A projected preconditioned conjugate gradient algorithm for computing many extreme eigenpairs of a Hermitian matrix [A projected preconditioned conjugate gradient algorithm for computing a large eigenspace of a Hermitian matrix

DOE PAGES

Vecharynski, Eugene; Yang, Chao; Pask, John E.

2015-02-25

Here, we present an iterative algorithm for computing an invariant subspace associated with the algebraically smallest eigenvalues of a large sparse or structured Hermitian matrix A. We are interested in the case in which the dimension of the invariant subspace is large (e.g., over several hundreds or thousands) even though it may still be small relative to the dimension of A. These problems arise from, for example, density functional theory (DFT) based electronic structure calculations for complex materials. The key feature of our algorithm is that it performs fewer Rayleigh–Ritz calculations compared to existing algorithms such as the locally optimalmore » block preconditioned conjugate gradient or the Davidson algorithm. It is a block algorithm, and hence can take advantage of efficient BLAS3 operations and be implemented with multiple levels of concurrency. We discuss a number of practical issues that must be addressed in order to implement the algorithm efficiently on a high performance computer.« less

A Robust Locally Preconditioned Semi-Coarsening Multigrid Algorithm for the 2-D Navier-Stokes Equations

NASA Technical Reports Server (NTRS)

Cain, Michael D.

1999-01-01

The goal of this thesis is to develop an efficient and robust locally preconditioned semi-coarsening multigrid algorithm for the two-dimensional Navier-Stokes equations. This thesis examines the performance of the multigrid algorithm with local preconditioning for an upwind-discretization of the Navier-Stokes equations. A block Jacobi iterative scheme is used because of its high frequency error mode damping ability. At low Mach numbers, the performance of a flux preconditioner is investigated. The flux preconditioner utilizes a new limiting technique based on local information that was developed by Siu. Full-coarsening and-semi-coarsening are examined as well as the multigrid V-cycle and full multigrid. The numerical tests were performed on a NACA 0012 airfoil at a range of Mach numbers. The tests show that semi-coarsening with flux preconditioning is the most efficient and robust combination of coarsening strategy, and iterative scheme - especially at low Mach numbers.

Accelerating nuclear configuration interaction calculations through a preconditioned block iterative eigensolver

DOE PAGES

Shao, Meiyue; Aktulga, H.  Metin; Yang, Chao; ...

2017-09-14

In this paper, we describe a number of recently developed techniques for improving the performance of large-scale nuclear configuration interaction calculations on high performance parallel computers. We show the benefit of using a preconditioned block iterative method to replace the Lanczos algorithm that has traditionally been used to perform this type of computation. The rapid convergence of the block iterative method is achieved by a proper choice of starting guesses of the eigenvectors and the construction of an effective preconditioner. These acceleration techniques take advantage of special structure of the nuclear configuration interaction problem which we discuss in detail. Themore » use of a block method also allows us to improve the concurrency of the computation, and take advantage of the memory hierarchy of modern microprocessors to increase the arithmetic intensity of the computation relative to data movement. Finally, we also discuss the implementation details that are critical to achieving high performance on massively parallel multi-core supercomputers, and demonstrate that the new block iterative solver is two to three times faster than the Lanczos based algorithm for problems of moderate sizes on a Cray XC30 system.« less

Accelerating nuclear configuration interaction calculations through a preconditioned block iterative eigensolver

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

Shao, Meiyue; Aktulga, H.  Metin; Yang, Chao

In this paper, we describe a number of recently developed techniques for improving the performance of large-scale nuclear configuration interaction calculations on high performance parallel computers. We show the benefit of using a preconditioned block iterative method to replace the Lanczos algorithm that has traditionally been used to perform this type of computation. The rapid convergence of the block iterative method is achieved by a proper choice of starting guesses of the eigenvectors and the construction of an effective preconditioner. These acceleration techniques take advantage of special structure of the nuclear configuration interaction problem which we discuss in detail. Themore » use of a block method also allows us to improve the concurrency of the computation, and take advantage of the memory hierarchy of modern microprocessors to increase the arithmetic intensity of the computation relative to data movement. Finally, we also discuss the implementation details that are critical to achieving high performance on massively parallel multi-core supercomputers, and demonstrate that the new block iterative solver is two to three times faster than the Lanczos based algorithm for problems of moderate sizes on a Cray XC30 system.« less

Block Preconditioning to Enable Physics-Compatible Implicit Multifluid Plasma Simulations

NASA Astrophysics Data System (ADS)

Phillips, Edward; Shadid, John; Cyr, Eric; Miller, Sean

2017-10-01

Multifluid plasma simulations involve large systems of partial differential equations in which many time-scales ranging over many orders of magnitude arise. Since the fastest of these time-scales may set a restrictively small time-step limit for explicit methods, the use of implicit or implicit-explicit time integrators can be more tractable for obtaining dynamics at time-scales of interest. Furthermore, to enforce properties such as charge conservation and divergence-free magnetic field, mixed discretizations using volume, nodal, edge-based, and face-based degrees of freedom are often employed in some form. Together with the presence of stiff modes due to integrating over fast time-scales, the mixed discretization makes the required linear solves for implicit methods particularly difficult for black box and monolithic solvers. This work presents a block preconditioning strategy for multifluid plasma systems that segregates the linear system based on discretization type and approximates off-diagonal coupling in block diagonal Schur complement operators. By employing multilevel methods for the block diagonal subsolves, this strategy yields algorithmic and parallel scalability which we demonstrate on a range of problems.

The role of 17-beta estradiol in ischemic preconditioning protection of the heart.

PubMed

Babiker, Fawzi A; Hoteit, Lamia J; Joseph, Shaji; Mustafa, Abu Salim; Juggi, Jasbir S

2012-09-01

The protective effects of 17-beta estradiol (E2) on cardiac tissue during ischemia/reperfusion (I/R) injury have not yet been fully elucidated. To assess the protective effects of short- and long-term E2 treatments on cardiac tissue exposed to I/R, and to assess the effects of these treatments in combination with ischemic preconditioning (IPC) on cardiac protection from I/R injury. SPRAGUE DAWLEY RATS WERE ASSIGNED TO THE FOLLOWING TREATMENT PROTOCOLS: control (no preconditioning); IPC (isolated hearts were subjected to two cycles of 5 min global ischemia followed by 10 min of reperfusion); E2 preconditioning (E2PC; isolated hearts were subjected to E2 pharmacological perfusion for 15 min); short-term in vivo E2 pretreatment for 3 h; long-term in vivo E2 pretreatment or withdrawal (ovariectomy followed by a six-week treatment with E2 or a placebo); combined IPC and E2PC; combined IPC and short- or long-term E2 pretreatments or withdrawal. All hearts were isolated and stabilized for at least 30 min before being subjected to 40 min of global ischemia followed by 30 min of reperfusion; left ventricular function and vascular hemodynamics were then assessed. IPC, E2PC and short-term E2 pretreatment led to the recovery of left ventricle function and vascular hemodynamics. Long-term E2 and placebo treatments did not result in any protection compared with untreated controls. The combination of E2PC or short-term E2 treatments with IPC did not block the IPC protection or result in any additional protection to the heart. Long-term E2 treatment blocked IPC protection; however, placebo treatment did not. Short-term treatment with E2 protected the heart against I/R injury through a pathway involving the regulation of tumour necrosis factor-alpha. The combination of short-term E2 treatment with IPC did not provide additional protection to the heart. Short-term E2 treatment may be a suitable alternative for classical estrogen replacement therapy.

Generalized Preconditioned Locally Harmonic Residual Eigensolver (GPLHR) v0.1

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

VECHARYNSKI, EUGENE; YANG, CHAO

The software contains a MATLAB implementation of the Generalized Preconditioned Locally Harmonic Residual (GPLHR) method for solving standard and generalized non-Hermitian eigenproblems. The method is particularly useful for computing a subset of eigenvalues, and their eigen- or Schur vectors, closest to a given shift. The proposed method is based on block iterations and can take advantage of a preconditioner if it is available. It does not need to perform exact shift-and-invert transformation. Standard and generalized eigenproblems are handled in a unified framework.

47 CFR 27.1315 - Establishment, execution, and application of the network sharing agreement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the NSA: (a) Approval of NSA as pre-condition for granting the Upper 700 MHz D Block License. The... Block license has negotiated the NSA and such other agreements as the Commission may require or allow with the Public Safety Broadband Licensee, and the NSA and related agreements or documents have been...

47 CFR 90.1415 - Establishment, execution, and application of the network sharing agreement.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the NSA: (a) Approval of NSA as pre-condition for granting the Upper 700 MHz D Block License. The Public Safety Broadband Licensee must negotiate an NSA and such other agreements as the Commission may require or allow with the winning bidder for the Upper 700 MHz D Block license. The NSA and related...

Efficient block preconditioned eigensolvers for linear response time-dependent density functional theory

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

Vecharynski, Eugene; Brabec, Jiri; Shao, Meiyue

Within this paper, we present two efficient iterative algorithms for solving the linear response eigenvalue problem arising from the time dependent density functional theory. Although the matrix to be diagonalized is nonsymmetric, it has a special structure that can be exploited to save both memory and floating point operations. In particular, the nonsymmetric eigenvalue problem can be transformed into an eigenvalue problem that involves the product of two matrices M and K. We show that, because MK is self-adjoint with respect to the inner product induced by the matrix K, this product eigenvalue problem can be solved efficiently by amore » modified Davidson algorithm and a modified locally optimal block preconditioned conjugate gradient (LOBPCG) algorithm that make use of the K-inner product. Additionally, the solution of the product eigenvalue problem yields one component of the eigenvector associated with the original eigenvalue problem. We show that the other component of the eigenvector can be easily recovered in an inexpensive postprocessing procedure. As a result, the algorithms we present here become more efficient than existing methods that try to approximate both components of the eigenvectors simultaneously. In particular, our numerical experiments demonstrate that the new algorithms presented here consistently outperform the existing state-of-the-art Davidson type solvers by a factor of two in both solution time and storage.« less

Efficient block preconditioned eigensolvers for linear response time-dependent density functional theory

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

Vecharynski, Eugene; Brabec, Jiri; Shao, Meiyue

In this article, we present two efficient iterative algorithms for solving the linear response eigenvalue problem arising from the time dependent density functional theory. Although the matrix to be diagonalized is nonsymmetric, it has a special structure that can be exploited to save both memory and floating point operations. In particular, the nonsymmetric eigenvalue problem can be transformed into an eigenvalue problem that involves the product of two matrices M and K. We show that, because MK is self-adjoint with respect to the inner product induced by the matrix K, this product eigenvalue problem can be solved efficiently by amore » modified Davidson algorithm and a modified locally optimal block preconditioned conjugate gradient (LOBPCG) algorithm that make use of the K-inner product. The solution of the product eigenvalue problem yields one component of the eigenvector associated with the original eigenvalue problem. We show that the other component of the eigenvector can be easily recovered in an inexpensive postprocessing procedure. As a result, the algorithms we present here become more efficient than existing methods that try to approximate both components of the eigenvectors simultaneously. In particular, our numerical experiments demonstrate that the new algorithms presented here consistently outperform the existing state-of-the-art Davidson type solvers by a factor of two in both solution time and storage.« less

Efficient block preconditioned eigensolvers for linear response time-dependent density functional theory

DOE PAGES

Vecharynski, Eugene; Brabec, Jiri; Shao, Meiyue; ...

2017-12-01

In this article, we present two efficient iterative algorithms for solving the linear response eigenvalue problem arising from the time dependent density functional theory. Although the matrix to be diagonalized is nonsymmetric, it has a special structure that can be exploited to save both memory and floating point operations. In particular, the nonsymmetric eigenvalue problem can be transformed into an eigenvalue problem that involves the product of two matrices M and K. We show that, because MK is self-adjoint with respect to the inner product induced by the matrix K, this product eigenvalue problem can be solved efficiently by amore » modified Davidson algorithm and a modified locally optimal block preconditioned conjugate gradient (LOBPCG) algorithm that make use of the K-inner product. The solution of the product eigenvalue problem yields one component of the eigenvector associated with the original eigenvalue problem. We show that the other component of the eigenvector can be easily recovered in an inexpensive postprocessing procedure. As a result, the algorithms we present here become more efficient than existing methods that try to approximate both components of the eigenvectors simultaneously. In particular, our numerical experiments demonstrate that the new algorithms presented here consistently outperform the existing state-of-the-art Davidson type solvers by a factor of two in both solution time and storage.« less

Efficient block preconditioned eigensolvers for linear response time-dependent density functional theory

DOE PAGES

Vecharynski, Eugene; Brabec, Jiri; Shao, Meiyue; ...

2017-08-24

Within this paper, we present two efficient iterative algorithms for solving the linear response eigenvalue problem arising from the time dependent density functional theory. Although the matrix to be diagonalized is nonsymmetric, it has a special structure that can be exploited to save both memory and floating point operations. In particular, the nonsymmetric eigenvalue problem can be transformed into an eigenvalue problem that involves the product of two matrices M and K. We show that, because MK is self-adjoint with respect to the inner product induced by the matrix K, this product eigenvalue problem can be solved efficiently by amore » modified Davidson algorithm and a modified locally optimal block preconditioned conjugate gradient (LOBPCG) algorithm that make use of the K-inner product. Additionally, the solution of the product eigenvalue problem yields one component of the eigenvector associated with the original eigenvalue problem. We show that the other component of the eigenvector can be easily recovered in an inexpensive postprocessing procedure. As a result, the algorithms we present here become more efficient than existing methods that try to approximate both components of the eigenvectors simultaneously. In particular, our numerical experiments demonstrate that the new algorithms presented here consistently outperform the existing state-of-the-art Davidson type solvers by a factor of two in both solution time and storage.« less

Bundle block adjustment of large-scale remote sensing data with Block-based Sparse Matrix Compression combined with Preconditioned Conjugate Gradient

NASA Astrophysics Data System (ADS)

Zheng, Maoteng; Zhang, Yongjun; Zhou, Shunping; Zhu, Junfeng; Xiong, Xiaodong

2016-07-01

In recent years, new platforms and sensors in photogrammetry, remote sensing and computer vision areas have become available, such as Unmanned Aircraft Vehicles (UAV), oblique camera systems, common digital cameras and even mobile phone cameras. Images collected by all these kinds of sensors could be used as remote sensing data sources. These sensors can obtain large-scale remote sensing data which consist of a great number of images. Bundle block adjustment of large-scale data with conventional algorithm is very time and space (memory) consuming due to the super large normal matrix arising from large-scale data. In this paper, an efficient Block-based Sparse Matrix Compression (BSMC) method combined with the Preconditioned Conjugate Gradient (PCG) algorithm is chosen to develop a stable and efficient bundle block adjustment system in order to deal with the large-scale remote sensing data. The main contribution of this work is the BSMC-based PCG algorithm which is more efficient in time and memory than the traditional algorithm without compromising the accuracy. Totally 8 datasets of real data are used to test our proposed method. Preliminary results have shown that the BSMC method can efficiently decrease the time and memory requirement of large-scale data.

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy.

PubMed

Oses, Carolina; Olivares, Belén; Ezquer, Marcelo; Acosta, Cristian; Bosch, Paul; Donoso, Macarena; Léniz, Patricio; Ezquer, Fernando

2017-01-01

Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment.

Preconditioning of adipose tissue-derived mesenchymal stem cells with deferoxamine increases the production of pro-angiogenic, neuroprotective and anti-inflammatory factors: Potential application in the treatment of diabetic neuropathy

PubMed Central

Oses, Carolina; Olivares, Belén; Ezquer, Marcelo; Acosta, Cristian; Bosch, Paul; Donoso, Macarena; Léniz, Patricio

2017-01-01

Diabetic neuropathy (DN) is one of the most frequent and troublesome complications of diabetes mellitus. Evidence from diabetic animal models and diabetic patients suggests that reduced availability of neuroprotective and pro-angiogenic factors in the nerves in combination with a chronic pro-inflammatory microenvironment and high level of oxidative stress, contribute to the pathogenesis of DN. Mesenchymal stem cells (MSCs) are of great interest as therapeutic agents for regenerative purposes, since they can secrete a broad range of cytoprotective and anti-inflammatory factors. Therefore, the use of the MSC secretome may represent a promising approach for DN treatment. Recent data indicate that the paracrine potential of MSCs could be boosted by preconditioning these cells with an environmental or pharmacological stimulus, enhancing their therapeutic efficacy. In the present study, we observed that the preconditioning of human adipose tissue-derived MSCs (AD-MSCs) with 150μM or 400μM of the iron chelator deferoxamine (DFX) for 48 hours, increased the abundance of the hypoxia inducible factor 1 alpha (HIF-1α) in a concentration dependent manner, without affecting MSC morphology and survival. Activation of HIF-1α led to the up-regulation of the mRNA levels of pro-angiogenic factors like vascular endothelial growth factor alpha and angiopoietin 1. Furthermore this preconditioning increased the expression of potent neuroprotective factors, including nerve growth factor, glial cell-derived neurotrophic factor and neurotrophin-3, and cytokines with anti-inflammatory activity like IL4 and IL5. Additionally, we observed that these molecules, which could also be used as therapeutics, were also increased in the secretome of MSCs preconditioned with DFX compared to the secretome obtained from non-preconditioned cells. Moreover, DFX preconditioning significantly increased the total antioxidant capacity of the MSC secretome and they showed neuroprotective effects when evaluated in an in vitro model of DN. Altogether, our findings suggest that DFX preconditioning of AD-MSCs improves their therapeutic potential and should be considered as a potential strategy for the generation of new alternatives for DN treatment. PMID:28542352

A scalable block-preconditioning strategy for divergence-conforming B-spline discretizations of the Stokes problem

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

Cortes, Adriano M.; Dalcin, Lisandro; Sarmiento, Adel F.

The recently introduced divergence-conforming B-spline discretizations allow the construction of smooth discrete velocity–pressure pairs for viscous incompressible flows that are at the same time inf–sup stable and pointwise divergence-free. When applied to the discretized Stokes problem, these spaces generate a symmetric and indefinite saddle-point linear system. The iterative method of choice to solve such system is the Generalized Minimum Residual Method. This method lacks robustness, and one remedy is to use preconditioners. For linear systems of saddle-point type, a large family of preconditioners can be obtained by using a block factorization of the system. In this paper, we show howmore » the nesting of “black-box” solvers and preconditioners can be put together in a block triangular strategy to build a scalable block preconditioner for the Stokes system discretized by divergence-conforming B-splines. Lastly, besides the known cavity flow problem, we used for benchmark flows defined on complex geometries: an eccentric annulus and hollow torus of an eccentric annular cross-section.« less

A scalable block-preconditioning strategy for divergence-conforming B-spline discretizations of the Stokes problem

DOE PAGES

Cortes, Adriano M.; Dalcin, Lisandro; Sarmiento, Adel F.; ...

2016-10-19

The recently introduced divergence-conforming B-spline discretizations allow the construction of smooth discrete velocity–pressure pairs for viscous incompressible flows that are at the same time inf–sup stable and pointwise divergence-free. When applied to the discretized Stokes problem, these spaces generate a symmetric and indefinite saddle-point linear system. The iterative method of choice to solve such system is the Generalized Minimum Residual Method. This method lacks robustness, and one remedy is to use preconditioners. For linear systems of saddle-point type, a large family of preconditioners can be obtained by using a block factorization of the system. In this paper, we show howmore » the nesting of “black-box” solvers and preconditioners can be put together in a block triangular strategy to build a scalable block preconditioner for the Stokes system discretized by divergence-conforming B-splines. Lastly, besides the known cavity flow problem, we used for benchmark flows defined on complex geometries: an eccentric annulus and hollow torus of an eccentric annular cross-section.« less

TRPV1 Agonist, Capsaicin, Induces Axon Outgrowth after Injury via Ca2+/PKA Signaling.

PubMed

Frey, Erin; Karney-Grobe, Scott; Krolak, Trevor; Milbrandt, Jeff; DiAntonio, Aaron

2018-01-01

Preconditioning nerve injuries activate a pro-regenerative program that enhances axon regeneration for most classes of sensory neurons. However, nociceptive sensory neurons and central nervous system neurons regenerate poorly. In hopes of identifying novel mechanisms that promote regeneration, we screened for drugs that mimicked the preconditioning response and identified a nociceptive ligand that activates a preconditioning-like response to promote axon outgrowth. We show that activating the ion channel TRPV1 with capsaicin induces axon outgrowth of cultured dorsal root ganglion (DRG) sensory neurons, and that this effect is blocked in TRPV1 knockout neurons. Regeneration occurs only in NF200-negative nociceptive neurons, consistent with a cell-autonomous mechanism. Moreover, we identify a signaling pathway in which TRPV1 activation leads to calcium influx and protein kinase A (PKA) activation to induce a preconditioning-like response. Finally, capsaicin administration to the mouse sciatic nerve activates a similar preconditioning-like response and induces enhanced axonal outgrowth, indicating that this pathway can be induced in vivo . These findings highlight the use of local ligands to induce regeneration and suggest that it may be possible to target selective neuronal populations for repair, including cell types that often fail to regenerate.

Feature Clustering for Accelerating Parallel Coordinate Descent

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

Scherrer, Chad; Tewari, Ambuj; Halappanavar, Mahantesh

2012-12-06

We demonstrate an approach for accelerating calculation of the regularization path for L1 sparse logistic regression problems. We show the benefit of feature clustering as a preconditioning step for parallel block-greedy coordinate descent algorithms.

Morphine Preconditioning Downregulates MicroRNA-134 Expression Against Oxygen-Glucose Deprivation Injuries in Cultured Neurons of Mice.

PubMed

Meng, Fanjun; Li, Yan; Chi, Wenying; Li, Junfa

2016-07-01

Brain protection by narcotics such as morphine is clinically relevant due to the extensive use of narcotics in the perioperative period. Morphine preconditioning induces neuroprotection in neurons, but it remains uncertain whether microRNA-134 (miR-134) is involved in morphine preconditioning against oxygen-glucose deprivation-induced injuries in primary cortical neurons of mice. The present study examined this issue. After cortical neurons of mice were cultured in vitro for 6 days, the neurons were transfected by respective virus vector, such as lentiviral vector (LV)-miR-control-GFP, LV-pre-miR-134-GFP, LV-pre-miR-134-inhibitor-GFP for 24 hours; after being normally cultured for 3 days again, morphine preconditioning was performed by incubating the transfected primary neurons with morphine (3 μM) for 1 hour, and then neuronal cells were exposed to oxygen-glucose deprivation (OGD) for 1 hour and oxygen-glucose recovery for 12 hours. The neuronal cells survival rate and the amount of apoptotic neurons were determined by MTT assay or TUNEL staining at designated time; and the expression levels of miR-134 were detected using real-time reverse transcription polymerase chain reaction at the same time. The neuronal cell survival rate was significantly higher, and the amount of apoptotic neurons was significantly decreased in neurons preconditioned with morphine before OGD than that of OGD alone. The neuroprotection induced by morphine preconditioning was partially blocked by upregulating miR-134 expression, and was enhanced by downregulating miR-134 expression. The expression of miR-134 was significantly decreased in morphine-preconditioned neurons alone without transfection. By downregulating miR-134 expression, morphine preconditioning protects primary cortical neurons of mice against injuries induced by OGD.

Implicit solvers for unstructured meshes

NASA Technical Reports Server (NTRS)

Venkatakrishnan, V.; Mavriplis, Dimitri J.

1991-01-01

Implicit methods were developed and tested for unstructured mesh computations. The approximate system which arises from the Newton linearization of the nonlinear evolution operator is solved by using the preconditioned GMRES (Generalized Minimum Residual) technique. Three different preconditioners were studied, namely, the incomplete LU factorization (ILU), block diagonal factorization, and the symmetric successive over relaxation (SSOR). The preconditioners were optimized to have good vectorization properties. SSOR and ILU were also studied as iterative schemes. The various methods are compared over a wide range of problems. Ordering of the unknowns, which affects the convergence of these sparse matrix iterative methods, is also studied. Results are presented for inviscid and turbulent viscous calculations on single and multielement airfoil configurations using globally and adaptively generated meshes.

Hypoxia preconditioning protection of corneal stromal cells requires HIF1alpha but not VEGF.

PubMed

Xing, Dongmei; Bonanno, Joseph A

2009-05-18

Hypoxia preconditioning protects corneal stromal cells from stress-induced death. This study determined whether the transcription factor HIF-1alpha (Hypoxia Inducible Factor) is responsible and whether this is promulgated by VEGF (Vascular Endothelial Growth Factor). Cultured bovine stromal cells were preconditioned with hypoxia in the presence of cadmium chloride, a chemical inhibitor of HIF-1alpha, and HIF-1alpha siRNA to test if HIF-1alpha activity is needed for hypoxia preconditioning protection from UV-irradiation induced cell death. TUNEL assay was used to detect cell apoptosis after UV-irradiation. RT-PCR and western blot were used to detect the presence of HIF-1alpha and VEGF in transcriptional and translational levels. During hypoxia (0.5% O2), 5 muM cadmium chloride completely inhibited HIF-1alpha expression and reversed the protection by hypoxia preconditioning. HIF-1alpha siRNA (15 nM) reduced HIF-1alpha expression by 90% and produced a complete loss of protection provided by hypoxia preconditioning. Since VEGF is induced by hypoxia, can be HIF-1alpha dependent, and is often protective, we examined the changes in transcription of VEGF and its receptors after 4 h of hypoxia preconditioning. VEGF and its receptors Flt-1 and Flk-1 are up-regulated after hypoxia preconditioning. However, the transcription and translation of VEGF were paradoxically increased by siHIF-1alpha, suggesting that VEGF expression in stromal cells is not down-stream of HIF-1alpha. These findings demonstrate that hypoxia preconditioning protection in corneal stromal cells requires HIF-1alpha, but that VEGF is not a component of the protection.

Preconditioned Mixed Spectral Element Methods for Elasticity and Stokes Problems

NASA Technical Reports Server (NTRS)

Pavarino, Luca F.

1996-01-01

Preconditioned iterative methods for the indefinite systems obtained by discretizing the linear elasticity and Stokes problems with mixed spectral elements in three dimensions are introduced and analyzed. The resulting stiffness matrices have the structure of saddle point problems with a penalty term, which is associated with the Poisson ratio for elasticity problems or with stabilization techniques for Stokes problems. The main results of this paper show that the convergence rate of the resulting algorithms is independent of the penalty parameter, the number of spectral elements Nu and mildly dependent on the spectral degree eta via the inf-sup constant. The preconditioners proposed for the whole indefinite system are block-diagonal and block-triangular. Numerical experiments presented in the final section show that these algorithms are a practical and efficient strategy for the iterative solution of the indefinite problems arising from mixed spectral element discretizations of elliptic systems.

A Note on Substructuring Preconditioning for Nonconforming Finite Element Approximations of Second Order Elliptic Problems

NASA Technical Reports Server (NTRS)

Maliassov, Serguei

1996-01-01

In this paper an algebraic substructuring preconditioner is considered for nonconforming finite element approximations of second order elliptic problems in 3D domains with a piecewise constant diffusion coefficient. Using a substructuring idea and a block Gauss elimination, part of the unknowns is eliminated and the Schur complement obtained is preconditioned by a spectrally equivalent very sparse matrix. In the case of quasiuniform tetrahedral mesh an appropriate algebraic multigrid solver can be used to solve the problem with this matrix. Explicit estimates of condition numbers and implementation algorithms are established for the constructed preconditioner. It is shown that the condition number of the preconditioned matrix does not depend on either the mesh step size or the jump of the coefficient. Finally, numerical experiments are presented to illustrate the theory being developed.

Pharmacological preconditioning by milrinone: memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice.

PubMed

Saklani, Reetu; Jaggi, Amteshwar; Singh, Nirmal

2010-07-01

We tested the neuroprotective effect of milrinone, a phosphodiesterase III inhibitor, in pharmacological preconditioning. Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h produced ischemia-reperfusion (I/R) cerebral injury in male Swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using the Morris water maze test, and motor coordination was evaluated using the inclined beam walking test, rota-rod test, and lateral push test. Milrinone (50 microg/kg & 100 microg/kg i.v.) was administered 24 h before surgery in a separate group of animals to induce pharmacological preconditioning. I/R increased cerebral infarct size and impaired memory and motor coordination. Milrinone treatment significantly decreased cerebral infarct size and reversed I/R-induced impairments in memory and motor coordination. This neuroprotective effect was blocked by ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker. These findings indicate that milrinone preconditioning exerts a marked neuroprotective effect on the ischemic brain, putatively due to increased intracellular calcium levels activating calcium-sensitive signal transduction cascades.

Factorizing the factorization - a spectral-element solver for elliptic equations with linear operation count

NASA Astrophysics Data System (ADS)

Huismann, Immo; Stiller, Jörg; Fröhlich, Jochen

2017-10-01

The paper proposes a novel factorization technique for static condensation of a spectral-element discretization matrix that yields a linear operation count of just 13N multiplications for the residual evaluation, where N is the total number of unknowns. In comparison to previous work it saves a factor larger than 3 and outpaces unfactored variants for all polynomial degrees. Using the new technique as a building block for a preconditioned conjugate gradient method yields linear scaling of the runtime with N which is demonstrated for polynomial degrees from 2 to 32. This makes the spectral-element method cost effective even for low polynomial degrees. Moreover, the dependence of the iterative solution on the element aspect ratio is addressed, showing only a slight increase in the number of iterations for aspect ratios up to 128. Hence, the solver is very robust for practical applications.

Mechanical preconditioning enables electrophysiologic coupling of skeletal myoblast cells to myocardium

PubMed Central

Treskes, Philipp; Cowan, Douglas B.; Stamm, Christof; Rubach, Martin; Adelmann, Roland; Wittwer, Thorsten; Wahlers, Thorsten

2015-01-01

Objective The effect of mechanical preconditioning on skeletal myoblasts in engineered tissue constructs was investigated to resolve issues associated with conduction block between skeletal myoblast cells and cardiomyocytes. Methods Murine skeletal myoblasts were used to generate engineered tissue constructs with or without application of mechanical strain. After in vitro myotube formation, engineered tissue constructs were co-cultured for 6 days with viable embryonic heart slices. With the use of sharp electrodes, electrical coupling between engineered tissue constructs and embryonic heart slices was assessed in the presence or absence of pharmacologic agents. Results The isolation and expansion procedure for skeletal myoblasts resulted in high yields of homogeneously desmin-positive (97.1% ± 0.1%) cells. Mechanical strain was exerted on myotubes within engineered tissue constructs during gelation of the matrix, generating preconditioned engineered tissue constructs. Electrical coupling between preconditioned engineered tissue constructs and embryonic heart slices was observed; however, no coupling was apparent when engineered tissue constructs were not subjected to mechanical strain. Coupling of cells from engineered tissue constructs to cells in embryonic heart slices showed slower conduction velocities than myocardial cells with the embryonic heart slices (preconditioned engineered tissue constructs vs embryonic heart slices: 0.04 ± 0.02 ms vs 0.10 ± 0.05 ms, P = .011), lower stimulation frequencies (preconditioned engineered tissue constructs vs maximum embryonic heart slices: 4.82 ± 1.42 Hz vs 10.58 ± 1.56 Hz; P = .0009), and higher sensitivities to the gap junction inhibitor (preconditioned engineered tissue constructs vs embryonic heart slices: 0.22 ± 0.07 mmol/L vs 0.93 ± 0.15 mmol/L; P = .0004). Conclusions We have generated skeletal myoblast–based transplantable grafts that electrically couple to myocardium. PMID:22980065

Hypoxic preconditioning protects photoreceptors against light damage independently of hypoxia inducible transcription factors in rods.

PubMed

Kast, Brigitte; Schori, Christian; Grimm, Christian

2016-05-01

Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kinetics Modeling of Hypergolic Propellants

DTIC Science & Technology

2013-07-01

comprehensive preconditioning and employs the line Gauss Seidel algorithm for the solution of the linear system. A multi-block unstructured mesh is...Explosives, Pyrotechnics, 33(3):209–212, 2008. 24Wei-Guang Liu, Shiqing Wang, Siddharth Dasgupta, Stefan T Thynell, William A Goddard III, Sergey Zybin

Design and Implementation of a CMOS Chip for a Prolog

DTIC Science & Technology

1988-03-01

generation scheme . We use the P -circuit [9] with pre-conditioning and post- conditioning 12,3] circuits to generate the carry. The implementation of...system generates vertical microcode for a general purpose processor, the NCR 9300 sys- S tem, from W- code [7]. Three significant pieces of software are...calculation block generating the pro- pagate ( P ) and generate (G) signals needed for carry calculation, and a sum block supplying the final result. The top

Effects of exercise preconditioning on intestinal ischemia-reperfusion injury.

PubMed

Gokbel, H; Oz, M; Okudan, N; Belviranli, M; Esen, H

2014-01-01

To investigate the effects of exercise preconditioning on oxidative injury in the intestinal tissue of rats. Sixty male Wistar rats were randomly divided into six groups as sham (n = 10), ischemia-reperfusion (n = 10), exercise (n = 10), exercise plus ischemia-reperfusion (n = 10), ischemic preconditioning (n = 10), and ischemic preconditioning plus ischemia-reperfusion groups (n = 10). Tissue levels of malondialdehyde and activities of myeloperoxidase and superoxide dismutase, and serum levels of tumor necrosis factor-alpha and interleukin-6 were measured. Intestinal tissue histopathology was also evaluated by light microscopy. Tumor necrosis factor-alpha concentrations significantly decreased in the exercise group compared to the sham group (p < 0.05). Myeloperoxidase activity significantly increased and superoxide dismutase activity significantly decreased in ischemia-reperfusion group compared to the sham group (p < 0.05). Superoxide dismutase activity in the ischemic preconditioning and ischemic preconditioning plus ischemia-reperfusion groups were significantly higher compared to the ischemia-reperfusion and exercise groups (p < 0.05). Histopathologically, intestinal injury significantly attenuated in the exercise plus ischemia-reperfusion group compared to the ischemia-reperfusion group. The results of the present study indicate that exercise training seems to have a protective role against intestinal ischemia-reperfusion injury (Tab. 3, Fig. 1, Ref. 35).

The role of hypoxia-inducible factor-1α and vascular endothelial growth factor in late-phase preconditioning with xenon, isoflurane and levosimendan in rat cardiomyocytes

PubMed Central

Goetzenich, Andreas; Hatam, Nima; Preuss, Stephanie; Moza, Ajay; Bleilevens, Christian; Roehl, Anna B.; Autschbach, Rüdiger; Bernhagen, Jürgen; Stoppe, Christian

2014-01-01

OBJECTIVES The protective effects of late-phase preconditioning can be triggered by several stimuli. Unfortunately, the transfer from bench to bedside still represents a challenge, as concomitant medication or diseases influence the complex signalling pathways involved. In an established model of primary neonatal rat cardiomyocytes, we analysed the cardioprotective effects of three different stimulating pharmaceuticals of clinical relevance. The effect of additional β-blocker treatment was studied as these were previously shown to negatively influence preconditioning. METHODS Twenty-four hours prior to hypoxia, cells pre-treated with or without metoprolol (0.55 µg/ml) were preconditioned with isoflurane, levosimendan or xenon. The influences of these stimuli on hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) as well as inducible and endothelial nitric synthase (iNOS/eNOS) and cyclooxygenase-2 (COX-2) were analysed by polymerase chain reaction and western blotting. The preconditioning was proved by trypan blue cell counts following 5 h of hypoxia and confirmed by fluorescence staining. RESULTS Five hours of hypoxia reduced cell survival in unpreconditioned control cells to 44 ± 4%. Surviving cell count was significantly higher in cells preconditioned either by 2 × 15 min isoflurane (70 ± 16%; P = 0.005) or by xenon (59 ± 8%; P = 0.049). Xenon-preconditioned cells showed a significantly elevated content of VEGF (0.025 ± 0.010 IDV [integrated density values when compared with GAPDH] vs 0.003 ± 0.006 IDV in controls; P = 0.0003). The protein expression of HIF-1α was increased both by levosimendan (0.563 ± 0.175 IDV vs 0.142 ± 0.042 IDV in controls; P = 0.0289) and by xenon (0.868 ± 0.222 IDV; P < 0.0001) pretreatment. A significant elevation of mRNA expression of iNOS was measureable following preconditioning by xenon but not by the other chosen stimuli. eNOS mRNA expression was found to be suppressed by β-blocker treatment for all stimuli. In our model, independently of the chosen stimulus, β-blocker treatment had no significant effect on cell survival. CONCLUSIONS We found that the stimulation of late-phase preconditioning involves several distinct pathways that are variably addressed by the different stimuli. In contrast to isoflurane treatment, xenon-induced preconditioning does not lead to an increase in COX-2 gene transcription but to a significant increase in HIF-1α and subsequently VEGF. PMID:24351506

The role of hypoxia-inducible factor-1α and vascular endothelial growth factor in late-phase preconditioning with xenon, isoflurane and levosimendan in rat cardiomyocytes.

PubMed

Goetzenich, Andreas; Hatam, Nima; Preuss, Stephanie; Moza, Ajay; Bleilevens, Christian; Roehl, Anna B; Autschbach, Rüdiger; Bernhagen, Jürgen; Stoppe, Christian

2014-03-01

The protective effects of late-phase preconditioning can be triggered by several stimuli. Unfortunately, the transfer from bench to bedside still represents a challenge, as concomitant medication or diseases influence the complex signalling pathways involved. In an established model of primary neonatal rat cardiomyocytes, we analysed the cardioprotective effects of three different stimulating pharmaceuticals of clinical relevance. The effect of additional β-blocker treatment was studied as these were previously shown to negatively influence preconditioning. Twenty-four hours prior to hypoxia, cells pre-treated with or without metoprolol (0.55 µg/ml) were preconditioned with isoflurane, levosimendan or xenon. The influences of these stimuli on hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) as well as inducible and endothelial nitric synthase (iNOS/eNOS) and cyclooxygenase-2 (COX-2) were analysed by polymerase chain reaction and western blotting. The preconditioning was proved by trypan blue cell counts following 5 h of hypoxia and confirmed by fluorescence staining. Five hours of hypoxia reduced cell survival in unpreconditioned control cells to 44 ± 4%. Surviving cell count was significantly higher in cells preconditioned either by 2 × 15 min isoflurane (70 ± 16%; P = 0.005) or by xenon (59 ± 8%; P = 0.049). Xenon-preconditioned cells showed a significantly elevated content of VEGF (0.025 ± 0.010 IDV [integrated density values when compared with GAPDH] vs 0.003 ± 0.006 IDV in controls; P = 0.0003). The protein expression of HIF-1α was increased both by levosimendan (0.563 ± 0.175 IDV vs 0.142 ± 0.042 IDV in controls; P = 0.0289) and by xenon (0.868 ± 0.222 IDV; P < 0.0001) pretreatment. A significant elevation of mRNA expression of iNOS was measureable following preconditioning by xenon but not by the other chosen stimuli. eNOS mRNA expression was found to be suppressed by β-blocker treatment for all stimuli. In our model, independently of the chosen stimulus, β-blocker treatment had no significant effect on cell survival. We found that the stimulation of late-phase preconditioning involves several distinct pathways that are variably addressed by the different stimuli. In contrast to isoflurane treatment, xenon-induced preconditioning does not lead to an increase in COX-2 gene transcription but to a significant increase in HIF-1α and subsequently VEGF.

Cardioprotective Effects of Transfusion of Late-Phase Preconditioned Plasma May Be Induced by Activating the Reperfusion Injury Salvage Kinase Pathway but Not the Survivor Activating Factor Enhancement Pathway in Rats.

PubMed

Zhao, Yang; Zheng, Zhi-Nan; Pi, Yan-Na; Liang, Xue; Jin, San-Qing

2017-01-01

A previous study in our laboratory demonstrated that transfusion of plasma collected at the late phase of remote ischemic preconditioning (RIPC) could reduce myocardial infarct size. Here, we tested whether the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways are involved in transferring protection. In a two-part study, donor rats ( n = 3) donated plasma 48 hours after RIPC (preconditioned plasma) or control (nonpreconditioned plasma). Normal (part 1) or ischemic (part 2) myocardia were collected from recipients ( n = 6) 24 hours after receiving normal saline, nonpreconditioned plasma, and preconditioned plasma or after further suffering ischemia reperfusion. Western blot was performed to analyze STAT3, Akt, and Erk1/2 phosphorylation in normal and ischemic myocardium (central area and border area). In normal myocardia, preconditioned plasma increased Akt and Erk1/2 phosphorylation significantly compared to nonpreconditioned plasma and normal saline; no STAT3 phosphorylation was detected. In ischemic myocardia, preconditioned plasma increased Akt and Erk1/2 phosphorylation significantly in both central and border areas compared to other fluids; no significant difference in STAT3 phosphorylation occurred among groups. Transfusion of preconditioned plasma collected at the late phase of RIPC could activate the RISK but not SAFE pathway, suggesting that RISK pathway may be involved in transferring protection.

Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.

PubMed

Joo, Jin Deok; Kim, Mihwa; D'Agati, Vivette D; Lee, H Thomas

2006-11-01

Acute as well as delayed ischemic preconditioning (IPC) provides protection against cardiac and neuronal ischemia reperfusion (IR) injury. This study determined whether delayed preconditioning occurs in the kidney and further elucidated the mechanisms of renal IPC in mice. Mice were subjected to IPC (four cycles of 5 min of ischemia and reperfusion) and then to 30 min of renal ischemia either 15 min (acute IPC) or 24 h (delayed IPC) later. Both acute and delayed renal IPC provided powerful protection against renal IR injury. Inhibition of Akt but not extracellular signal-regulated kinase phosphorylation prevented the protection that was afforded by acute IPC. Neither extracellular signal-regulated kinase nor Akt inhibition prevented protection that was afforded by delayed renal IPC. Pretreatment with an antioxidant, N-(2-mercaptopropionyl)-glycine, to scavenge free radicals prevented the protection that was provided by acute but not delayed renal IPC. Inhibition of protein kinase C or pertussis toxin-sensitive G-proteins attenuated protection from both acute and delayed renal IPC. Delayed renal IPC increased inducible nitric oxide synthase (iNOS) as well as heat-shock protein 27 synthesis, and the renal protective effects of delayed preconditioning were attenuated by a selective inhibitor of iNOS (l-N(6)[1-iminoethyl]lysine). Moreover, delayed IPC was not observed in iNOS knockout mice. Both acute and delayed IPC were independent of A(1) adenosine receptors (AR) as a selective A(1)AR antagonist failed to block preconditioning and acute and delayed preconditioning occurred in mice that lacked A(1)AR. Therefore, this study demonstrated that acute or delayed IPC provides renal protection against IR injury in mice but involves distinct signaling pathways.

Solving large test-day models by iteration on data and preconditioned conjugate gradient.

PubMed

Lidauer, M; Strandén, I; Mäntysaari, E A; Pösö, J; Kettunen, A

1999-12-01

A preconditioned conjugate gradient method was implemented into an iteration on a program for data estimation of breeding values, and its convergence characteristics were studied. An algorithm was used as a reference in which one fixed effect was solved by Gauss-Seidel method, and other effects were solved by a second-order Jacobi method. Implementation of the preconditioned conjugate gradient required storing four vectors (size equal to number of unknowns in the mixed model equations) in random access memory and reading the data at each round of iteration. The preconditioner comprised diagonal blocks of the coefficient matrix. Comparison of algorithms was based on solutions of mixed model equations obtained by a single-trait animal model and a single-trait, random regression test-day model. Data sets for both models used milk yield records of primiparous Finnish dairy cows. Animal model data comprised 665,629 lactation milk yields and random regression test-day model data of 6,732,765 test-day milk yields. Both models included pedigree information of 1,099,622 animals. The animal model ¿random regression test-day model¿ required 122 ¿305¿ rounds of iteration to converge with the reference algorithm, but only 88 ¿149¿ were required with the preconditioned conjugate gradient. To solve the random regression test-day model with the preconditioned conjugate gradient required 237 megabytes of random access memory and took 14% of the computation time needed by the reference algorithm.

The Role of Ionospheric Outflow Preconditioning in Determining Storm Geoeffectiveness

NASA Astrophysics Data System (ADS)

Welling, D. T.; Liemohn, M. W.; Ridley, A. J.

2012-12-01

It is now well accepted that ionospheric outflow plays an important role in the development of the plasma sheet and ring current during geomagnetic storms. Furthermore, even during quiet times, ionospheric plasma populates the magnetospheric lobes, producing a reservoir of hydrogen and oxygen ions. When the Interplanetary Magnetic Field (IMF) turns southward, this reservoir is connected to the plasma sheet and ring current through magnetospheric convection. Hence, the conditions of the ionosphere and magnetospheric lobes leading up to magnetospheric storm onset have important implications for storm development. Despite this, there has been little research on this preconditioning; most global simulations begin just before storm onset, neglecting preconditioning altogether. This work explores the role of preconditioning in determining the geoeffectiveness of storms using a coupled global model system. A model of ionospheric outflow (the Polar Wind Outflow Model, PWOM) is two-way coupled to a global magnetohydrodynamic model (the Block-Adaptive Tree Solar wind Roe-type Upwind Scheme, BATS-R-US), which in turn drives a ring current model (the Ring current Atmosphere interactions Model, RAM). This unique setup is used to simulate an idealized storm. The model is started at many different times, from 1 hour before storm onset to 12 hours before. The effects of storm preconditioning are examined by investigating the total ionospheric plasma content in the lobes just before onset, the total ionospheric contribution in the ring current just after onset, and the effects on Dst, magnetic elevation angle at geosynchronous, and total ring current energy density. This experiment is repeated for different solar activity levels as set by F10.7 flux. Finally, a synthetic double-dip storm is constructed to see how two closely spaced storms affect each other by changing the preconditioning environment. It is found that preconditioning of the magnetospheric lobes via ionospheric outflow greatly influences the geoeffectiveness of magnetospheric storms.

Hypoxic preconditioning facilitates acclimatization to hypobaric hypoxia in rat heart.

PubMed

Singh, Mrinalini; Shukla, Dhananjay; Thomas, Pauline; Saxena, Saurabh; Bansal, Anju

2010-12-01

Acute systemic hypoxia induces delayed cardioprotection against ischaemia-reperfusion injury in the heart. As cobalt chloride (CoCl₂) is known to elicit hypoxia-like responses, it was hypothesized that this chemical would mimic the preconditioning effect and facilitate acclimatization to hypobaric hypoxia in rat heart. Male Sprague-Dawley rats treated with distilled water or cobalt chloride (12.5 mg Co/kg for 7 days) were exposed to simulated altitude at 7622 m for different time periods (1, 2, 3 and 5 days). Hypoxic preconditioning with cobalt appreciably attenuated hypobaric hypoxia-induced oxidative damage as observed by a decrease in free radical (reactive oxygen species) generation, oxidation of lipids and proteins. Interestingly, the observed effect was due to increased expression of the antioxidant proteins hemeoxygenase and metallothionein, as no significant change was observed in antioxidant enzyme activity. Hypoxic preconditioning with cobalt increased hypoxia-inducible factor 1α (HIF-1α) expression as well as HIF-1 DNA binding activity, which further resulted in increased expression of HIF-1 regulated genes such as erythropoietin, vascular endothelial growth factor and glucose transporter. A significant decrease was observed in lactate dehydrogenase activity and lactate levels in the heart of preconditioned animals compared with non-preconditioned animals exposed to hypoxia. The results showed that hypoxic preconditioning with cobalt induces acclimatization by up-regulation of hemeoxygenase 1 and metallothionein 1 via HIF-1 stabilization. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.

Parallel Preconditioning for CFD Problems on the CM-5

NASA Technical Reports Server (NTRS)

Simon, Horst D.; Kremenetsky, Mark D.; Richardson, John; Lasinski, T. A. (Technical Monitor)

1994-01-01

Up to today, preconditioning methods on massively parallel systems have faced a major difficulty. The most successful preconditioning methods in terms of accelerating the convergence of the iterative solver such as incomplete LU factorizations are notoriously difficult to implement on parallel machines for two reasons: (1) the actual computation of the preconditioner is not very floating-point intensive, but requires a large amount of unstructured communication, and (2) the application of the preconditioning matrix in the iteration phase (i.e. triangular solves) are difficult to parallelize because of the recursive nature of the computation. Here we present a new approach to preconditioning for very large, sparse, unsymmetric, linear systems, which avoids both difficulties. We explicitly compute an approximate inverse to our original matrix. This new preconditioning matrix can be applied most efficiently for iterative methods on massively parallel machines, since the preconditioning phase involves only a matrix-vector multiplication, with possibly a dense matrix. Furthermore the actual computation of the preconditioning matrix has natural parallelism. For a problem of size n, the preconditioning matrix can be computed by solving n independent small least squares problems. The algorithm and its implementation on the Connection Machine CM-5 are discussed in detail and supported by extensive timings obtained from real problem data.

Management of Preconditioned Calves and Impacts of Preconditioning.

PubMed

Hilton, W Mark

2015-07-01

When studying the practice of preconditioning (PC) calves, many factors need to be examined to determine if cow-calf producers should make this investment. Factors such as average daily gain, feed efficiency, available labor, length of the PC period, genetics, and marketing options must be analyzed. The health sales price advantage is an additional benefit in producing and selling PC calves but not the sole determinant of PC's financially feasibility. Studies show that a substantial advantage of PC is the selling of additional pounds at a cost of gain well below the marginal return of producing those additional pounds. Copyright © 2015 Elsevier Inc. All rights reserved.

The mechanism of protection from 5 (N-ethyl-N-isopropyl)amiloride differs from that of ischemic preconditioning in rabbit heart.

PubMed

Sato, H; Miki, T; Vallabhapurapu, R P; Wang, P; Liu, G S; Cohen, M V; Downey, J M

1997-10-01

We investigated the effects of 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on infarction in isolated rabbit hearts and cardiomyocytes. Thirty min of regional ischemia caused 29.6 +/- 2.8% of the risk zone to infarct in untreated Krebs buffer-perfused hearts. Treatment with EIPA (1 microM) for 20 min starting either 15 min before ischemia or 15 min after the onset of ischemia significantly reduced infarction to 5.4 +/- 2.0% and 7.0 +/- 1.0%, respectively (p < 0.01 versus untreated hearts). In both cases salvage was very similar to that seen with ischemic preconditioning (PC) (7.1 +/- 1.5% infarction). Unlike the case with ischemic preconditioning, however, protection from EIPA was not blocked by 50 microM polymyxin B, a PKC inhibitor, or 1 microM glibenclamide, a KATP channel blocker. Forty-five min of regional ischemia caused 51.0 +/- 2.9% infarction in untreated hearts. Ischemic preconditioning reduced infarction to 23.4 +/- 3.1% (p < 0.001 versus untreated hearts). In these hearts with longer periods of ischemia pretreatment with EIPA reduced infarction similarly to 28.8 +/- 2.1% (p < 0.01 versus untreated hearts). However, when EIPA was combined with ischemic PC, no further reduction in infarction was seen (23.8 +/- 3.5% infarction). To further elucidate the mechanism of EIPA's cardioprotective effect, this agent was also examined in isolated rabbit cardiomyocytes. Preconditioning caused a delay of about 30 min in the progressive increase in osmotic fragility that occurs during simulated ischemia. In contrast, EIPA had no effect on the time course of ischemia-induced osmotic fragility. Furthermore, EIPA treatment did not alter the salutary effect of ischemic preconditioning when the two were combined in this model. We conclude that Na+/H+ exchange inhibition limits myocardial infarction in the isolated rabbit heart by a mechanism which is quite different from that of ischemic preconditioning. Despite the apparently divergent mechanisms, EIPA's cardioprotective effect could not be added to that of ischemic or metabolic preconditioning in these models.

Preconditioning with the traditional Chinese medicine Huang-Lian-Jie-Du-Tang initiates HIF-1α-dependent neuroprotection against cerebral ischemia in rats.

PubMed

Zhang, Qichun; Bian, Huimin; Li, Yu; Guo, Liwei; Tang, Yuping; Zhu, Huaxu

2014-06-11

Huang-Lian-Jie-Du-Tang (HLJDT) is a classical heat-clearing and detoxicating formula of traditional Chinese medicine that is widely used to treat stroke. The present study was designed to investigate the effects of HLJDT preconditioning on neurons under oxygen and glucose deprivation (OGD) and rats subjected to middle cerebral artery occlusion (MCAO). A stroke model of rats was obtained through MCAO. Following HLJDT preconditioning, the cerebral infarction volume, cerebral water content, and neurological deficient score were determined. Cerebral cortical neurons cultured in vitro were preconditioned with HLJDT and then subjected to OGD treatment. The release of lactate dehydrogenase (LDH) from neurons was detected. The levels of hypoxia-inducible factor-1α (HIF-1α) and PI3K/Akt signaling were analyzed by western blotting, and the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in the supernatant of the neurons and the plasma of MCAO rats were measured through a radioimmunological assay. The apoptosis and proliferation of neurons were analyzed by immunohistochemistry. HLJDT preconditioning significantly reduced the cerebral infarction volume and cerebral water content and ameliorated the neurological deficient score of MCAO rats. In addition, HLJDT preconditioning protected neurons against OGD. Increased HIF-1α, EPO, and VEGF levels and the activation of PI3K/Akt signaling were observed as a result of HLJDT preconditioning. Furthermore, HLJDT preconditioning was found to inhibit ischemia-induced neuron apoptosis and to promote neuron proliferation under conditions of ischemia/reperfusion. Both rats and neurons subjected to HLJDT preconditioning were able to resist ischemia/reperfusion or hypoxia injury through the inhibition of apoptosis and the enhancement of proliferation, and these effects were primarily dependent on the activation of the PI3K/Akt signaling pathway and HIF-1α. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Angiogenic Capacity of Periodontal Ligament Stem Cells Pretreated with Deferoxamine and/or Fibroblast Growth Factor-2

PubMed Central

Ratajczak, Jessica; Hilkens, Petra; Gervois, Pascal; Wolfs, Esther; Jacobs, Reinhilde; Lambrichts, Ivo; Bronckaers, Annelies

2016-01-01

Periodontal ligament stem cells (PDLSCs) represent a good source of multipotent cells for cell-based therapies in regenerative medicine. The success rate of these treatments is severely dependent on the establishment of adequate vasculature in order to provide oxygen and nutrients to the transplanted cells. Pharmacological preconditioning of stem cells has been proposed as a promising method to augment their therapeutic efficacy. In this study, the aim was to improve the intrinsic angiogenic properties of PDLSCs by in vitro pretreatment with deferoxamine (DFX; 100μM), fibroblast growth factor-2 (FGF-2; 10ng/mL) or both substances combined. An antibody array revealed the differential expression of several proteins, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). ELISA data confirmed a 1.5 to 1.8-fold increase in VEGF for all tested conditions. Moreover, 48 hours after the removal of DFX, VEGF levels remained elevated (1.8-fold) compared to control conditions. FGF-2 and combination treatment resulted in a 5.4 to 13.1-fold increase in PlGF secretion, whereas DFX treatment had no effect. Furthermore, both PDLSCs as pretreated PDLSCs induced endothelial migration. Despite the significant elevated VEGF levels of pretreated PDLSCs, the induced endothelial migration was not higher by pretreated PDLSCs. We find that the observed induced endothelial cell motility was not dependent on VEGF, since blocking the VEGFR1-3 with Axitinib (0.5nM) did not inhibit endothelial motility towards PDLSCs. Taken together, this study provides evidence that preconditioning with DFX and/or FGF-2 significantly improves the angiogenic secretome of PDLSCs, in particular VEGF and PlGF secretion. However, our data suggest that VEGF is not the only player when it comes to influencing endothelial behavior by the PDLSCs. PMID:27936076

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.

Efficient block preconditioned eigensolvers for linear response time-dependent density functional theory

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

Vecharynski, Eugene; Brabec, Jiri; Shao, Meiyue

We present two efficient iterative algorithms for solving the linear response eigen- value problem arising from the time dependent density functional theory. Although the matrix to be diagonalized is nonsymmetric, it has a special structure that can be exploited to save both memory and floating point operations. In particular, the nonsymmetric eigenvalue problem can be transformed into a product eigenvalue problem that is self-adjoint with respect to a K-inner product. This product eigenvalue problem can be solved efficiently by a modified Davidson algorithm and a modified locally optimal block preconditioned conjugate gradient (LOBPCG) algorithm that make use of the K-innermore » product. The solution of the product eigenvalue problem yields one component of the eigenvector associated with the original eigenvalue problem. However, the other component of the eigenvector can be easily recovered in a postprocessing procedure. Therefore, the algorithms we present here are more efficient than existing algorithms that try to approximate both components of the eigenvectors simultaneously. The efficiency of the new algorithms is demonstrated by numerical examples.« less

Using Chebyshev polynomials and approximate inverse triangular factorizations for preconditioning the conjugate gradient method

NASA Astrophysics Data System (ADS)

Kaporin, I. E.

2012-02-01

In order to precondition a sparse symmetric positive definite matrix, its approximate inverse is examined, which is represented as the product of two sparse mutually adjoint triangular matrices. In this way, the solution of the corresponding system of linear algebraic equations (SLAE) by applying the preconditioned conjugate gradient method (CGM) is reduced to performing only elementary vector operations and calculating sparse matrix-vector products. A method for constructing the above preconditioner is described and analyzed. The triangular factor has a fixed sparsity pattern and is optimal in the sense that the preconditioned matrix has a minimum K-condition number. The use of polynomial preconditioning based on Chebyshev polynomials makes it possible to considerably reduce the amount of scalar product operations (at the cost of an insignificant increase in the total number of arithmetic operations). The possibility of an efficient massively parallel implementation of the resulting method for solving SLAEs is discussed. For a sequential version of this method, the results obtained by solving 56 test problems from the Florida sparse matrix collection (which are large-scale and ill-conditioned) are presented. These results show that the method is highly reliable and has low computational costs.

Signal transduction of flumazenil-induced preconditioning in myocytes.

PubMed

Yao, Z; McPherson, B C; Liu, H; Shao, Z; Li, C; Qin, Y; Vanden Hoek, T L; Becker, L B; Schumacker, P T

2001-03-01

The objective of this study was to examine the role of oxygen radicals, protein kinase C (PKC), and ATP-sensitive K(+) (K(ATP)) channels in mediating flumazenil-produced preconditioning. Chick cardiomyocyte death was quantified using propidium iodide, and oxygen radical generation was assessed using 2',7'-dichlorofluorescin oxidation. Preconditioning was initiated with 10 min of ischemia followed by 10 min of reoxygenation. Alternatively, flumazenil was infused for 10 min and removed 10 min before ischemia. Flumazenil (10 microM) and preconditioning increased oxygen radicals [1,693 +/- 101 (n = 3) and 1,567 +/- 98 (n = 3), respectively, vs. 345 +/- 53 (n = 3) in control] and reduced cell death similarly [22 +/- 3% (n = 5) and 18 +/- 2% (n = 6), respectively, vs. controls 49 +/- 5% (n = 8)]. Protection and increased oxygen radicals by flumazenil were abolished by pretreatment with the antioxidant thiol reductant 2-mercaptopropionyl glycine (800 microM; 52 +/- 10%, n = 6). Specific PKC inhibitors Go-6976 (0.1 microM) and chelerythrine (2 microM), given during ischemia and reoxygenation, blocked flumazenil-produced protection (47 +/- 5%, n = 6). The PKC activator phorbol 12-myristate 13-acetate (0.2 microM), given during ischemia and reoxygenation, reduced cell death similarly to that with flumazenil [17 +/- 4% (n = 6) and 22 +/- 3% (n = 5)]. Finally, 5-hydroxydecanoate (1 mM), a selective mitochondrial K(ATP) channel antagonist given during ischemia and reoxygenation, abolished the protection of flumazenil and phorbol 12-myristate 13-acetate. Thus flumazenil mimics preconditioning to reduce cell death in cardiomyocytes. Oxygen radicals activate mitochondrial K(ATP) channels via PKC during the process.

Platelet rich plasma clot releasate preconditioning induced PI3K/AKT/NFκB signaling enhances survival and regenerative function of rat bone marrow mesenchymal stem cells in hostile microenvironments.

PubMed

Peng, Yan; Huang, Sha; Wu, Yan; Cheng, Biao; Nie, Xiaohu; Liu, Hongwei; Ma, Kui; Zhou, Jiping; Gao, Dongyun; Feng, Changjiang; Yang, Siming; Fu, Xiaobing

2013-12-15

Mesenchymal stem cells (MSCs) have been optimal targets in the development of cell based therapies, but their limited availability and high death rate after transplantation remains a concern in clinical applications. This study describes novel effects of platelet rich clot releasate (PRCR) on rat bone marrow-derived MSCs (BM-MSCs), with the former driving a gene program, which can reduce apoptosis and promote the regenerative function of the latter in hostile microenvironments through enhancement of paracrine/autocrine factors. By using reverse transcription-polymerase chain reaction, immunofluorescence and western blot analyses, we showed that PRCR preconditioning could alleviate the apoptosis of BM-MSCs under stress conditions induced by hydrogen peroxide (H2O2) and serum deprivation by enhancing expression of vascular endothelial growth factor and platelet-derived growth factor (PDGF) via stimulation of the platelet-derived growth factor receptor (PDGFR)/PI3K/AKT/NF-κB signaling pathways. Furthermore, the effects of PRCR preconditioned GFP-BM-MSCs subcutaneously transplanted into rats 6 h after wound surgery were examined by histological and other tests from days 0-22 after transplantation. Engraftment of the PRCR preconditioned BM-MSCs not only significantly attenuated apoptosis and wound size but also improved epithelization and blood vessel regeneration of skin via regulation of the wound microenvironment. Thus, preconditioning with PRCR, which reprograms BM-MSCs to tolerate hostile microenvironments and enhance regenerative function by increasing levels of paracrine factors through PDGFR-α/PI3K/AKT/NF-κB signaling pathways would be a safe method for boosting the effectiveness of transplantation therapy in the clinic.

Effects of hypoxic preconditioning on expression of transcription factor NGFI-A in the rat brain after unavoidable stress in the "learned helplessness" model.

PubMed

Baranova, K A; Rybnikova, E A; Mironova, V I; Samoilov, M O

2010-07-01

We report here our immunocytochemical studies establishing that the development of a depression-like state in rats following unavoidable stress in a "learned helplessness" model is accompanied by stable activation of the expression of transcription factor NGFI-A in the dorsal hippocampus (field CA1) and the magnocellular paraventricular nucleus of the hypothalamus, along with an early wave of post-stress expression, which died down rapidly, in the ventral hippocampus (the dentate gyrus) and a long period of up to five days of high-level expression in the neocortex. In rats subjected to three sessions of preconditioning consisting of moderate hypobaric hypoxia (360 mmHg, 2 h, with intervals of 24 h), which did not form depression in these circumstances, there were significant changes in the dynamics of immunoreactive protein content in the hippocampus, with a stable increase in expression in the ventral hippocampus and only transient and delayed (by five days) expression in field CA1. In the neocortex (layer II), preconditioning eliminated the effects of stress, preventing prolongation of the first wave of NGFI-A expression to five days, while in the magnocellular hypothalamus, conversely, preconditioning stimulated a second (delayed) wave of the expression of this transcription factor. The pattern of NGFI-A expression in the hippocampus, neocortex, and hypothalamus seen in non-preconditioned rats appears to reflect the pathological reaction to aversive stress, which, rather than adaptation, produced depressive disorders. Post-stress modification of the expression of the product of the early gene NGFI-A in the brain induced by hypoxic preconditioning probably plays an important role in increased tolerance to severe psychoemotional stresses and is an important component of antidepressant mechanisms.

Preconditioning of skeletal myoblast-based engineered tissue constructs enables functional coupling to myocardium in vivo

PubMed Central

Treskes, Philipp; Neef, Klaus; Srinivasan, Sureshkumar Perumal; Halbach, Marcel; Stamm, Christof; Cowan, Douglas; Scherner, Maximilian; Madershahian, Navid; Wittwer, Thorsten; Hescheler, Jürgen; Wahlers, Thorsten; Choi, Yeong-Hoon

2015-01-01

Objective Skeletal myoblasts fuse to form functional syncytial myotubes as an integral part of the skeletal muscle. During this differentiation process, expression of proteins for mechanical and electrical integration is seized, which is a major drawback for the application of skeletal myoblasts in cardiac regenerative cell therapy, because global heart function depends on intercellular communication. Methods Mechanically preconditioned engineered tissue constructs containing neonatal mouse skeletal myoblasts were transplanted epicardially. A Y-chromosomal specific polymerase chain reaction (PCR) was undertaken up to 10 weeks after transplantation to confirm the presence of grafted cells. Histologic and electrophysiologic analyses were carried out 1 week after transplantation. Results Cells within the grafted construct expressed connexin 43 at the interface to the host myocardium, indicating electrical coupling, confirmed by sharp electrode recordings. Analyses of the maximum stimulation frequency (5.65 ± 0.37 Hz), conduction velocity (0.087 ± 0.011 m/s) and sensitivity for pharmacologic conduction block (0.736 ± 0.080 mM 1-heptanol) revealed effective electrophysiologic coupling between graft and host cells, although significantly less robust than in native myocardial tissue (maximum stimulation frequency, 11.616 ± 0.238 Hz, P<.001; conduction velocity, 0.300 ± 0.057 m/s, P<.01; conduction block, 1.983 ± 0.077 mM 1-heptanol, P<.001). Conclusions Although untreated skeletal myoblasts cannot couple to cardiomyocytes, we confirm that mechanical preconditioning enables transplanted skeletal myoblasts to functionally interact with cardio-myocytes in vivo and, thus, reinvigorate the concept of skeletal myoblast-based cardiac cell therapy. PMID:25439779

40 CFR 86.1232-96 - Vehicle preconditioning.

Code of Federal Regulations, 2011 CFR

2011-07-01

... preconditioned separately. If production evaporative canisters are equipped with a functional service port... production evaporative canisters are equipped with a functional service port designed for vapor load or purge... provides at least a 4:1 safety factor against the lean flammability limit. (iii) The FID hydrocarbon...

Preconditioning the Helmholtz Equation for Rigid Ducts

NASA Technical Reports Server (NTRS)

Baumeister, Kenneth J.; Kreider, Kevin L.

1998-01-01

An innovative hyperbolic preconditioning technique is developed for the numerical solution of the Helmholtz equation which governs acoustic propagation in ducts. Two pseudo-time parameters are used to produce an explicit iterative finite difference scheme. This scheme eliminates the large matrix storage requirements normally associated with numerical solutions to the Helmholtz equation. The solution procedure is very fast when compared to other transient and steady methods. Optimization and an error analysis of the preconditioning factors are present. For validation, the method is applied to sound propagation in a 2D semi-infinite hard wall duct.

Fatigue characteristics of carbon nanotube blocks under compression

NASA Astrophysics Data System (ADS)

Suhr, J.; Ci, L.; Victor, P.; Ajayan, P. M.

2008-03-01

In this paper we investigate the mechanical response from repeated high compressive strains on freestanding, long, vertically aligned multiwalled carbon nanotube membranes and show that the arrays of nanotubes under compression behave very similar to soft tissue and exhibit viscoelastic behavior. Under compressive cyclic loading, the mechanical response of nanotube blocks shows initial preconditioning and hysteresis characteristic of viscoeleastic materials. Furthermore, no fatigue failure is observed even at high strain amplitudes up to half million cycles. The outstanding fatigue life and extraordinary soft tissue-like mechanical behavior suggest that properly engineered carbon nanotube structures could mimic artificial muscles.

Graph Embedding Techniques for Bounding Condition Numbers of Incomplete Factor Preconditioning

NASA Technical Reports Server (NTRS)

Guattery, Stephen

1997-01-01

We extend graph embedding techniques for bounding the spectral condition number of preconditioned systems involving symmetric, irreducibly diagonally dominant M-matrices to systems where the preconditioner is not diagonally dominant. In particular, this allows us to bound the spectral condition number when the preconditioner is based on an incomplete factorization. We provide a review of previous techniques, describe our extension, and give examples both of a bound for a model problem, and of ways in which our techniques give intuitive way of looking at incomplete factor preconditioners.

Ethanol preconditioning of rat cerebellar cultures targets NMDA receptors to the synapse and enhances peroxiredoxin 2 expression.

PubMed

Mitchell, Robert M; Tajuddin, Nuzhath; Campbell, Edward M; Neafsey, Edward J; Collins, Michael A

2016-07-01

Epidemiological studies indicate that light-moderate alcohol (ethanol) consumers tend to have reduced risks of cognitive impairment and progression to dementia during aging. Exploring possible mechanisms, we previously found that moderate ethanol preconditioning (MEP, 20-30mM) of rat brain cultures for several days instigated neuroprotection against β-amyloid peptides. Our biochemical evidence implicated the NMDA receptor (NMDAR) as a potential neuroprotective "sensor", specifically via synaptic NMDAR signaling. It remains unclear how ethanol modulates the receptor and its downstream targets to engender neuroprotection. Here we confirm with deconvolution microscopy that MEP of rat mixed cerebellar cultures robustly increases synaptic NMDAR localization. Phospho-activation of the non-receptor tyrosine kinases Src and Pyk2, known to be linked to synaptic NMDAR, is also demonstrated. Additionally, the preconditioning enhances levels of an antioxidant protein, peroxiredoxin 2 (Prx2), reported to be downstream of synaptic NMDAR signaling, and NMDAR antagonism with memantine (earlier found to abrogate MEP neuroprotection) blocks the Prx2 elevations. To further link Prx2 with antioxidant-based neuroprotection, we circumvented the ethanol preconditioning-NMDAR pathway by pharmacologically increasing Prx2 with the naturally-occurring cruciferous compound, 3H-1,2-dithiole-3-thione (D3T). Thus, D3T pretreatment elevated Prx2 expression to a similar extent as MEP, while concomitantly preventing β-amyloid neurotoxicity; D3T also protected the cultures from hydrogen peroxide toxicity. The findings support a mechanism that couples synaptic NMDAR signaling, Prx2 expression and augmented antioxidant defenses in ethanol preconditioning-induced neuroprotection. That this mechanism can be emulated by a cruciferous vegetable constituent suggests that such naturally-occurring "neutraceuticals" may be useful in therapy for oxidative stress-related dementias. Copyright © 2016 Elsevier B.V. All rights reserved.

A taxonomy and comparison of parallel block multi-level preconditioners for the incompressible Navier-Stokes equations.

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

Shadid, John Nicolas; Elman, Howard; Shuttleworth, Robert R.

2007-04-01

In recent years, considerable effort has been placed on developing efficient and robust solution algorithms for the incompressible Navier-Stokes equations based on preconditioned Krylov methods. These include physics-based methods, such as SIMPLE, and purely algebraic preconditioners based on the approximation of the Schur complement. All these techniques can be represented as approximate block factorization (ABF) type preconditioners. The goal is to decompose the application of the preconditioner into simplified sub-systems in which scalable multi-level type solvers can be applied. In this paper we develop a taxonomy of these ideas based on an adaptation of a generalized approximate factorization of themore » Navier-Stokes system first presented in [25]. This taxonomy illuminates the similarities and differences among these preconditioners and the central role played by efficient approximation of certain Schur complement operators. We then present a parallel computational study that examines the performance of these methods and compares them to an additive Schwarz domain decomposition (DD) algorithm. Results are presented for two and three-dimensional steady state problems for enclosed domains and inflow/outflow systems on both structured and unstructured meshes. The numerical experiments are performed using MPSalsa, a stabilized finite element code.« less

Protective role of vitamin E preconditioning of human dermal fibroblasts against thermal stress in vitro.

PubMed

Butt, Hira; Mehmood, Azra; Ali, Muhammad; Tasneem, Saba; Anjum, Muhammad Sohail; Tarar, Moazzam N; Khan, Shaheen N; Riazuddin, Sheikh

2017-09-01

Oxidative microenvironment of burnt skin restricts the outcome of cell based therapies of thermal skin injuries. The aim of this study was to precondition human dermal fibroblasts with an antioxidant such as vitamin E to improve their survival and therapeutic abilities in heat induced oxidative in vitro environment. Fibroblasts were treated with 100μM vitamin E for 24h at 37°C followed by heat shock for 10min at 51°C in fresh serum free medium. Preconditioning with vitamin E reduced cell injury as demonstrated by decreased expression of annexin-V, cytochrome p450 (CYP450) mediated oxidative reactions, senescence and release of lactate dehydrogenase (LDH) accomplished by down-regulated expression of pro-apoptotic BAX gene. Vitamin E preconditioned cells exhibited remarkable improvement in cell viability, release of paracrine factors such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), stromal derived factor-1alpha (SDF-1α) and also showed significantly up-regulated levels of PCNA, VEGF, BCL-XL, FGF7, FGF23, FLNβ and Col7α genes presumably through activation of phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. The results suggest that pretreatment of fibroblasts with vitamin E prior to transplantation in burnt skin speeds up the wound healing process by improving the antioxidant scavenging responses in oxidative environment of transplanted burn wounds. Copyright © 2017 Elsevier Inc. All rights reserved.

Attributes and Preconditions of Collaboration between and among Schools, Institutions of Higher Education, and State Education Agencies. Instructional Leadership and School Improvement.

ERIC Educational Resources Information Center

Reed, Patricia; Cejda, Brent

Recognizing that successful collaboration among schools, institutes of higher education, and state education agencies to is an important factor in the professional development of education personnel, this document examines existing knowledge of interorganizational collaboration and identifies organizational preconditions conducive to the…

Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1α Activation

PubMed Central

Ma, Daqing; Lim, Ta; Xu, Jing; Tang, Haidy; Wan, Yanjie; Zhao, Hailin; Hossain, Mahmuda; Maxwell, Patrick H.; Maze, Mervyn

2009-01-01

The mortality rate from acute kidney injury after major cardiovascular operations can be as high as 60%, and no therapies have been proved to prevent acute kidney injury in this setting. Here, we show that preconditioning with the anesthetic gas xenon activates hypoxia-inducible factor 1α (HIF-1α) and its downstream effectors erythropoietin and vascular endothelial growth factor in a time-dependent manner in the kidneys of adult mice. Xenon increased the efficiency of HIF-1α translation via modulation of the mammalian target of rapamycin pathway. In a model of renal ischemia-reperfusion injury, xenon provided morphologic and functional renoprotection; hydrodynamic injection of HIF-1α small interfering RNA demonstrated that this protection is HIF-1α dependent. These results suggest that xenon preconditioning is a natural inducer of HIF-1α and that administration of xenon before renal ischemia can prevent acute renal failure. If these data are confirmed in the clinical setting, then preconditioning with xenon may be beneficial before procedures that temporarily interrupt renal perfusion. PMID:19144758

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

PubMed Central

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

miR-21 Contributes to Xenon-conferred Amelioration of Renal Ischemia–Reperfusion Injury in Mice

PubMed Central

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Zhang, Xiaoyan; Bosnjak, Zeljko J.; Liang, Mingyu; Ding, Xiaoqiang

2015-01-01

Background MicroRNAs participate in the regulation of numerous physiological and disease processes. The in vivo role of microRNAs in anesthetics-conferred organoprotection is unknown. Methods Mice were exposed for 2 h to either 70% xenon, or 70% nitrogen, 24 h before the induction of renal ischemia-reperfusion injury. The role of microRNA, miR-21, in renal protection conferred by the delayed xenon preconditioning was examined using in vivo knockdown of miR-21 and analysis of miR-21 target pathways. Results Xenon preconditioning provided morphologic and functional protection against renal ischemia-reperfusion injury (n = 6), characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress. Xenon preconditioning significantly increased the expression of miR-21 in the mouse kidney. A locked nucleic acid-modified anti–miR-21, given before xenon preconditioning, knocked down miR-21 effectively, and exacerbated subsequent renal ischemia-reperfusion injury. Mice treated with anti–miR-21 and ischemia-reperfusion injury showed significantly higher serum creatinine than antiscrambled oligonucleotides-treated mice, 24 h after ischemia-reperfusion (1.37 ± 0.28 vs. 0.81 ± 0.14 mg/dl; n = 5; P < 0.05). Knockdown of miR-21 induced significant up-regulation of programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10, two proapoptotic target effectors of miR-21, and resulted in significant down-regulation of phosphorylated protein kinase B and increased tubular cell apoptosis. In addition, xenon preconditioning up-regulated hypoxia-inducible factor-1α and its downstream effector vascular endothelial growth factor in a time-dependent manner. Knockdown of miR-21 resulted in a significant decrease of hypoxia-inducible factor-1α. Conclusions These results indicate that miR-21 contributes to the renoprotective effect of xenon preconditioning. PMID:23681145

miR-21 contributes to xenon-conferred amelioration of renal ischemia-reperfusion injury in mice.

PubMed

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Zhang, Xiaoyan; Bosnjak, Zeljko J; Liang, Mingyu; Ding, Xiaoqiang

2013-09-01

MicroRNAs participate in the regulation of numerous physiological and disease processes. The in vivo role of microRNAs in anesthetics-conferred organoprotection is unknown. Mice were exposed for 2 h to either 70% xenon, or 70% nitrogen, 24 h before the induction of renal ischemia-reperfusion injury. The role of microRNA, miR-21, in renal protection conferred by the delayed xenon preconditioning was examined using in vivo knockdown of miR-21 and analysis of miR-21 target pathways. Xenon preconditioning provided morphologic and functional protection against renal ischemia-reperfusion injury (n = 6), characterized by attenuation of renal tubular damage, apoptosis, and oxidative stress. Xenon preconditioning significantly increased the expression of miR-21 in the mouse kidney. A locked nucleic acid-modified anti-miR-21, given before xenon preconditioning, knocked down miR-21 effectively, and exacerbated subsequent renal ischemia-reperfusion injury. Mice treated with anti-miR-21 and ischemia-reperfusion injury showed significantly higher serum creatinine than antiscrambled oligonucleotides-treated mice, 24 h after ischemia-reperfusion (1.37 ± 0.28 vs. 0.81 ± 0.14 mg/dl; n = 5; P < 0.05). Knockdown of miR-21 induced significant up-regulation of programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10, two proapoptotic target effectors of miR-21, and resulted in significant down-regulation of phosphorylated protein kinase B and increased tubular cell apoptosis. In addition, xenon preconditioning up-regulated hypoxia-inducible factor-1α and its downstream effector vascular endothelial growth factor in a time-dependent manner. Knockdown of miR-21 resulted in a significant decrease of hypoxia-inducible factor-1α. These results indicate that miR-21 contributes to the renoprotective effect of xenon preconditioning.

Weighted graph based ordering techniques for preconditioned conjugate gradient methods

NASA Technical Reports Server (NTRS)

Clift, Simon S.; Tang, Wei-Pai

1994-01-01

We describe the basis of a matrix ordering heuristic for improving the incomplete factorization used in preconditioned conjugate gradient techniques applied to anisotropic PDE's. Several new matrix ordering techniques, derived from well-known algorithms in combinatorial graph theory, which attempt to implement this heuristic, are described. These ordering techniques are tested against a number of matrices arising from linear anisotropic PDE's, and compared with other matrix ordering techniques. A variation of RCM is shown to generally improve the quality of incomplete factorization preconditioners.

Neuroprotective Effect of Antioxidants and Moderate Hypoxia as Combined Preconditioning in Cerebral Ischemia.

PubMed

Levchenkova, O S; Novikov, V E; Parfenov, E A; Kulagin, K N

2016-12-01

We studied combined effect of moderate hypoxia and compounds pQ-4, pQ-915, pQ-1032, and pQ-1104 on neurological deficit and survival of rats after bilateral ligation of common carotid arteries. Preconditioning including moderate hypoxia and treatment with compound pQ-4 produced a neuroprotective effect and increased animal survival during the early (by 51%) and late (by 33.5%) periods of modeled ischemia and reduced neurological deficit (by 50% and 41%, respectively). Moreover, this combination of preconditioning factors prevented postischemic excessive activation of free radical oxidation in brain hemispheres and blood serum.

The effect of brain death in rat steatotic and non-steatotic liver transplantation with previous ischemic preconditioning.

PubMed

Jiménez-Castro, Mónica B; Meroño, Noelia; Mendes-Braz, Mariana; Gracia-Sancho, Jordi; Martínez-Carreres, Laia; Cornide-Petronio, Maria Eugenia; Casillas-Ramirez, Araní; Rodés, Juan; Peralta, Carmen

2015-01-01

Most liver grafts undergoing transplantation derive from brain dead donors, which may also show hepatic steatosis, being both characteristic risk factors in liver transplantation. Ischemic preconditioning shows benefits when applied in non-brain dead clinical situations like hepatectomies, whereas it has been less promising in the transplantation from brain dead patients. This study examined how brain death affects preconditioned steatotic and non-steatotic liver grafts undergoing transplantation. Steatotic and non-steatotic grafts from non-brain dead and brain dead-donors were cold stored for 6h and then transplanted. After 2, 4, and 16 h of reperfusion, hepatic damage was analysed. In addition, two therapeutic strategies, ischemic preconditioning and/or acetylcholine pre-treatment, and their underlying mechanisms were characterized. Preconditioning benefits in non-brain dead donors were associated with nitric oxide and acetylcholine generation. In brain dead donors, preconditioning generated nitric oxide but did not promote acetylcholine upregulation, and this resulted in inflammation and damage. Acetylcholine treatment in brain dead donors, through PKC, increased antioxidants and reduced lipid peroxidation, nitrotyrosines and neutrophil accumulation, altogether protecting against damage. The combination of acetylcholine and preconditioning conferred stronger protection against damage, oxidative stress and neutrophil accumulation than acetylcholine treatment alone. These superior beneficial effects were due to a selective preconditioning-mediated generation of nitric oxide and regulation of PPAR and TLR4 pathways, which were not observed when acetylcholine was administered alone. Our findings propose the combination of acetylcholine+preconditioning as a feasible and highly protective strategy to reduce the adverse effects of brain death and to ultimately improve liver graft quality. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Pretreatment with the nitric oxide donor SNAP or nerve transection blocks humoral preconditioning by remote limb ischemia or intra-arterial adenosine.

PubMed

Steensrud, Tor; Li, Jing; Dai, Xiaojing; Manlhiot, Cedric; Kharbanda, Rajesh K; Tropak, Michael; Redington, Andrew

2010-11-01

We have previously shown that remote ischemic preconditioning (rIPC) by transient limb ischemia leads to the release of a circulating factor(s) that induces potent myocardial protection. Intra-arterial injection of adenosine into a limb also leads to cardioprotection, but the mechanism of its signal transduction is poorly understood. Eleven groups of rabbits received saline control or rIPC or adenosine administration with additional pretreatment with the nitric oxide (NO) synthase blocker N(G)-nitro-l-arginine methyl ester, the NO donor S-nitroso-N-acetylpenicillamine, its non-NO-donating derivative N-acetylpenicillamine, or femoral nerve section. Blood was then drawn from each animal, and the dialysate of the plasma was used to perfuse a naïve heart from an untreated donor. Infarct size was measured after 30 min of global ischemia and 120 min reperfusion. When compared with that of the control, mean infarct size was significantly smaller in groups treated with rIPC alone (P < 0.01) and intra-arterial adenosine (P < 0.01). Pretreatment with N(G)-nitro-l-arginine methyl ester or N-acetylpenicillamine did not affect the level of protection induced by rIPC (P = not significant, compared with rIPC alone) or intra-arterial adenosine (P = not significant, compared with intra-arterial adenosine alone), but prior femoral nerve transection or pretreatment with S-nitroso-N-acetylpenicillamine abolished the cardioprotective effect of intra-arterial adenosine and rIPC. Intra-arterial adenosine, like rIPC, releases a blood-borne cardioprotective factor(s) that is dependent on an intact femoral nerve and is inhibited by pretreatment with a NO donor. These results may be important when designing or assessing the results of clinical trials of adenosine or rIPC cardioprotection, where NO donors are used as part of therapy.

Analysis of Preconditioning and Relaxation Operators for the Discontinuous Galerkin Method Applied to Diffusion

NASA Technical Reports Server (NTRS)

Atkins, H. L.; Shu, Chi-Wang

2001-01-01

The explicit stability constraint of the discontinuous Galerkin method applied to the diffusion operator decreases dramatically as the order of the method is increased. Block Jacobi and block Gauss-Seidel preconditioner operators are examined for their effectiveness at accelerating convergence. A Fourier analysis for methods of order 2 through 6 reveals that both preconditioner operators bound the eigenvalues of the discrete spatial operator. Additionally, in one dimension, the eigenvalues are grouped into two or three regions that are invariant with order of the method. Local relaxation methods are constructed that rapidly damp high frequencies for arbitrarily large time step.

Preconditioned conjugate gradient methods for the Navier-Stokes equations

NASA Technical Reports Server (NTRS)

Ajmani, Kumud; Ng, Wing-Fai; Liou, Meng-Sing

1994-01-01

A preconditioned Krylov subspace method (GMRES) is used to solve the linear systems of equations formed at each time-integration step of the unsteady, two-dimensional, compressible Navier-Stokes equations of fluid flow. The Navier-Stokes equations are cast in an implicit, upwind finite-volume, flux-split formulation. Several preconditioning techniques are investigated to enhance the efficiency and convergence rate of the implicit solver based on the GMRES algorithm. The superiority of the new solver is established by comparisons with a conventional implicit solver, namely line Gauss-Seidel relaxation (LGSR). Computational test results for low-speed (incompressible flow over a backward-facing step at Mach 0.1), transonic flow (trailing edge flow in a transonic turbine cascade), and hypersonic flow (shock-on-shock interactions on a cylindrical leading edge at Mach 6.0) are presented. For the Mach 0.1 case, overall speedup factors of up to 17 (in terms of time-steps) and 15 (in terms of CPU time on a CRAY-YMP/8) are found in favor of the preconditioned GMRES solver, when compared with the LGSR solver. The corresponding speedup factors for the transonic flow case are 17 and 23, respectively. The hypersonic flow case shows slightly lower speedup factors of 9 and 13, respectively. The study of preconditioners conducted in this research reveals that a new LUSGS-type preconditioner is much more efficient than a conventional incomplete LU-type preconditioner.

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

Weston, Brian T.

This dissertation focuses on the development of a fully-implicit, high-order compressible ow solver with phase change. The work is motivated by laser-induced phase change applications, particularly by the need to develop large-scale multi-physics simulations of the selective laser melting (SLM) process in metal additive manufacturing (3D printing). Simulations of the SLM process require precise tracking of multi-material solid-liquid-gas interfaces, due to laser-induced melting/ solidi cation and evaporation/condensation of metal powder in an ambient gas. These rapid density variations and phase change processes tightly couple the governing equations, requiring a fully compressible framework to robustly capture the rapid density variations ofmore » the ambient gas and the melting/evaporation of the metal powder. For non-isothermal phase change, the velocity is gradually suppressed through the mushy region by a variable viscosity and Darcy source term model. The governing equations are discretized up to 4th-order accuracy with our reconstructed Discontinuous Galerkin spatial discretization scheme and up to 5th-order accuracy with L-stable fully implicit time discretization schemes (BDF2 and ESDIRK3-5). The resulting set of non-linear equations is solved using a robust Newton-Krylov method, with the Jacobian-free version of the GMRES solver for linear iterations. Due to the sti nes associated with the acoustic waves and thermal and viscous/material strength e ects, preconditioning the GMRES solver is essential. A robust and scalable approximate block factorization preconditioner was developed, which utilizes the velocity-pressure (vP) and velocity-temperature (vT) Schur complement systems. This multigrid block reduction preconditioning technique converges for high CFL/Fourier numbers and exhibits excellent parallel and algorithmic scalability on classic benchmark problems in uid dynamics (lid-driven cavity ow and natural convection heat transfer) as well as for laser-induced phase change problems in 2D and 3D.« less

The U.S. Geological Survey Modular Ground-Water Model - PCGN: A Preconditioned Conjugate Gradient Solver with Improved Nonlinear Control

USGS Publications Warehouse

Naff, Richard L.; Banta, Edward R.

2008-01-01

The preconditioned conjugate gradient with improved nonlinear control (PCGN) package provides addi-tional means by which the solution of nonlinear ground-water flow problems can be controlled as compared to existing solver packages for MODFLOW. Picard iteration is used to solve nonlinear ground-water flow equations by iteratively solving a linear approximation of the nonlinear equations. The linear solution is provided by means of the preconditioned conjugate gradient algorithm where preconditioning is provided by the modi-fied incomplete Cholesky algorithm. The incomplete Cholesky scheme incorporates two levels of fill, 0 and 1, in which the pivots can be modified so that the row sums of the preconditioning matrix and the original matrix are approximately equal. A relaxation factor is used to implement the modified pivots, which determines the degree of modification allowed. The effects of fill level and degree of pivot modification are briefly explored by means of a synthetic, heterogeneous finite-difference matrix; results are reported in the final section of this report. The preconditioned conjugate gradient method is coupled with Picard iteration so as to efficiently solve the nonlinear equations associated with many ground-water flow problems. The description of this coupling of the linear solver with Picard iteration is a primary concern of this document.

TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis

PubMed Central

Zhou, Jun-Hao; Zhang, Tong-Tong; Song, Dan-Dan; Xia, Yun-Fei; Qin, Zheng-Hong; Sheng, Rui

2016-01-01

Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis. PMID:27256465

On coupling fluid plasma and kinetic neutral physics models

DOE PAGES

Joseph, I.; Rensink, M. E.; Stotler, D. P.; ...

2017-03-01

The coupled fluid plasma and kinetic neutral physics equations are analyzed through theory and simulation of benchmark cases. It is shown that coupling methods that do not treat the coupling rates implicitly are restricted to short time steps for stability. Fast charge exchange, ionization and recombination coupling rates exist, even after constraining the solution by requiring that the neutrals are at equilibrium. For explicit coupling, the present implementation of Monte Carlo correlated sampling techniques does not allow for complete convergence in slab geometry. For the benchmark case, residuals decay with particle number and increase with grid size, indicating that theymore » scale in a manner that is similar to the theoretical prediction for nonlinear bias error. Progress is reported on implementation of a fully implicit Jacobian-free Newton–Krylov coupling scheme. The present block Jacobi preconditioning method is still sensitive to time step and methods that better precondition the coupled system are under investigation.« less

Peptide Nanofibers Preconditioned with Stem Cell Secretome Are Renoprotective

PubMed Central

Wang, Yin; Bakota, Erica; Chang, Benny H.J.; Entman, Mark; Hartgerink, Jeffrey D.

2011-01-01

Stem cells may contribute to renal recovery following acute kidney injury, and this may occur through their secretion of cytokines, chemokines, and growth factors. Here, we developed an acellular, nanofiber-based preparation of self-assembled peptides to deliver the secretome of embryonic stem cells (ESCs). Using an integrated in vitro and in vivo approach, we found that nanofibers preconditioned with ESCs could reverse cell hyperpermeability and apoptosis in vitro and protect against lipopolysaccharide-induced acute kidney injury in vivo. The renoprotective effect of preconditioned nanofibers associated with an attenuation of Rho kinase activation. We also observed that the combined presence of follistatin, adiponectin, and secretory leukoprotease during preconditioning was essential to the renoprotective properties of the nanofibers. In summary, we developed a designer-peptide nanofiber that can serve as a delivery platform for the beneficial effects of stem cells without the problems of teratoma formation or limited cell engraftment and viability. PMID:21415151

Acidic preconditioning of endothelial colony-forming cells (ECFC) promote vasculogenesis under proinflammatory and high glucose conditions in vitro and in vivo.

PubMed

Mena, Hebe Agustina; Zubiry, Paula Romina; Dizier, Blandine; Schattner, Mirta; Boisson-Vidal, Catherine; Negrotto, Soledad

2018-05-02

We have previously demonstrated that acidic preconditioning of human endothelial colony-forming cells (ECFC) increased proliferation, migration, and tubulogenesis in vitro, and increased their regenerative potential in a murine model of hind limb ischemia without baseline disease. We now analyze whether this strategy is also effective under adverse conditions for vasculogenesis, such as the presence of ischemia-related toxic molecules or diabetes, one of the main target diseases for cell therapy due to their well-known healing impairments. Cord blood-derived CD34 + cells were seeded in endothelial growth culture medium (EGM2) and ECFC colonies were obtained after 14-21 days. ECFC were exposed at pH 6.6 (preconditioned) or pH 7.4 (nonpreconditioned) for 6 h, and then pH was restored at 7.4. A model of type 2 diabetes induced by a high-fat and high-sucrose diet was developed in nude mice and hind limb ischemia was induced in these animals by femoral artery ligation. A P value < 0.05 was considered statistically significant (by one-way analysis of variance). We found that acidic preconditioning increased ECFC adhesion and the release of pro-angiogenic molecules, and protected ECFC from the cytotoxic effects of monosodium urate crystals, histones, and tumor necrosis factor (TNF)α, which induced necrosis, pyroptosis, and apoptosis, respectively. Noncytotoxic concentrations of high glucose, TNFα, or their combination reduced ECFC proliferation, stromal cell-derived factor (SDF)1-driven migration, and tubule formation on a basement membrane matrix, whereas almost no inhibition was observed in preconditioned ECFC. In type 2 diabetic mice, intravenous administration of preconditioned ECFC significantly induced blood flow recovery at the ischemic limb as measured by Doppler, compared with the phosphate-buffered saline (PBS) and nonpreconditioned ECFC groups. Moreover, the histologic analysis of gastrocnemius muscles showed an increased vascular density and reduced signs of inflammation in the animals receiving preconditioned ECFC. Acidic preconditioning improved ECFC survival and angiogenic activity in the presence of proinflammatory and damage signals present in the ischemic milieu, even under high glucose conditions, and increased their therapeutic potential for postischemia tissue regeneration in a murine model of type 2 diabetes. Collectively, our data suggest that acidic preconditioning of ECFC is a simple and inexpensive strategy to improve the effectiveness of cell transplantation in diabetes, where tissue repair is highly compromised.

Antecedent hydrogen sulfide elicits an anti-inflammatory phenotype in postischemic murine small intestine: role of BK channels

PubMed Central

Zuidema, Mozow Y.; Yang, Yan; Wang, Meifang; Kalogeris, Theodore; Liu, Yajun; Meininger, Cynthia J.; Hill, Michael A.; Davis, Michael J.

2010-01-01

The objectives of this study were to determine the role of calcium-activated, small (SK), intermediate (IK), and large (BK) conductance potassium channels in initiating the development of an anti-inflammatory phenotype elicited by preconditioning with an exogenous hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS). Intravital microscopy was used to visualize rolling and firmly adherent leukocytes in vessels of the small intestine of mice preconditioned with NaHS (in the absence and presence of SK, IK, and BK channel inhibitors, apamin, TRAM-34, and paxilline, respectively) or SK/IK (NS-309) or BK channel activators (NS-1619) 24 h before ischemia-reperfusion (I/R). I/R induced marked increases in leukocyte rolling and adhesion, effects that were largely abolished by preconditioning with NaHS, NS-309, or NS-1619. The postischemic anti-inflammatory effects of NaHS-induced preconditioning were mitigated by BKB channel inhibitor treatment coincident with NaHS, but not by apamin or TRAM-34, 24 h before I/R. Confocal imaging and immunohistochemistry were used to demonstrate the presence of BKα subunit staining in both endothelial and vascular smooth muscle cells of isolated, pressurized mesenteric venules. Using patch-clamp techniques, we found that BK channels in cultured endothelial cells were activated after exposure to NaHS. Bath application of the same concentration of NaHS used in preconditioning protocols led to a rapid increase in a whole cell K+ current; specifically, the component of K+ current blocked by the selective BK channel antagonist iberiotoxin. The activation of BK current by NaHS could also be demonstrated in single channel recording mode where it was independent of a change in intracellular Ca+ concentration. Our data are consistent with the concept that H2S induces the development of an anti-adhesive state in I/R in part mediated by a BK channel-dependent mechanism. PMID:20833953

Conditioning with compound stimuli in Drosophila melanogaster in the flight simulator.

PubMed

Brembs, B; Heisenberg, M

2001-08-01

Short-term memory in Drosophila melanogaster operant visual learning in the flight simulator is explored using patterns and colours as a compound stimulus. Presented together during training, the two stimuli accrue the same associative strength whether or not a prior training phase rendered one of the two stimuli a stronger predictor for the reinforcer than the other (no blocking). This result adds Drosophila to the list of other invertebrates that do not exhibit the robust vertebrate blocking phenomenon. Other forms of higher-order learning, however, were detected: a solid sensory preconditioning and a small second-order conditioning effect imply that associations between the two stimuli can be formed, even if the compound is not reinforced.

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.

Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat

PubMed Central

Serafín, Anna; Roselló-Catafau, Joan; Prats, Neus; Xaus, Carme; Gelpí, Emilio; Peralta, Carmen

2002-01-01

Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation. PMID:12163383

The noble gas xenon induces pharmacological preconditioning in the rat heart in vivo via induction of PKC-ɛ and p38 MAPK

PubMed Central

Weber, Nina C; Toma, Octavian; Wolter, Jessica I; Obal, Detlef; Müllenheim, Jost; Preckel, Benedikt; Schlack, Wolfgang

2004-01-01

Xenon is an anesthetic with minimal hemodynamic side effects, making it an ideal agent for cardiocompromised patients. We investigated if xenon induces pharmacological preconditioning (PC) of the rat heart and elucidated the underlying molecular mechanisms. For infarct size measurements, anesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received either the anesthetic gas xenon, the volatile anesthetic isoflurane or as positive control ischemic preconditioning (IPC) during three 5-min periods before 25-min ischemia. Control animals remained untreated for 45 min. To investigate the involvement of protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK), rats were pretreated with the PKC inhibitor calphostin C (0.1 mg kg−1) or the p38 MAPK inhibitor SB203580 (1 mg kg−1). Additional hearts were excised for Western blot and immunohistochemistry. Infarct size was reduced from 50.9±16.7% in controls to 28.1±10.3% in xenon, 28.6±9.9% in isoflurane and to 28.5±5.4% in IPC hearts. Both, calphostin C and SB203580, abolished the observed cardioprotection after xenon and isoflurane administration but not after IPC. Immunofluorescence staining and Western blot assay revealed an increased phosphorylation and translocation of PKC-ɛ in xenon treated hearts. This effect could be blocked by calphostin C but not by SB203580. Moreover, the phosphorylation of p38 MAPK was induced by xenon and this effect was blocked by calphostin C. In summary, we demonstrate that xenon induces cardioprotection by PC and that activation of PKC-ɛ and its downstream target p38 MAPK are central molecular mechanisms involved. Thus, the results of the present study may contribute to elucidate the beneficial cardioprotective effects of this anesthetic gas. PMID:15644876

Low level tumor necrosis factor-alpha protects cardiomyocytes against high level tumor necrosis factor-alpha: brief insight into a beneficial paradox.

PubMed

Cacciapaglia, Fabio; Salvatorelli, Emanuela; Minotti, Giorgio; Afeltra, Antonella; Menna, Pierantonio

2014-12-01

Whether tumor necrosis factor-alpha (TNFα) caused beneficial or detrimental cardiovascular effects remains poorly defined. Anti-TNFα agents improved cardiac end points in chronic rheumatic diseases characterized by progressive deterioration of cardiac function. In contrast, anti-TNFα agents did not always improve but actually worsened cardiac function in non-rheumatic patients with heart failure (HF), in spite of that HF usually accompanies with high circulating levels of TNFα. To shed light on these mixed findings, we characterized the effects of TNFα in H9c2 cardiomyocytes. Cells were incubated for 24 h with increasing concentrations of TNFα, hydrogen peroxide, aminotriazole, or etoposide. Posttreatment cell viability was assessed by antimycin A-inhibitable reduction of 3-(4,dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and the IC50 value of each test compound was defined. H9c2 cells were also preconditioned with a low non-toxic concentration of TNFα and then re-challenged with increasing concentrations of TNFα and other stressor agents. In re-challenge experiments, all of the IC50 values increased significantly, with the IC50 value of TNFα increasing approximately 16-fold. TNFα preconditioning increased cardiomyocytes shedding of the external portion of transmembrane type 1 and type 2 TNFα receptors [(soluble TNFα receptors (sTNFR)]. Levels of survival-oriented soluble TNFR2 (sTNFR2) always exceeded those of death-oriented sTNFR1. When exposed to TNFα at its IC50 value, preconditioned cardiomyocytes showed an increased release of sTNFR2 but not sTNFR1. These results denoted that preconditioning by "low TNFα" helped cardiomyocyte to withstand toxicity from "high TNFα" or other agents. These results also suggested that beneficial or detrimental effects of anti-TNFα agents might well depend on whether these agents spared or intercepted discrete amounts of TNFα that preconditioned cardiomyocytes and made them more resistant to high concentrations of TNFα.

On polynomial preconditioning for indefinite Hermitian matrices

NASA Technical Reports Server (NTRS)

Freund, Roland W.

1989-01-01

The minimal residual method is studied combined with polynomial preconditioning for solving large linear systems (Ax = b) with indefinite Hermitian coefficient matrices (A). The standard approach for choosing the polynomial preconditioners leads to preconditioned systems which are positive definite. Here, a different strategy is studied which leaves the preconditioned coefficient matrix indefinite. More precisely, the polynomial preconditioner is designed to cluster the positive, resp. negative eigenvalues of A around 1, resp. around some negative constant. In particular, it is shown that such indefinite polynomial preconditioners can be obtained as the optimal solutions of a certain two parameter family of Chebyshev approximation problems. Some basic results are established for these approximation problems and a Remez type algorithm is sketched for their numerical solution. The problem of selecting the parameters such that the resulting indefinite polynomial preconditioners speeds up the convergence of minimal residual method optimally is also addressed. An approach is proposed based on the concept of asymptotic convergence factors. Finally, some numerical examples of indefinite polynomial preconditioners are given.

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?

PubMed

Schäfer, Richard; Spohn, Gabriele; Baer, Patrick C

2016-07-01

Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy.

Enhanced cell volume regulation: a key protective mechanism of ischemic preconditioning in rabbit ventricular myocytes.

PubMed

Diaz, Roberto J; Armstrong, Stephen C; Batthish, Michelle; Backx, Peter H; Ganote, Charles E; Wilson, Gregory J

2003-01-01

Accumulation of osmotically active metabolites, which create an osmotic gradient estimated at ~60 mOsM, and cell swelling are prominent features of ischemic myocardial cell death. This study tests the hypothesis that reduction of ischemic swelling by enhanced cell volume regulation is a key mechanism in the delay of ischemic myocardial cell death by ischemic preconditioning (IPC). Experimental protocols address whether: (i) IPC triggers a cell volume regulation mechanism that reduces cardiomyocyte swelling during subsequent index ischemia; (ii) this reduction in ischemic cell swelling is sufficient in magnitude to account for the IPC protection; (iii) the molecular mechanism that mediates IPC also mediates cell volume regulation. Two experimental models with rabbit ventricular myocytes were studied: freshly isolated pelleted myocytes and 48-h cultured myocytes. Myocytes were preconditioned either by distinct short simulated ischemia (SI)/simulated reperfusion protocols (IPC), or by subjecting myocytes to a pharmacological preconditioning (PPC) protocol (1 microM calyculin A, or 1 microM N(6)-2-(4-aminophenyl)ethyladenosine (APNEA), prior to subjecting them to either different durations of long SI or 30 min hypo-osmotic stress. Cell death (percent blue square myocytes) was monitored by trypan blue staining. Cell swelling was determined by either the bromododecane cell flotation assay (qualitative) or video/confocal microscopy (quantitative). Simulated ischemia induced myocyte swelling in both the models. In pelleted myocytes, IPC or PPC with either calyculin A or APNEA produced a marked reduction of ischemic cell swelling as determined by the cell floatation assay. In cultured myocytes, IPC substantially reduced ischemic cell swelling (P < 0.001). This IPC effect on ischemic cell swelling was related to an IPC and PPC (with APNEA) mediated triggering of cell volume regulatory decrease (RVD). IPC and APNEA also significantly (P < 0.001) reduced hypo-osmotic cell swelling. This IPC and APNEA effect was blocked by either adenosine receptor, PKC or Cl(-) channel inhibition. The osmolar equivalent for IPC protection approximated 50-60 mOsM, an osmotic gradient similar to the estimated ischemic osmotic load for preconditioned and non-preconditioned myocytes. The results suggest that cell volume regulation is a key mechanism that accounts for most of the IPC protection in cardiomyocytes.

Parallel iterative solution for h and p approximations of the shallow water equations

USGS Publications Warehouse

Barragy, E.J.; Walters, R.A.

1998-01-01

A p finite element scheme and parallel iterative solver are introduced for a modified form of the shallow water equations. The governing equations are the three-dimensional shallow water equations. After a harmonic decomposition in time and rearrangement, the resulting equations are a complex Helmholz problem for surface elevation, and a complex momentum equation for the horizontal velocity. Both equations are nonlinear and the resulting system is solved using the Picard iteration combined with a preconditioned biconjugate gradient (PBCG) method for the linearized subproblems. A subdomain-based parallel preconditioner is developed which uses incomplete LU factorization with thresholding (ILUT) methods within subdomains, overlapping ILUT factorizations for subdomain boundaries and under-relaxed iteration for the resulting block system. The method builds on techniques successfully applied to linear elements by introducing ordering and condensation techniques to handle uniform p refinement. The combined methods show good performance for a range of p (element order), h (element size), and N (number of processors). Performance and scalability results are presented for a field scale problem where up to 512 processors are used. ?? 1998 Elsevier Science Ltd. All rights reserved.

Molecular mechanisms of liver preconditioning

PubMed Central

Alchera, Elisa; Dal Ponte, Caterina; Imarisio, Chiara; Albano, Emanuele; Carini, Rita

2010-01-01

Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery. PMID:21182220

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.

An HCG-rich microenvironment contributes to ovarian cancer cell differentiation into endothelioid cells in a three-dimensional culture system.

PubMed

Su, Min; Fan, Chao; Gao, Sainan; Shen, Aiguo; Wang, Xiaoying; Zhang, Yuquan

2015-11-01

We investigated the expression of human chorionic gonadotropin (HCG) and its effects on vasculogenic mimicry (VM) formation in ovarian cancer cells under normoxic and hypoxic conditions in three-dimensional matrices preconditioned by an endothelial-trophoblast cell co-culture system. The co-culture model was established using human umbilical vein endothelial cells (HUVECs) and HTR-8 trophoblast cells in a three-dimensional culture system. The co-cultured cells were removed with NH4OH, and ovarian cancer cells were implanted into the preconditioned matrix. VM was identified morphologically and by detecting vascular markers expressed by cancer cells. The specificity of the effects of exogenous HCG in the microenvironment was assessed by inhibition with a neutralizing anti-HCG antibody. HCG siRNA was used to knock down endogenous HCG expression in OVCAR-3 ovarian cancer cells. HTR-8 cells 'fingerprinted' HUVECs to form capillary-like tube structures in co-cultures. In the preconditioned HCG-rich microenvironment, the number of vessel-like network structures formed by HCG receptor-positive OVCAR-3 cells and the expression levels of CD31, VEGF and factor VIII were significantly increased. The preconditioned HCG-rich microenvironment significantly increased the expression of hypoxia inducible factor-1α (HIF‑1α) and VM formation in OVCAR-3 cells under hypoxic conditions. Treatment with a neutralizing anti-HCG antibody but not HCG siRNA significantly inhibited the formation of vessel-like network structures. HCG in the microenvironment contributes to OVCAR-3 differentiation into endothelioid cells in three-dimensional matrices preconditioned with an endothelial-trophoblast cell co-culture system. HCG may synergistically enhance hypoxia-induced vascular markers and HIF-1α expression. These findings would provide perspectives on new therapeutic targets for ovarian cancer.

Comparison of bacterial attachment to platelet bags with and without preconditioning with plasma.

PubMed

Loza-Correa, M; Kalab, M; Yi, Q-L; Eltringham-Smith, L J; Sheffield, W P; Ramirez-Arcos, S

2017-07-01

Canadian Blood Services produces apheresis and buffy coat pooled platelet concentrates (PCs) stored in bags produced by two different manufacturers (A and B, respectively), both made of polyvinyl chloride-butyryl trihexyl citrate. This study was aimed at comparing Staphylococcus epidermidis adhesion to the inner surface of both bag types in the presence or absence of plasma factors. Sets (N = 2-6) of bags type A and B were left non-coated (control) or preconditioned with platelet-rich, platelet-poor or defibrinated plasma (PRP, PPP and DefibPPP, respectively). Each bag was inoculated with a 200-ml S. epidermidis culture adjusted to 0·5 colony-forming units/ml. Bags were incubated under platelet storage conditions for 7 days. After culture removal, bacteria attached to the plastic surface were either dislodged by sonication for bacterial quantification or examined in situ by scanning electron microscopy (SEM). Higher bacterial adhesion was observed to preconditioned PC bags than control containers for both bag types (P < 0·0001). Bacterial attachment to preconditioned bags was confirmed by SEM. Bacteria adhered equally to both types of containers in the presence of PRP, PPP and DefibPPP residues (P > 0·05). By contrast, a significant increase in bacterial adherence was observed to type A bags compared with type B bags in the absence of plasma (P < 0·05) [Correction added on 16 June 2017, after first online publication: this sentence has been corrected]. The ability of S. epidermidis to adhere to preconditioned platelet collection bags depends on the presence of plasma factors. Future efforts should be focused on reducing plasma proteins' attachment to platelet storage containers to decrease subsequent bacterial adhesion. © 2017 International Society of Blood Transfusion.

Role of Rbp1 in the acquired chill-light tolerance of cyanobacteria.

PubMed

Tan, Xiaoming; Zhu, Tao; Shen, Si; Yin, Chuntao; Gao, Hong; Xu, Xudong

2011-06-01

Synechocystis sp. strain PCC 6803 cultured at 30°C losses viability quickly under chill (5°C)-light stress but becomes highly tolerant to the stress after conditioning at 15°C (Y. Yang, C. Yin, W. Li, and X. Xu, J. Bacteriol. 190:1554-1560, 2008). Hypothetically, certain factors induced during preconditioning are involved in acquisition of chill-light tolerance. In this study, Rbp1 (RNA-binding protein 1) rather than Rbp2 was found to be accumulated during preconditioning, and the accumulation of Rbp1 was correlated with the increase of chill-light tolerance. Inactivation of its encoding gene rbp1 led to a great reduction in the acquired chill-light tolerance, while ectopic expression of rbp1 enabled the cyanobacterium to survive the chill-light stress without preconditioning. Microarray analyses suggested that the Rbp1-dependent chill-light tolerance may not be based on its influence on mRNA abundance of certain genes. Similarly to that in Synechocystis, the Rbp1 homologue(s) can be accumulated in Microcystis cells collected from a subtropic lake in low-temperature seasons. Rbp1 is the first factor shown to be both accumulated early during preconditioning and directly involved in development of chill-light tolerance in Synechocystis. Its accumulation may greatly enhance the overwintering capability in certain groups of cyanobacteria.

Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury

PubMed Central

Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I.

2015-01-01

Abstract Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3–only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

Hypoxic Preconditioning Promotes the Bioactivities of Mesenchymal Stem Cells via the HIF-1α-GRP78-Akt Axis.

PubMed

Lee, Jun Hee; Yoon, Yeo Min; Lee, Sang Hun

2017-06-21

Mesenchymal stem cells (MSC) are ideal materials for stem cell-based therapy. As MSCs reside in hypoxic microenvironments (low oxygen tension of 1% to 7%), several studies have focused on the beneficial effects of hypoxic preconditioning on MSC survival; however, the mechanisms underlying such effects remain unclear. This study aimed to uncover the potential mechanism involving 78-kDa glucose-regulated protein (GRP78) to explain the enhanced MSC bioactivity and survival in hindlimb ischemia. Under hypoxia (2% O₂), the expression of GRP78 was significantly increased via hypoxia-inducible factor (HIF)-1α. Hypoxia-induced GRP78 promoted the proliferation and migration potential of MSCs through the HIF-1α-GRP78-Akt signal axis. In a murine hind-limb ischemia model, hypoxic preconditioning enhanced the survival and proliferation of transplanted MSCs through suppression of the cell death signal pathway and augmentation of angiogenic cytokine secretion. These effects were regulated by GRP78. Our findings indicate that hypoxic preconditioning promotes survival, proliferation, and angiogenic cytokine secretion of MSCs via the HIF-1α-GRP78-Akt signal pathway, suggesting that hypoxia-preconditioned MSCs might provide a therapeutic strategy for MSC-based therapies and that GRP78 represents a potential target for the development of functional MSCs.

Blocking and the detection of odor components in blends.

PubMed

Hosler, J S; Smith, B H

2000-09-01

Recent studies of olfactory blocking have revealed that binary odorant mixtures are not always processed as though they give rise to mixture-unique configural properties. When animals are conditioned to one odorant (A) and then conditioned to a mixture of that odorant with a second (X), the ability to learn or express the association of X with reinforcement appears to be reduced relative to animals that were not preconditioned to A. A recent model of odor-based response patterns in the insect antennal lobe predicts that the strength of the blocking effect will be related to the perceptual similarity between the two odorants, i.e. greater similarity should increase the blocking effect. Here, we test that model in the honeybee Apis mellifera by first establishing a generalization matrix for three odorants and then testing for blocking between all possible combinations of them. We confirm earlier findings demonstrating the occurrence of the blocking effect in olfactory learning of compound stimuli. We show that the occurrence and the strength of the blocking effect depend on the odorants used in the experiment. In addition, we find very good agreement between our results and the model, and less agreement between our results and an alternative model recently proposed to explain the effect.

Korean Affairs Report

DTIC Science & Technology

1986-03-26

with the "outrageous" measures recently taken by the police to block its headquarters, Floor leader Kim Tong- yong of the party said that he expects the... Kims on the party as a precondition, is too wide. In the wake of his recent meetings with Kim Yong -sam, Yi Min-u, and Kim Sang- hyon, Cho is...Initial police investigation showed that Yi was hit by a 50cm-long wooden bar carried by Yim Yong -chol, 23, a junior. Police apprehended Yim, Miss Kim

Mesenchymal Stem/Stromal Cells in Regenerative Medicine: Can Preconditioning Strategies Improve Therapeutic Efficacy?

PubMed Central

Schäfer, Richard; Spohn, Gabriele; Baer, Patrick C.

2016-01-01

Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for the development of cell therapeutics in regenerative medicine. Featuring immunomodulatory potential as well as secreting a variety of trophic factors, MSCs showed remarkable therapeutic effects in numerous preclinical disease models. However, sustainable translation of MSC therapies to the clinic is hampered by heterogeneity of MSCs and non-standardized in vitro culture technologies. Moreover, potent MSC therapeutics require MSCs with maximum regenerative capacity. There is growing evidence that in vitro preconditioning strategies of MSCs can optimize their therapeutic potential. In the following we will discuss achievements and challenges of the development of MSC therapies in regenerative medicine highlighting specific in vitro preconditioning strategies prior to cell transplantation to increase their therapeutic efficacy. PMID:27721701

Endoplasmic reticulum stress preconditioning attenuates methylmercury-induced cellular damage by inducing favorable stress responses

PubMed Central

Usuki, Fusako; Fujimura, Masatake; Yamashita, Akio

2013-01-01

We demonstrate that methylmercury (MeHg)-susceptible cells preconditioned with an inhibitor of endoplasmic reticulum (ER) Ca2+-ATPase, thapsigargin, showed resistance to MeHg cytotoxicity through favorable stress responses, which included phosphorylation of eukaryotic initiation factor 2 alpha (Eif2α), accumulation of activating transcription factor 4 (Atf4), upregulation of stress-related proteins, and activation of extracellular signal regulated kinase pathway. In addition, ER stress preconditioning induced suppression of nonsense-mediated mRNA decay (NMD) mainly through the phospho-Eif2α-mediated general suppression of translation initiation and possible combined effects of decreased several NMD components expression. Atf4 accumulation was not mediated by NMD inhibition but translation inhibition of its upstream open reading frame (uORF) and translation facilitation of its protein-coding ORF by the phospho-Eif2α. These results suggested that ER stress plays an important role in MeHg cytotoxicity and that the modulation of ER stress has therapeutic potential to attenuate MeHg cytotoxicity, the underlying mechanism being the induction of integrated stress responses. PMID:23907635

Identifying hydrological pre-conditions and rainfall triggers of slope failures for 2014 storm events in the Ialomita Subcarpathians, Romania

NASA Astrophysics Data System (ADS)

Chitu, Zenaida; Bogaard, Thom; Busuioc, Aristita; Burcea, Sorin; Adler, Mary-Jeanne; Sandric, Ionut

2015-04-01

Like in many parts of the world, in Romania, landslides represent recurrent phenomena that produce numerous damages to infrastructure every few years. Various studies on landslide occurrence in the Curvature Subcarpathians reveal that rainfall represents the most important triggering factor for landslides. Depending on rainfall characteristics and environmental factors different types of landslides were recorded in the Ialomita Subcarpathians: slumps, earthflows and complex landslides. This area, located in the western part of Curvature Subcarpathians, is characterized by a very complex geology whose main features are represented by the nappes system, the post tectonic covers, the diapirism phenomena and vertical faults. This work aims to investigate hydrological pre-conditions and rainfall characteristics which triggered slope failures in 2014 in the Ialomita Subcarpathians, Romania. Hydrological pre-conditions were investigated by means of water balance analysis and low flow techniques, while spatial and temporal patterns of rainfalls were estimated using radar data and six rain gauges. Additionally, six soil moisture stations that are fitted with volumetric soil moisture sensors and temperature soil sensors were used to estimate the antecedent soil moisture conditions.

A fast, preconditioned conjugate gradient Toeplitz solver

NASA Technical Reports Server (NTRS)

Pan, Victor; Schrieber, Robert

1989-01-01

A simple factorization is given of an arbitrary hermitian, positive definite matrix in which the factors are well-conditioned, hermitian, and positive definite. In fact, given knowledge of the extreme eigenvalues of the original matrix A, an optimal improvement can be achieved, making the condition numbers of each of the two factors equal to the square root of the condition number of A. This technique is to applied to the solution of hermitian, positive definite Toeplitz systems. Large linear systems with hermitian, positive definite Toeplitz matrices arise in some signal processing applications. A stable fast algorithm is given for solving these systems that is based on the preconditioned conjugate gradient method. The algorithm exploits Toeplitz structure to reduce the cost of an iteration to O(n log n) by applying the fast Fourier Transform to compute matrix-vector products. Matrix factorization is used as a preconditioner.

Disruption of model-based behavior and learning by cocaine self-administration in rats.

PubMed

Wied, Heather M; Jones, Joshua L; Cooch, Nisha K; Berg, Benjamin A; Schoenbaum, Geoffrey

2013-10-01

Addiction is characterized by maladaptive decision-making, in which individuals seem unable to use adverse outcomes to modify their behavior. Adverse outcomes are often infrequent, delayed, and even rare events, especially when compared to the reliable rewarding drug-associated outcomes. As a result, recognizing and using information about their occurrence put a premium on the operation of so-called model-based systems of behavioral control, which allow one to mentally simulate outcomes of different courses of action based on knowledge of the underlying associative structure of the environment. This suggests that addiction may reflect, in part, drug-induced dysfunction in these systems. Here, we tested this hypothesis. This study aimed to test whether cocaine causes deficits in model-based behavior and learning independent of requirements for response inhibition or perception of costs or punishment. We trained rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the rats began training on a sensory preconditioning and inferred value blocking task. Like devaluation, normal performance on this task requires representations of the underlying task structure; however, unlike devaluation, it does not require either response inhibition or adapting behavior to reflect aversive outcomes. Rats trained to self-administer cocaine failed to show conditioned responding or blocking to the preconditioned cue. These deficits were not observed in sucrose-trained rats nor did they reflect any changes in responding to cues paired directly with reward. These results imply that cocaine disrupts the operation of neural circuits that mediate model-based behavioral control.

Preconditioned conjugate-gradient methods for low-speed flow calculations

NASA Technical Reports Server (NTRS)

Ajmani, Kumud; Ng, Wing-Fai; Liou, Meng-Sing

1993-01-01

An investigation is conducted into the viability of using a generalized Conjugate Gradient-like method as an iterative solver to obtain steady-state solutions of very low-speed fluid flow problems. Low-speed flow at Mach 0.1 over a backward-facing step is chosen as a representative test problem. The unsteady form of the two dimensional, compressible Navier-Stokes equations is integrated in time using discrete time-steps. The Navier-Stokes equations are cast in an implicit, upwind finite-volume, flux split formulation. The new iterative solver is used to solve a linear system of equations at each step of the time-integration. Preconditioning techniques are used with the new solver to enhance the stability and convergence rate of the solver and are found to be critical to the overall success of the solver. A study of various preconditioners reveals that a preconditioner based on the Lower-Upper Successive Symmetric Over-Relaxation iterative scheme is more efficient than a preconditioner based on Incomplete L-U factorizations of the iteration matrix. The performance of the new preconditioned solver is compared with a conventional Line Gauss-Seidel Relaxation (LGSR) solver. Overall speed-up factors of 28 (in terms of global time-steps required to converge to a steady-state solution) and 20 (in terms of total CPU time on one processor of a CRAY-YMP) are found in favor of the new preconditioned solver, when compared with the LGSR solver.

Preconditioned Conjugate Gradient methods for low speed flow calculations

NASA Technical Reports Server (NTRS)

Ajmani, Kumud; Ng, Wing-Fai; Liou, Meng-Sing

1993-01-01

An investigation is conducted into the viability of using a generalized Conjugate Gradient-like method as an iterative solver to obtain steady-state solutions of very low-speed fluid flow problems. Low-speed flow at Mach 0.1 over a backward-facing step is chosen as a representative test problem. The unsteady form of the two dimensional, compressible Navier-Stokes equations are integrated in time using discrete time-steps. The Navier-Stokes equations are cast in an implicit, upwind finite-volume, flux split formulation. The new iterative solver is used to solve a linear system of equations at each step of the time-integration. Preconditioning techniques are used with the new solver to enhance the stability and the convergence rate of the solver and are found to be critical to the overall success of the solver. A study of various preconditioners reveals that a preconditioner based on the lower-upper (L-U)-successive symmetric over-relaxation iterative scheme is more efficient than a preconditioner based on incomplete L-U factorizations of the iteration matrix. The performance of the new preconditioned solver is compared with a conventional line Gauss-Seidel relaxation (LGSR) solver. Overall speed-up factors of 28 (in terms of global time-steps required to converge to a steady-state solution) and 20 (in terms of total CPU time on one processor of a CRAY-YMP) are found in favor of the new preconditioned solver, when compared with the LGSR solver.

Flagellin preconditioning enhances the efficacy of mesenchymal stem cells in an irradiation-induced proctitis model.

PubMed

Linard, Christine; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Benderitter, Marc

2016-09-01

The success of mesenchymal stem cell transplantation for proctitis depends not only on cell donors but also on host microenvironmental factors, which play a major role in conditioning mesenchymal stem cell immunosuppressive action and repair. This study sought to determine if flagellin, a TLR5 ligand, can enhance the mesenchymal stem cell treatment efficacy in radiation-induced proctitis. With the use of a colorectal model of 27 Gy irradiation in rats, we investigated and compared the effects on immune capacity and remodeling at 28 d after irradiation of the following: 1) systemic mesenchymal stem cell (5 × 10(6)) administration at d 7 after irradiation, 2) administration of flagellin at d 3 and systemic mesenchymal stem cell administration at d 7, and 3) in vitro preconditioning of mesenchymal stem cells with flagellin, 24 h before their administration on d 7. The mucosal CD8(+) T cell population was normalized after treatment with flagellin-preconditioned mesenchymal stem cells or flagellin plus mesenchymal stem cells, whereas mesenchymal stem cells alone did not alter the radiation-induced elevation of CD8(+) T cell frequency. Mesenchymal stem cell treatment returned the irradiation-elevated frequency of CD25(+) cells in the mucosa-to-control levels, whereas both flagellin-preconditioned mesenchymal stem cell and flagellin-plus-mesenchymal stem cell treatment each significantly increased not only CD25(+) cell frequency but also forkhead box p3 and IL-2Rα expression. Specifically, IL-10 was overexpressed after flagellin-preconditioned mesenchymal stem cell treatment. Analysis of collagen expression showed that the collagen type 1/collagen type 3 ratio, an indicator of wound-healing maturation, was low in the irradiated and mesenchymal stem cell-treated groups and returned to the normal level only after the flagellin-preconditioned mesenchymal stem cell treatment. This was associated with a reduction in myofibroblast accumulation. In a proctitis model, flagellin-preconditioned mesenchymal stem cells improved colonic immune capacity and enhanced tissue remodeling. © Society for Leukocyte Biology.

[Protection and its mechanism of catechin morphon on hypoxia-reoxygenation [corrected] induced injury in myocardial cells].

PubMed

Ye, Jin-Xia; Wang, Lan; Liang, Ri-Xin; Yang, Bin

2008-04-01

To observe the protective effects of catechin morphon (GCG and EGCG) on hypoxia-reoxygenation induced injury in myocardial cells and to explore the mechanisms. In cultured neonatal rat cardiomyocytes, we investigated the preconditioning protection by GCG and EGCG on the spontaneous beating, the survival rate, the release of LDH, MDA, SOD, GSH-Px and the ATP enzyme activity of cardiomyocyte cellular membrane in cultured rat cardiomyocytes treated during the reoxygenation 1h following hypoxia 3 h. The blocking agent of protien kinase C staurosporine (10 nmol x L(-1)) or the deactivator of Gi/o protein pertussis toxin (PTX, 200 microg x mL(-1)) were added before the catechin treatment. Preconditioning by GCG and EGCG increased the spontaneous beating and the survival rate, and decreased the release of LDH and MDA with the rise of SOD and ATP enzyme activity. Inhibition of PKC by staurosporine and Gi/o protein by PTX abolished the protection by catechin with the reduction of the beating, survival rate and activity of SOD, and the increase of the release of LDH and MDA. The results indicated that the activation of signal transduction pathway from PKC and Gi/o protein seemed to be involved in the cardioprotection of preconditioning by GCG and EGCG. The protection by GCG and EGCG on hypoxia-reoxygenation injury in cultured neonatal rat cardiomyocytes is found, which is related with scavenging of free radicals, and PKC Gi/o signal transduction pathway.

Multigrid and Krylov Subspace Methods for the Discrete Stokes Equations

NASA Technical Reports Server (NTRS)

Elman, Howard C.

1996-01-01

Discretization of the Stokes equations produces a symmetric indefinite system of linear equations. For stable discretizations, a variety of numerical methods have been proposed that have rates of convergence independent of the mesh size used in the discretization. In this paper, we compare the performance of four such methods: variants of the Uzawa, preconditioned conjugate gradient, preconditioned conjugate residual, and multigrid methods, for solving several two-dimensional model problems. The results indicate that where it is applicable, multigrid with smoothing based on incomplete factorization is more efficient than the other methods, but typically by no more than a factor of two. The conjugate residual method has the advantage of being both independent of iteration parameters and widely applicable.

Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway.

PubMed

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu; Ding, Xiaoqiang

2015-07-01

Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Experimental animal investigation. University research laboratory. Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20-25 g. We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide-induced acute kidney injury. Our findings demonstrated that xenon preconditioning protected against lipopolysaccharide-induced acute kidney injury via activation of miR-21 target signaling pathways.

An Empirical Evaluation of Factor Reliability.

ERIC Educational Resources Information Center

Jackson, Douglas N.; Morf, Martin E.

The psychometric reliability of a factor, defined as its generalizability across samples drawn from the same population of tests, is considered as a necessary precondition for the scientific meaningfulness of factor analytic results. A solution to the problem of generalizability is illustrated empirically on data from a set of tests designed to…

Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling

PubMed Central

Wittig, Christine; Scheuer, Claudia; Parakenings, Julia; Menger, Michael D.; Laschke, Matthias W.

2015-01-01

Geraniol exerts several direct pharmacological effects on tumor cells and, thus, has been suggested as a promising anti-cancer compound. Because vascularization is a major precondition for tumor growth, we analyzed in this study the anti-angiogenic action of geraniol. In vitro, geraniol reduced the migratory activity of endothelial-like eEND2 cells. Western blot analyses further revealed that geraniol downregulates proliferating cell nuclear antigen (PCNA) and upregulates cleaved caspase-3 (Casp-3) expression in eEND2 cells. Moreover, geraniol blocked vascular endothelial growth factor (VEGF)/VEGFR-2 signal transduction, resulting in a suppression of downstream AKT and ERK signaling pathways. In addition, geraniol significantly reduced vascular sprout formation in a rat aortic ring assay. In vivo, geraniol inhibited the vascularization of CT26 tumors in dorsal skinfold chambers of BALB/c mice, which was associated with a smaller tumor size when compared to vehicle-treated controls. Immunohistochemical analyses confirmed a decreased number of Ki67-positive cells and CD31-positive microvessels with reduced VEGFR-2 expression within geraniol-treated tumors. Taken together, these findings indicate that geraniol targets multiple angiogenic mechanisms and, therefore, is an attractive candidate for the anti-angiogenic treatment of tumors. PMID:26154255

Geraniol Suppresses Angiogenesis by Downregulating Vascular Endothelial Growth Factor (VEGF)/VEGFR-2 Signaling.

PubMed

Wittig, Christine; Scheuer, Claudia; Parakenings, Julia; Menger, Michael D; Laschke, Matthias W

2015-01-01

Geraniol exerts several direct pharmacological effects on tumor cells and, thus, has been suggested as a promising anti-cancer compound. Because vascularization is a major precondition for tumor growth, we analyzed in this study the anti-angiogenic action of geraniol. In vitro, geraniol reduced the migratory activity of endothelial-like eEND2 cells. Western blot analyses further revealed that geraniol downregulates proliferating cell nuclear antigen (PCNA) and upregulates cleaved caspase-3 (Casp-3) expression in eEND2 cells. Moreover, geraniol blocked vascular endothelial growth factor (VEGF)/VEGFR-2 signal transduction, resulting in a suppression of downstream AKT and ERK signaling pathways. In addition, geraniol significantly reduced vascular sprout formation in a rat aortic ring assay. In vivo, geraniol inhibited the vascularization of CT26 tumors in dorsal skinfold chambers of BALB/c mice, which was associated with a smaller tumor size when compared to vehicle-treated controls. Immunohistochemical analyses confirmed a decreased number of Ki67-positive cells and CD31-positive microvessels with reduced VEGFR-2 expression within geraniol-treated tumors. Taken together, these findings indicate that geraniol targets multiple angiogenic mechanisms and, therefore, is an attractive candidate for the anti-angiogenic treatment of tumors.

Preconditioning potential of purmorphamine: a hedgehog activator against ischaemic reperfusion injury in ovariectomised rat heart.

PubMed

Sharma, Shweta; Kaur, Avileen; Sharma, Saurabh

2018-04-01

The present study was been designed to investigate the role and pharmacological potential of hedgehog in oestrogen-deficient rat heart. Oestrogen deficiency was produced in female Wistar rats by the surgical removal of both ovaries and these animals were used four weeks later. Isolated rat heart was subjected to 30 min ischaemia followed by 120 min of reperfusion (I/R). The heart was subjected to pharmacological preconditioning with the hedgehog agonist purmorphamine (1μM) and GDC-0449, a hedgehog antagonist, in the last episode of reperfusion before I/R. Myocardial infarction was assessed in terms of the increase in lactate dehydrogenase (LDH), creatinine kinase-MB (CK-MB), myeloperoxidase (MPO) level and infarct size (triphenyltetrazolium chloride staining). Immunohistochemistry analysis was done for the assessment of tumour necrosis factor (TNF)-α level in cardiac tissue. eNOS expression was estimated by rt-PCR. Pharmacological preconditioning with purmorphamine significantly attenuated I/R-induced myocardial infarction, TNF-α, MPO level and release of LDH and CK-MB compared to the I/R control group. However, GDC-0449 prevented the ameliorative preconditioning effect of estradiol. It may be concluded that the hedgehog agonist purmorphamine prevents the ovariectomised heart from ischaemic reperfusion injury.

Domain decomposition methods for the parallel computation of reacting flows

NASA Technical Reports Server (NTRS)

Keyes, David E.

1988-01-01

Domain decomposition is a natural route to parallel computing for partial differential equation solvers. Subdomains of which the original domain of definition is comprised are assigned to independent processors at the price of periodic coordination between processors to compute global parameters and maintain the requisite degree of continuity of the solution at the subdomain interfaces. In the domain-decomposed solution of steady multidimensional systems of PDEs by finite difference methods using a pseudo-transient version of Newton iteration, the only portion of the computation which generally stands in the way of efficient parallelization is the solution of the large, sparse linear systems arising at each Newton step. For some Jacobian matrices drawn from an actual two-dimensional reacting flow problem, comparisons are made between relaxation-based linear solvers and also preconditioned iterative methods of Conjugate Gradient and Chebyshev type, focusing attention on both iteration count and global inner product count. The generalized minimum residual method with block-ILU preconditioning is judged the best serial method among those considered, and parallel numerical experiments on the Encore Multimax demonstrate for it approximately 10-fold speedup on 16 processors.

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

PubMed Central

Licht, Tamar; Rothe, Gadiel; Kreisel, Tirzah; Wolf, Brachi; Benny, Ofra; Rooney, Alasdair G.; ffrench-Constant, Charles; Enikolopov, Grigori; Keshet, Eli

2016-01-01

Several factors are known to enhance adult hippocampal neurogenesis but a factor capable of inducing a long-lasting neurogenic enhancement that attenuates age-related neurogenic decay has not been described. Here, we studied hippocampal neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to proceed at a markedly elevated level for many months later. Continual neurogenic increase over several months was not accompanied by accelerated exhaustion of the neuronal stem cell (NSC) reserve, thereby allowing neurogenesis to proceed at a markedly elevated rate also in old mice. Neurogenic enhancement by VEGF preconditioning was, in part, attributed to rescue of age-related NSC quiescence. Remarkably, VEGF caused extensive NSC remodelling manifested in transition of the enigmatic NSC terminal arbor onto long cytoplasmic processes engaging with and spreading over even remote blood vessels, a configuration reminiscent of early postnatal “juvenile” NSCs. Together, these findings suggest that VEGF preconditioning might be harnessed for long-term neurogenic enhancement despite continued exposure to an “aged” systemic milieu. PMID:27849577

Preconditioning 2D Integer Data for Fast Convex Hull Computations.

PubMed

Cadenas, José Oswaldo; Megson, Graham M; Luengo Hendriks, Cris L

2016-01-01

In order to accelerate computing the convex hull on a set of n points, a heuristic procedure is often applied to reduce the number of points to a set of s points, s ≤ n, which also contains the same hull. We present an algorithm to precondition 2D data with integer coordinates bounded by a box of size p × q before building a 2D convex hull, with three distinct advantages. First, we prove that under the condition min(p, q) ≤ n the algorithm executes in time within O(n); second, no explicit sorting of data is required; and third, the reduced set of s points forms a simple polygonal chain and thus can be directly pipelined into an O(n) time convex hull algorithm. This paper empirically evaluates and quantifies the speed up gained by preconditioning a set of points by a method based on the proposed algorithm before using common convex hull algorithms to build the final hull. A speedup factor of at least four is consistently found from experiments on various datasets when the condition min(p, q) ≤ n holds; the smaller the ratio min(p, q)/n is in the dataset, the greater the speedup factor achieved.

40 CFR 80.52 - Vehicle preconditioning.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 17 2013-07-01 2013-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed in...

40 CFR 80.52 - Vehicle preconditioning.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed in...

40 CFR 80.52 - Vehicle preconditioning.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 17 2014-07-01 2014-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed in...

40 CFR 80.52 - Vehicle preconditioning.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 17 2012-07-01 2012-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed in...

40 CFR 80.52 - Vehicle preconditioning.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Vehicle preconditioning. 80.52 Section...) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.52 Vehicle preconditioning. (a) Initial vehicle preconditioning and preconditioning between tests with different fuels shall be performed in...

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

PubMed

Mitchell, Duane A; Batich, Kristen A; Gunn, Michael D; Huang, Min-Nung; Sanchez-Perez, Luis; Nair, Smita K; Congdon, Kendra L; Reap, Elizabeth A; Archer, Gary E; Desjardins, Annick; Friedman, Allan H; Friedman, Henry S; Herndon, James E; Coan, April; McLendon, Roger E; Reardon, David A; Vredenburgh, James J; Bigner, Darell D; Sampson, John H

2015-03-19

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.

Tetanus toxoid and CCL3 improve DC vaccines in mice and glioblastoma patients

PubMed Central

Mitchell, Duane A.; Batich, Kristen A.; Gunn, Michael D.; Huang, Min-Nung; Sanchez-Perez, Luis; Nair, Smita K.; Congdon, Kendra L.; Reap, Elizabeth A.; Archer, Gary E.; Desjardins, Annick; Friedman, Allan H.; Friedman, Henry S.; Herndon, James E.; Coan, April; McLendon, Roger E.; Reardon, David A.; Vredenburgh, James J.; Bigner, Darell D.; Sampson, John H.

2015-01-01

Upon stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses1. As such, autologous DCs generated ex vivo have been pulsed with tumor antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers2–4 including glioblastoma (GBM),5–7 the factors dictating DC vaccine efficacy remain poorly understood. Here we demonstrate that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DCs. To assess the impact of vaccine site pre-conditioning in humans, we randomized patients with GBM to pre-conditioning with mature DCs8 or Td unilaterally before bilateral vaccination with Cytomegalovirus pp65 RNA-pulsed DCs. We and other laboratories have shown that pp65 is expressed in > 90% of GBM specimens but not surrounding normal brain9–12, providing an unparalleled opportunity to subvert this viral protein as a tumor-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve antitumor immunotherapy. PMID:25762141

The biomechanical strength of a hardware-free femoral press-fit method for ACL bone-tendon-bone graft fixation.

PubMed

Arnold, M P; Burger, L D; Wirz, D; Goepfert, B; Hirschmann, M T

2017-04-01

The purpose was to investigate graft slippage and ultimate load to failure of a femoral press-fit fixation technique for anterior cruciate ligament (ACL) reconstruction. Nine fresh-frozen knees were used. Standardized harvesting of the B-PT-B graft was performed. The femora were cemented into steel rods, and a tunnel was drilled outside-in into the native ACL footprint and expanded using a manual mill bit. The femoral bone block was fixed press-fit. To pull the free end of the graft, it was fixed to a mechanical testing machine using a deep-freezing technique. A motion capture system was used to assess three-dimensional micro-motion. After preconditioning of the graft, 1000 cycles of tensile loading were applied. Finally, an ultimate load to failure test was performed. Graft slippage in mm ultimate load to failure as well as type of failure was noted. In six of the nine measured specimens, a typical pattern of graft slippage was observed during cyclic loading. For technical reasons, the results of three knees had to be discarded. 78.6 % of total graft slippage occurred in the first 100 cycles. Once the block had settled, graft slippage converged to zero, highlighting the importance of initial preconditioning of the graft in the clinical setting. Graft slippage after 1000 cycles varied around 3.4 ± 3.2 mm (R = 1.3-9.8 mm) between the specimens. Ultimate loading (n = 9) revealed two characteristic patterns of failure. In four knees, the tendon ruptured, while in five knees the bone block was pulled out of the femoral tunnel. The median ultimate load to failure was 852 N (R = 448-1349 N). The implant-free femoral press-fit fixation provided adequate primary stability with ultimate load to failure pull forces at least equal to published results for interference screws; hence, its clinical application is shown to be safe.

Technical note: Avoiding the direct inversion of the numerator relationship matrix for genotyped animals in single-step genomic best linear unbiased prediction solved with the preconditioned conjugate gradient.

PubMed

Masuda, Y; Misztal, I; Legarra, A; Tsuruta, S; Lourenco, D A L; Fragomeni, B O; Aguilar, I

2017-01-01

This paper evaluates an efficient implementation to multiply the inverse of a numerator relationship matrix for genotyped animals () by a vector (). The computation is required for solving mixed model equations in single-step genomic BLUP (ssGBLUP) with the preconditioned conjugate gradient (PCG). The inverse can be decomposed into sparse matrices that are blocks of the sparse inverse of a numerator relationship matrix () including genotyped animals and their ancestors. The elements of were rapidly calculated with the Henderson's rule and stored as sparse matrices in memory. Implementation of was by a series of sparse matrix-vector multiplications. Diagonal elements of , which were required as preconditioners in PCG, were approximated with a Monte Carlo method using 1,000 samples. The efficient implementation of was compared with explicit inversion of with 3 data sets including about 15,000, 81,000, and 570,000 genotyped animals selected from populations with 213,000, 8.2 million, and 10.7 million pedigree animals, respectively. The explicit inversion required 1.8 GB, 49 GB, and 2,415 GB (estimated) of memory, respectively, and 42 s, 56 min, and 13.5 d (estimated), respectively, for the computations. The efficient implementation required <1 MB, 2.9 GB, and 2.3 GB of memory, respectively, and <1 sec, 3 min, and 5 min, respectively, for setting up. Only <1 sec was required for the multiplication in each PCG iteration for any data sets. When the equations in ssGBLUP are solved with the PCG algorithm, is no longer a limiting factor in the computations.

Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning

PubMed Central

Khaliulin, Igor; Parker, Joanna E.; Halestrap, Andrew P.

2010-01-01

Aims Temperature preconditioning (TP) provides very powerful protection against ischaemia/reperfusion. Understanding the signalling pathways involved may enable the development of effective pharmacological cardioprotection. We investigated the interrelationship between activation of protein kinase A (PKA) and protein kinase C (PKC) in the signalling mechanisms of TP and developed a potent pharmacological intervention based on this mechanism. Methods and results Isolated rat hearts were subjected to TP, 30 min global ischaemia, and 60 min reperfusion. Other control and TP hearts were perfused with either sotalol (β-adrenergic blocker) or H-89 (PKA inhibitor). Some hearts were pre-treated with either isoproterenol (β-adrenergic agonist) or adenosine (PKC activator) that were given alone, simultaneously, or sequentially. Pre-treatment with isoproterenol, adenosine, and the consecutive isoproterenol/adenosine treatment was also combined with the PKC inhibitor chelerythrine. Cardioprotection was evaluated by haemodynamic function recovery, lactate dehydrogenase release, measurement of mitochondrial permeability transition pore opening, and protein carbonylation during reperfusion. Cyclic AMP and PKA activity were increased in TP hearts. H-89 and sotalol blocked the cardioprotective effect of TP and TP-induced PKC activation. Isoproterenol, adenosine, and the consecutive treatment increased PKC activity during pre-ischaemia. Isoproterenol significantly reduced myocardial glycogen content. Isoproterenol and adenosine, alone or simultaneously, protected hearts but the consecutive treatment gave the highest protection. Cardioprotective effects of adenosine were completely blocked by chelerythrine but those of the consecutive treatment only attenuated. Conclusion The signal transduction pathway of TP involves PKA activation that precedes PKC activation. Pharmacologically induced consecutive PKA/PKC activation mimics TP and induces extremely potent cardioprotection. PMID:20558443

Pre-Conditions for Staff Development.

ERIC Educational Resources Information Center

Urick, Ronald V.; And Others

1981-01-01

Describes a short-term intervention program, the Awareness, Readiness, and Commitment (ARC) workshop, that provides the opportunity for school staffs to explore factors that have utility for effective change. (Author/MLF)

Algorithm and Application of Gcp-Independent Block Adjustment for Super Large-Scale Domestic High Resolution Optical Satellite Imagery

NASA Astrophysics Data System (ADS)

Sun, Y. S.; Zhang, L.; Xu, B.; Zhang, Y.

2018-04-01

The accurate positioning of optical satellite image without control is the precondition for remote sensing application and small/medium scale mapping in large abroad areas or with large-scale images. In this paper, aiming at the geometric features of optical satellite image, based on a widely used optimization method of constraint problem which is called Alternating Direction Method of Multipliers (ADMM) and RFM least-squares block adjustment, we propose a GCP independent block adjustment method for the large-scale domestic high resolution optical satellite image - GISIBA (GCP-Independent Satellite Imagery Block Adjustment), which is easy to parallelize and highly efficient. In this method, the virtual "average" control points are built to solve the rank defect problem and qualitative and quantitative analysis in block adjustment without control. The test results prove that the horizontal and vertical accuracy of multi-covered and multi-temporal satellite images are better than 10 m and 6 m. Meanwhile the mosaic problem of the adjacent areas in large area DOM production can be solved if the public geographic information data is introduced as horizontal and vertical constraints in the block adjustment process. Finally, through the experiments by using GF-1 and ZY-3 satellite images over several typical test areas, the reliability, accuracy and performance of our developed procedure will be presented and studied in this paper.

An approximate block Newton method for coupled iterations of nonlinear solvers: Theory and conjugate heat transfer applications

NASA Astrophysics Data System (ADS)

Yeckel, Andrew; Lun, Lisa; Derby, Jeffrey J.

2009-12-01

A new, approximate block Newton (ABN) method is derived and tested for the coupled solution of nonlinear models, each of which is treated as a modular, black box. Such an approach is motivated by a desire to maintain software flexibility without sacrificing solution efficiency or robustness. Though block Newton methods of similar type have been proposed and studied, we present a unique derivation and use it to sort out some of the more confusing points in the literature. In particular, we show that our ABN method behaves like a Newton iteration preconditioned by an inexact Newton solver derived from subproblem Jacobians. The method is demonstrated on several conjugate heat transfer problems modeled after melt crystal growth processes. These problems are represented by partitioned spatial regions, each modeled by independent heat transfer codes and linked by temperature and flux matching conditions at the boundaries common to the partitions. Whereas a typical block Gauss-Seidel iteration fails about half the time for the model problem, quadratic convergence is achieved by the ABN method under all conditions studied here. Additional performance advantages over existing methods are demonstrated and discussed.

Preconditioning with cations increases the attachment of Anoxybacillus flavithermus and Geobacillus species to stainless steel.

PubMed

Somerton, Ben; Flint, Steve; Palmer, Jon; Brooks, John; Lindsay, Denise

2013-07-01

Preconditioning of Anoxybacillus flavithermus E16 and Geobacillus sp. strain F75 with cations prior to attachment often significantly increased (P ≤ 0.05) the number of viable cells that attached to stainless steel (by up to 1.5 log CFU/cm(2)) compared with unconditioned bacteria. It is proposed that the transition of A. flavithermus and Geobacillus spp. from milk formulations to stainless steel product contact surfaces in milk powder manufacturing plants is mediated predominantly by bacterial physiological factors (e.g., surface-exposed adhesins) rather than the concentrations of cations in milk formulations surrounding bacteria.

Involvement of Erythropoietin in Retinal Ischemic Preconditioning

PubMed Central

Dreixler, John C.; Hagevik, Sarah; Hemmert, Jonathan W.; Shaikh, Afzhal R.; Rosenbaum, Daniel M.; Roth, Steven

2009-01-01

Background The purpose of this study was to examine the role of erythropoietin in retinal ischemic preconditioning (IPC). Methods Rats were subjected to retinal ischemia after IPC. Electroretinography assessed functional recovery after ischemia; retinal sections were examined to determine loss of retinal ganglion cells, and Terminal Deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling was used to assess apoptosis. Levels of downstream mediators were measured in retinal homogenates by Western blotting. To assess the involvement of erythropoietin in IPC, we measured levels of erythropoietin and its receptor (EPO-R) in retinal homogenates following IPC, using Western blotting. To examine erythropoietin’s role in IPC, we studied the impact of blocking erythropoietin via intravitreal injection of soluble EPO-R (sEPO-R) before IPC. Results Erythropoietin levels did not change following IPC, but EPO-R increased. Intravitreal injection of sEPO-R significantly attenuated both the functional and histological neuroprotection produced by IPC in comparison to control injection of denatured sEPO-R. Apoptotic damage after ischemia was enhanced in the sEPO-R treated retinas as indicated by fluorescent Terminal Deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling. Phosphorylated extracellular-signal-regulated kinase (ERK) and heat shock protein 27 (Hsp27), but not protein kinase B (Akt), upregulated in denatured sEPO-R treated retinae, were attenuated in eyes injected with sEPO-R. Conclusions These results indicate that EPO-R upregulation is a critical component of the functional, histological, and anti-apoptotic protective effect of ischemic preconditioning on ischemia in the retina and that several downstream effectors may be involved in the neuroprotective actions of erythropoietin. PMID:19322943

Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats.

PubMed

Hu, Zhaoyang; Chen, Mou; Zhang, Ping; Liu, Jin; Abbott, Geoffrey W

2017-04-26

Sudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9). We evaluated the impact of acute streptozotocin-induced DM on coronary artery ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats. Post-IRI arrhythmia induction was similar in nondiabetic and DM rats, but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing incidence and duration of, and increasing latency to, all classes of ventricular tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus not explaining the DM-specific resistance of AVB to therapy. Our findings uncover important acute DM-specific differences in responsiveness to remote preconditioning for ventricular tachyarrhythmias versus AVB, which may have clinical significance given that AVB is a malignant arrhythmia twofold more common in human diabetics than nondiabetics, and correlated to plasma glucose levels >10 mmol/L.

Techniques and Software for Monolithic Preconditioning of Moderately-sized Geodynamic Stokes Flow Problems

NASA Astrophysics Data System (ADS)

Sanan, Patrick; May, Dave A.; Schenk, Olaf; Bollhöffer, Matthias

2017-04-01

Geodynamics simulations typically involve the repeated solution of saddle-point systems arising from the Stokes equations. These computations often dominate the time to solution. Direct solvers are known for their robustness and ``black box'' properties, yet exhibit superlinear memory requirements and time to solution. More complex multilevel-preconditioned iterative solvers have been very successful for large problems, yet their use can require more effort from the practitioner in terms of setting up a solver and choosing its parameters. We champion an intermediate approach, based on leveraging the power of modern incomplete factorization techniques for indefinite symmetric matrices. These provide an interesting alternative in situations in between the regimes where direct solvers are an obvious choice and those where complex, scalable, iterative solvers are an obvious choice. That is, much like their relatives for definite systems, ILU/ICC-preconditioned Krylov methods and ILU/ICC-smoothed multigrid methods, the approaches demonstrated here provide a useful addition to the solver toolkit. We present results with a simple, PETSc-based, open-source Q2-Q1 (Taylor-Hood) finite element discretization, in 2 and 3 dimensions, with the Stokes and Lamé (linear elasticity) saddle point systems. Attention is paid to cases in which full-operator incomplete factorization gives an improvement in time to solution over direct solution methods (which may not even be feasible due to memory limitations), without the complication of more complex (or at least, less-automatic) preconditioners or smoothers. As an important factor in the relevance of these tools is their availability in portable software, we also describe open-source PETSc interfaces to the factorization routines.

Pre-Conditioning with Low-Level Laser (Light) Therapy: Light Before the Storm

PubMed Central

Agrawal, Tanupriya; Gupta, Gaurav K.; Rai, Vikrant; Carroll, James D.; Hamblin, Michael R.

2014-01-01

Pre-conditioning by ischemia, hyperthermia, hypothermia, hyperbaric oxygen (and numerous other modalities) is a rapidly growing area of investigation that is used in pathological conditions where tissue damage may be expected. The damage caused by surgery, heart attack, or stroke can be mitigated by pre-treating the local or distant tissue with low levels of a stress-inducing stimulus, that can induce a protective response against subsequent major damage. Low-level laser (light) therapy (LLLT) has been used for nearly 50 years to enhance tissue healing and to relieve pain, inflammation and swelling. The photons are absorbed in cytochrome(c) oxidase (unit four in the mitochondrial respiratory chain), and this enzyme activation increases electron transport, respiration, oxygen consumption and ATP production. A complex signaling cascade is initiated leading to activation of transcription factors and up- and down-regulation of numerous genes. Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance. PMID:25552961

Human Bone Marrow-Derived Mesenchymal Stem Cells Display Enhanced Clonogenicity but Impaired Differentiation With Hypoxic Preconditioning

PubMed Central

Boyette, Lisa B.; Creasey, Olivia A.; Guzik, Lynda; Lozito, Thomas

2014-01-01

Stem cells are promising candidate cells for regenerative applications because they possess high proliferative capacity and the potential to differentiate into other cell types. Mesenchymal stem cells (MSCs) are easily sourced but do not retain their proliferative and multilineage differentiative capabilities after prolonged ex vivo propagation. We investigated the use of hypoxia as a preconditioning agent and in differentiating cultures to enhance MSC function. Culture in 5% ambient O2 consistently enhanced clonogenic potential of primary MSCs from all donors tested. We determined that enhanced clonogenicity was attributable to increased proliferation, increased vascular endothelial growth factor secretion, and increased matrix turnover. Hypoxia did not impact the incidence of cell death. Application of hypoxia to osteogenic cultures resulted in enhanced total mineral deposition, although this effect was detected only in MSCs preconditioned in normoxic conditions. Osteogenesis-associated genes were upregulated in hypoxia, and alkaline phosphatase activity was enhanced. Adipogenic differentiation was inhibited by exposure to hypoxia during differentiation. Chondrogenesis in three-dimensional pellet cultures was inhibited by preconditioning with hypoxia. However, in cultures expanded under normoxia, hypoxia applied during subsequent pellet culture enhanced chondrogenesis. Whereas hypoxic preconditioning appears to be an excellent way to expand a highly clonogenic progenitor pool, our findings suggest that it may blunt the differentiation potential of MSCs, compromising their utility for regenerative tissue engineering. Exposure to hypoxia during differentiation (post-normoxic expansion), however, appears to result in a greater quantity of functional osteoblasts and chondrocytes and ultimately a larger quantity of high-quality differentiated tissue. PMID:24436440

The New LMK Primary Standard for Dew-Point Sensor Calibration: Evaluation of the High-Range Saturator Efficiency

NASA Astrophysics Data System (ADS)

Hudoklin, Domen; Drnovšek, Janko

2008-10-01

In the field of hygrometry, a primary dew-point standard can be realized according to several proven principles, such as single-pressure (1-P), two-pressure (2-P), or divided flow. Different realizations have been introduced by various national laboratories, each resulting in a stand-alone complex generation system. Recent trends in generator design favor the single-pressure principle without recirculation because it promises theoretically lower uncertainty and because it avoids problems regarding the leak tightness of the recirculation. Instead of recirculation, the efficiency of saturation, the key factor, is increased by preconditioning the inlet gas entering the saturator. For preconditioning, a presaturator or purifier is used to bring the dew point of the inlet stream close to the saturator temperature. The purpose of the paper is to identify the minimum requirements for the preconditioning system and the main saturator to assure efficient saturation for the LMK generator. Moreover, the aim is also to find out if the preconditioning system can be avoided despite the rather simple construction of the main saturator. If this proves to be the case, the generator design can be simplified while maintaining an accurate value of the generated dew point. Experiments were carried out within the scope of improving our existing primary generator in the above-ambient dew-point range up to +70°C. These results show the generated dew point is within the measurement uncertainty for any dew-point value of the inlet gas. Thus, the preconditioning subsystem can be avoided, which leads to a simplified generator design.

Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning

PubMed Central

Ren, Chuancheng; Gao, Xuwen; Steinberg, Gary K.; Zhao, Heng

2009-01-01

Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 minute occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 minute occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for 2 or 3 cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with 3 cycles of 15 minutes performed immediately before stroke reduced infarct size from 47.7±7.6% of control ischemia to 9.8±8.6%; at 2 cycles of 15 minutes, infarct was reduced to 24.7±7.3%; at 2 cycles of 5 minutes, infarct was not reduced. Delayed preconditioning with 3 cycles of 15 minutes conducted 2 days before stroke also reduced infarct to 23.0 ±10.9%, but with 2 cycles of 15 minutes it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with 3 cycles of 15 minutes performed 12 hours before stroke also reduced infarct to 24.7±4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia. PMID:18201834

Laparoscopic ischemic conditioning of the stomach increases neovascularization of the gastric conduit in patients undergoing esophagectomy for cancer.

PubMed

Pham, Thai H; Melton, Shelby D; McLaren, Patrick J; Mokdad, Ali A; Huerta, Sergio; Wang, David H; Perry, Kyle A; Hardaker, Hope L; Dolan, James P

2017-09-01

Gastric ischemic preconditioning has been proposed to improve blood flow and reduce the incidence of anastomotic complications following esophagectomy with gastric pull-up. This study aimed to evaluate the effect of prolonged ischemic preconditioning on the degree of neovascularization in the distal gastric conduit at the time of esophagectomy. A retrospective review of a prospectively maintained database identified 30 patients who underwent esophagectomy. The patients were divided into three groups: control (no preconditioning, n = 9), partial (short gastric vessel ligation only, n = 8), and complete ischemic preconditioning (left and short gastric vessel ligation, n = 13). Microvessel counts were assessed, using immunohistologic analysis to determine the degree of neovascularization at the distal gastric margin. The groups did not differ in age, gender, BMI, pathologic stage, or cancer subtype. Ischemic preconditioning durations were 163 ± 156 days for partial ischemic preconditioning, compared to 95 ± 50 days for complete ischemic preconditioning (P = 0.2). Immunohistologic analysis demonstrated an increase in microvessel counts of 29% following partial ischemic preconditioning (P = 0.3) and 67% after complete ischemic preconditioning (P < 0.0001), compared to controls. Our study indicates that prolonged ischemic preconditioning is safe and does not interfere with subsequent esophagectomy. Complete ischemic preconditioning increased neovascularization in the distal gastric conduit. © 2017 Wiley Periodicals, Inc.

The GRONORUN 2 study: effectiveness of a preconditioning program on preventing running related injuries in novice runners. The design of a randomized controlled trial.

PubMed

Bredeweg, Steef W; Zijlstra, Sjouke; Buist, Ida

2010-09-01

Distance running is a popular recreational exercise. It is a beneficial activity for health and well being. However, running may also cause injuries, especially of the lower extremities. In literature there is no agreement what intrinsic and extrinsic factors cause running related injuries (RRIs). In theory, most RRIs are elicited by training errors, this too much, too soon. In a preconditioning program runners can adapt more gradually to the high mechanical loads of running and will be less susceptible to RRIs. In this study the effectiveness of a 4-week preconditioning program on the incidence of RRIs in novice runners prior to a training program will be studied. The GRONORUN 2 (Groningen Novice Running) study is a two arm randomized controlled trial studying the effect of a 4-week preconditioning (PRECON) program in a group of novice runners. All participants wanted to train for the recreational Groningen 4-Mile running event. The PRECON group started a 4-week preconditioning program with walking and hopping exercises 4 weeks before the start of the training program. The control (CON) and PRECON group started a frequently used 9-week training program in preparation for the Groningen 4-Mile running event.During the follow up period participants registered their running exposure, other sporting activities and running related injuries in an Internet based running log. The primary outcome measure was the number of RRIs. RRI was defined as a musculoskeletal ailment or complaint of the lower extremities or back causing a restriction on running for at least three training sessions. The GRONORUN 2 study will add important information to the existing running science. The concept of preconditioning is easy to implement in existing training programs and will hopefully prevent RRIs especially in novice runners. The Netherlands National Trial Register NTR1906. The NTR is part of the WHO Primary Registries.

Preconditioning 2D Integer Data for Fast Convex Hull Computations

PubMed Central

2016-01-01

In order to accelerate computing the convex hull on a set of n points, a heuristic procedure is often applied to reduce the number of points to a set of s points, s ≤ n, which also contains the same hull. We present an algorithm to precondition 2D data with integer coordinates bounded by a box of size p × q before building a 2D convex hull, with three distinct advantages. First, we prove that under the condition min(p, q) ≤ n the algorithm executes in time within O(n); second, no explicit sorting of data is required; and third, the reduced set of s points forms a simple polygonal chain and thus can be directly pipelined into an O(n) time convex hull algorithm. This paper empirically evaluates and quantifies the speed up gained by preconditioning a set of points by a method based on the proposed algorithm before using common convex hull algorithms to build the final hull. A speedup factor of at least four is consistently found from experiments on various datasets when the condition min(p, q) ≤ n holds; the smaller the ratio min(p, q)/n is in the dataset, the greater the speedup factor achieved. PMID:26938221

Isoflurane preconditioning protects neurons from male and female mice against oxygen and glucose deprivation and is modulated by estradiol only in neurons from female mice.

PubMed

Johnsen, D; Murphy, S J

2011-12-29

The volatile anesthetic, isoflurane, can protect the brain if administered before an insult such as an ischemic stroke. However, this protective "preconditioning" response to isoflurane is specific to males, with females showing an increase in brain damage following isoflurane preconditioning and subsequent focal cerebral ischemia. Innate cell sex is emerging as an important player in neuronal cell death, but its role in the sexually dimorphic response to isoflurane preconditioning has not been investigated. We used an in vitro model of isoflurane preconditioning and ischemia (oxygen and glucose deprivation, OGD) to test the hypotheses that innate cell sex dictates the response to isoflurane preconditioning and that 17β-estradiol attenuates any protective effect from isoflurane preconditioning in neurons via nuclear estrogen receptors. Sex-segregated neuron cultures derived from postnatal day 0-1 mice were exposed to either 0% or 3% isoflurane preconditioning for 1 h. In separate experiments, 17β-estradiol and the non-selective estrogen receptor antagonist ICI 182,780 were added 24 h before preconditioning and then removed at the end of the preconditioning period. Twenty-three hours after preconditioning, all cultures underwent 2 h of OGD. Twenty-four hours following OGD, cell viability was quantified using calcein-AM fluorescence. We observed that isoflurane preconditioning increased cell survival following subsequent OGD regardless of innate cell sex, but that the presence of 17β-estradiol before and during isoflurane preconditioning attenuated this protection only in female neurons independent of nuclear estrogen receptors. We also found that independent of preconditioning treatment, female neurons were less sensitive to OGD compared with male neurons and that transient treatment with 17β-estradiol protected both male and female neurons from subsequent OGD. More studies are needed to determine how cell type, cell sex, and sex steroids like 17β-estradiol may impact on anesthetic preconditioning and subsequent ischemic outcomes in the brain. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Preconditioning, postconditioning and their application to clinical cardiology.

PubMed

Kloner, Robert A; Rezkalla, Shereif H

2006-05-01

Ischemic preconditioning is a well-established phenomenon first described in experimental preparations in which brief episodes of ischemia/reperfusion applied prior to a longer coronary artery occlusion reduce myocardial infarct size. There are ample correlates of ischemic preconditioning in the clinical realm. Preconditioning mimetic agents that stimulate the biochemical pathways of ischemic preconditioning and protect the heart without inducing ischemia have been examined in numerous experimental studies. However, despite the effectiveness of ischemic preconditioning and preconditioning mimetics for protecting ischemic myocardium, there are no preconditioning-based therapies that are routinely used in clinical medicine at the current time. Part of the problem is the need to administer therapy prior to the known ischemic event. Other issues are that percutaneous coronary intervention technology has advanced so far (with the development of stents and drug-eluting stents) that ischemic preconditioning or preconditioning mimetics have not been needed in most interventional cases. Recent clinical trials such as AMISTAD I and II (Acute Myocardial Infarction STudy of ADenosine) suggest that some preconditioning mimetics may reduce myocardial infarct size when given along with reperfusion or, as in the IONA trial, have benefit on clinical events when administered chronically in patients with known coronary artery disease. It is possible that some of the benefit described for adenosine in the AMISTAD 1 and 2 trials represents a manifestation of the recently described postconditioning phenomenon. It is probable that postconditioning--in which reperfusion is interrupted with brief coronary occlusions and reperfusion sequences--is more likely than preconditioning to be feasible as a clinical application to patients undergoing percutaneous coronary intervention for acute myocardial infarction.

In vivo inhibition of the mitochondrial H+-ATP synthase in neurons promotes metabolic preconditioning.

PubMed

Formentini, Laura; Pereira, Marta P; Sánchez-Cenizo, Laura; Santacatterina, Fulvio; Lucas, José J; Navarro, Carmen; Martínez-Serrano, Alberto; Cuezva, José M

2014-04-01

A key transducer in energy conservation and signaling cell death is the mitochondrial H(+)-ATP synthase. The expression of the ATPase inhibitory factor 1 (IF1) is a strategy used by cancer cells to inhibit the activity of the H(+)-ATP synthase to generate a ROS signal that switches on cellular programs of survival. We have generated a mouse model expressing a mutant of human IF1 in brain neurons to assess the role of the H(+)-ATP synthase in cell death in vivo. The expression of hIF1 inhibits the activity of oxidative phosphorylation and mediates the shift of neurons to an enhanced aerobic glycolysis. Metabolic reprogramming induces brain preconditioning affording protection against quinolinic acid-induced excitotoxicity. Mechanistically, preconditioning involves the activation of the Akt/p70S6K and PARP repair pathways and Bcl-xL protection from cell death. Overall, our findings provide the first in vivo evidence highlighting the H(+)-ATP synthase as a target to prevent neuronal cell death.

Repeated Red-Black ordering

NASA Astrophysics Data System (ADS)

Ciarlet, P.

1994-09-01

Hereafter, we describe and analyze, from both a theoretical and a numerical point of view, an iterative method for efficiently solving symmetric elliptic problems with possibly discontinuous coefficients. In the following, we use the Preconditioned Conjugate Gradient method to solve the symmetric positive definite linear systems which arise from the finite element discretization of the problems. We focus our interest on sparse and efficient preconditioners. In order to define the preconditioners, we perform two steps: first we reorder the unknowns and then we carry out a (modified) incomplete factorization of the original matrix. We study numerically and theoretically two preconditioners, the second preconditioner corresponding to the one investigated by Brand and Heinemann [2]. We prove convergence results about the Poisson equation with either Dirichlet or periodic boundary conditions. For a meshsizeh, Brand proved that the condition number of the preconditioned system is bounded byO(h-1/2) for Dirichlet boundary conditions. By slightly modifying the preconditioning process, we prove that the condition number is bounded byO(h-1/3).

Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway*

PubMed Central

Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu

2015-01-01

Objectives: Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Design: Experimental animal investigation. Setting: University research laboratory. Subjects: Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20–25 g. Interventions: We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Measurements and Main Results: Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide-induced acute kidney injury. Conclusion: Our findings demonstrated that xenon preconditioning protected against lipopolysaccharide-induced acute kidney injury via activation of miR-21 target signaling pathways. PMID:25844699

Implicit preconditioned WENO scheme for steady viscous flow computation

NASA Astrophysics Data System (ADS)

Huang, Juan-Chen; Lin, Herng; Yang, Jaw-Yen

2009-02-01

A class of lower-upper symmetric Gauss-Seidel implicit weighted essentially nonoscillatory (WENO) schemes is developed for solving the preconditioned Navier-Stokes equations of primitive variables with Spalart-Allmaras one-equation turbulence model. The numerical flux of the present preconditioned WENO schemes consists of a first-order part and high-order part. For first-order part, we adopt the preconditioned Roe scheme and for the high-order part, we employ preconditioned WENO methods. For comparison purpose, a preconditioned TVD scheme is also given and tested. A time-derivative preconditioning algorithm is devised and a discriminant is devised for adjusting the preconditioning parameters at low Mach numbers and turning off the preconditioning at intermediate or high Mach numbers. The computations are performed for the two-dimensional lid driven cavity flow, low subsonic viscous flow over S809 airfoil, three-dimensional low speed viscous flow over 6:1 prolate spheroid, transonic flow over ONERA-M6 wing and hypersonic flow over HB-2 model. The solutions of the present algorithms are in good agreement with the experimental data. The application of the preconditioned WENO schemes to viscous flows at all speeds not only enhances the accuracy and robustness of resolving shock and discontinuities for supersonic flows, but also improves the accuracy of low Mach number flow with complicated smooth solution structures.

Preconditioning with Cations Increases the Attachment of Anoxybacillus flavithermus and Geobacillus Species to Stainless Steel

PubMed Central

Flint, Steve; Palmer, Jon; Brooks, John; Lindsay, Denise

2013-01-01

Preconditioning of Anoxybacillus flavithermus E16 and Geobacillus sp. strain F75 with cations prior to attachment often significantly increased (P ≤ 0.05) the number of viable cells that attached to stainless steel (by up to 1.5 log CFU/cm2) compared with unconditioned bacteria. It is proposed that the transition of A. flavithermus and Geobacillus spp. from milk formulations to stainless steel product contact surfaces in milk powder manufacturing plants is mediated predominantly by bacterial physiological factors (e.g., surface-exposed adhesins) rather than the concentrations of cations in milk formulations surrounding bacteria. PMID:23645192

Role of decoy molecules in neuronal ischemic preconditioning

PubMed Central

Panneerselvam, Mathivadhani; Patel, Piyush M.; Roth, David M.; Kidd, Michael W.; Chin-Lee, Blake; Head, Brian P.; Niesman, Ingrid R.; Inoue, Satoki; Patel, Hemal H.; Davis, Daniel P.

2011-01-01

Decoy receptors bind with TNF related apoptosis inducing ligands (TRAIL) but do not contain the cytoplasmic domains necessary to transduce apoptotic signals. We hypothesized that decoy receptors may confer neuronal protection against lethal ischemia after ischemic preconditioning (IPC). Mixed cortical neurons were exposed to IPC one day prior to TRAIL treatment or lethal ischemia. IPC increased decoy receptor but reduced death receptor expression compared to lethal ischemia. IPC-induced increase in decoy receptor expression was reduced by prior treatment with CAPE, a nuclear factor-kappa B inhibitor (NFκB). Expression of decoy molecules, dependent on NFκB, may mediate neuronal survival induced by IPC. PMID:21315738

Nucleon matrix elements from lattice QCD with all-mode-averaging and a domain-decomposed solver: An exploratory study

NASA Astrophysics Data System (ADS)

von Hippel, Georg; Rae, Thomas D.; Shintani, Eigo; Wittig, Hartmut

2017-01-01

We study the performance of all-mode-averaging (AMA) when used in conjunction with a locally deflated SAP-preconditioned solver, determining how to optimize the local block sizes and number of deflation fields in order to minimize the computational cost for a given level of overall statistical accuracy. We find that AMA enables a reduction of the statistical error on nucleon charges by a factor of around two at the same cost when compared to the standard method. As a demonstration, we compute the axial, scalar and tensor charges of the nucleon in Nf = 2 lattice QCD with non-perturbatively O(a)-improved Wilson quarks, using O(10,000) measurements to pursue the signal out to source-sink separations of ts ∼ 1.5 fm. Our results suggest that the axial charge is suffering from a significant amount (5-10%) of excited-state contamination at source-sink separations of up to ts ∼ 1.2 fm, whereas the excited-state contamination in the scalar and tensor charges seems to be small.

An investigation into the stability of commercial versus MG63-derived hepatocyte growth factor under flow cultivation conditions.

PubMed

Meneghello, Giulia; Storm, Michael P; Chaudhuri, Julian B; De Bank, Paul A; Ellis, Marianne J

2015-03-01

The scale-up of tissue engineering cell culture must ensure that conditions are maintained while also being cost effective. Here we analyse the stability of hepatocyte growth factor (HGF) to investigate whether concentrations change under dynamic conditions, and compare commercial recombinant human HGF as an additive in 'standard medium', to HGF secreted by the osteosarcoma cell line MG63 as a 'preconditioned medium'. After 3 h under flow conditions, HGF in the standard medium degraded to 40% of its original concentration but HGF in the preconditioned medium remained at 100%. The concentration of secreted HGF was 10 times greater than the working concentration of commercially-available HGF. Thus HGF within this medium has increased stability; MG63-derived HGF should therefore be investigated as a cost-effective alternative to current lyophilised powders for use in in vitro models. Furthermore, we recommend that those intending to use HGF (or other growth factors) should consider similar stability testing before embarking on experiments with media flow.

Mechanical stretch endows mesenchymal stem cells stronger angiogenic and anti-apoptotic capacities via NFκB activation

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

Zhu, Zhuoli; Gan, Xueqi; Fan, Hongyi

Mesenchymal stem cells (MSCs) have been broadly used for tissue regeneration and repair due to their broad differentiation potential and potent paracrine properties such as angiogenic capacity. Strategies to increase their survival rate after transplantation and the angiogenic ability are of priority for the utility of MSCs. In this study, we found that mechanical stretch (10% extension, 30 cycles/min cyclic stretch) preconditioning increase the angiogenic capacity via VEGFA induction. In addition, mechanical stretch also increases the survival rate of mesenchymal stem cells under nutrients deprivation. Consistent with the increase VEGFA expression and resistance to apoptosis, nuclear localization of NFκB activity p65more » increased upon mechanical stretch. Inhibition of NFκB activity by BAY 11-708 blocks the pro-angiogenesis and anti-apoptosis function of mechanical stretch. Taken together, our findings here raise the possibility that mechanical stretch preconditioning might enhance the therapeutic efficacy of mesenchymal stem cells. - Highlights: • Mechanical stretch increases the angiogenic capacity via VEGFA induction in MSCs. • Mechanical stretch increases the survival rate of MSCs under nutrients deprivation. • Mechanical stretch manipulates MSCs via the activation of NFκB.« less

[The relationship between ischemic preconditioning-induced infarction size limitation and duration of test myocardial ischemia].

PubMed

Blokhin, I O; Galagudza, M M; Vlasov, T D; Nifontov, E M; Petrishchev, N N

2008-07-01

Traditionally infarction size reduction by ischemic preconditioning is estimated in duration of test ischemia. This approach limits the understanding of real antiischemic efficacy of ischemic preconditioning. Present study was performed in the in vivo rat model of regional myocardial ischemia-reperfusion and showed that protective effect afforded by ischemic preconditioning progressively decreased with prolongation of test ischemia. There were no statistically significant differences in infarction size between control and preconditioned animals when the duration of test ischemia was increased up to 1 hour. Preconditioning ensured maximal infarction-limiting effect in duration of test ischemia varying from 20 to 40 minutes.

SIMVASTATIN RESTORES ISCHEMIC PRECONDITIONING IN THE PRESENCE OF HYPERGLYCEMIA THROUGH A NITRIC OXIDE-MEDIATED MECHANISM

PubMed Central

Gu, Weidong; Kehl, Franz; Krolikowski, John G.; Pagel, Paul S.; Warltier, David C.; Kersten, Judy R.

2015-01-01

Background A growing body of evidence indicates that statins decrease perioperative cardiovascular risk and that these drugs may be particularly efficacious in diabetes. Diabetes or hyperglycemia abolish the cardioprotective effects of ischemic preconditioning (IPC). We tested the hypothesis that simvastatin restores the beneficial effects of IPC during hyperglycemia through a nitric oxide (NO)-mediated mechanism. Methods Myocardial infarct size was measured in dogs (n=76) subjected to coronary artery occlusion and reperfusion in the presence or absence of hyperglycemia (300 mg/dl) with or without IPC in separate groups. Additional dogs received simvastatin (20 mg orally daily for 3 days) in the presence or absence of IPC and hyperglycemia. Other dogs were pretreated with N-nitro-L-arginine methyl ester (L-NAME; 30 mg intracoronary) with or without IPC, hyperglycemia and simvastatin. Results IPC significantly (P<0.05) reduced infarct size (n=7, 7±2%) as compared to control (n=7, 29±3%). Hyperglycemia (n=7), simvastatin (n=7) and L-NAME alone (n=7), and simvastatin with hyperglycemia (n=6) did not alter infarct size. Hyperglycemia (n=7, 24±2%), but not L-NAME (n=5, 10±1%), blocked the protective effects of IPC. Simvastatin restored the protective effects of IPC in the presence of hyperglycemia (n=7, 14±1%), and this beneficial action was blocked by L-NAME (n=7, 29±4%). Conclusions The results indicate that simvastatin restored the cardioprotective effects of IPC during hyperglycemia by NO-mediated signaling. The results also suggest that enhanced cardioprotective signaling could be a mechanism for statin-induced decreases in perioperative cardiovascular risk. PMID:18362595

Hydrogen peroxide preconditioning enhances the therapeutic efficacy of Wharton's Jelly mesenchymal stem cells after myocardial infarction.

PubMed

Zhang, Jin; Chen, Guang-Hui; Wang, Yong-Wei; Zhao, Jing; Duan, Hai-Feng; Liao, Lian-Ming; Zhang, Xiao-Zhong; Chen, Yun-Dai; Chen, Hu

2012-10-01

Exposure of cells to sublethal concentrations of hydrogen peroxide (H2O2) can alleviate subsequent oxidative stress-induced apoptosis. We assessed the effects of H2O2 preconditioning on the therapeutic potential of human umbilical cord Wharton's Jelly mesenchymal stem cells (WJ-MSCs) in a murine model of myocardial infarction. WJ-MSCs were incubated in the media for 2 hours with or without 200 µmol/L H2O2. Mice underwent left anterior descending coronary artery ligation, and received injection of phosphate buffered saline, 1×10(6) WJ-MSCs, or 1×10(6) H2O2 preconditioned WJ-MSCs 3 hours later via tail vein. Echocardiography was performed 0, 7, 14 and 28 days after surgery, and the mice were euthanized on day 28 for histological analysis. In vitro cytokine concentrations in the WJ-MSC cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). The effect of WJ-MSC cell supernatant on the migration and proliferation of endothelial cells were observed by transwell migration and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide (MTT) assays. Echocardiographic measurements revealed a significant improvement in the left ventricular contractility of the WJ-MSCs-H2O2 group compared to the WJ-MSCs group. Histological analysis revealed increased neovascularization and reduced myocardial fibrosis in the WJ-MSCs-H2O2 group compared to the WJ-MSCs group. Pretreatment of WJ-MSCs with H2O2 increased the secretion of interleukin-6 (IL-6) into the cell culture supernatant by approximately 25-fold. The culture supernatant from WJ-MSCs-H2O2 significantly increased the migration and proliferation of endothelial cells; these effects could be blocked using an anti-IL-6 antibody. This study demonstrates that H2O2 preconditioning significantly enhanced the therapeutic potential of WJ-MSCs, possibly by stimulating the production of IL-6 by WJ-MSCs, which may cause migration and proliferation of endothelial cells and increase neovascularization.

Hypoxia preconditioning increases survival and decreases expression of Toll-like receptor 4 in pulmonary artery endothelial cells exposed to lipopolysaccharide.

PubMed

Ali, Irshad; Nanchal, Rahul; Husnain, Fouad; Audi, Said; Konduri, G Ganesh; Densmore, John C; Medhora, Meetha; Jacobs, Elizabeth R

2013-09-01

Abstract Pulmonary or systemic infections and hypoxemic respiratory failure are among the leading causes of admission to intensive care units, and these conditions frequently exist in sequence or in tandem. Inflammatory responses to infections are reproduced by lipopolysaccharide (LPS) engaging Toll-like receptor 4 (TLR4). Apoptosis is a hallmark of lung injury in sepsis. This study was conducted to determine whether preexposure to LPS or hypoxia modulated the survival of pulmonary artery endothelial cells (PAECs). We also investigated the role TLR4 receptor expression plays in apoptosis due to these conditions. Bovine PAECs were cultured in hypoxic or normoxic environments and treated with LPS. TLR4 antagonist TAK-242 was used to probe the role played by TLR4 receptors in cell survival. Cell apoptosis and survival were measured by caspase 3 activity and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) incorporation. TLR4 expression and tumor necrosis factor α (TNF-α) production were also determined. LPS increased caspase 3 activity in a TAK-242-sensitive manner and decreased MTT incorporation. Apoptosis was decreased in PAECs preconditioned with hypoxia prior to LPS exposure. LPS increased TNF-α production, and hypoxic preconditioning blunted it. Hypoxic preconditioning reduced LPS-induced TLR4 messenger RNA and TLR4 protein. TAK-242 decreased to baseline the LPS-stimulated expression of TLR4 messenger RNA regardless of environmental conditions. In contrast, LPS followed by hypoxia substantially increased apoptosis and cell death. In conclusion, protection from LPS-stimulated PAEC apoptosis by hypoxic preconditioning is attributable in part to reduction in TLR4 expression. If these signaling pathways apply to septic patients, they may account for differing sensitivities of individuals to acute lung injury depending on oxygen tensions in PAECs in vivo.

Ultraviolet B preconditioning enhances the hair growth-promoting effects of adipose-derived stem cells via generation of reactive oxygen species.

PubMed

Jeong, Yun-Mi; Sung, Young Kwan; Kim, Wang-Kyun; Kim, Ji Hye; Kwack, Mi Hee; Yoon, Insoo; Kim, Dae-Duk; Sung, Jong-Hyuk

2013-01-01

Hypoxia induces the survival and regenerative potential of adipose-derived stem cells (ASCs), but there are tremendous needs to find alternative methods for ASC preconditioning. Therefore, this work investigated: (1) the ability of low-dose ultraviolet B (UVB) radiation to stimulate the survival, migration, and tube-forming activity of ASCs in vitro; (2) the ability of UVB preconditioning to enhance the hair growth-promoting capacity of ASCs in vivo; and (3) the mechanism of action for ASC stimulation by UVB. Although high-dose UVB decreased the proliferation of ASCs, low-dose (10 or 20 mJ/cm(2)) treatment increased their survival, migration, and tube-forming activity. In addition, low-dose UVB upregulated the expression of ASC-derived growth factors, and a culture medium conditioned by UVB-irradiated ASCs increased the proliferation of dermal papilla and outer root sheet cells. Notably, injection of UVB-preconditioned ASCs into C(3)H/HeN mice significantly induced the telogen-to-anagen transition and increased new hair weight in vivo. UVB treatment significantly increased the generation of reactive oxygen species (ROS) in cultured ASCs, and inhibition of ROS generation by diphenyleneiodonium chloride (DPI) significantly attenuated UVB-induced ASC stimulation. Furthermore, NADPH oxidase 4 (Nox4) expression was induced in ASCs by UVB irradiation, and Nox4 silencing by small interfering RNA, like DPI, significantly reduced UVB-induced ROS generation. These results suggest that the primary involvement of ROS generation in UVB-mediated ASC stimulation occurs via the Nox4 enzyme. This is the first indication that a low dose of UVB radiation and/or the control of ROS generation could potentially be incorporated into a novel ASC preconditioning method for hair regeneration.

Voltage Preconditioning Allows Modulated Gene Expression in Neurons Using PEI-complexed siRNA

PubMed Central

Sridharan, Arati; Patel, Chetan; Muthuswamy, Jit

2013-01-01

We present here a high efficiency, high viability siRNA-delivery method using a voltage-controlled chemical transfection strategy to achieve modulated delivery of polyethylenimine (PEI) complexed with siRNA in an in vitro culture of neuro2A cells and neurons. Low voltage pulses were applied to adherent cells before the administration of PEI-siRNA complexes. Live assays of neuro2a cells transfected with fluorescently tagged siRNA showed an increase in transfection efficiency from 62 ± 14% to 98 ± 3.8% (after −1 V). In primary hippocampal neurons, transfection efficiencies were increased from 30 ± 18% to 76 ± 18% (after −1 V). Negligible or low-level transfection was observed after preconditioning at higher voltages, suggesting an inverse relationship with applied voltage. Experiments with propidium iodide ruled out the role of electroporation in the transfection of siRNAs suggesting an alternate electro-endocytotic mechanism. In addition, image analysis of preconditioned and transfected cells demonstrates siRNA uptake and loading that is tuned to preconditioning voltage levels. There is approximately a fourfold increase in siRNA loading after preconditioning at −1 V compared with the same at ±2–3 V. Modulated gene expression is demonstrated in a functional knockdown of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in neuro2A cells using siRNA. Cell density and dendritic morphological changes are also demonstrated in modulated knockdown of brain derived neurotrophic factor (BDNF) in primary hippocampal neurons. The method reported here has potential applications in the development of high-throughput screening systems for large libraries of siRNA molecules involving difficult-to-transfect cells like neurons. PMID:23531602

Voltage Preconditioning Allows Modulated Gene Expression in Neurons Using PEI-complexed siRNA.

PubMed

Sridharan, Arati; Patel, Chetan; Muthuswamy, Jit

2013-03-26

We present here a high efficiency, high viability siRNA-delivery method using a voltage-controlled chemical transfection strategy to achieve modulated delivery of polyethylenimine (PEI) complexed with siRNA in an in vitro culture of neuro2A cells and neurons. Low voltage pulses were applied to adherent cells before the administration of PEI-siRNA complexes. Live assays of neuro2a cells transfected with fluorescently tagged siRNA showed an increase in transfection efficiency from 62 ± 14% to 98 ± 3.8% (after -1 V). In primary hippocampal neurons, transfection efficiencies were increased from 30 ± 18% to 76 ± 18% (after -1 V). Negligible or low-level transfection was observed after preconditioning at higher voltages, suggesting an inverse relationship with applied voltage. Experiments with propidium iodide ruled out the role of electroporation in the transfection of siRNAs suggesting an alternate electro-endocytotic mechanism. In addition, image analysis of preconditioned and transfected cells demonstrates siRNA uptake and loading that is tuned to preconditioning voltage levels. There is approximately a fourfold increase in siRNA loading after preconditioning at -1 V compared with the same at ±2-3 V. Modulated gene expression is demonstrated in a functional knockdown of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in neuro2A cells using siRNA. Cell density and dendritic morphological changes are also demonstrated in modulated knockdown of brain derived neurotrophic factor (BDNF) in primary hippocampal neurons. The method reported here has potential applications in the development of high-throughput screening systems for large libraries of siRNA molecules involving difficult-to-transfect cells like neurons.Molecular Therapy-Nucleic Acids (2013) 2, e82; doi:10.1038/mtna.2013.10; published online 26 March 2013.

Research on the Changes to the Lipid/Polymer Membrane Used in the Acidic Bitterness Sensor Caused by Preconditioning

PubMed Central

Harada, Yuhei; Noda, Junpei; Yatabe, Rui; Ikezaki, Hidekazu; Toko, Kiyoshi

2016-01-01

A taste sensor that uses lipid/polymer membranes can evaluate aftertastes felt by humans using Change in membrane Potential caused by Adsorption (CPA) measurements. The sensor membrane for evaluating bitterness, which is caused by acidic bitter substances such as iso-alpha acid contained in beer, needs an immersion process in monosodium glutamate (MSG) solution, called “MSG preconditioning”. However, what happens to the lipid/polymer membrane during MSG preconditioning is not clear. Therefore, we carried out three experiments to investigate the changes in the lipid/polymer membrane caused by the MSG preconditioning, i.e., measurements of the taste sensor, measurements of the amount of the bitterness substance adsorbed onto the membrane and measurements of the contact angle of the membrane surface. The CPA values increased as the preconditioning process progressed, and became stable after 3 d of preconditioning. The response potentials to the reference solution showed the same tendency of the CPA value change during the preconditioning period. The contact angle of the lipid/polymer membrane surface decreased after 7 d of MSG preconditioning; in short, the surface of the lipid/polymer membrane became hydrophilic during MSG preconditioning. The amount of adsorbed iso-alpha acid was increased until 5 d preconditioning, and then it decreased. In this study, we revealed that the CPA values increased with the progress of MSG preconditioning in spite of the decrease of the amount of iso-alpha acid adsorbed onto the lipid/polymer membrane, and it was indicated that the CPA values increase because the sensor sensitivity was improved by the MSG preconditioning. PMID:26891299

Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis.

PubMed

Wu, Xiaomei; Qian, Zhongming; Ke, Ya; Du, Fang; Zhu, Li

2009-01-01

Ischaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre-treated with GB (120 micromol/l) for 24 hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia-inducible factor-1 alpha (HIF-1alpha), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p-Bad) and phosphorylated glycogen synthase kinase- 3beta at serine 9 (p-GSK-3beta), and decreased the percentage of apoptotic cells and the level of active caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the enhanced expression of HIF-1alpha, EPO and 136p-Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K signalling pathway.

Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis

PubMed Central

Wu, Xiaomei; Qian, Zhongming; Ke, Ya; Du, Fang; Zhu, Li

2009-01-01

Ischaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre-treated with GB (120 μmol/l) for 24 hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia-inducible factor-1 alpha (HIF-1α), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p-Bad) and phosphorylated glycogen synthase kinase- 3β at serine 9 (p-GSK-3β), and decreased the percentage of apoptotic cells and the level of active caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the enhanced expression of HIF-1α, EPO and 136p-Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K signalling pathway. PMID:19602048

Opening of mitochondrial ATP-sensitive potassium channels is a trigger of 3-nitropropionic acid-induced tolerance to transient focal cerebral ischemia in rats.

PubMed

Horiguchi, Takashi; Kis, Bela; Rajapakse, Nishadi; Shimizu, Katsuyoshi; Busija, David W

2003-04-01

The role of mitochondrial ATP-sensitive potassium channels (mitoK(ATP)) in ischemic tolerance has been well documented in heart, but little work has been done in brain. To investigate the involvement of mitoK(ATP) activation in chemical preconditioning in brain, we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoK(ATP) blocker, on neurotoxin 3-nitropropionic acid (3-NPA)-induced ischemic tolerance to transient focal cerebral ischemia in rats. Male Wistar rats were administrated 3-NPA (20 mg/kg IP; n=16) or vehicle (saline; n=16) 3 days before temporary occlusion (120 minutes) of the middle cerebral artery; 5-HD (40 mg/kg IP; n=16) was injected 20 minutes before 3-NPA administration. Infarct volumes were measured 4 days after reperfusion. To directly investigate whether chemical preconditioning activates mitoK(ATP), we tested the effect of prior incubation with 1 mmol/L 5-HD on 300 micromol/L 3-NPA-induced alterations of mitochondrial membrane potential (Delta(Psi)m) in cultured neurons and astrocytes using the fluorescent dye tetramethylrhodamine ethyl ester. Treatment with 3-NPA exhibited a 16% reduction (P<0.05) and 23% reduction in infarct volume (P<0.01) for total brain and cortex, respectively. Pretreatment with 5-HD completely abolished the neuroprotective effect of chemical preconditioning. In cultured cells, 3-NPA resulted in mitochondrial depolarization. This change of Delta(Psi)m was completely blocked by 5-HD pretreatment. These results strongly suggest that opening of mitoK(ATP) plays a key role as the trigger in the development of 3-NPA-induced ischemic tolerance in brain.

Role of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase during Early Anesthetic and Ischemic Preconditioning

PubMed Central

Amour, Julien; Brzezinska, Anna K.; Weihrauch, Dorothee; Billstrom, Amie R.; Zielonka, Jacek; Krolikowski, John G.; Bienengraeber, Martin W.; Warltier, David C.; Pratt, Philip F.; Kersten, Judy R.

2009-01-01

Background Nitric oxide is known to be essential for early anesthetic (APC) and ischemic (IPC) preconditioning of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, we tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Methods Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning with 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pre-treatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or NG-nitro-L-arginine methylester, a non-specific NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or NG-nitro-L-arginine methylester. Interactions between Hsp90 and eNOS, and eNOS activation were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. Results APC and IPC decreased infarct size (50% and 59%, respectively) and this action was abolished by Hsp90 inhibitors. NG-nitro-L-arginine methylester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells, concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes and eNOS was below the level of detection. Conclusion The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signalling during APC. PMID:19194158

Aerodynamic shape optimization using preconditioned conjugate gradient methods

NASA Technical Reports Server (NTRS)

Burgreen, Greg W.; Baysal, Oktay

1993-01-01

In an effort to further improve upon the latest advancements made in aerodynamic shape optimization procedures, a systematic study is performed to examine several current solution methodologies as applied to various aspects of the optimization procedure. It is demonstrated that preconditioned conjugate gradient-like methodologies dramatically decrease the computational efforts required for such procedures. The design problem investigated is the shape optimization of the upper and lower surfaces of an initially symmetric (NACA-012) airfoil in inviscid transonic flow and at zero degree angle-of-attack. The complete surface shape is represented using a Bezier-Bernstein polynomial. The present optimization method then automatically obtains supercritical airfoil shapes over a variety of freestream Mach numbers. Furthermore, the best optimization strategy examined resulted in a factor of 8 decrease in computational time as well as a factor of 4 decrease in memory over the most efficient strategies in current use.

Krylov subspace methods on supercomputers

NASA Technical Reports Server (NTRS)

Saad, Youcef

1988-01-01

A short survey of recent research on Krylov subspace methods with emphasis on implementation on vector and parallel computers is presented. Conjugate gradient methods have proven very useful on traditional scalar computers, and their popularity is likely to increase as three-dimensional models gain importance. A conservative approach to derive effective iterative techniques for supercomputers has been to find efficient parallel/vector implementations of the standard algorithms. The main source of difficulty in the incomplete factorization preconditionings is in the solution of the triangular systems at each step. A few approaches consisting of implementing efficient forward and backward triangular solutions are described in detail. Polynomial preconditioning as an alternative to standard incomplete factorization techniques is also discussed. Another efficient approach is to reorder the equations so as to improve the structure of the matrix to achieve better parallelism or vectorization. An overview of these and other ideas and their effectiveness or potential for different types of architectures is given.

Coral thermal tolerance: tuning gene expression to resist thermal stress.

PubMed

Bellantuono, Anthony J; Granados-Cifuentes, Camila; Miller, David J; Hoegh-Guldberg, Ove; Rodriguez-Lanetty, Mauricio

2012-01-01

The acclimatization capacity of corals is a critical consideration in the persistence of coral reefs under stresses imposed by global climate change. The stress history of corals plays a role in subsequent response to heat stress, but the transcriptomic changes associated with these plastic changes have not been previously explored. In order to identify host transcriptomic changes associated with acquired thermal tolerance in the scleractinian coral Acropora millepora, corals preconditioned to a sub-lethal temperature of 3°C below bleaching threshold temperature were compared to both non-preconditioned corals and untreated controls using a cDNA microarray platform. After eight days of hyperthermal challenge, conditions under which non-preconditioned corals bleached and preconditioned corals (thermal-tolerant) maintained Symbiodinium density, a clear differentiation in the transcriptional profiles was revealed among the condition examined. Among these changes, nine differentially expressed genes separated preconditioned corals from non-preconditioned corals, with 42 genes differentially expressed between control and preconditioned treatments, and 70 genes between non-preconditioned corals and controls. Differentially expressed genes included components of an apoptotic signaling cascade, which suggest the inhibition of apoptosis in preconditioned corals. Additionally, lectins and genes involved in response to oxidative stress were also detected. One dominant pattern was the apparent tuning of gene expression observed between preconditioned and non-preconditioned treatments; that is, differences in expression magnitude were more apparent than differences in the identity of genes differentially expressed. Our work revealed a transcriptomic signature underlying the tolerance associated with coral thermal history, and suggests that understanding the molecular mechanisms behind physiological acclimatization would be critical for the modeling of reefs in impending climate change scenarios.

Coral Thermal Tolerance: Tuning Gene Expression to Resist Thermal Stress

PubMed Central

Bellantuono, Anthony J.; Granados-Cifuentes, Camila; Miller, David J.; Hoegh-Guldberg, Ove; Rodriguez-Lanetty, Mauricio

2012-01-01

The acclimatization capacity of corals is a critical consideration in the persistence of coral reefs under stresses imposed by global climate change. The stress history of corals plays a role in subsequent response to heat stress, but the transcriptomic changes associated with these plastic changes have not been previously explored. In order to identify host transcriptomic changes associated with acquired thermal tolerance in the scleractinian coral Acropora millepora, corals preconditioned to a sub-lethal temperature of 3°C below bleaching threshold temperature were compared to both non-preconditioned corals and untreated controls using a cDNA microarray platform. After eight days of hyperthermal challenge, conditions under which non-preconditioned corals bleached and preconditioned corals (thermal-tolerant) maintained Symbiodinium density, a clear differentiation in the transcriptional profiles was revealed among the condition examined. Among these changes, nine differentially expressed genes separated preconditioned corals from non-preconditioned corals, with 42 genes differentially expressed between control and preconditioned treatments, and 70 genes between non-preconditioned corals and controls. Differentially expressed genes included components of an apoptotic signaling cascade, which suggest the inhibition of apoptosis in preconditioned corals. Additionally, lectins and genes involved in response to oxidative stress were also detected. One dominant pattern was the apparent tuning of gene expression observed between preconditioned and non-preconditioned treatments; that is, differences in expression magnitude were more apparent than differences in the identity of genes differentially expressed. Our work revealed a transcriptomic signature underlying the tolerance associated with coral thermal history, and suggests that understanding the molecular mechanisms behind physiological acclimatization would be critical for the modeling of reefs in impending climate change scenarios. PMID:23226355

Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

PubMed

Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

2016-07-01

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells. Our results suggest that preconditioning stem cells with the mood stabilizers lithium and VPA before transplantation may serve as an effective strategy for enhancing the therapeutic efficacy of stem cell-based therapies. Copyright © 2016. Published by Elsevier Inc.

Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high glucose conditions in-vitro and ameliorates drug induced diabetes in rats

PubMed Central

2013-01-01

Background Diabetes mellitus is affecting more than 300 million people worldwide. Current treatment strategies cannot prevent secondary complications. Stem cells due to their regenerative power have long been the attractive target for the cell-based therapies. Mesenchymal stem cells (MSCs) possess the ability to differentiate into several cell types and to escape immune recognition in vitro. MSCs can be differentiated into insulin-producing cells (IPCs) and could be an exciting therapy for diabetes but problems like poor engraftment and survivability need to be confronted. It was hypothesized that stromal cell derived factor- 1alpha (SDF-1alpha) will enhance therapeutic potential of stem cell derived IPCs by increasing their survival and proliferation rate. Methods Novel culture conditions were developed to differentiate bone marrow derived mesenchymal stem cells (BMSCs) into IPCs by using endocrine differentiation inducers and growth factors via a three stage protocol. In order to enhance their therapeutic potential, we preconditioned IPCs with SDF-1alpha. Results Our results showed that SDF-1alpha increases survival and proliferation of IPCs and protects them from glucotoxicity under high glucose conditions in vitro. SDF-1alpha also enhances the glucose responsive insulin secretion in IPCs in vitro. SDF-1alpha preconditioning reverses hyperglycemia and increase serum insulin in drug induced diabetic rats. Conclusions The differentiation of BMSCs into IPCs and enhancement of their therapeutic potential by SDF-1alpha preconditioning may contribute to cell based therapies for diabetes. PMID:23648189

CELES: CUDA-accelerated simulation of electromagnetic scattering by large ensembles of spheres

NASA Astrophysics Data System (ADS)

Egel, Amos; Pattelli, Lorenzo; Mazzamuto, Giacomo; Wiersma, Diederik S.; Lemmer, Uli

2017-09-01

CELES is a freely available MATLAB toolbox to simulate light scattering by many spherical particles. Aiming at high computational performance, CELES leverages block-diagonal preconditioning, a lookup-table approach to evaluate costly functions and massively parallel execution on NVIDIA graphics processing units using the CUDA computing platform. The combination of these techniques allows to efficiently address large electrodynamic problems (>104 scatterers) on inexpensive consumer hardware. In this paper, we validate near- and far-field distributions against the well-established multi-sphere T-matrix (MSTM) code and discuss the convergence behavior for ensembles of different sizes, including an exemplary system comprising 105 particles.

Scar revision - series (image)

MedlinePlus

... scar can be removed completely. The degree of improvement will depend on variables such as the direction and size of the scar, the age of the person, skin type and color, and hereditary factors that may precondition the extent of the healing process.

The in vitro preconditioning of myoblasts to enhance subsequent survival in an in vivo tissue engineering chamber model.

PubMed

Tilkorn, Daniel J; Davies, E Michele; Keramidaris, Effie; Dingle, Aaron M; Gerrand, Yi-Wen; Taylor, Caroline J; Han, Xiao Lian; Palmer, Jason A; Penington, Anthony J; Mitchell, Christina A; Morrison, Wayne A; Dusting, Gregory J; Mitchell, Geraldine M

2012-05-01

The effects of in vitro preconditioning protocols on the ultimate survival of myoblasts implanted in an in vivo tissue engineering chamber were examined. In vitro testing: L6 myoblasts were preconditioned by heat (42 °C; 1.5 h); hypoxia (<8% O(2); 1.5 h); or nitric oxide donors: S-nitroso-N-acetylpenicillamine (SNAP, 200 μM, 1.5 h) or 1-[N-(2-aminoethyl)-N-(2-aminoethyl)amino]-diazen-1-ium-1,2-diolate (DETA-NONOate, 500 μM, 7 h). Following a rest phase preconditioned cells were exposed to 24 h hypoxia, and demonstrated minimal overall cell loss, whilst controls (not preconditioned, but exposed to 24 h hypoxia) demonstrated a 44% cell loss. Phosphoimmunoblot analysis of pro-survival signaling pathways revealed significant activation of serine threonine kinase Akt with DETA-NONOate (p < 0.01) and heat preconditioning (p < 0.05). DETA-NONOate also activated ERK 1/2 signaling (p < 0.05). In vivo implantation: 100,000 preconditioned (heat, hypoxia, or DETA-NONOate) myoblasts were implanted in SCID mouse tissue engineering chambers. 100,000 (not preconditioned) myoblasts were implanted in control chambers. At 3 weeks, morphometric assessment of surviving myoblasts indicated myoblast percent volume (p = 0.012) and myoblasts/mm(2) (p = 0.0005) overall significantly increased in preconditioned myoblast chambers compared to control, with DETA-NONOate-preconditioned myoblasts demonstrating the greatest increase in survival (p = 0.007 and p = 0.001 respectively). DETA-NONOate therefore has potential therapeutic benefits to significantly improve survival of transplanted cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preconditioning Provides Neuroprotection in Models of CNS Disease: Paradigms and Clinical Significance

PubMed Central

Stetler, R. Anne; Leak, Rehana K.; Gan, Yu; Li, Peiying; Hu, Xiaoming; Jing, Zheng; Chen, Jun; Zigmond, Michael J.; Gao, Yanqin

2014-01-01

Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of “cross-tolerance,” in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning. In a subsequent components of this two-part series, we will discuss the cellular and molecular events that are likely to underlie these phenomena. PMID:24389580

Exploring the Role of TRPV and CGRP in Adenosine Preconditioning and Remote Hind Limb Preconditioning-Induced Cardioprotection in Rats.

PubMed

Singh, Amritpal; Randhawa, Puneet Kaur; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

2017-04-01

The cardioprotective effects of remote hind limb preconditioning (RIPC) are well known, but mechanisms by which protection occurs still remain to be explored. Therefore, the present study was designed to investigate the role of TRPV and CGRP in adenosine and remote preconditioning-induced cardioprotection, using sumatriptan, a CGRP release inhibitor and ruthenium red, a TRPV inhibitor, in rats. For remote preconditioning, a pressure cuff was tied around the hind limb of the rat and was inflated with air up to 150 mmHg to produce ischemia in the hind limb and during reperfusion pressure was released. Four cycles of ischemia and reperfusion, each consisting of 5 min of inflation and 5 min of deflation of pressure cuff were used to produce remote limb preconditioning. An ex vivo Langendorff's isolated rat heart model was used to induce ischemia reperfusion injury by 30 min of global ischemia followed by 120 min of reperfusion. RIPC demonstrated a significant decrease in ischemia reperfusion-induced significant myocardial injury in terms of increase in LDH, CK, infarct size and decrease in LVDP, +dp/dt max and -dp/dt min . Moreover, pharmacological preconditioning with adenosine produced cardioprotective effects in a similar manner to RIPC. Pretreatment with sumatriptan, a CGRP release blocker, abolished RIPC and adenosine preconditioning-induced cardioprotective effects. Administration of ruthenium red, a TRPV inhibitor, also abolished adenosine preconditioning-induced cardioprotection. It may be proposed that the cardioprotective effects of adenosine and remote preconditioning are possibly mediated through activation of a TRPV channels and consequent, release of CGRP.

Human Adipose-Derived Mesenchymal Stem Cells Respond to Short-Term Hypoxia by Secreting Factors Beneficial for Human Islets In Vitro and Potentiate Antidiabetic Effect In Vivo

PubMed Central

Schive, Simen W.; Mirlashari, Mohammad Reza; Hasvold, Grete; Wang, Mengyu; Josefsen, Dag; Gullestad, Hans Petter; Korsgren, Olle; Foss, Aksel; Kvalheim, Gunnar; Scholz, Hanne

2017-01-01

Adipose-derived mesenchymal stem cells (ASCs) release factors beneficial for islets in vitro and protect against hyperglycemia in rodent models of diabetes. Oxygen tension has been shown to induce metabolic changes and alter ASCs’ release of soluble factors. The effects of hypoxia on the antidiabetic properties of ASCs have not been explored. To investigate this, we incubated human ASCs for 48 h in 21% (normoxia) or 1% O2 (hypoxia) and compared viability, cell growth, surface markers, differentiation capability, and soluble factors in the conditioned media (CM). Human islets were exposed to CM from ASCs incubated in either normoxia or hypoxia, and islet function and apoptosis after culture with or without proinflammatory cytokines were measured. To test hypoxic preconditioned ASCs’ islet protective effects in vivo, ASCs were incubated for 48 h in normoxia or hypoxia before being injected into Balb/c Rag 1–/– immunodeficient mice with streptozotocin-induced insulitis. Progression of diabetes and insulin content of pancreas were measured. We found that incubation in hypoxia was well tolerated by ASCs and that levels of VEGF-A, FGF-2, and bNGF were elevated in CM from ASCs incubated in hypoxia compared to normoxia, while levels of HGF, IL-8, and CXCL1 were reduced. CM from ASCs incubated in hypoxia significantly improved human islet function and reduced apoptosis after culture, and reduced cytokine-induced apoptosis. In our mouse model, pancreas insulin content was higher in both groups receiving ASCs compared to control, but the mice receiving preconditioned ASCs had lower random and fasting blood glucose, as well as improved oral glucose tolerance compared to untreated mice. In conclusion, our in vitro results indicate that the islet protective potential of ASCs improves in hypoxia, and we give insight into factors involved in this. Finally we show that hypoxic preconditioning potentiates ASCs’ antidiabetic effect in vivo. PMID:28713640

High-intensity interval training (HIIT) increases insulin-like growth factor-I (IGF-I) in sedentary aging men but not masters' athletes: an observational study.

PubMed

Herbert, Peter; Hayes, Lawrence D; Sculthorpe, Nicholas; Grace, Fergal M

2017-03-01

The aim of this investigation was to examine the impact high-intensity interval training (HIIT) on serum insulin-like growth factor-I (IGF-I) in active compared with sedentary aging men. 22 lifetime sedentary (SED; 62 ± 2 years) and 17 masters' athletes (LEX; 60 ± 5 years) were recruited to the study. As HIIT requires preconditioning exercise in sedentary cohorts, the study required three assessment phases; enrollment (phase A), following preconditioning exercise (phase B), and post-HIIT (phase C). Serum IGF-I was determined by electrochemiluminescent immunoassay. IGF-I was higher in LEX compared to SED at baseline (p = 0.007, Cohen's d = 0.91), and phase B (p = 0.083, Cohen's d = 0.59), with only a small difference at C (p = 0.291, Cohen's d = 0.35). SED experienced a small increase in IGF-I following preconditioning from 13.1 ± 4.7 to 14.2 ± 6.0 μg·dl -1 (p = 0.376, Cohen's d = 0.22), followed by a larger increase post-HIIT (16.9 ± 4.4 μg·dl -1 ), which was significantly elevated compared with baseline (p = 0.002, Cohen's d = 0.85), and post-preconditioning (p = 0.005, Cohen's d = 0.51). LEX experienced a trivial changes in IGF-I from A to B (18.2 ± 6.4 to 17.2 ± 3.7 μg·dl -1 [p = 0.538, Cohen's d = 0.19]), and a small change post-HIIT (18.4 ± 4.1 μg·dl -1 [p = 0.283, Cohen's d = 0.31]). Small increases were observed in fat-free mass in both groups following HIIT (p < 0.05, Cohen's d = 0.32-0.45). In conclusion, HIIT with preconditioning exercise abrogates the age associated difference in IGF-I between SED and LEX, and induces small improvements in fat-free mass in both SED and LEX.

Preconditioning and the limit to the incompressible flow equations

NASA Technical Reports Server (NTRS)

Turkel, E.; Fiterman, A.; Vanleer, B.

1993-01-01

The use of preconditioning methods to accelerate the convergence to a steady state for both the incompressible and compressible fluid dynamic equations are considered. The relation between them for both the continuous problem and the finite difference approximation is also considered. The analysis relies on the inviscid equations. The preconditioning consists of a matrix multiplying the time derivatives. Hence, the steady state of the preconditioned system is the same as the steady state of the original system. For finite difference methods the preconditioning can change and improve the steady state solutions. An application to flow around an airfoil is presented.

Ischemic preconditioning protects against gap junctional uncoupling in cardiac myofibroblasts.

PubMed

Sundset, Rune; Cooper, Marie; Mikalsen, Svein-Ole; Ytrehus, Kirsti

2004-01-01

Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The purpose of this study was to investigate the role of gap junction communication in simulated preconditioning in cultured neonatal rat cardiac myofibroblasts. Gap junctional intercellular communication was assessed by Lucifer yellow dye transfer. Preconditioning preserved intercellular coupling after prolonged ischemia. An initial reduction in coupling in response to the preconditioning stimulus was also observed. This may protect neighboring cells from damaging substances produced during subsequent regional ischemia in vivo, and may preserve gap junctional communication required for enhanced functional recovery during subsequent reperfusion.

Role of Phosphatidylinositol-3 Kinase Pathway in NMDA Preconditioning: Different Mechanisms for Seizures and Hippocampal Neuronal Degeneration Induced by Quinolinic Acid.

PubMed

Constantino, Leandra C; Binder, Luisa B; Vandresen-Filho, Samuel; Viola, Giordano G; Ludka, Fabiana K; Lopes, Mark W; Leal, Rodrigo B; Tasca, Carla I

2018-04-20

N-methyl D-aspartate (NMDA) preconditioning is evoked by the administration of a subtoxic dose of NMDA and is protective against neuronal excitotoxicity. This effect may involve a diversity of targets and cell signaling cascades associated to neuroprotection. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinases (MAPKs) such as extracellular regulated protein kinase 1/2 (ERK1/2) and p38 MAPK pathways play a major role in neuroprotective mechanisms. However, their involvement in NMDA preconditioning was not yet fully investigated. The present study aimed to evaluate the effect of NMDA preconditioning on PI3K/Akt, ERK1/2, and p38 MAPK pathways in the hippocampus of mice and characterize the involvement of PI3K on NMDA preconditioning-evoked prevention of seizures and hippocampal cell damage induced by quinolinic acid (QA). Thus, mice received wortmannin (a PI3K inhibitor) and 15 min later a subconvulsant dose of NMDA (preconditioning) or saline. After 24 h of this treatment, an intracerebroventricular QA infusion was administered. Phosphorylation levels and total content of Akt, glycogen synthase protein kinase-3β (GSK-3β), ERK1/2, and p38 MAPK were not altered after 24 h of NMDA preconditioning with or without wortmmanin pretreatment. Moreover, after QA administration, behavioral seizures, hippocampal neuronal degeneration, and Akt activation were evaluated. Inhibition of PI3K pathway was effective in abolishing the protective effect of NMDA preconditioning against QA-induced seizures, but did not modify neuronal protection promoted by preconditioning as evaluated by Fluoro-Jade B staining. The study confirms that PI3K participates in the mechanism of protection induced by NMDA preconditioning against QA-induced seizures. Conversely, NMDA preconditioning-evoked protection against neuronal degeneration is not altered by PI3K signaling pathway inhibition. These results point to differential mechanisms regarding protection against a behavioral and cellular manifestation of neural damage.

Use of the preconditioned conjugate gradient algorithm as a generic solver for mixed-model equations in animal breeding applications.

PubMed

Tsuruta, S; Misztal, I; Strandén, I

2001-05-01

Utility of the preconditioned conjugate gradient algorithm with a diagonal preconditioner for solving mixed-model equations in animal breeding applications was evaluated with 16 test problems. The problems included single- and multiple-trait analyses, with data on beef, dairy, and swine ranging from small examples to national data sets. Multiple-trait models considered low and high genetic correlations. Convergence was based on relative differences between left- and right-hand sides. The ordering of equations was fixed effects followed by random effects, with no special ordering within random effects. The preconditioned conjugate gradient program implemented with double precision converged for all models. However, when implemented in single precision, the preconditioned conjugate gradient algorithm did not converge for seven large models. The preconditioned conjugate gradient and successive overrelaxation algorithms were subsequently compared for 13 of the test problems. The preconditioned conjugate gradient algorithm was easy to implement with the iteration on data for general models. However, successive overrelaxation requires specific programming for each set of models. On average, the preconditioned conjugate gradient algorithm converged in three times fewer rounds of iteration than successive overrelaxation. With straightforward implementations, programs using the preconditioned conjugate gradient algorithm may be two or more times faster than those using successive overrelaxation. However, programs using the preconditioned conjugate gradient algorithm would use more memory than would comparable implementations using successive overrelaxation. Extensive optimization of either algorithm can influence rankings. The preconditioned conjugate gradient implemented with iteration on data, a diagonal preconditioner, and in double precision may be the algorithm of choice for solving mixed-model equations when sufficient memory is available and ease of implementation is essential.

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

PubMed Central

Gomez, D; Homer-Vanniasinkam, S; Graham, AM; Prasad, KR

2007-01-01

Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords “liver”, “ischaemic reperfusion”, “ischaemic preconditioning”, “regeneration”, “hepatectomy” and “transplantation”. The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growth-promoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation. PMID:17278187

Use of upscaled elevation and surface roughness data in two-dimensional surface water models

USGS Publications Warehouse

Hughes, J.D.; Decker, J.D.; Langevin, C.D.

2011-01-01

In this paper, we present an approach that uses a combination of cell-block- and cell-face-averaging of high-resolution cell elevation and roughness data to upscale hydraulic parameters and accurately simulate surface water flow in relatively low-resolution numerical models. The method developed allows channelized features that preferentially connect large-scale grid cells at cell interfaces to be represented in models where these features are significantly smaller than the selected grid size. The developed upscaling approach has been implemented in a two-dimensional finite difference model that solves a diffusive wave approximation of the depth-integrated shallow surface water equations using preconditioned Newton–Krylov methods. Computational results are presented to show the effectiveness of the mixed cell-block and cell-face averaging upscaling approach in maintaining model accuracy, reducing model run-times, and how decreased grid resolution affects errors. Application examples demonstrate that sub-grid roughness coefficient variations have a larger effect on simulated error than sub-grid elevation variations.

Matrix preconditioning: a robust operation for optical linear algebra processors.

PubMed

Ghosh, A; Paparao, P

1987-07-15

Analog electrooptical processors are best suited for applications demanding high computational throughput with tolerance for inaccuracies. Matrix preconditioning is one such application. Matrix preconditioning is a preprocessing step for reducing the condition number of a matrix and is used extensively with gradient algorithms for increasing the rate of convergence and improving the accuracy of the solution. In this paper, we describe a simple parallel algorithm for matrix preconditioning, which can be implemented efficiently on a pipelined optical linear algebra processor. From the results of our numerical experiments we show that the efficacy of the preconditioning algorithm is affected very little by the errors of the optical system.

Development and acceleration of unstructured mesh-based cfd solver

NASA Astrophysics Data System (ADS)

Emelyanov, V.; Karpenko, A.; Volkov, K.

2017-06-01

The study was undertaken as part of a larger effort to establish a common computational fluid dynamics (CFD) code for simulation of internal and external flows and involves some basic validation studies. The governing equations are solved with ¦nite volume code on unstructured meshes. The computational procedure involves reconstruction of the solution in each control volume and extrapolation of the unknowns to find the flow variables on the faces of control volume, solution of Riemann problem for each face of the control volume, and evolution of the time step. The nonlinear CFD solver works in an explicit time-marching fashion, based on a three-step Runge-Kutta stepping procedure. Convergence to a steady state is accelerated by the use of geometric technique and by the application of Jacobi preconditioning for high-speed flows, with a separate low Mach number preconditioning method for use with low-speed flows. The CFD code is implemented on graphics processing units (GPUs). Speedup of solution on GPUs with respect to solution on central processing units (CPU) is compared with the use of different meshes and different methods of distribution of input data into blocks. The results obtained provide promising perspective for designing a GPU-based software framework for applications in CFD.

Identification af explosive power factors as predictors of player quality in young female volleyball players.

PubMed

Grgantov, Zoran; Milić, Mirjana; Katić, Ratko

2013-05-01

With the purpose of determining the factor structure of explosive power, as well as the influence of each factor on situational efficiency, 56 young female volleyball players were tested using 14 tests for assessing nonspecific and specific explosive power. By factor analysis, 4 significant factors were isolated which explained the total of over 80% of the common variability in young female volleyball players. The first factor was defined as volleyball-specific jumping, the second factor as nonspecific jumping and sprinting, the third factor as throwing explosive power, while the fourth factor was interpreted as volleyball-specific throwing and spiking speed from the ground. Results obtained by regression analysis in the latent space of explosive power indicate that the identified factors are good predictors of player quality in young female volleyball players. The fourth factor defined as throwing and spiking speed from the ground had the largest influence on player quality, followed by volleyball-specific jumping and nonspecific jumping and sprinting, and to a much lesser extent, by throwing explosive power The results obtained in this age group bring to the fore the ability of spiking and serving a ball of high speed, which hinders the opponents from playing those balls in serve reception and field defence. This ability, combined with a high standing vertical jump reach and spike approach vertical jump reach (which is the basis of the 1st varimax factor) enables successful performance of all volleyball elements by which points are won in complex 1 (spike) and complex 2 (serve and block). Even though the 2nd factor (nonspecific jumping and sprinting) has a slightly smaller impact on situational efficiency in young players, this ability provides preconditions i.e. preparation for successful realisation of all volleyball elements, so greater attention must be paid to perfecting it in young female volleyball players.

Hypoxia preconditioning increases survival and decreases expression of Toll-like receptor 4 in pulmonary artery endothelial cells exposed to lipopolysaccharide

PubMed Central

Nanchal, Rahul; Audi, Said; Konduri, G. Ganesh; Medhora, Meetha

2013-01-01

Abstract Pulmonary or systemic infections and hypoxemic respiratory failure are among the leading causes of admission to intensive care units, and these conditions frequently exist in sequence or in tandem. Inflammatory responses to infections are reproduced by lipopolysaccharide (LPS) engaging Toll-like receptor 4 (TLR4). Apoptosis is a hallmark of lung injury in sepsis. This study was conducted to determine whether preexposure to LPS or hypoxia modulated the survival of pulmonary artery endothelial cells (PAECs). We also investigated the role TLR4 receptor expression plays in apoptosis due to these conditions. Bovine PAECs were cultured in hypoxic or normoxic environments and treated with LPS. TLR4 antagonist TAK-242 was used to probe the role played by TLR4 receptors in cell survival. Cell apoptosis and survival were measured by caspase 3 activity and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) incorporation. TLR4 expression and tumor necrosis factor α (TNF-α) production were also determined. LPS increased caspase 3 activity in a TAK-242-sensitive manner and decreased MTT incorporation. Apoptosis was decreased in PAECs preconditioned with hypoxia prior to LPS exposure. LPS increased TNF-α production, and hypoxic preconditioning blunted it. Hypoxic preconditioning reduced LPS-induced TLR4 messenger RNA and TLR4 protein. TAK-242 decreased to baseline the LPS-stimulated expression of TLR4 messenger RNA regardless of environmental conditions. In contrast, LPS followed by hypoxia substantially increased apoptosis and cell death. In conclusion, protection from LPS-stimulated PAEC apoptosis by hypoxic preconditioning is attributable in part to reduction in TLR4 expression. If these signaling pathways apply to septic patients, they may account for differing sensitivities of individuals to acute lung injury depending on oxygen tensions in PAECs in vivo. PMID:24618542

Morphine-Induced Preconditioning: Involvement of Protein Kinase A and Mitochondrial Permeability Transition Pore

PubMed Central

Dorsch, Marianne; Behmenburg, Friederike; Raible, Miriam; Blase, Dominic; Grievink, Hilbert; Hollmann, Markus W.; Heinen, André; Huhn, Ragnar

2016-01-01

Background Morphine induces myocardial preconditioning (M-PC) via activation of mitochondrial large conductance Ca2+-sensitive potassium (mKCa) channels. An upstream regulator of mKCa channels is protein kinase A (PKA). Furthermore, mKCa channel activation regulates mitochondrial bioenergetics and thereby prevents opening of the mitochondrial permeability transition pore (mPTP). Here, we investigated in the rat heart in vivo whether 1) M-PC is mediated by activation of PKA, and 2) pharmacological opening of the mPTP abolishes the cardioprotective effect of M-PC and 3) M-PC is critically dependent on STAT3 activation, which is located upstream of mPTP within the signalling pathway. Methods Male Wistar rats were randomised to six groups (each n = 6). All animals underwent 25 minutes of regional myocardial ischemia and 120 minutes of reperfusion. Control animals (Con) were not further treated. Morphine preconditioning was initiated by intravenous administration of 0.3 mg/kg morphine (M-PC). The PKA blocker H-89 (10 μg/kg) was investigated with and without morphine (H-89+M-PC, H-89). We determined the effect of mPTP opening with atractyloside (5 mg/kg) with and without morphine (Atr+M-PC, Atr). Furthermore, the effect of morphine on PKA activity was tested in isolated adult rat cardiomyocytes. In further experiments in isolated hearts we tested the protective properties of morphine in the presence of STAT3 inhibition, and whether pharmacological prevention of the mPTP-opening by cyclosporine A (CsA) is cardioprotective in the presence of STAT3 inhibition. Results Morphine reduced infarct size from 64±5% to 39±9% (P<0.05 vs. Con). H-89 completely blocked preconditioning by morphine (64±9%; P<0.05 vs. M-PC), but H-89 itself had not effect on infarct size (61±10%; P>0.05 vs. Con). Also, atractyloside abolished infarct size reduction of morphine completely (65±9%; P<0.05 vs. M-PC) but had no influence on infarct size itself (64±5%; P>0.05 vs. Con). In isolated hearts STAT3 inhibitor Stattic completely abolished morphine-induced preconditioning. Administration of Stattic and mPTP inhibitor cyclosporine A reduced infarct size to 31±6% (Stat+CsA, P<0.05 vs. Con). Cyclosporine A alone reduced infarct size to 26±7% (CsA P<0.05 vs. Con). In cardiomyocytes, PKA activity was increased by morphine. Conclusion Our data suggest that morphine-induced cardioprotection is mediated by STAT3-activation and inhibition of mPTP, with STA3 located upstream of mPTP. There is some evidence that protein kinase A is involved within the signalling pathway. PMID:26968004

A new estimation of equivalent matrix block sizes in fractured media with two-phase flow applications in dual porosity models

NASA Astrophysics Data System (ADS)

Jerbi, Chahir; Fourno, André; Noetinger, Benoit; Delay, Frederick

2017-05-01

Single and multiphase flows in fractured porous media at the scale of natural reservoirs are often handled by resorting to homogenized models that avoid the heavy computations associated with a complete discretization of both fractures and matrix blocks. For example, the two overlapping continua (fractures and matrix) of a dual porosity system are coupled by way of fluid flux exchanges that deeply condition flow at the large scale. This characteristic is a key to realistic flow simulations, especially for multiphase flow as capillary forces and contrasts of fluid mobility compete in the extraction of a fluid from a capacitive matrix then conveyed through the fractures. The exchange rate between fractures and matrix is conditioned by the so-called mean matrix block size which can be viewed as the size of a single matrix block neighboring a single fracture within a mesh of a dual porosity model. We propose a new evaluation of this matrix block size based on the analysis of discrete fracture networks. The fundaments rely upon establishing at the scale of a fractured block the equivalence between the actual fracture network and a Warren and Root network only made of three regularly spaced fracture families parallel to the facets of the fractured block. The resulting matrix block sizes are then compared via geometrical considerations and two-phase flow simulations to the few other available methods. It is shown that the new method is stable in the sense it provides accurate sizes irrespective of the type of fracture network investigated. The method also results in two-phase flow simulations from dual porosity models very close to that from references calculated in finely discretized networks. Finally, calculations of matrix block sizes by this new technique reveal very rapid, which opens the way to cumbersome applications such as preconditioning a dual porosity approach applied to regional fractured reservoirs.

Efficient Iterative Methods Applied to the Solution of Transonic Flows

NASA Astrophysics Data System (ADS)

Wissink, Andrew M.; Lyrintzis, Anastasios S.; Chronopoulos, Anthony T.

1996-02-01

We investigate the use of an inexact Newton's method to solve the potential equations in the transonic regime. As a test case, we solve the two-dimensional steady transonic small disturbance equation. Approximate factorization/ADI techniques have traditionally been employed for implicit solutions of this nonlinear equation. Instead, we apply Newton's method using an exact analytical determination of the Jacobian with preconditioned conjugate gradient-like iterative solvers for solution of the linear systems in each Newton iteration. Two iterative solvers are tested; a block s-step version of the classical Orthomin(k) algorithm called orthogonal s-step Orthomin (OSOmin) and the well-known GMRES method. The preconditioner is a vectorizable and parallelizable version of incomplete LU (ILU) factorization. Efficiency of the Newton-Iterative method on vector and parallel computer architectures is the main issue addressed. In vectorized tests on a single processor of the Cray C-90, the performance of Newton-OSOmin is superior to Newton-GMRES and a more traditional monotone AF/ADI method (MAF) for a variety of transonic Mach numbers and mesh sizes. Newton-GMRES is superior to MAF for some cases. The parallel performance of the Newton method is also found to be very good on multiple processors of the Cray C-90 and on the massively parallel thinking machine CM-5, where very fast execution rates (up to 9 Gflops) are found for large problems.

Galilean-invariant preconditioned central-moment lattice Boltzmann method without cubic velocity errors for efficient steady flow simulations

NASA Astrophysics Data System (ADS)

Hajabdollahi, Farzaneh; Premnath, Kannan N.

2018-05-01

Lattice Boltzmann (LB) models used for the computation of fluid flows represented by the Navier-Stokes (NS) equations on standard lattices can lead to non-Galilean-invariant (GI) viscous stress involving cubic velocity errors. This arises from the dependence of their third-order diagonal moments on the first-order moments for standard lattices, and strategies have recently been introduced to restore Galilean invariance without such errors using a modified collision operator involving corrections to either the relaxation times or the moment equilibria. Convergence acceleration in the simulation of steady flows can be achieved by solving the preconditioned NS equations, which contain a preconditioning parameter that can be used to tune the effective sound speed, and thereby alleviating the numerical stiffness. In the present paper, we present a GI formulation of the preconditioned cascaded central-moment LB method used to solve the preconditioned NS equations, which is free of cubic velocity errors on a standard lattice, for steady flows. A Chapman-Enskog analysis reveals the structure of the spurious non-GI defect terms and it is demonstrated that the anisotropy of the resulting viscous stress is dependent on the preconditioning parameter, in addition to the fluid velocity. It is shown that partial correction to eliminate the cubic velocity defects is achieved by scaling the cubic velocity terms in the off-diagonal third-order moment equilibria with the square of the preconditioning parameter. Furthermore, we develop additional corrections based on the extended moment equilibria involving gradient terms with coefficients dependent locally on the fluid velocity and the preconditioning parameter. Such parameter dependent corrections eliminate the remaining truncation errors arising from the degeneracy of the diagonal third-order moments and fully restore Galilean invariance without cubic defects for the preconditioned LB scheme on a standard lattice. Several conclusions are drawn from the analysis of the structure of the non-GI errors and the associated corrections, with particular emphasis on their dependence on the preconditioning parameter. The GI preconditioned central-moment LB method is validated for a number of complex flow benchmark problems and its effectiveness to achieve convergence acceleration and improvement in accuracy is demonstrated.

Efficient Parallel Formulations of Hierarchical Methods and Their Applications

NASA Astrophysics Data System (ADS)

Grama, Ananth Y.

1996-01-01

Hierarchical methods such as the Fast Multipole Method (FMM) and Barnes-Hut (BH) are used for rapid evaluation of potential (gravitational, electrostatic) fields in particle systems. They are also used for solving integral equations using boundary element methods. The linear systems arising from these methods are dense and are solved iteratively. Hierarchical methods reduce the complexity of the core matrix-vector product from O(n^2) to O(n log n) and the memory requirement from O(n^2) to O(n). We have developed highly scalable parallel formulations of a hybrid FMM/BH method that are capable of handling arbitrarily irregular distributions. We apply these formulations to astrophysical simulations of Plummer and Gaussian galaxies. We have used our parallel formulations to solve the integral form of the Laplace equation. We show that our parallel hierarchical mat-vecs yield high efficiency and overall performance even on relatively small problems. A problem containing approximately 200K nodes takes under a second to compute on 256 processors and yet yields over 85% efficiency. The efficiency and raw performance is expected to increase for bigger problems. For the 200K node problem, our code delivers about 5 GFLOPS of performance on a 256 processor T3D. This is impressive considering the fact that the problem has floating point divides and roots, and very little locality resulting in poor cache performance. A dense matrix-vector product of the same dimensions would require about 0.5 TeraBytes of memory and about 770 TeraFLOPS of computing speed. Clearly, if the loss in accuracy resulting from the use of hierarchical methods is acceptable, our code yields significant savings in time and memory. We also study the convergence of a GMRES solver built around this mat-vec. We accelerate the convergence of the solver using three preconditioning techniques: diagonal scaling, block-diagonal preconditioning, and inner-outer preconditioning. We study the performance and parallel efficiency of these preconditioned solvers. Using this solver, we solve dense linear systems with hundreds of thousands of unknowns. Solving a 105K unknown problem takes about 10 minutes on a 64 processor T3D. Until very recently, boundary element problems of this magnitude could not even be generated, let alone solved.

Impact of sea-level rise on earthquake and landslide triggering offshore the Alentejo margin (SW Iberia)

NASA Astrophysics Data System (ADS)

Neves, M. C.; Roque, C.; Luttrell, K. M.; Vázquez, J. T.; Alonso, B.

2016-12-01

Earthquakes and submarine landslides are recurrent and widespread manifestations of fault activity offshore SW Iberia. The present work tests the effects of sea-level rise on offshore fault systems using Coulomb stress change calculations across the Alentejo margin. Large-scale faults capable of generating large earthquakes and tsunamis in the region, especially NE-SW trending thrusts and WNW-ESE trending dextral strike-slip faults imaged at basement depths, are either blocked or unaffected by flexural effects related to sea-level changes. Large-magnitude earthquakes occurring along these structures may, therefore, be less frequent during periods of sea-level rise. In contrast, sea-level rise promotes shallow fault ruptures within the sedimentary sequence along the continental slope and upper rise within distances of <100 km from the coast. The results suggest that the occurrence of continental slope failures may either increase (if triggered by shallow fault ruptures) or decrease (if triggered by deep fault ruptures) as a result of sea-level rise. Moreover, observations of slope failures affecting the area of the Sines contourite drift highlight the role of sediment properties as preconditioning factors in this region.

An implicit numerical scheme for the simulation of internal viscous flows on unstructured grids

NASA Technical Reports Server (NTRS)

Jorgenson, Philip C. E.; Pletcher, Richard H.

1994-01-01

The Navier-Stokes equations are solved numerically for two-dimensional steady viscous laminar flows. The grids are generated based on the method of Delaunay triangulation. A finite-volume approach is used to discretize the conservation law form of the compressible flow equations written in terms of primitive variables. A preconditioning matrix is added to the equations so that low Mach number flows can be solved economically. The equations are time marched using either an implicit Gauss-Seidel iterative procedure or a solver based on a conjugate gradient like method. A four color scheme is employed to vectorize the block Gauss-Seidel relaxation procedure. This increases the memory requirements minimally and decreases the computer time spent solving the resulting system of equations substantially. A factor of 7.6 speed up in the matrix solver is typical for the viscous equations. Numerical results are obtained for inviscid flow over a bump in a channel at subsonic and transonic conditions for validation with structured solvers. Viscous results are computed for developing flow in a channel, a symmetric sudden expansion, periodic tandem cylinders in a cross-flow, and a four-port valve. Comparisons are made with available results obtained by other investigators.

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.

Eigenmode Analysis of Boundary Conditions for One-Dimensional Preconditioned Euler Equations

NASA Technical Reports Server (NTRS)

Darmofal, David L.

1998-01-01

An analysis of the effect of local preconditioning on boundary conditions for the subsonic, one-dimensional Euler equations is presented. Decay rates for the eigenmodes of the initial boundary value problem are determined for different boundary conditions. Riemann invariant boundary conditions based on the unpreconditioned Euler equations are shown to be reflective with preconditioning, and, at low Mach numbers, disturbances do not decay. Other boundary conditions are investigated which are non-reflective with preconditioning and numerical results are presented confirming the analysis.

Capturing Flow in the Business Classroom

ERIC Educational Resources Information Center

Guo, Yi Maggie; Ro, Young K.

2008-01-01

This study focuses on the flow experience in business education. Flow experience, characterized by concentration, control, and enjoyment, can lead to better learning outcomes. Leading preconditions of flow include the balance of challenge and skill, feedback, and goal clarity. Other situational factors affect the flow experience through the…

Gadolinium and ruthenium red attenuate remote hind limb preconditioning-induced cardioprotection: possible role of TRP and especially TRPV channels.

PubMed

Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2016-08-01

Remote ischemic preconditioning is a well reported therapeutic strategy that induces cardioprotective effects but the underlying intracellular mechanisms have not been widely explored. The current study was designed to investigate the involvement of TRP and especially TRPV channels in remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 alternate cycles of inflation and deflation of 5 min each) was delivered using a blood pressure cuff tied on the hind limb of the anesthetized rat. Using Langendorff's system, the heart was perfused and subjected to 30-min ischemia and 120-min reperfusion. The myocardial injury was assessed by measuring infarct size, lactate dehydrogenase (LDH), creatine kinase (CK), LVDP, +dp/dtmax, -dp/dtmin, heart rate, and coronary flow rate. Gadolinium, TRP blocker, and ruthenium red, TRPV channel blocker, were employed as pharmacological tools. Remote hind limb preconditioning significantly reduced the infarct size, LDH release, CK release and improved coronary flow rate, hemodynamic parameters including LVDP, +dp/dtmax, -dp/dtmin, and heart rate. However, gadolinium (7.5 and 15 mg kg(-1)) and ruthenium red (4 and 8 mg kg(-1)) significantly attenuated the cardioprotective effects suggesting the involvement of TRP especially TRPV channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus possibly activates TRPV channels on the heart or sensory nerve fibers innervating the heart to induce cardioprotective effects. Alternatively, remote hind limb preconditioning stimulus may also activate the mechanosensitive TRP and especially TRPV channels on the sensory nerve fibers innervating the skeletal muscles to trigger cardioprotective neurogenic signaling cascade. The cardioprotective effects of remote hind limb preconditioning may be mediated via activation of mechanosensitive TRP and especially TRPV channels.

40 CFR 1065.518 - Engine preconditioning.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Engine preconditioning. 1065.518... CONTROLS ENGINE-TESTING PROCEDURES Performing an Emission Test Over Specified Duty Cycles § 1065.518 Engine preconditioning. (a) This section applies for engines where measured emissions are affected by prior operation...

GENE EXPRESSION CHANGES AFTER SEIZURE PRECONDITIONING IN THE THREE MAJOR HIPPOCAMPAL CELL LAYERS

PubMed Central

Borges, Karin; Shaw, Renee; Dingledine, Raymond

2008-01-01

Rodents experience hippocampal damage after status epilepticus (SE) mainly in pyramidal cells while sparing the dentate granule cell layer (DGCL). Hippocampal damage was prevented in rats that had been preconditioned by brief seizures on two consecutive days before SE. To identify neuroprotective genes and biochemical pathways changed after preconditioning we compared the effect of preconditioning on gene expression in the CA1 and CA3 pyramidal and DGCLs, harvested by laser capture microscopy. In the DGCL the expression of 632 genes was altered, compared to only 151 and 58 genes in CA1 and CA3 pyramidal cell layers. Most of the differentially expressed genes regulate tissue structure and intra- and extracellular signaling, including neurotransmission. A selective upregulation of energy metabolism transcripts occurred in CA1 pyramidal cells relative to the DGCL. These results reveal a broad transcriptional response of the DGCL to preconditioning, and suggest several mechanisms underlying the neuroprotective effect of preconditioning seizures. PMID:17239605

Analysis of physics-based preconditioning for single-phase subchannel equations

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

Hansel, J. E.; Ragusa, J. C.; Allu, S.

2013-07-01

The (single-phase) subchannel approximations are used throughout nuclear engineering to provide an efficient flow simulation because the computational burden is much smaller than for computational fluid dynamics (CFD) simulations, and empirical relations have been developed and validated to provide accurate solutions in appropriate flow regimes. Here, the subchannel equations have been recast in a residual form suitable for a multi-physics framework. The Eigen spectrum of the Jacobian matrix, along with several potential physics-based preconditioning approaches, are evaluated, and the the potential for improved convergence from preconditioning is assessed. The physics-based preconditioner options include several forms of reduced equations that decouplemore » the subchannels by neglecting crossflow, conduction, and/or both turbulent momentum and energy exchange between subchannels. Eigen-scopy analysis shows that preconditioning moves clusters of eigenvalues away from zero and toward one. A test problem is run with and without preconditioning. Without preconditioning, the solution failed to converge using GMRES, but application of any of the preconditioners allowed the solution to converge. (authors)« less

AMP-activated protein kinase (AMPK)-induced preconditioning in primary cortical neurons involves activation of MCL-1.

PubMed

Anilkumar, Ujval; Weisová, Petronela; Düssmann, Heiko; Concannon, Caoimhín G; König, Hans-Georg; Prehn, Jochen H M

2013-03-01

Neuronal preconditioning is a phenomenon where a previous exposure to a sub-lethal stress stimulus increases the resistance of neurons towards a second, normally lethal stress stimulus. Activation of the energy stress sensor, AMP-activated protein kinase (AMPK) has been shown to contribute to the protective effects of ischaemic and mitochondrial uncoupling-induced preconditioning in neurons, however, the molecular basis of AMPK-mediated preconditioning has been less well characterized. We investigated the effect of AMPK preconditioning using 5-aminoimidazole-4-carboxamide riboside (AICAR) in a model of NMDA-mediated excitotoxic injury in primary mouse cortical neurons. Activation of AMPK with low concentrations of AICAR (0.1 mM for 2 h) induced a transient increase in AMPK phosphorylation, protecting neurons against NMDA-induced excitotoxicity. Analysing potential targets of AMPK activation, demonstrated a marked increase in mRNA expression and protein levels of the anti-apoptotic BCL-2 family protein myeloid cell leukaemia sequence 1 (MCL-1) in AICAR-preconditioned neurons. Interestingly, over-expression of MCL-1 protected neurons against NMDA-induced excitotoxicity while MCL-1 gene silencing abolished the effect of AICAR preconditioning. Monitored intracellular Ca²⁺ levels during NMDA excitation revealed that MCL-1 over-expressing neurons exhibited improved bioenergetics and markedly reduced Ca²⁺ elevations, suggesting a potential mechanism through which MCL-1 confers neuroprotection. This study identifies MCL-1 as a key effector of AMPK-induced preconditioning in neurons. © 2012 International Society for Neurochemistry.

Optimal preconditioning of lattice Boltzmann methods

NASA Astrophysics Data System (ADS)

Izquierdo, Salvador; Fueyo, Norberto

2009-09-01

A preconditioning technique to accelerate the simulation of steady-state problems using the single-relaxation-time (SRT) lattice Boltzmann (LB) method was first proposed by Guo et al. [Z. Guo, T. Zhao, Y. Shi, Preconditioned lattice-Boltzmann method for steady flows, Phys. Rev. E 70 (2004) 066706-1]. The key idea in this preconditioner is to modify the equilibrium distribution function in such a way that, by means of a Chapman-Enskog expansion, a time-derivative preconditioner of the Navier-Stokes (NS) equations is obtained. In the present contribution, the optimal values for the free parameter γ of this preconditioner are searched both numerically and theoretically; the later with the aid of linear-stability analysis and with the condition number of the system of NS equations. The influence of the collision operator, single- versus multiple-relaxation-times (MRT), is also studied. Three steady-state laminar test cases are used for validation, namely: the two-dimensional lid-driven cavity, a two-dimensional microchannel and the three-dimensional backward-facing step. Finally, guidelines are suggested for an a priori definition of optimal preconditioning parameters as a function of the Reynolds and Mach numbers. The new optimally preconditioned MRT method derived is shown to improve, simultaneously, the rate of convergence, the stability and the accuracy of the lattice Boltzmann simulations, when compared to the non-preconditioned methods and to the optimally preconditioned SRT one. Additionally, direct time-derivative preconditioning of the LB equation is also studied.

40 CFR 92.125 - Pre-test procedures and preconditioning.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Pre-test procedures and preconditioning... PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and preconditioning. (a) Locomotive testing. (1) Determine engine lubricating...

WARP3D-Release 10.8: Dynamic Nonlinear Analysis of Solids using a Preconditioned Conjugate Gradient Software Architecture

NASA Technical Reports Server (NTRS)

Koppenhoefer, Kyle C.; Gullerud, Arne S.; Ruggieri, Claudio; Dodds, Robert H., Jr.; Healy, Brian E.

1998-01-01

This report describes theoretical background material and commands necessary to use the WARP3D finite element code. WARP3D is under continuing development as a research code for the solution of very large-scale, 3-D solid models subjected to static and dynamic loads. Specific features in the code oriented toward the investigation of ductile fracture in metals include a robust finite strain formulation, a general J-integral computation facility (with inertia, face loading), an element extinction facility to model crack growth, nonlinear material models including viscoplastic effects, and the Gurson-Tver-gaard dilatant plasticity model for void growth. The nonlinear, dynamic equilibrium equations are solved using an incremental-iterative, implicit formulation with full Newton iterations to eliminate residual nodal forces. The history integration of the nonlinear equations of motion is accomplished with Newmarks Beta method. A central feature of WARP3D involves the use of a linear-preconditioned conjugate gradient (LPCG) solver implemented in an element-by-element format to replace a conventional direct linear equation solver. This software architecture dramatically reduces both the memory requirements and CPU time for very large, nonlinear solid models since formation of the assembled (dynamic) stiffness matrix is avoided. Analyses thus exhibit the numerical stability for large time (load) steps provided by the implicit formulation coupled with the low memory requirements characteristic of an explicit code. In addition to the much lower memory requirements of the LPCG solver, the CPU time required for solution of the linear equations during each Newton iteration is generally one-half or less of the CPU time required for a traditional direct solver. All other computational aspects of the code (element stiffnesses, element strains, stress updating, element internal forces) are implemented in the element-by- element, blocked architecture. This greatly improves vectorization of the code on uni-processor hardware and enables straightforward parallel-vector processing of element blocks on multi-processor hardware.

Conceptual Basis of Educational Service Resource Support

ERIC Educational Resources Information Center

Ledyankina, Olga V.; Akimova, Olga B.; Fomin, Evgenii P.

2016-01-01

Topicality of the issue researched is preconditioned by the need to describe the conceptual basis and significance of educational service resource support of at the current development stage of Russian vocational education, classification of its main components as well as significance of the need to transform resource support from the factor that…

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior

PubMed Central

Cheng, Yuyan; Pardo, Marta; de Souza Armini, Rubia; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S.; Beurel, Eleonore

2016-01-01

Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6 to 12 hr after stress. A 24 hr prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine and chemokine increases, with most reaching peak levels after 1 to 3 hr, often without altering the maximal levels. Toll-like receptor 4 (TLR4) was involved in this response because most stress-induced hippocampal cytokines and chemokines were attenuated in TLR4 knockout mice. Stress activated glycogen synthase kinase-3 (GSK3) in wild-type mouse hippocampus, but not in TLR4 knockout mice. Administration of the antidepressant fluoxetine or the GSK3 inhibitor TDZD-8 reduced the stress-induced increases of most hippocampal cytokines and chemokines. Stress increased hippocampal levels of the danger-associated molecular pattern (DAMP) protein high mobility group box 1 (HMGB1), activated the inflammatory transcription factor NF-κB, and the NLRP3 inflammasome. Knockdown of HMGB1 blocked the acceleration of cytokine and chemokine increases in the hippocampus caused by two successive stresses. Fluoxetine treatment blocked stress-induced up-regulation of HMGB1 and subsequent NF-κB activation, whereas TDZD-8 administration attenuated NF-κB activation downstream of HMGB1. To test if stress-induced cytokines and chemokines contribute to depression-like behavior, the learned helplessness model was assessed. Antagonism of TNFα modestly reduced susceptibility to learned helplessness induction, whereas TLR4 knockout mice were resistant to learned helplessness. Thus, stress-induces a broad inflammatory response in mouse hippocampus that involves TLR4, GSK3, and downstream inflammatory signaling, and these stress responses contribute to susceptibility to depression-like behavior in mice. PMID:26772151

Stress-induced neuroinflammation is mediated by GSK3-dependent TLR4 signaling that promotes susceptibility to depression-like behavior.

PubMed

Cheng, Yuyan; Pardo, Marta; Armini, Rubia de Souza; Martinez, Ana; Mouhsine, Hadley; Zagury, Jean-Francois; Jope, Richard S; Beurel, Eleonore

2016-03-01

Most psychiatric and neurological diseases are exacerbated by stress. Because this may partially result from stress-induced inflammation, we examined factors involved in this stress response. After a paradigm of inescapable foot shock stress that causes learned helplessness depression-like behavior, eighteen cytokines and chemokines increased in mouse hippocampus, peaking 6-12h after stress. A 24h prior pre-conditioning stress accelerated the rate of stress-induced hippocampal cytokine and chemokine increases, with most reaching peak levels after 1-3h, often without altering the maximal levels. Toll-like receptor 4 (TLR4) was involved in this response because most stress-induced hippocampal cytokines and chemokines were attenuated in TLR4 knockout mice. Stress activated glycogen synthase kinase-3 (GSK3) in wild-type mouse hippocampus, but not in TLR4 knockout mice. Administration of the antidepressant fluoxetine or the GSK3 inhibitor TDZD-8 reduced the stress-induced increases of most hippocampal cytokines and chemokines. Stress increased hippocampal levels of the danger-associated molecular pattern (DAMP) protein high mobility group box 1 (HMGB1), activated the inflammatory transcription factor NF-κB, and the NLRP3 inflammasome. Knockdown of HMGB1 blocked the acceleration of cytokine and chemokine increases in the hippocampus caused by two successive stresses. Fluoxetine treatment blocked stress-induced up-regulation of HMGB1 and subsequent NF-κB activation, whereas TDZD-8 administration attenuated NF-κB activation downstream of HMGB1. To test if stress-induced cytokines and chemokines contribute to depression-like behavior, the learned helplessness model was assessed. Antagonism of TNFα modestly reduced susceptibility to learned helplessness induction, whereas TLR4 knockout mice were resistant to learned helplessness. Thus, stress-induces a broad inflammatory response in mouse hippocampus that involves TLR4, GSK3, and downstream inflammatory signaling, and these stress responses contribute to susceptibility to depression-like behavior in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Aldehyde dehydrogenase-2 inhibition blocks remote preconditioning in experimental and human models.

PubMed

Contractor, Hussain; Støttrup, Nicolaj B; Cunnington, Colin; Manlhiot, Cedric; Diesch, Jonathan; Ormerod, Julian O M; Jensen, Rebekka; Bøtker, Hans Erik; Redington, Andrew; Schmidt, Michael R; Ashrafian, Houman; Kharbanda, Rajesh K

2013-05-01

Mitochondrial aldehyde dehydrogenase-2 (ALDH-2) is involved in preconditioning pathways, but its role in remote ischaemic preconditioning (rIPC) is unknown. We investigated its role in animal and human models of rIPC. (i) In a rabbit model of myocardial infarction, rIPC alone reduced infarct size [69 ± 5.8 % (n = 11) to 40 ± 6.5 % (n = 12), P = 0.019]. However, rIPC protection was lost after pre-treatment with the ALDH-2 inhibitor cyanamide (62 ± 7.6 % controls, n = 10, versus 61 ± 6.9 % rIPC after cyanamide, n = 10, P > 0.05). (ii) In a forearm plethysmography model of endothelial ischaemia-reperfusion injury, 24 individuals of Asian ethnic origin underwent combined rIPC and ischaemia-reperfusion (IR). 11 had wild-type (WT) enzyme and 13 carried the Glu504Lys (ALDH2*2) polymorphism (rendering ALDH-2 functionally inactive). In WT individuals, rIPC protected against impairment of response to acetylcholine (P = 0.9), but rIPC failed to protect carriers of Glu504Lys polymorphism (P = 0.004). (iii) In a second model of endothelial IR injury, 12 individuals participated in a double-blind placebo-controlled crossover study, receiving the ALDH-2 inhibitor disulfiram 600 mg od or placebo for 48 h prior to assessment of flow-mediated dilation (FMD) before and after combined rIPC and IR. With placebo, rIPC was effective with no difference in FMD before and after IR (6.18 ± 1.03 % and 4.76 ± 0.93 % P = 0.1), but disulfiram inhibited rIPC with a reduction in FMD after IR (7.87 ± 1.27 % and 3.05 ± 0.53 %, P = 0.001). This study demonstrates that ALDH-2 is involved in the rIPC pathway in three distinct rabbit and human models. This has potential implications for future clinical studies of remote conditioning.

40 CFR 85.2218 - Preconditioned idle test-EPA 91.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements—(1) Exhaust gas sampling...

40 CFR 86.1232-96 - Vehicle preconditioning.

Code of Federal Regulations, 2013 CFR

2013-07-01

... awaiting testing, to prevent unusual loading of the canisters. During this time care must be taken to... vehicles with multiple canisters in a series configuration, the set of canisters must be preconditioned as... designed for vapor load or purge steps, the service port shall be used during testing to precondition the...

40 CFR 86.1232-96 - Vehicle preconditioning.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 20 2012-07-01 2012-07-01 false Vehicle preconditioning. 86.1232-96... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Evaporative... Methanol-Fueled Heavy-Duty Vehicles § 86.1232-96 Vehicle preconditioning. (a) Fuel tank cap(s) of gasoline...

40 CFR 85.2218 - Preconditioned idle test-EPA 91.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Preconditioned idle test-EPA 91. 85... Tests § 85.2218 Preconditioned idle test—EPA 91. (a) General requirements—(1) Exhaust gas sampling algorithm. The analysis of exhaust gas concentrations begins ten seconds after the applicable test mode...

Pseudo-compressibility methods for the incompressible flow equations

NASA Technical Reports Server (NTRS)

Turkel, Eli; Arnone, A.

1993-01-01

Preconditioning methods to accelerate convergence to a steady state for the incompressible fluid dynamics equations are considered. The analysis relies on the inviscid equations. The preconditioning consists of a matrix multiplying the time derivatives. Thus the steady state of the preconditioned system is the same as the steady state of the original system. The method is compared to other types of pseudo-compressibility. For finite difference methods preconditioning can change and improve the steady state solutions. An application to viscous flow around a cascade with a non-periodic mesh is presented.

The Galvanotactic Migration of Keratinocytes is Enhanced by Hypoxic Preconditioning

PubMed Central

Guo, Xiaowei; Jiang, Xupin; Ren, Xi; Sun, Huanbo; Zhang, Dongxia; Zhang, Qiong; Zhang, Jiaping; Huang, Yuesheng

2015-01-01

The endogenous electric field (EF)-directed migration of keratinocytes (galvanotaxis) into wounds is an essential step in wound re-epithelialization. Hypoxia, which occurs immediately after injury, acts as an early stimulus to initiate the healing process; however, the mechanisms for this effect, remain elusive. We show here that the galvanotactic migration of keratinocytes was enhanced by hypoxia preconditioning as a result of the increased directionality rather than the increased motility of keratinocytes. This enhancement was both oxygen tension- and preconditioning time-dependent, with the maximum effects achieved using 2% O2 preconditioning for 6 hours. Hypoxic preconditioning (2% O2, 6 hours) decreased the threshold voltage of galvanotaxis to < 25 mV/mm, whereas this value was between 25 and 50 mV/mm in the normal culture control. In a scratch-wound monolayer assay in which the applied EF was in the default healing direction, hypoxic preconditioning accelerated healing by 1.38-fold compared with the control conditions. Scavenging of the induced ROS by N-acetylcysteine (NAC) abolished the enhanced galvanotaxis and the accelerated healing by hypoxic preconditioning. Our data demonstrate a novel and unsuspected role of hypoxia in supporting keratinocyte galvanotaxis. Enhancing the galvanotactic response of cells might therefore be a clinically attractive approach to induce improved wound healing. PMID:25988491

The impact of personality on person-centred care: a study of care staff in Swedish nursing homes.

PubMed

Elfstrand Corlin, Tinna; Kajonius, Petri J; Kazemi, Ali

2017-06-01

In this study, we explore how personal and situational factors relate to the provision of person-centred care (PCC) in nursing homes. Specifically, we focus on the relationship between the care staff's personality traits and provision of PCC and to what extent perceptions of the working environment influences this relationship. The ultimate goal of elderly care is to meet the older person's needs and individual preferences (PCC). Interpersonal aspects of care and the quality of relationship between the care staff and the older person are therefore central in PCC. A cross-sectional Swedish sample of elderly care staff (N = 322) completed an electronic survey including measures of personality (Mini-IPIP) and person-centred care (Individualized Care Inventory, ICI). A principal component analysis was conducted on the ICI-data to separate the user orientation (process quality) of PCC from the preconditions (structure quality) of PCC. Among the five factors of personality, neuroticism was the strongest predictor of ICI user orientation. ICI preconditions significantly mediated this relationship, indicating the importance of a supportive working environment. In addition, stress was introduced as a potential explanation and was shown to mediate the impact of neuroticism on ICI preconditions. Personality traits have a significant impact on user orientation, and the perception of a supportive and stress free working environment is an important prerequisite for achieving high-quality person-centred elderly care. Understanding how personality is linked to the way care staff interacts with the older person adds a new perspective on provision of person-centred elderly care. © 2016 John Wiley & Sons Ltd.

Blended learning in CME: the perception of GP trainers.

PubMed

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

2016-05-01

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

The mitochondria-targeted antioxidants and remote kidney preconditioning ameliorate brain damage through kidney-to-brain cross-talk.

PubMed

Silachev, Denis N; Isaev, Nikolay K; Pevzner, Irina B; Zorova, Ljubava D; Stelmashook, Elena V; Novikova, Svetlana V; Plotnikov, Egor Y; Skulachev, Vladimir P; Zorov, Dmitry B

2012-01-01

Many ischemia-induced neurological pathologies including stroke are associated with high oxidative stress. Mitochondria-targeted antioxidants could rescue the ischemic organ by providing specific delivery of antioxidant molecules to the mitochondrion, which potentially suffers from oxidative stress more than non-mitochondrial cellular compartments. Besides direct antioxidative activity, these compounds are believed to activate numerous protective pathways. Endogenous anti-ischemic defense may involve the very powerful neuroprotective agent erythropoietin, which is mainly produced by the kidney in a redox-dependent manner, indicating an important role of the kidney in regulation of brain ischemic damage. The goal of this study is to track the relations between the kidney and the brain in terms of the amplification of defense mechanisms during SkQR1 treatment and remote renal preconditioning and provide evidence that the kidney can generate signals inducing a tolerance to oxidative stress-associated brain pathologies. We used the cationic plastoquinone derivative, SkQR1, as a mitochondria-targeted antioxidant to alleviate the deleterious consequences of stroke. A single injection of SkQR1 before cerebral ischemia in a dose-dependent manner reduces infarction and improves functional recovery. Concomitantly, an increase in the levels of erythropoietin in urine and phosphorylated glycogen synthase kinase-3β (GSK-3β) in the brain was detected 24 h after SkQR1 injection. However, protective effects of SkQR1 were not observed in rats with bilateral nephrectomy and in those treated with the nephrotoxic antibiotic gentamicin, indicating the protective role of humoral factor(s) which are released from functional kidneys. Renal preconditioning also induced brain protection in rats accompanied by an increased erythropoietin level in urine and kidney tissue and P-GSK-3β in brain. Co-cultivation of SkQR1-treated kidney cells with cortical neurons resulted in enchanced phosphorylation of GSK-3β in neuronal cells. The results indicate that renal preconditioning and SkQR1-induced brain protection may be mediated through the release of EPO from the kidney.

Sensory Preconditioning in Newborn Rabbits: From Common to Distinct Odor Memories

ERIC Educational Resources Information Center

Coureaud, Gerard; Tourat, Audrey; Ferreira, Guillaume

2013-01-01

This study evaluated whether olfactory preconditioning is functional in newborn rabbits and based on joined or independent memory of odorants. First, after exposure to odorants A+B, the conditioning of A led to high responsiveness to odorant B. Second, responsiveness to B persisted after amnesia of A. Third, preconditioning was also functional…

40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Preconditioned two speed idle test-EPA... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements—(1...-speed mode followed immediately by a first-chance idle mode. (ii) The second-chance test as described...

40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Preconditioned two speed idle test-EPA... Warranty Short Tests § 85.2220 Preconditioned two speed idle test—EPA 91. (a) General requirements—(1...-speed mode followed immediately by a first-chance idle mode. (ii) The second-chance test as described...

Neuroprotective effects of ischemic preconditioning on hippocampal CA1 pyramidal neurons through maintaining calbindin D28k immunoreactivity following subsequent transient cerebral ischemia

PubMed Central

Kim, In Hye; Jeon, Yong Hwan; Lee, Tae-Kyeong; Cho, Jeong Hwi; Lee, Jae-Chul; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Bich-Na; Kim, Yang Hee; Hong, Seongkweon; Yan, Bing Chun; Won, Moo-Ho; Lee, Yun Lyul

2017-01-01

Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning (2-minute transient cerebral ischemia) on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult (5-minute transient cerebral ischemia). A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity. PMID:28761424

S{sub 2}SA preconditioning for the S{sub n} equations with strictly non negative spatial discretization

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

Bruss, D. E.; Morel, J. E.; Ragusa, J. C.

2013-07-01

Preconditioners based upon sweeps and diffusion-synthetic acceleration have been constructed and applied to the zeroth and first spatial moments of the 1-D S{sub n} transport equation using a strictly non negative nonlinear spatial closure. Linear and nonlinear preconditioners have been analyzed. The effectiveness of various combinations of these preconditioners are compared. In one dimension, nonlinear sweep preconditioning is shown to be superior to linear sweep preconditioning, and DSA preconditioning using nonlinear sweeps in conjunction with a linear diffusion equation is found to be essentially equivalent to nonlinear sweeps in conjunction with a nonlinear diffusion equation. The ability to use amore » linear diffusion equation has important implications for preconditioning the S{sub n} equations with a strictly non negative spatial discretization in multiple dimensions. (authors)« less

Block recursive LU preconditioners for the thermally coupled incompressible inductionless MHD problem

NASA Astrophysics Data System (ADS)

Badia, Santiago; Martín, Alberto F.; Planas, Ramon

2014-10-01

The thermally coupled incompressible inductionless magnetohydrodynamics (MHD) problem models the flow of an electrically charged fluid under the influence of an external electromagnetic field with thermal coupling. This system of partial differential equations is strongly coupled and highly nonlinear for real cases of interest. Therefore, fully implicit time integration schemes are very desirable in order to capture the different physical scales of the problem at hand. However, solving the multiphysics linear systems of equations resulting from such algorithms is a very challenging task which requires efficient and scalable preconditioners. In this work, a new family of recursive block LU preconditioners is designed and tested for solving the thermally coupled inductionless MHD equations. These preconditioners are obtained after splitting the fully coupled matrix into one-physics problems for every variable (velocity, pressure, current density, electric potential and temperature) that can be optimally solved, e.g., using preconditioned domain decomposition algorithms. The main idea is to arrange the original matrix into an (arbitrary) 2 × 2 block matrix, and consider an LU preconditioner obtained by approximating the corresponding Schur complement. For every one of the diagonal blocks in the LU preconditioner, if it involves more than one type of unknowns, we proceed the same way in a recursive fashion. This approach is stated in an abstract way, and can be straightforwardly applied to other multiphysics problems. Further, we precisely explain a flexible and general software design for the code implementation of this type of preconditioners.

Activation of p38 MAPK participates in brain ischemic tolerance induced by limb ischemic preconditioning by up-regulating HSP 70.

PubMed

Sun, Xiao-Cai; Xian, Xiao-Hui; Li, Wen-Bin; Li, Li; Yan, Cai-Zhen; Li, Qing-Jun; Zhang, Min

2010-08-01

This study investigates whether activation of p38 MAPK by the up-regulation of HSP 70 participates in the induction of brain ischemic tolerance by limb ischemic preconditioning (LIP). Western blot and immunohistochemical assays indicated that p38 MAPK activation occurred earlier than HSP 70 induction in the CA1 region of the hippocampus after LIP. P-p38 MAPK expression was up-regulated at 6h and reached its peak 12h after LIP, while HSP 70 expression was not significantly increased until 1 day and peaked 2 days after LIP. Neuropathological evaluation by thionin staining showed that quercetin (4 ml/kg, 50mg/kg, intraperitoneal injection), an inhibitor of HSP 70, blocked the protective effect of LIP against delayed neuronal death that is normally induced by lethal brain ischemic insult, indicating that HSP 70 participates in the induction of brain ischemic tolerance by LIP. Furthermore, SB 203580, an inhibitor of HSP 70, inhibited HSP 70 activation in the CA1 region of the hippocampus induced by LIP either with or without the presence of subsequent brain ischemic insult. Based on the above results, it can be concluded that activation of p38 MAPK participates in the brain ischemic tolerance induced by LIP at least partly by the up-regulation of HSP 70 expression. (c) 2010 Elsevier Inc. All rights reserved.

Toll-like receptor 3 pre-conditioning increases the therapeutic efficacy of umbilical cord mesenchymal stromal cells in a dextran sulfate sodium-induced colitis model.

PubMed

Fuenzalida, Patricia; Kurte, Mónica; Fernández-O'ryan, Catalina; Ibañez, Cristina; Gauthier-Abeliuk, Melanie; Vega-Letter, Ana María; Gonzalez, Paz; Irarrázabal, Carlos; Quezada, Nataly; Figueroa, Fernando; Carrión, Flavio

2016-05-01

Immunomodulatory properties of human umbilical cord-derived mesenchymal stromal cells (UCMSCs) can be differentially modulated by toll-like receptors (TLR) agonists. Here, the therapeutic efficacy of short TLR3 and TLR4 pre-conditioning of UCMSCs was evaluated in a dextran sulfate sodium (DSS)-induced colitis in mice. The novelty of this study is that although modulation of human MSCs activity by TLRs is not a new concept, this is the first time that short TLR pre-conditioning has been carried out in a murine inflammatory model of acute colitis. C57BL/6 mice were exposed to 2.5% dextran sulfate sodium (DSS) in drinking water ad libitum for 7 days. At days 1 and 3, mice were injected intraperitoneally with 1 × 10(6) UCMSCs untreated or TLR3 and TLR4 pre-conditioned UCMSCs. UCMSCs were pre-conditioned with poly(I:C) for TLR3 and LPS for TLR4 for 1 h at 37°C and 5% CO2. We evaluated clinical signs of disease and body weights daily. At the end of the experiment, colon length and histological changes were assessed. poly(I:C) pre-conditioned UCMSCs significantly ameliorated the clinical and histopathological severity of DSS-induced colitis compared with UCMSCs or LPS pre-conditioned UCMSCs. In contrast, infusion of LPS pre-conditioned UCMSCs significantly increased clinical signs of disease, colon shortening and histological disease index in DSS-induced colitis. These results show that short in vitro TLR3 pre-conditioning with poly(I:C) enhances the therapeutic efficacy of UCMSCs, which is a major breakthrough for developing improved treatments to patients with inflammatory bowel disease. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping.

PubMed

Soman, S; Liu, Z; Kim, G; Nemec, U; Holdsworth, S J; Main, K; Lee, B; Kolakowsky-Hayner, S; Selim, M; Furst, A J; Massaband, P; Yesavage, J; Adamson, M M; Spincemallie, P; Moseley, M; Wang, Y

2018-04-01

Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology. Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident. Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping; they were worse on preconditioned quantitative susceptibility mapping. Preconditioned quantitative susceptibility mapping MR imaging can bring the benefits of quantitative susceptibility mapping imaging to clinical practice without the limitations of mask-based quantitative susceptibility mapping, especially for evaluating cerebral microhemorrhage-associated pathologies, such as traumatic brain injury. © 2018 by American Journal of Neuroradiology.

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay.

PubMed

Gersch, Robert P; Fourman, Mitchell S; Phillips, Brett T; Nasser, Ahmed; McClain, Steve A; Khan, Sami U; Dagum, Alexander B; Bui, Duc T

2015-08-01

Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (10(9) pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm(2), P < 0.01 and 12.4 ± 1.2 cm(2), P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm(2)). AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not.

AdVEGF-All6A+ Preconditioning of Murine Ischemic Skin Flaps Is Comparable to Surgical Delay

PubMed Central

Gersch, Robert P.; Fourman, Mitchell S.; Phillips, Brett T.; Nasser, Ahmed; McClain, Steve A.; Khan, Sami U.; Dagum, Alexander B.

2015-01-01

Background: Surgical flap delay is commonly used in preconditioning reconstructive flaps to prevent necrosis. However, staged procedures are not ideal. Pharmacologic up-regulation of angiogenic and arteriogenic factors before flap elevation poses a nonsurgical approach to improve flap survival. Methods: Male Sprague Dawley rats were divided into control (n = 16), surgical delay (Delay), AdNull, AdEgr-1, and AdVEGF (n ≥ 9/group) groups. Delay rats had a 9 cm × 3 cm cranial based pedicle skin flap incised 10 days prior to elevation. Adenoviral groups received 28 intradermal injections (109 pu/animal total) throughout the distal two thirds of the flap 1 week prior to elevation. At postoperative day (POD) 0 flaps were elevated and silicone sheeting was placed between flap and wound bed. Perfusion analysis in arbitrary perfusion units of the ischemic middle third of the flap using laser Doppler imaging was conducted preoperatively and on POD 0, 3, and 7. Clinical and histopathologic assessments of the skin flaps were performed on POD 7. Results: AdVEGF (50.8 ± 10.9 APU) and AdEgr-1 (39.3 ± 10.6 APU) perfusion levels were significantly higher than controls (16.5 ± 4.2 APU) on POD 7. Delay models were equivalent to controls (25.9 ± 6.8 APU). AdVEGF and Delay animals showed significantly more viable surface area on POD 7 (14.4 ± 1.3 cm2, P < 0.01 and 12.4 ± 1.2 cm2, P < 0.05, respectively) compared with Controls (8.7 ± 0.7 cm2). Conclusions: AdVEGF preconditioning resulted in flap survival comparable to surgical delay. Adenoviral preconditioning maintained perfusion levels postoperatively while surgical delay did not. PMID:26495207

Rational modulation of the innate immune system for neuroprotection in ischemic stroke

PubMed Central

Amantea, Diana; Micieli, Giuseppe; Tassorelli, Cristina; Cuartero, María I.; Ballesteros, Iván; Certo, Michelangelo; Moro, María A.; Lizasoain, Ignacio; Bagetta, Giacinto

2015-01-01

The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs) that contribute to blood–brain barrier (BBB) disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF)-β, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate toward several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13, or TGF-β. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair. Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction. PMID:25972779

40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... controlled to 50±25 grains of water vapor per pound of dry air) maintained at a nominal flow rate of 0.8 cfm... preconditioning; refueling test. (a) Vehicle and canister preconditioning. Vehicles and vapor storage canisters... at least 1200 canister bed volumes of ambient air (with humidity controlled to 50±25 grains of water...

40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... controlled to 50±25 grains of water vapor per pound of dry air) maintained at a nominal flow rate of 0.8 cfm... preconditioning; refueling test. (a) Vehicle and canister preconditioning. Vehicles and vapor storage canisters... at least 1200 canister bed volumes of ambient air (with humidity controlled to 50±25 grains of water...

40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... controlled to 50±25 grains of water vapor per pound of dry air) maintained at a nominal flow rate of 0.8 cfm... preconditioning; refueling test. (a) Vehicle and canister preconditioning. Vehicles and vapor storage canisters... at least 1200 canister bed volumes of ambient air (with humidity controlled to 50±25 grains of water...

40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... controlled to 50±25 grains of water vapor per pound of dry air) maintained at a nominal flow rate of 0.8 cfm... preconditioning; refueling test. (a) Vehicle and canister preconditioning. Vehicles and vapor storage canisters... at least 1200 canister bed volumes of ambient air (with humidity controlled to 50±25 grains of water...

40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... controlled to 50±25 grains of water vapor per pound of dry air) maintained at a nominal flow rate of 0.8 cfm... preconditioning; refueling test. (a) Vehicle and canister preconditioning. Vehicles and vapor storage canisters... at least 1200 canister bed volumes of ambient air (with humidity controlled to 50±25 grains of water...

Entrepreneurial Thinking and Action--An Educational Responsibility for Europe

ERIC Educational Resources Information Center

Eickhoff, Markus Th.

2008-01-01

In a general sense, entrepreneurial thinking and action relates to all those in employment, as an attitude to work and working behaviour, and it is accordingly becoming a key factor in competence. For independent entrepreneurs it is also, in a more specific sense, a fundamental precondition for successfully establishing and operating an…

Comparison of Implicit Schemes for the Incompressible Navier-Stokes Equations

NASA Technical Reports Server (NTRS)

Rogers, Stuart E.

1995-01-01

For a computational flow simulation tool to be useful in a design environment, it must be very robust and efficient. To develop such a tool for incompressible flow applications, a number of different implicit schemes are compared for several two-dimensional flow problems in the current study. The schemes include Point-Jacobi relaxation, Gauss-Seidel line relaxation, incomplete lower-upper decomposition, and the generalized minimum residual method preconditioned with each of the three other schemes. The efficiency of the schemes is measured in terms of the computing time required to obtain a steady-state solution for the laminar flow over a backward-facing step, the flow over a NACA 4412 airfoil, and the flow over a three-element airfoil using overset grids. The flow solver used in the study is the INS2D code that solves the incompressible Navier-Stokes equations using the method of artificial compressibility and upwind differencing of the convective terms. The results show that the generalized minimum residual method preconditioned with the incomplete lower-upper factorization outperforms all other methods by at least a factor of 2.

Preconditioning With Tauroursodeoxycholic Acid Protects Against Contrast-Induced HK-2 Cell Apoptosis by Inhibiting Endoplasmic Reticulum Stress.

PubMed

Peng, Pingan; Ma, Qian; Wang, Le; Zhang, Ou; Han, Hongya; Liu, Xiaoli; Zhou, Yujie; Zhao, Yingxin

2015-11-01

To investigate whether tauroursodeoxycholic acid (TUDCA) could attenuate contrast media (CM)-induced renal tubular cell apoptosis by inhibiting endoplasmic reticulum stress (ERS), we exposed HK-2 cells to increasing doses of meglumine diatrizoate (20, 40, and 80 mg I/mL) for 2 to 16 hours, with/without TUDCA preconditioning for 24 hours. Cell viability test, Hoechst 33258 staining, and flow cytometry were used to detect meglumine diatrizoate-induced cell apoptosis, while real-time polymerase chain reaction and Western blot analysis were used to measure the expressions of ERS markers of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and the apoptosis-related marker of caspase 12. Cell apoptosis and messenger RNA (mRNA) expression of GRP78 (P = .005), ATF4 (P = .01), and caspase 12 (P = .001) were significantly higher in the CM 4 hours group than the control as well as the protein expressions. The TUDCA preconditioning reduced the mRNA expression of GRP78, ATF4, and caspase 12 in the CM 4 hours groups (P = .009, .019, and .003, respectively) as well as the protein expression. In conclusion, TUDCA could protect renal tubular cells from meglumine diatrizoate-induced apoptosis by inhibiting ERS. © The Author(s) 2015.

Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.

PubMed

Cox-Limpens, Kimberly E M; Vles, Johan S H; LA van den Hove, Daniel; Zimmermann, Luc J I; Gavilanes, Antonio W D

2014-05-29

Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates.Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditioning (FAPA). Offspring were sacrificed 6 h and 96 h after birth, and whole-genome transcription was investigated using the Affymetrix Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma package. In addition to univariate analysis, we performed Gene Set Enrichment Analysis (GSEA) in order to derive results with maximum biological relevance. We observed minimal, 25% or less, overlap of differentially regulated transcripts across different experimental groups which leads us to conclude that the transcriptional phenotype of these groups is largely unique. In both the PA and FAPA group we observe an upregulation of transcripts involved in cellular stress. Contrastingly, transcripts with a function in the cell nucleus were mostly downregulated in PA animals, while we see considerable upregulation in the FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are exclusively regulated in FAPA animals. This study is the first to investigate whole-genome transcription in the neonatal brain after PA alone, and after perinatal asphyxia preceded by preconditioning (FAPA). We describe several genes/pathways, such as ubiquitination and proteolysis, which were not previously linked to preconditioning-induced neuroprotection. Furthermore, we observed that the majority of upregulated genes in preconditioned animals have a function in the cell nucleus, including several epigenetic players such as HDACs, which suggests that epigenetic mechanisms are likely to play a role in preconditioning-induced neuroprotection.

Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia

PubMed Central

2014-01-01

Background Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates. Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditioning (FAPA). Offspring were sacrificed 6 h and 96 h after birth, and whole-genome transcription was investigated using the Affymetrix Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma package. In addition to univariate analysis, we performed Gene Set Enrichment Analysis (GSEA) in order to derive results with maximum biological relevance. Results We observed minimal, 25% or less, overlap of differentially regulated transcripts across different experimental groups which leads us to conclude that the transcriptional phenotype of these groups is largely unique. In both the PA and FAPA group we observe an upregulation of transcripts involved in cellular stress. Contrastingly, transcripts with a function in the cell nucleus were mostly downregulated in PA animals, while we see considerable upregulation in the FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are exclusively regulated in FAPA animals. Conclusions This study is the first to investigate whole-genome transcription in the neonatal brain after PA alone, and after perinatal asphyxia preceded by preconditioning (FAPA). We describe several genes/pathways, such as ubiquitination and proteolysis, which were not previously linked to preconditioning-induced neuroprotection. Furthermore, we observed that the majority of upregulated genes in preconditioned animals have a function in the cell nucleus, including several epigenetic players such as HDACs, which suggests that epigenetic mechanisms are likely to play a role in preconditioning-induced neuroprotection. PMID:24885038

The time dependence of the effect of ischemic preconditioning on successive sprint swimming performance.

PubMed

Lisbôa, Felipe D; Turnes, Tiago; Cruz, Rogério S O; Raimundo, João A G; Pereira, Gustavo S; Caputo, Fabrizio

2017-05-01

The present study aimed to determine the effects of ischemic preconditioning on performance in three successive 50-m swimming trials and to measure stroke rate, stroke length and blood lactate accumulation. Counterbalanced, repeated-measures cross-over study. On two separate days, eleven competitive male swimmers (20±3 years, 182±5cm, 77±5kg) performed three successive 50-m trials in a 50-m swimming pool, preceded by intermittent bilateral cuff inflation (4× 5-min of blood flow restriction+5-min of cuff deflation) at either 220 for thighs and 180mmHg for arms (ischemic preconditioning) or 20mmHg for both limbs (control-treatment). The 50-m trials were conducted 1-, 2-, and 8-h after the procedure. While no ergogenic effect of ischemic preconditioning was observed for 1-h (0.4%, 95% confidence limits of ±0.6%, p=0.215), there were clear beneficial effects of ischemic preconditioning on 2- and 8-h (1.0% and 1.2%, respectively; 95% confidence limits of ±0.6% in both cases, p≤0.002). Furthermore, ischemic preconditioning increased blood lactate accumulation in 2-(p<0.001) and 8-h (p=0.010) and stroke rate for 2- and 8-h in specific 10-m segments (p<0.05). These findings suggest a time-dependent effect of ischemic preconditioning on 50-m swimming performance for competitive athletes, with the time window of the beneficial effect starting after about 2-h and lasting for at least 8-h after ischemic preconditioning. This change in performance was accompanied by an increase in blood lactate accumulation and faster strokes in front crawl. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Remote ischemic preconditioning and endothelial function in patients with acute myocardial infarction and primary PCI.

PubMed

Manchurov, Vladimir; Ryazankina, Nadezda; Khmara, Tatyana; Skrypnik, Dmitry; Reztsov, Roman; Vasilieva, Elena; Shpektor, Alexander

2014-07-01

Remote ischemic preconditioning by transient limb ischemia reduces myocardial ischemia-reperfusion injury in patients undergoing percutaneous coronary intervention. The aim of the study we report here was to assess the effect of remote ischemic preconditioning on endothelial function in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention. Forty-eight patients with acute myocardial infarction were enrolled. All participants were randomly divided into 2 groups. In Group I (n = 23), remote ischemic preconditioning was performed before primary percutaneous coronary intervention (intermittent arm ischemia-reperfusion through 4 cycles of 5-minute inflation and 5-minute deflation of a blood-pressure cuff to 200 mm Hg). In Group II (n = 25), standard percutaneous coronary intervention without preconditioning was performed. We assessed endothelial function using the flow-mediated dilation test on baseline, then within 1-3 hours after percutaneous coronary intervention, and again on days 2 and 7 after percutaneous coronary intervention. The brachial artery flow-mediated dilation results were significantly higher on the first day after primary percutaneous coronary intervention in the preconditioning group (Group I) than in the control group (Group II) (12.1% vs 0.0%, P = .03, and 11.1% vs 6.3%, P = .016, respectively), and this difference remained on the seventh day (12.3% vs 7.4%, P = .0005, respectively). We demonstrated for the first time that remote ischemic preconditioning before primary percutaneous coronary intervention significantly improves endothelial function in patients with acute myocardial infarction, and this effect remains constant for at least a week. We suppose that the improvement of endothelial function may be one of the possible explanations of the effect of remote ischemic preconditioning. Copyright © 2014 Elsevier Inc. All rights reserved.

Petrochronology of Granitoids in the Langshan Reveals Carboniferous Plutonism along the Northeast Edge of the Alxa Block (NW China)

NASA Astrophysics Data System (ADS)

Rea-Downing, G.; Lippert, P. C.; Stearns, M.

2017-12-01

The Alxa block is positioned between the western North China Craton (NCC) to the east and the Tarim Craton to the west. Several first-order characteristics of the Alxa region remain largely unresolved due to the limited outcrop exposure and remote nature of the region. For example, the crustal affinity and thermo-tectonic history of the Alxa block throughout Central Asian terrane accretion may have pre-conditioned the Cenozoic and Recent strain. Recent paleomagnetic and detrital zircon studies within the Alxa block indicate that its basement geology and apparent polar wander path are substantially different from the NCC. These data suggest that Alxa was not initially part of the NCC. Identification of a suture between Alxa and the NCC, timing of the incorporation of the Alxa block with the NCC, and the correlation of well-studied tectono-thermal events occurring in the NCC to the comparatively understudied Alxa block to the west are poorly constrained. Preliminary petrochronologic data from granitoid bodies within the Langshan range address these limitations by characterizing the bedrock age and affinity along the NE edge of the Alxa block. LA-Q-ICP-MS analysis of zircons including U-Pb dates, major and minor trace elemental data, and rare earth element compositions are combined with bulk rock geochemistry to place early-mid Carboniferous ( 350 Ma) Langshan plutons in a regional context. The relative rarity of plutons of this age in a region replete with Permo-Triassic plutonism indicates that the Langshan includes a record of relatively understudied magmatism along the periphery of the NCC. The approach utilized here allows for 1) direct age and compositional comparisons to other Carboniferous-Permian plutons in central Asia and 2) a robust provenance data point for future detrital zircon studies of the Paleozoic paleogeography in the heart of Central Asia.

PRECONDITIONED CONJUGATE-GRADIENT 2 (PCG2), a computer program for solving ground-water flow equations

USGS Publications Warehouse

Hill, Mary C.

1990-01-01

This report documents PCG2 : a numerical code to be used with the U.S. Geological Survey modular three-dimensional, finite-difference, ground-water flow model . PCG2 uses the preconditioned conjugate-gradient method to solve the equations produced by the model for hydraulic head. Linear or nonlinear flow conditions may be simulated. PCG2 includes two reconditioning options : modified incomplete Cholesky preconditioning, which is efficient on scalar computers; and polynomial preconditioning, which requires less computer storage and, with modifications that depend on the computer used, is most efficient on vector computers . Convergence of the solver is determined using both head-change and residual criteria. Nonlinear problems are solved using Picard iterations. This documentation provides a description of the preconditioned conjugate gradient method and the two preconditioners, detailed instructions for linking PCG2 to the modular model, sample data inputs, a brief description of PCG2, and a FORTRAN listing.

Age-related reduction of cerebral ischemic preconditioning: myth or reality?

PubMed Central

Della-Morte, David; Cacciatore, Francesco; Salsano, Elisa; Pirozzi, Gilda; Genio, Maria Teresa Del; D’Antonio, Iole; Gargiulo, Gaetano; Palmirotta, Raffaele; Guadagni, Fiorella; Rundek, Tatjana; Abete, Pasquale

2013-01-01

Stroke is one of the leading causes of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. The “cerebral” ischemic preconditioning mechanism is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators released and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Agents able to mimic the “cerebral” preconditioning effect may represent a new powerful tool for the treatment of acute ischemic stroke in the elderly. In this article, animal and human cerebral ischemic preconditioning, its age-related difference, and its potential therapeutical applications are discussed. PMID:24204128

Preconditioned alternating direction method of multipliers for inverse problems with constraints

NASA Astrophysics Data System (ADS)

Jiao, Yuling; Jin, Qinian; Lu, Xiliang; Wang, Weijie

2017-02-01

We propose a preconditioned alternating direction method of multipliers (ADMM) to solve linear inverse problems in Hilbert spaces with constraints, where the feature of the sought solution under a linear transformation is captured by a possibly non-smooth convex function. During each iteration step, our method avoids solving large linear systems by choosing a suitable preconditioning operator. In case the data is given exactly, we prove the convergence of our preconditioned ADMM without assuming the existence of a Lagrange multiplier. In case the data is corrupted by noise, we propose a stopping rule using information on noise level and show that our preconditioned ADMM is a regularization method; we also propose a heuristic rule when the information on noise level is unavailable or unreliable and give its detailed analysis. Numerical examples are presented to test the performance of the proposed method.

Preconditioning for Numerical Simulation of Low Mach Number Three-Dimensional Viscous Turbomachinery Flows

NASA Technical Reports Server (NTRS)

Tweedt, Daniel L.; Chima, Rodrick V.; Turkel, Eli

1997-01-01

A preconditioning scheme has been implemented into a three-dimensional viscous computational fluid dynamics code for turbomachine blade rows. The preconditioning allows the code, originally developed for simulating compressible flow fields, to be applied to nearly-incompressible, low Mach number flows. A brief description is given of the compressible Navier-Stokes equations for a rotating coordinate system, along with the preconditioning method employed. Details about the conservative formulation of artificial dissipation are provided, and different artificial dissipation schemes are discussed and compared. The preconditioned code was applied to a well-documented case involving the NASA large low-speed centrifugal compressor for which detailed experimental data are available for comparison. Performance and flow field data are compared for the near-design operating point of the compressor, with generally good agreement between computation and experiment. Further, significant differences between computational results for the different numerical implementations, revealing different levels of solution accuracy, are discussed.

Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice.

PubMed

Yin, Lele; Ye, Shasha; Chen, Zhen; Zeng, Yaoying

2012-12-01

Rapamycin, an mTOR inhibitor and immunosuppressive agent in clinic, has protective effects on traumatic brain injury and neurodegenerative diseases. But, its effects on transient focal ischemia/reperfusion disease are not very clear. In this study, we examined the effects of rapamycin preconditioning on mice treated with middle cerebral artery occlusion/reperfusion operation (MCAO/R). We found that the rapamycin preconditioning by intrahippocampal injection 20 hr before MCAO/R significantly improved the survival rate and longevity of mice. It also decreased the neurological deficit score, infracted areas and brain edema. In addition, rapamycin preconditioning decreased the production of NF-κB, TNF-α, and Bax, but not Bcl-2, an antiapoptotic protein in the ischemic area. From these results, we may conclude that rapamycin preconditioning attenuate transient focal cerebral ischemia/reperfusion injury and inhibits apoptosis induced by MCAO/R in mice.

Cobalt chloride attenuates hypobaric hypoxia induced vascular leakage in rat brain: Molecular mechanisms of action of cobalt chloride

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

Kalpana, S.; Dhananjay, S.; Anju, B.

2008-09-15

This study reports the efficacy of cobalt preconditioning in preventing hypobaric hypoxia induced vascular leakage (an indicator of cerebral edema) using male Sprague-Dawley rats as model system. Exposure of animals to hypobaric hypoxia led to a significant increase in vascular leakage, reactive oxygen species (ROS), nitric oxide (NO), and vascular endothelial growth factor (VEGF) levels. There was a marked increase in Nuclear Factor {kappa}B (NF{kappa}B) DNA binding activity and levels of pro-inflammatory cytokines such as Monocyte chemoattractant protein (MCP-1), Interferon-{gamma} (IFN-{gamma}), Interleukin-1 (IL-1), and Tumor Necrosis Factor-{alpha} (TNF-{alpha}) and cell adhesion molecules such as Vascular Cell Adhesion Molecule-1 (VCAM-1), andmore » P-selectin. Chemical preconditioning by cobalt for 7 days (12.5 mg Co/kg b.w., oral) significantly attenuated cerebral vascular leakage and the expression of inflammatory mediators induced by hypoxia. Administration of NF{kappa}B inhibitor, curcumin (50 mg/kg b.w.; i.p.) appreciably inhibited hypoxia induced vascular leakage indicating the involvement of NF{kappa}B in causing vascular leakage. Interestingly, cobalt when administered at 12.5 mg Co/kg b.w. (i.p.), 1 h before hypoxia could not prevent the vascular leakage indicating that cobalt per se did not have an effect on NF{kappa}B. The lower levels of NF{kappa}B observed in the brains of cobalt administered animals might be due to higher levels of antioxidant and anti-inflammatory proteins (hemeoxygenase-1 and metallothionein). To conclude cobalt preconditioning inhibited hypobaric hypoxia induced cerebral vascular leakage by lowering NF{kappa}B DNA binding activity and its regulated pro-inflammatory mediators. This is contemplated to be mediated by cobalt induced reduction in ROS/NO and increase in HO-1 and MT.« less

Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and osteogenesis in rabbit femoral head osteonecrosis.

PubMed

Fan, Lihong; Zhang, Chen; Yu, Zefeng; Shi, Zhibin; Dang, Xiaoqian; Wang, Kunzheng

2015-12-01

Osteonecrosis of the femoral head may be a disease resulting from abnormal proliferation or differentiation of mesenchymal stem cells. The present investigation explored the novel strategy of hypoxia-preconditioned BMMSCs to reverse the impairment of osteonecrosis BMMSCs and enhance the therapeutic potential of hypoxia-treated BMMSC transplantation. BMMSCs from the anterior superior iliac spine region of osteonecrosis rabbit were cultured under 20% O2 or 2% O2 conditions. Normal BMMSCs were cultured under 20% O2 condition as control. Growth factors secreted were examined by enzyme-linked immunosorbent assay. 20% O2 or 2% O2 BMMSCs were injected into the femoral head of rabbits after core decompression. Cell viability and apoptosis were assessed in vitro, and TUNEL staining of the femoral head was analyzed after transplantation. Angiogenesis (capillary-like structure formation, CD31 immunohistochemical staining and ink infusion angiography) and osteogenesis (Alizarin red-S staining, micro-CT scanning and OCN immunohistochemical staining) tests were conducted as well. 2% O2 exposure up-regulated growth factor secretion in BMMSCs. Apoptosis in 2% O2 group was lower when compared with that in 20% O2 osteonecrosis group. Cell viability in 2% O2 was significantly higher when compared with that in 20% O2 osteonecrosis group. Growth factor secretion, cell viability, apoptosis, capillary-like structure formation, Alizarin red-S staining, and ALP staining showed no difference between the 2% O2 BMMSC and normal BMMSC groups. Transplantation of 2% O2 versus 20% O2 mesenchymal stem cells after core decompression resulted in an increase in angiogenesis function and a decrease in local tissue apoptosis. Our study also found that osteogenesis function was improved after hypoxic stem cell transplantation. Hypoxic preconditioning of BMMSCs is an effective means of reversing the impairment of osteonecrosis BMMSCs, promoting their regenerative capability and therapeutic potential for the treatment of osteonecrosis. Copyright © 2015 Elsevier Inc. All rights reserved.

A preconditioned formulation of the Cauchy-Riemann equations

NASA Technical Reports Server (NTRS)

Phillips, T. N.

1983-01-01

A preconditioning of the Cauchy-Riemann equations which results in a second-order system is described. This system is shown to have a unique solution if the boundary conditions are chosen carefully. This choice of boundary condition enables the solution of the first-order system to be retrieved. A numerical solution of the preconditioned equations is obtained by the multigrid method.

Preconditioning principles for preventing sports injuries in adolescents and children.

PubMed

Dollard, Mark D; Pontell, David; Hallivis, Robert

2006-01-01

Preseason preconditioning can be accomplished well over a 4-week period with a mandatory period of rest as we have discussed. Athletic participation must be guided by a gradual increase of skills performance in the child assessed after a responsible preconditioning program applying physiologic parameters as outlined. Clearly, designing a preconditioning program is a dynamic process when accounting for all the variables in training discussed so far. Despite the physiologic demands of sport and training, we still need to acknowledge the psychologic maturity and welfare of the child so as to ensure that the sport environment is a wholesome and emotionally rewarding experience.

Implementation of Preconditioned Dual-Time Procedures in OVERFLOW

NASA Technical Reports Server (NTRS)

Pandya, Shishir A.; Venkateswaran, Sankaran; Pulliam, Thomas H.; Kwak, Dochan (Technical Monitor)

2003-01-01

Preconditioning methods have become the method of choice for the solution of flowfields involving the simultaneous presence of low Mach and transonic regions. It is well known that these methods are important for insuring accurate numerical discretization as well as convergence efficiency over various operating conditions such as low Mach number, low Reynolds number and high Strouhal numbers. For unsteady problems, the preconditioning is introduced within a dual-time framework wherein the physical time-derivatives are used to march the unsteady equations and the preconditioned time-derivatives are used for purposes of numerical discretization and iterative solution. In this paper, we describe the implementation of the preconditioned dual-time methodology in the OVERFLOW code. To demonstrate the performance of the method, we employ both simple and practical unsteady flowfields, including vortex propagation in a low Mach number flow, flowfield of an impulsively started plate (Stokes' first problem) arid a cylindrical jet in a low Mach number crossflow with ground effect. All the results demonstrate that the preconditioning algorithm is responsible for improvements to both numerical accuracy and convergence efficiency and, thereby, enables low Mach number unsteady computations to be performed at a fraction of the cost of traditional time-marching methods.

Efficient iterative methods applied to the solution of transonic flows

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

Wissink, A.M.; Lyrintzis, A.S.; Chronopoulos, A.T.

1996-02-01

We investigate the use of an inexact Newton`s method to solve the potential equations in the transonic regime. As a test case, we solve the two-dimensional steady transonic small disturbance equation. Approximate factorization/ADI techniques have traditionally been employed for implicit solutions of this nonlinear equation. Instead, we apply Newton`s method using an exact analytical determination of the Jacobian with preconditioned conjugate gradient-like iterative solvers for solution of the linear systems in each Newton iteration. Two iterative solvers are tested; a block s-step version of the classical Orthomin(k) algorithm called orthogonal s-step Orthomin (OSOmin) and the well-known GIVIRES method. The preconditionermore » is a vectorizable and parallelizable version of incomplete LU (ILU) factorization. Efficiency of the Newton-Iterative method on vector and parallel computer architectures is the main issue addressed. In vectorized tests on a single processor of the Cray C-90, the performance of Newton-OSOmin is superior to Newton-GMRES and a more traditional monotone AF/ADI method (MAF) for a variety of transonic Mach numbers and mesh sizes. Newton- GIVIRES is superior to MAF for some cases. The parallel performance of the Newton method is also found to be very good on multiple processors of the Cray C-90 and on the massively parallel thinking machine CM-5, where very fast execution rates (up to 9 Gflops) are found for large problems. 38 refs., 14 figs., 7 tabs.« less

Neuron specific metabolic adaptations following multi-day exposures to oxygen glucose deprivation.

PubMed

Zeiger, Stephanie L H; McKenzie, Jennifer R; Stankowski, Jeannette N; Martin, Jacob A; Cliffel, David E; McLaughlin, BethAnn

2010-11-01

Prior exposure to sub toxic insults can induce a powerful endogenous neuroprotective program known as ischemic preconditioning. Current models typically rely on a single stress episode to induce neuroprotection whereas the clinical reality is that patients may experience multiple transient ischemic attacks (TIAs) prior to suffering a stroke. We sought to develop a neuron-enriched preconditioning model using multiple oxygen glucose deprivation (OGD) episodes to assess the endogenous protective mechanisms neurons implement at the metabolic and cellular level. We found that neurons exposed to a five minute period of glucose deprivation recovered oxygen utilization and lactate production using novel microphysiometry techniques. Using the non-toxic and energetically favorable five minute exposure, we developed a preconditioning paradigm where neurons are exposed to this brief OGD for three consecutive days. These cells experienced a 45% greater survival following an otherwise lethal event and exhibited a longer lasting window of protection in comparison to our previous in vitro preconditioning model using a single stress. As in other models, preconditioned cells exhibited mild caspase activation, an increase in oxidized proteins and a requirement for reactive oxygen species for neuroprotection. Heat shock protein 70 was upregulated during preconditioning, yet the majority of this protein was released extracellularly. We believe coupling this neuron-enriched multi-day model with microphysiometry will allow us to assess neuronal specific real-time metabolic adaptations necessary for preconditioning. Copyright © 2010 Elsevier B.V. All rights reserved.

Sulforaphane preconditioning of the Nrf2/HO-1 defense pathway protects the cerebral vasculature against blood-brain barrier disruption and neurological deficits in stroke.

PubMed

Alfieri, Alessio; Srivastava, Salil; Siow, Richard C M; Cash, Diana; Modo, Michel; Duchen, Michael R; Fraser, Paul A; Williams, Steven C R; Mann, Giovanni E

2013-12-01

Disruption of the blood-brain barrier (BBB) and cerebral edema are the major pathogenic mechanisms leading to neurological dysfunction and death after ischemic stroke. The brain protects itself against infarction via activation of endogenous antioxidant defense mechanisms, and we here report the first evidence that sulforaphane-mediated preactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1) in the cerebral vasculature protects the brain against stroke. To induce ischemic stroke, Sprague-Dawley rats were subjected to 70 min middle cerebral artery occlusion (MCAo) followed by 4, 24, or 72 h reperfusion. Nrf2 and HO-1 protein expression was upregulated in cerebral microvessels of peri-infarct regions after 4-72 h, with HO-1 preferentially associated with perivascular astrocytes rather than the cerebrovascular endothelium. In naïve rats, treatment with sulforaphane increased Nrf2 expression in cerebral microvessels after 24h. Upregulation of Nrf2 by sulforaphane treatment prior to transient MCAo (1h) was associated with increased HO-1 expression in perivascular astrocytes in peri-infarct regions and cerebral endothelium in the infarct core. BBB disruption, lesion progression, as analyzed by MRI, and neurological deficits were reduced by sulforaphane pretreatment. As sulforaphane pretreatment led to a moderate increase in peroxynitrite generation, we suggest that hormetic preconditioning underlies sulforaphane-mediated protection against stroke. In conclusion, we propose that pharmacological or dietary interventions aimed to precondition the brain via activation of the Nrf2 defense pathway in the cerebral microvasculature provide a novel therapeutic approach for preventing BBB breakdown and neurological dysfunction in stroke. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

PubMed

Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

2015-10-01

Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

Preconditioning for the Navier-Stokes equations with finite-rate chemistry

NASA Technical Reports Server (NTRS)

Godfrey, Andrew G.

1993-01-01

The extension of Van Leer's preconditioning procedure to generalized finite-rate chemistry is discussed. Application to viscous flow is begun with the proper preconditioning matrix for the one-dimensional Navier-Stokes equations. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from nearly stagnant flow to hypersonic. Specific benefits are realized at the low and transonic flow speeds typical of complete propulsion-system simulations. The extended preconditioning matrix necessarily accounts for both thermal and chemical nonequilibrium. Numerical analysis reveals the possible theoretical improvements from using a preconditioner for all Mach number regimes. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number areas. Van Leer, Lee, and Roe recently developed an optimal, analytic preconditioning technique to reduce eigenvalue stiffness over the full Mach-number range. By multiplying the flux-balance residual with the preconditioning matrix, the acoustic wave speeds are scaled so that all waves propagate at the same rate, an essential property to eliminate inherent eigenvalue stiffness. This session discusses a synthesis of the thermochemical nonequilibrium flux-splitting developed by Grossman and Cinnella and the characteristic wave preconditioning of Van Leer into a powerful tool for implicitly solving two and three-dimensional flows with generalized finite-rate chemistry. For finite-rate chemistry, the state vector of unknowns is variable in length. Therefore, the preconditioning matrix extended to generalized finite-rate chemistry must accommodate a flexible system of moving waves. Fortunately, no new kind of wave appears in the system. The only existing waves are entropy and vorticity waves, which move with the fluid, and acoustic waves, which propagate in Mach number dependent directions. The nonequilibrium vibrational energies and species densities in the unknown state vector act strictly as convective waves. The essential concept for extending the preconditioning to generalized chemistry models is determining the differential variables which symmetrize the flux Jacobians. The extension is then straight-forward. This algorithm research effort will be released in a future version of the production level computational code coined the General Aerodynamic Simulation Program (GASP), developed by Walters, Slack, and McGrory.

[Effect of electroacupuncture and moxibustion preconditioning on blood endothelin and creatine kinase contents and myocardial HSP 70 expression in rabbits with myocardial ischemia-reperfusion injury].

PubMed

Wang, Chao; Xie, Wen-juan; Liu, Mi; Yan, Jie; Zhang, Jia-li; Liu, Zhao; Guo, Li-na

2014-10-01

To observe the effect of electroacupuncture (EA) and moxibustion (Moxi) preconditioning of bi- lateral "Neiguan" (PC 6) on plasma endothelin (ET) and serum creatine kinase (CK) contents and myocardial hot shock protein 70 (HSP 70) expression in myocardial ischemia-reperfusion injury (MIRI) rabbits, so as to revel their mechanisms underlying prevention of myocardial ischemia. A total of 72 New Zealand rabbits were randomly divided into sham operation, MIRI model, EA preconditioning and Moxi preconditioning groups (n = 18/group). Each group was further divided into 0 h, 24 h and 48 h (time-point) subgroups (n=6 in each subgroup). The MIRI model was established by occlusion of the anterior descending branch of the left coronary artery for 40 min and reperfusion for 60 min. The contents of plasma ET and serum CK were detected by ELISA, and myocardial HSP 70 expression was detected by immunohistochemistry. EA and Moxi preconditioning were respectively applied to bilateral PC 6 for 20 min, once daily for 5 days. Following MIRI, contents of plasma ET and serum CK contents were significantly increased at 0 h, 24 h and 48 h in comparison with the sham group (P<0.01, P<0.05), while myo- cardial HSP 70 expression at the 3 time-points was moderately increased (P>0.05). Compared with the model groups, plasma ET contents at both 24 h and 48 h in the EA preconditioning group and at 48 h in the Moxi preconditioning group, CK contents at both 24 h and 48 h only in the EA preconditioning group were significantly down-regulated (P<0.01, P<0.05). Myocardial HSP 70 expression levels in the EA and Moxi preconditioning groups were considerably up-regulated at the three time-points in comparison with the model group(P<0.05, P<0.01). Acupuncture and moxibustion pretreatment may suppress MIRI-induced increase of plasma ET and serum CK and up-regulate myocardial HSP 70 protein expression in MIRI rabbits, suggesting a preventive protection action on ischemic myocardium.

What does wildfire risk mean to the public?

Treesearch

Sarah McCaffrey

2006-01-01

Public risk perception that managers may see as inappropriately low may not necessarily be a result of poor understanding but instead may be a result of self-selection and of mental balancing of benefits and risk. This study highlights the complexity of factors considered when members of the public assess wildfire risk including environmental preconditions, ignition...

Factors predicting change in hospital safety climate and capability in a multi-site patient safety collaborative: a longitudinal survey study.

PubMed

Benn, Jonathan; Burnett, Susan; Parand, Anam; Pinto, Anna; Vincent, Charles

2012-07-01

The study had two specific objectives: (1) To analyse change in a survey measure of organisational patient safety climate and capability (SCC) resulting from participation in the UK Safer Patients Initiative and (2) To investigate the role of a range of programme and contextual factors in predicting change in SCC scores. Single group longitudinal design with repeated measurement at 12-month follow-up. Multiple service areas within NHS hospital sites across England, Wales, Scotland and Northern Ireland. Stratified sample of 284 respondents representing programme teams at 19 hospital sites. A complex intervention comprising a multi-component quality improvement collaborative focused upon patient safety and designed to impact upon hospital leadership, communication, organisation and safety climate. A survey including a 31-item SCC scale was administered at two time-points. Modest but significant positive movement in SCC score was observed between the study time-points. Individual programme responsibility, availability of early adopters, multi-professional collaboration and extent of process measurement were significant predictors of change in SCC. Hospital type and size, along with a range of programme preconditions, were not found to be significant. A range of social, cultural and organisational factors may be sensitive to this type of intervention but the measurable effect is small. Supporting critical local programme implementation factors may be an effective strategy in achieving development in organisational patient SCC, regardless of contextual factors and organisational preconditions.

The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells.

PubMed

Tian, Shan; Zhu, Fengping; Hu, Ruiping; Tian, Song; Chen, Xingxing; Lou, Dan; Cao, Bing; Chen, Qiulei; Li, Bai; Li, Fang; Bai, Yulong; Wu, Yi; Zhu, Yulian

2018-01-01

Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface. Copyright © 2017 Elsevier B.V. All rights reserved.

Wetting properties of Au/Sn solders for microelectronics

NASA Astrophysics Data System (ADS)

Peterson, K. A.; Williams, C. B.

Hermetic sealing of microelectronic packages with Au/Sn solder is critically dependent upon good wetting. In studying specific problems in hermetic sealing, a solderability test based on ASTM standard F-357-78 has proven useful. The test has helped isolate and quantify the effects of contamination due to epoxy die attach and related handling, thermal preconditioning of packages, gold plating thickness, time and temperature during sealing, and solder alloy composition as they affect wetting. Some differences in hardware have been documented between manufacturing lots, but the overriding factors have been contamination which occurs during packaging process flows and thermal preconditioning during processing. The paper includes a review of metallurgical aspects of soldering to a non-inert surface and an examination of microstructural differences in seal joints. The results also quantify the conventional wisdom that alloys which are on the tin-rich side of the eutectic composition offer superior wetting properties.

Multi-color incomplete Cholesky conjugate gradient methods for vector computers. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Poole, E. L.

1986-01-01

In this research, we are concerned with the solution on vector computers of linear systems of equations, Ax = b, where A is a larger, sparse symmetric positive definite matrix. We solve the system using an iterative method, the incomplete Cholesky conjugate gradient method (ICCG). We apply a multi-color strategy to obtain p-color matrices for which a block-oriented ICCG method is implemented on the CYBER 205. (A p-colored matrix is a matrix which can be partitioned into a pXp block matrix where the diagonal blocks are diagonal matrices). This algorithm, which is based on a no-fill strategy, achieves O(N/p) length vector operations in both the decomposition of A and in the forward and back solves necessary at each iteration of the method. We discuss the natural ordering of the unknowns as an ordering that minimizes the number of diagonals in the matrix and define multi-color orderings in terms of disjoint sets of the unknowns. We give necessary and sufficient conditions to determine which multi-color orderings of the unknowns correpond to p-color matrices. A performance model is given which is used both to predict execution time for ICCG methods and also to compare an ICCG method to conjugate gradient without preconditioning or another ICCG method. Results are given from runs on the CYBER 205 at NASA's Langley Research Center for four model problems.

Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning

PubMed Central

Regnier-Golanov, Angelique S.; Britz, Gavin W.

2017-01-01

Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN) renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO) global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1) hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS)-injected) animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as “diving response”. PMID:28934119

Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality.

PubMed

Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

2015-04-01

Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditionings with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in opposite to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a novel mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Life is 3D: Boosting Spheroid Function for Tissue Engineering.

PubMed

Laschke, Matthias W; Menger, Michael D

2017-02-01

Spheroids provide a 3D environment with intensive cell-cell contacts. As a result of their excellent regenerative properties and rapid progress in their high-throughput production, spheroids are increasingly suggested as building blocks for tissue engineering. In this review, we focus on innovative biotechnological approaches that increase the quality of spheroids for this specific type of application. These include in particular the fabrication of coculture spheroids, mimicking the complex morphology and physiological tasks of natural tissues. In vitro preconditioning under different culture conditions and incorporation of biomaterials improve the function of spheroids and their directed fusion into macrotissues of desired shapes. The continuous development of these sophisticated approaches may markedly contribute to a broad implementation of spheroid-based tissue engineering in future regenerative medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Layer-oriented multigrid wavefront reconstruction algorithms for multi-conjugate adaptive optics

NASA Astrophysics Data System (ADS)

Gilles, Luc; Ellerbroek, Brent L.; Vogel, Curtis R.

2003-02-01

Multi-conjugate adaptive optics (MCAO) systems with 104-105 degrees of freedom have been proposed for future giant telescopes. Using standard matrix methods to compute, optimize, and implement wavefront control algorithms for these systems is impractical, since the number of calculations required to compute and apply the reconstruction matrix scales respectively with the cube and the square of the number of AO degrees of freedom. In this paper, we develop an iterative sparse matrix implementation of minimum variance wavefront reconstruction for telescope diameters up to 32m with more than 104 actuators. The basic approach is the preconditioned conjugate gradient method, using a multigrid preconditioner incorporating a layer-oriented (block) symmetric Gauss-Seidel iterative smoothing operator. We present open-loop numerical simulation results to illustrate algorithm convergence.

Hyperbaric oxygen preconditioning protects against traumatic brain injury at high altitude.

PubMed

Hu, S L; Hu, R; Li, F; Liu, Z; Xia, Y Z; Cui, G Y; Feng, H

2008-01-01

Recent studies have shown that preconditioning with hyperbaric oxygen (HBO) can reduce ischemic and hemorrhagic brain injury. We investigated effects of HBO preconditioning on traumatic brain injury (TBI) at high altitude and examined the role of matrix metalloproteinase-9 (MMP-9) in such protection. Rats were randomly divided into 3 groups: HBO preconditioning group (HBOP; n = 13), high-altitude group (HA; n = 13), and high-altitude sham operation group (HASO; n = 13). All groups were subjected to head trauma by weight-drop device, except for HASO group. HBOP rats received 5 sessions of HBO preconditioning (2.5 ATA, 100% oxygen, 1 h daily) and then were kept in hypobaric chamber at 0.6 ATA (to simulate pressure at 4000m altitude) for 3 days before operation. HA rats received control pretreatment (1 ATA, room air, 1 h daily), then followed the same procedures as HBOP group. HASO rats were subjected to skull opening only without brain injury. Twenty-four hours after TBI, 7 rats from each group were examined for neurological function and brain water content; 6 rats from each group were killed for analysis by H&E staining and immunohistochemistry. Neurological outcome in HBOP group (0.71 +/- 0.49) was better than HA group (1.57 +/- 0.53; p < 0.05). Preconditioning with HBO significantly reduced percentage of brain water content (86.24 +/- 0.52 vs. 84.60 +/- 0.37; p < 0.01). Brain morphology and structure seen by light microscopy was diminished in HA group, while fewer pathological injuries occurred in HBOP group. Compared to HA group, pretreatment with HBO significantly reduced the number of MMP-9-positive cells (92.25 +/- 8.85 vs. 74.42 +/- 6.27; p < 0.01). HBO preconditioning attenuates TBI in rats at high altitude. Decline in MMP-9 expression may contribute to HBO preconditioning-induced protection of brain tissue against TBI.

Organisational readiness: exploring the preconditions for success in organisation-wide patient safety improvement programmes.

PubMed

Burnett, Susan; Benn, Jonathan; Pinto, Anna; Parand, Anam; Iskander, Sandra; Vincent, Charles

2010-08-01

Patient safety has been high on the agenda for more than a decade. Despite many national initiatives aimed at improving patient safety, the challenge remains to find coherent and sustainable organisation-wide safety-improvement programmes. In the UK, the Safer Patients' Initiative (SPI) was established to address this challenge. Important in the success of such an endeavour is understanding 'readiness' at the organisational level, identifying the preconditions for success in this type of programme. This article reports on a case study of the four NHS organisations participating in the first phase of SPI, examining the perceptions of organisational readiness and the relationship of these factors with impact by those actively involved in the initiative. A mixed-methods design was used, involving a survey and semistructured interviews with senior executive leads, the principal SPI programme coordinator and the four operational leads in each of the SPI clinical work areas in all four organisations taking part in the first phase of SPI. This preliminary work would suggest that prior to the start of organisation-wide quality- and safety-improvement programmes, organisations would benefit from an assessment of readiness with time spent in the preparation of the organisational infrastructure, processes and culture. Furthermore, a better understanding of the preconditions that mark an organisation as ready for improvement work would allow policymakers to set realistic expectations about the outcomes of safety campaigns.

Factors influencing poststocking dispersal of razorback sucker

USGS Publications Warehouse

Mueller, G.A.; Marsh, P.C.; Foster, D.; Ulibarri, M.; Burke, T.

2003-01-01

Efforts to reintroduce razorback suckers Xyrauchen texanus to specific river reaches have been plagued by downstream drift and poor survival, which have been attributed to stress, disorientation, predation, and poor conditioning. Poststocking dispersal of eight test groups (15 fish each) of razorback suckers was examined for 28 d with telemetry equipment. Fish were released in three different locations in the Colorado River basin of Utah, Arizona, and Nevada: (1) a 65,000-ha reservoir, (2) a small (<1-ha) backwater, and (3) a large (30-ha) backwater on the mainstem river. At each location, subgroups were released immediately (reference) or held to acclimate them to the site (3–7 d) before release. Two of four subgroups for the large-backwater test were preconditioned to flow. Dispersal from the stocking sites was rapid and declined with time for all tests, as fish appeared to seek and find cover. Downstream drift was most pronounced (x = 69.5 km) from the small backwater and significantly (Kruskal–Wallis test, P < 0.01) greater than either the reservoir (x = 3.7 km) or large-backwater sites (x = 7.7 km). Site-acclimation tests were inconclusive, but downstream movement was significantly (Wilcoxon two-sample test, Z = −2.298, P < 0.01) less for fish preconditioned to flow (x = 1.9 km) compared with pond-reared fish (x = 7.7 km). We concluded that poststocking dispersal may decrease if razorback suckers are preconditioned to flow.

Preconditioning for the Navier-Stokes equations with finite-rate chemistry

NASA Technical Reports Server (NTRS)

Godfrey, Andrew G.; Walters, Robert W.; Van Leer, Bram

1993-01-01

The preconditioning procedure for generalized finite-rate chemistry and the proper preconditioning for the one-dimensional Navier-Stokes equations are presented. Eigenvalue stiffness is resolved and convergence-rate acceleration is demonstrated over the entire Mach-number range from the incompressible to the hypersonic. Specific benefits are realized at low and transonic flow speeds. The extended preconditioning matrix accounts for thermal and chemical non-equilibrium and its implementation is explained for both explicit and implicit time marching. The effect of higher-order spatial accuracy and various flux splittings is investigated. Numerical analysis reveals the possible theoretical improvements from using proconditioning at all Mach numbers. Numerical results confirm the expectations from the numerical analysis. Representative test cases include flows with previously troublesome embedded high-condition-number regions.

A numerical solution for the diffusion equation in hydrogeologic systems

USGS Publications Warehouse

Ishii, A.L.; Healy, R.W.; Striegl, Robert G.

1989-01-01

The documentation of a computer code for the numerical solution of the linear diffusion equation in one or two dimensions in Cartesian or cylindrical coordinates is presented. Applications of the program include molecular diffusion, heat conduction, and fluid flow in confined systems. The flow media may be anisotropic and heterogeneous. The model is formulated by replacing the continuous linear diffusion equation by discrete finite-difference approximations at each node in a block-centered grid. The resulting matrix equation is solved by the method of preconditioned conjugate gradients. The conjugate gradient method does not require the estimation of iteration parameters and is guaranteed convergent in the absence of rounding error. The matrixes are preconditioned to decrease the steps to convergence. The model allows the specification of any number of boundary conditions for any number of stress periods, and the output of a summary table for selected nodes showing flux and the concentration of the flux quantity for each time step. The model is written in a modular format for ease of modification. The model was verified by comparison of numerical and analytical solutions for cases of molecular diffusion, two-dimensional heat transfer, and axisymmetric radial saturated fluid flow. Application of the model to a hypothetical two-dimensional field situation of gas diffusion in the unsaturated zone is demonstrated. The input and output files are included as a check on program installation. The definition of variables, input requirements, flow chart, and program listing are included in the attachments. (USGS)

Brain ischemic preconditioning protects against ischemic injury and preserves the blood-brain barrier via oxidative signaling and Nrf2 activation.

PubMed

Yang, Tuo; Sun, Yang; Mao, Leilei; Zhang, Meijuan; Li, Qianqian; Zhang, Lili; Shi, Yejie; Leak, Rehana K; Chen, Jun; Zhang, Feng

2018-05-06

Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199). Nrf2 then induces expression of its target genes, including a new target, cadherin 5, a key component of adherens junctions of the BBB. These effects culminate in mitigation of BBB leakage and of neurological deficits after stroke. Collectively, these studies are the first to demonstrate that IPC protects the BBB against ischemic injury by generation of endogenous electrophiles and activation of the Nrf2 pathway through inhibition of Keap1- and GSK3β-dependent Nrf2 degradation. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

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

Hong, Kyung-Soo; Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan; Park, Jun-Ik

2012-03-01

SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-cateninmore » expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia-exposed or hypoxic preconditioned cells. ► SIRT1 deacetylates c-Myc and β-catenin ► HIF-1α is up-regulated by down-regulation of c-Myc and β-catenin expression. ► Polyphenolic SIRT1 activators mimics hypoxic preconditioning.« less

Interfacial Fracture Toughness of Adhesive Resin Cement-Lithium-Disilicate/Resin-Composite Blocks.

PubMed

Mesmar, Samer; Ruse, N Dorin

2017-09-15

Resin composite blocks (RCB) are advocated as alternative to ceramic blocks (CB). Prior to use, adherence to these materials should characterized. This study aimed to test the null hypothesis (H 0 ) that material and surface treatment combinations do not influence interfacial fracture toughness (K IC ) of a self-cured adhesive resin cement [RelyX Ultimate (RXU)] to RCB or CB, under nonaged and aged conditions. Two RCB, Lava Ultimate (LU) and Enamic (EN), and one CB, IPS e.max Press (EMP) were used. Half-size [(6 × 6 × 6 × 6 mm)] specimens were prepared for EMP (n = 30), EN (n = 30), and LU (n = 60). RCB specimens were prepared by wet cutting/grinding, while CB specimens were pressed. Surfaces of EMP and EN were preconditioned with hydrofluoric acid (5%); surfaces of LU were sandblasted with either 27 μm alumina (LUS) or 30 μm silica-modified alumina Rocatec soft (LUR). All specimens were bonded with Scotchbond Universal adhesive and RXU. Additionally, twenty (4 × 4 × 4 × 8 mm) RXU specimens were prepared. All specimens were stored in water at 37°C and tested after 1 and 60 days. Interfacial K IC was determined with the notchless triangular prism specimen K IC test. Results were analyzed with two-way ANOVA and Scheffé multiple means comparisons (α = 0.05). Preconditioned and selected fractured surfaces were characterized with scanning electron microscopy. At 24 hours, LUS-RXU and LUR-RXU had significantly higher interfacial K IC than EN-RXU and EMP-RXU and were not different from K IC of RXU. Aging lead to a significant decrease in K IC of RXU and interfacial K IC of LUS-RXU, LUR-RXU, and EMP-RXU; interfacial K IC of EN-RXU was not affected. Based on the results, H 0 was rejected. Under the conditions of this study, at 24 hours, interfacial K IC of LUS-RXU and LUR-RXU was superior to EMP-RXU and EN-RXU. Aging in water at 37°C did not affect interfacial K IC of EN-RXU but adversely affected K IC of RXU and the other interfacial K IC . The results suggest that RXU and its adherence to LU and EMP deteriorates upon exposure to water at 37°C. In making clinical decisions related to material selection, practitioners should consider in vitro results. © 2017 by the American College of Prosthodontists.

Hypoxia preconditioning of mesenchymal stromal cells enhances PC3 cell lymphatic metastasis accompanied by VEGFR-3/CCR7 activation.

PubMed

Huang, Xin; Su, Kunkai; Zhou, Limin; Shen, Guofang; Dong, Qi; Lou, Yijia; Zheng, Shu

2013-12-01

Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastases through the secretion of chemokines. MSCs have been reported to home toward the hypoxic tumor microenvironment in vivo. In this study, we investigated prostate cancer PC3 cell behavior under the influence of hypoxia preconditioned MSCs and explored the related mechanism of prostate cancer lymphatic metastases in mice. Transwell assays revealed that VEGF-C receptor, VEGFR-3, as well as chemokine CCL21 receptor, CC chemokine receptor 7 (CCR7), were responsible for the migration of PC3 cells toward hypoxia preconditioned MSCs. Knock-in Ccr7 in PC3 cells also improved cell migration in vitro. Furthermore, when PC3 cells were labeled using the hrGfp-lentiviral vector, and were combined with hypoxia preconditioned MSCs for xenografting, it resulted in an enhancement of lymph node metastases accompanied by up-regulation of VEGFR-3 and CCR7 in primary tumors. Both PI3K/Akt/IκBα and JAK2/STAT3 signaling pathways were activated in xenografts in the presence of hypoxia-preconditioned MSCs. Unexpectedly, the p-VEGFR-2/VEGFR-2 ratio was attenuated accompanied by decreased JAK1 expression, indicating a switching-off of potential vascular signal within xenografts in the presence of hypoxia-preconditioned MSCs. Unlike results from other studies, VEGF-C maintained a stable expression in both conditions, which indicated that hypoxia preconditioning of MSCs did not influence VEGF-C secretion. Our results provide the new insights into the functional molecular events and signalings influencing prostate tumor metastases, suggesting a hopeful diagnosis and treatment in new approaches. © 2013 Wiley Periodicals, Inc.

The involvement of protein kinase C-ε in isoflurane induced preconditioning of human embryonic stem cell--derived Nkx2.5(+) cardiac progenitor cells.

PubMed

Song, In-Ae; Oh, Ah-Young; Kim, Jin-Hee; Choi, Young-Min; Jeon, Young-Tae; Ryu, Jung-Hee; Hwang, Jung-Won

2016-02-20

Anesthetic preconditioning can improve survival of cardiac progenitor cells exposed to oxidative stress. We investigated the role of protein kinase C and isoform protein kinase C-ε in isoflurane-induced preconditioning of cardiac progenitor cells exposed to oxidative stress. Cardiac progenitor cells were obtained from undifferentiated human embryonic stem cells. Immunostaining with anti-Nkx2.5 was used to confirm the differentiated cardiac progenitor cells. Oxidative stress was induced by H2O2 and FeSO4. For anesthetic preconditioning, cardiac progenitor cells were exposed to 0.25, 0.5, and 1.0 mM of isoflurane. PMA and chelerythrine were used for protein kinase C activation and inhibition, while εψRACK and εV1-2 were used for protein kinase C -ε activation and inhibition, respectively. Isoflurane-preconditioning decreased the death rate of Cardiac progenitor cells exposed to oxidative stress (death rates isoflurane 0.5 mM 12.7 ± 9.3%, 1.0 mM 12.0 ± 7.7% vs. control 31.4 ± 10.2%). Inhibitors of both protein kinase C and protein kinase C -ε abolished the preconditioning effect of isoflurane 0.5 mM (death rates 27.6 ± 13.5% and 25.9 ± 8.7% respectively), and activators of both protein kinase C and protein kinase C - ε had protective effects from oxidative stress (death rates 16.0 ± 3.2% and 10.6 ± 3.8% respectively). Both PKC and PKC-ε are involved in isoflurane-induced preconditioning of human embryonic stem cells -derived Nkx2.5(+) Cardiac progenitor cells under oxidative stress.

Exercise preconditioning improves behavioral functions following transient cerebral ischemia induced by 4-vessel occlusion (4-VO) in rats.

PubMed

Tahamtan, Mahshid; Allahtavakoli, Mohammad; Abbasnejad, Mehdi; Roohbakhsh, Ali; Taghipour, Zahra; Taghavi, Mohsen; Khodadadi, Hassan; Shamsizadeh, Ali

2013-12-01

There is evidence that exercise decreases ischemia/reperfusion injury in rats. Since behavioral deficits are the main outcome in patients after stroke, our study was designed to investigate whether exercise preconditioning improves the acute behavioral functions and also brain inflammatory injury following cerebral ischemia. Male rats weighing 250-300 g were randomly allocated into five experimental groups. Exercise was performed on a treadmill 30min/day for 3 weeks. Ischemia was induced by 4-vessel occlusion method. Recognition memory was assessed by novel object recognition task (NORT) and step-through passive avoidance task. Sensorimotor function and motor movements were evaluated by adhesive removal test and ledged beam-walking test, respectively. Brain inflammatory injury was evaluated by histological assessment. In NORT, the discrimination ratio was decreased after ischemia (P < 0.05) and exercise preconditioning improved it in ischemic animals. In the passive avoidance test, a significant reduction in response latency was observed in the ischemic group. Exercise preconditioning significantly decreased the response latency in the ischemic rats (P < 0.001). In the adhesive removal test, latency to touch and remove the sticky labels from forepaw was increased following induction of ischemia (all P < 0.001) and exercise preconditioning decreased these indices compared to the ischemic group (all P < 0.001). In the ledged beam-walking test, the slip ratio was increased following ischemia (P < 0.05).  In the ischemia group, marked neuronal injury in hippocampus was observed. These neuropathological changes were attenuated by exercise preconditioning (P < 0.001). Our results showed that exercise preconditioning improves behavioral functions and maintains more viable cells in the dorsal hippocampus of the ischemic brain.

Effects and interaction, of cariporide and preconditioning on cardiac arrhythmias and infarction in rat in vivo

PubMed Central

Aye, Nu Nu; Komori, Sadayoshi; Hashimoto, Keitaro

1999-01-01

Although Na+-H+ exchange (NHE) inhibitors are reported to protect the myocardium against ischaemic injury, NHE activation has also been proposed as a potential mechanism of ischaemic preconditioning-induced protection. This study was performed to test any modifiable effect of cariporide, an NHE inhibitor, on cardioprotective effects of preconditioning.Anaesthetized rats were subjected to 30 min of coronary artery occlusion and 150 min of reperfusion. The preconditioning (PC) was induced by 3 min of ischaemia and 10 min of reperfusion (1PC) or three episodes of 3 min ischaemia and 5 min reperfusion (3PC). Cariporide (0.3 mg kg−1) an NHE inhibitor, was administered 30 min (cari(30)) or 45 min (cari(45)) before coronary ligation (n=8–11 for each group).Ventricular arrhythmias during 30 min ischaemia and infarct size (measured by triphenyltetrazolium (TTC) and expressed as a per cent area at risk (%AAR)) were determined. Cari(30) reduced ventricular fibrillation (VF) incidence and infarct size (from 45 to 0% and 34±4 to 9±2%; each P<0.05), whereas cari(45) did not. Likewise, 3PC reduced these variables (to 0% and 10±2%; P<0.05 in each case) whereas 1PC did not. Moreover, subthreshold preconditioning (1PC) and cariporide (cari(45)), when combined, reduced VF incidence and infarct size (to 0% and 15+3%; each P<0.05).In conclusion, changes in NHE activity do not seem to be responsible for the cardioprotective action of ischaemic preconditioning. Protective effects of NHE inhibition and subthreshold preconditioning appear to act additively. PMID:10433514

Cardioprotection of ischaemic preconditioning is associated with inhibition of translocation of MLKL within the plasma membrane.

PubMed

Szobi, Adrián; Farkašová-Ledvényiová, Veronika; Lichý, Martin; Muráriková, Martina; Čarnická, Slávka; Ravingerová, Tatiana; Adameová, Adriana

2018-06-19

Necroptosis, a form of cell loss involving the RIP1-RIP3-MLKL axis, has been identified in cardiac pathologies while its inhibition is cardioprotective. We investigated whether the improvement of heart function because of ischaemic preconditioning is associated with mitigation of necroptotic signaling, and these effects were compared with a pharmacological antinecroptotic approach targeting RIP1. Langendorff-perfused rat hearts were subjected to ischaemic preconditioning with or without a RIP1 inhibitor (Nec-1s). Necroptotic signaling and the assessment of oxidative damage and a putative involvement of CaMKII in this process were analysed in whole tissue and subcellular fractions. Ischaemic preconditioning, Nec-1s and their combination improved postischaemic heart function recovery and reduced infarct size to a similar degree what was in line with the prevention of MLKL oligomerization and translocation to the membrane. On the other hand, membrane peroxidation and apoptosis were unchanged by either approach. Ischaemic preconditioning failed to ameliorate ischaemia-reperfusion-induced increase in RIP1 and RIP3 while pSer229-RIP3 levels were reduced only by Nec-1s. In spite of the additive phosphorylation of CaMKII and PLN because of ditherapy, the postischaemic contractile force and relaxation was comparably improved in all the intervention groups while antiarrhythmic effects were observed in the ischaemic preconditioning group only. Necroptosis inhibition seems to be involved in cardioprotection of ischaemic preconditioning and is comparable but not intensified by an anti-RIP1 agent. Changes in oxidative stress nor CaMKII signaling are unlikely to explain the beneficial effects. © 2018 Comenius University in Bratislava, Faculty of Pharmacy. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Effect of non-invasive remote ischemic preconditioning on intra-renal perfusion in volunteers.

PubMed

Robert, René; Vinet, Mathieu; Jamet, Angéline; Coudroy, Rémi

2017-06-01

Remote ischemic preconditioning may attenuate renal injury and protect the kidney during subsequent inflammatory or ischemic stress. However, the mechanism of such a protection is not well understood. The aim of this study was to investigate the impact of remote ischemic preconditioning on renal resistivity index (RRI) in nine healthy volunteers. In six volunteers, four cycles of 4-min inflation of a blood pressure cuff were applied to one upper arm, followed by 4-min reperfusion with the cuff deflated. RRI was determined using Doppler echography during each cuff deflated period. Measures were also performed in three volunteers without preconditioning. The median value of RRI significantly decreased progressively from 0.59 [0.53-0.62] before the remote conditioning (baseline) to 0.49 [0.46-0.53] at the end of the experiment (p < 0.001) whereas there was no change in controls. In this study, for the first time, we have clearly shown in a small group of subjects that remote ischemic preconditioning can induce a significantly decrease in RRI through increased intra-renal perfusion.

Alterations of hypoxia-inducible factor-1 alpha in the hippocampus of mice acutely and repeatedly exposed to hypoxia.

PubMed

Shao, Guo; Gao, Cui-Ying; Lu, Guo-Wei

2005-01-01

This work aims at investigating the effects of hypoxic preconditioning on hypoxia-inducible factor-1 alpha (HIF-1alpha) expression in the hippocampus of mice during acute and repeated hypoxic exposures. The mice were randomly divided into three groups and exposed, respectively, to hypoxia for 4 runs (group H4), 1 run (group H1), and 0 run (group H0). Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation were used to examine the HIF-1alpha responses in the mouse hippocampus following exposure to hypoxia. The tolerance of mice to hypoxia increased significantly following acute and repetitive exposure to autoprogressive hypoxia. Total mRNA, total protein, and nuclear protein were extracted from the hippocampus for RT-PCR, Western blot, and EMSA, respectively. The HIF-1alpha mRNA levels were found to be increased in group H1 and decreased in group H4. The HIF-1alpha protein levels and HIF-1 DNA-binding activities were increased in group H1 and markedly increased in group H4. One of the HIF-1 target genes, vascular endothelial growth factor, increased in group H4. HIF-1 activation is thought to be involved in the protection of the brain of hypoxic preconditioned mice. Copyright 2005 S. Karger AG, Basel

No influence of ischemic preconditioning on running economy.

PubMed

Kaur, Gungeet; Binger, Megan; Evans, Claire; Trachte, Tiffany; Van Guilder, Gary P

2017-02-01

Many of the potential performance-enhancing properties of ischemic preconditioning suggest that the oxygen cost for a given endurance exercise workload will be reduced, thereby improving the economy of locomotion. The aim of this study was to identify whether ischemic preconditioning improves exercise economy in recreational runners. A randomized sham-controlled crossover study was employed in which 18 adults (age 27 ± 7 years; BMI 24.6 ± 3 kg/m 2 ) completed two, incremental submaximal (65-85% VO 2max ) treadmill running protocols (3 × 5 min stages from 7.2-14.5 km/h) coupled with indirect calorimetry to assess running economy following ischemic preconditioning (3 × 5 min bilateral upper thigh ischemia) and sham control. Running economy was expressed as mlO 2 /kg/km and as the energy in kilocalories required to cover 1 km of horizontal distance (kcal/kg/km). Ischemic preconditioning did not influence steady-state heart rate, oxygen consumption, minute ventilation, respiratory exchange ratio, energy expenditure, and blood lactate. Likewise, running economy was similar (P = 0.647) between the sham (from 201.6 ± 17.7 to 204.0 ± 16.1 mlO 2 /kg/km) and ischemic preconditioning trials (from 202.8 ± 16.2 to 203.1 ± 15.6 mlO 2 /kg/km). There was no influence (P = 0.21) of ischemic preconditioning on running economy expressed as the caloric unit cost (from 0.96 ± 0.12 to 1.01 ± 0.11 kcal/kg/km) compared with sham (from 1.00 ± 0.10 to 1.00 ± 0.08 kcal/kg/km). The properties of ischemic preconditioning thought to affect exercise performance at vigorous to severe exercise intensities, which generate more extensive physiological challenge, are ineffective at submaximal workloads and, therefore, do not change running economy.

Block LU factorization

NASA Technical Reports Server (NTRS)

Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

1992-01-01

Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

Primary Commodity Dependency: A Limiting Factor for Achieving Democracy

DTIC Science & Technology

2010-03-24

two ~gricultural crops, minerals, petroleum, or fisheries can be considered primary commodity dependent. Tea, coffee, and cocoa ; peanuts and cotton...Rostow’s Development Model Pre-conditions for take-off mass consumption democracy. In 1960s, economists, associated democratization to a developmental...Commodities can be renewable or non-renewable. Petroleum, diamonds, cocoa , bananas, coffee, and timber are just a few of the commodities that have

Nested Conjugate Gradient Algorithm with Nested Preconditioning for Non-linear Image Restoration.

PubMed

Skariah, Deepak G; Arigovindan, Muthuvel

2017-06-19

We develop a novel optimization algorithm, which we call Nested Non-Linear Conjugate Gradient algorithm (NNCG), for image restoration based on quadratic data fitting and smooth non-quadratic regularization. The algorithm is constructed as a nesting of two conjugate gradient (CG) iterations. The outer iteration is constructed as a preconditioned non-linear CG algorithm; the preconditioning is performed by the inner CG iteration that is linear. The inner CG iteration, which performs preconditioning for outer CG iteration, itself is accelerated by an another FFT based non-iterative preconditioner. We prove that the method converges to a stationary point for both convex and non-convex regularization functionals. We demonstrate experimentally that proposed method outperforms the well-known majorization-minimization method used for convex regularization, and a non-convex inertial-proximal method for non-convex regularization functional.

On adaptive weighted polynomial preconditioning for Hermitian positive definite matrices

NASA Technical Reports Server (NTRS)

Fischer, Bernd; Freund, Roland W.

1992-01-01

The conjugate gradient algorithm for solving Hermitian positive definite linear systems is usually combined with preconditioning in order to speed up convergence. In recent years, there has been a revival of polynomial preconditioning, motivated by the attractive features of the method on modern architectures. Standard techniques for choosing the preconditioning polynomial are based only on bounds for the extreme eigenvalues. Here a different approach is proposed, which aims at adapting the preconditioner to the eigenvalue distribution of the coefficient matrix. The technique is based on the observation that good estimates for the eigenvalue distribution can be derived after only a few steps of the Lanczos process. This information is then used to construct a weight function for a suitable Chebyshev approximation problem. The solution of this problem yields the polynomial preconditioner. In particular, we investigate the use of Bernstein-Szego weights.

Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats.

PubMed

Rybnikova, Elena; Mironova, Vera; Pivina, Svetlana; Tulkova, Ekaterina; Ordyan, Natalia; Vataeva, Ludmila; Vershinina, Elena; Abritalin, Eugeny; Kolchev, Alexandr; Nalivaeva, Natalia; Turner, Anthony J; Samoilov, Michail

2007-05-07

The effects of preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 h each of 3 days) have been studied in the learned helplessness model of depression in rats. Male Wistar rats displayed persistent depressive symptoms (depressive-like behaviour in open field, increased anxiety levels in elevated plus maze, ahedonia, elevated plasma glucocorticoids and impaired dexamethasone test) following the exposure to unpredictable and inescapable footshock in the learned helplessness paradigm. Antidepressant treatment (ludiomil, 5 mg/kg i.p.) augmented the development of the depressive state. The hypoxic preconditioning had a clear antidepressive action returning the behavioural and hormonal parameters to the control values and was equally effective in terms of our study as the antidepressant. The findings suggest hypoxic preconditioning as an effective tool for the prophylaxis of post-stress affective pathologies in humans.

Preconditioned characteristic boundary conditions based on artificial compressibility method for solution of incompressible flows

NASA Astrophysics Data System (ADS)

Hejranfar, Kazem; Parseh, Kaveh

2017-09-01

The preconditioned characteristic boundary conditions based on the artificial compressibility (AC) method are implemented at artificial boundaries for the solution of two- and three-dimensional incompressible viscous flows in the generalized curvilinear coordinates. The compatibility equations and the corresponding characteristic variables (or the Riemann invariants) are mathematically derived and then applied as suitable boundary conditions in a high-order accurate incompressible flow solver. The spatial discretization of the resulting system of equations is carried out by the fourth-order compact finite-difference (FD) scheme. In the preconditioning applied here, the value of AC parameter in the flow field and also at the far-field boundary is automatically calculated based on the local flow conditions to enhance the robustness and performance of the solution algorithm. The code is fully parallelized using the Concurrency Runtime standard and Parallel Patterns Library (PPL) and its performance on a multi-core CPU is analyzed. The incompressible viscous flows around a 2-D circular cylinder, a 2-D NACA0012 airfoil and also a 3-D wavy cylinder are simulated and the accuracy and performance of the preconditioned characteristic boundary conditions applied at the far-field boundaries are evaluated in comparison to the simplified boundary conditions and the non-preconditioned characteristic boundary conditions. It is indicated that the preconditioned characteristic boundary conditions considerably improve the convergence rate of the solution of incompressible flows compared to the other boundary conditions and the computational costs are significantly decreased.

Condition number estimation of preconditioned matrices.

PubMed

Kushida, Noriyuki

2015-01-01

The present paper introduces a condition number estimation method for preconditioned matrices. The newly developed method provides reasonable results, while the conventional method which is based on the Lanczos connection gives meaningless results. The Lanczos connection based method provides the condition numbers of coefficient matrices of systems of linear equations with information obtained through the preconditioned conjugate gradient method. Estimating the condition number of preconditioned matrices is sometimes important when describing the effectiveness of new preconditionerers or selecting adequate preconditioners. Operating a preconditioner on a coefficient matrix is the simplest method of estimation. However, this is not possible for large-scale computing, especially if computation is performed on distributed memory parallel computers. This is because, the preconditioned matrices become dense, even if the original matrices are sparse. Although the Lanczos connection method can be used to calculate the condition number of preconditioned matrices, it is not considered to be applicable to large-scale problems because of its weakness with respect to numerical errors. Therefore, we have developed a robust and parallelizable method based on Hager's method. The feasibility studies are curried out for the diagonal scaling preconditioner and the SSOR preconditioner with a diagonal matrix, a tri-daigonal matrix and Pei's matrix. As a result, the Lanczos connection method contains around 10% error in the results even with a simple problem. On the other hand, the new method contains negligible errors. In addition, the newly developed method returns reasonable solutions when the Lanczos connection method fails with Pei's matrix, and matrices generated with the finite element method.

Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro.

PubMed

Bhuiyan, Mohammad Iqbal Hossain; Jung, Seo Yun; Kim, Hyoung Ja; Lee, Yong Sup; Jin, Changbae

2011-06-01

Ischemic preconditioning can provide protection to neurons from subsequent lethal ischemia. The molecular mechanisms of neuronal ischemic tolerance, however, are still not well-known. The present study, therefore, examined the role of MAPK and PI3K/Akt pathways in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. Ischemic tolerance was simulated by preconditioning of the neurons with sublethal 1-h OGD imposed 12 h before lethal 3-h OGD. The time-course studies of relative phosphorylation and expression levels of ERK1/2, JNK and p38 MAPK showed lack of their involvement in ischemic tolerance. However, there were significant increases in Akt phosphorylation levels during the reperfusion period following preconditioned lethal OGD. In addition, Bcl-2 associated death promoter (Bad) and GSK-3β were also found to be inactivated during that reperfusion period. Finally, treatment with an inhibitor of PI3K, wortmannin, applied from 15 min before and during lethal OGD abolished not only the preconditioning-induced neuroprotection but also the Akt activation. Concomitant with blockade of the Akt activation, PI3K inhibition also resulted in activation of Bad and GSK-3β. The results suggest that ischemic tolerance induced by sublethal OGD preconditioning is primarily mediated through activation of the PI3K/Akt pathway, but not the MAPK pathway, in rat cortical neurons.

Efficient Transplantation via Antibody-based Clearance of Hematopoietic Stem Cell Niches

PubMed Central

Czechowicz, Agnieszka; Kraft, Daniel; Weissman, Irving L.; Bhattacharya, Deepta

2008-01-01

Summary We demonstrate that administration of a depleting antibody specific for c-kit leads to the highly efficient removal of host hematopoietic stem cells (HSCs) and high levels of donor HSC chimerism following transplantation. Upon intravenous transplantation, hematopoietic stem cells (HSCs) can home to specialized niches, yet most HSCs fail to engraft unless recipients are subjected to toxic preconditioning. Here, we provide evidence that, aside from immune barriers, donor HSC engraftment is restricted by occupancy of appropriate niches by host HSCs. Administration of ACK2, an antibody that blocks c-kit function, led to the transient removal of >98% of endogenous HSCs in immunodeficient mice. Subsequent transplantation of these animals with donor HSCs led to chimerism levels of up to 90%. Extrapolation of these methods to humans may enable mild but effective conditioning regimens for transplantation. PMID:18033883

Human factors in spacecraft design

NASA Technical Reports Server (NTRS)

Harrison, Albert A.; Connors, Mary M.

1990-01-01

This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

Experimental analysis of insertion torques and forces of threaded and press-fit acetabular cups by means of ex vivo and in vivo measurements.

PubMed

Vogel, Danny; Rathay, Andreas; Teufel, Stephanie; Ellenrieder, Martin; Zietz, Carmen; Sander, Manuela; Bader, Rainer

2017-01-01

In THA a sufficient primary implant stability is the precondition for successful secondary stability. Industrial foams of different densities have been used for primary stability investigations. The aim of this study was to analyse and compare the insertion behaviour of threaded and press-fit cups in vivo and ex vivo using bone substitutes with various densities. Two threaded (Bicon Plus®, Trident® TC) and one press-fit cup (Trident PSL®) were inserted by orthopaedic surgeons (S1, S2) into 10, 20 and 31 pcf blocks, using modified surgical instruments allowing measurements of the insertion forces and torques. Furthermore, the insertion behaviour of two cups were analysed intraoperatively. Torques for the threaded cups increased while bone substitute density increased. Maximum insertion torques were observed for S2 with 102 Nm for the Bicon Plus® in 20 pcf blocks and 77 Nm for the Trident® TC in 31 pcf blocks, which compares to the in vivo measurement (85 Nm). The average insertion forces for the press-fit cup varied from 5.2 to 6.8 kN (S1) and 7.2-11.5 kN (S2) ex vivo. Intraoperatively an average insertion force of 8.0 kN was determined. Implantation behaviour was influenced by acetabular cup design, bone substitute and experience of the surgeon. No specific density of bone substitute could be favoured for ex vivo investigations on the implantation behaviour of acetabular cups. The use synthetic bone blocks of high density (31 pcf) led to problems regarding cup orientation and seating. Therefore, bone substitutes used should be critically scrutinized in terms of the comparability to the in vivo situation.

Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

PubMed Central

Sharma, Ashish Kumar; Munajjam, Arshee; Vaishnav, Bhawna; Sharma, Richa; Sharma, Ashok; Kishore, Kunal; Sharma, Akash; Sharma, Divya; Kumari, Rita; Tiwari, Ashish; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Srinivasan, Barthu Parthi; Agarwal, Shyam Sunder

2012-01-01

The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide. PMID:23554727

Impact of remote ischemic preconditioning on wound healing in small bowel anastomoses

PubMed Central

Holzner, Philipp Anton; Kulemann, Birte; Kuesters, Simon; Timme, Sylvia; Hoeppner, Jens; Hopt, Ulrich Theodor; Marjanovic, Goran

2011-01-01

AIM: To investigate the influence of remote ischemic preconditioning (RIPC) on anastomotic integrity. METHODS: Sixty male Wistar rats were randomized to six groups. The control group (n = 10) had an end-to-end ileal anastomosis without RIPC. The preconditioned groups (n = 34) varied in time of ischemia and time of reperfusion. One group received the amino acid L-arginine before constructing the anastomosis (n = 9). On postoperative day 4, the rats were re-laparotomized, and bursting pressure, hydroxyproline concentration, intra-abdominal adhesions, and a histological score concerning the mucosal ischemic injury were collected. The data are given as median (range). RESULTS: On postoperative day 4, median bursting pressure was 124 mmHg (60-146 mmHg) in the control group. The experimental groups did not show a statistically significant difference (P > 0.05). Regarding the hydroxyproline concentration, we did not find any significant variation in the experimental groups. We detected significantly less mucosal injury in the RIPC groups. Furthermore, we assessed more extensive intra-abdominal adhesions in the preconditioned groups than in the control group. CONCLUSION: RIPC directly before performing small bowel anastomosis does not affect anastomotic stability in the early period, as seen in ischemic preconditioning. PMID:21455330

Beneficial effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in the rat.

PubMed

Magyar, Zsuzsanna; Mester, Anita; Nadubinszky, Gabor; Varga, Gabor; Ghanem, Souleiman; Somogyi, Viktoria; Tanczos, Bence; Deak, Adam; Bidiga, Laszlo; Oltean, Mihai; Peto, Katalin; Nemeth, Norbert

2018-04-14

Remote ischemic preconditioning (RIPC) can be protective against the damage. However, there is no consensus on the optimal amount of tissue, the number and duration of the ischemic cycles, and the timing of the preconditioning. The hemorheological background of the process is also unknown. To investigate the effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in rats. In anesthetized rats 60-minute partial liver ischemia was induced with 120-minute reperfusion (Control, n = 7). In the preconditioned groups a tourniquet was applied on the left thigh for 3×10 minutes 1 hour (RIPC-1, n = 7) or 24 hours (RIPC-24, n = 7) prior to the liver ischemia. Blood samples were taken before the operation and during the reperfusion. Acid-base, hematological parameters, erythrocyte aggregation and deformability were tested. Lactate concentration significantly increased by the end of the reperfusion. Erythrocyte deformability was improved in the RIPC-1 group, erythrocyte aggregation increased during the reperfusion, particularly in the RIPC-24 group. RIPC alleviated several hemorheological changes caused by the liver I/R. However, the optimal timing of the RIPC cannot be defined based on these results.

Fast divide-and-conquer algorithm for evaluating polarization in classical force fields

NASA Astrophysics Data System (ADS)

Nocito, Dominique; Beran, Gregory J. O.

2017-03-01

Evaluation of the self-consistent polarization energy forms a major computational bottleneck in polarizable force fields. In large systems, the linear polarization equations are typically solved iteratively with techniques based on Jacobi iterations (JI) or preconditioned conjugate gradients (PCG). Two new variants of JI are proposed here that exploit domain decomposition to accelerate the convergence of the induced dipoles. The first, divide-and-conquer JI (DC-JI), is a block Jacobi algorithm which solves the polarization equations within non-overlapping sub-clusters of atoms directly via Cholesky decomposition, and iterates to capture interactions between sub-clusters. The second, fuzzy DC-JI, achieves further acceleration by employing overlapping blocks. Fuzzy DC-JI is analogous to an additive Schwarz method, but with distance-based weighting when averaging the fuzzy dipoles from different blocks. Key to the success of these algorithms is the use of K-means clustering to identify natural atomic sub-clusters automatically for both algorithms and to determine the appropriate weights in fuzzy DC-JI. The algorithm employs knowledge of the 3-D spatial interactions to group important elements in the 2-D polarization matrix. When coupled with direct inversion in the iterative subspace (DIIS) extrapolation, fuzzy DC-JI/DIIS in particular converges in a comparable number of iterations as PCG, but with lower computational cost per iteration. In the end, the new algorithms demonstrated here accelerate the evaluation of the polarization energy by 2-3 fold compared to existing implementations of PCG or JI/DIIS.

Improved quality and more attractive work by applying EBM in disability evaluations: a qualitative survey.

PubMed

Hoving, Jan L; Kok, Rob; Ketelaar, Sarah M; Smits, Paul B A; van Dijk, Frank J H; Verbeek, Jos H

2016-02-29

The uptake of evidence in practice by physicians, even if they are trained in the systematic method of evidence-based medicine (EBM), remains difficult to improve. The aim of this study was to explore perceptions and experiences of physicians doing disability evaluations regarding motivators and preconditions for the implementation of EBM in daily practice. This qualitative study was nested in a cluster randomized controlled trial (Trial registration NTR1767; 20-apr-2009) evaluating the effects of training in EBM. The 45 physicians that participated received a comprehensive 6-months training program in EBM of which the last course day included audio-recorded interviews in groups. During these interviews participating physicians discussed perceptions and experiences regarding EBM application in daily practice. In an iterative process we searched for common motivators or preconditions for the implementation of EBM. Three main concepts or themes emerged after analyzing the transcriptions of the discussions: 1) improved quality of physicians' actions, such as clients benefiting from the application of EBM; 2) improved work attractiveness of physicians; and 3) preconditions that have to be met in order to work in an evidence-based manner including professional competence, facilitating material conditions and organizational support and demands. Physicians trained in EBM are motivated to use EBM because they perceive it as a factor improving the quality of their work and making their work more attractive. In addition to personal investments and gains, organizational support should further facilitate the uptake of evidence in practice.

Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways.

PubMed

Guan, Junhong; Du, Shaonan; Lv, Tao; Qu, Shengtao; Fu, Qiang; Yuan, Ye

2016-01-01

Bone morphogenetic protein (BMP)-7 mediated neuroprotective effect of cerebral ischemic preconditioning (IPC) has been studied in an ischemic animal model, but the underlying cellular mechanisms have not been clearly clarified. In this study, primary cortical neurons and the SH-SY5Y cell line were used to investigate the role of BMP-7 and its downstream signals in the neuroprotective effects of oxygen-glucose deprivation preconditioning (OGDPC). Immunocytochemistry was used to detect the expression of neurofilament in neurons. MTT and lactate dehydrogenase activity assays were used to measure the cytotoxicity. Western blot was used to detect the protein expression of BMP-7 and downstream signals. BMP inhibitor, mitogen-activated protein kinase inhibitors, Smad inhibitor and siRNA of Smad 1 were used to investigate the role of corresponding signalling pathways in the OGDPC. Results showed that OGDPC-induced overexpression of BMP-7 in primary cortical neurons and SH-SY5Y cells. Both of endogenous and exogenous BMP-7 could replicate the neuroprotective effects seen in OGDPC pretreatment. In addition, extracellular regulated protein kinases, p38 and Smad signalling pathway were found to be involved in the neuroprotective effects mediated by OGDPC via BMP-7. This study primarily reveals the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia. © 2015 Wiley Publishing Asia Pty Ltd.

Why older workers work beyond the retirement age: a qualitative study.

PubMed

Sewdas, Ranu; de Wind, Astrid; van der Zwaan, Lennart G L; van der Borg, Wieke E; Steenbeek, Romy; van der Beek, Allard J; Boot, Cécile R L

2017-08-22

The aims of the present study were to: 1) gain insight into reasons for working beyond the statutory retirement age from older workers' perspectives, and 2) explore how the domains of the research framework Study on Transitions in Employment, Ability and Motivation (STREAM) can be applied to working beyond retirement age. A qualitative research design included individual interviews (n = 15) and three focus groups (n = 18 participants) conducted with older workers aged 65 years and older continuing in a paid job or self-employment. Interview participants were recruited from an existing STREAM cohort study. Focus group participants were recruited from companies and employment agencies. The data were subjected to thematic analysis. The most important motives for working beyond retirement age were maintaining daily routines and financial benefit. Good health and flexible work arrangements were mentioned as important preconditions. The themes emerging from the categorization of the motives and preconditions corresponded to the domains of health, work characteristics, skills and knowledge, and social and financial factors from the STREAM research framework. However, our analysis revealed one additional theme-purpose in life. This study offers important new insights into the various preconditions and motives that influence working beyond retirement age. In addition, the five domains of the STREAM research framework, including the additional domain of 'purpose in life', seem to be applicable to working beyond retirement age. This knowledge contributes to the development of work-related interventions that enhance older workers' motivation to prolong their working lives.

Application of acoustic agglomeration to enhance air filtration efficiency in air-conditioning and mechanical ventilation (ACMV) systems.

PubMed

Ng, Bing Feng; Xiong, Jin Wen; Wan, Man Pun

2017-01-01

The recent episodes of haze in Southeast Asia have caused some of the worst regional atmospheric pollution ever recorded in history. In order to control the levels of airborne fine particulate matters (PM) indoors, filtration systems providing high PM capturing efficiency are often sought, which inadvertently also results in high airflow resistance (or pressure drop) that increases the energy consumption for air distribution. A pre-conditioning mechanism promoting the formation of particle clusters to enhance PM capturing efficiency without adding flow resistance in the air distribution ductwork could provide an energy-efficient solution. This pre-conditioning mechanism can be fulfilled by acoustic agglomeration, which is a phenomenon that promotes the coagulation of suspended particles by acoustic waves propagating in the fluid medium. This paper discusses the basic mechanisms of acoustic agglomeration along with influencing factors that could affect the agglomeration efficiency. The feasibility to apply acoustic agglomeration to improve filtration in air-conditioning and mechanical ventilation (ACMV) systems is investigated experimentally in a small-scale wind tunnel. Experimental results indicate that this novel application of acoustic pre-conditioning improves the PM2.5 filtration efficiency of the test filters by up to 10% without introducing additional pressure drop. The fan energy savings from not having to switch to a high capturing efficiency filter largely outstrip the additional energy consumed by the acoustics system. This, as a whole, demonstrates potential energy savings from the combined acoustic-enhanced filtration system without compromising on PM capturing efficiency.

Application of acoustic agglomeration to enhance air filtration efficiency in air-conditioning and mechanical ventilation (ACMV) systems

PubMed Central

Xiong, Jin Wen; Wan, Man Pun

2017-01-01

The recent episodes of haze in Southeast Asia have caused some of the worst regional atmospheric pollution ever recorded in history. In order to control the levels of airborne fine particulate matters (PM) indoors, filtration systems providing high PM capturing efficiency are often sought, which inadvertently also results in high airflow resistance (or pressure drop) that increases the energy consumption for air distribution. A pre-conditioning mechanism promoting the formation of particle clusters to enhance PM capturing efficiency without adding flow resistance in the air distribution ductwork could provide an energy-efficient solution. This pre-conditioning mechanism can be fulfilled by acoustic agglomeration, which is a phenomenon that promotes the coagulation of suspended particles by acoustic waves propagating in the fluid medium. This paper discusses the basic mechanisms of acoustic agglomeration along with influencing factors that could affect the agglomeration efficiency. The feasibility to apply acoustic agglomeration to improve filtration in air-conditioning and mechanical ventilation (ACMV) systems is investigated experimentally in a small-scale wind tunnel. Experimental results indicate that this novel application of acoustic pre-conditioning improves the PM2.5 filtration efficiency of the test filters by up to 10% without introducing additional pressure drop. The fan energy savings from not having to switch to a high capturing efficiency filter largely outstrip the additional energy consumed by the acoustics system. This, as a whole, demonstrates potential energy savings from the combined acoustic-enhanced filtration system without compromising on PM capturing efficiency. PMID:28594862

Mitochondria in the middle: exercise preconditioning protection of striated muscle

PubMed Central

Rodriguez, Dinah A.; Hord, Jeffrey M.

2016-01-01

Abstract Cellular and physiological adaptations to an atmosphere which became enriched in molecular oxygen spurred the development of a layered system of stress protection, including antioxidant and stress response proteins. At physiological levels reactive oxygen and nitrogen species regulate cell signalling as well as intracellular and intercellular communication. Exercise and physical activity confer a variety of stressors on skeletal muscle and the cardiovascular system: mechanical, metabolic, oxidative. Transient increases of stressors during acute bouts of exercise or exercise training stimulate enhancement of cellular stress protection against future insults of oxidative, metabolic and mechanical stressors that could induce injury or disease. This phenomenon has been termed both hormesis and exercise preconditioning (EPC). EPC stimulates transcription factors such as Nrf‐1 and heat shock factor‐1 and up‐regulates gene expression of a cadre of cytosolic (e.g. glutathione peroxidase and heat shock proteins) and mitochondrial adaptive or stress proteins (e.g. manganese superoxide dismutase, mitochondrial KATP channels and peroxisome proliferator activated receptor γ coactivator‐1 (PGC‐1)). Stress response and antioxidant enzyme inducibility with exercise lead to protection against striated muscle damage, oxidative stress and injury. EPC may indeed provide significant clinical protection against ischaemia–reperfusion injury, Type II diabetes and ageing. New molecular mechanisms of protection, such as δ‐opioid receptor regulation and mitophagy, reinforce the notion that mitochondrial adaptations (e.g. heat shock proteins, antioxidant enzymes and sirtuin‐1/PGC‐1 signalling) are central to the protective effects of exercise preconditioning. PMID:27060608

Preconditioned upwind methods to solve 3-D incompressible Navier-Stokes equations for viscous flows

NASA Technical Reports Server (NTRS)

Hsu, C.-H.; Chen, Y.-M.; Liu, C. H.

1990-01-01

A computational method for calculating low-speed viscous flowfields is developed. The method uses the implicit upwind-relaxation finite-difference algorithm with a nonsingular eigensystem to solve the preconditioned, three-dimensional, incompressible Navier-Stokes equations in curvilinear coordinates. The technique of local time stepping is incorporated to accelerate the rate of convergence to a steady-state solution. An extensive study of optimizing the preconditioned system is carried out for two viscous flow problems. Computed results are compared with analytical solutions and experimental data.

Fourier analysis of finite element preconditioned collocation schemes

NASA Technical Reports Server (NTRS)

Deville, Michel O.; Mund, Ernest H.

1990-01-01

The spectrum of the iteration operator of some finite element preconditioned Fourier collocation schemes is investigated. The first part of the paper analyses one-dimensional elliptic and hyperbolic model problems and the advection-diffusion equation. Analytical expressions of the eigenvalues are obtained with use of symbolic computation. The second part of the paper considers the set of one-dimensional differential equations resulting from Fourier analysis (in the tranverse direction) of the 2-D Stokes problem. All results agree with previous conclusions on the numerical efficiency of finite element preconditioning schemes.

Choice of Variables and Preconditioning for Time Dependent Problems

NASA Technical Reports Server (NTRS)

Turkel, Eli; Vatsa, Verr N.

2003-01-01

We consider the use of low speed preconditioning for time dependent problems. These are solved using a dual time step approach. We consider the effect of this dual time step on the parameter of the low speed preconditioning. In addition, we compare the use of two sets of variables, conservation and primitive variables, to solve the system. We show the effect of these choices on both the convergence to a steady state and the accuracy of the numerical solutions for low Mach number steady state and time dependent flows.

Desiccant outdoor air preconditioners maximize heat recovery ventilation potentials

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

Meckler, M.

1995-12-31

Microorganisms are well protected indoors by the moisture surrounding them if the relative humidity is above 70%. They can cause many acute diseases, infections, and allergies. Humidity also has an effect on air cleanliness and causes the building structure and its contents to deteriorate. Therefore, controlling humidity is a very important factor to human health and comfort and the structural longevity of a building. To date, a great deal of research has been done, and is continuing, in the use of both solid and liquid desiccants. This paper introduces a desiccant-assisted system that combines dehumidification and mechanical refrigeration by meansmore » of a desiccant preconditioning module that can serve two or more conventional air-conditioning units. It will be demonstrated that the proposed system, also having indirect evaporative cooling within the preconditioning module, can reduce energy consumption and provide significant cost savings, independent humidity and temperature control, and, therefore, improved indoor air quality and enhanced occupant comfort.« less

Flap preconditioning by pressure-controlled cupping in a rat model.

PubMed

Koh, Kyung S; Park, Sung Woo; Oh, Tae Suk; Choi, Jong Woo

2016-08-01

Flap survival is essential for the success of soft-tissue reconstruction. Accordingly, various surgical and medical methods aim to increase flap survival. Because flap survival is affected by the innate vascular supply, traditional preconditioning methods mainly target vasodilatation or vascular reorientation to increase blood flow to the tissue. External stress on the skin, such as an external volume expander or cupping, induces vascular remodeling, and these approaches have been used in the fat grafting field and in traditional Asian medicine. In the present study, we used a rat random-pattern dorsal flap model to study the effectiveness of preconditioning with an externally applied device (cupping) at the flap site that directly applied negative pressure to the skin. The device, the pressure-controlled cupping, is connected to negative pressure vacuum device providing accurate pressure control from 0 mm Hg to -200 mm Hg. Flap surgery was performed after preconditioning under -25 mm Hg suction pressure for 30 min a day for 5 d, followed by 9 d of postoperative observation. Flap survival was assessed as the area of viable tissue and was compared between the preconditioned group and a control group. The preconditioned group showed absolute percentage increase of flap viability relative to the entire flap by 19.0± 7.6% (average 70.1% versus 51.0%). Tissue perfusion of entire flap, evaluated by laser Doppler imaging system, was improved with absolute percentage increase by 24.2± 10.4% (average 77.4% versus 53.1%). Histologic analysis of hematoxylin and eosin, CD31, and Masson-trichrome staining showed increased vascular density in the subdermal plexus and more organized collagen production with hypertrophy of the attached muscle. Our study suggests that flap preconditioning caused by controlled noninvasive suction induces vascular remodeling that increases tissue perfusion and improves flap survival in a rat model. Copyright © 2016 Elsevier Inc. All rights reserved.

Preconditioned conjugate gradient technique for the analysis of symmetric anisotropic structures

NASA Technical Reports Server (NTRS)

Noor, Ahmed K.; Peters, Jeanne M.

1987-01-01

An efficient preconditioned conjugate gradient (PCG) technique and a computational procedure are presented for the analysis of symmetric anisotropic structures. The technique is based on selecting the preconditioning matrix as the orthotropic part of the global stiffness matrix of the structure, with all the nonorthotropic terms set equal to zero. This particular choice of the preconditioning matrix results in reducing the size of the analysis model of the anisotropic structure to that of the corresponding orthotropic structure. The similarities between the proposed PCG technique and a reduction technique previously presented by the authors are identified and exploited to generate from the PCG technique direct measures for the sensitivity of the different response quantities to the nonorthotropic (anisotropic) material coefficients of the structure. The effectiveness of the PCG technique is demonstrated by means of a numerical example of an anisotropic cylindrical panel.

[The effect of hypoxia preconditioning no binding activity of HIF-1 on the HRE with EPO in the hippocampus of mice].

PubMed

Shao, Guo; Zhou, Wei-Hua; Gao, Cui-Ying; Zhang, Ran; Lu, Guo-Wei

2007-02-01

To observe change of binding activity of HIF-1 with erythropoietin (EPO) hypoxia response element (HRE) in the hippocampus of mice preconditioned to hypoxia and explore relationship between the changes and the preconditioning. The hippocampus was removed from mice exposed to hypoxia for 0 run (control group), 1 run (H1 group) and 4 runs(H4 group). Electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP)and real time PCR were used to detect the change of activity of HIF-1 on HRE of EPO. Both in vitro and in vivo binding tests showed that the HIF-1 DNA-binding activities were increased in group H1 and markedly increased in group H4. The increase of HIF-1 and HRE of EPO binding activities is thought be involved in hypoxic preconditioning.

Efficient Multi-Stage Time Marching for Viscous Flows via Local Preconditioning

NASA Technical Reports Server (NTRS)

Kleb, William L.; Wood, William A.; vanLeer, Bram

1999-01-01

A new method has been developed to accelerate the convergence of explicit time-marching, laminar, Navier-Stokes codes through the combination of local preconditioning and multi-stage time marching optimization. Local preconditioning is a technique to modify the time-dependent equations so that all information moves or decays at nearly the same rate, thus relieving the stiffness for a system of equations. Multi-stage time marching can be optimized by modifying its coefficients to account for the presence of viscous terms, allowing larger time steps. We show it is possible to optimize the time marching scheme for a wide range of cell Reynolds numbers for the scalar advection-diffusion equation, and local preconditioning allows this optimization to be applied to the Navier-Stokes equations. Convergence acceleration of the new method is demonstrated through numerical experiments with circular advection and laminar boundary-layer flow over a flat plate.

Redox signaling in remote ischemic preconditioning-induced cardioprotection: Evidences and mechanisms.

PubMed

Singh, Lovedeep; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

2017-08-15

Reactive oxygen species are the reactive molecules that are derived from molecular oxygen and play an important role as redox signaling molecules to confer cardioprotection. Various scientists have demonstrated the key role of redox signaling in cardioprotection by showing a transient increase in their levels during remote ischemic preconditioning (RIPC) phase. The transient increase in reactive oxygen species levels during remote preconditioning phase may take place either through activation of K ATP channels or through increased nitric oxide (NO) production. A transient increase in reactive oxygen species during preconditioning may also increase the expression of heat shock proteins (HSP), the level of antioxidant enzymes and decrease the expression of inflammatory genes (Egr-1) during ischemia-reperfusion phase to confer cardioprotection. The present review describes the role of redox signaling in RIPC-induced cardioprotective effect with possible mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels

PubMed Central

González, G; Zaldívar, D; Carrillo, ED; Hernández, A; García, MC; Sánchez, JA

2010-01-01

BACKGROUND AND PURPOSE Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K+ (mitoKATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca2+ homeostasis during PPC, particularly changes in Ca2+ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca2+ channels. EXPERIMENTAL APPROACH PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca2+ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the α1c subunit of L-type channels in the cellular membrane were measured by Western blot. KEY RESULTS PPC was accompanied by a 50% reduction in α1c subunit levels, and by a reversible fall in L-type current amplitude and Ca2+ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the α1c subunit and Ca2+ channel function were prevented in part by the protease inhibitor leupeptin. CONCLUSIONS AND IMPLICATIONS PPC downregulated the α1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca2+ channel, which in turn reduced Ca2+ influx, which may attenuate Ca2+ overload during reperfusion. PMID:20636393

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy.

PubMed

Wei, Zheng Z; Zhu, Yan-Bing; Zhang, James Y; McCrary, Myles R; Wang, Song; Zhang, Yong-Bo; Yu, Shan-Ping; Wei, Ling

2017-10-05

Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: "stem cells," "hypoxic preconditioning," "ischemic preconditioning," and "cell transplantation." Original articles and critical reviews on the topics were selected. Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications.

Condition Number Estimation of Preconditioned Matrices

PubMed Central

Kushida, Noriyuki

2015-01-01

The present paper introduces a condition number estimation method for preconditioned matrices. The newly developed method provides reasonable results, while the conventional method which is based on the Lanczos connection gives meaningless results. The Lanczos connection based method provides the condition numbers of coefficient matrices of systems of linear equations with information obtained through the preconditioned conjugate gradient method. Estimating the condition number of preconditioned matrices is sometimes important when describing the effectiveness of new preconditionerers or selecting adequate preconditioners. Operating a preconditioner on a coefficient matrix is the simplest method of estimation. However, this is not possible for large-scale computing, especially if computation is performed on distributed memory parallel computers. This is because, the preconditioned matrices become dense, even if the original matrices are sparse. Although the Lanczos connection method can be used to calculate the condition number of preconditioned matrices, it is not considered to be applicable to large-scale problems because of its weakness with respect to numerical errors. Therefore, we have developed a robust and parallelizable method based on Hager’s method. The feasibility studies are curried out for the diagonal scaling preconditioner and the SSOR preconditioner with a diagonal matrix, a tri-daigonal matrix and Pei’s matrix. As a result, the Lanczos connection method contains around 10% error in the results even with a simple problem. On the other hand, the new method contains negligible errors. In addition, the newly developed method returns reasonable solutions when the Lanczos connection method fails with Pei’s matrix, and matrices generated with the finite element method. PMID:25816331

Metformin Preconditioning of Human induced Pluripotent Stem Cell-derived Neural Stem Cells Promotes Their Engraftment and Improves Post-Stroke Regeneration and Recovery.

PubMed

Ould-Brahim, Fares; Sarma, Sailendra Nath; Syal, Charvi; Lu, Kevin Jiaqi; Seegobin, Matthew; Carter, Anthony; Jeffers, Matthew S; Doré, Carole; Stanford, William; Corbett, Dale; Wang, Jing

2018-06-12

While transplantation of hiPSC-derived neural stem cells (hiPSC-NSCs) shows therapeutic potential in animal stroke models, major concerns for translating hiPSC therapy to the clinic are efficacy and safety. Therefore, there is a demand to develop an optimal strategy to enhance the engraftment and regenerative capacity of transplanted hiPSC-NSCs in order to produce fully differentiated neural cells to replace lost brain tissues. Metformin, an FDA approved drug, is an optimal neuroregenerative agent that not only promotes NSC proliferation but also drives NSC towards differentiation. In this regard, we hypothesize that preconditioning of hiPSC-NSCs with metformin before transplantation into the stroke-damaged brain will improve engraftment and regenerative capabilities of hiPSC-NSCs, ultimately enhancing functional recovery. Here we show that pretreatment of hiPSC-NSCs with metformin enhances the proliferation and differentiation of hiPSC-NSCs in culture. Furthermore, metformin-preconditioned hiPSC-NSCs show increased engraftment 1-week post-transplant in a rat endothelin-1 focal ischemic stroke model. In addition, metformin preconditioned cell grafts exhibit increased survival compared to naïve cell grafts at 7-week post-transplant. Analysis of the grafts demonstrates that metformin preconditioning enhances the differentiation of hiPSC-NSCs. As an outcome, rats receiving metformin preconditioned cells display accelerated gross motor recovery and reduced infarct volume. These studies represent a vital step forward in the optimization of hiPSC-NSC based transplantation to promote post-stroke recovery.

Worldwide Report, Arms Control

DTIC Science & Technology

1985-12-19

disarmament shows that the decisive factor in Soviet-U.S. relations remains the sphere of security, the core of which is the organically linked ...actiye in the United States for whom the very prospect of preconditions for curbing the arms race is patently not to their linking . Certain quarters in...distorting the essence of the issue of the organic link between preventing the mili- tarization of space and the reduction of nuclear arms on earth

Routes to failure: analysis of 41 civil aviation accidents from the Republic of China using the human factors analysis and classification system.

PubMed

Li, Wen-Chin; Harris, Don; Yu, Chung-San

2008-03-01

The human factors analysis and classification system (HFACS) is based upon Reason's organizational model of human error. HFACS was developed as an analytical framework for the investigation of the role of human error in aviation accidents, however, there is little empirical work formally describing the relationship between the components in the model. This research analyses 41 civil aviation accidents occurring to aircraft registered in the Republic of China (ROC) between 1999 and 2006 using the HFACS framework. The results show statistically significant relationships between errors at the operational level and organizational inadequacies at both the immediately adjacent level (preconditions for unsafe acts) and higher levels in the organization (unsafe supervision and organizational influences). The pattern of the 'routes to failure' observed in the data from this analysis of civil aircraft accidents show great similarities to that observed in the analysis of military accidents. This research lends further support to Reason's model that suggests that active failures are promoted by latent conditions in the organization. Statistical relationships linking fallible decisions in upper management levels were found to directly affect supervisory practices, thereby creating the psychological preconditions for unsafe acts and hence indirectly impairing the performance of pilots, ultimately leading to accidents.

Orderings for conjugate gradient preconditionings

NASA Technical Reports Server (NTRS)

Ortega, James M.

1991-01-01

The effect of orderings on the rate of convergence of the conjugate gradient method with SSOR or incomplete Cholesky preconditioning is examined. Some results also are presented that help to explain why red/black ordering gives an inferior rate of convergence.

"Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice.

PubMed

Coughlan, Karen S; Mitchem, Mollie R; Hogg, Marion C; Prehn, Jochen H M

2015-02-01

Adenosine 5'-monophosphate-activated protein kinase (AMPK) is a master regulator of energy balance. As energy imbalance is documented as a key pathologic feature of amyotrophic lateral sclerosis (ALS), we investigated AMPK as a pharmacologic target in SOD1(G93A) mice. We noted a strong activation of AMPK in lumbar spinal cords of SOD1(G93A) mice. Pharmacologic activation of AMPK has shown protective effects in neuronal "preconditioning" models. We tested the hypothesis that "preconditioning" with a small molecule activator of AMPK, latrepirdine, exerts beneficial effects on disease progression. SOD1(G93A) mice (n = 24 animals per group; sex and litter matched) were treated with latrepirdine (1 μg/kg, intraperitoneal) or vehicle from postnatal day 70 to 120. Treatment with latrepirdine increased AMPK activity in primary mouse motor neuron cultures and in SOD1(G93A) lumbar spinal cords. Mice "preconditioned" with latrepirdine showed a delayed symptom onset and a significant increase in life span (p < 0.01). Our study suggests that "preconditioning" with latrepirdine may represent a possible therapeutic strategy for individuals harboring ALS-associated gene mutations who are at risk for developing ALS. Copyright © 2015 Elsevier Inc. All rights reserved.

Low-Dose Ethanol Preconditioning Protects Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury By Activating Large Conductance, Ca2+-Activated K+ Channels In Vitro.

PubMed

Su, Fang; Guo, An-Chen; Li, Wei-Wei; Zhao, Yi-Long; Qu, Zheng-Yi; Wang, Yong-Jun; Wang, Qun; Zhu, Yu-Lan

2017-02-01

Increasing evidence suggests that low to moderate ethanol ingestion protects against the deleterious effects of subsequent ischemia/reperfusion; however, the underlying mechanism has not been elucidated. In the present study, we showed that expression of the neuronal large-conductance, Ca 2+ -activated K + channel (BK Ca ) α-subunit was upregulated in cultured neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) compared with controls. Preconditioning with low-dose ethanol (10 mmol/L) increased cell survival rate in neurons subjected to OGD/R, attenuated the OGD/R-induced elevation of cytosolic Ca 2+ levels, and reduced the number of apoptotic neurons. Western blots revealed that ethanol preconditioning upregulated expression of the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic protein Bax. The protective effect of ethanol preconditioning was antagonized by a BK Ca channel inhibitor, paxilline. Inside-out patches in primary neurons also demonstrated the direct activation of the BK Ca channel by 10 mmol/L ethanol. The above results indicated that low-dose ethanol preconditioning exerts its neuroprotective effects by attenuating the elevation of cytosolic Ca 2+ and preventing neuronal apoptosis, and this is mediated by BK Ca channel activation.

Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection.

PubMed

Kolb, Alexander L; Corridon, Peter R; Zhang, Shijun; Xu, Weimin; Witzmann, Frank A; Collett, Jason A; Rhodes, George J; Winfree, Seth; Bready, Devin; Pfeffenberger, Zechariah J; Pomerantz, Jeremy M; Hato, Takashi; Nagami, Glenn T; Molitoris, Bruce A; Basile, David P; Atkinson, Simon J; Bacallao, Robert L

2018-04-01

Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine ( P <0.05) observed in controls and increased the mitochondria membrane potential ( P <0.05), maximal respiratory capacity ( P <0.05), and intracellular ATP levels ( P <0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning. Copyright © 2018 by the American Society of Nephrology.

Exercise Preconditioning Protects against Spinal Cord Injury in Rats by Upregulating Neuronal and Astroglial Heat Shock Protein 72

PubMed Central

Chang, Cheng-Kuei; Chou, Willy; Lin, Hung-Jung; Huang, Yi-Ching; Tang, Ling-Yu; Lin, Mao-Tsun; Chang, Ching-Ping

2014-01-01

The heat shock protein 72 (HSP 72) is a universal marker of stress protein whose expression can be induced by physical exercise. Here we report that, in a localized model of spinal cord injury (SCI), exercised rats (given pre-SCI exercise) had significantly higher levels of neuronal and astroglial HSP 72, a lower functional deficit, fewer spinal cord contusions, and fewer apoptotic cells than did non-exercised rats. pSUPER plasmid expressing HSP 72 small interfering RNA (SiRNA-HSP 72) was injected into the injured spinal cords. In addition to reducing neuronal and astroglial HSP 72, the (SiRNA-HSP 72) significantly attenuated the beneficial effects of exercise preconditioning in reducing functional deficits as well as spinal cord contusion and apoptosis. Because exercise preconditioning induces increased neuronal and astroglial levels of HSP 72 in the gray matter of normal spinal cord tissue, exercise preconditioning promoted functional recovery in rats after SCI by upregulating neuronal and astroglial HSP 72 in the gray matter of the injured spinal cord. We reveal an important function of neuronal and astroglial HSP 72 in protecting neuronal and astroglial apoptosis in the injured spinal cord. We conclude that HSP 72-mediated exercise preconditioning is a promising strategy for facilitating functional recovery from SCI. PMID:25334068

[Effects of xenon preconditioning against ischemia/reperfusion injury and oxidative stress in immature heart].

PubMed

Li, Qian; Lian, Chun-Wei; Fang, Li-Qun; Liu, Bin; Yang, Bo

2014-09-01

To investigate whether xenon preconditioning (PC) could protect immature myocardium against ischemia-reperfusion (I/R) injury in a dose-dependent manner and clarify the role of xenon PC on oxidative stress. Forty-eight isolated perfused immature rabbit hearts were randomly divided into four groups (n = 12): The sham group had the hearts perfused continuously for 300 min. In I/R group, the hearts were subjected to 60 min perfusion followed by 60 min ischemia and 180 min reperfusion. In 1 minimum alveolar concentration (MAC) and 0.5 MAC xenon PC groups, the hearts were preconditioned with 1 MAC or 0.5 MAC xenon respectively, following 60 min ischemia and 180 min reperfusion. The cardiac function, myocardial infarct size, mitochondrial structure, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in each group were determined after reperfusion. Compared with I/R group, both 1 MAC and 0. 5 MAC xenon preconditioning significantly improved cardiac function (P < 0.01), reduced myocardial infarct size (P < 0.01) and mitochondrial damage, increased SOD activity and decreased MDA level (P < 0.01). There were no differences between 1 MAC group and 0.5 MAC xenon group (P > 0.05). Xenon preconditioning at 0. 5 and 1 MAC produce similar cardioprotective effects against I/R injury in isolated perfused immature heart.

40 CFR 1066.407 - Vehicle preparation and preconditioning.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Vehicle preparation and...) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Vehicle Preparation and Running a Test § 1066.407 Vehicle preparation and preconditioning. This section describes steps to take before measuring exhaust...

40 CFR 1066.407 - Vehicle preparation and preconditioning.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Vehicle preparation and...) AIR POLLUTION CONTROLS VEHICLE-TESTING PROCEDURES Vehicle Preparation and Running a Test § 1066.407 Vehicle preparation and preconditioning. This section describes steps to take before measuring exhaust...

DenInv3D: a geophysical software for three-dimensional density inversion of gravity field data

NASA Astrophysics Data System (ADS)

Tian, Yu; Ke, Xiaoping; Wang, Yong

2018-04-01

This paper presents a three-dimensional density inversion software called DenInv3D that operates on gravity and gravity gradient data. The software performs inversion modelling, kernel function calculation, and inversion calculations using the improved preconditioned conjugate gradient (PCG) algorithm. In the PCG algorithm, due to the uncertainty of empirical parameters, such as the Lagrange multiplier, we use the inflection point of the L-curve as the regularisation parameter. The software can construct unequally spaced grids and perform inversions using such grids, which enables changing the resolution of the inversion results at different depths. Through inversion of airborne gradiometry data on the Australian Kauring test site, we discovered that anomalous blocks of different sizes are present within the study area in addition to the central anomalies. The software of DenInv3D can be downloaded from http://159.226.162.30.

An assessment of coupling algorithms for nuclear reactor core physics simulations

DOE PAGES

Hamilton, Steven; Berrill, Mark; Clarno, Kevin; ...

2016-04-01

This paper evaluates the performance of multiphysics coupling algorithms applied to a light water nuclear reactor core simulation. The simulation couples the k-eigenvalue form of the neutron transport equation with heat conduction and subchannel flow equations. We compare Picard iteration (block Gauss–Seidel) to Anderson acceleration and multiple variants of preconditioned Jacobian-free Newton–Krylov (JFNK). The performance of the methods are evaluated over a range of energy group structures and core power levels. A novel physics-based approximation to a Jacobian-vector product has been developed to mitigate the impact of expensive on-line cross section processing steps. Furthermore, numerical simulations demonstrating the efficiency ofmore » JFNK and Anderson acceleration relative to standard Picard iteration are performed on a 3D model of a nuclear fuel assembly. Both criticality (k-eigenvalue) and critical boron search problems are considered.« less

An assessment of coupling algorithms for nuclear reactor core physics simulations

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

Hamilton, Steven; Berrill, Mark; Clarno, Kevin

This paper evaluates the performance of multiphysics coupling algorithms applied to a light water nuclear reactor core simulation. The simulation couples the k-eigenvalue form of the neutron transport equation with heat conduction and subchannel flow equations. We compare Picard iteration (block Gauss–Seidel) to Anderson acceleration and multiple variants of preconditioned Jacobian-free Newton–Krylov (JFNK). The performance of the methods are evaluated over a range of energy group structures and core power levels. A novel physics-based approximation to a Jacobian-vector product has been developed to mitigate the impact of expensive on-line cross section processing steps. Furthermore, numerical simulations demonstrating the efficiency ofmore » JFNK and Anderson acceleration relative to standard Picard iteration are performed on a 3D model of a nuclear fuel assembly. Both criticality (k-eigenvalue) and critical boron search problems are considered.« less

An assessment of coupling algorithms for nuclear reactor core physics simulations

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

Hamilton, Steven, E-mail: hamiltonsp@ornl.gov; Berrill, Mark, E-mail: berrillma@ornl.gov; Clarno, Kevin, E-mail: clarnokt@ornl.gov

This paper evaluates the performance of multiphysics coupling algorithms applied to a light water nuclear reactor core simulation. The simulation couples the k-eigenvalue form of the neutron transport equation with heat conduction and subchannel flow equations. We compare Picard iteration (block Gauss–Seidel) to Anderson acceleration and multiple variants of preconditioned Jacobian-free Newton–Krylov (JFNK). The performance of the methods are evaluated over a range of energy group structures and core power levels. A novel physics-based approximation to a Jacobian-vector product has been developed to mitigate the impact of expensive on-line cross section processing steps. Numerical simulations demonstrating the efficiency of JFNKmore » and Anderson acceleration relative to standard Picard iteration are performed on a 3D model of a nuclear fuel assembly. Both criticality (k-eigenvalue) and critical boron search problems are considered.« less

Low-memory iterative density fitting.

PubMed

Grajciar, Lukáš

2015-07-30

A new low-memory modification of the density fitting approximation based on a combination of a continuous fast multipole method (CFMM) and a preconditioned conjugate gradient solver is presented. Iterative conjugate gradient solver uses preconditioners formed from blocks of the Coulomb metric matrix that decrease the number of iterations needed for convergence by up to one order of magnitude. The matrix-vector products needed within the iterative algorithm are calculated using CFMM, which evaluates them with the linear scaling memory requirements only. Compared with the standard density fitting implementation, up to 15-fold reduction of the memory requirements is achieved for the most efficient preconditioner at a cost of only 25% increase in computational time. The potential of the method is demonstrated by performing density functional theory calculations for zeolite fragment with 2592 atoms and 121,248 auxiliary basis functions on a single 12-core CPU workstation. © 2015 Wiley Periodicals, Inc.

Priming of the Cells: Hypoxic Preconditioning for Stem Cell Therapy

PubMed Central

Wei, Zheng Z; Zhu, Yan-Bing; Zhang, James Y; McCrary, Myles R; Wang, Song; Zhang, Yong-Bo; Yu, Shan-Ping; Wei, Ling

2017-01-01

Objective: Stem cell-based therapies are promising in regenerative medicine for protecting and repairing damaged brain tissues after injury or in the context of chronic diseases. Hypoxia can induce physiological and pathological responses. A hypoxic insult might act as a double-edged sword, it induces cell death and brain damage, but on the other hand, sublethal hypoxia can trigger an adaptation response called hypoxic preconditioning or hypoxic tolerance that is of immense importance for the survival of cells and tissues. Data Sources: This review was based on articles published in PubMed databases up to August 16, 2017, with the following keywords: “stem cells,” “hypoxic preconditioning,” “ischemic preconditioning,” and “cell transplantation.” Study Selection: Original articles and critical reviews on the topics were selected. Results: Hypoxic preconditioning has been investigated as a primary endogenous protective mechanism and possible treatment against ischemic injuries. Many cellular and molecular mechanisms underlying the protective effects of hypoxic preconditioning have been identified. Conclusions: In cell transplantation therapy, hypoxic pretreatment of stem cells and neural progenitors markedly increases the survival and regenerative capabilities of these cells in the host environment, leading to enhanced therapeutic effects in various disease models. Regenerative treatments can mobilize endogenous stem cells for neurogenesis and angiogenesis in the adult brain. Furthermore, transplantation of stem cells/neural progenitors achieves therapeutic benefits via cell replacement and/or increased trophic support. Combinatorial approaches of cell-based therapy with additional strategies such as neuroprotective protocols, anti-inflammatory treatment, and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the recent progress regarding cell types and applications in regenerative medicine as well as future applications. PMID:28937044

Hydrogen Sulfide Preconditioning Protects Rat Liver against Ischemia/Reperfusion Injury by Activating Akt-GSK-3β Signaling and Inhibiting Mitochondrial Permeability Transition

PubMed Central

Zhang, Hao; Xu, Fengying; Zou, Zui; Liu, Meng; Wang, Quanxing; Miao, Mingyong; Shi, Xueyin

2013-01-01

Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 μmol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 μmol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3β signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury. PMID:24058562

The role of adenosine in preconditioning by brief pressure overload in rats.

PubMed

Huang, Cheng-Hsiung; Tsai, Shen-Kou; Chiang, Shu-Chiung; Lai, Chang-Chi; Weng, Zen-Chung

2015-08-01

Brief pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits has been previously reported. Its effects in other species are not known. This study investigates effects of pressure overload and the role of adenosine in rats in this study. MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion. MI size was determined by triphenyl tetrazolium chloride staining. Brief pressure overload was induced by two 10-minute episodes of partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. The MI size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group as well as in the ischemic preconditioning group (17.4 ± 3.0% and 18.2 ± 1.5% vs. 26.6 ± 2.4% in the control group, p < 0.001). Pretreatment with 8-(p-sulfophenyl)-theophylline (SPT), an inhibitor of adenosine receptors, did not significantly limit the protection by pressure overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p < 0.001). SPT itself did not affect the extent of infarct (25.4 ± 2.0%). The hemodynamics, area at risk and mortality were not significantly different among all groups of animals. Brief pressure overload of the left ventricle preconditioned rat myocardium against infarction. Because SPT did not significantly alter MI size reduction, our results did not support a role of adenosine in preconditioning by pressure overload in rats. Copyright © 2013. Published by Elsevier B.V.

AZTEC: A parallel iterative package for the solving linear systems

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

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

1996-12-31

We describe a parallel linear system package, AZTEC. The package incorporates a number of parallel iterative methods (e.g. GMRES, biCGSTAB, CGS, TFQMR) and preconditioners (e.g. Jacobi, Gauss-Seidel, polynomial, domain decomposition with LU or ILU within subdomains). Additionally, AZTEC allows for the reuse of previous preconditioning factorizations within Newton schemes for nonlinear methods. Currently, a number of different users are using this package to solve a variety of PDE applications.

40 CFR 86.132-00 - Vehicle preconditioning.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Vehicle preconditioning. 86.132-00 Section 86.132-00 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...] (iii) If a manufacturer has concerns about fuel effects on adaptive memory systems, a manufacturer may...

40 CFR 92.125 - Pre-test procedures and preconditioning.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Pre-test procedures and... PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and preconditioning. (a) Locomotive testing. (1) Determine engine lubricating...

40 CFR 92.125 - Pre-test procedures and preconditioning.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Pre-test procedures and... PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and preconditioning. (a) Locomotive testing. (1) Determine engine lubricating...

40 CFR 92.125 - Pre-test procedures and preconditioning.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Pre-test procedures and... PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and preconditioning. (a) Locomotive testing. (1) Determine engine lubricating...

40 CFR 92.125 - Pre-test procedures and preconditioning.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Pre-test procedures and... PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.125 Pre-test procedures and preconditioning. (a) Locomotive testing. (1) Determine engine lubricating...

Ontario's daily physical activity policy for elementary schools: is everything in place for success?

PubMed

Robertson-Wilson, Jennifer E; Lévesque, Lucie

2009-01-01

The development, implementation, and evaluation of policies may play an important role in promoting health behaviours such as physical activity. The Ontario Ministry of Education (OME) recently mandated Memorandum No. 138 requiring daily physical activity (DPA) for Ontario elementary students in grades one through eight. The purpose of this paper is to examine implementation strategies. Hogwood and Gunn's 10 preconditions for "perfect implementation" are used to examine publicly available Ministry DPA policy documents to assess whether these implementation strategies have been considered in the policy documents. Several preconditions (e.g., allocation of resources, task specification) appear to have been considered, however a number of preconditions (e.g., the sustainability of resources, extent to which the policy is valued, and evaluation plans) thought to be important require additional attention to ensure optimal DPA implementation. Additional reflection upon Hogwood and Gunn's implementation preconditions would, in our opinion, assist in facilitating optimal DPA implementation as per Memorandum No. 138.

Silymarin and its constituents in cardiac preconditioning.

PubMed

Zholobenko, A; Modriansky, M

2014-09-01

Silymarin, a standardised extract of Silybum marianum (milk thistle), comprises mainly of silybin, with dehydrosilybin (DHSB), quercetin, taxifolin, silychristin and a number of other compounds which are known to possess a range of salutary effects. Indeed, there is evidence for their role in reducing tumour growth, preventing liver toxicity, and protecting a number of organs against ischemic damage. The hepatoprotective effects of silymarin, especially in preventing Amanita and alcohol intoxication induced damage to the liver, are a well established fact. Likewise, there is weighty evidence that silymarin possesses antimicrobial and anticancer activities. Additionally, it has emerged that in animal models, silymarin can protect the heart, brain, liver and kidneys against ischemia reperfusion injury, probably by preconditioning. The mechanisms of preconditioning are, in general, well studied, especially in the heart. On the other hand, the mechanism by which silymarin protects the heart from ischemia remains largely unexplored. This review, therefore, focuses on evaluating existing studies on silymarin induced cardioprotection in the context of the established mechanisms of preconditioning. Copyright © 2014. Published by Elsevier B.V.

Liquid hydrogen turbopump rapid start program. [thermal preconditioning using coatings

NASA Technical Reports Server (NTRS)

Wong, G. S.

1973-01-01

This program was to analyze, test, and evaluate methods of achieving rapid-start of a liquid hydrogen feed system (inlet duct and turbopump) using a minimum of thermal preconditioning time and propellant. The program was divided into four tasks. Task 1 includes analytical studies of the testing conducted in the other three tasks. Task 2 describes the results from laboratory testing of coating samples and the successful adherence of a KX-635 coating to the internal surfaces of the feed system tested in Task 4. Task 3 presents results of testing an uncoated feed system. Tank pressure was varied to determine the effect of flowrate on preconditioning. The discharge volume and the discharge pressure which initiates opening of the discharge valve were varied to determine the effect on deadhead (no through-flow) start transients. Task 4 describes results of testing a similar, internally coated feed system and illustrates the savings in preconditioning time and propellant resulting from the coatings.

Peri-operative anaesthetic myocardial preconditioning and protection – cellular mechanisms and clinical relevance in cardiac anaesthesia

PubMed Central

Kunst, G; Klein, A A

2015-01-01

Preconditioning has been shown to reduce myocardial damage caused by ischaemia–reperfusion injury peri-operatively. Volatile anaesthetic agents have the potential to provide myocardial protection by anaesthetic preconditioning and, in addition, they also mediate renal and cerebral protection. A number of proof-of-concept trials have confirmed that the experimental evidence can be translated into clinical practice with regard to postoperative markers of myocardial injury; however, this effect has not been ubiquitous. The clinical trials published to date have also been too small to investigate clinical outcome and mortality. Data from recent meta-analyses in cardiac anaesthesia are also not conclusive regarding intra-operative volatile anaesthesia. These inconclusive clinical results have led to great variability currently in the type of anaesthetic agent used during cardiac surgery. This review summarises experimentally proposed mechanisms of anaesthetic preconditioning, and assesses randomised controlled clinical trials in cardiac anaesthesia that have been aimed at translating experimental results into the clinical setting. PMID:25764404

Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery.

PubMed

Hausenloy, Derek J; Candilio, Luciano; Evans, Richard; Ariti, Cono; Jenkins, David P; Kolvekar, Shyam; Knight, Rosemary; Kunst, Gudrun; Laing, Christopher; Nicholas, Jennifer; Pepper, John; Robertson, Steven; Xenou, Maria; Clayton, Tim; Yellon, Derek M

2015-10-08

Whether remote ischemic preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote ischemic preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. We enrolled a total of 1612 patients (811 in the control group and 801 in the ischemic-preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life. Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical Research Council and National Institute of Health Research partnership] and the British Heart Foundation; ERICCA ClinicalTrials.gov number, NCT01247545.).

Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

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

Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju, E-mail: anjubansaldipas@gmail.com

High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmentedmore » the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl{sub 2} for 15 days along with training. ► CoCl{sub 2} supplementation augmented endurance performance and aerobic respiration. ► It increased glucose uptake and metabolism in muscle. ► It enhanced mitochondrial biogenesis in red gastrocnemius muscle.« less

Preconditioning and Formation Mechanisms of Maud Rise (Open Ocean) Polynyas in a High-Resolution CESM Simulation

NASA Astrophysics Data System (ADS)

Kurtakoti, P. K.; Veneziani, C.; Stoessel, A.; Weijer, W.

2016-12-01

Processes responsible for preconditioning and formation of Maud Rise Polynyas (MRP) were analyzed within the framework of a high-resolution fully coupled Community Earth System Model (CESM) simulation. Open Ocean Polynyas (OOPs) are large ice-free areas within the winter ice pack. These are regions of deep convection and strong atmosphere-ice-ocean interaction through which they play an important role in the formation of bottom waters. The data analyzed comes from a simulation conducted in a pre-industrial scenario as part of the Accelerated Climate Modeling for Energy (ACME) project. Within this simulation, persistent winter OOPs were simulated in the Weddell Sea (Weddell Sea Polynya) and over the Maud Rise seamount (Maud Rise Polynya). The sea ice concentration in the Weddell Sea shows that MRP acts as a precondition to Weddell Sea polynyas, which is consistent with mid 1970s observations of a westward expansion of MRP into the Weddell Sea. The OOPs in years 30-40 of the CESM simulation are largely over Maud Rise giving us an opportunity to investigate processes that trigger and maintain the OOP in winter over Maud Rise. The heat content of the Weddell Deep Water (WDW) is seen to be an important factor for MRPs, consistent with previous studies. The first MRP in the 30s coincides with the strongest negative wind stress curl over the Weddell Sea, which implies that this condition is a triggering mechanism for deep convection. The deep convective event associated with the OOP leads to a reduction of deep ocean heat reservoir up to 3000m depth. The simulation captures a westward flow of WDW impinging on Maud Rise seamount. Previous studies suggest Taylor column dynamics to be necessary for MRPs to emerge. We have explored how Taylor column dynamics could contribute to preconditioning and triggering deep open ocean convection over Maud Rise Seamount. We also investigate the importance of resolution of bottom topography for the formation of a strong enough Taylor column over Maud Rise to interact with the pycnocline to the point that an OOP develops.

Preconditioning electromyographic data for an upper extremity model using neural networks

NASA Technical Reports Server (NTRS)

Roberson, D. J.; Fernjallah, M.; Barr, R. E.; Gonzalez, R. V.

1994-01-01

A back propagation neural network has been employed to precondition the electromyographic signal (EMG) that drives a computational model of the human upper extremity. This model is used to determine the complex relationship between EMG and muscle activation, and generates an optimal muscle activation scheme that simulates the actual activation. While the experimental and model predicted results of the ballistic muscle movement are very similar, the activation function between the start and the finish is not. This neural network preconditions the signal in an attempt to more closely model the actual activation function over the entire course of the muscle movement.

Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection induced by ouabain preconditioning.

PubMed

Duan, Qiming; Madan, Namrata D; Wu, Jian; Kalisz, Jennifer; Doshi, Krunal Y; Haldar, Saptarsi M; Liu, Lijun; Pierre, Sandrine V

2015-03-01

Acute myocardial infarction, the clinical manifestation of ischemia-reperfusion (IR) injury, is a leading cause of death worldwide. Like ischemic preconditioning (IPC) induced by brief episodes of ischemia and reperfusion, ouabain preconditioning (OPC) mediated by Na/K-ATPase signaling protects the heart against IR injury. Class I PI3K activation is required for IPC, but its role in OPC has not been investigated. While PI3K-IB is critical to IPC, studies have suggested that ouabain signaling is PI3K-IA-specific. Hence, a pharmacological approach was used to test the hypothesis that OPC and IPC rely on distinct PI3K-I isoforms. In Langendorff-perfused mouse hearts, OPC was initiated by 4 min of ouabain 10 μM and IPC was triggered by 4 cycles of 5 min ischemia and reperfusion prior to 40 min of global ischemia and 30 min of reperfusion. Without affecting PI3K-IB, ouabain doubled PI3K-IA activity and Akt phosphorylation at Ser(473). IPC and OPC significantly preserved cardiac contractile function and tissue viability as evidenced by left ventricular developed pressure and end-diastolic pressure recovery, reduced lactate dehydrogenase release, and decreased infarct size. OPC protection was blunted by the PI3K-IA inhibitor PI-103, but not by the PI3K-IB inhibitor AS-604850. In contrast, IPC-mediated protection was not affected by PI-103 but was blocked by AS-604850, suggesting that PI3K-IA activation is required for OPC while PI3K-IB activation is needed for IPC. Mechanistically, PI3K-IA activity is required for ouabain-induced Akt activation but not PKCε translocation. However, in contrast to PKCε translocation which is critical to protection, Akt activity was not required for OPC. Further studies shall reveal the identity of the downstream targets of this new PI3K IA-dependent branch of OPC. These findings may be of clinical relevance in patients at risk for myocardial infarction with underlying diseases and/or medication that could differentially affect the integrity of cardiac PI3K-IA and IB pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroprotective Effects of Peptides during Ischemic Preconditioning.

PubMed

Zarubina, I V; Shabanov, P D

2016-02-01

Experiments on rats showed that neurospecific protein preparations reduce the severity of neurological deficit, restore the structure of individual behavior of the animals with different hypoxia tolerance, and exert antioxidant action during chronic ischemic damage to the brain unfolding during the early and late phases of ischemic preconditioning.

40 CFR 85.2218 - Preconditioned idle test-EPA 91.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF AIR POLLUTION FROM MOBILE SOURCES Emission Control System Performance Warranty Short...

A Three Year Comparison of Acute Respiratory Disease, Shrink and Weight Gain in Preconditioned and Non-preconditioned Illinois Beef Calves Sold at the Same Auction and Mixed in a Feedlot

PubMed Central

Woods, G. T.; Mansfield, M. E.; Webb, R. J.

1973-01-01

During 1969 to 1971, 78 preconditioned (PC) and 79 non-preconditioned (NPC) beef calves were purchased at the same auction and mixed in a feedlot. Preconditioned calves were weaned 30 days before the sale, used to drinking from a tank, and vaccinated against blackleg, malignant edema, infectious bovine rhinotracheitis (IBR), parainfluenza-3 (PI3) and bovine virus diarrhea (BVD) in 1970 and 1971, and Pasteurella hemolytica and multocida in 1971. All vaccinations were completed two to three weeks before the sale. PC calves were given thiabenzadole. PC calves had significantly less shrink after shipment and in 1971 significantly more rapid daily gain during the first weeks of the feeding period. In 1969 more PC calves were treated for acute respiratory disease than NPC calves during an outbreak of PI3 and BVD infection. In 1970 and 1971 fewer PC than NPC calves were treated for acute respiratory tract disease during outbreaks of PI3 infection. The differences in clinical respiratory disease were significant in 1971. Inclusion of two doses of P. hemolytica and P. multocida bacterin before the sale in 1971 and use of an intranasal PI3 vaccine was considered to improve the PC program. Fecal egg counts for gastrointestinal nematodes were much lower in PC calves treated with thiabenzadole than untreated NPC calves. PMID:4355470

NECA and bradykinin at reperfusion reduce infarction in rabbit hearts by signaling through PI3K, ERK, and NO.

PubMed

Yang, Xi-Ming; Krieg, Thomas; Cui, Lin; Downey, James M; Cohen, Michael V

2004-03-01

The adenosine A1/A2 adenosine agonist 5'-(N-ethylcarboxamido) adenosine (NECA) and bradykinin both limit infarction when administered at reperfusion in rabbits. This study compares the signal transduction pathways responsible for their anti-infarct effect. Receptor agonists were administered to isolated rabbit hearts starting 25 min after the onset of a 30-min period of ischemia and continued into the 2-h reperfusion period. Infarct size was measured. Both NECA and bradykinin decreased infarction from 31.5 +/- 2.4% of the risk zone in untreated hearts to 11.8 +/- 2.0% and 15.4 +/- 2.4%, respectively (P<0.05). Protection from both agents was blocked by PD98059, wortmannin, and Nomega-nitro-L-arginine methyl ester (L-NAME), thus demonstrating dependence on activation of extracellular regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) and stimulation of nitric oxide synthase (NOS). Both wortmannin and PD98059 prevented phosphorylation of ERK 1/2 in NECA-treated hearts, whereas only wortmannin and not PD98059 blocked Akt phosphorylation. These data suggest Akt is upstream of ERK 1/2. In addition, 8-(3-chlorostyryl) caffeine blocked NECA's protection indicating that A2 adenosine receptors trigger NECA's anti-infarct effect. Of note, both bradykinin and acetylcholine (ACh) administered before ischemia to trigger preconditioning's cardioprotection use PI3K and NOS in their signaling pathway. Curiously, however, ACh, unlike bradykinin, was not protective when administered at reperfusion. Hence, both NECA and bradykinin administered at reperfusion protect through a common signaling pathway that includes PI3K, NO, and ERK.

Late Triassic closure of the Paleo-Tethys Ocean in Central Tibet implied by paleomagnetism of Middle Triassic lavas from the Qiantang block

NASA Astrophysics Data System (ADS)

Song, P.; Lin, D.; Lippert, P. C.; Li, Z.

2017-12-01

The closure of the Paleo-Tethys Ocean is a major event not only in the tectonic history of the Tibetan Plateau that pre-conditioned the plateau for subsequent orogenic events, but also in the paleogeographic evolution of eastern Pangea. Final closure of this equatorial ocean, however, remains disputed, with ages ranging from the Late Permian to the Middle Cretaceous; this huge discrepancy is largely the result of the lack of high-quality paleomagnetic data and ambiguous stratigraphic data from Mesozoic rocks from Central Tibet. A recent Late Triassic paleopole derived from lavas of the Qiangtang block suggests that the Paleo-Tethys Ocean must have closed between Middle and Late Triassic (Song et al., EPSL 2015). We test this prediction with a paleomagnetic study of Middle Triassic lavas from the Qiangtang block. These lavas were previously dated to Middle Triassic (ca. 242-240 Ma) using zircon U-Pb geochonology. Rock magnetic experiments demonstrate that hematite and magnetite are the main carriers of remanence. Progressive thermal and alternating field demagnetization successfully isolated stable characteristic remanent magnetizations. Although these directions pass fold tests, suggesting a primary magnetization, we are conducting additional rock magnetic and petrographic studies to verify the primary nature of this magnetization. If these directions are primary, then they establish the first lava-based paleomagnetic pole of Middle Triassic age from the Qiangtang block. This pole was located at 63.4°N, 198.8°E, A95=4.1° (N=27) and yields a paleolatitude of 22.7±4.1°N at the reference point (33.5°N, 92.0°E). A comparison of our new Middle Triassic pole from the Qiangtang block with coeval paleopoles from the North China (NCB) and Tarim blocks indicates that the Paleo-Tethys Ocean was approximately 5-10° of latitude ( 550-1100 km) wide during the Middle Triassic. Within the context of our previous work that demonstrated the Qiangtang, NCB, and Tarim blocks share similar paleomagnetic poles during the Late Triassic (ca. 210 Ma), we conclude that the Paleo-Tethys Ocean at the longitude of Qiangtang must have closed during the Late Triassic (ca. 210-240 Ma). These paleomagnetic results help clarify stratigraphic and geochemical observations of suturing within the heart of the proto-Tibetan Plateau.

40 CFR 86.132-96 - Vehicle preconditioning.

Code of Federal Regulations, 2013 CFR

2013-07-01

... outdoors awaiting testing, to prevent unusual loading of the canisters. During this time care must be taken... idle again for 1 minute. (H) After the vehicle is turned off the last time, it may be tested for... preconditioned according to the following procedure. For vehicles with multiple canisters in a series...

40 CFR 86.132-00 - Vehicle preconditioning.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Vehicle preconditioning. 86.132-00... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete...

40 CFR 86.132-96 - Vehicle preconditioning.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Vehicle preconditioning. 86.132-96... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete...

40 CFR 86.132-96 - Vehicle preconditioning.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Vehicle preconditioning. 86.132-96... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete...

40 CFR 86.132-00 - Vehicle preconditioning.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 19 2013-07-01 2013-07-01 false Vehicle preconditioning. 86.132-00... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete...

40 CFR 86.132-00 - Vehicle preconditioning.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 19 2014-07-01 2014-07-01 false Vehicle preconditioning. 86.132-00... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete...

40 CFR 86.132-00 - Vehicle preconditioning.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 19 2012-07-01 2012-07-01 false Vehicle preconditioning. 86.132-00... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete...

Revealing Preconditions for Trustful Collaboration in CSCL

ERIC Educational Resources Information Center

Gerdes, Anne

2010-01-01

This paper analyses preconditions for trust in virtual learning environments. The concept of trust is discussed with reference to cases reporting trust in cyberspace and through a philosophical clarification holding that trust in the form of self-surrender is a common characteristic of all human co-existence. In virtual learning environments,…

Comparison results on preconditioned SOR-type iterative method for Z-matrices linear systems

NASA Astrophysics Data System (ADS)

Wang, Xue-Zhong; Huang, Ting-Zhu; Fu, Ying-Ding

2007-09-01

In this paper, we present some comparison theorems on preconditioned iterative method for solving Z-matrices linear systems, Comparison results show that the rate of convergence of the Gauss-Seidel-type method is faster than the rate of convergence of the SOR-type iterative method.

33 CFR 183.220 - Preconditioning for tests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Flotation Requirements for Outboard Boats Rated for Engines of More Than 2 Horsepower General § 183.220 Preconditioning for tests. A boat must meet the... boat. (b) The boat must be loaded with a quantity of weight that, when submerged, is equal to the sum...

Hypoxic preconditioning potentiates the trophic effects of mesenchymal stem cells on co-cultured human primary hepatocytes.

PubMed

Qin, Harry H; Filippi, Céline; Sun, Song; Lehec, Sharon; Dhawan, Anil; Hughes, Robin D

2015-12-01

Mesenchymal stem/stromal cells (MSCs) improve the metabolic function of co-cultured hepatocytes. The present study aimed to further enhance the trophic effects of co-culture with hepatocytes using hypoxic preconditioning (HPc) of the MSCs and also to investigate the underlying molecular mechanisms involved. Human adipose tissue-derived MSCs were subjected to hypoxia (2 % O2; HPc) or normoxia (20 % O2) for 24 h and then co-cultured with isolated human hepatocytes. Assays of metabolic function and apoptosis were performed to investigate the hepatotrophic and anti-apoptotic effects of co-culture. Indirect co-cultures and co-culture with MSC-conditioned medium investigated the role of paracrine factors in the hepatotrophic effects of co-culture. Reactive oxygen species (ROS) activity was antagonised with N-acetylcysteine to investigate whether HPc potentiated the effects of MSCs by intracellular ROS-dependent mechanisms. Tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and extracellular collagen production was determined and CASP9 and BAX/BCL-2 signalling pathways analysed to investigate the role of soluble factors, extracellular matrix deposition, and apoptosis-associated gene signalling in the effects of co-culture. HPc potentiated the hepatotrophic and anti-apoptotic effects of co-culture by ROS-dependent mechanisms. There was increased MSC TGF-β1 production, and enhanced MSC deposition of extracellular collagen, with reduced synthesis of TNF-α, as well as a downregulation of the expression of pro-apoptotic CASP9, BAX, BID and BLK genes and upregulated expression of anti-apoptotic BCL-2 in hepatocytes. HPc potentiated the trophic and anti-apoptotic effects of MSCs on hepatocytes via mechanisms including intracellular ROS, autocrine TGF-β, extracellular collagen and caspase and BAX/BCL-2 signalling pathways.

Exploring Spinal Cord Protection by Remote Ischemic Preconditioning: An Experimental Study.

PubMed

Herajärvi, Johanna; Anttila, Tuomas; Sarja, Henna; Mustonen, Caius; Haapanen, Henri; Mäkelä, Tuomas; Yannopoulos, Fredrik; Starck, Tuomo; Kallio, Mika; Tuominen, Hannu; Puistola, Ulla; Karihtala, Peeter; Kiviluoma, Kai; Anttila, Vesa; Juvonen, Tatu

2017-03-01

Paraplegia is one of the most severe complications occurring after the repair of thoracic and thoracoabdominal aortic aneurysms. Remote ischemic preconditioning (RIPC) has been shown to mitigate neurologic damage, and this study assessed its efficacy in preventing spinal cord ischemia. The study randomized 16 female pigs into an RIPC group (n = 8) and a control group (n = 8). The RIPC group underwent four cycles of 5-minute ischemia-reperfusion episodes by intermittent occlusion of the left iliac artery. All animals underwent systematic closure of the left subclavian artery and segmental arteries of the descending thoracic aorta to the level of diaphragm. Motor-evoked potential monitoring was performed in both hind limbs. Continuous electrocardiogram and hemodynamics were monitored, and pulmonary artery blood samples were collected. A neurologic assessment was performed 6 hours after the procedure. The thoracic and lumbar portions of the spinal cord were collected for histologic and immunohistochemical analysis. The bilateral motor-evoked potential amplitude responses were higher in the RIPC group (p < 0.05) than in the control group; the difference was detected already before spinal cord ischemia. Paraplegia occurred in 1 control animal. Immunohistochemical total scores of antioxidant response regulator nuclear factor erythroid 2-related factor 2 were better in the RIPC group (11.0; range, 8.5 to 14.0) than in the control group (5.2; range, 1.0 to 9.0; p = 0.023). RIPC induces electrophysiologic changes in the central nervous system that may confer spinal cord protection extending the resistance to ischemia. The significantly higher nuclear factor erythroid 2-related factor 2 scores suggest better neuronal cell protection against oxidative stress in the RIPC group. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Chronic methamphetamine administration causes differential regulation of transcription factors in the rat midbrain.

PubMed

Krasnova, Irina N; Ladenheim, Bruce; Hodges, Amber B; Volkow, Nora D; Cadet, Jean Lud

2011-04-25

Methamphetamine (METH) is an addictive and neurotoxic psychostimulant widely abused in the USA and throughout the world. When administered in large doses, METH can cause depletion of striatal dopamine terminals, with preservation of midbrain dopaminergic neurons. Because alterations in the expression of transcription factors that regulate the development of dopaminergic neurons might be involved in protecting these neurons after toxic insults, we tested the possibility that their expression might be affected by toxic doses of METH in the adult brain. Male Sprague-Dawley rats pretreated with saline or increasing doses of METH were challenged with toxic doses of the drug and euthanized two weeks later. Animals that received toxic METH challenges showed decreases in dopamine levels and reductions in tyrosine hydroxylase protein concentration in the striatum. METH pretreatment protected against loss of striatal dopamine and tyrosine hydroxylase. In contrast, METH challenges caused decreases in dopamine transporters in both saline- and METH-pretreated animals. Interestingly, METH challenges elicited increases in dopamine transporter mRNA levels in the midbrain in the presence but not in the absence of METH pretreatment. Moreover, toxic METH doses caused decreases in the expression of the dopamine developmental factors, Shh, Lmx1b, and Nurr1, but not in the levels of Otx2 and Pitx3, in saline-pretreated rats. METH pretreatment followed by METH challenges also decreased Nurr1 but increased Otx2 and Pitx3 expression in the midbrain. These findings suggest that, in adult animals, toxic doses of METH can differentially influence the expression of transcription factors involved in the developmental regulation of dopamine neurons. The combined increases in Otx2 and Pitx3 expression after METH preconditioning might represent, in part, some of the mechanisms that served to protect against METH-induced striatal dopamine depletion observed after METH preconditioning.

Effect of Preconditioning and Soldering on Failures of Chip Tantalum Capacitors

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander A.

2014-01-01

Soldering of molded case tantalum capacitors can result in damage to Ta205 dielectric and first turn-on failures due to thermo-mechanical stresses caused by CTE mismatch between materials used in the capacitors. It is also known that presence of moisture might cause damage to plastic cases due to the pop-corning effect. However, there are only scarce literature data on the effect of moisture content on the probability of post-soldering electrical failures. In this work, that is based on a case history, different groups of similar types of CWR tantalum capacitors from two lots were prepared for soldering by bake, moisture saturation, and longterm storage at room conditions. Results of the testing showed that both factors: initial quality of the lot, and preconditioning affect the probability of failures. Baking before soldering was shown to be effective to prevent failures even in lots susceptible to pop-corning damage. Mechanism of failures is discussed and recommendations for pre-soldering bake are suggested based on analysis of moisture characteristics of materials used in the capacitors' design.

Fetal asphyxia induces acute and persisting changes in the ceramide metabolism in rat brain[S

PubMed Central

Vlassaks, Evi; Mencarelli, Chiara; Nikiforou, Maria; Strackx, Eveline; Ferraz, Maria J.; Aerts, Johannes M.; De Baets, Marc H.; Martinez-Martinez, Pilar; Gavilanes, Antonio W. D.

2013-01-01

Fetal asphyctic preconditioning, induced by a brief episode of experimental hypoxia-ischemia, offers neuroprotection to a subsequent more severe asphyctic insult at birth. Extensive cell stress and apoptosis are important contributing factors of damage in the asphyctic neonatal brain. Because ceramide acts as a second messenger for multiple apoptotic stimuli, including hypoxia/ischemia, we sought to investigate the possible involvement of the ceramide pathway in endogenous neuroprotection induced by fetal asphyctic preconditioning. Global fetal asphyxia was induced in rats by clamping both uterine and ovarian vasculature for 30 min. Fetal asphyxia resulted in acute changes in brain ceramide/sphingomyelin metabolic enzymes, ceramide synthase 1, 2, and 5, acid sphingomyelinase, sphingosine-1-phosphate phosphatase, and the ceramide transporter. This observation correlated with an increase in neuronal apoptosis and in astrocyte number. After birth, ceramide and sphingomyelin levels remained high in fetal asphyxia brains, suggesting that a long-term regulation of the ceramide pathway may be involved in the mechanism of tolerance to a subsequent, otherwise lethal, asphyctic event. PMID:23625371

Simulations of Continuous Descent Operations with Arrival-management Automation and Mixed Flight-deck Interval Management Equipage

NASA Technical Reports Server (NTRS)

Callantine, Todd J.; Kupfer, Michael; Martin, Lynne Hazel; Prevot, Thomas

2013-01-01

Air traffic management simulations conducted in the Airspace Operations Laboratory at NASA Ames Research Center have addressed the integration of trajectory-based arrival-management automation, controller tools, and Flight-Deck Interval Management avionics to enable Continuous Descent Operations (CDOs) during periods of sustained high traffic demand. The simulations are devoted to maturing the integrated system for field demonstration, and refining the controller tools, clearance phraseology, and procedures specified in the associated concept of operations. The results indicate a variety of factors impact the concept's safety and viability from a controller's perspective, including en-route preconditioning of arrival flows, useable clearance phraseology, and the characteristics of airspace, routes, and traffic-management methods in use at a particular site. Clear understanding of automation behavior and required shifts in roles and responsibilities is important for controller acceptance and realizing potential benefits. This paper discusses the simulations, drawing parallels with results from related European efforts. The most recent study found en-route controllers can effectively precondition arrival flows, which significantly improved route conformance during CDOs. Controllers found the tools acceptable, in line with previous studies.

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.

Factors Affecting Availability of Essential Medicines among Community Health Workers in Ethiopia, Malawi, and Rwanda: Solving the Last Mile Puzzle

PubMed Central

Chandani, Yasmin; Noel, Megan; Pomeroy, Amanda; Andersson, Sarah; Pahl, Michelle K.; Williams, Timothy

2012-01-01

To understand how supply chain factors affect product availability at the community level, the Improving Supply Chains for Community Case Management of Pneumonia and Other Common Diseases of Childhood Project developed a theory of change (TOC) framework for gathering, organizing, and interpreting evidence about supply constraints to community case management (CCM). Baseline assessments in Ethiopia, Malawi, and Rwanda conducted in 2010 provided information on the strengths and weaknesses of existing CCM supply chains for five main products: antibiotics for pneumonia, oral rehydration solution, ready to use therapeutic food, zinc, and artemether/lumefantrine. The assessments tested the strength and validity of causal pathways identified in the TOC that were believed to influence availability of CCM products among community health workers (CHWs) for treating common childhood illnesses. Results of the assessments showed product availability to be weak in each country, with more than half of CHWs stocked out of at least one tracer product on the day of the assessment. This report will focus on the findings related to three key preconditions of the TOC and how these were used to inform the design of the CCM supply chain improvement strategy in each country. The three key preconditions include product availability at CHW resupply points, supply chain knowledge and capacity among CHWs and their supervisors, and availability of appropriate transportation. PMID:23136287

Short-term preconditioning enhances the therapeutic potential of adipose-derived stromal/stem cell-conditioned medium in cisplatin-induced acute kidney injury.

PubMed

Overath, Jürgen M; Gauer, Stefan; Obermüller, Nicholas; Schubert, Ralf; Schäfer, Richard; Geiger, Helmut; Baer, Patrick C

2016-03-15

The development of new strategies to preserve renal function after acute kidney injury (AKI) is necessary due to limited clinical intervention options. The organ-protective effects of mesenchymal stromal/stem cells (MSCs) and their conditioned medium (CM) have been investigated demonstrating that both separately promoted tubular recovery and ameliorated the outcome of AKI. Nevertheless, strategies to optimise the regenerative potential of both are highly needed. Here we investigated the effects of CM from adipose-derived MSCs (ASCs) preincubated in a hypoxic environment (Hyp). Protective factors were investigated by PCR analysis and a protein array in vitro. The expression of 64 of the 308 proteins assayed was found to be more than two-fold increased after Hyp. CM of Hyp-pretreated ASCs (pCM) was used to enhance regeneration in a mouse model of cisplatin-induced AKI (cisAKI). Renal function was assessed by measurements of markers for AKI and serum cytokine levels. The pCM significantly ameliorated serum creatinine and neutrophil gelatinase-associated lipocalin values, and also the levels of inflammatory cytokines IL-1β and IL-6 in the serum of mice with AKI. Our work clearly showed that a Hyp preconditioning significantly increases the release of protective factors in ASCs and enhances the therapeutic effects of CM in cisAKI in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Minimally invasive hip arthroplasty: what role does patient preconditioning play?

PubMed

Pour, Aidin Eslam; Parvizi, Javad; Sharkey, Peter F; Hozack, William J; Rothman, Richard H

2007-09-01

The benefits of minimally invasive total hip arthroplasty continue to be debated. The objective of this study was to investigate the role of patient education, accelerated rehabilitation, and improved pain control on the outcome of total hip arthroplasty performed through a small incision. One hundred patients undergoing total hip arthroplasty at our institution were randomized into one of four groups on the basis of the size of the incision, preoperative counseling, the type of preoperative and postoperative rehabilitation, and the analgesia protocol. The operative parameters, complications, time to discharge to home, functional improvement, and patient satisfaction were assessed. The demographic distribution among the four groups was similar. The extent of functional improvement at the time of discharge to home, patient satisfaction, and walking ability at the time of discharge were better in patients who had received an accelerated preoperative and postoperative rehabilitation regimen regardless of the size of the incision. There was no difference in estimated blood loss, mean operative time, transfusion needs, or complications among the groups. This study highlights the importance of factors such as family education, patient preconditioning, preemptive analgesia, and accelerated preoperative and postoperative rehabilitation in influencing the outcome of total hip arthroplasty. The aforementioned factors, and not the surgical technique per se, may play a major role in imparting the better outcome after minimally invasive total hip arthroplasty that has been reported by various investigators.

Characteristics and frequency of large submarine landslides at the western tip of the Gulf of Corinth

NASA Astrophysics Data System (ADS)

Beckers, Arnaud; Hubert-Ferrari, Aurelia; Beck, Christian; Papatheodorou, George; de Batist, Marc; Sakellariou, Dimitris; Tripsanas, Efthymios; Demoulin, Alain

2018-05-01

Coastal and submarine landslides are frequent at the western tip of the Gulf of Corinth, where small to medium failure events (106-107 m3) occur on average every 30-50 years. These landslides trigger tsunamis and consequently represent a significant hazard. We use here a dense grid of high-resolution seismic profiles to realize an inventory of the large mass transport deposits (MTDs) that result from these submarine landslides. Six large mass wasting events are identified, and their associated deposits locally represent 30 % of the sedimentation since 130 ka in the main western basin. In the case of a large MTD of ˜ 1 km3 volume, the simultaneous occurrence of different slope failures is inferred and suggests an earthquake triggering. However, the overall temporal distribution of MTDs would result from the time-dependent evolution of pre-conditioning factors rather than from the recurrence of external triggers. Two likely main pre-conditioning factors are (1) the reloading time of slopes, which varied with the sedimentation rate, and (2) dramatic changes in water depth and water circulation that occurred 10-12 ka ago during the last post-glacial transgression. Such sliding events likely generated large tsunami waves in the whole Gulf of Corinth, possibly larger than those reported in historical sources considering the observed volume of the MTDs.

Factors affecting availability of essential medicines among community health workers in Ethiopia, Malawi, and Rwanda: solving the last mile puzzle.

PubMed

Chandani, Yasmin; Noel, Megan; Pomeroy, Amanda; Andersson, Sarah; Pahl, Michelle K; Williams, Timothy

2012-11-01

To understand how supply chain factors affect product availability at the community level, the Improving Supply Chains for Community Case Management of Pneumonia and Other Common Diseases of Childhood Project developed a theory of change (TOC) framework for gathering, organizing, and interpreting evidence about supply constraints to community case management (CCM). Baseline assessments in Ethiopia, Malawi, and Rwanda conducted in 2010 provided information on the strengths and weaknesses of existing CCM supply chains for five main products: antibiotics for pneumonia, oral rehydration solution, ready to use therapeutic food, zinc, and artemether/lumefantrine. The assessments tested the strength and validity of causal pathways identified in the TOC that were believed to influence availability of CCM products among community health workers (CHWs) for treating common childhood illnesses. Results of the assessments showed product availability to be weak in each country, with more than half of CHWs stocked out of at least one tracer product on the day of the assessment. This report will focus on the findings related to three key preconditions of the TOC and how these were used to inform the design of the CCM supply chain improvement strategy in each country. The three key preconditions include product availability at CHW resupply points, supply chain knowledge and capacity among CHWs and their supervisors, and availability of appropriate transportation.

Effect of hypercholesterolaemia on myocardial function, ischaemia–reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning

PubMed Central

Iliodromitis, Efstathios K; Lazou, Antigone; Görbe, Anikó; Giricz, Zoltán; Schulz, Rainer

2017-01-01

Hypercholesterolaemia is considered to be a principle risk factor for cardiovascular disease, having direct negative effects on the myocardium itself, in addition to the development of atherosclerosis. Since hypercholesterolaemia affects the global cardiac gene expression profile, among many other factors, it results in increased myocardial oxidative stress, mitochondrial dysfunction and inflammation triggered apoptosis, all of which may account for myocardial dysfunction and increased susceptibility of the myocardium to infarction. In addition, numerous experimental and clinical studies have revealed that hyperlcholesterolaemia may interfere with the cardioprotective potential of conditioning mechanisms. Although not fully elucidated, the underlying mechanisms for the lost cardioprotection in hypercholesterolaemic animals have been reported to involve dysregulation of the endothelial NOS‐cGMP, reperfusion injury salvage kinase, peroxynitrite‐MMP2 signalling pathways, modulation of ATP‐sensitive potassium channels and apoptotic pathways. In this review article, we summarize the current knowledge on the effect of hypercholesterolaemia on the non‐ischaemic and ischaemic heart as well as on the cardioprotection induced by drugs or ischaemic preconditioning, postconditioning and remote conditioning. Future perspectives concerning the mechanisms and the design of preclinical and clinical trials are highlighted. Linked Articles This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc PMID:28060997

PBMC: Pre-conditioned Backward Monte Carlo code for radiative transport in planetary atmospheres

NASA Astrophysics Data System (ADS)

García Muñoz, A.; Mills, F. P.

2017-08-01

PBMC (Pre-Conditioned Backward Monte Carlo) solves the vector Radiative Transport Equation (vRTE) and can be applied to planetary atmospheres irradiated from above. The code builds the solution by simulating the photon trajectories from the detector towards the radiation source, i.e. in the reverse order of the actual photon displacements. In accounting for the polarization in the sampling of photon propagation directions and pre-conditioning the scattering matrix with information from the scattering matrices of prior (in the BMC integration order) photon collisions, PBMC avoids the unstable and biased solutions of classical BMC algorithms for conservative, optically-thick, strongly-polarizing media such as Rayleigh atmospheres.

Fractal-like kinetics, a possible link between preconditioning and sepsis immunodepression. On the chemical basis of innate immunity.

PubMed

Vasilescu, C; Olteanu, M; Flondor, P

2012-01-01

In a recent paper the authors hypothesized that the so called fractal-like enzyme kinetics of intracellular reactions may explain the preconditioning effect in biology (Vasilescu C, Olteanu M, Flondor P, Revue Roumaine de Chimie. 2011; 56(7): 751-7). Inside cells the reaction kinetics is very well described by fractal-like kinetics. In the present work some clinical implications of this model are analyzed. Endotoxin tolerance is a particular case of preconditioning and shows similarities with the immunodepression seen in some sepsis patients. This idea offers a theoretical support for modulation of the enzymatic activity of the cell by changing the fractal dimension of the cytoskeleton.

41 CFR 102-72.68 - What preconditions must be satisfied before an Executive agency may exercise the delegated...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What preconditions must... ancillary repair and alteration project? 102-72.68 Section 102-72.68 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL...

41 CFR 102-72.68 - What preconditions must be satisfied before an Executive agency may exercise the delegated...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What preconditions must... ancillary repair and alteration project? 102-72.68 Section 102-72.68 Public Contracts and Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION REAL...

TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

EPA Science Inventory

Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.

Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning

Craig...

40 CFR 86.532-78 - Vehicle preconditioning.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 1978 and Later New Motorcycles; Test Procedures § 86.532-78 Vehicle preconditioning. (a) The vehicle shall be moved to the test area and the following operations performed: (1) The fuel tank(s) shall be drained through the provided fuel tank(s) drain(s) and charged with the specified test fuel, § 86.513, to...

40 CFR 86.532-78 - Vehicle preconditioning.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 1978 and Later New Motorcycles; Test Procedures § 86.532-78 Vehicle preconditioning. (a) The vehicle shall be moved to the test area and the following operations performed: (1) The fuel tank(s) shall be drained through the provided fuel tank(s) drain(s) and charged with the specified test fuel, § 86.513, to...

40 CFR 86.532-78 - Vehicle preconditioning.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1978 and Later New Motorcycles; Test Procedures § 86.532-78 Vehicle preconditioning. (a) The vehicle shall be moved to the test area and the following operations performed: (1) The fuel tank(s) shall be drained through the provided fuel tank(s) drain(s) and charged with the specified test fuel, § 86.513, to...

40 CFR 86.532-78 - Vehicle preconditioning.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1978 and Later New Motorcycles; Test Procedures § 86.532-78 Vehicle preconditioning. (a) The vehicle shall be moved to the test area and the following operations performed: (1) The fuel tank(s) shall be drained through the provided fuel tank(s) drain(s) and charged with the specified test fuel, § 86.513, to...

40 CFR 86.532-78 - Vehicle preconditioning.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 1978 and Later New Motorcycles; Test Procedures § 86.532-78 Vehicle preconditioning. (a) The vehicle shall be moved to the test area and the following operations performed: (1) The fuel tank(s) shall be drained through the provided fuel tank(s) drain(s) and charged with the specified test fuel, § 86.513, to...

The survey of preconditioners used for accelerating the rate of convergence in the Gauss-Seidel method

NASA Astrophysics Data System (ADS)

Niki, Hiroshi; Harada, Kyouji; Morimoto, Munenori; Sakakihara, Michio

2004-03-01

Several preconditioned iterative methods reported in the literature have been used for improving the convergence rate of the Gauss-Seidel method. In this article, on the basis of nonnegative matrix, comparisons between some splittings for such preconditioned matrices are derived. Simple numerical examples are also given.

Remote ischaemic preconditioning and prevention of cerebral injury.

PubMed

Rehni, Ashish K; Shri, Richa; Singh, Manjeet

2007-03-01

Bilateral carotid artery occlusion of 10 min followed by reperfusion for 24 hr was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Short-term memory was evaluated using elevated plus maze. Inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired short-term memory, motor co-ordination and lateral push response. A preceding episode of mesenteric artery occlusion for 15 min and reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented markedly ischaemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of short-term memory, motor coordination and lateral push response. Glibenclamide (5 mg/kg, iv) a KATP channel blocker and caffeine (7 mg/kg, iv) an adenosine receptor blocker attenuated the neuroprotective effect of remote mesenteric ischaemic preconditioning. It may be concluded that neuroprotective effect of remote mesenteric ischaemic preconditioning may be due to activation of adenosine receptors and consequent activation of KATP channels in mice.

Preconditioning for traumatic brain injury

PubMed Central

Yokobori, Shoji; Mazzeo, Anna T; Hosein, Khadil; Gajavelli, Shyam; Dietrich, W. Dalton; Bullock, M. Ross

2016-01-01

Traumatic brain injury (TBI) treatment is now focused on the prevention of primary injury and reduction of secondary injury. However, no single effective treatment is available as yet for the mitigation of traumatic brain damage in humans. Both chemical and environmental stresses applied before injury, have been shown to induce consequent protection against post-TBI neuronal death. This concept termed “preconditioning” is achieved by exposure to different pre-injury stressors, to achieve the induction of “tolerance” to the effect of the TBI. However, the precise mechanisms underlying this “tolerance” phenomenon are not fully understood in TBI, and therefore even less information is available about possible indications in clinical TBI patients. In this review we will summarize TBI pathophysiology, and discuss existing animal studies demonstrating the efficacy of preconditioning in diffuse and focal type of TBI. We will also review other non-TBI preconditionng studies, including ischemic, environmental, and chemical preconditioning, which maybe relevant to TBI. To date, no clinical studies exist in this field, and we speculate on possible futureclinical situation, in which pre-TBI preconditioning could be considered. PMID:24323189

Myocardial protection using diadenosine tetraphosphate with pharmacological preconditioning.

PubMed

Ahmet, I; Sawa, Y; Nishimura, M; Yamaguchi, T; Kitakaze, M; Matsuda, H

2000-09-01

We have reported a similar cardioprotective effect and mechanism of diadenosine tetraphosphate (AP4A) and ischemic preconditioning in rat hearts. In this study, the applicability of AP4A administration to cardiac surgery was tested by using a canine cardiopulmonary bypass model. Hearts underwent 60 minutes of cardioplegic arrest (34 degrees C) by a single dose of cardioplegia. Cardioplegia contained either AP4A (40 micromol/L; n = 6) or saline (n = 6). Beagles were weaned from cardiopulmonary bypass 30 minutes after reperfusion, and left ventricular function was evaluated after another 30 minutes by using the cardiac loop analysis system. Administration of AP4A significantly improved the postischemic recovery of cardiac function and reduced the leakage of serum creatine kinase compared with saline. Systemic vascular resistance, mean aortic blood pressure, and the electrocardiographic indices were not significantly altered by AP4A administration. Administration of AP4A was cardioprotective without apparent adverse effects. Because the cardioprotective mechanism may be similar to that of ischemic preconditioning, the addition of AP4A into cardioplegia may be a novel safe method for clinical application of preconditioning cardioprotection.

Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

PubMed

Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

2009-11-30

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

Preconditioned Alternating Projection Algorithms for Maximum a Posteriori ECT Reconstruction

PubMed Central

Krol, Andrzej; Li, Si; Shen, Lixin; Xu, Yuesheng

2012-01-01

We propose a preconditioned alternating projection algorithm (PAPA) for solving the maximum a posteriori (MAP) emission computed tomography (ECT) reconstruction problem. Specifically, we formulate the reconstruction problem as a constrained convex optimization problem with the total variation (TV) regularization. We then characterize the solution of the constrained convex optimization problem and show that it satisfies a system of fixed-point equations defined in terms of two proximity operators raised from the convex functions that define the TV-norm and the constrain involved in the problem. The characterization (of the solution) via the proximity operators that define two projection operators naturally leads to an alternating projection algorithm for finding the solution. For efficient numerical computation, we introduce to the alternating projection algorithm a preconditioning matrix (the EM-preconditioner) for the dense system matrix involved in the optimization problem. We prove theoretically convergence of the preconditioned alternating projection algorithm. In numerical experiments, performance of our algorithms, with an appropriately selected preconditioning matrix, is compared with performance of the conventional MAP expectation-maximization (MAP-EM) algorithm with TV regularizer (EM-TV) and that of the recently developed nested EM-TV algorithm for ECT reconstruction. Based on the numerical experiments performed in this work, we observe that the alternating projection algorithm with the EM-preconditioner outperforms significantly the EM-TV in all aspects including the convergence speed, the noise in the reconstructed images and the image quality. It also outperforms the nested EM-TV in the convergence speed while providing comparable image quality. PMID:23271835

Amelioration of rCBF and PbtO2 following TBI at high altitude by hyperbaric oxygen pre-conditioning.

PubMed

Hu, Shengli; Li, Fei; Luo, Haishui; Xia, Yongzhi; Zhang, Jiuquan; Hu, Rong; Cui, Gaoyu; Meng, Hui; Feng, Hua

2010-03-01

Hypobaric hypoxia at high altitude can lead to brain damage and pre-conditioning with hyperbaric oxygen (HBO) can reduce ischemic/hypoxic brain injury. This study investigates the effects of high altitude on traumatic brain injury (TBI) and examines the neuroprotection provided by HBO preconditioning against TBI. Rats were randomly divided into four groups: HBO pre-conditioning group (HBOP, n=10), high altitude group (HA, n=10), plain control group (PC, n=10) and plain sham operation group (sham, n=10). All groups were subjected to head trauma by weight drop device except for the sham group. Rats from each group were examined for neurological function, regional cerebral blood flow (rCBF) and brain tissue oxygen pressure (PbtO(2)) and were killed for analysis by transmission electron microscope. The score of neurological deficits in the HA group was highest, followed by the HBOP group and the PC group, respectively. Both rCBF and PbtO(2) were the lowest in the HA group. Brain morphology and structure seen via the transmission electron microscope was diminished in the HA group, while fewer pathological injuries occurred in the HBOP and PC groups. High altitude aggravates TBI significantly and HBO pre-conditioning can attenuate TBI in rats at high altitude by improvement of rCBF and PbtO(2). Pre-treatment with HBO might be beneficial for people traveling to high altitude locations.

Hypoxic-Preconditioned Bone Marrow Stem Cell Medium Significantly Improves Outcome After Retinal Ischemia in Rats

PubMed Central

Roth, Steven; Dreixler, John C.; Mathew, Biji; Balyasnikova, Irina; Mann, Jacob R.; Boddapati, Venkat; Xue, Lai; Lesniak, Maciej S.

2016-01-01

Purpose We have previously demonstrated the protective effect of bone marrow stem cell (BMSC)-conditioned medium in retinal ischemic injury. We hypothesized here that hypoxic preconditioning of stem cells significantly enhances the neuroprotective effect of the conditioned medium and thereby augments the protective effect in ischemic retina. Methods Rats were subjected to retinal ischemia by increasing intraocular pressure to 130 to 135 mm Hg for 55 minutes. Hypoxic-preconditioned, hypoxic unconditioned, or normoxic medium was injected into the vitreous 24 hours after ischemia ended. Recovery was assessed 7 days after injections by comparing electroretinography measurements, histologic examination, and apoptosis (TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay). To compare proteins secreted into the medium in the groups and the effect of hypoxic exposure, we used rat cytokine arrays. Results Eyes injected with hypoxic BMSC–conditioned medium 24 hours after ischemia demonstrated significantly enhanced return of retinal function, decreased retinal ganglion cell layer loss, and attenuated apoptosis compared to those administered normoxic or hypoxic unconditioned medium. Hypoxic-preconditioned medium had 21 significantly increased protein levels compared to normoxic medium. Conclusions The medium from hypoxic-preconditioned BMSCs robustly restored retinal function and prevented cell loss after ischemia when injected 24 hours after ischemia. The protective effect was even more pronounced than in our previous studies of normoxic conditioned medium. Prosurvival signals triggered by the secretome may play a role in this neuroprotective effect. PMID:27367588

Acetylation of histones in neocortex and hippocampus of rats exposed to different modes of hypobaric hypoxia: Implications for brain hypoxic injury and tolerance.

PubMed

Samoilov, Mikhail; Churilova, Anna; Gluschenko, Tatjana; Vetrovoy, Oleg; Dyuzhikova, Natalia; Rybnikova, Elena

2016-03-01

Acetylation of nucleosome histones results in relaxation of DNA and its availability for the transcriptional regulators, and is generally associated with the enhancement of gene expression. Although it is well known that activation of a variety of pro-adaptive genes represents a key event in the development of brain hypoxic/ischemic tolerance, the role of epigenetic mechanisms, in particular histone acetylation, in this process is still unexplored. The aim of the present study was to investigate changes in acetylation of histones in vulnerable brain neurons using original well-standardized model of hypobaric hypoxia and preconditioning-induced tolerance of the brain. Using quantitative immunohistochemistry and Western blot, effects of severe injurious hypobaric hypoxia (SH, 180mm Hg, 3h) and neuroprotective preconditioning mode (three episodes of 360mm Hg for 2h spaced at 24h) on the levels of the acetylated proteins and acetylated H3 Lys24 (H3K24ac) in the neocortex and hippocampus of rats were studied. SH caused global repression of the acetylation processes in the neocortex (layers II-III, V) and hippocampus (CA1, CA3) by 3-24h, and this effect was prevented by the preconditioning. Moreover, hypoxic preconditioning remarkably increased the acetylation of H3K24 in response to SH in the brain areas examined. The preconditioning hypoxia without subsequent SH also stimulated acetylation processes in the neocortex and hippocampus. The moderately enhanced expression of the acetylated proteins in the preconditioned rats was maintained for 24h, whereas acetylation of H3K24 was intense but transient, peaked at 3h. The novel data obtained in the present study indicate that large activation of the acetylation processes, in particular acetylation of histones might be essential for the development of brain hypoxic tolerance. Copyright © 2015 Elsevier GmbH. All rights reserved.

Active Focal Zone Sharpening for High-Precision Treatment Using Histotripsy

PubMed Central

Wang, Tzu-Yin; Xu, Zhen; Hall, Timothy L.; Fowlkes, J. Brian; Roberts, William W.; Cain, Charles A.

2011-01-01

The goal of this study is to develop a focal zone sharpening strategy that produces more precise lesions for pulsed cavitational ultrasound therapy, or histotripsy. Precise and well-confined lesions were produced by locally suppressing cavitation in the periphery of the treatment focus without affecting cavitation in the center. The local suppression of cavitation was achieved using cavitation nuclei preconditioning pulses to actively control cavitation in the periphery of the focus. A 1-MHz 513-element therapeutic array was used to generate both the therapy and the nuclei preconditioning pulses. For therapy, 10-cycle bursts at 100-Hz pulse repetition frequency with P−/P+ pressure of 21/76 MPa were delivered to the geometric focus of the therapeutic array. For nuclei preconditioning, a different pulse was delivered to an annular region immediately surrounding the focus before each therapy pulse. A parametric study on the effective pressure, pulse duration, and delivery time of the preconditioning pulse was conducted in red blood cell-gel phantoms, where cavitational damage was indicated by the color change resulting from local cell lysis. Results showed that a short-duration (20 µs) preconditioning pulse at a medium pressure (P−/P+ pressure of 7.2/13.6 MPa) delivered shortly before (30 µs) the therapy pulse substantially suppressed the peripheral damage by 77 ± 13% while complete fractionation in the focal center was maintained. High-speed imaging of the bubble cloud showed a substantial decrease in the maximum width of the bubble cloud by 48 ± 24% using focal zone sharpening. Experiments in ex vivo livers confirmed that highly confined lesions were produced in real tissues as well as in the phantoms. This study demonstrated the feasibility of active focal zone sharpening using cavitation nuclei preconditioning, allowing for increased treatment precision compared with the natural focal width of the therapy transducer. PMID:21342816

Active focal zone sharpening for high-precision treatment using histotripsy.

PubMed

Wang, Tzu-Yin; Xu, Zhen; Hall, Timothy; Fowlkes, J; Roberts, William; Cain, Charles

2011-02-01

The goal of this study is to develop a focal zone sharpening strategy that produces more precise lesions for pulsed cavitational ultrasound therapy, or histotripsy. Precise and well-confined lesions were produced by locally suppressing cavitation in the periphery of the treatment focus without affecting cavitation in the center. The local suppression of cavitation was achieved using cavitation nuclei preconditioning pulses to actively control cavitation in the periphery of the focus. A 1-MHz 513-element therapeutic array was used to generate both the therapy and the nuclei preconditioning pulses. For therapy, 10-cycle bursts at 100-Hz pulse repetition frequency with P-/P+ pressure of 21/76 MPa were delivered to the geometric focus of the therapeutic array. For nuclei preconditioning, a different pulse was delivered to an annular region immediately surrounding the focus before each therapy pulse. A parametric study on the effective pressure, pulse duration, and delivery time of the preconditioning pulse was conducted in red blood cell-gel phantoms, where cavitational damage was indicated by the color change resulting from local cell lysis. Results showed that a short-duration (20 μs) preconditioning pulse at a medium pressure (P-/P+ pressure of 7.2/13.6 MPa) delivered shortly before (30 μs) the therapy pulse substantially suppressed the peripheral damage by 77 ± 13% while complete fractionation in the focal center was maintained. High-speed imaging of the bubble cloud showed a substantial decrease in the maximum width of the bubble cloud by 48 ± 24% using focal zone sharpening. Experiments in ex vivo livers confirmed that highly confined lesions were produced in real tissues as well as in the phantoms. This study demonstrated the feasibility of active focal zone sharpening using cavitation nuclei preconditioning, allowing for increased treatment precision compared with the natural focal width of the therapy transducer.

Morphine preconditioning confers cardioprotection in doxorubicin-induced failing rat hearts via ERK/GSK-3β pathway independent of PI3K/Akt

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

He, Shu-Fang; Jin, Shi-Yun; Wu, Hao

Preconditioning against myocardial ischemia–reperfusion (I/R) injury can be suppressed in some pathological conditions. This study was designed to investigate whether morphine preconditioning (MPC) exerts cardioprotection in doxorubicin (DOX)-induced heart failure in rats and the mechanisms involved. Phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt), extracellular signal-regulated kinase (ERK) and glycogen synthase kinase (GSK)-3β pathways were examined. Normal and DOX-induced failing rat hearts were subjected to I/R injury using a Langendorff perfusion system with or without MPC or ischemic preconditioning (IPC). The PI3K inhibitor (wortmannin) or ERK inhibitor (PD98059) was infused before MPC. In normal hearts, both MPC and IPC significantly reduced infarct sizemore » and the rise in lactate dehydrogenase (LDH) level caused by I/R injury. Pretreatment with wortmannin or PD98059 abrogated the protective effects of MPC and suppressed the phosphorylation of Akt, ERK and GSK-3β. In failing rat hearts, however, MPC retained its cardioprotection while IPC did not. This protective effect was abolished by PD98059 but not wortmannin. MPC increased the level of p-ERK rather than p-Akt. The phosphorylation of GSK-3β induced by MPC was reversed by PD98059 only. IPC did not elevate the expression of p-ERK, p-Akt and p-GSK-3β in failing rat hearts. We conclude that MPC is cardioprotective in rats with DOX-induced heart failure while IPC is not. The effect of MPC appears to be mediated via the ERK/GSK-3β pathway independent of PI3K/Akt. - Highlights: • Morphine and ischemic preconditioning are cardioprotective in normal rat hearts. • Ischemic preconditioning fails to confer cardioprotection in rats with heart failure. • Morphine retains cardioprotection in doxorubicin-induced heart failure. • Morphine exerts cardioprotection via the ERK/GSK-β pathway independent of PI3K/Akt.« less

Involvement of miR-1 in the protective effect of hydrogen sulfide against cardiomyocyte apoptosis induced by ischemia/reperfusion.

PubMed

Kang, Bo; Hong, Jiang; Xiao, Jian; Zhu, Xiaoyan; Ni, Xin; Zhang, Yufeng; He, Bin; Wang, Zhinong

2014-10-01

The protective effect of hydrogen sulfide (H2S) against myocardial ischemia/reperfusion (IR) injury via anti-apoptotic signaling is well established, but the underlying mechanism remains unclear. Recently, miRNAs have been identified as important mediators of myocardial injury by regulating apoptosis-related genes. It was found in our previous preliminary study that microRNA-1 (miR-1) expression underwent a significant change in IR group compared to H2S preconditioned group, indicating that miR-1 possessed myocyte-specific properties. In the present study, we intended to see whether miR-1 participated in H2S protection of cardiomyocytes against IR-induced apoptosis by regulating apoptosis-related genes. Cardiomyocytes of neonatal rats were subjected to hypoxia/reoxygenation (HR) injury with or without H2S preconditioning, while the myocardium of adult SD rats was subjected to IR with or without H2S preconditioning. It was found that HR injury increased apoptosis of cardiac myocytes, up-regulated the expression of miR-1, and down-regulated the expression of Bcl-2. H2S preconditioning attenuated cardiomyocyte apoptosis and LDH release, as well as enhanced cell viability following HR injury. MiR-1 was up-regulated by HR and down-regulated by H2S preconditioning. In contrast, Bcl-2 was down-regulated by HR and up-regulated by H2S preconditioning. In addition, Bcl-2 protein was down-regulated by the miR-1 mimic in a dose-dependent manner. H2S also attenuated IR-induced cardiomyocyte apoptosis in vivo. MiR-1 regulated H2S protection of cardiomyocytes against IR-induced apoptosis by stimulating Bcl-2. These results implicate miR-1 as an important regulator of H2S on the IR myocardium.

Progressive exercise preconditioning protects against circulatory shock during experimental heatstroke.

PubMed

Hung, Ching-Hsia; Chang, Nen-Chung; Cheng, Bor-Chih; Lin, Mao-Tsun

2005-05-01

Heat shock protein (HSP) 72 expression protects against arterial hypotension in rat heatstroke. HSP72 can also be induced in multiple organs, including hearts from rats with endurance exercise. We validated the hypothesis that progressive exercise preconditioning may confer cardiovascular protection during heatstroke by inducing the overexpression of HSP72 in multiple organs. To deal with the matter, we assessed the effects of heatstroke on mean arterial pressure, heart rate, cardiac output, stroke volume, total peripheral vascular resistance, colonic temperature, blood gases, and serum or tissue levels of tumor necrosis factor-alpha (TNF-alpha) in urethane-anesthetized rats pretreated without or with progressive exercise training for 1, 2, or 3 weeks. In addition, HSP72 expression in multiple organs was determined in different groups of animals. Heatstroke was induced by exposing the rats to a high blanket temperature (43 degrees C); the moment at which mean arterial pressure decreased from the peak value was taken as the time of heatstroke onset. Previous exercise training for 3 weeks, but not 1 or 2 weeks, conferred significant protection against hyperthermia, arterial hypotension, decreased cardiac output, decreased stroke volume, decreased peripheral vascular resistance, and increased levels of serum or tissue TNF-alpha during heatstroke and correlated with overexpression of HSP72 in multiple organs, including heart, liver, and adrenal gland. However, 10 days after 3 weeks of progressive exercise training, when HSP72 expression in multiple organs returned to basal values, the beneficial effects exerted by 3 weeks of exercise training were no longer observed. These results strongly suggest that HSP72 preconditioning with progressive exercise training protects against hyperthermia, circulatory shock, and TNF-alpha overproduction during heatstroke.

Elasmobranch qPCR reference genes: a case study of hypoxia preconditioned epaulette sharks

PubMed Central

2010-01-01

Background Elasmobranch fishes are an ancient group of vertebrates which have high potential as model species for research into evolutionary physiology and genomics. However, no comparative studies have established suitable reference genes for quantitative PCR (qPCR) in elasmobranchs for any physiological conditions. Oxygen availability has been a major force shaping the physiological evolution of vertebrates, especially fishes. Here we examined the suitability of 9 reference candidates from various functional categories after a single hypoxic insult or after hypoxia preconditioning in epaulette shark (Hemiscyllium ocellatum). Results Epaulette sharks were caught and exposed to hypoxia. Tissues were collected from 10 controls, 10 individuals with single hypoxic insult and 10 individuals with hypoxia preconditioning (8 hypoxic insults, 12 hours apart). We produced sequence information for reference gene candidates and monitored mRNA expression levels in four tissues: cerebellum, heart, gill and eye. The stability of the genes was examined with analysis of variance, geNorm and NormFinder. The best ranking genes in our study were eukaryotic translation elongation factor 1 beta (eef1b), ubiquitin (ubq) and polymerase (RNA) II (DNA directed) polypeptide F (polr2f). The performance of the ribosomal protein L6 (rpl6) was tissue-dependent. Notably, in one tissue the analysis of variance indicated statistically significant differences between treatments for genes that were ranked as the most stable candidates by reference gene software. Conclusions Our results indicate that eef1b and ubq are generally the most suitable reference genes for the conditions and tissues in the present epaulette shark studies. These genes could also be potential reference gene candidates for other physiological studies examining stress in elasmobranchs. The results emphasise the importance of inter-group variation in reference gene evaluation. PMID:20416043

Allogeneic Stem Cells Alter Gene Expression and Improve Healing of Distal Limb Wounds in Horses

PubMed Central

Textor, Jamie A.; Clark, Kaitlin C.; Walker, Naomi J.; Aristizobal, Fabio A.; Kol, Amir; LeJeune, Sarah S.; Bledsoe, Andrea; Davidyan, Arik; Gray, Sarah N.; Bohannon‐Worsley, Laurie K.; Woolard, Kevin D.

2017-01-01

Abstract Distal extremity wounds are a significant clinical problem in horses and humans and may benefit from mesenchymal stem cell (MSC) therapy. This study evaluated the effects of direct wound treatment with allogeneic stem cells, in terms of gross, histologic, and transcriptional features of healing. Three full‐thickness cutaneous wounds were created on each distal forelimb in six healthy horses, for a total of six wounds per horse. Umbilical cord‐blood derived equine MSCs were applied to each wound 1 day after wound creation, in one of four forms: (a) normoxic‐ or (b) hypoxic‐preconditioned cells injected into wound margins, or (c) normoxic‐ or (d) hypoxic‐preconditioned cells embedded in an autologous fibrin gel and applied topically to the wound bed. Controls were one blank (saline) injected wound and one blank fibrin gel‐treated wound per horse. Data were collected weekly for 6 weeks and included wound surface area, thermography, gene expression, and histologic scoring. Results indicated that MSC treatment by either delivery method was safe and improved histologic outcomes and wound area. Hypoxic‐preconditioning did not offer an advantage. MSC treatment by injection resulted in statistically significant increases in transforming growth factor beta and cyclooxygenase‐2 expression at week 1. Histologically, significantly more MSC‐treated wounds were categorized as pro‐healing than pro‐inflammatory. Wound area was significantly affected by treatment: MSC‐injected wounds were consistently smaller than gel‐treated or control wounds. In conclusion, MSC therapy shows promise for distal extremity wounds in horses, particularly when applied by direct injection into the wound margin. stem cells translational medicine 2018;7:98–108 PMID:29063737

An overview of protective strategies against ischemia/reperfusion injury: The role of hyperbaric oxygen preconditioning.

PubMed

Hentia, Ciprian; Rizzato, Alex; Camporesi, Enrico; Yang, Zhongjin; Muntean, Danina M; Săndesc, Dorel; Bosco, Gerardo

2018-05-01

Ischemia/reperfusion (I/R) injury, such as myocardial infarction, stroke, and peripheral vascular disease, has been recognized as the most frequent causes of devastating disorders and death currently. Protective effect of various preconditioning stimuli, including hyperbaric oxygen (HBO), has been proposed in the management of I/R. In this study, we searched and reviewed up-to-date published papers to explore the pathophysiology of I/R injury and to understand the mechanisms underlying the protective effect of HBO as conditioning strategy. Animal study and clinic observation support the notion that HBO therapy and conditioning provide beneficial effect against the deleterious effects of postischemic reperfusion. Several explanations have been proposed. The first likely mechanism may be that HBO counteracts hypoxia and reduces I/R injury by improving oxygen delivery to an area with diminished blood flow. Secondly, by reducing hypoxia-ischemia, HBO reduces all the pathological events as a consequence of hypoxia, including tissue edema, increased affective area permeability, postischemia derangement of tissue metabolism, and inflammation. Thirdly, HBO may directly affect cell apoptosis, signal transduction, and gene expression in those that are sensitive to oxygen or hypoxia. HBO provides a reservoir of oxygen at cellular level not only carried by blood, but also by diffusion from the interstitial tissue where it reaches high concentration that may last for several hours, improves endothelial function and rheology, and decreases local inflammation and edema. Evidence suggests the benefits of HBO when used as a preconditioning stimulus in the setting of I/R injury. Translating the beneficial effects of HBO into current practice requires, as for the "conditioning strategies", a thorough consideration of risk factors, comorbidities, and comedications that could interfere with HBO-related protection.

An M-step preconditioned conjugate gradient method for parallel computation

NASA Technical Reports Server (NTRS)

Adams, L.

1983-01-01

This paper describes a preconditioned conjugate gradient method that can be effectively implemented on both vector machines and parallel arrays to solve sparse symmetric and positive definite systems of linear equations. The implementation on the CYBER 203/205 and on the Finite Element Machine is discussed and results obtained using the method on these machines are given.

40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false PM sampling media (e.g., filters... Specified Duty Cycles § 1065.590 PM sampling media (e.g., filters) preconditioning and tare weighing. Before an emission test, take the following steps to prepare PM sampling media (e.g., filters) and equipment...

40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 34 2012-07-01 2012-07-01 false PM sampling media (e.g., filters... Specified Duty Cycles § 1065.590 PM sampling media (e.g., filters) preconditioning and tare weighing. Before an emission test, take the following steps to prepare PM sampling media (e.g., filters) and equipment...

40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 34 2013-07-01 2013-07-01 false PM sampling media (e.g., filters... Specified Duty Cycles § 1065.590 PM sampling media (e.g., filters) preconditioning and tare weighing. Before an emission test, take the following steps to prepare PM sampling media (e.g., filters) and equipment...

40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 33 2011-07-01 2011-07-01 false PM sampling media (e.g., filters... Specified Duty Cycles § 1065.590 PM sampling media (e.g., filters) preconditioning and tare weighing. Before an emission test, take the following steps to prepare PM sampling media (e.g., filters) and equipment...

40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 33 2014-07-01 2014-07-01 false PM sampling media (e.g., filters... Specified Duty Cycles § 1065.590 PM sampling media (e.g., filters) preconditioning and tare weighing. Before an emission test, take the following steps to prepare PM sampling media (e.g., filters) and equipment...

Cognitive Preconditions of Early Reading and Spelling: A Latent-Variable Approach with Longitudinal Data

ERIC Educational Resources Information Center

Preßler, Anna-Lena; Könen, Tanja; Hasselhorn, Marcus; Krajewski, Kristin

2014-01-01

The aim of the present study was to empirically disentangle the interdependencies of the impact of nonverbal intelligence, working memory capacities, and phonological processing skills on early reading decoding and spelling within a latent variable approach. In a sample of 127 children, these cognitive preconditions were assessed before the onset…

Measuring Five Preconditions of Success for African American Male Students in Community Colleges

ERIC Educational Resources Information Center

McManus, Kimberly Ozella

2017-01-01

The purpose of this study was to measure and compare five preconditions for success of African American male community college students at community colleges by determining if there is a relationship between a) GPA and credits earned, utilizing Wood and Harris' (2012; 2016) Community College Survey of Men (CCSM, 2014) and Community College Success…

An iterative method for the Helmholtz equation

NASA Technical Reports Server (NTRS)

Bayliss, A.; Goldstein, C. I.; Turkel, E.

1983-01-01

An iterative algorithm for the solution of the Helmholtz equation is developed. The algorithm is based on a preconditioned conjugate gradient iteration for the normal equations. The preconditioning is based on an SSOR sweep for the discrete Laplacian. Numerical results are presented for a wide variety of problems of physical interest and demonstrate the effectiveness of the algorithm.

The Interaction of High-Speed Turbulence with Flames: Global Properties and Internal Flame Structure

DTIC Science & Technology

2009-09-28

S L, on all scales, including that of the laminar flame thickness, presents a number of both experimental and numerical challenges. Hereafter, we...fuel preconditioning, compression of the overall system, or propagation of large-scale shocks . Probing such regimes experimentally requires either...reactions are modeled using the first-order Arrhenius kinetics dY dt ≡ ẇ = −AρY exp ( − Q RT ) , (5) where A is the pre-exponential factor, Q is the

HMC algorithm with multiple time scale integration and mass preconditioning

NASA Astrophysics Data System (ADS)

Urbach, C.; Jansen, K.; Shindler, A.; Wenger, U.

2006-01-01

We present a variant of the HMC algorithm with mass preconditioning (Hasenbusch acceleration) and multiple time scale integration. We have tested this variant for standard Wilson fermions at β=5.6 and at pion masses ranging from 380 to 680 MeV. We show that in this situation its performance is comparable to the recently proposed HMC variant with domain decomposition as preconditioner. We give an update of the "Berlin Wall" figure, comparing the performance of our variant of the HMC algorithm to other published performance data. Advantages of the HMC algorithm with mass preconditioning and multiple time scale integration are that it is straightforward to implement and can be used in combination with a wide variety of lattice Dirac operators.

On linearization and preconditioning for radiation diffusion coupled to material thermal conduction equations

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

Feng, Tao, E-mail: fengtao2@mail.ustc.edu.cn; Graduate School of China Academy Engineering Physics, Beijing 100083; An, Hengbin, E-mail: an_hengbin@iapcm.ac.cn

2013-03-01

Jacobian-free Newton–Krylov (JFNK) method is an effective algorithm for solving large scale nonlinear equations. One of the most important advantages of JFNK method is that there is no necessity to form and store the Jacobian matrix of the nonlinear system when JFNK method is employed. However, an approximation of the Jacobian is needed for the purpose of preconditioning. In this paper, JFNK method is employed to solve a class of non-equilibrium radiation diffusion coupled to material thermal conduction equations, and two preconditioners are designed by linearizing the equations in two methods. Numerical results show that the two preconditioning methods canmore » improve the convergence behavior and efficiency of JFNK method.« less

Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

PubMed Central

2015-01-01

Finding transition paths for chemical reactions can be computationally costly owing to the level of quantum-chemical theory needed for accuracy. Here, we show that a multilevel preconditioning scheme that was recently introduced (Tempkin et al. J. Chem. Phys.2014, 140, 184114) can be used to accelerate quantum-chemical string calculations. We demonstrate the method by finding minimum-energy paths for two well-characterized reactions: tautomerization of malonaldehyde and Claissen rearrangement of chorismate to prephanate. For these reactions, we show that preconditioning density functional theory (DFT) with a semiempirical method reduces the computational cost for reaching a converged path that is an optimum under DFT by several fold. The approach also shows promise for free energy calculations when thermal noise can be controlled. PMID:25516726

Investigation of Reperfusion Injury and Ischemic Preconditioning in Microsurgry

PubMed Central

Wang, Wei Zhong

2008-01-01

Ischemia/reperfusion (I/R) is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive surgeries in the extremities. Salvage of a prolonged ischemic extremity or flap still remains a challenge for the microvascular surgeon. One of the common complications after microsurgery is I/R-induced tissue death or I/R injury. Twenty years after the discovery, ischemic preconditioning (IPC) has emerged as a powerful method for attenuating I/R injury in a variety of organs or tissues. However, its therapeutic expectations still need to be fulfilled. In this article, the author reviews some important experimental evidences of I/R injury as well as preconditioning-induced protection in the fields relevant to microsurgery. PMID:18946882

Automatic Blocking Of QR and LU Factorizations for Locality

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

Yi, Q; Kennedy, K; You, H

2004-03-26

QR and LU factorizations for dense matrices are important linear algebra computations that are widely used in scientific applications. To efficiently perform these computations on modern computers, the factorization algorithms need to be blocked when operating on large matrices to effectively exploit the deep cache hierarchy prevalent in today's computer memory systems. Because both QR (based on Householder transformations) and LU factorization algorithms contain complex loop structures, few compilers can fully automate the blocking of these algorithms. Though linear algebra libraries such as LAPACK provides manually blocked implementations of these algorithms, by automatically generating blocked versions of the computations, moremore » benefit can be gained such as automatic adaptation of different blocking strategies. This paper demonstrates how to apply an aggressive loop transformation technique, dependence hoisting, to produce efficient blockings for both QR and LU with partial pivoting. We present different blocking strategies that can be generated by our optimizer and compare the performance of auto-blocked versions with manually tuned versions in LAPACK, both using reference BLAS, ATLAS BLAS and native BLAS specially tuned for the underlying machine architectures.« less

The Nucleation Rate of Single O2 Nanobubbles at Pt Nanoelectrodes.

PubMed

Soto, Álvaro Moreno; German, Sean R; Ren, Hang; van der Meer, Devaraj; Lohse, Detlef; Edwards, Martin A; White, Henry S

2018-06-13

Nanobubble nucleation is a problem that affects efficiency in electrocatalytic reactions since those bubbles can block the surface of the catalytic sites. In this article, we focus on the nucleation rate of O 2 nanobubbles resulting from the electrooxidation of H 2 O 2 at Pt disk nanoelectrodes. Bubbles form almost instantaneously when a critical peak current, i nb p , is applied, but for lower currents, bubble nucleation is a stochastic process in which the nucleation (induction) time, t ind , dramatically decreases as the applied current approaches i nb p , a consequence of the local supersaturation level, ζ, increasing at high currents. Here, by applying different currents below i nb p , nanobubbles take some time to nucleate and block the surface of the Pt electrode at which the reaction occurs, providing a means to measure the stochastic t ind . We study in detail the different conditions in which nanobubbles appear, concluding that the electrode surface needs to be preconditioned to achieve reproducible results. We also measure the activation energy for bubble nucleation, E a , which varies in the range from (6 to 30) kT, and assuming a spherically cap-shaped nanobubble nucleus, we determine the footprint diameter L = 8-15 nm, the contact angle to the electrode surface θ = 135-155°, and the number of O 2 molecules contained in the nucleus (50 to 900 molecules).

Cloning and characterization of the canine receptor for advanced glycation end products.

PubMed

Murua Escobar, Hugo; Soller, Jan T; Sterenczak, Katharina A; Sperveslage, Jan D; Schlueter, Claudia; Burchardt, Birgit; Eberle, Nina; Fork, Melanie; Nimzyk, Rolf; Winkler, Susanne; Nolte, Ingo; Bullerdiek, Jörn

2006-03-15

Metastasis is one of the major problems when dealing with malignant neoplasias. Accordingly, the finding of molecular targets, which can be addressed to reduce tumour metastasising, will have significant impact on the development of new therapeutic approaches. Recently, the receptor for advanced glycation end products (RAGE)-high mobility group B1 (HMGB1) protein complex has been shown to have significant influence on invasiveness, growth and motility of tumour cells, which are essential characteristics required for metastatic behaviour. A set of in vitro and in vivo approaches showed that blocking of this complex resulted in drastic suppression of tumour cell growth. Due to the similarities of human and canine cancer the dog has joined the common rodent animal model for therapeutic and preclinical studies. However, complete characterisation of the protein complex is a precondition to a therapeutic approach based on the blocking of the RAGE-HMGB1 complex to spontaneously occurring tumours in dogs. We recently characterised the canine HMGB1 gene and protein completely. Here we present the complete characterisation of the canine RAGE gene including its 1384 bp mRNA, the 1215 bp protein coding sequence, the 2835 bp genomic structure, chromosomal localisation, gene expression pattern, and its 404 amino acid protein. Furthermore we compared the CDS of six different canine breeds and screened them for single nucleotide polymorphisms.

Oxytocin signaling in basolateral and central amygdala nuclei differentially regulates the acquisition, expression, and extinction of context-conditioned fear in rats

PubMed Central

Campbell-Smith, Emma J.; Holmes, Nathan M.; Lingawi, Nura W.; Panayi, Marios C.

2015-01-01

The present study investigated how oxytocin (OT) signaling in the central (CeA) and basolateral (BLA) amygdala affects acquisition, expression, and extinction of context-conditioned fear (freezing) in rats. In the first set of experiments, acquisition of fear to a shocked context was impaired by a preconditioning infusion of synthetic OT into the CeA (Experiment 1) or BLA (Experiment 2). In the second set of experiments, expression of context fear was enhanced by a pre- or post-extinction CeA infusion of synthetic OT (Experiments 3–6) or a selective OT receptor agonist, TGOT (Experiment 4). This enhancement of fear was blocked by coadministration of an OT receptor antagonist, OTA (Experiment 5) and context fear was suppressed by administration of the antagonist alone (Experiment 6). In the third set of experiments, expression of context fear was suppressed, not enhanced, by a preextinction BLA infusion of synthetic OT or a selective OT receptor agonist, TGOT (Experiments 7 and 8). This suppression of fear was blocked by coadministration of the OT receptor antagonist, OTA (Experiment 8). Taken together, these findings show that the involvement of the CeA and BLA in expression and extinction of context-conditioned fear is dissociable, and imply a critical role for oxytocin signaling in amygdala-based regulation of aversive learning. PMID:25878137

Effect of preconditioning on silver leaching and bromide removal properties of silver-impregnated activated carbon (SIAC).

PubMed

Rajaeian, Babak; Allard, Sébastien; Joll, Cynthia; Heitz, Anna

2018-07-01

Silver impregnated activated carbon (SIAC) has been found to be effective in mitigating the formation of brominated-disinfection by products during drinking water treatment. However, there are still uncertainties regarding its silver leaching properties, and strategies for the prevention of silver leaching have remained elusive. This study focused on the evaluation of one type of commercially available SIAC for its ability to remove bromide while minimising silver leaching from the material. Both synthetic and real water matrices were tested. Depending on solution pH, it was found that changing the surface charge properties of SIAC, as measured by the point of zero charge pH, can result in additional bromide removal while minimising the extent of silver leaching. To better understand the mechanism of silver leaching from the SIAC, eight preconditioning environments, i.e. variable pH and ionic strength were tested for a fixed amount of SIAC and two preconditioning environments were selected for a more detailed investigation. Experiments carried out in synthetic water showed that preconditioning at pH 10.4 did not deteriorate the capacity of SIAC to remove bromide, but significantly decreased the release of silver in the form of ionic silver (Ag + ), silver bromide (AgBr) and silver chloride (AgCl) from 40% for the pristine to 3% for the treated SIAC. This was confirmed using a groundwater sample. These results suggest that preconditioned SIAC has the potential to be an effective method for bromide removal with minimised silver leaching in a long-term field application for drinking water production. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sleep Is Critical for Remote Preconditioning-Induced Neuroprotection.

PubMed

Brager, Allison J; Yang, Tao; Ehlen, J Christopher; Simon, Roger P; Meller, Robert; Paul, Ketema N

2016-11-01

Episodes of brief limb ischemia (remote preconditioning) in mice induce tolerance to modeled ischemic stroke (focal brain ischemia). Since stroke outcomes are in part dependent on sleep-wake history, we sought to determine if sleep is critical for the neuroprotective effect of limb ischemia. EEG/EMG recording electrodes were implanted in mice. After a 24 h baseline recording, limb ischemia was induced by tightening an elastic band around the left quadriceps for 10 minutes followed by 10 minutes of release for two cycles. Two days following remote preconditioning, a second 24 h EEG/EMG recording was completed and was immediately followed by a 60-minute suture occlusion of the middle cerebral artery (modeled ischemic stroke). This experiment was then repeated in a model of circadian and sleep abnormalities ( Bmal1 knockout [KO] mice sleep 2 h more than wild-type littermates). Brain infarction was determined by vital dye staining, and sleep was assessed by trained identification of EEG/EMG recordings. Two days after limb ischemia, wild-type mice slept an additional 2.4 h. This additional sleep was primarily comprised of non-rapid eye movement (NREM) sleep during the middle of the light-phase (i.e., naps). Repeating the experiment but preventing increases in sleep after limb ischemia abolished tolerance to ischemic stroke. In Bmal1 knockout mice, remote preconditioning did not increase daily sleep nor provide tolerance to subsequent focal ischemia. These results suggest that sleep induced by remote preconditioning is both sufficient and necessary for its neuroprotective effects on stroke outcome. © 2016 Associated Professional Sleep Societies, LLC.

Exercise and Cardiac Preconditioning Against Ischemia Reperfusion Injury

PubMed Central

Quindry, John C; Hamilton, Karyn L

2013-01-01

Cardiovascular disease (CVD), including ischemia reperfusion (IR) injury, remains a major cause of morbidity and mortality in industrialized nations. Ongoing research is aimed at uncovering therapeutic interventions against IR injury. Regular exercise participation is recognized as an important lifestyle intervention in the prevention and treatment of CVD and IR injury. More recent understanding reveals that moderate intensity aerobic exercise is also an important experimental model for understanding the cellular mechanisms of cardioprotection against IR injury. An important discovery in this regard was the observation that one-to-several days of exercise will attenuate IR injury. This phenomenon has been observed in young and old hearts of both sexes. Due to the short time course of exercise induced protection, IR injury prevention must be mediated by acute biochemical alterations within the myocardium. Research over the last decade reveals that redundant mechanisms account for exercise induced cardioprotection against IR. While much is now known about exercise preconditioning against IR injury, many questions remain. Perhaps most pressing, is what mechanisms mediate cardioprotection in aged hearts and what sex-dependent differences exist. Given that that exercise preconditioning is a polygenic effect, it is likely that multiple mediators of exercise induced cardioprotection have yet to be uncovered. Also unknown, is whether post translational modifications due to exercise are responsible for IR injury prevention. This review will provide an overview the major mechanisms of IR injury and exercise preconditioning. The discussion highlights many promising avenues for further research and describes how exercise preconditioning may continue to be an important scientific paradigm in the translation of cardioprotection research to the clinic. PMID:23909636

Low-energy shock wave preconditioning reduces renal ischemic reperfusion injury caused by renal artery occlusion.

PubMed

Xue, Yuquan; Xu, Zhibin; Chen, Haiwen; Gan, Weimin; Chong, Tie

2017-07-01

To evaluate whether low energy shock wave preconditioning could reduce renal ischemic reperfusion injury caused by renal artery occlusion. The right kidneys of 64 male Sprague Dawley rats were removed to establish an isolated kidney model. The rats were then divided into four treatment groups: Group 1 was the sham treatment group; Group 2, received only low-energy (12 kv, 1 Hz, 200 times) shock wave preconditioning; Group 3 received the same low-energy shock wave preconditioning as Group 2, and then the left renal artery was occluded for 45 minutes; and Group 4 had the left renal artery occluded for 45 minutes. At 24 hours and one-week time points after reperfusion, serum inducible nitric oxide synthase (iNOS), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), creatinine (Cr), and cystatin C (Cys C) levels were measured, malondialdehyde (MDA) in kidney tissue was detected, and changes in nephric morphology were evaluated by light and electron microscopy. Twenty-four hours after reperfusion, serum iNOS, NGAL, Cr, Cys C, and MDA levels in Group 3 were significantly lower than those in Group 4; light and electron microscopy showed that the renal tissue injury in Group 3 was significantly lighter than that in Group 4. One week after reperfusion, serum NGAL, KIM-1, and Cys C levels in Group 3 were significantly lower than those in Group 4. Low-energy shock wave preconditioning can reduce renal ischemic reperfusion injury caused by renal artery occlusion in an isolated kidney rat model.

Possible role of thromboxane A2 in remote hind limb preconditioning-induced cardioprotection.

PubMed

Sharma, Roohani; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

2016-01-01

Remote hind limb preconditioning (RIPC) is a protective strategy in which short episodes of ischemia and reperfusion in a remote organ (hind limb) protects the target organ (heart) against sustained ischemic reperfusion injury. The present study was designed to investigate the possible role of thromboxane A2 in RIPC-induced cardioprotection in rats. Remote hind limb preconditioning was performed by four episodes of 5 min of inflation and 5 min of deflation of pressure cuff. Occlusion of the hind limb with blood pressure cuff is most feasible, non-invasive, clinically relevant, and safe method for inducing RIPC. Isolated rat hearts were perfused on Langendorff apparatus and were subjected to global ischemia for 30 min followed by 120-min reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) were measured in coronary effluent to assess the degree of myocardial injury. The extent of myocardial infarct size along with the functional parameters including left ventricular developed pressure (LVDP), dp/dtmax, and dp/dtmin were also measured. Ozagrel (thromboxane synthase inhibitor) and seratrodast (thromboxane A2 receptor antagonist) were employed as pharmacological modulators of thromboxane A2. Remote hind limb preconditioning significantly attenuated ischemia/reperfusion-induced myocardial injury and produced cardioprotective effects. However, administration of ozagrel and seratrodast completely abolished the cardioprotective effects of RIPC suggesting the key role of thromboxane A2 in RIPC-induced cardioprotection. It may be concluded that brief episodes of preconditioning ischemia and reperfusion activates the thromboxane synthase enzyme that produces thromboxane A2, which may elicit cardioprotection either involving humoral or neurogenic pathway.

Modeling of frequency-domain scalar wave equation with the average-derivative optimal scheme based on a multigrid-preconditioned iterative solver

NASA Astrophysics Data System (ADS)

Cao, Jian; Chen, Jing-Bo; Dai, Meng-Xue

2018-01-01

An efficient finite-difference frequency-domain modeling of seismic wave propagation relies on the discrete schemes and appropriate solving methods. The average-derivative optimal scheme for the scalar wave modeling is advantageous in terms of the storage saving for the system of linear equations and the flexibility for arbitrary directional sampling intervals. However, using a LU-decomposition-based direct solver to solve its resulting system of linear equations is very costly for both memory and computational requirements. To address this issue, we consider establishing a multigrid-preconditioned BI-CGSTAB iterative solver fit for the average-derivative optimal scheme. The choice of preconditioning matrix and its corresponding multigrid components is made with the help of Fourier spectral analysis and local mode analysis, respectively, which is important for the convergence. Furthermore, we find that for the computation with unequal directional sampling interval, the anisotropic smoothing in the multigrid precondition may affect the convergence rate of this iterative solver. Successful numerical applications of this iterative solver for the homogenous and heterogeneous models in 2D and 3D are presented where the significant reduction of computer memory and the improvement of computational efficiency are demonstrated by comparison with the direct solver. In the numerical experiments, we also show that the unequal directional sampling interval will weaken the advantage of this multigrid-preconditioned iterative solver in the computing speed or, even worse, could reduce its accuracy in some cases, which implies the need for a reasonable control of directional sampling interval in the discretization.

Enhanced shock wave generation via pre-breakdown acceleration using water electrolysis in negative streamer pulsed spark discharges

NASA Astrophysics Data System (ADS)

Lee, Kern; Chung, Kyoung-Jae; Hwang, Y. S.

2018-03-01

This paper presents a method for enhancement of shock waves generated from underwater pulsed spark discharges with negative (anode-directed) subsonic streamers, for which the pre-breakdown process is accelerated by preconditioning a gap with water electrolysis. Hydrogen microbubbles are produced at the cathode by the electrolysis and move towards the anode during the preconditioning phase. The numbers and spatial distributions of the microbubbles vary with the amplitude and duration of each preconditioning pulse. Under our experimental conditions, the optimum pulse duration is determined to be ˜250 ms at a pulse voltage of 400 V, where the buoyancy force overwhelms the electric force and causes the microbubbles to be swept out from the water gap. When a high-voltage pulse is applied to the gap just after the preconditioning pulse, the pre-breakdown process is significantly accelerated in the presence of the microbubbles. At the optimum preconditioning pulse duration, the average breakdown delay is reduced by 87% and, more importantly, the energy consumed during the pre-breakdown period decreases by 83%. This reduced energy consumption during the pre-breakdown period, when combined with the morphological advantages of negative streamers, such as thicker and longer stalks, leads to a significant improvement in the measured peak pressure (˜40%) generated by the underwater pulsed spark discharge. This acceleration of pre-breakdown using electrolysis overcomes the biggest drawback of negative subsonic discharges, which is slow vapor bubble formation due to screening effects, and thus enhances the efficiency of the shock wave generation process using pulsed spark discharges in water.

Detailed qualitative dynamic knowledge representation using a BioNetGen model of TLR-4 signaling and preconditioning.

PubMed

An, Gary C; Faeder, James R

2009-01-01

Intracellular signaling/synthetic pathways are being increasingly extensively characterized. However, while these pathways can be displayed in static diagrams, in reality they exist with a degree of dynamic complexity that is responsible for heterogeneous cellular behavior. Multiple parallel pathways exist and interact concurrently, limiting the ability to integrate the various identified mechanisms into a cohesive whole. Computational methods have been suggested as a means of concatenating this knowledge to aid in the understanding of overall system dynamics. Since the eventual goal of biomedical research is the identification and development of therapeutic modalities, computational representation must have sufficient detail to facilitate this 'engineering' process. Adding to the challenge, this type of representation must occur in a perpetual state of incomplete knowledge. We present a modeling approach to address this challenge that is both detailed and qualitative. This approach is termed 'dynamic knowledge representation,' and is intended to be an integrated component of the iterative cycle of scientific discovery. BioNetGen (BNG), a software platform for modeling intracellular signaling pathways, was used to model the toll-like receptor 4 (TLR-4) signal transduction cascade. The informational basis of the model was a series of reference papers on modulation of (TLR-4) signaling, and some specific primary research papers to aid in the characterization of specific mechanistic steps in the pathway. This model was detailed with respect to the components of the pathway represented, but qualitative with respect to the specific reaction coefficients utilized to execute the reactions. Responsiveness to simulated lipopolysaccharide (LPS) administration was measured by tumor necrosis factor (TNF) production. Simulation runs included evaluation of initial dose-dependent response to LPS administration at 10, 100, 1000 and 10,000, and a subsequent examination of preconditioning behavior with increasing LPS at 10, 100, 1000 and 10,000 and a secondary dose of LPS at 10,000 administered at approximately 27h of simulated time. Simulations of 'knockout' versions of the model allowed further examination of the interactions within the signaling cascade. The model demonstrated a dose-dependent TNF response curve to increasing stimulus by LPS. Preconditioning simulations demonstrated a similar dose-dependency of preconditioning doses leading to attenuation of response to subsequent LPS challenge - a 'tolerance' dynamic. These responses match dynamics reported in the literature. Furthermore, the simulated 'knockout' results suggested the existence and need for dual negative feedback control mechanisms, represented by the zinc ring-finger protein A20 and inhibitor kappa B proteins (IkappaB), in order for both effective attenuation of the initial stimulus signal and subsequent preconditioned 'tolerant' behavior. We present an example of detailed, qualitative dynamic knowledge representation using the TLR-4 signaling pathway, its control mechanisms and overall behavior with respect to preconditioning. The intent of this approach is to demonstrate a method of translating the extensive mechanistic knowledge being generated at the basic science level into an executable framework that can provide a means of 'conceptual model verification.' This allows for both the 'checking' of the dynamic consequences of a mechanistic hypothesis and the creation of a modular component of an overall model directed at the engineering goal of biomedical research. It is hoped that this paper will increase the use of knowledge representation and communication in this fashion, and facilitate the concatenation and integration of community-wide knowledge.

HSP70.1 AND -70.3 ARE REQUIRED FOR LATE-PHASE PROTECTION INDUCED BY ISCHEMIC PRECONDITIONING OF MOUSE HEARTS

EPA Science Inventory

Heat-Shock Proteins 70.1 and 70.3 Are Required for Late-phase Protection
Induced by Ischemic Preconditioning of the Mouse Heart
Craig R. Hampton 1 , Akira Shimamoto 1 , Christine L. Rothnie 1 , Jeaneatte Griscavage-Ennis 1 ,
Albert Chong 1 , David J. Dix 2 , Edward D. Ve...

Audiovisual preconditioning enhances the efficacy of an anatomical dissection course: A randomised study.

PubMed

Collins, Anne M; Quinlan, Christine S; Dolan, Roisin T; O'Neill, Shane P; Tierney, Paul; Cronin, Kevin J; Ridgway, Paul F

2015-07-01

The benefits of incorporating audiovisual materials into learning are well recognised. The outcome of integrating such a modality in to anatomical education has not been reported previously. The aim of this randomised study was to determine whether audiovisual preconditioning is a useful adjunct to learning at an upper limb dissection course. Prior to instruction participants completed a standardised pre course multiple-choice questionnaire (MCQ). The intervention group was subsequently shown a video with a pre-recorded commentary. Following initial dissection, both groups completed a second MCQ. The final MCQ was completed at the conclusion of the course. Statistical analysis confirmed a significant improvement in the performance in both groups over the duration of the three MCQs. The intervention group significantly outperformed their control group counterparts immediately following audiovisual preconditioning and in the post course MCQ. Audiovisual preconditioning is a practical and effective tool that should be incorporated in to future course curricula to optimise learning. Level of evidence This study appraises an intervention in medical education. Kirkpatrick Level 2b (modification of knowledge). Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Substitution of Hospital Care with Primary Care: Defining the Conditions of Primary Care Plus

PubMed Central

Kroese, Mariëlle Elisabeth Aafje Lydia; Spreeuwenberg, Marieke Dingena; Elissen, Arianne Mathilda Josephus; Meerlo, Ronald Johan; Hanraets, Monique Margaretha Henriëtte; Ruwaard, Dirk

2016-01-01

Objective: To analyse barriers and facilitators in substituting hospital care with primary care to define preconditions for successful implementation. Methods: A descriptive feasibility study was performed to collect information on the feasibility of substituting hospital care with primary care. General practitioners were able to refer patients, about whom they had doubts regarding diagnosis, treatment and/or the need to refer to hospital care, to medical specialists who performed low-complex consultations at general practitioner practices. Qualitative data were collected through interviews with general practitioners and medical specialists, focus groups and notes from meetings in the Netherlands between April 2013 and January 2014. Data were analysed using a conventional content analysis which resulted in categorised barriers, facilitators and policy adjustments, after which preconditions were formulated. Results: The most important preconditions were make arrangements on governmental level, arrange a collective integrated IT-system, determine the appropriate profile for medical specialists, design a referral protocol for eligible patients, arrange deliberation possibilities for general practitioners and medical specialists and formulate a diagnostic protocol. Conclusions: The barriers, facilitators and formulated preconditions provided relevant input to change the design of substituting hospital care with primary care. PMID:27616956

Reperfusion kinase phosphorylation is essential but not sufficient in the mediation of pharmacological preconditioning: Characterisation in the bi-phasic profile of early and late protection.

PubMed

Bell, Robert M; Clark, James E; Hearse, David J; Shattock, Michael J

2007-01-01

Pharmacological preconditioning (PPC) triggers early (ePPC) and delayed protection (dPPC), occurring within 1 h or after 24 h following the preconditioning stimulus, respectively, through recruitment of protein kinase signalling. Angiotensin II (ATII) is a recognised trigger of PPC, recruiting kinases and transcription factors known to be involved in both phases of protection. Our objectives were to determine whether ATII is capable of triggering dPPC and whether recruitment of pro-survival kinases, Akt and extracellular signal-regulated kinase (ERK), following the injurious ischaemic insult is essential for the mediation of PPC. In a mouse Langendorff model of ischaemia/reperfusion injury, we undertook to determine whether ATII triggers both ePPC and dPPC. Western blot analysis was used to determine kinase phosphorylation at reperfusion, and kinase inhibitors wortmannin and PD98059 were used to ascertain the significance of kinase regulation. We demonstrated that ATII triggered PPC with attenuation of infarction at 1 and 24 h (19+/-4% and 25+/-4% versus control, 35+/-4% of risk zone, p < 0.05), consistent with the ePPC and dPPC time-course. This bi-phasic protection was associated with significant post-ischaemic phosphorylation of both Akt and ERK within the first 5 min of reperfusion. Akt and ERK phosphorylation was increased following ePPC by 4.5+/-0.5 and 1.9+/-0.6 fold, respectively (p < 0.001), and dPPC by 24+/-2.0 and 2.1+/-0.1 fold, respectively (p < 0.001). Both wortmannin and PD98059 administered during reperfusion ameliorated the phosphorylation of Akt and ERK and abrogated the resistance to infarction resulting from both ePPC and dPPC (33+/-3% and 35+/-4%, respectively, versus controls 33+/-4% and 33+/-5%, p = NS). There was no evidence of augmented phosphorylation of either p38 kinase or JNK at either time point. We demonstrate that PPC results in a clearly delineated time-course of bi-phasic protection against injurious ischemic injury that is correlated with reperfusion kinase phosphorylation of both Akt and ERK. These data indicate a novel mechanism of early and particularly delayed preconditioning.

Fourier domain preconditioned conjugate gradient algorithm for atmospheric tomography.

PubMed

Yang, Qiang; Vogel, Curtis R; Ellerbroek, Brent L

2006-07-20

By 'atmospheric tomography' we mean the estimation of a layered atmospheric turbulence profile from measurements of the pupil-plane phase (or phase gradients) corresponding to several different guide star directions. We introduce what we believe to be a new Fourier domain preconditioned conjugate gradient (FD-PCG) algorithm for atmospheric tomography, and we compare its performance against an existing multigrid preconditioned conjugate gradient (MG-PCG) approach. Numerical results indicate that on conventional serial computers, FD-PCG is as accurate and robust as MG-PCG, but it is from one to two orders of magnitude faster for atmospheric tomography on 30 m class telescopes. Simulations are carried out for both natural guide stars and for a combination of finite-altitude laser guide stars and natural guide stars to resolve tip-tilt uncertainty.

Low-Rank Correction Methods for Algebraic Domain Decomposition Preconditioners

DOE PAGES

Li, Ruipeng; Saad, Yousef

2017-08-01

This study presents a parallel preconditioning method for distributed sparse linear systems, based on an approximate inverse of the original matrix, that adopts a general framework of distributed sparse matrices and exploits domain decomposition (DD) and low-rank corrections. The DD approach decouples the matrix and, once inverted, a low-rank approximation is applied by exploiting the Sherman--Morrison--Woodbury formula, which yields two variants of the preconditioning methods. The low-rank expansion is computed by the Lanczos procedure with reorthogonalizations. Numerical experiments indicate that, when combined with Krylov subspace accelerators, this preconditioner can be efficient and robust for solving symmetric sparse linear systems. Comparisonsmore » with pARMS, a DD-based parallel incomplete LU (ILU) preconditioning method, are presented for solving Poisson's equation and linear elasticity problems.« less

Finding Chemical Reaction Paths with a Multilevel Preconditioning Protocol

DOE PAGES

Kale, Seyit; Sode, Olaseni; Weare, Jonathan; ...

2014-11-07

Finding transition paths for chemical reactions can be computationally costly owing to the level of quantum-chemical theory needed for accuracy. Here, we show that a multilevel preconditioning scheme that was recently introduced (Tempkin et al. J. Chem. Phys. 2014, 140, 184114) can be used to accelerate quantum-chemical string calculations. We demonstrate the method by finding minimum-energy paths for two well-characterized reactions: tautomerization of malonaldehyde and Claissen rearrangement of chorismate to prephanate. For these reactions, we show that preconditioning density functional theory (DFT) with a semiempirical method reduces the computational cost for reaching a converged path that is an optimum undermore » DFT by several fold. In conclusion, the approach also shows promise for free energy calculations when thermal noise can be controlled.« less

Shape reanalysis and sensitivities utilizing preconditioned iterative boundary solvers

NASA Technical Reports Server (NTRS)

Guru Prasad, K.; Kane, J. H.

1992-01-01

The computational advantages associated with the utilization of preconditined iterative equation solvers are quantified for the reanalysis of perturbed shapes using continuum structural boundary element analysis (BEA). Both single- and multi-zone three-dimensional problems are examined. Significant reductions in computer time are obtained by making use of previously computed solution vectors and preconditioners in subsequent analyses. The effectiveness of this technique is demonstrated for the computation of shape response sensitivities required in shape optimization. Computer times and accuracies achieved using the preconditioned iterative solvers are compared with those obtained via direct solvers and implicit differentiation of the boundary integral equations. It is concluded that this approach employing preconditioned iterative equation solvers in reanalysis and sensitivity analysis can be competitive with if not superior to those involving direct solvers.

Preconditioning of the background error covariance matrix in data assimilation for the Caspian Sea

NASA Astrophysics Data System (ADS)

Arcucci, Rossella; D'Amore, Luisa; Toumi, Ralf

2017-06-01

Data Assimilation (DA) is an uncertainty quantification technique used for improving numerical forecasted results by incorporating observed data into prediction models. As a crucial point into DA models is the ill conditioning of the covariance matrices involved, it is mandatory to introduce, in a DA software, preconditioning methods. Here we present first studies concerning the introduction of two different preconditioning methods in a DA software we are developing (we named S3DVAR) which implements a Scalable Three Dimensional Variational Data Assimilation model for assimilating sea surface temperature (SST) values collected into the Caspian Sea by using the Regional Ocean Modeling System (ROMS) with observations provided by the Group of High resolution sea surface temperature (GHRSST). We also present the algorithmic strategies we employ.

Low-Rank Correction Methods for Algebraic Domain Decomposition Preconditioners

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

Li, Ruipeng; Saad, Yousef

This study presents a parallel preconditioning method for distributed sparse linear systems, based on an approximate inverse of the original matrix, that adopts a general framework of distributed sparse matrices and exploits domain decomposition (DD) and low-rank corrections. The DD approach decouples the matrix and, once inverted, a low-rank approximation is applied by exploiting the Sherman--Morrison--Woodbury formula, which yields two variants of the preconditioning methods. The low-rank expansion is computed by the Lanczos procedure with reorthogonalizations. Numerical experiments indicate that, when combined with Krylov subspace accelerators, this preconditioner can be efficient and robust for solving symmetric sparse linear systems. Comparisonsmore » with pARMS, a DD-based parallel incomplete LU (ILU) preconditioning method, are presented for solving Poisson's equation and linear elasticity problems.« less

Using HFACS-Healthcare to Identify Systemic Vulnerabilities During Surgery.

PubMed

Cohen, Tara N; Francis, Sarah E; Wiegmann, Douglas A; Shappell, Scott A; Gewertz, Bruce L

2018-03-01

The Human Factors Analysis and Classification System for Healthcare (HFACS-Healthcare) was used to classify surgical near miss events reported via a hospital's event reporting system over the course of 1 year. Two trained analysts identified causal factors within each event narrative and subsequently categorized the events using HFACS-Healthcare. Of 910 original events, 592 could be analyzed further using HFACS-Healthcare, resulting in the identification of 726 causal factors. Most issues (n = 436, 60.00%) involved preconditions for unsafe acts, followed by unsafe acts (n = 257, 35.39%), organizational influences (n = 27, 3.72%), and supervisory factors (n = 6, 0.82%). These findings go beyond the traditional methods of trending incident data that typically focus on documenting the frequency of their occurrence. Analyzing near misses based on their underlying contributing human factors affords a greater opportunity to develop process improvements to reduce reoccurrence and better provide patient safety approaches.

A Comparison of Solver Performance for Complex Gastric Electrophysiology Models

PubMed Central

Sathar, Shameer; Cheng, Leo K.; Trew, Mark L.

2016-01-01

Computational techniques for solving systems of equations arising in gastric electrophysiology have not been studied for efficient solution process. We present a computationally challenging problem of simulating gastric electrophysiology in anatomically realistic stomach geometries with multiple intracellular and extracellular domains. The multiscale nature of the problem and mesh resolution required to capture geometric and functional features necessitates efficient solution methods if the problem is to be tractable. In this study, we investigated and compared several parallel preconditioners for the linear systems arising from tetrahedral discretisation of electrically isotropic and anisotropic problems, with and without stimuli. The results showed that the isotropic problem was computationally less challenging than the anisotropic problem and that the application of extracellular stimuli increased workload considerably. Preconditioning based on block Jacobi and algebraic multigrid solvers were found to have the best overall solution times and least iteration counts, respectively. The algebraic multigrid preconditioner would be expected to perform better on large problems. PMID:26736543

Dynamic Vibration Cooperates with Connective Tissue Growth Factor to Modulate Stem Cell Behaviors

PubMed Central

Tong, Zhixiang; Zerdoum, Aidan B.; Duncan, Randall L.

2014-01-01

Vocal fold disorders affect 3–9% of the U.S. population. Tissue engineering offers an alternative strategy for vocal fold repair. Successful engineering of vocal fold tissues requires a strategic combination of therapeutic cells, biomimetic scaffolds, and physiologically relevant mechanical and biochemical factors. Specifically, we aim to create a vocal fold-like microenvironment to coax stem cells to adopt the phenotype of vocal fold fibroblasts (VFFs). Herein, high frequency vibratory stimulations and soluble connective tissue growth factor (CTGF) were sequentially introduced to mesenchymal stem cells (MSCs) cultured on a poly(ɛ-caprolactone) (PCL)-derived microfibrous scaffold for a total of 6 days. The initial 3-day vibratory culture resulted in an increased production of hyaluronic acids (HA), tenascin-C (TNC), decorin (DCN), and matrix metalloproteinase-1 (MMP1). The subsequent 3-day CTGF treatment further enhanced the cellular production of TNC and DCN, whereas CTGF treatment alone without the vibratory preconditioning significantly promoted the synthesis of collagen I (Col 1) and sulfated glycosaminoglycans (sGAGs). The highest level of MMP1, TNC, Col III, and DCN production was found for cells being exposed to the combined vibration and CTGF treatment. Noteworthy, the vibration and CTGF elicited a differential stimulatory effect on elastin (ELN), HA synthase 1 (HAS1), and fibroblast-specific protein-1 (FSP-1). The mitogenic activity of CTGF was only elicited in naïve cells without the vibratory preconditioning. The combined treatment had profound, but opposite effects on mitogen-activated protein kinase (MAPK) pathways, Erk1/2 and p38, and the Erk1/2 pathway was critical for the observed mechano-biochemical responses. Collectively, vibratory stresses and CTGF signals cooperatively coaxed MSCs toward a VFF-like phenotype and accelerated the synthesis and remodeling of vocal fold matrices. PMID:24456068

Ischemic Preconditioning Protects Astrocytes against Oxygen Glucose Deprivation Via the Nuclear Erythroid 2-Related Factor 2 Pathway.

PubMed

Narayanan, Srinivasan V; Dave, Kunjan R; Perez-Pinzon, Miguel A

2018-04-01

Induction of ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia by activation of adaptive pathways and modulation of mitochondria to induce ischemic tolerance to various cells and tissues. Mitochondrial dysfunction has been ascribed to contribute to numerous neurodegenerative conditions and cerebral ischemia. Nuclear erythroid 2-related factor 2 (Nrf2) is a transcription factor that has traditionally been involved in upregulating cellular antioxidant systems to combat oxidative stress in the brain; however, the association of Nrf2 with mitochondria in the brain remains unclear. In the present study, we investigated the effects of Nrf2 on (i) IPC-induced protection of astrocytes; (ii) OXPHOS protein expression; and (iii) mitochondrial supercomplex formation.Oxygen-glucose deprivation (OGD) was used as an in vitro model of cerebral ischemia and IPC in cultured rodent astrocytes derived from WT C57Bl/6J and Nrf2 -/- mice. OXPHOS proteins were probed via western blotting, and supercomplexes were determined by blue native gel electrophoresis.IPC-induced cytoprotection in wild-type, but not Nrf2 -/- mouse astrocyte cultures following a lethal duration of OGD. In addition, our results suggest that Nrf2 localizes to the outer membrane in non-synaptic brain mitochondria, and that a lack of Nrf2 in vivo produces altered supercomplex formation in mitochondria.Our findings support a role of Nrf2 in mediating IPC-induced protection in astrocytes, which can profoundly impact the ischemic tolerance of neurons. In addition, we provide novel evidence for the association of Nrf2 to brain mitochondria and supercomplex formation. These studies offer new targets and pathways of Nrf2, which may be heavily implicated following cerebral ischemia.

The Hsp72 and Hsp90α mRNA Responses to Hot Downhill Running Are Reduced Following a Prior Bout of Hot Downhill Running, and Occur Concurrently within Leukocytes and the Vastus Lateralis.

PubMed

Tuttle, James A; Chrismas, Bryna C R; Gibson, Oliver R; Barrington, James H; Hughes, David C; Castle, Paul C; Metcalfe, Alan J; Midgley, Adrian W; Pearce, Oliver; Kabir, Chindu; Rayanmarakar, Faizal; Al-Ali, Sami; Lewis, Mark P; Taylor, Lee

2017-01-01

The leukocyte heat shock response (HSR) is used to determine individual's thermotolerance. The HSR and thermotolerance are enhanced following interventions such as preconditioning and/or acclimation/acclimatization. However, it is unclear whether the leukocyte HSR is an appropriate surrogate for the HSR in other tissues implicated within the pathophysiology of exertional heat illnesses (e.g., skeletal muscle), and whether an acute preconditioning strategy (e.g., downhill running) can improve subsequent thermotolerance. Physically active, non-heat acclimated participants were split into two groups to investigate the benefits of hot downhill running as preconditioning strategy. A hot preconditioning group (HPC; n = 6) completed two trials (HPC1 HOTDOWN and HPC2 HOTDOWN ) of 30 min running at lactate threshold (LT) on -10% gradient in 30°C and 50% relative humidity (RH) separated by 7 d. A temperate preconditioning group (TPC; n = 5) completed 30 min running at LT on a -1% gradient in 20°C and 50% (TPC1 TEMPFLAT ) and 7 d later completed 30 min running at LT on -10% gradient in 30°C and 50% RH (TPC2 HOTDOWN ). Venous blood samples and muscle biopsies (vastus lateralis; VL) were obtained before, immediately after, 3, 24, and 48 h after each trial. Leukocyte and VL Hsp72, Hsp90α, and Grp78 mRNA relative expression was determined via RT-QPCR. Attenuated leukocyte and VL Hsp72 (2.8 to 1.8 fold and 5.9 to 2.4 fold; p < 0.05) and Hsp90α mRNA (2.9 to 2.4 fold and 5.2 to 2.4 fold; p < 0.05) responses accompanied reductions ( p < 0.05) in physiological strain [exercising rectal temperature (-0.3°C) and perceived muscle soreness (~ -14%)] during HPC2 HOTDOWN compared to HPC1 HOTDOWN (i.e., a preconditioning effect). Both VL and leukocyte Hsp72 and Hsp90α mRNA increased ( p < 0.05) simultaneously following downhill runs and demonstrated a strong relationship ( p < 0.01) of similar magnitudes with one another. Hot downhill running is an effective preconditioning strategy which ameliorates physiological strain, soreness and Hsp72 and Hsp90α mRNA responses to a subsequent bout. Leukocyte and VL analyses are appropriate tissues to infer the extent to which the HSR has been augmented.

Effects of organic complexed or inorganic Co, Cu, Mn and Zn supplementation during a 45-day preconditioning period on productive and health responses of feeder cattle.

PubMed

Lippolis, K D; Cooke, R F; Silva, L G T; Schubach, K M; Brandao, A P; Marques, R S; Larson, C K; Russell, J R; Arispe, S A; DelCurto, T; Bohnert, D W

2017-11-01

This experiment evaluated production and health parameters among cattle offered concentrates containing inorganic or organic complexed sources of supplemental Cu, Co, Mn and Zn during a 45-day preconditioning period. In total, 90 Angus×Hereford calves were weaned at 7 months (day -1), sorted by sex, weaning BW and age (261±2 kg; 224±2 days), and allocated to 18 drylot pens (one heifer and four steers per pen) on day 0; thus, all pens had equivalent initial BW and age. Pens were randomly assigned to receive a corn-based preconditioning concentrate containing: (1) Cu, Co, Mn and Zn sulfate sources (INR), (2) Cu, Mn, Co and Zn complexed organic source (AAC) or (3) no Cu, Co, Mn and Zn supplementation (CON). From day 0 to 45, cattle received concentrate treatments (2.7 kg/animal daily, as-fed basis) and had free-choice access to orchardgrass (Dactylis glomerata L.), long-stem hay and water. The INR and AAC treatments were formulated to provide the same daily amount of Co, Cu, Mn and Zn at a 50-, 16-, 8- and ninefold increase, respectively, compared with the CON treatment. On day 46, cattle were transported to a commercial feedlot, maintained as a single pen, and offered a free-choice receiving diet until day 103. Calf full BW was recorded on days -1 and 0, 45 and 46, and 102 and 103 for average daily gain (ADG) calculation. Liver biopsy was performed on days 0 (used as covariate), 22 and 45. Cattle were vaccinated against respiratory pathogens on days 15, 29 and 46. Blood samples were collected on days 15, 29, 45, 47, 49, 53 and 60. During preconditioning, mean liver concentrations of Co, Zn and Cu were greater (P⩽0.03) in AAC and INR compared with CON. No treatment effects were detected (P⩾0.17) for preconditioning feed intake, ADG or feed efficiency. No treatment effects were detected (P⩾0.48) for plasma concentrations of antibodies against Mannheimia haemolytica, bovine viral diarrhea types 1 and 2 viruses. Plasma haptoglobin concentrations were similar among treatments (P=0.98). Mean plasma cortisol concentration was greater (P⩽0.04) in CON compared with INR and AAC. No treatment effects were detected (P⩾0.37) for cattle ADG during feedlot receiving. Hence, INR and AAC increased liver concentrations of Co, Zn and Cu through preconditioning, but did not impact cattle performance and immunity responses during preconditioning and feedlot receiving.

Geographical and temporal differences in electric vehicle range due to cabin conditioning energy consumption

NASA Astrophysics Data System (ADS)

Kambly, Kiran; Bradley, Thomas H.

2015-02-01

Electric vehicles (EVs) are vehicles that are propelled by electric motors powered by rechargeable battery. They are generally asserted to have GHG emissions, driveability and life cycle cost benefits over conventional vehicles. Despite this, EVs face significant challenges due to their limited on-board energy storage capacity. In addition to providing energy for traction, the energy storage device operates HVAC systems for cabin conditioning. This results in reduced driving range. The factors such as local ambient temperature, local solar radiation, local humidity, duration and thermal soak have been identified to affect the cabin conditions. In this paper, the development of a detailed system-level approach to HVAC energy consumption in EVs as a function of transient environmental parameters is described. The resulting vehicle thermal comfort model is used to address several questions such as 1) How does day to day environmental conditions affect EV range? 2) How does frequency of EV range change geographically? 3) How does trip start time affect EV range? 4) Under what conditions does cabin preconditioning assist in increasing the EV range? 5) What percentage increase in EV range can be expected due to cabin preconditioning at a given location?

Molecular strategies of the Caenorhabditis elegans dauer larva to survive extreme desiccation.

PubMed

Erkut, Cihan; Vasilj, Andrej; Boland, Sebastian; Habermann, Bianca; Shevchenko, Andrej; Kurzchalia, Teymuras V

2013-01-01

Massive water loss is a serious challenge for terrestrial animals, which usually has fatal consequences. However, some organisms have developed means to survive this stress by entering an ametabolic state called anhydrobiosis. The molecular and cellular mechanisms underlying this phenomenon are poorly understood. We recently showed that Caenorhabditis elegans dauer larva, an arrested stage specialized for survival in adverse conditions, is resistant to severe desiccation. However, this requires a preconditioning step at a mild desiccative environment to prepare the organism for harsher desiccation conditions. A systems approach was used to identify factors that are activated during this preconditioning. Using microarray analysis, proteomics, and bioinformatics, genes, proteins, and biochemical pathways that are upregulated during this process were identified. These pathways were validated via reverse genetics by testing the desiccation tolerances of mutants. These data show that the desiccation response is activated by hygrosensation (sensing the desiccative environment) via head neurons. This leads to elimination of reactive oxygen species and xenobiotics, expression of heat shock and intrinsically disordered proteins, polyamine utilization, and induction of fatty acid desaturation pathway. Remarkably, this response is specific and involves a small number of functional pathways, which represent the generic toolkit for anhydrobiosis in plants and animals.

Preconditioned augmented Lagrangian formulation for nearly incompressible cardiac mechanics.

PubMed

Campos, Joventino Oliveira; Dos Santos, Rodrigo Weber; Sundnes, Joakim; Rocha, Bernardo Martins

2018-04-01

Computational modeling of the heart is a subject of substantial medical and scientific interest, which may contribute to increase the understanding of several phenomena associated with cardiac physiological and pathological states. Modeling the mechanics of the heart have led to considerable insights, but it still represents a complex and a demanding computational problem, especially in a strongly coupled electromechanical setting. Passive cardiac tissue is commonly modeled as hyperelastic and is characterized by quasi-incompressible, orthotropic, and nonlinear material behavior. These factors are known to be very challenging for the numerical solution of the model. The near-incompressibility is known to cause numerical issues such as the well-known locking phenomenon and ill-conditioning of the stiffness matrix. In this work, the augmented Lagrangian method is used to handle the nearly incompressible condition. This approach can potentially improve computational performance by reducing the condition number of the stiffness matrix and thereby improving the convergence of iterative solvers. We also improve the performance of iterative solvers by the use of an algebraic multigrid preconditioner. Numerical results of the augmented Lagrangian method combined with a preconditioned iterative solver for a cardiac mechanics benchmark suite are presented to show its improved performance. Copyright © 2017 John Wiley & Sons, Ltd.

Molecular Strategies of the Caenorhabditis elegans Dauer Larva to Survive Extreme Desiccation

PubMed Central

Erkut, Cihan; Vasilj, Andrej; Boland, Sebastian; Habermann, Bianca; Shevchenko, Andrej; Kurzchalia, Teymuras V.

2013-01-01

Massive water loss is a serious challenge for terrestrial animals, which usually has fatal consequences. However, some organisms have developed means to survive this stress by entering an ametabolic state called anhydrobiosis. The molecular and cellular mechanisms underlying this phenomenon are poorly understood. We recently showed that Caenorhabditis elegans dauer larva, an arrested stage specialized for survival in adverse conditions, is resistant to severe desiccation. However, this requires a preconditioning step at a mild desiccative environment to prepare the organism for harsher desiccation conditions. A systems approach was used to identify factors that are activated during this preconditioning. Using microarray analysis, proteomics, and bioinformatics, genes, proteins, and biochemical pathways that are upregulated during this process were identified. These pathways were validated via reverse genetics by testing the desiccation tolerances of mutants. These data show that the desiccation response is activated by hygrosensation (sensing the desiccative environment) via head neurons. This leads to elimination of reactive oxygen species and xenobiotics, expression of heat shock and intrinsically disordered proteins, polyamine utilization, and induction of fatty acid desaturation pathway. Remarkably, this response is specific and involves a small number of functional pathways, which represent the generic toolkit for anhydrobiosis in plants and animals. PMID:24324795

A Dangerous Context Changes the Way That Rats Learn about and Discriminate between Innocuous Events in Sensory Preconditioning

ERIC Educational Resources Information Center

Holmes, Nathan M.; Westbrook, R. Frederick

2017-01-01

Four experiments used a sensory preconditioning protocol to examine how a dangerous context influences learning about innocuous events. In Experiments 1, 2, and 3, rats were exposed to presentations of a tone followed immediately or 20-sec later by presentations of a light. These tone-light pairings occurred in a context that was either familiar…

M-step preconditioned conjugate gradient methods

NASA Technical Reports Server (NTRS)

Adams, L.

1983-01-01

Preconditioned conjugate gradient methods for solving sparse symmetric and positive finite systems of linear equations are described. Necessary and sufficient conditions are given for when these preconditioners can be used and an analysis of their effectiveness is given. Efficient computer implementations of these methods are discussed and results on the CYBER 203 and the Finite Element Machine under construction at NASA Langley Research Center are included.

Hypoxic Conditioned Medium From Human Adipose-Derived Stem Cells Promotes Mouse Liver Regeneration Through JAK/STAT3 Signaling

PubMed Central

Lee, Sang Chul; Jeong, Hye Jin; Lee, Sang Kuon

2016-01-01

Adipose-derived stem cells (ASCs) mainly exert their function by secreting materials that are collectively termed the secretome. Despite recent attention to the secretome as an alternative to stem cell therapy, the culture conditions for generating optimal secretome contents have not been determined. Therefore, we investigated the role of hypoxic-conditioned media (HCM) from ASCs. Normoxic-conditioned media (NCM) and HCM were obtained after culturing ASCs in 20% O2 or 1% O2 for 24 hours, respectively. Subsequently, partially hepatectomized mice were infused with saline, control medium, NCM, or HCM, and then sera and liver specimens were obtained for analyses. Hypoxia (1% O2) significantly increased mRNA expression of mediators from ASCs, including interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF). HCM infusion significantly increased the number of Ki67-positive cells in the liver (p < .05). HCM infusion significantly increased phospho-signal transducer and activator of transcription 3 (STAT3) and decreased suppressor of cytokine signaling 3 (SOCS3) expression in the liver (p < .05). To determine the role of IL-6 in liver regeneration, we then performed IL-6 RNA interference study. Conditioned media (CM) obtained from ASCs, which were transfected with either siIL-6 or siControl, were administered to partially hepatectomized mice. The siIL-6 CM groups exhibited lower liver proliferation (Ki67-positive cells) and markers of regeneration (protein expression of proliferating cell nuclear antigen, p-STAT3, HGF, and VEGF and liver weights) than the siControl CM groups (p < .05). Taken together, hypoxic preconditioning of ASCs increased expression of mediators promoting anti-inflammatory and regenerative responses. The liver regenerative effects of HCM appear to be mediated by persistent and uninhibited expression of STAT3 in the liver, which results from decreased expression of SOCS3. Significance In this study, it was found that treatment with the medium from hypoxic-preconditioned adipose-derived stem cells (ASCs) increased the viability of hepatotoxic hepatocytes and enhance liver regeneration in partially hepatectomized mice. In addition, the researchers first revealed that the hepatoprotective effects of hypoxic-conditioned media are mediated by persistent and uninhibited expression of signal transducer and activator of transcription 3 in the liver, which result from a decreased expression of suppressor of cytokine signaling 3. Therefore, the hypoxic preconditioning of ASCs is expected to play a crucial role in regenerative medicine by optimizing the production of a highly effective secretome from ASCs. PMID:27102647

Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain.

PubMed

Ara, Jahan; De Montpellier, Sybille

2013-09-01

Perinatal hypoxia-ischemia (HI) results in brain injury, whereas mild hypoxic episodes result in preconditioning, which can significantly reduce the vulnerability of the brain to subsequent severe hypoxia-ischemia. Hypoxic-preconditioning (PC) has been shown to enhance cell survival and differentiation of progenitor cells in the central nervous system (CNS). The purpose of this study was to determine whether pretreatment with PC prior to HI stimulates subventricular zone (SVZ) proliferation and neurogenesis in newborn piglets. One-day-old piglets were subjected to PC (8% O2/92% N2) for 3h and 24h later were exposed to HI produced by combination of hypoxia (5% FiO2) for a pre-defined period of 30min and ischemia induced by a period of 10min of hypotension. Here we demonstrate that SVZ derived neural stem/progenitor cells (NSPs) from PC, HI and PC+HI piglets proliferated as neurospheres, expressed neural progenitor and neurodevelopmental markers, and that greater proportion of the spheres generated are multipotential. Neurosphere assay revealed that preconditioning pretreatment increased the number of NSP-derived neurospheres in SVZ following HI compared to normoxic and HI controls. NSPs from preconditioned SVZ generated twice as many neurons and astrocytes in vitro. Injections with 5-Bromo-2-deoxyuridine (BrdU) after PC revealed a robust proliferative response within the SVZ that continued for one week. PC also increased neurogenesis in vivo, doublecortin positive cells with migratory profiles were observed streaming from the SVZ to striatum and neocortex. These findings show that the induction of proliferation and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of a hypoxic-ischemic insult. Copyright © 2013 Elsevier B.V. All rights reserved.

Preconditioning Triggered by Carbon Monoxide (CO) Provides Neuronal Protection Following Perinatal Hypoxia-Ischemia

PubMed Central

Widerøe, Marius; Alves, Paula M.; Vercelli, Alessandro; Vieira, Helena L. A.

2012-01-01

Perinatal hypoxia-ischemia is a major cause of acute mortality in newborns and cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play a major role. Increased resistance against major damage can be achieved by preconditioning triggered by subtle insults. CO, a toxic molecule that is also generated endogenously, may have a role in preconditioning as low doses can protect against inflammation and apoptosis. In this study, the role of CO-induced preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h of CO treatment on neuronal death (plasmatic membrane permeabilization and chromatin condensation) and bcl-2 expression was studied in cerebellar granule cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were counted with a stereological approach and cleaved caspase 3-positive profiles in the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c released from mitochondria and reduced activation of caspase-3. Still, Bcl-2 protein levels were higher in hippocampus of CO pre-treated rat pups. Our results show that CO preconditioning elicits a molecular cascade that limits neuronal apoptosis. This could represent an innovative therapeutic strategy for high-risk cerebral hypoxia-ischemia patients, in particular neonates. PMID:22952602

Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

PubMed

Nehra, Sarita; Bhardwaj, Varun; Bansal, Anju; Saraswat, Deepika

2017-09-26

Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO2~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile and bio-energetic homeostasis.

Preconditioning methods influence tumor property in an orthotopic bladder urothelial carcinoma rat model

PubMed Central

MIYAZAKI, KOZO; MORIMOTO, YUJI; NISHIYAMA, NOBUHIRO; SATOH, HIROYUKI; TANAKA, MASAMITSU; SHINOMIYA, NARIYOSHI; ITO, KEIICHI

2014-01-01

Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of preconditioning methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×106 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the preconditioning methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm3 in the PBS and acid-base-treated groups and <10 mm3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ∼75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on preconditioning methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate preconditioning condition. PMID:24649309

Preconditioning to Reduce Decompression Stress in Scuba Divers.

PubMed

Germonpré, Peter; Balestra, Costantino

2017-02-01

Using ultrasound imaging, vascular gas emboli (VGE) are observed after asymptomatic scuba dives and are considered a key element in the potential development of decompression sickness (DCS). Diving is also accompanied with vascular dysfunction, as measured by flow-mediated dilation (FMD). Previous studies showed significant intersubject variability to VGE for the same diving exposure and demonstrated that VGE can be reduced with even a single pre-dive intervention. Several preconditioning methods have been reported recently, seemingly acting either on VGE quantity or on endothelial inflammatory markers. Nine male divers who consistently showed VGE postdive performed a standardized deep pool dive (33 m/108 ft, 20 min in 33°C water temperature) to investigate the effect of three different preconditioning interventions: heat exposure (a 30-min session of dry infrared sauna), whole-body vibration (a 30-min session on a vibration mattress), and dark chocolate ingestion (30 g of chocolate containing 86% cocoa). Dives were made one day per week and interventions were administered in a randomized order. These interventions were shown to selectively reduce VGE, FMD, or both compared to control dives. Vibration had an effect on VGE (39.54%, SEM 16.3%) but not on FMD postdive. Sauna had effects on both parameters (VGE: 26.64%, SEM 10.4%; FMD: 102.7%, SEM 2.1%), whereas chocolate only improved FMD (102.5%, SEM 1.7%). This experiment, which had the same subjects perform all control and preconditioning dives in wet but completely standardized diving conditions, demonstrates that endothelial dysfunction appears to not be solely related to VGE.Germonpré P, Balestra C. Preconditioning to reduce decompression stress in scuba divers. Aerosp Med Hum Perform. 2017; 88(2):114-120.

Effects of ischemic preconditioning and iloprost on myocardial ischemia-reperfusion damage in rats.

PubMed

Ay, Yasin; Kara, Ibrahim; Aydin, Cemalettin; Ay, Nuray Kahraman; Teker, Melike Elif; Senol, Serkan; Inan, Bekir; Basel, Halil; Uysal, Omer; Zeybek, Rahmi

2013-01-01

This study investigates the effects of cardiac ischemic preconditioning and iloprost on reperfusion damage in rats with myocardial ischemia/reperfusion. 38 male Wistar Albino rats used in this study were divided into 5 groups. The control group (Group 1) (n=6), ischemia/reperfusion (IR) group (Group 2) (n=8), cardiac ischemic preconditioning (CIP) group (Group 3) (n=8), iloprost (ILO) group (Group 4) (n=8), and cardiac ischemic preconditioning + iloprost (CIP+ILO) group (Group 5) (n=8). Pre-ischemia, 15 minutes post-ischemia, 45 minutes post-reperfusion, mean blood pressure (MBP), and heart rates (HR) were recorded. The rate-pressure product (RPP) was calculated. Post-reperfusion plasma creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin (cTn) vlaues, and infarct size/area at risk (IS/AAR) were calculated from myocardial tissue samples. Arrhythmia and ST segment elevations were evaluated during the ischemia and reperfusion stages. Although the MBP, HR, RPP values, biochemical parameters of CK-MB and LDH levels, IS/AAR rates, ST segment elevation values were found to be similar in CIP and CIP+ILO groups and the IR and ILO groups (p>0.05), CIP-containing group values had a positively meaningful difference (p<0.05) compared with the IR and ILO group. While mild-moderate findings of damage were observed in Group 3 and Group 5, severely findings of damage were releaved in Group 2 and Group 4. The arrhythmia score of the ILO group was meaningfully lower (F: 41.4, p<0.001) than the IR group. We can conclude that the effects of myocardial reperfusion damage can be reduced by cardiac ischemic preconditioning, intravenous iloprost reduced the incidence of ventricular arrhythmia associated with reperfusion, and its use with CIP caused no additional changes.

A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.

PubMed

Amini, Elham; Rezaei, Mohsen; Mohamed Ibrahim, Norlinah; Golpich, Mojtaba; Ghasemi, Rasoul; Mohamed, Zahurin; Raymond, Azman Ali; Dargahi, Leila; Ahmadiani, Abolhassan

2015-08-01

Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.

Histone Deacetylases Exert Class-Specific Roles in Conditioning the Brain and Heart Against Acute Ischemic Injury

PubMed Central

Aune, Sverre E.; Herr, Daniel J.; Kutz, Craig J.; Menick, Donald R.

2015-01-01

Ischemia-reperfusion (IR) injury comprises a significant portion of morbidity and mortality from heart and brain diseases worldwide. This enduring clinical problem has inspired myriad reports in the scientific literature of experimental interventions seeking to elucidate the pathology of IR injury. Elective cardiac surgery presents perhaps the most viable scenario for protecting the heart and brain from IR injury due to the opportunity to condition the organs prior to insult. The physiological parameters for the preconditioning of vital organs prior to insult through mechanical and pharmacological maneuvers have been heavily examined. These investigations have revealed new insights into how preconditioning alters cellular responses to IR injury. However, the promise of preconditioning remains unfulfilled at the clinical level, and research seeking to implicate cell signals essential to this protection continues. Recent discoveries in molecular biology have revealed that gene expression can be controlled through posttranslational modifications, without altering the chemical structure of the genetic code. In this scenario, gene expression is repressed by enzymes that cause chromatin compaction through catalytic removal of acetyl moieties from lysine residues on histones. These enzymes, called histone deacetylases (HDACs), can be inhibited pharmacologically, leading to the de-repression of protective genes. The discovery that HDACs can also alter the function of non-histone proteins through posttranslational deacetylation has expanded the potential impact of HDAC inhibitors for the treatment of human disease. HDAC inhibitors have been applied in a very small number of experimental models of IR. However, the scientific literature contains an increasing number of reports demonstrating that HDACs converge on preconditioning signals in the cell. This review will describe the influence of HDACs on major preconditioning signaling pathways in the heart and brain. PMID:26175715

ACL graft constructs: In-vitro fatigue testing highlights the occurrence of irrecoverable lengthening and the need for adequate (pre)conditioning to avert the recurrence of knee instability.

PubMed

Blythe, A; Tasker, T; Zioupos, P

2006-01-01

The performance of ACL grafts in both the short and long term is only as good as the condition of the graft at the time of surgery. If the graft lengthens under load at the two fixation ends incorporation will take longer to occur. Previous studies have shown that the various grafts currently used are strong enough. However, data on strength came primarily from quasistatic single pull to failure tests with, in some cases, modest cycling to precondition the grafts. The present study examined the in-vitro biomechanical behaviour of model ACL grafts, which have been fatigue cycled to failure over a wide range of loads in physiological ambient conditions. Load/deformation curves and the stretch of the grafts was continuously recorded until final rupture. The grafts demonstrated typical creep-rupture like behaviour with elongation (non-recoverable stretch) and loss of stiffness leading to gradual failure. Some of the graft designs were consistently shown to elongate up to 20 mm in length within the first 2000 cycles at moderate physiological loads and a further 10 mm of elongation occurred between the initial preconditioned state and just prior to complete rupture. Not enough attention has been paid previously to the likely long term elongation patterns of ACL grafts post-surgery and even after the usual empirical preconditioning has been performed by the surgeon. Increased graft dimensions may result in recurrent knee instability and may also lead to failure of the graft to incorporate. Preconditioning in-vitro may still be a way to remove some slack and prepare the graft for its operational environment by stiffening in particular the tissue/fixation interface for those grafts that use soft polymer fixation ends.

Smooth muscle cell seeding of decellularized scaffolds: the importance of bioreactor preconditioning to development of a more native architecture for tissue-engineered blood vessels.

PubMed

Yazdani, Saami K; Watts, Benjamin; Machingal, Masood; Jarajapu, Yagna P R; Van Dyke, Mark E; Christ, George J

2009-04-01

Vascular smooth muscle cells (VSMCs) impart important functional characteristics in the native artery and, therefore, should logically be incorporated in the development of tissue-engineered blood vessels. However, the native architecture and low porosity of naturally derived biomaterials (i.e., decellularized vessels) have impeded efforts to seed and incorporate a VSMC layer in tissue-engineered blood vessels. To this end, the goal of this study was to develop improved methods for seeding, proliferation, and maturation of VSMCs on decellularized porcine carotid arteries. Decellularized vessels were prepared in the absence and presence of the adventitial layer, and statically seeded with a pipette containing a suspension of rat aortic VSMCs. After cell seeding, recellularized engineered vessels were placed in a custom bioreactor system for 1-2 weeks to enhance cellular proliferation, alignment, and maturation. Initial attachment of VSMCs was dramatically enhanced by removing the adventitial layer of the decellularized porcine artery. Moreover, cyclic bioreactor conditioning (i.e., flow and pressure) resulted in increased VSMC proliferation and accelerated formation of a muscularized medial layer in the absence of the adventitial layer during the first week of preconditioning. Fura-2-based digital imaging microscopy revealed marked and reproducible depolarization-induced calcium mobilization after bioreactor preconditioning in the absence, but not in the presence, of the adventitia. The major finding of this investigation is that bioreactor preconditioning accelerates the formation of a significant muscular layer on decellularized scaffolds, in particular on adventitia-denuded scaffolds. Further, the VSMC layer of bioreactor-preconditioned vessels was capable of mobilizing calcium in response to cellular depolarization. These findings represent an important first step toward the development of tissue-engineered vascular grafts that more closely mimic native vasculature.

Realization of preconditioned Lanczos and conjugate gradient algorithms on optical linear algebra processors.

PubMed

Ghosh, A

1988-08-01

Lanczos and conjugate gradient algorithms are important in computational linear algebra. In this paper, a parallel pipelined realization of these algorithms on a ring of optical linear algebra processors is described. The flow of data is designed to minimize the idle times of the optical multiprocessor and the redundancy of computations. The effects of optical round-off errors on the solutions obtained by the optical Lanczos and conjugate gradient algorithms are analyzed, and it is shown that optical preconditioning can improve the accuracy of these algorithms substantially. Algorithms for optical preconditioning and results of numerical experiments on solving linear systems of equations arising from partial differential equations are discussed. Since the Lanczos algorithm is used mostly with sparse matrices, a folded storage scheme to represent sparse matrices on spatial light modulators is also described.

Pre-conditioning procedure suitable for internal-RF-antenna of J-PARC RF-driven H{sup −} ion source

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

Ueno, A., E-mail: akira.ueno@j-parc.jp; Ohkoshi, K.; Ikegami, K.

The Japan Proton Accelerator Research Complex (J-PARC) cesiated RF-driven H{sup −} ion source has been successfully operated for about 1 yr. By the world brightest level beam, the J-PARC design beam power of 1 MW was successfully demonstrated. Although no internal-RF-antenna failure, except for the once caused by an excess cesium due to a misoperation, occurred in the operation, many antennas failed in pre-conditionings for the first hundred days. The antenna failure rate was drastically decreased by using an antenna with coating thicker than a standard value and the pre-conditioning procedure repeating 15 min 25 kW RF-power operation and impurity-gasmore » evacuation a few times, before the full power (50 kW) operation.« less

A multilevel preconditioner for domain decomposition boundary systems

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

Bramble, J.H.; Pasciak, J.E.; Xu, Jinchao.

1991-12-11

In this note, we consider multilevel preconditioning of the reduced boundary systems which arise in non-overlapping domain decomposition methods. It will be shown that the resulting preconditioned systems have condition numbers which be bounded in the case of multilevel spaces on the whole domain and grow at most proportional to the number of levels in the case of multilevel boundary spaces without multilevel extensions into the interior.

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

PubMed

Healy, D A; Khan, W A; Wong, C S; Moloney, M Clarke; Grace, P A; Coffey, J C; Dunne, C; Walsh, S R; Sadat, U; Gaunt, M E; Chen, S; Tehrani, S; Hausenloy, D J; Yellon, D M; Kramer, R S; Zimmerman, R F; Lomivorotov, V V; Shmyrev, V A; Ponomarev, D N; Rahman, I A; Mascaro, J G; Bonser, R S; Jeon, Y; Hong, D M; Wagner, R; Thielmann, M; Heusch, G; Zacharowski, K; Meybohm, P; Bein, B; Tang, T Y

2014-09-01

A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Protection of Hippocampal CA1 Neurons Against Ischemia/Reperfusion Injury by Exercise Preconditioning via Modulation of Bax/Bcl-2 Ratio and Prevention of Caspase-3 Activation.

PubMed

Aboutaleb, Nahid; Shamsaei, Nabi; Rajabi, Hamid; Khaksari, Mehdi; Erfani, Sohaila; Nikbakht, Farnaz; Motamedi, Pezhman; Shahbazi, Ali

2016-01-01

Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia. Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining . The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001). This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli.

LONG-TERM PRECONDITIONING OF PLANTLETS: A PRACTICAL METHOD FOR ENHANCING SURVIVAL OF PINEAPPLE (Ananas comosus Merr.) SHOOT TIPS CRYOPRESERVED USING VITRIFICATION.

PubMed

Hu, W H; Liu, S F; Liaw, S I

2015-01-01

The purpose of this study was to develop an efficient cryopreservation protocol for pineapple (Ananas comosus Merr.) shoot tips. The optimal state of pineapple plantlets was investigated by using sucrose preconditioning to enhance survival after cryostorage. To achieve a suitable state of plantlets before cryopreservation, 0.2 M to 0.4 M sucrose concentrations combined with short- (0-7 days), medium- (15-30 days), and long-term (75-150 days) preconditioning periods were compared. The highest survival (100 %) was achieved using the following procedure: intact plantlets underwent long-term preconditioning with 0.2 M sucrose for 135 days, dissected shoot tips were treated with a loading solution containing 2.0 M glycerol + 0.4 M sucrose for 60 min at 25 degree and the shoot tips were dehydrated in PVS2 for 2h at 0 degree C before being plunged in liquid nitrogen. Rewarming was conducted in a water-bath for 30 s at 40 degree C and PVS2 was replaced with a 1.2 M sucrose solution for 30 min at 25 degree C. The shoot tips were transferred on semisolid medium and left in the dark for 1 week, then in dim light for 3 weeks.

Research report: the effects of hyperbaric oxygen preconditioning on myocardial biomarkers of cardioprotection in patients having coronary artery bypass graft surgery.

PubMed

Jeysen, Zivan Yogaratnam; Gerard, Laden; Levant, Guvendik; Cowen, Mike; Cale, Alex; Griffin, Steve

2011-01-01

We have previously conducted and reported on the primary endpoint of a clinical study which demonstrated that hyperbaric oxygen (HBO2) preconditioning consisting of two 30-minute intervals of 100% oxygen at 2.4 atmospheres absolute (ATA) prior to coronary artery bypass graft (CABG) surgery leads to an improvement in left ventricular stroke work (LVSW) 24 hours following CABG. In that study, 81 patients were randomized to treatment with HBO2 (HBO2; n = 41) or routine treatment (Control Group; n = 40) prior to surgery. The objective of this manuscript is to further report on the result of the exploratory secondary endpoints from that study, specifically the effects of HBO2 preconditioning on biomarkers of myocardial protection. Intraoperative right atrial biopsies were assessed, via an Enzyme Linked ImmunoSorbent Assay (ELISA), for the expression of eNOS and HSP72. In this study, no significant differences were observed between the groups with respect to the quantity of myocardial eNOS and HSP72. However, in the HBO2 Group, following ischemia and reperfusion, the quantities of myocardial eNOS and HSP72 were increased. This suggests that HBO2 preconditioning in this group of patients may be capable of inducing endogenous cardioprotection following ischemic reperfusion injury (IRI).

Studies on cerebral protection of digoxin against hypoxic-ischemic brain damage in neonatal rats.

PubMed

Peng, Kaiwei; Tan, Danfeng; He, Miao; Guo, Dandan; Huang, Juan; Wang, Xia; Liu, Chentao; Zheng, Xiangrong

2016-08-17

Hypoxic-ischemic brain damage (HIBD) is a major cause of neonatal acute deaths and chronic nervous system damage. Our present study was designed to investigate the possible neuroprotective effect of digoxin-induced pharmacological preconditioning after hypoxia-ischemia and underlying mechanisms. Neonatal rats were assigned randomly to control, HIBD, or HIBD+digoxin groups. Pharmacological preconditioning was induced by administration of digoxin 72 h before inducing HIBD by carotid occlusion+hypoxia. Behavioral assays, and neuropathological and apoptotic assessments were performed to examine the effects; the expression of Na/K ATPase was also assessed. Rats in the HIBD group showed deficiencies on the T-maze, radial water maze, and postural reflex tests, whereas the HIBD+digoxin group showed significant improvements on all behavioral tests. The rats treated with digoxin showed recovery of pathological conditions, increased number of neural cells and proliferative cells, and decreased number of apoptotic cells. Meanwhile, an increased expression level of Na/K ATPase was observed after digoxin preconditioning treatment. The preconditioning treatment of digoxin contributed toward an improved functional recovery and exerted a marked neuroprotective effect including promotion of cell proliferation and reduction of apoptosis after HIBD, and the neuroprotective action was likely associated with increased expression of Na/K ATPase.

Factors influencing postpartum women's willingness to participate in a preventive pelvic floor muscle training program: a web-based survey.

PubMed

Moossdorff-Steinhauser, Heidi F A; Albers-Heitner, Pytha; Weemhoff, Mirjam; Spaanderman, Marc E A; Nieman, Fred H M; Berghmans, Bary

2015-12-01

Pregnancy and delivery are the most prominent risk factors for the onset of pelvic floor injuries and - later-on - urinary incontinence. Supervised pelvic floor muscle training during and after pregnancy is proven effective for the prevention of urinary incontinence on the short term. However, only a minority of women do participate in preventive pelvic floor muscle training programs. Our aim was to analyze willingness to participate (WTP) in an intensive preventive pelvic floor muscle training (PFMT) program and influencing factors, from the perspective of postpartum women, for participation. We included 169 three-month postpartum women in a web-based survey in the Netherlands. Demographic and clinical characteristics, knowledge and experience with PFMT and preconditions for actual WTP were assessed. Main outcome measures were frequencies and percentages for categorical data. Cross tabulations were used to explore the relationship between WTP and various independent categorical variables. A linear regression analysis was done to analyze which variables are associated with WTP. A response rate of 64% (n=169) was achieved. 31% of the women was WTP, 41% was hesitating, 12% already participated in PFMT and 15% was not interested (at all). No statistically significant association was found between WTP and risk or prognostic pelvic floor dysfunction factors. Women already having symptoms of pelvic floor dysfunction such as incontinence and pelvic organ prolapse symptoms were more WTP (p=0.010, p=0.001, respectively) as were women perceiving better general health (p<0.001). Preconditions for women to participate were program costs, and travel time not exceeding 15min. From the perspective of postpartum women, there is room for improvement of preventive pelvic floor management. Further research should focus on strategies to tackle major barriers and to introduce facilitators for postpartum women to participate in PFMT programs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

BCYCLIC: A parallel block tridiagonal matrix cyclic solver

NASA Astrophysics Data System (ADS)

Hirshman, S. P.; Perumalla, K. S.; Lynch, V. E.; Sanchez, R.

2010-09-01

A block tridiagonal matrix is factored with minimal fill-in using a cyclic reduction algorithm that is easily parallelized. Storage of the factored blocks allows the application of the inverse to multiple right-hand sides which may not be known at factorization time. Scalability with the number of block rows is achieved with cyclic reduction, while scalability with the block size is achieved using multithreaded routines (OpenMP, GotoBLAS) for block matrix manipulation. This dual scalability is a noteworthy feature of this new solver, as well as its ability to efficiently handle arbitrary (non-powers-of-2) block row and processor numbers. Comparison with a state-of-the art parallel sparse solver is presented. It is expected that this new solver will allow many physical applications to optimally use the parallel resources on current supercomputers. Example usage of the solver in magneto-hydrodynamic (MHD), three-dimensional equilibrium solvers for high-temperature fusion plasmas is cited.

Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress.

PubMed

Triacca, Valentina; Güç, Esra; Kilarski, Witold W; Pisano, Marco; Swartz, Melody A

2017-04-28

The transport of interstitial fluid and solutes into lymphatic vessels is important for maintaining interstitial homeostasis and delivering antigens and soluble factors to the lymph node for immune surveillance. Transendothelial transport across lymphatic endothelial cells (LECs) is commonly considered to occur paracellularly, or between cell-cell junctions, and driven by local pressure and concentration gradients. However, emerging evidence suggests that LECs also play active roles in regulating interstitial solute balance and can scavenge and store antigens, raising the possibility that vesicular or transcellular pathways may be important in lymphatic solute transport. The aim of this study was to determine the relative importance of transcellular (vesicular) versus paracellular transport pathways by LECs and how mechanical stress (ie, fluid flow conditioning) alters either pathway. We demonstrate that transcellular transport mechanisms substantially contribute to lymphatic solute transport and that solute uptake occurs in both caveolae- and clathrin-coated vesicles. In vivo, intracelluar uptake of fluorescently labeled albumin after intradermal injection by LECs was similar to that of dermal dendritic cells. In vitro, we developed a method to differentially quantify intracellular solute uptake versus transendothelial transport by LECs. LECs preconditioned to 1 µm/s transmural flow demonstrated increased uptake and basal-to-apical solute transport, which could be substantially reversed by blocking dynamin-dependent vesicle formation. These findings reveal the importance of intracellular transport in steady-state lymph formation and suggest that LECs use transcellular mechanisms in parallel to the well-described paracellular route to modulate solute transport from the interstitium according to biomechanical cues. © 2017 American Heart Association, Inc.

Interleukin-3 enhances the migration of human mesenchymal stem cells by regulating expression of CXCR4.

PubMed

Barhanpurkar-Naik, Amruta; Mhaske, Suhas T; Pote, Satish T; Singh, Kanupriya; Wani, Mohan R

2017-07-14

Mesenchymal stem cells (MSCs) represent an important source for cell therapy in regenerative medicine. MSCs have shown promising results for repair of damaged tissues in various degenerative diseases in animal models and also in human clinical trials. However, little is known about the factors that could enhance the migration and tissue-specific engraftment of exogenously infused MSCs for successful regenerative cell therapy. Previously, we have reported that interleukin-3 (IL-3) prevents bone and cartilage damage in animal models of rheumatoid arthritis and osteoarthritis. Also, IL-3 promotes the differentiation of human MSCs into functional osteoblasts and increases their in-vivo bone regenerative potential in immunocompromised mice. However, the role of IL-3 in migration of MSCs is not yet known. In the present study, we investigated the role of IL-3 in migration of human MSCs under both in-vitro and in-vivo conditions. MSCs isolated from human bone marrow, adipose and gingival tissues were used for in-vitro cell migration, motility and wound healing assays in the presence or absence of IL-3. The effect of IL-3 preconditioning on expression of chemokine receptors and integrins was examined by flow cytometry and real-time PCR. The in-vivo migration of IL-3-preconditioned MSCs was investigated using a subcutaneous matrigel-releasing stromal cell-derived factor-1 alpha (SDF-1α) model in immunocompromised mice. We observed that human MSCs isolated from all three sources express IL-3 receptor-α (IL-3Rα) both at gene and protein levels. IL-3 significantly enhances in-vitro migration, motility and wound healing abilities of MSCs. Moreover, IL-3 preconditioning upregulates expression of chemokine (C-X-C motif) receptor 4 (CXCR4) on MSCs, which leads to increased migration of cells towards SDF-1α. Furthermore, CXCR4 antagonist AMD3100 decreases the migration of IL-3-treated MSCs towards SDF-1α. Importantly, IL-3 also induces in-vivo migration of MSCs towards subcutaneously implanted matrigel-releasing-SDF-1α in immunocompromised mice. The present study demonstrates for the first time that IL-3 has an important role in enhancing the migration of human MSCs through regulation of the CXCR4/SDF-1α axis. These findings suggest a potential role of IL-3 in improving the efficacy of MSCs in regenerative cell therapy.

Anti-inflammatory effects on ischemia/reperfusion-injured lung transplants by the cluster of differentiation 26/dipeptidylpeptidase 4 (CD26/DPP4) inhibitor vildagliptin.

PubMed

Jang, Jae-Hwi; Yamada, Yoshito; Janker, Florian; De Meester, Ingrid; Baerts, Lesley; Vliegen, Gwendolyn; Inci, Ilhan; Chatterjee, Shampa; Weder, Walter; Jungraithmayr, Wolfgang

2017-03-01

We showed previously that stromal cell-derived factor 1 (SDF-1) is a substrate of cluster of differentiation 26/dipeptidylpeptidase 4 (CD26/DPP4) and exerts regenerative properties on acute lung ischemia-reperfusion injury on CD26/DPP4 inhibition. Here, we extend our studies to test whether an intermediate recovery of lung transplants from ischemia/reperfusion injury by CD26/DPP4 inhibition can be achieved for up to 14 days. Syngeneic mouse lung transplantation (Tx) was performed in C57BL/6 and in CD26-/- mice by applying 18 hours of cold ischemia. Donor lungs were preconditioned with saline or the CD26/DPP4 inhibitor vildagliptin (1 μg/mL [3 μM]). In vitro, the influence of vildagliptin and SDF-1 on the macrophage cell line RAW 264.7 was tested. Transplants were analyzed up to 14 days after Tx for the expression of SDF-1, tumor necrosis factor-α (TNF-α), interleukin-10, intercellular adhesion molecule-1 (ICAM-1), immune cell infiltration, and oxygenation. Cold ischemic time of 18 hours with vildagliptin preconditioning elevated lung SDF-1 levels (P = .0011) and increased interleukin-10-producing macrophages (P = .0165) compared with the control. SDF-1 reduced macrophage-derived TNF-α (P = .0248) in vitro. Five hours after Tx, vildagliptin significantly reduced macrophages and neutrophils (P = .0306), decreased ICAM-1 expression (P = .002), and improved transplant oxygenation (P = .0181). Seven days after Tx, grafts were preserved on CD26/DPP4-inhibition: perivascular macrophages (P = .0046) and TNF-α (P = .0013) were reduced as well as T and B cells. ICAM-1 was absent in CD26/DPP4-inhibited grafts at all time points. This study proves an intermediate improvement of ischemia/reperfusion-injured lung transplants by the CD26/DPP4-inhibitor vildagliptin up to 14 days. Enhanced levels of SDF-1 induced an anti-inflammatory effect on a cellular and protein level, and render CD26/DPP4 inhibition preconditioning effective for the protection from lung ischemia/reperfusion injury. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

2-D weighted least-squares phase unwrapping

DOEpatents

Ghiglia, Dennis C.; Romero, Louis A.

1995-01-01

Weighted values of interferometric signals are unwrapped by determining the least squares solution of phase unwrapping for unweighted values of the interferometric signals; and then determining the least squares solution of phase unwrapping for weighted values of the interferometric signals by preconditioned conjugate gradient methods using the unweighted solutions as preconditioning values. An output is provided that is representative of the least squares solution of phase unwrapping for weighted values of the interferometric signals.

2-D weighted least-squares phase unwrapping

DOEpatents

Ghiglia, D.C.; Romero, L.A.

1995-06-13

Weighted values of interferometric signals are unwrapped by determining the least squares solution of phase unwrapping for unweighted values of the interferometric signals; and then determining the least squares solution of phase unwrapping for weighted values of the interferometric signals by preconditioned conjugate gradient methods using the unweighted solutions as preconditioning values. An output is provided that is representative of the least squares solution of phase unwrapping for weighted values of the interferometric signals. 6 figs.

Microglial ablation and lipopolysaccharide preconditioning affects pilocarpine-induced seizures in mice

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

Mirrione, M.M.; Mirrione, M.M.; Konomosa, D.K.

2010-04-01

Activated microglia have been associated with neurodegeneration in patients and in animal models of Temporal Lobe Epilepsy (TLE), however their precise functions as neurotoxic or neuroprotective is a topic of significant investigation. To explore this, we examined the effects of pilocarpine-induced seizures in transgenic mice where microglia/macrophages were conditionally ablated. We found that unilateral ablation of microglia from the dorsal hippocampus did not alter acute seizure sensitivity. However, when this procedure was coupled with lipopolysaccharide (LPS) preconditioning (1 mg/kg given 24 h prior to acute seizure), we observed a significant pro-convulsant phenomenon. This effect was associated with lower metabolic activationmore » in the ipsilateral hippocampus during acute seizures, and could be attributed to activity in the mossy fiber pathway. These findings reveal that preconditioning with LPS 24 h prior to seizure induction may have a protective effect which is abolished by unilateral hippocampal microglia/macrophage ablation.« less

Parallelization of the preconditioned IDR solver for modern multicore computer systems

NASA Astrophysics Data System (ADS)

Bessonov, O. A.; Fedoseyev, A. I.

2012-10-01

This paper present the analysis, parallelization and optimization approach for the large sparse matrix solver CNSPACK for modern multicore microprocessors. CNSPACK is an advanced solver successfully used for coupled solution of stiff problems arising in multiphysics applications such as CFD, semiconductor transport, kinetic and quantum problems. It employs iterative IDR algorithm with ILU preconditioning (user chosen ILU preconditioning order). CNSPACK has been successfully used during last decade for solving problems in several application areas, including fluid dynamics and semiconductor device simulation. However, there was a dramatic change in processor architectures and computer system organization in recent years. Due to this, performance criteria and methods have been revisited, together with involving the parallelization of the solver and preconditioner using Open MP environment. Results of the successful implementation for efficient parallelization are presented for the most advances computer system (Intel Core i7-9xx or two-processor Xeon 55xx/56xx).

Mechanisms of acetylcholine- and bradykinin-induced preconditioning.

PubMed

Critz, Stuart D; Cohen, Michael V; Downey, James M

2005-01-01

Acetylcholine (ACh) and bradykinin (BK) are potent pharmacological agents which mimic ischemic preconditioning (IPC) enabling hearts to resist infarction during a subsequent period of ischemia. The cardioprotective pathways activated by BK but not ACh may also protect when activated at reperfusion. ACh and BK stimulate Gi/o-linked receptors and ultimately mediate protection by opening mitochondrial ATP-sensitive potassium channels with the generation of reactive oxygen species that act as second messengers to activate protein kinase C (PKC). There appear to be key differences, however, in the pathways prior to potassium channel opening for these two receptors. This review aims to summarize what is currently known about pharmacological preconditioning by ACh and BK with an emphasis on differences that are seen in the signal transduction cascades. Understanding the cellular basis of protection by ACh and BK is a critical step towards developing pharmacological agents that will prevent infarction during ischemia resulting from coronary occlusion or heart attack.

Factors affecting professional ethics in nursing practice in Iran: a qualitative study.

PubMed

Dehghani, Ali; Mosalanejad, Leili; Dehghan-Nayeri, Nahid

2015-09-09

Professional ethics refers to the use of logical and consistent communication, knowledge, clinical skills, emotions and values in nursing practice. This study aimed to explore and describe factors that affect professional ethics in nursing practice in Iran. This qualitative study was conducted using conventional content analysis approach. Thirty nurses with at least 5 years of experience participated in the study; they were selected using purposive sampling. Data were collected through semi-structured interviews and analyzed using thematic analysis. After encoding and classifying the data, five major categories were identified: individual character and responsibility, communication challenges, organizational preconditions, support systems, educational and cultural development. Awareness of professional ethics and its contributing factors could help nurses and healthcare professionals provide better services for patients. At the same time, such understanding would be valuable for educational administrators for effective planning and management.

Improvements in world-wide intercomparison of PV module calibration

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

Salis, E.; Pavanello, D.; Field, M.

The calibration of the electrical performance of seven photovoltaic (PV) modules was compared between four reference laboratories on three continents. The devices included two samples in standard and two in high-efficiency crystalline silicon technology, two CI(G)S and one CdTe module. The reference value for each PV module parameter was calculated from the average of the results of all four laboratories, weighted by the respective measurement uncertainties. All single results were then analysed with respect to this reference value using the E n number approach. For the four modules in crystalline silicon technology, the results agreed in general within +/-0.5%, withmore » all values within +/-1% and all E n numbers well within [-1, 1], indicating further scope for reducing quoted measurement uncertainty. Regarding the three thin-film modules, deviations were on average roughly twice as large, i.e. in general from +/-1% to +/-2%. A number of inconsistent results were observable, although within the 5% that can be statistically expected on the basis of the E n number approach. Most inconsistencies can be traced to the preconditioning procedure of one participant, although contribution of other factors cannot be ruled out. After removing these obvious inconsistent results, only two real outliers remained, representing less than 2% of the total number of measurands. The results presented show improved agreement for the calibration of PV modules with respect to previous international exercises. For thin-film PV modules, the preconditioning of the devices prior to calibration measurements is the most critical factor for obtaining consistent results, while the measurement processes seem consistent and repeatable.« less