undergoing routine fertility treatment. The hCGβ was detectable in media from 2 pronuclear (2PN) stage embryos through to the blastocyst stage. The hCGβ was absent in 1PN and arrested embryos as well as all media controls. Prior to hatching, hyperglycosylated hCG (hCGh) was observed selectively in 3PN embryos, but after hatching, along with hCG, became the dominant hCG molecule observed. We have reported at the 2PN stage the earliest evidence of hCGβ expression in embryos. There is a suggestion this may be indicative of quality in early embryos, and hCGh seen at the pronuclear stage may suggest triploid abnormality. The dominance of hCG, and hCGh expression, seen after blastocyst hatching may be indicative of potential implantation success. Thus, hCG isoforms have potential roles as biomarkers of embryo viability for embryo/blastocyst transfer.

Urine reference intervals for human chorionic gonadotropin (hCG) isoforms by immunoextraction-tandem mass spectrometry to detect hCG use.

PubMed

Butch, Anthony W; Ahrens, Brian D; Avliyakulov, Nuraly K

2017-11-03

Human chorionic gonadotropin (hCG) stimulates testosterone production by the testicles and can normalize suppressed testosterone concentrations in males following prolonged anabolic steroid use. Because of the potential for abuse by males, hCG is on the World Anti-Doping Agency (WADA) list of prohibited substances. The majority of WADA-accredited laboratories measure urinary hCG using an automated immunoassay. Only immunoassays that recognize the intact alpha and beta heterodimer of hCG (intact hCG) should be used to measure urinary hCG for doping control purposes since intact hCG is the only biologically active molecule. WADA further requires that confirmation testing is performed using an intact hCG immunoassay that is different from the one used in the initial testing procedure or by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study we measured the concentration of intact hCG, free β-subunit (hCGβ) and β-subunit core fragment (hCGβcf) in 570, 275, and 256 male urine samples, respectively, by an immunoextraction LC-MS/MS method. Mean concentrations of intact hCG, hCGβ and hCGβcf were 0.04 IU/L, 0.47 pmol/L and 0.16 pmol/L, respectively. The upper reference limits (97.5 th percentile) for intact hCG, hCGβ and hCGβcf were 0.21 IU/L, 0.40 pmol/L, and 1.86 pmol/L, respectively. Based on these data, we recommend a threshold of 1.0 IU/L for intact hCG (false positive rate of <1 in 10 000) for detecting male athletes that dope with hCG. Copyright © 2017 John Wiley & Sons, Ltd.

Toward an Integrated Framwork for Data-Efficient Parametric Adaptive Detection

DTIC Science & Technology

2012-02-27

any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a ...SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON a . REPORT...2012-0534 Distribution A - Approved for Public Release The conjugate-gradient (CG) algorithm is investigated for reduced-rank STAP detection. A family

Analytical and Clinical Validation of the Immulite 1000 hCG Assay for Quantitative Analysis in Urine

PubMed Central

Cate, Frances L.; Moffett, Courtney; Gronowski, Ann M.; Grenache, David G.; Hartmann, Katherine E.; Woodworth, Alison

2013-01-01

Background The Siemens Immulite hCG assay detects all major hCG variants in serum. Currently, this assay is only FDA approved for qualitative measurement of hCG in urine. Methods Complete validation of the hCG assay in urine was performed on the Siemens Immulite 1000 immunoassay platform. Reference intervals were established for females <55 y, females ≥55 y, and males 20–70 y. Results The limit of quantitation was 2.0 IU/l. The Immulite hCG assay was precise for measuring hCG in urine from pregnant patients with intra- and inter-assay imprecision of <11% CV. The assay was linear over a dynamic range of 2–2600 IU/l and 2–3500 IU/l for hCG and hCGβ respectively. The assay was non-linear for hCGβcf. No hook effect was observed at concentrations up to 1,200,000 pmol/l, for hCGβ or hCGβcf. The reference intervals were <2.0 IU/l for males, <2.2 IU/l for females <55 y, and <12.2 IU/l for females ≥55 y. Conclusion The Immulite 1000 hCG assay can accurately quantify hCG in urine. PMID:23470427

Lipid modulatory activities of Cichorium glandulosum Boiss et Huet are mediated by multiple components within hepatocytes

PubMed Central

Ding, Lin; Liu, Jun-Lin; Hassan, Waseem; Wang, Lu-Lu; Yan, Fang-Rong; Shang, Jing

2014-01-01

To investigate a possible methodology of exploiting herbal medicine and design polytherapy for the treatment of non-alcoholic fatty liver disease (NAFLD), we have made use of Cichorium glandulosum Boiss et Huet (CG), a traditional Chinese herbal medicine that has been proven to be effective in treating hepatic diseases. Here, we report that the extract of CG effectively reduced lipid accumulation under conditions of lipid overloading in vivo and in vitro (in a rat high-fat diet model and a hepG2 cell model of free fatty acid treatment). CG extract also protected hepatocytes from injury and inflammation to aid its lipid-lowering properties (in a rat high-fat diet model and a L02 cell model of acetaminophen treatment). Serum chemistry analysis accompanied by in vitro drug screening confirmed that CG-4, CG-10 and CG-14 are the lipo-effective components of CG. Western blotting analysis revealed that these components can regulate key lipid targets at the molecular level, including CD36, FATP5 and PPAR-α, thus the lipid oxidation and lipid absorption pathways. Finally, we adopted the experimental design and statistical method to calculate the best combination proportion (CG-4: CG-10: CG-14 = 2.065: 1.782: 2.153) to optimize its therapeutic effect. PMID:24797163

Hook effect in Abbott i-STAT β-human chorionic gonadotropin (β-hCG) point of care assay.

PubMed

Wilgen, Urs; Pretorius, Carel J; Gous, Rehna S; Martin, Cameron; Hale, Vincent J; Ungerer, Jacobus P J

2014-09-01

Point-of-care testing for β-hCG has been widely advocated to allow rapid diagnosis/exclusion of pregnancy in the emergency department. A quantitative blood β-hCG assay has the additional benefit of being able to monitor the viability of pregnancy, using serial measurements, to determine the appropriate expected increase in β-hCG levels over time (e.g. ectopic pregnancy), and aiding in determining if an intrauterine gestational sac should be visible on sonographic imaging. Evaluation of the newly released Abbott i-STAT β-hCG point-of-care assay with the Beckman Coulter β-hCG laboratory assay in use. Whole blood, plasma and serum samples with a wide range of β-hCG concentrations were analysed by both methods. The Abbott I-STAT β-hCG compares favourably, can be performed on heparinised whole blood, plasma and serum, and shows acceptable accuracy and precision. However a hook effect at elevated β-hCG was shown in gestational trophoblastic disease as well as normal pregnancies. The i-STAT β-hCG performs acceptably in its intended use in the early detection of pregnancy, but results should always be interpreted within the clinical context, as a hook effect may occur. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Development of Mycoplasma synoviae (MS) core genome multilocus sequence typing (cgMLST) scheme.

PubMed

Ghanem, Mostafa; El-Gazzar, Mohamed

2018-05-01

Mycoplasma synoviae (MS) is a poultry pathogen with reported increased prevalence and virulence in recent years. MS strain identification is essential for prevention, control efforts and epidemiological outbreak investigations. Multiple multilocus based sequence typing schemes have been developed for MS, yet the resolution of these schemes could be limited for outbreak investigation. The cost of whole genome sequencing became close to that of sequencing the seven MLST targets; however, there is no standardized method for typing MS strains based on whole genome sequences. In this paper, we propose a core genome multilocus sequence typing (cgMLST) scheme as a standardized and reproducible method for typing MS based whole genome sequences. A diverse set of 25 MS whole genome sequences were used to identify 302 core genome genes as cgMLST targets (35.5% of MS genome) and 44 whole genome sequences of MS isolates from six countries in four continents were used for typing applying this scheme. cgMLST based phylogenetic trees displayed a high degree of agreement with core genome SNP based analysis and available epidemiological information. cgMLST allowed evaluation of two conventional MLST schemes of MS. The high discriminatory power of cgMLST allowed differentiation between samples of the same conventional MLST type. cgMLST represents a standardized, accurate, highly discriminatory, and reproducible method for differentiation between MS isolates. Like conventional MLST, it provides stable and expandable nomenclature, allowing for comparing and sharing the typing results between different laboratories worldwide. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Complicated grief among individuals with major depression: Prevalence, comorbidity, and associated features

PubMed Central

Sung, Sharon C.; Dryman, M. Taylor; Marks, Elizabeth; Shear, M. Katherine; Ghesquiere, Angela; Fava, Maurizio; Simon, Naomi M.

2011-01-01

Background Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders. Methods The present study examined rates of bereavement and threshold CG symptoms (defined as a score ≥ 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD + CG) to those without (MDD – CG). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support. Results Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Amongst those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder. Limitations Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability. Conclusions We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG. PMID:21621849

The multiscale coarse-graining method. XI. Accurate interactions based on the centers of charge of coarse-grained sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao, Zhen; Voth, Gregory A., E-mail: gavoth@uchicago.edu

It is essential to be able to systematically construct coarse-grained (CG) models that can efficiently and accurately reproduce key properties of higher-resolution models such as all-atom. To fulfill this goal, a mapping operator is needed to transform the higher-resolution configuration to a CG configuration. Certain mapping operators, however, may lose information related to the underlying electrostatic properties. In this paper, a new mapping operator based on the centers of charge of CG sites is proposed to address this issue. Four example systems are chosen to demonstrate this concept. Within the multiscale coarse-graining framework, CG models that use this mapping operatormore » are found to better reproduce the structural correlations of atomistic models. The present work also demonstrates the flexibility of the mapping operator and the robustness of the force matching method. For instance, important functional groups can be isolated and emphasized in the CG model.« less

Differentiation of the root of Cultivated Ginseng, Mountain Cultivated Ginseng and Mountain Wild Ginseng using FT-IR and two-dimensional correlation IR spectroscopy

NASA Astrophysics Data System (ADS)

Liu, Dan; Li, Yong-Guo; Xu, Hong; Sun, Su-Qin; Wang, Zheng-Tao

2008-07-01

Ginseng is one of the most widely used herbal medicines. Based on the grown environments and the cultivate method, three kinds of ginseng, Cultivated Ginseng (CG), Mountain Cultivated Ginseng (MCG) and Mountain Wild Ginseng (MWG) are classified. A novel and scientific-oriented method was developed and established to discriminate and identify three kinds of ginseng using Fourier transform infrared spectroscopy (FT-IR), secondary derivative IR spectra and two-dimensional correlation infrared spectroscopy (2D-IR). The findings indicated that the relative contents of starch in the CG were more than that in MCG and MWG, while the relative contents of calcium oxalate and lipids in MWG were more than that in CG and MCG, and the relative contents of fatty acid in MCG were more than that in CG and MWG. The hierarchical cluster analysis was applied to data analysis of MWG, CG and MWG, which could be classified successfully. The results demonstrated the macroscopic IR fingerprint method, including FT-IR, secondary derivative IR and 2D-IR, can be applied to discriminate different ginsengs rapidly, effectively and non-destructively.

Highly sensitive radioimmunoassay for chorionic gonadotropin in human urine. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ayala, A.R.; Nisula, B.C.; Chen, H.C.

1978-10-01

The value of RIAs that measure hCG levels in human urine has been limited principally because of cross-reactivity with human LH. Recently, antisera generated to antigenic determinants on the intact hCG..beta.. subunit and its carboxyl-terminal peptide have been shown to exhibit substantially reduced human LH cross-reactivity. To take maximal advantage of these antisera and to minimize interference by nonspecific substances in urine, a procedure for extracting and concentrating hCG from 24-h urine samples was developed. The procedure involves preparation of a standard kaolin-acetone urine concentrate and adsorption of the hCG in the concentrate to Concanavalin A covalently linked to agarosemore » for purification and subsequent RIA. In urine samples obtained from patients with gestational trophoblastic disease, there was a direct correlation between hCG levels measured by RIA and those estimated by mouse uterine weight bioassy. In individual subjects, hCG levels were determined in serum and urine obtained the same day. When hCG was clearly detectable in the serum at levels greater than 1 ng/ml, the quantity of hCG measured in the urine concentrate exceeded 500 ng/24 h. The concentrates prepared from the urine of normal persons contained an hCG-like glycoprotein substance with antigenic determinants similar to those of the carboxyl-terminal peptide of hCG..beta... As the range of hCG immunoreactivity measured in the urine concentrates of normal subjects was 6 to 52 ng/24 h, specific and sensitive detection of urinary hCG could be accomplished in patients whose sera contained hCG undetectable by conventional RIA. Partial purification and concentration of urinary hCG by this procedure with subsequent RIA provides a sensitive and reliable method for detecting hCG in urine.« less

Genomic analysis of NF-κB signaling pathway reveals its complexity in Crassostrea gigas.

PubMed

Yu, Mingjia; Chen, Jianming; Bao, Yongbo; Li, Jun

2018-01-01

NF-κB signaling pathway is an evolutionarily conserved pathway that plays highly important roles in several developmental, cellular and immune response processes. With the recent release of the draft Pacific oyster (Crassostra gigas) genome sequence, we have sought to identify the various components of the NF-κB signaling pathway in these mollusks and investigate their gene structure. We further constructed phylogenetic trees to establish the evolutionary relationship of the oyster proteins with their homologues in vertebrates and invertebrates using BLASTX and neighbor-joining method. We report the presence of two classic NF-κB/Rel homologues in the pacific oyster namely Cgp100 and CgRel, which possess characteristic RHD domain and a consensus nuclear localization signal, similar to mammalian homologues and an additional CgRel-like protein, unique to C. gigas. Further, in addition to two classical IκB homologues, CgIκB1 and CgIκB2, we have identified three atypical IκB family members namely CgIκB3, CgIκB4 and CgBCL3 which lack the IκB degradation motif and consist of only one exon that might have arisen by retrotransposition from CgIκB1. Finally, we report the presence of three IKKs and one NEMO genes in oyster genome, named CgIKK1, CgIKK2, CgIKK3 and CgNEMO, respectively. While CgIKK1 and CgIKK3 domain structure is similar to their mammalian homologues, CgIKK2 was found to lack the HLH and NBD domains. Overall, the high conservation of the NF-κB/Rel, IκB and IKK family components in the pacific oyster and their structural similarity to the vertebrate and invertebrate homologues underline the functional importance of this pathway in regulation of critical cellular processes across species. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical governance implementation in a selected teaching emergency department: a systems approach

PubMed Central

2012-01-01

Background Clinical governance (CG) is among the different frameworks proposed to improve the quality of healthcare. Iran, like many other countries, has put healthcare quality improvement in its top health policy priorities. In November 2009, implementation of CG became a task for all hospitals across the country. However, it has been a challenge to clarify the notion of CG and the way to implement it in Iran. The purpose of this action research study is to understand how CG can be defined and implemented in a selected teaching emergency department (ED). Methods/design We will use Soft Systems Methodology for both designing the study and inquiring into its content. As we considered a complex problem situation regarding the quality of care in the selected ED, we initially conceptualized CG as a cyclic set of purposeful activities designed to explore the situation and find relevant changes to improve the quality of care. Then, implementation of CG will conceptually be to carry out that set of purposeful activities. The activities will be about: understanding the situation and finding out relevant issues concerning the quality of care; exploring different stakeholders’ views and ideas about the situation and how it can be improved; and defining actions to improve the quality of care through structured debates and development of accommodations among stakeholders. We will flexibly use qualitative methods of data collection and analysis in the course of the study. To ensure the study rigor, we will use different strategies. Discussion Successful implementation of CG, like other quality improvement frameworks, requires special consideration of underlying complexities. We believe that addressing the complex situation and reflections on involvement in this action research will make it possible to understand the concept of CG and its implementation in the selected setting. By describing the context and executed flexible methods of implementation, the results of this study would contribute to the development of implementation science and be employed by boards and executives governing other clinical settings to facilitate CG implementation. PMID:22963589

Detection of urinary leakage after radical retropubic prostatectomy by contrast enhanced ultrasound - do we still need conventional retrograde cystography?

PubMed

Schoeppler, Gita M; Buchner, Alexander; Zaak, Dirk; Khoder, Wael; Staehler, Michael; Stief, Christian G; Reiser, Maximilian F; Clevert, Dirk-Andre

2010-12-01

To prospectively evaluate the accuracy of transvesical contrast-enhanced ultrasound (CEUS) as an alternative method for the detection of anastomotic leakage after radical retropubic prostatectomy (RRP) in comparison with the current standard method of conventional retrograde cystography (CG). Forty-three patients underwent RRP for histologically proven localized prostate cancer. The vesico-urethral anastomosis was evaluated 8 days after RRP by CG and CEUS. Any peri-anastomotic leakage was assessed and determined in CG and CEUS as follows: no extravasation (EV), small leakage (≤0.5 cm), moderate leakage (>0.5 cm to ≤2 cm), large leakage (>2 cm diameter of EV seen). In total, 21 (49%) patients showed a watertight anastomosis. Ten (23%), two (4.7%) and ten (23%) patients showed a small, intermediate and large EV, respectively. In 31 cases (72%) there was 100% agreement of CG and CEUS for detection of no, moderate and large EV, respectively. In nine cases a small and in two cases a moderate EV was categorized as watertight anastomosis by CEUS. Only in one case did CG detect a small EV where a large EV was detected in CEUS. The agreement between both methods was 95% for detecting absence or large leakages. CEUS is a promising imaging modality that seems to be equivalent to CG for detecting the presence of a large anastomotic leakage that is clinically relevant for postoperative persistence of the indwelling catheter. CEUS could be a cheap and time-saving alternative to the CG without exposure of the patient to radiation. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

Senior managers' viewpoints toward challenges of implementing clinical governance: a national study in iran.

PubMed

Ravaghi, Hamid; Heidarpour, Peigham; Mohseni, Maryam; Rafiei, Sima

2013-11-01

Quality improvement should be assigned as the main mission for healthcare providers. Clinical Governance (CG) is used not only as a strategy focusing on responding to public and government's intolerance of poor healthcare standards, but also it is implemented for quality improvement in a number of countries. This study aims to identify the key contributing factors in the implementation process of CG from the viewpoints of senior managers in curative deputies of Medical Universities in Iran. A quantitative method was applied via a questionnaire distributed to 43 senior managers in curative deputies of Iran Universities of Medical Sciences. Data were analyzed using SPSS. Analysis revealed that a number of items were important in the successful implementation of CG from the senior managers' viewpoints. These items included: knowledge and attitude toward CG, supportive culture, effective communication, teamwork, organizational commitment, and the support given by top managers. Medical staff engagement in CG implementation process, presence of an official position for CG officers, adequate resources, and legal challenges were also regarded as important factors in the implementation process. Knowledge about CG, organizational culture, managerial support, ability to communicate goals and strategies, and the presence of effective structures to support CG, were all related to senior managers' attitude toward CG and ultimately affected the success of quality improvement activities.

Adjoint Sensitivity Computations for an Embedded-Boundary Cartesian Mesh Method and CAD Geometry

NASA Technical Reports Server (NTRS)

Nemec, Marian; Aftosmis,Michael J.

2006-01-01

Cartesian-mesh methods are perhaps the most promising approach for addressing the issues of flow solution automation for aerodynamic design problems. In these methods, the discretization of the wetted surface is decoupled from that of the volume mesh. This not only enables fast and robust mesh generation for geometry of arbitrary complexity, but also facilitates access to geometry modeling and manipulation using parametric Computer-Aided Design (CAD) tools. Our goal is to combine the automation capabilities of Cartesian methods with an eficient computation of design sensitivities. We address this issue using the adjoint method, where the computational cost of the design sensitivities, or objective function gradients, is esseutially indepeudent of the number of design variables. In previous work, we presented an accurate and efficient algorithm for the solution of the adjoint Euler equations discretized on Cartesian meshes with embedded, cut-cell boundaries. Novel aspects of the algorithm included the computation of surface shape sensitivities for triangulations based on parametric-CAD models and the linearization of the coupling between the surface triangulation and the cut-cells. The objective of the present work is to extend our adjoint formulation to problems involving general shape changes. Central to this development is the computation of volume-mesh sensitivities to obtain a reliable approximation of the objective finction gradient. Motivated by the success of mesh-perturbation schemes commonly used in body-fitted unstructured formulations, we propose an approach based on a local linearization of a mesh-perturbation scheme similar to the spring analogy. This approach circumvents most of the difficulties that arise due to non-smooth changes in the cut-cell layer as the boundary shape evolves and provides a consistent approximation tot he exact gradient of the discretized abjective function. A detailed gradient accurace study is presented to verify our approach. Thereafter, we focus on a shape optimization problem for an Apollo-like reentry capsule. The optimization seeks to enhance the lift-to-drag ratio of the capsule by modifyjing the shape of its heat-shield in conjunction with a center-of-gravity (c.g.) offset. This multipoint and multi-objective optimization problem is used to demonstrate the overall effectiveness of the Cartesian adjoint method for addressing the issues of complex aerodynamic design. This abstract presents only a brief outline of the numerical method and results; full details will be given in the final paper.

Complicated grief associated with Hurricane Katrina

PubMed Central

Shear, M. Katherine; McLaughlin, Katie A.; Ghesquiere, Angela; Gruber, Michael J.; Sampson, Nancy A.; Kessler, Ronald C.

2011-01-01

Background Although losses are important consequences of disasters, few epidemiological studies of disasters have assessed complicated grief (CG) and none assessed CG associated with losses other than death of loved one. Methods Data come from the baseline survey of the Hurricane Katrina Community Advisory Group (CAG), a representative sample of 3,088 residents of the areas directly affected by Hurricane Katrina. A brief screen for CG was included containing four items consistent with the proposed DSM 5 criteria for a diagnosis of bereavement-related adjustment disorder. Results 58.5% of respondents reported a significant hurricane-related loss: Most-severe losses were 29.0% tangible, 9.5% interpersonal, 8.1% intangible, 4.2% work-financial, and 3.7% death of loved one. 26.1% of respondents with significant loss had possible CG and 7.0% moderate-severe CG. Death of loved one was associated with the highest conditional probability of moderate-severe CG (18.5%, compared to 1.1–10.5% conditional probabilities for other losses) but accounted for only 16.5% of moderate-severe CG due to its comparatively low prevalence. Most moderate-severe CG was due to tangible (52.9%) or interpersonal (24.0%) losses. Significant predictors of CG were mostly unique to either bereavement (racial-ethnic minority status, social support) or other losses (pre-hurricane history of psychopathology, social competence.). Conclusions Non-bereavement losses accounted for the vast majority of hurricane-related possible CG despite risk of CG being much higher in response to bereavement than to other losses. This result argues for expansion of research on CG beyond bereavement and alerts clinicians to the need to address post-disaster grief associated with a wide range of losses. PMID:21796740

Human chorionic gonadotropin radioantibodies in the radioimmunodetection of cancer and for disclosure of occult metastases.

PubMed Central

Goldenberg, D M; Kim, E E; DeLand, F H

1981-01-01

Radioimmunodetection (RaID) of tumors containing human chorionic gonadotropin (hCG; choriogonadotropin) was evaluated in 25 patients by injecting 131I-labeled goat antibody IgG against hCG and performing total-body photoscans with a gamma scintillation camera 24 and 48 hr later. All 10 testicular cancer patients with proven tumor sites had positive RaID results, whereas three cases without known tumor were negative. Four patients with hydatidiform mole and one with degenerative products of conception showed positive RaID results consistent with elevated serum hCG titers. Two putatively false-positive results were obtained in patients with lung or ovarian cancer, whereas a false-negative metastasis to the liver of a patient with lung cancer and an elevated serum hCG titer was observed. Of 14 tumor sites found by RaID in 10 testicular cancer patients, 4 were revealed by RaID prior to any other detection method used and provided a lead time to definitive diagnosis by other measures of a few days to greater than 1 yr. Although a number of patients had high serum hCG levels, even exceeding 3 microgram/ml, the xenogeneic antibody was capable of localizing in tumor. No adverse effects were noted in any of the patients studied. Thus, hCG RaID appears to be a safe and effective method of detecting and locating hCG-producing tumors and has been found to disclose occult testicular cancers. Images PMID:6278487

MR elastography of prostate cancer: quantitative comparison with histopathology and repeatability of methods.

PubMed

Sahebjavaher, Ramin S; Nir, Guy; Honarvar, Mohammad; Gagnon, Louis O; Ischia, Joseph; Jones, Edward C; Chang, Silvia D; Fazli, Ladan; Goldenberg, S Larry; Rohling, Robert; Kozlowski, Piotr; Sinkus, Ralph; Salcudean, Septimiu E

2015-01-01

The purpose of this work was to assess trans-perineal prostate magnetic resonance elastography (MRE) for (1) repeatability in phantoms/volunteers and (2) diagnostic power as correlated with histopathology in prostate cancer patients. The three-dimensional (3D) displacement field was obtained using a fractionally encoded gradient echo sequence using a custom-made transducer. The repeatability of the method was assessed based on three repeat studies and by changing the driving frequency by 3% in studies on a phantom and six healthy volunteers. Subsequently, 11 patients were examined with MRE prior to radical prostatectomy. The areas under the receiver operating characteristic curves were calculated using a windowed voxel-to-voxel approach by comparing the 2D registered slides, masked with the Gleason score. For the repeatability study, the average intraclass correlation coefficient for elasticity images was 99% for repeat phantom studies, 98% for ±6 Hz phantom studies, 95% for volunteer repeat studies with 2 min acquisition time, 82% for ±2 Hz volunteer studies with 2 min acquisition time and 73% for repeat volunteer studies with 8 min acquisition time. For the patient study, the average elasticity was 8.2 ± 1.7 kPa in the prostate capsule, 7.5 ± 1.9 kPa in the peripheral zone (PZ), 9.7 ± 3.0 kPa in the central gland (CG) and 9.0 ± 3.4 kPa in the transition zone. In the patient study, cancerous tissue with Gleason score at least 3 + 3 was significantly (p < 0.05) different from normal tissue in 10 out of 11 cases with tumors in the PZ, and 6 out of 9 cases with tumors in the CG. However, the overall case-averaged area under the curve was 0.72 in the PZ and 0.67 in the CG. Cancerous tissue was not always stiffer than normal tissue. The inversion algorithm was sensitive to (i) vibration amplitude and displacement nodes and (ii) misalignment of the 3D wave field due to subject movement. Copyright © 2014 John Wiley & Sons, Ltd.

Validating and determining the weight of items used for evaluating clinical governance implementation based on analytic hierarchy process model.

PubMed

Hooshmand, Elaheh; Tourani, Sogand; Ravaghi, Hamid; Vafaee Najar, Ali; Meraji, Marziye; Ebrahimipour, Hossein

2015-04-08

The purpose of implementing a system such as Clinical Governance (CG) is to integrate, establish and globalize distinct policies in order to improve quality through increasing professional knowledge and the accountability of healthcare professional toward providing clinical excellence. Since CG is related to change, and change requires money and time, CG implementation has to be focused on priority areas that are in more dire need of change. The purpose of the present study was to validate and determine the significance of items used for evaluating CG implementation. The present study was descriptive-quantitative in method and design. Items used for evaluating CG implementation were first validated by the Delphi method and then compared with one another and ranked based on the Analytical Hierarchy Process (AHP) model. The items that were validated for evaluating CG implementation in Iran include performance evaluation, training and development, personnel motivation, clinical audit, clinical effectiveness, risk management, resource allocation, policies and strategies, external audit, information system management, research and development, CG structure, implementation prerequisites, the management of patients' non-medical needs, complaints and patients' participation in the treatment process. The most important items based on their degree of significance were training and development, performance evaluation, and risk management. The least important items included the management of patients' non-medical needs, patients' participation in the treatment process and research and development. The fundamental requirements of CG implementation included having an effective policy at national level, avoiding perfectionism, using the expertise and potentials of the entire country and the coordination of this model with other models of quality improvement such as accreditation and patient safety. © 2015 by Kerman University of Medical Sciences.

Whole-Genome Sequencing of Recent Listeria monocytogenes Isolates from Germany Reveals Population Structure and Disease Clusters.

PubMed

Halbedel, Sven; Prager, Rita; Fuchs, Stephan; Trost, Eva; Werner, Guido; Flieger, Antje

2018-06-01

Listeria monocytogenes causes foodborne outbreaks with high mortality. For improvement of outbreak cluster detection, the German consiliary laboratory for listeriosis implemented whole-genome sequencing (WGS) in 2015. A total of 424 human L. monocytogenes isolates collected in 2007 to 2017 were subjected to WGS and core-genome multilocus sequence typing (cgMLST). cgMLST grouped the isolates into 38 complexes, reflecting 4 known and 34 unknown disease clusters. Most of these complexes were confirmed by single nucleotide polymorphism (SNP) calling, but some were further differentiated. Interestingly, several cgMLST cluster types were further subtyped by pulsed-field gel electrophoresis, partly due to phage insertions in the accessory genome. Our results highlight the usefulness of cgMLST for routine cluster detection but also show that cgMLST complexes require validation by methods providing higher typing resolution. Twelve cgMLST clusters included recent cases, suggesting activity of the source. Therefore, the cgMLST nomenclature data presented here may support future public health actions. Copyright © 2018 American Society for Microbiology.

[Study on the analytical methods of catechins in tea and green tea polyphenol samples by high performance liquid chromatography].

PubMed

Dai, J; Wang, H X; Chen, S W; Tang, J

2001-09-01

Hypersil BDS C18 and Zorbax SB C18, suitable to separate simultaneously seven kinds of catechins and caffeine, were screened out from seven brands of reversed-phase columns. Mobile phase was a solution of methanol-water-acetic acid (or trifluoro acetic acid). Seven kinds of catechins in tea samples from six places in China and three green tea polyphenol(GTP) samples from different producers were separated and determined in 30 min by isocratic and gradient elutions. The effects of mobile phase components and temperature of column on retention parameters of catechins and caffeine are reviewed. Chromatographic conditions and pretreatment methods of samples were optimized. Gallocatechin gallate(GCG) and (-)-catechin gallate(CG) were identified by electrospray ionization mass spectrometry(ESI-MS) and prepared by high performance liquid chromatography for quantitative analysis. The other catechins, (-)-epigallocatechin (EGC), (+)-catechin (D-C), (-)-epicatechin(EC), (-)-epigallocatechin gallate(EGCG), (-)-epicatechin gallate(ECG) were identified with standards.

Coarse-grained molecular dynamics simulations for giant protein-DNA complexes

NASA Astrophysics Data System (ADS)

Takada, Shoji

Biomolecules are highly hierarchic and intrinsically flexible. Thus, computational modeling calls for multi-scale methodologies. We have been developing a coarse-grained biomolecular model where on-average 10-20 atoms are grouped into one coarse-grained (CG) particle. Interactions among CG particles are tuned based on atomistic interactions and the fluctuation matching algorithm. CG molecular dynamics methods enable us to simulate much longer time scale motions of much larger molecular systems than fully atomistic models. After broad sampling of structures with CG models, we can easily reconstruct atomistic models, from which one can continue conventional molecular dynamics simulations if desired. Here, we describe our CG modeling methodology for protein-DNA complexes, together with various biological applications, such as the DNA duplication initiation complex, model chromatins, and transcription factor dynamics on chromatin-like environment.

Genetic variants in 3'-UTRs of MTHFR in the pregnancies complicated with preeclampsia and bioinformatics analysis.

PubMed

Mohammadpour-Gharehbagh, Abbas; Salimi, Saeedeh; Keshavarzi, Farshid; Saeidian, Foozieh; Mousavi, Mahdieh; Teimoori, Batool; Esmaeilipour, Maryam; Mokhtari, Mojgan

2018-01-01

Preeclampsia (PE) as a pregnancy-specific disorder is the major cause of mortality and morbidity of mothers and fetuses. This study attempts to investigate the possible association between the 2572C>A (rs4846049) and 4869C>G (rs1537514) polymorphisms in the 3'- untranslated region of MTHFR gene and the risk of PE. A total of 198 patients diagnosed with PE and 171 unrelated, age matched healthy pregnant women, were recruited for this case-control study. The MTHFR 2572C>A and 4869C>G genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The CG genotype of MTHFR 4869C>G was associated with decreased risk of PE, and this genotype was found to be a protective factor for PE susceptibility. There was no significant difference in the genotypes of MTHFR 2572C>A polymorphism between PE patients and control group. The frequency of combined AC/CG genotypes of MTHFR 2572C>A and 4869C>G polymorphisms were less frequent in PE patients and were associated with a lower risk of PE. The C-G and A-G haplotypes of MTHFR 2572C>A and 4869C>G polymorphisms were significantly lower in PE patients. In conclusion, the CG genotype of MTHFR 4869C>G polymorphism was associated with a lower risk of PE. No association was found between MTHFR 2572C>A polymorphism and PE. © 2017 Wiley Periodicals, Inc.

Star formation, structure, and formation mechanism of cometary globules: near-infrared observations of CG 1 and CG 2

NASA Astrophysics Data System (ADS)

Mäkelä, M. M.; Haikala, L. K.

2013-02-01

Context. Cometary globule (CG) 1 and CG 2 are "classic" cometary globules in the Gum Nebula. They have compact heads and long dusty tails that point away from the centre of the Gum Nebula. Aims: We study the structure of CG 1 and CG 2 and the star formation in them to find clues to the CG formation mechanism. The two possible CG formation mechanisms, radiation-driven implosion (RDI) and a supernova blast wave, produce a characteristic mass distribution where the major part of the mass is situated in either the head (RDI) or the tail (supernova blast). Methods: CG 1 and CG 2 were imaged in the near infrared (NIR) JsHKs bands. NIR photometry was used to locate NIR excess objects and to create visual extinction maps of the CGs. The AV maps allow us to analyse the large-scale structure of CG 1 and CG 2. Archival images from the WISE and Spitzer satellites and HIRES-processed IRAS images were used to study the globule's small-scale structure. Fits were made to the spectral energy distribution plots of the NIR-excess stars to estimate their age and mass. Results: In addition to the previously known CG 1 IRS 1 we discovered three new NIR-excess objects in IR imaging, two in CG 1 and one in CG 2. CG 2 IRS 1 is the first detection of star formation in CG 2. The objects are young low-mass stars. CG 1 IRS 1 is probably a class I protostar in the head of CG 1. CG 1 IRS 1 drives a bipolar outflow, which is very weak in CO, but the cavity walls are seen in reflected light in our NIR and in the Spitzer 3.6 and 4.5 μm images. Strong emission from excited polycyclic aromatic hydrocarbon particles and very small grains were detected in the CG 1 tail. The total mass of CG 1 in the observed area is 41.9 M⊙ of which 16.8 M⊙ lies in the head. For CG 2 these values are 31.0 M⊙ total and 19.1 M⊙ in the head. The observed mass distribution does not offer a firm conclusion for the formation mechanism of the two CGs: CG 1 is in too evolved a state, and in CG 2 part of the globule tail was outside the observed area. Conclusions: Even though the masses of the two CGs are similar, star formation has been more efficient in CG 1. By now, altogether six young low-mass stars have been detected in CG 1 and only one in CG 2. A possible new outflow was discovered to be emanating from CG 1 IRS 1. Based partly on observations done at the European Southern Observatory, La Silla, Chile (ESO programme 078.C-0490).Appendices A and B are available in electronic form at http://www.aanda.orgTables 1-3 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr 130.79.128.5 or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/550/A83

Antistaphylococcal activities of CG400549, a new bacterial enoyl-acyl carrier protein reductase (FabI) inhibitor.

PubMed

Park, Hee Soo; Yoon, Yu Min; Jung, Sung Ji; Kim, Cheol Min; Kim, Jeong Mi; Kwak, Jin-Hwan

2007-09-01

This study was performed to analyse in vitro and in vivo activities of CG400549, a new FabI inhibitor, against clinical isolates of staphylococci. The mode of action of CG400549 and resistance mechanism of Staphylococcus aureus against CG400549 were also investigated by genetic approaches. In vitro activity of CG400549 was evaluated by the 2-fold agar sdilution method as described by the CLSI, and compared with those of oxacillin, erythromycin, ciprofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, vancomycin, linezolid and quinupristin-dalfopristin. In vivo activity of CG400549 was determined against systemic infections in mice. Time-kill curves of CG400549 were analysed at concentrations of 1 x , 2 x and 4 x MIC against S. aureus strains. CG400549 had the lowest MICs among the test compounds against 238 clinical isolates of S. aureus (MIC90, 0.25 mg/L) and 51 clinical isolates of coagulase-negative staphylococci (MIC90, 1 mg/L). The activity of CG400549 was irrespective of whether the strains were methicillin-susceptible or -resistant. Furthermore, CG400549 was effective by oral or subcutaneous administration against systemic infections in mice. In a time-kill study, CG400549 at concentrations of 1 x MIC, 2 x MIC and 4 x MIC had a bacteriostatic activity during 24 h. A FabI-overexpressing S. aureus strain gave rise to an increase in the MIC of CG400549 compared with the parental strain, while the susceptibilities of the FabI-overexpressing S. aureus strain to the other antibacterial agents such as oxacillin, erythromycin and ciprofloxacin were not affected. This result showed that the mode of action of CG400549 was via inhibition of FabI, which is involved in biosynthesis of fatty acids in bacteria. Study of the resistance mechanism of S. aureus showed that CG400549-resistant mutants of S. aureus had an alteration in FabI at Phe-204 to Leu. CG400549 had potent in vitro and in vivo activity against staphylococci, including methicillin-, ciprofloxacin- and multidrug-resistant staphylococci strains. This compound could be a good candidate for clinical development as a novel anti-MRSA drug.

Overview of the Cancer Genetics and Pathway Curation tasks of BioNLP Shared Task 2013

PubMed Central

2015-01-01

Background Since their introduction in 2009, the BioNLP Shared Task events have been instrumental in advancing the development of methods and resources for the automatic extraction of information from the biomedical literature. In this paper, we present the Cancer Genetics (CG) and Pathway Curation (PC) tasks, two event extraction tasks introduced in the BioNLP Shared Task 2013. The CG task focuses on cancer, emphasizing the extraction of physiological and pathological processes at various levels of biological organization, and the PC task targets reactions relevant to the development of biomolecular pathway models, defining its extraction targets on the basis of established pathway representations and ontologies. Results Six groups participated in the CG task and two groups in the PC task, together applying a wide range of extraction approaches including both established state-of-the-art systems and newly introduced extraction methods. The best-performing systems achieved F-scores of 55% on the CG task and 53% on the PC task, demonstrating a level of performance comparable to the best results achieved in similar previously proposed tasks. Conclusions The results indicate that existing event extraction technology can generalize to meet the novel challenges represented by the CG and PC task settings, suggesting that extraction methods are capable of supporting the construction of knowledge bases on the molecular mechanisms of cancer and the curation of biomolecular pathway models. The CG and PC tasks continue as open challenges for all interested parties, with data, tools and resources available from the shared task homepage. PMID:26202570

A facile and sensitive peptide-modulating graphene oxide nanoribbon catalytic nanoplasmon analytical platform for human chorionic gonadotropin.

PubMed

Liang, Aihui; Li, Chongning; Li, Dan; Luo, Yanghe; Wen, Guiqing; Jiang, Zhiliang

2017-01-01

The nanogold reaction between HAuCl 4 and citrate is very slow, and the catalyst graphene oxide nanoribbon (GONR) enhanced the nanoreaction greatly to produce gold nanoparticles (AuNPs) that exhibited strong surface plasmon resonance (SPR) absorption (Abs) at 550 nm and resonance Rayleigh scattering (RRS) at 550 nm. Upon addition of the peptide of human chorionic gonadotropin (hCG), the peptide could adsorb on the GONR surface, which inhibited the catalysis. When hCG was added, peptides were separated from the GONR surface due to the formation of stable peptide-hCG complex, which led to the activation of GONR catalytic effect. With the increase in hCG concentration, the RRS and Abs signal enhanced linearly. The enhanced RRS value showed a good linear relationship with hCG concentration in the range of 0.2-20 ng/mL, with a detection limit of 70 pg/mL. Accordingly, two new GONR catalytic RRS/Abs methods were established for detecting hCG in serum samples.

Urinary hCG patterns during the week following implantation

PubMed Central

Nepomnaschy, PA; Weinberg, CR; Wilcox, AJ; Baird, DD

2013-01-01

BACKGROUND Human chorionic gonadotropin (hCG) is used to monitor pregnancy status. Yet the pattern of hCG excretion in the first week following implantation has not been adequately described. OBJECTIVE To describe hCG's average profile and its variability during the 7 days following estimated implantation in a population of naturally-conceived pregnancies. METHODS We measured daily hCG concentrations in first-morning urine for 142 clinical pregnancies from women with no known fertility problems. Mixed-effects regression models were used to estimate the hCG trajectory and its variability in relation to pregnancy outcomes. RESULTS HCG rose three-fold between the day of detection and the next day (95% CI = 2.7–3.4). The relative rate of rise decreased thereafter, reaching 1.6-fold (95% CI = 1.5–1.8) between days 6 and 7. HCG levels followed a log-quadratic trajectory, and the patterns of rise were unrelated to number of fetuses, risk of miscarriage, or sex of the baby. Later implantations (after 10 luteal days) produced slower rates of increase. CONCLUSIONS While mean hCG follows a log-quadratic trajectory during the first week of detectability, there is high variability across pregnancies. Later implantation may reflect characteristics of the uterus or conceptus that slow hCG production. PMID:18083748

Oral Health, Temporomandibular Disorder, and Masticatory Performance in Patients with Charcot-Marie-Tooth Type 2

PubMed Central

Rezende, Rejane L. S.; Bonjardim, Leonardo R.; Neves, Eduardo L. A.; Santos, Lidiane C. L.; Nunes, Paula S.; Garcez, Catarina A.; Souza, Cynthia C.; Araújo, Adriano A. S.

2013-01-01

Background. The aim of this study was to evaluate the oral health status of temporomandibular disorders (TMD) and bruxism, as well as to measure masticatory performance of subjects with Charcot-Marie-Tooth type 2 (CMT2). Methods and Results. The average number of decayed, missing, and filled teeth (DMFT) for both groups, control (CG) and CMT2, was considered low (CG = 2.46; CMT2 = 1.85, P = 0.227). The OHIP-14 score was considered low (CG = 2.86, CMT2 = 5.83, P = 0.899). The prevalence of self-reported TMD was 33.3% and 38.9% (P = 0.718) in CG and CMT2 respectively and for self-reported bruxism was 4.8% (CG) and 22.2% (CMT2), without significant difference between groups (P = 0.162). The most common clinical sign of TMD was masseter (CG = 38.1%; CMT2 = 66.7%) and temporalis (CG = 19.0%; GCMT2 = 33.3%) muscle pain. The geometric mean diameter (GMD) was not significantly different between groups (CG = 4369; CMT2 = 4627, P = 0.157). Conclusion. We conclude that the CMT2 disease did not negatively have influence either on oral health status in the presence and severity of TMD and bruxism or on masticatory performance. PMID:24391462

Modeling Structural Dynamics of Biomolecular Complexes by Coarse-Grained Molecular Simulations.

PubMed

Takada, Shoji; Kanada, Ryo; Tan, Cheng; Terakawa, Tsuyoshi; Li, Wenfei; Kenzaki, Hiroo

2015-12-15

Due to hierarchic nature of biomolecular systems, their computational modeling calls for multiscale approaches, in which coarse-grained (CG) simulations are used to address long-time dynamics of large systems. Here, we review recent developments and applications of CG modeling methods, focusing on our methods primarily for proteins, DNA, and their complexes. These methods have been implemented in the CG biomolecular simulator, CafeMol. Our CG model has resolution such that ∼10 non-hydrogen atoms are grouped into one CG particle on average. For proteins, each amino acid is represented by one CG particle. For DNA, one nucleotide is simplified by three CG particles, representing sugar, phosphate, and base. The protein modeling is based on the idea that proteins have a globally funnel-like energy landscape, which is encoded in the structure-based potential energy function. We first describe two representative minimal models of proteins, called the elastic network model and the classic Go̅ model. We then present a more elaborate protein model, which extends the minimal model to incorporate sequence and context dependent local flexibility and nonlocal contacts. For DNA, we describe a model developed by de Pablo's group that was tuned to well reproduce sequence-dependent structural and thermodynamic experimental data for single- and double-stranded DNAs. Protein-DNA interactions are modeled either by the structure-based term for specific cases or by electrostatic and excluded volume terms for nonspecific cases. We also discuss the time scale mapping in CG molecular dynamics simulations. While the apparent single time step of our CGMD is about 10 times larger than that in the fully atomistic molecular dynamics for small-scale dynamics, large-scale motions can be further accelerated by two-orders of magnitude with the use of CG model and a low friction constant in Langevin dynamics. Next, we present four examples of applications. First, the classic Go̅ model was used to emulate one ATP cycle of a molecular motor, kinesin. Second, nonspecific protein-DNA binding was studied by a combination of elaborate protein and DNA models. Third, a transcription factor, p53, that contains highly fluctuating regions was simulated on two perpendicularly arranged DNA segments, addressing intersegmental transfer of p53. Fourth, we simulated structural dynamics of dinucleosomes connected by a linker DNA finding distinct types of internucleosome docking and salt-concentration-dependent compaction. Finally, we discuss many of limitations in the current approaches and future directions. Especially, more accurate electrostatic treatment and a phospholipid model that matches our CG resolutions are of immediate importance.

First service pregnancy rates following post-AI use of HCG in Ovsynch and Heatsynch programmes in lactating dairy cows.

PubMed

Shabankareh, H Karami; Zandi, M; Ganjali, M

2010-08-01

Lactating dairy cows (n = 667) at random stages of the oestrous cycle were assigned to either ovsynch (O, n = 228), heatsynch (H, n = 252) or control (C, n = 187) groups. Cows in O and H groups received 100 microg of GnRH agonist, i.m. (day 0) starting at 44 +/- 3 days in milk (DIM), and 500 microg of cloprostenol, i.m. (day 7). In O group, cows received 100 microg of GnRH (day 9) and were artificially inseminated without oestrus detection 16-20 h later. In H group, cows received 1 mg oestradiol benzoate (EB) i.m., 24 h after the cloprostenol injection and were artificially inseminated without oestrus detection 48-52 h after the EB injection. Cows in C group were inseminated at natural oestrus. On the day of artificial insemination (AI), cows in all groups were assigned to subgroups as follows: human Chorionic Gonadotrophin (O-hCG) (n = 112), O-saline (n = 116), H-hCG (n = 123), H-saline (n = 129), C-hCG (n = 94) and C-saline (n = 93) subgroups. Cows in hCG and saline subgroups received 3000 IU hCG i.m. and or 10 ml saline at day 5 post-AI (day 15), respectively. Pregnancy status was assessed by palpation per rectum at days 40 to 45 after AI. The logistic regression model using just main effects of season (summer and winter), parity (primiparous and pluriparous), method(1) (O, H and C) and method(2) (hCG and saline) showed that all factors, except method(1), were significant. Significant effects of season (p < 0.01), hCG and parity (p < 0.01), and a trend of parity and season (p < 0.1) were detected. A clear negative effect of warm period on first service pregnancy rate was noted (p < 0.01). The pregnancy rate was the lowest in the H protocol during warm period (p < 0.05). Treatment with hCG 5 days after AI significantly improved pregnancy rates in those cows that were treated with the H protocol compared with saline treatments (41.5% vs 24.8%; p < 0.01). O and H were more effective in primiparous than in pluriparous cows (46.1% vs 29.9%; p < 0.1 and 43.6% vs 24.6%; p < 0.01). First service pregnancy rates were higher in primiparous hCG-treated than in pluriparous hCG-treated cows (57.9% vs 32.3%; p < 0.01). The pregnancy rate was higher for the hCG-treated cows compared with saline-treated cows during warm period (37.9% vs 23.6%; p < 0.001).

Docking and free energy simulations to predict conformational domains involved in hCG-LH receptor interactions using recombinant antibodies.

PubMed

Majumdar, Ritankar; Railkar, Reema; Dighe, Rajan R

2011-11-01

Single chain fragment variables (ScFvs) have been extensively employed in studying the protein-protein interactions. ScFvs derived from phage display libraries have an additional advantage of being generated against a native antigen, circumventing loss of information on conformational epitopes. In the present study, an attempt has been made to elucidate human chorionic gonadotropin (hCG)-luteinizing hormone (LH) receptor interactions by using a neutral and two inhibitory ScFvs against hCG. The objective was to dock a computationally derived model of these ScFvs onto the crystal structure of hCG and understand the differential roles of the mapped epitopes in hCG-LH receptor interactions. An anti-hCG ScFv, whose epitope was mapped previously using biochemical tools, served as the positive control for assessing the quality of docking analysis. To evaluate the role of specific side chains at the hCG-ScFv interface, binding free energy as well as residue interaction energies of complexes in solution were calculated using molecular mechanics Poisson-Boltzmann/surface area method after performing the molecular dynamic simulations on the selected hCG-ScFv models and validated using biochemical and SPR analysis. The robustness of these calculations was demonstrated by comparing the theoretically determined binding energies with the experimentally obtained kinetic parameters for hCG-ScFv complexes. Superimposition of hCG-ScFv model onto a model of hCG complexed with the 51-266 residues of LH receptor revealed importance of the residues previously thought to be unimportant for hormone binding and response. This analysis provides an alternate tool for understanding the structure-function analysis of ligand-receptor interactions. Copyright © 2011 Wiley-Liss, Inc.

Many Masses on One Stroke:. Economic Computation of Quark Propagators

NASA Astrophysics Data System (ADS)

Frommer, Andreas; Nöckel, Bertold; Güsken, Stephan; Lippert, Thomas; Schilling, Klaus

The computational effort in the calculation of Wilson fermion quark propagators in Lattice Quantum Chromodynamics can be considerably reduced by exploiting the Wilson fermion matrix structure in inversion algorithms based on the non-symmetric Lanczos process. We consider two such methods: QMR (quasi minimal residual) and BCG (biconjugate gradients). Based on the decomposition M/κ = 1/κ-D of the Wilson mass matrix, using QMR, one can carry out inversions on a whole trajectory of masses simultaneously, merely at the computational expense of a single propagator computation. In other words, one has to compute the propagator corresponding to the lightest mass only, while all the heavier masses are given for free, at the price of extra storage. Moreover, the symmetry γ5M = M†γ5 can be used to cut the computational effort in QMR and BCG by a factor of two. We show that both methods then become — in the critical regime of small quark masses — competitive to BiCGStab and significantly better than the standard MR method, with optimal relaxation factor, and CG as applied to the normal equations.

[PCR-based evaluation of sequence specificity of DNA fragmentation by ultrasound].

PubMed

Garafutdinov, R R; Galimova, A A; Sakhabutdinova, A R; Chemeris, A V

2016-01-01

Ultrasonic fragmentation, which is a simple and convenient method for the mechanical degradation of DNA, is widely used in modern genome studies as one of the sample preparation steps. It has been recently found that the DNA breaks occur more often in the regions containing 5'-CG-3' dinucleotides. We studied the influence of the 5'-CG-3' dinucleotides on the efficiency of the 28S rRNA gene amplification during PCR with sonicated DNA of Mantis religiosa. It was shown that the amplification rate depends on the template length and the number of 5'-CG-3' dinucleotides. Amplification of the DNA regions with a higher 5'-CG-3' density is less efficient because of their higher sensitivity to ultrasound. The amount of the amplified DNA templates is inversely proportional to the 5'-CG-3'number.

Bottom-up coarse-grained models that accurately describe the structure, pressure, and compressibility of molecular liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dunn, Nicholas J. H.; Noid, W. G., E-mail: wnoid@chem.psu.edu

2015-12-28

The present work investigates the capability of bottom-up coarse-graining (CG) methods for accurately modeling both structural and thermodynamic properties of all-atom (AA) models for molecular liquids. In particular, we consider 1, 2, and 3-site CG models for heptane, as well as 1 and 3-site CG models for toluene. For each model, we employ the multiscale coarse-graining method to determine interaction potentials that optimally approximate the configuration dependence of the many-body potential of mean force (PMF). We employ a previously developed “pressure-matching” variational principle to determine a volume-dependent contribution to the potential, U{sub V}(V), that approximates the volume-dependence of the PMF.more » We demonstrate that the resulting CG models describe AA density fluctuations with qualitative, but not quantitative, accuracy. Accordingly, we develop a self-consistent approach for further optimizing U{sub V}, such that the CG models accurately reproduce the equilibrium density, compressibility, and average pressure of the AA models, although the CG models still significantly underestimate the atomic pressure fluctuations. Additionally, by comparing this array of models that accurately describe the structure and thermodynamic pressure of heptane and toluene at a range of different resolutions, we investigate the impact of bottom-up coarse-graining upon thermodynamic properties. In particular, we demonstrate that U{sub V} accounts for the reduced cohesion in the CG models. Finally, we observe that bottom-up coarse-graining introduces subtle correlations between the resolution, the cohesive energy density, and the “simplicity” of the model.« less

The Glu27 genotypes of the Beta2-adrenergic receptor are predictors for severe coronary artery disease

PubMed Central

Abu-Amero, Khaled K; Al-Boudari, Olayan M; Mohamed, Gamal H; Dzimiri, Nduna

2006-01-01

Background The role of the Beta2-adrenoceptor (beta2-AR) Gln27Glu polymorphism in the manifestation of cardiovascular diseases is still unclear. Methods In the present study, we evaluated the potential relevance of the c.79 C>G (p.Gln27Glu) polymorphism of this receptor gene for coronary artery disease (CAD) and its associated risk factors in Saudi Arabs. Genotyping was performed by PCR using the confronting two-pair primer (PCR-CTPP) method. Results In the general population group (BD) (n = 895), 68.5% were homozygous wild-type C/C, 28.3% were heterozygous C/G and 3.2% were homozygous mutant G/G. Among the CAD patients (n = 773), 50.6% were homozygous wild-type C/C, 43.6% were heterozygous C/G and 5.8% were homozygous mutant G/G, while in the angiographed control group (CON) (n = 528), 71.8% were C/C, 24.4% C/G and 3.8% G/G genotypes. These results indicate that both the C/G (p = < .001) and G/G (p = .005) genotypes are significantly associated with CAD, when compared to the CON group. In addition, C/G (p = < .001) and G/G (p = < .001) were significantly associated with CAD, when compared to the BD group. Furthermore, stepwise logistic regression showed that the genotype [C/G (p < .001) and G/G (p < .001)] increase the risk of CAD. Conclusion These results shows that the Gln27Glu genotypes (homo- or heterozygous) of the beta2-AR may be independent predictors of severe CAD. PMID:16573811

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM)

NASA Astrophysics Data System (ADS)

Sinitskiy, Anton V.; Voth, Gregory A.

2018-01-01

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

Quantum mechanics/coarse-grained molecular mechanics (QM/CG-MM).

PubMed

Sinitskiy, Anton V; Voth, Gregory A

2018-01-07

Numerous molecular systems, including solutions, proteins, and composite materials, can be modeled using mixed-resolution representations, of which the quantum mechanics/molecular mechanics (QM/MM) approach has become the most widely used. However, the QM/MM approach often faces a number of challenges, including the high cost of repetitive QM computations, the slow sampling even for the MM part in those cases where a system under investigation has a complex dynamics, and a difficulty in providing a simple, qualitative interpretation of numerical results in terms of the influence of the molecular environment upon the active QM region. In this paper, we address these issues by combining QM/MM modeling with the methodology of "bottom-up" coarse-graining (CG) to provide the theoretical basis for a systematic quantum-mechanical/coarse-grained molecular mechanics (QM/CG-MM) mixed resolution approach. A derivation of the method is presented based on a combination of statistical mechanics and quantum mechanics, leading to an equation for the effective Hamiltonian of the QM part, a central concept in the QM/CG-MM theory. A detailed analysis of different contributions to the effective Hamiltonian from electrostatic, induction, dispersion, and exchange interactions between the QM part and the surroundings is provided, serving as a foundation for a potential hierarchy of QM/CG-MM methods varying in their accuracy and computational cost. A relationship of the QM/CG-MM methodology to other mixed resolution approaches is also discussed.

Development of New Transferable Coarse-Grained Models of Hydrocarbons.

PubMed

An, Yaxin; Bejagam, Karteek K; Deshmukh, Sanket A

2018-06-21

We have utilized an approach that integrates molecular dynamics (MD) simulations with particle swarm optimization (PSO) to accelerate the development of coarse-grained (CG) models of hydrocarbons. Specifically, we have developed new transferable CG beads, which can be used to model the hydrocarbons (C5 to C17) and reproduce their experimental properties with good accuracy. Firstly, the PSO method was used to develop the CG beads of the decane model represented with 2:1 (2-2-2-2-2) mapping scheme. This was followed by the development of the nonane model described with hybrid 2-2-3-2, and 3:1 (3-3-3) mapping schemes. The force-field (FF) parameters for these three CG models were optimized to reproduce four experimentally observed properties including density, enthalpy of vaporization, surface tension, and self-diffusion coefficient at 300 K. The CG MD simulations conducted with these new CG models of decane and nonane, at different timesteps, for various system sizes, and at a range of different temperatures, were able to predict their density, enthalpy of vaporization, surface tension, self-diffusion coefficient, expansibility, and isothermal compressibility with a good accuracy. Moreover, comparison of structural features obtained from the CG MD simulations and the CG beads of mapped all-atom (AA) trajectories of decane and nonane showed very good agreement. To test the chemical transferability of these models, we have constructed the models for hydrocarbons ranging from pentane to heptadecane, by using different combination of the CG beads of decane and nonane. The properties of pentane to heptadecane predicted by these new CG models showed an excellent agreement with the experimental data.

Informing the Symptom Profile of Complicated Grief

PubMed Central

Simon, Naomi M.; Wall, Melanie M.; Keshaviah, Aparna; Dryman, M. Taylor; LeBlanc, Nicole J.; Shear, M. Katherine

2010-01-01

Background Complicated Grief (CG) is under consideration as a new diagnosis in DSM5. We sought to add empirical support to the current dialogue by examining the commonly used Inventory of Complicated Grief (ICG) scale completed by 782 bereaved individuals. Methods We employed IRT analyses, factor analyses, and sensitivity and specificity analyses utilizing our full sample (n=782), and also compared confirmed CG cases (n=288) to non-cases (n=377). Confirmed CG cases were defined as individuals bereaved at least 6 months who were seeking care for CG, had an ICG ≥ 30, and received a structured clinical interview for CG by a certified clinician confirming CG as their primary illness. Non-cases were bereaved individuals who did not present with CG as a primary complaint (including those with depression, bipolar disorder, anxiety disorders and controls) and had an ICG<25. Results IRT analyses provided guidance about the most informative individual items and their association with CG severity. Factor analyses demonstrated a single factor solution when the full sample was considered, but within CG cases, six symptom clusters emerged: 1) yearning and preoccupation with the deceased, 2) anger and bitterness, 3) shock and disbelief, 4) estrangement from others, 5) hallucinations of the deceased, and 6) behavior change, including avoidance and proximity seeking. The presence of at least one symptom from three different symptom clusters optimized sensitivity (94.8%) and specificity (98.1%). Conclusions These data, derived from a diverse and predominantly clinical help seeking population, add an important perspective to existing suggestions for DSM5 criteria for CG. PMID:21284064

A prediction model of drug-induced ototoxicity developed by an optimal support vector machine (SVM) method.

PubMed

Zhou, Shu; Li, Guo-Bo; Huang, Lu-Yi; Xie, Huan-Zhang; Zhao, Ying-Lan; Chen, Yu-Zong; Li, Lin-Li; Yang, Sheng-Yong

2014-08-01

Drug-induced ototoxicity, as a toxic side effect, is an important issue needed to be considered in drug discovery. Nevertheless, current experimental methods used to evaluate drug-induced ototoxicity are often time-consuming and expensive, indicating that they are not suitable for a large-scale evaluation of drug-induced ototoxicity in the early stage of drug discovery. We thus, in this investigation, established an effective computational prediction model of drug-induced ototoxicity using an optimal support vector machine (SVM) method, GA-CG-SVM. Three GA-CG-SVM models were developed based on three training sets containing agents bearing different risk levels of drug-induced ototoxicity. For comparison, models based on naïve Bayesian (NB) and recursive partitioning (RP) methods were also used on the same training sets. Among all the prediction models, the GA-CG-SVM model II showed the best performance, which offered prediction accuracies of 85.33% and 83.05% for two independent test sets, respectively. Overall, the good performance of the GA-CG-SVM model II indicates that it could be used for the prediction of drug-induced ototoxicity in the early stage of drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reentry-Vehicle Shape Optimization Using a Cartesian Adjoint Method and CAD Geometry

NASA Technical Reports Server (NTRS)

Nemec, Marian; Aftosmis, Michael J.

2006-01-01

A DJOINT solutions of the governing flow equations are becoming increasingly important for the development of efficient analysis and optimization algorithms. A well-known use of the adjoint method is gradient-based shape. Given an objective function that defines some measure of performance, such as the lift and drag functionals, its gradient is computed at a cost that is essentially independent of the number of design variables (e.g., geometric parameters that control the shape). Classic aerodynamic applications of gradient-based optimization include the design of cruise configurations for transonic and supersonic flow, as well as the design of high-lift systems. are perhaps the most promising approach for addressing the issues of flow solution automation for aerodynamic design problems. In these methods, the discretization of the wetted surface is decoupled from that of the volume mesh. This not only enables fast and robust mesh generation for geometry of arbitrary complexity, but also facilitates access to geometry modeling and manipulation using parametric computer-aided design (CAD). In previous work on Cartesian adjoint solvers, Melvin et al. developed an adjoint formulation for the TRANAIR code, which is based on the full-potential equation with viscous corrections. More recently, Dadone and Grossman presented an adjoint formulation for the two-dimensional Euler equations using a ghost-cell method to enforce the wall boundary conditions. In Refs. 18 and 19, we presented an accurate and efficient algorithm for the solution of the adjoint Euler equations discretized on Cartesian meshes with embedded, cut-cell boundaries. Novel aspects of the algorithm were the computation of surface shape sensitivities for triangulations based on parametric-CAD models and the linearization of the coupling between the surface triangulation and the cut-cells. The accuracy of the gradient computation was verified using several three-dimensional test cases, which included design variables such as the free stream parameters and the planform shape of an isolated wing. The objective of the present work is to extend our adjoint formulation to problems involving general shape changes. Factors under consideration include the computation of mesh sensitivities that provide a reliable approximation of the objective function gradient, as well as the computation of surface shape sensitivities based on a direct-CAD interface. We present detailed gradient verification studies and then focus on a shape optimization problem for an Apollo-like reentry vehicle. The goal of the optimization is to enhance the lift-to-drag ratio of the capsule by modifying the shape of its heat-shield in conjunction with a center-of-gravity (c.g.) offset. This multipoint and multi-objective optimization problem is used to demonstrate the overall effectiveness of the Cartesian adjoint method for addressing the issues of complex aerodynamic design.

Enhanced bonding property of cold-sprayed Zn-Al coating on interstitial-free steel substrate with a nanostructured surface layer

NASA Astrophysics Data System (ADS)

Liang, Y. L.; Wang, Z. B.; Zhang, J.; Zhang, J. B.; Lu, K.

2016-11-01

By means of surface mechanical attrition treatment (SMAT), a gradient nanostructured surface layer was fabricated on a hot-rolled interstitial-free steel plate. A Zn-Al coating was subsequently deposited on the SMAT sample by using cold spray process. The bonding property of the coating on the SMAT substrate was compared with that on the coarse-grained (CG) sample. Stud-pull tests showed that the bonding strength in the as-sprayed SMAT sample is ∼30% higher than that in the as-sprayed CG sample. No further improvement in bonding strength was achieved in the coated SMAT sample after annealing at 400 °C, mostly due to the formation of cracks and intermetallic compounds at the coating/substrate interface in an earlier stage (<30 min) and in a final stage (>90 min), respectively. The enhanced bonding property of the Zn-Al coating on the SMAT sample might be related with the promoted atomic diffusion and hardness in the nanostructured surface layer.

Evidence that the subunit structure of gonadotropin receptor is preserved during regression of rat corpus luteum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hwang, J.; Menon, K.N.J.

1986-05-29

The level of hCG/LH receptor has been shown to undergo marked changes during the life span of rat corpus luteum. To evaluate whether these fluctuations are due to changes in the receptor subunit structure or receptor protein content, the /sup 125/I-hCG binding activity and the receptor subunit structure were determined during different time periods of pseudopregnancy. The maximum /sup 125/I-hCG binding activity was observed on day 7, after which it decreased by 20 and 45% on day 11 and day 14, respectively. The Scatchard analysis of /sup 125/I-hCG binding data showed that the decrease in binding activity was caused bymore » a change in the number of binding sites rather than a change in the binding affinity. The LH/hCG receptor in ovarian membranes obtained on days 7, 11 and 14 were characterized by the method of affinity cross-linking. All four subunits of the LH/hCG receptor were detected in the ovarian membranes at all stages while the intensity decreased parallel to a decrease in hCG binding from day 7 to day 14.« less

Thermodynamic forces in coarse-grained simulations

NASA Astrophysics Data System (ADS)

Noid, William

Atomically detailed molecular dynamics simulations have profoundly advanced our understanding of the structure and interactions in soft condensed phases. Nevertheless, despite dramatic advances in the methodology and resources for simulating atomically detailed models, low-resolution coarse-grained (CG) models play a central and rapidly growing role in science. CG models not only empower researchers to investigate phenomena beyond the scope of atomically detailed simulations, but also to precisely tailor models for specific phenomena. However, in contrast to atomically detailed simulations, which evolve on a potential energy surface, CG simulations should evolve on a free energy surface. Therefore, the forces in CG models should reflect the thermodynamic information that has been eliminated from the CG configuration space. As a consequence of these thermodynamic forces, CG models often demonstrate limited transferability and, moreover, rarely provide an accurate description of both structural and thermodynamic properties. In this talk, I will present a framework that clarifies the origin and impact of these thermodynamic forces. Additionally, I will present computational methods for quantifying these forces and incorporating their effects into CG MD simulations. As time allows, I will demonstrate applications of this framework for liquids, polymers, and interfaces. We gratefully acknowledge the support of the National Science Foundation via CHE 1565631.

Exploring structural properties of small carbon clusters Cn (n = 1, 2, 3) using molecular mechanics and energy minimization

NASA Astrophysics Data System (ADS)

Miswan, M. A.; Gopir, G.; Anas, M. M.

2016-11-01

Geometry optimization is one of the most widely used methods to study in carbon cluster Cn to understand its structural properties. The total energy for each of the structures was calculated using Octopus software with conjugate gradient Broyden-Fletcher-Goldfarb-Shanno (CG-BFGS). Our calculation and other studies indicate that the linear forms are the most stable structures. However, the C3 isomers have equal probability to form, as the differences in our calculation of total energy are statistically insignificant. Despite there are two cohort of total energy, the calculations are acceptable due to the energy ratio between C3 to C2 and C2 to C1 are comparable to others work. Meanwhile, the bond properties of the C2 and C3 bonds also gives significant difference between our work and previous study.

Physical characteristics of the gonadotropin receptor-hormone complexes formed in vivo and in vitro.

PubMed Central

Dufau, M L; Podesta, E J; Catt, K J

1975-01-01

The physical properties of detergent-solubilized gonadotropin receptor-hormone complexes, determined by density gradient centrifugation and gel filtration, were compared after in vivo and in vitro labeling of specific ovarian binding sites with radioiodinated human chorionic gonadotropin (hCG). Following intravenous administration of biologically active 125I-labeled hCG, up to 50% of the gonadotropin tracer was bound to the luteinized ovaries of immature female rats treated with pregnant mare serum/human chorionic gonadotropin. Comparable binding of 125I-labeled hCG was observed after equilibration of ovarian particles with the labeled hormone in vitro. The sedimentation properties of the solubilized receptor-hormone complexes formed in vivo were identical with those derived for the corresponding complexes formed in vitro and extracted with Triton X-100 and Lubrol PX, with sedimentation constants of 8.8 S for the Triton-solubilized complex and 7.0 S for the complex extracted with Lubrol PX. During analytical gel filtration of the Triton-solubilized receptor-hormone complex on Sepharose 6B in 0.1% Triton X-100, the partition coefficient (Kav) of the "in vivo" complex (0.32) was not significantly different from that of the complex formed in vitro (0.29). Gel filtration of the Lubrol-solubilized ovarian particles on Sepharose 6B in 0.5% Lubrol PX gave Kav values for the "in vivo" and "in vitro" labeled complexes of 0.36 and 0.32, respectively. These findings demonstrate that the physical properties of size and shape which determine the partition coefficient and sedimentation characteristics of detergent-solubilized gonadotropin receptor-hormone complexes formed in vitro are not distinguishable from those of the complexes extracted after specific interaction of the ovarian gonadotropin receptors with radioiodinated hCG in vivo. PMID:165502

Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route.

PubMed

Mittal, Deepti; Md, Shadab; Hasan, Quamrul; Fazil, Mohammad; Ali, Asgar; Baboota, Sanjula; Ali, Javed

2016-01-01

The aim of the present study was to prepare and evaluate a rasagiline-loaded chitosan glutamate nanoparticles (RAS-CG-NPs) by ionic gelation of CG with tripolyphosphate anions (TPP). RAS-loaded CG-NPs were characterized for particle size, size distribution, encapsulation efficiency and in vitro drug release. The mean particles size, polydispersity index (PDI) and encapsulation efficiency was found to be 151.1 ± 10.31, 0.380 ± 0.01 and 96.43 ± 4.23, respectively. Biodistribution of RAS formulations in the brain and blood of mice following intranasal (i.n.) and intravenous (i.v.) administration was performed using HPLC analytical method. The drug concentrations in brain following the i.n. of CG-NPs were found to be significantly higher at all the time points compared to both drug (i.n.) and drug CG-NPs (i.v.). The Cmax (999.25 ng/ml) and AUC (2086.60 ng h/ml) of formulation CG-NPs (i.n) were found to be significantly higher than CG-NPs (i.v.) and RAS solution (i.n.). The direct transport percentage (DTP%) values of RAS-loaded CG-NPs (i.n.) as compared to drug solution (i.n.) increased from 66.27 ± 1.8 to 69.27 ± 2.1%. The results showed significant enhancement of bioavailability in brain, after administration of the RAS-loaded CG-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson's disease therapy.

Storm-based Cloud-to-Ground Lightning Probabilities and Warnings

NASA Astrophysics Data System (ADS)

Calhoun, K. M.; Meyer, T.; Kingfield, D.

2017-12-01

A new cloud-to-ground (CG) lightning probability algorithm has been developed using machine-learning methods. With storm-based inputs of Earth Networks' in-cloud lightning, Vaisala's CG lightning, multi-radar/multi-sensor (MRMS) radar derived products including the Maximum Expected Size of Hail (MESH) and Vertically Integrated Liquid (VIL), and near storm environmental data including lapse rate and CAPE, a random forest algorithm was trained to produce probabilities of CG lightning up to one-hour in advance. As part of the Prototype Probabilistic Hazard Information experiment in the Hazardous Weather Testbed in 2016 and 2017, National Weather Service forecasters were asked to use this CG lightning probability guidance to create rapidly updating probability grids and warnings for the threat of CG lightning for 0-60 minutes. The output from forecasters was shared with end-users, including emergency managers and broadcast meteorologists, as part of an integrated warning team.

Defining and Evaluating a Core Genome Multilocus Sequence Typing Scheme for Genome-Wide Typing of Clostridium difficile.

PubMed

Bletz, Stefan; Janezic, Sandra; Harmsen, Dag; Rupnik, Maja; Mellmann, Alexander

2018-06-01

Clostridium difficile , recently renamed Clostridioides difficile , is the most common cause of antibiotic-associated nosocomial gastrointestinal infections worldwide. To differentiate endogenous infections and transmission events, highly discriminatory subtyping is necessary. Today, methods based on whole-genome sequencing data are increasingly used to subtype bacterial pathogens; however, frequently a standardized methodology and typing nomenclature are missing. Here we report a core genome multilocus sequence typing (cgMLST) approach developed for C. difficile Initially, we determined the breadth of the C. difficile population based on all available MLST sequence types with Bayesian inference (BAPS). The resulting BAPS partitions were used in combination with C. difficile clade information to select representative isolates that were subsequently used to define cgMLST target genes. Finally, we evaluated the novel cgMLST scheme with genomes from 3,025 isolates. BAPS grouping ( n = 6 groups) together with the clade information led to a total of 11 representative isolates that were included for cgMLST definition and resulted in 2,270 cgMLST genes that were present in all isolates. Overall, 2,184 to 2,268 cgMLST targets were detected in the genome sequences of 70 outbreak-associated and reference strains, and on average 99.3% cgMLST targets (1,116 to 2,270 targets) were present in 2,954 genomes downloaded from the NCBI database, underlining the representativeness of the cgMLST scheme. Moreover, reanalyzing different cluster scenarios with cgMLST were concordant to published single nucleotide variant analyses. In conclusion, the novel cgMLST is representative for the whole C. difficile population, is highly discriminatory in outbreak situations, and provides a unique nomenclature facilitating interlaboratory exchange. Copyright © 2018 American Society for Microbiology.

Standardization of Epitopes for Human Chorionic Gonadotropin (hCG) Immunoassays.

PubMed

Berger, Peter; Lapthorn, Adrian J

2016-01-01

hCG and its variants are markers for pregnancy tests, pregnancyrelated complications, trophoblastic diseases, pre-natal screening of Down's syndrome and doping controls. Strong demands are imposed on diagnostic methods by the dynamic changes in the absolute and relative levels of hCG protein backbone variants and glycosylation isoforms in serum and urine during development of pregnancy or the progression/remission of tumors. Observed differences in the results between commercial diagnostic immunoassays reflect the unequal molar recognition of the different metabolic hCG variants, in particular the hCG beta core fragment (hCGβcf), by the diagnostic antibodies (Abs), as their epitopes are not standardized, and the fact that suboptimal hCG standards are used. To rapidly characterize Abs by their epitope recognition and specificity to evaluate their suitability for diagnostic immunoassays a procedure of comparative epitope mapping has been developed using epitope-defined reference Abs. Comparative epitope mapping of diagnostic Abs will provide the basis for the standardization of diagnostic antigenic domains/epitopes and consequently for improved reliability of hCG measurements. Diagnostic first line assays likely consist of pairs of Abs that recognize specific epitopes at the top of the neighboring peptide loops 1 and 3 (Ł1+3) and the cystine knot (ck) of hCGβ, respectively. In future, significant improvements of reliability, robustness and comparability of the results of immunoassays for complex glycoproteins such as hCG will be achieved by the use (i) of standardized diagnostic Abs against welldefined epitopes and (ii) of the new International Standards for hCG and for five hCG variants established by WHO, that are calibrated in molar (SI) units.

Human Chorionic Gonadotropine in Cul-de-sac Fluid in Tubal Ectopic Pregnacy; A New Diagnostic Approach

PubMed Central

Karahasanoglu, Ayse; Ozdemir, Mucize; Yazicioglu, Fehmi

2016-01-01

Introduction Although new diagnostic abilities are being utilised increasingly yet early detection of tubal pregnancy remains a challenge. The use of highly sensitive hCG kits has facilitated the early diagnosis of a pregnancy. But it takes time to determine the localisation of the pregnancy. Early diagnosis of ectopic pregnancy may reduce the morbidity of ectopic pregnancy. Aim This study was conducted to analyse the cul-de-sac and serum βhCG ratio in tubal ectopic pregnancy cases which may be a new diagnostic approach for ectopic pregnancy. Materials and Methods Between January 2004 and July 2011, 263 patients with ectopic pregnancy were included in the study. Risk factors of patients and treatment modalities were evaluated. hCG was measured in peripheral serum and peritoneal fluid, obtained by puncture of Douglas pouch in 52 patients with tubal ectopic pregnancy. hCG level was determined in the cul-de-sac fluid and in the maternal serum for comparison. Results Tubectomy (5.3%), history of abortion (9.5%), history of previous surgery (14.8%), previous cesarean section (8%) and pelvic infamatorry disease (15.9 %) were the important risk factors for ectopic pregnancy in our cases. In 51 of 52 patients with tubal pregnancy, the cul-de-sac hCG vaule and the serum hCG value ratio was >1. Conclusion It is concluded that the ratio of hCG in cul-de –sac and serum can be used for the verification of tubal ectopic pregnancy in addition to other diagnostic methods. This may help rapid confirmation of the diagnosis of ectopic pregnancy. PMID:27190895

Ten tandem repeats of {beta}-hCG 109-118 enhance immunogenicity and anti-tumor effects of {beta}-hCG C-terminal peptide carried by mycobacterial heat-shock protein HSP65

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Yankai; Yan Rong; He Yi

2006-07-14

The {beta}-subunit of human chorionic gonadotropin ({beta}-hCG) is secreted by many kinds of tumors and it has been used as an ideal target antigen to develop vaccines against tumors. In view of the low immunogenicity of this self-peptide,we designed a method based on isocaudamer technique to repeat tandemly the 10-residue sequence X of {beta}-hCG (109-118), then 10 tandemly repeated copies of the 10-residue sequence combined with {beta}-hCG C-terminal 37 peptides were fused to mycobacterial heat-shock protein 65 to construct a fusion protein HSP65-X10-{beta}hCGCTP37 as an immunogen. In this study, we examined the effect of the tandem repeats of this 10-residuemore » sequence in eliciting an immune by comparing the immunogenicity and anti-tumor effects of the two immunogens, HSP65-X10-{beta}hCGCTP37 and HSP65-{beta}hCGCTP37 (without the 10 tandem repeats). Immunization of mice with the fusion protein HSP65-X10-{beta}hCGCTP37 elicited much higher levels of specific anti-{beta}-hCG antibodies and more effectively inhibited the growth of Lewis lung carcinoma (LLC) in vivo than with HSP65-{beta}hCGCTP37, which should suggest that HSP65-X10-{beta}hCGCTP37 may be an effective protein vaccine for the treatment of {beta}-hCG-dependent tumors and multiple tandem repeats of a certain epitope are an efficient method to overcome the low immunogenicity of self-peptide antigens.« less

Distribution of the P2X2 receptor and chemical coding in ileal enteric neurons of obese male mice (ob/ob)

PubMed Central

Mizuno, Márcia Sanae; Crisma, Amanda Rabello; Borelli, Primavera; Schäfer, Bárbara Tavares; Silveira, Mariana Póvoa; Castelucci, Patricia

2014-01-01

AIM: To investigate the colocalization, density and profile of neuronal areas of enteric neurons in the ileum of male obese mice. METHODS: The small intestinal samples of male mice in an obese group (OG) (C57BL/6J ob/ob) and a control group (CG) (+/+) were used. The tissues were analyzed using a double immunostaining technique for immunoreactivity (ir) of the P2X2 receptor, nitric oxide synthase (NOS), choline acetyl transferase (ChAT) and calretinin (Calr). Also, we investigated the density and profile of neuronal areas of the NOS-, ChAT- and Calr-ir neurons in the myenteric plexus. Myenteric neurons were labeled using an NADH-diaphorase histochemical staining method. RESULTS: The analysis demonstrated that the P2X2 receptor was expressed in the cytoplasm and in the nuclear and cytoplasmic membranes only in the CG. Neuronal density values (neuron/cm2) decreased 31% (CG: 6579 ± 837; OG: 4556 ± 407) and 16.5% (CG: 7796 ± 528; OG: 6513 ± 610) in the NOS-ir and calretinin-ir neurons in the OG, respectively (P < 0.05). Density of ChAT-ir (CG: 6200 ± 310; OG: 8125 ± 749) neurons significantly increased 31% in the OG (P < 0.05). Neuron size studies demonstrated that NOS, ChAT, and Calr-ir neurons did not differ significantly between the CG and OG groups. The examination of NADH-diaphorase-positive myenteric neurons revealed an overall similarity between the OG and CG. CONCLUSION: Obesity may exert its effects by promoting a decrease in P2X2 receptor expression and modifications in the density of the NOS-ir, ChAT-ir and CalR-ir myenteric neurons. PMID:25320527

Coarse-Grained Molecular Models of Water: A Review

PubMed Central

Hadley, Kevin R.; McCabe, Clare

2012-01-01

Coarse-grained (CG) models have proven to be very effective tools in the study of phenomena or systems that involve large time- and length-scales. By decreasing the degrees of freedom in the system and using softer interactions than seen in atomistic models, larger timesteps can be used and much longer simulation times can be studied. CG simulations are widely used to study systems of biological importance that are beyond the reach of atomistic simulation, necessitating a computationally efficient and accurate CG model for water. In this review, we discuss the methods used for developing CG water models and the relative advantages and disadvantages of the resulting models. In general, CG water models differ with regards to how many waters each CG group or bead represents, whether analytical or tabular potentials have been used to describe the interactions, and how the model incorporates electrostatic interactions. Finally, how the models are parameterized depends on their application, so, while some are fitted to experimental properties such as surface tension and density, others are fitted to radial distribution functions extracted from atomistic simulations. PMID:22904601

Extending the eigCG algorithm to nonsymmetric Lanczos for linear systems with multiple right-hand sides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdel-Rehim, A M; Stathopoulos, Andreas; Orginos, Kostas

2014-08-01

The technique that was used to build the EigCG algorithm for sparse symmetric linear systems is extended to the nonsymmetric case using the BiCG algorithm. We show that, similarly to the symmetric case, we can build an algorithm that is capable of computing a few smallest magnitude eigenvalues and their corresponding left and right eigenvectors of a nonsymmetric matrix using only a small window of the BiCG residuals while simultaneously solving a linear system with that matrix. For a system with multiple right-hand sides, we give an algorithm that computes incrementally more eigenvalues while solving the first few systems andmore » then uses the computed eigenvectors to deflate BiCGStab for the remaining systems. Our experiments on various test problems, including Lattice QCD, show the remarkable ability of EigBiCG to compute spectral approximations with accuracy comparable to that of the unrestarted, nonsymmetric Lanczos. Furthermore, our incremental EigBiCG followed by appropriately restarted and deflated BiCGStab provides a competitive method for systems with multiple right-hand sides.« less

Identification and quantification of cardiac glycosides in blood and urine samples by HPLC/MS/MS.

PubMed

Guan, F; Ishii, A; Seno, H; Watanabe-Suzuki, K; Kumazawa, T; Suzuki, O

1999-09-15

Cardiac glycosides (CG) are of forensic importance because of their toxicity and the fact that very limited methods are available for identification of CG in biological samples. In this study, we have developed an identification and quantification method for digoxin, digitoxin, deslanoside, digoxigenin, and digitoxigenin by high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS). CG formed abundant [M + NH4]+ ions and much less abundant [M + H]+ ions as observed with electrospray ionization (ESI) source and ammonium formate buffer. Under mild conditions for collision-induced dissociation (CID), each [M + NH4]+ ion fragmented to produce a dominant daughter ion, which was essential to the sensitive method of selected reaction monitoring (SRM) quantification of CG achieved in this study. SRM was compared with selected ion monitoring (SIM) regarding the effects of sample matrixes on the methodology. SRM produced lower detection limits with biological samples than SIM, while both methods produced equal detection limits with CG standards. On the basis of the HPLC/MS/MS results for CG, we have proposed some generalized points for conducting sensitive SRM measurements, in view of the property of analytes as well as instrumental conditions such as the type of HPLC/MS interface and CID parameters. Analytes of which the molecular ion can produce one abundant daughter ion with high yield under CID conditions may be sensitively measured by SRM. ESI is the most soft ionization source developed so far and can afford formation of the fragile molecular ions that are necessary for sensitive SRM detection. Mild CID conditions such as low collision energy and low pressure of collision gas favor production of an abundant daughter ion that is essential to sensitive SRM detection. This knowledge may provide some guidelines for conducting sensitive SRM measurements of very low concentrations of drugs or toxicants in biological samples.

Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model

PubMed Central

Ooi, Mian L.; Richter, Katharina; Drilling, Amanda J.; Thomas, Nicky; Prestidge, Clive A.; James, Craig; Moratti, Stephen; Vreugde, Sarah; Psaltis, Alkis J.; Wormald, Peter-John

2018-01-01

Objectives: Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against S. aureus biofilms in vivo. Methods: To assess safety, 8 sheep were divided into two groups of 7 day treatments (n = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a S. aureus sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments (n = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Results: Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Conclusion: Results indicate that CG-DG is safe and effective against S. aureus biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.

Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model.

PubMed

Ooi, Mian L; Richter, Katharina; Drilling, Amanda J; Thomas, Nicky; Prestidge, Clive A; James, Craig; Moratti, Stephen; Vreugde, Sarah; Psaltis, Alkis J; Wormald, Peter-John

2018-01-01

Objectives: Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against S. aureus biofilms in vivo . Methods: To assess safety, 8 sheep were divided into two groups of 7 day treatments ( n = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a S. aureus sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments ( n = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Results: Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Conclusion: Results indicate that CG-DG is safe and effective against S. aureus biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.

Dynamics in entangled polyethylene melts using coarse-grained models

NASA Astrophysics Data System (ADS)

Peters, Brandon L.; Grest, Gary S.; Salerno, K. Michael; Agrawal, Anupriya; Perahia, Dvora

Polymer dynamics creates distinctive viscoelastic behavior as a result of a coupled interplay of motion on multiple length scales. Capturing the broad time and length scales of polymeric motion however, remains a challenge. Using polyethylene (PE) as a model system, we probe the effects of the degree of coarse graining on polymer dynamics. Coarse-grained (CG) potentials are derived using iterative Boltzmann inversion (iBi) with 2-6 methyl groups per CG bead from all fully atomistic melt simulations for short chains. While the iBi methods produces non-bonded potentials which give excellent agreement for the atomistic and CG pair correlation functions, the pressure P = 100-500MPa for the CG model. Correcting for potential so P 0 leads to non-bonded models with slightly smaller effective diameter and much deeper minimum. However, both the pressure and non-pressure corrected CG models give similar results for mean squared displacement (MSD) and the stress auto correlation function G(t) for PE melts above the melting point. The time rescaling factor between CG and atomistic models is found to be nearly the same for both CG models. Transferability of potential for different temperatures was tested by comparing the MSD and G(t) for potentials generated at different temperatures.

Facilitators and Barriers to Implementing Clinical Governance: A Qualitative Study among Senior Managers in Iran

PubMed Central

RAVAGHI, Hamid; RAFIEI, Sima; HEIDARPOUR, Peigham; MOHSENI, Maryam

2014-01-01

Abstract Background Health care systems should assign quality improvement as their main mission. Clinical governance (CG) is a key strategy to improve quality of health care services. The Iranian Ministry of Health and Medical Education (MOHME) has promoted CG as a framework for safeguarding quality and safety in all hospitals since 2009. The purpose of this study was to explore perceived facilitators and barriers to implementing CG by deputies for curative affairs of Iranian medical universities. Methods A qualitative study was conducted using face to face interviews with a purposeful sample of 43 deputies for curative affairs of Iranian Medical Universities and documents review. Thematic analysis was used to analyze the data Results Five themes were explored including: knowledge and attitude toward CG, culture, organizational factors, managerial factors and barriers. The main perceived facilitating factors were adequate knowledge and positive attitude toward CG, supporting culture, managers’ commitment, effective communication and well designed incentives. Pe rceived barriers were the reverse of facilitators noted above in addition to insufficient resources, legal challenges, workload and parallel quality programs. Conclusions Successful implementation of CG in Iran will require identifying barriers and challenges existing in the way of CG implementation and try to mitigate them by using appropriate facilitators. PMID:26175981

Structure-based coarse-graining for inhomogeneous liquid polymer systems.

PubMed

Fukuda, Motoo; Zhang, Hedong; Ishiguro, Takahiro; Fukuzawa, Kenji; Itoh, Shintaro

2013-08-07

The iterative Boltzmann inversion (IBI) method is used to derive interaction potentials for coarse-grained (CG) systems by matching structural properties of a reference atomistic system. However, because it depends on such thermodynamic conditions as density and pressure of the reference system, the derived CG nonbonded potential is probably not applicable to inhomogeneous systems containing different density regimes. In this paper, we propose a structure-based coarse-graining scheme to devise CG nonbonded potentials that are applicable to different density bulk systems and inhomogeneous systems with interfaces. Similar to the IBI, the radial distribution function (RDF) of a reference atomistic bulk system is used for iteratively refining the CG nonbonded potential. In contrast to the IBI, however, our scheme employs an appropriately estimated initial guess and a small amount of refinement to suppress transfer of the many-body interaction effects included in the reference RDF into the CG nonbonded potential. To demonstrate the application of our approach to inhomogeneous systems, we perform coarse-graining for a liquid perfluoropolyether (PFPE) film coated on a carbon surface. The constructed CG PFPE model favorably reproduces structural and density distribution functions, not only for bulk systems, but also at the liquid-vacuum and liquid-solid interfaces, demonstrating that our CG scheme offers an easy and practical way to accurately determine nonbonded potentials for inhomogeneous systems.

Cashew gum and gelatin blend for food packaging application

USDA-ARS?s Scientific Manuscript database

Cashew gum (CG) and gelatin (G) films were developed using the casting method and response surface methodology. The objective was produce packaging films from CG/G blends that exhibit effective barrier properties. A study of zeta potential versus pH was first carried out to determine the isoelectric...

X-ray solution scattering combined with computation characterizing protein folds and multiple conformational states : computation and application.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, S.; Park, S.; Makowski, L.

Small angle X-ray scattering (SAXS) is an increasingly powerful technique to characterize the structure of biomolecules in solution. We present a computational method for accurately and efficiently computing the solution scattering curve from a protein with dynamical fluctuations. The method is built upon a coarse-grained (CG) representation of the protein. This CG approach takes advantage of the low-resolution character of solution scattering. It allows rapid determination of the scattering pattern from conformations extracted from CG simulations to obtain scattering characterization of the protein conformational landscapes. Important elements incorporated in the method include an effective residue-based structure factor for each aminomore » acid, an explicit treatment of the hydration layer at the surface of the protein, and an ensemble average of scattering from all accessible conformations to account for macromolecular flexibility. The CG model is calibrated and illustrated to accurately reproduce the experimental scattering curve of Hen egg white lysozyme. We then illustrate the computational method by calculating the solution scattering pattern of several representative protein folds and multiple conformational states. The results suggest that solution scattering data, when combined with a reliable computational method, have great potential for a better structural description of multi-domain complexes in different functional states, and for recognizing structural folds when sequence similarity to a protein of known structure is low. Possible applications of the method are discussed.« less

Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ha, Ye J.; Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul; Kim, Chan W.

Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and testedmore » for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.« less

Non-Cartesian Parallel Imaging Reconstruction

PubMed Central

Wright, Katherine L.; Hamilton, Jesse I.; Griswold, Mark A.; Gulani, Vikas; Seiberlich, Nicole

2014-01-01

Non-Cartesian parallel imaging has played an important role in reducing data acquisition time in MRI. The use of non-Cartesian trajectories can enable more efficient coverage of k-space, which can be leveraged to reduce scan times. These trajectories can be undersampled to achieve even faster scan times, but the resulting images may contain aliasing artifacts. Just as Cartesian parallel imaging can be employed to reconstruct images from undersampled Cartesian data, non-Cartesian parallel imaging methods can mitigate aliasing artifacts by using additional spatial encoding information in the form of the non-homogeneous sensitivities of multi-coil phased arrays. This review will begin with an overview of non-Cartesian k-space trajectories and their sampling properties, followed by an in-depth discussion of several selected non-Cartesian parallel imaging algorithms. Three representative non-Cartesian parallel imaging methods will be described, including Conjugate Gradient SENSE (CG SENSE), non-Cartesian GRAPPA, and Iterative Self-Consistent Parallel Imaging Reconstruction (SPIRiT). After a discussion of these three techniques, several potential promising clinical applications of non-Cartesian parallel imaging will be covered. PMID:24408499

Determination of green tea catechins in human plasma using liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Masukawa, Yoshinori; Matsui, Yuji; Shimizu, Namii; Kondou, Naoki; Endou, Hidenori; Kuzukawa, Michiya; Hase, Tadashi

2006-04-13

A method for the sensitive and specific determination of eight green tea catechins, consisting of catechin (C), epicatechin (EC), gallocatechin (GC), epigallocatechin (EGC), catechin-3-gallate (CG), epicatechin-3-gallate (ECG), gallocatechin-3-gallate (GCG) and epigallocatechin-3-gallate (EGCG), in human plasma was established. For optimization of conditions for LC-ESIMS, the separation of the eight catechins was achieved chromatographically using Inertsil ODS-2 column combined with a gradient elution system of 0.1M aqueous acetic acid and 0.1M acetic acid in acetonitrile. Detection using a mass spectrometer was performed with selected ion monitoring at m/z=289 for E and EC, 305 for GC and EGC, 441 for CG and ECG, and 457 for GCG and EGCG under negative ESI. A preparative procedure, consisting of the addition of perchloric acid and acetonitrile to the plasma for deproteinizing and the subsequent addition of potassium carbonate solution to remove excess acid, was developed. In six different plasma with the eight catechins spiked at two different concentrations, the average recoveries were in the range between 72.7 and 84.1%, which resulted from the matrix effect and preparative loss, with coefficients of variance being 8.2-19.8% among individuals. The levels of the catechins in prepared plasma solutions that were kept at 5 degrees C within 24h were stable, which allows us to simply analyze many prepared plasma solutions using an autosampler overnight. When using this method to analyze the eight catechins in human plasma after oral ingestion of a commercial green tea beverage, we detected all the catechins absorbed into human blood for the first time. This also suggested that extremely small amounts of the eight catechins orally ingested may be absorbed based on each absorptive property for the catechins. The method should enable pharmacokinetic studies of green tea catechins in humans.

TMFF-A Two-Bead Multipole Force Field for Coarse-Grained Molecular Dynamics Simulation of Protein.

PubMed

Li, Min; Liu, Fengjiao; Zhang, John Z H

2016-12-13

Coarse-grained (CG) models are desirable for studying large and complex biological systems. In this paper, we propose a new two-bead multipole force field (TMFF) in which electric multipoles up to the quadrupole are included in the CG force field. The inclusion of electric multipoles in the proposed CG force field enables a more realistic description of the anisotropic electrostatic interactions in the protein system and, thus, provides an improvement over the standard isotropic two-bead CG models. In order to test the accuracy of the new CG force field model, extensive molecular dynamics simulations were carried out for a series of benchmark protein systems. These simulation studies showed that the TMFF model can realistically reproduce the structural and dynamical properties of proteins, as demonstrated by the close agreement of the CG results with those from the corresponding all-atom simulations in terms of root-mean-square deviations (RMSDs) and root-mean-square fluctuations (RMSFs) of the protein backbones. The current two-bead model is highly coarse-grained and is 50-fold more efficient than all-atom method in MD simulation of proteins in explicit water.

Enhanced Sampling of an Atomic Model with Hybrid Nonequilibrium Molecular Dynamics-Monte Carlo Simulations Guided by a Coarse-Grained Model.

PubMed

Chen, Yunjie; Roux, Benoît

2015-08-11

Molecular dynamics (MD) trajectories based on a classical equation of motion provide a straightforward, albeit somewhat inefficient approach, to explore and sample the configurational space of a complex molecular system. While a broad range of techniques can be used to accelerate and enhance the sampling efficiency of classical simulations, only algorithms that are consistent with the Boltzmann equilibrium distribution yield a proper statistical mechanical computational framework. Here, a multiscale hybrid algorithm relying simultaneously on all-atom fine-grained (FG) and coarse-grained (CG) representations of a system is designed to improve sampling efficiency by combining the strength of nonequilibrium molecular dynamics (neMD) and Metropolis Monte Carlo (MC). This CG-guided hybrid neMD-MC algorithm comprises six steps: (1) a FG configuration of an atomic system is dynamically propagated for some period of time using equilibrium MD; (2) the resulting FG configuration is mapped onto a simplified CG model; (3) the CG model is propagated for a brief time interval to yield a new CG configuration; (4) the resulting CG configuration is used as a target to guide the evolution of the FG system; (5) the FG configuration (from step 1) is driven via a nonequilibrium MD (neMD) simulation toward the CG target; (6) the resulting FG configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-ends momentum reversal prescription is used for the neMD trajectories of the FG system to guarantee that the CG-guided hybrid neMD-MC algorithm obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The enhanced sampling achieved with the method is illustrated with a model system with hindered diffusion and explicit-solvent peptide simulations. Illustrative tests indicate that the method can yield a speedup of about 80 times for the model system and up to 21 times for polyalanine and (AAQAA)3 in water.

Enhanced Sampling of an Atomic Model with Hybrid Nonequilibrium Molecular Dynamics—Monte Carlo Simulations Guided by a Coarse-Grained Model

PubMed Central

2015-01-01

Molecular dynamics (MD) trajectories based on a classical equation of motion provide a straightforward, albeit somewhat inefficient approach, to explore and sample the configurational space of a complex molecular system. While a broad range of techniques can be used to accelerate and enhance the sampling efficiency of classical simulations, only algorithms that are consistent with the Boltzmann equilibrium distribution yield a proper statistical mechanical computational framework. Here, a multiscale hybrid algorithm relying simultaneously on all-atom fine-grained (FG) and coarse-grained (CG) representations of a system is designed to improve sampling efficiency by combining the strength of nonequilibrium molecular dynamics (neMD) and Metropolis Monte Carlo (MC). This CG-guided hybrid neMD-MC algorithm comprises six steps: (1) a FG configuration of an atomic system is dynamically propagated for some period of time using equilibrium MD; (2) the resulting FG configuration is mapped onto a simplified CG model; (3) the CG model is propagated for a brief time interval to yield a new CG configuration; (4) the resulting CG configuration is used as a target to guide the evolution of the FG system; (5) the FG configuration (from step 1) is driven via a nonequilibrium MD (neMD) simulation toward the CG target; (6) the resulting FG configuration at the end of the neMD trajectory is then accepted or rejected according to a Metropolis criterion before returning to step 1. A symmetric two-ends momentum reversal prescription is used for the neMD trajectories of the FG system to guarantee that the CG-guided hybrid neMD-MC algorithm obeys microscopic detailed balance and rigorously yields the equilibrium Boltzmann distribution. The enhanced sampling achieved with the method is illustrated with a model system with hindered diffusion and explicit-solvent peptide simulations. Illustrative tests indicate that the method can yield a speedup of about 80 times for the model system and up to 21 times for polyalanine and (AAQAA)3 in water. PMID:26574442

INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp; Ohno, Hideki; Yamada, Yumi

2013-03-22

Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique markermore » of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.« less

Proprotein convertase 1 mediated proneuropeptide proteolytic processing in ischemic neuron injury.

PubMed

Tang, S S; Liang, Z Y; Guo, L R; Zhang, J H; Zhou, D

2017-01-01

Pro-protein processing mechanism plays an important role in neuron injury. To study the protein convertase 1 (PC1) mediated processing mechanism, the ischemic cellular or tissue proPC1/PC1 or proCgA/CgA (pro-chromogranin A) was analyzed. NS20Y differentiated cells were stressed by 0-6 h of oxygen and glucose deprivation (OGD) in glucose-free DMEM and an anaerobic jar environment. Ischemic C57BL/J mouse model was established by performing 60-min of middle cerebral artery occlusion (MCAO) operation and subsequent 4 or 24-h reperfusion. The TUNEL, immunochemistry, and Western blot methods were used to detect protein expression in ischemic cells or tissues. The OGD or MCAO stress caused substantial cell death in a dose-dependent manner (p < 0.05 or 0.01). With the increasing OGD dose, proPC1 and PC1 proteins gradually increased (p < 0.05 or 0.01) whereas proCgA and CgA proteins decreased (p < 0.05). In vivo the proPC1 and PC1 expressions presented with a peak at 4-h and then decreased at 24-h reperfusion (p < 0.05 or 0.01). The tissue proCgA and CgA proteins decreased with the increasing reperfusion time (p < 0.05). The results suggest that the increasing PC1 expression promoted the transformation of proCgA into CgA or smaller peptides, i.e. Pancreastatin or Secretoneurin, and the PC1 mediated processing plays a critical role (Fig. 4, Ref. 15).

The effect of practical cooling strategies on physiological response and cognitive function during simulated firefighting tasks

PubMed Central

Hemmatjo, Rasoul; Motamedzade, Majid; Aliabadi, Mohsen; Kalatpour, Omid; Farhadian, Maryam

2017-01-01

Background: Firefighters often perform multiple tasks during firefighting operations under unknown and unpredictable conditions in hot and hostile environments. Methods: In this interventional study each firefighters engaged in 4 conditions: namely (1) no cooling device; control (NC), (2) cooling gel (CG), (3) cool vest (CV), and (4) CG+CV. Cooling effects of the employed interventions were evaluated based on heart rate (HR), temporal temperature (TT), reaction time (RT), and the correct response (CR). Results: HR and TT values for use of CG+CV (147.47 bpm [SD 4.8]; 37.88°C [SD 0.20]) and CV bpm (147.53 [SD 4.67]; 37.90°C [SD 0.22]) were significantly lower than the CG (153.67 bpm [SD 4.82]; 38.10°C [SD 0.22]) and NC (154.4 bpm [SD 4.91]; 38.11°C [SD 0.23]) at the end of the activity. RT and CR for use of CG + CV (389.87 ms [SD 6.12]; 143.53 [SD 1.24]) and CV (389.53 ms [SD 6.24]; 143.47 [SD 1.18]) were significantly higher than the CG (385.73 [SD 7.25] ms; 143.07 [SD 0.88]) and NC (385.67 ms [SD 7.19]; 143.00 [SD 0.84]) at the end of the activity. Conclusion: It is concluded that CV was more effective than the CG in attenuating physiological responses and cognitive functions during firefighting operations. Furthermore, combining CV with CG provides no additional benefit. PMID:28326286

Geostationary Enhanced Temporal Interpolation for CERES Flux Products

NASA Technical Reports Server (NTRS)

Doelling, David R.; Loeb, Norman G.; Keyes, Dennis F.; Nordeen, Michele L.; Morstad, Daniel; Nguyen, Cathy; Wielicki, Bruce A.; Young, David F.; Sun, Moguo

2013-01-01

The Clouds and the Earth's Radiant Energy System (CERES) instruments on board the Terra and Aqua spacecraft continue to provide an unprecedented global climate record of the earth's top-of-atmosphere (TOA) energy budget since March 2000. A critical step in determining accurate daily averaged flux involves estimating the flux between CERES Terra or Aqua overpass times. CERES employs the CERES-only (CO) and the CERES geostationary (CG) temporal interpolation methods. The CO method assumes that the cloud properties at the time of the CERES observation remain constant and that it only accounts for changes in albedo with solar zenith angle and diurnal land heating, by assuming a shape for unresolved changes in the diurnal cycle. The CG method enhances the CERES data by explicitly accounting for changes in cloud and radiation between CERES observation times using 3-hourly imager data from five geostationary (GEO) satellites. To maintain calibration traceability, GEO radiances are calibrated against Moderate Resolution Imaging Spectroradiometer (MODIS) and the derived GEO fluxes are normalized to the CERES measurements. While the regional (1 deg latitude x 1 deg longitude) monthly-mean difference between the CG and CO methods can exceed 25 W m(sub -2) over marine stratus and land convection, these regional biases nearly cancel in the global mean. The regional monthly CG shortwave (SW) and longwave (LW) flux uncertainty is reduced by 20%, whereas the daily uncertainty is reduced by 50% and 20%, respectively, over the CO method, based on comparisons with 15-min Geostationary Earth Radiation Budget (GERB) data.

Effect of additional human chorionic gonadotrophin (hCG) on follicular growth and ovulation in gonadotrophin-treated gilts

PubMed Central

Manjarín, Rodrigo; Cassar, Glen; Friendship, Robert M.; Garcia, José C.; Dominguez, J. Carlos; Kirkwood, Roy N.

2015-01-01

The objective of this study was to determine the effect of additional human chorionic gonadotrophin (hCG) on the ovarian response of gilts previously treated with 200 IU hCG combined with 400 IU equine chorionic gonadotrophin (eCG) (eCG/hCG). Seventy-one prepuberal gilts (105 ± 7.5 kg) were assigned to groups: i) eCG/hCG (hCG-0; n = 25); ii) eCG/hCG followed by 100 IU of hCG at 24 h (hCG-100; n = 24); iii) eCG/hCG followed by 200 IU hCG at 24 h (hCG-200; n = 10); and iv) controls (CON; n = 12). Ovulation response was assessed by ovarian dissection or real-time ultrasonography. Additional hCG did not significantly improve numbers of gilts ovulating. Numbers of corpora lutea increased with hCG, and was higher in hCG-200 (P < 0.01). Compared to hCG-0, the frequency of cysts in gilts was higher in hCG-100 (P < 0.05) and further increased in hCG-200 (P < 0.01). The number of cysts per gilt was dose-dependently increased by additional hCG. We conclude that supplemental hCG will increase the number of corpora lutea but will be associated with follicular cyst development in a dose dependent manner. PMID:26130853

Quantitative ELISAs for serum soluble LHCGR and hCG-LHCGR complex: potential diagnostics in first trimester pregnancy screening for stillbirth, Down’s syndrome, preterm delivery and preeclampsia

PubMed Central

2012-01-01

Background Soluble LH/hCG receptor (sLHCGR) released from placental explants and transfected cells can be detected in sera from pregnant women. To determine whether sLHCGR has diagnostic potential, quantitative ELISAs were developed and tested to examine the correlation between pregnancy outcome and levels of serum sLHCGR and hCG-sLHCGR complex. Methods Anti-LHCGR poly- and monoclonal antibodies recognizing defined LHCGR epitopes, commerical anti-hCGbeta antibody, together with recombinant LHCGR and yoked hCGbeta-LHCGR standard calibrators were used to develop two ELISAs. These assays were employed to quantify serum sLHCGR and hCG-sLHCGR at first trimester human pregnancy. Results Two ELISAs were developed and validated. Unlike any known biomarker, sLHCGR and hCG-sLHCGR are unique because Down’s syndrome (DS), preeclampsia and preterm delivery are linked to both low (less than or equal to 5 pmol/mL), and high (equal to or greater than 170 pmol/mL) concentrations. At these cut-off values, serum hCG-sLHCGR together with PAPP-A detected additional DS pregnancies (21%) which were negative by free hCGbeta plus PAPP-A screening procedure. Therefore, sLHCGR/hCG-sLHCGR has an additive effect on the current primary biochemical screening of aneuploid pregnancies. More than 88% of pregnancies destined to end in fetal demise (stillbirth) exhibited very low serum hCG-sLHCGR(less than or equal to 5 pmol/mL) compared to controls (median 16.15 pmol/mL, n = 390). The frequency of high hCG-sLHCGR concentrations (equal to or greater than 170 pmol/mL) in pathological pregnancies was at least 3-6-fold higher than that of the control, suggesting possible modulation of the thyrotropic effect of hCG by sLHCGR. Conclusions Serum sLHCGR/hCG-sLHCGR together with PAPP-A, have significant potential as first trimester screening markers for predicting pathological outcomes in pregnancy. PMID:23245345

Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years

PubMed Central

Simpson, Angela; Lazic, Nevena; Belgrave, Danielle C.M.; Johnson, Phil; Bishop, Christopher; Mills, Clare; Custovic, Adnan

2015-01-01

Background The relationship between sensitization to allergens and disease is complex. Objective We sought to identify patterns of response to a broad range of allergen components and investigate associations with asthma, eczema, and hay fever. Methods Serum specific IgE levels to 112 allergen components were measured by using a multiplex array (Immuno Solid-phase Allergen Chip) in a population-based birth cohort. Latent variable modeling was used to identify underlying patterns of component-specific IgE responses; these patterns were then related to asthma, eczema, and hay fever. Results Two hundred twenty-one of 461 children had IgE to 1 or more components. Seventy-one of the 112 components were recognized by 3 or more children. By using latent variable modeling, 61 allergen components clustered into 3 component groups (CG1, CG2, and CG3); protein families within each CG were exclusive to that group. CG1 comprised 27 components from 8 plant protein families. CG2 comprised 7 components of mite allergens from 3 protein families. CG3 included 27 components of plant, animal, and fungal origin from 12 protein families. Each CG included components from different biological sources with structural homology and also nonhomologous proteins arising from the same biological source. Sensitization to CG3 was most strongly associated with asthma (odds ratio [OR], 8.20; 95% CI, 3.49-19.24; P < .001) and lower FEV1 (P < .001). Sensitization to CG1 was associated with hay fever (OR, 12.79; 95% CI, 6.84-23.90; P < .001). Sensitization to CG2 was associated with both asthma (OR, 3.60; 95% CI, 2.05-6.29) and hay fever (OR, 2.52; 95% CI, 1.38-4.61). Conclusions Latent variable modeling with a large number of allergen components identified 3 patterns of IgE responses, each including different protein families. In 11-year-old children the pattern of response to components of multiple allergens appeared to be associated with current asthma and hay fever but not eczema. PMID:25935108

Identification of Thyroid Hormones and Functional Characterization of Thyroid Hormone Receptor in the Pacific Oyster Crassostrea gigas Provide Insight into Evolution of the Thyroid Hormone System

PubMed Central

Huang, Wen; Xu, Fei; Qu, Tao; Zhang, Rui; Li, Li; Que, Huayong; Zhang, Guofan

2015-01-01

Thyroid hormones (THs) play important roles in development, metamorphosis, and metabolism in vertebrates. During the past century, TH functions were regarded as a synapomorphy of vertebrates. More recently, accumulating evidence has gradually convinced us that TH functions also occur in invertebrate chordates. To date, however, TH-related studies in non-chordate invertebrates have been limited. In this study, THs were qualitatively detected by two reliable methods (HPLC and LC/MS) in a well-studied molluscan species, the Pacific oyster Crassostrea gigas. Quantitative measurement of THs during the development of C. gigas showed high TH contents during embryogenesis and that oyster embryos may synthesize THs endogenously. As a first step in elucidating the TH signaling cascade, an ortholog of vertebrate TH receptor (TR), the most critical gene mediating TH effects, was cloned in C. gigas. The sequence of CgTR has conserved DNA-binding and ligand-binding domains that normally characterize these receptors. Experimental results demonstrated that CgTR can repress gene expression through binding to promoters of target genes and can interact with oyster retinoid X receptor. Moreover, CgTR mRNA expression was activated by T4 and the transcriptional activity of CgTR promoter was repressed by unliganded CgTR protein. An atypical thyroid hormone response element (CgDR5) was found in the promoter of CgTR, which was verified by electrophoretic mobility shift assay (EMSA). These results indicated that some of the CgTR function is conserved. However, the EMSA assay showed that DNA binding specificity of CgTR was different from that of the vertebrate TR and experiments with two dual-luciferase reporter systems indicated that l-thyroxine, 3,3′,5-triiodothyronine, and triiodothyroacetic acid failed to activate the transcriptional activity of CgTR. This is the first study to functionally characterize TR in mollusks. The presence of THs and the functions of CgTR in mollusks contribute to better understanding of the evolution of the TH system. PMID:26710071

A comparative study of coarse-graining methods for polymeric fluids: Mori-Zwanzig vs. iterative Boltzmann inversion vs. stochastic parametric optimization

NASA Astrophysics Data System (ADS)

Li, Zhen; Bian, Xin; Yang, Xiu; Karniadakis, George Em

2016-07-01

We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamics based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.

Simultaneous measurement of proguanil and its metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography, and its preliminary application in relation to genetically determined S-mephenytoin 4'-hydroxylation status.

PubMed

Kusaka, M; Setiabudy, R; Chiba, K; Ishizaki, T

1996-02-01

A simple high-performance liquid chromatographic (HPLC) assay method was developed for the measurement of proguanil (PG) and its major metabolites, cycloguanil (CG) and 4-chlorophenyl-biguanide (CPB), in human plasma and urine. The assay allowed the simultaneous determination of all analytes in 1 ml of plasma or 0.1 ml of urine. The detection limits of PG, CG, and CPB, defined as the signal-to-noise ratio of 3, were 1 and 5 ng/ml for plasma and urine samples, respectively. Recoveries of the analytes and the internal standard (pyrimethamine) were > 62% from plasma and > 77% from urine. Intra-assay and interassay coefficients of variation for all analytes in plasma and urine were < 10% except for the values of CG and CPB, which ranged from 10% to 15% at one or two concentrations among 4-5 concentrations studied. The clinical applicability of the method was assessed by the preliminary pharmacokinetic study of PG, CG, and CPB in six healthy volunteers with the individually known phenotypes (extensive and poor metabolizers) of S-mephenytoin 4'-hydroxylation, suggesting that individuals with a poor metabolizer phenotype of S-mephenytoin have a much lower capacity to bioactivate PG to CG compared with the extensive metabolizers.

A comparative study of coarse-graining methods for polymeric fluids: Mori-Zwanzig vs. iterative Boltzmann inversion vs. stochastic parametric optimization.

PubMed

Li, Zhen; Bian, Xin; Yang, Xiu; Karniadakis, George Em

2016-07-28

We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamics based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.

Effects of a Controlled Family-Based Health Education/Counseling Intervention

ERIC Educational Resources Information Center

Salminen, Marika; Vahlberg, Tero; Ojanlatva, Ansa; Kivela, Sirkka-Liisa

2005-01-01

Objective: To describe the effects of a controlled family-based health education/counseling intervention on health behaviors of children with a familial history of cardiovascular diseases (FH-CVDs). Methods: The intervention group (IG, n=432) received 5 counseling sessions. The control groups 1 (CG1, n=200) and 2 (CG2, n=423) received no…

Protease-Activated Receptor 2 Activation Inhibits N-Type Ca2+ Currents in Rat Peripheral Sympathetic Neurons

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Kim, Myeong Ok; Joeng, Ji-Hyun; Chung, Seungsoo

2014-01-01

The protease-activated receptor (PAR)-2 is highly expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although several mechanisms have been suggested to explain PAR-2-induced hypotension, the precise mechanism remains to be elucidated. To investigate this possibility, we investigated the effects of PAR-2 activation on N-type Ca2+ currents (ICa-N) in isolated neurons of the celiac ganglion (CG), which is involved in the sympathetic regulation of mesenteric artery vascular tone. PAR-2 agonists irreversibly diminished voltage-gated Ca2+ currents (ICa), measured using the patch-clamp method, in rat CG neurons, whereas thrombin had little effect on ICa. This PAR-2-induced inhibition was almost completely prevented by ω-CgTx, a potent N-type Ca2+ channel blocker, suggesting the involvement of N-type Ca2+ channels in PAR-2-induced inhibition. In addition, PAR-2 agonists inhibited ICa–N in a voltage-independent manner in rat CG neurons. Moreover, PAR-2 agonists reduced action potential (AP) firing frequency as measured using the current-clamp method in rat CG neurons. This inhibition of AP firing induced by PAR-2 agonists was almost completely prevented by ω-CgTx, indicating that PAR-2 activation may regulate the membrane excitability of peripheral sympathetic neurons through modulation of N-type Ca2+ channels. In conclusion, the present findings demonstrate that the activation of PAR-2 suppresses peripheral sympathetic outflow by modulating N-type Ca2+ channel activity, which appears to be involved in PAR-2-induced hypotension, in peripheral sympathetic nerve terminals. PMID:25410909

A model system for the evaluation of radioimmunoimaging of tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koizumi, M.; Endo, K.; Sakahara, H.

1985-05-01

The authors have developed a simple model system that can be used to evaluate methods of radioimmunoimaging of tumors, using human chorionic gonadropin (hCG) as a model antigen, and a monoclonal antibody against hCG ..beta..-subunit as a model antibody. HCG was coated on a polystylene spherical bead with a quarter inch in diameter, and coated beads were washed extensively with phosphate buffered saline, and glycine acid buffer to remove the easily dissociable antigen. HCG-coated beads were put into the subcutaneous tissue on the back of mice. At 24 hr after the transplantation, when serum hCG was not detectable by themore » conventional RIA, radiolabeled antibodies were injected and its bio-distribution monitored. The %ID/g for the hCG coated beads increased to a maximum of 48 hr after the injection of radioiodinad antibody, whereas the %ID/g for most organs decreased with time. As a nonspecific antigen, beads coated with bovine serum albumin were transplanted and its uptake was as low as about one 50th of hCG-coated ones. The %ID/g of radioiodinated monoclonal antibody against human thyroglobulin (a nonspecific antibody) for hCG-coated beads was also negligible. Thus, the localization index (%ID of specific antibody / %ID of nonspecific antibody) reached to 15.0 at 24 hr, 35.5 at 48 hr and 57.8 at 96 hr after the injection. The biodistribution of In-111 labeled specific monoclonal antibody, prepared through the chelation with DTPA, demonstrated similar results with radioiodinated ones. This mouse model system that did not involve the use of tumors, yielded high localization index and reproducibilities and could be used to evaluate different methods for radiolabelng monoclonal antibodies.« less

Coarse-grained versus atomistic simulations: realistic interaction free energies for real proteins.

PubMed

May, Ali; Pool, René; van Dijk, Erik; Bijlard, Jochem; Abeln, Sanne; Heringa, Jaap; Feenstra, K Anton

2014-02-01

To assess whether two proteins will interact under physiological conditions, information on the interaction free energy is needed. Statistical learning techniques and docking methods for predicting protein-protein interactions cannot quantitatively estimate binding free energies. Full atomistic molecular simulation methods do have this potential, but are completely unfeasible for large-scale applications in terms of computational cost required. Here we investigate whether applying coarse-grained (CG) molecular dynamics simulations is a viable alternative for complexes of known structure. We calculate the free energy barrier with respect to the bound state based on molecular dynamics simulations using both a full atomistic and a CG force field for the TCR-pMHC complex and the MP1-p14 scaffolding complex. We find that the free energy barriers from the CG simulations are of similar accuracy as those from the full atomistic ones, while achieving a speedup of >500-fold. We also observe that extensive sampling is extremely important to obtain accurate free energy barriers, which is only within reach for the CG models. Finally, we show that the CG model preserves biological relevance of the interactions: (i) we observe a strong correlation between evolutionary likelihood of mutations and the impact on the free energy barrier with respect to the bound state; and (ii) we confirm the dominant role of the interface core in these interactions. Therefore, our results suggest that CG molecular simulations can realistically be used for the accurate prediction of protein-protein interaction strength. The python analysis framework and data files are available for download at http://www.ibi.vu.nl/downloads/bioinformatics-2013-btt675.tgz.

Glomerular filtration rate estimation from plasma creatinine after inhibition of tubular secretion: relevance of the creatinine assay.

PubMed

Kemperman, F A; Silberbusch, J; Slaats, E H; van Zanten, A P; Weber, J A; Krediet, R T; Arisz, L

1999-05-01

Estimation of glomerular filtration rate (GFR) from plasma creatinine concentration after inhibition of tubular creatinine secretion with cimetidine provides a good assessment in patients with various nephropathies and with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to compare cimetidine-aided GFR estimations using various creatinine assays. In 30 outpatients with NIDDM GFR was measured as the urinary clearance of continuously infused [125I]iothalamate. Plasma creatinine concentration was analysed after oral cimetidine with an alkaline picrate (AP) method, with an enzymatic (PAP) assay and with HPLC. GFR estimations were calculated with the Cockcroft Gault formula (CG). AP creatinine concentrations were significantly higher than PAP or HPLC values. GFR estimations by AP (CG(AP) 66 +/- 19 ml/min/1.73 m2, mean SD) were significantly lower than GFR (89 +/- 30), whereas CG(PAP) (85 +/- 30) and CG(HPLC) (84 +/- 34 ml/min/1.73 m2) were not. Bland and Altman analysis showed a difference between CG(AP) and GFR of -22.4 +/- 17.7 ml/min/1.73 m2; this difference becomes larger when the GFR increases. The difference between CG and GFR was only -3.8 +/- 14.8 ml/min/1.73 m2 for PAP and -4.4 +/- 17.5 ml/min/1.73 m2 for HPLC, without any systematic difference. A good assessment of the GFR from plasma creatinine after cimetidine administration is possible when creatinine is measured with an enzymatic assay or with the less convenient HPLC method. The more widespread and cheaper alkaline picrate assay is not suitable for GFR-estimation.

Layer-by-layer assembly of gold nanoparticles and cysteamine on gold electrode for immunosensing of human chorionic gonadotropin at picogram levels.

PubMed

Roushani, Mahmoud; Valipour, Akram; Valipour, Mehdi

2016-04-01

The development of an electrochemical immunosensor for the detection of human chorionic gonadotropin (hCG) is described with a limit of detection as low as 0.3 pg mL(-1) in phosphate buffer. In this immunosensor, cysteamine (Cys) and gold nanoparticles (AuNPs) were used to immobilize an anti-hCG monoclonal antibody onto a gold electrode (GE). The structure of AuNPs has been confirmed by EDS, SEM, and TEM analysis. Due to the large specific surface area and excellent electrical conductivity of AuNPs, electron transfer was promoted and the amount of hCG antibody was enhanced significantly. A systematic study on the effects of experimental parameters such as pH, incubation time in the hCG solution and urea solution used for experiments on the binding between the immobilized antibody and hCG has been carried out. Under optimal experimental parameters, differential pulse voltammetry (DPV) signal changes of the [Fe(CN)6](3-/4-) are used to detect hCG with two broad linear ranges: 0.001 to 0.2 and 0.2 to 60.7 ng mL(-1). The LOD value proves more sensitive in comparison with previously reported methods. The prepared immunosensor showed high sensitivity and stability. In addition, the immunosensor was successfully used for the determination of hCG in human serum. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential processing of the two subunits of human choriogonadotropin (hCG) by granulosa cells. I. Preparation and characterization of selectively labeled hCG

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landefeld, T.D.; Byrne, M.D.; Campbell, K.L.

1981-12-01

The alpha- and beta-subunits of hCG were radioiodinated and recombined with unlabeled complementary subunits. The resultant recombined hormones, selectively labeled in either the alpha- or beta-subunit, were separated from unrecombined subunit by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, extracted with Triton X-100, and characterized by binding analysis. The estimates of maximum binding (active fraction) of the two resultant selectively labeled, recombined hCG preparations, determined with excess receptor were 0.41 and 0.59. These values are similar to those obtained when hCG is labeled as an intact molecule. The specific activities of the recombined preparations were estimated by four different methods, and themore » resulting values were used in combination with the active fraction estimates to determine the concentrations of active free and bound hormone. Binding analyses were run using varying concentrations of both labeled and unlabeled hormone. Estimates of the equilibrium dissociation binding constant (Kd) and receptor capacity were calculated in three different ways. The mean estimates of capacity (52.6 and 52.7 fmol/mg tissue) and Kd (66.6 and 65.7 pM) for the two preparations were indistinguishable. Additionally, these values were similar to values reported previously for hCG radioiodinated as an intact molecule. The availability of well characterized, selectively labeled hCG preparations provides new tools for studying the mechanism of action and the target cell processing of the subunits of this hormone.« less

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

PubMed Central

Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung

2016-01-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats. PMID:27610034

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

PubMed

Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

2016-09-01

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Coarse-Graining of Polymer Dynamics via Energy Renormalization

NASA Astrophysics Data System (ADS)

Xia, Wenjie; Song, Jake; Phelan, Frederick; Douglas, Jack; Keten, Sinan

The computational prediction of the properties of polymeric materials to serve the needs of materials design and prediction of their performance is a grand challenge due to the prohibitive computational times of all-atomistic (AA) simulations. Coarse-grained (CG) modeling is an essential strategy for making progress on this problem. While there has been intense activity in this area, effective methods of coarse-graining have been slow to develop. Our approach to this fundamental problem starts from the observation that integrating out degrees of freedom of the AA model leads to a strong modification of the configurational entropy and cohesive interaction. Based on this observation, we propose a temperature-dependent systematic renormalization of the cohesive interaction in the CG modeling to recover the thermodynamic modifications in the system and the dynamics of the AA model. Here, we show that this energy renormalization approach to CG can faithfully estimate the diffusive, segmental and glassy dynamics of the AA model over a large temperature range spanning from the Arrhenius melt to the non-equilibrium glassy states. Our proposed CG strategy offers a promising strategy for developing thermodynamically consistent CG models with temperature transferability.

A coarse-grained model of microtubule self-assembly

NASA Astrophysics Data System (ADS)

Regmi, Chola; Cheng, Shengfeng

Microtubules play critical roles in cell structures and functions. They also serve as a model system to stimulate the next-generation smart, dynamic materials. A deep understanding of their self-assembly process and biomechanical properties will not only help elucidate how microtubules perform biological functions, but also lead to exciting insight on how microtubule dynamics can be altered or even controlled for specific purposes such as suppressing the division of cancer cells. Combining all-atom molecular dynamics (MD) simulations and the essential dynamics coarse-graining method, we construct a coarse-grained (CG) model of the tubulin protein, which is the building block of microtubules. In the CG model a tubulin dimer is represented as an elastic network of CG sites, the locations of which are determined by examining the protein dynamics of the tubulin and identifying the essential dynamic domains. Atomistic MD modeling is employed to directly compute the tubulin bond energies in the surface lattice of a microtubule, which are used to parameterize the interactions between CG building blocks. The CG model is then used to study the self-assembly pathways, kinetics, dynamics, and nanomechanics of microtubules.

Can prostatic arterial embolisation (PAE) reduce the volume of the peripheral zone? MRI evaluation of zonal anatomy and infarction after PAE.

PubMed

Lin, Yen-Ting; Amouyal, Grégory; Correas, Jean-Michel; Pereira, Héléna; Pellerin, Olivier; Del Giudice, Costantino; Déan, Carole; Thiounn, Nicolas; Sapoval, Marc

2016-10-01

To assess the impact of prostatic arterial embolisation (PAE) on various prostate gland anatomical zones. We retrospectively reviewed paired MRI scans obtained before and after PAE for 25 patients and evaluated changes in volumes of the median lobe (ML), central gland (CG), peripheral zone (PZ) and whole prostate gland (WPV) following PAE. We used manual segmentation to calculate volume on axial view T2-weighted images for ML, CG and WPV. We calculated PZ volume by subtracting CG volume from WPV. Enhanced phase on dynamic contrasted-enhanced MRI was used to evaluate the infarction areas after PAE. Clinical results of International Prostate Symptom Score and International Index of Erectile Function questionnaires and the urodynamic study were evaluated before and after PAE. Significant reductions in volume were observed after PAE for ML (26.2 % decrease), CG (18.8 %), PZ (16.4 %) and WPV (19.1 %; p < 0.001 for all these volumes). Patients with clinical failure had smaller volume reductions for WPV, ML and CG (all p < 0.05). Patients with significant CG infarction after PAE displayed larger WPV, ML and CG volume reductions (all p < 0.01). PAE can significantly decrease WPV, ML, CG and PZ volumes, and poor clinical outcomes are associated with smaller volume reductions. • The MRI segmentation method provides detailed comparisons of prostate volume change. • Prostatic arterial embolisation (PAE) decreased central gland and peripheral zone volumes. • Prostates with infarction after PAE showed larger decreases in volume. • A larger decrease in prostate volume is associated with clinical success.

Influence of multiple injections of human chorionic gonadotropin (hCG) on urine and serum endogenous steroids concentrations.

PubMed

Strahm, Emmanuel; Marques-Vidal, Pedro; Pralong, François; Dvorak, Jiri; Saugy, Martial; Baume, Norbert

2011-12-10

Since it is established that human chorionic gonadotropin (hCG) affects testosterone production and release in the human body, the use of this hormone as a performance enhancing drug has been prohibited by the World Anti-Doping Agency. Nowadays, the only validated biomarker of a hCG doping is its direct quantification in urine. However, this specific parameter is subjected to large inter-individual variability and its determination is directly dependent on the reliability of hCG immunoassays used. In order to counteract these weaknesses, new biomarkers need to be evidenced. To address this issue, a pilot clinical study was performed on 10 volunteers submitted to 3 subsequent hCG injections. Blood and urine samples were collected during two weeks in order to follow the physiological effects on related compounds such as the steroid profile or hormones involved in the hypothalamo-pituitary axis. The hCG pharmacokinetic observed in all subjects was, as expected, prone to important inter-individual variations. Using ROC plots, level of testosterone and testosterone on luteinizing hormone ratio in both blood and urine were found to be the most relevant biomarker of a hCG abuse, regardless of inter-individual variations. In conclusion, this study showed the crucial importance of reliable quantification methods to assess low differences in hormonal patterns. In regard to these results and to anti-doping requirements and constraints, blood together with urine matrix should be included in the anti-doping testing program. Together with a longitudinal follow-up approach it could constitute a new strategy to detect a hCG abuse, applicable to further forms of steroid or other forbidden drug manipulation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

SAHA Suppresses Peritoneal Fibrosis in Mice

PubMed Central

Io, Kumiko; Nishino, Tomoya; Obata, Yoko; Kitamura, Mineaki; Koji, Takehiko; Kohno, Shigeru

2015-01-01

♦ Objective: Long-term peritoneal dialysis causes peritoneal fibrosis in submesothelial areas. However, the mechanism of peritoneal fibrosis is unclear. Epigenetics is the mechanism to induce heritable changes without any changes in DNA sequences. Among epigenetic modifications, histone acetylation leads to the transcriptional activation of genes. Recent studies indicate that histone acetylation is involved in the progression of fibrosis. Therefore, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on the progression of peritoneal fibrosis in mice. ♦ Methods: Peritoneal fibrosis was induced by the injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. SAHA, or a dimethylsulfoxide and saline vehicle, was administered subcutaneously every day from the start of the CG injections for 3 weeks. Morphologic peritoneal changes were assessed by Masson’s trichrome staining, and fibrosis-associated factors were assessed by immunohistochemistry. ♦ Results: In CG-injected mice, a marked thickening of the submesothelial compact zone was observed. In contrast, the administration of SAHA suppressed the progression of submesothelial thickening and type III collagen accumulation in CG-injected mice. The numbers of fibroblast-specific protein-1-positive cells and α-smooth muscle actin α-positive cells were significantly decreased in the CG + SAHA group compared to that of the CG group. The level of histone acetylation was reduced in the peritoneum of the CG group, whereas it was increased in the CG + SAHA group. ♦ Conclusions: Our results indicate that SAHA can suppress peritoneal thickening and fibrosis in mice through up-regulation of histone acetylation. These results suggest that SAHA may have therapeutic potential for treating peritoneal fibrosis. PMID:24584598

Enrichment of Secondary Wastewater Sludge for Production of Hydrogen from Crude Glycerol and Comparative Evaluation of Mono-, Co- and Mixed-Culture Systems

PubMed Central

Pachapur, Vinayak Laxman; Kutty, Prianka; Brar, Satinder Kaur; Ramirez, Antonio Avalos

2016-01-01

Anaerobic digestion using mixed-culture with broader choice of pretreatments for hydrogen (H2) production was investigated. Pretreatment of wastewater sludge by five methods, such as heat, acid, base, microwave and chloroform was conducted using crude glycerol (CG) as substrate. Results for heat treatment (100 °C for 15 min) showed the highest H2 production across the pretreatment methods with 15.18 ± 0.26 mmol/L of medium at 30 °C in absence of complex media and nutrient solution. The heat-pretreated inoculum eliminated H2 consuming bacteria and produced twice as much as H2 as compared to other pretreatment methods. The fermentation conditions, such as CG concentration (1.23 to 24 g/L), percentage of inoculum size (InS) (1.23% to 24% v/v) along with initial pH (2.98 to 8.02) was tested using central composite design (CCD) with H2 production as response parameter. The maximum H2 production of 29.43 ± 0.71 mmol/L obtained at optimum conditions of 20 g/L CG, 20% InS and pH 7. Symbiotic correlation of pH over CG and InS had a significant (p-value: 0.0011) contribution to H2 production. The mixed-culture possessed better natural acclimatization activity for degrading CG, at substrate inhibition concentration and provided efficient inoculum conditions in comparison to mono- and co-culture systems. The heat pretreatment step used across mixed-culture system is simple, cheap and industrially applicable in comparison to mono-/co-culture systems for H2 production. PMID:26771607

Controlled Ovarian Hyperstimulation with Intrauterine Insemination Is More Successful After r-hCG Administration Than Spontaneous LH Surge.

PubMed

Taerk, Evan; Hughes, Edward; Greenberg, Cassandra; Neal, Michael; Amin, Shilpa; Faghih, Mehrnoosh; Karnis, Megan

2017-01-01

The purpose of this study was to evaluate whether clinical pregnancy rate is affected by timing intrauterine insemination (IUI) according to serum LH surge, r-hCG trigger, or a combination of LH surge and r-hCG trigger in controlled ovarian hyperstimulation (COH) cycles for patients with a variety of infertility etiologies. The last 365 consecutive COH-IUI cycles performed at ONE Fertility Burlington in 2014 were reviewed and categorized according to method of IUI timing. Associations between categorical variables were analyzed using a combination of Chi-square and Fisher's Exact tests, and between continuous variables using independent sample t-tests and logistic regression to a level of significance of p<0.05. The overall clinical pregnancy rate in this sample was 18.1% (66/365). Administration of r-hCG prior to IUI resulted in a higher clinical pregnancy rate compared with spontaneous serum LH surge: 18.2% vs . 5.8%, p=0.012. Patients in whom r-hCG was administered concomitantly with a serum LH surge had a higher clinical pregnancy than the r-hCG trigger group (30.8% vs . 18.2%, p=0.004) and LH surge group (30.8% vs . 5.8%, p<0.001). A sub-group analysis revealed that patients receiving r-FSH, rather than clomiphene or letrozole, had a significantly higher clinical pregnancy rate after r-hCG trigger as compared to the LH surge group (21.7% vs . 2.1%, p=0.01). In subfertile couples undergoing COH-IUI, r-hCG administration was associated with an increased clinical pregnancy rate compared with spontaneous serum LH surge. When r-hCG was administered concomitantly with a serum LH surge, this benefit was amplified. The effect appears to be of particular importance in r-FSH-medicated cycles.

Treatment with eCG decreases the vascular density and increases the glandular density of the bovine uterus.

PubMed

Mona e Pinto, J; Pavanelo, V; Alves de Fátima, L; Medeiros de Carvalho Sousa, L M; Pacheco Mendes, G; Machado Ferreira, R; Ayres, H; Sampaio Baruselli, P; Palma Rennó, F; de Carvallo Papa, P

2014-06-01

The uterus plays an essential role in mammalian reproduction and is a target of several hormonal protocols used to improve fertility in cattle. Many studies highlighted the importance of eCG treatment following fixed-time artificial insemination in improving follicular growth, ovulation and pregnancy rates in cattle. Moreover, eCG has been implicated in angiogenesis, leading to important changes in uterine blood flow and vascularisation. However, there is still a lack of information regarding the specific alterations induced by eCG upon glandular and vascular characteristics of bovine uterus. To investigate the influence of eCG on: uterine thickness and area; uterine artery diameter and area; uterine vascular and gland density; and the expression of the VEGFA-system, the uteri of crossbred beef cows were collected. All cows were submitted to follicular wave emergence synchronization. On day four of protocol, cows submitted to superovulation (n = 6) received 2000 IU eCG, on day eight, after expected follicular deviation, cows submitted to stimulatory treatment (n = 5) received 400 IU eCG. Control cows (n = 5) did not receive eCG. On day five po cows were subjected to ultrassonographic evaluation and slaughtered for uterine tissue sampling on day six po. Uterine vessels and glands were quantified by the counting point stereological method. The VEGFA-system was localized in different cellular types, showing no qualitative or quantitative differences in the site of expression or the intensity of the positive signal among the groups. Vascular density was decreased in the endometrium of stimulated and myometrium of superovulated cows compared with the control ones, which showed higher vascular density in the myometrium and endometrium of the ipsilateral uterine horn. The uterine gland density was higher in superovulated compared with stimulated and control cows. Thus, we can infer that stimulatory or superovulatory treatments with eCG influence the vascular density in the endometrium and myometrium in cattle. © 2014 Blackwell Verlag GmbH.

The association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease in a southern Chinese population.

PubMed

Zhang, Li; Wang, Jinxin; Che, Di; Wang, Yanfei; Rong, Xing; Pi, Lei; Xu, Yufen; Li, Wei; Huang, Ping; Chu, Maoping; Gu, Xiaoqiong

2018-06-14

miRNA-146a plays a critical role in innate immune and inflammatory responses. Kawasaki disease involves immune-mediated inflammatory responses, which lead to vascular endothelial injury. However, there has been no study on the association between the miRNA-146a rs2910164 C>G polymorphism and Kawasaki disease risk. We enrolled 532 Kawasaki disease patients and 623 healthy controls from a southern Chinese population, and the miRNA-146a rs2910164 C>G polymorphism was genotyped by the TaqMan method. There was no evidence that this polymorphism was associated with Kawasaki disease. Stratified analysis also showed no significant association. This study indicates that the miRNA-146a rs2910164 C>G polymorphism may not be associated with Kawasaki disease in a southern Chinese population. Larger, multicenter studies are needed to confirm our conclusions. ©2018 The Author(s).

Assessing ESA on What It Is Designed For: A Reply to Cooper and Glaesser

ERIC Educational Resources Information Center

Schneider, Carsten Q.; Wagemann, Claudius

2016-01-01

We appreciate Barry Cooper and Judith Glaesser's (henceforth CG) energy and effort put into reflecting on parts of our proposals laid out in "Set-theoretic Methods for the Social Sciences" (2012). We use our response to explain what enhanced standard analysis (ESA) is meant to achieve and what not, an issue about which CG hold erroneous…

Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

PubMed

Cole, Laurence A

2014-11-01

Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

[Influence of water fluoride exposure on sex hormone binding globulin and testosterone in adult male].

PubMed

Zhou, Tong; Yang, Rupu; Li, Shihong; Zheng, Guoqing; Xi, Yu; Cheng, Xuemin; Hou, Jiaxiang; Cui, Liuxin; Ba, Yue

2013-03-01

To explore the influence of water fluoride exposure on sex hormone binding globulin (SHBG) and testosterone in adult male. Cross-sectional study was conducted in three villages of Tongxu county including high fluoride group (HFG), defluoridation project group (DFPG) and control group (CG) based on the fluoride concentration in drinking water. Adult male who were born and raised in the village and aged 18 - 50 years old were recruited using cluster sampling. Fasting blood and morning urine samples were collected. The fluoride levels in drinking water and urine were detected by fluoride-ion selective electrode method. Serum SHBG level was determined using enzyme-linked immunosorbent assay (ELISA). The chemical luminescence immune analysis method was used to detect serum testosterone content. Serum SHBG level was 47.85 nmol/L in CG, 31.37 nmol/L in DFPG and 24.52 nmol/L in HFG respectively. There were significant difference among of three groups (P < 0.05). Serum testosterone level was 3.69 ng/ml in CG, 4.61 ng/ml in DFPG and 4.83 ng/ml in HFG respectively. Serum testosterone level in HFG was significantly higher than that in CG (P < 0.05). Serum SHBG level in HFG has positive correlation with serum testosterone (r = 0.230, P = 0.049), which has not been observed in DFPG and CG. Long-time fluorine exposure may affect serum SHBG and testosterone level in adult male.

Ultrasensitive colorimetric immunoassay for hCG detection based on dual catalysis of Au@Pt core-shell nanoparticle functionalized by horseradish peroxidase

NASA Astrophysics Data System (ADS)

Wang, Weiguo; Zou, Yake; Yan, Jinwu; Liu, Jing; Chen, Huixiong; Li, Shan; Zhang, Lei

2018-03-01

In this paper, an ultrasensitive colorimetric biosensor for human chorionic gonadotrophin (hCG) detection was designed from bottom-up method based on the dual catalysis of the horseradish peroxidase (HRP) and Au@Pt nanoparticles (NPs) relative to H2O2-TEM system. HRP and monoclonal mouse anti-hCG antibody (β-submit, mAb1) were co-immobilized onto the Au@Pt NP surface to improve catalytic efficiency and specificity, which formed a dual functionalized Au@Pt-HRP probe with the mean size of 42.8 nm (D50). The colorimetric immunoassay was developed for the hCG detection, and the Au@Pt-HRP probe featured a higher sensitivity in the concentration range of 0.4-12.8 IU L- 1 with a low limit of detection (LOD) of 0.1 IU L- 1 compared with the LODs of 0.8 IU L- 1 for BA-ELISA and of 2.0 IU L- 1 for Au@Pt, which indicated that the Au@Pt-HRP probe possessed higher catalytic efficiency with 2.8-fold increase over Au@Pt and 33.8-fold increase over HRP. Also, the Au@Pt-HRP probe exhibited good precision and reproducibility, high specificity and acceptable accuracy with CV being less than 15%. The dual functionalized Au@Pt-HRP probe as a type of signal amplified method was firstly applied in the colorimetric immunoassay for the hCG detection.

Immunochemical mapping of gonadotropins.

PubMed

Berger, P; Bidart, J M; Delves, P S; Dirnhofer, S; Hoermann, R; Isaacs, N; Jackson, A; Klonisch, T; Lapthorn, A; Lund, T; Mann, K; Roitt, I; Schwarz, S; Wick, G

1996-12-20

As a glycoprotein hormone, human chorionic gonadotropic (hCG) is not a single molecular entity but this term rather comprises an array of molecular variants such as hCG, hCG beta, hCGn, hCG beta n, hCG beta cf, -CTPhCG, hCG beta CTP, deglyhCG, asialohCG, hCGav and the closely related molecules hLH, hLH beta and hLH beta ef. The advent of monoclonal antibodies (MCA), the availability of ultrasensitive detection systems and the recent determination of the crystal structure of hCG, made it possible to design special purpose diagnostic and clinical research immunoassays for hCG-like molecules. For more than a decade we and others have tried to refine epitope maps for hCG and related molecules by means of a large panel of MCA, naturally occurring metabolic variants of hCG (hCGn, hCG beta, hCG alpha, hCG beta cf, hCG beta CTP), homologous hormones and subunits of various species (e.g. hLH, hLH beta, hFSH, hTSH, oLH, rLH beta), chemically modified molecules (deglyhCG, asialohCG, tryptic and chymotryptic hCG beta and hCG alpha fragments) and synthetic peptides (octapeptides and longer). It appeared that all epitopes on molecular hCG-variants recognized by our MCA are determined by the protein backbone. Except for the two major epitopes on hCG beta CTP and parts of two antigenic domains on hCG alpha, epitopes on hCG-derived molecules are determined by the tertiary and quarternary structure. Operationally useful descriptive epitope maps were designed including information on assay suitability of antigenic determinants. On this basis we established ultrasensitive time-resolved fluoroimmuno-assays for hCG, hCG and hCGn, hCG beta and hCG beta n and hCG beta cf, hCG alpha and additional assays recognizing different spectra of hCG-variants. Such assay have been applied by us and others to the detection of pregnancy, early pregnancy loss, choriocarcinoma, testicular cancer, other cancers and prenatal diagnosis. However, as the molecular structure of many epitopes utilized in immunoassays of different laboratories was not resolved, comparability of results was not satisfactory. Consequently, attempts were made to compare schematic epitope maps from different research institutions. The situation has been much improved by solving the three-dimensional (3D) structure of hCG. It has been shown that hCG is a member of the structural superfamily of cystine knot growth factors like NGF, PDGF-B and TGF-beta. Each of its subunits is stabilized in its topology by three disulfide bonds forming a cystine knot. Moreover, it turned out that the disulfide bridges in their majority have previously been wrongly assigned. Computer molecular modeling of crystallographic coordinates of hCG and subsequent selective combined--PCR-based and immunological--mutational analyses of hCG beta expressed via the transmembrane region of a MHC molecule made it possible to more precisely localize epitopes on hCG-derived molecules. Although the entire surface of hCG has to be regarded as potentially immunogenic there seems to be hot spots where epitopes are clustered in antigenic domains. These are located on the first and third loops protuding from the cystine knots of both subunits and are possibly centered around the knot itself. Ultimate answers on epitope localizations will be given by the crystal structure determination of hCG complexed with different Fabs.

Fast inversion of gravity data using the symmetric successive over-relaxation (SSOR) preconditioned conjugate gradient algorithm

NASA Astrophysics Data System (ADS)

Meng, Zhaohai; Li, Fengting; Xu, Xuechun; Huang, Danian; Zhang, Dailei

2017-02-01

The subsurface three-dimensional (3D) model of density distribution is obtained by solving an under-determined linear equation that is established by gravity data. Here, we describe a new fast gravity inversion method to recover a 3D density model from gravity data. The subsurface will be divided into a large number of rectangular blocks, each with an unknown constant density. The gravity inversion method introduces a stabiliser model norm with a depth weighting function to produce smooth models. The depth weighting function is combined with the model norm to counteract the skin effect of the gravity potential field. As the numbers of density model parameters is NZ (the number of layers in the vertical subsurface domain) times greater than the observed gravity data parameters, the inverse density parameter is larger than the observed gravity data parameters. Solving the full set of gravity inversion equations is very time-consuming, and applying a new algorithm to estimate gravity inversion can significantly reduce the number of iterations and the computational time. In this paper, a new symmetric successive over-relaxation (SSOR) iterative conjugate gradient (CG) method is shown to be an appropriate algorithm to solve this Tikhonov cost function (gravity inversion equation). The new, faster method is applied on Gaussian noise-contaminated synthetic data to demonstrate its suitability for 3D gravity inversion. To demonstrate the performance of the new algorithm on actual gravity data, we provide a case study that includes ground-based measurement of residual Bouguer gravity anomalies over the Humble salt dome near Houston, Gulf Coast Basin, off the shore of Louisiana. A 3D distribution of salt rock concentration is used to evaluate the inversion results recovered by the new SSOR iterative method. In the test model, the density values in the constructed model coincide with the known location and depth of the salt dome.

Very narrow band model calculations of atmospheric fluxes and cooling rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernstein, L.S.; Berk, A.; Acharya, P.K.

1996-10-15

A new very narrow band model (VNBM) approach has been developed and incorporated into the MODTRAN atmospheric transmittance-radiance code. The VNBM includes a computational spectral resolution of 1 cm{sup {minus}1}, a single-line Voigt equivalent width formalism that is based on the Rodgers-Williams approximation and accounts for the finite spectral width of the interval, explicit consideration of line tails, a statistical line overlap correction, a new sublayer integration approach that treats the effect of the sublayer temperature gradient on the path radiance, and the Curtis-Godson (CG) approximation for inhomogeneous paths. A modified procedure for determining the line density parameter 1/d ismore » introduced, which reduces its magnitude. This results in a partial correction of the VNBM tendency to overestimate the interval equivalent widths. The standard two parameter CG approximation is used for H{sub 2}O and CO{sub 2}, while the Goody three parameter CG approximation is used for O{sub 3}. Atmospheric flux and cooling rate predictions using a research version of MODTRAN, MODR, are presented for H{sub 2}O (with and without the continuum), CO{sub 2}, and O{sub 3} for several model atmospheres. The effect of doubling the CO{sub 2} concentration is also considered. These calculations are compared to line-by-line (LBL) model calculations using the AER, GLA, GFDL, and GISS codes. The MODR predictions fall within the spread of the LBL results. The effects of decreasing the band model spectral resolution are illustrated using CO{sub 2} cooling rate and flux calculations. 36 refs., 18 figs., 1 tab.« less

Chromogranin A: Novel biomarker between periodontal disease and psychosocial stress

PubMed Central

Reshma, Arunima Padmakumar; Arunachalam, Rajeev; Pillai, Jayakumar Kochu; Kurra, Sarath Babu; Varkey, Vini K.; Prince, Mohanraj J.

2013-01-01

Context: The psychosocial stress has long been regarded as a significant pre-disposing factor for periodontal disease. The association between the periodontal disease and the neuroendocrine hormones has been observed. Chromogranin A (CgA) is supposed to link the activity of the neuroendocrine system to local and systemic immune functions and to be related to periodontitis. Aims: The aim of this study was to determine the CgA levels in saliva and plasma in periodontal health and disease and to assess their potential relationship to periodontitis. Settings and Designs: In this case-control study, the association between periodontal disease and stress marker has been assessed. Materials and Methods: Sixty subjects were chosen for this study: With case group comprising of 30 subjects with chronic periodontitis and control group comprising of 30 healthy subjects. Salivary and plasma CgA levels were determined by ELISA technique. Clinical parameters included were plaque index, papillary bleeding index and clinical attachment loss and probing depth. Correlation analysis was calculated by independent sample t-test. Results: Significantly higher CgA levels were found in saliva and plasma of patients with chronic periodontitis compared with healthy individuals (P < 0.05). No significant difference were observed between salivary and plasma CgA levels. Conclusions: The elevated level CgA in the plasma and saliva of subjects with stress induced chronic periodontitis has yielded insights into biological plausible association between the psychosocial stress and chronic periodontitis. Thus, our results suggest that CgA is a useful biomarker for evaluating at least in part the etiopathogenesis of periodontitis. PMID:23869129

Human Chorionic Gonadotropine in Cul-de-sac Fluid in Tubal Ectopic Pregnacy; A New Diagnostic Approach.

PubMed

Karahasanoglu, Ayse; Uzun, Isil; Ozdemir, Mucize; Yazicioglu, Fehmi

2016-04-01

Although new diagnostic abilities are being utilised increasingly yet early detection of tubal pregnancy remains a challenge. The use of highly sensitive hCG kits has facilitated the early diagnosis of a pregnancy. But it takes time to determine the localisation of the pregnancy. Early diagnosis of ectopic pregnancy may reduce the morbidity of ectopic pregnancy. This study was conducted to analyse the cul-de-sac and serum βhCG ratio in tubal ectopic pregnancy cases which may be a new diagnostic approach for ectopic pregnancy. Between January 2004 and July 2011, 263 patients with ectopic pregnancy were included in the study. Risk factors of patients and treatment modalities were evaluated. hCG was measured in peripheral serum and peritoneal fluid, obtained by puncture of Douglas pouch in 52 patients with tubal ectopic pregnancy. hCG level was determined in the cul-de-sac fluid and in the maternal serum for comparison. Tubectomy (5.3%), history of abortion (9.5%), history of previous surgery (14.8%), previous cesarean section (8%) and pelvic infamatorry disease (15.9 %) were the important risk factors for ectopic pregnancy in our cases. In 51 of 52 patients with tubal pregnancy, the cul-de-sac hCG vaule and the serum hCG value ratio was >1. It is concluded that the ratio of hCG in cul-de -sac and serum can be used for the verification of tubal ectopic pregnancy in addition to other diagnostic methods. This may help rapid confirmation of the diagnosis of ectopic pregnancy.

Cockcroft-Gault revisited: New de-liver-ance on recommendations for use in cirrhosis.

PubMed

Scappaticci, Gianni B; Regal, Randolph E

2017-01-28

The Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the "rounding up" approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance (CrCl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure CrCl. Furthermore, "rounding up" of SCr values often underestimated CrCl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

Characterisation and functional comparison of single-CRD and multidomain containing galectins CgGal-2 and CgGal-3 from oyster Crassostrea gigas.

PubMed

Huang, Mengmeng; Zhou, Tao; Wu, Yuehong; Fei, Hui; Wang, Gaoyang; Li, Zhi; Lei, Yutong; Liu, Qian; Sun, Cong; Lv, Zhengbing; Xu, Xue-Wei

2018-04-18

Galectins are β-galactoside binding lectins that play crucial roles in innate immunity in vertebrates and invertebrates through their conserved carbohydrate-recognition domains (CRDs). In the present study, single- and four-CRD-containing galectins were identified in oyster Crassostrea gigas (designated CgGal-2 and CgGal-3). The open reading frames (ORFs) of CgGal-2 and CgGal-3 encode polypeptides of 200 and 555 amino acids, respectively. All CRDs of CgGal-3 include two consensus motifs essential for ligand-binding, and a novel motif is present in CgGal-2. Pathogen-associated molecular pattern (PAMP) profiles were determined for recombinant rCgGal-2 and rCgGal-3, and rCgGal-2 displayed low binding affinity for PAMPs, while rCgGal-3 bound various PAMPs including glucan, lipopolysaccharide (LPS), and peptidoglycan (PGN) with relatively high affinity. Furthermore, rCgGal-2 and rCgGal-3 exhibited different microbe binding profiles; rCgGal-2 bound to Gram-negative bacteria (Escherichia coli and Vibrio vulnificus) and fungi (Saccharomyces cerevisiae and Pichia pastoris), while rCgGal-3 bound to these microbes but also to Gram-positive bacteria (Micrococcus luteus). In addition, rCgGal-3 possessed microbial agglutinating activity and coagulation activity against fungi and erythrocytes, respectively, but rCgGal-2 lacked any agglutinating activity. Carbohydrate binding specificity analysis showed that rCgGal-3 specifically bound D-galactose. Furthermore, rCgGal-2 and rCgGal-3 functioned as opsonin participating in the clearance against invaders in C. gigas. Thus, CgGal-2 with one CRD and CgGal-3 with four CRDs are new members of the galectin family involved in immune responses against bacterial infection. Differences in the organisation and amino acid sequences of CRDs may affect their specificity and affinity for nonself substances. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative analysis of core genome MLST and SNP typing within a European Salmonella serovar Enteritidis outbreak.

PubMed

Pearce, Madison E; Alikhan, Nabil-Fareed; Dallman, Timothy J; Zhou, Zhemin; Grant, Kathie; Maiden, Martin C J

2018-06-02

Multi-country outbreaks of foodborne bacterial disease present challenges in their detection, tracking, and notification. As food is increasingly distributed across borders, such outbreaks are becoming more common. This increases the need for high-resolution, accessible, and replicable isolate typing schemes. Here we evaluate a core genome multilocus typing (cgMLST) scheme for the high-resolution reproducible typing of Salmonella enterica (S. enterica) isolates, by its application to a large European outbreak of S. enterica serovar Enteritidis. This outbreak had been extensively characterised using single nucleotide polymorphism (SNP)-based approaches. The cgMLST analysis was congruent with the original SNP-based analysis, the epidemiological data, and whole genome MLST (wgMLST) analysis. Combination of the cgMLST and epidemiological data confirmed that the genetic diversity among the isolates predated the outbreak, and was likely present at the infection source. There was consequently no link between country of isolation and genetic diversity, but the cgMLST clusters were congruent with date of isolation. Furthermore, comparison with publicly available Enteritidis isolate data demonstrated that the cgMLST scheme presented is highly scalable, enabling outbreaks to be contextualised within the Salmonella genus. The cgMLST scheme is therefore shown to be a standardised and scalable typing method, which allows Salmonella outbreaks to be analysed and compared across laboratories and jurisdictions. Copyright © 2018. Published by Elsevier B.V.

Intrauterine administration of recombinant human chorionic gonadotropin before embryo transfer on outcome of in vitro fertilization/ intracytoplasmic sperm injection: A randomized clinical trial

PubMed Central

Zarei, Afsoon; Parsanezhad, Mohammad Ebrahim; Younesi, Masoumeh; Alborzi, Saeed; Zolghadri, Jaleh; Samsami, Alamtaj; Amooee, Sedigheh; Aramesh, Shahintaj

2014-01-01

Background: The direct effect of hCG on the human endometrium was studied several times. Objective: The objectives of this study were to evaluate the effectiveness of intrauterine injection of recombinant human chorionic gonadotropin (rhCG) before embryo transfer (ET). Materials and Methods: In this randomized placebo-controlled clinical trial, a total number of 182 infertile patients undergoing their first in vitro fertilization/ intracytoplasmic sperm injection (IVF-ICSI) cycles were randomly assigned to receive 250μg intrauterine rhCG (n=84) or placebo (n=98) before ET. The implantation and pregnancy rates were compared between groups. Results: Patients who received intrauterine rhCG before ET had significantly higher implantation (36.9% vs. 22.4%; p=0.035), clinical pregnancy rates (34.5% vs. 20.4%; p=0.044) and ongoing pregnancy rate (32.1% vs. 18.4%; p=0.032) when compared to those who received placebo. The abortion (2.4% vs. 2.0%; p=0.929) and ectopic pregnancy rates (1.2% vs. 1.0%; p=0.976) were comparable between groups of rhCG and placebo, respectively. Conclusion: Intrauterine injection of 250μg of rhCG before ET significantly improves the implantation and pregnancy rates in IVF/ICSI cycles. Registration ID in IRCT: IRCT2012121711790N1 This article extracted from fellowship course thesis. (Masoumeh Younesi) PMID:24799855

New methods of pregnancy testing in adolescent girls.

PubMed

Saxena, B B

1981-05-01

The knowledge and use of newer, more sensitive, and reliable pregnancy tests which are easily accessible and of moderate cost are the 1st steps in the early diagnosis and management of pregnancy, especially in adolescent girls. Accurate diagnosis of pregnancy soon after conception offers the option of abortion by simple, effective, and inexpensive procedures or early initiation of prenatal maternity care. Discussion focuses on the symptoms of pregnancy and the historical development and basis of pregnancy tests as well as the specific types of pregnancy tests. The most familiar sign of pregnancy is the missed period. Other symptoms that provide presumptive evidence of pregnancy include fatigue and lassitude, increased body temperature, and breast fullness or pain. Feelings of nausea, vomiting, and weight gain may appear after 2 weeks. The diagnosis of pregnancy by the detection of the human chorionic gonadotropin was initially described 53 years ago by Selmar Aschheim and Bernhardt Zondek. Improvements in the techniques for the measurement of human chorionic gonadotropin (hCG) have been directly related to the progress in the purification and isolation of hCG and elucidation of the amino acid sequence of the hormone-nonspecific alpha subunit and hormone-specific beta subunit of hCG. The history, physical examination, and pregnancy tests will generally provide sufficient information for a definite diagnosis of pregnancy. The presence of hCG in the urine or blood is the most accurate of all the indications of pregnancy. During the last century, 4 different techniques for the determination of hCG in blood and/or urine have been developed. These include the following and are reviewed in detail: 1) bioassays in intact laboratory animals; 2) immunologic tube or slide methods with heme- or latex-agglutination inhibition, as well as the more recently developed competitive protein binding method such as 3) radioimmunoassay (RIA) for the use of radioisotope labeled hormone and the specific antiserum against hCG; and 4) radioreceptorassay by the use of radioisotope-labeled hormone with biological activity and the specific receptors as the binding proteins.

Transferable Coarse-Grained Models for Ionic Liquids.

PubMed

Wang, Yanting; Feng, Shulu; Voth, Gregory A

2009-04-14

The effective force coarse-graining (EF-CG) method was applied to the imidazolium-based nitrate ionic liquids with various alkyl side-chain lengths. The nonbonded EF-CG forces for the ionic liquid with a short side chain were extended to generate the nonbonded forces for the ionic liquids with longer side chains. The EF-CG force fields for the ionic liquids exhibit very good transferability between different systems at various temperatures and are suitable for investigating the mesoscopic structural properties of this class of ionic liquids. The good additivity and ease of manipulation of the EF-CG force fields can allow for an inverse design methodology of ionic liquids at the coarse-grained level. With the EF-CG force field, the molecular dynamics (MD) simulation at a very large scale has been performed to check the significance of finite size effects on the structural properties. From these MD simulation results, it can be concluded that the finite size effect on the phenomenon of ionic liquid spatial heterogeneity (Wang, Y.; Voth, G. A. J. Am. Chem. Soc. 2005, 127, 12192) is small and that this phenomenon is indeed a nanostructural behavior which leads to the experimentally observed mesoscopic heterogeneous structure of ionic liquids.

Replica exchange Monte-Carlo simulations of helix bundle membrane proteins: rotational parameters of helices

NASA Astrophysics Data System (ADS)

Wu, H.-H.; Chen, C.-C.; Chen, C.-M.

2012-03-01

We propose a united-residue model of membrane proteins to investigate the structures of helix bundle membrane proteins (HBMPs) using coarse-grained (CG) replica exchange Monte-Carlo (REMC) simulations. To demonstrate the method, it is used to identify the ground state of HBMPs in a CG model, including bacteriorhodopsin (BR), halorhodopsin (HR), and their subdomains. The rotational parameters of transmembrane helices (TMHs) are extracted directly from the simulations, which can be compared with their experimental measurements from site-directed dichroism. In particular, the effects of amphiphilic interaction among the surfaces of TMHs on the rotational angles of helices are discussed. The proposed CG model gives a reasonably good structure prediction of HBMPs, as well as a clear physical picture for the packing, tilting, orientation, and rotation of TMHs. The root mean square deviation (RMSD) in coordinates of Cα atoms of the ground state CG structure from the X-ray structure is 5.03 Å for BR and 6.70 Å for HR. The final structure of HBMPs is obtained from the all-atom molecular dynamics simulations by refining the predicted CG structure, whose RMSD is 4.38 Å for BR and 5.70 Å for HR.

Novel adducts from the reaction of 1-chloro-3-buten-2-one with 2'-deoxyguanosine. Structural characterization and potential as tools to investigate 1,3-butadiene carcinogenicity.

PubMed

Zheng, Jin; Li, Yan; Yu, Ying-Xin; An, Jing; Zhang, Xin-Yu; Elfarra, Adnan A

2015-01-25

1-Chloro-3-buten-2-one (CBO) is a potential reactive metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. To develop tools that may help investigate the role of CBO in BD carcinogenicity and to develop biomarkers that can be used to assess BD exposure, the reaction of CBO with 2'-deoxyguanosine (dG) under in vitro physiological conditions (pH 7.4, 37°C) was investigated and the products (designated as CG-1, CG-2, CG-3, CG-4, CG-5, and CG-6 based on their retention times on HPLC) were characterized by MS and NMR spectroscopy. The structures of CG-1, CG-2, CG-3, and CG-4 were 1,N2-(3-hydroxy-3-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine, N7-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, N7,8-(3-hydroxy-3-chloromethylpropan-1,3-diyl)guanine and N2-(4-chloro-3-oxobutyl)-2'-deoxyguanosine, respectively. CG-5 and CG-6, a pair of diastereomers, were characterized as 1,N2-(3-hydroxy-3-chloromethylpropan-1,3-diyl)-2'-deoxyguanosine. CG-1 was stable under in vitro physiological conditions, whereas CG-2, CG-3, CG-4, and CG-5/6 were unstable and exhibited the half-lives at <1.0, 4.8±0.1, 6.7±0.3, and 2.7±0.1 h, respectively. CG-2 decomposed primarily via a retro-Michael reaction to produce dG and CBO, with only a small fraction of CG-2 degrading to CG-3. Decomposition of CG-4 proceeded via a cyclization reaction and/or replacement of the chlorine atom by a hydroxyl group to form 1,N2-(1-hydroxy-1-hydroxymethylpropan-1,3-diyl)-2'-deoxyguanosine (CG-4D1) and N(2)-(4-hydroxy-3-oxobutyl)-2'-deoxyguanosine (CG-4D2), whereas decomposition of CG-5/6 yielded CG-1. Collectively, the newly characterized CBO adducts could be used to investigate the role of CBO in the mechanism of BD carcinogenicity and could also be used to develop biomarkers for BD exposure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

hCG Test (Pregnancy Test)

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... Us Also Known As Pregnancy Test Qualitative hCG Quantitative hCG Beta hCG Total hCG Total beta hCG ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maiolo, M., E-mail: massimo.maiolo@zhaw.ch; ZHAW, Institut für Angewandte Simulation, Grüental, CH-8820 Wädenswil; Vancheri, A., E-mail: alberto.vancheri@supsi.ch

In this paper, we apply Multiresolution Analysis (MRA) to develop sparse but accurate representations for the Multiscale Coarse-Graining (MSCG) approximation to the many-body potential of mean force. We rigorously framed the MSCG method into MRA so that all the instruments of this theory become available together with a multitude of new basis functions, namely the wavelets. The coarse-grained (CG) force field is hierarchically decomposed at different resolution levels enabling to choose the most appropriate wavelet family for each physical interaction without requiring an a priori knowledge of the details localization. The representation of the CG potential in this new efficientmore » orthonormal basis leads to a compression of the signal information in few large expansion coefficients. The multiresolution property of the wavelet transform allows to isolate and remove the noise from the CG force-field reconstruction by thresholding the basis function coefficients from each frequency band independently. We discuss the implementation of our wavelet-based MSCG approach and demonstrate its accuracy using two different condensed-phase systems, i.e. liquid water and methanol. Simulations of liquid argon have also been performed using a one-to-one mapping between atomistic and CG sites. The latter model allows to verify the accuracy of the method and to test different choices of wavelet families. Furthermore, the results of the computer simulations show that the efficiency and sparsity of the representation of the CG force field can be traced back to the mathematical properties of the chosen family of wavelets. This result is in agreement with what is known from the theory of multiresolution analysis of signals.« less

Hospitals’ readiness to implement clinical governance

PubMed Central

Ebadi Fardazar, Farbod; Safari, Hossein; Habibi, Farhad; Akbari Haghighi, Feyzollah; Rezapour, Aziz

2015-01-01

Background: Quality of health services is one of the most important factors for delivery of these services. Regarding the importance and vital role of quality in the health sector, a concept known as "Clinical Governance" (CG) has been introduced into the health area which aims to enhance quality of health services. Thus, this study aimed to assess private and public hospitals’ readiness to implement CG in Iran. Methods: This descriptive and cross-sectional study was carried out in 2012. Four hundred thirty participants including doctors, nurses, diagnostic departments personnel, and support staff were chosen randomly from four hospitals (equally divided into private and public hospitals). Clinical Governance Climate Questionnaire (CGCQ) was used for data collection. Finally, data were entered into the SPSS 18 and were analyzed using statistical methods. Results: Among the CG dimensions, "organizational learning" and "planned and integrated quality improvement program" scored the highest and the lowest respectively for both types of hospitals. Hospitals demonstrated the worst condition with regard to the latter dimension. Furthermore, both types of hospitals had positive picture regarding "training and development opportunities". Private hospitals scored better than public ones in all dimensions but there was only a significant difference in "proactive risk management" dimension between both types of hospitals (P< 0.05). Conclusion: Hospitals’ readiness for CG implementation was "average or weak". In order to implement CG successfully, it is essential to have a quality-centered culture, a culture specified by less paperwork, more self-sufficiency, and flexibility in hospitals’ affairs as well as centring on shared vision and goals with an emphasis on continuous improvement and innovation. PMID:25674566

Exemplary Care as a Mediator of the Effects of Caregiver Subjective Appraisal and Emotional Outcomes

PubMed Central

Harris, Grant M.; Durkin, Daniel W.; Allen, Rebecca S.; DeCoster, Jamie; Burgio, Louis D.

2011-01-01

Purpose: Exemplary care (EC) is a new construct encompassing care behaviors that warrants further study within stress process models of dementia caregiving. Previous research has examined EC within the context of cognitively intact older adult care recipients (CRs) and their caregivers (CGs). This study sought to expand our knowledge of quality of care by investigating EC within a diverse sample of dementia CGs. Design and Methods: We examined the relation between CG subjective appraisal (daily care bother, burden, and behavioral bother), EC, and CG emotional outcomes (depression and positive aspects of caregiving [PAC]). Specifically, EC was examined as a possible mediator of the effects of CG subjective appraisals on emotional outcomes. Using a bootstrapping method and an SPSS macro developed by Preacher and Hayes (2008 Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models), we tested the indirect effect of EC on the relation between CG subjective appraisals and CG emotional outcomes. Results: Overall, EC partially mediates the relation between the subjective appraisal variables (daily care bother, burden, and behavioral bother) and PAC. Results for depression were similar except that EC did not mediate the relation between burden and depression. This pattern of results varied by race/ethnicity. Implications: Overall, CGs’ perception of providing EC to individuals with dementia partially explains the relation between subjective appraisal and symptoms of depression and PAC. Results of this study suggest that interventions may benefit from training CGs to engage in EC to improve their emotional outcomes and quality of care. PMID:21350038

Quantification of Trunk Postural Stability Using Convex Polyhedron of the Time-Series Accelerometer Data

PubMed Central

Melecky, Roman; Socha, Vladimir; Kutilek, Patrik; Hanakova, Lenka; Takac, Peter; Schlenker, Jakub; Svoboda, Zdenek

2016-01-01

Techniques to quantify postural stability usually rely on the evaluation of only two variables, that is, two coordinates of COP. However, by using three variables, that is, three components of acceleration vector, it is possible to describe human movement more precisely. For this purpose, a single three-axis accelerometer was used, making it possible to evaluate 3D movement by use of a novel method, convex polyhedron (CP), together with a traditional method, based on area of the confidence ellipse (ACE). Ten patients (Pts) with cerebellar ataxia and eleven healthy individuals of control group (CG) participated in the study. The results show a significant increase of volume of the CP (CPV) in Pts or CG standing on foam surface with eyes open (EO) and eyes closed (EC) after the EC phase. Significant difference between Pts and CG was found in all cases as well. Correlation coefficient indicates strong correlation between the CPV and ACE in most cases of patient examinations, thus confirming the possibility of quantification of postural instability by the introduced method of CPV. PMID:27195465

Quantification of Trunk Postural Stability Using Convex Polyhedron of the Time-Series Accelerometer Data.

PubMed

Melecky, Roman; Socha, Vladimir; Kutilek, Patrik; Hanakova, Lenka; Takac, Peter; Schlenker, Jakub; Svoboda, Zdenek

2016-01-01

Techniques to quantify postural stability usually rely on the evaluation of only two variables, that is, two coordinates of COP. However, by using three variables, that is, three components of acceleration vector, it is possible to describe human movement more precisely. For this purpose, a single three-axis accelerometer was used, making it possible to evaluate 3D movement by use of a novel method, convex polyhedron (CP), together with a traditional method, based on area of the confidence ellipse (ACE). Ten patients (Pts) with cerebellar ataxia and eleven healthy individuals of control group (CG) participated in the study. The results show a significant increase of volume of the CP (CPV) in Pts or CG standing on foam surface with eyes open (EO) and eyes closed (EC) after the EC phase. Significant difference between Pts and CG was found in all cases as well. Correlation coefficient indicates strong correlation between the CPV and ACE in most cases of patient examinations, thus confirming the possibility of quantification of postural instability by the introduced method of CPV.

HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

PubMed Central

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

2014-01-01

Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

Clinical correlates of complicated grief among individuals with acute coronary syndromes

PubMed Central

Pini, Stefano; Gesi, Camilla; Abelli, Marianna; Cardini, Alessandra; Lari, Lisa; Felice, Francesca; Di Stefano, Rossella; Mazzotta, Gianfranco; Bovenzi, Francesco; Bertoli, Daniele; Borelli, Lucia; Michi, Paola; Oligeri, Claudia; Balbarini, Alberto; Manicavasagar, Vijaya

2015-01-01

Objective The study aimed at exploring bereavement and complicated grief (CG) symptoms among subjects without a history of coronary heart disease (CHD) at the time of a first acute coronary syndrome (ACS) and to evaluate the relationship of CG symptoms and ACS. Method Overall, 149 subjects with ACS (namely, acute myocardial infarct with or without ST-segment elevation or unstable angina), with no previous history of CHD, admitted to three cardiac intensive care units were included and evaluated by the Structured Clinical Interview for Complicated Grief (SCI-CG), Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and the 36-item Short-Form Health Survey (MOS-SF-36). Results Of the total sample of 149 subjects with ACS, 118 (79.2%) met criteria for DSM-5 persistent complex bereavement disorder. Among these, subjects who lost a partner, child, or sibling were older (P=0.008), less likely to be working (P=0.032), and more likely to be suffering from hypertension (P=0.021), returned higher scores on the SCI-CG (P=0.001) and developed the index ACS more frequently between 12 and 48 months after the death than those who lost a parent or another relative (P≤0.0001). The occurrence of ACS 12–48 months (P=0.019) after the loss was positively correlated with SCI-CG scores. An inverse relationship with SCI-CG scores was observed for patients who experienced ACS more than 48 months after the loss (P=0.005). The SCI-CG scores significantly predicted lower scores on the “general health” domain of MOS-SF-36 (P=0.030), as well as lower scores on “emotional well-being” domain (P=0.010). Conclusion A great proportion of subjects with ACS report the loss of a loved one. Among these, the loss of a close relative and the severity of CG symptoms are associated with poorer health status. Our data corroborate previous data indicating a strong relationship between CG symptoms and severe cardiac problems. PMID:26504390

Role of Community Group Exposure in Reducing Sexually Transmitted Infection-Related Risk among Female Sex Workers in India

PubMed Central

Yadav, Diwakar; Ramanathan, Shreena; Goswami, Prabuddhagopal; Ramakrishnan, Lakshmi; Saggurti, Niranjan; Sen, Shrabanti; George, Bitra; Paranjape, Ramesh

2013-01-01

Background Empowering female sex workers (FSWs) to address structural barriers and forming community groups (CGs) through community mobilization are seen as essential components of HIV prevention programs in India. Taking the membership of a CG as an exposure intervention, we hypothesized whether participation in a CG lead to reduced sexually transmitted infections (STIs) and increased treatment-seeking behavior among FSWs in three selected states of India — Andhra Pradesh, Maharashtra and Tamil Nadu. Methods and Findings The propensity score matching (PSM) approach examined the effect of CG membership, as against no membership, on STI-related risk, described as selected outcome measures — presence of any STI, self-reported STI symptoms, and treatment-seeking behavior among FSWs. A cross sectional bio-behavioral survey was administered in 2009–2010 and covered 7,806 FSWs through two-stage probability-based conventional and time location cluster sampling in 23 administrative districts of Andhra Pradesh, Maharashtra and Tamil Nadu. Only 2,939 FSWs were reported to be members of a CG and among them 4.5% had any STIs. A majority of FSWs were aged above 24 years (86.4%), had ever been married (73%), operated from a public place for solicitation (81.5%), and had ever received HIV test results (75.6%). The average effect of CG exposure was reduction in STI prevalence by 4%, while self-reported STI symptom treatment-seeking behavior increased by 13.7%. Conclusion FSWs who were exposed to a CG were at a substantially lower risk of STIs than those who were unexposed. The FSWs exposed to a CG had a higher chance of seeking STI treatment from public and private health facilities. Collectivization related challenges must be overcome to provide access to tailored STI prevention and care services. PMID:24205210

The postantifungal effect and phospholipase production of oral Candida albicans from smokers, diabetics, asthmatics, denture wearers and healthy individuals following brief exposure to subtherapeutic concentrations of chlorhexidine gluconate.

PubMed

Ellepola, Arjuna N B; Joseph, Bobby K; Khan, Z U

2014-09-01

Candida albicans is the major aetiological agent of oral candidosis and one of its important virulent factors is the production of extracellular phospholipases, which can be modulated by subtherapeutic concentrations of antifungal agents thus decreasing their pathogenicity. Hence, considering that chlorhexidine gluconate (CG) is a common antimicrobial mouthwash used in dentistry and that its concentration in the mouth reaches subtherapeutic levels during dosage intervals due to the diluent effect of saliva and cleansing effect of the oral musculature, the postantifungal effect (PAFE) and the phospholipase production of oral C. albicans following brief exposure to subtherapeutic concentrations of CG was studied. Fifty C. albicans planktonic oral isolates obtained from smokers, diabetics, asthmatics using steroid inhalers, partial denture wearers and healthy individuals were exposed to three subtherapeutic concentrations of CG (0.005%, 0.0025% and 0.00125%) for 1 h. Isolates unexposed to CG was the control group. Thereafter the antiseptic was removed and the PAFE and phospholipase production was determined by a turbidometric method and a plate assay using an egg yolk agar medium respectively. Mean PAFE (hours) of 50 oral isolates of C. albicans following 1-h exposure to 0.005%, 0.0025% and 0.00125% CG was 6.97, 1.85 and 0.62 respectively. The phospholipase production of these isolates was significantly suppressed with a percentage reduction of 21.68, 18.20 and 14.04% following exposure to 0.005%, 0.0025% and 0.00125% CG respectively. Brief exposure of C. albicans isolates to subtherapeutic concentrations of CG would wield an antifungal effect by suppressing growth and phospholipase production, thereby quelling its pathogenicity. © 2014 Blackwell Verlag GmbH.

miRNA-Processing Gene Methylation and Cancer Risk.

PubMed

Joyce, Brian T; Zheng, Yinan; Zhang, Zhou; Liu, Lei; Kocherginsky, Masha; Murphy, Robert; Achenbach, Chad J; Musa, Jonah; Wehbe, Firas; Just, Allan; Shen, Jincheng; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A; Hou, Lifang

2018-05-01

Background: Dysregulation of miRNA and methylation levels are epigenetic hallmarks of cancer, potentially linked via miRNA-processing genes. Studies have found genetic alterations to miRNA-processing genes in cancer cells and human population studies. Our objective was to prospectively examine changes in DNA methylation of miRNA-processing genes and their associations with cancer risk. Methods: We examined cohort data from the Department of Veterans' Affairs Normative Aging Study. Participants were assessed every 3 to 5 years starting in 1999 through 2013 including questionnaires, medical record review, and blood collection. Blood from 686 consenting participants was analyzed using the Illumina 450K BeadChip array to measure methylation at CpG sites throughout the genome. We selected 19 genes based on a literature review, with 519 corresponding CpG sites. We then used Cox proportional hazards models to examine associations with cancer incidence, and generalized estimating equations to examine associations with cancer prevalence. Associations at false discovery rate < 0.05 were considered statistically significant. Results: Methylation of three CpGs ( DROSHA : cg23230564, TNRC6B : cg06751583, and TNRC6B : cg21034183) was prospectively associated with time to cancer development (positively for cg06751583, inversely for cg23230564 and cg21034183), whereas methylation of one CpG site ( DROSHA : cg16131300) was positively associated with cancer prevalence. Conclusions: DNA methylation of DROSHA , a key miRNA-processing gene, and TNRC6B may play a role in early carcinogenesis. Impact: Changes in miRNA processing may exert multiple effects on cancer development, including protecting against it via altered global miRNAs, and may be a useful early detection biomarker of cancer. Cancer Epidemiol Biomarkers Prev; 27(5); 550-7. ©2018 AACR . ©2018 American Association for Cancer Research.

The complex nature of discordant severe calcified aortic valve disease grading: new insights from combined Doppler echocardiographic and computed tomographic study.

PubMed

Clavel, Marie-Annick; Messika-Zeitoun, David; Pibarot, Philippe; Aggarwal, Shivani R; Malouf, Joseph; Araoz, Phillip A; Michelena, Hector I; Cueff, Caroline; Larose, Eric; Capoulade, Romain; Vahanian, Alec; Enriquez-Sarano, Maurice

2013-12-17

With concomitant Doppler echocardiography and multidetector computed tomography (MDCT) measuring aortic valve calcification (AVC) load, this study aimed at defining: 1) independent physiologic/structural determinants of aortic valve area (AVA)/mean gradient (MG) relationship; 2) AVC thresholds best associated with severe aortic stenosis (AS); and 3) whether, in AS with discordant MG, severe calcified aortic valve disease is generally detected. Aortic stenosis with discordant markers of severity, AVA in severe range but low MG, is a conundrum, unresolved by outcome studies. Patients (n = 646) with normal left ventricular ejection fraction AS underwent Doppler echocardiography and AVC measurement by MDCT. On the basis of AVA-indexed-to-body surface area (AVAi) and MG, patients were categorized as concordant severity grading (CG) with moderate AS (AVAi >0.6 cm²/m², MG <40 mm Hg), severe AS (AVAi ≤0.6 cm²/m², MG ≥ 40 mm Hg), discordant-severity-grading (DG) with low-MG (AVAi ≤0.6 cm(2)/m(2), MG <40 mm Hg), or high-MG (AVAi >0.6 cm(2)/m(2), MG ≥40 mm Hg). The MG (discordant in 29%) was strongly determined by AVA and flow but also independently and strongly influenced by AVC-load (p < 0.0001) and systemic arterial compliance (p < 0.0001). The AVC-load (median [interquartile range]) was similar within patients with DG (low-MG: 1,619 [965 to 2,528] arbitrary units [AU]; high-MG: 1,736 [1,209 to 2,894] AU; p = 0.49), higher than CG-moderate-AS (861 [427 to 1,519] AU; p < 0.0001) but lower than CG-severe-AS (2,931 [1,924 to 4,292] AU; p < 0.0001). The AVC-load thresholds separating severe/moderate AS were defined in CG-AS with normal flow (stroke-volume-index >35 ml/m(2)). The AVC-load, absolute or indexed, identified severe AS accurately (area under the curve ≥0.89, sensitivity ≥86%, specificity ≥79%) in men and women. Upon application of these criteria to DG-low MG, at least one-half of the patients were identified as severe calcified aortic valve disease, irrespective of flow. Among patients with AS, MG is often discordant from AVA and is determined by multiple factors, valvular (AVC) and non-valvular (arterial compliance) independently of flow. The AVC-load by MDCT, strongly associated with AS severity, allows diagnosis of severe calcified aortic valve disease. At least one-half of the patients with discordant low gradient present with heavy AVC-load reflective of severe calcified aortic valve disease, emphasizing the clinical yield of AVC quantification by MDCT to diagnose and manage these complex patients. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The effect of administering equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG) post artificial insemination on fertility of lactating dairy cows.

PubMed

Bartolome, J A; Wallace, S Perez; de la Sota, R L; Thatcher, W W

2012-09-15

The objective was to evaluate the effect of equine chorionic gonadotropin (eCG) and hCG post artificial insemination (AI) on fertility of lactating dairy cows. In Experiment 1, cows were either treated with eCG on Day 22 post AI (400 IU; n = 80) or left untreated (n = 84). On Day 29, pregnant cows were either treated with hCG (2500 IU; n = 32) or left untreated (n = 36). Pregnancy and progesterone were evaluated on Days 29 and 45. In Experiment 2, cows (n = 28) were either treated with eCG on Day 22 (n = 13) or left untreated (n = 15) and either treated with hCG on Day 29 (n = 14) or left untreated (n = 14). Blood sampling and ultrasonography were conducted between Days 22 and 45. In Experiment 3, cows were either treated with eCG on Day 22 post AI (n = 229) or left untreated (n = 241). Pregnancy was evaluated on Days 36 and 85. In Experiment 1, eCG on Day 22 increased (P < 0.02) the number of pregnant cows on Day 29 (50.0 vs. 33.3%) and on Day 45, the increase was higher (P < 0.01) in cows with timed AI (41.2 vs. 6.5%) than in cows AI at detected estrus (50.0 vs. 37.8%). Pregnancy losses were reduced by eCG and hCG, but increased in cows that did not receive eCG but were given hCG (P < 0.01). Treatment with hCG tended (P < 0.06) to increase progesterone in control cows, but not in cows treated with eCG. In Experiment 2, hCG increased (P < 0.01) the number of accessory CLs on Day 35 (28.5 vs. 0.0%) and tended (P < 0.07) to increase progesterone. In Experiment 3, eCG increased the number of pregnant cows (P < 0.05) on Days 36 and 85, but only in cows with low body condition (eCG = 45.6 and 43.5%; Control = 22.9 and 22.9%). In conclusion, eCG at 22 days post insemination increased fertility, primarily in cows with low body condition and reduced pregnancy losses when given 7 days before hCG; hCG induced accessory CLs and slightly increased progesterone, but hCG given in the absence of a prior eCG treatment reduced fertility. Copyright © 2012 Elsevier Inc. All rights reserved.

Dose Response and Prediction Characteristics of a Methylation Sensitive Digital PCR Assay for Cigarette Consumption in Adults.

PubMed

Philibert, Robert; Dogan, Meesha; Noel, Amanda; Miller, Shelly; Krukow, Brianna; Papworth, Emma; Cowley, Joseph; Long, Jeffrey D; Beach, Steven R H; Black, Donald W

2018-01-01

The tobacco use disorders are the largest preventable cause of morbidity and mortality in the world. A substantial barrier to the development of better intervention and screening measures is the lack of clinically employable biomarkers to detect the existence and extent of tobacco consumption. In prior work, we and others have shown that array based assessment of DNA methylation status at cg05575921 is a sensitive and quantitative method for assessing cigarette consumption. Unfortunately, in general, arrays are not practical clinical tools. Herein, we detail the prediction performance metrics and dose dependency of a clinically implementable droplet digital PCR (ddPCR) assay for cigarette consumption in adults. First, we demonstrate that measurements of cg05575921 as determined by Illumina array and ddPCR are highly correlated ( R 2 = 0.98, n = 92). Second, using clinical data and biomaterial from 177 subjects ranging from 18 to 78 years of age, we show that the Receiver Operating Characteristic (ROC) area under the curve (AUC) for classifying smoking status using methylation status at cg05575921 is 0.99. Finally, we conduct modeling analyses of cigarette consumption over discrete time periods to show that methylation status is best correlated with mean cigarette consumption over the past year ( R 2 = 0.5) and that demethylation at cg05575921 is dose dependent with a demethylation (delta beta) of 1% being equivalent to 1.2 cigarettes per day. But we do not find a relationship between Fagerstrom score and DNA methylation. We conclude that ddPCR assessment of cg05575921 methylation is an accurate method for assessing the presence and extent of cigarette consumption in adult subjects. We suggest that skillful clinical implementation of this approach alone or in combination with other assessment methods could lead to substantial reduction of cigarette consumption related morbidity and mortality.

Dose Response and Prediction Characteristics of a Methylation Sensitive Digital PCR Assay for Cigarette Consumption in Adults

PubMed Central

Philibert, Robert; Dogan, Meesha; Noel, Amanda; Miller, Shelly; Krukow, Brianna; Papworth, Emma; Cowley, Joseph; Long, Jeffrey D.; Beach, Steven R. H.; Black, Donald W.

2018-01-01

The tobacco use disorders are the largest preventable cause of morbidity and mortality in the world. A substantial barrier to the development of better intervention and screening measures is the lack of clinically employable biomarkers to detect the existence and extent of tobacco consumption. In prior work, we and others have shown that array based assessment of DNA methylation status at cg05575921 is a sensitive and quantitative method for assessing cigarette consumption. Unfortunately, in general, arrays are not practical clinical tools. Herein, we detail the prediction performance metrics and dose dependency of a clinically implementable droplet digital PCR (ddPCR) assay for cigarette consumption in adults. First, we demonstrate that measurements of cg05575921 as determined by Illumina array and ddPCR are highly correlated (R2 = 0.98, n = 92). Second, using clinical data and biomaterial from 177 subjects ranging from 18 to 78 years of age, we show that the Receiver Operating Characteristic (ROC) area under the curve (AUC) for classifying smoking status using methylation status at cg05575921 is 0.99. Finally, we conduct modeling analyses of cigarette consumption over discrete time periods to show that methylation status is best correlated with mean cigarette consumption over the past year (R2 = 0.5) and that demethylation at cg05575921 is dose dependent with a demethylation (delta beta) of 1% being equivalent to 1.2 cigarettes per day. But we do not find a relationship between Fagerstrom score and DNA methylation. We conclude that ddPCR assessment of cg05575921 methylation is an accurate method for assessing the presence and extent of cigarette consumption in adult subjects. We suggest that skillful clinical implementation of this approach alone or in combination with other assessment methods could lead to substantial reduction of cigarette consumption related morbidity and mortality. PMID:29740475

Three-Dimensional Viscous Alternating Direction Implicit Algorithm and Strategies for Shape Optimization

NASA Technical Reports Server (NTRS)

Pandya, Mohagna J.; Baysal, Oktay

1997-01-01

A gradient-based shape optimization based on quasi-analytical sensitivities has been extended for practical three-dimensional aerodynamic applications. The flow analysis has been rendered by a fully implicit, finite-volume formulation of the Euler and Thin-Layer Navier-Stokes (TLNS) equations. Initially, the viscous laminar flow analysis for a wing has been compared with an independent computational fluid dynamics (CFD) code which has been extensively validated. The new procedure has been demonstrated in the design of a cranked arrow wing at Mach 2.4 with coarse- and fine-grid based computations performed with Euler and TLNS equations. The influence of the initial constraints on the geometry and aerodynamics of the optimized shape has been explored. Various final shapes generated for an identical initial problem formulation but with different optimization path options (coarse or fine grid, Euler or TLNS), have been aerodynamically evaluated via a common fine-grid TLNS-based analysis. The initial constraint conditions show significant bearing on the optimization results. Also, the results demonstrate that to produce an aerodynamically efficient design, it is imperative to include the viscous physics in the optimization procedure with the proper resolution. Based upon the present results, to better utilize the scarce computational resources, it is recommended that, a number of viscous coarse grid cases using either a preconditioned bi-conjugate gradient (PbCG) or an alternating-direction-implicit (ADI) method, should initially be employed to improve the optimization problem definition, the design space and initial shape. Optimized shapes should subsequently be analyzed using a high fidelity (viscous with fine-grid resolution) flow analysis to evaluate their true performance potential. Finally, a viscous fine-grid-based shape optimization should be conducted, using an ADI method, to accurately obtain the final optimized shape.

Mixing coarse-grained and fine-grained water in molecular dynamics simulations of a single system.

PubMed

Riniker, Sereina; van Gunsteren, Wilfred F

2012-07-28

The use of a supra-molecular coarse-grained (CG) model for liquid water as solvent in molecular dynamics simulations of biomolecules represented at the fine-grained (FG) atomic level of modelling may reduce the computational effort by one or two orders of magnitude. However, even if the pure FG model and the pure CG model represent the properties of the particular substance of interest rather well, their application in a hybrid FG/CG system containing varying ratios of FG versus CG particles is highly non-trivial, because it requires an appropriate balance between FG-FG, FG-CG, and CG-CG energies, and FG and CG entropies. Here, the properties of liquid water are used to calibrate the FG-CG interactions for the simple-point-charge water model at the FG level and a recently proposed supra-molecular water model at the CG level that represents five water molecules by one CG bead containing two interaction sites. Only two parameters are needed to reproduce different thermodynamic and dielectric properties of liquid water at physiological temperature and pressure for various mole fractions of CG water in FG water. The parametrisation strategy for the FG-CG interactions is simple and can be easily transferred to interactions between atomistic biomolecules and CG water.

Luteal phase support for in vitro fertilization-embryo transfer--present and future methods to improve successful implantation.

PubMed

Check, J H

2012-01-01

To present reasons for luteal phase deficiency when taking controlled ovarian hyperstimulation (COH) for purposes of inducing multiple oocytes for in vitro fertilization (IVF), and to suggest strategies to overcome the defect. Treatment options presented include luteal phase support with human chorionic gonadotropin (hCG) injection, progesterone, estradiol, gonadotropin releasing hormone agonists, cytokines, e.g., granulocyte colony stimulating factor, and lymphocyte immunotherapy. hCG and progesterone produce the best results and are comparable or at best a slight edge to hCG but the latter is associated with too high a risk for ovarian hyperstimulation syndrome. Vaginal progesterone is the most efficacious with the least side-effects. Better methods are needed to adequately assess full correction of the luteal phase defect. In some cases the luteal phase defect associated with COH is not correctable and FSH stimulation should be reduced or all embryos frozen and defer transfer to an artificial estrogen progesterone or natural cycle.

Center of gravity estimation using a reaction board instrumented with fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Oliveira, Rui; Roriz, Paulo; Marques, Manuel B.; Frazão, Orlando

2018-03-01

The purpose of the present work is to construct a reaction board based on fiber Bragg gratings (FBGs) that could be used for estimation of the 2D coordinates of the projection of center of gravity (CG) of an object. The apparatus is consisted of a rigid equilateral triangular board mounted on three supports at the vertices, two of which have cantilevers instrumented with FBGs. When an object of known weight is placed on the board, the bending strain of the cantilevers is measured by a proportional wavelength shift of the FBGs. Applying the equilibrium conditions of a rigid body and proper calibration procedures, the wavelength shift is used to estimate the vertical reaction forces and moments of force at the supports and the coordinates of the object's CG projection on the board. This method can be used on a regular basis to estimate the CG of the human body or objects with complex geometry and density distribution. An example is provided for the estimation of the CG projection coordinates of two orthopaedic femur bone models, one intact, and the other with a hip stem implant encased. The clinical implications of changing the normal CG location by means of a prosthesis have been discussed.

Collapsing glomerulopathy, the Saudi Arabian scenario

PubMed Central

Husain, Sufia

2017-01-01

Objectives: To compare the clinico-pathological features of collapsing glomerulopathy (CG) at a tertiary hospital in Saudi Arabia with the world literature. Methods: In a retrospective study, all biopsy-diagnosed cases of CG between 2004-2015 were identified and analyzed, at King Khalid University Hospital, King Saud University, Riyadh. The clinico-pathological findings along with prognosis were reviewed and compared with the reported literature. Results: Thirty-one CG patients were identified, most were adult males. All the CG cases were idiopathic, all Arabs, none HIV positive, none of African descent, and none with a history of drug abuse. The number of glomeruli with collapsing lesions per biopsy ranged from 1 to 9. Other types of FSGS lesions (not otherwise specified and perihilar) were also noted. There was extensive podocyte effacement. Upon treatment, remission (complete/partial) was noted in almost half the patients; around one fourth did not respond to treatment; and one fourth progressed to end stage kidney disease (ESKD). The median time taken to develop ESKD from the time of biopsy diagnosis was 23 months. Conclusion: The clinico-pathological and prognostic correlates of CG in Saudi Arabia are comparable with that of the world literature. The management protocol at our center is the same as that practiced in different parts of the world, and the prognosis is overall poor. PMID:28439601

Factors Associated with Complicated Grief in Students Who Survived the Sewol Ferry Disaster in South Korea

PubMed Central

Lee, So Hee; Nam, Hee Sun; Kim, Hak Beom; Kim, Eun Ji; Noh, Jin-Won; Chae, Jeong-Ho

2018-01-01

Objective The Sewol ferry disaster caused shock and grief in South Korea. The aim of this study was to identify the factors associated with symptoms of complicated grief (CG) among the surviving students 20 months after that disaster. Methods This study was conducted using a cross-sectional design and a sample of 57 students who survived the Sewol ferry disaster. Data were collected using the following instruments: Inventory of Complicated Grief (ICG), the Lifetime Incidence of Traumatic Events-Child, the Child Report of Post-Traumatic Symptoms (CROPS), KIDSCREEN-27, Family Adaptability and Cohesion Evaluation Scales-III, the Peri-traumatic Dissociation–Post-traumatic Negative Beliefs–Post-traumatic Social Support scale, and the Strengths and Difficulties Questionnaire. A generalized linear model using a log link and Poisson distribution was performed to identify factors associated with symptoms of CG. Results The mean score on the ICG was 15.57 (standard deviation: 12.72). Being born in 1999, a higher score on the CROPS and a lower score in autonomy and relationship with parents on the KIDSCREEN-27 were related to higher levels of CG. Conclusion Twenty months after the Sewol ferry disaster, 24.5% of surviving students were suffering from CG. This study uncovered a vulnerable population of bereaved children at high risk for CG. PMID:29475240

Resistin -420C>G promoter variant and colorectal cancer risk.

PubMed

Mahmoudi, Touraj; Karimi, Khatoon; Arkani, Maral; Farahani, Hamid; Vahedi, Mohsen; Dabiri, Reza; Nobakht, Hossein; Asadi, Asadollah; Mirakhorli, Mojgan; Arshi, Benafsheh; Derakhshan, Arash; Zali, Mohammad Reza

2014-09-30

Obesity is associated with an increased risk of colorectal cancer (CRC), and ghrelin (GHRL) and resistin (RETN) are thought to be related to obesity. Our aim was to investigate whether GHRL and RETN gene variants are associated with CRC risk. All 414 subjects, including 197 cases with CRC and 217 controls, were genotyped for the GHRL (rs26802) and RETN (rs1862513) or -420 C>G gene variants using the PCR-RFLP method. Our findings indicated that the RETN -420 C>G "CC" genotype, compared with the "GG" and "GC" genotypes, was a marker of decreased CRC susceptibility; the difference remained significant after adjustment for age, BMI, gender, smoking status, NSAID use, and family history of CRC (p=0.020; OR=0.52, 95% CI=0.30-0.90). Furthermore, after adjustment for confounding factors, the -420 C>G "CC" genotype, compared with the "GG" genotype, was associated with a decreased risk for CRC (p=0.044; OR=0.53, 95% CI=0.29-0.98). In addition, no significant difference was observed for the GHRL (rs26802) gene variant. To our knowledge, this is the first study suggesting that the RETN -420 C>G "CC" genotype is a marker of decreased CRC susceptibility. This observation is relevant from a scientific perspective and deserves further investigations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhen; Bian, Xin; Yang, Xiu

We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamics basedmore » on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models are not interchangeable. If the free parameters are properly selected, the reverse CG procedure also yields an effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhen; Bian, Xin; Karniadakis, George Em, E-mail: george-karniadakis@brown.edu

We construct effective coarse-grained (CG) models for polymeric fluids by employing two coarse-graining strategies. The first one is a forward-coarse-graining procedure by the Mori-Zwanzig (MZ) projection while the other one applies a reverse-coarse-graining procedure, such as the iterative Boltzmann inversion (IBI) and the stochastic parametric optimization (SPO). More specifically, we perform molecular dynamics (MD) simulations of star polymer melts to provide the atomistic fields to be coarse-grained. Each molecule of a star polymer with internal degrees of freedom is coarsened into a single CG particle and the effective interactions between CG particles can be either evaluated directly from microscopic dynamicsmore » based on the MZ formalism, or obtained by the reverse methods, i.e., IBI and SPO. The forward procedure has no free parameters to tune and recovers the MD system faithfully. For the reverse procedure, we find that the parameters in CG models cannot be selected arbitrarily. If the free parameters are properly defined, the reverse CG procedure also yields an accurate effective potential. Moreover, we explain how an aggressive coarse-graining procedure introduces the many-body effect, which makes the pairwise potential invalid for the same system at densities away from the training point. From this work, general guidelines for coarse-graining of polymeric fluids can be drawn.« less

A Unique Human Chorionic Gonadotropin Antagonist Suppresses Ovarian Hyperstimulation Syndrome in Rats

PubMed Central

Vardhana, Pratibhasri A.; Julius, Martin A.; Pollak, Susan V.; Lustbader, Evan G.; Trousdale, Rhonda K.; Lustbader, Joyce W.

2009-01-01

Ovarian hyperstimulation syndrome (OHSS) is a complication of in vitro fertilization associated with physiological changes after hCG administration to induce final oocyte maturation. It presents as widespread increases in vascular permeability and, in rare cases, results in cycle cancellation, multi-organ dysfunction, and pregnancy termination. These physiological changes are due primarily to activation of the vascular endothelial growth factor (VEGF) system in response to exogenous human chorionic gonadotropin (hCG). An hCG antagonist (hCG-Ant) could attenuate these effects by competitively binding to the LH/CG receptor, thereby blocking LH activity in vivo. We expressed a form of hCG that lacks three of its four N-linked glycosylation sites and tested its efficacy as an antagonist. The hCG-Ant binds the LH receptor with an affinity similar to native hCG and inhibits cAMP response in vitro. In a rat model for ovarian stimulation, hCG-Ant dramatically reduces ovulation and steroid hormone production. In a well-established rat OHSS model, vascular permeability and vascular endothelial growth factor (VEGF) expression are dramatically reduced after hCG-Ant treatment. Finally, hCG-Ant does not appear to alter blastocyst development when given after hCG in mice. These studies demonstrate that removing specific glycosylation sites on native hCG can produce an hCG-Ant that is capable of binding without activating the LH receptor and blocking the actions of hCG. Thus hCG-Ant will be investigated as a potential therapy for OHSS. PMID:19443574

Familial HCG syndrome.

PubMed

Cole, Laurence A

2012-01-01

An explanation is needed for why some men and women show positive in hCG screening tests when they are not pregnant, do not have cancer and are otherwise asymptomatic. In this study, a total of 10 families comprising 30 persons with a history of positive hCG tests were investigated. Total hCG was measured in serum and urine samples using the Siemens Immulite hCG test. Total hCG, C-terminal peptide determinant, and hCGβ were measured in 96 well plate assays. Twenty-four of 30 family members produced only hCGβ, and hCG or hCGβ missing the β-subunit C-terminal peptide, two rarely detected hCG degradation products as the only source of hCG immunoreactivity. In every one of the 10 families, hCG related molecules were detected first in one member and then later detected in other family members. In 8 of 10 families, all members produced comparable hCG concentration (Cases 1-8). All of the 10 original family members investigated were otherwise asymptomatic, and tested negative in ordered head and pelvis MRI scans and CT chest cancer tests. None had been administered hCG for dietary, anabolic or fertility reasons. Therefore Familial hCG Syndrome, a genetic defect, was indicated in each of the 10 families. In these cases of Familial hCG Syndrome only biologically inactive variants of hCG were detected. It is inferred that in Familial hCG Syndrome, hCG gene expression does not interfere with fertility. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aguilera, G.; Millan, M.A.; Harwood, J.P.

The presence of components of the renin-angiotensin system in ovaries and testes suggests that angiotensin II (AII) is involved in gonadal function, and thus we sought to characterize receptors for AII in rat and primate gonads. In the testes, autoradiographic studies showed receptors in the interstitium in all species. In rat interstitial cells fractionated by Percoll gradient, AII receptors coincided with hCG receptors indicating that AII receptors are located on the Leydig cells. In Leydig cells and membranes from rat and rhesus monkey prepuberal testes, AII receptors were specific for AII analogues and of high affinity (Kd=nM). During development, AIImore » receptor content in rat testes decreases with age parallel to a fall in the ratio of interstitial to tubular tissue. In the ovary, the distribution of AII receptors was dependent on the stage of development, being high in the germinal epithelium and stromal tissue between five and 15 days, and becoming localized in secondary follicles in 20-and 40-day-old rats. No binding was found in primordial or primary follicles. In rhesus monkey ovary, AII receptors were higher in stromal tissue and lower in granulosa and luteal cells of the follicles. Characterization of the binding in rat and monkey ovarian membranes showed a single class of sites with a Kd in the nmol/L range and specificity similar to that of the adrenal glomerulosa and testicular AII receptors. Receptors for AII were also present in membrane fractions from PMSG/hCG primed rat ovaries. Infusion of AII (25 ng/min) or captopril (1.4 micrograms/min) during the PMSG/hCG induction period had no effect on ovarian weight or AII receptor concentration in the ovaries.« less

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

PubMed

Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

2017-03-01

Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

PubMed

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

2014-02-01

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Analytical sensitivity of four commonly used hCG point of care devices.

PubMed

Kamer, Sandy M; Foley, Kevin F; Schmidt, Robert L; Greene, Dina N

2015-04-01

Point of care (POC) hCG assays are often used to rule-out pregnancy and therefore diagnostic sensitivity, especially at low concentrations of hCG, is important. There are very few studies in the literature that seek to verify the claimed analytical sensitivity of hCG POC devices. The analytical sensitivity of four commonly used hCG POC devices (Alere hCG Combo Cassette, ICON 20 hCG, OSOM hCG Combo Test, and Sure-Vue Serum/Urine hCG-STAT) was challenged using urine samples (n=50) selected based on quantitative hCG concentrations. The majority of these specimens (n=40) had an hCG concentration between 20 and 200 U/L. Each specimen/device combination was reviewed by three individuals. Statistical calculations were performed using Stata 12. The analytical sensitivity of the OSOM was significantly lower inferior than that of the other POC devices. There was no significant difference in the sensitivity of the Alere, ICON 20 and Sure-Vue devices. There was no significant difference in the individual interpretation of the hCG POC results. All hCG POC devices evaluated in this study were susceptible to false negative results at low concentrations of urine hCG. Laboratorians and clinicians should be aware that there are limitations when using urine hCG POC devices to rule out early pregnancy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Using a simulation model to assess risk of false negative point-of-care urinary human chorionic gonadotropin device results due to high-dose hook interference.

PubMed

Milhorn, Denise; Korpi-Steiner, Nichole

2015-02-01

It is unclear if the point-of-care (POC) Clinitest hCG device is subject to high-dose hook interference from physiological concentrations of intact human chorionic gonadotropin (hCG), β-core fragment of hCG (hCGβcf), and hCG free β-subunit (hCGβ) found in urine during pregnancy. We used a simulation model to address this question and related our findings to our institution's pregnant population in order to assess risk for potential false-negative hCG results. The expected distribution of days relative to ovulation during routine POC hCG testing was estimated from 182 patients. Clinitest-Clinitek Status hCG device susceptibility to high-dose hook interference from hCG variants and potential risk of false-negative results as it relates to this population were evaluated by testing increasing concentrations of hCG, hCGβcf, hCGβ as well as urine simulating physiological hCG, hCGβcf and hCGβ concentrations expected during early pregnancy (≤44 days post-ovulation). The Clinitest-Clinitek Status hCG device exhibited high-dose hook interference from hCGβcf alone, but not from hCG, hCGβ, or simulated physiological urinary concentrations of combined hCG, hCGβcf and hCGβ expected during early pregnancy. The majority of our patient population had urinary hCG testing conducted during early pregnancy. The Clinitest-Clinitek Status hCG device is unlikely to exhibit false-negative urinary hCG results due to high-dose hook interference for women in early healthy pregnancy, although additional studies are necessary to determine potential risk in other patient populations. Visual interpretation of POC urinary hCG device results is an important failure mode to consider in risk analyses for erroneous urinary hCG device results. Published by Elsevier Inc.

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

PubMed Central

Gu, Yan

2018-01-01

Background To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. Purpose The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. Materials and methods CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). Results CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. Conclusions The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site. PMID:29491707

QTL mapping of genes controlling plasma insulin and leptin concentrations: metabolic effect of obesity QTLs identified in an F2 intercross between C57BL/6J and DDD.Cg-A(y) inbred mice.

PubMed

Suto, Jun-ichi

2013-07-31

DDD.Cg-A(y) female mice developed massive obesity as compared with B6.Cg-A(y) female mice. We previously identified quantitative trait loci (QTLs) for obesity on chromosomes 1, 6, 9 and 17 in F2 female mice, including F2A(y) (F2 mice with the A(y) allele) and F2 non- A(y) mice (F2 mice without the A(y) allele), produced by crossing C57BL/6J and DDD.Cg-A(y) strains. We here addressed the question whether the obesity QTLs share genetic bases with putative QTLs for plasma glucose, insulin and leptin concentrations. We performed QTL analyses for the first principal component (PC1) extracted from these metabolic measurements to identify the genes that contributed to the comprehensive evaluation of metabolic traits. By single QTL scans, we identified two significant QTLs for insulin concentration on chromosomes 6 and 12, three for leptin concentration on chromosomes 1, 6 and 17, and five for PC1 on chromosomes 1, 6, 12 (two loci) and 17. Although insulin and leptin concentrations and PC1 were not normally distributed in combined F2 mice, results of single QTL scans by parametric and non-parametric methods were very similar. Therefore, QTL scan by the parametric method was performed with the agouti locus genotype as a covariate. A significant QTL × covariate interaction was found for PC1 on chromosome 9. All obesity QTLs had significant metabolic effects. Thus, obesity- and diabetes-related traits in DDD.Cg-A(y) mice were largely controlled by QTLs on chromosomes 1, 6, 9, 12 and 17.

hCG, the wonder of today's science

PubMed Central

2012-01-01

Background hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail. Content These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies. Conclusions The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death. PMID:22455390

Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

PubMed

Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

2013-08-01

The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

Detrended Fluctuation Analysis and Adaptive Fractal Analysis of Stride Time Data in Parkinson's Disease: Stitching Together Short Gait Trials

PubMed Central

Liebherr, Magnus; Haas, Christian T.

2014-01-01

Variability indicates motor control disturbances and is suitable to identify gait pathologies. It can be quantified by linear parameters (amplitude estimators) and more sophisticated nonlinear methods (structural information). Detrended Fluctuation Analysis (DFA) is one method to measure structural information, e.g., from stride time series. Recently, an improved method, Adaptive Fractal Analysis (AFA), has been proposed. This method has not been applied to gait data before. Fractal scaling methods (FS) require long stride-to-stride data to obtain valid results. However, in clinical studies, it is not usual to measure a large number of strides (e.g., strides). Amongst others, clinical gait analysis is limited due to short walkways, thus, FS seem to be inapplicable. The purpose of the present study was to evaluate FS under clinical conditions. Stride time data of five self-paced walking trials ( strides each) of subjects with PD and a healthy control group (CG) was measured. To generate longer time series, stride time sequences were stitched together. The coefficient of variation (CV), fractal scaling exponents (DFA) and (AFA) were calculated. Two surrogate tests were performed: A) the whole time series was randomly shuffled; B) the single trials were randomly shuffled separately and afterwards stitched together. CV did not discriminate between PD and CG. However, significant differences between PD and CG were found concerning and . Surrogate version B yielded a higher mean squared error and empirical quantiles than version A. Hence, we conclude that the stitching procedure creates an artificial structure resulting in an overestimation of true . The method of stitching together sections of gait seems to be appropriate in order to distinguish between PD and CG with FS. It provides an approach to integrate FS as standard in clinical gait analysis and to overcome limitations such as short walkways. PMID:24465708

The systematic regulation of oyster CgIL17-1 and CgIL17-5 in response to air exposure.

PubMed

Xin, Lusheng; Zhang, Huan; Du, Xinyu; Li, Yiqun; Li, Meijia; Wang, Lingling; Wang, Hao; Qiu, Limei; Song, Linsheng

2016-10-01

As a proinflammatory cytokine, vertebrate interleukin 17 (IL17) plays a vital role in the balance of inflammation and homeostasis, and is involved in a systemic regulation of glucose homeostasis. In the present study, a remarkable increase of glucose concentration was observed in oyster serum after 2 d air exposure, which was followed by a rapid up-regulation of CgIL17-1 and CgIL17-5. After oysters was received an injection of extra glucose, the mRNA expressions of CgIL17-1 and CgIL17-5 were also significantly up-regulated. The histopathological changes of hepatopancreas were observed after the oysters were treated by the recombinant proteins of CgIL17-1 and CgIL17-5 in vivo or subjected to air exposure. A significant decrease of GSK3β (Glycogen synthase kinase-3β) protein was also observed after the injection of CgIL17-1 and CgIL17-5 recombinant proteins in vivo. When the oysters with CgIL17-1 and CgIL17-5 genes knocked down were subjected to air exposure, the decline of GSK3β concentration was slowed down and it could still be obviously detected after 7 d compared with that in the control. Meanwhile, the expression of CgDefensin and CgDFFA was inhibited, while CgIAP was up-regulated when CgIL17-1 and CgIL17-5 genes were knocked down, and the oysters exhibited higher mortality (p < 0.05) at 3 d, whereas lower at the late stage of air exposure compared with that in the controls. The results collectively suggested that once oysters were exposed to air, the synthesis of proinflammatory cytokines CgIL17-1 and CgIL17-5 was induced by the up-regulated glucose concentration in oyster serum, which would be not only a negative feedback to the high glucose concentration through mediating the regulation of GSK3β, but also an inducer on tissue damage and immunocompetence as well as the adaptability to stresses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retrospective analysis of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy

PubMed Central

Var, Altan; Özyurt, Ramazan; Şık, Bulat Aytek; Kumbasar, Serkan; Sever, Erman; Deveci, Mustafa; Çöt, Özgür; Salman, Süleyman; Güzel, Yılmaz

2015-01-01

Objective: Detection of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy. Materials and Methods: We investigated 99 patients who had been treated with single-dose methotrexate for ectopic pregnancy in our clinic between January 2009 and June 2014. Demographic, clinical, and laboratory results of possible factors that affect treatment success were retrospectively analyzed. Successfully and unsuccessfully treated patients were compared based on their pre-treatment results. Results: The success rate of single-dose methotrexate treatment was found to be 70.7%. No significant difference was found between succesfully and unsuccessfully treated patients before treatment in terms of factors such as gestational weeks, mass size, presence of yolk sac, and presence of free fluid (p=0.224, p=0.201, p=0.200, p=0.200). Serum β-hCG values in patients whose treatment was unsuccessful was found to be higher compared with the successfully treated group (mean β-hCG value of unsuccessful group: 4412±3501 mIU/mL; mean β-hCG value of successful group: 1079±942 mIU/mL; p<0.001). Conclusion: Single-dose methotrexate treatment is an effective and reliable method in the treatment of ectopic pregnancy. Elevation of serum β-hCG value stands as the main prognostic factor that affects the success of single-dose methotrexate treatment. PMID:28913072

Solid-liquid work of adhesion of coarse-grained models of n-hexane on graphene layers derived from the conditional reversible work method.

PubMed

Ardham, Vikram Reddy; Deichmann, Gregor; van der Vegt, Nico F A; Leroy, Frédéric

2015-12-28

We address the question of how reducing the number of degrees of freedom modifies the interfacial thermodynamic properties of heterogeneous solid-liquid systems. We consider the example of n-hexane interacting with multi-layer graphene which we model both with fully atomistic and coarse-grained (CG) models. The CG models are obtained by means of the conditional reversible work (CRW) method. The interfacial thermodynamics of these models is characterized by the solid-liquid work of adhesion WSL calculated by means of the dry-surface methodology through molecular dynamics simulations. We find that the CRW potentials lead to values of WSL that are larger than the atomistic ones. Clear understanding of the relationship between the structure of n-hexane in the vicinity of the surface and WSL is elucidated through a detailed study of the energy and entropy components of WSL. We highlight the crucial role played by the solid-liquid energy fluctuations. Our approach suggests that CG potentials should be designed in such a way that they preserve the range of solid-liquid interaction energies, but also their fluctuations in order to preserve the reference atomistic value of WSL. Our study thus opens perspectives into deriving CG interaction potentials that preserve the thermodynamics of solid-liquid contacts and will find application in studies that intend to address materials driven by interfaces.

A 43-year-old woman with unexplained elevation of hCG.

PubMed

Johnson, Lisa M; Gniadek, Thomas J; Cohn, Claudia S; Bachowski, Gary; Karger, Amy B

2018-05-01

This case report investigates an unusual hCG result in a woman who is not pregnant. A 43-year-old woman was admitted for recurrence of thrombotic thrombocytopenic purpura (TTP) and therapeutic plasma exchange (TPE) was initiated. Prior to transitioning the patient from TPE to immunosuppressive therapy, a serum qualitative hCG test was performed and was positive. Several etiologies for elevated hCG were considered and investigated, including heterophile antibody interference, endogenous hCG from pituitary or malignancy, and exogenous hCG. Retrospective measurement of hCG levels in remnant samples, including a sample obtained prior to TPE initiation, demonstrated that the hCG elevation occurred with plasma administration for TPE. Further investigation with the American Red Cross confirmed that a plasma donor was unknowingly pregnant and in the latter half of the first trimester at the time of donation, when hCG levels peak. In plasma recipients with unexplained hCG elevation, passive transfer of hCG from plasma should be considered in the differential diagnosis. Retrospective measurement of hCG in remnant samples obtained prior to plasma exchange can assist in confirming the source. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Sand amendment enhances bioelectrochemical remediation of petroleum hydrocarbon contaminated soil.

PubMed

Li, Xiaojing; Wang, Xin; Ren, Zhiyong Jason; Zhang, Yueyong; Li, Nan; Zhou, Qixing

2015-12-01

Bioelectrochemical system is an emerging technology for the remediation of soils contaminated by petroleum hydrocarbons. However, performance of such systems can be limited by the inefficient mass transport in soil. Here we report a new method of sand amendment, which significantly increases both oxygen and proton transports, resulting to increased soil porosity (from 44.5% to 51.3%), decreased Ohmic resistance (by 46%), and increased charge output (from 2.5 to 3.5Cg(-1)soil). The degradation rates of petroleum hydrocarbons increased by up to 268% in 135d. The degradation of n-alkanes and polycyclic aromatic hydrocarbons with high molecular weight was accelerated, and denaturing gradient gel electrophoresis showed that the microbial community close to the air-cathode was substantially stimulated by the induced current, especially the hydrocarbon degrading bacteria Alcanivorax. The bioelectrochemical stimulation imposed a selective pressure on the microbial community of anodes, including that far from the cathode. These results suggested that sand amendment can be an effective approach for soil conditioning that will enhances the bioelectrochemical removal of hydrocarbons in contaminated soils. Copyright © 2015 Elsevier Ltd. All rights reserved.

Single-dose pharmacokinetic study comparing the pharmacokinetics of recombinant human chorionic gonadotropin in healthy Japanese and Caucasian women and recombinant human chorionic gonadotropin and urinary human chorionic gonadotropin in healthy Japanese women.

PubMed

Bagchus, Wilhelmina; Wolna, Peter; Uhl, Wolfgang

2018-01-01

Recombinant hCG (r-hCG) was approved in Japan in 2016. As a prerequisite for a Phase III study in Japan related to this approval, the pharmacokinetic (PK) profile of r-hCG was investigated. An open-label, partly randomized, single-center, single-dose, group-comparison, Phase I PK-bridging study was done that compared a single 250 μg dose of r-hCG with a single 5000 IU dose of urinary hCG (u-hCG) in healthy Japanese women, as well as comparing a single 250 μg dose of r-hCG in Japanese and Caucasian women. The Japanese participants were randomized 1:1 to receive either r-hCG or u-hCG, while the Caucasian participants were weight-matched to the Japanese participants who were receiving r-hCG in a 1:1 fashion. The primary PK parameters were the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC 0-∞ ) and the maximum serum concentration (C max ). The mean serum hCG concentration-time profiles of r-hCG in the Japanese and Caucasian participants were a similar shape, but the level of overall exposure was ~20% lower in the Japanese participants. For the Japanese participants, r-hCG resulted in an 11% lower C max but a 19% higher AUC 0-∞ compared with u-hCG. No new safety signal was identified. This study cannot exclude a potential difference in the PK profile of r-hCG between Japanese and Caucasian participants. However, this study does not indicate that there are clinically relevant differences in the serum PK of r-hCG and u-hCG in the Japanese participants.

Thyrotropic action of human chorionic gonadotropin.

PubMed

Yoshimura, M; Hershman, J M

1995-10-01

Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent with the finding that the beta-CTP truncated hCG with higher thyrotropic potency is substantially deglycosylated and desialylated in the beta-subunit relative to intact hCG because all four O-linked glycosylation sites occur within the missing C-terminal extension. The desialylated hCG variant also interacts directly with recombinant hTSH receptors transfected into human thyroid cancer cells. There is thyroid-stimulating activity in sera of normal pregnant women, and this correlates with serum hCG levels. The thyroid gland of normal pregnant women may be stimulated by hCG to secrete slightly excessive quantities of T4 and induce a slight suppression of TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid hormone during early pregnancy in response to the thyrotropic activity of hCG that overrides the normal operation of the hypothalamic-pituitary-thyroid feedback system. Biochemical hyperthyroidism associated with hyperemesis gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum, thyrotropic in serum correlated with hCG immunoreactivity, and the severity of vomiting as indicated by clinical and biochemical parameters correlated with the degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is necessary to know whether hCG activates the same domain of the TSH receptor as does TSH. The identification of the molecular structure of the hCG isoform with the highest thyrotropic potency will resolve the enigma of gestational thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and hCG-producing tumors.

Body posture changes in women with migraine with or without temporomandibular disorders

PubMed Central

Ferreira, Mariana C.; Bevilaqua-Grossi, Débora; Dach, Fabíola É.; Speciali, José G.; Gonçalves, Maria C.; Chaves, Thais C.

2014-01-01

Background Migraine and temporomandibular disorders (TMDs) are reported to be associated. However, there are no reports on the association among migraines, TMDs and changes in body posture. Objectives To assess changes in body posture in women suffering migraines with or without TMD compared with a control group. Method Sixty-six women with a mean age of 18 to 45 years participated in this study. The groups were composed of 22 volunteers with migraine and TMD (MTMD), 22 volunteers with migraines without TMD (MG) and 22 women in the control group (CG). Static posture was assessed by photogrammetry, and 19 angles were measured. Results Postural asymmetry was observed in the face for 4 angles measured on the frontal plane in the MG group and for 4 angles of the trunk in the MG and MTMD groups with respect to CG. However, for comparisons between MTMD and CG, clinical relevance was identified for two angles of the sagittal plane (Cervical and Lumbar Lordosis, Effect Size - ES - moderate: 0.53 and 0.60). For comparisons between the MG and CG, the clinical relevance/potential was verified for three angles with moderate ES (ES>0.42). The clinical relevance when comparing MTMD and CG was identified for four angles of facial symmetry head inclination (ES>0.54) and for two angles between MG and CG (ES>0.48). Conclusion The results demonstrated the presence of postural changes compared with a control group in women with migraines with or without TMD, and there were similar clinically relevant postural changes among the patients with migraines with and without TMD. PMID:24675909

Dried blood spot measurement of pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin (β-hCG) from a low-resource setting.

PubMed

Browne, J L; Schielen, P C J I; Belmouden, I; Pennings, J L A; Klipstein-Grobusch, K

2015-06-01

The objectives of the article is to compare pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin (β-hCG) concentrations in dried blood spots (DBSs) with serum of samples obtained from a public hospital in a low-resource setting and to evaluate their stability. Serum and DBS samples were obtained by venipuncture and finger prick from 50 pregnant participants in a cohort study in a public hospital in Accra, Ghana. PAPP-A and β-hCG concentrations from serum and DBS were measured with an AutoDELFIA® (PerkinElmer, PerkinElmer, Turku, Finland) automatic immunoassay. Correlation and Passing-Bablok regression analyses were performed to compare marker levels. High correlation (>0.9) was observed for PAPP-A and β-hCG levels between various sampling techniques. The β-hCG concentration was stable between DBS and serum, PAPP-A concentration consistently lower in DBS. Our findings suggest that β-hCG can be reliably collected from DBS in low-resource tropical settings. The exact conditions of the clinical workflow necessary for reliable PAPP-A measurement in these settings need to be further developed in the future. These findings could have implications for prenatal screening programs feasibility in low-income and middle-income countries, as DBS provides an alternative minimally invasive sampling method, with advantages in sampling technique, stability, logistics, and potential application in low-resource settings. © 2015 John Wiley & Sons, Ltd.

Functions of ectopically transplanted invasive horse trophoblast

PubMed Central

de Mestre, Amanda M.; Hanlon, David; Adams, A. Paige; Runcan, Erin; Leadbeater, Jane C.; Erb, Hollis N.; Costa, Christina C.; Miller, Donald; Allen, W. R; Antczak, Douglas F.

2013-01-01

The invasive and fully antigenic trophoblast of the chorionic girdle portion of the equine fetal membranes has the capacity to survive and differentiate after transplantation to ectopic sites. The objectives of this study were to determine: (i) the survival time of ectopically transplanted allogeneic trophoblast cells in non-pregnant recipient mares, (ii) whether equine Chorionic Gonadotrophin (eCG) can be delivered systemically by transplanted chorionic girdle cells, and (iii) if eCG delivered by the transplanted cells is biologically active and can suppress behavioral signs associated with estrus. Ectopically transplanted chorionic girdle survived for up to 105 days with a mean lifespan of 75 days (95% CI 55–94), and secreted sufficient eCG for the hormone to be measurable in the recipients’ circulation. Immunohistochemical labeling of serial biopsies of the transplant sites and measurement of eCG profiles demonstrated that graft survival was similar to the lifespan of equine endometrial cups in normal horse pregnancy. The eCG secreted by the transplanted cells induced corpora lutea formation and sustained systemic progesterone levels in the recipient mares, effects that are also observed during pregnancy. This in turn caused suppression of estrus behavior in the recipients for up to three months. Thus, ectopically transplanted equine trophoblast provides an unusual example of sustained viability and function of an immunogenic transplant in a recipient with an intact immune system. This model highlights the importance of innate immunoregulatory capabilities of invasive trophoblast cells and describes a new method to deliver sustained circulating concentrations of eCG in non-pregnant mares. PMID:21389079

Protocols for efficient simulations of long-time protein dynamics using coarse-grained CABS model.

PubMed

Jamroz, Michal; Kolinski, Andrzej; Kmiecik, Sebastian

2014-01-01

Coarse-grained (CG) modeling is a well-acknowledged simulation approach for getting insight into long-time scale protein folding events at reasonable computational cost. Depending on the design of a CG model, the simulation protocols vary from highly case-specific-requiring user-defined assumptions about the folding scenario-to more sophisticated blind prediction methods for which only a protein sequence is required. Here we describe the framework protocol for the simulations of long-term dynamics of globular proteins, with the use of the CABS CG protein model and sequence data. The simulations can start from a random or a selected (e.g., native) structure. The described protocol has been validated using experimental data for protein folding model systems-the prediction results agreed well with the experimental results.

A framework for multi-scale simulation of crystal growth in the presence of polymers.

PubMed

Mandal, Taraknath; Huang, Wenjun; Mecca, Jodi M; Getchell, Ashley; Porter, William W; Larson, Ronald G

2017-03-01

We present a multi-scale simulation method for modeling crystal growth in the presence of polymer excipients. The method includes a coarse-grained (CG) model for small molecules of known crystal structure whose force field is obtained using structural properties from atomistic simulations. This CG model is capable of stabilizing the molecular crystal structure and capturing the crystal growth from the melt for a wide range of small organic molecules, as demonstrated by application of our method to the molecules isoniazid, urea, sulfamethoxazole, prilocaine, oxcarbazepine, and phenytoin. This CG model can also be used to study the effect of additives, such as polymers, on the inhibition of crystal growth by polymers, as exemplified by our simulation of suppression of the rate of crystal growth of phenytoin, an active pharmaceutical ingredient (API), by a cellulose excipient, functionalized with acetate (Ac), hydroxy-propyl (Hp) and succinate (Su) groups. We show that the efficacy of the cellulosic polymers in slowing crystal growth of small molecules strongly depends on the functional group substitution on the cellulose backbone, with the acetate substituent group slowing crystal growth more than does the deprotonated succinate group, which we confirm by experimental drug supersaturation studies.

The serum level of C-reactive protein in patients undergoing GnRH agonist protocols for in vitro fertilization cycle.

PubMed

Liu, B; Zhang, L; Guo, R W; Wang, W J; Duan, X Q; Liu, Y W

2014-01-01

The synchronization of the uterus and mature eggs at the molecular level is the key factor in embryo transfer, and the regulation of synchronization depends on a variety of cytokines. C-reactive protein (CRP), as the first acute phase reaction protein, is involved in the entire process of embryo transfer. The study is designed to investigate the correlation among CRP, sex hormone, controlled ovarian hyperstimulation (COH) cycle, and pregnancy outcome. Ninety-two patients who accepted in vitro fertilization (IVF) treatment cycles because of tubal factor were included in the study. Seventy treated cases were included to complete final analysis with the full set of results. Respectively on the second day of the menstruation (Day-2) in gonadotropin-releasing hormone agonist (GnRH-a) short program treatment, on the morning in human chorionic gonadotropin (hCG) treatment (Day-hCG) and the embryo transplant day (Day-ET), plasma CRP level was tested by enzyme-linked immunosorbent assay (ELISA). The correlativity among CRP level, sex hormone, COH, and pregnancy outcome was analyzed by statistical methods. In the short program GnRH-a of 70 cases, there was no relationship between serum CRP level and the infertility age, gonadotropin (Gn) dosage, number of oocytes retrieved, the number of normal fertilization, and sex hormone. In the short program of GnRH-a, the change of serum CRP levels in Day-2, Day-hCG, Day-ET: serum CRP in Day-2 < Day-hCG < Day-ET and the level of serum CRP gradually increased in Day-2, Day-hCG, and Day-ET in both the pregnant group and non-pregnant group. In non-pregnant group, the ratio of hCG/D2 and ET/hCG-day were significantly higher than the pregnant group. The area under receiver operating characteristic (ROC) curve was 0.806, indicating the accuracy of diagnostic tests is medium, the authors chose the point which presents the ratio of CRP in Day-ET to Day-hCG which was less than 1.752 as a predictor of treatment outcome, the sensitivity of the experiment was 77.8%, and the specificity 75%. CRP as a sensitive inflammatory marker, CRP ratio of Day-ET/Day-hCG could be a predictor of treatment outcome by ROC curve analysis in COH program.

Tumor-associated antigen human chorionic gonadotropin beta contains numerous antigenic determinants recognized by in vitro-induced CD8+ and CD4+ T lymphocytes.

PubMed

Dangles, Virginie; Halberstam, Ilan; Scardino, Antonio; Choppin, Jeannine; Wertheimer, Mireille; Richon, Sophie; Quelvennec, Erwann; Moirand, Romain; Guillet, Jean-Gérard; Kosmatopoulos, Kostas; Bellet, Dominique; Zeliszewski, Dominique

2002-02-01

The beta subunit of human chorionic gonadotropin (hCG beta) is markedly overexpressed by neoplastic cells of differing histological origin including those present in colon, breast, prostate and bladder tumors. We have previously shown that some patients with hCG beta-producing urothelial tumors have circulating T cells that proliferate in response to hCG beta. To make a comprehensive study of hCG beta as a potential target for cancer immunotherapy, we investigated whether hCG beta peptides could induce CD4+ or CD8+ T-cell responses in vitro. By stimulating peripheral blood mononuclear cells (PBMCs) from three donors with mixtures of overlapping 16-mer synthetic peptides analogous to portions of either the hCG beta 20-71 or the hCG beta 102-129 region, we established six CD4+ T-cell lines that proliferated specifically in response to five distinct determinants located within these two hCG beta regions. Three antigenic determinants (hCG beta 52-67, 106-121 and 114-125) were presented by HLA-DR molecules, while the two other antigenic determinants (hCG beta 48-63 and 56-67) were presented by HLA-DQ molecules. Interestingly, one T-cell line specific for peptide hCG beta 106-121 recognized hCG beta peptides comprising, at position 117, either an alanine or an aspartic acid residue, with the latter residue being present within the protein expressed by some tumor cells. In addition, three other hCG beta-derived peptides that exhibited HLA-A*0201 binding ability were able to stimulate CD8+ cytotoxic T cells from two HLA-A*0201 donors. These three immunogenic peptides corresponded to regions hCG beta 40-48, hCG beta 44-52 and hCG beta 75-84. Our results indicate that the tumor-associated antigen hCG beta possesses numerous antigenic determinants liable to stimulate CD4+ and CD8+ T lymphocytes, and might thus be an effective target antigen for the immunotherapy of hCG beta-producing tumors.

Intrauterine administration of human chorionic gonadotropin (hCG) for subfertile women undergoing assisted reproduction.

PubMed

Craciunas, Laurentiu; Tsampras, Nikolaos; Coomarasamy, Arri; Raine-Fenning, Nick

2016-05-20

Subfertility affects 15% of couples and represents the inability to conceive naturally following 12 months of regular unprotected sexual intercourse. Assisted reproduction refers to procedures involving the in vitro handling of both human gametes and represents a key option for many subfertile couples. Most women undergoing assisted reproduction treatment will reach the stage of embryo transfer (ET) but the proportion of embryos that successfully implant following ET has remained small since the mid-1990s. Human chorionic gonadotropin (hCG) is a hormone synthesised and released by the syncytiotrophoblast and has a fundamental role in embryo implantation and the early stages of pregnancy. Intrauterine administration of synthetic or natural hCG via an ET catheter during a mock procedure around the time of ET is a novel approach that has recently been suggested to improve the outcomes of assisted reproduction. To investigate whether the intrauterine administration of hCG around the time of ET improves the clinical outcomes in subfertile women undergoing assisted reproduction. We performed a comprehensive literature search of the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, registers of ongoing trials andreference lists of all included studies and relevant reviews (from inception to 10 November 2015), in consultation with the Cochrane Gynaecology and Fertility Group Trials Search Co-ordinator. We included all randomised controlled trials (RCTs) evaluating intrauterine administration of hCG around the time of ET in this review irrespective of language and country of origin. Two authors independently selected studies, assessed risk of bias, extracted data from studies and attempted to contact the authors where data were missing. We performed statistical analysis using Review Manager 5 in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. We assessed evidence quality using GRADE methods. Twelve RCTs investigated the effect of intrauterine administration of hCG for 4038 subfertile women undergoing assisted reproduction. The intra-cavity hCG (IC-hCG) was administered in variable doses at different timings before the ET. The source of hCG was from the urine of pregnant women or from cell cultures using recombinant DNA technology.Most of the studies (9/12) were at high risk of bias in at least one of the seven domains assessed. Common problems were unclear reporting of study methods and lack of blinding. The main limitations in the overall quality of the evidence were high risk of bias and serious imprecision.For the analyses of live birth and clinical pregnancy, there was considerable heterogeneity (I(2) greater than 75%) and we did not undertake a meta-analysis. Exploration for the sources of heterogeneity identified two key pre-specified variables as important determinants: stage of ET (cleavage versus blastocyst stage) and dose of IC-hCG (less than 500 international units (IU) versus 500 IU or greater). We then performed meta-analysis for these analyses within the subgroups defined by stage of embryo and dose of IC-hCG.There was an increase in live birth rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (risk ratio (RR) 1.57, 95% confidence interval (CI) 1.32 to 1.87, three RCTs, n = 914, I(2) = 0%, moderate quality evidence). In a clinic with a live birth rate of 25% per cycle then the use of IC-hCG -500 IU or greater would be associated with a live birth rate that varies from 33% to 46%. We did not observe a significant effect on live birth in any of the other subgroups.The was an increase in clinical pregnancy rate in the subgroup of women having cleavage-stage ETs with an IC-hCG dose of 500 IU or greater compared to women having cleavage-stage ETs with no IC-hCG (RR 1.41, 95% CI 1.25 to 1.58, seven RCTs, n = 1414, I(2) = 0%, moderate quality evidence). We did not observe a significant effect on clinical pregnancy in either of the other subgroups.There was no evidence that miscarriage was influenced by intrauterine hCG administration (RR 1.09, 95% CI 0.83 to 1.43, seven RCTs, n = 3395, I(2) = 0%, very low quality evidence).Other complications reported in the included studies were ectopic pregnancy (three RCTs, n = 915, three events overall), heterotopic pregnancy (one RCT, n = 495, one event), intrauterine death (two RCTs, n = 978, 21 events) and triplets (one RCT, n = 48, three events). There was no evidence of a difference between the groups, but there were too few events to allow any conclusions to be drawn and the evidence was very low quality. The pregnancy outcome for cleavage-stage ETs using an IC-hCG dose of 500 IU or greater is promising. However, given the small size and the variable quality of the trials and the fact that the positive finding was from a subgroup analysis, the current evidence for IC-hCG treatment does not support its use in assisted reproduction cycles. A definitive large clinical trial with live birth as the primary outcome is recommended. There was no evidence that miscarriage was influenced by intrauterine hCG administration, irrespective of embryo stage at transfer or dose of IC-hCG. There were too few events to allow any conclusions to be drawn with regard to other complications.

Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial

PubMed Central

Strug, Michael R.; Su, Renwei; Young, James E.; Dodds, William G.; Shavell, Valerie I.; Díaz-Gimeno, Patricia; Ruíz-Alonso, Maria; Simón, Carlos; Lessey, Bruce A.; Leach, Richard E.; Fazleabas, Asgerally T.

2016-01-01

STUDY QUESTION Does a single intrauterine infusion of human chorionic gonadotropin (hCG) at the time corresponding to a Day 3 embryo transfer in oocyte donors induce favorable molecular changes in the endometrium for embryo implantation? SUMMARY ANSWER Intrauterine hCG was associated with endometrial synchronization between endometrial glands and stroma following ovarian stimulation and the induction of early decidual markers associated with stromal cell survival. WHAT IS KNOWN ALREADY The clinical potential for increasing IVF success rates using an intrauterine hCG infusion prior to embryo transfer remains unclear based on previously reported positive and non-significant findings. However, infusion of CG in the non-human primate increases the expression of pro-survival early decidual markers important for endometrial receptivity, including α-smooth muscle actin (α-SMA) and NOTCH1. STUDY DESIGN, SIZE, DURATION Oocyte donors (n=15) were randomly assigned to receive an intrauterine infusion of 500 IU hCG (n=7) or embryo culture media vehicle (n=8) 3 days following oocyte retrieval during their donor stimulation cycle. Endometrial biopsies were performed 2 days later, followed by either RNA isolation or tissue fixation in formalin and paraffin embedding. PARTICIPANTS/MATERIALS, SETTING, METHODS Reverse transcription of total RNA from endometrial biopsies generated cDNA, which was used for analysis in the endometrial receptivity array (ERA; n = 5/group) or quantitative RT–PCR to determine relative expression of ESR1, PGR, C3 and NOTCH1. Tissue sections were stained with hematoxylin and eosin followed by blinded staging analysis for dating of endometrial glands and stroma. Immunostaining for ESR1, PGR, α-SMA, C3 and NOTCH1 was performed to determine their tissue localization. MAIN RESULTS AND THE ROLE OF CHANCE Intrauterine hCG infusion was associated with endometrial synchrony and reprograming of stromal development following ovarian stimulation. ESR1 and PGR were significantly elevated in the endometrium of hCG-treated patients, consistent with earlier staging. The ERA did not predict an overall positive impact of intrauterine hCG on endometrial receptivity. However, ACTA2, encoding α-SMA was significantly increased in response to intrauterine hCG. Similar to the hCG-treated non-human primate, sub-epithelial and peri-vascular α-SMA expression was induced in women following hCG infusion. Other known targets of hCG in the baboon were also found to be increased, including C3 and NOTCH1, which have known roles in endometrial receptivity. LIMITATIONS, REASONS FOR CAUTION This study differs from our previous work in the hCG-treated non-human primate along with clinical studies in infertile patients. Specifically, we performed a single intrauterine infusion in oocyte donors instead of either continuous hCG via an osmotic mini-pump in the baboon or infusion followed by blastocyst-derived hCG in infertile women undergoing embryo transfer. Therefore, the full impact of intrauterine hCG in promoting endometrial receptivity may not have been evident. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest a potential clinical benefit for intrauterine hCG prior to embryo transfer on Day 3 in counteracting endometrial dyssynchrony from ovarian stimulation and promoting expression of markers important for stromal survival. Finally, there were no obvious negative effects of intrauterine hCG treatment. STUDY FUNDING/COMPETING INTEREST(S) Funding for this work was provided by NICHD R01 HD042280 (A.T.F.) and NICHD F30 HD082951 (M.R.S.). C.S. and P.D.-G are co-inventors of the patented ERA, which is owned by IGENOMIX SL and was used in this study, and C.S. is a shareholder in IGENOMIX SL. M.R.-A. is employed by IGENOMIX SL. No other authors have any conflicts of interest to report. TRIAL REGISTRATION NUMBER This study was registered with ClinicalTrials.gov (NCT01786252). TRIAL REGISTRATION DATE 5 February 2013. DATE OF FIRST PATIENT'S ENROLLMENT 10 May 2013. PMID:27122490

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matzuk, M.M.; Krieger, M.; Corless, C.L.

1987-09-01

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common ..cap alpha.. subunit but differ in their hormone-specific ..beta..-subunits. The ..beta.. subunit of hCG (hCG..beta..) is unique among the ..beta.. subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either hCG..beta.. gene alone or together with the hCG..cap alpha.. gene were transfected into a mutant Chinese hamster ovary cell line, 1d1D, which exhibits a reversible defect in O-glycosylation. The results revealmore » that hCG..beta.. can be secreted normally in the absence of its O-linked oligosaccharides. hCG..beta.. devoid of O-linked carbohydrate can also combine efficiently with hCG..cap alpha.. and be secreted as an intact dimer. The authors conclude that in Chinese hamster ovary cells, the hCG..beta.. O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG.« less

Investigation of co-combustion characteristics of sewage sludge and coffee grounds mixtures using thermogravimetric analysis coupled to artificial neural networks modeling.

PubMed

Chen, Jiacong; Liu, Jingyong; He, Yao; Huang, Limao; Sun, Shuiyu; Sun, Jian; Chang, KenLin; Kuo, Jiahong; Huang, Shaosong; Ning, Xunan

2017-02-01

Artificial neural network (ANN) modeling was applied to thermal data obtained by non-isothermal thermogravimetric analysis (TGA) from room temperature to 1000°C at three different heating rates in air to predict the TG curves of sewage sludge (SS) and coffee grounds (CG) mixtures. A good agreement between experimental and predicted data verified the accuracy of the ANN approach. The results of co-combustion showed that there were interactions between SS and CG, and the impacts were mostly positive. With the addition of CG, the mass loss rate and the reactivity of SS were increased while charring was reduced. Measured activation energies (E a ) determined by the Kissinger-Akahira-Sunose (KAS) and Ozawa-Flynn-Wall (OFW) methods deviated by <5%. The average value of E a (166.8kJ/mol by KAS and 168.8kJ/mol by OFW, respectively) was the lowest when the fraction of CG in the mixture was 40%. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hyperglycosylated human chorionic gonadotropin does not increase progesterone production by luteinized granulosa cells.

PubMed

Crochet, John R; Shah, Anish A; Schomberg, David W; Price, Thomas M

2012-09-01

Trophoblast-derived human chorionic gonadotropin (hCG) promotes corpus luteum progesterone (P4) production, and wide ranges of serum P4 levels are noted in various pregnancy outcomes, despite similar hCG concentrations. There are five unique biologically active hCG variants in human pregnancy urine, and previous studies of P4 production in response to hCG have used only preparations containing all isoforms. Understanding exactly which hCG variant is primarily responsible for stimulating corpus luteum steroidogenesis may have great clinical and diagnostic implications, including in the setting of ectopic pregnancy. Our objective was to delineate the role of the standard and hyperglycosylated (H)-hCG isoforms in stimulating P4 production by luteinized granulosa cells. Cell culture, ELISA, and fluorometric-based protein assays were done at Duke University Medical Center. Patients were anonymous oocyte donors. Cultured luteinized granulosa cells were treated with 0.25, 0.5, and 1.0 ng/ml total hCG, which contains all isoforms, purified standard hCG (37.1 kDa), and purified H-hCG (42.8 kDa). P4 produced per total cellular protein (nanograms per microgram) was measured via ELISA and fluorometric protein determination kits. Both total hCG (P = 0.0003) and purified standard hCG (P < 0.0001) stimulated a dose-dependent increase in P4 production. Purified H-hCG did not change the P4 produced per total cellular protein response (P value not significant). Standard hCG stimulated P4 production by cultured granulosa cells and likely supports corpus luteum function via interactions with the LH/hCG receptor. In contrast, H-hCG did not increase P4 production, which indicates a nonsteroidogenic role for this protein during early gestation.

Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts

PubMed Central

Barrera, David; Avila, Euclides; Hernández, Guillermo; Méndez, Isabel; González, Leticia; Halhali, Ali; Larrea, Fernando; Morales, Angélica; Díaz, Lorenza

2008-01-01

Background In pregnancy, maternal serum concentrations of calcitriol significantly rise as a result of increased renal and placental contribution in order to assure calcium supply for the developing fetus. Considering that placenta is a site for vitamin D activation, and the versatility and potency of calcitriol, it is feasible that this hormone participates in fetal/placental development and physiology. In the present work we studied calcitriol actions upon human chorionic gonadotropin (hCG) secretion and expression in cultured trophoblasts, as well as vitamin D receptor (VDR) and CYP27B1 immunolocalization in placental villi. Methods Quantification of hCG in culture media was performed by immunoassay. Expression studies were carried out by real time PCR. Analysis of CYP27B1 and VDR localization in placental slides were performed by immunohistochemistry. Statistical significance was established by one way ANOVA using Tukey test for comparisons. Results Calcitriol regulated hCG in a time-dependent manner: at 6 h the secosteroid stimulated hCG, whereas longer incubations (24 h) showed opposite effects. Interestingly, calcitriol stimulatory effects on hCG were accompanied by an increase in intracellular cAMP content and were abolished by pre-incubation of the cells with a selective protein kinase A inhibitor. Immunohistochemical techniques showed differential VDR localization in the syncytiotrophoblast layer or in the vascular smooth muscle cells depending on the epitope to which the antibodies were raised (specific for the carboxy- or amino-terminal regions, respectively). CYP27B1 was immunolocalized in the syncytiotrophoblast layer of placental villi. Conclusion The presence and location of the vitamin D activating enzyme CYP27B1 as well as the specific receptor for vitamin D were shown in placental sections. The latter, together with findings demonstrating specific effects of calcitriol acting through the VDR and the cAMP/PKA signaling pathway upon hCG expression and secretion, indicate that there is a functional vitamin D endocrine system in the placenta, and recognize calcitriol as an autocrine regulator of hCG. PMID:18211694

Coarse-graining using the relative entropy and simplex-based optimization methods in VOTCA

NASA Astrophysics Data System (ADS)

Rühle, Victor; Jochum, Mara; Koschke, Konstantin; Aluru, N. R.; Kremer, Kurt; Mashayak, S. Y.; Junghans, Christoph

2014-03-01

Coarse-grained (CG) simulations are an important tool to investigate systems on larger time and length scales. Several methods for systematic coarse-graining were developed, varying in complexity and the property of interest. Thus, the question arises which method best suits a specific class of system and desired application. The Versatile Object-oriented Toolkit for Coarse-graining Applications (VOTCA) provides a uniform platform for coarse-graining methods and allows for their direct comparison. We present recent advances of VOTCA, namely the implementation of the relative entropy method and downhill simplex optimization for coarse-graining. The methods are illustrated by coarse-graining SPC/E bulk water and a water-methanol mixture. Both CG models reproduce the pair distributions accurately. SYM is supported by AFOSR under grant 11157642 and by NSF under grant 1264282. CJ was supported in part by the NSF PHY11-25915 at KITP. K. Koschke acknowledges funding by the Nestle Research Center.

Identification and Functional Characterization of the Glycogen Synthesis Related Gene Glycogenin in Pacific Oysters (Crassostrea gigas).

PubMed

Li, Busu; Meng, Jie; Li, Li; Liu, Sheng; Wang, Ting; Zhang, Guofan

2017-09-06

High glycogen levels in the Pacific oyster (Crassostrea gigas) contribute to its flavor, quality, and hardiness. Glycogenin (CgGN) is the priming glucosyltransferase that initiates glycogen biosynthesis. We characterized the full sequence and function of C. gigas CgGN. Three CgGN isoforms (CgGN-α, β, and γ) containing alternative exon regions were isolated. CgGN expression varied seasonally in the adductor muscle and gonadal area and was the highest in the adductor muscle. Autoglycosylation of CgGN can interact with glycogen synthase (CgGS) to complete glycogen synthesis. Subcellular localization analysis showed that CgGN isoforms and CgGS were located in the cytoplasm. Additionally, a site-directed mutagenesis experiment revealed that the Tyr200Phe and Tyr202Phe mutations could affect CgGN autoglycosylation. This is the first study of glycogenin function in marine bivalves. These findings will improve our understanding of glycogen synthesis and accumulation mechanisms in mollusks. The data are potentially useful for breeding high-glycogen oysters.

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity.

PubMed

Levy, Gary; Hill, Micah J; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S; Segars, James H; Csokmay, John

2013-05-01

To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Retrospective cohort study. Military assisted reproductive technology (ART) program. Fresh autologous ART cycles. Serum hCG level the day before oocyte retrieval. Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. Copyright © 2013. Published by Elsevier Inc.

A paralogue of the phosphomutase-like gene family in Candida glabrata, CgPmu2, gained broad-range phosphatase activity due to a small number of clustered substitutions.

PubMed

Orlando, Kelly A; Iosue, Christine L; Leone, Sarah G; Davies, Danielle L; Wykoff, Dennis D

2015-10-15

Inorganic phosphate is required for a range of cellular processes, such as DNA/RNA synthesis and intracellular signalling. The phosphate starvation-inducible phosphatase activity of Candida glabrata is encoded by the gene CgPMU2 (C. glabrata phosphomutase-like protein). CgPMU2 is part of a three-gene family (∼75% identical) created through gene duplication in the C. glabrata clade; only CgPmu2 is a PHO-regulated broad range acid phosphatase. We identified amino acids that confer broad range phosphatase activity on CgPmu2 by creating fusions of sections of CgPMU2 with CgPMU1, a paralogue with little broad range phosphatase activity. We used site-directed mutagenesis on various fusions to sequentially convert CgPmu1 to CgPmu2. Based on molecular modelling of the Pmu proteins on to a histidine phosphatase crystal structure, clusters of amino acids were found in two distinct regions that were able to confer phosphatase activity. Substitutions in these two regions together conferred broad phosphatase activity on CgPmu1. Interestingly, one change is a histidine adjacent to the active site histidine of CgPmu2 and it exhibits a novel ability to partially replace the conserved active site histidine in CgPmu2. Additionally, a second amino acid change was able to confer nt phosphatase activity to CgPmu1, suggesting single amino acid changes neofunctionalize CgPmu2. © 2015 Authors; published by Portland Press Limited.

A test of systematic coarse-graining of molecular dynamics simulations: Thermodynamic properties

NASA Astrophysics Data System (ADS)

Fu, Chia-Chun; Kulkarni, Pandurang M.; Scott Shell, M.; Gary Leal, L.

2012-10-01

Coarse-graining (CG) techniques have recently attracted great interest for providing descriptions at a mesoscopic level of resolution that preserve fluid thermodynamic and transport behaviors with a reduced number of degrees of freedom and hence less computational effort. One fundamental question arises: how well and to what extent can a "bottom-up" developed mesoscale model recover the physical properties of a molecular scale system? To answer this question, we explore systematically the properties of a CG model that is developed to represent an intermediate mesoscale model between the atomistic and continuum scales. This CG model aims to reduce the computational cost relative to a full atomistic simulation, and we assess to what extent it is possible to preserve both the thermodynamic and transport properties of an underlying reference all-atom Lennard-Jones (LJ) system. In this paper, only the thermodynamic properties are considered in detail. The transport properties will be examined in subsequent work. To coarse-grain, we first use the iterative Boltzmann inversion (IBI) to determine a CG potential for a (1-ϕ)N mesoscale particle system, where ϕ is the degree of coarse-graining, so as to reproduce the radial distribution function (RDF) of an N atomic particle system. Even though the uniqueness theorem guarantees a one to one relationship between the RDF and an effective pairwise potential, we find that RDFs are insensitive to the long-range part of the IBI-determined potentials, which provides some significant flexibility in further matching other properties. We then propose a reformulation of IBI as a robust minimization procedure that enables simultaneous matching of the RDF and the fluid pressure. We find that this new method mainly changes the attractive tail region of the CG potentials, and it improves the isothermal compressibility relative to pure IBI. We also find that there are optimal interaction cutoff lengths for the CG system, as a function of ϕ, that are required to attain an adequate potential while maintaining computational speedup. To demonstrate the universality of the method, we test a range of state points for the LJ liquid as well as several LJ chain fluids.

Multi-scale and multi-physics simulations using the multi-fluid plasma model

DTIC Science & Technology

2017-04-25

small The simulation uses 512 second-order elements Bz = 1.0, Te = Ti = 0.01, ui = ue = 0 ne = ni = 1.0 + e−10(x−6) 2 Baboolal, Math . and Comp. Sim. 55...DISTRIBUTION Clearance No. 17211 23 / 31 SUMMARY The blended finite element method (BFEM) is presented DG spatial discretization with explicit Runge...Kutta (i+, n) CG spatial discretization with implicit Crank-Nicolson (e−, fileds) DG captures shocks and discontinuities CG is efficient and robust for

A Theory of Preference Reversals.

DTIC Science & Technology

1984-08-01

the subject mst find sme way to transform-the basic evaluation, uCG ), into a monetary amonnt. we hypothesize that subjects do : this by a process of...the basic equations as follows; MS() = (1 - ()w 7) where, A -[C)- uCG )I/uCW)C) .. Furthermore, we can solve for ulC) by using equation (8); thus, u (a...monetary value of gambles by a method which avoids references to market -type behavior. Grether and Plott asked subjects to give Othe exact dollar

The effects of omega-3 polyunsaturated fatty acids and genetic variants on methylation levels of the interleukin-6 gene promoter

PubMed Central

Ma, Yiyi; Smith, Caren E.; Lai, Chao-Qiang; Irvin, Marguerite R.; Parnell, Laurence D.; Lee, Yu-Chi; Pham, Lucia D.; Aslibekyan, Stella; Claas, Steven A.; Tsai, Michael Y.; Borecki, Ingrid B.; Kabagambe, Edmond K.; Ordovás, José M.; Absher, Devin M.; Arnett, Donna K.

2016-01-01

Scope Omega-3 PUFAs (n-3 PUFAs) reduce IL-6 gene expression, but their effects on transcription regulatory mechanisms are unknown. We aimed to conduct an integrated analysis with both population and in vitro studies to systematically explore the relationships among n-3 PUFA, DNA methylation, single nucleotide polymorphisms (SNPs), gene expression, and protein concentration of IL6. Methods and results Using data in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study and the Encyclopedia of DNA Elements (ENCODE) consortium, we found that higher methylation of IL6 promoter cg01770232 was associated with higher IL-6 plasma concentration (p = 0.03) and greater IL6 gene expression (p = 0.0005). Higher circulating total n-3 PUFA was associated with lower cg01770232 methylation (p = 0.007) and lower IL-6 concentration (p = 0.02). Moreover, an allele of IL6 rs2961298 was associated with higher cg01770232 methylation (p = 2.55 × 10−7). The association between n-3 PUFA and cg01770232 methylation was dependent on rs2961298 genotype (p = 0.02), but higher total n-3 PUFA was associated with lower cg01770232 methylation in the heterozygotes (p = 0.04) not in the homozygotes. Conclusion Higher n-3 PUFA is associated with lower methylation at IL6 promoter, which may be modified by IL6 SNPs. PMID:26518637

Alteration of Cyclic-AMP Response Element Binding Protein in the Postmortem Brain of Subjects with Bipolar Disorder and Schizophrenia

PubMed Central

Ren, Xinguo; Rizavi, Hooriyah S.; Khan, Mansoor A.; Bhaumik, Runa; Dwivedi, Yogesh; Pandey, Ghanshyam N.

2013-01-01

Background Abnormalities of cyclic-AMP (cAMP) response element binding protein (CREB) function has been suggested in bipolar (BP) illness and schizophrenia (SZ), based on both indirect and direct evidence. To further elucidate the role of CREB in these disorders, we studied CREB expression and function in two brain areas implicated in these disorders, i.e., dorsolateral prefrontal cortex (DLPFC) and cingulate gyrus (CG). Methods We determined CREB protein expression using Western blot technique, CRE-DNA binding using gel shift assay, and mRNA expression using real-time RT-polymerase chain reaction (qPCR) in DLPFC and CG of the postmortem brain of BP (n = 19), SZ (n = 20), and normal control (NC, n = 20) subjects. Results We observed that CREB protein and mRNA expression and CRE-DNA binding activity were significantly decreased in the nuclear fraction of DLPFC and CG obtained from BP subjects compared with NC subjects. However, the protein and mRNA expression and CRE-DNA binding in SZ subjects was significantly decreased in CG, but not in DLPFC, compared with NC. Conclusion These studies thus indicate region-specific abnormalities of CREB expression and function in both BP and SZ. They suggest that abnormalities of CREB in CG may be associated with both BP and SZ, but its abnormality in DLPFC is specific to BP illness. PMID:24148789

Hormonal Evidence Supports the Theory of Selection in Utero

PubMed Central

Catalano, RA; Saxton, KB; Bruckner, TA; Pearl, M; Anderson, E; Goldman-Mellor, S; Margerison-Zilko, C; Subbaraman, M; Currier, RJ; Kharrazi, M

2012-01-01

Objectives Antagonists in the debate over whether the maternal stress response during pregnancy damages or culls fetuses have invoked the theory of selection in utero to support opposing positions. We describe how these opposing arguments arise from the same theory and offer a novel test to discriminate between them. Our test, rooted in reports from population endocrinology that human chorionic gonadotropin (hCG) signals fetal fitness, contributes not only to the debate over the fetal origins of illness, but also to the more basic literature concerned with whether and how natural selection in utero affects contemporary human populations. Methods We linked maternal serum hCG measurements from prenatal screening tests with data from the California Department of Public Health birth registry for the years 2001–2007. We used time series analysis to test the association between the number of live born male singletons and median hCG concentration among males in monthly gestational cohorts. Results Among the 1.56 million gestations in our analysis, we find that median hCG levels among male survivors of monthly conception cohorts rise as the number of male survivors falls. Conclusions Elevated median hCG among relatively small male birth cohorts supports the theory of selection in utero and suggests that the maternal stress response culls cohorts in gestation by raising the fitness criterion for survival to birth. PMID:22411168

Contact allergy to a contaminant in Kathon CG in the guinea pig.

PubMed

Bruze, M; Gruvberger, B; Persson, K

1987-01-01

Kathon CG is a commercial preservative, consisting of the two active ingredients, 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one (5243-K-CG) and other components. 4,5-dichloro-2-methyl-4-isothiazolin-3-one (45243-K-CG) is a contaminant in Kathon CG. The chemically related active ingredients are known to be contact sensitizers in humans and guinea pigs. Aims of this study were to determine the sensitizing capacity of this contaminant and also to investigate the cross-reaction pattern by guinea pig sensitization tests. 45243-K-CG was demonstrated to be a strong sensitizer; all animals reacting to 45243-K-CG also reacted to 5243-K-CG when rechallenged.

HCG-. beta. -subunit radioimmunoassay: potential error in HCG measurement related to choice of labeled antigen. [/sup 125/I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyrey, L.; Hammond, C.B.

1976-05-15

Antiserum generated against the hormone-specific ..beta..-subunit of hCG was used with different labeled antigens to measure circulating hCG in patients having trophoblastic disease. When /sup 125/I-hCG..beta.. served as the labeled antigen, a small number of patient sera failed to show parallelism with the second IS-hCG reference and erroneous estimates of hormone concentrations were obtained. Replacement of the /sup 125/I-hCG..beta.. with labeled hCG corrected the nonparallelism exhibited by these samples. Inhibition curves obtained with purified hCG and hCG..beta.. suggested that both the nonparallelism and its correction with the change in labeled antigen would be consistent with the possibility that this assaymore » aberration may result from the presence of free hCG..beta.. in these sera. (auth)« less

hCG - related molecules and their measurement.

PubMed

Szczerba, Anna; Białas, Piotr; Pięta, Paweł Piotr; Jankowska, Anna

2016-01-01

Measurements of human chorionic gonadotropin (hCG) synthesized by trophoblast cells is a powerful tool of pregnancy monitoring. It was showed that similarly to pregnancy also trophoblastic and nontrophoblastic malignancies produce variety of hCG molecules. In urine and serum of both pregnant women and tumors patients a fifteen various forms of hCG, such as: regular hCG, hyperglycosylated hCG and predominant hyperglycosylated hCG free β, were identified. These forms might be useful in order to recognize between physiological and pathological pregnancies as well as cancers. Even the presence of these different hormone variants is well documented the commercially available biochemical tests detecting hCG failed to identified and distinguish among these forms. Especially hard is to identify glycan chains linked to heterodimer. Thus, a detailed analysis of hCG-related molecules produced during physiological and pathological condition, together with a new tests development are needed.

Anxiety Sensitivity in Bereaved Adults with and without Complicated Grief

PubMed Central

Robinaugh, Donald J.; McNally, Richard J.; LeBlanc, Nicole J.; Pentel, Kimberly Z.; Schwarz, Noah R.; Shah, Riva M.; Nadal-Vicens, Mireya F.; Moore, Cynthia W.; Marques, Luana; Bui, Eric; Simon, Naomi M.

2014-01-01

Complicated grief (CG) is a bereavement specific syndrome chiefly characterized by symptoms of persistent separation distress. Physiological reactivity to reminders of the loss and repeated acute pangs or waves of severe anxiety and psychological pain are prominent features of CG. Fear of this grief-related physiological arousal may contribute to CG by increasing the distress associated with grief reactions and increasing the likelihood of maladaptive coping strategies and grief-related avoidance. Here, we examined anxiety sensitivity (i.e., the fear of anxiety-related sensations; AS) in two studies of bereaved adults with and without CG. In both studies, bereaved adults with CG exhibited elevated AS relative to those without CG. In Study 2, AS was positively associated with CG symptom severity among those with CG. These findings are consistent with the possibility that AS contributes to the development or maintenance of CG symptoms. PMID:25075646

SDS-PAGE Electrophoretic Property of Human Chorionic Gonadotropin (hCG) and its β-subunit

PubMed Central

2005-01-01

The microheterogeneity property of hCG with regards to its sialic acid contents resulted in variable mobility of the glycoprotein in SDS-PAGE. The intact hCG molecule is composed of two dissimilar subunits, namely α- and β-subunits. The identification of hCG bands in SDS-PAGE was accomplished by the immunoblotting experiment, whereby the antibody directed toward the specific region of β-subunit of hCG was used. The data shows that the different mobility of intact hCG was attributed to the different degree of desialylation of the glycoprotein. Nevertheless, unlike the intact hCG, the mobility of its β-subunit was not affected by its variety sialic acid content. This characteristic of β-hCG is beneficial when semi-quantification of total hCG is required. Quantification of hCG using the HPLC-reversed phase C18 analytical column is not possible as the glycoprotein was eluted in multiple fractions at different retention times. The identification of denatured hCG (HPLC eluted fractions) was carried out by immunoblotting experiment whilst immunoassay technique failed to detect its presence in any fraction. PMID:16094462

Effect of carrageenan addition on the rennet-induced gelation of skim milk.

PubMed

Wang, Fang; Zhang, Wei; Ren, Fazheng

2016-09-01

Carrageenan (CG) (κ-CG, ι-CG and λ-CG) was added to skim milk and the rennet-induced aggregation was studied. Caseinomacropeptide (CMP) release, diffusing wave spectroscopy (DWS) and rheology were used to follow the structural dynamics of casein micelles during gelation. The influence of carrageenan on the nature of protein interactions in the gels was investigated using a combination of ultracentrifugation and specific dissociating agents. For the recombined samples containing κ-CG and low concentrations of ι-CG and λ-CG, the CMP release was slowed down; however, the development of DWS and rheological parameters was similar to that of the control sample, and the increase in the incorporation of proteins through calcium bridges and hydrophobic interactions may be the most likely contributors. For the recombined samples containing high concentrations of ι-CG and λ-CG, other factors may impede the gel formation process. High concentrations of ι-CG and λ-CG strongly interfered with the rennet-induced aggregation, interrupted the interaction of caseins and therefore may contribute to good quality of low-fat cheese. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Pituitary origin of persistently elevated human chorionic gonadotropin in a patient with gonadal failure.

PubMed

Merhi, Zaher; Pollack, Staci E

2013-01-01

To report a case of persistently elevated low levels of hCG to increase awareness of pituitary origin of persistently elevated hCG in patients with gonadal failure. Case report and literature review. Large university-affiliated infertility practice. A 16-year-old patient with primary amenorrhea, normal secondary sex characteristics, ovarian failure, and a 46,XY karyotype. Her past medical history was significant for focal segmental glomerulosclerosis, leading to a diagnosis of Frasier syndrome. At age 31 years, she desired pregnancy by oocyte donation and was found to have persistently elevated low levels of hCG (>35 mIU/mL). Pituitary hCG. Both serum free β-hCG and hyperglycosylated hCG were undetectable. Total serum hCG diluted appropriately was not blocked by blocking agent and was detected in the urine. Subsequent treatment with exogenous E(2), in preparation of a donor oocyte cycle, suppressed her hCG levels (down to 8 mIU/mL). These results indicated a pituitary source of the serum hCG. This report reinforces the need to consider pituitary hCG as the origin of persistently elevated hCG levels in patients with gonadal failure. Although levels of hCG <14 mIU/mL have been considered normal in postmenopausal women, our case suggests that patients with gonadal failure at younger ages might have a higher pituitary output of hCG. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

New discoveries on the biology and detection of human chorionic gonadotropin

PubMed Central

Cole, Laurence A

2009-01-01

Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic disease, diagnosing placental site trophoblastic tumor, managing testicular germ cell malignancies, and monitoring other human malignancies. There are very few molecules with such wide and varying functions as regular hCG and its variants, and very few tests with such a wide spectrum of clinical applications as total hCG. PMID:19171054

Cloud-to-ground lightning and surface rainfall in warm-season Florida thunderstorms

USGS Publications Warehouse

Gungle, B.; Krider, E.P.

2006-01-01

Relationships between cloud-to-ground (CG) lightning and surface rainfall have been examined in nine isolated, warm-season thunderstorms on the east coast of central Florida. CG flashes and the associated rain volumes were measured as a function of time in storm-centered reference frames that followed each storm over a network of rain gauges. Values of the storm-average rain volume per CG flash ranged from 0.70 ?? 104 to 6.4 ?? 104 m3/CG flash, with a mean (and standard deviation) of 2.6 ?? 104 ?? 2.1 ?? 104 m3/CG flash. Values of the rain volume concurrent with CG flashes ranged from 0.11 ?? 104 to 4.9 ?? 104 m3/CG flash with a mean of 2.1 ?? 104 ?? 2.0 ?? 104 m3/CG flash. The lag-time between the peak CG flash rate and the peak rainfall rate (using 5 min bins), and the results of a lag correlation analysis, show that surface rainfall tends to follow the lightning (positive lag) by up to 20 min in six storms. In one storm the rainfall preceded the lightning by 5 min, and two storms had nonsignificant lags. Values of the lagged rain volume concurrent with CG flashes ranged from 0.43 ?? 104 to 4.9 ?? 104 m3/CG flash, and the mean was 1.9 ?? 104 ?? 1.7 ?? 104 m3/CG flash. For the five storms that produced 12 or more flashes and had significant lags, a plot of the optimum lag time versus the total number of CG flashes shows a linear trend (R2 = 0.56). The number of storms is limited, but the lag results do indicate that large storms tend to have longer lags. A linear fit to the lagged rain volume vs. the number of concurrent CG flashes has a slope of 1.9 ?? 104 m3/CG flash (R2 = 0.83). We conclude that warm-season Florida thunderstorms produce a roughly constant rain volume per CG flash and that CG lightning can be used to estimate the location and intensity of convective rainfall in that weather regime. Copyright 2006 by the American Geophysical Union.

Human Chorionic Gonadotropin: Unknown about Known.

PubMed

Borisova, M A; Moiseenko, D Yu; Smirnova, O V

2017-01-01

The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.

Density gradient centrifugation of sperm from a subfertile stallion and effect of seminal plasma addition on fertility.

PubMed

Mari, Gaetano; Castagnetti, Carolina; Rizzato, Giovanni; Mislei, Beatrice; Iacono, Eleonora; Merlo, Barbara

2011-06-01

Stallions are not selected for fertility but for other criteria (pedigree, conformation, performances, progeny), therefore valuable but subfertile stallions with poor semen quality are frequently used in commercial breeding programs. The object of this study was to evaluate whether sperm selection through a silane-coated silica colloid gradient centrifugation, with or without the addition of seminal plasma of a high fertile stallion, could improve the pregnancy rates of an oligospermic valuable stallion in a commercial breeding program. In 2008 breeding season (experiment 1, n=104 mares), simple centrifugation and density gradient centrifugation of the sperm were compared. In 2009 and 2010 breeding seasons (experiment 2, n=125 mares), the effect of the addition of 5% seminal plasma to the extender after sperm selection was evaluated. In all mares deep horn uterine insemination was performed with 1 ml containing 50×10(6) morphologically normal progressive motile spermatozoa, 24-30 h after induction of ovulation with hCG. Pregnancy diagnosis by ultrasonography was performed 14 days following ovulation. Results showed a higher per cycle pregnancy rate (P>0.05) when sperm selection through a density gradient was used (62% vs. 42.3%, exp 1), while the addition of 5% seminal plasma did not influence the outcome (45.9% vs. 47.6%, exp 2) (P>0.05). An age-related decrease in the fertility of the stallion was observed when comparing the results from the different breeding seasons (P<0.05). In conclusion, sperm selection through a discontinuous density gradient enabled a normal per cycle pregnancy rate to be achieved from an oligospermic-subfertile stallion in a commercial breeding program, and no differences were observed regarding the addition of seminal plasma. Copyright © 2011 Elsevier B.V. All rights reserved.

Transfer of Motor Learning Is More Pronounced in Proximal Compared to Distal Effectors in Upper Extremities

PubMed Central

Aune, Tore K.; Aune, Morten A.; Ingvaldsen, Rolf P.; Vereijken, Beatrix

2017-01-01

The current experiment investigated generalizability of motor learning in proximal versus distal effectors in upper extremities. Twenty-eight participants were divided into three groups: training proximal effectors, training distal effectors, and no training control group (CG). Performance was tested pre- and post-training for specific learning and three learning transfer conditions: (1) bilateral learning transfer between homologous effectors, (2) lateral learning transfer between non-homologous effectors, and (3) bilateral learning transfer between non-homologous effectors. With respect to specific learning, both training groups showed significant, similar improvement for the trained proximal and distal effectors, respectively. In addition, there was significant learning transfer to all three transfer conditions, except for bilateral learning transfer between non-homologous effectors for the distal training group. Interestingly, the proximal training group showed significantly larger learning transfer to other effectors compared to the distal training group. The CG did not show significant improvements from pre- to post-test. These results show that learning is partly effector independent and generalizable to different effectors, even though transfer is suboptimal compared to specific learning. Furthermore, there is a proximal-distal gradient in generalizability, in that learning transfer from trained proximal effectors is larger than from trained distal effectors, which is consistent with neuroanatomical differences in activation of proximal and distal muscles. PMID:28943857

Micromechanical properties of single crystals and polycrystals of pure α-titanium: anisotropy of microhardness, size effect, effect of the temperature (77-300 K)

NASA Astrophysics Data System (ADS)

Lubenets, S. V.; Rusakova, A. V.; Fomenko, L. S.; Moskalenko, V. A.

2018-01-01

The anisotropy of microhardness of pure α-Ti single crystals, indentation size effect in single-crystal, course grained (CG) pure and nanocrystalline (NC) VT1-0 titanium, as well as the temperature dependences of the microhardness of single-crystal and CG Ti in the temperature range 77-300 K were studied. The minimum value of hardness was obtained when indenting into the basal plane (0001). The indentation size effect (ISE) was clearly observed in the indentation of soft high-purity single-crystal iodide titanium while it was the least pronounced in a sample of nanocrystalline VT1-0 titanium. It has been demonstrated that the ISE can be described within the model of geometrically necessary dislocations (GND), which follows from the theory of strain gradient plasticity. The true hardness and others parameters of the GND model were determined for all materials. The temperature dependence of the microhardness is in agreement with the idea of the governing role of Peierls relief in the dislocation thermally-activated plastic deformation of pure titanium as has been earlier established and justified in macroscopic tensile investigations at low temperatures. The activation energy and activation volume of dislocation motion in the strained region under the indenter were estimated.

A new deadlock resolution protocol and message matching algorithm for the extreme-scale simulator

DOE PAGES

Engelmann, Christian; Naughton, III, Thomas J.

2016-03-22

Investigating the performance of parallel applications at scale on future high-performance computing (HPC) architectures and the performance impact of different HPC architecture choices is an important component of HPC hardware/software co-design. The Extreme-scale Simulator (xSim) is a simulation toolkit for investigating the performance of parallel applications at scale. xSim scales to millions of simulated Message Passing Interface (MPI) processes. The overhead introduced by a simulation tool is an important performance and productivity aspect. This paper documents two improvements to xSim: (1)~a new deadlock resolution protocol to reduce the parallel discrete event simulation overhead and (2)~a new simulated MPI message matchingmore » algorithm to reduce the oversubscription management overhead. The results clearly show a significant performance improvement. The simulation overhead for running the NAS Parallel Benchmark suite was reduced from 102% to 0% for the embarrassingly parallel (EP) benchmark and from 1,020% to 238% for the conjugate gradient (CG) benchmark. xSim offers a highly accurate simulation mode for better tracking of injected MPI process failures. Furthermore, with highly accurate simulation, the overhead was reduced from 3,332% to 204% for EP and from 37,511% to 13,808% for CG.« less

Serum Human Chorionic Gonadotropin (β- hCG) Clearance Curves in Women with Successfully Expectantly Managed Tubal Ectopic Pregnancies: A Retrospective Cohort Study

PubMed Central

Helmy, Samir; Mavrelos, Dimitrios; Sawyer, Elinor; Ben-Nagi, Jara; Koch, Marianne; Day, Andrea; Jurkovic, Davor

2015-01-01

Objective To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies. Design Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative. Setting Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006). Patients We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management. Main outcome measure Serum β hCG level. Results Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05). Conclusion We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management. PMID:26135923

A novel HLA-A*0201 restricted peptide derived from cathepsin G is an effective immunotherapeutic target in acute myeloid leukemia.

PubMed

Zhang, Mao; Sukhumalchandra, Pariya; Enyenihi, Atim A; St John, Lisa S; Hunsucker, Sally A; Mittendorf, Elizabeth A; Sergeeva, Anna; Ruisaard, Kathryn; Al-Atrache, Zein; Ropp, Patricia A; Jakher, Haroon; Rodriguez-Cruz, Tania; Lizee, Gregory; Clise-Dwyer, Karen; Lu, Sijie; Molldrem, Jeffrey J; Glish, Gary L; Armistead, Paul M; Alatrash, Gheath

2013-01-01

Immunotherapy targeting aberrantly expressed leukemia-associated antigens has shown promise in the management of acute myeloid leukemia (AML). However, because of the heterogeneity and clonal evolution that is a feature of myeloid leukemia, targeting single peptide epitopes has had limited success, highlighting the need for novel antigen discovery. In this study, we characterize the role of the myeloid azurophil granule protease cathepsin G (CG) as a novel target for AML immunotherapy. We used Immune Epitope Database and in vitro binding assays to identify immunogenic epitopes derived from CG. Flow cytometry, immunoblotting, and confocal microscopy were used to characterize the expression and processing of CG in AML patient samples, leukemia stem cells, and normal neutrophils. Cytotoxicity assays determined the susceptibility of AML to CG-specific cytotoxic T lymphocytes (CTL). Dextramer staining and cytokine flow cytometry were conducted to characterize the immune response to CG in patients. CG was highly expressed and ubiquitinated in AML blasts, and was localized outside granules in compartments that facilitate antigen presentation. We identified five HLA-A*0201 binding nonameric peptides (CG1-CG5) derived from CG, and showed immunogenicity of the highest HLA-A*0201 binding peptide, CG1. We showed killing of primary AML by CG1-CTL, but not normal bone marrow. Blocking HLA-A*0201 abrogated CG1-CTL-mediated cytotoxicity, further confirming HLA-A*0201-dependent killing. Finally, we showed functional CG1-CTLs in peripheral blood from AML patients following allogeneic stem cell transplantation. CG is aberrantly expressed and processed in AML and is a novel immunotherapeutic target that warrants further development.

A novel siglec (CgSiglec-1) from the Pacific oyster (Crassostrea gigas) with broad recognition spectrum and inhibitory activity to apoptosis, phagocytosis and cytokine release.

PubMed

Liu, Conghui; Jiang, Shuai; Wang, Mengqiang; Wang, Lingling; Chen, Hao; Xu, Jiachao; Lv, Zhao; Song, Linsheng

2016-08-01

Sialic acid binding immunoglobulin-type lectin (siglec) belongs to the immunoglobulin superfamily (IgSF), which acts as regulator involved in glycan recognition and signal transduction in the immune and nervous systems. In the present study, a siglec gene (designated CgSiglec-1) was characterized from the Pacific oyster, Crassostrea gigas. The cDNA of CgSiglec-1 was of 1251 bp encoding a predicted polypeptide of 416 amino acids. CgSiglec-1 was composed of two I-set immunoglobulin (Ig) domains, one transmembrane (TM) domain and two ITIM motifs, sharing a sequence similarity with vertebrate CD22 homologs. The mRNA expression of CgSiglec-1 could be detected in all the selected tissues, with the highest level in hemocytes and labial palps. The confocal analysis revealed that CgSiglec-1 mainly distributed on the cytoplasmic membrane of the oyster hemocytes. In addition, the mRNA transcripts of CgSiglec-1 in hemocytes increased significantly (4.29-fold to that of control group, p < 0.05) after Vibrio splendidus stimulation. The recombinant CgSiglec-1 protein (rCgSiglec-1) could bind to poly sialic acid (pSIAS), lipopolysaccharides (LPS) and peptidoglycan (PGN) in a dose-dependent manner. The blockade of CgSiglec-1 by specific polyclonal antibodies could enhance the LPS-induced cell apoptosis, phagocytosis towards V. splendidus and the release of cytokines, such as CgTNF-1, CgIFNLP and CgIL-17. The results collectively indicated that CgSiglec-1 could act as a bridge molecule between invader recognition and signal transduction cascade, and modulate the immune response by inhibiting various important processes of immunity in oyster. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bayesian calibration of coarse-grained forces: Efficiently addressing transferability

NASA Astrophysics Data System (ADS)

Patrone, Paul N.; Rosch, Thomas W.; Phelan, Frederick R.

2016-04-01

Generating and calibrating forces that are transferable across a range of state-points remains a challenging task in coarse-grained (CG) molecular dynamics. In this work, we present a coarse-graining workflow, inspired by ideas from uncertainty quantification and numerical analysis, to address this problem. The key idea behind our approach is to introduce a Bayesian correction algorithm that uses functional derivatives of CG simulations to rapidly and inexpensively recalibrate initial estimates f0 of forces anchored by standard methods such as force-matching. Taking density-temperature relationships as a running example, we demonstrate that this algorithm, in concert with various interpolation schemes, can be used to efficiently compute physically reasonable force curves on a fine grid of state-points. Importantly, we show that our workflow is robust to several choices available to the modeler, including the interpolation schemes and tools used to construct f0. In a related vein, we also demonstrate that our approach can speed up coarse-graining by reducing the number of atomistic simulations needed as inputs to standard methods for generating CG forces.

Water-Soluble Dried Blood Spot in Protein Analysis: A Proof-of-Concept Study.

PubMed

Rosting, Cecilie; Gjelstad, Astrid; Halvorsen, Trine Grønhaug

2015-08-04

In the present work human chorionic gonadotropin (hCG) was used as a model protein in a proof-of-concept study combining water-soluble dried blood spot (DBS) material in liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based protein analysis. A water-soluble material consisting of commercially available carboxymethyl cellulose (CMC) was evaluated as sampling material for this purpose. The material dissolved readily at physiological pH. Different sample preparation methods were evaluated, and in the final method, 15 μL of whole blood was deposited and dried on CMC before the whole spot was dissolved prior to cleanup by immunoaffinity extraction, tryptic digest, and preconcentration by solid-phase extraction (SPE). The results indicated complete dissolution of hCG from the spots, acceptable limit of detection (LOD) (0.1 IU/mL), linearity (R(2) = 0.959), accuracy (16%), and precision (≤22%). Long-term stability (45 days) of hCG in dried spots at reduced temperatures (≤8 °C) was also demonstrated. The analyte recovery was comparable to the commercially available nonsolvable cellulose material (FTA DMPK-C card).

Serum human chorionic gonadotropin levels on the day before oocyte retrieval do not correlate with oocyte maturity

PubMed Central

Levy, Gary; Hill, Micah J.; Ramirez, Christina; Plowden, Torrie; Pilgrim, Justin; Howard, Robin S.; Segars, James H.; Csokmay, John

2014-01-01

Objective To evaluate the correlation of preretrieval quantitative serum hCG level with oocyte maturity. Design Retrospective cohort study. Setting Military assisted reproductive technology (ART) program. Patient(s) Fresh autologous ART cycles. Intervention(s) Serum hCG level the day before oocyte retrieval. Main Outcome Measure(s) Linear regression was used to correlate serum hCG levels and oocyte maturity rates. Normal oocyte maturity was defined as ≥ 75% and the Wilcoxon rank sum test was used to compare serum hCG levels in patients with normal and low oocyte maturity. Threshold analysis was performed to determine hCG levels that could predict oocyte maturity. Result(s) A total of 468 ART cycles were analyzed. Serum hCG level was not correlated with hCG dose; however, it was negatively correlated with body mass index (BMI). Serum hCG levels did not differ between patients with oocyte maturity of <75% and ≥ 75%. Serum hCG levels did not correlate with oocyte maturity rates. Receiver operator characteristic and less than efficiency curves failed to demonstrate thresholds at which hCG could predict oocyte maturity. Conclusion(s) Serum hCG levels were not correlated with oocyte maturity. Although a positive hCG was reassuring that mature oocytes would be retrieved for most patients, the specific value was not helpful. PMID:23375205

Serum hCG Levels following the Ovulatory Injection: Associations with Patient Weight and Implantation Time

PubMed Central

Noorhasan, Dorette J.; McGovern, Peter G.; Cho, Michael; Seungdamrong, Aimee; Ahmad, Khaliq; McCulloh, David H.

2015-01-01

Objective. To test if serum hCG levels the morning after the ovulatory hCG injection correlate with (1) retrieval efficiency, (2) oocyte maturity, (3) embryo quality, (4) pregnancy, and/or (5) time to implantation in patients undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). Design. Retrospective cohort analysis. Setting. University-based IVF clinic. Patient(s). All IVF/ICSI cycles from April 2005 to February 2008 whose hCG administration was confirmed (n = 472 patients). Intervention(s). Serum hCG was measured the morning following the ovulatory injection, on the 16th day following retrieval, and repeated on day 18 for those with positive results. Main Outcome Measure(s). Number of follicles on the day of hCG injection, number of oocytes retrieved, maturity of oocytes, embryo quality, pregnancy outcome, and time to implantation. Result(s). hCG levels did not correlate with retrieval efficiency, oocyte maturity, embryo quality, or pregnancy. Postinjection hCG levels were inversely associated with patient weight and time to implantation. Conclusion(s). No correlation was found between hCG level and any parameter of embryo quality. Patient weight affected hCG levels following hCG injection and during the early period of pregnancy following implantation. No association between postinjection hCG level and time of implantation (adjusted for patient weight) was apparent. PMID:26587025

Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations.

PubMed

Koistinen, Hannu; Hautala, Laura; Koli, Katri; Stenman, Ulf-Håkan

2015-12-01

Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies.

Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations

PubMed Central

Hautala, Laura; Koli, Katri; Stenman, Ulf-Håkan

2015-01-01

Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-β receptor (TGFβR) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-β1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGFβR in mink lung epithelial cells transfected with a reporter gene for TGFβR activation. No such activation was found with highly purified hCG or its free β-subunit (hCGβ), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGFβR and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies. PMID:26495869

On the representability problem and the physical meaning of coarse-grained models

NASA Astrophysics Data System (ADS)

Wagner, Jacob W.; Dama, James F.; Durumeric, Aleksander E. P.; Voth, Gregory A.

2016-07-01

In coarse-grained (CG) models where certain fine-grained (FG, i.e., atomistic resolution) observables are not directly represented, one can nonetheless identify indirect the CG observables that capture the FG observable's dependence on CG coordinates. Often, in these cases it appears that a CG observable can be defined by analogy to an all-atom or FG observable, but the similarity is misleading and significantly undermines the interpretation of both bottom-up and top-down CG models. Such problems emerge especially clearly in the framework of the systematic bottom-up CG modeling, where a direct and transparent correspondence between FG and CG variables establishes precise conditions for consistency between CG observables and underlying FG models. Here we present and investigate these representability challenges and illustrate them via the bottom-up conceptual framework for several simple analytically tractable polymer models. The examples provide special focus on the observables of configurational internal energy, entropy, and pressure, which have been at the root of controversy in the CG literature, as well as discuss observables that would seem to be entirely missing in the CG representation but can nonetheless be correlated with CG behavior. Though we investigate these problems in the framework of systematic coarse-graining, the lessons apply to top-down CG modeling also, with crucial implications for simulation at constant pressure and surface tension and for the interpretations of structural and thermodynamic correlations for comparison to experiment.

Scaling Analysis of Ocean Surface Turbulent Heterogeneities from Satellite Remote Sensing: Use of 2D Structure Functions.

PubMed

Renosh, P R; Schmitt, Francois G; Loisel, Hubert

2015-01-01

Satellite remote sensing observations allow the ocean surface to be sampled synoptically over large spatio-temporal scales. The images provided from visible and thermal infrared satellite observations are widely used in physical, biological, and ecological oceanography. The present work proposes a method to understand the multi-scaling properties of satellite products such as the Chlorophyll-a (Chl-a), and the Sea Surface Temperature (SST), rarely studied. The specific objectives of this study are to show how the small scale heterogeneities of satellite images can be characterised using tools borrowed from the fields of turbulence. For that purpose, we show how the structure function, which is classically used in the frame of scaling time series analysis, can be used also in 2D. The main advantage of this method is that it can be applied to process images which have missing data. Based on both simulated and real images, we demonstrate that coarse-graining (CG) of a gradient modulus transform of the original image does not provide correct scaling exponents. We show, using a fractional Brownian simulation in 2D, that the structure function (SF) can be used with randomly sampled couple of points, and verify that 1 million of couple of points provides enough statistics.

AtPP2CG1, a protein phosphatase 2C, positively regulates salt tolerance of Arabidopsis in abscisic acid-dependent manner

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xin, E-mail: fangfei6073@126.com; Zhu, Yanming, E-mail: ymzhu2001@neau.edu.cn; Zhai, Hong, E-mail: Zhai.h@neigaehrb.ac.cn

2012-06-15

Highlights: Black-Right-Pointing-Pointer AtPP2CG1 positively regulates salt tolerance in ABA-dependent manner. Black-Right-Pointing-Pointer AtPP2CG1 up-regulates the expression of marker genes in different pathways. Black-Right-Pointing-Pointer AtPP2CG1 expresses in the vascular system and trichomes of Arabidopsis. -- Abstract: AtPP2CG1 (Arabidopsis thaliana protein phosphatase 2C G Group 1) was predicted as an abiotic stress candidate gene by bioinformatic analysis in our previous study. The gene encodes a putative protein phosphatase 2C that belongs to Group G of PP2C. There is no report of Group G genes involved in abiotic stress so far. Real-time RT-PCR analysis showed that AtPP2CG1 expression was induced by salt, drought, andmore » abscisic acid (ABA) treatment. The expression levels of AtPP2CG1 in the ABA synthesis-deficient mutant abi2-3 were much lower than that in WT plants under salt stress suggesting that the expression of AtPP2CG1 acts in an ABA-dependent manner. Over-expression of AtPP2CG1 led to enhanced salt tolerance, whereas its loss of function caused decreased salt tolerance. These results indicate that AtPP2CG1 positively regulates salt stress in an ABA-dependent manner. Under salt treatment, AtPP2CG1 up-regulated the expression levels of stress-responsive genes, including RD29A, RD29B, DREB2A and KIN1. GUS activity was detected in roots, leaves, stems, flower, and trichomes of AtPP2CG1 promoter-GUS transgenic plants. AtPP2CG1 protein was localized in nucleus and cytoplasm via AtPP2CG1:eGFP and YFP:AtPP2CG1 fusion approaches.« less

hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG.

PubMed

Norman, R J; Buchholz, M M; Somogyi, A A; Amato, F

2000-03-01

The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the beta core fragment of hCG (hCGbetacf). Serum and urine samples were collected from six subjects, after an intravenous injection of 2 mg (equivalent to 44 000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGbeta). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGbetacf and hCG. r-hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4+/-0.7 l (mean+/-s.d.) and then in 6.5+/-1.15 l at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5+/-0.7 h and a terminal half-life of 29.0+/-4.6 h. The mean residence time was 28. 6+/- 3.6 h and the total systemic clearance rate of r-hCG was 226+/-18 ml/h. The renal clearance rate was 28.75+/-6.2 ml/h (mean+/-s.d). hCGbetacf was detected in all urine samples collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3% ) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGbetacf, in 4 subjects. The molar ratio of hCGbetacf to hCG in urine increased from 3.1+/-1.7%, on day 1, to 76+/-34.3% (mean+/-s.e.m.) on day 5, after r-hCG infusion, suggesting that hCGbetacf is a metabolic product of the infused r-hCG.

Circadian gene methylation profiles are associated with obesity, metabolic disturbances and carbohydrate intake.

PubMed

Ramos-Lopez, Omar; Samblas, Mirian; Milagro, Fermin I; Riezu-Boj, Jose I; Crujeiras, A B; Martinez, J Alfredo; Project, Mena

2018-03-26

The circadian clock regulates the daily rhythms of several physiological and behavioral processes. Disruptions in clock genes have been associated with obesity and related comorbidities. This study aimed to analyze the association of DNA methylation signatures at circadian rhythm pathway genes with body mass index (BMI), metabolic profiles and dietary intakes. DNA methylation profiling was determined by microarray in white blood cells from 474 adults from the Methyl Epigenome Network Association (MENA) project. Kyoto Encyclopedia of Genes and Genomes database was used to identify the genes integrating the circadian rhythm pathway. Network enrichment analyses were performed with the PathDIP platform. Associations between circadian methylation patterns with anthropometric measurements, the metabolic profile, clinical data and dietary intakes were analyzed. DNA methylation patterns of nine CpG sites at six circadian rhythm pathway genes were strongly correlated with BMI (false discovery rates <0.0001). These CpGs encompassed cg09578018 (RORA), cg20406576 (PRKAG2), cg10059324 (PER3), cg01180628 (BHLHE40), cg23871860 (FBXL3), cg16964728 (RORA), cg14129040 (CREB1), cg07012178 (PRKAG2) and cg24061580 (PRKAG2). Interestingly, network enrichment analyses revealed that the six BMI-associated genes statistically contributed to the regulation of the circadian rhythm pathway (p = 1.9E-10). In addition, methylation signatures at cg09578018 (RORA), cg24061580 (PRKAG2), cg01180628 (BHLHE40) and cg10059324 (PER3) also correlated with insulin resistance (p < 0.0001) and mean arterial blood pressure (p < 0.0001). Furthermore, relevant correlations (p < 0.05) between methylation at cg09578018 (RORA) and cg01180628 (BHLHE40) with total energy and carbohydrate intakes were found. This investigation revealed potential associations of DNA methylation profiles at circadian genes with obesity, metabolic disturbances and carbohydrate intake, with potential impact on weight homeostasis.

Orthodontic treatment outcomes obtained by application of a finishing protocol

PubMed Central

Carvajal-Flórez, Alvaro; Barbosa-Lis, Diana María; Zapata-Noreña, Oscar Arturo; Marín-Velásquez, Julissa Andrea; Afanador-Bayona, Sergio Andrés

2016-01-01

ABSTRACT Objective: To evaluate the results of a finishing protocol implemented in patients treated in the Orthodontics graduate program at Universidad de Antioquia. Evaluation was carried out by means of the criteria set by the Objective Grading System (OGS) of the American Board of Orthodontics (ABO). Methods: Cast models and panoramic radiographs of 34 patients were evaluated. The intervention group (IG) consisted of 17 patients (19.88 ± 4.4 years old) treated under a finishing protocol. This protocol included training in finishing, application of a finishing guide, brackets repositioning and patient's follow-up. Results of the IG were compared to a control group of 17 patients (21.88 ± 7.0 years old) selected by stratified randomization without finishing intervention (CG). Results: The scores for both CG and IG were 38.00 ± 9.0 and 31.41 ± 9.6 (p = 0.048), respectively. The score improved significantly in the IG group, mainly regarding marginal ridges (CG: 5.59 ± 2.2; IG: 3.65 ± 1.8) (p = 0.009) and root angulation (CG: 7.59 ± 2.8; IG: 4.88 ± 2.6) (p = 0.007). Criteria that did not improve, but had the highest scores were: alignment (CG: 6.35 ± 2.7; IG: 6.82 ± 2.8) (p = 0.62) and buccolingual inclination (CG: 3.6 ± 5.88; IG: 5.29 ± 3.9) (p = 0.65). Conclusions: Standardization and implementation of a finishing protocol contributed to improve clinical performance in the Orthodontics graduate program, as expressed by occlusal outcomes. Greater emphasis should be given on the finishing phase to achieve lower scores in the ABO grading system. PMID:27275620

A prospective controlled study: Minimally invasive stereotactic puncture therapy versus conventional craniotomy in the treatment of acute intracerebral hemorrhage

PubMed Central

2011-01-01

Background Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke with the high mortality twofold to sixfold higher than that for ischemic stroke. But the treatment of haematomas within the basal ganglia continues to be a matter of debate among neurologists and neurosurgeons. The purpose of this study is to judge the clinical value of minimally invasive stereotactic puncture therapy (MISPT) on acute ICH. Methods A prospective controlled study was undertaken. The clinical trial was in compliance with the WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. According to the enrollment criterion, there were 168 acute ICH cases analyzed, of which 90 cases were performed by MISPT ( MISPT group, MG) and 78 cases by Conventional craniotomy (CC group, CG), by means of compare of Glasgow Coma Scale(GCS) score, postoperative complications(PC) and rebleeding incidence(RI), moreover, long-term outcome of 1 year postoperation judged by Glasgow Outcome Scale (GOS), Barthel Index (BI), modified Rankin Scale (mRS) and case fatality(CF). Results MG patients showed obvious amelioration in GCS score compared with that of CG. The total incidence of PC in MG decreased obviously compared with that of CG. The incidences of rebleeding in MG and CG were 10.0% and 15.4% respectively. There was no obvious difference between CFs of MG and CG. For three parameters representing long-term outcome, the GOS, BI and mRS in MG were ameliorated significantly than that of CG. Conclusion These data suggested that the advantage of MISPT was displayed in minute trauma and safety, and seemed to be feasible and to had a trend towards improved long-term outcome. Trial Registration The Australian New Zealand Clinical Trials Registry (ANZCTR), the registration number:ACTRN12610000945022. PMID:21699716

Development of an assay for a biomarker of pregnancy and early fetal loss

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canfield, R.E.; O'Connor, J.F.; Birken, S.

1987-10-01

Human chorionic gonadotropin (hCG) is a glycoprotein hormone, secreted by the syncytiotrophoblast cells of the fertilized ovum, that enters the maternal circulation at the time of endometrial implantation. It is composed of two nonidentical subunits; ..cap alpha.. and ..beta.., with molecular weights of 14 kD and 23 kD, respectively. Human chorionic gonadotropin binds to the same receptor as hLH and displays the same biological response, namely, to stimulate the declining function of the corpus luteum to produce progestins and estrogen late in the menstrual cycle. The differences in the structures of hCG and hLH have been exploited to develop antibodiesmore » that can measure hCG specifically in the presence of hLH. Two-site antibody binding assays have been developed, based on a surface immunological concept of hCG epitopes, that involve four distinct regions to which antibodies against hCG can bind simultaneously. Antibody cooperative effects, in conjunction with kinetic advantages derived from the concentration factors by use of the sandwich assay technique (immunoradiometric assay, IRMA), have enabled development of extremely sensitive and specific measurement protocols for urinary hCG. The assay described herein permits the detection of pregnancy on an average 25.4 days after the first day of the preceding menses, as opposed to 29.5 days for conventional radioimmunoassay techniques. In addition, the greater sensitivity and specificity of this assay method has permitted the detection of episodes of fetal loss not detected by radioimmunoassay of urine specimens. A large scale epidemiological study is in progress using this assay technique as a way to identify pregnancies that are lost before becoming clinically apparent.« less

Meta-analysis comparing chewing gum versus standard postoperative care after colorectal resection

PubMed Central

Zhou, Jian-Guo; Tian, Xu

2016-01-01

Background Previous incomplete studies investigating the potential of chewing gum (CG) in patients undergoing colorectal resection did not obtain definitive conclusions. This updated meta-analysis was therefore conducted to evaluate the effect and safety of CG versus standard postoperative care protocols (SPCPs) after colorectal surgery. Results Total 26 RCTs enrolling 2214 patients were included in this study. The CG can be well-tolerated by all patients. Compared with SPCPs, CG was associated with shorter time to first flatus (weighted mean difference (WMD) −12.14 (95 per cent c.i. −15.71 to −8.56) hours; P < 0.001), bowl movement (WMD −17.32 (−23.41 to −11.22) hours; P < 0.001), bowel sounds (WMD −6.02 (−7.42 to −4.63) hours; P < 0.001), and length of hospital stay (WMD −0.95 (−1.55 to −0.35) days; P < 0.001), a lower risk of postoperative ileus (risk ratio (RR) 0.61 (0.44 to 0.83); P = 0.002), net beneficial and quality of life. There were no significant differences between the two groups in overall complications, nausea, vomiting, bloating, wound infection, bleeding, dehiscence, readmission, reoperation, mortality. Materials and Methods The potentially eligible randomized controlled trials (RCTs) that compared CG with SPCPs for colorectal resection were searched in PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI), and Chinese Wanfang databases through May 2016. The trial sequential analysis was adopted to examine whether a firm conclusion for specific outcome can be drawn. Conclusions CG is benefit for enhancing return of gastrointestinal function after colorectal resection, and may be associated with lower risk of postoperative ileus. PMID:27588405

The Efficacy of Wrestling-Style Compression Suits to Improve Maximum Isometric Force and Movement Velocity in Well-Trained Male Rugby Athletes.

PubMed

McMaster, Daniel T; Beaven, Christopher M; Mayo, Brad; Gill, Nicholas; Hébert-Losier, Kim

2017-01-01

Purpose: The prevalence of compression garment (CG) use is increasing with athletes striving to take advantage of the purported benefits to recovery and performance. Here, we investigated the effect of CG on muscle force and movement velocity performance in athletes. Methods: Ten well-trained male rugby athletes wore a wrestling-style CG suit applying 13-31 mmHg of compressive pressure during a training circuit in a repeated-measures crossover design. Force and velocity data were collected during a 5-s isometric mid-thigh pull (IMTP) and repeated countermovement jump (CMJ), respectively; and time to complete a 5-m horizontal loaded sled push was also measured. Results: IMTP peak force was enhanced in the CG condition by 139 ± 142 N (effect size [ES] = 0.36). Differences in CMJ peak velocity (ES = 0.08) and loaded sled-push sprint time between the conditions were trivial (ES = -0.01). A qualitative assessment of the effects of CG wear suggested that the likelihood of harm was unlikely in the CMJ and sled push, while a beneficial effect in the CMJ was possible, but not likely. Half of the athletes perceived a functional benefit in the IMTP and CMJ exercises. Conclusion: Consistent with other literature, there was no substantial effect of wearing a CG suit on CMJ and sprint performance. The improvement in peak force generation capability in an IMTP may be of benefit to rugby athletes involved in scrummaging or lineout lifting. The mechanism behind the improved force transmission is unclear, but may involve alterations in neuromuscular recruitment and proprioceptive feedback.

Home Telehealth and Caregiving Appraisal in Chronic Illness.

PubMed

Wakefield, Bonnie J; Vaughan-Sarrazin, Mary

2017-04-01

Remote health monitoring applications are being adopted to improve the health of chronically ill individuals. Little work has focused on the effects of these technologies on informal caregivers (CG) of patients with chronic illnesses. To examine differences in caregiving appraisal between CG of enrolled and nonenrolled Veterans in the home telehealth (HT) program. Cross-sectional survey methodology in 244 dyads (Veteran and CG) from 6 rural Midwestern Veterans Affairs Medical Centers. Survey variables were derived from the 2004 National Alliance for Caregiving survey, along with measures of caregiving strain, burden, and satisfaction. We found no differences when comparing HT and non-HT CG. In multivariate analyses combining the two groups, CG characteristics associated with CG strain included younger age, providing help with activities of daily living and instrumental activities of daily living, use of coping skills, depressive symptoms, and less use of unpaid help (all p ≤ 0.001). Burden was associated with CG use of coping skills, caregiving confidence, and relationship quality with the Veteran (all p < 0.0001). CG satisfaction was associated with presence of social support (p < 0.0001). High CG strain was associated with Veteran hospitalization in the combined group (p = 0.03). Burden (p = 0.0002) was significantly associated with CG satisfaction. Existing HT infrastructure provides an opportunity to incorporate training and support programs for CG of chronically ill patients. Such programs could improve CG confidence and use of positive coping skills, lower strain and burden, and potentially improve the health of both the care recipient and CG.

Complicated grief among individuals with major depression: prevalence, comorbidity, and associated features.

PubMed

Sung, Sharon C; Dryman, M Taylor; Marks, Elizabeth; Shear, M Katherine; Ghesquiere, Angela; Fava, Maurizio; Simon, Naomi M

2011-11-01

Growing data suggest that complicated grief (CG) may be common in clinical care settings, but there are few prior reports about CG in outpatients presenting with primary mood disorders. The present study examined rates of bereavement and threshold CG symptoms (defined as a score ≥ 25 on the Inventory of Complicated Grief scale) in 111 outpatients with major depressive disorder (MDD) and 142 healthy controls participating in a study of stress and depression. Clinical and demographic characteristics were also compared for bereaved individuals with CG (MDD+CG) to those without (MDD-CG). Participants completed structured diagnostic interviews as well as measures of CG, depression, anxiety, exposure to traumatic events, and perceived social support. Lifetime history of a significant loss did not differ for the MDD and control groups (79.3% vs. 76.1%), but bereaved participants with MDD had higher rates of threshold CG (25.0% vs. 2.8%). Among those with MDD, CG was associated with a higher prevalence of lifetime alcohol dependence, greater exposure to traumatic events, and lower perceived social support. Depressed women, but not men, with CG also had higher rates of panic disorder, social anxiety disorder, and posttraumatic stress disorder. Our findings are limited by the lack of a clinician confirmatory assessment of CG diagnosis, absence of complete information about the nature and timing of the loss, and relatively narrow generalizability. We found high rates of CG in a group of psychiatric outpatients with chronic MDD, suggesting that patients with depression should be routinely screened for CG. Copyright © 2011 Elsevier B.V. All rights reserved.

Optimization of an Optical Inspection System Based on the Taguchi Method for Quantitative Analysis of Point-of-Care Testing

PubMed Central

Yeh, Chia-Hsien; Zhao, Zi-Qi; Shen, Pi-Lan; Lin, Yu-Cheng

2014-01-01

This study presents an optical inspection system for detecting a commercial point-of-care testing product and a new detection model covering from qualitative to quantitative analysis. Human chorionic gonadotropin (hCG) strips (cut-off value of the hCG commercial product is 25 mIU/mL) were the detection target in our study. We used a complementary metal-oxide semiconductor (CMOS) sensor to detect the colors of the test line and control line in the specific strips and to reduce the observation errors by the naked eye. To achieve better linearity between the grayscale and the concentration, and to decrease the standard deviation (increase the signal to noise ratio, S/N), the Taguchi method was used to find the optimal parameters for the optical inspection system. The pregnancy test used the principles of the lateral flow immunoassay, and the colors of the test and control line were caused by the gold nanoparticles. Because of the sandwich immunoassay model, the color of the gold nanoparticles in the test line was darkened by increasing the hCG concentration. As the results reveal, the S/N increased from 43.48 dB to 53.38 dB, and the hCG concentration detection increased from 6.25 to 50 mIU/mL with a standard deviation of less than 10%. With the optimal parameters to decrease the detection limit and to increase the linearity determined by the Taguchi method, the optical inspection system can be applied to various commercial rapid tests for the detection of ketamine, troponin I, and fatty acid binding protein (FABP). PMID:25256108

Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

PubMed

Tanigawa, Tohru; Shibata, Rei; Kondo, Kazuhisa; Katahira, Nobuyuki; Kambara, Takahiro; Inoue, Yoko; Nonoyama, Hiroshi; Horibe, Yuichiro; Ueda, Hiromi; Murohara, Toyoaki

2015-01-01

Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG), one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months) were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV), which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

Persistent low levels of serum hCG due to heterophilic mouse antibodies: an unrecognized pitfall in the diagnosis of trophoblastic disease.

PubMed

González Aguilera, B; Syrios, P; Gadisseur, R; Luyckx, F; Cavalier, E; Beckers, A; Valdes-Socin, H

2016-06-01

Phantom hCG refers to persistent mild elevations of hCG, leading physicians to unnecessary treatments whereas neither a true hCG nor a trophoblastic disease is present. We report the case of a 23-year-old woman with persistent low levels of serum hCG detected one month after miscarriage. As choriocarcinoma was suspected, a chemotherapy trial of methotrexate was prescribed, without any hCG reduction. Subsequently, laparoscopy ruled out a trophoblastic residue and the patient was referred to the Endocrine Unit for further investigations. While low levels of hCG were still detected in serum, no hCG was detected in the urine. In addition, when serum was processed in a HBT tube for revealing heterophilic antibodies, hCG was no longer detected. Such finding indicated the presence of phantom hCG due to heterophilic mouse antibodies interaction. This case raises the need of clinico-biological discussion to avoid inappropriate therapeutic decisions. Based on this case experience and after review of the literature, we suggest that current gynecological protocols for the diagnosis and treatment of trophoblastic disease should consider the inclusion of urinary hCG and/or a test for serum heterophilic antibodies when appropriate.

Modification of waste coal gangue and its application in the removal of Mn(2+) from aqueous solution.

PubMed

Qiu, Ruifang; Cheng, Fangqin

We developed a new calcination method to convert coal gangue (CG), a common waste generated from coal production process, into a modified form, which could be used as an adsorbent to remove Mn(2+) from aqueous solution. Sodium tetraborate (Na2B4O7·10H2O) was added into the CG calcination process as an additive, and the concentrations of Na2B4O7·10H2O were optimized along with the calcination temperature to obtain the best adsorbent capacity of modified coal gangue (MCG). We applied multiple analytical methods such as scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and Brunauer-Emmett-Teller analysis to characterize the MCG. The results showed it had a smaller particle size and a larger specific surface area and pore volume after modification. It also indicated that the phase of CG transformed from kaolinite to metakaolinite after calcination. Moreover, a new substance was generated with two new peaks at 1,632 cm(-1) and 799 cm(-1). The Mn(2+) absorption capacity of MCG was evaluated using a series of experiments with different adsorbent doses, pH values and initial Mn(2+) concentrations during the adsorption process. We found that Mn(2+) adsorbent capacity of MCG increased by more than seven-fold compared to that of CG. The Langmuir isotherm model and the pseudo-second-order kinetic model provided the best fit to the adsorption processes.

Optimization of Analytical Potentials for Coarse-Grained Biopolymer Models.

PubMed

Mereghetti, Paolo; Maccari, Giuseppe; Spampinato, Giulia Lia Beatrice; Tozzini, Valentina

2016-08-25

The increasing trend in the recent literature on coarse grained (CG) models testifies their impact in the study of complex systems. However, the CG model landscape is variegated: even considering a given resolution level, the force fields are very heterogeneous and optimized with very different parametrization procedures. Along the road for standardization of CG models for biopolymers, here we describe a strategy to aid building and optimization of statistics based analytical force fields and its implementation in the software package AsParaGS (Assisted Parameterization platform for coarse Grained modelS). Our method is based on the use and optimization of analytical potentials, optimized by targeting internal variables statistical distributions by means of the combination of different algorithms (i.e., relative entropy driven stochastic exploration of the parameter space and iterative Boltzmann inversion). This allows designing a custom model that endows the force field terms with a physically sound meaning. Furthermore, the level of transferability and accuracy can be tuned through the choice of statistical data set composition. The method-illustrated by means of applications to helical polypeptides-also involves the analysis of two and three variable distributions, and allows handling issues related to the FF term correlations. AsParaGS is interfaced with general-purpose molecular dynamics codes and currently implements the "minimalist" subclass of CG models (i.e., one bead per amino acid, Cα based). Extensions to nucleic acids and different levels of coarse graining are in the course.

Solid-liquid work of adhesion of coarse-grained models of n-hexane on graphene layers derived from the conditional reversible work method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ardham, Vikram Reddy; Leroy, Frédéric, E-mail: vandervegt@csi.tu-darmstadt.de, E-mail: f.leroy@theo.chemie.tu-darmstadt.de; Deichmann, Gregor

We address the question of how reducing the number of degrees of freedom modifies the interfacial thermodynamic properties of heterogeneous solid-liquid systems. We consider the example of n-hexane interacting with multi-layer graphene which we model both with fully atomistic and coarse-grained (CG) models. The CG models are obtained by means of the conditional reversible work (CRW) method. The interfacial thermodynamics of these models is characterized by the solid-liquid work of adhesion W{sub SL} calculated by means of the dry-surface methodology through molecular dynamics simulations. We find that the CRW potentials lead to values of W{sub SL} that are larger thanmore » the atomistic ones. Clear understanding of the relationship between the structure of n-hexane in the vicinity of the surface and W{sub SL} is elucidated through a detailed study of the energy and entropy components of W{sub SL}. We highlight the crucial role played by the solid-liquid energy fluctuations. Our approach suggests that CG potentials should be designed in such a way that they preserve the range of solid-liquid interaction energies, but also their fluctuations in order to preserve the reference atomistic value of W{sub SL}. Our study thus opens perspectives into deriving CG interaction potentials that preserve the thermodynamics of solid-liquid contacts and will find application in studies that intend to address materials driven by interfaces.« less

Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo

PubMed Central

2011-01-01

Background Boron neutron capture therapy (BNCT) is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the 10B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface. To extend the therapeutic use of BNCT from surface tumors to visceral tumors will require 10B compounds that accumulate strongly in tumor cells without significant accumulation in normal cells, and an appropriate delivery method for deeper tissues. Hemagglutinating Virus of Japan Envelope (HVJ-E) is used as a vehicle for gene delivery because of its high ability to fuse with cells. However, its strong hemagglutination activity makes HVJ-E unsuitable for systemic administration. In this study, we developed a novel vector for 10B (sodium borocaptate: BSH) delivery using HVJ-E and cationized gelatin for treating multiple liver tumors with BNCT without severe adverse events. Methods We developed cationized gelatin conjugate HVJ-E combined with BSH (CG-HVJ-E-BSH), and evaluated its characteristics (toxicity, affinity for tumor cells, accumulation and retention in tumor cells, boron-carrying capacity to multiple liver tumors in vivo, and bio-distribution) and effectiveness in BNCT therapy in a murine model of multiple liver tumors. Results CG-HVJ-E reduced hemagglutination activity by half and was significantly less toxic in mice than HVJ-E. Higher 10B concentrations in murine osteosarcoma cells (LM8G5) were achieved with CG-HVJ-E-BSH than with BSH. When administered into mice bearing multiple LM8G5 liver tumors, the tumor/normal liver ratios of CG-HVJ-E-BSH were significantly higher than those of BSH for the first 48 hours (p < 0.05). In suppressing the spread of tumor cells in mice, BNCT treatment was as effective with CG-HVJ-E-BSH as with BSH containing a 35-fold higher 10B dose. Furthermore, CG-HVJ-E-BSH significantly increased the survival time of tumor-bearing mice compared to BSH at a comparable dosage of 10B. Conclusion CG-HVJ-E-BSH is a promising strategy for the BNCT treatment of visceral tumors without severe adverse events to surrounding normal tissues. PMID:21247507

Kathon CG and cosmetic products.

PubMed

Rastogi, S C

1990-03-01

Kathon CG was determined in 156 of the most commonly used cosmetic products in Denmark. 42% of the cosmetic products were found to contain Kathon CG. Kathon CG was present in 48% of "rinse off" and 31% of "leave on" cosmetic products. The 3:1 ratio of chloromethyl isothiazolinone (CMI): methyl isothiazolinone (MI) in Kathon CG was found to be disturbed in 41% of Kathon CG preserved cosmetic products. The disturbed CMI/MI ratio was shown in 29% "rinse off" and 73% "leave on" cosmetic products. It is suggested that the chemical reaction of the ketone group of the isothizaolinones with other ingredients in cosmetic products may disturb the CMI/MI ratio of Kathon CG. The results of the study have been discussed in relation to the use of Kathon CG in cosmetic products as well as test material for allergic reaction.

How Well Do Computer-Generated Faces Tap Face Expertise?

PubMed

Crookes, Kate; Ewing, Louise; Gildenhuys, Ju-Dith; Kloth, Nadine; Hayward, William G; Oxner, Matt; Pond, Stephen; Rhodes, Gillian

2015-01-01

The use of computer-generated (CG) stimuli in face processing research is proliferating due to the ease with which faces can be generated, standardised and manipulated. However there has been surprisingly little research into whether CG faces are processed in the same way as photographs of real faces. The present study assessed how well CG faces tap face identity expertise by investigating whether two indicators of face expertise are reduced for CG faces when compared to face photographs. These indicators were accuracy for identification of own-race faces and the other-race effect (ORE)-the well-established finding that own-race faces are recognised more accurately than other-race faces. In Experiment 1 Caucasian and Asian participants completed a recognition memory task for own- and other-race real and CG faces. Overall accuracy for own-race faces was dramatically reduced for CG compared to real faces and the ORE was significantly and substantially attenuated for CG faces. Experiment 2 investigated perceptual discrimination for own- and other-race real and CG faces with Caucasian and Asian participants. Here again, accuracy for own-race faces was significantly reduced for CG compared to real faces. However the ORE was not affected by format. Together these results signal that CG faces of the type tested here do not fully tap face expertise. Technological advancement may, in the future, produce CG faces that are equivalent to real photographs. Until then caution is advised when interpreting results obtained using CG faces.

On the representability problem and the physical meaning of coarse-grained models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, Jacob W.; Dama, James F.; Durumeric, Aleksander E. P.

2016-07-28

In coarse-grained (CG) models where certain fine-grained (FG, i.e., atomistic resolution) observables are not directly represented, one can nonetheless identify indirect the CG observables that capture the FG observable’s dependence on CG coordinates. Often, in these cases it appears that a CG observable can be defined by analogy to an all-atom or FG observable, but the similarity is misleading and significantly undermines the interpretation of both bottom-up and top-down CG models. Such problems emerge especially clearly in the framework of the systematic bottom-up CG modeling, where a direct and transparent correspondence between FG and CG variables establishes precise conditions formore » consistency between CG observables and underlying FG models. Here we present and investigate these representability challenges and illustrate them via the bottom-up conceptual framework for several simple analytically tractable polymer models. The examples provide special focus on the observables of configurational internal energy, entropy, and pressure, which have been at the root of controversy in the CG literature, as well as discuss observables that would seem to be entirely missing in the CG representation but can nonetheless be correlated with CG behavior. Though we investigate these problems in the framework of systematic coarse-graining, the lessons apply to top-down CG modeling also, with crucial implications for simulation at constant pressure and surface tension and for the interpretations of structural and thermodynamic correlations for comparison to experiment.« less

Interactions of chromogranin A-derived vasostatins and monolayers of phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine.

PubMed

Blois, Anna; Holmsen, Holm; Martino, Guglielmo; Corti, Angelo; Metz-Boutigue, Marie-Hélène; Helle, Karen B

2006-03-15

Vasostatin-I (CgA1-76) is a naturally occurring and biologically active N-terminal peptide derived from chromogranin A (CgA), produced and secreted at high concentrations by neuroendocrine tissues and also from a range of neuroendocrine tumors. This study aims to examine the hypothesis that in the absence of classical protein receptors CgA1-76 may, like its two derived peptides CgA1-40 and CgA47-66, perturb the lipid microenvironment of other membrane receptors, as a basis for the largely inhibitory activities of these CgA peptides. The nature of the interactions between phospholipids and vasostatin-derived fragments was studied in the Langmuir film balance apparatus at 37 degrees C. The synthetic peptides CgA1-40 and CgA47-66 and a recombinant fragment (VS-I) containing vasostatin-I (Ser-Thr-Ala-CgA1-78) were compared for their effects on monolayers of phosphatidylcholine and phosphatidylethanolamine from pig brain and defined species of phosphatidylserine. Marked differences in surface pressure-area isotherms and phase-transition plateaus were apparent with the three classes of phospholipids on VS-I, CgA1-40 and CgA47-66 in physiological buffer or pure water. The results indicate that VS-I and CgA47-66 at 5-10 nM concentrations may engage in electrostatic as well as hydrophobic interactions with membrane-relevant phospholipids at physiological conditions, VS-I in particular enhancing the fluidity of saturated species of phosphatidylserine.

Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2017-09-01

Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy. Copyright © 2017 Endocrine Society

Biological functions of hCG and hCG-related molecules

PubMed Central

2010-01-01

Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID:20735820

Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner.

PubMed

Barjaktarovic, Mirjana; Korevaar, Tim I M; Jaddoe, Vincent W V; de Rijke, Yolanda B; Visser, Theo J; Peeters, Robin P; Steegers, Eric A P

2017-02-01

Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1-26.2), estimated fetal weight (measured by ultrasound during 18-25th weeks and >25th weeks) and birth weight were measured in 7987 mother-child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; de Rijke, Yolanda B; Schalekamp-Timmermans, Sarah; Visser, W Edward; Hofman, Albert; Jaddoe, Vincent W V; Tiemeier, Henning; Visser, Theo J; Medici, Marco; Peeters, Robin P

2015-09-01

Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on reference range (RR) methodology and determinants of gestational hCG levels is crucial. Moreover, a better understanding of gestational hCG physiology can improve current screening programs and future clinical management. Serum total hCG levels were determined in 8195 women participating in the Generation R Study. Gestational age specific RRs using 'ultrasound derived gestational age' (US RRs) were calculated and compared with 'last menstrual period derived gestational age' (LMP RRs) and a model-based RR. We also investigated which pregnancy characteristics were associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most notably for the median and lower limit levels. No considerable differences were found between RRs calculated in the general population or in uncomplicated pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. We provide gestational RRs for total hCG and show that total hCG values and RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This is likely due to the influence of hCG on embryonic growth, suggesting that ultrasound based pregnancy dating might be less reliable in women with high/low hCG levels. Furthermore, we identify different pregnancy characteristics that influence total hCG levels considerably and should therefore be accounted for in clinical studies.

The CgHaa1-Regulon Mediates Response and Tolerance to Acetic Acid Stress in the Human Pathogen Candida glabrata

PubMed Central

Bernardo, Ruben T.; Cunha, Diana V.; Wang, Can; Pereira, Leonel; Silva, Sónia; Salazar, Sara B.; Schröder, Markus S.; Okamoto, Michiyo; Takahashi-Nakaguchi, Azusa; Chibana, Hiroji; Aoyama, Toshihiro; Sá-Correia, Isabel; Azeredo, Joana; Butler, Geraldine; Mira, Nuno Pereira

2016-01-01

To thrive in the acidic vaginal tract, Candida glabrata has to cope with high concentrations of acetic acid. The mechanisms underlying C. glabrata tolerance to acetic acid at low pH remain largely uncharacterized. In this work, the essential role of the CgHaa1 transcription factor (encoded by ORF CAGL0L09339g) in the response and tolerance of C. glabrata to acetic acid is demonstrated. Transcriptomic analysis showed that CgHaa1 regulates, directly or indirectly, the expression of about 75% of the genes activated under acetic acid stress. CgHaa1-activated targets are involved in multiple physiological functions including membrane transport, metabolism of carbohydrates and amino acids, regulation of the activity of the plasma membrane H+-ATPase, and adhesion. Under acetic acid stress, CgHaa1 increased the activity and the expression of the CgPma1 proton pump and contributed to increased colonization of vaginal epithelial cells by C. glabrata. CgHAA1, and two identified CgHaa1-activated targets, CgTPO3 and CgHSP30, are herein demonstrated to be determinants of C. glabrata tolerance to acetic acid. The protective effect of CgTpo3 and of CgHaa1 was linked to a role of these proteins in reducing the accumulation of acetic acid inside C. glabrata cells. In response to acetic acid stress, marked differences were found in the regulons controlled by CgHaa1 and by its S. cerevisiae ScHaa1 ortholog, demonstrating a clear divergent evolution of the two regulatory networks. The results gathered in this study significantly advance the understanding of the molecular mechanisms underlying the success of C. glabrata as a vaginal colonizer. PMID:27815348

Disulfide bond rearrangement during formation of the chorionic gonadotropin beta-subunit cystine knot in vivo.

PubMed

Wilken, Jason A; Bedows, Elliott

2004-05-04

The intracellular kinetic folding pathway of the human chorionic gonadotropin beta-subunit (hCG-beta) reveals the presence of a disulfide between Cys residues 38-57 that is not detected by X-ray analysis of secreted hCG-beta. This led us to propose that disulfide rearrangement is an essential feature of cystine knot formation during CG-beta folding. To test this, we used disulfide bond formation to monitor progression of intracellular folding intermediates of a previously uncharacterized protein, the CG-beta subunit of cynomolgous macaque (Macaca fascicularis). Like its human counterpart hCG-beta with which it shares 81% identity, macaque (m)CG-beta is a cystine knot-containing subunit that assembles with an alpha-subunit common to all glycoprotein hormone members of its species to form a biologically active heterodimer, mCG, which, like hCG, is required for pregnancy maintenance. An early mCG-beta folding intermediate, mpbeta1, contained two disulfide bonds, one between Cys34 and Cys88 and the other between Cys38 and Cys57. The subsequent folding intermediate, mpbeta2-early, was represented by an ensemble of folding forms that, in addition to the two disulfides mentioned above, included disulfide linkages between Cys9 and Cys57 and between Cys38 and Cys90. These latter two disulfides are those contained within the beta-subunit cystine knot and reveal that a disulfide exchange occurred during the mpbeta2-early folding step leading to formation of the mCG-beta knot. Thus, while defining the intracellular kinetic protein folding pathway of a monkey homologue of CG-beta, we detected the previously predicted disulfide exchange event crucial for CG-beta cystine knot formation and attainment of CG-beta assembly competence.

Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the A(y) allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss.

PubMed

Suto, Jun-ichi; Satou, Kunio

2013-05-04

Mice carrying the A(y) allele at the agouti locus become obese and are heavier than their non-A(y) littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-A(y) females are heavier than DDD females, whereas DDD.Cg-A(y) males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-A(y) males. Growth curves of DDD.Cg-A(y) mice were analyzed and compared with those of B6.Cg-A(y) mice from 5 to 25 weeks. In DDD.Cg-A(y) males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-A(y)) F(1)-A(y) mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the A(y) allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC A(y) males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-A(y) males. The lower body weight of DDD.Cg-A(y) male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes. This QTL interacted with the Ay allele, implying the reason why body weight loss occurs in DDD.Cg-Ay but not in DDD males.

Genetic background (DDD/Sgn versus C57BL/6J) strongly influences postnatal growth of male mice carrying the Ay allele at the agouti locus: identification of quantitative trait loci associated with diabetes and body weight loss

PubMed Central

2013-01-01

Background Mice carrying the Ay allele at the agouti locus become obese and are heavier than their non-Ay littermates. However, this does not hold true for the genetic background of the DDD mouse strain. At 22 weeks of age, DDD.Cg-Ay females are heavier than DDD females, whereas DDD.Cg-Ay males are lighter than DDD males. This study aimed to determine the possible cause and identify the genes responsible for the lower body weight of DDD.Cg-Ay males. Results Growth curves of DDD.Cg-Ay mice were analyzed and compared with those of B6.Cg-Ay mice from 5 to 25 weeks. In DDD.Cg-Ay males, body weight gain stopped between 16 and 17 weeks and the body weight gradually decreased; thus, the lower body weight was a consequence of body weight loss. Quantitative trait locus (QTL) mapping was performed in backcrossed (BC) males of DDD × (B6 × DDD.Cg-Ay) F1-Ay mice. For the body weight at 25 weeks, significant QTLs were identified on chromosomes 1 and 4. The DDD allele was associated with a lower body weight at both loci. In particular, the QTL on chromosome 4 interacted with the Ay allele. Furthermore, suggestive QTLs for plasma glucose and high molecular weight adiponectin levels were coincidentally mapped to chromosome 4. The DDD allele was associated with increased glucose and decreased adiponectin levels. When the body weight at 25 weeks and plasma glucose levels were considered as dependent and independent variables, respectively, BC Ay males were classified into two groups according to statistical analysis using the partition method. Mice of one group had significantly higher glucose and lower adiponectin levels than those of the other group and exhibited body weight loss as observed with DDD-Ay males. Conclusions The lower body weight of DDD.Cg-Ay male mice was a consequence of body weight loss. Diabetes mellitus has been suggested to be a possible contributory factor causing body weight loss. The QTL on distal chromosome 4 contained the major responsible genes. This QTL interacted with the Ay allele, implying the reason why body weight loss occurs in DDD.Cg-Ay but not in DDD males. PMID:23641944

[Children with hyperthyroidism due to elevated hCG levels].

PubMed

Jöbsis, Jasper J; van Trotsenburg, A S Paul; Merks, Johannes H M; Kamp, Gerdine A

2014-01-01

We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking effect, hCG can induce high oestradiol levels, resulting in stormy pubertal development. False negative hCG tests due to the high-dose hook effect may complicate the diagnostic process. In patients with antibody-negative thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered.

Species differences in the formation of vabicaserin carbamoyl glucuronide.

PubMed

Tong, Zeen; Chandrasekaran, Appavu; DeMaio, William; Jordan, Ronald; Li, Hongshan; Moore, Robin; Poola, Nagaraju; Burghart, Peter; Hultin, Theresa; Scatina, JoAnn

2010-04-01

Vabicaserin is a potent 5-hydroxtryptamine 2C full agonist with therapeutic potential for a wide array of psychiatric disorders. Metabolite profiles indicated that vabicaserin was extensively metabolized via carbamoyl glucuronidation after oral administration in humans. In the present study, the differences in the extent of vabicaserin carbamoyl glucuronide (CG) formation in humans and in animals used for safety assessment were investigated. After oral dosing, the systemic exposure ratios of CG to vabicaserin were approximately 12 and up to 29 in monkeys and humans, respectively, and the ratios of CG to vabicaserin were approximately 1.5 and 1.7 in mice and dogs, respectively. These differences in systemic levels of CG are likely related to species differences in the rate and extent of CG formation and elimination. Whereas CG was the predominant circulating metabolite in humans and a major metabolite in mice, dogs, and monkeys, it was a relatively minor metabolite in rats, in which oxidative metabolism was the major metabolic pathway. Although the CG was not detected in plasma or urine of rats, approximately 5% of the dose was excreted in bile as CG in the 24-h collection postdose, indicating the rat had the metabolic capability of producing the CG. In vitro, in a CO(2)-enriched environment, the CG was the predominant metabolite in dog and human liver microsomes, a major metabolite in monkey and mice, and only a very minor metabolite in rats. Carbamoyl glucuronidation and hydroxylation had similar contributions to vabicaserin metabolism in mouse and monkey liver microsomes. However, only trace amounts of CG were formed in rat liver microsomes, and other metabolites were more prominent than the CG. In conclusion, significant differences in the extent of formation of the CG were observed among the various species examined. The exposure ratios of CG to vabicaserin were highest in humans, followed by monkeys, then mice and dogs, and lowest in rats, and the in vitro metabolite profiles generally correlated well with the in vivo metabolites.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sprague, E.R.; Wang, C.; Baker, D.

Herpes simplex virus type-1 expresses a heterodimeric Fc receptor, gE-gI, on the surfaces of virions and infected cells that binds the Fc region of host immunoglobulin G and is implicated in the cell-to-cell spread of virus. gE-gI binds immunoglobulin G at the basic pH of the cell surface and releases it at the acidic pH of lysosomes, consistent with a role in facilitating the degradation of antiviral antibodies. Here we identify the C-terminal domain of the gE ectodomain (CgE) as the minimal Fc-binding domain and present a 1.78-{angstrom} CgE structure. A 5-{angstrom} gE-gI/Fc crystal structure, which was independently verified bymore » a theoretical prediction method, reveals that CgE binds Fc at the C{sub H}2-C{sub H}3 interface, the binding site for several mammalian and bacterial Fc-binding proteins. The structure identifies interface histidines that may confer pH-dependent binding and regions of CgE implicated in cell-to-cell spread of virus. The ternary organization of the gE-gI/Fc complex is compatible with antibody bipolar bridging, which can interfere with the antiviral immune response.« less

A simulation study of capacity utilization to predict future capacity for manufacturing system sustainability

NASA Astrophysics Data System (ADS)

Rimo, Tan Hauw Sen; Chai Tin, Ong

2017-12-01

Capacity utilization (CU) measurement is an important task in a manufacturing system, especially in make-to-order (MTO) type manufacturing system with product customization, in predicting capacity to meet future demand. A stochastic discrete-event simulation is developed using ARENA software to determine CU and capacity gap (CG) in short run production function. This study focused on machinery breakdown and product defective rate as random variables in the simulation. The study found that the manufacturing system run in 68.01% CU and 31.99% CG. It is revealed that machinery breakdown and product defective rate have a direct relationship with CU. By improving product defective rate into zero defect, manufacturing system can improve CU up to 73.56% and CG decrease to 26.44%. While improving machinery breakdown into zero breakdowns will improve CU up to 93.99% and the CG decrease to 6.01%. This study helps operation level to study CU using “what-if” analysis in order to meet future demand in more practical and easier method by using simulation approach. Further study is recommended by including other random variables that affect CU to make the simulation closer with the real-life situation for a better decision.

hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells.

PubMed

Schanz, Andrea; Lukosz, Margarete; Hess, Alexandra P; Baston-Büst, Dunja M; Krüssel, Jan S; Heiss, Christian

2015-08-01

Human chorionic gonadotropin (hCG) has long been associated with the initiation and maintenance of pregnancy, where angiogenesis plays an important role. However, the function of hCG in angiogenesis and the recruitment of vascular active cells are not fully understood. In this study, the role of hCG and its receptor in circulating angiogenic and human endothelial cells, including lymphatic, uterine microvascular, and umbilical vein endothelial cells, was examined. Immunohistochemistry and immunoblot analysis were used to detect LH/hCG receptor expression and the expression of hCG-induced angiogenic molecules. HIF-1α was determined via ELISA and downstream molecules, such as CXCL12 and CXCR4, via real-time PCR. Chemotaxis was analyzed using Boyden chambers. Our results show that the LH/hCG receptor was present in all tested cells. Furthermore, hCG was able to stimulate LH/hCG-receptor-specific migration in a dose-dependent fashion and induce key angiogenic molecules, including HIF-1α, CXCL12, and CXCR4. In conclusion, our findings underscore the importance of hCG as one of the first angiogenic molecules produced by the conceptus. hCG itself alters endothelial motility, recruitment, and expression of pro-angiogenic molecules and may therefore play an important role in vascular adaption during implantation and early placental formation. Copyright © 2015. Published by Elsevier Ireland Ltd.

Determination of serum hCG levels by radioreactor assay in the clinical laboratory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyko, W.L.

1979-09-01

The radioreceptorassay (RRA) has been used for measuring human chorionic gonadotropin (hCG) in sera from 751 individuals. The RRA is shown to be sensitive (98%) and specific (99.8%) in detecting hCG in a wide variety of conditions, including normal pregnancy and threatened or missed abortions. As a rapid qualitative or semiquantitative assay for hCG, the RRA is a valuable adjunct in the laboratory to less sensitive tests for hCG. Variation among different quantitative assays for hCG is examined, and it is concluded that the same assay system should be used for monitoring hCG levels in a single individual over amore » period of time in order to avoid inconsistent results. Application of the quantitative RRA for hCG in detecting the midcycle luteinizing hormone surge in infertillity is also presented.« less

[Influence of hCG glycosylation on its functions in female reproduction].

PubMed

Oborná, I; Fingerová, H

To review contemporary knowledge of the hCG molecule, its isoforms and the importance of glycosylation. Biologic variants and glycoforms of hCG have different biological activities and functions related to the control of menstrual cycle, conception, gestation as well as gynaecologic and non-gynaecologic malignancies. A review. Department of Obstetrics and Gynaecology, University Hospital Olomouc. To present own experience and an overview of recent literature in molecular biology, clinical biochemistry and clinical practice. Recent knowledge of the role of hCG glycosylation in physiologic and pathologic events in female organism will provide a better understanding of regulation of processes like ovulation (co-operation of pituitary hCG with LH), implantation and hemochorial placentation (invasivity of hyperglycosylated hCG). Some biologic variants and isoforms of hCG are important for the prediction of certain pathologies of pregnancy, prenatal screening of inborn errors (free beta hCG) as well as in the treatment of infertility.

Segmentation of anatomical structures of the heart based on echocardiography

NASA Astrophysics Data System (ADS)

Danilov, V. V.; Skirnevskiy, I. P.; Gerget, O. M.

2017-01-01

Nowadays, many practical applications in the field of medical image processing require valid and reliable segmentation of images in the capacity of input data. Some of the commonly used imaging techniques are ultrasound, CT, and MRI. However, the main difference between the other medical imaging equipment and EchoCG is that it is safer, low cost, non-invasive and non-traumatic. Three-dimensional EchoCG is a non-invasive imaging modality that is complementary and supplementary to two-dimensional imaging and can be used to examine the cardiovascular function and anatomy in different medical settings. The challenging problems, presented by EchoCG image processing, such as speckle phenomena, noise, temporary non-stationarity of processes, unsharp boundaries, attenuation, etc. forced us to consider and compare existing methods and then to develop an innovative approach that can tackle the problems connected with clinical applications. Actual studies are related to the analysis and development of a cardiac parameters automatic detection system by EchoCG that will provide new data on the dynamics of changes in cardiac parameters and improve the accuracy and reliability of the diagnosis. Research study in image segmentation has highlighted the capabilities of image-based methods for medical applications. The focus of the research is both theoretical and practical aspects of the application of the methods. Some of the segmentation approaches can be interesting for the imaging and medical community. Performance evaluation is carried out by comparing the borders, obtained from the considered methods to those manually prescribed by a medical specialist. Promising results demonstrate the possibilities and the limitations of each technique for image segmentation problems. The developed approach allows: to eliminate errors in calculating the geometric parameters of the heart; perform the necessary conditions, such as speed, accuracy, reliability; build a master model that will be an indispensable assistant for operations on a beating heart.

Clinical effectiveness of multiple-drug injection treatment in unruptured ectopic pregnancies: a retrospective study.

PubMed

Dai, Quan; Wang, Lu-Lu; Shao, Xiao-Hui; Wang, Si-Ming; Dong, Xiao-Qiu

2012-10-01

To study the effect of local interventional treatment of unruptured ectopic pregnancies with multiple-drug injection guided by color Doppler sonography. In this retrospective analysis, 49 patients with an unruptured ectopic pregnancy were treated with two different local injection methods administered under sonographic guidance. The patients were divided into single-drug (n = 23) and multiple-drug (n = 26) injection groups, and they received a locally administered injection of methotrexate alone or a combination including methotrexate, hemocoagulase, antibiotics, and anti-inflammatory drugs, respectively. Overall, local injection treatment was successful in 44 patients. The 5 patients with failed treatment underwent laparotomy about 1 week after single-drug injection. Serum β-human chorionic gonadotropin (β-hCG ) levels, ectopic pregnancy mass sizes, blood flow at various points after treatment, the incidence of pelvic bleeding, and the time for serum β-hCG levels to return to normal and the mass to resolve were analyzed in the remaining 44 patients. Single-drug treatment was successful in 18 patients; 10 of 23 had low to moderate pelvic bleeding after treatment, and 5 were referred for surgery. All 26 patients were successfully treated by multiple-drug injection. Only 2 patients had a small amount of pelvic bleeding. Differences between groups were statistically significant (P < .05) for surgery rates, the incidence of pelvic bleeding, transient increases in serum β-hCG levels, mean days to normal β-hCG levels, mean days of mass resolution, and mean mass diameters 1 to 6 weeks after treatment. Local multiple-drug injection under color Doppler guidance is a new, safe, and effective method for treating unruptured ectopic pregnancies. It accelerates the serum β-hCG decline and facilitates mass resolution. This regimen is associated with a very low rate of pelvic bleeding, improves the success rate of conservative treatment, and, therefore, has value as an important clinical application.

Interventions to increase immunisation coverage among children 12–23 months of age in India through participatory learning and community engagement: pilot study for a cluster randomised trial

PubMed Central

Johri, Mira; Chandra, Dinesh; Koné, Georges K; Dudeja, Sakshi; Sylvestre, Marie-Pierre; Sharma, Jitendar K; Pahwa, Smriti

2015-01-01

Objective With the aim of conducting a future cluster randomised trial to assess intervention impact on child vaccination coverage, we designed a pilot study to assess feasibility and aid in refining methods for the larger study. Trial design Cluster-randomised design with a 1:1 allocation ratio. Methods Clusters were 12 villages in rural Uttar Pradesh. All women residing in a selected village who were mothers of a child 0–23 months of age were eligible; participants were chosen at random. Over 4 months, intervention group (IG) villages received: (1) home visits by volunteers; (2) community mobilisation events to promote immunisation. Control group (CG) villages received community mobilisation to promote nutrition. A toll-free number for immunisation was offered to all IG and CG village residents. Primary outcomes were ex-ante criteria for feasibility of the main study related to processes for recruitment and randomisation (50% of villages would agree to participate and accept randomisation; 30 women could be recruited in 70% of villages), and retention of participants (50% of women retained from baseline to endline). Clusters were assigned to IG or CG using a computer-generated randomisation schedule. Neither participants nor those delivering interventions were blinded, but those assessing outcomes were blinded to group assignment. Results All villages contacted agreed to participate and accepted randomisation. 36 women were recruited per village; 432 participants were randomised (IG n=216; CG n=216). No clusters were lost to follow-up. The main analysis included 86% (373/432) of participants, 90% (195/216) from the IG and 82% (178/216) from the CG. Conclusions Criteria related to feasibility were satisfied, giving us confidence that we can successfully conduct a larger cluster randomised trial. Methodological lessons will inform design of the main study. Trial registration number ISRCTN16703097 PMID:26384721

Effects of whole body vibration on bone mineral density and falls: results of the randomized controlled ELVIS study with postmenopausal women.

PubMed

von Stengel, S; Kemmler, W; Engelke, K; Kalender, W A

2011-01-01

We determined whether the effect of exercise on bone mineral density (BMD) and falls can be enhanced by whole body vibration (WBV). In summary, the multi-purpose exercise training was effective to increase lumbar BMD but added WBV did not enhance this effect. However, falls were lowest in the exercise program combined with WBV. WBV is a new approach to reduce the risk of osteoporotic fractures. In the "Erlangen Longitudinal Vibration Study" (ELVIS), we investigated whether WBV enhances the effect of multifunctional exercise on BMD and falls. One hundred fifty-one postmenopausal women (68.5 ± 3.1 years) were randomly assigned to a: (1) conventional training group (TG); (2) conventional training group including vibration (TGV); and (3) wellness control group (CG). TG conducted an exercise program consisting of 20 min dancing aerobics, 5 min balance training, 20 min functional gymnastics, and 15 min dynamic leg-strength training on vibration plates (without vibration) twice a week. TGV performed an identical exercise regimen with vibration (25-35 Hz) during the leg-strengthening sequence. CG performed a low-intensity wellness program. BMD was measured at the hip and lumbar spine at baseline and follow-up using the DXA method. Falls were recorded daily via the calendar method. After 18 months, an increase in BMD at the lumbar spine was observed in both training groups (TGV: +1.5% vs. TG: +2.1%). The difference between the TG and the CG (1.7%) was significant. At the hip no changes were determined in either group. The fall frequency was significantly lower in TGV (0.7 falls/person) compared with CG (1.5), whereas the difference between TG (0.96) and CG was not significant. A multifunctional training program had a positive impact on lumbar BMD. The application of vibration did not enhance these effects. However, only the training including WBV affected the number of falls significantly.

Reproductive performance of lactating dairy cows after inducing ovulation using hCG in a five-day progesterone-based fixed-time AI protocol.

PubMed

Garcia-Ispierto, I; De Rensis, F; Casas, X; Caballero, F; Mur-Novales, R; López-Gatius, F

2018-02-01

This study compares the effects of inducing ovulation using human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) at the end of a 5-day progesterone(P4)-based protocol for fixed-time artificial insemination (FTAI) in lactating dairy cows on ovarian dynamics and fertility. A P4 intravaginal device (PRID) was fitted for five days and GnRH administered upon PRID insertion and a double dose (24 h apart) of prostaglandin F 2α upon PRID removal. Cows received either GnRH (GnRH group; n = 98), 1000 IU hCG (hCG-1 group; n = 97), or 3000 IU hCG (hCG-2 group; n = 104) 36 h after PRID removal and were inseminated 50-56 h after PRID removal. Based on Tukey-Kramer tests, cows in hCG-1 and hCG-2 showed a larger follicle diameter at AI than cows in GnRH (P < 0.05). HCG-2 treatment increased corpus luteum (CL) size on Day 7 post-AI compared with the GnRH and hCG-1 treatments (P < 0.05). Based on odds ratios, the likelihood of ovulation failure decreased with increasing follicle diameter at AI (P = 0.002). Cows in hCG-1 or hCG-2 that did not become pregnant were more likely to return to estrus than cows in GnRH (P < 0.01). A larger CL size post-AI was related to an increased conception rate at FTAI (P = 0.003). Cows given hCG-2 treatment showed a 1.9-fold cumulative pregnancy rate after two rounds of AI compared to cows receiving GnRH. Our results indicate that hCG treatment hCG treatment used to induce ovulation at the end of a short protocol for FTAI improves follicular/luteal dynamics compared to GnRH treatment. Of the two hCG treatments tested, better results were obtained with the 3000 IU dose. Copyright © 2017 Elsevier Inc. All rights reserved.

The Alternative Epac/cAMP Pathway and the MAPK Pathway Mediate hCG Induction of Leptin in Placental Cells

PubMed Central

Maymó, Julieta Lorena; Pérez Pérez, Antonio; Maskin, Bernardo; Dueñas, José Luis; Calvo, Juan Carlos; Sánchez Margalet, Víctor; Varone, Cecilia Laura

2012-01-01

Pleiotropic effects of leptin have been identified in reproduction and pregnancy, particularly in the placenta, where it works as an autocrine hormone. In this work, we demonstrated that human chorionic gonadotropin (hCG) added to JEG-3 cell line or to placental explants induces endogenous leptin expression. We also found that hCG increased cAMP intracellular levels in BeWo cells in a dose-dependent manner, stimulated cAMP response element (CRE) activity and the cotransfection with an expression plasmid of a dominant negative mutant of CREB caused a significant inhibition of hCG stimulation of leptin promoter activity. These results demonstrate that hCG indeed activates cAMP/PKA pathway, and that this pathway is involved in leptin expression. Nevertheless, we found leptin induction by hCG is dependent on cAMP levels. Treatment with (Bu)2cAMP in combination with low and non stimulatory hCG concentrations led to an increase in leptin expression, whereas stimulatory concentrations showed the opposite effect. We found that specific PKA inhibition by H89 caused a significant increase of hCG leptin induction, suggesting that probably high cAMP levels might inhibit hCG effect. It was found that hCG enhancement of leptin mRNA expression involved the MAPK pathway. In this work, we demonstrated that hCG leptin induction through the MAPK signaling pathway is inhibited by PKA. We observed that ERK1/2 phosphorylation increased when hCG treatment was combined with H89. In view of these results, the involvement of the alternative cAMP/Epac signaling pathway was studied. We observed that a cAMP analogue that specifically activates Epac (CPT-OMe) stimulated leptin expression by hCG. In addition, the overexpression of Epac and Rap1 proteins increased leptin promoter activity and enhanced hCG. In conclusion, we provide evidence suggesting that hCG induction of leptin gene expression in placenta is mediated not only by activation of the MAPK signaling pathway but also by the alternative cAMP/Epac signaling pathway. PMID:23056265

CgIκB3, the third novel inhibitor of NF-kappa B (IκB) protein, is involved in the immune defense of the Pacific oyster, Crassostrea gigas.

PubMed

Xu, Fengjiao; Li, Jun; Zhang, Yuehuan; Li, Xiaomei; Zhang, Yang; Xiang, Zhiming; Yu, Ziniu

2015-10-01

Inhibitor of NF-κB (IκB), the important regulator of NF-κB/Rel signaling pathway, plays the crucial role in immune response of both vertebrates and invertebrates. Here, a novel homologue of IκB was cloned from Crassostrea gigas, and designated as CgIκB3. The complete CgIκB3 cDNA was 1282 bp in length, including a 942 bp open reading frame (ORF), a 51 bp 5' UTR and a 289 bp 3' UTR. The ORF encodes a putative protein of 313 amino acids with a predicted molecular weight of approximately 34.7 kDa. Sequence analysis reveals that CgIκB3 contains a conserved degradation motif but with only five ankyrin repeats. Neither a PEST domain nor a C-terminal casein kinase II phosphorylation site was identified through either alignment or bioinformatic prediction. Phylogenetic analysis suggested that CgIκB3 shares common ancestor with CgIκB1 rather CgIκB2, and theoretically it may originate from one duplication event prior to divergence of CgIκB1 and CgIκB2. Tissue expression analyses demonstrated that CgIκB3 mRNA is the most abundant in gills and heart. The expression following PAMP infection showed that CgIκB3 was significantly up-regulated in a similar pattern when challenged with LPS, HKLM or HKVA, respectively. Moreover, similar to CgIκB1 and CgIκB2, CgIκB3 can also inhibit Rel dependent NF-κB activation in HEK293 cells in a dose-dependent manner. In summary, these findings suggest that CgIκB3 can be as the functional inhibitor of NF-κB/Rel and involved in the host defense of C. gigas. The discovery of the third IκB emphasizes the complexity and importance of the regulation on NF-κB activation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Decomposed direct matrix inversion for fast non-cartesian SENSE reconstructions.

PubMed

Qian, Yongxian; Zhang, Zhenghui; Wang, Yi; Boada, Fernando E

2006-08-01

A new k-space direct matrix inversion (DMI) method is proposed here to accelerate non-Cartesian SENSE reconstructions. In this method a global k-space matrix equation is established on basic MRI principles, and the inverse of the global encoding matrix is found from a set of local matrix equations by taking advantage of the small extension of k-space coil maps. The DMI algorithm's efficiency is achieved by reloading the precalculated global inverse when the coil maps and trajectories remain unchanged, such as in dynamic studies. Phantom and human subject experiments were performed on a 1.5T scanner with a standard four-channel phased-array cardiac coil. Interleaved spiral trajectories were used to collect fully sampled and undersampled 3D raw data. The equivalence of the global k-space matrix equation to its image-space version, was verified via conjugate gradient (CG) iterative algorithms on a 2x undersampled phantom and numerical-model data sets. When applied to the 2x undersampled phantom and human-subject raw data, the decomposed DMI method produced images with small errors (< or = 3.9%) relative to the reference images obtained from the fully-sampled data, at a rate of 2 s per slice (excluding 4 min for precalculating the global inverse at an image size of 256 x 256). The DMI method may be useful for noise evaluations in parallel coil designs, dynamic MRI, and 3D sodium MRI with fixed coils and trajectories. Copyright 2006 Wiley-Liss, Inc.

Glucose Prediction Algorithms from Continuous Monitoring Data: Assessment of Accuracy via Continuous Glucose Error-Grid Analysis.

PubMed

Zanderigo, Francesca; Sparacino, Giovanni; Kovatchev, Boris; Cobelli, Claudio

2007-09-01

The aim of this article was to use continuous glucose error-grid analysis (CG-EGA) to assess the accuracy of two time-series modeling methodologies recently developed to predict glucose levels ahead of time using continuous glucose monitoring (CGM) data. We considered subcutaneous time series of glucose concentration monitored every 3 minutes for 48 hours by the minimally invasive CGM sensor Glucoday® (Menarini Diagnostics, Florence, Italy) in 28 type 1 diabetic volunteers. Two prediction algorithms, based on first-order polynomial and autoregressive (AR) models, respectively, were considered with prediction horizons of 30 and 45 minutes and forgetting factors (ff) of 0.2, 0.5, and 0.8. CG-EGA was used on the predicted profiles to assess their point and dynamic accuracies using original CGM profiles as reference. Continuous glucose error-grid analysis showed that the accuracy of both prediction algorithms is overall very good and that their performance is similar from a clinical point of view. However, the AR model seems preferable for hypoglycemia prevention. CG-EGA also suggests that, irrespective of the time-series model, the use of ff = 0.8 yields the highest accurate readings in all glucose ranges. For the first time, CG-EGA is proposed as a tool to assess clinically relevant performance of a prediction method separately at hypoglycemia, euglycemia, and hyperglycemia. In particular, we have shown that CG-EGA can be helpful in comparing different prediction algorithms, as well as in optimizing their parameters.

Superovulation induction in the house musk shrew (Suncus murinus).

PubMed

Matsuzaki, T; Matsuzaki, K; Yokoyama, M; Yamada, S; Saito, M

1997-07-01

The number of ovulated oocytes in the adult house musk shrews was examined by natural mating. The positive rate of ovulation was 83.3%, and the mean number of ovulated oocytes was 4.4 +/- 1.9 (Mean +/- SD). The induction of superovulation was examined by administering either pregnant mare's serum gonadotropin (PMSG) or human chorionic gonadotropin (hCG), exogenous gonadotropin, to house musk shrews. As a result, the number of ovulated oocytes were within the number of oocytes ovulated spontaneously. The method of superovulation induction by administering both PMSG and hCG to house musk shrews was investigated. In the group intraperitoneally with 7.5 i.u. of PMSG followed by 7.5 i.u. of hCG 48 hr later, the positive rate of ovulation was as high as 94.6% and the mean number of ovulated oocytes was 11.7 +/- 13.4. Moreover, in 15 out of these 35 animals positive for ovulation, 10 oocytes or more were observed and the mean number of ovulated oocytes was 21.0 +/- 16.5, showing the superovulatory response. In the group of 5.0 i.u. PMSG and 5.0 i.u. hCG injected at an interval of 72 hr, every animal was induced to ovulate and the mean number of ovulated oocytes was 41.3 +/- 19.9. Thus, the injection of PMSG and hCG at a longer interval increased the number of superovulated oocytes. Furthermore, 97.5% of eggs recovered from superovulating animals contained cumulus cells.

Implementing clinical governance in Isfahan hospitals: Barriers and solutions, 2014.

PubMed

Ferdosi, Masoud; Ziyari, Farhad Bahman; Ollahi, Mehran Nemat; Salmani, Amaneh Rahim; Niknam, Noureddin

2016-01-01

In the new approach, all health care providers have been obligated to maintain and improve the quality and have been accountable for it. One of the ways is the implementation of clinical governance (CG). More accurate understanding of its challenges can help to improve its performance. In this study, barriers of CG implementation are investigated from the perspective of the hospitals involved. Besides, some solutions are suggested based on stakeholders' opinions. This study used combined method (qualitative content analysis and questionnaire) in hospitals affiliated to Isfahan University of Medical Sciences in 2014. First, experts, and stakeholders talked about CG implementation obstacles in a semi-structured interview. Interviews were confirmed by the interviewee (double check). After analyzing the interviews using reduction coding the questionnaire was drawn up. The questionnaire "validity was confirmed by Cronbach's alpha (0/891)" and its reliability was obtained using experts confirmation. Data analyzing was performed using SPSS (18) software. According to results staffing and management factors were the main obstacles. After them, were factors related to organizational culture, infrastructure elements, information, sociocultural and then process factors. The learning barriers were in final rank. Thirty-four solutions was proposed by experts and divided into subset of eight major barriers. Most solutions were offered on modifying processes and minimal solutions about modifying of organizational culture, sociocultural, and educational factors. Removing the obstacles, especially management and human resource factors can be effective by facilitating and accelerating CG. Furthermore, use of experts and stakeholders opinions can help to remove CG barriers.

TMV-Cg Coat Protein stabilizes DELLA proteins and in turn negatively modulates salicylic acid-mediated defense pathway during Arabidopsis thaliana viral infection.

PubMed

Rodriguez, Maria Cecilia; Conti, Gabriela; Zavallo, Diego; Manacorda, Carlos Augusto; Asurmendi, Sebastian

2014-08-03

Plant viral infections disturb defense regulatory networks during tissue invasion. Emerging evidence demonstrates that a significant proportion of these alterations are mediated by hormone imbalances. Although the DELLA proteins have been reported to be central players in hormone cross-talk, their role in the modulation of hormone signaling during virus infections remains unknown. This work revealed that TMV-Cg coat protein (CgCP) suppresses the salicylic acid (SA) signaling pathway without altering defense hormone SA or jasmonic acid (JA) levels in Arabidopsis thaliana. Furthermore, it was observed that the expression of CgCP reduces plant growth and delays the timing of floral transition. Quantitative RT-qPCR analysis of DELLA target genes showed that CgCP alters relative expression of several target genes, indicating that the DELLA proteins mediate transcriptional changes produced by CgCP expression. Analyses by fluorescence confocal microscopy showed that CgCP stabilizes DELLA proteins accumulation in the presence of gibberellic acid (GA) and that the DELLA proteins are also stabilized during TMV-Cg virus infections. Moreover, DELLA proteins negatively modulated defense transcript profiles during TMV-Cg infection. As a result, TMV-Cg accumulation was significantly reduced in the quadruple-DELLA mutant Arabidopsis plants compared to wild type plants. Taken together, these results demonstrate that CgCP negatively regulates the salicylic acid-mediated defense pathway by stabilizing the DELLA proteins during Arabidopsis thaliana viral infection, suggesting that CgCP alters the stability of DELLAs as a mechanism of negative modulation of antiviral defense responses.

Elevated β-hCG associated with aggressive Osteoblastoma.

PubMed

Morris, Carol D; Hameed, Meera R; Agaram, Narasimhan P; Hwang, Sinchun

2017-09-01

We present a unique case of an aggressive scapular osteoblastoma that produced β-hCG as a paraneoplastic manifestation in a 20-year-old woman. Serum β-hCG was found to be elevated during presurgical workup and consequently delayed surgical resection of the increasingly painful tumor because of suspected pregnancy. The paraneoplastic production of β-hCG was later proven by positive immunohistochemical stain of β-hCG in a curettage specimen and normalization of β-hCG levels after surgical resection of the aggressive osteoblastoma. Production of beta-human chorionic gonadotropin (β-hCG) has been reported in several carcinomas and sarcomas but, to our knowledge, it has not been reported in osteoblastoma in the English-language literature.

Extraction method of interfacial injected charges for SiC power MOSFETs

NASA Astrophysics Data System (ADS)

Wei, Jiaxing; Liu, Siyang; Li, Sheng; Song, Haiyang; Chen, Xin; Li, Ting; Fang, Jiong; Sun, Weifeng

2018-01-01

An improved novel extraction method which can characterize the injected charges along the gate oxide interface for silicon carbide (SiC) power metal-oxide-semiconductor field-effect transistors (MOSFETs) is proposed. According to the different interface situations of the channel region and the junction FET (JFET) region, the gate capacitance versus gate voltage (Cg-Vg) curve of the device can be divided into three relatively independent parts, through which the locations and the types of the charges injected in to the oxide above the interface can be distinguished. Moreover, the densities of these charges can also be calculated by the amplitudes of the shifts in the Cg-Vg curve. The correctness of this method is proved by TCAD simulations. Moreover, experiments on devices stressed by unclamped-inductive-switching (UIS) stress and negative bias temperature stress (NBTS) are performed to verify the validity of this method.

Environmental investigation on co-combustion of sewage sludge and coal gangue: SO2, NOx and trace elements emissions.

PubMed

Yang, Zhenzhou; Zhang, Yingyi; Liu, Lili; Wang, Xidong; Zhang, Zuotai

2016-04-01

To promote the utilization of waste material as alternative fuel, the mono- and co-combustion characteristics of sewage sludge (SS) and coal gangue (CG) were systematically investigated, with emphasis on environmental influences. The emission of SO2, NOx as well as the trace elements during combustion of SS and CG were studied with regard to the effects of their chemistries, structures and interactions. Results showed that co-combustion can be beneficial for ignition performance. A synergic effect on both desulfurization and denitrification can be expected at ca. 800°C. Further, an enhanced retention of trace elements during co-combustion was also observed, especially for Pb and Zn. On the basis of the results, it can be expected that, with proper operation, co-combustion of SS and CG can be a promising method for the disposal of these two wastes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Infra-red technique for cerebral blood flow: comparison with /sup 133/Xenon clearance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colacino, J.M.; Grubb, B.; Joebsis, F.F.

A rapid infra-red optical technique has been developed for the measurement of cerebral blood flow. The method measures optical density changes across the intact skull during the passage of a bolus of the dye. Cardio-Green (CG). The clearance curves obtained for CG boluses are very short (less than 30 sec) in comparison with those obtained with tracers such as /sup 133/Xenon (10-30 min) that distribute into cerebral tissue. The volume of distribution of CG is totally intravascular, and the dye is relatively slowly cleared from the body. The important advantages of this spectrophotometric technique are its speed, versatility, and themore » avoidance of radioactive materials. The differential spectrophotometer used in this study, with trivial modifications, has been used to monitor changes in brain blood volume, oxygen saturation of hemoglobin, and cortical mitochondrial respiratory function, which illustrate the versatility of the technique for neurological assessments.« less

Serum human chorionic gonadotropin (hCG) trend within the first few days after medical abortion: a prospective study.

PubMed

Pocius, Katherine D; Bartz, Deborah; Maurer, Rie; Stenquist, Asha; Fortin, Jennifer; Goldberg, Alisa B

2017-03-01

To prospectively describe the decline in serum human chorionic gonadotropin (hCG) in the first 5 days after complete medical abortion and evaluate the influence of initial hCG and gestational duration. We conducted a prospective, physiologic study of women ≤63 days gestation who underwent medical abortion with 200 mg mifepristone and 800 mcg buccal misoprostol. We stratified enrollment into two gestational cohorts, <49 days and 49-63 days, to ensure gestational variability. We collected serum quantitative hCG values on Day 1 (day of mifepristone), Day 3, Day 5 and a routine follow up hCG on Days 7-14. We calculated the percent hCG decline from Day 1 to each repeat measure and evaluated trends based on initial serum hCG level and gestation. We enrolled 66 women; 59 were protocol-adherent and included in our analysis. Mean gestation on Day 1 was 49 days and mean baseline hCG was 72,332 IU. Fifty-seven subjects (97%) had a complete medical abortion without further intervention. The mean serum hCG decline among subjects with complete medical abortion was 70.0±10.6% [range 36.9-98.6%] on Day 3 and 91.4±4.4% [range 68.4-97.7%] on Day 5. The mean serum hCG decline from Day 1 to routine follow-up on Days 7-9 was 97.1±1.7% [range 92.4-99.2%], from Day 1 to Day 10-11 was 98.5±1.4% [range 94.7-99.6%] and from Day 1 to Day 12-14 was 98.7±2.8% [range 86.7-99.9%]. There was no difference in percent hCG decline stratified by initial hCG or gestation. There is a rapid and predictable decline in serum hCG as early as Day 5 after complete medical abortion through 63 days gestation. Rate of hCG decline is not affected by initial hCG or gestational duration. For women who require confirmation of complete abortion sooner than 1 week after mifepristone, due to patient preference, logistical constraints or in the setting of pregnancy of unconfirmed location, a single repeat hCG on Day 5 may be clinically useful. Copyright © 2016 Elsevier Inc. All rights reserved.

Changes in pain and concurrent pain medication use following compounded topical analgesic treatment for chronic pain: 3- and 6-month follow-up results from the prospective, observational Optimizing Patient Experience and Response to Topical Analgesics study

PubMed Central

Gudin, Jeffrey A; Brennan, Michael J; Harris, E Dennis; Hurwitz, Peter L; Dietze, Derek T; Strader, James D

2017-01-01

Background Opioids and other controlled substances prescribed for chronic pain are associated with abuse, addiction, and death, prompting national initiatives to identify safe and effective pain management strategies including topical analgesics. Methods This prospective, observational study evaluated changes from baseline in overall mean severity and interference scores on the Brief Pain Inventory scale and the use of concurrent pain medications at 3- and 6-month follow-up assessments in chronic pain patients treated with topical analgesics. Changes in pain severity and interference and medication usage were compared between treated patients and unmatched and matched controls. Results The unmatched intervention group (unmatched-IG) included 631 patients who completed baseline and 3-month follow-up surveys (3-month unmatched-IG) and 158 who completed baseline and 6-month follow-up assessments (6-month unmatched-IG). Baseline and 3-month follow-up data were provided by 76 unmatched controls and 76 matched controls (3-month unmatched-CG and matched-CG), and 51 unmatched and 36 matched patients completed baseline and 6-month follow-up surveys (6-month unmatched-CG and matched-CG). Baseline demographic characteristics and mean pain severity and interference scores were similar between groups. There were statistically significant decreases from baseline in mean pain severity and interference scores within the 3- and 6-month unmatched-IG (all P<0.001). Significantly greater decreases in the mean change from baseline in pain severity and interference scores were evident for the 3- and 6-month unmatched-IG versus unmatched-CG (all P<0.001), with similar results when the 3- and 6-month matched-IG and matched-CG were compared. A higher percentage of the 3- and 6-month unmatched-IG and matched-IG de-escalated use of concurrent pain medications (all P<0.001), while significantly higher percentages of the unmatched-CG and matched-CG escalated medication use. Side effects were reported by <1% of the unmatched-IG. Conclusion Topical analgesics appear to be effective and safe for the treatment of chronic pain, with randomized controlled trials needed to confirm these findings. PMID:29042810

“I Was Just Trying To Stick It Out Until I Realized That I Couldn't”: A Phenomenological Investigation of Support Seeking Among Older Adults With Complicated Grief*

PubMed Central

Ghesquiere, Angela

2014-01-01

Complicated Grief (CG) is a prolonged, impairing mental health condition affecting about 7% of the bereaved. CG may be especially prevalent in older adults. Though evidence-based treatments for CG have been developed, little is known about support-seeking in older adults with CG. This study used the descriptive phenomenological approach to explore the CG support-seeking process. In-depth interviews were conducted with 8 CG-positive older adults who had completed participation in a randomized clinical trial of CG treatment. Five primary themes arose: observing that grief was causing a great deal of distress and impairment; grief not meeting expectations of what grief “should be”; an important influence of social relationships on support-seeking; lack of effectiveness of grief support groups and/or care from mental health professionals prior to study enrollment; and strong reactions to the label of CG. Themes may hep inform efforts to engage older adults with CG in effective care. PMID:24547662

Convenient radioimmunoassay for urinary human choriogonadotropin without interference by urinary human lutropin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wehmann, R.E.; Harman, S.M.; Birken, S.

1981-12-01

We have devised a radioimmunoassay (RIA) for human choriogonadotropin (hCG) in first morning-voided urine specimens. Concanavalin A, a lectin, is used to extract and concentrate the hCG from urine. A high-affinity antiserum is used, directed to the hCG..beta.. carboxy-terminal peptide, a unique immunological determinant not shared by the beta subunit of human lutropin. This ensures that urinary human lutropin-related molecules, which interfere with RIAs involving antisera to the intact hCG..beta.. subunit, will not cross react in this assay. A concentration of hCG as low as 0.4 ..mu..g/L can be detected in the first morning-voided urine. The effective sensitivity of thismore » assay for the unequivocal detection of hCG production is somewhat better than that achieved with the serum hCG RIA involving antisera to the hCG..beta.. subunit. The improved specificity and sensitivity of this assay, and the greater convenience of collecting samples of urine rather than blood, are clinically useful advantages of this approach to assessing hCG production in humans.« less

hCG Triggering in ART: An Evolutionary Concept.

PubMed

Hershko Klement, Anat; Shulman, Adrian

2017-05-17

Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering GnRH agonist followed by hCG triggering. According to this new concept, GnRH agonist enables successful ovum maturation, while hCG supports the luteal phase and pregnancy until placental shift.

beta-Citryl-L-glutamate is an endogenous iron chelator that occurs naturally in the developing brain.

PubMed

Hamada-Kanazawa, Michiko; Kouda, Makiko; Odani, Akira; Matsuyama, Kaori; Kanazawa, Kiyoka; Hasegawa, Tatsuya; Narahara, Masanori; Miyake, Masaharu

2010-01-01

The compound beta-citryl-L-glutamate (beta-CG) was initially isolated from developing brains, while it has also been found in high concentrations in testes and eyes. However, its functional roles are unclear. To evaluate its coordination with metal ions, we performed pH titration experiments. The stability constant, logbeta(pqr) for M(p)(beta-CG)(q)H(r) was calculated from pH titration data, which showed that beta-CG forms relatively strong complexes with Fe(III), Cu(II), Fe(II) and Zn(II). beta-CG was also found able to solubilize Fe more effectively from Fe(OH)(2) than from Fe(OH)(3). Therefore, we examined the effects of beta-CG on Fe-dependent reactive oxygen species (ROS)-generating systems, as well as the potential ROS-scavenging activities of beta-CG and metal ion-(beta-CG) complexes. beta-CG inhibited the Fe-dependent degradation of deoxyribose and Fe-dependent damage to DNA or plasmid DNA in a dose-dependent manner, whereas it had no effect on Cu-mediated DNA damage. In addition, thermodynamic data showed that beta-CG in a physiological pH solution is an Fe(II) chelator rather than an Fe(III) chelator. Taken together, these findings suggest that beta-CG is an endogenous low molecular weight Fe chelator.

[The influence of high fluoride exposure in drinking water on endocrine hormone in female].

PubMed

Hou, Jia-xiang; Yang, Yue-jin; Gong, Biao; Li, Shi-hong; Ding, Zhong; Wen, Shi-bao; Li, Shi-qun; Cheng, Xue-min; Cui, Liu-xin; Ba, Yue

2013-02-01

To explore the influence of water fluoride exposure on reproductive hormones in female. Cross-sectional study was conducted in seven villages of a county in Henan province by using simple random sampling including high fluoride area, defluoridation project area and control area on April, 2011 based on the preliminary study results of fluoride concentration in drinking water. Women who were born and growth or lived in the village at least 5 years and aged 18-48 years old were recruited using cluster sampling. They were divided into high fluoride group (HFG, 116 subjects), defluoridation project group (DFPG, 132 subjects) and control group (CG, 227 subjects) in accordance with the above areas. All subjects accepted questionnaire and physical checkup. Fasting blood and morning urine samples were collected. The concentration of fluoride in urine was determined by fluoride ion selective electrode method. The serum level of GnRH was detected using enzyme linked immunosorbent assay (ELISA). The serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) were determined by chemiluminesence immunoassay (CLIA). The average age was (39.44 ± 7.34), (38.84 ± 8.03), (37.45 ± 7.70) years old in female from DFPG, HFG and CG respectively, there were no significant differences among the three groups (F = 3.02, P = 0.05). The urine fluoride levels were (1.34 ± 1.07), (2.59 ± 1.57), (0.92 ± 0.46) mg/ml in female from DFPG, HFG and CG respectively, there was a significant difference among three groups (F = 105.38, P < 0.01). No significant differences were observed of serum GnRH, LH, T, FSH and E2 among three groups in follicular phase (P > 0.05). The serum levels of E2 in Ovulatory period were 67.73, 58.09, 84.96 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in CG (H = 4.00, P < 0.05). The serum levels of T in Ovulatory period were 0.55, 0.45, 0.55 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 6.47, P < 0.05), but no significant difference was observed between HFG and CG (H = 2.41, P > 0.05). The serum levels of GnRH in Luteal phase were 24.09, 20.16, 23.50 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 14.14, P < 0.05) and CG (H = 12.53, P < 0.05). The serum level of E2 in luteal phase were 81.47, 64.60, 74.55 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 5.69, P < 0.05). As for LH, FSH and T, no significant differences were observed among the three groups (P > 0.05 respectively). The abnormal rates of E2 level were 22.73 (30/102), 37.93 (44/72), 20.26 (46/181) in female from DFPG, HFG and CG respectively. The E2 abnormal rate in female from HFG was higher that from DFPG (χ(2) = 6.82, P < 0.05) and CG (χ(2) = 12.38, P < 0.05). Fluoride exposure may influence reproductive hormones in female, especially in ovulatory and luteal phase of menstrual cycle.

Protease nexin-1 promotes secretory granule biogenesis by preventing granule protein degradation.

PubMed

Kim, Taeyoon; Loh, Y Peng

2006-02-01

Dense-core secretory granule (DCG) biogenesis is a prerequisite step for the sorting, processing, and secretion of neuropeptides and hormones in (neuro)endocrine cells. Previously, chromogranin A (CgA) has been shown to play a key role in the regulation of DCG biogenesis in vitro and in vivo. However, the underlying mechanism of CgA-mediated DCG biogenesis has not been explored. In this study, we have uncovered a novel mechanism for the regulation of CgA-mediated DCG biogenesis. Transfection of CgA into endocrine 6T3 cells lacking CgA and DCGs not only recovered DCG formation and regulated secretion but also prevented granule protein degradation. Genetic profiling of CgA-expressing 6T3 versus CgA- and DCG-deficient 6T3 cells, followed by real-time reverse transcription-polymerase chain reaction and Western blotting analyses, revealed that a serine protease inhibitor, protease nexin-1 (PN-1), was significantly up-regulated in CgA-expressing 6T3 cells. Overexpression of PN-1 in CgA-deficient 6T3 cells prevented degradation of DCG proteins at the Golgi apparatus, enhanced DCG biogenesis, and recovered regulated secretion. Moreover, depletion of PN-1 by antisense RNAs in CgA-expressing 6T3 cells resulted in the specific degradation of DCG proteins. We conclude that CgA increases DCG biogenesis in endocrine cells by up-regulating PN-1 expression to stabilize granule proteins against degradation.

Protease Nexin-1 Promotes Secretory Granule Biogenesis by Preventing Granule Protein Degradation

PubMed Central

Kim, Taeyoon; Loh, Y. Peng

2006-01-01

Dense-core secretory granule (DCG) biogenesis is a prerequisite step for the sorting, processing, and secretion of neuropeptides and hormones in (neuro)endocrine cells. Previously, chromogranin A (CgA) has been shown to play a key role in the regulation of DCG biogenesis in vitro and in vivo. However, the underlying mechanism of CgA-mediated DCG biogenesis has not been explored. In this study, we have uncovered a novel mechanism for the regulation of CgA-mediated DCG biogenesis. Transfection of CgA into endocrine 6T3 cells lacking CgA and DCGs not only recovered DCG formation and regulated secretion but also prevented granule protein degradation. Genetic profiling of CgA-expressing 6T3 versus CgA- and DCG-deficient 6T3 cells, followed by real-time reverse transcription-polymerase chain reaction and Western blotting analyses, revealed that a serine protease inhibitor, protease nexin-1 (PN-1), was significantly up-regulated in CgA-expressing 6T3 cells. Overexpression of PN-1 in CgA-deficient 6T3 cells prevented degradation of DCG proteins at the Golgi apparatus, enhanced DCG biogenesis, and recovered regulated secretion. Moreover, depletion of PN-1 by antisense RNAs in CgA-expressing 6T3 cells resulted in the specific degradation of DCG proteins. We conclude that CgA increases DCG biogenesis in endocrine cells by up-regulating PN-1 expression to stabilize granule proteins against degradation. PMID:16319172

Preparation of cashew gum-based flocculants by microwave- and ultrasound-assisted methods.

PubMed

Klein, Jalma Maria; de Lima, Vanessa Silva; da Feira, José Manoel Couto; Camassola, Marli; Brandalise, Rosmary Nichele; Forte, Maria Madalena de Camargo

2018-02-01

In this work, copolymers based on cashew gum (CG) grafted with polyacrylamide (PAM) were synthesized by microwave- and ultrasound-assisted methods, using potassium persulfate as an initiator in aqueous medium. The graft copolymers were characterized by Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and thermogravimetric analysis. The efficiency of the graft copolymers (CG-g-PAM) in flocculation of a kaolin suspension was studied. Results indicated that the graft copolymers synthesized by ultrasound energy had better flocculation properties than the ones synthesized by the microwave-assisted method. The biodegradability of the graft copolymers was tested by inoculation with the basidiomycete Trametes villosa in liquid medium. The higher formation of biomass than that observed with the commercial flocculant Flonex-9045 indicated that the graft copolymer was accessible to enzymatic attack. Copyright © 2017 Elsevier B.V. All rights reserved.

Complicated grief associated with hurricane Katrina.

PubMed

Shear, M Katherine; McLaughlin, Katie A; Ghesquiere, Angela; Gruber, Michael J; Sampson, Nancy A; Kessler, Ronald C

2011-08-01

Although losses are important consequences of disasters, few epidemiological studies of disasters have assessed complicated grief (CG) and none assessed CG associated with losses other than death of loved one. Data come from the baseline survey of the Hurricane Katrina Community Advisory Group, a representative sample of 3,088 residents of the areas directly affected by Hurricane Katrina. A brief screen for CG was included containing four items consistent with the proposed DSM-V criteria for a diagnosis of bereavement-related adjustment disorder. Fifty-eight and half percent of respondents reported a significant hurricane-related loss: Most-severe losses were 29.0% tangible, 9.5% interpersonal, 8.1% intangible, 4.2% work/financial, and 3.7% death of loved one. Twenty-six point one percent respondents with significant loss had possible CG and 7.0% moderate-to-severe CG. Death of loved one was associated with the highest conditional probability of moderate-to-severe CG (18.5%, compared to 1.1-10.5% conditional probabilities for other losses), but accounted for only 16.5% of moderate-to-severe CG due to its comparatively low prevalence. Most moderate-to-severe CG was due to tangible (52.9%) or interpersonal (24.0%) losses. Significant predictors of CG were mostly unique to either bereavement (racial-ethnic minority status, social support) or other losses (prehurricane history of psychopathology, social competence.). Nonbereavement losses accounted for the vast majority of hurricane-related possible CG despite risk of CG being much higher in response to bereavement than to other losses. This result argues for expansion of research on CG beyond bereavement and alerts clinicians to the need to address postdisaster grief associated with a wide range of losses. © 2011 Wiley-Liss, Inc.

Cholesterol-α-glucosyltransferase gene is present in most Helicobacter species including gastric non-Helicobacter pylori helicobacters obtained from Japanese patients.

PubMed

Kawakubo, Masatomo; Horiuchi, Kazuki; Matsumoto, Takehisa; Nakayama, Jun; Akamatsu, Taiji; Katsuyama, Tsutomu; Ota, Hiroyoshi; Sagara, Junji

2018-02-01

Non-Helicobacter pylori helicobacters (NHPHs) besides H. pylori infect human stomachs and cause chronic gastritis and mucosa-associated lymphoid tissue lymphoma. Cholesteryl-α-glucosides have been identified as unique glycolipids present in H. pylori and some Helicobacter species. Cholesterol-α-glucosyltransferase (αCgT), a key enzyme for the biosynthesis of cholesteryl-α-glucosides, plays crucial roles in the pathogenicity of H. pylori. Therefore, it is important to examine αCgTs of NHPHs. Six gastric NHPHs were isolated from Japanese patients and maintained in mouse stomachs. The αCgT genes were amplified by PCR and inverse PCR. We retrieved the αCgT genes of other Helicobacter species by BLAST searches in GenBank. αCgT genes were present in most Helicobacter species and in all Japanese isolates examined. However, we could find no candidate gene for αCgT in the whole genome of Helicobacter cinaedi and several enterohepatic species. Phylogenic analysis demonstrated that the αCgT genes of all Japanese isolates show high similarities to that of a zoonotic group of gastric NHPHs including Helicobacter suis, Helicobacter heilmannii, and Helicobacter ailurogastricus. Of 6 Japanese isolates, the αCgT genes of 4 isolates were identical to that of H. suis, and that of another 2 isolates were similar to that of H. heilmannii and H. ailurogastricus. All gastric NHPHs examined showed presence of αCgT genes, indicating that αCgT may be beneficial for these helicobacters to infect human and possibly animal stomachs. Our study indicated that NHPHs could be classified into 2 groups, NHPHs with αCgT genes and NHPHs without αCgT genes. © 2017 John Wiley & Sons Ltd.

Altered newborn gender distribution in patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG).

PubMed

Santolaya-Forgas, J; Meyer, W J; Burton, B K; Scommegna, A

1997-01-01

to determine if the sex ratio (male/female) is altered in infants born to patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG). Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG, and maternal serum unconjugated estriol (MSuE3). Among these, there were 132 patients with low second-trimester MShCG (< 0.4 MoM), normal MSAFP and MSuE3. The gender distribution of these term, normal newborns was compared to that of 237 controls, matched for race, maternal age, and referral source and delivered at term to mothers with normal mid-trimester MSAFP, MSuE3, and MShCG. The gender distribution of these two groups of newborns was also compared to that of 78 term newborns from the same obstetrical population delivered to mothers with second-trimester MShCG > 2.5 MoM and normal MSAFP and MSuE3. All patients had a complete obstetrical history. Forty-nine percent of the controls were male vs. 62% of the group with slow second-trimester MShCG (P < .01). Within the group with low MShCG, 59% of infants were male when the MShCG was between 0.19 and 0.4 MoM (A) and 80% when the MShCG was < 0.2 MoM (B) (control vs. A vs. B P < .005). The sex ratio in the high-MShCG group was similar to control. The data suggest that gender distribution is different from normal in patients with low mid-trimester MShCG.

Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor.

PubMed

Evans, Jemma

2016-03-01

Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effect of post-mating hCG or progesterone administration on reproductive performance of Afshari × Booroola-Merino crossbred ewes.

PubMed

Rostami, Behnam; Hajizadeh, Rahman; Shahir, Mohammad-Hossein; Aliyari, Davood

2017-02-01

To investigate the efficiency of hCG/CIDR after breeding to increase the reproductive performance, 35 synchronized ewes were mated with fertile rams and were assigned to three treatment groups. Ewes in hCG group (n = 12) received 400 IU hCG on day 11 post-mating, and ewes in CIDR group (n = 11) received CIDR from day 7 until day 19 post-mating. Ewes in the control group (n = 12) did not receive any treatment. Blood samples were collected on days 7, 12, 17, and 22 post-mating. Plasma P 4 concentrations were higher on days 12 and 17 post-mating in hCG- and CIDR-treated groups (P < 0.05). However, the concentrations of P 4 on day 22 post-mating in hCG and control groups were higher than that in CIDR group (P < 0.05). Ewes in hCG group produced more quadruplets (P < 0.05) and triplets, and as a result, they had a larger litter size (P < 0.05). The lamb mortality rate by weaning in hCG group (3.6%) was less than that in control (11.8%; P < 0.05) and CIDR (9.1%; P > 0.05) groups. Post-mating administration of hCG or CIDR did not affect the lamb birth weight in single and quadruplet births (P > 0.05), but the birth weight of twin lambs was higher in the hCG and CIDR groups (P < 0.05). Weaning weights of twin lambs were higher in the hCG and CIDR groups (P < 0.05). In conclusion, hCG/CIDR administration post-mating increased the maternal P 4 concentrations and enhanced reproductive performance.

Change of maternal thyroid function in twin-twin transfusion syndrome.

PubMed

Hanaoka, Masachi; Arata, Naoko; Sago, Haruhiko

2015-01-01

Human chorionic gonadotropin (hCG) has weak thyroid-stimulating activity because of its homology with thyroid stimulating hormone (TSH). In twin-twin transfusion syndrome (TTTS), which is a severe complication of monochorionic twin pregnancies, a close association between maternal serum hCG concentration and TTTS has been reported. And, TTTS can be treated by fetoscopic laser coagulation of the communicating vessels. To clarify the relationship between maternal serum hCG and maternal thyroid function in TTTS, the present study investigated the change in thyroid hormone and hCG levels after laser therapy. The protocol included collection of serial maternal blood samples in TTTS before laser therapy, and at two and four weeks after laser therapy. For 131 cases of TTTS, the following parameters were determined at each point: hCG, TSH, free triiodothyronine (fT3), and free thyroxine (fT4). The multiple of the median (MoM) of pre-operative hCG concentration in TTTS was 5.39 MoM (interquartile range, 2.83 - 8.64). There was a moderate positive correlation between hCG and fT3 in TTTS pre-operatively (R = 0.22, P = 0.030). fT4 was also positively correlated with hCG (R = 0.33, P < 0.001). Some cases showed very high concentration in fT3. When laser therapy for TTTS was effective, the hCG concentration significantly decreased, and fT3 and fT4 decreased progressively in concert with the decrease in hCG. The relationship between hCG and thyroid function in TTTS supports the finding of TTTS as a novel etiology of hCG-mediated hyperthyroidism during pregnancy.

A single dose of a MIV-150/Zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use.

PubMed

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Zydowsky, Thomas M; Robbiani, Melissa

2012-11-01

Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4-24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8-24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8-24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure.

A Single Dose of a MIV-150/Zinc Acetate Gel Provides 24 h of Protection Against Vaginal Simian Human Immunodeficiency Virus Reverse Transcriptase Infection, with More Limited Protection Rectally 8–24 h After Gel Use

PubMed Central

Kenney, Jessica; Singer, Rachel; Derby, Nina; Aravantinou, Meropi; Abraham, Ciby J.; Menon, Radhika; Seidor, Samantha; Zhang, Shimin; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D.; Fernández-Romero, José A.; Zydowsky, Thomas M.

2012-01-01

Abstract Previously we showed that repeated vaginal application of a MIV-150/zinc acetate carrageenan (MIV-150/ZA/CG) gel and a zinc acetate carrageenan (ZA/CG) gel significantly protected macaques from vaginal simian human immunodeficiency virus reverse transcriptase (SHIV-RT) infection. Gels were applied either daily for 2 weeks or every other day for 4 weeks, and the animals were challenged 4–24 h later. Herein, we examined the effects of a single vaginal dose administered either before or after virus challenge. Encouraged by the vaginal protection seen with MIV-150/ZA/CG, we also tested it rectally. Vaginal applications of MIV-150/ZA/CG, ZA/CG, and CG gel were performed once 8–24 h before, 1 h after, or 24 h before and 1 h after vaginal challenge. Rectal applications of MIV-150/ZA/CG and CG gel were performed once 8 or 24 h before rectal challenge. While vaginal pre-challenge and pre/post-challenge application of MIV-150/ZA/CG gel offered significant protection (88%, p<0.002), post-challenge application alone did not significantly protect. ZA/CG gel reduced infection prechallenge, but not significantly, and the effect was completely lost post-challenge. Rectal application of MIV-150/ZA/CG gel afforded limited protection against rectal challenge when applied 8–24 h before challenge. Thus, MIV-150/ZA/CG gel is a highly effective vaginal microbicide that demonstrates 24 h of protection from vaginal infection and may demonstrate efficacy against rectal infection when given close to the time of HIV exposure. PMID:22737981

D1 dopamine receptor is involved in shell formation in larvae of Pacific oyster Crassostrea gigas.

PubMed

Liu, Zhaoqun; Wang, Lingling; Yan, Yunchen; Zheng, Yan; Ge, Wenjing; Li, Meijia; Wang, Weilin; Song, Xiaorui; Song, Linsheng

2018-07-01

Dopamine (DA), a significant member of catecholamines, is reported to induce biomineralization of calcium carbonate vaterite microspheres via dopamine receptor (DR) in bivalves, implying the modulation of dopaminergic system on shell formation during larval development. In this research, a homologue of D1 type DR (CgD1DR-1) was identified from oyster Crassostrea gigas, whose full length cDNA was 1197 bp. It was widely expressed in various tissues of C. gigas, with the significantly higher levels in hepatopancreas, mantle, muscle and gill. During developmental stages, the mRNA transcripts of CgD1DR-1 in D-shape larvae were obviously higher (p < 0.05) than those in trochophore and umbo larvae, and CO 2 exposure could inhibit the synthesis of DA and mRNA expression of CgD1DR-1. After cell transfection and DA treatment, intracellular cAMP in cells with the expression of CgD1DR-1 increased significantly (p < 0.05). Furthermore, the incubation with SCH 23390 for the blockage of CgD1DR-1 significantly restrained the expressions of six shell formation-related genes including CgTyrosinase-1, CgTyrosinase-3, CgChitinaseLP, CgAMC, CgBMP and CgBMPR in trochophore and D-shape larvae. These results jointly suggested that DA together with its receptor CgD1DR-1 might be involved in shell formation during oyster larval development from trochophore to D-shape larvae, and CO 2 -induced ocean acidification (OA) might influence marine bivalves by inhibiting the DA-D1DR pathway to prohibit their shell formation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-A(y.).

PubMed

Suto, Jun-ichi; Satou, Kunio

2015-02-01

The A(y) allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-A(y) male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-A(y) males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-A(y) males. Using a backcross progeny of DDD × (B6 × DDD.Cg-A(y)) F1-A(y), we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-A(y) males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-A(y) and DDD males), individual housing (single DDD.Cg-A(y) male) and single male housing with females (single DDD.Cg-A(y) male with DDD.Cg-A(y) or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-A(y) males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-A(y) males.

Further characterization of diabetes mellitus and body weight loss in males of the congenic mouse strain DDD.Cg-Ay

PubMed Central

SUTO, Jun-ichi; SATOU, Kunio

2014-01-01

The Ay allele at the agouti locus causes obesity and promotes linear growth in mice. However, body weight gain stops between 16 and 17 weeks after birth, and then, body weight decreases gradually in DDD.Cg-Ay male mice. Body weight loss is a consequence of diabetes mellitus, which is genetically controlled mainly by a quantitative trait locus (QTL) on chromosome 4. This study aimed to further characterize diabetes mellitus and body weight loss in DDD.Cg-Ay males. The number of β-cells was markedly reduced, and plasma insulin levels were very low in the DDD.Cg-Ay males. Using a backcross progeny of DDD × (B6 × DDD.Cg-Ay) F1-Ay, we identified one significant QTL for plasma insulin levels on distal chromosome 4, which was coincidental with QTL for hyperglycemia and lower body weight. The DDD allele was associated with decreased plasma insulin levels. When the DDD.Cg-Ay males were housed under three different housing conditions [group housing (4 or 5 DDD.Cg-Ay and DDD males), individual housing (single DDD.Cg-Ay male) and single male housing with females (single DDD.Cg-Ay male with DDD.Cg-Ay or DDD females)], diabetes mellitus and body weight loss were most severely expressed in individually housed mice. Thus, the severity of diabetes and body weight loss in the DDD.Cg-Ay males was strongly influenced by the housing conditions. These results demonstrate that both genetic and nongenetic environmental factors are involved in the development of diabetes mellitus and body weight loss in the DDD.Cg-Ay males. PMID:25373882

The influence of applying insurance medicine guidelines for depression on disability assessments

PubMed Central

2013-01-01

Background In the current study we report on the effects of an implementation strategy in the form of a training programme on the assessed work limitations of a client with depression by insurance physicians (IPs) participating in a RCT. These assessed work limitations of a client were in the form of scores on the List of Functional Abilities (LFA). Method We conducted a randomised controlled trial (RCT) for IPs in which we compared the intervention of a specially developed training programme with the usual methods of implementation and training currently used. The outcome was the mean sum score and the inter-rater reliability (Intraclass Correlation Coefficient, ICC) of the LFA scores. These LFA scores were scored by the IPs participating in the RCT for the work limitations of the cases presented in different videos, two videos before the training and two after the training of the intervention group. Results At baseline, the intervention group (IG) consisted of 21 IPs and the control group (CG) of 19. For one participant of the IG and for one of the CG the LFAs of the two case reports after training were not available. Before training the sum scores for the first case report did not differ significantly between the groups, while the mean sum score was higher in the IG than in the CG for the second case report. For both case reports after training a higher score was found in the IG than in the CG. The inter-rater reliability measured for the two case reports before training was about the same in the IG and the CG: 0.64 and 0.65, respectively. For the two case reports after training, the ICC was higher in the IG than in the CG: 0.69 and 0.54, respectively. This difference was not significant however. Conclusion It would appear that the implementation of a specially designed training programme on guidelines for depression may lead to greater inter-rater reliability in the assessments by insurance physicians of the work limitations of clients with depression. It is, however, important to note that insurance physicians who receive training may find more work limitations than those who do not. Trial registration Netherlands’ Trial Register NTR1863 PMID:23758690

The Discontinuous Galerkin Finite Element Method for Solving the MEG and the Combined MEG/EEG Forward Problem

PubMed Central

Piastra, Maria Carla; Nüßing, Andreas; Vorwerk, Johannes; Bornfleth, Harald; Oostenveld, Robert; Engwer, Christian; Wolters, Carsten H.

2018-01-01

In Electro- (EEG) and Magnetoencephalography (MEG), one important requirement of source reconstruction is the forward model. The continuous Galerkin finite element method (CG-FEM) has become one of the dominant approaches for solving the forward problem over the last decades. Recently, a discontinuous Galerkin FEM (DG-FEM) EEG forward approach has been proposed as an alternative to CG-FEM (Engwer et al., 2017). It was shown that DG-FEM preserves the property of conservation of charge and that it can, in certain situations such as the so-called skull leakages, be superior to the standard CG-FEM approach. In this paper, we developed, implemented, and evaluated two DG-FEM approaches for the MEG forward problem, namely a conservative and a non-conservative one. The subtraction approach was used as source model. The validation and evaluation work was done in statistical investigations in multi-layer homogeneous sphere models, where an analytic solution exists, and in a six-compartment realistically shaped head volume conductor model. In agreement with the theory, the conservative DG-FEM approach was found to be superior to the non-conservative DG-FEM implementation. This approach also showed convergence with increasing resolution of the hexahedral meshes. While in the EEG case, in presence of skull leakages, DG-FEM outperformed CG-FEM, in MEG, DG-FEM achieved similar numerical errors as the CG-FEM approach, i.e., skull leakages do not play a role for the MEG modality. In particular, for the finest mesh resolution of 1 mm sources with a distance of 1.59 mm from the brain-CSF surface, DG-FEM yielded mean topographical errors (relative difference measure, RDM%) of 1.5% and mean magnitude errors (MAG%) of 0.1% for the magnetic field. However, if the goal is a combined source analysis of EEG and MEG data, then it is highly desirable to employ the same forward model for both EEG and MEG data. Based on these results, we conclude that the newly presented conservative DG-FEM can at least complement and in some scenarios even outperform the established CG-FEM approaches in EEG or combined MEG/EEG source analysis scenarios, which motivates a further evaluation of DG-FEM for applications in bioelectromagnetism. PMID:29456487

1NON-INVASIVE RADIOIODINE IMAGING FOR ACCURATE QUANTITATION OF NIS REPORTER GENE EXPRESSION IN TRANSPLANTED HEARTS

PubMed Central

Ricci, Davide; Mennander, Ari A; Pham, Linh D; Rao, Vinay P; Miyagi, Naoto; Byrne, Guerard W; Russell, Stephen J; McGregor, Christopher GA

2008-01-01

Objectives We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 minutes prior to transplantation with University of Wisconsin (UW) solution (n=3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-βhCG (Ad-NIS-CG; n=6). On post-operative day (POD) 5, 10, 15 all animals underwent micro-SPECT/CT imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1±0.2; 0.9±0.07), Ad-NIS-CEA (1.2±0.3; 0.9±0.1) and Ad-NIS-CG (1.1±0.1; 0.9±0.1) compared to UW group (0.44±0.03; 0.47±0.06) on POD 5 and 10 (p<0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2=0.99 and R2=0.96 respectively). Conclusions These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic single photon emission computed tomography (SPECT) imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5. PMID:17980613

Effects of blood contamination on microtensile bond strength to dentin of three self-etch adhesives.

PubMed

Chang, Seok Woo; Cho, Byeong Hoon; Lim, Ran Yeob; Kyung, Seung Hyun; Park, Dong Sung; Oh, Tae Seok; Yoo, Hyun Mi

2010-01-01

This study evaluated the effects of blood contamination and decontamination methods during different steps of bonding procedures on the microtensile bond strength of two-step self-etch adhesives to dentin. Sixty extracted human molars were ground flat to expose occlusal dentin. The 60 molars were randomly assigned to three groups, each treated with a different two-step self-etch adhesive: Clearfil SE Bond, AdheSE and Tyrian SPE. In turn, these groups were subdivided into five subgroups (n = 20), each treated using different experimental conditions as follows: control group-no contamination; contamination group 1-CG1: primer application/ contamination/primer re-application; contamination group 2-CG2: primer application/contamination/wash/dry/primer re-application; contamination group 3-CG3: primer application/adhesive application/light curing/contamination/ adhesive re-application/light curing; contamina- tion group 4-CG4: primer application/adhesive application/light curing/contamination/wash/ dry/adhesive re-application/light curing. Composite buildup was performed using Z250. After 24 hours of storage in distilled water at 37 degrees C, the bonded specimens were trimmed to an hourglass shape and serially sectioned into slabs with 0.6 mm2 cross-sectional areas. Microtensile bond strengths (MTBS) were assessed for each specimen using a universal testing machine. The data were analyzed by two-way ANOVA followed by a post hoc LSD test. SEM evaluations of the fracture modes were also performed. The contaminated specimens showed lower bond strengths than specimens in the control group (p < 0.05), with the exception of CG1 in the Clearfil SE group and CG2 and CG3 in the Tyrian SPE group. Among the three self-etch adhesives, the Tyrian SPE group exhibited a significantly lower average MTBS compared to the Clearfil SE Bond and AdheSE (p < 0.05) groups. Based on the results of the current study, it was found that blood contamination reduced the MTBS of all three self-etch adhesives to dentin, and water-rinsing was unable to overcome the effects of blood contamination.

Oral Progestin Priming Increases Ovarian Sensitivity to Gonadotropin Stimulation and Improves Luteal Function in the Cat1

PubMed Central

Stewart, Rosemary A.; Pelican, Katharine M.; Crosier, Adrienne E.; Pukazhenthi, Budhan S.; Wildt, David E.; Ottinger, Mary Ann; Howard, JoGayle

2012-01-01

ABSTRACT As the only domesticated species known to exhibit both induced and spontaneous ovulation, the cat is a model for understanding the nuances of ovarian control. To explore ovarian sensitivity to exogenous gonadotropins and the influence of progestin priming, we conducted a study of queens that were down-regulated with oral progestin or allowed to cycle normally, followed by low or high doses of equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG). Our metrics included 1) fecal steroid metabolite profiles before and after ovulation induction, 2) laparoscopic examination of ovarian follicles and corpora lutea (CL) on Days 2 and 17 (Day 0 = hCG administration), and 3) ovariohysterectomy (Day 17) to assess CL progesterone concentrations, morphometrics, and histology. Reproductive tracts from time-matched, naturally mated queens (n = 6) served as controls. Every progestin-primed cat (n = 12) produced the desired response of morphologically similar, fresh CL (regardless of eCG/hCG dose) by Day 2, whereas 41.7% of unprimed counterparts (n = 12) failed to ovulate or had variable-aged CL suggestive of prior spontaneous ovulation (P < 0.05). The ovarian response to low, but not high, eCG/hCG was improved (P < 0.05) in primed compared to unprimed cats, indicating increased sensitivity to gonadotropin in the progestin-primed ovary. Progestin priming prevented hyperelevated fecal steroid metabolites and normalized CL progesterone capacity, but only when combined with low eCG/hCG. However, priming failed to prevent ancillary CL formation, smaller CL mass, or abnormal luteal cell density, which were common to all eCG/hCG-treated cats. Thus, the domestic cat exposed to eCG/hCG produces CL with structural and functional aberrations. These anomalies can be partially mitigated by progestin priming, possibly due to a protective effect of progestin associated with enhanced ovarian sensitivity to gonadotropins. PMID:23100619

A regulatory network of two galectins mediates the earliest steps of avian limb skeletal morphogenesis

PubMed Central

2011-01-01

Background The skeletal elements of vertebrate embryonic limbs are prefigured by rod- and spot-like condensations of precartilage mesenchymal cells. The formation of these condensations depends on cell-matrix and cell-cell interactions, but how they are initiated and patterned is as yet unresolved. Results Here we provide evidence that galectins, β-galactoside-binding lectins with β-sandwich folding, play fundamental roles in these processes. We show that among the five chicken galectin (CG) genes, two, CG-1A, and CG-8, are markedly elevated in expression at prospective sites of condensation in vitro and in vivo, with their protein products appearing earlier in development than any previously described marker. The two molecules enhance one another's gene expression but have opposite effects on condensation formation and cartilage development in vivo and in vitro: CG-1A, a non-covalent homodimer, promotes this process, while the tandem-repeat-type CG-8 antagonizes it. Correspondingly, knockdown of CG-1A inhibits the formation of skeletal elements while knockdown of CG-8 enhances it. The apparent paradox of mutual activation at the gene expression level coupled with antagonistic roles in skeletogenesis is resolved by analysis of the direct effect of the proteins on precartilage cells. Specifically, CG-1A causes their aggregation, whereas CG-8, which has no adhesive function of its own, blocks this effect. The developmental appearance and regulation of the unknown cell surface moieties ("ligands") to which CG-1A and CG-8 bind were indicative of specific cognate- and cross-regulatory interactions. Conclusion Our findings indicate that CG-1A and CG-8 constitute a multiscale network that is a major mediator, earlier-acting than any previously described, of the formation and patterning of precartilage mesenchymal condensations in the developing limb. This network functions autonomously of limb bud signaling centers or other limb bud positional cues. PMID:21284876

46 CFR 1.01-10 - Organization.

Code of Federal Regulations, 2014 CFR

2014-10-01

... resources; plans, acquires, develops, and allocates resources for development and execution of the Coast... Assistant Commandant for Prevention Policy (CG-5P), and the Director of Operations Resource Management (CG... Standards Evaluation and Development (CG-REG); and (ii) The Director of Inspections and Compliance (CG-5PC...

Impact of the choice of reference genome on the ability of the core genome SNV methodology to distinguish strains of Salmonella enterica serovar Heidelberg.

PubMed

Usongo, Valentine; Berry, Chrystal; Yousfi, Khadidja; Doualla-Bell, Florence; Labbé, Genevieve; Johnson, Roger; Fournier, Eric; Nadon, Celine; Goodridge, Lawrence; Bekal, Sadjia

2018-01-01

Salmonella enterica serovar Heidelberg (S. Heidelberg) is one of the top serovars causing human salmonellosis. The core genome single nucleotide variant pipeline (cgSNV) is one of several whole genome based sequence typing methods used for the laboratory investigation of foodborne pathogens. SNV detection using this method requires a reference genome. The purpose of this study was to investigate the impact of the choice of the reference genome on the cgSNV-informed phylogenetic clustering and inferred isolate relationships. We found that using a draft or closed genome of S. Heidelberg as reference did not impact the ability of the cgSNV methodology to differentiate among 145 S. Heidelberg isolates involved in foodborne outbreaks. We also found that using a distantly related genome such as S. Dublin as choice of reference led to a loss in resolution since some sporadic isolates were found to cluster together with outbreak isolates. In addition, the genetic distances between outbreak isolates as well as between outbreak and sporadic isolates were overall reduced when S. Dublin was used as the reference genome as opposed to S. Heidelberg.

The Zur regulon of Corynebacterium glutamicum ATCC 13032

PubMed Central

2010-01-01

Background Zinc is considered as an essential element for all living organisms, but it can be toxic at large concentrations. Bacteria therefore tightly regulate zinc metabolism. The Cg2502 protein of Corynebacterium glutamicum was a candidate to control zinc metabolism in this species, since it was classified as metalloregulator of the zinc uptake regulator (Zur) subgroup of the ferric uptake regulator (Fur) family of DNA-binding transcription regulators. Results The cg2502 (zur) gene was deleted in the chromosome of C. glutamicum ATCC 13032 by an allelic exchange procedure to generate the zur-deficient mutant C. glutamicum JS2502. Whole-genome DNA microarray hybridizations and real-time RT-PCR assays comparing the gene expression in C. glutamicum JS2502 with that of the wild-type strain detected 18 genes with enhanced expression in the zur mutant. The expression data were combined with results from cross-genome comparisons of shared regulatory sites, revealing the presence of candidate Zur-binding sites in the mapped promoter regions of five transcription units encoding components of potential zinc ABC-type transporters (cg0041-cg0042/cg0043; cg2911-cg2912-cg2913), a putative secreted protein (cg0040), a putative oxidoreductase (cg0795), and a putative P-loop GTPase of the COG0523 protein family (cg0794). Enhanced transcript levels of the respective genes in C. glutamicum JS2502 were verified by real-time RT-PCR, and complementation of the mutant with a wild-type zur gene reversed the effect of differential gene expression. The zinc-dependent expression of the putative cg0042 and cg2911 operons was detected in vivo with a gfp reporter system. Moreover, the zinc-dependent binding of purified Zur protein to double-stranded 40-mer oligonucleotides containing candidate Zur-binding sites was demonstrated in vitro by DNA band shift assays. Conclusion Whole-genome expression profiling and DNA band shift assays demonstrated that Zur directly represses in a zinc-dependent manner the expression of nine genes organized in five transcription units. Accordingly, the Zur (Cg2502) protein is the key transcription regulator for genes involved in zinc homeostasis in C. glutamicum. PMID:20055984

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer.

PubMed

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R K; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-09-04

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors.

LH and hCG Action on the Same Receptor Results in Quantitatively and Qualitatively Different Intracellular Signalling

PubMed Central

Casarini, Livio; Lispi, Monica; Longobardi, Salvatore; Milosa, Fabiola; La Marca, Antonio; Tagliasacchi, Daniela; Pignatti, Elisa; Simoni, Manuela

2012-01-01

Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hCG we evaluated the kinetics of cAMP production in COS-7 and hGL5 cells permanently expressing LHCGR (COS-7/LHCGR, hGL5/LHCGR), as well as cAMP, ERK1/2, AKT activation and progesterone production in primary human granulosa cells (hGLC). The expression of selected target genes was measured in the presence or absence of ERK- or AKT-pathways inhibitors. In COS-7/LHCGR cells, hCG is 5-fold more potent than hLH (cAMP ED50: 107.1±14.3 pM and 530.0±51.2 pM, respectively). hLH maximal effect was significantly faster (10 minutes by hLH; 1 hour by hCG). In hGLC continuous exposure to equipotent doses of gonadotropins up to 36 hours revealed that intracellular cAMP production is oscillating and significantly higher by hCG versus hLH. Conversely, phospho-ERK1/2 and -AKT activation was more potent and sustained by hLH versus hCG. ERK1/2 and AKT inhibition removed the inhibitory effect on NRG1 (neuregulin) expression by hLH but not by hCG; ERK1/2 inhibition significantly increased hLH- but not hCG-stimulated CYP19A1 (aromatase) expression. We conclude that: i) hCG is more potent on cAMP production, while hLH is more potent on ERK and AKT activation; ii) hGLC respond to equipotent, constant hLH or hCG stimulation with a fluctuating cAMP production and progressive progesterone secretion; and iii) the expression of hLH and hCG target genes partly involves the activation of different pathways depending on the ligand. Therefore, the LHCGR is able to differentiate the activity of hLH and hCG. PMID:23071612

BRCA1 regulation on β-hCG: a mechanism for tumorigenicity in BRCA1 defective breast cancer

PubMed Central

Sengodan, S K; Nadhan, R; Nair, R S; Hemalatha, S K; Somasundaram, V; Sushama, R R; Rajan, A; Latha, N R; Varghese, G R; Thankappan, R k; Kumar, J M; Chil, A; Anilkumar, T V; Srinivas, P

2017-01-01

Human chorionic gonadotropin β (β-hCG) has been implicated in breast tumorigenesis. However, the role of this hormone is highly controversial as certain studies suggest it has anti-tumor properties while others have found it to be pro-tumorigenic. To unveil the truth, we have analyzed the expression of β-hCG in breast cancer. We identified for the first time that β-hCG expression is linked to BRCA1 status and its overexpression is seen in BRCA1 mutated breast cancer cells, BRCA1 conditional knockout mouse breast cancer tissues and BRCA1 floxed basal cell carcinoma (BCC) tissues. An analysis of three large, transcriptomic data sets from TCGA (The Cancer Genome Atlas) expression profile confirmed the inverse correlation between BRCA1 and β-hCG in human breast cancer. Using ChIP and luciferase assays, we also demonstrated that the cancer cells with wild-type but not mutant BRCA1 directly repress the expression of β-hCG by binding to its promoter. Further, β-hCG promotes migration and invasion predominantly in BRCA1 mutant breast cancer cells. Interestingly, stable overexpression of β-hCG in BRCA1 mutant but not wild-type breast cancer cells results in the formation of spheres even on monolayer cultures. The cells of these spheres show high expression of both EMT and stem cell markers. Since β-hCG belongs to a cysteine knot family of proteins like TGFβ and TGFβ signaling is deregulated in BRCA1 defective tumors, we checked whether β-hCG can mediate signaling through TGFβRII in BRCA1 mutated cells. We found for the first time that β-hCG can bind and phosphorylate TGFβRII, irrespective of LHCGR status and induce proliferation in BRCA1 defective cells. Our results confirmed that there exists a transcriptional regulation of BRCA1 on β-hCG and BRCA1 mutation promotes β-hCG mediated tumorigenesis through TGFβRII signaling. Thus inhibiting β-hCG-TGFβRII could prove an effective treatment strategy for BRCA1 mutated tumors. PMID:28869585

Establishing reference intervals for hCG in postmenopausal women.

PubMed

Patel, Khushbu K; Qavi, Abraham J; Hock, Karl G; Gronowski, Ann M

2017-03-01

Plasma concentrations of human chorionic gonadotropin (hCG) have been shown to increase with age due to pituitary secretion. We previously recommended that an hCG cutoff of 14.0IU/L be used for women ≥55years of age. However, it remains unknown whether concentrations >14.0IU/L can be expected in women with advanced age. Our objectives were to establish plasma hCG reference intervals and correlate follicle stimulating hormone (FSH) and hCG concentrations in postmenopausal females ≥55years. Residual plasma samples from 798 women ≥55years were utilized with 303, 269, and 226 samples belonging to the age groups 55-69, 70-84, and ≥85years, respectively. FSH and hCG were measured using the Abbott ARCHITECT. All positive hCG samples (hCG ≥5IU/L) were analyzed for potential heterophile antibody interference and 3 were excluded. Electronic medical records were reviewed and patients with malignancy were excluded. 8% (56/666) of women age≥55years had plasma hCG ≥5IU/L. There were 19, 16, and 21 patients with hCG ≥5IU/L in the age groups 55-69, 70-84, and ≥85years, respectively. The highest hCG concentrations observed in each age group were: 55-69years maximum=11.7IU/L and 97.5th percentile=9.6IU/L; 70-84years maximum=18.09IU/L, 97.5th percentile=6.2IU/L; ≥85years maximum=11.1IU/L and 97.5th percentile=10.0IU/L, and the overall 97.5th percentile=8.5IU/L for all women ≥55years of age. Neither hCG nor FSH concentrations continued to increase with age in women ≥55years. The prevalence of positive hCG in women ≥55years is 8%. This study confirms our previously recommended cutoff of 14IU/L for women ≥55years of age. In women ≥55years of age, FSH concentrations do not predict hCG concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The use of altrenogest to avoid hyperestrogenism after eCG-hCG ovulation induction in southern tigrina (Leopardus guttulus).

PubMed

Micheletti, Tatiane; Brown, Janine L; Walker, Susan L; Cubas, Zalmir S; Furtado, Priscila V; Putman, Sarah B; de Moraes, Wanderlei; de Oliveira, Marcos J; de Oliveira, Claudio A; Moreira, Nei

2015-09-01

The goal of this study was to optimize an ovulation induction protocol for use with artificial insemination in the southern tigrina (Leopardus guttulus). The specific aims were to report the efficacy of using altrenogest, an oral progestin (Regumate, MSD Animal Health, Merck Animal Health), to suppress ovarian activity and prevent follicular hyperstimulation and hyperestrogenism after the administration of exogenous eCG and hCG. To monitor ovarian responses, fecal estrogen and progestogen metabolites were quantified by enzyme immunoassay in females before and after intramuscular administration of 200-IU eCG and 150-IU hCG in two trials, 4 months apart. During the first trial, there was no use of altrenogest, only the eCG-hCG ovulation induction protocol. In the second trial, the ovulation induction protocol was preceded by the administration of oral altrenogest for 14 days (minimum of 0.192 mg per kg per day). Altrenogest administration resulted in a suppression of follicular activity in three out of six females before eCG-hCG administration on the basis of lower mean estrogen concentrations (P < 0.05). It also resulted in four out of six females presenting lower fecal estrogen metabolite concentrations (P < 0.05) after ovulation induction, and two out of six individuals showed a reduction (P < 0.05) in postovulatory fecal progestogen metabolite concentrations, all when compared to the same female's cycles without the progestin. Fecal estrogen metabolite concentrations were closer to baseline in 50% of these individuals after altrenogest and eCG-hCG treatments when compared to basal concentrations before gonadotropins without the use of altrenogest. This study reported that use of altrenogest in southern tigrina can suppress ovarian activity and avoid hyperestrogenism after administration of eCG and hCG treatment. However, not all females responded uniformly, so more studies are needed to increase the efficacy of ovulation induction for use with artificial insemination in this species. Copyright © 2015 Elsevier Inc. All rights reserved.

SU-G-TeP1-15: Toward a Novel GPU Accelerated Deterministic Solution to the Linear Boltzmann Transport Equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, R; Fallone, B; Cross Cancer Institute, Edmonton, AB

Purpose: To develop a Graphic Processor Unit (GPU) accelerated deterministic solution to the Linear Boltzmann Transport Equation (LBTE) for accurate dose calculations in radiotherapy (RT). A deterministic solution yields the potential for major speed improvements due to the sparse matrix-vector and vector-vector multiplications and would thus be of benefit to RT. Methods: In order to leverage the massively parallel architecture of GPUs, the first order LBTE was reformulated as a second order self-adjoint equation using the Least Squares Finite Element Method (LSFEM). This produces a symmetric positive-definite matrix which is efficiently solved using a parallelized conjugate gradient (CG) solver. Themore » LSFEM formalism is applied in space, discrete ordinates is applied in angle, and the Multigroup method is applied in energy. The final linear system of equations produced is tightly coupled in space and angle. Our code written in CUDA-C was benchmarked on an Nvidia GeForce TITAN-X GPU against an Intel i7-6700K CPU. A spatial mesh of 30,950 tetrahedral elements was used with an S4 angular approximation. Results: To avoid repeating a full computationally intensive finite element matrix assembly at each Multigroup energy, a novel mapping algorithm was developed which minimized the operations required at each energy. Additionally, a parallelized memory mapping for the kronecker product between the sparse spatial and angular matrices, including Dirichlet boundary conditions, was created. Atomicity is preserved by graph-coloring overlapping nodes into separate kernel launches. The one-time mapping calculations for matrix assembly, kronecker product, and boundary condition application took 452±1ms on GPU. Matrix assembly for 16 energy groups took 556±3s on CPU, and 358±2ms on GPU using the mappings developed. The CG solver took 93±1s on CPU, and 468±2ms on GPU. Conclusion: Three computationally intensive subroutines in deterministically solving the LBTE have been formulated on GPU, resulting in two orders of magnitude speedup. Funding support from Natural Sciences and Engineering Research Council and Alberta Innovates Health Solutions. Dr. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).« less

Shape analysis of the cingulum, uncinate and arcuate fasciculi in patients with bipolar disorder

PubMed Central

Sun, Zhong Yi; Houenou, Josselin; Duclap, Delphine; Sarrazin, Samuel; Linke, Julia; Daban, Claire; Hamdani, Nora; d’Albis, Marc-Antoine; Le Corvoisier, Philippe; Guevara, Pamela; Delavest, Marine; Bellivier, Frank; Almeida, Jorge; Versace, Amelia; Poupon, Cyril; Leboyer, Marion; Phillips, Mary; Wessa, Michèle; Mangin, Jean-François

2017-01-01

Background Abnormal maturation of brain connectivity is supposed to underlie the dysfunctional emotion regulation in patients with bipolar disorder (BD). To test this hypothesis, white matter integrity is usually investigated using measures of water diffusivity provided by MRI. Here we consider a more intuitive aspect of the morphometry of the white matter tracts: the shape of the fibre bundles, which is associated with neurodevelopment. We analyzed the shape of 3 tracts involved in BD: the cingulum (CG), uncinate fasciculus (UF) and arcuate fasciculus (AF). Methods We analyzed diffusion MRI data in patients with BD and healthy controls. The fibre bundles were reconstructed using Q-ball–based tractography and automated segmentation. Using Isomap, a manifold learning method, the differences in the shape of the reconstructed bundles were visualized and quantified. Results We included 112 patients and 82 controls in our analysis. We found the left AF of patients to be further extended toward the temporal pole, forming a tighter hook than in controls. We found no significant difference in terms of shape for the left UF, the left CG or the 3 right fasciculi. However, in patients compared with controls, the ventrolateral branch of the left UF in the orbitofrontal region had a tendency to be larger, and the left CG of patients had a tendency to be smaller in the frontal lobe and larger in the parietal lobe. Limitations This was a cross-sectional study. Conclusion Our results suggest neurodevelopmental abnormalities in the left AF in patients with BD. The statistical tendencies observed for the left UF and left CG deserve further study. PMID:28234596

Fractal dimension approach in postural control of subjects with Prader-Willi Syndrome

PubMed Central

2011-01-01

Background Static posturography is user-friendly technique suitable for the study of the centre of pressure (CoP) trajectory. However, the utility of static posturography in clinical practice is somehow limited and there is a need for reliable approaches to extract physiologically meaningful information from stabilograms. The aim of this study was to quantify the postural strategy of Prader-Willi patients with the fractal dimension technique in addition to the CoP trajectory analysis in time and frequency domain. Methods 11 adult patients affected by Prader-Willi Syndrome (PWS) and 20 age-matched individuals (Control group: CG) were included in this study. Postural acquisitions were conducted by means of a force platform and the participants were required to stand barefoot on the platform with eyes open and heels at standardized distance and position for 30 seconds. Platform data were analysed in time and frequency domain. Fractal Dimension (FD) was also computed. Results The analysis of CoP vs. time showed that in PWS participants all the parameters were statistically different from CG, with greater displacements along both the antero-posterior and medio-lateral direction and longer CoP tracks. As for frequency analysis, our data showed no significant differences between PWS and CG. FD evidenced that PWS individuals were characterized by greater value in comparison with CG. Conclusions Our data showed that while the analysis in the frequency domain did not seem to explain the postural deficit in PWS, the FD method appears to provide a more informative description of it and to complement and integrate the time domain analysis. PMID:21854639

High gamma-aminobutyric acid level in cortical tubers in epileptic infants with tuberous sclerosis complex measured with the MEGA-editing J-difference method and a three-Tesla clinical MRI Instrument.

PubMed

Taki, Masako Minato; Harada, Masafumi; Mori, Kenji; Kubo, Hitoshi; Nose, Ayumi; Matsuda, Tsuyoshi; Nishitani, Hiromu

2009-10-01

The purpose of this study was to estimate the gamma-aminobutyric acid (GABA) and glutamate plus glutamine (Glx) concentrations in the cortical tubers of patients with tuberous sclerosis complex (TSC) using the MEGA-editing J-difference method and a stimulated echo-acquisition mode with a short echo time, and to determine which abnormality was more dominant between GABA and Glx in patients with TSC with epilepsy. This study included six patients with TSC (mean age, 4.3 years) and seven control subjects (mean age, 4.8 years). Measurements were obtained with a three-Tesla apparatus and postprocessing was conducted with an LCModel. The GABA level in the cortical gray matter (cgGABA) was calculated as a result of segmentation in voxels and from the literature values for gray and white matter ratios for GABA. Increased GABA and myo-inositol (mI) concentrations and a decreased N-acetyl aspartate (NAA) concentration were observed in the cortical tubers. The cgGABA level, and cgGABA/NAA and cgGABA/Glx ratios were also higher in patients with TSC than in control subjects. No significant difference was found in Glx concentration between patients with TSC and control subjects. Although the number of patients with TSC in this study was small, the increase in GABA and no significant change in Glx were consistent with previous neurochemical studies and support the hypothesis that brain GABA plays a key role in the pathophysiology of epilepsy during the process of neuronal development.

Cheilitis Glandularis: Two Case Reports of Asian-Japanese Men and Literature Review of Japanese Cases

PubMed Central

Yanagawa, Toru; Yamaguchi, Akira; Harada, Hiroyuki; Yamagata, Kenji; Ishibashi, Naomi; Noguchi, Masayuki; Onizawa, Kojiro; Bukawa, Hiroki

2011-01-01

Cheilitis glandularis (CG) is a rare disorder characterized by swelling of the lip with hyperplasia of the labial salivary glands. CG is most frequently encountered in the lower lip, in middle-aged to older Caucasian men; however Asian cases were rarely reported. In this paper we present two cases of CG in Asian-Japanese men. One was a 23-year-old male with CG of the superficial suppurative type. The other was a 54-year-old male with deep suppurative type. We also reviewed the Japanese cases of CG in the literature and discussed about clinical feature of Japanese CG. PMID:21991474

46 CFR 1.01-10 - Organization.

Code of Federal Regulations, 2013 CFR

2013-10-01

... resource issues in support of the Standards and Operations Directorates; and oversees the development and... Assistant Commandant for Prevention Policy (CG-5P), and the Director of Operations Resource Management (CG... Standards Evaluation and Development (CG-REG); and (ii) The Director of Inspections and Compliance (CG-5PC...

Serum chromogranin A concentration in hyperthyroidism before and after medical treatment.

PubMed

Al-Shoumer, Kamal A S; Vasanthy, Bagavathy A

2009-07-01

The aim was to evaluate changes in chromogranin A (CgA) concentration in hyperthyroidism and to assess its metabolic correlations. We studied CgA levels in hyperthyroidism. First, 38 hyperthyroid patients matched with 86 normal controls were studied after an overnight fast. Second, 30 if the 38 patients were followed up for 6 months with medical antithyroid drug therapy (carbimazole). In the first study, after 10-12 h overnight fasting, blood was collected for measurement of CgA, glucose, insulin, intact proinsulin, and thyroid function. These variables were remeasured in the second study for the patients after attainment of euthyroidism with the antithyroid drug carbimazole for 6 months. Pretreatment CgA level was significantly higher in patients compared with controls. CgA levels dropped significantly to levels similar to those of controls after antithyroid therapy. Although baseline and follow-up fasting glucose, insulin, and intact proinsulin demonstrated similar pattern of CgA changes before and after medical treatment, CgA did not correlate with any of them. However, CgA levels demonstrated a significant positive correlation with free T(3) and free T(4) only. These studies demonstrate that untreated hyperthyroidism is associated with elevated CgA level that changes in parallel to thyroid status. It is therefore possible to use CgA concentration as a potential marker of disease activity in hyperthyroidism.

Effects of a single administration of different gonadotropins on day 7 post-insemination on pregnancy outcomes of rabbit does.

PubMed

Hashem, N M; Aboul-Ezz, Z R

2018-01-01

This study aimed to investigate the effects of a single administration of one of three different gonadotropins on Day 7 post-insemination on ovarian activity, progesterone (P 4 ) concentration and pregnancy outcomes of rabbit does. Multiparous, non-lactating, V-line does were artificially inseminated after synchronization and ovulation induction with equine chorionic gonadotropin (eCG; 25 IU im) and gonadotropin releasing hormone (GnRH; 0.8  μg buserelin im) 48 h later. On Day 7 post-inseminarion, does were randomly allocated into four groups (n = 40/group). Does of each group were intramuscularly injected with a single dose of one of physiological saline (placebo; control), GnRH (0.8  μg buserelin), human chorionic gonadotropin (hCG; 25 IU) or eCG (25 IU). Concentration of serum P 4 was determined on Days 6, 9, 11 and 18 post-insemination. On Day 14 post-insemination, the ovaries and reproductive tracts of pregnant does were removed and weighed. Also, numbers of visible follicles, hemorrhagic follicles, corpora lutea of pregnancy (pCLs), new CLs (nCLs; formed after Day 7 post-insemination) and implantation sites were recorded. Conception rate, parturition rate, abortion rate, litter size/weight and litter viability were recorded. The highest (P < 0.05) reproductive tract and ovary weights were for eCG. The highest (P < 0.05) number of visible ovarian follicles was for eCG, whereas the lowest (P < 0.05) was for GnRH. Treatment with eCG increased (P < 0.05) numbers of pCLs and total implantation sites compared to the other groups. Treatment with GnRH or hCG increased (P < 0.05) number of nCLs compared to control and eCG. The highest rate of fetal loss was in does treated with GnRH. The concentration of serum P 4 decreased (P < 0.05) following the treatment with GnRH and continued low until Day 18. However, it remained in line for control, hCG and eCG groups up to Day 11, then decreased (P < 0.05) for control and hCG on Day 18, being lower for hCG than control, while continued to increase for eCG up to Day 18. Compared to control, treatment with eCG improved (P < 0.05) conception and parturition rates by 24 and 22%; respectively, while GnRH and hCG treatments decreased (P < 0.05) them by 57 and 47.6%; respectively. Litter size and litter weight at birth were improved by eCG, but were adversely affectd by GnRH and hCG. In conclusion, a single administration of eCG 7 Days post-insemination could be recommended for improving pregnancy outcomes in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictive value of serum β-hCG for early pregnancy outcomes among women with recurrent spontaneous abortion.

PubMed

Liu, Yinglin; Liu, Yukun; Li, Xuejiao; Jiao, Xuedan; Zhang, Rui; Zhang, Jianping

2016-10-01

To examine peak serum levels of the β-subunit of human chorionic gonadotropin (β-hCG) for prediction of early pregnancy outcomes among women with recurrent spontaneous abortion (RSA). In a retrospective study, the medical records of pregnant women with a history of RSA treated at Sun Yat-sen Memorial Hospital, China, between January 2011 and July 2013 were reviewed. Serum β-hCG had been measured twice weekly from 5 to 13weeks of pregnancy, and pregnancy was monitored by transvaginal ultrasonography to 13(+6)weeks. Optimal cutoff for peak β-hCG level was determined by receiver operator characteristic curve analysis and Youden index. Women were divided into four groups on the basis of optimal peak β-hCG cutoff and pregnancy outcome (pregnancy at 13weeks or spontaneous abortion). Peak β-hCG levels and length of pregnancy at this peak were examined. Overall, 1240 patients were included. The optimal cutoff value of peak β-hCG was 88 468IU/L, with a sensitivity, specificity, positive predictive value, and negative predictive value for successful pregnancy of 95.6%, 88.0%, 95.6%, and 89.0%, respectively. A faster rise in β-hCG, higher peak β-hCG, and longer pregnancy length at peak β-hCG were associated with successful early pregnancy. A cutoff value of serum β-hCG of 88 000IU/L could be used to predict early pregnancy outcomes for women with a history of RSA. Copyright © 2016. Published by Elsevier Ireland Ltd.

Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin-neuraminidase (HN) glycoprotein.

PubMed

Sun, Junfeng; Han, Zongxi; Qi, Tianming; Zhao, Ran; Liu, Shengwang

2017-12-08

Galectin-1 is an important immunoregulatory factor and can mediate the host-pathogen interaction via binding glycans on the surface of various viruses. We previously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs. We also found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro We confirmed that CG-1B interacted with NDV hemagglutinin-neuraminidase (HN) glycoprotein, in which the specific G4 N -glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N -glycans on HN glycoprotein. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

46 CFR 147.5 - Commandant (CG-522); address.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Commandant (CG-522); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-522); address. Commandant (CG-522) is the Office of Operating...

46 CFR 147.5 - Commandant (CG-OES); address.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Commandant (CG-OES); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-OES); address. Commandant (CG-ENG) is the Office of Design and...

46 CFR 147.5 - Commandant (CG-522); address.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 5 2010-10-01 2010-10-01 false Commandant (CG-522); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-522); address. Commandant (CG-522) is the Office of Operating...

46 CFR 147.5 - Commandant (CG-OES); address.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Commandant (CG-OES); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-OES); address. Commandant (CG-ENG) is the Office of Design and...

46 CFR 147.5 - Commandant (CG-OES); address.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Commandant (CG-OES); address. 147.5 Section 147.5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES HAZARDOUS SHIPS' STORES General Provisions § 147.5 Commandant (CG-OES); address. Commandant (CG-OES) is the Office of Operating...

75 FR 34114 - Pesticide Products; Registration Applications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... & 16); vegetables, legume, including soybeans (CG 6 & 7); canola, borage, crambe, cuphea, echium, flax... use as seed treatment on alfalfa, beans and peas including soybean and legume (CG 6 & 7); cotton... treatment on alfalfa, beans and peas including soybean and legume (CG 6 & 7); cotton, cereal grains (CG 15...

46 CFR 1.01-10 - Organization.

Code of Federal Regulations, 2012 CFR

2012-10-01

... coordinates the activities of the Operations Resource Management Directorate (CG-DCO-R), consisting of the Office of Workforce Management (CG-DCO-R-1), the Office of Budget Development (CG-DCO-R-2), the Office of... administrative control over the NMC detachments. (iii) The Director of Operations Resource Management (CG-DCO-R...

Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of the Cockcroft-Gault equation, in the determination of the dosage of direct oral anticoagulants in patients with non-valvular atrial fibrillation.

PubMed

Pérez Cabeza, Alejandro Isidoro; Chinchurreta Capote, Pedro Antonio; González Correa, Jose Antonio; Ruiz Mateas, Francisco; Rosas Cervantes, Gabriel; Rivas Ruiz, Francisco; Valle Alberca, Almudena; Bravo Marqués, Rafael

2018-02-09

Direct oral anticoagulants (DOACs) require dose adjustment according to estimated clearance creatinine (eClCr) using the Cockcroft-Gault (CG) equation. There are discrepancies with the equations that estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI and MDRD-4 IDMS equations affect the recommended dosage for ACODs. Retrospective study of patients with non-valvular atrial fibrillation seen at a cardiology clinic between November 2012 and August 2014. Patients were reclassified according to the recommended dosage for dabigatran, rivaroxaban, apixaban and edoxaban, based on the eGFR equation used. Other clinical factors are taken into account, according to the product label. We analysed the percentage of discordance. Four hundred and fifty-four patients, 53.3% men, with a mean age of 68.7±13.8 years were studied. The mean intra-individual differences recorded for the CG equation were 3.9ml/min/1.73m 2 with MDRD-4 IDMS (95% CI 1.4-6.4, P=.003) and 11.3ml/min/1.73m 2 with CKD-EPI (95% CI 8.9-13.7, P<.001). A gradient is observed in the discordance of the posology (apixaban 1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS). Differences were limited to patients with eClCr<60ml/min and were more evident in≥75 years in which the eGFR equations overestimate renal function. In patients with non-valvular atrial fibrillation, especially with renal failure and in the elderly, eGFR equations tend to overestimate renal function relative to CG and therefore suggest an overdose of DOACs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

PubMed

Sung, Nayoung; Kwak-Kim, Joanne; Koo, H S; Yang, K M

2016-09-01

To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen cycles, the cutoff values of POD 12 and 14 serum hCG-β level for clinical pregnancy were 31.5 IU/L (sensitivity 80.4 %, specificity 71.1 % and PPV 90 %) and 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %). In pregnancies with POD 12 serum hCG-β level ≥31.5 mIU/mL, the cutoff value for fold increase of hCG-β was 2.38 for clinical pregnancy (sensitivity 81.6 %, specificity 71.4 % and PPV 87.9 %). The cutoff values of POD 12 and 14 for live birth were 43.5 mIU/mL (sensitivity 72.6 %, specificity 71.7 %, PPV 77.2 %) and 101.6 mIU/mL (sensitivity 79.6 %, specificity 71.1 %, PPV 78.4 %). Sequential application of cutoff values for POD 12 hCG-β level and fold increase of hCG-β significantly increased PPV for live birth but not clinical pregnancy in frozen cycles. Early prediction of pregnancy outcome by using POD 12 and 14 cutoff levels and sequential application of cutoff value of fold increase could provide appropriate reference to health care providers to initiate earlier management of high-risk pregnancies and precise follow-up of abnormal pregnancies.

Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels

PubMed Central

2010-01-01

Background Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Results Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. Conclusions This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG. PMID:20716347

Effect of dietary boron on 5-fluorouracil induced oral mucositis in rats

PubMed Central

Aras, Mutan Hamdi; Sezer, Ufuk; Erkilic, Suna; Demir, Tuncer; Dagli, Seyda Nur

2013-01-01

Objective: The aim of this study was to evaluate the effect of boron on 5-fluorouracil (5-FU)–induced oral mucositis in rats. Materials and Methods: Sixty-four male Wistar albino rats were injected with 5-FU on days 1 and 3. The right cheek pouch mucosa was scratched with the tip of an 18-G needle, dragged twice in a linear movement, on days 3 and 5. The animals were randomly divided into two groups of 32: boron group (BG) and control group (CG). Rats in the CG did not receive any treatment, whereas the others were fed boron (3 mg·kg-1·day-1) by gavage. The animals were sacrificed on day 3 (n = 8), 6 (n = 8), 9 (n = 8), and 12 (n = 8), and the cheek pouch was removed for histopathological analysis. Results: On day 3, both groups showed necrosis and active inflammation, but the inflammation was mild in CG and moderate in BG. On day 6, both BG and CG showed necrosis; in the CG, there was moderate inflammation, and in the BG, there was severe inflammation and granulation tissue around the necrotic area. On day 9, re-epithelization began in both groups, and there were no differences between groups. Re-epithelization was complete in both groups on day 12. Conclusion: We found no beneficial effect of boron in healing oral mucositis. Additional research is warranted to elucidate the pathogenic inflammatory mechanisms involved in mucositis and the prophylactic and therapeutic roles of antioxidants. PMID:24926211

Upper Tract Urological Laparoendoscopic Single-Site Surgery (LESS)

PubMed Central

Tugcu, Volkan; Sahin, Selcuk; Seker, Gokhan; Kargi, Taner; Tasci, Ali Ihsan

2015-01-01

Background and Objectives: Our objective is to report intermediate-term outcomes for patients who have undergone upper tract urologic laparoendoscopic single-site surgery (LESS) at a single institution. Methods: From January 1, 2008, through November 30, 2012, 107 cases treated with LESS were identified, including pyeloplasty (n = 30), ureterolithotomy (n = 32), nephrectomy (n = 35; simple = 31, partial = 4), and cyst decortication (n = 10). Perioperative data were reviewed, and conversion and complication rates were noted. Results: The median follow-up was 21.5 months for pyeloplasty, 20.5 for ureterolithotomy, 28.0 for simple nephrectomy, 14.0 for partial nephrectomy, and 19.0 for cyst decortication. Major complications were encountered in 8 patients, including 3 intraoperative complications (2 bowel injury with serosal tearing and 1 intraoperative bleeding), which were recognized and repaired with LESS or conversion to conventional laparoscopy (CL). During the intermediate postoperative period (30–90 days) major complications occurred in 5 patients: 4 ureteral strictures (Clavien-Dindo grade [CG] IIIb) and 1 urinoma formation (CG IIIa). During the early postoperative period (<30 days), the most common minor complications were flank pain (CG I) in 16 patients and urinary tract infection (CG II) in 11, followed by urinary leakage (CG I) in 8. Conclusions: Intermediate-term functional outcomes of this single-center study confirm that upper tract LESS is a challenging procedure that can be safe and effective when performed by an experienced team. Prospective studies with longer follow-up periods are needed to investigate the safety of LESS in the treatment of various upper urinary tract conditions. PMID:26648679

Opportunity for academic research in a low-gravity environment - Crystal growth

NASA Technical Reports Server (NTRS)

Matthiesen, D. H.; Wargo, M. J.; Witt, A. F.

1986-01-01

The history of basic and applied research on crystal growth (CG), especially of semiconductor materials, is reviewed, stressing the dominance (at least in the U.S.) of industrial R&D projects over academic programs and the need for more extensive fundamental investigations. The NASA microgravity research program and the recommendations of the University Space Research Association are examined as they affect the availability of space facilities for academic CG research. Also included is a report on ground experiments on the effectiveness of magnetic fields in controlling vertical Bridgman CG and melt stability, using the apparatus employed in the Apollo-Soyuz experiments (Witt et al., 1978); the results are presented in graphs and briefly characterized. The role of NASA's microgravity CG program in stimulating academic work on CG, the importance of convection effects, CG work on materials other than semiconductors, and NSF support of CG research are discussed in a comment by R. F. Sekerka.

Coarse-graining of proteins based on elastic network models

NASA Astrophysics Data System (ADS)

Sinitskiy, Anton V.; Voth, Gregory A.

2013-08-01

To simulate molecular processes on biologically relevant length- and timescales, coarse-grained (CG) models of biomolecular systems with tens to even hundreds of residues per CG site are required. One possible way to build such models is explored in this article: an elastic network model (ENM) is employed to define the CG variables. Free energy surfaces are approximated by Taylor series, with the coefficients found by force-matching. CG potentials are shown to undergo renormalization due to roughness of the energy landscape and smoothing of it under coarse-graining. In the case study of hen egg-white lysozyme, the entropy factor is shown to be of critical importance for maintaining the native structure, and a relationship between the proposed ENM-mode-based CG models and traditional CG-bead-based models is discussed. The proposed approach uncovers the renormalizable character of CG models and offers new opportunities for automated and computationally efficient studies of complex free energy surfaces.

NEEMO 14: Evaluation of Human Performance for Rover, Cargo Lander, Crew Lander, and Exploration Tasks in Simulated Partial Gravity

NASA Technical Reports Server (NTRS)

Chappell, Steven P.; Abercromby, Andrew F.; Gernhardt, Michael L.

2011-01-01

The ultimate success of future human space exploration missions is dependent on the ability to perform extravehicular activity (EVA) tasks effectively, efficiently, and safely, whether those tasks represent a nominal mode of operation or a contingency capability. To optimize EVA systems for the best human performance, it is critical to study the effects of varying key factors such as suit center of gravity (CG), suit mass, and gravity level. During the 2-week NASA Extreme Environment Mission Operations (NEEMO) 14 mission, four crewmembers performed a series of EVA tasks under different simulated EVA suit configurations and used full-scale mockups of a Space Exploration Vehicle (SEV) rover and lander. NEEMO is an underwater spaceflight analog that allows a true mission-like operational environment and uses buoyancy effects and added weight to simulate different gravity levels. Quantitative and qualitative data collected during NEEMO 14, as well as from spacesuit tests in parabolic flight and with overhead suspension, are being used to directly inform ongoing hardware and operations concept development of the SEV, exploration EVA systems, and future EVA suits. OBJECTIVE: To compare human performance across different weight and CG configurations. METHODS: Four subjects were weighed out to simulate reduced gravity and wore either a specially designed rig to allow adjustment of CG or a PLSS mockup. Subjects completed tasks including level ambulation, incline/decline ambulation, standing from the kneeling and prone position, picking up objects, shoveling, ladder climbing, incapacitated crewmember handling, and small and large payload transfer. Subjective compensation, exertion, task acceptability, and duration data as well as photo and video were collected. RESULTS: There appear to be interactions between CG, weight, and task. CGs nearest the subject s natural CG are the most predictable in terms of acceptable performance across tasks. Future research should focus on understanding the interactions between CG, mass, and subject differences.

Prostate Zonal Volumetry as a Predictor of Clinical Outcomes for Prostate Artery Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Assis, André Moreira de, E-mail: andre.assis@criep.com.br, E-mail: andre.maa@gmail.com; Maciel, Macello Sampaio, E-mail: macielmjs@gmail.com; Moreira, Airton Mota, E-mail: airton.mota@criep.com.br

PurposeTo determine prostate baseline zonal volumetry and correlate these findings with clinical outcomes for patients who underwent prostate artery embolization (PAE) for lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH).Materials and MethodsThis is a retrospective study that included patients treated by PAE from 2010 to 2014. Baseline and 6-month follow-up evaluations included prostate MRI with whole prostate (WP) and central gland (CG) volume measurements—as well as prostate zonal volumetry index (ZVi) calculation, defined as the CG/WP volumes relation—the International Prostate Symptom Score (IPSS), and the Quality of life (QoL) index. Baseline WP, CG, and ZVi were statistical compared to IPSS andmore » QoL values at 6 months.ResultsA total of 93 consecutive patients were included, with mean age of 63.4 years (range, 51–86). Clinical failure, defined as IPSS > 7 or QoL > 2, was seen in four cases (4.3%). Mean reductions in prostate volumes after PAE were of 30.6% and 31.2% for WP and CG, respectively (p < 0.0001). Clinical parameters had mean decrease from 21 to 3.3 points for IPSS, and from 4.7 to 1.2 points for QoL (p < 0.0001). Baseline WP, CG, and ZVi correlated to the degree of clinical improvement (p < 0.05 for all). The baseline ZVi cut-off calculated for better clinical outcomes was > 0.45, with 85% sensitivity and 75% specificity.ConclusionsBaseline CG and WP volumes as well as ZVi presented strong correlation with clinical outcomes in patients undergoing PAE, and its assessment should be considered in pre-treatment evaluation whenever possible. Both patients and medical team should be aware of the possibility of less favorable outcomes when ZVi < 0.45.« less

Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure

PubMed Central

Szummer, Karolina; Evans, Marie; Carrero, Juan Jesus; Alehagen, Urban; Dahlström, Ulf; Benson, Lina; Lund, Lars H

2017-01-01

Background It is unknown how the creatinine-based renal function estimations differ for dose adjustment cut-offs and risk prediction in patients with heart failure. Method and results The renal function was similar with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (median 59 mL/min/1.73 m2, IQR 42 to 77) and Modification of Diet in Renal Disease Study (MDRD) (59 mL/min/1.73 m2, IQR 43 to 75) and slightly lower with the Cockcroft-Gault (CG) equation (57 mL/min, IQR 39 to 82). Across the commonly used renal function stages, the CKD-EPI and the MDRD classified patients into the same stage in 87.2% (kappa coefficient 0.83, p<0.001); the CKD-EPI and the CG equation agreed in 52.3% (kappa coefficient 0.39, p<0.001). Hence, a differing number of patients will receive dose adjustment depending on which formula is used as cut-off. The CG equation predicted worse prognosis better (c-statistics 0.740, 95% CI 0.734 to 0.746) than CKD-EPI (0.697, 95% CI 0.690 to 0.703, p<0.001) and MDRD (0.680, 95% CI 0.734 to 0.746). Using net reclassification improvement (NRI), the CG identified 12.8% more patients at higher risk of death as compared with the CKD-EPI equation. Patients registered in the Swedish Heart Failure Registry (n= 40 736) with standardised creatinine values between 2000 and 2012 had their renal function estimated with the CKD-EPI, the MDRD and the CG. Agreement between the formulas was compared for categories. Prediction of death was assessed with c-statistics and with NRI. Conclusion The choice of renal function estimation formula has clinical implications and differing results at various cut-off levels. For prognosis, the CG predicts mortality better than the CKD-EPI and MDRD. PMID:28761677

Prevention of endometrial apoptosis: randomized prospective comparison of human chorionic gonadotropin versus progesterone treatment in the luteal phase.

PubMed

Lovely, Laurie P; Fazleabas, Asgerally T; Fritz, Marc A; McAdams, Devin G; Lessey, Bruce A

2005-04-01

To study control of apoptosis in human endometrium, we examined late luteal-phase endometrial biopsies obtained in the late luteal phase for evidence of apoptosis and compared the effects of exogenous human chorionic gonadotropin (hCG) and progesterone on this process. Using a controlled, prospective, and randomized study design, 12 healthy, fertile, reproductive-age women (ages 20-34 yr) with regular menstrual cycles (range, 26-32 d) were recruited. Each underwent an endometrial biopsy 12 d after a urinary LH surge in a control and treatment cycle. After biopsy in a natural cycle, subjects were randomized to receive luteal doses of either 200 mg intravaginal progesterone (d 18-27) or a single im injection of 10,000 IU of hCG (d 19) followed by repeat endometrial biopsy and collection of serum on d 26. Apoptosis was assessed by DNA laddering, localizing apoptotic bodies using immunofluorescent labeling of DNA fragments (the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method), and immunohistochemical assessment of apoptosis markers bcl-2, bcl-x, and bax. Serum progesterone levels were compared between treatment groups. Evidence of apoptosis in control cycles was significantly reduced in endometrium after both luteal-phase treatments. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling results demonstrated significantly less apoptosis in the hCG treatment group compared with controls. Immunostaining for bcl-2 was higher in hCG- and progesterone-treated cycles, whereas bax expression was decreased and bcl-x immunostaining was not different between treatments. Serum progesterone levels were highest in the hCG-treated group, although statistical significance was not reached (P = 0.08). These results demonstrate that signs of apoptosis, already apparent by d 26 of the menstrual cycle can be reduced with either hCG or progesterone treatment. The clinical utility of these findings includes a rational use of luteal-phase support for treatment of women with infertility and/or recurrent pregnancy loss.

Circulating miR-323-3p as a Biomarker of Ectopic Pregnancy

PubMed Central

Zhao, Zhen; Zhao, Qiuhong; Warrick, Joshua; Lockwood, Christina M.; Woodworth, Alison; Moley, Kelle H.; Gronowski, Ann M.

2013-01-01

BACKGROUND The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS This was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping, and were diagnosed with viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were determined by immunoassays. Serum miR-323-3p, miR-517a, miR-519d, and miR-525-3p concentrations were measured using TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP. RESULTS Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA than in VIP. In contrast, the concentration of miR-323-3p was significantly elevated in EP as compared to SA and VIP. As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed-specificity of 90%). Comparatively, combined hCG, progesterone, and miR-323-3p panel yielded the highest sensitivity of 77.8% (at a fixed-specificity of 90%). A stepwise analysis using hCG, then progesterone, and then miR-323-3p resulted in 96.3% sensitivity and 72.6% specificity. CONCLUSIONS Pregnancy-associated miRNAs, especially miR-323-3p, added significant diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP. PMID:22395025

An attachment-based model of complicated grief including the role of avoidance

PubMed Central

Monk, Timothy; Houck, Patricia; Melhem, Nadine; Frank, Ellen; Reynolds, Charles; Sillowash, Russell

2009-01-01

Introduction Complicated grief is a prolonged grief disorder with elements of a stress response syndrome. We have previously proposed a biobehavioral model showing the pathway to complicated grief. Avoidance is a component that can be difficult to assess and pivotal to treatment. Therefore we developed an avoidance questionnaire to characterize avoidance among patients with CG. Methods We further explain our complicated grief model and provide results of a study of 128 participants in a treatment study of CG who completed a 15-item Grief-related Avoidance Questionnaire (GRAQ). Results of Avoidance Assessment Mean (SD) GRAQ score was 25. 0 ± 12.5 with a range of 0–60. Cronbach's alpha was 0.87 and test re-test correlation was 0.88. Correlation analyses showed good convergent and discriminant validity. Avoidance of reminders of the loss contributed to functional impairment after controlling for other symptoms of complicated grief. Discussion In this paper we extend our previously described attachment-based biobehavioral model of CG. We envision CG as a stress response syndrome that results from failure to integrate information about death of an attachment figure into an effectively functioning secure base schema and/or to effectively re-engage the exploratory system in a world without the deceased. Avoidance is a key element of the model. PMID:17629727

RNA-guided genome editing for target gene mutations in wheat.

PubMed

Upadhyay, Santosh Kumar; Kumar, Jitesh; Alok, Anshu; Tuli, Rakesh

2013-12-09

The clustered, regularly interspaced, short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) system has been used as an efficient tool for genome editing. We report the application of CRISPR-Cas-mediated genome editing to wheat (Triticum aestivum), the most important food crop plant with a very large and complex genome. The mutations were targeted in the inositol oxygenase (inox) and phytoene desaturase (pds) genes using cell suspension culture of wheat and in the pds gene in leaves of Nicotiana benthamiana. The expression of chimeric guide RNAs (cgRNA) targeting single and multiple sites resulted in indel mutations in all the tested samples. The expression of Cas9 or sgRNA alone did not cause any mutation. The expression of duplex cgRNA with Cas9 targeting two sites in the same gene resulted in deletion of DNA fragment between the targeted sequences. Multiplexing the cgRNA could target two genes at one time. Target specificity analysis of cgRNA showed that mismatches at the 3' end of the target site abolished the cleavage activity completely. The mismatches at the 5' end reduced cleavage, suggesting that the off target effects can be abolished in vivo by selecting target sites with unique sequences at 3' end. This approach provides a powerful method for genome engineering in plants.

Occurrence of oral habits among preschool children with Autism Spectrum Disorder

PubMed Central

Al-Sehaibany, Fares S.

2017-01-01

Objective: To determine occurrence of oral habits among Saudi preschool children with autism spectrum disorder (ASD) and compare it with healthy preschool children. Methods: This study was conducted over a 14-months period in Riyadh, Saudi Arabia. The sample consisted of two groups; a study group (SG) of 150 ASD children, and a control group (CG) of age- and gender-matched 150 healthy children. The parents of the children in both the groups were administered a questionnaire that included questions about the children’s demographic information and previous or persistent oral habits. Results: The prevalence of oral habits was higher (87.3%) among the SG children as compared to CG children (49.3%). The most prevalent oral habit among the SG was bruxism (n = 82; 54.7%), followed by object biting (n = 67; 44.7%) and mouth breathing (n = 40; 26.7 %). Among the CG; the most prevalent oral habit was mouth breathing (n = 40; 26.7%) followed by nail biting (n=18; 12%) and object biting (n = 7; 4.7%). The prevalence of bruxism, object biting, thumb sucking and tongue biting was significantly (p<0.05) higher in the SG than the CG. Conclusions: The prevalence of oral habits was higher in the ASD group children than the healthy children. PMID:29142556

Influence of pilates training on the quality of life of chronic stroke patients.

PubMed

Yun, Seok-Min; Park, Sang-Kyoon; Lim, Hee Sung

2017-10-01

[Purpose] This study was to observe the influence of Pilates training on the quality of life in chronic stoke patients. [Subjects and Methods] Forty chronic stroke patients participated in this study. They were divided into same number of experimental group (EG) and control group (CG). EG participated in a 60-min Pilates training program, twice a week for 12 weeks, while the CG did not participate in any exercise-related activities for the duration and participating in general occupational therapy without any exercise-related activities. Then the MMSE-K was performed before and after Pilates training to observe the influence of Pilates training on the quality of life in chronic stroke patients. [Results] Statistically significant improvement in the physical, social, and psychological domains was found in EG after the training. No statistically significant difference was found in all three quality of life domains for the CG. EG experienced a statistically significant improvement in all quality of life domains compared with that of CG. [Conclusion] Therefore, participation in Pilates training was found to effectively improve the quality of life in stroke patients. Pilates training involves low and intermediate intensity resistance and repetition that match the patient's physical ability and can be a remedial exercise program that can improve physical ability and influence quality of life.

Influence of pilates training on the quality of life of chronic stroke patients

PubMed Central

Yun, Seok-Min; Park, Sang-Kyoon; Lim, Hee Sung

2017-01-01

[Purpose] This study was to observe the influence of Pilates training on the quality of life in chronic stoke patients. [Subjects and Methods] Forty chronic stroke patients participated in this study. They were divided into same number of experimental group (EG) and control group (CG). EG participated in a 60-min Pilates training program, twice a week for 12 weeks, while the CG did not participate in any exercise-related activities for the duration and participating in general occupational therapy without any exercise-related activities. Then the MMSE-K was performed before and after Pilates training to observe the influence of Pilates training on the quality of life in chronic stroke patients. [Results] Statistically significant improvement in the physical, social, and psychological domains was found in EG after the training. No statistically significant difference was found in all three quality of life domains for the CG. EG experienced a statistically significant improvement in all quality of life domains compared with that of CG. [Conclusion] Therefore, participation in Pilates training was found to effectively improve the quality of life in stroke patients. Pilates training involves low and intermediate intensity resistance and repetition that match the patient’s physical ability and can be a remedial exercise program that can improve physical ability and influence quality of life. PMID:29184300

Photogrammetric Technique for Center of Gravity Determination

NASA Technical Reports Server (NTRS)

Jones, Thomas W.; Johnson, Thomas H.; Shemwell, Dave; Shreves, Christopher M.

2012-01-01

A new measurement technique for determination of the center of gravity (CG) for large scale objects has been demonstrated. The experimental method was conducted as part of an LS-DYNA model validation program for the Max Launch Abort System (MLAS) crew module. The test was conducted on the full scale crew module concept at NASA Langley Research Center. Multi-camera photogrammetry was used to measure the test article in several asymmetric configurations. The objective of these measurements was to provide validation of the CG as computed from the original mechanical design. The methodology, measurement technique, and measurement results are presented.

A Quasi-experimental Study to Assess an Interactive Educational Intervention on Nurses' Knowledge of Pressure Ulcer Prevention in Nigeria.

PubMed

Ekama Ilesanmi, Rose; Morohunfoluwa Oluwatosin, Odunayo

2016-04-01

Educational intervention programs are an important element to improve nurses' knowledge of pressure ulcer (PU) prevention. Various teaching methods have been used with diverse results but none have been analyzed in Nigeria. A quasi- experimental study using a pretest/post test design was conducted among 193 registered nurses with >6 months experience who worked in purposefully selected wards (neuroscience, orthopedics, renal, and cardiac) in 3 teaching hospitals to examine the level of knowledge retention after interactive instruction. Participants were randomized to intervention (IG, n = 127 from 2 hospitals) and control (CG, n = 66 from 1 hospital) groups; the IG was provided a 5-day, face-to-face interactive lecture, and the CG engaged in a 1-day, 4-hour discussion of PU prevention practices. The Pressure Ulcer Knowledge Tool, a 47-item questionnaire in which a correct answer = 1 point and an incorrect/"I don't know" answer = 0 (maximum score 47), was used to assess and compare knowledge retention at 3 time points: baseline (T1), immediately after instruction (T2), and after 3 months (T3). Three trained research assistants assisted with registration of participants and distribution and collection of the questionnaires. All questionnaires were retrieved at T1 before the intervention be- gan. Respondents were encouraged to respond to all questions. Data were analyzed using t-test and ANOVA (P = 0.05). At T1, knowledge scores were comparable between the IG and CG (32.5 ± 4.2 and 30.8 ± 5.0 for IG and CG, respectively). At T2, knowledge scores increased significantly only in the IG to 40.7 ± 3.4 (d = 1.94, P less than 0.05). The mean difference between T1 and T2 was -8.2 ± 5.4, t = -17.0, P = 0.000. Similarly, mean scores increased significantly from T2 to T3 in the IG (mean= -2.0 ± 5.5, t = -4.1, P = 0.000); scores in the CG were -6.2 ± 7.2, t = -6.3 (P = 0.000). A face-to-face interactive lecture was shown to be an effective method of program delivery for nurses; other educational methods should be assessed and their effects on PU prevention practices and outcomes evaluated.

bZIP transcription factor CgAP1 is essential for oxidative stress tolerance and full virulence of the poplar anthracnose fungus Colletotrichum gloeosporioides.

PubMed

Sun, Yingjiao; Wang, Yonglin; Tian, Chengming

2016-10-01

Yeast AP1 transcription factor is a regulator of oxidative stress response. Here, we report the identification and characterization of CgAP1, an ortholog of YAP1 in poplar anthracnose fungus Colletotrichum gloeosporioides. The expression of CgAP1 was highly induced by reactive oxygen species. CgAP1 deletion mutants displayed enhanced sensitivity to oxidative stress compared with the wild-type strain, and their poplar leaf virulence was obviously reduced. However, the mutants exhibited no obvious defects in aerial hyphal growth, conidia production, and appressoria formation. CgAP1::eGFP fusion protein localized to the nucleus after TBH (tert-Butyl hydroperoxide) treatment, suggesting that CgAP1 functions as a redox sensor in C. gloeosporioides. In addition, CgAP1 prevented the accumulation of ROS during early stages of biotrophic growth. CgAP1 also acted as a positive regulator of several ROS-related genes (i.e., Glr1, Hyr1, and Cyt1) involved in the antioxidative response. These results highlight the key regulatory role of CgAP1 transcription factor in oxidative stress response and provide insights into the function of ROS detoxification in virulence of C. gloeosporioides. Copyright © 2016 Elsevier Inc. All rights reserved.

Biochemical markers of trisomy 21 in amniotic fluid.

PubMed

Spencer, K; Muller, F; Aitken, D A

1997-01-01

In a study of amniotic fluid from 91 Down's syndrome cases and 240 controls, we have shown that the median values of four biochemical markers (AFP, total hCG, free beta hCG, and unconjugated oestriol) in the amniotic fluid of pregnancies affected by Down's syndrome on the whole reflect those observed in the maternal serum of affected cases. The median MOM for AFP was lower than average (0.56), as was that for unconjugated oestriol (0.55), whilst those for total hCG (1.82) and free beta hCG (2.10) were increased on average. The width of the distribution of marker levels in amniotic fluid is similar to that in serum for free beta hCG and total hCG but between 1.5 and 2 times wider for unconjugated oestriol and AFP. Analysis of data by fetal sex showed a significantly higher median MOM in female control cases compared with male controls for the analytes free beta hCG, total hCG, and unconjugated oestriol, but not for AFP. Amongst the Down's syndrome cases, this trend was not statistically significant and we cannot confirm a previous study which reported that elevated levels of amniotic fluid total and free beta hCG were associated only with female fetuses.

Molecular Characterization of Voltage-Gated Sodium Channels and Their Relations with Paralytic Shellfish Toxin Bioaccumulation in the Pacific Oyster Crassostrea gigas

PubMed Central

Boullot, Floriane; Castrec, Justine; Bidault, Adeline; Dantas, Natanael; Payton, Laura; Perrigault, Mickael; Tran, Damien; Amzil, Zouher; Boudry, Pierre; Soudant, Philippe; Hégaret, Hélène; Fabioux, Caroline

2017-01-01

Paralytic shellfish toxins (PST) bind to voltage-gated sodium channels (Nav) and block conduction of action potential in excitable cells. This study aimed to (i) characterize Nav sequences in Crassostrea gigas and (ii) investigate a putative relation between Nav and PST-bioaccumulation in oysters. The phylogenetic analysis highlighted two types of Nav in C. gigas: a Nav1 (CgNav1) and a Nav2 (CgNav2) with sequence properties of sodium-selective and sodium/calcium-selective channels, respectively. Three alternative splice transcripts of CgNav1 named A, B and C, were characterized. The expression of CgNav1, analyzed by in situ hybridization, is specific to nervous cells and to structures corresponding to neuromuscular junctions. Real-time PCR analyses showed a strong expression of CgNav1A in the striated muscle while CgNav1B is mainly expressed in visceral ganglia. CgNav1C expression is ubiquitous. The PST binding site (domain II) of CgNav1 variants possess an amino acid Q that could potentially confer a partial saxitoxin (STX)-resistance to the channel. The CgNav1 genotype or alternative splicing would not be the key point determining PST bioaccumulation level in oysters. PMID:28106838

Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis.

PubMed

Chen, Chi-Huang; Tzeng, Chii-Ruey; Wang, Peng-Hui; Liu, Wei-Min; Chang, Heng-Yu; Chen, Huang-Hui; Chen, Ching-Hui

2018-03-29

To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes. A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation. Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups. Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

Hyperglycosylated hCG and Placenta Accreta Spectrum.

PubMed

Einerson, Brett D; Straubhar, Alli; Soisson, Sean; Szczotka, Kathryn; Dodson, Mark K; Silver, Robert M; Soisson, Andrew P

2018-02-28

 We aimed to evaluate the relationship between hyperglycosylated human chorionic gonadotropin (hCG-H) and placenta accreta spectrum (PAS) in the second and third trimesters of pregnancy.  This was a case-control study of PAS and controls. hCG-H was measured in the second and third trimesters of pregnancy in women with pathologically confirmed cases of PAS and in gestational age-matched controls without PAS. We compared serum hCG-H levels in cases and controls, calculated summary statistics for diagnostic accuracy, and used receiver operating characteristic (ROC) curves to define an optimal cut-point for diagnosis of PAS using hCG-H.  Thirty case samples and 30 control samples were evaluated for hCG-H. Mean hCG-H was lower in the case compared with control group (7.8 ± 5.9 μg/L vs. 11.8 ± 8.8 μg/L, p  = 0.03). At an optimal cut-point for hCG-H of ≤7.6 μg/L, the sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and area under the ROC curve were 66.7%, 69.7%, 2.20%, 0.48%, and 0.68%, respectively.  Hyperglycosylated hCG levels in the second and third trimesters of pregnancy were lower in patients with PAS than in controls, but hCG-H showed only modest capability as a diagnostic test for PAS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

PubMed

Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

2016-10-01

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

Mechanistic insights into the recognition of 5-methylcytosine oxidation derivatives by the SUVH5 SRA domain.

PubMed

Rajakumara, Eerappa; Nakarakanti, Naveen Kumar; Nivya, M Angel; Satish, Mutyala

2016-02-04

5-Methylcytosine (5 mC) is associated with epigenetic gene silencing in mammals and plants. 5 mC is consecutively oxidized to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by ten-eleven translocation enzymes. We performed binding and structural studies to investigate the molecular basis of the recognition of the 5 mC oxidation derivatives in the context of a CG sequence by the SET- and RING-associated domain (SRA) of the SUVH5 protein (SUVH5 SRA). Using calorimetric measurements, we demonstrate that the SRA domain binds to the hydroxymethylated CG (5hmCG) DNA duplex in a similar manner to methylated CG (5mCG). Interestingly, the SUVH5 SRA domain exhibits weaker affinity towards carboxylated CG (5caCG) and formylated CG (5fCG). We report the 2.6 Å resolution crystal structure of the SUVH5 SRA domain in a complex with fully hydroxymethyl-CG and demonstrate a dual flip-out mechanism, whereby the symmetrical 5hmCs are simultaneously extruded from the partner strands of the DNA duplex and are positioned within the binding pockets of individual SRA domains. The hydroxyl group of 5hmC establishes both intra- and intermolecular interactions in the binding pocket. Collectively, we show that SUVH5 SRA recognizes 5hmC in a similar manner to 5 mC, but exhibits weaker affinity towards 5 hmC oxidation derivatives.

New Coarse-Grained Model and Its Implementation in Simulations of Graphene Assemblies.

PubMed

Shang, Jun-Jun; Yang, Qing-Sheng; Liu, Xia

2017-08-08

Graphene is a one-atom thick layer of carbon atoms arranged in a hexagonal pattern, which makes it the strongest material in the world. The Tersoff potential is a suitable potential for simulating the mechanical behavior of the complex covalently bonded system of graphene. In this paper, we describe a new coarse-grained (CG) potential, TersoffCG, which is based on the function form of the Tersoff potential. The TersoffCG applies to a CG model of graphene that uses the same hexagonal pattern as the atomistic model. The parameters of the TersoffCG potential are determined using structural feature and potential-energy fitting between the CG model and the atomic model. The modeling process of graphene is highly simplified using the present CG model as it avoids the necessity to define bonds/angles/dihedrals connectivity. What is more, the present CG model provides a new perspective of coarse-graining scheme for crystal structures of nanomaterials. The structural changes and mechanical properties of multilayer graphene were calculated using the new potential. Furthermore, a CG model of a graphene aerogel was built in a specific form of assembly. The chemical bonding in the joints of graphene-aerogel forms automatically during the energy relaxation process. The compressive and recover test of the graphene aerogel was reproduced to study its high elasticity. Our computational examples show that the TersoffCG potential can be used for simulations of graphene and its assemblies, which have many applications in areas of environmental protection, aerospace engineering, and others.

Minimally-aggressive gestational trophoblastic neoplasms.

PubMed

Cole, Laurence A

2012-04-01

We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, <40% of total hCG. It can also be identified by hCG doubling rate, with doubling time greater than 2 weeks. Nineteen new cases were identified as having minimally aggressive gestational trophoblastic disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml. Copyright © 2011 Elsevier Inc. All rights reserved.

Chromogranin A promotes peptide hormone sorting to mobile granules in constitutively and regulated secreting cells: role of conserved N- and C-terminal peptides.

PubMed

Montero-Hadjadje, Maité; Elias, Salah; Chevalier, Laurence; Benard, Magalie; Tanguy, Yannick; Turquier, Valérie; Galas, Ludovic; Yon, Laurent; Malagon, Maria M; Driouich, Azeddine; Gasman, Stéphane; Anouar, Youssef

2009-05-01

Chromogranin A (CgA) has been proposed to play a major role in the formation of dense-core secretory granules (DCGs) in neuroendocrine cells. Here, we took advantage of unique features of the frog CgA (fCgA) to assess the role of this granin and its potential functional determinants in hormone sorting during DCG biogenesis. Expression of fCgA in the constitutively secreting COS-7 cells induced the formation of mobile vesicular structures, which contained cotransfected peptide hormones. The fCgA and the hormones coexpressed in the newly formed vesicles could be released in a regulated manner. The N- and C-terminal regions of fCgA, which exhibit remarkable sequence conservation with their mammalian counterparts were found to be essential for the formation of the mobile DCG-like structures in COS-7 cells. Expression of fCgA in the corticotrope AtT20 cells increased pro-opiomelanocortin levels in DCGs, whereas the expression of N- and C-terminal deletion mutants provoked retention of the hormone in the Golgi area. Furthermore, fCgA, but not its truncated forms, promoted pro-opiomelanocortin sorting to the regulated secretory pathway. These data demonstrate that CgA has the intrinsic capacity to induce the formation of mobile secretory granules and to promote the sorting and release of peptide hormones. The conserved terminal peptides are instrumental for these activities of CgA.

Medical comorbidity in complicated grief: Results from the HEAL collaborative trial.

PubMed

Robbins-Welty, Gregg; Stahl, Sarah; Zhang, Jun; Anderson, Stewart; Schenker, Yael; Shear, M Katherine; Simon, Naomi M; Zisook, Sidney; Skritskaya, Natalia; Mauro, Christina; Lebowitz, Barry D; Reynolds, Charles F

2018-01-01

To describe medical comorbidity in persons with Complicated Grief (CG) and to test whether medical comorbidity in individuals with CG is associated with the severity and duration of CG, after adjusting for age, sex, race, and current depressive symptoms. In exploratory analyses, we compared data from participants in an NIMH-sponsored multisite clinical trial of CG ("HEAL": "Healing Emotions After Loss") to archival data from participants matched on age, gender, and race/ethnicity, stratified by the presence or absence of current major depression. We used the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) as a measure of medical polymorbidity. We investigated the association between CG and medical comorbidity via multiple linear regression, adjusting for sociodemographic and clinical variables, including severity of depressive symptoms. Chronological age and severity of co-occurring symptoms of major depression correlated with cumulative medical polymorbidity in persons with Complicated Grief. The severity of CG and the time since loss did not correlate with global medical polymorbidity (CIRS-G score). Nor was there an interaction between severity of depressive symptoms and severity of CG symptoms in predicting global CIRS-G score. Cumulative medical comorbidity, as measured by CIRS-G scores, was greater in subjects with current major depression ("DEPRESSED") than in CG subjects, and both DEPRESSED and CG subjects had greater medical morbidity than CONTROLS. Medical comorbidity is prevalent in Complicated Grief, associated with increasing age and co-occurring depressive symptoms but apparently not with chronicity and severity of Complicated Grief per se. This observation suggests that treating depression in the context of CG may be important to managing medical conditions in individuals with Complicated Grief to attenuate or prevent the long-term medical sequelae of CG. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reproductive performance of seasonally anovular mixed-bred dairy goats induced to ovulate with a combination of progesterone and eCG or estradiol.

PubMed

Contreras-Villarreal, Viridiana; Meza-Herrera, César A; Rivas-Muñoz, Raymundo; Angel-Garcia, Oscar; Luna-Orozco, Juan R; Carrillo, Evaristo; Mellado, Miguel; Véliz-Deras, Francisco G

2016-06-01

Adult goats (n = 32) were randomly assigned to one of four treatments (n = 8, each): (i) progesterone (P4 ) + equine chorionic gonadotropin (eCG), treated with 25 mg progesterone intramuscularly (i.m.) + 250 IU eCG 24 h later; (ii) cronolone + eCG, treated with vaginal sponges - 20 mg cronolone × 7 days + 250 IU eCG at pessary removal; (ii) P4 + estradiol (E2 ), treated with 25 mg progesterone i.m. + 1 mg estradiol 24 h later; (iv) cronolone + E2 , treated with vaginal sponges - 20 mg cronolone × 7 days + 1 mg of estradiol i.m. at pessary removal. Goats were tested for estrus throughout the presence of a buck. Seven days prior and after treatment, an ovarian ultrasonographic scanning was performed to determine ovarian function and structures. An ultrasonographic pregnancy diagnosis was performed on day 30 post-service. In all groups, 100% estrus response was observed within 96 h post-treatment. While ovulation occurred in 100% of P4 + eCG and cronolone + eCG treated goats, the other groups only depicted 50% ovulatory activity (P < 0.05). Pregnancy rate was higher (P <0.05) in the P4 + eCG and cronolone + eCG groups (88 and 100%, respectively), compared with 38% in P4 + E2 and cronolone + E2 groups. The best treatments were those in which eCG was applied. The P4 + eCG treatment was a pessary-free, cheaper and effective protocol to induce ovulation in goats during the seasonal anovulatory period. © 2015 Japanese Society of Animal Science.

Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe 1-Tyr 3-octreotide and chromogranin A assay in patients with neuroendocrine tumours.

PubMed

Rodrigues, Margarida; Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Griesmacher, Andrea; Virgolini, Irene

2008-10-01

Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with (111)In-DOTA-DPhe(1)-Tyr(3)-octreotide ((111)In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p<0.05) in patients with PDNECs and tumours of hindgut origin. Overall, (111)In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels.

Regulation of gonadotropin receptors, gonadotropin responsiveness, and cell multiplication by somatomedin-C and insulin in cultured pig Leydig cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernier, M.; Chatelain, P.; Mather, J.P.

1986-11-01

The author have investigated the effects of insulin and somatomedin-C/insulin like growth factor I(Sm-C) in purified porcine Leydig cells in vitro on gonadotrophins (hCG) receptor number, hCG responsiveness (cAMP and testosterone production), and thymidine incorporation into DNA. Leydig cells cultured in a serum-free medium containing transferrin, vitamin E, and insulin (5 ..mu..g/ml) maintained fairly constant both hCG receptors and hCG responsiveness. When they were cultured for 3 days in the same medium without insulin, there was a dramatic decline (more than 80%) in both hCG receptor number and hCG responsiveness. However the cAMP but not the testosterone response to forskolinmore » was normal. Both insulin and Sm-C at nanomolar concentrations prevent the decline of both hCG receptors and hCG-induced cAMP production. At nanomolar concentrations, Sm-C and insulin enhanced hCG-induced testosterone production but the effect of Sm-C was significantly higher than that of insulin. However, the effect of insulin at higher concentrations (5 ..mu..g/ml) was significantly higher than that of Sm-C at 50 ng/ml. In contrast, at nanomolar concentrations only Sm-C stimulated (/sup 3/H)-thymidine incorporation into DNA and cell multiplication, the stimulatory effect of insulin on these parameters, was seen only at micromolar concentrations. These results indicate that both Sm-C and insulin acting through the receptors increase Leydig cell steroidogenic responsiveness to hCG by increasing hCG receptor number and improving some step beyond cAMP formation. In contrast, the mitogenic effects of insulin are mediated only through Sm-C receptors.« less

Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL.

PubMed

Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong-Su; Ro, Seonggu; Cho, Joong Myung; Kim, Hwan-Mook; Lee, Sang-Jin; Oh, Seung Hyun

2015-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.

The B-cell translocation gene 1 (CgBTG1) identified in oyster Crassostrea gigas exhibit multiple functions in immune response.

PubMed

Liu, Rui; Cheng, Qi; Wang, Xiudan; Chen, Hao; Wang, Weilin; Zhang, Huan; Wang, Lingling; Song, Linsheng

2017-02-01

B-cell translocation gene 1 (BTG1) is a member of the anti-proliferative gene family, which plays important roles in regulation of cell cycle. In the present study, a B-cell translocation gene 1 molecule homologue (designed CgBTG1) are identified and characterized in oyster Crassostrea gigas. CgBTG1 contains a conserved BTG domain with Box A and Box B motifs, and it shares high similarities with both BTG1 and BTG2 proteins in vertebrates. CgBTG1 mRNA is predominantly expressed in hemocytes, and its expression level in hemocytes is significantly up-regulated at 6 h (5.40-fold, p < 0.01) post Vibrio splendidus stimulation. The apoptosis rate of oyster hemocytes is significantly decreased (p < 0.05) after CgBTG1 interfered by dsRNA (dsCgBTG1). This is indicated that CgBTG1 participated in the regulation of oyster hemocytes apoptosis. Furthermore, CgBTG1 could also induce the apoptosis of cancer cells (HeLa, A549 and BEL7402) in vitro. Compared with normal oysters, both vessel-like structures and muscle fibers in CgBTG1 interfered oysters are severely damaged after V. splendidus challenge in paraffin section, considering that CgBTG1 possessed an analogous feature of angiogenesis for maintenance of vessel-like structures in adductor muscle of oyster. The results suggests that CgBTG1 is a multi-functional molecule involved in the immune response of C. gigas against pathogen infection, which provides more clues for intensive studies of BTG family proteins in invertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel histone deacetylase inhibitor CG200745 induces clonogenic cell death by modulating acetylation of p53 in cancer cells.

PubMed

Oh, Eun-Taex; Park, Moon-Taek; Choi, Bo-Hwa; Ro, Seonggu; Choi, Eun-Kyung; Jeong, Seong-Yun; Park, Heon Joo

2012-04-01

Histone deacetylase (HDAC) plays an important role in cancer onset and progression. Therefore, inhibition of HDAC offers potential as an effective cancer treatment regimen. CG200745, (E)-N(1)-(3-(dimethylamino)propyl)-N(8)-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide, is a novel HDAC inhibitor presently undergoing a phase I clinical trial. Enhancement of p53 acetylation by HDAC inhibitors induces cell cycle arrest, differentiation, and apoptosis in cancer cells. The purpose of the present study was to investigate the role of p53 acetylation in the cancer cell death caused by CG200745. CG200745-induced clonogenic cell death was 2-fold greater in RKO cells expressing wild-type p53 than in p53-deficient RC10.1 cells. CG200745 treatment was also cytotoxic to PC-3 human prostate cancer cells, which express wild-type p53. CG200745 increased acetylation of p53 lysine residues K320, K373, and K382. CG200745 induced the accumulation of p53, promoted p53-dependent transactivation, and enhanced the expression of MDM2 and p21(Waf1/Cip1) proteins, which are encoded by p53 target genes. An examination of CG200745 effects on p53 acetylation using cells transfected with various p53 mutants showed that cells expressing p53 K382R mutants were significantly resistant to CG200745-induced clonogenic cell death compared with wild-type p53 cells. Moreover, p53 transactivation in response to CG200745 was suppressed in all cells carrying mutant forms of p53, especially K382R. Taken together, these results suggest that acetylation of p53 at K382 plays an important role in CG200745-induced p53 transactivation and clonogenic cell death.

Variation, Evolution, and Correlation Analysis of C+G Content and Genome or Chromosome Size in Different Kingdoms and Phyla

PubMed Central

Li, Xiu-Qing; Du, Donglei

2014-01-01

C+G content (GC content or G+C content) is known to be correlated with genome/chromosome size in bacteria but the relationship for other kingdoms remains unclear. This study analyzed genome size, chromosome size, and base composition in most of the available sequenced genomes in various kingdoms. Genome size tends to increase during evolution in plants and animals, and the same is likely true for bacteria. The genomic C+G contents were found to vary greatly in microorganisms but were quite similar within each animal or plant subkingdom. In animals and plants, the C+G contents are ranked as follows: monocot plants>mammals>non-mammalian animals>dicot plants. The variation in C+G content between chromosomes within species is greater in animals than in plants. The correlation between average chromosome C+G content and chromosome length was found to be positive in Proteobacteria, Actinobacteria (but not in other analyzed bacterial phyla), Ascomycota fungi, and likely also in some plants; negative in some animals, insignificant in two protist phyla, and likely very weak in Archaea. Clearly, correlations between C+G content and chromosome size can be positive, negative, or not significant depending on the kingdoms/groups or species. Different phyla or species exhibit different patterns of correlation between chromosome-size and C+G content. Most chromosomes within a species have a similar pattern of variation in C+G content but outliers are common. The data presented in this study suggest that the C+G content is under genetic control by both trans- and cis- factors and that the correlation between C+G content and chromosome length can be positive, negative, or not significant in different phyla. PMID:24551092

Three-dimensional carbon fibers and method and apparatus for their production

DOEpatents

Muradov, Nazim Z [Melbourne, FL

2012-02-21

This invention relates to novel three-dimensional (3D) carbon fibers which are original (or primary) carbon fibers (OCF) with secondary carbon filaments (SCF) grown thereon, and, if desired, tertiary carbon filaments (TCF) are grown from the surface of SCF forming a filamentous carbon network with high surface area. The methods and apparatus are provided for growing SCF on the OCF by thermal decomposition of carbonaceous gases (CG) over the hot surface of the OCF without use of metal-based catalysts. The thickness and length of SCF can be controlled by varying operational conditions of the process, e.g., the nature of CG, temperature, residence time, etc. The optional activation step enables one to produce 3D activated carbon fibers with high surface area. The method and apparatus are provided for growing TCF on the SCF by thermal decomposition of carbonaceous gases over the hot surface of the SCF using metal catalyst particles.

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles.

PubMed

Gunnala, Vinay; Melnick, Alexis; Irani, Mohamad; Reichman, David; Schattman, Glenn; Davis, Owen; Rosenwaks, Zev

2017-01-01

To evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity. Retrospective cohort. Academic medical center. Fresh IVF cycles from 9/2004-12/2011. 10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI. Oocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose. Post-trigger serum b-hCG 20-30, 30-40, and 40-50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20-50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41-0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. Moderate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity.

Topographic antigenic determinants recognized by monoclonal antibodies on human choriogonadotropin beta-subunit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bidart, J.M.; Troalen, F.; Salesse, R.

1987-06-25

We describe a first attempt to study the antibody-combining sites recognized by monoclonal antibodies raised against the beta-subunit of human choriogonadotropin (hCG). Two groups of antibodies were first defined by their ability to recognize only the free beta-subunit or the free and combined subunit. Antibodies FBT-11 and FBT-11-L bind only to hCG beta-subunit but not to hCG, whereas antibodies FBT-10 and D1E8 bind to both the beta-subunit and the hormone. In both cases, the antigenic determinants were localized to the core of the protein (residues 1-112), indicating the weak immunogenicity of the specific carboxyl-terminal extension of hCG-beta. Nine synthetic peptidesmore » spanning different regions of hCG-beta and lutropin-beta were assessed for their capacity to inhibit antibody binding. A synthetic peptide inclusive of the NH2-terminal region (residues 1-7) of the hCG beta-subunit was found to inhibit binding to the radiolabeled subunit of a monoclonal antibody specific for free hCG-beta (FBT-11). Further delineation of the antigenic site recognized by this antibody provided evidence for the involvement of fragment 82-92. Moreover, monoclonal antibody FBT-11 inhibited the recombination of hCG-beta to hCG-alpha, indicating that its antigenic determinant might be located nearby or in the hCG-beta portion interacting with the alpha-subunit. Binding of monoclonal antibody FBT-10, corresponding to the second antigenic determinant, was weakly inhibited by fragment 82-105 and did not impair the recombination of the hCG beta-subunit to the hCG alpha-subunit. Its combining site appeared to be located in a region of the intact native choriogonadotropin present at the surface of the hormone-receptor complex.« less

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles

PubMed Central

Schattman, Glenn; Davis, Owen; Rosenwaks, Zev

2017-01-01

Objective To evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity. Design Retrospective cohort. Setting Academic medical center. Patients Fresh IVF cycles from 9/2004–12/2011. Intervention 10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI. Main outcome measures Oocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose. Results Post-trigger serum b-hCG 20–30, 30–40, and 40–50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20–50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41–0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. Conclusions Moderate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity. PMID:28441461

Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

PubMed

Nome, Ragnhild V; Bjøro, Trine; Paus, Elisabeth; Bjerner, Johan; Fosså, Sophie D; Steen, Rita; Nustad, Kjell; Bolstad, Nils

2018-02-01

Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay. We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function. We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels. The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice. Copyright © 2017 Oslo University Hospital. Published by Elsevier Inc. All rights reserved.

Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain

PubMed Central

2011-01-01

Background The anterior cingulate cortex (ACC) has been related to the affective component of pain. Dopaminergic mesocortical circuits, including the ACC, are able to inhibit neuropathic nociception measured as autotomy behaviour. We determined the changes in dopamine D1 and D2 (D1R and D2R) receptor expression in the ACC (cg1 and cg2) in an animal model of neuropathic pain. The neuropathic group had noxious heat applied in the right hind paw followed 30 min. later by right sciatic denervation. Autotomy score (AS) was recorded for eight days and subsequently classified in low, medium and high AS groups. The control consisted of naïve animals. A semiquantitative RT-PCR procedure was done to determine mRNA levels for D1R and D2R in cg1 and cg2, and protein levels were measured by Western Blot. Results The results of D1R mRNA in cg1 showed a decrease in all groups. D2R mRNA levels in cg1 decreased in low AS and increased in medium and high AS. Regarding D1R in cg2, there was an increase in all groups. D2R expression levels in cg2 decreased in all groups. In cg1, the D2R mRNA correlated positively with autotomy behaviour. Protein levels of D2R in cg1 increased in all groups but to a higher degree in low AS. In cg2 D2R protein only decreased discretely. D1R protein was not found in either ACC region. Conclusions This is the first evidence of an increase of inhibitory dopaminergic receptor (D2R) mRNA and protein in cg1 in correlation with nociceptive behaviour in a neuropathic model of pain in the rat. PMID:22171983

Predictive value of modeled AUC(AFP-hCG), a dynamic kinetic parameter characterizing serum tumor marker decline in patients with nonseminomatous germ cell tumor.

PubMed

You, Benoit; Fronton, Ludivine; Boyle, Helen; Droz, Jean-Pierre; Girard, Pascal; Tranchand, Brigitte; Ribba, Benjamin; Tod, Michel; Chabaud, Sylvie; Coquelin, Henri; Fléchon, Aude

2010-08-01

The early decline profile of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in patients with nonseminomatous germ cell tumors (NSGCT) treated with chemotherapy may be related to the risk of relapse. We assessed the predictive values of areas under the curve of hCG (AUC(hCG)) and AFP (AUC(AFP)) of modeled concentration-time equations on progression-free survival (PFS). Single-center retrospective analysis of hCG and AFP time-points from 65 patients with IGCCCG intermediate-poor risk NSGCT treated with 4 cycles of bleomycin-etoposide-cisplatin (BEP). To determine AUC(hCG) and AUC(AFP) for D0-D42, AUCs for D0-D7 were calculated using the trapezoid rule and AUCs for D7-D42 were calculated using the mathematic integrals of equations modeled with NONMEM. Combining AUC(AFP) and AUC(hCG) enabled us to define 2 predictive groups: namely, patients with favorable and unfavorable AUC(AFP-hCG). Survival analyses and ROC curves assessed the predictive values of AUC(AFP-hCG) groups regarding progression-free survival (PFS) and compared them with those of half-life (HL) and time-to-normalization (TTN). Mono-exponential models best fit the patterns of marker decreases. Patients with a favorable AUC(AFP-hCG) had a significantly better PFS (100% vs 71.5%, P = .014). ROC curves confirmed the encouraging predictive accuracy of AUC(AFP-hCG) against HL or TTN regarding progression risk (ROC AUCs = 79.6 vs 71.9 and 70.2 respectively). Because of the large number of patients with missing data, multivariate analysis could not be performed. AUC(AFP-hCG) is a dynamic parameter characterizing tumor marker decline in patients with NSGCT during BEP treatment. Its value as a promising predictive factor should be validated. Copyright 2010 Elsevier Inc. All rights reserved.

"Hook-like effect" causes false-negative point-of-care urine pregnancy testing in emergency patients.

PubMed

Griffey, Richard T; Trent, Caleb J; Bavolek, Rebecca A; Keeperman, Jacob B; Sampson, Christopher; Poirier, Robert F

2013-01-01

Failure to detect pregnancy in the emergency department (ED) can have important consequences. Urine human chorionic gonadotropin (uhCG) point-of-care (POC) assays are valued for rapidly detecting early pregnancy with high sensitivity. However, under certain conditions, POC uhCG tests can fail to detect pregnancy. In investigating a series of late first-trimester false-negative pregnancy tests in our ED, a novel and distinct causative phenomenon was recently elucidated in our institution. We discuss uhCG POC tests, review our false-negative rate, and describe mechanisms for false negatives and potential remedies. The false-negative POC uhCG rate is very low, but in the setting of a large volume of tests, the numbers are worth consideration. In positive uhCG POC tests, free and fixed antibodies bind hCG to form a "sandwich"; hCG is present in several variant forms that change in their concentrations at different stages of pregnancy. When in excess, intact hCG can saturate the antibodies, preventing sandwich formation (hook effect phenomenon). Some assays may include an antibody that does not recognize certain variants present in later stages of pregnancy. When this variant is in excess, it can bind one antibody avidly and the other not at all, resulting in a false-negative test (hook-like phenomenon). In both situations, dilution is key to an accurate test. Manufacturers should consider that uhCG tests are routinely used at many stages of pregnancy. Characterizing uhCG variants recognized by their tests and eliminating lot-to-lot variability may help improve uhCG test performance. Clinicians need to be aware of and familiarize themselves with the limitations of the specific type of uhCG POC tests used in their practice, recognizing that under certain circumstances, false-negative tests can occur. Copyright © 2013 Elsevier Inc. All rights reserved.

A novel junctional adhesion molecule A (CgJAM-A-L) from oyster (Crassostrea gigas) functions as pattern recognition receptor and opsonin.

PubMed

Liu, Conghui; Wang, Mengqiang; Jiang, Shuai; Wang, Lingling; Chen, Hao; Liu, Zhaoqun; Qiu, Limei; Song, Linsheng

2016-02-01

Junctional adhesion molecule (JAM), a subfamily of immunoglobulin superfamily (IgSF) with a couple of immunoglobulin domains, can act as regulator in homeostasis and inflammation of vertebrates. In the present study, a structural homolog of JAM-A (designated CgJAM-A-L) was screened out from oyster, Crassostrea gigas, through a search of JAM-A D1 domain (N-terminal Ig domain in JAM-A). The cDNA of CgJAM-A-L was of 1188 bp encoding a predicted polypeptide of 395 amino acids. The immunoreactive area of CgJAM-A-L mainly distributed over the plasma membrane of hemocytes. After Vibro splendidus or tumor necrosis factor (CgTNF-1) stimulation, the mRNA transcripts of CgJAM-A-L in hemocytes increased significantly by 4.46-fold and 9.00-fold (p < 0.01) of those in control group, respectively. The recombinant CgJAM-A-L protein (rCgJAM-A-L) could bind multiple PAMPs including lipopolysaccharides (LPS), peptidoglycan (PGN), lipoteichoic acid (LTA), mannose (MAN), β-glucan (GLU) and poly(I:C), and various microorganisms including Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Vibro anguillarum, V. splendidus, Pastoris pastoris and Yarrowia lipolytica. The phagocytic rates of oyster hemocytes towards Gram-negative bacteria V. anguillarum and yeast P. pastoris were significantly enhanced after the incubation of rCgJAM-A-L, and even increased more significantly after the pre-incubation of rCgJAM-A-L with microbes (p < 0.01). The results collectively indicated that CgJAM-A-L functioned as an important pattern recognition receptor (PRR) and opsonin in the immune defense against invading pathogen in oyster. Moreover, as the most primitive specie with homolog of JAMs, the information of CgJAM-A-L in oyster would provide useful clues for the evolutionary study of JAMs and immunoglobulins. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulation of the CgPdr1 Transcription Factor from the Pathogen Candida glabrata ▿

PubMed Central

Paul, Sanjoy; Schmidt, Jennifer A.; Moye-Rowley, W. Scott

2011-01-01

Candida glabrata is an opportunistic human pathogen that is increasingly associated with candidemia, owing in part to the intrinsic and acquired high tolerance the organism exhibits for the important clinical antifungal drug fluconazole. This elevated fluconazole resistance often develops through gain-of-function mutations in the zinc cluster-containing transcriptional regulator C. glabrata Pdr1 (CgPdr1). CgPdr1 induces the expression of an ATP-binding cassette (ABC) transporter-encoding gene, CgCDR1. Saccharomyces cerevisiae has two CgPdr1 homologues called ScPdr1 and ScPdr3. These factors control the expression of an ABC transporter-encoding gene called ScPDR5, which encodes a homologue of CgCDR1. Loss of the mitochondrial genome (ρ0 cell) or overexpression of the mitochondrial enzyme ScPsd1 induces ScPDR5 expression in a strictly ScPdr3-dependent fashion. ScPdr3 requires the presence of a transcriptional Mediator subunit called Gal11 (Med15) to fully induce ScPDR5 transcription in response to ρ0 signaling. ScPdr1 does not respond to either ρ0 signals or ScPsd1 overproduction. In this study, we employed transcriptional fusions between CgPdr1 target promoters, like CgCDR1, to demonstrate that CgPdr1 stimulates gene expression via binding to elements called pleiotropic drug response elements (PDREs). Deletion mapping and electrophoretic mobility shift assays demonstrated that a single PDRE in the CgCDR1 promoter was capable of supporting ρ0-induced gene expression. Removal of one of the two ScGal11 homologues from C. glabrata caused a major defect in drug-induced expression of CgCDR1 but had a quantitatively minor effect on ρ0-stimulated transcription. These data demonstrate that CgPdr1 appears to combine features of ScPdr1 and ScPdr3 to produce a transcription factor with chimeric regulatory properties. PMID:21131438

Pharmacokinetics and pharmacodynamics of human chorionic gonadotropin (hCG) after rectal administration of hollow-type suppositories containing hCG.

PubMed

Kowari, Kouji; Hirosawa, Iori; Kurai, Hirono; Utoguchi, Naoki; Fujii, Makiko; Watanabe, Yoshiteru

2002-05-01

To determine the effectiveness of human chorionic gonadotropin (hCG) administered rectally, we studied the pharmacokinetics and pharmacodynamics of hCG using a hollow-type suppository. HCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4,000 IU/kg body weight) than intravenous injection, because of its low bioavailability due to high molecular weight or degradation by proteolytic activity. To enhance the rectal absorption of hCG, the effectiveness of its coadministration with alpha-cyclodextrin (alpha-CyD), an absorption-enhancing agent, was investigated in male rabbits. HCG was detected in plasma following coadministration of hCG and alpha-CyD (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of alpha-CyD. The AUC(0-48) observed after coadministration of hCG and alpha-CyD at 30 mg/kg body weight was approximately four times higher than that of hCG and alpha-CyD at 10mg/kg body weight. HCG at a high concentration induced a rapid increase in the plasma testosterone concentration (74.2 +/- 3.4 ng/ml) 2 h after intravenous administration. However, the testosterone concentration 24 h after intravenous administration decreased to the physiological level (approximately 20 ng/ml) which had been observed before such administration. On the other hand, the maximum level of testosterone concentration (40.0 +/- 12.6 ng/ml) was observed 24 h after rectal administration of hCG (400 IU/kg body weight) in combination with alpha-CyD (30 mg/kg body weight). Moreover, the plasma testosterone concentration (31.0 +/- 11.4 ng/ml) obtained 72 h after rectal administration tended to be maintained at a higher level than that (14.4 +/- 0.9ng/ml) observed before the administration. These results suggest that the hollow-type suppository as a rectal delivery system of hCG is promising as a new mode of hCG therapy.

Sphere-shaped nano-hydroxyapatite/chitosan/gelatin 3D porous scaffolds increase proliferation and osteogenic differentiation of human induced pluripotent stem cells from gingival fibroblasts.

PubMed

Ji, Jun; Tong, Xin; Huang, Xiaofeng; Wang, Tiancong; Lin, Zitong; Cao, Yazhou; Zhang, Junfeng; Dong, Lei; Qin, Haiyan; Hu, Qingang

2015-07-08

Hydroxyapatite (HA) is an important component of human bone and bone tissue engineering scaffolds. A plethora of bone tissue engineering scaffolds have been synthesized so far, including nano-HA/chitosan/gelatin (nHA/CG) scaffolds; and for seeding cells, stem cells, especially induced pluripotent stem cells (iPSCs), have been a promising cell source for bone tissue engineering recently. However, the influence of different HA nano-particle morphologies on the osteogenic differentiation of human iPSCs (hiPSCs) from human gingival fibroblasts (hGFs) is unknown. The purpose of this study was to investigate the osteogenic differentiation of hiPSCs from hGFs seeded on nHA/CG scaffolds with 2 shapes (rod and sphere) of nHA particles. Firstly, hGFs isolated from discarded normal gingival tissues were reprogrammed into hiPSCs. Secondly, hiPSCs were seeded on rod-like nHA/CG (rod-nHA/CG) and sphere-shaped nHA/CG (sphere-nHA/CG) scaffolds respectively and then cell/scaffold complexes were cultured in vitro. Scanning electron microscope, hematoxyline and eosin (HE) staining, Masson's staining, and quantitative real-time polymerase chain reaction techniques were used to examine hiPSC morphology, proliferation, and differentiation on rod-nHA/CG and sphere-nHA/CG scaffolds. Finally, hiPSCs composited with 2 kinds of nHA/CG were transplanted in vivo in a subcutaneous implantation model for 12 weeks; pure scaffolds were also transplanted as a blank control. HE, Masson's, and immunohistochemistry staining were applied to detect new bone regeneration ability. The results showed that sphere-nHA/CG significantly increased hiPSCs from hGF proliferation and osteogenic differentiation in vitro. hiPSCs and sphere-nHA/CG composities generated large bone, whereas hiPSCs and rod-nHA/CG composities produced tiny bone in vivo. Moreover, pure scaffolds without cells almost produced no bone. In conclusion, our work provided a potential innovative bone tissue engineering approach using clinically discarded gingival tissues and sphere-nHA/CG scaffolds.

A Novel Corynebacterium glutamicum l-Glutamate Exporter.

PubMed

Wang, Yu; Cao, Guoqiang; Xu, Deyu; Fan, Liwen; Wu, Xinyang; Ni, Xiaomeng; Zhao, Shuxin; Zheng, Ping; Sun, Jibin; Ma, Yanhe

2018-03-15

Besides metabolic pathways and regulatory networks, transport systems are also pivotal for cellular metabolism and hyperproduction of biochemicals using microbial cell factories. The identification and characterization of transporters are therefore of great significance for the understanding and engineering of transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists extensively in Corynebacterium glutamicum strains but is distinct from the only known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate-producing C. glutamicum strain. MscCG2 was predicted to possess three transmembrane helices in the N-terminal region and located in the cytoplasmic membrane, which are typical structural characteristics of the mechanosensitive channel of small conductance. MscCG2 has a low amino acid sequence identity (23%) to MscCG and evolved separately from MscCG with four transmembrane helices. Despite the considerable differences between MscCG2 and MscCG in sequence and structure, gene deletion and complementation confirmed that MscCG2 also functioned as an l-glutamate exporter and an osmotic safety valve in C. glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes were transcribed in similar patterns and not induced by l-glutamate-producing conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion was activated by biotin limitation or penicillin treatment and that constitutive l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2 (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino acid transport and provide additional targets for exporter engineering. IMPORTANCE The exchange of matter, energy, and information with surroundings is fundamental for cellular metabolism. Therefore, studying transport systems that are essential for these processes is of great significance. Besides, transport systems of bacterial cells are usually related to product excretion as well as product reuptake, making transporter engineering a useful strategy for strain improvement. The significance of our research is in identifying and characterizing a novel l-glutamate exporter from the industrial workhorse Corynebacterium glutamicum , which will enrich the understanding of l-glutamate excretion and provide a new target for studying bacterial amino acid transport and engineering transport reactions. Copyright © 2018 American Society for Microbiology.

Longitudinal Changes in Active Bone Marrow for Cervical Cancer Patients Treated With Concurrent Chemoradiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noticewala, Sonal S.; Li, Nan; Williamson, Casey W.

Purpose: To quantify longitudinal changes in active bone marrow (ABM) distributions within unirradiated (extrapelvic) and irradiated (pelvic) bone marrow (BM) in cervical cancer patients treated with concurrent chemoradiation therapy (CRT). Methods and Materials: We sampled 39 cervical cancer patients treated with CRT, of whom 25 were treated with concurrent cisplatin (40 mg/m{sup 2}) and 14 were treated with cisplatin (40 mg/m{sup 2}) plus gemcitabine (50-125 mg/m{sup 2}) (C/G). Patients underwent {sup 18}F-fluorodeoxyglucose positron emission tomographic/computed tomographic imaging at baseline and 1.5 to 6.0 months after treatment. ABM was defined as the subvolume of bone with standardized uptake value (SUV) above the mean SUV ofmore » the total bone. The primary aim was to measure the compensatory response, defined as the change in the log of the ratio of extrapelvic versus pelvic ABM percentage from baseline to after treatment. We also quantified the change in the proportion of ABM and mean SUV in pelvic and extrapelvic BM using a 2-sided paired t test. Results: We observed a significant increase in the overall extrapelvic compensatory response after CRT (0.381; 95% confidence interval [CI]: 0.312, 0.449) and separately in patients treated with cisplatin (0.429; 95% CI: 0.340, 0.517) and C/G (0.294; 95% CI: 0.186, 0.402). We observed a trend toward higher compensatory response in patients treated with cisplatin compared with C/G (P=.057). Pelvic ABM percentage was reduced after CRT both in patients receiving cisplatin (P<.001) and in those receiving C/G (P<.001), whereas extrapelvic ABM percentage was increased in patients receiving cisplatin (P<.001) and C/G (P<.001). The mean SUV in pelvic structures was lower after CRT with both cisplatin (P<.001) and C/G (P<.001). The mean SUV appeared lower in extrapelvic structures after CRT in patients treated with C/G (P=.076) but not with cisplatin (P=.942). We also observed that older age and more intense chemotherapy regimens were correlated with a decreased compensatory response on multivariable analysis. In patients treated with C/G, mean pelvic bone marrow dose was found to be negatively correlated with the compensatory response. Conclusion: Patients have differing subacute compensatory responses after CRT, owing to variable recovery in unirradiated marrow. Intensive chemotherapy regimens appear to decrease the extrapelvic compensatory response, which may lead to increased hematologic toxicity.« less

5-Methylation of Cytosine in CG:CG Base-Pair Steps: A Physicochemical Mechanism for the Epigenetic Control of DNA Nanomechanics

NASA Astrophysics Data System (ADS)

Yusufaly, Tahir; Olson, Wilma; Li, Yun

2014-03-01

Van der Waals density functional theory is integrated with analysis of a non-redundant set of protein-DNA crystal structures from the Nucleic Acid Database to study the stacking energetics of CG:CG base-pair steps, specifically the role of cytosine 5-methylation. Principal component analysis of the steps reveals the dominant collective motions to correspond to a tensile ``opening'' mode and two shear ``sliding'' and ``tearing'' modes in the orthogonal plane. The stacking interactions of the methyl groups are observed to globally inhibit CG:CG step overtwisting while simultaneously softening the modes locally via potential energy modulations that create metastable states. The results have implications for the epigenetic control of DNA mechanics.

Significance of pregnancy test false negative results due to elevated levels of β-core fragment hCG.

PubMed

Johnson, Sarah; Eapen, Saji; Smith, Peter; Warren, Graham; Zinaman, Michael

2017-01-01

Very high levels of β-core fragment human chorionic gonadotrophin (βcf-hCG) are reported to potentially cause false negative results in point-of-care (POC)/over-the-counter (OTC) pregnancy tests. To investigate this further, women's daily early morning urine samples, collected prior to conception and during pregnancy, were analysed for intact, free β-, and βcf-hCG. The proportion of βcf-hCG was found to be related to that of hCG produced and in circulation. Therefore, best practice for accuracy testing of POC/OTC pregnancy tests would be to test devices against clinical samples containing high levels of βcf-hCG as well as standards spiked with biologically relevant ratios.

Heterogeneous hCG and hMG commercial preparations result in different intracellular signalling but induce a similar long-term progesterone response in vitro.

PubMed

Riccetti, Laura; Klett, Danièle; Ayoub, Mohammed Akli; Boulo, Thomas; Pignatti, Elisa; Tagliavini, Simonetta; Varani, Manuela; Trenti, Tommaso; Nicoli, Alessia; Capodanno, Francesco; La Sala, Giovanni Battista; Reiter, Eric; Simoni, Manuela; Casarini, Livio

2017-10-01

Are four urinary hCG/menotropin (hMG) and one recombinant preparation characterized by different molecular features and do they mediate specific intracellular signaling and steroidogenesis? hCG and hMG preparations have heterogeneous compositions and mediate preparation-specific cell signaling and early steroidogenesis, although similar progesterone plateau levels are achieved in 24 h-treated human primary granulosa cells in vitro. hCG is the pregnancy hormone marketed as a drug for ARTs to induce final oocyte maturation and ovulation, and to support FSH action. Several hCG formulations are commercially available, differing in source, purification methods and biochemical composition. Commercial hCG preparations for ART or research purposes were compared in vitro. The different preparations were quantified by immunoassay with calibration against the hCG standard (Fifth IS; NIBSC 07/364). Immunoreactivity patterns, isoelectric points and oligosaccharide contents of hCGs were evaluated using reducing and non-reducing Western blotting, capillary isoelectric-focusing immunoassay and lectin-ELISA, respectively. Functional studies were performed in order to evaluate intracellular and total cAMP, progesterone production and β-arrestin 2 recruitment by ELISA and BRET, in both human primary granulosa lutein cells (hGLC) and luteinizing hormone (LH)/hCG receptor (LHCGR)-transfected HEK293 cells, stimulated by increasing hormone concentrations. Statistical analysis was performed using two-way ANOVA and Bonferroni post-test or Mann-Whitney's U-test as appropriate. Heterogeneous profiles were found among preparations, revealing specific molecular weight patterns (20-75 KDa range), isoelectric points (4.0-9.0 pI range) and lectin binding (P < 0.05; n = 7-10). These drug-specific compositions were linked to different potencies on cAMP production (EC50 1.0-400.0 ng/ml range) and β-arrestin 2 recruitment (EC50 0.03-2.0 μg/ml) in hGLC and transfected HEK293 cells (P < 0.05; n = 3-5). In hGLC, these differences were reflected by preparation-specific 8-h progesterone production although similar plateau levels of progesterone were acheived by 24-h treatment (P ≥ 0.05; n = 3). N/A. The biological activity of commercial hCG/hMG preparations is provided in International Units (IU) by in-vivo bioassay and calibration against an International Standard, although it is an unsuitable unit of measure for in-vitro studies. The re-calibration against recombinant hCG,quantified in grams, is based on the assumption that all of the isoforms and glycosylation variants have similar immunoreactivity. hCG/hMG preparation-specific cell responses in vitro may be proposed to ART patients affected by peculiar ovarian response, such as that caused by polycystic ovary syndrome. Otherwise, all the preparations available for ART may provide a similar clinical outcome in healthy women. This study was supported by a grant of the Italian Ministry of Education, University and Research (PRIN 2015XCR88M). The authors have no conflict of interest. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Numerical modeling of an enhanced very early time electromagnetic (VETEM) prototype system

USGS Publications Warehouse

Cui, T.J.; Chew, W.C.; Aydiner, A.A.; Wright, D.L.; Smith, D.V.; Abraham, J.D.

2000-01-01

In this paper, two numerical models are presented to simulate an enhanced very early time electromagnetic (VETEM) prototype system, which is used for buried-object detection and environmental problems. Usually, the VETEM system contains a transmitting loop antenna and a receiving loop antenna, which run on a lossy ground to detect buried objects. In the first numerical model, the loop antennas are accurately analyzed using the Method of Moments (MoM) for wire antennas above or buried in lossy ground. Then, Conjugate Gradient (CG) methods, with the use of the fast Fourier transform (FFT) or MoM, are applied to investigate the scattering from buried objects. Reflected and scattered magnetic fields are evaluated at the receiving loop to calculate the output electric current. However, the working frequency for the VETEM system is usually low and, hence, two magnetic dipoles are used to replace the transmitter and receiver in the second numerical model. Comparing these two models, the second one is simple, but only valid for low frequency or small loops, while the first modeling is more general. In this paper, all computations are performed in the frequency domain, and the FFT is used to obtain the time-domain responses. Numerical examples show that simulation results from these two models fit very well when the frequency ranges from 10 kHz to 10 MHz, and both results are close to the measured data.

Simultaneous analysis and design

NASA Technical Reports Server (NTRS)

Haftka, R. T.

1984-01-01

Optimization techniques are increasingly being used for performing nonlinear structural analysis. The development of element by element (EBE) preconditioned conjugate gradient (CG) techniques is expected to extend this trend to linear analysis. Under these circumstances the structural design problem can be viewed as a nested optimization problem. There are computational benefits to treating this nested problem as a large single optimization problem. The response variables (such as displacements) and the structural parameters are all treated as design variables in a unified formulation which performs simultaneously the design and analysis. Two examples are used for demonstration. A seventy-two bar truss is optimized subject to linear stress constraints and a wing box structure is optimized subject to nonlinear collapse constraints. Both examples show substantial computational savings with the unified approach as compared to the traditional nested approach.

High-throughput engineering of a mammalian genome reveals building principles of methylation states at CG rich regions.

PubMed

Krebs, Arnaud R; Dessus-Babus, Sophie; Burger, Lukas; Schübeler, Dirk

2014-09-26

The majority of mammalian promoters are CpG islands; regions of high CG density that require protection from DNA methylation to be functional. Importantly, how sequence architecture mediates this unmethylated state remains unclear. To address this question in a comprehensive manner, we developed a method to interrogate methylation states of hundreds of sequence variants inserted at the same genomic site in mouse embryonic stem cells. Using this assay, we were able to quantify the contribution of various sequence motifs towards the resulting DNA methylation state. Modeling of this comprehensive dataset revealed that CG density alone is a minor determinant of their unmethylated state. Instead, these data argue for a principal role for transcription factor binding sites, a prediction confirmed by testing synthetic mutant libraries. Taken together, these findings establish the hierarchy between the two cis-encoded mechanisms that define the DNA methylation state and thus the transcriptional competence of CpG islands.

The Effect of Response Scale, Administration Mode, and Format on Responses to the CAHPS Clinician and Group Survey

PubMed Central

Drake, Keith M; Hargraves, J Lee; Lloyd, Stephanie; Gallagher, Patricia M; Cleary, Paul D

2014-01-01

Objective To examine how different response scales, methods of survey administration, and survey format affect responses to the CAHPS (Consumer Assessment of Healthcare Providers and Systems) Clinician and Group (CG-CAHPS) survey. Study Design A total of 6,500 patients from a university health center were randomly assigned to receive the following: standard 12-page mail surveys using 4-category or 6-category response scales (on CG-CAHPS composite items), telephone surveys using 4-category or 6-category response scales, or four-page mail surveys. Principal Findings A total of 3,538 patients completed surveys. Composite score means and provider-level reliabilities did not differ between respondents receiving 4-category or 6-category response scale surveys or between 12-page and four-page mail surveys. Telephone respondents gave more positive responses than mail respondents. Conclusions We recommend using 4-category response scales and the four-page mail CG-CAHPS survey. PMID:24471975