Numerical Investigation of the Acoustic Damping of Plane Acoustic Waves by Perforated Liners with Bias Flow

NASA Astrophysics Data System (ADS)

Zhao, Dan; Zhong, Zhi Yuan

Perforated liners are extensively used in aero-engines and gas turbine combustors to suppress combustion instabilities. These liners, typically subjected to a low Mach number bias flow (a cooling flow through perforated holes), are fitted along the bounding walls of a combustor to convert acoustic energy into flow energy by generating vorticity at the rims of the perforated apertures. To investigate the acoustic damping of such liners with bias flow on plane acoustic waves, a time-domain numerical model is developed to compute acoustic wave propagation in a cylindrical duct with a single-layer liner attached. The damping mechanism of the liner is characterized in real-time by using a 'compliance', developed especially for this work. It is a rational function representation of the frequency-domain homogeneous compliance adapted from the Rayleigh conductivity of a single aperture with mean bias flow in the z-domain. The liner 'compliance' model is then incorporated into partial differential equations of the duct system, which are solved by using the method of lines. The numerical results are then evaluated by comparing with the numerical results of Eldredge and Dowling's frequency-domain model. Good agreement is observed. This confirms that the model and the approach developed are suitable for real-time characterizing the acoustic damping of perforated liners.

A review of bias flow liners for acoustic damping in gas turbine combustors

NASA Astrophysics Data System (ADS)

Lahiri, C.; Bake, F.

2017-07-01

The optimized design of bias flow liner is a key element for the development of low emission combustion systems in modern gas turbines and aero-engines. The research of bias flow liners has a fairly long history concerning both the parameter dependencies as well as the methods to model the acoustic behaviour of bias flow liners under the variety of different bias and grazing flow conditions. In order to establish an overview over the state of the art, this paper provides a comprehensive review about the published research on bias flow liners and modelling approaches with an extensive study of the most relevant parameters determining the acoustic behaviour of these liners. The paper starts with a historical description of available investigations aiming on the characterization of the bias flow absorption principle. This chronological compendium is extended by the recent and ongoing developments in this field. In a next step the fundamental acoustic property of bias flow liner in terms of the wall impedance is introduced and the different derivations and formulations of this impedance yielding the different published model descriptions are explained and compared. Finally, a parametric study reveals the most relevant parameters for the acoustic damping behaviour of bias flow liners and how this is reflected by the various model representations. Although the general trend of the investigated acoustic behaviour is captured by the different models fairly well for a certain range of parameters, in the transition region between the resonance dominated and the purely bias flow related regime all models lack the correct damping prediction. This seems to be connected to the proper implementation of the reactance as a function of bias flow Mach number.

Optimization and Control of Acoustic Liner Impedance with Bias Flow

NASA Technical Reports Server (NTRS)

Wood, Houston; Follet, Jesse

2000-01-01

Because communities are impacted by steady increases in aircraft traffic, aircraft noise continues to be a growing problem for the growth of commercial aviation. Research has focused on improving the design of specific high noise source areas of aircraft and on noise control measures to alleviate noise radiated from aircraft to the surrounding environment. Engine duct liners have long been a principal means of attenuating engine noise. The ability to control in-situ the acoustic impedance of a liner would provide a valuable tool to improve the performance of liners. The acoustic impedance of a liner is directly related to the sound absorption qualities of that liner. Increased attenuation rates, the ability to change liner acoustic impedance to match various operating conditions, or the ability to tune a liner to more precisely match design impedance represent some ways that in-situ impedance control could be useful. With this in mind, the research to be investigated will focus on improvements in the ability to control liner impedance using a mean flow through the liner which is referred to as bias flow.

Super-resolved calibration-free flow cytometric characterization of platelets and cell-derived microparticles in platelet-rich plasma.

PubMed

Konokhova, Anastasiya I; Chernova, Darya N; Moskalensky, Alexander E; Strokotov, Dmitry I; Yurkin, Maxim A; Chernyshev, Andrei V; Maltsev, Valeri P

2016-02-01

Importance of microparticles (MPs), also regarded as extracellular vesicles, in many physiological processes and clinical conditions motivates one to use the most informative and precise methods for their characterization. Methods based on individual particle analysis provide statistically reliable distributions of MP population over characteristics. Although flow cytometry is one of the most powerful technologies of this type, the standard forward-versus-side-scattering plots of MPs and platelets (PLTs) overlap considerably because of similarity of their morphological characteristics. Moreover, ordinary flow cytometry is not capable of measurement of size and refractive index (RI) of MPs. In this study, we 1) employed the potential of the scanning flow cytometer (SFC) for identification and characterization of MPs from light scattering; 2) suggested the reference method to characterize MP morphology (size and RI) with high precision; and 3) determined the lowest size of a MP that can be characterized from light scattering with the SFC. We equipped the SFC with 405 and 488 nm lasers to measure the light-scattering profiles and side scattering from MPs, respectively. The developed two-stage method allowed accurate separation of PLTs and MPs in platelet-rich plasma. We used two optical models for MPs, a sphere and a bisphere, in the solution of the inverse light-scattering problem. This solution provides unprecedented precision in determination of size and RI of individual spherical MPs-median uncertainties (standard deviations) were 6 nm and 0.003, respectively. The developed method provides instrument-independent quantitative information on MPs, which can be used in studies of various factors affecting MP population. © 2015 International Society for Advancement of Cytometry.

Advanced liner-cooling techniques for gas turbine combustors

NASA Technical Reports Server (NTRS)

Norgren, C. T.; Riddlebaugh, S. M.

1985-01-01

Component research for advanced small gas turbine engines is currently underway at the NASA Lewis Research Center. As part of this program, a basic reverse-flow combustor geometry was being maintained while different advanced liner wall cooling techniques were investigated. Performance and liner cooling effectiveness of the experimental combustor configuration featuring counter-flow film-cooled panels is presented and compared with two previously reported combustors featuring: splash film-cooled liner walls; and transpiration cooled liner walls (Lamilloy).

Small gas turbine combustor experimental study - Compliant metal/ceramic liner and performance evaluation

NASA Technical Reports Server (NTRS)

Acosta, W. A.; Norgren, C. T.

1986-01-01

Combustor research relating to the development of fuel efficient small gas turbine engines capable of meeting future commercial and military aviation needs is currently underway at NASA Lewis. As part of this combustor research, a basic reverse-flow combustor has been used to investigate advanced liner wall cooling techniques. Liner temperature, performance, and exhaust emissions of the experimental combustor utilizing compliant metal/ceramic liners were determined and compared with three previously reported combustors that featured: (1)splash film-cooled liner walls; (2) transpiration cooled liner walls; and (3) counter-flow film cooled panels.

Small gas turbine combustor experimental study: Compliant metal/ceramic liner and performance evaluation

NASA Technical Reports Server (NTRS)

Acosta, W. A.; Norgren, C. T.

1986-01-01

Combustor research relating to the development of fuel efficient small gas turbine engines capable of meeting future commercial and military aviation needs is currently underway at NASA Lewis. As part of this combustor research, a basic reverse-flow combustor has been used to investigate advanced liner wall cooling techniques. Liner temperature, performance, and exhaust emissions of the experimental combustor utilizing compliant metal/ceramic liners were determined and compared with three previously reported combustors that featured: (1) splash film-cooled liner walls; (2) transpiration cooled liner walls; and (3) counter-flow film cooled panels.

Numerical and Experimental Investigations of the Flow in a Stationary Pelton Bucket

NASA Astrophysics Data System (ADS)

Nakanishi, Yuji; Fujii, Tsuneaki; Kawaguchi, Sho

A numerical code based on one of mesh-free particle methods, a Moving-Particle Semi-implicit (MPS) Method has been used for the simulation of free surface flows in a bucket of Pelton turbines so far. In this study, the flow in a stationary bucket is investigated by MPS simulation and experiment to validate the numerical code. The free surface flow dependent on the angular position of the bucket and the corresponding pressure distribution on the bucket computed by the numerical code are compared with that obtained experimentally. The comparison shows that numerical code based on MPS method is useful as a tool to gain an insight into the free surface flows in Pelton turbines.

A method to determine the acoustical properties of locally and nonlocally reacting duct liners in grazing flow

NASA Technical Reports Server (NTRS)

Succi, G.

1982-01-01

The acoustical properties of locally and nonlocally reacting acoustical liners in grazing flow are described. The effect of mean flow and shear flow are considered as well as the application to rigid and limp bulk reacting materials. The axial wavenumber of the least attenuated mode in a flow duct is measured. The acoustical properties of duct liners is then deduced from the measured axial wavenumber and known flow profile and boundary conditions. This method is a natural extension of impedance-like measurements.

Combustor assembly in a gas turbine engine

DOEpatents

Wiebe, David J; Fox, Timothy A

2015-04-28

A combustor assembly in a gas turbine engine includes a combustor device, a fuel injection system, a transition duct, and an intermediate duct. The combustor device includes a flow sleeve for receiving pressurized air and a liner surrounded by the flow sleeve. The fuel injection system provides fuel to be mixed with the pressurized air and ignited in the liner to create combustion products. The intermediate duct is disposed between the liner and the transition duct so as to define a path for the combustion products to flow from the liner to the transition duct. The intermediate duct is associated with the liner such that movement may occur therebetween, and the intermediate duct is associated with the transition duct such that movement may occur therebetween. The flow sleeve includes structure that defines an axial stop for limiting axial movement of the intermediate duct.

Shock wave absorber having a deformable liner

DOEpatents

Youngdahl, C.K.; Wiedermann, A.H.; Shin, Y.W.; Kot, C.A.; Ockert, C.E.

1983-08-26

This invention discloses a shock wave absorber for a piping system carrying liquid. The absorber has a plastically deformable liner defining the normal flow boundary for an axial segment of the piping system, and a nondeformable housing is spaced outwardly from the liner so as to define a gas-tight space therebetween. The flow capacity of the liner generally corresponds to the flow capacity of the piping system line, but the liner has a noncircular cross section and extends axially of the piping system line a distance between one and twenty times the diameter thereof. Gas pressurizes the gas-tight space equal to the normal liquid pressure in the piping system. The liner has sufficient structural capacity to withstand between one and one-half and two times this normal liquid pressures; but at greater pressures it begins to plastically deform initially with respect to shape to a more circular cross section, and then with respect to material extension by circumferentially stretching the wall of the liner. A high energy shock wave passing through the liner thus plastically deforms the liner radially into the gas space and progressively also as needed in the axial direction of the shock wave to minimize transmission of the shock wave beyond the absorber.

A Conventional Liner Acoustic/Drag Interaction Benchmark Database

NASA Technical Reports Server (NTRS)

Howerton, Brian M.; Jones, Michael G.

2017-01-01

The aerodynamic drag of acoustic liners has become a significant topic in the design of such for aircraft noise applications. In order to evaluate the benefits of concepts designed to reduce liner drag, it is necessary to establish the baseline performance of liners employing the typical design features of conventional configurations. This paper details a set of experiments in the NASA Langley Grazing Flow Impedance Tube to quantify the relative drag of a number of perforate-over-honeycomb liner configurations at flow speeds of M=0.3 and 0.5. These conventional liners are investigated to determine their resistance factors using a static pressure drop approach. Comparison of the resistance factors gives a relative measurement of liner drag. For these same flow conditions, acoustic measurements are performed with tonal excitation from 400 to 3000 Hz at source sound pressure levels of 140 and 150 dB. Educed impedance and attenuation spectra are used to determine the interaction between acoustic performance and drag.

Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions

PubMed Central

Roca, Elisa; Lacroix, Romaric; Judicone, Coralie; Laroumagne, Sophie; Robert, Stéphane; Cointe, Sylvie; Muller, Alexandre; Kaspi, Elise; Roll, Patrice; Brisson, Alain R.; Tantucci, Claudio

2016-01-01

Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign (n = 14) and malignant (n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions. PMID:26689993

Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions.

PubMed

Roca, Elisa; Lacroix, Romaric; Judicone, Coralie; Laroumagne, Sophie; Robert, Stéphane; Cointe, Sylvie; Muller, Alexandre; Kaspi, Elise; Roll, Patrice; Brisson, Alain R; Tantucci, Claudio; Astoul, Philippe; Dignat-George, Françoise

2016-01-19

Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign (n = 14) and malignant (n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions.

Investigation of Liner Characteristics in the NASA Langley Curved Duct Test Rig

NASA Technical Reports Server (NTRS)

Gerhold, Carl H.; Brown, Martha C.; Watson, Willie R.; Jones, Michael G.

2007-01-01

The Curved Duct Test Rig (CDTR), which is designed to investigate propagation of sound in a duct with flow, has been developed at NASA Langley Research Center. The duct incorporates an adaptive control system to generate a tone in the duct at a specific frequency with a target Sound Pressure Level and a target mode shape. The size of the duct, the ability to isolate higher order modes, and the ability to modify the duct configuration make this rig unique among experimental duct acoustics facilities. An experiment is described in which the facility performance is evaluated by measuring the sound attenuation by a sample duct liner. The liner sample comprises one wall of the liner test section. Sound in tones from 500 to 2400 Hz, with modes that are parallel to the liner surface of order 0 to 5, and that are normal to the liner surface of order 0 to 2, can be generated incident on the liner test section. Tests are performed in which sound is generated without axial flow in the duct and with flow at a Mach number of 0.275. The attenuation of the liner is determined by comparing the sound power in a hard wall section downstream of the liner test section to the sound power in a hard wall section upstream of the liner test section. These experimentally determined attenuations are compared to numerically determined attenuations calculated by means of a finite element analysis code. The code incorporates liner impedance values educed from measured data from the NASA Langley Grazing Incidence Tube, a test rig that is used for investigating liner performance with flow and with (0,0) mode incident grazing. The analytical and experimental results compare favorably, indicating the validity of the finite element method and demonstrating that finite element prediction tools can be used together with experiment to characterize the liner attenuation.

Fracture Mechanics Analysis of LH2 Feed Line Flow Liners

NASA Technical Reports Server (NTRS)

James, Mark A.; Dawicke, David S.; Brzowski, Matthew B.; Raju, Ivatury S.; Elliott, Kenny B.; Harris, Charles E.

2006-01-01

Inspections of the Space Shuttle Main Engine revealed fatigue cracks growing from slots in the flow liner of the liquid hydrogen (LH2) feed lines. During flight, the flow liners experience complex loading induced by flow of LH2 and the resonance characteristics of the structure. The flow liners are made of Inconel 718 and had previously not been considered a fracture critical component. However, fatigue failure of a flow liner could have catastrophic effect on the Shuttle engines. A fracture mechanics study was performed to determine if a damage tolerance approach to life management was possible and to determine the sensitivity to the load spectra, material properties, and crack size. The load spectra were derived separately from ground tests and material properties were obtained from coupon tests. The stress-intensity factors for the fatigue cracks were determined from a shell-dynamics approach that simulated the dominant resonant frequencies. Life predictions were obtained using the NASGRO life prediction code. The results indicated that adequate life could not be demonstrated for initial crack lengths of the size that could be detected by traditional NDE techniques.

Avoiding false positive antigen detection by flow cytometry on blood cell derived microparticles: the importance of an appropriate negative control.

PubMed

Crompot, Emerence; Van Damme, Michael; Duvillier, Hugues; Pieters, Karlien; Vermeesch, Marjorie; Perez-Morga, David; Meuleman, Nathalie; Mineur, Philippe; Bron, Dominique; Lagneaux, Laurence; Stamatopoulos, Basile

2015-01-01

Microparticles (MPs), also called microvesicles (MVs) are plasma membrane-derived fragments with sizes ranging from 0.1 to 1μm. Characterization of these MPs is often performed by flow cytometry but there is no consensus on the appropriate negative control to use that can lead to false positive results. We analyzed MPs from platelets, B-cells, T-cells, NK-cells, monocytes, and chronic lymphocytic leukemia (CLL) B-cells. Cells were purified by positive magnetic-separation and cultured for 48h. Cells and MPs were characterized using the following monoclonal antibodies (CD19,20 for B-cells, CD3,8,5,27 for T-cells, CD16,56 for NK-cells, CD14,11c for monocytes, CD41,61 for platelets). Isolated MPs were stained with annexin-V-FITC and gated between 300nm and 900nm. The latex bead technique was then performed for easy detection of MPs. Samples were analyzed by Transmission (TEM) and Scanning Electron microscopy (SEM). Annexin-V positive events within a gate of 300-900nm were detected and defined as MPs. Our results confirmed that the characteristic antigens CD41/CD61 were found on platelet-derived-MPs validating our technique. However, for MPs derived from other cell types, we were unable to detect any antigen, although they were clearly expressed on the MP-producing cells in the contrary of several data published in the literature. Using the latex bead technique, we confirmed detection of CD41,61. However, the apparent expression of other antigens (already deemed positive in several studies) was determined to be false positive, indicated by negative controls (same labeling was used on MPs from different origins). We observed that mother cell antigens were not always detected on corresponding MPs by direct flow cytometry or latex bead cytometry. Our data highlighted that false positive results could be generated due to antibody aspecificity and that phenotypic characterization of MPs is a difficult field requiring the use of several negative controls.

Avoiding False Positive Antigen Detection by Flow Cytometry on Blood Cell Derived Microparticles: The Importance of an Appropriate Negative Control

PubMed Central

Crompot, Emerence; Van Damme, Michael; Duvillier, Hugues; Pieters, Karlien; Vermeesch, Marjorie; Perez-Morga, David; Meuleman, Nathalie; Mineur, Philippe; Bron, Dominique; Lagneaux, Laurence; Stamatopoulos, Basile

2015-01-01

Background Microparticles (MPs), also called microvesicles (MVs) are plasma membrane-derived fragments with sizes ranging from 0.1 to 1μm. Characterization of these MPs is often performed by flow cytometry but there is no consensus on the appropriate negative control to use that can lead to false positive results. Materials and Methods We analyzed MPs from platelets, B-cells, T-cells, NK-cells, monocytes, and chronic lymphocytic leukemia (CLL) B-cells. Cells were purified by positive magnetic-separation and cultured for 48h. Cells and MPs were characterized using the following monoclonal antibodies (CD19,20 for B-cells, CD3,8,5,27 for T-cells, CD16,56 for NK-cells, CD14,11c for monocytes, CD41,61 for platelets). Isolated MPs were stained with annexin-V-FITC and gated between 300nm and 900nm. The latex bead technique was then performed for easy detection of MPs. Samples were analyzed by Transmission (TEM) and Scanning Electron microscopy (SEM). Results Annexin-V positive events within a gate of 300-900nm were detected and defined as MPs. Our results confirmed that the characteristic antigens CD41/CD61 were found on platelet-derived-MPs validating our technique. However, for MPs derived from other cell types, we were unable to detect any antigen, although they were clearly expressed on the MP-producing cells in the contrary of several data published in the literature. Using the latex bead technique, we confirmed detection of CD41,61. However, the apparent expression of other antigens (already deemed positive in several studies) was determined to be false positive, indicated by negative controls (same labeling was used on MPs from different origins). Conclusion We observed that mother cell antigens were not always detected on corresponding MPs by direct flow cytometry or latex bead cytometry. Our data highlighted that false positive results could be generated due to antibody aspecificity and that phenotypic characterization of MPs is a difficult field requiring the use of several negative controls. PMID:25978814

Impedance Eduction in Sound Fields With Peripherally Varying Liners and Flow

NASA Technical Reports Server (NTRS)

Watson, W. R.; Jones, M. G.

2015-01-01

A two-dimensional impedance eduction theory is extended to three-dimensional sound fields and peripherally varying duct liners. The approach is to first measure the acoustic pressure field at a series of flush-mounted wall microphones located around the periphery of the flow duct. The numerical solution for the acoustic pressure field at these microphones is also obtained by solving the three-dimensional convected Helmholtz equation using the finite element method. A quadratic objective function based on the difference between the measured and finite element solution is constructed and the unknown impedance function is obtained by minimizing this objective function. Impedance spectra educed for two uniform-structure liners (a wire-mesh and a conventional liner) and a hard-soft-hard peripherally varying liner (for which the soft segment is that of the conventional liner) are presented. Results are presented at three mean flow Mach numbers and fourteen sound source frequencies. The impedance spectra of the uniform-structure liners are also computed using a two-dimensional impedance eduction theory. The primary conclusions of the study are: 1) when measured data is used with the uniform-structure liners, the three-dimensional theory reproduces the same impedance spectra as the two-dimensional theory except for frequencies corresponding to very low or very high liner attenuation; and 2) good agreement between the educed impedance spectra of the uniform structure conventional liner and the soft segment of the peripherally varying liner is obtained.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension.

PubMed

Rose, Jonathan A; Wanner, Nicholas; Cheong, Hoi I; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH.

Flow Cytometric Quantification of Peripheral Blood Cell β-Adrenergic Receptor Density and Urinary Endothelial Cell-Derived Microparticles in Pulmonary Arterial Hypertension

PubMed Central

Rose, Jonathan A.; Wanner, Nicholas; Cheong, Hoi I.; Queisser, Kimberly; Barrett, Patrick; Park, Margaret; Hite, Corrine; Naga Prasad, Sathyamangla V.; Erzurum, Serpil; Asosingh, Kewal

2016-01-01

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by severe angiogenic remodeling of the pulmonary artery wall and right ventricular hypertrophy. Thus, there is an increasing need for novel biomarkers to dissect disease heterogeneity, and predict treatment response. Although β-adrenergic receptor (βAR) dysfunction is well documented in left heart disease while endothelial cell-derived microparticles (Ec-MPs) are established biomarkers of angiogenic remodeling, methods for easy large clinical cohort analysis of these biomarkers are currently absent. Here we describe flow cytometric methods for quantification of βAR density on circulating white blood cells (WBC) and Ec-MPs in urine samples that can be used as potential biomarkers of right heart failure in PAH. Biotinylated β-blocker alprenolol was synthesized and validated as a βAR specific probe that was combined with immunophenotyping to quantify βAR density in circulating WBC subsets. Ec-MPs obtained from urine samples were stained for annexin-V and CD144, and analyzed by a micro flow cytometer. Flow cytometric detection of alprenolol showed that βAR density was decreased in most WBC subsets in PAH samples compared to healthy controls. Ec-MPs in urine was increased in PAH compared to controls. Furthermore, there was a direct correlation between Ec-MPs and Tricuspid annular plane systolic excursion (TAPSE) in PAH patients. Therefore, flow cytometric quantification of peripheral blood cell βAR density and urinary Ec-MPs may be useful as potential biomarkers of right ventricular function in PAH. PMID:27270458

Multi-resolution MPS method

NASA Astrophysics Data System (ADS)

Tanaka, Masayuki; Cardoso, Rui; Bahai, Hamid

2018-04-01

In this work, the Moving Particle Semi-implicit (MPS) method is enhanced for multi-resolution problems with different resolutions at different parts of the domain utilising a particle splitting algorithm for the finer resolution and a particle merging algorithm for the coarser resolution. The Least Square MPS (LSMPS) method is used for higher stability and accuracy. Novel boundary conditions are developed for the treatment of wall and pressure boundaries for the Multi-Resolution LSMPS method. A wall is represented by polygons for effective simulations of fluid flows with complex wall geometries and the pressure boundary condition allows arbitrary inflow and outflow, making the method easier to be used in flow simulations of channel flows. By conducting simulations of channel flows and free surface flows, the accuracy of the proposed method was verified.

Acoustic Characteristics of Various Treatment Panel Designs for HSCT Ejector Liner Acoustic Technology Development Program

NASA Technical Reports Server (NTRS)

Salikuddin, M.; Kraft, R. E.; Syed, A. a.; Vu, D. D.; Mungur, P.; Langenbrunner, L. E.; Majjigi, R. K.

2006-01-01

The objectives of the initial effort (Phase I) of HSR Liner Technology Program, the selection of promising liner concepts, design and fabrication of these concepts for laboratory tests, testing these liners in the laboratory by using impedance tube and flow ducts, and developing empirical impedance/suppression correlation, are successfully completed. Acoustic and aerodynamic criteria for the liner design are established. Based on these criteria several liners are designed. The liner concepts designed and fabricated include Single-Degree-of-Freedom (SDOF), Two-Degree-of-Freedom (2DOF), and Bulk Absorber. Two types of SDOF treatment are fabricated, one with a perforated type face plate and the other with a wiremesh (woven) type faceplate. In addition, special configurations of these concepts are also included in the design. Several treatment panels are designed for parametric study. In these panels the facesheets of different porosity, hole diameter, and sheet thickness are utilized. Several deep panels (i.e., 1 in. deep) are designed and instrumented to measure DC flow resistance and insitu impedance in the presence of grazing flow. Basic components of these panels (i.e., facesheets, bulk materials, etc.) are also procured and tested. The results include DC flow resistance, normal impedance, and insertion loss.

Suppression of Helmholtz resonance using inside acoustic liner

NASA Astrophysics Data System (ADS)

Hong, Zhiliang; Dai, Xiwen; Zhou, Nianfa; Sun, Xiaofeng; Jing, Xiaodong

2014-08-01

When a Helmholtz resonator is exposed to grazing flow, an unstable shear layer at the opening can cause the occurrence of acoustic resonance under appropriate conditions. In this paper, in order to suppress the flow-induced resonance, the effects of inside acoustic liners placed on the side wall or the bottom of a Helmholtz resonator are investigated. Based on the one-dimensional sound propagation theory, the time domain impedance model of a Helmholtz resonator with inside acoustic liner is derived, and then combined with a discrete vortex model the resonant behavior of the resonator under grazing flow is simulated. Besides, an experiment is conducted to validate the present model, showing significant reduction of the peak sound pressure level achieved by the use of the side-wall liners. And the simulation results match reasonably well with the experimental data. The present results reveal that the inside acoustic liner can not only absorb the resonant sound pressure, but also suppress the fluctuation motion of the shear layer over the opening of the resonator. In all, the impact of the acoustic liners is to dampen the instability of the flow-acoustic coupled system. This demonstrates that it is a convenient and effective method for suppressing Helmholtz resonance by using inside acoustic liner.

KSC-02pd1273

NASA Image and Video Library

2002-08-28

KENNEDY SPACE CENTER, FLA. -- U.S. Sen. Bill Nelson congratulates Rick Beckwith, with the Flow Liner Inspection & Repair team. Nelson presented gold seal Senate certificates to the team for their work on finding the cracks in orbiter flow liners and repairing them. Other team members behind Nelson are Mike Young (center) and Jerry Gouding (right). Not pictured are Tony Nesotas and David Strait. Strait first spotted the fuel-line crack; Goudy performed arc welding on one of Atlantis' flow liners.

Acoustic Liner Drag: Measurements on Novel Facesheet Perforate Geometries

NASA Technical Reports Server (NTRS)

Howerton, Brian M.; Jones, Michael G.

2016-01-01

Interest in characterization of the aerodynamic drag of acoustic liners has increased in the past several years. This paper details experiments in the NASA Langley Grazing Flow Impedance Tube to quantify the relative drag of several perforate-over-honeycomb liner configurations at flow speeds of centerline flow Mach number equals 0.3 and 0.5. Various perforate geometries and orientations are investigated to determine their resistance factors using a static pressure drop approach. Comparison of these resistance factors gives a relative measurement of liner drag. For these same flow conditions, acoustic measurements are performed with tonal excitation from 400 to 3000 hertz at source sound pressure levels of 140 and 150 decibels. Educed impedance and attenuation spectra are used to determine the impact of variations in perforate geometry on acoustic performance.

APPLICATION OF FLOW SIMULATION FOR EVALUATION OF FILLING-ABILITY OF SELF-COMPACTING CONCRETE

NASA Astrophysics Data System (ADS)

Urano, Shinji; Nemoto, Hiroshi; Sakihara, Kohei

In this paper, MPS method was applied to fluid an alysis of self-compacting concrete. MPS method is one of the particle method, and it is suitable for the simulation of moving boundary or free surface problems and large deformation problems. The constitutive equation of self-compacting concrete is assumed as bingham model. In order to investigate flow Stoppage and flow speed of self-compacting concrete, numerical analysis examples of slump flow and L-flow test were performed. In addition, to evaluate verification of compactability of self-compacting concrete, numerical analys is examples of compaction at the part of CFT diaphragm were performed. As a result, it was found that the MPS method was suitable for the simulation of compaction of self-compacting concrete, and a just appraisal was obtained by setting shear strain rate of flow-limit πc and limitation point of segregation.

Materials experiment carrier concepts definition study. Volume 2: Technical report, part 2

NASA Technical Reports Server (NTRS)

1981-01-01

A materials experiment carrier (MEC) that provides effective accommodation of the given baseline materials processing in space (MPS) payloads and demonstration of the MPS platform concept for high priority materials processing science, multidiscipline MPS investigations, host carrier for commercial MPS payloads, and system economy of orbital operations is defined. The study flow of task work is shown. Study tasks featured analysis and trades to identify the MEC system concept options.

Experimental Evaluation of Acoustic Engine Liner Models Developed with COMSOL Multiphysics

NASA Technical Reports Server (NTRS)

Schiller, Noah H.; Jones, Michael G.; Bertolucci, Brandon

2017-01-01

Accurate modeling tools are needed to design new engine liners capable of reducing aircraft noise. The purpose of this study is to determine if a commercially-available finite element package, COMSOL Multiphysics, can be used to accurately model a range of different acoustic engine liner designs, and in the process, collect and document a benchmark dataset that can be used in both current and future code evaluation activities. To achieve these goals, a variety of liner samples, ranging from conventional perforate-over-honeycomb to extended-reaction designs, were installed in one wall of the grazing flow impedance tube at the NASA Langley Research Center. The liners were exposed to high sound pressure levels and grazing flow, and the effect of the liner on the sound field in the flow duct was measured. These measurements were then compared with predictions. While this report only includes comparisons for a subset of the configurations, the full database of all measurements and predictions is available in electronic format upon request. The results demonstrate that both conventional perforate-over-honeycomb and extended-reaction liners can be accurately modeled using COMSOL. Therefore, this modeling tool can be used with confidence to supplement the current suite of acoustic propagation codes, and ultimately develop new acoustic engine liners designed to reduce aircraft noise.

The Aerodynamic Performance of an Over-the-Rotor Liner With Circumferential Grooves on a High Bypass Ratio Turbofan Rotor

NASA Technical Reports Server (NTRS)

Bozak, Richard F.; Hughes, Christopher E.; Buckley, James

2013-01-01

While liners have been utilized throughout turbofan ducts to attenuate fan noise, additional attenuation is obtainable by placing an acoustic liner over-the-rotor. Previous experiments have shown significant fan performance losses when acoustic liners are installed over-the-rotor. The fan blades induce an oscillating flow in the acoustic liners which results in a performance loss near the blade tip. An over-the-rotor liner was designed with circumferential grooves between the fan blade tips and the acoustic liner to reduce the oscillating flow in the acoustic liner. An experiment was conducted in the W-8 Single-Stage Axial Compressor Facility at NASA Glenn Research Center on a 1.5 pressure ratio fan to evaluate the impact of this over-the-rotor treatment design on fan aerodynamic performance. The addition of a circumferentially grooved over-the-rotor design between the fan blades and the acoustic liner reduced the performance loss, in terms of fan adiabatic efficiency, to less than 1 percent which is within the repeatability of this experiment.

The Aerodynamic Performance of an Over-The-Rotor Liner with Circumferential Grooves on a High Bypass Ratio Turbofan Rotor

NASA Technical Reports Server (NTRS)

Bozak, Rick; Hughes, Christopher; Buckley, James

2013-01-01

While liners have been utilized throughout turbofan ducts to attenuate fan noise, additional attenuation is obtainable by placing an acoustic liner over-the-rotor. Previous experiments have shown significant fan performance losses when acoustic liners are installed over-the-rotor. The fan blades induce an oscillating flow in the acoustic liners which results in a performance loss near the blade tip. An over-the-rotor liner was designed with circumferential grooves between the fan blade tips and the acoustic liner to reduce the oscillating flow in the acoustic liner. An experiment was conducted in the W-8 Single-Stage Axial Compressor Facility at NASA Glenn Research Center on a 1.5 pressure ratio fan to evaluate the impact of this over-the-rotor treatment design on fan aerodynamic performance. The addition of a circumferentially grooved over-the-rotor design between the fan blades and the acoustic liner reduced the performance loss, in terms of fan adiabatic efficiency, to less than 1% which is within the repeatability of this experiment.

Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay.

PubMed

Ayers, Lisa; Kohler, Malcolm; Harrison, Paul; Sargent, Ian; Dragovic, Rebecca; Schaap, Marianne; Nieuwland, Rienk; Brooks, Susan A; Ferry, Berne

2011-04-01

Circulating cell-derived microparticles (MPs) have been implicated in several disease processes and elevated levels are found in many pathological conditions. The detection and accurate measurement of MPs, although attracting widespread interest, is hampered by a lack of standardisation. The aim of this study was to establish a reliable flow cytometric assay to measure distinct subtypes of MPs in disease and to identify any significant causes of variability in MP quantification. Circulating MPs within plasma were identified by their phenotype (platelet, endothelial, leukocyte and annexin-V positivity (AnnV+). The influence of key variables (i.e. time between venepuncture and centrifugation, washing steps, the number of centrifugation steps, freezing/long-term storage and temperature of thawing) on MP measurement were investigated. Increasing time between venepuncture and centrifugation leads to increased MP levels. Washing samples results in decreased AnnV+MPs (P=0.002) and platelet-derived MPs (PMPs) (P=0.002). Double centrifugation of MPs prior to freezing decreases numbers of AnnV+MPs (P=0.0004) and PMPs (P=0.0004). A single freeze thaw cycle of samples led to an increase in AnnV+MPs (P=0.0020) and PMPs (P=0.0039). Long-term storage of MP samples at -80° resulted in decreased MP levels. This study found that minor protocol changes significantly affected MP levels. This is one of the first studies attempting to standardise a method for obtaining and measuring circulating MPs. Standardisation will be essential for successful development of MP technologies, allowing direct comparison of results between studies and leading to a greater understanding of MPs in disease. Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.

Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice

PubMed Central

Thomas, G. M.; Brill, A.; Mezouar, S.; Crescence, L.; Gallant, M.; Dubois, C.; Wagner, D. D.

2015-01-01

Background The risk of thrombotic complications such as deep vein thrombosis (DVT) during tumor development is well known. Tumors release into circulation procoagulant microparticles (MPs) that can participate in thrombus formation following vessel injury. The importance of this MP tissue factor (TF) in the initiation of cancer-associated DVT remains uncertain. Objective To address how pancreatic cancer MPs promote DVT in vivo. Methods We combined a DVT mouse model where thrombosis is induced by flow restriction of the inferior vena cava with one of subcutaneous pancreatic cancer in C57BL/6J mice. We infused high and low TF tumor MPs to determine the importance of TF in experimental cancer-associated DVT. Results Both tumor-bearing mice and mice infused with tumor MPs submitted to 3 hours of partial flow restriction developed an occlusive thrombus; fewer than a third of the control mice did. We observed that MPs adhered to neutrophil extracellular traps (NETs), functionally important players during DVT, whereas neither P-selectin nor GPIb were required for the MP recruitment in DVT. The thrombotic phenotype induced by MP infusion was suppressed by hirudin suggesting the importance of thrombin generation. TF carried by tumor MPs was essential to promote DVT as mice infused with low TF tumor MPs had less thrombosis than mice infused with high TF tumor MPs. Conclusions TF expressed on tumor MPs contributes to the increased incidence of cancer-associated venous thrombosis in mice in vivo. These MPs may adhere to NETs formed at the site of thrombosis. PMID:25955268

Tissue factor expressed by circulating cancer cell-derived microparticles drastically increases the incidence of deep vein thrombosis in mice.

PubMed

Thomas, G M; Brill, A; Mezouar, S; Crescence, L; Gallant, M; Dubois, C; Wagner, D D

2015-07-01

The risk of thrombotic complications such as deep vein thrombosis (DVT) during tumor development is well known. Tumors release into the circulation procoagulant microparticles (MPs) that can participate in thrombus formation following vessel injury. The importance of this MP tissue factor (TF) in the initiation of cancer-associated DVT remains uncertain. To investigate how pancreatic cancer MPs promote DVT in vivo. We combined a DVT mouse model in which thrombosis is induced by flow restriction in the inferior vena cava with one of subcutaneous pancreatic cancer in C57BL/6J mice. We infused high-TF and low-TF tumor MPs to determine the importance of TF in experimental cancer-associated DVT. Both tumor-bearing mice and mice infused with tumor MPs subjected to 3 h of partial flow restriction developed an occlusive thrombus; fewer than one-third of the control mice did. We observed that MPs adhered to neutrophil extracellular traps (NETs), which are functionally important players during DVT, whereas neither P-selectin nor glycoprotein Ib were required for MP recruitment in DVT. The thrombotic phenotype induced by MP infusion was suppressed by hirudin, suggesting the importance of thrombin generation. TF carried by tumor MPs was essential to promote DVT, as mice infused with low-TF tumor MPs had less thrombosis than mice infused with high-TF tumor MPs. TF expressed on tumor MPs contributes to the increased incidence of cancer-associated venous thrombosis in mice in vivo. These MPs may adhere to NETs formed at the site of thrombosis. © 2015 International Society on Thrombosis and Haemostasis.

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters.

PubMed

György, Bence; Módos, Károly; Pállinger, Eva; Pálóczi, Krisztina; Pásztói, Mária; Misják, Petra; Deli, Mária A; Sipos, Aron; Szalai, Anikó; Voszka, István; Polgár, Anna; Tóth, Kálmán; Csete, Mária; Nagy, György; Gay, Steffen; Falus, András; Kittel, Agnes; Buzás, Edit I

2011-01-27

Numerous diseases, recently reported to associate with elevated microvesicle/microparticle (MP) counts, have also long been known to be characterized by accelerated immune complex (IC) formation. The goal of this study was to investigate the potential overlap between parameters of protein complexes (eg, ICs or avidin-biotin complexes) and MPs, which might perturb detection and/or isolation of MPs. In this work, after comprehensive characterization of MPs by electron microscopy, atomic force microscopy, dynamic light-scattering analysis, and flow cytometry, for the first time, we drive attention to the fact that protein complexes, especially insoluble ICs, overlap in biophysical properties (size, light scattering, and sedimentation) with MPs. This, in turn, affects MP quantification by flow cytometry and purification by differential centrifugation, especially in diseases in which IC formation is common, including not only autoimmune diseases, but also hematologic disorders, infections, and cancer. These data may necessitate reevaluation of certain published data on patient-derived MPs and contribute to correct the clinical laboratory assessment of the presence and biologic functions of MPs in health and disease.

Duct wall impedance control as an advanced concept for acoustic suppression enhancement. [engine noise reduction

NASA Technical Reports Server (NTRS)

Dean, P. D.

1978-01-01

A systems concept procedure is described for the optimization of acoustic duct liner design for both uniform and multisegment types. The concept was implemented by the use of a double reverberant chamber flow duct facility coupled with sophisticated computer control and acoustic analysis systems. The optimization procedure for liner insertion loss was based on the concept of variable liner impedance produced by bias air flow through a multilayer, resonant cavity liner. A multiple microphone technique for in situ wall impedance measurements was used and successfully adapted to produce automated measurements for all liner configurations tested. The complete validation of the systems concept was prevented by the inability to optimize the insertion loss using bias flow induced wall impedance changes. This inability appeared to be a direct function of the presence of a higher order energy carrying modes which were not influenced significantly by the wall impedance changes.

Combustor assembly in a gas turbine engine

DOEpatents

Wiebe, David J; Fox, Timothy A

2013-02-19

A combustor assembly in a gas turbine engine. The combustor assembly includes a combustor device coupled to a main engine casing, a first fuel injection system, a transition duct, and an intermediate duct. The combustor device includes a flow sleeve for receiving pressurized air and a liner disposed radially inwardly from the flow sleeve. The first fuel injection system provides fuel that is ignited with the pressurized air creating first working gases. The intermediate duct is disposed between the liner and the transition duct and defines a path for the first working gases to flow from the liner to the transition duct. An intermediate duct inlet portion is associated with a liner outlet and allows movement between the intermediate duct and the liner. An intermediate duct outlet portion is associated with a transition duct inlet section and allows movement between the intermediate duct and the transition duct.

Comparison of Two Acoustic Waveguide Methods for Determining Liner Impedance

NASA Technical Reports Server (NTRS)

Jones, Michael G.; Watson, Willie R.; Tracy, Maureen B.; Parrott, Tony L.

2001-01-01

Acoustic measurements taken in a flow impedance tube are used to assess the relative accuracy of two waveguide methods for impedance eduction in the presence of grazing flow. The aeroacoustic environment is assumed to contain forward and backward-traveling acoustic waves, consisting of multiple modes, and uniform mean flow. Both methods require a measurement of the complex acoustic pressure profile over the length of the test liner. The Single Mode Method assumes that the sound pressure level and phase decay-rates of a single progressive mode can be extracted from this measured complex acoustic pressure profile. No a priori assumptions are made in the Finite Element. Method regarding the modal or reflection content in the measured acoustic pressure profile. The integrity of each method is initially demonstrated by how well their no-flow impedances match those acquired in a normal incidence impedance tube. These tests were conducted using ceramic tubular and conventional perforate liners. Ceramic tubular liners were included because of their impedance insensitivity to mean flow effects. Conversely, the conventional perforate liner was included because its impedance is known to be sensitive to mean flow velocity effects. Excellent comparisons between impedance values educed with the two waveguide methods in the absence of mean flow and the corresponding values educed with the normal incident impedance tube were observed. The two methods are then compared for mean flow Mach numbers up to 0.5, and are shown to give consistent results for both types of test liners. The quality of the results indicates that the Single Mode Method should be used when the measured acoustic pressure profile is clearly dominated by a single progressive mode, and the Finite Element Method should be used for all other cases.

Comparison of Acoustic Impedance Eduction Techniques for Locally-Reacting Liners

NASA Technical Reports Server (NTRS)

Jones, M. G.; Parrott, T. L.; Watson, W. R.

2003-01-01

Typical acoustic liners used in current aircraft inlets and aft-fan ducts consist of some type of perforated facesheet bonded to a honeycomb core. A number of techniques for determining the acoustic impedance of these locallyreacting liners have been developed over the last five decades. In addition, a number of models have been developed to predict the acoustic impedance of locallyreacting liners in the presence of grazing flow, and to use that information together with aeroacoustic propagation codes to assess the noise absorption provided by these liners. These prediction models have incorporated the results from databases acquired with specific impedance eduction techniques. Thus, while these prediction models are acceptable for liners that are similar to those tested in these databases, their application to new liner configurations must be viewed with caution. The primary purpose of this paper is to provide a comparison of impedance eduction techniques that have been implemented at various aerospace research laboratories in the United States (NASA Langley Research Center, General Electric Aircraft Engines, B. F. Goodrich and Boeing). A secondary purpose is to provide data for liner configurations that extend the porosity range beyond that which has been previously used in common aircraft engine nacelles. Two sets of liners were designed to study the effects of three parameters: perforate hole diameter, facesheet thickness and porosity. These two sets of liners were constructed for testing in each of the laboratories listed above. The first set of liners was designed to fit into the NASA Langley and Boeing test facilities. The second set was designed to fit into the General Electric Aircraft Engines and B. F. Goodrich test facilities. By using the same parent material, both sets of liners were identical to within the limits of material and fabrication variability. Baseline data were obtained in the normal incidence impedance tubes at NASA Langley and B. F. Goodrich. The results were found to compare extremely well. The samples were then tested in the grazing flow ducts of each of the four laboratories. Perhaps the most significant result of these comparisons is that the educed acoustic resistances for the liners used in this study increase as the mean flow profile is modified from uniform to 3-D shear. This realization has demonstrated the need for an frequency-dependent impedance eduction technique that incorporates 3-D shear flow and is efficient.

Climatology of summer midtropospheric perturbations in the U.S. northern plains. Part I: Influence on northwest flow severe weather outbreaks

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

Wang, Shih-Yu; Chen, Tsing-Chang; Correia, James

Northwest flow severe weather outbreaks (NWF outbreaks) describe a type of summer convective storm that occurs in areas of mid-level NWF in the central United States. Convective storms associated with NWF outbreaks are often progressive (i.e. traveling a long distance) along systematic, northwestsoutheast oriented tracks throughout the northern plains. Previous studies have observed that progressive convective storms under NWF are often coupled with subsynoptic-scale midtropospheric perturbations (MPs) coming from the Rocky Mountains. This study traces such MPs for the decade of 1997-2006 using the North American Regional Reanalysis to examine their climatology and possible influence on NWF outbreaks. MPs initiatedmore » over the Rocky Mountains have a maximum frequency in July when the North American anticyclone fully develops and forms prevailing NWF over the northern plains. MPs developed under this anticyclone appear restricted in their vertical extension. Nevertheless, persistent upward motion is apparent in the leading edge (east) of MPs soon after their genesis subsequently inducing or intensifying convective storms. MPs propagate along systematic tracks similar to those of NWF outbreaks. The propagation of MPs also synchronizes with the progressive behavior of the associated convective storms. When encountering strong low-level jets (LLJs), upward motion and convergence of water vapor flux associated with MPs intensify substantially, resulting in strongly enhanced convection and precipitation. Convective wind and hail frequencies associated with MPs in strong LLJs reveal a pattern and magnitude very similar to that of NWF outbreaks. While about 60% of summer rainfall in the northern plains is linked to MPs, 75% of these instances occur in strong LLJs.« less

Optimized multisectioned acoustic liners

NASA Technical Reports Server (NTRS)

Baumeister, K. J.

1979-01-01

New calculations show that segmenting is most efficient at high frequencies with relatively long duct lengths where the attenuation is low for both uniform and segmented liners. Statistical considerations indicate little advantage in using optimized liners with more than two segments while the bandwidth of an optimized two-segment liner is shown to be nearly equal to that of a uniform liner. Multielement liner calculations show a large degradation in performance due to changes in assumed input modal structure. Computer programs are used to generate theoretical attenuations for a number of liner configurations for liners in a rectangular duct with no mean flow. Overall, the use of optimized multisectioned liners fails to offer sufficient advantage over a uniform liner to warrant their use except in low frequency single mode application.

A Unique Test Facility to Measure Liner Performance with a Summary of Initial Test Results

NASA Technical Reports Server (NTRS)

Ahuja, K. K.; Gaeta, R. J., Jr.

1997-01-01

A very ambitious study was initiated to obtain detailed acoustic and flow data with and without a liner in a duct containing a mean flow so that available theoretical models of duct liners can be validated. A unique flow-duct facility equipped with a sound source, liner box, flush-walled microphones, traversable microphones and traversable pressure and temperature probes was built. A unique set of instrumentation boxes equipped with computer controlled traverses were designed and built that allowed measurements of Mach number, temperature, SPLs and phases in two planes upstream of a liner section and two planes downstream at a large number of measurement points. Each pair of planes provided acoustic pressure gradients for use in estimating the particle velocities. Specially-built microphone probes were employed to make measurements in the presence of the flow. A microphone traverse was also designed to measure the distribution of SPLs and phases from the beginning of the liner to its end along the duct axis. All measurements were made with the help of cross-correlation techniques to reject flow noise and/or other obtrusive noise, if any. The facility was designed for future use at temperatures as high as 1500 F. In order to validate 2-D models in the presence of mean flow, the flow duct was equipped with a device to modify boundary layer flow on the smaller sides of a rectangular duct to simulate 2-D flow. A massive amount of data was acquired for use in validating duct liner models and will be provided to NASA in an electronic form. It was found that the sound in the plane-wave regime is well behaved within the duct and the results are repeatable from one run to another. At the higher frequencies corresponding to the higher-order modes, the SPLs within a duct are not repeatable from run to run. In fact, when two or more modes have the same frequency (i.e., for the degenerate modes), the SPLs in the duct varied between 2 dB to 12 dB from run to run. This made the calibration of the microphone probes extremely difficult at the higher frequencies.

Direct numerical simulation and reduced-order modeling of the sound-induced flow through a cavity-backed circular under a turbulent boundary layer

NASA Astrophysics Data System (ADS)

Zhang, Qi; Bodony, Daniel

2014-11-01

Commercial jet aircraft generate undesirable noise from several sources, with the engines being the most dominant sources at take-off and major contributors at all other stages of flight. Acoustic liners, which are perforated sheets of metal or composite mounted within the engine, have been an effective means of reducing internal engine noise from the fan, compressor, combustor, and turbine but their performance suffers when subjected to a turbulent grazing flow or to high-amplitude incident sound due to poorly understood interactions between the liner orifices and the exterior flow. Through the use of direct numerical simulations, the flow-orifice interaction is examined numerically, quantified, and modeled over a range of conditions that includes current and envisioned uses of acoustic liners and with detail that exceeds experimental capabilities. A new time-domain model of acoustic liners is developed that extends currently-available reduced-order models to more complex flow conditions but is still efficient for use at the design stage.

Configuration Effects on Liner Performance

NASA Technical Reports Server (NTRS)

Gerhold, Carl H.; Brown, Martha C.; Jones, Michael G.; Howerton, Brian M.

2012-01-01

The acoustic performance of a duct liner depends not only on the intrinsic properties of the liner but also on the configuration of the duct in which it is used. A series of experiments is performed in the NASA Langley Research Center Curved Duct Test Rig (at Mach 0.275) to evaluate the effect of duct configuration on the acoustic performance of single degree of freedom perforate-over-honeycomb liners. The liners form the sidewalls of the duct's test section. Variations of duct configuration include: asymmetric (liner on one side and hard wall opposite) and symmetric (liner on both sides) wall treatment; inlet and exhaust orientation, in which the sound propagates either against or with the flow; and straight and curved flow path. The effect that duct configuration has on the overall acoustic performance, particularly the shift in frequency and magnitude of peak attenuation, is quantified. The redistribution of incident mode content is shown. The liners constitute the side walls of the liner test section and the scatter of incident horizontal order 1 mode by the asymmetric treatment and order 2 mode by the symmetric treatment into order 0 mode is shown. Scatter of order 0 incident modes into higher order modes is also shown. This redistribution of mode content is significant because it indicates that the liner design can be manipulated such that energy is scattered into more highly attenuated modes, thus enhancing liner performance.

Sound Absorption of a 2DOF Resonant Liner with Negative Bias Flow

NASA Technical Reports Server (NTRS)

Ahuja, K. K.; Cataldi, P.; Gaeta, R. J., Jr.

2000-01-01

This report describes an experimental study conducted to determine the effect of negative bias flow on the sound absorption of a two degree-of-freedom liner. The backwall for the liner was designed to act as a double-Helmholtz resonator so as to act as a hard wall at all frequencies except at its resonant frequencies. The effect of bias flow is investigated for a buried septum porosity of 2% and 19.5% for bias flow orifice Mach numbers up to 0.311. The bias flow appears to modify the resistance and reactance of the backwall alone at lower frequencies up to about 2 kHz, with marginal effects at higher frequencies. Absorption coefficients close to unity are achieved for a frequency range of 500 - 4000 Hz for the overall liner for a septum porosity of 2% and orifice Mach number of 0.128. Insertion loss tests performed in a flow duct facility for grazing flow Mach numbers up to 0.2 and septum Mach numbers up to 0.15 showed that negative bias flow can increase insertion loss by as much as 10 dB at frequencies in the range of 500 D 1400 Hz compared to no grazing flow. The effectiveness of the negative bias flow is diminished as the grazing flow velocity is increased.

Flap Side Edge Liners for Airframe Noise Reduction

NASA Technical Reports Server (NTRS)

Jones, Michael G. (Inventor); Khorrami, Mehdi R. (Inventor); Choudhari, Meelan M. (Inventor); Howerton, Brian M. (Inventor)

2014-01-01

One or more acoustic liners comprising internal chambers or passageways that absorb energy from a noise source on the aircraft are disclosed. The acoustic liners may be positioned at the ends of flaps of an aircraft wing to provide broadband noise absorption and/or dampen the noise producing unsteady flow features, and to reduce the amount of noise generated due to unsteady flow at the inboard and/or outboard end edges of a flap.

Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids

PubMed Central

Orozco, Aaron F.; Jorgez, Carolina J.; Horne, Cassandra; Marquez-Do, Deborah A.; Chapman, Matthew R.; Rodgers, John R.; Bischoff, Farideh Z.; Lewis, Dorothy E.

2008-01-01

Microparticles (MPs) that circulate in blood may be a source of DNA for molecular analyses, including prenatal genetic diagnoses. Because MPs are heterogeneous in nature, however, further characterization is important before use in clinical settings. One key question is whether DNA is either bound to aggregates of blood proteins and lipid micelles or intrinsically associated with MPs from dying cells. To test the latter hypothesis, we asked whether MPs derived in vitro from dying cells were similar to those in maternal plasma. JEG-3 cells model extravillous trophoblasts, which predominate during the first trimester of pregnancy when prenatal diagnosis is most relevant. MPs were derived from apoptosis and increased over 48 hours. Compared with necrotic MPs, DNA in apoptotic MPs was more fragmented and resistant to plasma DNases. Membrane-specific dyes indicated that apoptotic MPs had more membranous material, which protects nucleic acids, including RNA. Flow cytometry showed that MPs derived from dying cells displayed light scatter and DNA staining similar to MPs found in maternal plasma. Quantification of maternal MPs using characteristics defined by MPs generated in vitro revealed a significant increase of DNA+ MPs in the plasma of women with preeclampsia compared with plasma from women with normal pregnancies. Apoptotic MPs are therefore a likely source of stable DNA that could be enriched for both early genetic diagnosis and monitoring of pathological pregnancies. PMID:18974299

Aerodynamic design of the contoured wind-tunnel liner for the NASA supercritical, laminar-flow-control, swept-wing experiment

NASA Technical Reports Server (NTRS)

Newman, P. A.; Anderson, E. C.; Peterson, J. B., Jr.

1984-01-01

An overview is presented of the entire procedure developed for the aerodynamic design of the contoured wind tunnel liner for the NASA supercritical, laminar flow control (LFC), swept wing experiment. This numerical design procedure is based upon the simple idea of streamlining and incorporates several transonic and boundary layer analysis codes. The liner, presently installed in the Langley 8 Foot Transonic Pressure Tunnel, is about 54 ft long and extends from within the existing contraction cone, through the test section, and into the diffuser. LFC model testing has begun and preliminary results indicate that the liner is performing as intended. The liner design results presented in this paper, however, are examples of the calculated requirements and the hardware implementation of them.

Modeling of Passive Acoustic Liners from High Fidelity Numerical Simulations

NASA Astrophysics Data System (ADS)

Ferrari, Marcello do Areal Souto

Noise reduction in aviation has been an important focus of study in the last few decades. One common solution is setting up acoustic liners in the internal walls of the engines. However, measurements in the laboratory with liners are expensive and time consuming. The present work proposes a nonlinear physics-based time domain model to predict the acoustic behavior of a given liner in a defined flow condition. The parameters of the model are defined by analysis of accurate numerical solutions of the flow obtained from a high-fidelity numerical code. The length of the cavity is taken into account by using an analytical procedure to account for internal reflections in the interior of the cavity. Vortices and jets originated from internal flow separations are confirmed to be important mechanisms of sound absorption, which defines the overall efficiency of the liner. Numerical simulations at different frequency, geometry and sound pressure level are studied in detail to define the model parameters. Comparisons with high-fidelity numerical simulations show that the proposed model is accurate, robust, and can be used to define a boundary condition simulating a liner in a high-fidelity code.

The absorption of sound by perforated linings

NASA Astrophysics Data System (ADS)

Hughes, I. J.; Dowling, A. P.

1990-09-01

This paper describes a practical application for sound-absorbent perforated screen with a bias flow through the screen. It is postulated that, if a perforated liner with a bias flow of cooling air through the liner is inserted in the afterburner section of a jet engine, all the incident sound may be absorbed at a particular frequency. Experimental results are presented on the absorptive properties of plane liners with circular apertures, showing an agreement with the theoretical model.

Shuttle Main Propulsion System LH2 Feed Line and Inducer Simulations

NASA Technical Reports Server (NTRS)

Dorney, Daniel J.; Rothermel, Jeffry

2002-01-01

This viewgraph presentation includes simulations of the unsteady flow field in the LH2 feed line, flow line, flow liner, backing cavity and inducer of Shuttle engine #1. It also evaluates aerodynamic forcing functions which may contribute to the formation of the cracks observed on the flow liner slots. The presentation lists the numerical methods used, and profiles a benchmark test case.

Evaluation of Variable-Depth Liner Configurations for Increased Broadband Noise Reduction

NASA Technical Reports Server (NTRS)

Jones, M. G.; Watson, W. R.; Nark, D. M.; Howerton, B. M.

2015-01-01

This paper explores the effects of variable-depth geometry on the amount of noise reduction that can be achieved with acoustic liners. Results for two variable-depth liners tested in the NASA Langley Grazing Flow Impedance Tube demonstrate significant broadband noise reduction. An impedance prediction model is combined with two propagation codes to predict corresponding sound pressure level profiles over the length of the Grazing Flow Impedance Tube. The comparison of measured and predicted sound pressure level profiles is sufficiently favorable to support use of these tools for investigation of a number of proposed variable-depth liner configurations. Predicted sound pressure level profiles for these proposed configurations reveal a number of interesting features. Liner orientation clearly affects the sound pressure level profile over the length of the liner, but the effect on the total attenuation is less pronounced. The axial extent of attenuation at an individual frequency continues well beyond the location where the liner depth is optimally tuned to the quarter-wavelength of that frequency. The sound pressure level profile is significantly affected by the way in which variable-depth segments are distributed over the length of the liner. Given the broadband noise reduction capability for these liner configurations, further development of impedance prediction models and propagation codes specifically tuned for this application is warranted.

Damping parameter study of a perforated plate with bias flow

NASA Astrophysics Data System (ADS)

Mazdeh, Alireza

One of the main impediments to successful operation of combustion systems in industrial and aerospace applications including gas turbines, ramjets, rocket motors, afterburners (augmenters) and even large heaters/boilers is the dynamic instability also known as thermo-acoustic instability. Concerns with this ongoing problem have grown with the introduction of Lean Premixed Combustion (LPC) systems developed to address the environmental concerns associated with the conventional combustion systems. The most common way to mitigate thermo-acoustic instability is adding acoustic damping to the combustor using acoustic liners. Recently damping properties of bias flow initially introduced to liners only for cooling purposes have been recognized and proven to be an asset in enhancing the damping effectiveness of liners. Acoustic liners are currently being designed using empirical design rules followed by build-test-improve steps; basically by trial and error. There is growing concerns on the lack of reliability associated with the experimental evaluation of the acoustic liners with small size apertures. The development of physics-based tools in assisting the design of such liners has become of great interest to practitioners recently. This dissertation focuses primarily on how Large-Eddy Simulations (LES) or similar techniques such as Scaled Adaptive Simulation (SAS) can be used to characterize damping properties of bias flow. The dissertation also reviews assumptions made in the existing analytical, semi-empirical, and numerical models, provides a criteria to rank order the existing models, and identifies the best existing theoretical model. Flow field calculations by LES provide good insight into the mechanisms that led to acoustic damping. Comparison of simulation results with empirical and analytical studies shows that LES simulation is a viable alternative to the empirical and analytical methods and can accurately predict the damping behavior of liners. Currently the role of LES for research studies concerned with damping properties of liners is limited to validation of other empirical or theoretical approaches. This research has shown that LES can go beyond that and can be used for performing parametric studies to characterize the sensitivity of acoustic properties of multi--perforated liners to the changes in the geometry and flow conditions and be used as a tool to design acoustic liners. The conducted research provides an insightful understanding about the contribution of different flow and geometry parameters such as perforated plate thickness, aperture radius, porosity factors and bias flow velocity. While the study agrees with previous observations obtained by analytical or experimental methods, it also quantifies the impact from these parameters on the acoustic impedance of perforated plate, a key parameter to determine the acoustic performance of any system. The conducted study has also explored the limitations and capabilities of commercial tool when are applied for performing simulation studies on damping properties of liners. The overall agreement between LES results and previous studies proves that commercial tools can be effectively used for these applications under certain conditions.

Measurement of liner slips, milking time, and milk yield.

PubMed

O'Callaghan, E J

1996-03-01

Liner slip or rapid air leakage past the mouthpiece of the milking machine liner is related to high rates of new cases of mastitis. A real time technique was developed to monitor the air flow into the milking machine cluster during liner slips as well as to monitor milking time and milk yield using a commercial type pipeline milking system. The air flow into the cluster was measured by recording the pressure differences across an orifice plate placed in the air bypass of an air-milk separator using a differential pressure transducer. Milk yield was recorded by counting the number of milk releases from an electronic milk meter. The release solenoids of the milk meter were linked to a computer. The start and end of milking were manually recorded by switching a two-pole switch connected to a digital input card on the computer, which was programmed to record air flow, milk yield, and milking time. Milk yield, milking time, and air flows during liner slips were recorded simultaneously at each milking unit in an 11-unit herringbone parlor. The system was tested with an experiment with a 4 x 4 Latin square design using four treatments (clusters) and four treatment groups (22 cows per group).

Magnetic tagging of cell-derived microparticles: new prospects for imaging and manipulation of these mediators of biological information.

PubMed

Vats, Nidhi; Wilhelm, Claire; Rautou, Pierre-Emmanuel; Poirier-Quinot, Marie; Péchoux, Christine; Devue, Cécile; Boulanger, Chantal M; Gazeau, Florence

2010-07-01

Submicron membrane fragments termed microparticles (MPs), which are released by apoptotic or activated cells, are newly considered as vectors of biological information and actors of pathology development. We propose the tagging of MPs with magnetic nanoparticles as a new approach allowing imaging, manipulation and targeting of cell-derived MPs. MPs generated in vitro from human endothelial cells or isolated from atherosclerotic plaques were labeled using citrate-coated 8 nm iron-oxide nanoparticles. MPs were tagged with magnetic nanoparticles on their surface and detected as Annexin-V positive by flow cytometry. Labeled MPs could be mobilized, isolated and manipulated at a distance in a magnetic field gradient. Magnetic mobility of labeled MPs was quantified by micromagnetophoresis. Interactions of labeled MPs with endothelial cells could be triggered and modulated by magnetic guidance. Nanoparticles served as tracers at different scales: at the subcellular level by electron microscopy, at the cellular level by histology and at the macroscopic level by MRI. Magnetic labeling of biogenic MPs opens new prospects for noninvasive monitoring and distal manipulations of these biological effectors.

Advanced Computational and Experimental Techniques for Nacelle Liner Performance Evaluation

NASA Technical Reports Server (NTRS)

Gerhold, Carl H.; Jones, Michael G.; Brown, Martha C.; Nark, Douglas

2009-01-01

The Curved Duct Test Rig (CDTR) has been developed to investigate sound propagation through a duct of size comparable to the aft bypass duct of typical aircraft engines. The axial dimension of the bypass duct is often curved and this geometric characteristic is captured in the CDTR. The semiannular bypass duct is simulated by a rectangular test section in which the height corresponds to the circumferential dimension and the width corresponds to the radial dimension. The liner samples are perforate over honeycomb core and are installed on the side walls of the test section. The top and bottom surfaces of the test section are acoustically rigid to simulate a hard wall bifurcation or pylon. A unique feature of the CDTR is the control system that generates sound incident on the liner test section in specific modes. Uniform air flow, at ambient temperature and flow speed Mach 0.275, is introduced through the duct. Experiments to investigate configuration effects such as curvature along the flow path on the acoustic performance of a sample liner are performed in the CDTR and reported in this paper. Combinations of treated and acoustically rigid side walls are investigated. The scattering of modes of the incident wave, both by the curvature and by the asymmetry of wall treatment, is demonstrated in the experimental results. The effect that mode scattering has on total acoustic effectiveness of the liner treatment is also shown. Comparisons of measured liner attenuation with numerical results predicted by an analytic model based on the parabolic approximation to the convected Helmholtz equation are reported. The spectra of attenuation produced by the analytic model are similar to experimental results for both walls treated, straight and curved flow path, with plane wave and higher order modes incident. The numerical model is used to define the optimized resistance and reactance of a liner that significantly improves liner attenuation in the frequency range 1900-2400 Hz. A liner impedance descriptor is used to determine the liner parameters that achieve the optimum impedance.

Correlating shaped charge performance with processing conditions and microstructure of an aluminum alloy 1100 liner enabled by a new method to arrest nascent jet formation

NASA Astrophysics Data System (ADS)

Scheid, James Eric

Aluminum-lined shaped charges are used in special applications where jet and / or slug residue in the target is undesired. The three different microstructures of the aluminum liners studied herein resulted from three different manufacturing interpretations of the same design. One interpretation was completely machining the liners from best available annealed round stock. The second was to cold-forge the liners from annealed round-stock in an open-die forge to near-final dimensions, and then machine the liners to the final dimensions. The third variant in this study was to use the above forged liner, but with annealing after the machining. These three manufacturing choices resulted in significant variations in shaped charge performance. The goal of this research was to clarify the relationships between the liner metal microstructure and properties, and the corresponding shaped charge dynamic flow behavior. What began as an investigation into user-reported performance problems associated inherently with liner manufacturing processes and resultant microstructure, resolved into new understandings of the relationships between aluminum liner microstructure and shaped charge collapse kinetics. This understanding was achieved through an extensive literature review and the comprehensive characterization of the material properties of three variants of an 1100 aluminum shaped charge liner with a focus on collapse and nascent jet formation. The machined liner had a microstructure with large millimeter-sized grains and fine particles aligned in bands parallel to the charge axis. The forged liner microstructure consisted of very small one micrometer-sized (1 mum) subgrains and fine particles aligned largely in bands elongated parallel to the liner contour. The annealed liner was characterized by ten micrometer (10 mum) sized equiaxed grains with residual fine particles in the forged alignment. This characterization was enabled by the development, execution and validation of a custom explosive experiment that delivered meaningful, full-scale shock deformed samples for analysis. The experiment arrested the collapse of actual, as-fabricated liners in the first microseconds of development. This experiment, performed with only 2% of the explosive mass of the full charge, revealed new insights into material-dependent variations in liner collapse including a striking image of the formation of a shaped charge jet axial hole. The highly strain-hardened and elongated forged liner was the best performer of the three. Less energy from the explosive was dissipated by dislocation generation. This translated to more efficient flow whereas the softer materials behaved as shock absorbers delaying flow. A set of hypotheses was formulated and critiqued based on these observations. The key findings were the effects of grain size, and shear bands induced in the microstructure through cold work enabled efficient liner flow. These bands provide highly localized dislocation highways enabling the matrix adjacent to the bands to deform plastically at higher velocity. Where such bands are unavailable, the pressure must first develop bands of smaller grains, thus decreasing energy available for flow. Collapse velocities were then associated with the number of shear bands, the organization of mobile dislocations, material strain, and liner geometry. Microstructures with the ability to deform with the direction of liner collapse at lower stresses will form jets with a higher velocity and elongate earlier. The effect is higher performance at shorter standoffs. This relationship can be used to predict material behavior under explosive load, guiding engineering choices while designing with respect to anticipated shock loading. The explosive experiment designed here has obvious application in refining the performance of other warheads, and in the hydrodynamic modeling of material properties.

Boundary layer effects on liners for aircraft engines

NASA Astrophysics Data System (ADS)

Gabard, Gwénaël

2016-10-01

The performance of acoustic treatments installed on aircraft engines is strongly influenced by the boundary layer of the grazing flow on the surface of the liner. The parametric study presented in this paper illustrates the extent of this effect and identifies when it is significant. The acoustic modes of a circular duct with flow are calculated using a finite difference method. The parameters are representative of the flow conditions, liners and sound fields found in current turbofan engines. Both the intake and bypass ducts are considered. Results show that there is a complex interplay between the boundary layer thickness, the direction of propagation and the liner impedance and that the boundary layer can have a strong impact on liner performance for typical configurations (including changes of the order of 30 dB on the attenuation of modes associated with tonal fan noise). A modified impedance condition including the effect of a small but finite boundary layer thickness is considered and compared to the standard Myers condition based on an infinitely thin boundary layer. We show how this impedance condition can be implemented in a mode calculation method by introducing auxiliary variables. This condition is able to capture the trends associated with the boundary layer effects and in most cases provides improved predictions of liner performance.

Variable-Depth Liner Evaluation Using Two NASA Flow Ducts

NASA Technical Reports Server (NTRS)

Jones, M. G.; Nark, D. M.; Watson, W. R.; Howerton, B. M.

2017-01-01

Four liners are investigated experimentally via tests in the NASA Langley Grazing Flow Impedance Tube. These include an axially-segmented liner and three liners that use reordering of the chambers. Chamber reordering is shown to have a strong effect on the axial sound pressure level profiles, but a limited effect on the overall attenuation. It is also shown that bent chambers can be used to reduce the liner depth with minimal effects on the attenuation. A numerical study is also conducted to explore the effects of a planar and three higher-order mode sources based on the NASA Langley Curved Duct Test Rig geometry. A four-segment liner is designed using the NASA Langley CDL code with a Python-based optimizer. Five additional liner designs, four with rearrangements of the first liner segments and one with a redistribution of the individual chambers, are evaluated for each of the four sources. The liner configuration affects the sound pressure level profile much more than the attenuation spectra for the planar and first two higher-order mode sources, but has a much larger effect on the SPL profiles and attenuation spectra for the last higher-order mode source. Overall, axially variable-depth liners offer the potential to provide improved fan noise reduction, regardless of whether the axially variable depths are achieved via a distributed array of chambers (depths vary from chamber to chamber) or a group of zones (groups of chambers for which the depth is constant).

Analysis of synthetic and biological microparticles on several flow cytometric platforms***

EPA Science Inventory

Biological microparticles (MPs) are potentially important biomarkers for thrombosis, cancer, glomerulonephritis and other disease states. These MPs are generally accepted to be membrane vesicles extruded following cellular activation. While human blood cells range from 10-15 micr...

Recent advances in engineering microparticles and their nascent utilization in biomedical delivery and diagnostic applications.

PubMed

Choi, Andrew; Seo, Kyoung Duck; Kim, Do Wan; Kim, Bum Chang; Kim, Dong Sung

2017-02-14

Complex microparticles (MPs) bearing unique characteristics such as well-tailored sizes, various morphologies, and multi-compartments have been attempted to be produced by many researchers in the past decades. However, a conventionally used method of fabricating MPs, emulsion polymerization, has a limitation in achieving the aforementioned characteristics and several approaches such as the microfluidics-assisted (droplet-based microfluidics and flow lithography-based microfluidics), electrohydrodynamics (EHD)-based, centrifugation-based, and template-based methods have been recently suggested to overcome this limitation. The outstanding features of complex MPs engineered through these suggested methods have provided new opportunities for MPs to be applied in a wider range of applications including cell carriers, drug delivery agents, active pigments for display, microsensors, interface stabilizers, and catalyst substrates. Overall, the engineered MPs expose their potential particularly in the field of biomedical engineering as the increased complexity in the engineered MPs fulfills well the requirements of the high-end applications. This review outlines the current trends of newly developed techniques used for engineered MPs fabrication and focuses on the current state of engineered MPs in biomedical applications.

Acoustic Liner Drag: A Parametric Study of Conventional Configurations

NASA Technical Reports Server (NTRS)

Howerton, Brian M.; Jones, Michael G.

2015-01-01

Interest in the characterization of the aerodynamic drag performance of acoustic liners has increased in the past several years. This paper details experiments in NASA Langley's Grazing Flow Impedance Tube to quantify the relative drag of several conventional perforate-over-honeycomb liner configurations. For a fixed porosity, facesheet hole diameter and cavity depth are varied to study the effect of each. These configurations are selected to span the range of conventional liner geometries used in commercial aircraft engines. Detailed static pressure and acoustic measurements are made for grazing flows up to M=0.5 at 140 dB SPL for tones between 400 and 2800 Hz. These measurements are used to calculate a resistance factor (?) for each configuration. Analysis shows a correlation between perforate hole size and the resistance factor but cavity depth seems to have little influence. Acoustic effects on liner drag are observed to be limited to the lower Mach numbers included in this investigation.

Coolant mass flow equalizer for nuclear fuel

DOEpatents

Betten, Paul R.

1978-01-01

The coolant mass flow distribution in a liquid metal cooled reactor is enhanced by restricting flow in sub-channels defined in part by the peripheral fuel elements of a fuel assembly. This flow restriction, which results in more coolant flow in interior sub-channels, is achieved through the use of a corrugated liner positioned between the bundle of fuel elements and the inner wall of the fuel assembly coolant duct. The corrugated liner is expandable to accommodate irradiation induced growth of fuel assembly components.

Variable volume combustor with an air bypass system

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

Johnson, Thomas Edward; Ziminsky, Willy Steve; Ostebee, Heath Michael

The present application provides a combustor for use with flow of fuel and a flow of air in a gas turbine engine. The combustor may include a number of micro-mixer fuel nozzles positioned within a liner and an air bypass system position about the liner. The air bypass system variably allows a bypass portion of the flow of air to bypass the micro-mixer fuel nozzles.

Influence of newly designed monorail pressure sensor catheter on coronary diagnostic parameters: an in vitro study.

PubMed

Banerjee, Rupak K; Peelukhana, Srikara V; Goswami, Ishan

2014-02-07

The decision to perform intervention on a patient with coronary stenosis is often based on functional diagnostic parameters obtained from pressure and flow measurements using sensor-tipped guidewire at maximal vasodilation (hyperemia). Recently, a rapid exchange Monorail Pressure Sensor catheter of 0.022″ diameter (MPS22), with pressure sensor at distal end has been developed for improved assessment of stenosis severity. The hollow shaft of the MPS22 is designed to slide over any standard 0.014″ guidewire (G14). Hence, influence of MPS22 diameter on coronary diagnostic parameters needs investigation. An in vitro experiment was conducted to replicate physiologic flows in three representative area stenosis (AS): mild (64% AS), intermediate (80% AS), and severe (90% AS), for two arterial diameters, 3mm (N2; more common) and 2.5mm (N1). Influence of MPS22 on diagnostic parameters: fractional flow reserve (FFR) and pressure drop coefficient (CDP) was evaluated both at hyperemic and basal conditions, while comparing it with G14. The FFR values decreased for the MPS22 in comparison to G14, (Mild: 0.87 vs 0.88, Intermediate: 0.68 vs 0.73, Severe: 0.48 vs 0.56) and CDP values increased (Mild: 16 vs 14, Intermediate: 75 vs 56, Severe: 370 vs 182) for N2. Similar trend was observed in the case of N1. The FFR values were found to be well above (mild) and below (intermediate and severe) the diagnostic cut-off of 0.75. Therefore, MPS22 catheter can be used as a possible alternative to G14. Further, irrespective of the MPS22 or G14, basal FFR (FFRb) had overlapping ranges in close proximity for clinically relevant mild and intermediate stenoses that will lead to diagnostic uncertainty under both N1 and N2. However, CDPb had distinct ranges for different stenosis severities and could be a potential diagnostic parameter under basal conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design and preliminary results of a semitranspiration cooled (Lamilloy) liner for a high-pressure high-temperature combustor

NASA Technical Reports Server (NTRS)

Wear, J. D.; Trout, A. M.; Smith, J. M.; Jones, R. E.

1978-01-01

A Lamilloy combustor liner was designed, fabricated and tested in a combustor at pressures up to 8 atmospheres. The liner was fabricated of a three layer Lamilloy structure and designed to replace a conventional step louver liner. The liner is to be used in a combustor that provides hot gases to a turbine cooling test facility at pressures up to 40 atmospheres. The Lamilloy liner was tested extensively at lower pressures and demonstrated lower metal temperatures than the conventional liner, while at the same time requiring about 40 percent less cooling air flow. Tests conducted at combustor exit temperatures in excess of 2200 K have not indicated any cooling or durability problems with the Lamilloy linear.

Sound Absorption of a 2DOF Resonant Liner with Negative Bias Flow

NASA Technical Reports Server (NTRS)

Ahuja, K. K.; Cataldi, P.; Gaeta, R. J., Jr.; Jones, Mike (Technical Monitor)

2000-01-01

This report describes an experimental study conducted to determine the effect of negative bias flow on the sound absorption of a two degree-of-freedom liner. The backwall for the liner was designed to act as a double-Helmholtz resonator so as to act as a hard wall at all frequencies except at its resonant frequencies. All normal incident impedance data presented herein was acquired in an impedance tube. The effect of bias flow is investigated for a buried septum porosity of 2% and 19.5% for bias flow orifice mach numbers up to 03 11. As a porous backwall is needed for the flow to pass through, the effect of bias flow on this backwall all had to be evaluated first. The bias flow appears to modify the resistance and reactance of the backwall alone at lower frequencies up to about 2 kHz, with marginal effects at higher frequencies. Absorption coefficients close to unity are achieved for a frequency range of 500-4000 Hz for the overall liner for a septum porosity of 2% and orifice mach number of 0.128. Insertion loss tests performed in a flow duct facility for grazing flow Mach numbers up to 0.2 and septum mach numbers up to 0.15 showed that negative bias flow can increase insertion loss by as much as 10 dB at frequencies in the range of 500 - 1400 Hz compared to no grazing flow. The effectiveness of the negative bias flow is diminished as the grazing flow velocity is increased.

STS-112 final main engine is installed after welding/polishing process

NASA Technical Reports Server (NTRS)

2002-01-01

KENNEDY SPACE CENTER, FLA. -- The last engine is installed in orbiter Atlantis after a welding and polishing process was undertaken on flow liners where cracks were detected. All engines were removed for inspection of flow liners. Atlantis will next fly on mission STS-112, scheduled for launch no earlier than Oct. 2.

Micro- and Macro-Fluid Dynamics and Acoustics of Resonant Liners

NASA Technical Reports Server (NTRS)

Tam, Christopher K. W.; Watson, Willie (Technical Monitor)

2002-01-01

The objectives of this project are to perform direct numerical simulation of the micro-fluid and acoustic fields of a resonant acoustic liner and to investigate the physical processes by which incident sound waves are damped by the acoustic liner. We would like to report that our research work and results have fulfilled both objectives of the grant. The following is a summary of the important accomplishments: (1) Two dimensional direct numerical simulation of the flow and acoustic field around the cavity of resonant liner were successfully carried out; (2) The simulations of (1) were extended to include a laminar grazing flow; (3) The numerical simulations provided strong evidence that there are two principal mechanisms by which a resonant liner damps out an incident acoustic wave; (4) A validation test was performed by comparing the computed dissipation coefficients (not impedance) with impedance tube measurements done at GTRI; and (5) Some resources of this grant were used to support the development of new CAA methods. (Our work on numerical simulation of acoustic liners has benefited by the availability of these improved methods).

Characterization of pulmonary function impairments in patients with mucopolysaccharidoses--changes with age and treatment.

PubMed

Lin, Shuan-Pei; Shih, Shou-Chuan; Chuang, Chih-Kuang; Lee, Kuo-Sheng; Chen, Ming-Ren; Niu, Dau-Ming; Chiu, Pao Chin; Lin, Shio Jean; Lin, Hsiang-Yu

2014-03-01

The mucopolysaccharidoses (MPS) comprise a group of inherited lysosomal storage disorders characterized by deficiencies in enzymes catalyzing the degradation of glycosaminoglycans. Impairment of pulmonary function is an important health problem for patients with MPS. However, there are few published reports on the prevalence and severity of pulmonary dysfunction in relation to age and treatment in this disorder. To evaluate pulmonary function in patients with MPS, we performed spirometry in 35 patients (22 males and 13 females; 1 with MPS I, 12 with MPS II, 16 with MPS IVA, and 6 with MPS VI; mean age, 14.6 ± 5.9 years; age range, 6.4 years to 33 years). Forced vital capacity (FVC), forced expired volume in 1 sec (FEV1), FEV1 to FVC ratio (FEV1/FVC), peak expiratory flow (PEF), and mean forced expiratory flow during the middle half of FVC (FEF25-75% ) were measured. Mean FVC, FEV1 , PEF, and FEF25-75% were 74.2%, 73.9%, 64.7%, and 37.1% of the predicted values, respectively. By spirometric classification, 32 patients (91%) had small airway disease (FEF25-75%  < 65%), 17 (48%) had restrictive lung disease, and 3 (9%) had obstructive lung disease. Percent predicted FVC, FEV1 , and PEF, as well as FEV1 /FVC, were all negatively correlated with age (P < 0.01), such that pubertal and post-pubertal patients had significantly lower values than younger patients. Of eight attenuated MPS II and VI patients who underwent follow-up pulmonary function testing after receiving enzyme replacement therapy (ERT) for 1.5-7.4 years, six showed improvements in % predicted FVC and five improved in % predicted FEV1 . Our additional characterization of the types and prevalence of pulmonary function abnormalities seen in MPS patients should be useful for clinical care. © 2013 Wiley Periodicals, Inc.

Microparticles in the blood of patients with systemic lupus erythematosus (SLE): phenotypic characterization and clinical associations

PubMed Central

Mobarrez, Fariborz; Vikerfors, Anna; Gustafsson, Johanna T.; Gunnarsson, Iva; Zickert, Agneta; Larsson, Anders; Pisetsky, David S.; Wallén, Håkan; Svenungsson, Elisabet

2016-01-01

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by circulating autoantibodies and the formation of immune complexes. In these responses, the selecting self-antigens likely derive from the remains of dead and dying cells, as well as from disturbances in clearance. During cell death/activation, microparticles (MPs) can be released to the circulation. Previous MP studies in SLE have been limited in size and differ regarding numbers and phenotypes. Therefore, to characterize MPs more completely, we investigated 280 SLE patients and 280 individually matched controls. MPs were measured with flow cytometry and phenotyped according to phosphatidylserine expression (PS+/PS−), cellular origin and inflammatory markers. MPs, regardless of phenotype, are 2–10 times more abundant in SLE blood compared to controls. PS− MPs predominated in SLE, but not in controls (66% vs. 42%). Selectively in SLE, PS− MPs were more numerous in females and smokers. MP numbers decreased with declining renal function, but no clear association with disease activity was observed. The striking abundance of MPs, especially PS− MPs, suggests a generalized disturbance in SLE. MPs may be regarded as “liquid biopsies” to assess the production and clearance of dead, dying and activated cells, i.e. pivotal events for SLE pathogenesis. PMID:27777414

Statistically Based Approach to Broadband Liner Design and Assessment

NASA Technical Reports Server (NTRS)

Jones, Michael G. (Inventor); Nark, Douglas M. (Inventor)

2016-01-01

A broadband liner design optimization includes utilizing in-duct attenuation predictions with a statistical fan source model to obtain optimum impedance spectra over a number of flow conditions for one or more liner locations in a bypass duct. The predicted optimum impedance information is then used with acoustic liner modeling tools to design liners having impedance spectra that most closely match the predicted optimum values. Design selection is based on an acceptance criterion that provides the ability to apply increasing weighting to specific frequencies and/or operating conditions. One or more broadband design approaches are utilized to produce a broadband liner that targets a full range of frequencies and operating conditions.

Cause or Effect of Arteriogenesis: Compositional Alterations of Microparticles from CAD Patients Undergoing External Counterpulsation Therapy

PubMed Central

Stutz, Monika; Buchs, Natasha; Heller, Manfred

2012-01-01

Recently, a clinical study on patients with stable coronary artery disease (CAD) showed that external counterpulsation therapy (ECP) at high (300 mmHg) but not at low inflation pressure (80 mmHg) promoted coronary collateral growth, most likely due to shear stress-induced arteriogenesis. The exact molecular mechanisms behind shear stress-induced arteriogenesis are still obscure. We therefore characterized plasma levels of circulating microparticles (MPs) from these CAD patients because of their ambivalent nature as a known cardiovascular risk factor and as a promoter of neovascularization in the case of platelet-derived MPs. MPs positive for Annexin V and CD31CD41 were increased, albeit statistically significant (P<0.05, vs. baseline) only in patients receiving high inflation pressure ECP as determined by flow cytometry. MPs positive for CD62E, CD146, and CD14 were unaffected. In high, but not in low, inflation pressure treatment, change of CD31CD41 was inversely correlated to the change in collateral flow index (CFI), a measure for collateral growth. MPs from the high inflation pressure group had a more sustained pro-angiogenic effect than the ones from the low inflation pressure group, with the exception of one patient showing also an increased CFI after treatment. A total of 1005 proteins were identified by a label-free proteomics approach from MPs of three patients of each group applying stringent acceptance criteria. Based on semi-quantitative protein abundance measurements, MPs after ECP therapy contained more cellular proteins and increased CD31, corroborating the increase in MPs. Furthermore, we show that MP-associated factors of the innate immune system were decreased, many membrane-associated signaling proteins, and the known arteriogenesis stimulating protein transforming growth factor beta-1 were increased after ECP therapy. In conclusion, our data show that ECP therapy increases platelet-derived MPs in patients with CAD and that the change in protein cargo of MPs is likely in favor of a pro angiogenic/arteriogenic property. Trial Registration ClinicalTrials.gov NCT00414297 PMID:23056467

Transition duct system with straight ceramic liner for delivering hot-temperature gases in a combustion turbine engine

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

Wiebe, David J.

A transition duct system (10) for delivering hot-temperature gases from a plurality of combustors in a combustion turbine engine is provided. The system includes an exit piece (16) for each combustor. The exit piece may include a straight path segment (26) for receiving a gas flow from a respective combustor. A straight ceramic liner (40) may be inwardly disposed onto a metal outer shell (38) along the straight path segment of the exit piece. Structural arrangements are provided to securely attach the ceramic liner in the presence of substantial flow path pressurization. Cost-effective serviceability of the transition duct systems ismore » realizable since the liner can be readily removed and replaced as needed.« less

Time courses and value of circulating microparticles in patients with operable stage non-small cell lung cancer undergoing surgical intervention.

PubMed

Tseng, Chia-Cheng; Wang, Chin-Chou; Hsiao, Chang-Chun; Lu, Hung-I; Leu, Steve; Chang, Huang-Chih; Huang, Kuo-Tung; Fang, Wen-Feng; Chen, Yu-Mu; Liu, Shih-Feng; Yang, Cheng-Ta; Lin, Meng-Chih; Yip, Hon-Kan

2016-09-01

Microparticles (MPs) are substantially increased in patients with operable stage non-small cell lung cancer (NSCLC) prior to lung resection surgery. This study tested the hypothesis that there is a decrease in MPs after surgical intervention. Between March 2012 and January 2015, 33 patients who had operable stage NSCLC were consecutively and prospectively enrolled into the study. Additionally, 31 healthy subjects who were consecutively enrolled in the study period served as age- and gender-matched controls. Circulating MPs (EDAc-MPs, EDAp-MPs, PDAc-MPs, PDAp-MPs) were measured by flow cytometry once in control subjects and twice (i.e., prior to and three months later after surgical intervention) in NSCLC patients. Compared with control subjects, these four types of circulating MPs were significantly higher in NSCLC patients prior to operation (all P < 0.005), but did not differ among the controls and NSCLC patients at 3 months after surgery (all P > 0.2). Additionally, a receiver operating characteristic curve (ROC) showed that these four types of MPs were significantly valuable predictors for detecting early stage NSCLC (all P < 0.004). Circulating MPs which were remarkably increased in the operable stage of NSCLC prior to surgery were substantially decreased 3 months later after surgery. These findings show that circulating MPs might be an accessory biomarker for monitoring those of NSCLC after receiving lung resection surgery.

Endothelial Cell-Derived Microparticles from Patients with Obstructive Sleep Apnea Hypoxia Syndrome and Coronary Artery Disease Increase Aortic Endothelial Cell Dysfunction.

PubMed

Jia, Lixin; Fan, Jingyao; Cui, Wei; Liu, Sa; Li, Na; Lau, Wayne Bond; Ma, Xinliang; Du, Jie; Nie, Shaoping; Wei, Yongxiang

2017-01-01

Obstructive sleep apnea hypoxia syndrome (OSAHS) is an independent risk factor for coronary artery disease (CAD). Treatment of OSAHS improves clinical outcome in some CAD patients, but the relationship between OSAHS and CAD is complex. Microparticles (MPs) are shed by the plasma membrane by either physiologic or pathologic stimulation. In the current study, we investigated the role of MPs in the context of OSAHS. 54 patients with both suspected coronary artery stenosis and OSAHS were recruited and underwent both coronary arteriography and polysomnography. Circulating MPs were isolated and analyzed by flow cytometry. CAD+OSAHS patients exhibited greater levels of total MPs (Annexin V+), erythrocyte-derived MPs (CD235+ Annexin V+), platelet-derived MPs (CD41+ Annexin V+), and leukocyte-derived MPs (CD45+ Annexin V+) compared to CAD alone patients or control. CAD+OSAHS patients expressed the greatest level of endothelial-derived MPs of all cellular origin types (CD144+ Annexin V +). Treatment of human aortic endothelial cells (HAECs) with MPs isolated from CAD+OSAHS patients markedly increased HAEC permeability (as detected by FITC-dextran), and significantly upregulated mRNA levels of ICAM-1, VCAM-1, and MCP-1. OSAHS+CAD patients harbor increased levels of MPs, particularly the endothelial cell-derived subtype. When administered to HAECs, OSAHS+CAD patients MPs increase endothelial cell permeability and dysfunction. © 2017 The Author(s). Published by S. Karger AG, Basel.

STS-112 final main engine is installed after welding/polishing process

NASA Technical Reports Server (NTRS)

2002-01-01

KENNEDY SPACE CENTER, FLA. - Workers get ready to install the last engine in orbiter Atlantis after a welding and polishing process was undertaken on flow liners where cracks were detected. All engines were removed for inspection of flow liners. Atlantis will next fly on mission STS-112, scheduled for launch no earlier than Oct. 2.

Uncertainty Analysis of the Grazing Flow Impedance Tube

NASA Technical Reports Server (NTRS)

Brown, Martha C.; Jones, Michael G.; Watson, Willie R.

2012-01-01

This paper outlines a methodology to identify the measurement uncertainty of NASA Langley s Grazing Flow Impedance Tube (GFIT) over its operating range, and to identify the parameters that most significantly contribute to the acoustic impedance prediction. Two acoustic liners are used for this study. The first is a single-layer, perforate-over-honeycomb liner that is nonlinear with respect to sound pressure level. The second consists of a wire-mesh facesheet and a honeycomb core, and is linear with respect to sound pressure level. These liners allow for evaluation of the effects of measurement uncertainty on impedances educed with linear and nonlinear liners. In general, the measurement uncertainty is observed to be larger for the nonlinear liners, with the largest uncertainty occurring near anti-resonance. A sensitivity analysis of the aerodynamic parameters (Mach number, static temperature, and static pressure) used in the impedance eduction process is also conducted using a Monte-Carlo approach. This sensitivity analysis demonstrates that the impedance eduction process is virtually insensitive to each of these parameters.

Numerical and Physical Modeling of the Response of Resonator Liners to Intense Sound and Grazing Flow

NASA Technical Reports Server (NTRS)

Hersh, Alan S.; Tam, Christopher

2009-01-01

Two significant advances have been made in the application of computational aeroacoustics methodology to acoustic liner technology. The first is that temperature effects for discrete sound are not the same as for broadband noise. For discrete sound, the normalized resistance appears to be insensitive to temperature except at high SPL. However, reactance is lower, significantly lower in absolute value, at high temperature. The second is the numerical investigation the acoustic performance of a liner by direct numerical simulation. Liner impedance is affected by the non-uniformity of the incident sound waves. This identifies the importance of pressure gradient. Preliminary design one and two-dimensional impedance models were developed to design sound absorbing liners in the presence of intense sound and grazing flow. The two-dimensional model offers the potential to empirically determine incident sound pressure face-plate distance from resonator orifices. This represents an important initial step in improving our understanding of how to effectively use the Dean Two-Microphone impedance measurement method.

Ground Runup Noise Suppression Program. Part 3. Dry Suppressor Technology Base.

DTIC Science & Technology

1982-06-20

ref 7) used mineral wool to fill the bays. A facing of corrugated metal liner supports the mineral wool . During operation two types of problems...1978 52 tube. The hot jet velocity exhaust flow shifted/decinerated the mineral wool and caused the metal liner to crack/break off. Programs were...PREDICTED) 0 MINERAL WOOL FIBROUS LINER 315 630 1250 2500 5000 10000 20000 1/15 SCALE FREQUENCY Figure 2-30. Noise attenuation of liners in augmenter. K

Modular assembly for supporting, straining, and directing flow to a core in a nuclear reactor

DOEpatents

Pennell, William E.

1977-01-01

A reactor core support arrangement for supporting, straining, and providing fluid flow to the core and periphery of a nuclear reactor during normal operation. A plurality of removable inlet modular units are contained within permanent liners in the lower supporting plate of the reactor vessel lower internals. During normal operation (1) each inlet modular unit directs main coolant flow to a plurality of core assemblies, the latter being removably supported in receptacles in the upper portion of the modular unit and (2) each inlet modular unit may direct bypass flow to a low pressure annular region of the reactor vessel. Each inlet modular unit may include special fluid seals interposed between mating surfaces of the inlet modular units and the core assemblies and between the inlet modular units and the liners, to minimize leakage and achieve an hydraulic balance. Utilizing the hydraulic balance, the modular units are held in the liners and the assemblies are held in the modular unit receptacles by their own respective weight. Included as part of the permanent liners below the horizontal support plate are generally hexagonal axial debris barriers. The axial debris barriers collectively form a bottom boundary of a secondary high pressure plenum, the upper boundary of which is the bottom surface of the horizontal support plate. Peripheral liners include radial debris barriers which collectively form a barrier against debris entry radially. During normal operation primary coolant inlet openings in the liner, below the axial debris barriers, pass a large amount of coolant into the inlet modular units, and secondary coolant inlet openings in the portion of the liners within the secondary plenum pass a small amount of coolant into the inlet modular units. The secondary coolant inlet openings also provide alternative coolant inlet flow paths in the unlikely event of blockage of the primary inlet openings. The primary inlet openings have characteristics which limit the entry of debris and minimize the potential for debris entering the primary inlets blocking the secondary inlets from inside the modular unit.

Magnetized Target Fusion Driven by Plasma Liners

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Cassibry, Jason; Eskridge, Richard; Kirkpatrick, Ronald C.; Knapp, Charles E.; Lee, Michael; Martin, Adam; Smith, James; Wu, S. T.; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

For practical applications of magnetized target fusion, standoff drivers to deliver the imploding momentum flux to the target plasma remotely are required. Quasi-spherically converging plasma jets have been proposed as standoff drivers for this purpose. The concept involves the dynamic formation of a quasi-spherical plasma liner by the merging of plasma jets, and the use of the liner so formed to compress a spheromak or a field reversed configuration (FRC). Theoretical analysis and computer modeling of the concept are presented. It is shown that, with the appropriate choice of the flow parameters in the liner and the target, the impact between the liner and the target plasma can be made to be shockless in the liner or to generate at most a very weak shock in the liner. Additional information is contained in the original extended abstract.

STS-112 final main engine is installed after welding/polishing process

NASA Technical Reports Server (NTRS)

2002-01-01

KENNEDY SPACE CENTER, FLA. -- Workers on the engine lift get ready to install the last engine in orbiter Atlantis after a welding and polishing process was undertaken on flow liners where cracks were detected. All engines were removed for inspection of flow liners. Atlantis will next fly on mission STS-112, scheduled for launch no earlier than Oct. 2.

Unsteady Flow Interactions Between the LH2 Feed Line and SSME LPFP Inducer

NASA Technical Reports Server (NTRS)

Dorney, Dan; Griffin, Lisa; Marcu, Bogdan; Williams, Morgan

2006-01-01

An extensive computational effort has been performed in order to investigate the nature of unsteady flow in the fuel line supplying the three Space Shuttle Main Engines during flight. Evidence of high cycle fatigue (HCF) in the flow liner one diameter upstream of the Low Pressure Fuel Pump inducer has been observed in several locations. The analysis presented in this report has the objective of determining the driving mechanisms inducing HCF and the associated fluid flow phenomena. The simulations have been performed using two different computational codes, the NASA MSFC PHANTOM code and the Pratt and Whitney Rocketdyne ENIGMA code. The fuel flow through the flow liner and the pump inducer have been modeled in full three-dimensional geometry, and the results of the computations compared with test data taken during hot fire tests at NASA Stennis Space Center, and cold-flow water flow test data obtained at NASA MSFC. The numerical results indicate that unsteady pressure fluctuations at specific frequencies develop in the duct at the flow-liner location. Detailed frequency analysis of the flow disturbances is presented. The unsteadiness is believed to be an important source for fluctuating pressures generating high cycle fatigue.

Duct wall impedance control as an advanced concept for acoustic impression

NASA Technical Reports Server (NTRS)

Dean, P. D.; Tester, B. J.

1975-01-01

Models and tests on an acoustic duct liner system which has the property of controlled-variable acoustic impedance are described. This is achieved by a novel concept which uses the effect of steady air flow through a multi-layer, locally reacting, resonant-cavity absorber. The scope of this work was limited to a 'proof of concept.' The test of the concept was implemented by means of a small-scale, square-section flow duct facility designed specifically for acoustic measurements, with one side of the duct acoustically lined. The test liners were designed with the aid of previously established duct acoustic theory and a semi-empirical impedance model of the liner system. Over the limited range tested, the liner behaved primarily as predicted, exhibiting significant changes in resistance and reactance, thus providing the necessary concept validation.

Testing and Characterization of CMC Combustor Liners

NASA Technical Reports Server (NTRS)

Robinson, R. Craig; Verrilli, Michael J.

2003-01-01

Multiple combustor liner applications, both segmented and fully annular designs, have been configured for exposure in NASA's High Pressure Burner Rig (HPBR). The segmented liners were attached to the rig structure with SiC/SiC fasteners and exposed to simulated gas turbine conditions for nearly 200 hours. Test conditions included pressures of 6 atm., gas velocity of 42 m/s, and gas temperatures near 1450 C. The temperatures of both the cooled and combustion flow sides of the liners were measured using optical and contact measurement techniques. Minor weight loss was observed, but the liners remained structural sound, although damage was noted in some fasteners.

Circulating microparticles and the risk of thromboembolic events in Egyptian beta thalassemia patients.

PubMed

Youssry, Ilham; Soliman, Nohair; Ghamrawy, Mona; Samy, Rania Mohamed; Nasr, Amal; Abdel Mohsen, Mohamed; ElShahaat, Mohamed; Bou Fakhredin, Rayan; Taher, Ali

2017-04-01

The presence of elevated numbers of circulating microparticles (MPs) has been hypothesized to be responsible for the occurrence of thromboembolic events (TEEs) in thalassemic patients. Our aim is to evaluate the presence and the thrombotic risk of circulating MPs in thalassemia patients and to determine the difference in MPs between β-thalassemia major (β-TM) and thalassemia intermedia (TI). The percentage of the annexin-labeled MPs, platelet-derived MPs (PMPs), erythrocyte-derived MPs (RMPs), and endothelial-derived MPs (EMPs) was measured by flow cytometry, in 87 thalassemia patients (39 β-TM and 48 TI). By multiple regression analysis, we then assessed the various independent risk factors for the occurrence of TEE. The thalassemic patients who experienced TEE had a significantly higher platelet count, higher percentage of annexin-labeled MPs, and higher percentage of PMPs (p value = 0.014, 0.003, and 0.014, respectively). There was no significant difference between β-TM and TI patients at the level of any of the studied MPs. The predictive risk factors for TEE in thalassemic patients were splenectomy, total and direct bilirubin, the RMPs, and the EMPs (OR = 10.07 (CI = 3.7-27.1), 4.3 (CI = 2.1-8.7), 1.4 (CI = 1.5-6.2), 1.6 (CI = 1.1-2.2), 3.0 (CI = 1.9-4.9), respectively). In conclusion, the elevated numbers of circulating MPs is a risk factor for the TEE in thalassemia patients.

Urinary Podocyte Microparticles Identify Prealbuminuric Diabetic Glomerular Injury

PubMed Central

Burger, Dylan; Thibodeau, Jean-Francois; Holterman, Chet E.; Burns, Kevin D.; Touyz, Rhian M.

2014-01-01

Microparticles (MPs) are small (0.1–1.0 µm) vesicles shed from the surface of cells in response to stress. Whether podocytes produce MPs and whether this production reflects glomerular injury are unclear. We examined MP formation in cultured human podocytes (hPODs) and diabetic mice. hPODs were exposed to cyclical stretch, high glucose (HG; 25 mM), angiotensin II, or TGF-β. Urinary podocyte MPs were assessed in three mouse models of diabetic nephropathy: streptozotocin (STZ)-treated, OVE26, and Akita mice. Cyclic stretch and HG increased MP release as assessed by flow cytometry (P<0.01 and P<0.05, respectively, versus controls). Inhibition of Rho-kinase (ROCK) with fasudil blocked HG-induced podocyte MP formation. STZ-treated (8 weeks) mice exhibited increased urinary podocyte MPs compared with age-matched nondiabetic mice. Similarly, 16-week-old OVE26 mice had elevated levels of urinary podocyte MPs compared with wild-type littermates (P<0.01). In 1 week post-STZ–treated and 6- and 12-week-old Akita mice, urinary podocyte MPs increased significantly compared with those MPs in nondiabetic mice, despite normal urinary albumin levels. Our results indicate that podocytes produce MPs that are released into urine. Podocyte-derived MPs are generated by exposure to mechanical stretch and high glucose in vitro and could represent early markers of glomerular injury in diabetic nephropathy. PMID:24676640

Placental release of distinct DNA-associated microparticles into maternal circulation: reflective of gestation time and preeclampsia

PubMed Central

Orozco, Aaron F.; Jorgez, Carolina J.; Ramos-Perez, William D.; Popek, Edwina J.; Yu, Xiaoying; Kozinetz, Claudia A.; Bischoff, Farideh Z.; Lewis, Dorothy E.

2009-01-01

Background The aim of this study was to determine whether DNA-associated micro-particles (MPs) in maternal plasma express fetal-derived human leukocyte antigen-G (HLA-G) or placental alkaline phosphatase (PLAP) and whether the levels differ between women with normotensive pregnancies and preeclampsia. Methods DNA-associated MPs expressing HLA-G or PLAP were examined in the plasma of normal pregnant women and preeclamptic patients using flow cytometric analysis. Results DNA-associated HLA-G+ MPs were significantly increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.005), with highest levels found in first and second trimesters. DNA-associated PLAP+ MPs were also increased in maternal plasma compared to plasma from non-pregnant controls (p < 0.006), with highest levels in second and third trimesters. Term preeclamptic women had higher levels of DNA-associated MPs than control pregnant women. HLA-G+ MPs from the plasma of preeclamptic women had more DNA per MP than HLA-G+ MPs from the plasma of normal pregnant women (p < 0.03). Conclusions HLA-G and PLAP MPs increase in maternal circulation at different times during gestation. DNA amounts per HLA-G+ MP increase in preeclamptic women which might indicate dysfunctional extravillous cytotrophoblasts. PMID:19692120

Microparticle and mitochondrial release during extended storage of different types of platelet concentrates.

PubMed

Marcoux, Geneviève; Duchez, Anne-Claire; Rousseau, Matthieu; Lévesque, Tania; Boudreau, Luc H; Thibault, Louis; Boilard, Eric

2017-05-01

On activation, platelets release vesicles called microparticles (MPs). MPs are heterogeneous with regard to the presence or absence of mitochondria. We quantified MPs in platelet concentrates (PCs) taking their mitochondrial content into account. Platelet-rich plasma (PRP), buffy coat (BC) and apheresis (AP) PCs were tested through 7 days of storage. A combination of flow cytometry and spanning-tree progression analysis of density-normalized events (SPADE) was used to determine MP and mitochondrial release during storage. All the PC biochemical parameters complied with transfusion standards at all times. Platelet activation markers increased during storage and were higher for PRP than other types of PCs. Concentrations of MPs and extracellular mitochondria interpreted by SPADE algorithm were significantly higher in PRP than other in PCs and were stable throughout storage. The mode of preparation, rather than storage duration, impacts the release of MPs and mitochondria in PCs.

Identification of CD4+ T-cell-derived CD161+ CD39+ and CD39+CD73+ microparticles as new biomarkers for rheumatoid arthritis.

PubMed

Fan, Wenqiang; Wang, Wenxiang; Wu, Jie; Ma, Ling; Guo, Jinyan

2017-02-01

This study aimed to identify CD4 + T-cell-derived microparticles (MPs) and investigate their roles in rheumatoid arthritis (RA). Synovial fluids from 34 RA, 33 osteoarthritis patients and 42 healthy individuals were analyzed by flow cytometry. Human fibroblast-like synoviocytes and peripheral blood mononuclear cells were cultured with or without isolated MPs, chemokines and cytokines were measured by ELISA. CD4 + CD161 + CD39 + and CD4 + CD39 + CD73 + MPs were abundantly present in RA patients, which were positively or negatively correlated with RA features, respectively. Chemokines CCL20, CCL17 and CCL22, and cytokines IL-17 and IL-10 were influenced by these MPs in human fibroblast-like synoviocytes (HFLS) or PMBCs. CD4 + T-cell-derived CD161 + CD39 + and CD39 + CD73 + MPs could serve as new reciprocal biomarkers for RA evaluation.

Simulations of Flow Through the SSME LH2 Feed Line and LPFP Inducer

NASA Technical Reports Server (NTRS)

Dorney, Daniel J.; Rothermel, Jeffry

2003-01-01

During a post-flight inspection of the liquid hydrogen feed lines leading the Space Shuttle main engines cracks were discover in slots on a flow liner just upstream of the low pressure fuel pump inducer. Numerical simulations have been performed for the feed line, the flow liner (including the slots and backing cavity) and the inducer. The predicted results have been compared with experimental data taken during hot-fire tests at NASA Stennis Space Center.

Optimization of Acoustic Pressure Measurements for Impedance Eduction

NASA Technical Reports Server (NTRS)

Jones, M. G.; Watson, W. R.; Nark, D. M.

2007-01-01

As noise constraints become increasingly stringent, there is continued emphasis on the development of improved acoustic liner concepts to reduce the amount of fan noise radiated to communities surrounding airports. As a result, multiple analytical prediction tools and experimental rigs have been developed by industry and academia to support liner evaluation. NASA Langley has also placed considerable effort in this area over the last three decades. More recently, a finite element code (Q3D) based on a quasi-3D implementation of the convected Helmholtz equation has been combined with measured data acquired in the Langley Grazing Incidence Tube (GIT) to reduce liner impedance in the presence of grazing flow. A new Curved Duct Test Rig (CDTR) has also been developed to allow evaluation of liners in the presence of grazing flow and controlled, higher-order modes, with straight and curved waveguides. Upgraded versions of each of these two test rigs are expected to begin operation by early 2008. The Grazing Flow Impedance Tube (GFIT) will replace the GIT, and additional capabilities will be incorporated into the CDTR. The current investigation uses the Q3D finite element code to evaluate some of the key capabilities of these two test rigs. First, the Q3D code is used to evaluate the microphone distribution designed for the GFIT. Liners ranging in length from 51 to 610 mm are investigated to determine whether acceptable impedance eduction can be achieved with microphones placed on the wall opposite the liner. This analysis indicates the best results are achieved for liner lengths of at least 203 mm. Next, the effects of moving this GFIT microphone array to the wall adjacent to the liner are evaluated, and acceptable results are achieved if the microphones are placed off the centerline. Finally, the code is used to investigate potential microphone placements in the CDTR rigid wall adjacent to the wall containing an acoustic liner, to determine if sufficient fidelity can be achieved with 32 microphones available for this purpose. Initial results indicate 32 microphones can provide acceptable measurements to support impedance eduction with this test rig.

KSC-02pd1272

NASA Image and Video Library

2002-08-28

KENNEDY SPACE CENTER, FLA. -- U.S. Sen. Bill Nelson congratulates Jerry Goudy with the Flow Liner Inspection & Repair team. Nelson presented gold seal Senate certificates to the team for their work on finding the cracks in orbiter flow liners and repairing them. At left is Mike Young, behind Nelson is Tony Nesotas, at right is David Strait, who found the first fuel-line crack. Not pictured is Rick Beckwith.

Sectoral combustor for burning low-BTU fuel gas

DOEpatents

Vogt, Robert L.

1980-01-01

A high-temperature combustor for burning low-BTU coal gas in a gas turbine is disclosed. The combustor includes several separately removable combustion chambers each having an annular sectoral cross section and a double-walled construction permitting separation of stresses due to pressure forces and stresses due to thermal effects. Arrangements are described for air-cooling each combustion chamber using countercurrent convective cooling flow between an outer shell wall and an inner liner wall and using film cooling flow through liner panel grooves and along the inner liner wall surface, and for admitting all coolant flow to the gas path within the inner liner wall. Also described are systems for supplying coal gas, combustion air, and dilution air to the combustion zone, and a liquid fuel nozzle for use during low-load operation. The disclosed combustor is fully air-cooled, requires no transition section to interface with a turbine nozzle, and is operable at firing temperatures of up to 3000.degree. F. or within approximately 300.degree. F. of the adiabatic stoichiometric limit of the coal gas used as fuel.

Interfacial Stability of Spherically Converging Plasma Jets for Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Cassibry, Jason; Wu, S. T.; Eskridge, Richard; Smith, James; Lee, Michael; Rodgers, Stephen L. (Technical Monitor)

2000-01-01

A fusion propulsion scheme has been proposed that makes use of the merging of a spherical distribution of plasma jets to dynamically form a gaseous liner to implode a magnetized target to produce the fusion reaction. In this paper, a study is made of the interfacial stability of the interaction of these jets. Specifically, the Orr-Sommerfeld equation is integrated to obtain the growth rate of a perturbation to the primary flow at the interface between the colliding jets. The results lead to an estimate on the tolerances on the relative flow velocities of the merging plasma jets to form a stable, imploding liner. The results show that the maximum temporal growth rate of the perturbed flow at the jet interface is very small in comparison with the time to full compression of the liner. These data suggest that, as far as the stability of the interface between the merging jets is concerned, the formation of the gaseous liner can withstand velocity variation of the order of 10% between the neighboring jets over the density and temperature ranges investigated.

Diagnostic Techniques to Elucidate the Aerodynamic Performance of Acoustic Liners

NASA Technical Reports Server (NTRS)

June, Jason; Bertolucci, Brandon; Ukeiley, Lawrence; Cattafesta, Louis N., III; Sheplak, Mark

2017-01-01

In support of Topic A.2.8 of NASA NRA NNH10ZEA001N, the University of Florida (UF) has investigated the use of flow field optical diagnostic and micromachined sensor-based techniques for assessing the wall shear stress on an acoustic liner. Stereoscopic particle image velocimetry (sPIV) was used to study the velocity field over a liner in the Grazing Flow Impedance Duct (GFID). The results indicate that the use of a control volume based method to determine the wall shear stress is prone to significant error. The skin friction over the liner as measured using velocity curve fitting techniques was shown to be locally reduced behind an orifice, relative to the hard wall case in a streamwise plane centered on the orifice. The capacitive wall shear stress sensor exhibited a linear response for a range of shear stresses over a hard wall. PIV over the liner is consistent with lifting of the near wall turbulent structure as it passes over an orifice, followed by a region of low wall shear stress.

Gene expression profiling and functional characterization of macrophages in response to circulatory microparticles produced during Trypanosoma cruzi infection and Chagas disease

PubMed Central

Chowdhury, Imran; Koo, Sue-jie; Gupta, Shivali; Liang, Lisa Yi; Bahar, Bojlul; Silla, Laura; Burgos, Julio Nuñez; Barrientos, Natalia; Zago, Maria Paola; Garg, Nisha Jain

2016-01-01

BACKGROUND Chronic inflammation and oxidative stress are hallmarks of chagasic cardiomyopathy (CCM). In this study, we determined if microparticles (MPs) generated during Trypanosoma cruzi (Tc) infection carry the host’s signature of inflammatory/oxidative state and provide information regarding the progression of clinical disease. METHDOS The MPs were harvested from supernatants of human PBMCs in vitro incubated with T. cruzi (control: LPS-treated), plasma of seropositive humans with clinically asymptomatic (CA) or symptomatic (CS) disease state (normal/healthy (NH) controls) and plasma of mice immunized with a protective vaccine before challenge infection (control: unvaccinated/infected). Macrophages (mφs) were incubated with MPs, and we probed the gene expression profile using the inflammatory signaling cascade and cytokine/chemokine arrays, phenotypic markers of macrophage activation by flow cytometry, cytokine profile by an ELISA and Bioplex assay, and oxidative/nitrosative stress and mitotoxicity by colorimetric and fluorometric assays. RESULTS Tc- and LPS-induced MPs stimulated proliferation, inflammatory gene expression profile and •NO release in human THP-1 mφs. LPS-MPs were more immunostimulatory than Tc-MPs. Endothelial cells, T lymphocytes and mφs were the major source of MPs shed in plasma of chagasic humans and experimentally infected mice. The CS-MPs and CA-MPs (vs. NH-MPs) elicited >2-fold increase in •NO and mitochondrial oxidative stress in THP-1 mφs; however, CS-MPs (vs. CA-MPs) elicited a more pronounced and disease-state-specific inflammatory gene expression profile (IKBKB, NR3C1, and TIRAP vs. CCR4, EGR2 and CCL3), cytokine release (IL2+IFNγ>GCSF), and surface markers of mφ activation (CD14 and CD16). The circulatory MPs of non-vaccinated/infected mice induced 7.5-fold and 40% increase in •NO and IFNγ production, respectively, while these responses were abolished when RAW264.7 mφs were incubated with circulatory MPs of vaccinated/infected mice. CONCLUSION Circulating MPs reflect in vivo levels of oxidative, nitrosative, and inflammatory state and have potential utility in evaluating disease severity and efficacy of vaccines and drug therapies against CCM. PMID:27902980

Analytical and experimental studies of an optimum multisegment phased liner noise suppression concept

NASA Technical Reports Server (NTRS)

Sawdy, D. T.; Beckemeyer, R. J.; Patterson, J. D.

1976-01-01

Results are presented from detailed analytical studies made to define methods for obtaining improved multisegment lining performance by taking advantage of relative placement of each lining segment. Properly phased liner segments reflect and spatially redistribute the incident acoustic energy and thus provide additional attenuation. A mathematical model was developed for rectangular ducts with uniform mean flow. Segmented acoustic fields were represented by duct eigenfunction expansions, and mode-matching was used to ensure continuity of the total field. Parametric studies were performed to identify attenuation mechanisms and define preliminary liner configurations. An optimization procedure was used to determine optimum liner impedance values for a given total lining length, Mach number, and incident modal distribution. Optimal segmented liners are presented and it is shown that, provided the sound source is well-defined and flow environment is known, conventional infinite duct optimum attenuation rates can be improved. To confirm these results, an experimental program was conducted in a laboratory test facility. The measured data are presented in the form of analytical-experimental correlations. Excellent agreement between theory and experiment verifies and substantiates the analytical prediction techniques. The results indicate that phased liners may be of immediate benefit in the development of improved aircraft exhaust duct noise suppressors.

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men.

PubMed

Phillips, Bethan E; Atherton, Philip J; Varadhan, Krishna; Limb, Marie C; Williams, John P; Smith, Kenneth

2016-05-01

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.

Metformin reduces total microparticles and microparticles-expressing tissue factor in women with polycystic ovary syndrome.

PubMed

Carvalho, Laura M L; Ferreira, Cláudia N; Candido, Ana L; Reis, Fernando M; Sóter, Mirelle O; Sales, Mariana F; Silva, Ieda F O; Nunes, Fernanda F C; Gomes, Karina Braga

2017-10-01

The objective of this study was to evaluate the levels of total microparticles (MPs) and microparticles-expressing tissue factor (TFMPs) in women with polycystic ovarian syndrome (PCOS) who use metformin comparing to those who do not take metformin. We quantified total MPs and TFMPs in the plasma of 50 patients with PCOS-13 of these women used metformin (850 mg 2×/day during at least 6 months) and the other 37 did not. For this purpose, the microparticles (MPs) were purified by differential centrifugation of the plasma and, subsequently, by flow cytometry, using annexin-V and CD142 as markers. Total MPs levels were lower in treated patients (59.58 ± 28.43 MPs/µL) when compared to untreated group (97.32 ± 59.42; p = 0.033). Plasma levels of TFMPs were also significantly lower in the group of patients who used metformin (1.10 ± 0.94 MPs/µL) when compared to untreated patients (2.20 ± 1.42 MPs/µL) (p = 0.003). Considering that metformin reduced the levels of total MPs and TFMPs, our results suggest that this mechanism could be involved in the antithrombotic metformin effect, corroborating with the indication of this drug in the PCOS treatment.

A finite element simulation of sound attenuation in a finite duct with a peripherally variable liner

NASA Technical Reports Server (NTRS)

Watson, W. R.

1977-01-01

Using multimodal analysis, a variational finite element method is presented for analyzing sound attenuation in a three-dimensional finite duct with a peripherally variable liner in the absence of flow. A rectangular element, with cubic shaped functions, is employed. Once a small portion of a peripheral liner is removed, the attenuation rate near the frequency where maximum attenuation occurs drops significantly. The positioning of the liner segments affects the attenuation characteristics of the liner. Effects of the duct termination are important in the low frequency ranges. The main effect of peripheral variation of the liner is a broadening of the attenuation characteristics in the midfrequency range. Because of matrix size limitations of the presently available computer program, the eigenvalue equations should be solved out of core in order to handle realistic sources.

Numerical simulation of a slit resonator in a grazing flow under acoustic excitation

NASA Astrophysics Data System (ADS)

Tam, Christopher K. W.; Ju, Hongbin; Walker, Bruce E.

2008-06-01

It is known experimentally that a grazing flow has significant influence on the performance of a resonant acoustic liner. As yet, detailed understanding of the effect in fluid dynamics or acoustics terms is not available. One principal reason for this is the small size of the openings of the resonators of present day jet engine acoustic liners. The small size of the holes makes in-depth experimental observation and mapping of the fluid flow field around the opening of a resonator in the presence of a grazing flow extremely difficult. As a result, there is a genuine lack of data leading directly to a lack of understanding. The face sheet of an acoustic liner is entirely covered with holes (the openings of resonators underneath). There is, therefore, a possibility of fluid mechanical interaction between neighboring resonators. However, evidence for such interaction is not available at this time. One of the objectives of the present work is to shed light on whether this is possible and what is a possible interaction mechanism. In this study, numerical simulations of the flow field around a slit resonator in the presence of a grazing flow under acoustic forcing are carried out. It is observed that at high sound pressure level, vortices are shed from the corners of the resonator opening. Some of these vortices merge together. Others are absorbed by the wall boundary layer or dissipated by viscosity. The simulated results indicate that a strong merged vortex is convected downstream by the grazing flow and persists for a long distance. This suggests that possible fluid mechanical interaction between neighboring resonators of an acoustic liner could, indeed, be possible because of the interference of this convected vortex with the flow field of the downstream resonator. This interaction, as far as is known, has not been included in any theoretical or semi-empirical model of acoustic liners. Detailed formulation of the computational model, as well as computational algorithm, is provided. The computation code is verified by comparing computed results with an exact linear solution and also validated by comparing with measurements of a companion experiment.

Platelet-, monocyte-derived and tissue factor-carrying circulating microparticles are related to acute myocardial infarction severity.

PubMed

Chiva-Blanch, Gemma; Laake, Kristian; Myhre, Peder; Bratseth, Vibeke; Arnesen, Harald; Solheim, Svein; Badimon, Lina; Seljeflot, Ingebjørg

2017-01-01

Circulating microparticles (cMPs) are phospholipid-rich vesicles released from cells when activated or injured, and contribute to the formation of intracoronary thrombi. Tissue factor (TF, CD142) is the main trigger of fibrin formation and TF-carrying cMPs are considered one of the most procoagulant cMPs. Similar types of atherosclerotic lesions may lead to different types of AMI, although the mechanisms behind are unresolved. Therefore, we aimed to investigate the phenotype of cMPs found in plasma of ACS patients and its relation to AMI severity and thrombotic burden. In a cross-sectional study, two hundred patients aged 75±4 years were included in the study 2-8 weeks after suffering an AMI. Annexin V positive (AV+)-cMPs derived from blood and vascular cells were measured by flow cytometry. Plasma procoagulant activity (TF-PCA) was measured through a chromogenic assay. STEMI patients (n = 75) showed higher levels of platelet-derived cMPs [CD61+/AV+, CD31+/AV+, CD42b+/AV+ and CD31+/CD42b+/AV+, P = 0.048, 0.038, 0.009 and 0.006, respectively], compared to NSTEMI patients (n = 125). Patients who suffered a heart failure during AMI (n = 17) had increased levels of platelet (CD61+)-and monocyte (CD14+)-derived cMPs carrying TF (CD142+) (P<0.0001 and 0.004, respectively). Additionally, NYHA class III (n = 23) patients showed higher levels of CD142+/AV+, CD14+/AV+ and CD14+/CD142+/AV+ cMPs than those in class I/II (P = 0.001, 0.015 and 0.014, respectively). The levels of these cMPs positively correlated with TF-PCA (r≥0.166, P≤0.027, all). Platelets and monocytes remain activated in AMI patients treated as per guidelines and release cMPs that discriminate AMI severity. Therefore, TF-MPs, and platelet- and monocyte-MPs may reflect thrombotic burden in AMI patients.

Vitreous Microparticle Shedding in Retinal Detachment: A Prospective Comparative Study.

PubMed

Tumahai, Perle; Saas, Philippe; Ricouard, Fanny; Biichlé, Sabéha; Puyraveau, Marc; Laheurte, Caroline; Delbosc, Bernard; Saleh, Maher

2016-01-01

Microparticles (MPs) are membrane-derived vesicles measuring less than 1 μm in diameter. They are shed from nearly every activated or preapoptotic cell and may exhibit biologic activities in inflammation or apoptosis settings. The main purpose of this study was to determine whether MP shedding was higher in the vitreous of patients with retinal detachment (RD). This was a prospective, comparative study. Levels of vitreous MPs (including phosphatidylserine [PS]-expressing MPs, photoreceptor cell-derived MPs, and photoreceptor cell-derived MPs expressing PS) and soluble proinflammatory factors (i.e., monocyte chemoattractant protein-1, intercellular adhesion molecule-1, and IL-6) were analyzed by flow cytometry. Samples were obtained from 49 eyes undergoing RD surgery and 41 control eyes. Vitreous levels of all the MPs studied were significantly increased in the RD group. Vitreous MP levels were correlated with levels of at least one proinflammatory factor depending on MP subsets. Concerning clinical parameters, vitreous PS-expressing MP and PS-expressing photoreceptor cell-derived MP levels were higher depending on the duration of RD at surgery, the detached retina surface, and the macula status and were found more sensitive than proinflammatory factors only for the duration of RD at surgery. Vitreous concentrations of MPs (mainly derived from photoreceptor cells) are higher after rhegmatogenous RD and found to be correlated with soluble proinflammatory factors.

Tips and tricks for flow cytometry-based analysis and counting of microparticles.

PubMed

Poncelet, Philippe; Robert, Stéphane; Bailly, Nicolas; Garnache-Ottou, Francine; Bouriche, Tarik; Devalet, Bérangère; Segatchian, Jerard H; Saas, Philippe; Mullier, François

2015-10-01

Submicron-sized extra-cellular vesicles generated by budding from the external cell membranes, microparticles (MPs) are important actors in transfusion as well as in other medical specialties. After briefly positioning their role in the characterization of labile blood products, this technically oriented chapter aims to review practical points that need to be considered when trying to use flow cytometry for the analysis, characterization and absolute counting of MP subsets. Subjects of active discussions relative to instrumentation will include the choice of the trigger parameter, possible standardization approaches requiring instrument quality-control, origin and control of non-specific background and of coincidence artifacts, choice of the type of electronic signals, optimal sheath fluid and sample speed. Questions related to reagents will cover target antigens and receptors, multi-color reagents, negative controls, enumeration of MPs and limiting artifacts due to unexpected (micro-) coagulation of plasma samples. Newly detected problems are generating innovative solutions and flow cytometry will continue to remain the technology of choice for the analysis of MPs, in the domain of transfusion as well as in many diverse specialties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Apparatus for controlling coolant level in a liquid-metal-cooled nuclear reactor

DOEpatents

Jones, Robert D.

1978-01-01

A liquid-metal-cooled fast-breeder reactor which has a thermal liner spaced inwardly of the pressure vessel and includes means for passing bypass coolant through the annulus between the thermal liner and the pressure vessel to insulate the pressure vessel from hot outlet coolant includes control ports in the thermal liner a short distance below the normal operating coolant level in the reactor and an overflow nozzle in the pressure vessel below the control ports connected to an overflow line including a portion at an elevation such that overflow coolant flow is established when the coolant level in the reactor is above the top of the coolant ports. When no makeup coolant is added, bypass flow is inwardly through the control ports and there is no overflow; when makeup coolant is being added, coolant flow through the overflow line will maintain the coolant level.

The acoustic and instability waves of jets confined inside an acoustically lined rectangular duct

NASA Technical Reports Server (NTRS)

Hu, Fang Q.

1993-01-01

An analysis of linear wave modes associated with supersonic jets confined inside an acoustically lined rectangular duct is presented. Mathematical formulations are given for the vortex-sheet model and continuous mean flow model of the jet flow profiles. Detailed dispersion relations of these waves in a two-dimensional confined jet as well as an unconfined free jet are computed. Effects of the confining duct and the liners on the jet instability and acoustic waves are studied numerically. It is found that the effect of the liners is to attenuate waves that have supersonic phase velocities relative to the ambient flow. Numerical results also show that the growth rates of the instability waves could be reduced significantly by the use of liners. In addition, it is found that the upstream propagating neutral waves of an unconfined jet could become attenuated when the jet is confined.

N-Acetylcysteine Amide Protects Against Oxidative Stress–Induced Microparticle Release From Human Retinal Pigment Epithelial Cells

PubMed Central

Carver, Kyle A.; Yang, Dongli

2016-01-01

Purpose Oxidative stress is a major factor involved in retinal pigment epithelium (RPE) apoptosis that underlies AMD. Drusen, extracellular lipid- and protein-containing deposits, are strongly associated with the development of AMD. Cell-derived microparticles (MPs) are small membrane-bound vesicles shed from cells. The purpose of this study was to determine if oxidative stress drives MP release from RPE cells, to assess whether these MPs carry membrane complement regulatory proteins (mCRPs: CD46, CD55, and CD59), and to evaluate the effects of a thiol antioxidant on oxidative stress–induced MP release. Methods Retinal pigment epithelium cells isolated from human donor eyes were cultured and treated with hydrogen peroxide (H2O2) to induce oxidative stress. Isolated MPs were fixed for transmission electron microscopy or processed for component analysis by flow cytometry, Western blot analysis, and confocal microscopy. Results Transmission electron microscopy showed that MPs ranged in diameter from 100 to 1000 nm. H2O2 treatment led to time- and dose-dependent elevations in MPs with externalized phosphatidylserine and phosphatidylethanolamine, known markers of MPs. These increases were strongly correlated to RPE apoptosis. Oxidative stress significantly increased the release of mCRP-positive MPs, which were prevented by a thiol antioxidant, N-acetylcysteine amide (NACA). Conclusions This is the first evidence that oxidative stress induces cultured human RPE cells to release MPs that carry mCRPs on their surface. The levels of released MPs are strongly correlated with RPE apoptosis. N-acetylcysteine amide prevents oxidative stress–induced effects. Our findings indicate that oxidative stress reduces mCRPs on the RPE surface through releasing MPs. PMID:26842754

Optimization of Microphone Locations for Acoustic Liner Impedance Eduction

NASA Technical Reports Server (NTRS)

Jones, M. G.; Watson, W. R.; June, J. C.

2015-01-01

Two impedance eduction methods are explored for use with data acquired in the NASA Langley Grazing Flow Impedance Tube. The first is an indirect method based on the convected Helmholtz equation, and the second is a direct method based on the Kumaresan and Tufts algorithm. Synthesized no-flow data, with random jitter to represent measurement error, are used to evaluate a number of possible microphone locations. Statistical approaches are used to evaluate the suitability of each set of microphone locations. Given the computational resources required, small sample statistics are employed for the indirect method. Since the direct method is much less computationally intensive, a Monte Carlo approach is employed to gather its statistics. A comparison of results achieved with full and reduced sets of microphone locations is used to determine which sets of microphone locations are acceptable. For the indirect method, each array that includes microphones in all three regions (upstream and downstream hard wall sections, and liner test section) provides acceptable results, even when as few as eight microphones are employed. The best arrays employ microphones well away from the leading and trailing edges of the liner. The direct method is constrained to use microphones opposite the liner. Although a number of arrays are acceptable, the optimum set employs 14 microphones positioned well away from the leading and trailing edges of the liner. The selected sets of microphone locations are also evaluated with data measured for ceramic tubular and perforate-over-honeycomb liners at three flow conditions (Mach 0.0, 0.3, and 0.5). They compare favorably with results attained using all 53 microphone locations. Although different optimum microphone locations are selected for the two impedance eduction methods, there is significant overlap. Thus, the union of these two microphone arrays is preferred, as it supports usage of both methods. This array contains 3 microphones in the upstream hard wall section, 14 microphones opposite the liner, and 3 microphones in the downstream hard wall section.

Effects of Liner Length and Attenuation on NASA Langley Impedance Eduction

NASA Technical Reports Server (NTRS)

Jones, M. G.; Watson, W. R.

2016-01-01

This study explores the effects of liner length and attenuation on the CHE (convected Helmholtz equation) impedance eduction method, in which the surface impedance of an acoustic liner is inferred through an iterative process based on repeated solutions to the convected Helmholtz equation. Wire mesh-over-honeycomb and perforate-over-honeycomb acoustic liners are tested in the NASA Langley Grazing Flow Impedance Tube, and the resultant data are processed using two impedance eduction methods. The first is the CHE method, and the second is a direct method (labeled the KT method) that uses the Kumaresan and Tufts algorithm to compute the impedance directly. The CHE method has been extensively used for acoustic liner evaluation, but experiences anomalous behavior under some test conditions. It is postulated that the anomalies are related to the liner length and/or attenuation. Since the KT method only employs data measured over the length of the liner, it is expected to be unaffected by liner length. A comparison of results achieved with the two impedance eduction methods is used to explore the interactive effects of liner length and attenuation on the CHE impedance eduction method.

Optimization of Variable-Depth Liner Configurations for Increased Broadband Noise Reduction

NASA Technical Reports Server (NTRS)

Jones, M. G.; Watson, W. R.; Nark, D. M.; Schiller, N. H.; Born, J. C.

2016-01-01

This paper employs three acoustic propagation codes to explore variable-depth liner configurations for the NASA Langley Grazing Flow Impedance Tube (GFIT). The initial study demonstrates that a variable impedance can acceptably be treated as a uniform impedance if the spatial extent over which this variable impedance occurs is less than one-third of a wavelength of the incident sound. A constrained optimization study is used to design a variable-depth liner and to select an optimization metric. It also provides insight regarding how much attenuation can be achieved with variable-depth liners. Another optimization study is used to design a liner with much finer chamber depth resolution for the Mach 0.0 and 0.3 test conditions. Two liners are designed based on spatial rearrangement of chambers from this liner to determine whether the order is critical. Propagation code predictions suggest this is not the case. Both liners are fabricated via additive manufacturing and tested in the GFIT for the Mach 0.0 condition. Predicted and measured attenuations compare favorably across the full frequency range. These results clearly suggest that the chambers can be arranged in any order, thus offering the potential for innovative liner designs to minimize depth and weight.

Hybrid Active/Passive Jet Engine Noise Suppression System

NASA Technical Reports Server (NTRS)

Parente, C. A.; Arcas, N.; Walker, B. E.; Hersh, A. S.; Rice, E. J.

1999-01-01

A novel adaptive segmented liner concept has been developed that employs active control elements to modify the in-duct sound field to enhance the tone-suppressing performance of passive liner elements. This could potentially allow engine designs that inherently produce more tone noise but less broadband noise, or could allow passive liner designs to more optimally address high frequency broadband noise. A proof-of-concept validation program was undertaken, consisting of the development of an adaptive segmented liner that would maximize attenuation of two radial modes in a circular or annular duct. The liner consisted of a leading active segment with dual annuli of axially spaced active Helmholtz resonators, followed by an optimized passive liner and then an array of sensing microphones. Three successively complex versions of the adaptive liner were constructed and their performances tested relative to the performance of optimized uniform passive and segmented passive liners. The salient results of the tests were: The adaptive segmented liner performed well in a high flow speed model fan inlet environment, was successfully scaled to a high sound frequency and successfully attenuated three radial modes using sensor and active resonator arrays that were designed for a two mode, lower frequency environment.

Numerical simulation of sloshing with large deforming free surface by MPS-LES method

NASA Astrophysics Data System (ADS)

Pan, Xu-jie; Zhang, Huai-xin; Sun, Xue-yao

2012-12-01

Moving particle semi-implicit (MPS) method is a fully Lagrangian particle method which can easily solve problems with violent free surface. Although it has demonstrated its advantage in ocean engineering applications, it still has some defects to be improved. In this paper, MPS method is extended to the large eddy simulation (LES) by coupling with a sub-particle-scale (SPS) turbulence model. The SPS turbulence model turns into the Reynolds stress terms in the filtered momentum equation, and the Smagorinsky model is introduced to describe the Reynolds stress terms. Although MPS method has the advantage in the simulation of the free surface flow, a lot of non-free surface particles are treated as free surface particles in the original MPS model. In this paper, we use a new free surface tracing method and the key point is "neighbor particle". In this new method, the zone around each particle is divided into eight parts, and the particle will be treated as a free surface particle as long as there are no "neighbor particles" in any two parts of the zone. As the number density parameter judging method has a high efficiency for the free surface particles tracing, we combine it with the neighbor detected method. First, we select out the particles which may be mistreated with high probabilities by using the number density parameter judging method. And then we deal with these particles with the neighbor detected method. By doing this, the new mixed free surface tracing method can reduce the mistreatment problem efficiently. The serious pressure fluctuation is an obvious defect in MPS method, and therefore an area-time average technique is used in this paper to remove the pressure fluctuation with a quite good result. With these improvements, the modified MPS-LES method is applied to simulate liquid sloshing problems with large deforming free surface. Results show that the modified MPS-LES method can simulate the large deforming free surface easily. It can not only capture the large impact pressure accurately on rolling tank wall but also can generate all physical phenomena successfully. The good agreement between numerical and experimental results proves that the modified MPS-LES method is a good CFD methodology in free surface flow simulations.

Single Mode Theory for Impedance Eduction in Large-Scale Ducts with Grazing Flow

NASA Technical Reports Server (NTRS)

Watson, Willie R.; Gerhold, Carl H.; Jones, Michael G.; June, Jason C.

2014-01-01

An impedance eduction theory for a rigid wall duct containing an acoustic liner with an unknown impedance and uniform grazing flow is presented. The unique features of the theory are: 1) non-planar waves propagate in the hard wall sections of the duct, 2) input data consist solely of complex acoustic pressures acquired on a wall adjacent to the liner, and 3) multiple higher-order modes may exist in the direction perpendicular to the liner and the opposite rigid wall. The approach is to first measure the axial propagation constant of a dominant higher-order mode in the liner sample section. This axial propagation constant is then used in conjunction with a closed-form solution to a reduced form of the convected Helmholtz equation and the wall impedance boundary condition to educe the liner impedance. The theory is validated on a conventional liner whose impedance spectrum is educed in two flow ducts with different cross sections. For the frequencies and Mach numbers of interest, no higher-order modes propagate in the hard wall sections of the smaller duct. A benchmark method is used to educe the impedance spectrum in this duct. A dominant higher-order vertical mode propagates in the larger duct for similar test conditions, and the current theory is applied to educe the impedance spectrum. Results show that when the theory is applied to data acquired in the larger duct with a dominant higher-order vertical mode, the same impedance spectra is educed as that obtained in the small duct where only the plane wave mode is present and the benchmark method is used. This result holds for each higher-order vertical mode that is considered.

Preliminary Investigation of Curved Liner Sample in the NASA LaRC Curved Duct Test Rig

NASA Technical Reports Server (NTRS)

Gerhold, Carl H.; Jones, Michael G.; Brown, Martha C.

2007-01-01

This viewgraph presentation reviews the preliminary investigation of the curved liner sample in the NASA LaRC Curved Duct Test Rig (CDTR). It reviews the purpose of the Curved Duct Test Rig. Its purpose is to develop capability to investigate acoustic and aerodynamic properties in ducts. It has several features to accomplish that purpose: (1) Large scale (2) Flow rate to M = 0.275 (3) Higher order mode control (4) Curved flow path (5) Adaptable test section (6) Flexible test configurations. The liner has minimal effect on turbulence or boundary layer growth in duct. The curved duct sample attenuation is affected by mode scattering. In conclusion, the CDTR is valid tool for aerodynamic and acoustic evaluation of duct treatment

Gas-cooled nuclear reactor

DOEpatents

Peinado, Charles O.; Koutz, Stanley L.

1985-01-01

A gas-cooled nuclear reactor includes a central core located in the lower portion of a prestressed concrete reactor vessel. Primary coolant gas flows upward through the core and into four overlying heat-exchangers wherein stream is generated. During normal operation, the return flow of coolant is between the core and the vessel sidewall to a pair of motor-driven circulators located at about the bottom of the concrete pressure vessel. The circulators repressurize the gas coolant and return it back to the core through passageways in the underlying core structure. If during emergency conditions the primary circulators are no longer functioning, the decay heat is effectively removed from the core by means of natural convection circulation. The hot gas rising through the core exits the top of the shroud of the heat-exchangers and flows radially outward to the sidewall of the concrete pressure vessel. A metal liner covers the entire inside concrete surfaces of the concrete pressure vessel, and cooling tubes are welded to the exterior or concrete side of the metal liner. The gas coolant is in direct contact with the interior surface of the metal liner and transfers its heat through the metal liner to the liquid coolant flowing through the cooling tubes. The cooler gas is more dense and creates a downward convection flow in the region between the core and the sidewall until it reaches the bottom of the concrete pressure vessel when it flows radially inward and up into the core for another pass. Water is forced to flow through the cooling tubes to absorb heat from the core at a sufficient rate to remove enough of the decay heat created in the core to prevent overheating of the core or the vessel.

Microparticle Analysis in Disorders of Hemostasis and Thrombosis

PubMed Central

Mooberry, Micah J.; Key, Nigel S.

2015-01-01

Microparticles (MPs) are submicron vesicles released from the plasma membrane of eukaryotic cells in response to activation or apoptosis. MPs are known to be involved in numerous biologic processes, including inflammation, the immune response, cancer metastasis, and angiogenesis. Their earliest recognized and most widely accepted role, however, is the ability to promote and support the process of blood coagulation. Consequently, there is ongoing interest in studying MPs in disorders of hemostasis and thrombosis. Both phosphatidylserine (PS) exposure and the presence of tissue factor (TF) in the MP membrane may account for their procoagulant properties, and elevated numbers of MPs in plasma have been reported in numerous prothrombotic conditions. To date, however, there are few data on true causality linking MPs to the genesis of thrombosis. A variety of methodologies have been employed to characterize and quantify MPs, although detection is challenging due to their submicron size. Flow cytometry (FCM) remains the most frequently utilized strategy for MP detection; however, it is associated with significant technological limitations. Additionally, pre-analytical and analytical variables can influence the detection of MPs by FCM, rendering data interpretation difficult. Lack of methodologic standardization in MP analysis by FCM confounds the issue further, although efforts are currently underway to address this limitation. Moving forward, it will be important to address these technical challenges as a scientific community if we are to better understand the role that MPs play in disorders of hemostasis and thrombosis. PMID:25704723

Acoustic-Liner Admittance in a Duct

NASA Technical Reports Server (NTRS)

Watson, W. R.

1986-01-01

Method calculates admittance from easily obtainable values. New method for calculating acoustic-liner admittance in rectangular duct with grazing flow based on finite-element discretization of acoustic field and reposing of unknown admittance value as linear eigenvalue problem on admittance value. Problem solved by Gaussian elimination. Unlike existing methods, present method extendable to mean flows with two-dimensional boundary layers as well. In presence of shear, results of method compared well with results of Runge-Kutta integration technique.

Tumour-associated circulating microparticles: A novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia.

PubMed

Willms, Arnulf; Müller, Clara; Julich, Henrike; Klein, Niklas; Schwab, Robert; Güsgen, Christoph; Richardsen, Ines; Schaaf, Sebastian; Krawczyk, Marcin; Krawczyk, Marek; Lammert, Frank; Schuppan, Detlef; Lukacs-Kornek, Veronika; Kornek, Miroslaw

2016-05-24

Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the so-called liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM+ and EpCAM+CD147+ taMPs. The presence of CD147+EpCAM+ taMPs were specific to tumour-bearing patients thus allowing the specific distinction of malignancies from patients with thyroid nodules. Increased level of EpCAM single positive MPs were, in turn, also detected in patients with thyroid nodules. Importantly, EpCAM+CD147+ taMPs correlated with the measured tumour-volume in CRC patients. EpCAM+ taMPs decreased at 7 days after curative R0 tumour resection suggesting a close dependence with tumour presence. AUROC values (up to 0.85 and 0.90), sensitivity/specificity scores, and positive/negative predictive values indicated a high diagnostic accuracy of EpCAM+CD147+ taMPs. Taken together, EpCAM+CD147+ double positive taMPs could potentially serve as novel promising clinical parameter for cancer screening, diagnosis, surveillance and therapy monitoring.

Phosphatidylserine-exposing blood cells and microparticles induce procoagulant activity in non-valvular atrial fibrillation.

PubMed

Wang, Lixiu; Bi, Yayan; Yu, Muxin; Li, Tao; Tong, Dongxia; Yang, Xiaoyan; Zhang, Cong; Guo, Li; Wang, Chunxu; Kou, Yan; Dong, Zengxiang; Novakovic, Valerie A; Tian, Ye; Kou, Junjie; Shammas, Masood A; Shi, Jialan

2018-05-01

The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA). NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy. PCA was evaluated using clotting time, factor Xa (FXa), thrombin and fibrin formation. PS + blood cells and MPs were significantly higher in NVAF patients without and with left atrial thrombi (both P < 0.01) than in controls. Patients with left atrial thrombi showed increased PS + platelets, neutrophils, erythrocytes and MPs compared with patients without thrombi (all P < 0.05). Moreover, in patients with left atrial thrombi, MPs primarily originated from platelets (56.1%) followed by leukocytes (21.9%, including MPs from neutrophils, monocytes and lymphocytes), erythrocytes (12.2%) and endothelial cells (8.9%). Additionally, PS + blood cells and MPs contributed to markedly shortened coagulation time and dramatically increased FXa/thrombin/fibrin (all P < 0.001) generation in both NVAF groups. Furthermore, blockade of exposed PS on blood cells and MPs with lactadherin inhibited PCA by approximately 80%. Lastly, we found that the amount of PS + platelets and MPs was positively correlated with thrombus diameter (all p < 0.005). Our results suggest that exposed PS on blood cells and MPs play a procoagulant role in NVAF patients. Blockade of PS prior to thrombus formation might be a novel therapeutic approach in these patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Further Development and Assessment of a Broadband Liner Optimization Process

NASA Technical Reports Server (NTRS)

Nark, Douglas M.; Jones, Michael G.; Sutliff, Daniel L.

2016-01-01

The utilization of advanced fan designs (including higher bypass ratios) and shorter engine nacelles has highlighted a need for increased fan noise reduction over a broader frequency range. Thus, improved broadband liner designs must account for these constraints and, where applicable, take advantage of advanced manufacturing techniques that have opened new possibilities for novel configurations. This work focuses on the use of an established broadband acoustic liner optimization process to design a variable-depth, multi-degree of freedom liner for a high speed fan. Specifically, in-duct attenuation predictions with a statistical source model are used to obtain optimum impedance spectra over the conditions of interest. The predicted optimum impedance information is then used with acoustic liner modeling tools to design a liner aimed at producing impedance spectra that most closely match the predicted optimum values. The multi-degree of freedom design is carried through design, fabrication, and testing. In-duct attenuation predictions compare well with measured data and the multi-degree of freedom liner is shown to outperform a more conventional liner over a range of flow conditions. These promising results provide further confidence in the design tool, as well as the enhancements made to the overall design process.

Energy transfer through a multi-layer liner for shaped charges

DOEpatents

Skolnick, Saul; Goodman, Albert

1985-01-01

This invention relates to the determination of parameters for selecting materials for use as liners in shaped charges to transfer the greatest amount of energy to the explosive jet. Multi-layer liners constructed of metal in shaped charges for oil well perforators or other applications are selected in accordance with the invention to maximize the penetrating effect of the explosive jet by reference to four parameters: (1) Adjusting the explosive charge to liner mass ratio to achieve a balance between the amount of explosive used in a shaped charge and the areal density of the liner material; (2) Adjusting the ductility of each layer of a multi-layer liner to enhance the formation of a longer energy jet; (3) Buffering the intermediate layers of a multi-layer liner by varying the properties of each layer, e.g., composition, thickness, ductility, acoustic impedance and areal density, to protect the final inside layer of high density material from shattering upon impact of the explosive force and, instead, flow smoothly into a jet; and (4) Adjusting the impedance of the layers in a liner to enhance the transmission and reduce the reflection of explosive energy across the interface between layers.

A Method for Optimizing Non-Axisymmetric Liners for Multimodal Sound Sources

NASA Technical Reports Server (NTRS)

Watson, W. R.; Jones, M. G.; Parrott, T. L.; Sobieski, J.

2002-01-01

Central processor unit times and memory requirements for a commonly used solver are compared to that of a state-of-the-art, parallel, sparse solver. The sparse solver is then used in conjunction with three constrained optimization methodologies to assess the relative merits of non-axisymmetric versus axisymmetric liner concepts for improving liner acoustic suppression. This assessment is performed with a multimodal noise source (with equal mode amplitudes and phases) in a finite-length rectangular duct without flow. The sparse solver is found to reduce memory requirements by a factor of five and central processing time by a factor of eleven when compared with the commonly used solver. Results show that the optimum impedance of the uniform liner is dominated by the least attenuated mode, whose attenuation is maximized by the Cremer optimum impedance. An optimized, four-segmented liner with impedance segments in a checkerboard arrangement is found to be inferior to an optimized spanwise segmented liner. This optimized spanwise segmented liner is shown to attenuate substantially more sound than the optimized uniform liner and tends to be more effective at the higher frequencies. The most important result of this study is the discovery that when optimized, a spanwise segmented liner with two segments gives attenuations equal to or substantially greater than an optimized axially segmented liner with the same number of segments.

Broadband Liner Optimization for the Source Diagnostic Test Fan

NASA Technical Reports Server (NTRS)

Nark, Douglas M.; Jones, Michael G.

2012-01-01

The broadband component of fan noise has grown in relevance with the utilization of increased bypass ratio and advanced fan designs. Thus, while the attenuation of fan tones remains paramount, the ability to simultaneously reduce broadband fan noise levels has become more appealing. This paper describes a broadband acoustic liner optimization study for the scale model Source Diagnostic Test fan. Specifically, in-duct attenuation predictions with a statistical fan source model are used to obtain optimum impedance spectra over a number of flow conditions for three liner locations in the bypass duct. The predicted optimum impedance information is then used with acoustic liner modeling tools to design liners aimed at producing impedance spectra that most closely match the predicted optimum values. Design selection is based on an acceptance criterion that provides the ability to apply increased weighting to specific frequencies and/or operating conditions. Typical tonal liner designs targeting single frequencies at one operating condition are first produced to provide baseline performance information. These are followed by multiple broadband design approaches culminating in a broadband liner targeting the full range of frequencies and operating conditions. The broadband liner is found to satisfy the optimum impedance objectives much better than the tonal liner designs. In addition, the broadband liner is found to provide better attenuation than the tonal designs over the full range of frequencies and operating conditions considered. Thus, the current study successfully establishes a process for the initial design and evaluation of novel broadband liner concepts for complex engine configurations.

Subsystem Analysis/Optimization for the X-34 Main Propulsion System

NASA Technical Reports Server (NTRS)

McDonald, J. P.; Hedayat, A.; Brown, T. M.; Knight, K. C.; Champion, R. H., Jr.

1998-01-01

The Orbital Sciences Corporation X-34 vehicle demonstrates technologies and operations key to future reusable launch vehicles. The general flight performance goal of this unmanned rocket plane is Mach 8 flight at an altitude of 250,000 feet. The Main Propulsion System (MPS) supplies liquid propellants to the main engine, which provides the primary thrust for attaining mission goals. Major MPS design and operational goals are aircraft-like ground operations, quick turnaround between missions, and low initial/operational costs. Analyses related to optimal MPS subsystem design are reviewed in this paper. A pressurization system trade weighs maintenance/reliability concerns against those for safety in a comparison of designs using pressure regulators versus orifices to control pressurant flow. A propellant dump/feed system analysis weighs the issues of maximum allowable vehicle landing weight, trajectory, and MPS complexity to arrive at a final configuration for propellant dump/feed systems.

Hydrocephalus and mucopolysaccharidoses: what do we know and what do we not know?

PubMed

Dalla Corte, Amauri; de Souza, Carolina F M; Anés, Maurício; Giugliani, Roberto

2017-07-01

The precise incidence of hydrocephalus in patients with mucopolysaccharidoses (MPS) is hard to determine, because the condition lacks a formal, consensus-based definition. The diagnosis of hydrocephalus depends on symptom profile, presence of neuroimaging features, and the outcome of diagnostic tests. Although numerous techniques are used to identify MPS patients who are most likely to have hydrocephalus and respond to treatment, no definitive method exists to prove diagnosis. The authors propose an algorithm to aid in the diagnosis and management of hydrocephalus in MPS patients. The theory of venous hypertension associated with the morphological changes in the skull base and craniocervical junction indicate the need for future neuroimaging studies including cerebrospinal fluid (CSF) and venous flow measurements to monitor hydrocephalus progression and select therapeutic interventions in MPS patients. Preoperative planning should also be based on the increased risk of intraoperative and postoperative hemorrhagic complications.

Transition duct system with metal liners for delivering hot-temperature gases in a combustion turbine engine

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

Wiebe, David J.

A transition duct system (10) for delivering hot-temperature gases from a plurality of combustors in a combustion turbine engine is provided. The system includes an exit piece (16) for each combustor. The exit piece may include a straight path segment (26) and an arcuate connecting segment (36). A respective straight metal liner (92) and an arcuate metal liner (94) may be each inwardly disposed onto a metal outer shell (38) along the straight path segment and the arcuate connecting segment (36) of the exit piece. Structural arrangements are provided to securely attach the respective liners in the presence of substantialmore » flow path pressurization. Cost-effective serviceability of the transition duct systems is realizable since the liners can be readily removed and replaced as needed.« less

Evaluation of Skin Friction Drag for Liner Applications in Aircraft

NASA Technical Reports Server (NTRS)

Gerhold, Carl H.; Brown, Martha C.; Jasinski, Christopher M.

2016-01-01

A parameter that is gaining significance in the evaluation of acoustic liner performance is the skin friction drag induced by air flow over the liner surface. Estimates vary widely regarding the amount of drag the liner induces relative to a smooth wall, from less than a 20% increase to nearly 100%, and parameters such as face sheet perforate hole diameter, percent open area, and sheet thickness are expected to figure prominently in the skin friction drag. Even a small increase in liner drag can impose an economic penalty, and current research is focused on developing 'low drag' liner concepts, with the goal being to approach the skin friction drag of a smooth wall. The issue of skin friction drag takes on greater significance as airframe designers investigate the feasibility of putting sound absorbing liners on the non-lifting surfaces of the wings and fuselage, for the purpose of reducing engine noise reflected and scattered toward observers on the ground. Researchers at the NASA Langley Research Center have embarked on investigations of liner skin friction drag with the aims of: developing a systematic drag measurement capability, establishing the drag of current liners, and developing liners that produce reduced drag without compromising acoustic performance. This paper discusses the experimental procedures that have been developed to calculate the drag coefficient based on the change in momentum thickness and the companion research program being carried out to measure the drag directly using a force balance. Liner samples that are evaluated include a solid wall with known roughness and conventional liners with perforated facesheets of varying hole diameter and percent open area.

Transition duct system with arcuate ceramic liner for delivering hot-temperature gases in a combustion turbine engine

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

Wiebe, David J.

A transition duct system (10) for delivering hot-temperature gases from a plurality of combustors in a combustion turbine engine is provided. The system includes an exit piece (16) for each combustor. The exit piece may include an arcuate connecting segment (36). An arcuate ceramic liner (60) may be inwardly disposed onto a metal outer shell (38) along the arcuate connecting segment of the exit piece. Structural arrangements are provided to securely attach the ceramic liner in the presence of substantial flow path pressurization. Cost-effective serviceability of the transition duct systems is realizable since the liner can be readily removed andmore » replaced as needed.« less

Assessment of urinary microparticles in normotensive patients with type 1 diabetes.

PubMed

Lytvyn, Yuliya; Xiao, Fengxia; Kennedy, Christopher R J; Perkins, Bruce A; Reich, Heather N; Scholey, James W; Cherney, David Z; Burger, Dylan

2017-03-01

Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes. In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls. Urinary vesicles were assessed by electron microscopy and nanoparticle tracking while podocyte MPs were assessed by flow cytometry. Neither vesicle size nor total number were significantly altered in type 1 diabetes or acute hyperglycaemia. By contrast, urinary podocyte MP levels were higher in type 1 diabetes (0.47 [0.00-3.42] MPs/μmol creatinine [Cr]) compared with healthy controls (0.00 [0.00-0.00] MPs/μmol Cr, p < 0.05) and increased under hyperglycaemic clamp (0.36 [0.00-4.15] MPs/μmol Cr during euglycaemia vs 2.70 [0.00-15.91] MPs/μmol Cr during hyperglycaemia, p < 0.05). Levels of urinary albumin to creatinine ratio and nephrin (surrogates of podocyte injury) were unchanged by type 1 diabetes or acute hyperglycaemia. Taken together, our data show that urinary podocyte MP levels are higher in patients with type 1 diabetes in advance of changes in other biomarkers (albuminuria, nephrin). Examination of podocyte MPs may serve as an early biomarker of glomerular injury in uncomplicated type 1 diabetes.

Microparticles and blood cells induce procoagulant activity via phosphatidylserine exposure in NSTEMI patients following stent implantation.

PubMed

Wang, Lixiu; Bi, Yayan; Cao, Muhua; Ma, Ruishuang; Wu, Xiaoming; Zhang, Yan; Ding, Wenbo; Liu, Yan; Yu, Qian; Zhang, Yingqian; Jiang, Hua; Sun, Yingchun; Tong, Dongxia; Guo, Li; Dong, Zengxiang; Tian, Ye; Kou, Junjie; Shi, Jialan

2016-11-15

Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with non-ST-elevated myocardial infarction (NSTEMI) after stent implantation. This study was designed to evaluate whether exposed PS on microparticles (MPs) and blood cells were involved in the hypercoagulable state in NSTEMI patients with stent implantation. NSTEMI patients (n=90) and healthy controls (n=20) were included in our study. PS exposure on MPs and blood cells was analyzed with flow cytometer and confocal microscope. PCA was evaluated by clotting time, purified coagulation complex assays and fibrin production assays. Baseline levels of MPs and PS + blood cells were significantly higher (P<0.001) in the patients than in controls. After stent implantation, a remarkable increase was observed in both MPs and PS + blood cells. Specifically, PS + MPs, PS + platelets and erythrocytes peaked at 18h following stent implantation, while PS + leukocytes peaked on day 2. In addition, circulating MPs (mostly derived from platelets, leukocytes, erythrocytes and endothelial cells) cooperating with PS + blood cells, contributed to markedly shortened coagulation time and markedly increased FXa/thrombin/fibrin (all P<0.01) generation in patient group. Moreover, blockade of exposed PS on MPs and cells with lactadherin inhibited PCA by approximately 70%. Our results suggest that PS + MPs and blood cells play a procoagulant role in NSTEMI patients following stent implantation. Blockade of PS could become a novel therapeutic modality for the prevention of thrombosis in these patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of long-time immersion of soft denture liners in water on viscoelastic properties.

PubMed

Iwasaki, Naohiko; Yamaki, Chisato; Takahashi, Hidekazu; Oki, Meiko; Suzuki, Tetsuya

2017-09-26

Aim of this study was to investigate the effect of long-time immersion of soft denture liners in 37°C water on viscoelastic properties. Six silicone-based and two acrylic resin-based soft denture liners were selected. Cylindrical specimens were stored in distilled water at 37°C for 6 months. Viscoelastic properties, which were instantaneous and delayed elastic displacements, viscous flow, and residual displacement, were determined using a creep meter, and analyzed with 2-way analysis of variance and Tukey's comparison (α=0.05). Viscoelastic properties and their time-dependent changes were varied among materials examined. The observed viscoelastic properties of three from six silicone-based liners did not significantly change after 6-month immersion, but those of two acrylic resin-based liners significantly changed with the increase of immersion time. However, the sum of initial instantaneous elastic displacement and delayed elastic displacement of two acrylic resin-based liners during 6-month immersion changed less than 10%, which might indicate clinically sufficient elastic performance.

Implementation of In-Situ Impedance Techniques on a Full Scale Aero-Engine System

NASA Technical Reports Server (NTRS)

Gaeta, R. J.; Mendoza, J. M.; Jones, M. G.

2007-01-01

Determination of acoustic liner impedance for jet engine applications remains a challenge for the designer. Although suitable models have been developed that take account of source amplitude and the local flow environment experienced by the liner, experimental validation of these models has been difficult. This is primarily due to the inability of researchers to faithfully mimic the environment in jet engine nacelles in the laboratory. An in-situ measurement technique, one that can be implemented in an actual engine, is desirable so an accurate impedance can be determined for future modeling and quality control. This paper documents the implementation of such a local acoustic impedance measurement technique that is used under controlled laboratory conditions as well as on full scale turbine engine liner test article. The objective for these series of in-situ measurements is to substantiate treatment design, provide understanding of flow effects on installed liner performance, and provide modeling input for fan noise propagation computations. A series of acoustic liner evaluation tests are performed that includes normal incidence tube, grazing incidence tube, and finally testing on a full scale engine on a static test stand. Lab tests were intended to provide insight and guidance for accurately measuring the impedance of the liner housed in the inlet of a Honeywell Tech7000 turbofan. Results have shown that one can acquire very reasonable liner impedance data for a full scale engine under realistic test conditions. Furthermore, higher fidelity results can be obtained by using a three-microphone coherence technique that can enhance signal-to-noise ratio at high engine power settings. This research has also confirmed the limitations of this particular type of in-situ measurement. This is most evident in the installation of instrumentation and its effect on what is being measured.

Control of reactor coolant flow path during reactor decay heat removal

DOEpatents

Hunsbedt, Anstein N.

1988-01-01

An improved reactor vessel auxiliary cooling system for a sodium cooled nuclear reactor is disclosed. The sodium cooled nuclear reactor is of the type having a reactor vessel liner separating the reactor hot pool on the upstream side of an intermediate heat exchanger and the reactor cold pool on the downstream side of the intermediate heat exchanger. The improvement includes a flow path across the reactor vessel liner flow gap which dissipates core heat across the reactor vessel and containment vessel responsive to a casualty including the loss of normal heat removal paths and associated shutdown of the main coolant liquid sodium pumps. In normal operation, the reactor vessel cold pool is inlet to the suction side of coolant liquid sodium pumps, these pumps being of the electromagnetic variety. The pumps discharge through the core into the reactor hot pool and then through an intermediate heat exchanger where the heat generated in the reactor core is discharged. Upon outlet from the heat exchanger, the sodium is returned to the reactor cold pool. The improvement includes placing a jet pump across the reactor vessel liner flow gap, pumping a small flow of liquid sodium from the lower pressure cold pool into the hot pool. The jet pump has a small high pressure driving stream diverted from the high pressure side of the reactor pumps. During normal operation, the jet pumps supplement the normal reactor pressure differential from the lower pressure cold pool to the hot pool. Upon the occurrence of a casualty involving loss of coolant pump pressure, and immediate cooling circuit is established by the back flow of sodium through the jet pumps from the reactor vessel hot pool to the reactor vessel cold pool. The cooling circuit includes flow into the reactor vessel liner flow gap immediate the reactor vessel wall and containment vessel where optimum and immediate discharge of residual reactor heat occurs.

Space Shuttle Main Propulsion System Gaseous Hydrogen Flow Control Valve Poppet Failure

NASA Technical Reports Server (NTRS)

Zeitler, Rick

2010-01-01

The presentation provides background information pertinent to the MPS GH2 Flow Control Valve Poppet failure which occurred on the Space Shuttle Endeavour during STS-126 flight. The presentation provides general MPS system operating information which is pertinent to understanding the failure causes and affects. The presentation provides additional background information on the operating environment in which the FCV functions and basic design history of the flow control valve. The presentation provides an overview of the possible flight failure modes and a brief summary of the flight rationale which was developed for this failure event. This presentation is an introductory presentation to 3 other speakers at the conference who will be speaking on M&P aspects of the investigation, non destructive inspection techniques development, and particle impact testing.

Transition mixing study

NASA Technical Reports Server (NTRS)

Reynolds, R.; White, C.

1986-01-01

A computer model capable of analyzing the flow field in the transition liner of small gas turbine engines is developed. A FORTRAN code has been assembled from existing codes and physical submodels and used to predict the flow in several test geometries which contain characteristics similar to transition liners, and for which experimental data was available. Comparisons between the predictions and measurements indicate that the code produces qualitative results but that the turbulence models, both K-E and algebraic Reynolds Stress, underestimate the cross-stream diffusion. The code has also been used to perform a numerical experiment to examine the effect of a variety of parameters on the mixing process in transition liners. Comparisons illustrate that geometries with significant curvature show a drift of the jet trajectory toward the convex wall and weaker wake region vortices and decreased penetration for jets located on the convex wall of the liner, when compared to jets located on concave walls. Also shown were the approximate equivalency of angled slots and round holes and a technique by which jet mixing correlations developed for rectangular channels can be used for can geometries.

Duct modes damping through an adjustable electroacoustic liner under grazing incidence

NASA Astrophysics Data System (ADS)

Boulandet, R.; Lissek, H.; Karkar, S.; Collet, M.; Matten, G.; Ouisse, M.; Versaevel, M.

2018-07-01

This paper deals with active sound attenuation in lined ducts with flow and its application to duct modes damping in aircraft engine nacelles. It presents an active lining concept based on an arrangement of electroacoustic absorbers flush mounted in the duct wall. Such feedback-controlled loudspeaker membranes are used to achieve locally reacting impedances with adjustable resistance and reactance. A broadband impedance model is formulated from the loudspeaker parameters and a design procedure is proposed to achieve specified acoustic resistances and reactances. The performance is studied for multimodal excitation by simulation using the finite element method and the results are compared to measurements made in a flow duct facility. This electroacoustic liner has an attenuation potential comparable to that of a conventional passive liner, but also offers greater flexibility to achieve the target acoustic impedance in the low frequencies. In addition, it is adaptive in real time to track variable engine speeds. It is shown with the liner prototype that the duct modes can be attenuated over a bandwidth of two octaves around the resonance frequency of the loudspeakers.

Methods and apparatus for radially compliant component mounting

DOEpatents

Bulman, David Edward [Cincinnati, OH; Darkins, Jr., Toby George; Stumpf, James Anthony [Columbus, IN; Schroder, Mark S [Greenville, SC; Lipinski, John Joseph [Simpsonville, SC

2012-03-27

Methods and apparatus for a mounting assembly for a liner of a gas turbine engine combustor are provided. The combustor includes a combustor liner and a radially outer annular flow sleeve. The mounting assembly includes an inner ring surrounding a radially outer surface of the liner and including a plurality of axially extending fingers. The mounting assembly also includes a radially outer ring coupled to the inner ring through a plurality of spacers that extend radially from a radially outer surface of the inner ring to the outer ring.

Acoustic Panel Liner for an Engine Nacelle

NASA Technical Reports Server (NTRS)

Nark, Douglas M. (Inventor); Ayle, Earl (Inventor); Jones, Michael G. (Inventor); Ichihashi, Fumitaka (Inventor)

2016-01-01

An acoustic panel liner includes a face sheet, back plate, and liner core positioned there-between, which may be used in an engine nacelle. Elongated chambers contain variable amounts of septa at a calibrated depth or depths. The septa may have varying DC flow resistance. The chambers may have a hexagonal or other polygonal cross sections. The septa, such as mesh caps, may be bonded to an inner wall of a corresponding chamber. The insertion depths may be the same or different. If different, the pattern of distribution of the depths may be randomized.

Towards development of enhanced fully-Lagrangian mesh-free computational methods for fluid-structure interaction

NASA Astrophysics Data System (ADS)

Khayyer, Abbas; Gotoh, Hitoshi; Falahaty, Hosein; Shimizu, Yuma

2018-02-01

Simulation of incompressible fluid flow-elastic structure interactions is targeted by using fully-Lagrangian mesh-free computational methods. A projection-based fluid model (moving particle semi-implicit (MPS)) is coupled with either a Newtonian or a Hamiltonian Lagrangian structure model (MPS or HMPS) in a mathematically-physically consistent manner. The fluid model is founded on the solution of Navier-Stokes and continuity equations. The structure models are configured either in the framework of Newtonian mechanics on the basis of conservation of linear and angular momenta, or Hamiltonian mechanics on the basis of variational principle for incompressible elastodynamics. A set of enhanced schemes are incorporated for projection-based fluid model (Enhanced MPS), thus, the developed coupled solvers for fluid structure interaction (FSI) are referred to as Enhanced MPS-MPS and Enhanced MPS-HMPS. Besides, two smoothed particle hydrodynamics (SPH)-based FSI solvers, being developed by the authors, are considered and their potential applicability and comparable performance are briefly discussed in comparison with MPS-based FSI solvers. The SPH-based FSI solvers are established through coupling of projection-based incompressible SPH (ISPH) fluid model and SPH-based Newtonian/Hamiltonian structure models, leading to Enhanced ISPH-SPH and Enhanced ISPH-HSPH. A comparative study is carried out on the performances of the FSI solvers through a set of benchmark tests, including hydrostatic water column on an elastic plate, high speed impact of an elastic aluminum beam, hydroelastic slamming of a marine panel and dam break with elastic gate.

HepPar1-Positive Circulating Microparticles Are Increased in Subjects with Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection

PubMed Central

Abbate, Valeria; Marcantoni, Margherita; Giuliante, Felice; Vecchio, Fabio M.; Gatto, Ilaria; Mele, Caterina; Saviano, Antonio; Arciuolo, Damiano; Gaetani, Eleonora; Ferrari, Maria C.; Giarretta, Igor; Ardito, Francesco; Riccardi, Laura; Nicoletti, Alberto; Ponziani, Francesca R.; Gasbarrini, Antonio; Pompili, Maurizio; Pola, Roberto

2017-01-01

Circulating microparticles (MPs) are novel potential biomarkers in cancer patients. Their role in hepatocellular carcinoma (HCC) is under intensive investigation. In this study, we tested the hypothesis that MPs expressing the antigen HepPar1 are increased in the blood of subjects with HCC and may serve as markers of early recurrence after liver resection (LR). We studied 15 patients affected by HCC undergoing LR, and used flow cytometry to assess the number of circulating HepPar1+ MPs. Ten subjects without HCC (five with liver cirrhosis and five with healthy livers) were used as controls. After LR, HCC patients underwent a follow-up to check for early recurrence, which occurred in seven cases. The number of circulating HepPar1+ MPs was significantly higher in subjects affected by HCC, compared to individuals without cancer (p < 0.01). We also found that, among HCC patients, the number of circulating HepPar1+ MPs, measured before LR, was significantly higher in those who displayed early recurrence compared to those without recurrence (p = 0.02). Of note, other types of circulating MPs, such as those derived from endothelial cells (CD144+) or those produced by the activated endothelium (CD144+/CD62+), were not associated with HCC, nor could they predict HCC recurrence. HepPar1+ MPs deserve further investigation as novel biomarkers of disease and prognosis in HCC patients. PMID:28498353

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

Schock, Sarah C.; Edrissi, Hamidreza; Burger, Dylan

Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPsmore » were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells.« less

Direct numerical simulation of turbulent flow with an impedance condition

NASA Astrophysics Data System (ADS)

Olivetti, Simone; Sandberg, Richard D.; Tester, Brian J.

2015-05-01

DNS solutions for a pipe/jet configuration are re-computed with the pipe alone to investigate suppression of previously identified internal noise source(s) with an acoustic liner, using a time domain acoustic liner model developed by Tam and Auriault (AIAA Journal, 34 (1996) 913-917). Liner design parameters are chosen to achieve up to 30 dB attenuation of the broadband pressure field over the pipe length without affecting the velocity field statistics. To understand the effect of the liner on the acoustic and turbulent components of the unsteady wall pressure, an azimuthal/axial Fourier transform is applied and the acoustic and turbulent wavenumber regimes clearly identified. It is found that the spectral component occupying the turbulent wavenumber range is unaffected by the liner whereas the acoustic wavenumber components are strongly attenuated, with individual radial modes being evident as each cuts on with increasing Strouhal number.

CrossWater - Modelling micropollutant loads from different sources in the Rhine basin

NASA Astrophysics Data System (ADS)

Moser, Andreas; Bader, Hans-Peter; Fenicia, Fabrizio; Scheidegger, Ruth; Stamm, Christian

2016-04-01

The pressure on rivers from micropollutants (MPs) originating from various sources is a growing environmental issue and requiring political regulations. The challenges for the water management are numerous, particularly for international water basins. Spatial knowledge of MP sources and the water quality are prerequisites for an effective water quality policy. In this study we analyze the sources of MPs in the international Rhine basin in Europe, and model their transport to the streams. The spatial patterns of MP loads and concentrations from different use classes are investigated with a mass flow analysis and compared to the territorial jurisdictions that shape the spatial arrangement of water management. The source area of MPs depends on the specific use of a compound. Here, we focus on i) herbicides from agricultural land use, ii) biocides from material protection on buildings and iii) human pharmaceuticals from households. The total mass of MPs available for release to the stream network is estimated from statistical application and consumption data. The available mass of MPs is spatially distributed to the catchments areas based on GIS data of agricultural land use, vector data of buildings and wastewater treatment plant (WWTP) locations, respectively. The actual release of MPs to the stream network is calculated with empirical loss rates related to river discharge for agricultural herbicides and to precipitation for biocides. For the pharmaceuticals the release is coupled to the human metabolism rates and elimination rates in WWTP. The released loads from the catchments are propagated downstream with hydraulic routing. Water flow, transport and fate of the substances are simulated within linked river reaches. Time series of herbicide concentrations and loads are simulated for the main rivers in the Rhine basin. Accordingly the loads from the primary catchments are aggregated and constitute lateral or upstream input to the simulated river reaches. Pronounced differences in the spatial patterns of concentrations in the aquatic system are observed between the different compounds. The comparison with measurements from monitoring stations along the Rhine yield satisfactory results.

Method of lining a vertical mine shaft with concrete

DOEpatents

Eklund, James D.; Halter, Joseph M.; Rasmussen, Donald E.; Sullivan, Robert G.; Moffat, Robert B.

1981-01-01

The apparatus includes a cylindrical retainer form spaced inwardly of the wall of the shaft by the desired thickness of the liner to be poured and having overlapping edges which seal against concrete flow but permit the form to be contracted to a smaller circumference after the liner has hardened and is self-supporting. A curb ring extends downwardly and outwardly toward the shaft wall from the bottom of the retainer form to define the bottom surface of each poured liner section. An inflatable toroid forms a seal between the curb ring and the shaft wall. A form support gripper ring having gripper shoes laterally extendable under hydraulic power to engage the shaft wall supports the retainer form, curb ring and liner until the newly poured liner section becomes self-supporting. Adjusting hydraulic cylinders permit the curb ring and retainer form to be properly aligned relative to the form support gripper ring. After a liner section is self-supporting, an advancing system advances the retainer form, curb ring and form support gripper ring toward a shaft boring machine above which the liner is being formed. The advancing system also provides correct horizontal alignment of the form support gripper ring.

Formation of functionalized nanoclusters by solvent evaporation and their effect on the physicochemical properties of dental composite resins.

PubMed

Rodríguez, Henry A; Giraldo, Luis F; Casanova, Herley

2015-07-01

The aim of this work was to study the effect of silica nanoclusters (SiNC), obtained by a solvent evaporation method and functionalized by 3-methacryloxypropyltrimethoxysilane (MPS) and MPS+octyltrimethoxysilane (OTMS) (50/50wt/wt), on the rheological, mechanical and sorption properties of urethane dimethylacrylate (UDMA)/triethylenglycol dimethacrylate (TEGDMA) (80/20wt/wt) resins blend. Silica nanoparticles (SiNP) were silanized with MPS or MPS+OTMS (50/50wt/wt) and incorporated in an UDMA-isopropanol mix to produce functionalized silica nanoclusters after evaporating the isopropanol. The effect of functionalized SiNC on resins rheological properties was determined by large and small deformation tests. Mechanical, thermal, sorption and solubility properties were evaluated for composite materials. The UDMA/TEGDMA (80/20wt/wt) resins blend with added SiNC (ca. 350nm) and functionalized with MPS showed a Newtonian flow behavior associated to their spheroidal shape, whereas the resins blend with nanoclusters silanized with MPS+OTMS (50/50wt/wt) (ca. 400nm) showed a shear-thinning behavior due to nanoclusters irregular shape. Composite materials prepared with bare silica nanoclusters showed lower compressive strength than functionalized silica nanoclusters. MPS functionalized nanoclusters showed better mechanical properties but higher water sorption than functionalized nanoclusters with both silane coupling agents, MPS and OTMS. The solvent evaporation method applied to functionalized nanoparticles showed to be an alternative way to the sinterization method for producing nanoclusters, which improved some dental composite mechanical properties and reduced water sorption. The shape of functionalized silica nanoclusters showed to have influence on the rheological properties of SiNC resin suspensions and the mechanical and sorption properties of light cured composites. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Characterization of Microparticles after Hepatic Ischemia-Reperfusion Injury

PubMed Central

Freeman, Christopher M.; Quillin, Ralph C.; Wilson, Gregory C.; Nojima, Hiroyuki; Johnson, Bobby L.; Sutton, Jeffrey M.; Schuster, Rebecca M.; Blanchard, John; Edwards, Michael J.; Caldwell, Charles C.; Lentsch, Alex B.

2014-01-01

Background Hepatic ischemia-reperfusion (I/R) is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs) are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins–platelets, neutrophils, and endolethial cells–following hepatic ischemia-reperfusion injury. Methods A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. Results MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. Conclusion This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver. PMID:24879335

Hydrology [Chapter 9

Treesearch

V. C. Hasfurther; G. L. Kerr; G. Parks; J. Wetstein

1994-01-01

Three Parshall flumes were installed within East and West Glacier Lakes watersheds during the summer of 1987. Each Parshall flume was prefabricated fiberglass construction fitted with a hypolon liner to bring as much groundwater flow as possible to the surface so that it could be measured by passing the water through the flume. The liner was buried as deep as was...

Acoustic Treatment Design Scaling Methods. Volume 4; Numerical Simulation of the Nonlinear Acoustic Impedance of a Perforated Plate Single-Degree-of-Freedom Resonator Using a Time-Domain Finite Difference Method

NASA Technical Reports Server (NTRS)

Kraft, R. E.

1999-01-01

Single-degree-of-freedom resonators consisting of honeycomb cells covered by perforated facesheets are widely used as acoustic noise suppression liners in aircraft engine ducts. The acoustic resistance and mass reactance of such liners are known to vary with the intensity of the sound incident upon the panel. Since the pressure drop across a perforated liner facesheet increases quadratically with the flow velocity through the facesheet, this is known as the nonlinear resistance effect. In the past, two different empirical frequency domain models have been used to predict the Sound Pressure Level effect of the incident wave on the perforated liner impedance, one that uses the incident particle velocity in isolated narrowbands, and one that models the particle velocity as the overall velocity. In the absence of grazing flow, neither frequency domain model is entirely accurate in predicting the nonlinear effect that is measured for typical perforated sheets. The time domain model is developed in an attempt to understand and improve the model for the effect of spectral shape and amplitude of multi-frequency incident sound pressure on the liner impedance. A computer code for the time-domain finite difference model is developed and predictions using the models are compared to current frequency-domain models.

Numerical study of effect of compressor swirling flow on combustor design in a MTE

NASA Astrophysics Data System (ADS)

Mu, Yong; Wang, Chengdong; Liu, Cunxi; Liu, Fuqiang; Hu, Chunyan; Xu, Gang; Zhu, Junqiang

2017-08-01

An effect of the swirling flow on the combustion performance is studied by the computational fluid dynamics (CFD) in a micro-gas turbine with a centrifugal compressor, dump diffuser and forward-flow combustor. The distributions of air mass and the Temperature Pattern Factor (as: Overall Temperature Distribution Factor -OTDF) in outlet are investigated with two different swirling angles of compressed air as 0° and 15° in three combustors. The results show that the influences of swirling flow on the air distribution and OTDF cannot be neglected. Compared with no-swirling flow, the air through outer liner is more, and the air through the inner liner is less, and the pressure loss is bigger under the swirling condition in the same combustor. The Temperature Pattern Factor changes under the different swirling conditions.

Investigation of air stream from combustor-liner air entry holes, 3

NASA Technical Reports Server (NTRS)

Aiba, T.; Nakano, T.

1979-01-01

Jets flowing from air entry holes of the combustor liner of a gas turbine were investigated. Cold air was supplied through the air entry holes into the primary hot gas flows. The mass flow of the primary hot gas and issuing jets was measured, and the behavior of the air jets was studied by the measurement of the temperature distribution of the gas mixture. The air jets flowing from three circular air entry holes, single streamwise long holes, and two opposing circular holes, parallel to the primary flow were studied along with the effects of jet and gas stream velocities, and of gas temperature. The discharge coefficient, the maximum penetration of the jets, the jet flow path, the mixing of the jets, and temperature distribution across the jets were investigated. Empirical expressions which describe the characteristics of the jets under the conditions of the experiments were formulated.

AS-7 improved in vitro quality of red blood cells prepared from whole blood held overnight at room temperature.

PubMed

Veale, Margaret F; Healey, Geraldine; Sran, Amrita; Payne, Katherine A; Zia, Majid; Sparrow, Rosemary L

2015-01-01

Extended room temperature (RT) hold of whole blood (WB) may affect the quality of red blood cell (RBC) components produced from these donations. The availability of better RBC additive solutions (ASs) may help reduce the effects. A new AS, AS-7 (SOLX, Haemonetics Corporation), was investigated for improved in vitro quality of RBCs prepared from WB held overnight at RT. Sixteen WB units were held for 21.4 hours ± 40 minutes at 22°C on cooling plates before processing. Each pair of ABO-matched WB units were pooled, divided into a WB filter pack containing saline-adenine-glucose-mannitol (control) and a LEUKOSEP WB-filter pack containing SOLX, and processed according to manufacturer's instructions. RBCs were stored at 2 to 6°C and sampled weekly until expiry. Glycophorin A (GPA+) and annexin V-binding microparticles (MPs) were quantitated using flow cytometry. Osmotic fragility, intracellular pH (pHi), adenosine triphosphate (ATP), 2,3-diphosphoglycerate (2,3-DPG), and routine quality variables were measured. Adhesion of RBCs to human endothelial cells (ECs) was evaluated by flow perfusion under low shear stress (0.5 dyne/cm(2) ), similar to low blood flow in microvessels. ATP and 2,3-DPG levels were improved for SOLX-RBCs. SOLX-RBCs maintained higher pHi, increased resistance to hypotonic stress, and reduced numbers of GPA+ MPs. No significant difference was observed between annexin V binding to MPs or adhesion of RBCs to ECs under shear stress. SOLX-stored RBCs showed increased osmotic resistance, pHi, and reduced GPA+ MPs and together with higher ATP and 2,3-DPG levels demonstrated improved in vitro RBC quality measures during 42 days of storage. © 2014 AABB.

A Finite Element Theory for Predicting the Attenuation of Extended-Reacting Liners

NASA Technical Reports Server (NTRS)

Watson, W. R.; Jones, M. G.

2009-01-01

A non-modal finite element theory for predicting the attenuation of an extended-reacting liner containing a porous facesheet and located in a no-flow duct is presented. The mathematical approach is to solve separate wave equations in the liner and duct airway and to couple these two solutions by invoking kinematic constraints at the facesheet that are consistent with a continuum theory of fluid motion. Given the liner intrinsic properties, a weak Galerkin finite element formulation with cubic polynomial basis functions is used as the basis for generating a discrete system of acoustic equations that are solved to obtain the coupled acoustic field. A state-of-the-art, asymmetric, parallel, sparse equation solver is implemented that allows tens of thousands of grid points to be analyzed. A grid refinement study is presented to show that the predicted attenuation converges. Excellent comparison of the numerically predicted attenuation to that of a mode theory (using a Haynes 25 metal foam liner) is used to validate the computational approach. Simulations are also presented for fifteen porous plate, extended-reacting liners. The construction of some of the porous plate liners suggest that they should behave as resonant liners while the construction of others suggest that they should behave as broadband attenuators. In each case the finite element theory is observed to predict the proper attenuation trend.

Modifications to the Langley 8-foot transonic pressure tunnel for the laminar flow control experiment

NASA Technical Reports Server (NTRS)

Harris, Charles D.; Brooks, Cuyler W., Jr.

1988-01-01

Modifications to the NASA Langley 8 Foot Transonic Pressure Tunnel in support of the Lamina Flow Control (LFC) Experiment included the installation of a honeymoon and five screens in the settling chamber upstream of the test section 41-long test section liner that extended from the upstream end of the test section contraction region, through the best section, and into the diffuser. The honeycomb and screens were installed as permanent additions to the facility, and the liner was a temporary addition to be removed at the conclusion of the LFC Experiment. These modifications are briefly described.

Performance of a Liner-on-Target Injector for Staged Z-Pinch Experiments

NASA Astrophysics Data System (ADS)

Conti, F.; Valenzuela, J. C.; Narkis, J.; Krasheninnikov, I.; Beg, F.; Wessel, F. J.; Ruskov, E.; Rahman, H. U.; McGee, E.

2016-10-01

We present the design and characterization of a compact liner-on-target injector, used in the Staged Z-pinch experiments conducted on the UNR-NTF Zebra Facility. Previous experiments and analysis indicate that high-Z gas liners produce a uniform and efficient implosion on a low-Z target plasma. The liner gas shell is produced by an annular solenoid valve and a converging-diverging nozzle designed to achieve a collimated, supersonic, Mach-5 flow. The on-axis target is produced by a coaxial plasma gun, where a high voltage pulse is applied to ionize neutral gas and accelerate the plasma by the J-> × B-> force. Measurements of the liner and target dynamics, resolved by interferometry in space and time, fast imaging, and collection of the emitted light, are presented. The results are compared to the predictions from Computational Fluid Dynamics and MHD simulations that model the injector. Optimization of the design parameters, for upcoming Staged Z-pinch experiments, will be discussed. Advanced Research Projects Agency - Energy, DE-AR0000569.

Cross-hole fracture connectivity assessed using hydraulic responses during liner installations in crystalline bedrock boreholes

NASA Astrophysics Data System (ADS)

Persaud, Elisha; Levison, Jana; Pehme, Peeter; Novakowski, Kentner; Parker, Beth

2018-01-01

In order to continually improve the current understanding of flow and transport in crystalline bedrock environments, developing and improving fracture system characterization techniques is an important area of study. The presented research examines the installation of flexible, impermeable FLUTe™ liners as a means for assessing cross-hole fracture connectivity. FLUTe™ liners are used to generate a new style of hydraulic pulse, with pressure response monitored in a nearby network of open boreholes drilled in gneissic rock of the Canadian Shield in eastern Ontario, Canada. Borehole liners were installed in six existing 10-15 cm diameter boreholes located 10-35 m apart and drilled to depths ranging between 25-45 m. Liner installation tests were completed consecutively with the number of observation wells available for each test ranging between one and six. The collected pressure response data have been analyzed to identify significant groundwater flow paths between source and observation boreholes as well as to estimate inter-well transmissivity and storativity using a conventional type-curve analysis. While the applied solution relies on a number of general assumptions, it has been found that reasonable comparison can be made to previously completed pulse interference and pumping tests. Results of this research indicate areas where method refinement is necessary, but, nonetheless, highlight the potential for use in crystalline bedrock environments. This method may provide value to future site characterization efforts given that it is complementary to, and can be used in conjunction with, other currently employed borehole liner applications, such as the removal of cross-connection at contaminated sites and the assessment of discrete fracture distributions when boreholes are sealed, recreating natural hydraulic gradient conditions.

A new method for determining acoustic-liner admittance in a rectangular duct with grazing flow from experimental data

NASA Technical Reports Server (NTRS)

Watson, W. R.

1984-01-01

A method is developed for determining acoustic liner admittance in a rectangular duct with grazing flow. The axial propagation constant, cross mode order, and mean flow profile is measured. These measured data are then input into an analytical program which determines the unknown admittance value. The analytical program is based upon a finite element discretization of the acoustic field and a reposing of the unknown admittance value as a linear eigenvalue problem on the admittance value. Gaussian elimination is employed to solve this eigenvalue problem. The method used is extendable to grazing flows with boundary layers in both transverse directions of an impedance tube (or duct). Predicted admittance values are compared both with exact values that can be obtained for uniform mean flow profiles and with those from a Runge Kutta integration technique for cases involving a one dimensional boundary layer.

Space Shuttle Program (SSP) Orbiter Main Propulsion System (MPS) Gaseous Hydrogen (GH2) Flow Control Valve (FCV) Poppet Eddy Current (EC) Inspection Probability of Detection (POD) Study. Volume 1

NASA Technical Reports Server (NTRS)

Piascik, Robert S.; Prosser, William H.

2011-01-01

The Director of the NASA Engineering and Safety Center (NESC), requested an independent assessment of the anomalous gaseous hydrogen (GH2) flow incident on the Space Shuttle Program (SSP) Orbiter Vehicle (OV)-105 during the Space Transportation System (STS)-126 mission. The main propulsion system (MPS) engine #2 GH2 flow control valve (FCV) LV-57 transition from low towards high flow position without being commanded. Post-flight examination revealed that the FCV LV-57 poppet had experienced a fatigue failure that liberated a section of the poppet flange. The NESC assessment provided a peer review of the computational fluid dynamics (CFD), stress analysis, and impact testing. A probability of detection (POD) study was requested by the SSP Orbiter Project for the eddy current (EC) nondestructive evaluation (NDE) techniques that were developed to inspect the flight FCV poppets. This report contains the findings and recommendations from the NESC assessment.

Space Shuttle Program (SSP) Orbiter Main Propulsion System (MPS) Gaseous Hydrogen (GH2) Flow Control Valve (FCV) Poppet Eddy Current (EC) Inspection Probability of Detection (POD) Study. Volume 2; Appendices

NASA Technical Reports Server (NTRS)

Piascik, Robert S.; Prosser, William H.

2011-01-01

The Director of the NASA Engineering and Safety Center (NESC), requested an independent assessment of the anomalous gaseous hydrogen (GH2) flow incident on the Space Shuttle Program (SSP) Orbiter Vehicle (OV)-105 during the Space Transportation System (STS)-126 mission. The main propulsion system (MPS) engine #2 GH2 flow control valve (FCV) LV-57 transition from low towards high flow position without being commanded. Post-flight examination revealed that the FCV LV-57 poppet had experienced a fatigue failure that liberated a section of the poppet flange. The NESC assessment provided a peer review of the computational fluid dynamics (CFD), stress analysis, and impact testing. A probability of detection (POD) study was requested by the SSP Orbiter Project for the eddy current (EC) nondestructive evaluation (NDE) techniques that were developed to inspect the flight FCV poppets. This report contains the Appendices to the main report.

A Quasi-3-D Theory for Impedance Eduction in Uniform Grazing Flow

NASA Technical Reports Server (NTRS)

Watson, W. R.; Jones, M. G.; Parrott, T. L.

2005-01-01

A 2-D impedance eduction methodology is extended to quasi-3-D sound fields in uniform or shearing mean flow. We introduce a nonlocal, nonreflecting boundary condition to terminate the duct and then educe the impedance by minimizing an objective function. The introduction of a parallel, sparse, equation solver significantly reduces the wall clock time for educing the impedance when compared to that of the sequential band solver used in the 2-D methodology. The accuracy, efficiency, and robustness of the methodology is demonstrated using two examples. In the first example, we show that the method reproduces the known impedance of a ceramic tubular test liner. In the second example, we illustrate that the approach educes the impedance of a four-segment liner where the first, second, and fourth segments consist of a perforated face sheet bonded to honeycomb, and the third segment is a cut from the ceramic tubular test liner. The ability of the method to educe the impedances of multisegmented liners has the potential to significantly reduce the amount of time and cost required to determine the impedance of several uniform liners by allowing them to be placed in series in the test section and to educe the impedance of each segment using a single numerical experiment. Finally, we probe the objective function in great detail and show that it contains a single minimum. Thus, our objective function is ideal for use with local, inexpensive, gradient-based optimizers.

Integral Field Spectroscopy of Markarian 273: Mapping High-Velocity Gas Flows and an Off-Nucleus Seyfert 2 Nebula.

PubMed

Colina; Arribas; Borne

1999-12-10

Integral field optical spectroscopy with the INTEGRAL fiber-based system is used to map the extended ionized regions and gas flows in Mrk 273, one of the closest ultraluminous infrared galaxies. The Hbeta and [O iii] lambda5007 maps show the presence of two distinct regions separated by 4&arcsec; (3.1 kpc) along position angle (P.A.) 240 degrees. The northeastern region coincides with the optical nucleus of the galaxy and shows the spectral characteristics of LINERs. The southwestern region is dominated by [O iii] emission and is classified as a Seyfert 2. Therefore, in the optical, Mrk 273 is an ultraluminous infrared galaxy with a LINER nucleus and an extended off-nucleus Seyfert 2 nebula. The kinematics of the [O iii] ionized gas shows (1) the presence of highly disturbed gas in the regions around the LINER nucleus, (2) a high-velocity gas flow with a peak-to-peak amplitude of 2.4x103 km s-1, and (3) quiescent gas in the outer regions (at 3 kpc). We hypothesize that the high-velocity flow is the starburst-driven superwind generated in an optically obscured nuclear starburst and that the quiescent gas is directly ionized by a nuclear source, similar to the ionization cones typically seen in Seyfert galaxies.

Measured and calculated acoustic attenuation rates of tuned resonator arrays for two surface impedance distribution models with flow

NASA Technical Reports Server (NTRS)

Parrott, Tony L.; Abrahamson, A. Louis; Jones, Michael G.

1988-01-01

An experiment was performed to validate two analytical models for predicting low frequency attenuation of duct liner configurations built from an array of seven resonators that could be individually tuned via adjustable cavity depths. These analytical models had previously been developed for high frequency aero-engine inlet duct liner design. In the low frequency application, the liner surface impedance distribution is unavoidably spatially varying by virtue of available fabrication techniques. The characteristic length of this spatial variation may be a significant fraction of the acoustic wavelength. Comparison of measured and predicted attenuation rates and transmission losses for both modal decomposition and finite element propagation models were in good to excellent agreement for a test frequency range that included the first and second cavity resonance frequencies. This was true for either of two surface impedance distribution modeling procedures used to simplify the impedance boundary conditions. In the presence of mean flow, measurements revealed a fine scale structure of acoustic hot spots in the attenuation and phase profiles. These details were accurately predicted by the finite element model. Since no impedance changes due to mean flow were assumed, it is concluded that this fine scale structure was due to convective effects of the mean flow interacting with the surface impedance nonuniformities.

Endothelial Microparticles From Acute Coronary Syndrome Patients Induce Premature Coronary Artery Endothelial Cell Aging and Thrombogenicity: Role of the Ang II/AT1 Receptor/NADPH Oxidase-Mediated Activation of MAPKs and PI3-Kinase Pathways.

PubMed

Abbas, Malak; Jesel, Laurence; Auger, Cyril; Amoura, Lamia; Messas, Nathan; Manin, Guillaume; Rumig, Cordula; León-González, Antonio J; Ribeiro, Thais P; Silva, Grazielle C; Abou-Merhi, Raghida; Hamade, Eva; Hecker, Markus; Georg, Yannick; Chakfe, Nabil; Ohlmann, Patrick; Schini-Kerth, Valérie B; Toti, Florence; Morel, Olivier

2017-01-17

Microparticles (MPs) have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. This study examined the potential of MPs from senescent endothelial cells (ECs) or from patients with acute coronary syndrome (ACS) to promote premature EC aging and thrombogenicity. Primary porcine coronary ECs were isolated from the left circumflex coronary artery. MPs were prepared from ECs and venous blood from patients with ACS (n=30) and from healthy volunteers (n=4) by sequential centrifugation. The level of endothelial senescence was assessed as senescence-associated β-galactosidase activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, tissue factor activity using an enzymatic Tenase assay, the level of target protein expression by Western blot analysis, platelet aggregation using an aggregometer, and shear stress using a cone-and-plate viscometer. Senescence, as assessed by senescence-associated β-galactosidase activity, was induced by the passaging of porcine coronary artery ECs from passage P1 to P4, and was associated with a progressive shedding of procoagulant MPs. Exposure of P1 ECs to MPs shed from senescent P3 cells or circulating MPs from ACS patients induced increased senescence-associated β-galactosidase activity, oxidative stress, early phosphorylation of mitogen-activated protein kinases and Akt, and upregulation of p53, p21, and p16. Ex vivo, the prosenescent effect of circulating MPs from ACS patients was evidenced only under conditions of low shear stress. Depletion of endothelial-derived MPs from ACS patients reduced the induction of senescence. Prosenescent MPs promoted EC thrombogenicity through tissue factor upregulation, shedding of procoagulant MPs, endothelial nitric oxide synthase downregulation, and reduced nitric oxide-mediated inhibition of platelet aggregation. These MPs exhibited angiotensin-converting enzyme activity and upregulated AT1 receptors and angiotensin-converting enzyme in P1 ECs. Losartan, an AT1 receptor antagonist, and inhibitors of either mitogen-activated protein kinases or phosphoinositide 3-kinase prevented the MP-induced endothelial senescence. These findings indicate that endothelial-derived MPs from ACS patients induce premature endothelial senescence under atheroprone low shear stress and thrombogenicity through angiotensin II-induced redox-sensitive activation of mitogen-activated protein kinases and phosphoinositide 3-kinase/Akt. They further suggest that targeting endothelial-derived MP shedding and their bioactivity may be a promising therapeutic strategy to limit the development of an endothelial dysfunction post-ACS. © 2016 American Heart Association, Inc.

Cell Derived Microparticles in Gingival Crevicular Fluid from Periodontitis Patients with Type 2 Diabetes.

PubMed

Figueredo, Carlos Marcelo; Lira, Ronaldo; Sete, Manuela Rubim; Fischer, Ricardo Guimarães

2017-01-01

Cell-derived microparticles (MPs) have been described as vital contributors to the inflammatory process. However, its role in the periodontal disease pathogenesis remains unclear. Therefore, we aimed to detect the presence neutrophil (CD66b+) and platelet (CD41b+) derived microparticles in gingival crevicular fluid from individuals having periodontitis aggravated by type 2 diabetes. Twelve patients (56.2 ±7.2 yrs) with severe form of chronic periodontitis aggravated by type 2 diabetes were included. Clinical and metabolic data were gathered. Gingival crevicular fluid was collected using filter strips from deep and shallow sites. MPs were detected by flow cytometry according to their size (< 1 µm) and the expression of surface markers (CD66b for neutrophil-derived MPs and CD41b for platelet-derived MPs). All samples were positive for the antibodies. Median levels of CD66b+ MPs and CD41b+ MPs were, respectively, 3,677.0 (2,553.2 - 9,059.8) MP/µL and 520.7 (432.9 - 766.1) MP/µL in deep sites. In shallow sites, the corresponding values were 2,644.9 (1,451.5 - 3,858.9) MP/µL and 371.2 (287.2 - 692.7) MP/µL. There was no significant difference between deep and shallow sites (p>0.05). In conclusion, this study reported the presence of neutrophil and platelet derived microparticles in gingival crevicular fluid from individuals having severe periodontitis and type 2 diabetes.

Gene editing of MPS I human fibroblasts by co-delivery of a CRISPR/Cas9 plasmid and a donor oligonucleotide using nanoemulsions as nonviral carriers.

PubMed

Schuh, Roselena Silvestri; de Carvalho, Talita Giacomet; Giugliani, Roberto; Matte, Ursula; Baldo, Guilherme; Teixeira, Helder Ferreira

2018-01-01

Mucopolysaccharidosis type I (MPS I) is an inherited disease caused by the deficiency of alpha-L-iduronidase (IDUA). This study shows the use of nanoemulsions co-complexed with the plasmid of CRISPR/Cas9 system and a donor oligonucleotide aiming at MPS I gene editing in vitro. Nanoemulsions composed of MCT, DOPE, DOTAP, DSPE-PEG, and water were prepared by high-pressure homogenization. The DNA was complexed by adsorption (NA) or encapsulation (NE) of preformed DNA/DOTAP complexes with nanoemulsions at +4/-1 charge ratio. The incubation in pure DMEM or supplemented with serum showed that the complexation with DNA was stable after 1 h of incubation, but the complexes tended to release the adsorbed DNA after 24 h of incubation, while the encapsulated DNA remained complexed in the oil core of the nanoemulsions even 48 h after incubation with DMEM. The treatment of MPS I patient's fibroblasts homozygous for the p.Trp402 ∗ mutation led to a significant increase in IDUA activity at 2, 15, and 30 days when compared to MPS I untreated fibroblasts. Flow cytometry and confocal microscopy demonstrated that there was a reduction in the area of lysosomes to values similar to normal, an indicator of correction of the cellular phenotype. These results show that the nanoemulsions co-complexed with the CRISPR/Cas9 system and a donor oligonucleotide could effectively transfect MPS I p.Trp402 ∗ patient's fibroblasts, as well as enable the production of IDUA, and represent a potential new treatment option for MPS I. Copyright © 2017 Elsevier B.V. All rights reserved.

Adiponectin limits monocytic microparticle-induced endothelial activation by modulation of the AMPK, Akt and NFκB signaling pathways.

PubMed

Ehsan, Mehroz; Singh, Krishna K; Lovren, Fina; Pan, Yi; Quan, Adrian; Mantella, Laura-Eve; Sandhu, Paul; Teoh, Hwee; Al-Omran, Mohammed; Verma, Subodh

2016-02-01

Monocyte-derived microparticles (mono-MPs) are emerging as critical transducers of inflammatory signals, and have been suggested to link cardiovascular risk factors to vascular injury. Since adiponectin has been proposed to exert multiple anti-inflammatory and vasculoprotective effects, we hypothesized that it might serve to limit the production and/or action of mono-MPs. Flow cytometry and western blot studies were conducted on THP-1 cells, THP-1-derived MPs, human umbilical vein endothelial cells (HUVECs), peripheral blood CD14+ monocytes and mice to evaluate the effects of adiponectin on mono-MPs. Adiponectin attenuated lipopolysaccharide (LPS)-evoked MP release from THP-1 monocytes (30% difference) and peripheral blood monocytes (both P < 0.05) as well as dampened LPS-induced mono-MP generation in vivo. Furthermore, peritoneal monocytes from Adipoq(-/-) mice generated significantly greater MPs than those from Adipoq(+/+) littermates in the absence (2.3 fold difference, P < 0.05) and presence (1.6 fold difference, P < 0.05) of LPS. LPS-induced MP expression of NLRP3 inflammasome and its key components, namely cleaved ASC, caspase-1 and IL-1β (pro- and cleaved), were markedly attenuated by adiponectin. HUVECs incubated with MPs from LPS-treated THP-1 cells exhibited increased VCAM-1 levels and adhesion to THP-1 cells. Adiponectin abrogated these effects. From a mechanistic standpoint, the effects of adiponectin on MP release and molecular signaling occurred at least in part through the AMPK, Akt and NFκB pathways. Adiponectin exerts novel effects to limit the production and action of mono-MPs, underscoring yet another pleiotropic effect of this adipokine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Flow through in situ reactors with suction lysimeter sampling capability and methods of using

DOEpatents

Radtke, Corey W [Idaho Falls, ID; Blackwelder, D Brad [Blackfoot, ID; Hubbell, Joel M [Idaho Falls, ID

2009-11-17

An in situ reactor for use in a geological strata includes a liner defining a centrally disposed passageway and a sampling conduit received within the passageway. The sampling conduit may be used to receive a geological speciment derived from geological strata therein and a lysimeter is disposed within the sampling conduit in communication with the geological specimen. Fluid may be added to the geological specimen through the passageway defined by the liner, between an inside surface of the liner and an outside surface of the sampling conduit. A distal portion of the sampling conduit may be in fluid communication with the passageway.

Theory of formation of helical structures in a perfectly conducting, premagnetized Z-pinch liner

NASA Astrophysics Data System (ADS)

Yu, Edmund; Velikovich, Alexander; Peterson, Kyle

2014-10-01

The magnetized liner inertial fusion (MagLIF) concept uses an azimuthal magnetic field to collapse a thick metallic liner containing preheated fusion fuel. A critical component of the concept is an axial magnetic field, permeating both the fuel and surrounding liner, which reduces the compression necessary to achieve fusion conditions. Recent experiments demonstrate that a liner premagnetized with a 10 T axial field develops helical structures with a pitch significantly larger than an estimate of Bz /Bθ would suggest. The cause of the helical perturbations is still not understood. In this work, we present an analytic, linear theory in which we model the liner as a perfectly conducting metal, and study how bumps and divots on its surface redirect current flow, resulting in perturbations to B as well as j × B . We show that in the presence of axial and azimuthal magnetic field, the theory predicts divots will grow and deform at an angle determined by the magnetic field. We compare theoretical results with three dimensional, resistive MHD simulations. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the National Nuclear Security Administration under DE-AC04-94AL85000.

Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women.

PubMed

Wilkinson, Daniel J; Bukhari, Syed S I; Phillips, Bethan E; Limb, Marie C; Cegielski, Jessica; Brook, Matthew S; Rankin, Debbie; Mitchell, William K; Kobayashi, Hisamine; Williams, John P; Lund, Jonathan; Greenhaff, Paul L; Smith, Kenneth; Atherton, Philip J

2017-09-23

Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP). Twenty-four older women (65 ± 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V infusion of 13 C 6 -phenylalanine was used to determine MPS at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 × 8 unilateral leg extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling via immunoblotting. Plasma insulineamia and EAAemia were greater and more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP. Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0-2 h, with MPS significantly higher than basal in the LEAA_6 and WP groups only over 0-4 h. However, FED-EX increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p-p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P < 0.05). In conclusion, LEAA_1.5, despite only providing 0.6 g of leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP. Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Development of a fluorescence-based in vivo phagocytosis assay to measure mononuclear phagocyte system function in the rat.

PubMed

Tartaro, Karrie; VanVolkenburg, Maria; Wilkie, Dean; Coskran, Timothy M; Kreeger, John M; Kawabata, Thomas T; Casinghino, Sandra

2015-01-01

The mononuclear phagocyte system (MPS) which provides protection against infection is made up of phagocytic cells that engulf and digest bacteria or other foreign substances. Suppression of the MPS may lead to decreased clearance of pathogenic microbes. Drug delivery systems and immunomodulatory therapeutics that target phagocytes have a potential to inhibit MPS function. Available methods to measure inhibition of MPS function use uptake of radioactively-labeled cells or labor-intensive semi-quantitative histologic techniques. The objective of this work was to develop a non-radioactive quantitative method to measure MPS function in vivo by administering heat-killed E. coli conjugated to a pH-sensitive fluorescent dye (Bioparticles(®)). Fluorescence of the Bioparticles(®) is increased at low pH when they are in phagocytic lysosomes. The amount of Bioparticles(®) phagocytosed by MPS organs in rats was determined by measuring fluorescence intensity in livers and spleens ex vivo using an IVIS(®) Spectrum Pre-clinical In Vivo Imaging System. Phagocytosis of the particles by peripheral blood neutrophils was measured by flow cytometry. To assess method sensitivity, compounds likely to suppress the MPS [clodronate-containing liposomes, carboxylate-modified latex particles, maleic vinyl ether (MVE) polymer] were administered to rats prior to injection of the Bioparticles(®). The E. coli particles consistently co-localized with macrophage markers in the liver but not in the spleen. All of the compounds tested decreased phagocytosis in the liver, but had no consistent effects on phagocytic activity in the spleen. In addition, administration of clodronate liposomes and MVE polymer increased the percentage of peripheral blood neutrophils that phagocytosed the Bioparticles(®). In conclusion, an in vivo rat model was developed that measures phagocytosis of E. coli particles in the liver and may be used to assess the impact of test compounds on MPS function. Still, the detection of inhibition of splenic macrophage function will require further assay development.

Comparison of a Convected Helmholtz and Euler Model for Impedance Eduction in Flow

NASA Technical Reports Server (NTRS)

Watson, Willie R.; Jones, Michael G.

2006-01-01

Impedances educed from a well-tested convected Helmholtz model are compared to that of a recently developed linearized Euler model using two ceramic test liners under the assumed conditions or uniform flow and a plane wave source. The convected Helmholtz model is restricted to uniform mean flow whereas the linearized Euler model can account for the effect or the shear layer. Test data to educe the impedance is acquired from measurements obtained in the NASA Langley Research Center Grazing Incidence Tube for mean flow Mach numbers ranging from 0.0 to 0.5 and source frequencies ranging from 0.5 kHz to 3.0 kHz. The unknown impedance of the liner b educed by judiciously chooingth e impedance via an optimization method to match the measured acoustic pressure on the wall opposite the test liner. Results are presented on four spatial grids using three different optimization methods (contour deformation, Davidon-Fletcher Powell, and the Genetic Algorithm). All three optimization methods converge to the same impedance when used with the same model and to nearly identical impedances when used on different models. h anomaly was observed only at 0.5 kHz for high mean flow speeds. The anomaly is likely due to the use of measured data in a flow regime where shear layer effects are important but are neglected in the math models. Consistency between the impedances educed using the two models provides confidence that the linearized Euler model is ready For application to more realistic flows, such as those containing shear layers.

Bayesian identification of acoustic impedance in treated ducts.

PubMed

Buot de l'Épine, Y; Chazot, J-D; Ville, J-M

2015-07-01

The noise reduction of a liner placed in the nacelle of a turbofan engine is still difficult to predict due to the lack of knowledge of its acoustic impedance that depends on grazing flow profile, mode order, and sound pressure level. An eduction method, based on a Bayesian approach, is presented here to adjust an impedance model of the liner from sound pressures measured in a rectangular treated duct under multimodal propagation and flow. The cost function is regularized with prior information provided by Guess's [J. Sound Vib. 40, 119-137 (1975)] impedance of a perforated plate. The multi-parameter optimization is achieved with an Evolutionary-Markov-Chain-Monte-Carlo algorithm.

Dispersion, dissipation and refraction of shock waves in acoustically treated turbofan inlets

NASA Astrophysics Data System (ADS)

Prasad, Dilip; Li, Ding; A. Topol, David

2015-09-01

This paper describes a numerical investigation of the effects of the inlet duct liner on the acoustics of a high-bypass ratio turbofan rotor operating at supersonic tip relative flow conditions. The near field of the blade row is then composed of periodic shocks that evolve spatially both because of the varying mean flow and because of the presence of acoustic treatment. The evolution of this shock system is studied using a Computational Fluid Dynamics-based method incorporating a wall impedance boundary condition. The configuration examined is representative of a fan operating near the takeoff condition. The behavior of the acoustic power and the associated waveforms reveal that significant dispersion occurs to the extent that there are no shocks in the perturbation field leaving the entrance plane of the duct. The effect of wave refraction due to the high degree of shear in the mean flow near the entrance plane of the inlet is examined, and numerical experiments are conducted to show that the incorporation of liners in this region can be highly beneficial. The implications of these results for the design of aircraft engine acoustic liners are discussed.

Acoustic Treatment Design Scaling Methods. Volume 3; Test Plans, Hardware, Results, and Evaluation

NASA Technical Reports Server (NTRS)

Yu, J.; Kwan, H. W.; Echternach, D. K.; Kraft, R. E.; Syed, A. A.

1999-01-01

The ability to design, build, and test miniaturized acoustic treatment panels on scale-model fan rigs representative of the full-scale engine provides not only a cost-savings, but an opportunity to optimize the treatment by allowing tests of different designs. To be able to use scale model treatment as a full-scale design tool, it is necessary that the designer be able to reliably translate the scale model design and performance to an equivalent full-scale design. The primary objective of the study presented in this volume of the final report was to conduct laboratory tests to evaluate liner acoustic properties and validate advanced treatment impedance models. These laboratory tests include DC flow resistance measurements, normal incidence impedance measurements, DC flow and impedance measurements in the presence of grazing flow, and in-duct liner attenuation as well as modal measurements. Test panels were fabricated at three different scale factors (i.e., full-scale, half-scale, and one-fifth scale) to support laboratory acoustic testing. The panel configurations include single-degree-of-freedom (SDOF) perforated sandwich panels, SDOF linear (wire mesh) liners, and double-degree-of-freedom (DDOF) linear acoustic panels.

Analysis of synthetic and biological microparticles on several flow cytometric platforms

EPA Science Inventory

Microparticles (MPs) are membrane vesicles (0.1 to 1 urn) released from cells upon activation. The limit of detection ofmost standard flow cytometers is just below 1 urn. Recent advances enable detection of particles lower than 0.5 urn, Synthetic. beads are used to define size ra...

Impedance Eduction in Large Ducts Containing Higher-Order Modes and Grazing Flow

NASA Technical Reports Server (NTRS)

Watson, Willie R.; Jones, Michael G.

2017-01-01

Impedance eduction test data are acquired in ducts with small and large cross-sectional areas at the NASA Langley Research Center. An improved data acquisition system in the large duct has resulted in increased control of the acoustic energy in source modes and more accurate resolution of higher-order duct modes compared to previous tests. Two impedance eduction methods that take advantage of the improved data acquisition to educe the liner impedance in grazing flow are presented. One method measures the axial propagation constant of a dominant mode in the liner test section (by implementing the Kumarsean and Tufts algorithm) and educes the impedance from an exact analytical expression. The second method solves numerically the convected Helmholtz equation and minimizes an objective function to obtain the liner impedance. The two methods are tested first on data synthesized from an exact mode solution and then on measured data. Results show that when the methods are applied to data acquired in the larger duct with a dominant higher-order mode, the same impedance spectra are educed as that obtained in the small duct where only the plane wave mode propagates. This result holds for each higher-order mode in the large duct provided that the higher-order mode is sufficiently attenuated by the liner.

Image flows and one-liner graphical image representation.

PubMed

Makhervaks, Vadim; Barequet, Gill; Bruckstein, Alfred

2002-10-01

This paper introduces a novel graphical image representation consisting of a single curve-the one-liner. The first step of the algorithm involves the detection and ranking of image edges. A new edge exploration technique is used to perform both tasks simultaneously. This process is based on image flows. It uses a gradient vector field and a new operator to explore image edges. Estimation of the derivatives of the image is performed by using local Taylor expansions in conjunction with a weighted least-squares method. This process finds all the possible image edges without any pruning, and collects information that allows the edges found to be prioritized. This enables the most important edges to be selected to form a skeleton of the representation sought. The next step connects the selected edges into one continuous curve-the one-liner. It orders the selected edges and determines the curves connecting them. These two problems are solved separately. Since the abstract graph setting of the first problem is NP-complete, we reduce it to a variant of the traveling salesman problem and compute an approximate solution to it. We solve the second problem by using Dijkstra's shortest-path algorithm. The full software implementation for the entire one-liner determination process is available.

An in vitro study of magnetic particle targeting in small blood vessels

NASA Astrophysics Data System (ADS)

Udrea, Laura Elena; Strachan, Norval J. C.; Bădescu, Vasile; Rotariu, Ovidiu

2006-10-01

The magnetic guidance and capture of particles inside the human body, via the circulatory system, is a novel method for the targeted delivery of drugs. This experimental study confirms in vitro that a dipolar capturing device, based on high-energy magnets with an active space of 8.7 cm × 10 cm × 10 cm, retains colloidal magnetic particles (MPs) (<30 nm) injected in the capillary tubes, where flow velocities are comparable to that encountered in the capillary beds of tumours (<0.5 cm s-1). The build-up of the deposition of the MPs was investigated using video imaging techniques that enabled continuous monitoring of the blocking of the vessel whilst simultaneously recording the colloid's flow rate. The parameters of practical importance (length of MP deposit, time of capillary blocking) were estimated and were found to be dependent on the initial fluid velocity, the MP concentration and the distance between the capillary tube and the polar magnetic pieces. Although the tube used in this experiment is larger (diameter = 0.75 mm, length = 100 mm) than that of real capillaries (diameter = 0.01 mm, length ~1.5 mm), the flow velocities chosen were similar to those encountered in the capillary beds of tumours and the length/diameter ratio was approximately equal (133 for the present set-up, 100-150 for real capillaries). In these circumstances and using the same magnetic field conditions (intensity, gradient) and MPs, there is close similarity with magnetic capture in a microscopic capillary system. Moreover, the macroscopic system permits analysis of the distribution of MPs in the active magnetic space, and consequently the maximum targetable volume. This study revealed that the capture of particles within the active space was strongly influenced by the gradient of the magnetic field and the flow velocity. Thus, when the magnetic field gradient had medium values (0.1-0.3 T cm-1) and the fluid velocity was small (0.15 cm s-1), the particles were captured in small, compact and stable deposits (L < 4 cm) and the time necessary for blocking of the capillary was <150 s. Doubling the value for the flow velocity did not influence significantly either the length of MP deposits nor the blocking time. However, lower gradients (<0.1 T cm-1) and larger velocities (0.3-0.9 cm s-1) result in the formation of larger deposits (4 cm < L < 10 cm) that are unstable at the beginning of the capture process. These large deposits do become stable given sufficient time for the deposition process to take place in conjunction with a decrease in the flow rate. As a consequence, the time necessary for blocking of the capillary increased up to 450 s. Decreasing the MP concentration from 0.02 g cm-3 to 0.005 g cm-3 decreased the deposit lengths by approximately 20% and doubled the values of the blocking time. The maximum targetable volume obtained by the present method is ~350 cm3, which corresponds to medium-sized tumours. The capillary vessels were blocked only for the situation that occurs for microcirculation within a tumour. This reduces the concentration of MPs trapped within the normal tissues, which occurs when using particles of micrometre size. This work showed the potential of using colloidal MPs and dipolar magnetic devices for treatment of human patients, when the affected sites are positioned at medium distances from the surface of the body (e.g. head, neck, breast, hands and legs).

Liner cooling research at NASA Lewis Research Center. [for gas turbine combustion chambers

NASA Technical Reports Server (NTRS)

Acosta, Waldo A.

1987-01-01

Described are recently completed and current advanced liner research applicable to advanced small gas turbine engines. Research relating to the evolution of fuel efficient small gas turbine engines capable of meeting future commercial and military aviation needs is currently under way at NASA Lewis Research Center. As part of this research, a reverse-flow combustor geometry was maintained while different advanced liner wall cooling techniques were investigated and compared to a baseline combustor. The performance of the combustors featuring counterflow film-cooled (CFFC) panels, transpiration cooled liner walls (TRANS), and compliant metal/ceramic (CMC) walls was obtained over a range of simulated flight conditions of a 16:1 pressure ratio gas turbine engine and fuel/air ratios up to 0.034. All the combustors featured an identical fuel injection system, identical geometric configuration outline, and similar designed internal aerothermodynamics.

Optimal one-section and two-section circular sound-absorbing duct liners for plane-wave and monopole sources without flow

NASA Technical Reports Server (NTRS)

Lester, H. C.; Posey, J. W.

1976-01-01

A discrete frequency study is made of the influence of source characteristics on the optimal properties of acoustically lined uniform and two section ducts. Two simplified sources, a plane wave and a monopole, are considered in some detail and over a greater frequency range than has been previously studied. Source and termination impedance effects are given limited examination. An example of a turbomachinery source and three associated source variants is also presented. Optimal liner designs based on modal theory approach the Cremer criterion at low frequencies and the geometric acoustics limit at high frequencies. Over an intermediate frequency range, optimal two section liners produced higher transmission losses than did the uniform configurations. Source distribution effects were found to have a significant effect on optimal liner design, but source and termination impedance effects appear to be relatively unimportant.

Metal liner-driven quasi-isentropic compression of deuterium

NASA Astrophysics Data System (ADS)

Weinwurm, Marcus; Bland, Simon N.; Chittenden, Jeremy P.

2013-09-01

Properties of degenerate hydrogen and deuterium (D) at pressures of the order of terapascals are of key interest to Planetary Science and Inertial Confinement Fusion. In order to recreate these conditions in the laboratory, we present a scheme, where a metal liner drives a cylindrically convergent quasi-isentropic compression in a D fill. We first determined an external pressure history for driving a self-similar implosion of a D shell from a fictitious flow simulation [D. S. Clark and M. Tabak, Nucl. Fusion 47, 1147 (2007)]. Then, it is shown that this D implosion can be recreated inside a beryllium liner by shaping the current pulse. For a peak current of 10.8 MA cold and nearly isochoric D is assembled at around 12 500 kg/m3. Finally, our two-dimensional Gorgon simulations show the robustness of the implosion method to the magneto-Rayleigh-Taylor instability when using a sufficiently thick liner.

Modeling the Compression of Merged Compact Toroids by Multiple Plasma Jets

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Knapp, Charles E.; Kirkpatrick, Ron; Rodgers, Stephen L. (Technical Monitor)

2000-01-01

A fusion propulsion scheme has been proposed that makes use of the merging of a spherical distribution of plasma jets to dynamically form a gaseous liner. The gaseous liner is used to implode a magnetized target to produce the fusion reaction in a standoff manner. In this paper, the merging of the plasma jets to form the gaseous liner is investigated numerically. The Los Alamos SPHINX code, based on the smoothed particle hydrodynamics method is used to model the interaction of the jets. 2-D and 3-D simulations have been performed to study the characteristics of the resulting flow when these jets collide. The results show that the jets merge to form a plasma liner that converge radially which may be used to compress the central plasma to fusion conditions. Details of the computational model and the SPH numerical methods will be presented together with the numerical results.

Comparative Study of Impedance Eduction Methods, Part 2: NASA Tests and Methodology

NASA Technical Reports Server (NTRS)

Jones, Michael G.; Watson, Willie R.; Howerton, Brian M.; Busse-Gerstengarbe, Stefan

2013-01-01

A number of methods have been developed at NASA Langley Research Center for eduction of the acoustic impedance of sound-absorbing liners mounted in the wall of a flow duct. This investigation uses methods based on the Pridmore-Brown and convected Helmholtz equations to study the acoustic behavior of a single-layer, conventional liner fabricated by the German Aerospace Center and tested in the NASA Langley Grazing Flow Impedance Tube. Two key assumptions are explored in this portion of the investigation. First, a comparison of results achieved with uniform-flow and shear-flow impedance eduction methods is considered. Also, an approach based on the Prony method is used to extend these methods from single-mode to multi-mode implementations. Finally, a detailed investigation into the effects of harmonic distortion on the educed impedance is performed, and the results are used to develop guidelines regarding acceptable levels of harmonic distortion

Increased blood cell phosphatidylserine exposure and circulating microparticles contribute to procoagulant activity after carotid artery stenting.

PubMed

Zhao, Lu; Wu, Xiaoming; Si, Yu; Yao, Zhipeng; Dong, Zengxiang; Novakovic, Valerie A; Guo, Li; Tong, Dongxia; Chen, He; Bi, Yayan; Kou, Junjie; Shi, Huaizhang; Tian, Ye; Hu, Shaoshan; Zhou, Jin; Shi, Jialan

2017-11-01

OBJECTIVE Phosphatidylserine (PS) is a major component of the inner leaflet of membrane bilayers. During cell activation or apoptosis, PS is externalized to the outer membrane, providing an important physiological signal necessary for the release of the microparticles (MPs) that are generated through the budding of cellular membranes. MPs express PS and membrane antigens that reflect their cellular origin. PS exposure on the cell surface and the release of MPs provide binding sites for factor Xa and prothrombinase complexes that promote thrombin formation. Relatively little is known about the role of PS exposure on blood cells and MPs in patients with internal carotid artery (ICA) stenosis who have undergone carotid artery stenting (CAS). The authors aimed to investigate the extent of PS exposure on blood cells and MPs and to define its role in procoagulant activity (PCA) in the 7 days following CAS. METHODS The study included patients with ICA stenosis who had undergone CAS (n = 70), matched patients who had undergone catheter angiography only (n = 30), and healthy controls (n = 30). Blood samples were collected from all patients just before the procedure after an overnight fast and at 2, 6, 24, 48, and 72 hours and 7 days after the CAS procedure. Blood was collected from healthy controls after an overnight fast. Phosphatidylserine-positive (PS+) MPs and blood cells were analyzed by flow cytometry, while PCA was assessed with clotting time analysis, purified coagulation complex assays, and fibrin formation assays. RESULTS The authors found that levels of PS+ blood cells and PS+ blood cell-derived MPs (platelets and platelet-derived MPs [PMPs], neutrophils and neutrophil-derived MPs [NMPs], monocytes and monocyte-derived MPs [MMPs], erythrocytes and erythrocyte-derived MPs [RMPs], and endothelial cells and endothelial cell-derived MPs [EMPs]) were increased in the 7 days following the CAS procedure. Specifically, elevation of PS exposure on platelets/PMPs, neutrophils/NMPs, and monocytes/MMPs was detected within 2 hours of CAS, whereas PS exposure was delayed on erythrocytes/RMPs and EMPs, with an increase detected 24 hours after CAS. In addition, PS+ platelets/PMPs peaked at 2 hours, while PS+ neutrophils/NMPs, monocytes/MMPs, and erythrocytes/RMPs peaked at 48 hours. After their peak, all persisted at levels above baseline for 7 days post-CAS. Moreover, the level of PS+ blood cells/MPs was correlated with shortened coagulation time and significantly increased intrinsic and extrinsic Xase, thrombin generation, and fibrin formation. Pretreatment of blood cells with lactadherin at their peak time point after CAS blocked PS, resulting in prolonged coagulation times, decreased procoagulant enzyme activation, and fibrin production. CONCLUSIONS The results of this study suggest that increased exposure of PS on blood cells and MPs may contribute to enhanced PCA in patients with ICA stenosis who have undergone CAS, explaining the risk of perioperative thromboembolic complications in these patients. PS on blood cells and MPs may serve as an important biomarker for predicting, and as a pivotal target for monitoring and treating, acute postoperative complications after CAS. ■ CLASSIFICATION OF EVIDENCE Type of question: association; study design: prospective cohort trial; evidence: Class I.

Aspiration thrombectomy and intracoronary tirofiban via GuideLiner® catheter for a thrombosed aneurysmal vessel.

PubMed

Fry, James; Naqvi, Ali; Bahia, Amit; Seto, Arnold

2017-03-01

A 52-year-old Asian male with no traditional risk factors for coronary artery disease presented with acute coronary syndrome. Coronary angiography showed complete thrombotic occlusion of the left circumflex with a large thrombus burden in the setting of diffuse aneurysmal enlargement of the coronary arteries consistent with antecedent Kawasaki disease. Manual thrombectomy with adjunctive intracoronary tirofiban was performed utilizing the GuideLiner catheter ® (Vascular Solutions, Inc., MN, USA). Stent implantation was deferred. Follow-up imaging 48 h later showed preserved coronary flow and decreased thrombus burden. The GuideLiner catheter, a monorail guiding device, served a novel role in thrombus aspiration and intracoronary medication delivery.

Pharmacological enhancement of leg and muscle microvascular blood flow does not augment anabolic responses in skeletal muscle of young men under fed conditions.

PubMed

Phillips, Bethan E; Atherton, Philip J; Varadhan, Krishna; Wilkinson, Daniel J; Limb, Marie; Selby, Anna L; Rennie, Michael J; Smith, Kenneth; Williams, John P

2014-01-15

Skeletal muscle anabolism associated with postprandial plasma aminoacidemia and insulinemia is contingent upon amino acids (AA) and insulin crossing the microcirculation-myocyte interface. In this study, we hypothesized that increasing muscle microvascular blood volume (flow) would enhance fed-state anabolic responses in muscle protein turnover. We studied 10 young men (23.2 ± 2.1 yr) under postabsorptive and fed [iv Glamin (∼10 g AA), glucose ∼7.5 mmol/l] conditions. Methacholine was infused into the femoral artery of one leg to determine, via bilateral comparison, the effects of feeding alone vs. feeding plus pharmacological vasodilation. We measured leg blood flow (LBF; femoral artery) by Doppler ultrasound, muscle microvascular blood volume (MBV) by contrast-enhanced ultrasound (CEUS), muscle protein synthesis (MPS) and breakdown (MPB; a-v balance modeling), and net protein balance (NPB) using [1,2-(13)C2]leucine and [(2)H5]phenylalanine tracers via gas chromatography-mass spectrometry (GC-MS). Indexes of anabolic signaling/endothelial activation (e.g., Akt/mTORC1/NOS) were assessed using immunoblotting techniques. Under fed conditions, LBF (+12 ± 5%, P < 0.05), MBV (+25 ± 10%, P < 0.05), and MPS (+129 ± 33%, P < 0.05) increased. Infusion of methacholine further enhanced LBF (+126 ± 12%, P < 0.05) and MBV (+79 ± 30%, P < 0.05). Despite these radically different blood flow conditions, neither increases in MPS in response to feeding (0.04 ± 0.004 vs. 0.08 ± 0.01%/h, P < 0.05) nor improvements in NPB (-4.4 ± 2.4 vs. 16.4 ± 5.7 nmol Phe·100 ml leg(-1)·min(-1), P < 0.05) were affected by methacholine infusion (MPS 0.07 ± 0.01%/h; NPB 24.0 ± 7.7 nmol Phe·100 ml leg(-1)·min(-1)), whereas MPB was unaltered by either feeding or infusion of methacholine. Thus, enhancing LBF/MBV above that occurring naturally with feeding alone does not improve muscle anabolism.

Small gas turbine combustor study - Fuel injector performance in a transpiration-cooled liner

NASA Technical Reports Server (NTRS)

Riddlebaugh, S. M.; Norgren, C. T.

1985-01-01

The effect of fuel injection technique on the performance of an advanced reverse flow combustor liner constructed of Lamilloy (a multilaminate transpiration type material) was determined. Performance and emission levels are documented over a range of simulated flight conditions using simplex pressure atomizing, spill return, and splash cone airblast injectors. A parametric evaluation of the effect of increased combustor loading with each of the fuel injector types is obtained.

Small gas turbine combustor study: Fuel injector performance in a transpiration-cooled liner

NASA Technical Reports Server (NTRS)

Riddlebaugh, S. M.; Norgren, C. T.

1985-01-01

The effect of fuel injection technique on the performance of an advanced reverse flow combustor liner constructed of Lamilloy (a multilaminate transpiration type material) was determined. Performance and emission levels are documented over a range of simulated flight conditions using simplex pressure atomizing, spill return, and splash cone airblast injectors. A parametric evaluation of the effect of increased combustor loading with each of the fuel injector types is obtained.

Quasi-steady acoustic response of wall perforations subject to a grazing-bias flow combination

NASA Astrophysics Data System (ADS)

Tonon, D.; Moers, E. M. T.; Hirschberg, A.

2013-04-01

Well known examples of acoustical dampers are the aero-engine liners, the IC-engine exhaust mufflers, and the liners in combustion chambers. These devices comprise wall perforations, responsible for their sound absorbing features. Understanding the effect of the flow on the acoustic properties of a perforation is essential for the design of acoustic dampers. In the present work the effect of a grazing-bias flow combination on the impedance of slit shaped wall perforations is experimentally investigated by means of a multi-microphone impedance tube. Measurements are carried out for perforation geometries relevant for in technical applications. The focus of the experiments is on the low Strouhal number (quasi-steady) behavior. Analytical models of the steady flow and of the low frequency aeroacoustic behavior of a two-dimensional wall perforation are proposed for the case of a bias flow directed from the grazing flow towards the opposite side of the perforated wall. These theoretical results compare favorably with the experiments, when a semi-empirical correction is used to obtain the correct limit for pure bias flow.

On the use of multiple-point statistics to improve groundwater flow modeling in karst aquifers: A case study from the Hydrogeological Experimental Site of Poitiers, France

NASA Astrophysics Data System (ADS)

Le Coz, Mathieu; Bodin, Jacques; Renard, Philippe

2017-02-01

Limestone aquifers often exhibit complex groundwater flow behaviors resulting from depositional heterogeneities and post-lithification fracturing and karstification. In this study, multiple-point statistics (MPS) was applied to reproduce karst features and to improve groundwater flow modeling. For this purpose, MPS realizations were used in a numerical flow model to simulate the responses to pumping test experiments observed at the Hydrogeological Experimental Site of Poitiers, France. The main flow behaviors evident in the field data were simulated, particularly (i) the early-time inflection of the drawdown signal at certain observation wells and (ii) the convex behavior of the drawdown curves at intermediate times. In addition, it was shown that the spatial structure of the karst features at various scales is critical with regard to the propagation of the depletion wave induced by pumping. Indeed, (i) the spatial shape of the cone of depression is significantly affected by the karst proportion in the vicinity of the pumping well, and (ii) early-time inflection of the drawdown signal occurs only at observation wells crossing locally well-developed karst features.

A Numerical Study of the Effects of Curvature and Convergence on Dilution Jet Mixing

NASA Technical Reports Server (NTRS)

Holdeman, J. D.; Reynolds, R.; White, C.

1987-01-01

An analytical program was conducted to assemble and assess a three-dimensional turbulent viscous flow computer code capable of analyzing the flow field in the transition liners of small gas turbine engines. This code is of the TEACH type with hybrid numerics, and uses the power law and SIMPLER algorithms, an orthogonal curvilinear coordinate system, and an algebraic Reynolds stress turbulence model. The assessments performed in this study, consistent with results in the literature, showed that in its present form this code is capable of predicting trends and qualitative results. The assembled code was used to perform a numerical experiment to investigate the effects of curvature and convergence in the transition liner on the mixing of single and opposed rows of cool dilution jets injected into a hot mainstream flow.

A numerical study of the effects of curvature and convergence on dilution jet mixing

NASA Technical Reports Server (NTRS)

Holdeman, J. D.; Reynolds, R.; White, C.

1987-01-01

An analytical program was conducted to assemble and assess a three-dimensional turbulent viscous flow computer code capable of analyzing the flow field in the transition liners of small gas turbine engines. This code is of the TEACH type with hybrid numerics, and uses the power law and SIMPLER algorithms, an orthogonal curvilinear coordinate system, and an algebraic Reynolds stress turbulence model. The assessments performed in this study, consistent with results in the literature, showed that in its present form this code is capable of predicting trends and qualitative results. The assembled code was used to perform a numerical experiment to investigate the effects of curvature and convergence in the transition liner on the mixing of single and opposed rows of cool dilution jets injected into a hot mainstream flow.

Are healthcare workers' mobile phones a potential source of nosocomial infections? Review of the literature.

PubMed

Ulger, Fatma; Dilek, Ahmet; Esen, Saban; Sunbul, Mustafa; Leblebicioglu, Hakan

2015-10-29

Mobile communication devices help accelerate in-hospital flow of medical information, information sharing and querying, and contribute to communications in the event of emergencies through their application and access to wireless media technology. Healthcare-associated infections remain a leading and high-cost problem of global health systems despite improvements in modern therapies. The objective of this article was to review different studies on the relationship between mobile phones (MPs) and bacterial cross-contamination and report common findings. Thirty-nine studies published between 2005 and 2013 were reviewed. Of these, 19 (48.7%) identified coagulase-negative staphylococci (CoNS), and 26 (66.7%) identified Staphylococcus aureus; frequency of growth varied. The use of MPs by healthcare workers increases the risk of repetitive cyclic contamination between the hands and face (e.g., nose, ears, and lips), and differences in personal hygiene and behaviors can further contribute to the risks. MPs are rarely cleaned after handling. They may transmit microorganisms, including multiple resistant strains, after contact with patients, and can be a source of bacterial cross-contamination. To prevent bacterial contamination of MPs, hand-washing guidelines must be followed and technical standards for prevention strategies should be developed.

Characteristics of Artemether-Loaded Poly(lactic-co-glycolic) Acid Microparticles Fabricated by Coaxial Electrospray: Validation of Enhanced Encapsulation Efficiency and Bioavailability.

PubMed

Mangrio, Farhana Akbar; Dwivedi, Pankaj; Han, Shuya; Zhao, Gang; Gao, Dayong; Si, Ting; Xu, Ronald X

2017-12-04

Artemether is one of the most effective drugs for the treatment of chloroquine-resistant and Plasmodium falciparum strains of malaria. However, its therapeutic potency is hindered by its poor bioavailability. To overcome this limitation, we have encapsulated artemether in poly(lactic-co-glycolic) acid (PLGA) core-shell microparticles (MPs) using the coaxial electrospray method. With optimized process parameters including liquid flow rates and applied electric voltages, experiments are systematically carried out to generate a stable cone-jet mode to produce artemether-loaded PLGA-MPs with an average size of 2 μm, an encapsulation efficiency of 78 ± 5.6%, and a loading efficiency of 11.7%. The in vitro release study demonstrates the sustained release of artemether from the core-shell structure in comparison with that of plain artemether and that of MPs produced by single-axial electrospray without any relevant cytotoxicity. The in vivo studies are performed to evaluate the pharmacokinetic characteristics of the artemether-loaded PLGA-MPs. Our study implies that artemether can be effectively encapsulated in a protective shell of PLGA for controlled release kinetics and enhanced oral bioavailability.

CD142+/CD61+, CD146+ and CD45+ microparticles predict cardiovascular events in high risk patients following a Mediterranean diet supplemented with nuts.

PubMed

Chiva-Blanch, Gemma; Crespo, Javier; Suades, Rosa; Arderiu, Gemma; Padro, Teresa; Vilahur, Gemma; Cubedo, Judith; Corella, Dolores; Salas-Salvadó, Jordi; Arós, Fernando; Martínez-González, Miguel-Angel; Ros, Emilio; Fitó, Montse; Estruch, Ramon; Badimon, Lina

2016-07-04

Circulating microparticles (cMPs) are small phospholipid-rich microvesicles shed by activated cells that play a pivotal role in cell signalling related to the pathogenesis of atherothrombosis. We aimed to investigate the prognostic value of cMPs released from different vascular cells for cardiovascular event (CVE) presentation in asymptomatic patients at high cardiovascular risk factors under nutritional and pharmacologic treatment. This is a nested case-control study of 50 patients from the five-year follow-up prospective PREDIMED trial enrolled in the nuts arm of the Mediterranean diet (MedDiet-nuts). We randomly selected 25 patients who had suffered a CVE during follow-up and pair-matched them for sex, age, and classical CV risk factors to 25 patients who remained asymptomatic (no-CVE). Total Annexin V-(AV)+ cMPs and cMPs from cells of the vascular compartment were quantified by flow cytometry at baseline and after one year follow-up. MedDiet-nuts and pharmacological treatment neither modified levels nor source of MP shedding in CVE patients. However, no-CVE patients showed 40-86 % decreased total AV+, PAC-1+/AV+, CD61+/AV+, CD142+/CD61+/AV+, CD62P+/AV+, CD146+/AV+, CD63+/AV+ and CD11a+/AV+ cMPs at one year follow-up (p≤0.046, all). CD142+/CD61+/AV+, CD146+/AV+ and CD45+/AV+ cMPs were decreased in no-CVE patients compared to CVE patients. A ROC-curve clustered model for CD142+/CD61+/AV+, CD45+/AV+ and CD146+/AV+ cMPs predicted a future CVE [p<0.0001, AUC=0.805 (0.672 to 0.938)]. In patients at high CV risk profile treated with a controlled MedDiet supplemented with nuts and receiving up-to-date CV drug treatment, reduced cMPs derived from activated platelets, leukocytes and endothelial cells are predictive of protection against CVE within the next four years.

On the concept of virtual current as a means to enhance verification of electromagnetic flowmeters

NASA Astrophysics Data System (ADS)

Baker, Roger C.

2011-10-01

Electromagnetic flowmeters are becoming increasingly widely used in the water industry and other industries which handle electrically conducting liquids. When installed they are often difficult to remove for calibration without disturbing the liquid flow. Interest has therefore increased in the possibility of in situ calibration. The result has been the development of verification which attempts to approach calibration. However, while it checks on magnetic field and amplification circuits, it does not check adequately on the internals of the flowmeter pipe. This paper considers the use of the virtual voltage, a key element of the weight function theory of the flowmeter, to identify changes which have occurred in the flow tube and its liner. These could include a deformed insulating liner to the flow tube, or a deposit in the tube resulting from solids in the flow. The equation for virtual voltage is solved using a finite difference approach and the results are checked using a tank to simulate the flow tube, and tests on a flow rig. The concept is shown to be promising as a means of approaching verification of calibration.

Decrease in oral bioavailability of ciclosporin by intravenous pulse of methylprednisolone succinate in rats.

PubMed

Konishi, Hiroki; Sumi, Masaki; Shibata, Nobuhito; Takada, Kanji; Minouchi, Tokuzo; Yamaji, Akira

2004-10-01

We examined the effects of high-dose methylprednisolone on the bioavailability of orally administered ciclosporin in rats. To emulate the clinical protocol of methylprednisolone pulse therapy, methylprednisolone sodium succinate (MPS), a prodrug of methylprednisolone, was intravenously administered as repeated doses (66.3 mg kg(-1)) for 3 days. The area under the blood ciclosporin concentration versus time curve after oral administration was significantly reduced by 60% by pulse treatment with MPS. Based on our previous finding that the total body clearance of ciclosporin was reduced by about 20% by the same methylprednisolone pulse protocol, the extent of reduction in the oral bioavailability of ciclosporin was estimated to be approximately 50%, indicating a drug interaction between high-dose methylprednisolone and orally administered ciclosporin, which affected the absorption process. In rats treated with MPS, an in-situ efflux experiment using rhodamine-123 demonstrated that the reverse transport function of P-glycoprotein (P-gp) in the small intestine was significantly enhanced, although there was no significant increase in the intestinal microsomal activity of triazolam alpha- and 4-hydroxylation, metabolic probes for CYP3A. In addition, a significant decrease was observed in the amount of secreted bile acids serving as an enhancer of gastrointestinal absorption of ciclosporin in MPS treatment. To directly estimate the absorptive capacity, an in-situ absorption test was conducted using a closed-loop of small intestine in control and MPS-treated rats. Intestinal absorption of ciclosporin was significantly decreased, not only in the absence of bile flow but also by treatment with MPS, which well reflected the change in the in-vivo pharmacokinetic behaviour of ciclosporin after methylprednisolone pulsing. These results demonstrate that bioavailability of ciclosporin is markedly reduced by MPS pulse treatment, and the mechanism of this interaction was confirmed to involve enhancement of small-intestinal P-gp function and decrease in bile secretion.

Report on Recent Upgrades to the Curved Duct Test Rig at NASA Langley Research Center

NASA Technical Reports Server (NTRS)

Gerhold, Carl H.; Brown, Martha C.; Jones, Michael G.; Howerton, Brian M.

2011-01-01

The Curved Duct Test Rig (CDTR) is an experimental facility that is designed to assess the acoustic and aerodynamic performance of aircraft engine nacelle liners in close to full scale. The test section is between 25% and 100% of the scale of aft bypass ducts of aircraft engines ranging in size from business jet to large commercial passenger jet. The CDTR has been relocated and now shares space with the Grazing Flow Impedance Tube in the Liner Technology Facility at NASA Langley Research Center. As a result of the relocation, research air is supplied to the CDTR from a 50,000 cfm centrifugal fan. This new air supply enables testing of acoustic liner samples at up to Mach 0.500. This paper documents experiments and analysis on a baseline liner sample, which the authors had analyzed and reported on prior to the move to the new facility. In the present paper, the experimental results are compared to those obtained previously in order to ensure continuity of the experimental capability. Experiments that take advantage of the facility s expanded capabilities are also reported. Data analysis features that enhance understanding of the physical properties of liner performance are introduced. The liner attenuation is shown to depend on the mode that is incident on the liner test section. The relevant parameter is the mode cut-on ratio, which determines the angle at which the sound wave is incident on the liner surface. The scattering of energy from the incident mode into higher order, less attenuated modes is demonstrated. The configuration of the acoustic treatment, in this case lined on one surface and hard wall on the opposite surface, is shown to affect the mode energy redistribution.

Study of Plasma Liner Driven Magnetized Target Fusion Via Advanced Simulations

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

Samulyak, Roman V.; Brookhaven National Lab.; Parks, Paul

The feasibility of the plasma liner driven Magnetized Target Fusion (MTF) via terascale numerical simulations will be assessed. In the MTF concept, a plasma liner, formed by merging of a number (60 or more) of radial, highly supersonic plasma jets, implodes on the target in the form of two compact plasma toroids, and compresses it to conditions of the fusion ignition. By avoiding major difficulties associated with both the traditional laser driven inertial confinement fusion and solid liner driven MTF, the plasma liner driven MTF potentially provides a low-cost and fast R&D path towards the demonstration of practical fusion energy.more » High fidelity numerical simulations of full nonlinear models associated with the plasma liner MTF using state-of-art numerical algorithms and terascale computing are necessary in order to resolve uncertainties and provide guidance for future experiments. At Stony Brook University, we have developed unique computational capabilities that ideally suite the MTF problem. The FronTier code, developed in collaboration with BNL and LANL under DOE funding including SciDAC for the simulation of 3D multi-material hydro and MHD flows, has beenbenchmarked and used for fundamental and engineering problems in energy science applications. We have performed 3D simulations of converging supersonic plasma jets, their merger and the formation of the plasma liner, and a study of the corresponding oblique shock problem. We have studied the implosion of the plasma liner on the magnetized plasma target by resolving Rayleigh-Taylor instabilities in 2D and 3D and other relevant physics and estimate thermodynamic conditions of the target at the moment of maximum compression and the hydrodynamic efficiency of the method.« less

A theoretical assessment of microplastic transport in river catchments and their retention by soils and river sediments.

PubMed

Nizzetto, Luca; Bussi, Gianbattista; Futter, Martyn N; Butterfield, Dan; Whitehead, Paul G

2016-08-10

The presence of microplastics (MPs) in the environment is a problem of growing concern. While research has focused on MP occurrence and impacts in the marine environment, very little is known about their release on land, storage in soils and sediments and transport by run-off and rivers. This study describes a first theoretical assessment of these processes. A mathematical model of catchment hydrology, soil erosion and sediment budgets was upgraded to enable description of MP fate. The Thames River in the UK was used as a case study. A general lack of data on MP emissions to soils and rivers and the mass of MPs in agricultural soils, limits the present work to serve as a purely theoretical, nevertheless rigorous, assessment that can be used to guide future monitoring and impact evaluations. The fundamental assumption on which modelling is based is that the same physical controls on soil erosion and natural sediment transport (for which model calibration and validation are possible), also control MP transport and storage. Depending on sub-catchment soil characteristics and precipitation patterns, approximately 16-38% of the heavier-than-water MPs hypothetically added to soils (e.g. through routine applications of sewage sludge) are predicted to be stored locally. In the stream, MPs < 0.2 mm are generally not retained, regardless of their density. Larger MPs with densities marginally higher than water can instead be retained in the sediment. It is, however, anticipated that high flow periods can remobilize this pool. Sediments of river sections experiencing low stream power are likely hotspots for deposition of MPs. Exposure and impact assessments should prioritize these environments.

Clinical Significance of Tissue Factor and CD13 Double-Positive Microparticles in Sirs Patients with Trauma and Severe Sepsis.

PubMed

Matsumoto, Hisatake; Yamakawa, Kazuma; Ogura, Hiroshi; Koh, Taichin; Matsumoto, Naoya; Shimazu, Takeshi

2017-04-01

Activated immune cells such as monocytes are key factors in systemic inflammatory response syndrome (SIRS) following trauma and sepsis. Activated monocytes induce almost all tissue factor (TF) expression contributing to inflammation and coagulation. TF and CD13 double-positive microparticles (TF/CD13MPs) are predominantly released from these activated monocytes. This study aimed to evaluate TF/CD13MPs and assess their usefulness as a biomarker of pathogenesis in early SIRS following trauma and sepsis. This prospective study comprising 24 trauma patients, 25 severe sepsis patients, and 23 healthy controls was conducted from November 2012 to February 2015. Blood samples were collected from patients within 24 h after injury and diagnosis of severe sepsis and from healthy controls. Numbers of TF/CD13MPs were measured by flow cytometry immediately thereafter. Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were calculated at patient enrollment. APACHE II and SOFA scores and International Society of Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) diagnostic criteria algorithm were calculated at the time of enrollment of severe sepsis patients. Numbers of TF/CD13MPs were significantly increased in both trauma and severe sepsis patients versus controls and correlated significantly with ISS and APACHE II score in trauma patients and with APACHE II and ISTH DIC scores in severe sepsis patients. Increased numbers of TF/CD13MPs correlated significantly with severities in the acute phase in trauma and severe sepsis patients, suggesting that TF/CD13MPs are important in the pathogenesis of early SIRS following trauma and sepsis.

Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

PubMed

Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

2014-03-01

Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

Evaluation of Wall Boundary Conditions for Impedance Eduction Using a Dual-Source Method

NASA Technical Reports Server (NTRS)

Watson, W. R.; Jones, M. G.

2012-01-01

The accuracy of the Ingard-Myers boundary condition and a recently proposed modified Ingard-Myers boundary condition is evaluated for use in impedance eduction under the assumption of uniform mean flow. The evaluation is performed at three centerline Mach numbers, using data acquired in a grazing flow impedance tube, using both upstream and downstream propagating sound sources, and on a database of test liners for which the expected behavior of the impedance spectra is known. The test liners are a hard-wall insert consisting of 12.6 mm thick aluminum, a linear liner without a facesheet consisting of a number of small diameter but long cylindrical channels embedded in a ceramic material, and two conventional nonlinear liners consisting of a perforated facesheet bonded to a honeycomb core. The study is restricted to a frequency range for which only plane waves are cut on in the hard-wall sections of the flow impedance tube. The metrics used to evaluate each boundary condition are 1) how well it educes the same impedance for upstream and downstream propagating sources, and 2) how well it predicts the expected behavior of the impedance spectra over the Mach number range. The primary conclusions of the study are that the same impedance is educed for upstream and downstream propagating sources except at the highest Mach number, that an effective impedance based on both the upstream and downstream measurements is more accurate than an impedance based on the upstream or downstream data alone, and that the Ingard-Myers boundary condition with an effective impedance produces results similar to that achieved with the modified Ingard-Myers boundary condition.

Innovative Liner Concepts: Experiments and Impedance Modeling of Liners Including the Effect of Bias Flow

NASA Technical Reports Server (NTRS)

Kelly, Jeff; Betts, Juan Fernando; Fuller, Chris

2000-01-01

The study of normal impedance of perforated plate acoustic liners including the effect of bias flow was studied. Two impedance models were developed by modeling the internal flows of perforate orifices as infinite tubes with the inclusion of end corrections to handle finite length effects. These models assumed incompressible and compressible flows, respectively, between the far field and the perforate orifice. The incompressible model was used to predict impedance results for perforated plates with percent open areas ranging from 5% to 15%. The predicted resistance results showed better agreement with experiments for the higher percent open area samples. The agreement also tended to deteriorate as bias flow was increased. For perforated plates with percent open areas ranging from 1% to 5%, the compressible model was used to predict impedance results. The model predictions were closer to the experimental resistance results for the 2% to 3% open area samples. The predictions tended to deteriorate as bias flow was increased. The reactance results were well predicted by the models for the higher percent open area, but deteriorated as the percent open area was lowered (5%) and bias flow was increased. A fit was done on the incompressible model to the experimental database. The fit was performed using an optimization routine that found the optimal set of multiplication coefficients to the non-dimensional groups that minimized the least squares slope error between predictions and experiments. The result of the fit indicated that terms not associated with bias flow required a greater degree of correction than the terms associated with the bias flow. This model improved agreement with experiments by nearly 15% for the low percent open area (5%) samples when compared to the unfitted model. The fitted model and the unfitted model performed equally well for the higher percent open area (10% and 15%).

Acoustic theory of axisymmetric multisectioned ducts. [reduction of turbofan engine noise

NASA Technical Reports Server (NTRS)

Zorumski, W. E.

1974-01-01

Equations are developed for the acoustic field in a duct system which is made up of a number of connected circular and annular ducts. These equations are suitable for finding the acoustic field inside of and radiated from an aircraft turbofan engine. Acoustic modes are used as generalized coordinates in order to develop a set of matrix equations for the acoustic field. Equations for these modes are given for circular and annular ducts with uniform flow. Modal source equations are derived for point acoustic sources. General equations for mode transmission and reflection are developed and detailed equations are derived for ducts with multiple sections of acoustic treatment and for ducts with circumferential splitter rings. The general theory is applied to the special case of a uniform area circular duct with multisection liners and it is shown that the mode reflection effects are proportional to differences of the acoustic admittances of adjacent liners. A numerical example is given which shows that multisection liners may provide greater noise suppression than uniform liners.

Evolution of helical perturbations in a thin-shell model of an imploding liner

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

Ryutov, D. D.; Dorf, M. A.

A thin-shell model of the liner stability has been revisited and applied to the stability of the helical perturbations. Several stages of the implosion have been identified, starting from a long initial “latent” phase of an almost resting liner, continuing to the second stage of a rapid contraction and significant perturbation growth, and then transitioning to the third stage where perturbations become ballistic and highly non-linear. The stage of stagnation and rebound is beyond the scope of this paper. An importance of vorticity conservation during the late stages is emphasized. Nonlinear evolution of perturbations is followed up to the pointmore » of the formation of cusp structures. Effects of in-surface flows and of their enhancement due to the vorticity conservation are discussed. It is shown that the pre-machined perturbations created only on the outer surface of the liner grow much slower than one could anticipate. The limitations on the thin-shell description are discussed.« less

Comparison of the sampling rates and partitioning behaviour of polar and non-polar contaminants in the polar organic chemical integrative sampler and a monophasic mixed polymer sampler for application as an equilibrium passive sampler.

PubMed

Jeong, Yoonah; Schäffer, Andreas; Smith, Kilian

2018-06-15

In this work, Oasis HLB® beads were embedded in a silicone matrix to make a single phase passive sampler with a higher affinity for polar and ionisable compounds than silicone alone. The applicability of this mixed polymer sampler (MPS) was investigated for 34 aquatic contaminants (log K OW -0.03 to 6.26) in batch experiments. The influence of flow was investigated by comparing uptake under static and stirred conditions. The sampler characteristics of the MPS was assessed in terms of sampling rates (R S ) and sampler-water partition coefficients (K SW ), and these were compared to those of the polar organic chemical integrative sampler (POCIS) as a reference kinetic passive sampler. The MPS was characterized as an equilibrium sampler for both polar and non-polar compounds, with faster uptake rates and a shorter time to reach equilibrium than the POCIS. Water flow rate impacted sampling rates by up to a factor of 12 when comparing static and stirred conditions. In addition, the relative accumulation of compounds in the polyethersulfone (PES) membranes versus the inner Oasis HLB sorbent was compared for the POCIS, and ranged from <1% to 83% depending on the analyte properties. This is indicative of a potentially significant lag-phase for less polar compounds within POCIS. The findings of this study can be used to quantitatively describe the partitioning and kinetic behaviour of MPS and POCIS for a range of aquatic organic contaminants for application in field sampling. Copyright © 2018 Elsevier B.V. All rights reserved.

How to quantify microparticles in RBCs? A validated flow cytometry method allows the detection of an increase in microparticles during storage.

PubMed

Gamonet, Clémentine; Mourey, Guillaume; Aupet, Sophie; Biichle, Sabéha; Petitjean, Régis; Vidal, Chrystelle; Pugin, Aurore; Naegelen, Christian; Tiberghien, Pierre; Morel, Pascal; Angelot-Delettre, Fanny; Seilles, Estelle; Saas, Philippe; Bardiaux, Laurent; Garnache-Ottou, Francine

2017-03-01

The procoagulant and proinflammatory microparticles (MPs) released during storage of packed red blood cells (pRBCs) can potentially modify transfusion benefits. A robust method to quantify MPs in pRBCs is needed to evaluate their impact in clinical trials. The objective was to validate the preanalytic conditions required to prepare pRBC supernatant as well as a method to quantify and evaluate MP variations over 42 days of pRBC storage.A flow cytometry method with size-calibrated beads was developed and fully validated. Quantification of MPs in pRBCs (n = 109) was assessed during short-term (7 days) and long-term (42 days) storage at 4°C, during short-term storage (8 hours) at room temperature, and after 2 years frozen. Repeatability, reproducibility, and linearity of the quantification method were validated, and variations during conservation are presented. There was high variability in RBC (erythrocyte) MP (ERMP) and platelet MP (PMP) levels between RBC units, depending on the filter used for leukocyte reduction. During the 42 days of storage at 4°C, significant increases in ERMPs and PMPs occurred (from 58 to 138 ERMPs/µL from Day 2 to Day 42; p = 0.0002; and from 326 to 771 PMPs/µL from Day 2 to Day 42; p = 0.00026). We use a robust method to confirm that ERMPs and PMPs are present to various degrees in pRBCs and that storage for 42 days significantly increases their generation. This method is robust enough to allow MP quantification in pRBCs and is adapted to evaluate the clinical impact of transfused MPs in prospective clinical trials. © 2017 AABB.

Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise

PubMed Central

Gundermann, David M.; Fry, Christopher S.; Dickinson, Jared M.; Walker, Dillon K.; Timmerman, Kyle L.; Drummond, Micah J.; Volpi, Elena

2012-01-01

Blood flow restriction (BFR) to contracting skeletal muscle during low-intensity resistance exercise training increases muscle strength and size in humans. However, the mechanism(s) underlying these effects are largely unknown. We have previously shown that mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis (MPS) are stimulated following an acute bout of BFR exercise. The purpose of this study was to test the hypothesis that reactive hyperemia is the mechanism responsible for stimulating mTORC1 signaling and MPS following BFR exercise. Six young men (24 ± 2 yr) were used in a randomized crossover study consisting of two exercise trials: low-intensity resistance exercise with BFR (BFR trial) and low-intensity resistance exercise with sodium nitroprusside (SNP), a pharmacological vasodilator infusion into the femoral artery immediately after exercise to simulate the reactive hyperemia response after BFR exercise (SNP trial). Postexercise mixed-muscle fractional synthetic rate from the vastus lateralis increased by 49% in the BFR trial (P < 0.05) with no change in the SNP trial (P > 0.05). BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2, and Mnk1-interacting kinase 1 (P < 0.05) with no changes in mTORC1 signaling in the SNP trial (P > 0.05). We conclude that reactive hyperemia is not a primary mechanism for BFR exercise-induced mTORC1 signaling and MPS. Further research is necessary to elucidate the cellular mechanism(s) responsible for the increase in mTOR signaling, MPS, and hypertrophy following acute and chronic BFR exercise. PMID:22362401

Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise.

PubMed

Gundermann, David M; Fry, Christopher S; Dickinson, Jared M; Walker, Dillon K; Timmerman, Kyle L; Drummond, Micah J; Volpi, Elena; Rasmussen, Blake B

2012-05-01

Blood flow restriction (BFR) to contracting skeletal muscle during low-intensity resistance exercise training increases muscle strength and size in humans. However, the mechanism(s) underlying these effects are largely unknown. We have previously shown that mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis (MPS) are stimulated following an acute bout of BFR exercise. The purpose of this study was to test the hypothesis that reactive hyperemia is the mechanism responsible for stimulating mTORC1 signaling and MPS following BFR exercise. Six young men (24 ± 2 yr) were used in a randomized crossover study consisting of two exercise trials: low-intensity resistance exercise with BFR (BFR trial) and low-intensity resistance exercise with sodium nitroprusside (SNP), a pharmacological vasodilator infusion into the femoral artery immediately after exercise to simulate the reactive hyperemia response after BFR exercise (SNP trial). Postexercise mixed-muscle fractional synthetic rate from the vastus lateralis increased by 49% in the BFR trial (P < 0.05) with no change in the SNP trial (P > 0.05). BFR exercise increased the phosphorylation of mTOR, S6 kinase 1, ribosomal protein S6, ERK1/2, and Mnk1-interacting kinase 1 (P < 0.05) with no changes in mTORC1 signaling in the SNP trial (P > 0.05). We conclude that reactive hyperemia is not a primary mechanism for BFR exercise-induced mTORC1 signaling and MPS. Further research is necessary to elucidate the cellular mechanism(s) responsible for the increase in mTOR signaling, MPS, and hypertrophy following acute and chronic BFR exercise.

A novel broadband impedance method for detection of cell-derived microparticles

PubMed Central

Lvovich, Vadim; Srikanthan, Sowmya; Silverstein, Roy L.

2010-01-01

A novel label-free method is presented to detect and quantify cell-derived microparticles (MPs) by the electrochemical potential-modulated electrochemical impedance spectroscopy (EIS). MPs are present in elevated concentrations during pathological conditions and play a major role in the establishment and pathogenesis of many diseases. Considering this, accurate detection and quantification of MPs is very important in clinical diagnostics and therapeutics. A combination of bulk solution electrokinetic sorting and interfacial impedance responses allows achieving detection limits as low as several MPs per µL. By fitting resulting EIS spectra with an equivalent electrical circuit, the bulk solution electrokinetic and interfacial impedance responses were characterized. In the bulk solution two major relaxations were prominent - β-relaxation in low MHz region due to the MP capacitive membrane bridging, and α-relaxation at ∼ 10 kHz due to counter ions diffusion. At low frequencies (10-0.1 Hz) at electrochemical potentials exceeding −100 mV, a facile interfacial Faradaic process of oxidation in MPs coupled with diffusion and non Faradaic double layer charging dominate, probably due to oxidation of phospholipids and/or proteins on the MP surface and MP lysis. Buffer influence on the MP detection demonstrated that that a relatively low conductivity Tyrode’s buffer background solution is preferential for the MP electrokinetic separation and characterization. This study also demonstrated that standard laboratory methods such as flow cytometry underestimate MP concentrations, especially those with smaller average sizes, by as much as a factor of 2 to 40. PMID:20729061

A Comparison of Signal Enhancement Methods for Extracting Tonal Acoustic Signals

NASA Technical Reports Server (NTRS)

Jones, Michael G.

1998-01-01

The measurement of pure tone acoustic pressure signals in the presence of masking noise, often generated by mean flow, is a continual problem in the field of passive liner duct acoustics research. In support of the Advanced Subsonic Technology Noise Reduction Program, methods were investigated for conducting measurements of advanced duct liner concepts in harsh, aeroacoustic environments. This report presents the results of a comparison study of three signal extraction methods for acquiring quality acoustic pressure measurements in the presence of broadband noise (used to simulate the effects of mean flow). The performance of each method was compared to a baseline measurement of a pure tone acoustic pressure 3 dB above a uniform, broadband noise background.

Advanced Turbofan Duct Liner Concepts

NASA Technical Reports Server (NTRS)

Bielak, Gerald W.; Premo, John W.; Hersh, Alan S.

1999-01-01

The Advanced Subsonic Technology Noise Reduction Program goal is to reduce aircraft noise by 10 EPNdB by the year 2000 relative, to 1992 technology. The improvement goal for nacelle attenuation is 25% relative to 1992 technology by 1997 and 50% by 2000. The Advanced Turbofan Duct Liner Concepts Task work by Boeing presented in this document was in support of these goals. The basis for the technical approach was a Boeing study conducted in 1993-94 under NASA/FAA contract NAS1-19349, Task 6, investigating broadband acoustic liner concepts. As a result of this work, it was recommended that linear double layer, linear and perforate triple layer, parallel element, and bulk absorber liners be further investigated to improve nacelle attenuations. NASA LaRC also suggested that "adaptive" liner concepts that would allow "in-situ" acoustic impedance control also be considered. As a result, bias flow and high-temperature liner concepts were also added to the investigation. The major conclusion from the above studies is that improvements in nacelle liner average acoustic impedance characteristics alone will not result in 25% increased nacelle noise reduction relative to 1992 technology. Nacelle design advancements currently being developed by Boeing are expected to add 20-40% more acoustic lining to hardwall regions in current inlets, which is predicted to result in and additional 40-80% attenuation improvement. Similar advancements are expected to allow 10-30% more acoustic lining in current fan ducts with 10-30% more attenuation expected. In addition, Boeing is currently developing a scarf inlet concept which is expected to give an additional 40-80% attenuation improvement for equivalent lining areas.

The Role of Structural Dynamics and Testing in the Shuttle Flowliner Crack Investigation

NASA Technical Reports Server (NTRS)

Frady, Gregory P.

2005-01-01

During a normal inspection of the main propulsion system at Kennedy Space Center, small cracks were noticed near a slotted region of a gimbal joint flowliner located just upstream from one of the Space Shuttle Main Engines (SSME). These small cracks sparked an investigation of the entire Space Shuttle fleet main propulsion feedlines. The investigation was initiated to determine the cause of the small cracks and a repair method that would be needed to return the Shuttle fleet back to operation safely. The cracks were found to be initiated by structural resonance caused by flow fluctuations from the SSME low pressure fuel turbopump interacting with the flowliner. The pump induced backward traveling wakes that excited the liner and duct acoustics which also caused the liner to vibrate in complex mode shapes. The investigation involved an extensive effort by a team of engineers from the NASA civil servant and contractor workforce with the goal to characterize the root cause of the cracking behavior of the fuel side gimbal joint flowliners. In addition to working to identify the root cause, a parallel path was taken to characterize the material properties and fatigue capabilities of the liner material such that the life of the liners could be ascertained. As the characterization of the material and the most probable cause matured, the combination of the two with pump speed restrictions provided a means to return the Shuttle to flight in a safe manner. This paper traces the flowliner investigation results with respect to the structural dynamics analysis, component level testing and hot-fire flow testing on a static testbed. The paper will address the unique aspects of a very complex problem involving backflow from a high performance pump that has never been characterized nor understood to such detail. In addition, the paper will briefly address the flow phenomena that excited the liners, the unique structural dynamic modal characteristics and the variability of SSME operation which has ultimately ensured the safe and reliable operation of the shuttle main engines for each flight.

Component testing of a ground based gas turbine steam cooled rich-burn primary zone combustor for emissions control of nitrogeneous fuels

NASA Technical Reports Server (NTRS)

Schultz, D. F.

1986-01-01

This effort summarizes the work performed on a steam cooled, rich-burn primary zone, variable geometry combustor designed for combustion of nitrogeneous fuels such as heavy oils or synthetic crude oils. The steam cooling was employed to determine its feasibility and assess its usefulness as part of a ground based gas turbine bottoming cycle. Variable combustor geometry was employed to demonstrate its ability to control primary and secondary zone equivalence ratios and overall pressure drop. Both concepts proved to be highly successful in achieving their desired objectives. The steam cooling reduced peak liner temperatures to less than 800 K. This low temperature offers the potential of both long life and reduced use of strategic materials for liner fabrication. These degrees of variable geometry were successfully employed to control air flow distribution within the combustor. A variable blade angle axial flow air swirler was used to control primary zone air flow, while the secondary and tertiary zone air flows were controlled by rotating bands which regulated air flow to the secondary zone quench holes and the dilutions holes respectively.

The Steady Flow Resistance of Perforated Sheet Materials in High Speed Grazing Flows

NASA Technical Reports Server (NTRS)

Syed, Asif A.; Yu, Jia; Kwan, H. W.; Chien, E.; Jones, Michael G. (Technical Monitor)

2002-01-01

A study was conducted to determine the effects of high speed grazing air flow on the acoustic resistance of perforated sheet materials used in the construction of acoustically absorptive liners placed in commercial aircraft engine nacelles. Since DC flow resistance of porous sheet materials is known to be a major component of the acoustic resistance of sound suppression liners, the DC flow resistance of a set of perforated face-sheets and linear 'wiremesh' face-sheets was measured in a flow duct apparatus (up to Mach 0.8). Samples were fabricated to cover typical variations in perforated face-sheet parameters, such as hole diameter, porosity and sheet thickness, as well as those due to different manufacturing processes. The DC flow resistance data from perforated sheets were found to correlate strongly with the grazing flow Mach number and the face-sheet porosity. The data also show correlation against the boundary layer displacement thickness to hole-diameter ratio. The increase in resistance with grazing flow for punched aluminum sheets is in good agreement with published results up to Mach 0.4, but is significantly larger than expected above Mach 0.4. Finally, the tests demonstrated that there is a significant increase in the resistance of linear 'wiremesh' type face-sheet materials.

Analysis of RBC-microparticles in stored whole blood bags - a promising marker to detect blood doping in sports?

PubMed

Voss, Sven Christian; Jaganjac, Morana; Al-Thani, Amna Mohamed; Grivel, Jean-Charles; Raynaud, Christophe Michel; Al-Jaber, Hind; Al-Menhali, Afnan Saleh; Merenkov, Zeyed Ahmad; Alsayrafi, Mohammed; Latiff, Aishah; Georgakopoulos, Costas

2017-11-01

Blood doping in sports is prohibited by the World Anti-Doping Agency (WADA). To find a possible biomarker for the detection of blood doping, we investigated the changes in blood stored in CPDA-1 blood bags of eight healthy subjects who donated one unit of blood. Aliquots were taken on days 0, 14, and 35. Platelet-free plasma was prepared and stored at -80°C until analysis on a flow cytometer dedicated for the analysis of microparticles (MPs). Changes in the number of red blood cell (RBC) -MPs were highly significant (p < 0.0001) with a mean of 219 (10^3/μL) on day 0 changing to 23 120 (10^3/μL) on day 14 and 29 310 (10^3/μL) on day 35. We conclude that RBC-MPs seem to be a promising biomarker for doping control but confirmation by a transfusion study is necessary. Copyright © 2017 John Wiley & Sons, Ltd.

High Dynamic Velocity Range Particle Image Velocimetry Using Multiple Pulse Separation Imaging

PubMed Central

Persoons, Tim; O’Donovan, Tadhg S.

2011-01-01

The dynamic velocity range of particle image velocimetry (PIV) is determined by the maximum and minimum resolvable particle displacement. Various techniques have extended the dynamic range, however flows with a wide velocity range (e.g., impinging jets) still challenge PIV algorithms. A new technique is presented to increase the dynamic velocity range by over an order of magnitude. The multiple pulse separation (MPS) technique (i) records series of double-frame exposures with different pulse separations, (ii) processes the fields using conventional multi-grid algorithms, and (iii) yields a composite velocity field with a locally optimized pulse separation. A robust criterion determines the local optimum pulse separation, accounting for correlation strength and measurement uncertainty. Validation experiments are performed in an impinging jet flow, using laser-Doppler velocimetry as reference measurement. The precision of mean flow and turbulence quantities is significantly improved compared to conventional PIV, due to the increase in dynamic range. In a wide range of applications, MPS PIV is a robust approach to increase the dynamic velocity range without restricting the vector evaluation methods. PMID:22346564

Alternative design of pipe sleeve for liquid removal mechanism in mortar slab layer

NASA Astrophysics Data System (ADS)

Nazri, W. M. H. Wan; Anting, N.; Lim, A. J. M. S.; Prasetijo, J.; Shahidan, S.; Din, M. F. Md; Anuar, M. A. Mohd

2017-11-01

Porosity is one of the mortar’s characteristics that can cause problems, especially in the room space that used high amount of water, such as bathrooms. Waterproofing is one of the technology that normally used to minimize this problem which is preventing deep penetration of liquid water or moisture into underlying concrete layers. However, without the proper mechanism to remove liquid water and moisture from mortar system, waterproofing layer tends to be damaged after a long period of time by the static formation of liquid water and moisture at mortar layer. Thus, a solution has been proposed to drain out water that penetrated into the mortar layer. This paper introduces a new solution using a Modified Pipe Sleeve (MPS) that installed at the mortar layer. The MPS has been designed considering the percentage surface area of the pipe sleeve that having contact with mortar layer (2%, 4%, 6%, 8% and 10%) with angle of holes of 60°. Infiltration test and flow rate test have been conducted to identify the effectiveness of the MPS in order to drain out liquid water or moisture from the mortar layer. In this study shows that, MPS surface area 10%, angled 60°, function effectively as a water removal compared to other design.

LCDRS FLOW FROM DOUBLE-LINED LANDFILLS AND SURFACE IMPOUNDMENTS. Project Summary (EPA/600/SR-93/070)

EPA Science Inventory

A study, sponsored by the U.S. Environmental Protection Agency (EPA), on measured flows from leakage detection, collection, and removal systems (LDCRSs) of 28 double-lined landfills and 8 double-lined surface impoundments indicated — all landfills with geomembrane top liners l...

Soot loading in a generic gas turbine combustor

NASA Technical Reports Server (NTRS)

Eckerle, W. A.; Rosfjord, T. J.

1987-01-01

Variation in soot loading along the centerline of a generic gas turbine combustor was experimentally investigated. The 12.7-cm dia burner consisted of six sheet-metal louvers. Soot loading along the burner length was quantified by acquiring measurements first at the exit of the full-length combustor and then at upstream stations by sequential removal of liner louvers to shorten the burner length. Alteration of the flow field approaching removed louvers, maintaining a constant liner pressure drop. Burner exhaust flow was sampled at the burner centerline to determine soot mass concentration and smoke number. Characteristic particle size and number density, transmissivity of the exhaust flow, and local radiation from luminous soot particles in the exhaust flow were determined by optical techniques. Four test fuels were burned at three fuel-air ratios to determine fuel chemical property and flow temperature influences. Data were acquired at two combustor pressures. Particulate concentration data indicated a strong oxidation mechanism in the combustor secondary zone, though the oxidation was significantly affected by flow temperature. Soot production was directly related to fuel smoke point. Less soot production and lower secondary-zone oxidation rates were observed at reduced combustor pressure.

An Experimental and Numerical Investigation of Endwall Aerodynamics and Heat Transfer in a Gas Turbine Nozzle Guide Vane with Slot Film Cooling

NASA Astrophysics Data System (ADS)

Alqefl, Mahmood Hasan

In many regions of the high-pressure gas turbine, film cooling flows are used to protect the turbine components from the combustor exit hot gases. Endwalls are challenging to cool because of the complex system of secondary flows that disturb surface film coolant coverage. The secondary flow vortices wash the film coolant from the surface into the mainstream significantly decreasing cooling effectiveness. In addition to being effected by secondary flow structures, film cooling flow can also affect these structures by virtue of their momentum exchange. In addition, many studies in the literature have shown that endwall contouring affects the strength of passage secondary flows. Therefore, to develop better endwall cooling schemes, a good understanding of passage aerodynamics and heat transfer as affected by interactions of film cooling flows with secondary flows is required. This experimental and computational study presents results from a linear, stationary, two-passage cascade representing the first stage nozzle guide vane of a high-pressure gas turbine with an axisymmetrically contoured endwall. The sources of film cooling flows are upstream combustor liner coolant and endwall slot film coolant injected immediately upstream of the cascade passage inlet. The operating conditions simulate combustor exit flow features, with a high Reynolds number of 390,000 and approach flow turbulence intensity of 11% with an integral length scale of 21% of the chord length. Measurements are performed with varying slot film cooling mass flow to mainstream flow rate ratios (MFR). Aerodynamic effects are documented with five-hole probe measurements at the exit plane. Heat transfer is documented through recovery temperature measurements with a thermocouple. General secondary flow features are observed. Total pressure loss measurements show that varying the slot film cooling MFR has some effects on passage loss. Velocity vectors and vorticity distributions show a very thin, yet intense, cross-pitch flow on the contoured endwall side. Endwall adiabatic effectiveness values and coolant distribution thermal fields show minimal effects of varying slot film coolant MFR. This suggests the dominant effects of combustor liner coolant. show dominant effects of combustor liner coolant on cooling the endwall. A coolant vorticity correlation presenting the advective mixing of the coolant due to secondary flow vorticity at the exit plane is also discussed.

Development of Experimental and Computational Aeroacoustic Tools for Advanced Liner Evaluation

NASA Technical Reports Server (NTRS)

Jones, Michael G.; Watson, Willie R.; Nark, Douglas N.; Parrott, Tony L.; Gerhold, Carl H.; Brown, Martha C.

2006-01-01

Acoustic liners in aircraft engine nacelles suppress radiated noise. Therefore, as air travel increases, increasingly sophisticated tools are needed to maximize noise suppression. During the last 30 years, NASA has invested significant effort in development of experimental and computational acoustic liner evaluation tools. The Curved Duct Test Rig is a 152-mm by 381- mm curved duct that supports liner evaluation at Mach numbers up to 0.3 and source SPLs up to 140 dB, in the presence of user-selected modes. The Grazing Flow Impedance Tube is a 51- mm by 63-mm duct currently being fabricated to operate at Mach numbers up to 0.6 with source SPLs up to at least 140 dB, and will replace the existing 51-mm by 51-mm duct. Together, these test rigs allow evaluation of advanced acoustic liners over a range of conditions representative of those observed in aircraft engine nacelles. Data acquired with these test ducts are processed using three aeroacoustic propagation codes. Two are based on finite element solutions to convected Helmholtz and linearized Euler equations. The third is based on a parabolic approximation to the convected Helmholtz equation. The current status of these computational tools and their associated usage with the Langley test rigs is provided.

Constraining the Accretion Mode in LINER 1.9s

NASA Astrophysics Data System (ADS)

Sabra, Bassem; Der Sahaguian, Elias; Badr, Elie

2016-01-01

The accretion mode and the dominant power source in low-ionization nuclear emission-line regions (LINERs), a class of active galactic nuclei (AGN), are still elusive. We focus on a sample of 22 LINER 1.9s (Ho et al. 1997), a subclass of LINERs that show broad Halpha lines, a signature of blackhole-powered accretion, to test the hypothesis that the ionizing continuum emitted by a radiatively inefficient accretion flow (RIAF) could lead to the LINER ultraviolet (UV) emission-line ratios. Optical line-ratio diagrams are a weak diagnostic tool in distinguishing between possible power sources (Sabra et al. 2003). We search the Mikulski Archive for Space Telescopes (MAST) for UV spectra of the objects in the above sample and also perform photoionization simulations using CLOUDY (Ferland et al. 2013). Unfortunately, only one object (NGC 1052; Gabel et al. 2000) of the 22 LINER 1.9s has UV spectra that cover many emission lines; the rest of the objects either do not have any UV spectra, the spectral coverage is in-adequate, or the spectra have very low signal-to-noise ratios. Our photoionization simulations set up two identical grids of clouds with a range of densities and ionization parameters. We illuminate one grid with radiation emitted by a thin accretion disk (AD) and we illuminate the other grid with radiation from a RIAF. We overplot the UV emission-line ratio predictions for AD and RIAF illumination, together with the available line ratios for NGC 1052. Initial results show that UV lines could be used as diagnostics for the accretion mode in AGN. More UV spectral coverage of LINER 1.9s is needed in order to more fully utilize the diagnostic powers of UV emission line ratios.

A novel broadband impedance method for detection of cell-derived microparticles.

PubMed

Lvovich, Vadim; Srikanthan, Sowmya; Silverstein, Roy L

2010-10-15

A novel label-free method is presented to detect and quantify cell-derived microparticles (MPs) by the electrochemical potential-modulated electrochemical impedance spectroscopy (EIS). MPs are present in elevated concentrations during pathological conditions and play a major role in the establishment and pathogenesis of many diseases. Considering this, accurate detection and quantification of MPs is very important in clinical diagnostics and therapeutics. A combination of bulk solution electrokinetic sorting and interfacial impedance responses allows achieving detection limits as low as several MPs per μL. By fitting resulting EIS spectra with an equivalent electrical circuit, the bulk solution electrokinetic and interfacial impedance responses were characterized. In the bulk solution two major relaxations were prominent-β-relaxation in low MHz region due to the MP capacitive membrane bridging, and α-relaxation at ∼10 kHz due to counter ions diffusion. At low frequencies (10-0.1 Hz) at electrochemical potentials exceeding -100 mV, a facile interfacial Faradaic process of oxidation in MPs coupled with diffusion and non-Faradaic double layer charging dominate, probably due to oxidation of phospholipids and/or proteins on the MP surface and MP lysis. Buffer influence on the MP detection demonstrated that a relatively low conductivity Tyrode's buffer background solution is preferential for the MP electrokinetic separation and characterization. This study also demonstrated that standard laboratory methods such as flow cytometry underestimate MP concentrations, especially those with smaller average sizes, by as much as a factor of 2-40. Copyright © 2010 Elsevier B.V. All rights reserved.

Microparticles shed from multidrug resistant breast cancer cells provide a parallel survival pathway through immune evasion.

PubMed

Jaiswal, Ritu; Johnson, Michael S; Pokharel, Deep; Krishnan, S Rajeev; Bebawy, Mary

2017-02-06

Breast cancer is the most frequently diagnosed cancer in women. Resident macrophages at distant sites provide a highly responsive and immunologically dynamic innate immune response against foreign infiltrates. Despite extensive characterization of the role of macrophages and other immune cells in malignant tissues, there is very little known about the mechanisms which facilitate metastatic breast cancer spread to distant sites of immunological integrity. The mechanisms by which a key healthy defense mechanism fails to protect distant sites from infiltration by metastatic cells in cancer patients remain undefined. Breast tumors, typical of many tumor types, shed membrane vesicles called microparticles (MPs), ranging in size from 0.1-1 μm in diameter. MPs serve as vectors in the intercellular transfer of functional proteins and nucleic acids and in drug sequestration. In addition, MPs are also emerging to be important players in the evasion of cancer cell immune surveillance. A comparative analysis of effects of MPs isolated from human breast cancer cells and non-malignant human brain endothelial cells were examined on THP-1 derived macrophages in vitro. MP-mediated effects on cell phenotype and functionality was assessed by cytokine analysis, cell chemotaxis and phagocytosis, immunolabelling, flow cytometry and confocal imaging. Student's t-test or a one-way analysis of variance (ANOVA) was used for comparison and statistical analysis. In this paper we report on the discovery of a new cellular basis for immune evasion, which is mediated by breast cancer derived MPs. MPs shed from multidrug resistant (MDR) cells were shown to selectively polarize macrophage cells to a functionally incapacitated state and facilitate their engulfment by foreign cells. We propose this mechanism may serve to physically disrupt the inherent immune response prior to cancer cell colonization whilst releasing mediators required for the recruitment of distant immune cells. These findings introduce a new paradigm in cancer cell biology with significant implications in understanding breast cancer colonization at distant sites. Most importantly, this is also the first demonstration that MPs serve as conduits in a parallel pathway supporting the cellular survival of MDR cancer cells through immune evasion.

High Thermal Conductivity NARloy-Z-Diamond Composite Combustion Chamber Liner For Advanced Rocket Engines

NASA Technical Reports Server (NTRS)

Bhat, Biliyar N.; Ellis, David; Singh, Jogender

2014-01-01

Advanced high thermal conductivity materials research conducted at NASA Marshall Space Flight Center (MSFC) with state of the art combustion chamber liner material NARloy-Z showed that its thermal conductivity can be increased significantly by adding diamond particles and sintering it at high temperatures. For instance, NARloy-Z containing 40 vol. percent diamond particles, sintered at 975C to full density by using the Field assisted Sintering Technology (FAST) showed 69 percent higher thermal conductivity than baseline NARloy-Z. Furthermore, NARloy-Z-40vol. percent D is 30 percent lighter than NARloy-Z and hence the density normalized thermal conductivity is 140 percent better. These attributes will improve the performance and life of the advanced rocket engines significantly. By one estimate, increased thermal conductivity will directly translate into increased turbopump power up to 2X and increased chamber pressure for improved thrust and ISP, resulting in an expected 20 percent improvement in engine performance. Follow on research is now being conducted to demonstrate the benefits of this high thermal conductivity NARloy-Z-D composite for combustion chamber liner applications in advanced rocket engines. The work consists of a) Optimizing the chemistry and heat treatment for NARloy-Z-D composite, b) Developing design properties (thermal and mechanical) for the optimized NARloy-Z-D, c) Fabrication of net shape subscale combustion chamber liner, and d) Hot fire testing of the liner for performance. FAST is used for consolidating and sintering NARlo-Z-D. The subscale cylindrical liner with built in channels for coolant flow is also fabricated near net shape using the FAST process. The liner will be assembled into a test rig and hot fire tested in the MSFC test facility to determine performance. This paper describes the development of this novel high thermal conductivity NARloy-Z-D composite material, and the advanced net shape technology to fabricate the combustion chamber liner. Properties of optimized NARloy-Z-D composite material will also be presented.

A Computational Study of the Flow Physics of Acoustic Liners

NASA Technical Reports Server (NTRS)

Tam, Christopher

2006-01-01

The present investigation is a continuation of a previous joint project between the Florida State University and the NASA Langley Research Center Liner Physics Team. In the previous project, a study of acoustic liners, in two dimensions, inside a normal incidence impedance tube was carried out. The study consisted of two parts. The NASA team was responsible for the experimental part of the project. This involved performing measurements in an impedance tube with a large aspect ratio slit resonator. The FSU team was responsible for the computation part of the project. This involved performing direct numerical simulation (DNS) of the NASA experiment in two dimensions using CAA methodology. It was agreed that upon completion of numerical simulation, the computed values of the liner impedance were to be sent to NASA for validation with experimental results. On following this procedure good agreements were found between numerical results and experimental measurements over a wide range of frequencies and sound-pressure-level. Broadband incident sound waves were also simulated numerically and measured experimentally. Overall, good agreements were also found.

Apparatus and method for sealing perforated well casing

DOEpatents

Blount, Curtis G.; Benham, Robert A.; Brock, Jerry L.; Emerson, John A.; Ferguson, Keith R.; Scheve, Donald F.; Schmidt, Joseph H.; Schuler, Karl W.; Stanton, Philip L.

1997-01-01

Perforations and other openings in well casings, liners and other conduits may be substantially blocked or sealed to prevent fluid flow between the casing or liner interior and an earth formation by placing a radially expansible sleeve adjacent the perforations or openings and urging the sleeve into forcible engagement with the casing or inner wall using an explosive charge. An apparatus including a radially contracted sleeve formed by a coiled plate member or a tubular member having flutes defined by external and internal folds, may be deployed into a well casing or liner through a production or injection tubing string and on the end of a flexible cable or coilable tubing. An explosive charge disposed on the apparatus and within the sleeve may be detonated to urge the sleeve into forcible engagement with the casing inner wall.

Apparatus and method for sealing perforated well casing

DOEpatents

Blount, C.G.; Benham, R.A.; Brock, J.L.; Emerson, J.A.; Ferguson, K.R.; Scheve, D.F.; Schmidt, J.H.; Schuler, K.W.; Stanton, P.L.

1997-03-25

Perforations and other openings in well casings, liners and other conduits may be substantially blocked or sealed to prevent fluid flow between the casing or liner interior and an earth formation by placing a radially expansible sleeve adjacent the perforations or openings and urging the sleeve into forcible engagement with the casing or inner wall using an explosive charge. An apparatus including a radially contracted sleeve formed by a coiled plate member or a tubular member having flutes defined by external and internal folds, may be deployed into a well casing or liner through a production or injection tubing string and on the end of a flexible cable or coilable tubing. An explosive charge disposed on the apparatus and within the sleeve may be detonated to urge the sleeve into forcible engagement with the casing inner wall. 17 figs.

75 FR 14634 - Dominion Nuclear Connecticut, Inc.; Millstone Power Station, Unit Nos. 1, 2, and 3; Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

... Power Station, Unit Nos. 1, 2, and 3 (MPS1, MPS2, and MPS3, respectively), located in New London County.... Environmental Assessment Identification of the Proposed Action The proposed action would exempt MPS1, MPS2, and... part 73. Specifically, MPS1, MPS2, and MPS3 would be granted an exemption from being in full compliance...

Serial cooling of a combustor for a gas turbine engine

DOEpatents

Abreu, Mario E.; Kielczyk, Janusz J.

2001-01-01

A combustor for a gas turbine engine uses compressed air to cool a combustor liner and uses at least a portion of the same compressed air for combustion air. A flow diverting mechanism regulates compressed air flow entering a combustion air plenum feeding combustion air to a plurality of fuel nozzles. The flow diverting mechanism adjusts combustion air according to engine loading.

An examination of the misuse of prescription stimulants among college students using the theory of planned behavior.

PubMed

Gallucci, Andrew; Martin, Ryan; Beaujean, Alex; Usdan, Stuart

2015-01-01

The misuse of prescription stimulants (MPS) is an emergent adverse health behavior among undergraduate college students. However, current research on MPS is largely atheoretical. The purpose of this study was to validate a survey to assess MPS-related theory of planned behavior (TPB) constructs (i.e. attitudes, subjective norms, and perceived behavioral control) and determine the relationship between these constructs, MPS-related risk factors (e.g. gender and class status), and current MPS (i.e. past 30 days use) among college students. Participants (N = 978, 67.8% female and 82.9% Caucasian) at a large public university in the southeastern USA completed a survey assessing MPS and MPS-related TPB constructs during fall 2010. To examine the relationship between MPS-related TPB constructs and current MPS, we conducted (1) confirmatory factor analyses to validate that our survey items assessed MPS-related TPB constructs and (2) a series of regression analyses to examine associations between MPS-related TPB constructs, potential MPS-related risk factors, and MPS in this sample. Our factor analyses indicated that the survey items assessed MPS-related TPB constructs and our multivariate logistic regression analysis indicated that perceived behavioral control was significantly associated with current MPS. In addition, analyses found that having a prescription stimulant was a protective factor against MPS when the model included MPS-related TPB variables.

Post-Closure Performance of liner Systems at RCRA Subtitle C Landfills

EPA Science Inventory

In general, field data showed a decline in leachate flow from the LCRS and LDS. In all cases, placement of cover led to a reduction in the LCRS flow rate, including where only 12 inches of intermediate cover soil had been placed. Rainfall has an effect on leachate generation, wit...

Aero-thermo-dynamic analysis of the Spaceliner-7.1 vehicle in high altitude flight

NASA Astrophysics Data System (ADS)

Zuppardi, Gennaro; Morsa, Luigi; Sippel, Martin; Schwanekamp, Tobias

2014-12-01

SpaceLiner, designed by DLR, is a visionary, extremely fast passenger transportation concept. It consists of two stages: a winged booster, a vehicle. After separation of the two stages, the booster makes a controlled re-entry and returns to the launch site. According to the current project, version 7-1 of SpaceLiner (SpaceLiner-7.1), the vehicle should be brought at an altitude of 75 km and then released, undertaking the descent path. In the perspective that the vehicle of SpaceLiner-7.1 could be brought to altitudes higher than 75 km, e.g. 100 km or above and also for a speculative purpose, in this paper the aerodynamic parameters of the SpaceLiner-7.1 vehicle are calculated in the whole transition regime, from continuum low density to free molecular flows. Computer simulations have been carried out by three codes: two DSMC codes, DS3V in the altitude interval 100-250 km for the evaluation of the global aerodynamic coefficients and DS2V at the altitude of 60 km for the evaluation of the heat flux and pressure distributions along the vehicle nose, and the DLR HOTSOSE code for the evaluation of the global aerodynamic coefficients in continuum, hypersonic flow at the altitude of 44.6 km. The effectiveness of the flaps with deflection angle of -35 deg. was evaluated in the above mentioned altitude interval. The vehicle showed longitudinal stability in the whole altitude interval even with no flap. The global bridging formulae verified to be proper for the evaluation of the aerodynamic coefficients in the altitude interval 80-100 km where the computations cannot be fulfilled either by CFD, because of the failure of the classical equations computing the transport coefficients, or by DSMC because of the requirement of very high computer resources both in terms of the core storage (a high number of simulated molecules is needed) and to the very long processing time.

Tolerance requirements to prevent fluid leakage in the crucible/plunger MEA experiment MPS 770030

NASA Technical Reports Server (NTRS)

Rathz, T. J.

1982-01-01

Molten Al-In leaked unexpectedly out of the crucible of a proposed MEA materials processing in space experiment. The molten metals use a spring loaded plunger to eliminate most free surfaces. The critical criteria necessary to initiate flow and the rate of fluid flow into the crucible/plunger annulus is calculated. Experimental in situ X-radiographs are interpreted according to the calculations. A note on possible effects of capillary flow if wetting occurs between crucible/plunger and liquids is included.

Development of Lightweight, Compact, Structurally-Integrated Acoustic Liners for Broadband Low-Frequency Noise Mitigation

NASA Astrophysics Data System (ADS)

Chambers, Andrew T.

Airborne noise with a low dominant frequency content (< 500 Hz) has detrimental effects in many applications, but is as yet beyond the scope of conventional acoustic noise mitigation techniques using liners, foams or claddings owing to mass and volume considerations. Its low evanescence contributes significantly to environmental noise pollution, and unwanted structural vibrations causing diminished efficiency, comfort, payload integrity and mission capabilities. An alternative approach using liner configurations with realistic mass and volume constraints having innovative 'folded' core geometries is investigated to ascertain its low-frequency noise absorption characteristics. In contrast to mass-driven approaches, the folded core approach relies on tailoring interactions between acoustic resonances to tune the liner's impedance to suit the dominant low-frequency content of the source. This allows to keep non-structural mass-addition to a minimum, while retaining an overall thickness comparable to conventional liners for these low-frequency liner designs. The relative acoustic performance of various candidate folded core designs is evaluated by means of a new composite metric termed the Low-Frequency Performance (LFP) factor, which is educed from the absorption coefficient spectrum obtained using Zwikker-Kosten Transmission Line (ZKTL) theory-based numerical studies. An LFP-based software tool is developed to determine optimal 3D cavity packing for a prescribed liner volume and target frequency range. ZKTL-based parametric studies on core dimensions and face sheet porosity are utilized for detailed design of test articles. Experimental verification of absorption coefficient spectra conducted using 3D printed test articles in a normal incidence acoustic impedance tube yield good correlation with simulations. More than 100 Hz of continuous bandwidth with an absorption coefficient greater than 0.6 is shown to be possible in the 300 to 400 Hz range with a 38.1-mm (1.5-inch) thick liner. Further, the influence of face sheet type, Mach number, and sound pressure level on the attenuation across folded core liners is evaluated using grazing flow impedance tube tests. Up to 20 dB of attenuation is observed in the targeted frequency range in these tests indicating potential for performance retention in an operational scenario. With current additive and hybrid manufacturing techniques attaining critical commercial maturity, lightweight and compact acoustic liners employing folded cores could provide a promising practical solution to mitigate low-frequency airborne noise, especially in aerospace applications.

Liquid-absorption preconcentrator sampling instrument

DOEpatents

Zaromb, Solomon

1990-01-01

A system for detecting trace concentrations of an analyte in air and includes a preconcentrator for the analyte and an analyte detector. The preconcentrator includes an elongated tubular container in which is disposed a wettable material extending substantially the entire length of the container. One end of the wettable material is continuously wetted with an analyte-sorbing liquid, which flows to the other end of the container. Sample air is flowed through the container in contact with the wetted material for trapping and preconcentrating the traces of analyte in the sorbing liquid, which is then collected at the other end of the container and discharged to the detector. The wetted material may be a wick comprising a bundle of fibers, one end of which is immersed in a reservoir of the analyte-sorbing liquid, or may be a liner disposed on the inner surface of the container, with the sorbing liquid being centrifugally dispersed onto the liner at one end thereof. The container is preferably vertically oriented so that gravity effects the liquid flow.

Liquid-absorption preconcentrator sampling instrument

DOEpatents

Zaromb, S.

1990-12-11

A system is described for detecting trace concentrations of an analyte in air and includes a preconcentrator for the analyte and an analyte detector. The preconcentrator includes an elongated tubular container in which is disposed a wettable material extending substantially the entire length of the container. One end of the wettable material is continuously wetted with an analyte-sorbing liquid, which flows to the other end of the container. Sample air is flowed through the container in contact with the wetted material for trapping and preconcentrating the traces of analyte in the sorbing liquid, which is then collected at the other end of the container and discharged to the detector. The wetted material may be a wick comprising a bundle of fibers, one end of which is immersed in a reservoir of the analyte-sorbing liquid, or may be a liner disposed on the inner surface of the container, with the sorbing liquid being centrifugally dispersed onto the liner at one end thereof. The container is preferably vertically oriented so that gravity effects the liquid flow. 4 figs.

Antizyme restrains centrosome amplification by regulating the accumulation of Mps1 at centrosomes.

PubMed

Kasbek, Christopher; Yang, Ching-Hui; Fisk, Harold A

2010-11-15

Extra centrosomes are found in many tumors, and their appearance is an early event that can generate aberrant mitotic spindles and aneuploidy. Because the failure to appropriately degrade the Mps1 protein kinase correlates with centrosome overproduction in tumor-derived cells, defects in the factors that promote Mps1 degradation may contribute to extra centrosomes in tumors. However, while we have recently characterized an Mps1 degradation signal, the factors that regulate Mps1 centrosomal Mps1 are unknown. Antizyme (OAZ), a mediator of ubiquitin-independent degradation and a suspected tumor suppressor, was recently shown to localize to centrosomes and modulate centrosome overproduction, but the known OAZ substrates were not responsible for its effect on centrosomes. We have found that OAZ exerts its effect on centrosomes via Mps1. OAZ promotes the removal of Mps1 from centrosomes, and centrosome overproduction caused by reducing OAZ activity requires Mps1. OAZ binds to Mps1 via the Mps1 degradation signal and modulates the function of Mps1 in centrosome overproduction. Moreover, OAZ regulates the canonical centrosome duplication cycle, and reveals a function for Mps1 in procentriole assembly. Together, our data suggest that OAZ restrains the assembly of centrioles by controlling the levels of centrosomal Mps1 through the Cdk2-regulated Mps1 degradation signal.

Techniques for enhancing durability and equivalence ratio control in a rich-lean, three-stage ground power gas turbine combustor

NASA Technical Reports Server (NTRS)

Schultz, D. F.

1982-01-01

Rig tests of a can-type combustor were performed to demonstrate two advanced ground power engine combustor concepts: steam cooled rich-burn combustor primary zones for enhanced durability; and variable combustor geometry for three stage combustion equivalence ratio control. Both concepts proved to be highly successful in achieving their desired objectives. The steam cooling reduced peak liner temperatures to less than 800 K. This offers the potential of both long life and reduced use of strategic materials for liner fabrication. Three degrees of variable geometry were successfully implemented to control airflow distribution within the combustor. One was a variable blade angle axial flow air swirler to control primary airflow while the other two consisted of rotating bands to control secondary and tertiary or dilution air flow.

Liners for ion transport membrane systems

DOEpatents

Carolan, Michael Francis; Miller, Christopher Francis

2010-08-10

Ion transport membrane system comprising (a) a pressure vessel comprising an interior, an exterior, an inlet, an inlet conduit, an outlet, and an outlet conduit; (b) a plurality of planar ion transport membrane modules disposed in the interior of the pressure vessel and arranged in series, each membrane module comprising mixed metal oxide ceramic material and having an interior region and an exterior region, wherein the inlet and the outlet of the pressure vessel are in flow communication with exterior regions of the membrane modules; (c) a gas manifold having an interior surface wherein the gas manifold is in flow communication with the interior region of each of the planar ion transport membrane modules and with the exterior of the pressure vessel; and (d) a liner disposed within any of the inlet conduit, the outlet conduit, and the interior surface of the gas manifold.

Anti-fatigue activity of polysaccharide fractions from Lepidium meyenii Walp. (maca).

PubMed

Li, Jing; Sun, Qingrui; Meng, Qingran; Wang, Lei; Xiong, Wentao; Zhang, Lianfu

2017-02-01

The two fractions of polysaccharide MPS-1 and MPS-2 were extracted from Lepidium meyenii Walp. (maca) by water, and purified using a DEAE-52 and a Sephadex G-100 column. The molecular weight (M W ) of MPS-1 was 7.6kDa, and the M W of MPS-2 was 6.7kDa. The MPS-1 was composed of xylose, arabinose, galactose and glucose, with the mole ratio 1:1.7:3.3:30.5; the MPS-2 was composed of arabinose, galactose and glucose, with the mole ratio 1:1.3:36.8. The IR spectrum implied that only α-pyranose existed in MPS-1, and both α-pyranose and β-pyranose existed in MPS-2. The anti-fatigue activities of MPS-1 and MPS-2 were measured by the forced swimming test, along with the determination of blood lactate (BLA), urea nitrogen (BUN), lactic dehydrogenase (LDH) activity and liver glycogen (LG). The results indicated that both MPS-1 and MPS-2 presented dose-dependently positive effects on the fatigue related parameters. Additionally, MPS-2 has a better anti-fatigue effect than MPS-1. Copyright © 2016 Elsevier B.V. All rights reserved.

Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells.

PubMed

Bebawy, M; Combes, V; Lee, E; Jaiswal, R; Gong, J; Bonhoure, A; Grau, G E R

2009-09-01

Multidrug resistance (MDR), a significant impediment to the successful treatment of cancer clinically, has been attributed to the overexpression of P-glycoprotein (P-gp), a plasma membrane multidrug efflux transporter. P-gp maintains sublethal intracellular drug concentrations by virtue of its drug efflux capacity. The cellular regulation of P-gp expression is currently known to occur at either pre- or post-transcriptional levels. In this study, we identify a 'non-genetic' mechanism whereby microparticles (MPs) serve as vectors in the acquisition and spread of MDR. MPs isolated from drug-resistant cancer cells (VLB(100)) were co-cultured with drug sensitive cells (CCRF-CEM) over a 4 h period to allow for MP binding and P-gp transfer. Presence of P-gp on MPs was established using flow cytometry (FCM) and western blotting. Whole-cell drug accumulation assays using rhodamine 123 and daunorubicin (DNR) were carried out to validate the transfer of functional P-gp after co-culture. We establish that MPs shed in vitro from drug-resistant cancer cells incorporate cell surface P-gp from their donor cells, effectively bind to drug-sensitive recipient cells and transfer functional P-gp to the latter. These findings serve to substantially advance our understanding of the molecular basis for the emergence of MDR in cancer clinically and lead to new treatment strategies which target and inhibit MP mediated transfer of P-gp during the course of treatment.

Graft Product for Autologous Peripheral Blood Stem Cell Transplantation Enhances Thrombin Generation and Expresses Procoagulant Microparticles and Tissue Factor.

PubMed

Sidibe, Fatoumata; Spanoudaki, Anastasia; Vanneaux, Valerie; Mbemba, Elisabeth; Larghero, Jerome; Van Dreden, Patrick; Lotz, Jean-Pierre; Elalamy, Ismail; Larsen, Annette K; Gerotziafas, Grigoris T

2018-05-01

The beneficial effect of autologous peripheral blood stem cell transplantation (APBSCT) may be compromised by acute vascular complications related to hypercoagulability. We studied the impact of graft product on thrombin generation of normal plasma and the expression of tissue factor (TF) and procoagulant platelet-derived procoagulant microparticles (Pd-MPs) in samples of graft products. Graft products from 10 patients eligible for APBSCT were mixed with platelet-poor plasma (PPP) or platelet-rich plasma (PRP) from healthy volunteers and assessed for in vitro thrombin generation. In control experiments, thrombin generation was assessed in (1) PPP and PRP without any exogenous TF and/or procoagulant phospholipids, (2) PPP with the addition of TF (5 pM) and procoagulant phospholipids (4 μM), (3) in PRP with the addition of TF (5 pM). Graft products were assessed with Western blot assay for TF expression, with a specific clotting assay for TF activity and with flow cytometry assay for Pd-MPs. The graft product enhanced thrombin generation and its procoagulant activity was related to the presence of Pd-MPs and TF. The concentration of Pd-MPs in the graft product was characterized by a significant interindividual variability. The present study reveals the need for a thorough quality control of the graft products regarding their procoagulant potential.

Validation of structural analysis methods using the in-house liner cyclic rigs

NASA Technical Reports Server (NTRS)

Thompson, R. L.

1982-01-01

Test conditions and variables to be considered in each of the test rigs and test configurations, and also used in the validation of the structural predictive theories and tools, include: thermal and mechanical load histories (simulating an engine mission cycle; different boundary conditions; specimens and components of different dimensions and geometries; different materials; various cooling schemes and cooling hole configurations; several advanced burner liner structural design concepts; and the simulation of hot streaks. Based on these test conditions and test variables, the test matrices for each rig and configurations can be established to verify the predictive tools over as wide a range of test conditions as possible using the simplest possible tests. A flow chart for the thermal/structural analysis of a burner liner and how the analysis relates to the tests is shown schematically. The chart shows that several nonlinear constitutive theories are to be evaluated.

Characterization of Pump-Induced Acoustics in Space Launch System Main Propulsion System Liquid Hydrogen Feedline Using Airflow Test Data

NASA Technical Reports Server (NTRS)

Eberhart, C. J.; Snellgrove, L. M.; Zoladz, T. F.

2015-01-01

High intensity acoustic edgetones located upstream of the RS-25 Low Pressure Fuel Turbo Pump (LPFTP) were previously observed during Space Launch System (STS) airflow testing of a model Main Propulsion System (MPS) liquid hydrogen (LH2) feedline mated to a modified LPFTP. MPS hardware has been adapted to mitigate the problematic edgetones as part of the Space Launch System (SLS) program. A follow-on airflow test campaign has subjected the adapted hardware to tests mimicking STS-era airflow conditions, and this manuscript describes acoustic environment identification and characterization born from the latest test results. Fluid dynamics responsible for driving discrete excitations were well reproduced using legacy hardware. The modified design was found insensitive to high intensity edgetone-like discretes over the bandwidth of interest to SLS MPS unsteady environments. Rather, the natural acoustics of the test article were observed to respond in a narrowband-random/mixed discrete manner to broadband noise thought generated by the flow field. The intensity of these responses were several orders of magnitude reduced from those driven by edgetones.

Cellular abundance of Mps1 and the role of its carboxyl terminal tail in substrate recruitment.

PubMed

Sun, Tingting; Yang, Xiaomei; Wang, Wei; Zhang, Xiaojuan; Xu, Quanbin; Zhu, Songcheng; Kuchta, Robert; Chen, Guanjun; Liu, Xuedong

2010-12-03

Mps1 is a protein kinase that regulates normal mitotic progression and the spindle checkpoint in response to spindle damage. The levels of Mps1 are relatively low in cells during interphase but elevated in mitosis or upon activation of the spindle checkpoint, although the dynamic range of Mps1 expression and the Mps1 catalytic mechanism have not been carefully characterized. Our recent structural studies of the Mps1 kinase domain revealed that the carboxyl-terminal tail region of Mps1 is unstructured, raising the question of whether this region has any functional role in Mps1 catalysis. Here we first determined the cellular abundance of Mps1 during cell cycle progression and found that Mps1 levels vary between 60,000 per cell in early G(1) and 110,000 per cell during mitosis. We studied phosphorylation of a number of Mps1 substrates in vitro and in culture cells. Unexpectedly, we found that the unstructured carboxyl-terminal region of Mps1 plays an essential role in substrate recruitment. Kinetics studies using the purified recombinant wild type and mutant kinases indicate that the carboxyl-terminal tail is largely dispensable for autophosphorylation of Mps1 but critical for trans-phosphorylation of substrates in vitro and in cultured cells. Mps1 mutant without the unstructured tail region is defective in mediating spindle assembly checkpoint activation. Our results underscore the importance of the unstructured tail region of Mps1 in kinase activation.

Oxide ceramic femoral heads contribute to the oxidation of polyethylene liners in artificial hip joints.

PubMed

Pezzotti, Giuseppe; Zhu, Wenliang; Sugano, Nobuhiko; Marin, Elia; Yamamoto, Kengo; Nishiike, Naomichi; Hori, Tsubasa; Rondinella, Alfredo; McEntire, Bryan J; Bock, Ryan; Sonny Bal, B

2018-06-01

Experimental evidence demonstrates that a loss of stoichiometry at the surface of oxide bioceramic femoral heads enhances the oxidation rate of polyethylene acetabular liners in artificial hip joints. Contradicting the common notion that ceramics are bioinert, three independent experiments confirmed substantial chemical interactions between the ceramic femoral heads and their polyethylene counterparts. The experiments reported herein included hydrothermal tests, frictional tests, and hip-simulator experiments. It was discovered that oxide and non-oxide femoral heads differently affected the oxidation processes at the surface of the polyethylene liners, all other testing parameters being equal. Analytical data from X-ray photoelectron (XPS), cathodoluminescence (CL), Fourier-transform infrared (FTIR), and Raman spectroscopies unequivocally and consistently showed that the oxidation rate of polyethylene liners was greater when coupled with oxide as opposed to non-oxide ceramic heads. XPS analyses of O-Al-O bond fractions at the surface of a zirconia-toughened alumina (ZTA) short-term (20 months in vivo) femoral heads retrieval showed a ~50% reduction in favor of oxygen vacancy O-Al-V O and hydroxylated Al-O-H bonds. Off-stoichiometry drifts were confirmed in vitro under both static and dynamic conditions. They triggered oxidation and tangibly affected an advanced highly cross-linked sequentially irradiated and annealed ultra-high molecular weight polyethylene (UHMWPE) liner (increase in oxidation index up to ΔOI~1.2 after 5 × 10 5 cycles under dynamic swing conditions). Second-generation UHMWPE liners infused with vitamin E were also affected by the free flow of oxygen from the oxide femoral heads, although to a lesser extent. The fundamental findings of this study, which were also confirmed on retrievals, call for revised standards in material design and testing. Adopting these new criteria will provide an improved understanding of the importance of off-stoichiometry at the head/liner interface and may lead to significant extensions in artificial joint lifetimes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nuclear reactor

DOEpatents

Pennell, William E.; Rowan, William J.

1977-01-01

A nuclear reactor in which the core components, including fuel-rod assemblies, control-rod assemblies, fertile rod-assemblies, and removable shielding assemblies, are supported by a plurality of separate inlet modular units. These units are referred to as inlet module units to distinguish them from the modules of the upper internals of the reactor. The modular units are supported, each removable independently of the others, in liners in the supporting structure for the lower internals of the reactor. The core assemblies are removably supported in integral receptacles or sockets of the modular units. The liners, units, sockets and assmblies have inlet openings for entry of the fluid. The modular units are each removably mounted in the liners with fluid seals interposed between the opening in the liner and inlet module into which the fluid enters and the upper and lower portion of the liner. Each assembly is similarly mounted in a corresponding receptacle with fluid seals interposed between the openings where the fluid enters and the lower portion of the receptacle or fitting closely in these regions. As fluid flows along each core assembly a pressure drop is produced along the fluid so that the fluid which emerges from each core assembly is at a lower pressure than the fluid which enters the core assembly. However because of the seals interposed in the mountings of the units and assemblies the pressures above and below the units and assemblies are balanced and the units are held in the liners and the assemblies are held in the receptacles by their weights as they have a higher specific gravity than the fluid. The low-pressure spaces between each module and its liner and between each core assembly and its module is vented to the low-pressure regions of the vessel to assure that fluid which leaks through the seals does not accumulate and destroy the hydraulic balance.

Extended MHD Effects in High Energy Density Experiments

NASA Astrophysics Data System (ADS)

Seyler, Charles

2016-10-01

The MHD model is the workhorse for computational modeling of HEDP experiments. Plasma models are inheritably limited in scope, but MHD is expected to be a very good model for studying plasmas at the high densities attained in HEDP experiments. There are, however, important ways in which MHD fails to adequately describe the results, most notably due to the omission of the Hall term in the Ohm's law (a form of extended MHD or XMHD). This talk will discuss these failings by directly comparing simulations of MHD and XMHD for particularly relevant cases. The methodology is to simulate HEDP experiments using a Hall-MHD (HMHD) code based on a highly accurate and robust Discontinuous Galerkin method, and by comparison of HMHD to MHD draw conclusions about the impact of the Hall term. We focus on simulating two experimental pulsed power machines under various scenarios. We examine the MagLIF experiment on the Z-machine at Sandia National Laboratories and liner experiments on the COBRA machine at Cornell. For the MagLIF experiment we find that power flow in the feed leads to low density plasma ablation into the region surrounding the liner. The inflow of this plasma compresses axial magnetic flux onto the liner. In MHD this axial flux tends to resistively decay, whereas in HMHD a force-free current layer sustains the axial flux on the liner leading to a larger ratio of axial to azimuthal flux. During the liner compression the magneto-Rayleigh-Taylor instability leads to helical perturbations due to minimization of field line bending. Simulations of a cylindrical liner using the COBRA machine parameters can under certain conditions exhibit amplification of an axial field due to a force-free low-density current layer separated by some distance from the liner. This results in a configuration in which there is predominately axial field on the liner inside the current layer and azimuthal field outside the layer. We are currently attempting to experimentally verify the simulation results. Collaborator: Nathaniel D. Hamlin, School of Electrical and Computer Engineering, Cornell University, Ithaca, New York.

Two LXXLL motifs in the N terminus of Mps1 are required for Mps1 nuclear import during G(2)/M transition and sustained spindle checkpoint responses.

PubMed

Zhang, Xiaojuan; Yin, Qingqing; Ling, Youguo; Zhang, Yanhong; Ma, Runlin; Ma, Qingjun; Cao, Cheng; Zhong, Hui; Liu, Xuedong; Xu, Quanbin

2011-08-15

Spindle assembly checkpoint kinase Mps1 is spatially and temporally regulated during cell cycle progression. Mps1 is predominately localized to the cytosol in interphase cells, whereas it is concentrated on kinetochores in prophase and prometaphase cells. The timing and mechanism of Mps1 redistribution during cell cycle transition is currently poorly understood. Here, we show that Mps1 relocates from the cytosol to the nucleus at the G 2/M boundary prior to nuclear envelope breakdown (NEB). This timely translocation depends on two tandem LXXLL motifs in the N terminus of Mps1, and mutations in either motif abolish Mps1 nuclear accumulation. Furthermore, we found that phosphorylation of Mps1 Ser80 (which is located between the two LXXLL motifs) also plays a role in regulating timely nuclear entry of Mps1. Mps1 that is defective in LXXLL motifs has near wild-type kinase activity. Moreover, the kinase activity of Mps1 appears to be dispensable for nuclear translocation, as inhibition of Mps1 by a highly specific small-molecule inhibitor did not perturb its nuclear entry. Remarkably, translocation-deficient Mps1 can mediate activation of spindle assembly checkpoint response; however, it fails to support a sustained mitotic arrest upon prolonged treatment with nocodazole. The mitotic slippage can be attributed to precocious degradation of Mps1 in the arrested cells. Our studies reveal a novel cell cycle-dependent nuclear translocation signal in the N terminus of Mps1 and suggest that timely nuclear entry could be important for sustaining spindle assembly checkpoint responses.

Mps1 kinase regulates tumor cell viability via its novel role in mitochondria

PubMed Central

Zhang, X; Ling, Y; Guo, Y; Bai, Y; Shi, X; Gong, F; Tan, P; Zhang, Y; Wei, C; He, X; Ramirez, A; Liu, X; Cao, C; Zhong, H; Xu, Q; Ma, R Z

2016-01-01

Targeting mitotic kinase monopolar spindle 1 (Mps1) for tumor therapy has been investigated for many years. Although it was suggested that Mps1 regulates cell viability through its role in spindle assembly checkpoint (SAC), the underlying mechanism remains less defined. In an endeavor to reveal the role of high levels of mitotic kinase Mps1 in the development of colon cancer, we unexpectedly found the amount of Mps1 required for cell survival far exceeds that of maintaining SAC in aneuploid cell lines. This suggests that other functions of Mps1 besides SAC are also employed to maintain cell viability. Mps1 regulates cell viability independent of its role in cytokinesis as the genetic depletion of Mps1 spanning from metaphase to cytokinesis affects neither cytokinesis nor cell viability. Furthermore, we developed a single-cycle inhibition strategy that allows disruption of Mps1 function only in mitosis. Using this strategy, we found the functions of Mps1 in mitosis are vital for cell viability as short-term treatment of mitotic colon cancer cell lines with Mps1 inhibitors is sufficient to cause cell death. Interestingly, Mps1 inhibitors synergize with microtubule depolymerizing drug in promoting polyploidization but not in tumor cell growth inhibition. Finally, we found that Mps1 can be recruited to mitochondria by binding to voltage-dependent anion channel 1 (VDAC1) via its C-terminal fragment. This interaction is essential for cell viability as Mps1 mutant defective for interaction fails to main cell viability, causing the release of cytochrome c. Meanwhile, deprivation of VDAC1 can make tumor cells refractory to loss of Mps1-induced cell death. Collectively, we conclude that inhibition of the novel mitochondrial function Mps1 is sufficient to kill tumor cells. PMID:27383047

Mps1 kinase regulates tumor cell viability via its novel role in mitochondria.

PubMed

Zhang, X; Ling, Y; Guo, Y; Bai, Y; Shi, X; Gong, F; Tan, P; Zhang, Y; Wei, C; He, X; Ramirez, A; Liu, X; Cao, C; Zhong, H; Xu, Q; Ma, R Z

2016-07-07

Targeting mitotic kinase monopolar spindle 1 (Mps1) for tumor therapy has been investigated for many years. Although it was suggested that Mps1 regulates cell viability through its role in spindle assembly checkpoint (SAC), the underlying mechanism remains less defined. In an endeavor to reveal the role of high levels of mitotic kinase Mps1 in the development of colon cancer, we unexpectedly found the amount of Mps1 required for cell survival far exceeds that of maintaining SAC in aneuploid cell lines. This suggests that other functions of Mps1 besides SAC are also employed to maintain cell viability. Mps1 regulates cell viability independent of its role in cytokinesis as the genetic depletion of Mps1 spanning from metaphase to cytokinesis affects neither cytokinesis nor cell viability. Furthermore, we developed a single-cycle inhibition strategy that allows disruption of Mps1 function only in mitosis. Using this strategy, we found the functions of Mps1 in mitosis are vital for cell viability as short-term treatment of mitotic colon cancer cell lines with Mps1 inhibitors is sufficient to cause cell death. Interestingly, Mps1 inhibitors synergize with microtubule depolymerizing drug in promoting polyploidization but not in tumor cell growth inhibition. Finally, we found that Mps1 can be recruited to mitochondria by binding to voltage-dependent anion channel 1 (VDAC1) via its C-terminal fragment. This interaction is essential for cell viability as Mps1 mutant defective for interaction fails to main cell viability, causing the release of cytochrome c. Meanwhile, deprivation of VDAC1 can make tumor cells refractory to loss of Mps1-induced cell death. Collectively, we conclude that inhibition of the novel mitochondrial function Mps1 is sufficient to kill tumor cells.

Two LXXLL motifs in the N terminus of Mps1 are required for Mps1 nuclear import during G2/M transition and sustained spindle checkpoint responses

PubMed Central

Zhang, Xiaojuan; Yin, Qingqing; Ling, Youguo; Zhang, Yanhong; Ma, Runlin; Ma, Qingjun; Cao, Cheng; Zhong, Hui

2011-01-01

Spindle assembly checkpoint kinase Mps1 is spatially and temporally regulated during cell cycle progression. Mps1 is predominately localized to the cytosol in interphase cells, whereas it is concentrated on kinetochores in prophase and prometaphase cells. The timing and mechanism of Mps1 redistribution during cell cycle transition is currently poorly understood. Here, we show that Mps1 relocates from the cytosol to the nucleus at the G2/M boundary prior to nuclear envelope breakdown (NEB). This timely translocation depends on two tandem LXXLL motifs in the N terminus of Mps1, and mutations in either motif abolish Mps1 nuclear accumulation. Furthermore, we found that phosphorylation of Mps1 Ser80 (which is located between the two LXXLL motifs) also plays a role in regulating timely nuclear entry of Mps1. Mps1 that is defective in LXXLL motifs has near wild-type kinase activity. Moreover, the kinase activity of Mps1 appears to be dispensable for nuclear translocation, as inhibition of Mps1 by a highly specific small-molecule inhibitor did not perturb its nuclear entry. Remarkably, translocation-deficient Mps1 can mediate activation of spindle assembly checkpoint response; however, it fails to support a sustained mitotic arrest upon prolonged treatment with nocodazole. The mitotic slippage can be attributed to precocious degradation of Mps1 in the arrested cells. Our studies reveal a novel cell cycle-dependent nuclear translocation signal in the N terminus of Mps1 and suggest that timely nuclear entry could be important for sustaining spindle assembly checkpoint responses. PMID:21778823

Analysis and calculation of macrosegregation in a casting ingot. MPS solidification model. Volume 2: Software documentation

NASA Technical Reports Server (NTRS)

Maples, A. L.

1980-01-01

The software developed for the solidification model is presented. A link between the calculations and the FORTRAN code is provided, primarily in the form of global flow diagrams and data structures. A complete listing of the solidification code is given.

Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.

PubMed

Kwiatkowski, Nicholas; Jelluma, Nannette; Filippakopoulos, Panagis; Soundararajan, Meera; Manak, Michael S; Kwon, Mijung; Choi, Hwan Geun; Sim, Taebo; Deveraux, Quinn L; Rottmann, Sabine; Pellman, David; Shah, Jagesh V; Kops, Geert J P L; Knapp, Stefan; Gray, Nathanael S

2010-05-01

Mps1, a dual-specificity kinase, is required for the proper functioning of the spindle assembly checkpoint and for the maintenance of chromosomal stability. As Mps1 function has been implicated in numerous phases of the cell cycle, the development of a potent, selective small-molecule inhibitor of Mps1 should facilitate dissection of Mps1-related biology. We describe the cellular effects and Mps1 cocrystal structures of new, selective small-molecule inhibitors of Mps1. Consistent with RNAi studies, chemical inhibition of Mps1 leads to defects in Mad1 and Mad2 establishment at unattached kinetochores, decreased Aurora B kinase activity, premature mitotic exit and gross aneuploidy, without any evidence of centrosome duplication defects. However, in U2OS cells having extra centrosomes (an abnormality found in some cancers), Mps1 inhibition increases the frequency of multipolar mitoses. Lastly, Mps1 inhibitor treatment resulted in a decrease in cancer cell viability.

A Computational and Experimental Study of Resonators in Three Dimensions

NASA Technical Reports Server (NTRS)

Tam, C. K. W.; Ju, H.; Jones, Michael G.; Watson, Willie R.; Parrott, Tony L.

2009-01-01

In a previous work by the present authors, a computational and experimental investigation of the acoustic properties of two-dimensional slit resonators was carried out. The present paper reports the results of a study extending the previous work to three dimensions. This investigation has two basic objectives. The first is to validate the computed results from direct numerical simulations of the flow and acoustic fields of slit resonators in three dimensions by comparing with experimental measurements in a normal incidence impedance tube. The second objective is to study the flow physics of resonant liners responsible for sound wave dissipation. Extensive comparisons are provided between computed and measured acoustic liner properties with both discrete frequency and broadband sound sources. Good agreements are found over a wide range of frequencies and sound pressure levels. Direct numerical simulation confirms the previous finding in two dimensions that vortex shedding is the dominant dissipation mechanism at high sound pressure intensity. However, it is observed that the behavior of the shed vortices in three dimensions is quite different from those of two dimensions. In three dimensions, the shed vortices tend to evolve into ring (circular in plan form) vortices, even though the slit resonator opening from which the vortices are shed has an aspect ratio of 2.5. Under the excitation of discrete frequency sound, the shed vortices align themselves into two regularly spaced vortex trains moving away from the resonator opening in opposite directions. This is different from the chaotic shedding of vortices found in two-dimensional simulations. The effect of slit aspect ratio at a fixed porosity is briefly studied. For the range of liners considered in this investigation, it is found that the absorption coefficient of a liner increases when the open area of the single slit is subdivided into multiple, smaller slits.

Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure

NASA Astrophysics Data System (ADS)

Deng, Yongfeng; Zhang, Yan; Lemos, Bernardo; Ren, Hongqiang

2017-04-01

Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs.

Tissue accumulation of microplastics in mice and biomarker responses suggest widespread health risks of exposure

PubMed Central

Deng, Yongfeng; Zhang, Yan; Lemos, Bernardo; Ren, Hongqiang

2017-01-01

Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs. PMID:28436478

Methotrexate loaded gellan gum microparticles for drug delivery.

PubMed

Dhanka, Mukesh; Shetty, Chaitra; Srivastava, Rohit

2018-04-15

Recently, polysaccharides based microparticles have been found to offer an attractive potential as a carrier in drug delivery field. In this study, bare gellan gum microparticles (GG MPs) and methotrexate (MTX) loaded gellan gum microparticles (MTX-GG MPs) prepared by using simple water-in-oil (W/O) emulsion solvent diffusion method. The developed microparticles (MPs) were found discretely distributed in a spherical shape. MTX has been encapsulated in microparticles with 84.8 ± 1.68% encapsulation efficiency (%EE) and 6.45 ± 0.07% loading capacity (%LC). The Fourier Transform Infrared Spectroscopy (FTIR) characterization of the MPs clearly indicated the physical encapsulation of MTX into polymeric matrix of MPs. Thermogravimetric analysis (TGA) characterization showed slightly higher thermal stability of MTX-GG MPs in comparison to the GG MPs. In vitro release study of MTX-GG MPs showed 84% drug release within 24 h. The hemolysis study of GG MPs and MTX-GG MPs on human red blood cells (RBCs) showed <1.0% hemolysis. The cell viability studies on L929 showed GG MPs, and MTX-GG MPs are biocompatible. Copyright © 2017 Elsevier B.V. All rights reserved.

The Tumor Suppressor Cdkn3 Is Required for Maintaining the Proper Number of Centrosomes by Regulating the Centrosomal Stability of Mps1.

PubMed

Srinivas, Vinayaka; Kitagawa, Mayumi; Wong, Jasmine; Liao, Pei-Ju; Lee, Sang Hyun

2015-11-24

Supernumerary centrosomes promote the assembly of abnormal spindles in many human cancers. The observation that modest changes in the centrosomal levels of Mps1 kinase can cause centrosome overduplication in human cells suggests the existence of a regulatory system that may tightly control its centrosomal stability. Here, we show that Cdkn3, a Cdk-associated phosphatase, prevents Mps1-mediated centrosome overduplication. We identify Cdkn3 as a direct binding partner of Mps1. The interaction between Mps1 and Cdkn3 is required for Mps1 to recruit Cdkn3 to centrosomes. Subsequently, Mps1-bound Cdkn3 forms a regulatory system that controls the centrosomal levels of Mps1 through proteasome-mediated degradation and thereby prevents Mps1-mediated centrosome overduplication. Conversely, knockdown of Cdkn3 stabilizes Mps1 at centrosomes, which promotes centrosome overduplication. We suggest that Mps1 and Cdkn3 form a self-regulated feedback loop at centrosomes to tightly control the centrosomal levels of Mps1, which prevents centrosome overduplication in human cells. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Epidemiology of mucopolysaccharidoses.

PubMed

Khan, Shaukat A; Peracha, Hira; Ballhausen, Diana; Wiesbauer, Alfred; Rohrbach, Marianne; Gautschi, Matthias; Mason, Robert W; Giugliani, Roberto; Suzuki, Yasuyuki; Orii, Kenji E; Orii, Tadao; Tomatsu, Shunji

2017-07-01

The aim of this study was to obtain data about the epidemiology of the different types of mucopolysaccharidoses in Japan and Switzerland and to compare with similar data from other countries. Data for Japan was collected between 1982 and 2009, and 467 cases with MPS were identified. The combined birth prevalence was 1.53 per 100,000 live births. The highest birth prevalence was 0.84 for MPS II, accounting for 55% of all MPS. MPS I, III, and IV accounted for 15, 16, and 10%, respectively. MPS VI and VII were more rare and accounted for 1.7 and 1.3%, respectively. A retrospective epidemiological data collection was performed in Switzerland between 1975 and 2008 (34years), and 41 living MPS patients were identified. The combined birth prevalence was 1.56 per 100,000 live births. The highest birth prevalence was 0.46 for MPS II, accounting for 29% of all MPS. MPS I, III, and IV accounted for 12, 24, and 24%, respectively. As seen in the Japanese population, MPS VI and VII were more rare and accounted for 7.3 and 2.4%, respectively. The high birth prevalence of MPS II in Japan was comparable to that seen in other East Asian countries where this MPS accounted for approximately 50% of all forms of MPS. Birth prevalence was also similar in some European countries (Germany, Northern Ireland, Portugal and the Netherlands) although the prevalence of other forms of MPS is also reported to be higher in these countries. Birth prevalence of MPS II in Switzerland and other European countries is comparatively lower. The birth prevalence of MPS III and IV in Switzerland is higher than in Japan but comparable to that in most other European countries. Moreover, the birth prevalence of MPS VI and VII was very low in both, Switzerland and Japan. Overall, the frequency of MPS varies for each population due to differences in ethnic backgrounds and/or founder effects that affect the birth prevalence of each type of MPS, as seen for other rare genetic diseases. Methods for identification of MPS patients are not uniform across all countries, and consequently, if patients are not identified, recorded prevalence rates will be aberrantly low. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical genetic inhibition of Mps1 in stable human cell lines reveals novel aspects of Mps1 function in mitosis.

PubMed

Sliedrecht, Tale; Zhang, Chao; Shokat, Kevan M; Kops, Geert J P L

2010-04-22

Proper execution of chromosome segregation relies on tight control of attachment of chromosomes to spindle microtubules. This is monitored by the mitotic checkpoint that allows chromosome segregation only when all chromosomes are stably attached. Proper functioning of the attachment and checkpoint processes is thus important to prevent chromosomal instability. Both processes rely on the mitotic kinase Mps1. We present here two cell lines in which endogenous Mps1 has been stably replaced with a mutant kinase (Mps1-as) that is specifically inhibited by bulky PP1 analogs. Mps1 inhibition in these cell lines is highly penetrant and reversible. Timed inhibition during bipolar spindle assembly shows that Mps1 is critical for attachment error-correction and confirms its role in Aurora B regulation. We furthermore show that Mps1 has multiple controls over mitotic checkpoint activity. Mps1 inhibition precludes Mad1 localization to unattached kinetochores but also accelerates mitosis. This acceleration correlates with absence of detectable mitotic checkpoint complex after Mps1 inhibition. Finally, we show that short-term inhibition of Mps1 catalytic activity is sufficient to kill cells. Mps1 is involved in the regulation of multiple key processes that ensure correct chromosome segregation and is a promising target for inhibition in anti-cancer strategies. We report here two cell lines that allow specific and highly penetrant inhibition of Mps1 in a reproducible manner through the use of chemical genetics. Using these cell lines we confirm previously suggested roles for Mps1 activity in mitosis, present evidence for novel functions and examine cell viability after short and prolonged Mps1 inhibition. These cell lines present the best cellular model system to date for investigations into Mps1 biology and the effects of penetrance and duration of Mps1 inhibition on cell viability.

Mps1 is SUMO-modified during the cell cycle

PubMed Central

Chen, Changyan; Lu, Lou; Dai, Wei

2016-01-01

Mps1 is a dual specificity protein kinase that regulates the spindle assembly checkpoint and mediates proper microtubule attachment to chromosomes during mitosis. However, the molecular mechanism that controls Mps1 protein level and its activity during the cell cycle remains unclear. Given that sumoylation plays an important role in mitotic progression, we investigated whether Mps1 was SUMO-modified and whether sumoylation affects its activity in mitosis. Our results showed that Mps1 was sumoylated in both asynchronized and mitotic cell populations. Mps1 was modified by both SUMO-1 and SUMO-2. Our further studies revealed that lysine residues including K71, K287, K367 and K471 were essential for Mps1 sumoylation. Sumoylation appeared to play a role in mediating kinetochore localization of Mps1, thus affecting normal mitotic progression. Furthermore, SUMO-resistant mutants of Mps1 interacted with BubR1 more efficiently than it did with the wild-type control. Combined, our results indicate that Mps1 is SUMO-modified that plays an essential role in regulating Mps1 functions during mitosis. PMID:26675261

N-terminal regions of Mps1 kinase determine functional bifurcation.

PubMed

Araki, Yasuhiro; Gombos, Linda; Migueleti, Suellen P S; Sivashanmugam, Lavanya; Antony, Claude; Schiebel, Elmar

2010-04-05

Mps1 is a conserved kinase that in budding yeast functions in duplication of the spindle pole body (SPB), spindle checkpoint activation, and kinetochore biorientation. The identity of Mps1 targets and the subdomains that convey specificity remain largely unexplored. Using a novel combination of systematic deletion analysis and chemical biology, we identified two regions within the N terminus of Mps1 that are essential for either SPB duplication or kinetochore biorientation. Suppression analysis of the MPS1 mutants defective in SPB duplication and biochemical enrichment of Mps1 identified the essential SPB components Spc29 and the yeast centrin Cdc31 as Mps1 targets in SPB duplication. Our data suggest that phosphorylation of Spc29 by Mps1 in G1/S recruits the Mps2-Bbp1 complex to the newly formed SPB to facilitate its insertion into the nuclear envelope. Mps1 phosphorylation of Cdc31 at the conserved T110 residue controls substrate binding to Kar1 protein. These findings explain the multiple SPB duplication defects of mps1 mutants on a molecular level.

Mps1 is SUMO-modified during the cell cycle.

PubMed

Restuccia, Agnese; Yang, Feikun; Chen, Changyan; Lu, Lou; Dai, Wei

2016-01-19

Mps1 is a dual specificity protein kinase that regulates the spindle assembly checkpoint and mediates proper microtubule attachment to chromosomes during mitosis. However, the molecular mechanism that controls Mps1 protein level and its activity during the cell cycle remains unclear. Given that sumoylation plays an important role in mitotic progression, we investigated whether Mps1 was SUMO-modified and whether sumoylation affects its activity in mitosis. Our results showed that Mps1 was sumoylated in both asynchronized and mitotic cell populations. Mps1 was modified by both SUMO-1 and SUMO-2. Our further studies revealed that lysine residues including K71, K287, K367 and K471 were essential for Mps1 sumoylation. Sumoylation appeared to play a role in mediating kinetochore localization of Mps1, thus affecting normal mitotic progression. Furthermore, SUMO-resistant mutants of Mps1 interacted with BubR1 more efficiently than it did with the wild-type control. Combined, our results indicate that Mps1 is SUMO-modified that plays an essential role in regulating Mps1 functions during mitosis.

Mip1 associates with both the Mps1 kinase and actin and is required for cell cortex stability and anaphase spindle positioning

USDA-ARS?s Scientific Manuscript database

The Mps1 family of protein kinases contributes to cell cycle control by regulating multiple microtubule cytoskeleton activities. We have uncovered a new Mps1 substrate that provides a novel link between Mps1 and the actin cytoskeleton. We have identified a conserved human Mps1 (hMps1) interacting pr...

Cu-Cr-Nb-Zr Alloy for Rocket Engines and Other High-Heat- Flux Applications

NASA Technical Reports Server (NTRS)

Ellis, David L.

2013-01-01

Rocket-engine main combustion chamber liners are used to contain the burning of fuel and oxidizer and provide a stream of high-velocity gas for propulsion. The liners in engines such as the Space Shuttle Main Engine are regeneratively cooled by flowing fuel, e.g., cryogenic hydrogen, through cooling channels in the back side of the liner. The heat gained by the liner from the flame and compression of the gas in the throat section is transferred to the fuel by the liner. As a result, the liner must either have a very high thermal conductivity or a very high operating temperature. In addition to the large heat flux (>10 MW/sq m), the liners experience a very large thermal gradient, typically more than 500 C over 1 mm. The gradient produces thermally induced stresses and strains that cause low cycle fatigue (LCF). Typically, a liner will experience a strain differential in excess of 1% between the cooling channel and the hot wall. Each time the engine is fired, the liner undergoes an LCF cycle. The number of cycles can be as few as one for an expendable booster engine, to as many as several thousand for a reusable launch vehicle or reaction control system. Finally, the liners undergo creep and a form of mechanical degradation called thermal ratcheting that results in the bowing out of the cooling channel into the combustion chamber, and eventual failure of the liner. GRCop-84, a Cu-Cr-Nb alloy, is generally recognized as the best liner material available at the time of this reporting. The alloy consists of 14% Cr2Nb precipitates in a pure copper matrix. Through experimental work, it has been established that the Zr will not participate in the formation of Laves phase precipitates with Cr and Nb, but will instead react with Cu to form the desired Cu-Zr compounds. It is believed that significant improvements in the mechanical properties of GRCop-84 will be realized by adding Zr. The innovation is a Cu-Cr-Nb-Zr alloy covering the composition range of 0.8 to 8.1 weight percent Cr, 0.7 to 7.2 weight percent Nb, 0.1 to 1.5 weight percent Zr, and balance Cu. The alloy combines two known strengthening mechanisms - dispersion strengthening by Cr2Nb precipitates (GRCop-84), and precipitation strengthening by CuxZr (AMZIRC) - to produce a synergistic increase in the capabilities of the alloy with the goal of achieving properties greater than either of the methods could achieve alone. The anticipated advantages of the alloy are higher strength at temperatures up to 700 C, improved creep strength, and significantly higher LCF lives relative to GRCop-84. The thermal expansion, thermal conductivity, and processing of the alloy are anticipated to remain largely unchanged relative to GRCop-84.

CD39 is incorporated into plasma microparticles where it maintains functional properties and impacts endothelial activation.

PubMed

Banz, Yara; Beldi, Guido; Wu, Yan; Atkinson, Ben; Usheva, Anny; Robson, Simon C

2008-08-01

Plasma microparticles (MPs, <1.5 mum) originate from platelet and cell membrane lipid rafts and possibly regulate inflammatory responses and thrombogenesis. These actions are mediated through their phospholipid-rich surfaces and associated cell-derived surface molecules. The ectonucleotidase CD39/ecto-nucleoside triphosphate diphosphohydrolase1 (E-NTPDase1) modulates purinergic signalling through pericellular ATP and ADP phosphohydrolysis and is localized within lipid rafts in the membranes of endothelial- and immune cells. This study aimed to determine whether CD39 associates with circulating MPs and might further impact phenotype and function. Plasma MPs were found to express CD39 and exhibited classic E-NTPDase ecto-enzymatic activity. Entpd1 (Cd39) deletion in mice produced a pro-inflammatory phenotype associated with quantitative and qualitative differences in the MP populations, as determined by two dimensional-gel electrophoresis, western blot and flow cytometry. Entpd1-null MPs were also more abundant, had significantly higher proportions of platelet- and endothelial-derived elements and decreased levels of interleukin-10, tumour necrosis factor receptor 1 and matrix metalloproteinase 2. Consequently, Cd39-null MP augment endothelial activation, as determined by inflammatory cytokine release and upregulation of adhesion molecules in vitro. In conclusion, CD39 associates with circulating MP and may directly or indirectly confer functional properties. Our data also suggest a modulatory role for CD39 within MP in the exchange of regulatory signals between leucocytes and vascular cells.

The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles

PubMed Central

Xu, Bing; Fu, Ying; Liu, Yan; Agvanian, Sosse; Wirka, Robert C.; Baum, Rachel; Zhou, Kang; Shaw, Robin M.

2017-01-01

Microparticles (MPs) are cell–cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold-generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus. We explored the possibility that cBIN1-microfolds are externally released from cardiomyocytes. Using electron microscopy imaging with immunogold labeling, we found in mouse plasma that cBIN1 exists in membrane vesicles about 200 nm in size, which is consistent with the size of MPs. In mice with cardiac-specific heterozygous Bin1 deletion, flow cytometry identified 47% less cBIN1-MPs in plasma, supporting cardiac origin. Cardiac release was also evidenced by the detection of cBIN1-MPs in medium bathing a pure population of isolated adult mouse cardiomyocytes. In human plasma, osmotic shock increased cBIN1 detection by enzyme-linked immunosorbent assay (ELISA), and cBIN1 level decreased in humans with heart failure, a condition with reduced cardiac muscle cBIN1, both of which support cBIN1 release in MPs from human hearts. Exploring putative mechanisms of MP release, we found that the membrane fission complex endosomal sorting complexes required for transport (ESCRT)-III subunit charged multivesicular body protein 4B (CHMP4B) colocalizes and coimmunoprecipitates with cBIN1, an interaction enhanced by actin stabilization. In HeLa cells with cBIN1 overexpression, knockdown of CHMP4B reduced the release of cBIN1-MPs. Using truncation mutants, we identified that the N-terminal BAR (N-BAR) domain in cBIN1 is required for CHMP4B binding and MP release. This study links the BAR protein superfamily to the ESCRT pathway for MP biogenesis in mammalian cardiac ventricular cells, identifying elements of a pathway by which cytoplasmic cBIN1 is released into blood. PMID:28806752

The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles.

PubMed

Xu, Bing; Fu, Ying; Liu, Yan; Agvanian, Sosse; Wirka, Robert C; Baum, Rachel; Zhou, Kang; Shaw, Robin M; Hong, TingTing

2017-08-01

Microparticles (MPs) are cell-cell communication vesicles derived from the cell surface plasma membrane, although they are not known to originate from cardiac ventricular muscle. In ventricular cardiomyocytes, the membrane deformation protein cardiac bridging integrator 1 (cBIN1 or BIN1+13+17) creates transverse-tubule (t-tubule) membrane microfolds, which facilitate ion channel trafficking and modulate local ionic concentrations. The microfold-generated microdomains continuously reorganize, adapting in response to stress to modulate the calcium signaling apparatus. We explored the possibility that cBIN1-microfolds are externally released from cardiomyocytes. Using electron microscopy imaging with immunogold labeling, we found in mouse plasma that cBIN1 exists in membrane vesicles about 200 nm in size, which is consistent with the size of MPs. In mice with cardiac-specific heterozygous Bin1 deletion, flow cytometry identified 47% less cBIN1-MPs in plasma, supporting cardiac origin. Cardiac release was also evidenced by the detection of cBIN1-MPs in medium bathing a pure population of isolated adult mouse cardiomyocytes. In human plasma, osmotic shock increased cBIN1 detection by enzyme-linked immunosorbent assay (ELISA), and cBIN1 level decreased in humans with heart failure, a condition with reduced cardiac muscle cBIN1, both of which support cBIN1 release in MPs from human hearts. Exploring putative mechanisms of MP release, we found that the membrane fission complex endosomal sorting complexes required for transport (ESCRT)-III subunit charged multivesicular body protein 4B (CHMP4B) colocalizes and coimmunoprecipitates with cBIN1, an interaction enhanced by actin stabilization. In HeLa cells with cBIN1 overexpression, knockdown of CHMP4B reduced the release of cBIN1-MPs. Using truncation mutants, we identified that the N-terminal BAR (N-BAR) domain in cBIN1 is required for CHMP4B binding and MP release. This study links the BAR protein superfamily to the ESCRT pathway for MP biogenesis in mammalian cardiac ventricular cells, identifying elements of a pathway by which cytoplasmic cBIN1 is released into blood.

Carbohydrate restriction with postmeal walking effectively mitigates postprandial hyperglycemia and improves endothelial function in type 2 diabetes.

PubMed

Francois, Monique E; Myette-Cote, Etienne; Bammert, Tyler D; Durrer, Cody; Neudorf, Helena; DeSouza, Christopher A; Little, Jonathan P

2018-01-01

Postprandial hyperglycemia has deleterious effects on endothelial function. Restricting carbohydrate intake and postmeal walking have each been shown to reduce postprandial hyperglycemia, but their combination and subsequent effects on endothelial function have not been investigated. Here, we sought to examine the effect of blunting postprandial hyperglycemia by following a low-carbohydrate diet, with or without postmeal walking exercise, on markers of vascular health in type 2 diabetes (T2D). In a randomized crossover design, individuals with T2D ( n = 11) completed three 4-day controlled diet interventions consisting of 1) low-carbohydrate diet alone (LC), 2) low-carbohydrate diet with 15-min postmeal walks (LC + Ex), and 3) low-fat control diet (CON). Fasting blood samples and brachial artery flow-mediated dilation (%FMD) were measured before and after each intervention. Total circulating microparticles (MPs), endothelial MPs, platelet MPs, monocyte-platelet aggregates, and adhesion molecules were assessed as biomarkers of vascular health. There was a significant condition × time interaction for %FMD ( P = 0.01), with post hoc tests revealing improved %FMD after LC + Ex (+0.8 ± 1.0%, P = 0.02), with no change after LC or CON. Endothelial MPs were significantly reduced with the LC diet by ~45% (from 99 ± 60 to 44 ± 31 MPs/μl, P = 0.02), with no change after LC + Ex or CON (interaction: P = 0.04). Total MPs were lower (main effect time: P = 0.02), whereas monocyte-platelet aggregates were higher (main effect time: P < 0.01) after all interventions. Plasma adhesion molecules and C-reactive protein were unaltered. Attenuating postprandial hyperglycemic excursions using a low-carbohydrate diet combined with postmeal walking appears to be an effective strategy to improve endothelial function in individuals with T2D. NEW & NOTEWORTHY Carbohydrate restriction and postmeal walking lower postprandial hyperglycemia in individuals with type 2 diabetes. Here, we show that the combination significantly improved endothelial function and that carbohydrate restriction alone reduced circulating endothelial microparticles in individuals with type 2 diabetes. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/low-carb-diet-and-exercise-improve-endothelial-health/ .

Increased levels of circulating microparticles are associated with increased procoagulant activity in patients with cutaneous malignant melanoma.

PubMed

Laresche, Claire; Pelletier, Fabien; Garnache-Ottou, Francine; Lihoreau, Thomas; Biichlé, Sabeha; Mourey, Guillaume; Saas, Philippe; Humbert, Philippe; Seilles, Estelle; Aubin, François

2014-01-01

Microparticles (MPs) are known to be increased in various malignancies and are involved in tumor invasion, angiogenesis, coagulation, and metastasis. We investigated the plasma levels of annexin-V MPs (AV(+)MPs), platelet-derived MPs (PMPs), and endothelial-derived MPs (EMPs) in patients with melanoma (n=129) and in healthy controls (n=49). A functional coagulation test STA Procoag-PPL measuring the clotting time was performed on samples containing MPs to evaluate their procoagulant potential. The plasma levels of PMPs, EMPs, and AV(+)MPs were significantly higher, and the clotting time-PPL was significantly lower in melanoma patients than in healthy controls. The plasma levels of PMPs, EMPs, and AV(+)MPs were higher in stage IV than in the other stages of melanoma, but with no significant difference. In addition, we observed an inverse correlation between PMPs, AV(+)MPs, and clotting times. Our data suggest that MPs are involved in the progression of melanoma and may be associated to melanoma-associated thrombogenesis.

Pilot points method for conditioning multiple-point statistical facies simulation on flow data

NASA Astrophysics Data System (ADS)

Ma, Wei; Jafarpour, Behnam

2018-05-01

We propose a new pilot points method for conditioning discrete multiple-point statistical (MPS) facies simulation on dynamic flow data. While conditioning MPS simulation on static hard data is straightforward, their calibration against nonlinear flow data is nontrivial. The proposed method generates conditional models from a conceptual model of geologic connectivity, known as a training image (TI), by strategically placing and estimating pilot points. To place pilot points, a score map is generated based on three sources of information: (i) the uncertainty in facies distribution, (ii) the model response sensitivity information, and (iii) the observed flow data. Once the pilot points are placed, the facies values at these points are inferred from production data and then are used, along with available hard data at well locations, to simulate a new set of conditional facies realizations. While facies estimation at the pilot points can be performed using different inversion algorithms, in this study the ensemble smoother (ES) is adopted to update permeability maps from production data, which are then used to statistically infer facies types at the pilot point locations. The developed method combines the information in the flow data and the TI by using the former to infer facies values at selected locations away from the wells and the latter to ensure consistent facies structure and connectivity where away from measurement locations. Several numerical experiments are used to evaluate the performance of the developed method and to discuss its important properties.

Assimilating Flow Data into Complex Multiple-Point Statistical Facies Models Using Pilot Points Method

NASA Astrophysics Data System (ADS)

Ma, W.; Jafarpour, B.

2017-12-01

We develop a new pilot points method for conditioning discrete multiple-point statistical (MPS) facies simulation on dynamic flow data. While conditioning MPS simulation on static hard data is straightforward, their calibration against nonlinear flow data is nontrivial. The proposed method generates conditional models from a conceptual model of geologic connectivity, known as a training image (TI), by strategically placing and estimating pilot points. To place pilot points, a score map is generated based on three sources of information:: (i) the uncertainty in facies distribution, (ii) the model response sensitivity information, and (iii) the observed flow data. Once the pilot points are placed, the facies values at these points are inferred from production data and are used, along with available hard data at well locations, to simulate a new set of conditional facies realizations. While facies estimation at the pilot points can be performed using different inversion algorithms, in this study the ensemble smoother (ES) and its multiple data assimilation variant (ES-MDA) are adopted to update permeability maps from production data, which are then used to statistically infer facies types at the pilot point locations. The developed method combines the information in the flow data and the TI by using the former to infer facies values at select locations away from the wells and the latter to ensure consistent facies structure and connectivity where away from measurement locations. Several numerical experiments are used to evaluate the performance of the developed method and to discuss its important properties.

Gas-core reactor power transient analysis

NASA Technical Reports Server (NTRS)

Kascak, A. F.

1972-01-01

The gas core reactor is a proposed device which features high temperatures. It has applications in high specific impulse space missions, and possibly in low thermal pollution MHD power plants. The nuclear fuel is a ball of uranium plasma radiating thermal photons as opposed to gamma rays. This thermal energy is picked up before it reaches the solid cavity liner by an inflowing seeded propellant stream and convected out through a rocket nozzle. A wall-burnout condition will exist if there is not enough flow of propellant to convect the energy back into the cavity. A reactor must therefore operate with a certain amount of excess propellant flow. Due to the thermal inertia of the flowing propellant, the reactor can undergo power transients in excess of the steady-state wall burnout power for short periods of time. The objective of this study was to determine how long the wall burnout power could be exceeded without burning out the cavity liner. The model used in the heat-transfer calculation was one-dimensional, and thermal radiation was assumed to be a diffusion process.

Behavioural phenotypes of the mucopolysaccharide disorders: a systematic literature review of cognitive, motor, social, linguistic and behavioural presentation in the MPS disorders.

PubMed

Cross, E M; Hare, D J

2013-03-01

The mucopolysaccharide disorders (MPS) are a group of recessively inherited metabolic disorders resulting in progressive physical and cognitive decline. MEDLINE, PsycINFO and Embase databases were searched, alongside manual screening, to identify relevant literature. Papers were included in the review if they were published in a peer reviewed journal and conducted empirical research into cognitive, motor, social or linguistic development or behaviour in one or more MPS disorders. Twenty-five papers were reviewed. Two papers used methodology of a sufficiently high standard to demonstrate a behavioural phenotype; both found sleep disturbance to be part of the phenotype of MPS III. Fearfulness and sleep disturbance were frequently observed in people with MPS I and II. Cognitive and motor impairment and decline, and challenging behaviour were highly prevalent in the severe form of MPS II. Cognitive decline and severe behavioural problems relating to aggression, hyperactivity, orality, unusual affect and temper tantrums were seen in MPS III. Sleep disturbance is part of the behavioural phenotype of MPS III, and challenging behaviour is highly prevalent in MPS II and MPS III, therefore the efficacy of behavioural interventions for these populations should be investigated. Further research into the behaviour and adaptive skills of children with MPS III and MPS IV is required.

TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability.

PubMed

Choi, Minji; Min, Yoo Hong; Pyo, Jaehyuk; Lee, Chang-Woo; Jang, Chang-Young; Kim, Ja-Eun

2017-06-01

Chromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle assembly checkpoint (SAC). Pharmacological inhibition of Mps1 has been suggested as a cancer therapeutic; however, despite the existence of a novel Mps1 inhibitor, TC Mps1 12, no such studies have been performed. The effects of TC Mps1 12 on cell viability, chromosome alignment, centrosome number, mitotic duration, apoptosis and SAC were determined in hepatocellular carcinoma (HCC) cells. In addition, the association of Mps1 expression with the overall survival of HCC patients was analysed. Treatment of human HCC cells with TC Mps1 12 led to chromosome misalignment and missegregation, and disorganization of centrosomes. Even in the presence of these errors, TC Mps1 12-treated cells overrode the SAC, resulting in a shortened mitotic duration and mitotic slippage. This mitotic catastrophe triggered apoptosis and, finally, inhibited the growth of HCC cells. In addition, the expression of the Mps1-encoding TTK gene was associated with poor overall survival of HCC patients. TC Mps1 12 results in the accumulation of chromosomal instabilities and mitotic catastrophe in HCC cells. Overall, these data demonstrate that the inhibition of Mps1 kinase using TC Mps1 12 is a promising therapeutic approach for liver cancer. © 2017 The British Pharmacological Society.

Effects of the selective MPS1 inhibitor MPS1-IN-3 on glioblastoma sensitivity to antimitotic drugs.

PubMed

Tannous, Bakhos A; Kerami, Mariam; Van der Stoop, Petra M; Kwiatkowski, Nicholas; Wang, Jinhua; Zhou, Wenjun; Kessler, Almuth F; Lewandrowski, Grant; Hiddingh, Lotte; Sol, Nik; Lagerweij, Tonny; Wedekind, Laurine; Niers, Johanna M; Barazas, Marco; Nilsson, R Jonas A; Geerts, Dirk; De Witt Hamer, Philip C; Hagemann, Carsten; Vandertop, W Peter; Van Tellingen, Olaf; Noske, David P; Gray, Nathanael S; Würdinger, Thomas

2013-09-04

Glioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest. We used glioblastoma cells to determine the expression of MPS1 and to determine the effects of MPS1 inhibition on mitotic errors and cell viability in combination with vincristine and taxol. The effect of MPS1 inhibition was assessed in different orthotopic glioblastoma mouse models (n = 3-7 mice/group). MPS1 expression levels were examined in relation to patient survival. Using publicly available gene expression data, we determined that MPS1 overexpression corresponds positively with tumor grade and negatively with patient survival (two-sided t test, P < .001). Patients with high MPS1 expression (n = 203) had a median and mean survival of 487 and 913 days (95% confidence intervals [CI] = 751 to 1075), respectively, and a 2-year survival rate of 35%, whereas patients with intermediate MPS1 expression (n = 140) had a median and mean survival of 858 and 1183 days (95% CI = 1177 to 1189), respectively, and a 2-year survival rate of 56%. We demonstrate that MPS1 inhibition by RNAi results in sensitization to antimitotic agents. We developed a selective small-molecule inhibitor of MPS1, MPS1-IN-3, which caused mitotic aberrancies in glioblastoma cells and, in combination with vincristine, induced mitotic checkpoint override, increased aneuploidy, and augmented cell death. MPS1-IN-3 sensitizes glioblastoma cells to vincristine in orthotopic mouse models (two-sided log-rank test, P < .01), resulting in prolonged survival without toxicity. Our results collectively demonstrate that MPS1, a putative therapeutic target in glioblastoma, can be selectively inhibited by MPS1-IN-3 sensitizing glioblastoma cells to antimitotic drugs.

Effects of the Selective MPS1 Inhibitor MPS1-IN-3 on Glioblastoma Sensitivity to Antimitotic Drugs

PubMed Central

2013-01-01

Background Glioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest. Methods We used glioblastoma cells to determine the expression of MPS1 and to determine the effects of MPS1 inhibition on mitotic errors and cell viability in combination with vincristine and taxol. The effect of MPS1 inhibition was assessed in different orthotopic glioblastoma mouse models (n = 3–7 mice/group). MPS1 expression levels were examined in relation to patient survival. Results Using publicly available gene expression data, we determined that MPS1 overexpression corresponds positively with tumor grade and negatively with patient survival (two-sided t test, P < .001). Patients with high MPS1 expression (n = 203) had a median and mean survival of 487 and 913 days (95% confidence intervals [CI] = 751 to 1075), respectively, and a 2-year survival rate of 35%, whereas patients with intermediate MPS1 expression (n = 140) had a median and mean survival of 858 and 1183 days (95% CI = 1177 to 1189), respectively, and a 2-year survival rate of 56%. We demonstrate that MPS1 inhibition by RNAi results in sensitization to antimitotic agents. We developed a selective small-molecule inhibitor of MPS1, MPS1-IN-3, which caused mitotic aberrancies in glioblastoma cells and, in combination with vincristine, induced mitotic checkpoint override, increased aneuploidy, and augmented cell death. MPS1-IN-3 sensitizes glioblastoma cells to vincristine in orthotopic mouse models (two-sided log-rank test, P < .01), resulting in prolonged survival without toxicity. Conclusions Our results collectively demonstrate that MPS1, a putative therapeutic target in glioblastoma, can be selectively inhibited by MPS1-IN-3 sensitizing glioblastoma cells to antimitotic drugs. PMID:23940287

Development of a Liner Design Methodology and Relevant Results of Acoustic Suppression in the Farfield for Mixer-Ejector Nozzles

NASA Technical Reports Server (NTRS)

Salikuddin, M.

2006-01-01

We have developed a process to predict noise field interior to the ejector and in the farfield for any liner design for a mixer-ejector of arbitrary scale factor. However, a number of assumptions, not verified for the current application, utilized in this process, introduce uncertainties in the final result, especially, on a quantitative basis. The normal impedance model for bulk with perforated facesheet is based on homogeneous foam materials of low resistivity. The impact of flow conditions for HSCT application as well as the impact of perforated facesheet on predicted impedance is not properly accounted. Based on the measured normal impedance for deeper bulk samples (i.e., 2.0 in.) the predicted reactance is much higher compared to the data at frequencies above 2 kHz for T-foam and 200 ppi SiC. The resistance is under predicted at lower frequencies (below 4 kHz) for these samples. Thus, the use of such predicted data in acoustic suppression is likely to introduce inaccuracies. It should be noted that the impedance prediction methods developed recently under liner technology program are not utilized in the studies described in this report due to the program closeout. Acoustic suppression prediction is based on the uniform flow and temperature conditions in a two-sided treated constant area rectangular duct. In addition, assumptions of equal energy per mode noise field and interaction of all frequencies with the treated surface for the entire ejector length may not be accurate. While, the use of acoustic transfer factor minimizes the inaccuracies associated with the prediction for a known test case, the assumption of the same factor for other liner designs and with different linear scale factor ejectors seems to be very optimistic. As illustrated in appendix D that the predicted noise suppression for LSM-1 is lower compared to the measured data is an indication of the above argument. However, the process seems to be more reliable when used for the same scale models for different liner designs as demonstrated for Gen. 1 mixer-ejectors.

Incidence of the mucopolysaccharidoses in Northern Ireland.

PubMed

Nelson, J

1997-12-01

An epidemiological study of the mucopolysaccharidoses (MPS) in Northern Ireland using multiple ascertainment sources was carried out and the incidence rate for the period 1958-1985 was estimated. An incidence of approximately 1 in 76,000 live births was obtained for MPS 1H (Hurler phenotype); 1 in 280,000 for MPS 1 H/S (Hurler/Scheie phenotype); 1 in 140,000 live births (1 in 72,000 male live births) for MPS II (Hunter syndrome); 1 in 280,000 for MPS III (Sanfilippo syndrome) and 1 in 76,000 for MPS IV A (Morquio syndrome type A). No cases of MPS IS (Scheie phenotype), MPS IV B (Morquio syndrome type B) or MPS VI (Maroteaux-Lamy syndrome) were ascertained during the study period. Three cases of non-immune hydrops fetalis born to consanguineous parents were thought to be due to beta-glucuronidase deficiency (MPS VII) on the basis of placental histology and enzyme studies on both parents but no living cases of MPS VII were ascertained. The overall incidence for all types of mucopolysaccharidosis was approximately 1 in 25,000 live births. A comparison is made with incidence estimates obtained from other published studies.

[Study of negative feedback between wild-type BRAF or RAFV600E and Mps1 in melanoma].

PubMed

Zhang, Ling; He, Chanting; Bi, Yanghui; Liu, Feng; Cui, Heyang; Wang, Juan; Song, Bin; Shi, Ruyi; Yang, Bin; Wang, Fang; Jia, Zhiwu; Zhao, Zhenxiang; Liu, Jing

2015-04-01

To study the effect of Mps1 on BRAFWT/MEK/ERK pathway in the presence of wild type BRAF or BRAFV600E in melanoma. Melanoma cells harboring BRAFWT genotype were transfected either with pBabe-puro-GST-BRAF-WT and/or pBabe-puro-GFP-Mps1-WT or pBabe-puro-GST-BRAFV600E and/or pBabe-puro-GFP-Mps1-WT, followed by Western blot to detect Mps1 and p-ERK expression. The melanoma cells harboring BRAFWT and BRAFV600E genotype were infected with pSUPER-Mps1 retrovirus to knockdown the endogenous Mps1 protein, followed by Western blot to detect Mps1 and p-ERK expression. Meanwhile, melanoma cells harboring BRAFV600E genotype were infected with pBabe-puro-GFP-Mps1 and Western blot was performed to detect Mps1 and p-ERK expression. In melanoma cells harboring BRAFWT genotype and transfected with pBabe-puro-GST-BRAF-WT and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels were notably reduced as compared to either negative control or empty vector. However, cells transfected with pBabe-puro-GST-BRAFV600E and pBabe-puro-GFP-Mps1-WT, phospho-ERK levels did not change significantly compared with either negative control or empty vector. Knockout of Mps1 in BRAF wild-type cell lines led to an increased ERK activity. However, there was no significant change of ERK activity in BRAFV600E cell lines in the absence of Mps1. The expression of p-ERK in BRAFV600E mutant cell lines infected with pBabe-puro-GFP-Mps1-WT did not show any significant difference from either negative control or empty vector. Based on these findings, it suggests that there exists an auto-regulatory negative feedback loop between the Mps1 kinase and BRAFWT/ERK signaling. Oncogenic BRAFV600E abrogates the regulatory negative feedback loop of Mps1 on the MAPK pathway.

Microplastics have a more profound impact than elevated temperatures on the predatory performance, digestion and energy metabolism of an Amazonian cichlid.

PubMed

Wen, Bin; Zhang, Nan; Jin, Shi-Rong; Chen, Zai-Zhong; Gao, Jian-Zhong; Liu, Ying; Liu, Han-Peng; Xu, Zhe

2018-02-01

Knowledge on the impacts of microplastics (MPs) pollution on freshwater environments and biota remains limited. Meanwhile, freshwater ecosystems have been threatened by elevated temperatures caused by climate change. To date, no information exists on how MPs-especially under elevated temperature conditions-affect predatory performance, digestive processes and metabolic pathways in freshwater organisms. Here, we examined MPs, elevated temperature and their combined effects on juveniles (0+ group) of an Amazonian cichlid, the discus fish (Symphysodon aequifasciatus). For 30 days, fish were exposed to ambient or elevated temperatures (i.e., 28 or 31 °C) in the absence or presence of MPs (i.e., 0 or 200 μg/L). The following metrics were quantified: MPs accumulation; predatory performance; and biomarkers involved in neurotransmission, digestion and energy production. The results showed that survival rate and body length were not affected by MPs, elevated temperatures or their combination. Elevated temperatures resulted in an increase in MP concentrations in fish bodies. Exposure to MPs decreased the post-exposure predatory performance (PEPP) at ambient temperatures but not at elevated temperatures. Elevated temperatures, however, had no effect on the PEPP but antagonistically interacted with MPs, leading to similar predatory performances under present and future conditions. Acetylcholinesterase (AChE) activity was only affected by MPs and decreased in the presence of MPs, indicating adverse effects in nervous and neuromuscular function and, thus, potentially in predatory performance. Trypsin activity was only influenced by MPs and decreased during exposure to MPs. Elevated temperatures or MPs alone increased the amylase activity but interacted antagonistically. Lipase activity was not influenced by either of the two stressors. In contrast, alkaline phosphatase (ALP) activity was affected by MPs or elevated temperatures alone and decreased with both stressors. Such results indicate deficits in the digestive capabilities of early-stage S. aequifasciatus under elevated temperature conditions and especially during exposure to MPs. Electron transport system (ETS) activity was not influenced by either of the two stressors. Both elevated temperatures and MPs alone increased LDH activity; however, the interaction between the two stressors cancelled activity but was still higher than activity in present conditions. Citrate synthase (CS) activity decreased with elevated temperature but increased during exposure to MPs. Cytochrome c oxidase (COX) activity was only influenced by MPs and increased in the presence of MPs. Thus, S. aequifasciatus juveniles exposed to elevated temperatures and MPs not only relied on anaerobic glycolysis for energy production but also depended on aerobic metabolism in the presence of MPs. Overall, these findings suggested that MPs showed a greater impact than elevated temperatures on the predatory performance, digestion and energy production of S. aequifasciatus. Nevertheless, juvenile survival and growth were minimally impacted, and thus, S. aequifasciatus could cope with near-future temperature increases and MP exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

Carotid Intima-Media Thickness Is Increased In Patients With Treated Mucopolysaccharidoses Types I and II, And Correlates With Arterial Stiffness

PubMed Central

Wang, Raymond Y.; Braunlin, Elizabeth A.; Rudser, Kyle D.; Dengel, Donald R.; Metzig, Andrea M.; Covault, Kelly K.; Polgreen, Lynda E.; Shapiro, Elsa; Steinberger, Julia; Kelly, Aaron S.

2013-01-01

Background Treatments for mucopolysaccharidoses (MPS) have increased longevity, but coronary artery disease (CAD) and cardiovascular complications cause mortality in a high percentage of patients. Non-invasive measures of sub-clinical atherosclerosis, such as carotid intima-media thickness (cIMT) and arterial stiffness, may be useful for prediction of CAD outcomes in MPS patients. Objectives To determine if cIMT and arterial stiffness are abnormal in MPS I and II patients compared to healthy controls. Methods MPS patients underwent carotid artery ultrasonography, and electronic wall-tracking software was used to measure cIMT, carotid artery compliance (cCSC), distensibility (cCSD), and incremental elastic modulus (cIEM). Control data from healthy subjects were obtained from a different study that utilized identical testing within the same laboratory. Results A total of 406 healthy controls and 25 MPS patients (16 MPS I, 9 MPS II) were studied. All MPS patients had or were receiving treatment: 15 patients (6 MPS I, 9 MPS II) were receiving enzyme replacement therapy (ERT), 9 patients (all MPS I) had received hematopoietic stem cell transplant (HSCT), and 1 patient with MPS I had received HSCT and was receiving enzyme replacement therapy (ERT). MPS patients had significantly higher mean (±SD) cIMT (0.56 ± 0.05 mm) compared to controls (0.44 ± 0.04 mm; adjusted p < 0.001). MPS patients also had increased stiffness compared to controls, showing significantly lower cCSC (0.14 ± 0.09 mm2/mmHg versus 0.16 ± 0.05 mm2/mmHg; adjusted p = 0.019), and higher cIEM (1362 ± 877 mmHg versus 942 ± 396 mmHg; adjusted p < 0.001). cCSD in MPS patients was lower than control (29.7 ± 16.4% versus 32.0 ± 8.2%) but was not statistically; p = 0.12. Among MPS patients, cCSD showed a significant association with cIMT (p = 0.047), while the association between cIEM and cIMT approached significance (p = 0.077). No significant differences were observed in cIMT, cCSD, cCSC, and cIEM between MPS I and MPS II patients. Conclusions Despite treatment, MPS patients had higher cIMT compared to healthy controls, indicating this marker of sub-clinical atherosclerosis may be a useful predictor of CAD outcomes. The association of arterial stiffness measures with cIMT suggests that mechanical and structural changes may occur in concert among MPS patients. Although yet to be confirmed, increased cIMT and arterial stiffness in MPS I and II patients may be a consequence of inflammatory signaling pathways triggered by heparan or dermatan sulfate-derived oligosaccharides. Prospective, longitudinal studies will need to be performed in order to evaluate the usefulness of these carotid measurements as predictors of adverse CAD outcomes in MPS patients. PMID:24268528

Glycosaminoglycan levels in dried blood spots of patients with mucopolysaccharidoses and mucolipidoses

PubMed Central

Kubaski, Francyne; Suzuki, Yasuyuki; Orii, Kenji; Giugliani, Roberto; Church, Heather J.; Mason, Robert W.; Dũng, Vũ Chí; Ngoc, Can Thi Bich; Yamaguchi, Seiji; Kobayashi, Hironori; Girisha, Katta M.; Fukao, Toshiyuki; Orii, Tadao; Tomatsu, Shunji

2017-01-01

Mucopolysaccharidoses (MPSs) and mucolipidoses (ML) are groups of lysosomal storage disorders in which lysosomal hydrolases are deficient leading to accumulation of undegraded glycosaminoglycans (GAGs), throughout the body, subsequently resulting in progressive damage to multiple tissues and organs. Assays using tandem mass spectrometry (MS/MS) have been established to measure GAGs in serum or plasma from MPS and ML patients, but few studies were performed to determine whether these assays are sufficiently robust to measure GAG levels in dried blood spots (DBS) of patients with MPS and ML. Material and methods In this study, we evaluated GAG levels in DBS samples from 124 MPS and ML patients (MPS I = 16; MPS II = 21; MPS III = 40; MPS IV = 32; MPS VI =10; MPS VII = 1; ML= 4), and compared them with 115 age-matched controls. Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Subsequently, dermatan sulfate (DS), heparan sulfate (HS-0S, HS-NS), and keratan sulfate (mono-sulfated KS, di-sulfated KS, and ratio of di-sulfated KS in total KS) were measured by MS/MS. Results Untreated patients with MPS I, II, VI, and ML had higher levels of DS compared to control samples. Untreated patients with MPS I, II, III, VI, and ML had higher levels of HS-0S; and untreated patients with MPS II, III and VI and ML had higher levels of HS-NS. Levels of KS were age dependent, so although levels of both mono-sulfated KS and di-sulfated KS were generally higher in patients, particularly for MPS II and MPS IV, age group numbers were not sufficient to determine significance of such changes. However, the ratio of di-sulfated KS in total KS was significantly higher in all MPS patients younger than 5 years old, compared to age-matched controls. MPS I and VI patients treated with HSCT had normal levels of DS, and MPS I, VI, and VII treated with ERT or HSCT had normal levels of HS-0S and HS-NS, indicating that both treatments are effective in decreasing blood GAG levels. Conclusion Measurement of GAG levels in DBS is useful for diagnosis and potentially for monitoring the therapeutic efficacy in MPS. PMID:28065440

Design and Evaluation of Modifications to the NASA Langley Flow Impedance Tube

NASA Technical Reports Server (NTRS)

Jones, Michael G.; Watson, Willie R.; Parrott, Tony L.; Smith, Charles D.

2004-01-01

The need to minimize fan noise radiation from commercial aircraft engine nacelles continues to provide an impetus for developing new acoustic liner concepts. If the full value of such concepts is to be attained, an understanding of grazing flow effects is crucial. Because of this need for improved understanding of grazing flow effects, the NASA Langley Research Center Liner Physics Group has invested a large effort over the past decade into the development of a 2-D finite element method that characterizes wave propagation through a lined duct. The original test section in the Langley Grazing IncidenceTube was used to acquire data needed for implementation of this finite element method. This test section employed a stepper motor-driven axial-traversing bar, embedded in the wall opposite the test liner, to position a flush-mounted microphone at pre-selected locations. Complex acoustic pressure data acquired with this traversing microphone were used to educe the acoustic impedance of test liners using this 2-D finite element method and a local optimization technique. Results acquired in this facility have been extensively reported, and were compared with corresponding results from various U.S. aeroacoustics laboratories in the late 1990 s. Impedance data comparisons acquired from this multi-laboratory study suggested that it would be valuable to incorporate more realistic 3-D aeroacoustic effects into the impedance eduction methodology. This paper provides a description of modifications that have been implemented to facilitate studies of 3-D effects. The two key features of the modified test section are (1) the replacement of the traversing bar and its flush-mounted microphone with an array of 95 fixed-location microphones that are flush-mounted in all four walls of the duct, and (2) the inclusion of a suction device to modify the boundary layer upstream of the lined portion of the duct. The initial results achieved with the modified test section are provided in this report, and a comparison of these results with those achieved using the original test section is used to demonstrate that the data acquisition and analysis with the new test section can be confidently used for impedance eduction.

Proteomic Discovery and Development of a Multiplexed Targeted MRM-LC-MS/MS Assay for Urine Biomarkers of Extracellular Matrix Disruption in Mucopolysaccharidoses I, II, and VI.

PubMed

Heywood, Wendy E; Camuzeaux, Stephane; Doykov, Ivan; Patel, Nina; Preece, Rhian-Lauren; Footitt, Emma; Cleary, Maureen; Clayton, Peter; Grunewald, Stephanie; Abulhoul, Lara; Chakrapani, Anupam; Sebire, Neil J; Hindmarsh, Peter; de Koning, Tom J; Heales, Simon; Burke, Derek; Gissen, Paul; Mills, Kevin

2015-12-15

The mucopolysaccharidoses (MPS) are lysosomal storage disorders that result from defects in the catabolism of glycosaminoglycans. Impaired muscle, bone, and connective tissue are typical clinical features of MPS due to disruption of the extracellular matrix. Markers of MPS disease pathology are needed to determine disease severity and monitor effects of existing and emerging new treatments on disease mechanisms. Urine samples from a small cohort of MPS-I, -II, and -VI patients (n = 12) were analyzed using label-free quantative proteomics. Fifty-three proteins including many associated with extracellular matrix organization were differently expressed. A targeted multiplexed peptide MRM LC-MS/MS assay was used on a larger validation cohort of patient samples (MPS-I n = 18, MPS-II n = 12, MPS-VI n = 6, control n = 20). MPS-I and -II groups were further subdivided according to disease severity. None of the markers assessed were altered significantly in the mild disease groups compared to controls. β-galactosidase, a lysosomal protein, was elevated 3.6-5.7-fold significantly (p < 0.05) in all disease groups apart from mild MPS-I and -II. Collagen type Iα, fatty-acid-binding-protein 5, nidogen-1, cartilage oligomeric matrix protein, and insulin-like growth factor binding protein 7 concentrations were elevated in severe MPS I and II groups. Cartilage oligomeric matrix protein, insulin-like growth factor binding protein 7, and β-galactosidase were able to distinguish the severe neurological form of MPS-II from the milder non-neurological form. Protein Heg1 was significantly raised only in MPS-VI. This work describes the discovery of new biomarkers of MPS that represent disease pathology and allows the stratification of MPS-II patients according to disease severity.

TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability

PubMed Central

Choi, Minji; Min, Yoo Hong; Pyo, Jaehyuk; Lee, Chang‐Woo; Jang, Chang‐Young

2017-01-01

Background and Purpose Chromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle assembly checkpoint (SAC). Pharmacological inhibition of Mps1 has been suggested as a cancer therapeutic; however, despite the existence of a novel Mps1 inhibitor, TC Mps1 12, no such studies have been performed. Experimental Approach The effects of TC Mps1 12 on cell viability, chromosome alignment, centrosome number, mitotic duration, apoptosis and SAC were determined in hepatocellular carcinoma (HCC) cells. In addition, the association of Mps1 expression with the overall survival of HCC patients was analysed. Key Results Treatment of human HCC cells with TC Mps1 12 led to chromosome misalignment and missegregation, and disorganization of centrosomes. Even in the presence of these errors, TC Mps1 12‐treated cells overrode the SAC, resulting in a shortened mitotic duration and mitotic slippage. This mitotic catastrophe triggered apoptosis and, finally, inhibited the growth of HCC cells. In addition, the expression of the Mps1‐encoding TTK gene was associated with poor overall survival of HCC patients. Conclusion and Implications TC Mps1 12 results in the accumulation of chromosomal instabilities and mitotic catastrophe in HCC cells. Overall, these data demonstrate that the inhibition of Mps1 kinase using TC Mps1 12 is a promising therapeutic approach for liver cancer. PMID:28299790

Myocardial Perfusion SPECT 2015 in Germany

PubMed Central

Burchert, Wolfgang; Schäfer, Wolfgang; Hacker, Marcus

2016-01-01

Summary Aim The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. Method 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. Results MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201. 78 % [79 %] of all patients were studied in PR, 14 % [15 %] in HO, and 8 % [6 %] in UH. A pharmacological stress test was performed in 43 % [39 %] (22 % [24 %] adenosine, 20 % [9 %] regadenoson, 1% [6 %] dipyridamole or dobutamine). Attenuation correction was applied in 25 % [2009: 10 %] of MPS. Gated SPECT was performed in 78 % [70 %] of all rest MPS, in 80 % [73 %] of all stress and in 76 % [67 %] of all stress and rest MPS. 53 % [33 %] of all nuclear medicine departments performed MPS scoring by default, whereas 24 % [41 %] did not apply any quantification. 31 % [26 %] of all departments noticed an increase in their counted MPS and 29 % [29 %] no changes. Data from 89 departments which participated in all surveys showed an increase in MPS count of 11.1 % (PR: 12.2 %, HO: 4.8 %, UH: 18.4 %). 70 % [60 %] of the MPS were requested by ambulatory care cardiologists. Conclusion The 2015 MPS survey reveals a high-grade adherence of routine MPS practice to current guidelines. The positive trend in MPS performance and number of MPS already observed in 2012 continues. Educational training remains necessary in the field of SPECT scoring. PMID:27909712

Mps1 Phosphorylates Its N-Terminal Extension to Relieve Autoinhibition and Activate the Spindle Assembly Checkpoint.

PubMed

Combes, Guillaume; Barysz, Helena; Garand, Chantal; Gama Braga, Luciano; Alharbi, Ibrahim; Thebault, Philippe; Murakami, Luc; Bryne, Dominic P; Stankovic, Stasa; Eyers, Patrick A; Bolanos-Garcia, Victor M; Earnshaw, William C; Maciejowski, John; Jallepalli, Prasad V; Elowe, Sabine

2018-03-19

Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC. Whether the NTE regulates other mitotic functions of Mps1 remains unknown. Here, we report that phosphorylation within the NTE contributes to Mps1 activation through relief of catalytic autoinhibition that is mediated by the NTE itself. Moreover, we find that this regulatory NTE function is independent of its role in Mps1 kinetochore recruitment. We demonstrate that the NTE autoinhibitory mechanism impinges most strongly on Mps1-dependent SAC functions and propose that Mps1 activation likely occurs sequentially through dimerization of a "prone-to-autophosphorylate" Mps1 conformer followed by autophosphorylation of the NTE prior to maximal kinase activation segment trans-autophosphorylation. Our observations underline the importance of autoregulated Mps1 activity in generation and maintenance of a robust SAC in human cells. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Evolution of sausage and helical modes in magnetized thin-foil cylindrical liners driven by a Z-pinch

NASA Astrophysics Data System (ADS)

Yager-Elorriaga, D. A.; Lau, Y. Y.; Zhang, P.; Campbell, P. C.; Steiner, A. M.; Jordan, N. M.; McBride, R. D.; Gilgenbach, R. M.

2018-05-01

In this paper, we present experimental results on axially magnetized (Bz = 0.5 - 2.0 T), thin-foil (400 nm-thick) cylindrical liner-plasmas driven with ˜600 kA by the Michigan Accelerator for Inductive Z-Pinch Experiments, which is a linear transformer driver at the University of Michigan. We show that: (1) the applied axial magnetic field, irrespective of its direction (e.g., parallel or anti-parallel to the flow of current), reduces the instability amplitude for pure magnetohydrodynamic (MHD) modes [defined as modes devoid of the acceleration-driven magneto-Rayleigh-Taylor (MRT) instability]; (2) axially magnetized, imploding liners (where MHD modes couple to MRT) generate m = 1 or m = 2 helical modes that persist from the implosion to the subsequent explosion stage; (3) the merging of instability structures is a mechanism that enables the appearance of an exponential instability growth rate for a longer than expected time-period; and (4) an inverse cascade in both the axial and azimuthal wavenumbers, k and m, may be responsible for the final m = 2 helical structure observed in our experiments. These experiments are particularly relevant to the magnetized liner inertial fusion program pursued at Sandia National Laboratories, where helical instabilities have been observed.

Assessment of Soft Vane and Metal Foam Engine Noise Reduction Concepts

NASA Technical Reports Server (NTRS)

Jones, Michael G.; Parrott, Tony L.; Sutliff, Daniel L.; Hughes, Chris

2009-01-01

Two innovative fan-noise reduction concepts developed by NASA are presented - soft vanes and over-the-rotor metal foam liners. Design methodologies are described for each concept. Soft vanes are outlet guide vanes with internal, resonant chambers that communicate with the exterior aeroacoustic environment via a porous surface. They provide acoustic absorption via viscous losses generated by interaction of unsteady flows with the internal solid structure. Over-the-rotor metal foam liners installed at or near the fan rotor axial plane provide rotor noise absorption. Both concepts also provide pressure-release surfaces that potentially inhibit noise generation. Several configurations for both concepts are evaluated with a normal incidence tube, and the results are used to guide designs for implementation in two NASA fan rigs. For soft vanes, approximately 1 to 2 dB of broadband inlet and aft-radiated fan noise reduction is achieved. For over-the-rotor metal foam liners, up to 3 dB of fan noise reduction is measured in the low-speed fan rig, but minimal reduction is measured in the high-speed fan rig. These metal foam liner results are compared with a static engine test, in which inlet sound power level reductions up to 5 dB were measured. Brief plans for further development are also provided.

Launch Vehicle Sizing Benefits Utilizing Main Propulsion System Crossfeed and Project Status

NASA Technical Reports Server (NTRS)

Chandler, Frank; Scheiern, M.; Champion, R.; Mazurkivich, P.; Lyles, Garry (Technical Monitor)

2002-01-01

To meet the goals for a next generation Reusable Launch Vehicle (RLV), a unique propulsion feed system concept was identified using crossfeed between the booster and orbiter stages that could reduce the Two-Stage-to-Orbit (TSTO) vehicle weight and Design, Development, Test and Evaluation (DDT&E) costs by approximately 25%, while increasing safety and reliability. The Main Propulsion System (MPS) crossfeed water demonstration test program addresses all activities required to reduce the risks for the MPS crossfeed system from a Technology Readiness Level (TRL) of 2 to 4 by the completion of testing and analysis by June 2003. During the initial period, that ended in March 2002, a subscale water flow test article was defined. Procurement of a subscale crossfeed check valve was initiated and the specifications for the various components were developed. The fluid transient and pressurization analytical models were developed separately and successfully integrated. The test matrix for the water flow test was developed to correlate the integrated model. A computational fluid dynamics (CFD) model of the crossfeed check valve was developed to assess flow disturbances and internal flow dynamics. Based on the results, the passive crossfeed system concept was very feasible and offered a safe system to be used in an RLV architecture. A water flow test article was designed to accommodate a wide range of flows simulating a number of different types of propellant systems. During the follow-on period, the crossfeed system model will be further refined, the test article will be completed, the water flow test will be performed, and finally the crossfeed system model will be correlated with the test data. This validated computer model will be used to predict the full-scale vehicle crossfeed system performance.

Characterization of a Putative Spindle Assembly Checkpoint Kinase Mps1, Suggests Its Involvement in Cell Division, Morphogenesis and Oxidative Stress Tolerance in Candida albicans

PubMed Central

Ruhela, Deepa; Kamthan, Ayushi; Maiti, Protiti; Datta, Asis

2014-01-01

In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys) mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC) activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus. PMID:25025778

Characterization of a putative spindle assembly checkpoint kinase Mps1, suggests its involvement in cell division, morphogenesis and oxidative stress tolerance in Candida albicans.

PubMed

Kamthan, Mohan; Nalla, Vijaya Kumar; Ruhela, Deepa; Kamthan, Ayushi; Maiti, Protiti; Datta, Asis

2014-01-01

In Saccharomyces cerevisiae MPS1 is one of the major protein kinase that governs the spindle checkpoint pathway. The S. cerevisiae structural homolog of opportunistic pathogen Candida albicans CaMPS1, is indispensable for the cell viability. The essentiality of Mps1 was confirmed by Homozygote Trisome test. To determine its biological function in this pathogen conditional mutant was generated through regulatable MET3 promoter. Examination of heterozygous and conditional (+Met/Cys) mps1 mutants revealed a mitosis specific arrest phenotype, where mutants showed large buds with undivided nuclei. Flowcytometry analysis revealed abnormal ploidy levels in mps1 mutant. In presence of anti-microtubule drug Nocodazole, mps1 mutant showed a dramatic loss of viability suggesting a role of Mps1 in Spindle Assembly Checkpoint (SAC) activation. These mutants were also defective in microtubule organization. Moreover, heterozygous mutant showed defective in-vitro yeast to hyphae morphological transition. Growth defect in heterozygous mutant suggest haploinsufficiency of this gene. qRT PCR analysis showed around 3 fold upregulation of MPS1 in presence of serum. This expression of MPS1 is dependent on Efg1 and is independent of other hyphal regulators like Ras1 and Tpk2. Furthermore, mps1 mutants were also sensitive to oxidative stress. Heterozygous mps1 mutant did not undergo morphological transition and showed 5-Fold reduction in colony forming units in response to macrophage. Thus, the vital checkpoint kinase, Mps1 besides cell division also has a role in morphogenesis and oxidative stress tolerance, in this pathogenic fungus.

Abnormal polyamine metabolism is unique to the neuropathic forms of MPS: potential for biomarker development and insight into pathogenesis.

PubMed

Hinderer, Christian; Katz, Nathan; Louboutin, Jean-Pierre; Bell, Peter; Tolar, Jakub; Orchard, Paul J; Lund, Troy C; Nayal, Mohamad; Weng, Liwei; Mesaros, Clementina; de Souza, Carolina F M; Dalla Corte, Amauri; Giugliani, Roberto; Wilson, James M

2017-10-01

The mucopolysaccharidoses (MPS) are rare genetic disorders marked by severe somatic and neurological symptoms. Development of treatments for the neurological manifestations of MPS has been hindered by the lack of objective measures of central nervous system disease burden. Identification of biomarkers for central nervous system disease in MPS patients would facilitate the evaluation of new agents in clinical trials. High throughput metabolite screening of cerebrospinal fluid (CSF) samples from a canine model of MPS I revealed a marked elevation of the polyamine, spermine, in affected animals, and gene therapy studies demonstrated that reduction of CSF spermine reflects correction of brain lesions in these animals. In humans, CSF spermine was elevated in neuropathic subtypes of MPS (MPS I, II, IIIA, IIIB), but not in subtypes in which cognitive function is preserved (MPS IVA, VI). In MPS I patients, elevated CSF spermine was restricted to patients with genotypes associated with CNS disease and was reduced following hematopoietic stem cell transplantation, which is the only therapy currently capable of improving cognitive outcomes. Additional studies in cultured neurons from MPS I mice showed that elevated spermine was essential for the abnormal neurite overgrowth exhibited by MPS neurons. These findings offer new insights into the pathogenesis of CNS disease in MPS patients, and support the use of spermine as a new biomarker to facilitate the development of next generation therapeutics for MPS. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radiographic evaluation of bones and joints in mucopolysaccharidosis I and VII dogs after neonatal gene therapy.

PubMed

Herati, Ramin Sedaghat; Knox, Van W; O'Donnell, Patricia; D'Angelo, Marina; Haskins, Mark E; Ponder, Katherine P

2008-11-01

Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the glycosaminoglycan-degrading lysosomal enzymes alpha-L-iduronidase and beta-glucuronidase, respectively, and result in abnormal bones and joints. Here, the severity of skeletal disease in MPS I and MPS VII dogs and the effects of neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal, respectively, and bone dysplasia and articular erosions, and joint subluxation were severe. Previously, we reported that neonatal intravenous injection of a retroviral vector (RV) with the appropriate gene resulted in expression in liver and blood cells, and high serum enzyme activity. In this study, we demonstrate that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of normal, respectively, and there were partial improvements of qualitative abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and 96% of normal, respectively) were not significantly different from normal dogs. Qualitative changes in MPS I bones and joints were generally modest and were partially improved with RV treatment, although cervical spine disease was severe and was difficult to correct with gene therapy in both models. The greater severity of skeletal disease in MPS VII than in MPS I dogs may reflect accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does not prevent, skeletal disease in MPS I and MPS VII dogs.

Aerothermal modeling program. Phase 2, element B: Flow interaction experiment

NASA Technical Reports Server (NTRS)

Nikjooy, M.; Mongia, H. C.; Murthy, S. N. B.; Sullivan, J. P.

1987-01-01

NASA has instituted an extensive effort to improve the design process and data base for the hot section components of gas turbine engines. The purpose of element B is to establish a benchmark quality data set that consists of measurements of the interaction of circular jets with swirling flow. Such flows are typical of those that occur in the primary zone of modern annular combustion liners. Extensive computations of the swirling flows are to be compared with the measurements for the purpose of assessing the accuracy of current physical models used to predict such flows.

Clinical characterization of cardiovascular abnormalities associated with feline mucopolysaccharidosis I and VI

PubMed Central

Sleeper, Meg M.; Kusiak, Catherine M.; Shofer, Frances S.; O’Donnell, Patricia; Bryan, Caroline; Ponder, Katherine P.; Haskins, Mark E.

2009-01-01

Summary Objective The purpose of this study was to define the cardiovascular abnormalities present in young and adult cats affected with the lysosomal storage diseases mucopolysaccharidosis (MPS) I and MPS VI. Method Eighteen cats affected with MPS I and fifteen cats affected with MPS VI were evaluated by physical examination, electrocardiography and echocardiography. Electrocardiograms were performed on all MPS I and all but 7 of the MPS VI cats. Ten unaffected cats underwent complete examinations for comparison purposes. Results No cardiovascular physical examination abnormalities were noted. ECG intervals were normal in affected cats; however, changes consistent with aberrant conduction were noted more frequently than in unaffected cats. Significant echocardiographic abnormalities included valve thickening and regurgitation (aortic and mitral) and aortic root dilation, particularly in the older cats. Conclusion As affected animals increased in age, more cardiac abnormalities were found with increasing severity. MPS I and MPS VI cats have similar cardiovascular findings to those seen in children and MPS VII dogs. PMID:18509743

Release of Mps1 from kinetochores is crucial for timely anaphase onset.

PubMed

Jelluma, Nannette; Dansen, Tobias B; Sliedrecht, Tale; Kwiatkowski, Nicholas P; Kops, Geert J P L

2010-10-18

Mps1 kinase activity is required for proper chromosome segregation during mitosis through its involvements in microtubule-chromosome attachment error correction and the mitotic checkpoint. Mps1 dynamically exchanges on unattached kinetochores but is largely removed from kinetochores in metaphase. Here we show that Mps1 promotes its own turnover at kinetochores and that removal of Mps1 upon chromosome biorientation is a prerequisite for mitotic checkpoint silencing. Inhibition of Mps1 activity increases its half-time of recovery at unattached kinetochores and causes accumulation of Mps1 protein at these sites. Strikingly, preventing dissociation of active Mps1 from kinetochores delays anaphase onset despite normal chromosome attachment and alignment, and high interkinetochore tension. This delay is marked by continued recruitment of Mad1 and Mad2 to bioriented chromosomes and is attenuated by Mad2 depletion, indicating chronic engagement of the mitotic checkpoint in metaphase. We propose that release of Mps1 from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition.

Phosphorylation of Mps1 by BRAFV600E prevents Mps1 degradation and contributes to chromosome instability in melanoma.

PubMed

Liu, J; Cheng, X; Zhang, Y; Li, S; Cui, H; Zhang, L; Shi, R; Zhao, Z; He, C; Wang, C; Zhao, H; Zhang, C; Fisk, H A; Guadagno, T M; Cui, Y

2013-02-07

Activating BRAF mutations that deregulate the mitogen-activated protein kinase (MAPK) pathway commonly occur in cancer. BRAF(V600E) induces centrosome amplification and spindle abnormalities that result in aneuploidy. We find modification of Mps1 is critical for contributing to centrosome amplification and chromosome instability induced by BRAF(V600E). Phosphorylation of Mps1 at residue S281 induced by BRAF(V600E) stabilizes Mps1 protein by preventing its ubiquitination by APC/C and subsequent degradation, allowing the non-degraded protein to accumulate at centrosomes. Cells in which endogenous Mps1 was replaced with a phospho-mimetic Mps1 mutant are viable but amplify centrosomes and missegregate chromosomes frequently. Importantly, analysis of tumor micro arrays revealed that phospho-MAPK and S281-phosphorylated Mps1 were highly correlated in human melanoma tissues, implying that MAPK contributes to defects in the degradation of Mps1 in situ. We propose that continuously activated BRAF(V600E) signaling may be a possible mechanism for the deregulation of Mps1 stability and kinase activity in human tumors, and that persistent phosphorylation of Mps1 through BRAF(V600E) signaling is a key event in disrupting the control of centrosome duplication and chromosome stability that may contribute to tumorigenesis. Our findings raise the possibility that targeting the oncogenic BRAF and S281-phosphorylated Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment.

A unique hinge binder of extremely selective aminopyridine-based Mps1 (TTK) kinase inhibitors with cellular activity.

PubMed

Kusakabe, Ken-ichi; Ide, Nobuyuki; Daigo, Yataro; Itoh, Takeshi; Yamamoto, Takahiko; Kojima, Eiichi; Mitsuoka, Yasunori; Tadano, Genta; Tagashira, Sachie; Higashino, Kenichi; Okano, Yousuke; Sato, Yuji; Inoue, Makiko; Iguchi, Motofumi; Kanazawa, Takayuki; Ishioka, Yukichi; Dohi, Keiji; Kido, Yasuto; Sakamoto, Shingo; Ando, Shigeru; Maeda, Masahiro; Higaki, Masayo; Yoshizawa, Hidenori; Murai, Hitoshi; Nakamura, Yusuke

2015-05-01

Mps1, also known as TTK, is a dual-specificity kinase that regulates the spindle assembly check point. Increased expression levels of Mps1 are observed in cancer cells, and the expression levels correlate well with tumor grade. Such evidence points to selective inhibition of Mps1 as an attractive strategy for cancer therapeutics. Starting from an aminopyridine-based lead 3a that binds to a flipped-peptide conformation at the hinge region in Mps1, elaboration of the aminopyridine scaffold at the 2- and 6-positions led to the discovery of 19c that exhibited no significant inhibition for 287 kinases as well as improved cellular Mps1 and antiproliferative activities in A549 lung carcinoma cells (cellular Mps1 IC₅₀=5.3 nM, A549 IC₅₀=26 nM). A clear correlation between cellular Mps1 and antiproliferative IC₅₀ values indicated that the antiproliferative activity observed in A549 cells would be responsible for the cellular inhibition of Mps1. The X-ray structure of 19c in complex with Mps1 revealed that this compound retains the ability to bind to the peptide flip conformation. Finally, comparative analysis of the X-ray structures of 19c, a deamino analogue 33, and a known Mps1 inhibitor bound to Mps1 provided insights into the unique binding mode at the hinge region. Copyright © 2015 Elsevier Ltd. All rights reserved.

GEOSYNTHETIC DESIGN GUIDANCE FOR HAZARDOUS WASTE LANDFILL CELLS AND SURFACE IMPOUNDMENTS

EPA Science Inventory

The report provides guidance design procedures for the use of geosynthetic materials in hazardous waste land disposal cells. Primary geosynthetic components include flexible membrane liners (FML) used to limit the flow of leachate, and leachate collection and removal systems (LCR...

High glucose increases the formation and pro-oxidative activity of endothelial microparticles.

PubMed

Burger, Dylan; Turner, Maddison; Xiao, Fengxia; Munkonda, Mercedes N; Akbari, Shareef; Burns, Kevin D

2017-09-01

Individuals with diabetes exhibit increases in circulating endothelial microparticles (eMPs, also referred to as endothelial microvesicles), which are associated with endothelial dysfunction and a heightened risk of cardiovascular complications. We have shown that eMPs are markers and mediators of vascular injury although their role in diabetes is unclear. We hypothesised that the composition and biological activity of eMPs are altered in response to high glucose exposure. We assessed the effects of high glucose on eMP formation, composition and signalling in cultured HUVECs. eMPs were isolated from the media of HUVECs cultured under conditions of normal glucose (eMP NG ), high glucose (eMP HG ) or osmotic control of L-glucose (eMP LG ). eMP size, concentration and surface charge were assessed by nanoparticle tracking analysis and flow cytometry. eMP protein composition was assessed by liquid chromatography-tandem mass spectrometry, and eMP-mediated effects on coagulation, reactive oxygen species (ROS) production and vessel function were assessed. Exposure of HUVECs to high glucose for 24 h caused a threefold increase in eMP formation, increased mean particle size (269 ± 18 nm vs 226 ± 11 nm) and decreased surface charge. Compared with eMP NG or eMP LG , eMP HG possessed approximately threefold greater pro-coagulant activity, stimulated HUVEC ROS production to a greater extent (~250% of eMP NG ) and were more potent inhibitors of endothelial-dependent relaxation. Proteomic analysis of eMPs identified 1212 independent proteins of which 68 were exclusively found in eMP HG . Gene ontology analysis revealed that eMP HG -exclusive proteins were associated with signalling pathways related to blood coagulation, cell signalling and immune cell activation. Our results indicate that elevated glucose is a potent stimulus for eMP formation that also alters their molecular composition leading to increased bioactivity. Such effects may contribute to progressive endothelial injury and subsequent cardiovascular complications in diabetes.

Phosphatidylserine on microparticles and associated cells contributes to the hypercoagulable state in diabetic kidney disease.

PubMed

Yu, Muxin; Xie, Rujuan; Zhang, Yan; Liang, Hui; Hou, Li; Yu, Chengyuan; Zhang, Jinming; Dong, Zengxiang; Tian, Ye; Bi, Yayan; Kou, Junjie; Novakovic, Valerie A; Shi, Jialan

2018-02-26

Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30). Lactadherin was used to quantify PS exposure on MPs and their original cells. Healthy blood cells (BCs) and human umbilical vein endothelial cells (HUVECs) were treated with 25, 5 or 2.5 mmol/L glucose as well as 3-12 mg/dL uric acid and cells were evaluated by clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. PS exposure and fibrin strands were observed using confocal microscopy. Using flow cytometry, we found that PS+ MPs (derived from platelets, erythrocytes, HUVECs, neutrophils, monocytes and lymphocytes) and BCs were significantly higher in patients than in controls. Furthermore, the number of PS+ MPs and BCs in patients with Ma-A was significantly higher than in patients with No-A. Similarly, we observed markedly elevated PS exposure on HUVECs cultured with serum from patients with Ma-A versus serum from patients with Mi-A or normoalbuminuria. In addition, circulating PS+ MPs cooperated with PS+ cells, contributing to markedly shortened coagulation time and dramatically increased FXa/thrombin generation and fibrin formation in each DKD group. Confocal microscopy images demonstrated colocalization of fibrin with PS on HUVECs. Moreover, blockade of exposed PS on MPs and cells with lactadherin inhibited PCA by ∼80%. In vitro, BCs and endothelial cells exposed more PS in hypoglycemia or hyperglycemia. Interestingly, reconstitution experiments showed that hypoglycemia-treated cells could be further activated or injured when recovery is obtained reaching hyperglycemia. Moreover, uric acid induced PS exposure on cells (excluding platelets) at concentrations >6 mg/dL. Linear regression analysis showed that levels of PS+ BCs and microparticles were positively correlated with uric acid and proteinuria, but negatively correlated with glomerular filtration rate. Our results suggest that PS+ MPs and MP-origin cells play procoagulant roles in patients with DKD. Blockade of PS could become a novel therapeutic modality for the prevention of thrombosis in these patients.

Device and method for imploding a microsphere with a fast liner

DOEpatents

Thode, Lester E.

1981-01-01

A device and method for relativistic electron beam heating of a high-density plasma in a small localized region. A relativistic electron beam generator or accelerator produces a high-voltage electron beam which propagates along a vacuum drift tube and is modulated to initiate electron bunching within the beam. The beam is then directed through a low-density gas chamber which provides isolation between the vacuum modulator and the relativistic electron beam target. The relativistic beam is then applied to a high-density target plasma which typically comprises DT, DD, hydrogen boron or similar thermonuclear gas at a density of 10.sup.17 to 10.sup.20 electrons per cubic centimeter. The target gas is ionized prior to application of the electron beam by means of a laser or other preionization source to form a plasma. Utilizing a relativistic electron beam with an individual particle energy exceeding 3 MeV, classical scattering by relativistic electrons passing through isolation foils is negligible. As a result, relativistic streaming instabilities are initiated within the high-density target plasma causing the relativistic electron beam to efficiently deposit its energy and momentum into a small localized region of the high-density plasma target. Fast liners disposed in the high-density target plasma are explosively or ablatively driven to implosion by a heated annular plasma surrounding the fast liner generated by an annular relativistic electron beam. An azimuthal magnetic field produced by axial current flow in the annular plasma, causes the energy in the heated annular plasma to converge on the fast liner to drive the fast liner to implode a microsphere.

Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex.

PubMed

Hewitt, Laura; Tighe, Anthony; Santaguida, Stefano; White, Anne M; Jones, Clifford D; Musacchio, Andrea; Green, Stephen; Taylor, Stephen S

2010-07-12

Mps1 is an essential component of the spindle assembly checkpoint. In this study, we describe a novel Mps1 inhibitor, AZ3146, and use it to probe the role of Mps1's catalytic activity during mitosis. When Mps1 is inhibited before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished. However, if Mps1 is inhibited after mitotic entry, the Mad1-C-Mad2 core complex remains kinetochore bound, but O-Mad2 is not recruited to the core. Although inhibiting Mps1 also interferes with chromosome alignment, we see no obvious effect on aurora B activity. In contrast, kinetochore recruitment of centromere protein E (CENP-E), a kinesin-related motor protein, is severely impaired. Strikingly, inhibition of Mps1 significantly increases its own abundance at kinetochores. Furthermore, we show that Mps1 can dimerize and transphosphorylate in cells. We propose a model whereby Mps1 transphosphorylation results in its release from kinetochores, thus facilitating recruitment of O-Mad2 and CENP-E and thereby simultaneously promoting checkpoint signaling and chromosome congression.

Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network.

PubMed

Salazar, Diego A; Rodríguez-López, Alexander; Herreño, Angélica; Barbosa, Hector; Herrera, Juliana; Ardila, Andrea; Barreto, George E; González, Janneth; Alméciga-Díaz, Carlos J

2016-02-01

Mucopolysaccharidosis (MPS) is a group of lysosomal storage diseases (LSD), characterized by the deficiency of a lysosomal enzyme responsible for the degradation of glycosaminoglycans (GAG). This deficiency leads to the lysosomal accumulation of partially degraded GAG. Nevertheless, deficiency of a single lysosomal enzyme has been associated with impairment in other cell mechanism, such as apoptosis and redox balance. Although GAG analysis represents the main biomarker for MPS diagnosis, it has several limitations that can lead to a misdiagnosis, whereby the identification of new biomarkers represents an important issue for MPS. In this study, we used a system biology approach, through the use of a genome-scale human metabolic reconstruction to understand the effect of metabolism alterations in cell homeostasis and to identify potential new biomarkers in MPS. In-silico MPS models were generated by silencing of MPS-related enzymes, and were analyzed through a flux balance and variability analysis. We found that MPS models used approximately 2286 reactions to satisfy the objective function. Impaired reactions were mainly involved in cellular respiration, mitochondrial process, amino acid and lipid metabolism, and ion exchange. Metabolic changes were similar for MPS I and II, and MPS III A to C; while the remaining MPS showed unique metabolic profiles. Eight and thirteen potential high-confidence biomarkers were identified for MPS IVB and VII, respectively, which were associated with the secondary pathologic process of LSD. In vivo evaluation of predicted intermediate confidence biomarkers (β-hexosaminidase and β-glucoronidase) for MPS IVA and VI correlated with the in-silico prediction. These results show the potential of a computational human metabolic reconstruction to understand the molecular mechanisms this group of diseases, which can be used to identify new biomarkers for MPS. Copyright © 2015. Published by Elsevier Inc.

Radiographic Evaluation of Bones and Joints in Mucopolysaccharidosis I and VII Dogs After Neonatal Gene Therapy

PubMed Central

Herati, Ramin Sedaghat; Knox, Van W.; O’Donnell, Patricia; D’Angelo, Marina; Haskins, Mark E.; Ponder, Katherine P.

2009-01-01

Mucopolysaccharidosis I (MPS I) and MPS VII are due to deficient activity of the glycosaminoglycan-degrading lysosomal enzymes α-L-iduronidase and β-glucuronidase, respectively, and result in abnormal bones and joints. Here, the severity of skeletal disease in MPS I and MPS VII dogs and the effects of neonatal gene therapy were evaluated. For untreated MPS VII dogs, the lengths of the second cervical vertebrae (C2) and the femur were only 56% and 84% of normal, respectively, and bone dysplasia and articular erosions, and joint subluxation were severe. Previously, we reported that neonatal intravenous injection of a retroviral vector (RV) with the appropriate gene resulted in expression in liver and blood cells, and high serum enzyme activity. In this study, we demonstrate that C2 and femurs of RV-treated MPS VII dogs were longer at 82% and 101% of normal, respectively, and there were partial improvements of qualitative abnormalities. For untreated MPS I dogs, the lengths of C2 and femurs (91% and 96% of normal, respectively) were not significantly different from normal dogs. Qualitative changes in MPS I bones and joints were generally modest and were partially improved with RV treatment, although cervical spine disease was severe and was difficult to correct with gene therapy in both models. The greater severity of skeletal disease in MPS VII than in MPS I dogs may reflect accumulation of chondroitin sulfate in cartilage in MPS VII, or could relate to the specific mutations. Neonatal RV-mediated gene therapy ameliorates, but does not prevent, skeletal disease in MPS I and MPS VII dogs. PMID:18707908

Laser Doppler imaging of cutaneous blood flow through transparent face masks: a necessary preamble to computer-controlled rapid prototyping fabrication with submillimeter precision.

PubMed

Allely, Rebekah R; Van-Buendia, Lan B; Jeng, James C; White, Patricia; Wu, Jingshu; Niszczak, Jonathan; Jordan, Marion H

2008-01-01

A paradigm shift in management of postburn facial scarring is lurking "just beneath the waves" with the widespread availability of two recent technologies: precise three-dimensional scanning/digitizing of complex surfaces and computer-controlled rapid prototyping three-dimensional "printers". Laser Doppler imaging may be the sensible method to track the scar hyperemia that should form the basis of assessing progress and directing incremental changes in the digitized topographical face mask "prescription". The purpose of this study was to establish feasibility of detecting perfusion through transparent face masks using the Laser Doppler Imaging scanner. Laser Doppler images of perfusion were obtained at multiple facial regions on five uninjured staff members. Images were obtained without a mask, followed by images with a loose fitting mask with and without a silicone liner, and then with a tight fitting mask with and without a silicone liner. Right and left oblique images, in addition to the frontal images, were used to overcome unobtainable measurements at the extremes of face mask curvature. General linear model, mixed model, and t tests were used for data analysis. Three hundred seventy-five measurements were used for analysis, with a mean perfusion unit of 299 and pixel validity of 97%. The effect of face mask pressure with and without the silicone liner was readily quantified with significant changes in mean cutaneous blood flow (P < .5). High valid pixel rate laser Doppler imager flow data can be obtained through transparent face masks. Perfusion decreases with the application of pressure and with silicone. Every participant measured differently in perfusion units; however, consistent perfusion patterns in the face were observed.

Validation of a New Procedure for Impedance Eduction in Flow

NASA Technical Reports Server (NTRS)

Watson, W. R.; Jones, M. G.

2010-01-01

A new impedance eduction procedure is validated by comparing the educed impedance spectrum to that of an older but well-tested eduction procedure. The older procedure requires the installation of a microphone array in the liner test section but the new procedure removes this requirement. A 12.7-mm stainless steel plate and a conventional liner consisting of a perforated plate bonded to a honeycomb core are tested. Test data is acquired from a grazing flow, impedance tube facility for a range of source frequencies and mean flow Mach numbers for which only plane waves are cut on. For the stainless steel plate, the educed admittance spectrum using the new procedure shows an improvement over that of the old procedure. This improvement shows up primarily in the educed conductance spectrum. Both eduction procedures show discrepancies in educed admittance in the mid-frequency range. Indications are that this discrepancy is triggered by an inconsistency between the measured eduction data (that contains boundary layer effects) and the two eduction models (for which the boundary layer is neglected). For the conventional liner, both eduction procedures are in very good agreement with each other. Small discrepancies occur for one or two frequencies in the mid-frequency range and for frequencies beyond the cut on frequency of higher-order duct modes. This discrepancy in the midfrequency range occurs because an automated optimizer is used to educe the impedance and the objective function used by the optimizer is extremely flat and therefore sensitive to initial starting values. The discrepancies at frequencies beyond the cut on frequency of higher order duct modes are due to the assumption of only plane waves in the impedance eduction model, although higher order modes are propagating in the impedance tube facility.

Materials Processing in Space (MPS) program description

NASA Technical Reports Server (NTRS)

1981-01-01

Insight is provided into the scientific rotationale for materials processing in space (MPS), and a comprehensive and cohesive approach for implementation and integration of the many, diverse aspects of MPS is described. The programmatic and management functions apply to all projects and activities implemented under MPS. It is intended that specific project plans, providing project unique details, will be appended to this document for endeavors such as the Space Processing Applications Rocket (SPAR) Project, the Materials Experiment Assembly (MEA) Project, the MPS/Spacelab (MPS/SL) Project, and the Materials Experiment Carrier (MEC) Payloads.

Degradation of the human mitotic checkpoint kinase Mps1 is cell cycle-regulated by APC-cCdc20 and APC-cCdh1 ubiquitin ligases.

PubMed

Cui, Yongping; Cheng, Xiaolong; Zhang, Ce; Zhang, Yanyan; Li, Shujing; Wang, Chuangui; Guadagno, Thomas M

2010-10-22

Mps1 is a dual specificity protein kinase with key roles in regulating the spindle assembly checkpoint and chromosome-microtubule attachments. Consistent with these mitotic functions, Mps1 protein levels fluctuate during the cell cycle, peaking at early mitosis and abruptly declining during mitotic exit and progression into the G(1) phase. Although evidence in budding yeast indicates that Mps1 is targeted for degradation at anaphase by the anaphase-promoting complex (APC)-c(Cdc20) complex, little is known about the regulatory mechanisms that govern Mps1 protein levels in human cells. Here, we provide evidence for the ubiquitin ligase/proteosome pathway in regulating human Mps1 levels during late mitosis through G(1) phase. First, we showed that treatment of HEK 293T cells with the proteosome inhibitor MG132 resulted in an increase in both the polyubiquitination and the accumulation of Mps1 protein levels. Next, Mps1 was shown to co-precipitate with APC and its activators Cdc20 and Cdh1 in a cell cycle-dependent manner. Consistent with this, overexpression of Cdc20 or Cdh1 led to a marked reduction of endogenous Mps1 levels during anaphase or G(1) phase, respectively. In contrast, depletion of Cdc20 or Cdh1 by RNAi treatment both led to the stabilization of Mps1 protein during mitosis or G(1) phase, respectively. Finally, we identified a single D-box motif in human Mps1 that is required for its ubiquitination and degradation. Failure to appropriately degrade Mps1 is sufficient to trigger centrosome amplification and mitotic abnormalities in human cells. Thus, our results suggest that the sequential actions of the APC-c(Cdc20) and APC-c(Cdh1) ubiquitin ligases regulate the clearance of Mps1 levels and are critical for Mps1 functions during the cell cycle in human cells.

Myocardial perfusion SPECT 2015 in Germany. Results of the 7th survey.

PubMed

Lindner, Oliver; Burchert, Wolfgang; Schäfer, Wolfgang; Hacker, Marcus

2017-02-14

The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201. 78 % [79 %] of all patients were studied in PR, 14 % [15 %] in HO, and 8 % [6 %] in UH. A pharmacological stress test was performed in 43 % [39 %] (22 % [24 %] adenosine, 20 % [9 %] regadenoson, 1 % [6 %] dipyridamole or dobutamine). Attenuation correction was applied in 25 % [2009: 10 %] of MPS. Gated SPECT was performed in 78 % [70 %] of all rest MPS, in 80 % [73 %] of all stress and in 76 % [67 %] of all stress and rest MPS. 53 % [33 %] of all nuclear medicine departments performed MPS scoring by default, whereas 24 % [41 %] did not apply any quantification. 31 % [26 %] of all departments noticed an increase in their counted MPS and 29 % [29 %] no changes. Data from 89 departments which participated in all surveys showed an increase in MPS count of 11.1 % (PR: 12.2 %, HO: 4.8 %, UH: 18.4 %). 70 % [60 %] of the MPS were requested by ambulatory care cardiologists. The 2015 MPS survey reveals a high-grade adherence of routine MPS practice to current guidelines. The positive trend in MPS performance and number of MPS already observed in 2012 continues. Educational training remains necessary in the field of SPECT scoring.

Parliamentary privilege--mortality in members of the Houses of Parliament compared with the UK general population: retrospective cohort analysis, 1945-2011.

PubMed

Dennis, John; Crayford, Tim

2015-12-14

To examine mortality in members of the two UK Houses of Parliament compared with the general population, 1945-2011. Retrospective cohort analysis of death rates and predictors of mortality in Members of Parliament (MPs) and members of the House of Lords (Lords). UK. 4950 MPs and Lords first joining the UK parliament in 1945-2011. Standardised mortality ratios, comparing all cause death rates of MPs and Lords from first election or appointment with those in the age, sex, and calendar year matched general population. Between 1945 and 2011, mortality was lower in MPs (standardised mortality ratio 0.72, 95% confidence interval 0.67 to 0.76) and Lords (0.63, 0.60 to 0.67) than in the general population. Over the same period, death rates among MPs also improved more quickly than in the general population. For every 100 expected deaths, 22 fewer deaths occurred among MPs first elected in 1990-99 compared with MPs first elected in 1945-49. Labour party MPs had 19% higher death rates compared with the general population than did Conservative MPs (relative mortality ratio 1.19, 95% confidence interval 1.01 to 1.40). The effect of political party on mortality disappeared when controlling for education level. From 1945 to 2011, MPs and Lords experienced lower mortality than the UK general population, and, at least until 1999, the mortality gap between newly elected MPs and the general population widened. Even among MPs, educational background was an important predictor of mortality, and education possibly explains much of the mortality difference between Labour and Conservative MPs. Social inequalities are alive and well in UK parliamentarians, and at least in terms of mortality, MPs are likely to have never had it so good. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Novel Marker for Purkinje Cells, Ribosomal Protein MPS1/S27: Expression of MPS1 in Human Cerebellum.

PubMed

Fernandez-Pol, J Alberto

2016-01-01

The ribosomal protein metallopanstimulin-1 (MPS1/S27) serves critical survival purposes in cell division, in normal and cancerous cells; for this reason, selective pressures of evolution have conserved the DNA sequences encoding MPS1/S27 in Archaea and Eukariotic cells. The expression of MPS1/S27 protein in human adult cerebellum has not been established. The presence of MPS1/S27, was screened in paraffin-embedded human adult brain specimens processed for tissue inmunohistochemistry. Affinity-purified specific antibodies were directed against the N-terminus of MPS1. The antibodies to MPS1 detected Purkinje cells (PC) and their dendrites. In PC, MPS1 antigen-positive staining was found in: the nucleolus, which was strongly stained; ribosomes attached to the external nuclear membrane; cytoplasm of PC, with strong staining in a punctuate fashion; the soma-attached large dendrite trunks of PC, which were MPS1 antigen-positive; and the granular cell layer, where cellular staining in a few cells that appeared to resemble smaller PC was observed. Since MPS1 is involved in cell division, DNA repair, and ribosomal biogenesis, it may be a useful antigen for studying processes such as protein synthesis, oncogenesis, regeneration, aging, and perhaps diseases of the human cerebellum. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Modulation of miR-21 signaling by MPS1 in human glioblastoma

PubMed Central

Maachani, Uday B.; Tandle, Anita; Shankavaram, Uma; Kramp, Tamalee; Camphausen, Kevin A.

2016-01-01

Monopolar spindle 1 (MPS1) is an essential spindle assembly checkpoint (SAC) kinase involved in determining spindle integrity. Beyond its mitotic functions, it has been implicated in several other signaling pathways. Our earlier studies have elaborated on role of MPS1 in glioblastoma (GBM) radiosensitization. In this study using reverse phase protein arrays (RPPAs), we assessed MPS1 mediated cell signaling pathways and demonstrated that inhibiting MPS1 could upregulate the expression of the tumor suppressor PDCD4 and MSH2 genes, by down regulating micro RNA-21 (miR-21). In GBMs miR-21 expression is significantly elevated and is associated with chemo and radioresistance. Both MPS1 and miR-21 depletion suppressed GBM cell proliferation, whereas, ectopic expression of miR-21 rescued GBM cell growth from MPS1 inhibition. Further, we demonstrate that MPS1 mediates phosphorylation of SMAD3 but not SMAD2 in GBM cells; A possible mechanism behind miR-21 modulation by MPS1. Collectively, our results shed light onto an important role of MPS1 in TGF-β/SMAD signaling via miR-21 regulation. We also, show the prognostic effect of miR-21, PDCD4 and MSH2 levels to patient survival across different GBM molecular subtypes. This scenario in which miR-21 is modulated by MPS1 inhibition may be exploited as a potential target for effective GBM therapy. PMID:25991676

Modulation of miR-21 signaling by MPS1 in human glioblastoma.

PubMed

Maachani, Uday B; Tandle, Anita; Shankavaram, Uma; Kramp, Tamalee; Camphausen, Kevin

2016-08-16

Monopolar spindle 1 (MPS1) is an essential spindle assembly checkpoint (SAC) kinase involved in determining spindle integrity. Beyond its mitotic functions, it has been implicated in several other signaling pathways. Our earlier studies have elaborated on role of MPS1 in glioblastoma (GBM) radiosensitization. In this study using reverse phase protein arrays (RPPAs), we assessed MPS1 mediated cell signaling pathways and demonstrated that inhibiting MPS1 could upregulate the expression of the tumor suppressor PDCD4 and MSH2 genes, by down regulating micro RNA-21 (miR-21). In GBMs miR-21 expression is significantly elevated and is associated with chemo and radioresistance. Both MPS1 and miR-21 depletion suppressed GBM cell proliferation, whereas, ectopic expression of miR-21 rescued GBM cell growth from MPS1 inhibition. Further, we demonstrate that MPS1 mediates phosphorylation of SMAD3 but not SMAD2 in GBM cells; A possible mechanism behind miR-21 modulation by MPS1. Collectively, our results shed light onto an important role of MPS1 in TGF-β/SMAD signaling via miR-21 regulation. We also, show the prognostic effect of miR-21, PDCD4 and MSH2 levels to patient survival across different GBM molecular subtypes. This scenario in which miR-21 is modulated by MPS1 inhibition may be exploited as a potential target for effective GBM therapy.

A putative N-terminal nuclear export sequence is sufficient for Mps1 nuclear exclusion during interphase.

PubMed

Jia, Haiwei; Zhang, Xiaojuan; Wang, Wenjun; Bai, Yuanyuan; Ling, Youguo; Cao, Cheng; Ma, Runlin Z; Zhong, Hui; Wang, Xue; Xu, Quanbin

2015-02-27

Mps1, an essential component of the mitotic checkpoint, is also an important interphase regulator and has roles in DNA damage response, cytokinesis and centrosome duplication. Mps1 predominantly resides in the cytoplasm and relocates into the nucleus at the late G2 phase. So far, the mechanism underlying the Mps1 translocation between the cytoplasm and nucleus has been unclear. In this work, a dynamic export process of Mps1 from the nucleus to cytoplasm in interphase was revealed- a process blocked by the Crm1 inhibitor, Leptomycin B, suggesting that export of Mps1 is Crm1 dependent. Consistent with this speculation, a direct association between Mps1 and Crm1 was found. Furthermore, a putative nuclear export sequence (pNES) motif at the N-terminal of Mps1 was identified by analyzing the motif of Mps1. This motif shows a high sequence similarity to the classic NES, a fusion of this motif with EGFP results in dramatic exclusion of the fusion protein from the nucleus. Additionally, Mps1 mutant loss of pNES integrity was shown by replacing leucine with alanine which produced a diffused subcellular distribution, compared to the wild type protein which resides predominantly in cytoplasm. Taken these findings together, it was concluded that the pNES sequence is sufficient for the Mps1 export from nucleus during interphase.

Flow Coupling Effects in Jet-in-Crossflow Flowfields

NASA Technical Reports Server (NTRS)

Bain, D. B.; Smith, C. E.; Liscinsky, D. S.; Holdeman, J. D.

1996-01-01

The combustor designer is typically required to design liner orifices that effectively mix air jets with crossflow effluent. CFD combustor analysis is typically used in the design process; however the jets are usually assumed to enter the combustor with a uniform velocity and turbulence profile. The jet-mainstream flow coupling is usually neglected because of the computational expense. This CFD study was performed to understand the effect of jet-mainstream flow coupling, and to assess the accuracy of jet boundary conditions that are commonly used in combustor internal calculations. A case representative of a plenum-fed quick-mix section of a Rich Burn/Quick Mix/Lean Burn combustor (i.e. a jet-mainstream mass-flow ratio of about 3 and a jet-mainstream momentum-flux ratio of about 30) was investigated. This case showed that the jet velocity entering the combustor was very non-uniform, with a low normal velocity at the leading edge of the orifice and a high normal velocity at the trailing edge of the orifice. Three different combustor-only cases were analyzed with uniform inlet jet profile. None of the cases matched the plenum-fed calculations. To assess liner thickness effects, a thin-walled case was also analyzed. The CFD analysis showed the thin-walled jets had more penetration than the thick-walled jets.

Microplastics in gut contents of coastal freshwater fish from Río de la Plata estuary.

PubMed

Pazos, Rocío S; Maiztegui, Tomás; Colautti, Darío C; Paracampo, Ariel H; Gómez, Nora

2017-09-15

The presence of microplastics (MPs) in gut contents of coastal freshwater fish of the Rio de la Plata estuary was studied. Samples were taken in six sites where 87 fish belonging to 11 species and four feeding habits were captured. Presence of MPs was verified in the 100% of fish. The fibres represented the 96% of MPs found. The number of MPs in gut contents was significantly higher close to sewage discharge. There was not found relationship between number of MPs and fish length, weight or feeding habit. The spatial differences in mean number of MPs in fish observed in this study, suggest that environmental availability of MPs could be of great importance to explain the differences found among sampling sites analysed. This work represents the first study about the interaction between MPs and aquatic organisms in this important estuarine ecosystem of South America. Copyright © 2017 Elsevier Ltd. All rights reserved.

[THROMBIN-MEDIATED EFFECTS OF BLOOD MICROPARTICLES ON FORMATION, STRUCTURE, AND STABILITY OF FIBRIN CLOTS].

PubMed

Nabiullina, R M; Mustafin, I G; Ataullakhanov, F I; Litvinov, R I; Zubairova, L D

2015-07-01

The effects of blood microparticles (MPs) on the dynamics of fibrin polymerization, clot structure and susceptibility to fibrinolysis were studied. Kinetics of fibrin polymerization, fibrinolysis, thrombin generation in platelet-free, microparticle-depleted and microparticle-depleted plasma replenished with cephalin, from healthy donors were analyzed in parallel. MPs have profound effects on all stages of fibrin formation, decrease its turbidity. All parameters obtained in the absence of MPs were recovered after reconstitution of phospholipids. Thrombin generation rates were reduced in the absence of MPs. In the presence of MPs the fibrin networks had less poro us structures with thinner fibers, while clots formed in the absence of MPs had larger pores and were built of thicker fibers. Clots formed in the presence of MPs were significantly more resistant to fibrinolysis. Results show that normally circulating MPs can support the formation of stable clots at the sites of vascular injury.

The MPS1 family of protein kinases.

PubMed

Liu, Xuedong; Winey, Mark

2012-01-01

MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways. Family members are identified by virtue of a conserved C-terminal kinase domain, though the N-terminal domain is quite divergent. The kinase domain of the human enzyme has been crystallized, revealing an unusual ATP-binding pocket. The activity, level, and subcellular localization of Mps1 family members are tightly regulated during cell-cycle progression. The mitotic functions of Mps1 kinases and their overexpression in some tumors have prompted the identification of Mps1 inhibitors and their active development as anticancer drugs.

MULTIPOLAR SPINDLE 1 (MPS1), a novel coiled-coil protein of Arabidopsis thaliana, is required for meiotic spindle organization.

PubMed

Jiang, Hua; Wang, Fen-Fei; Wu, Yu-Ting; Zhou, Xi; Huang, Xue-Yong; Zhu, Jun; Gao, Ju-Fang; Dong, Rui-Bin; Cao, Kai-Ming; Yang, Zhong-Nan

2009-09-01

The spindle is essential for chromosome segregation during meiosis, but the molecular mechanism of meiotic spindle organization in higher plants is still not well understood. Here, we report on the identification and characterization of a plant-specific protein, MULTIPOLAR SPINDLE 1 (MPS1), which is involved in spindle organization in meiocytes of Arabidopsis thaliana. The homozygous mps1 mutant exhibits male and female sterility. Light microscopy showed that mps1 mutants produced multiple uneven spores during anther development, most of which aborted in later stages. Cytological analysis showed that chromosome segregation was abnormal in mps1 meiocytes. Immunolocalization showed unequal bipolar or multipolar spindles in mps1 meiocytes, which indicated that aberrant spindles resulted in disordered chromosome segregation. MPS1 encodes a 377-amino-acid protein with putative coiled-coil motifs. In situ hybridization analysis showed that MPS1 is strongly expressed in meiocytes.

Dissimilarity of increased phosphatidylserine-positive microparticles and associated coagulation activation in acute coronary syndromes.

PubMed

Liu, Yan; He, Zhangxiu; Zhang, Yan; Dong, Zengxiang; Bi, Yayan; Kou, Junjie; Zhou, Jin; Shi, Jialan

2016-08-01

We evaluated cellular origin, numbers, and procoagulant activity of phosphatidylserine-positive microparticles (MPs) among subgroups in acute coronary syndromes (ACS). Parameters were measured on admission, days 1 (within 24 h of admission), 2, 3, and 7. All ST-elevated myocardial infarction (STEMI) patients presented more than 3 h from symptom onset and received fibrinolysis treatment; controls included unstable angina and non-STEMI patients as well as healthy controls. Phosphatidylserine-positive MPs were detected by flow cytometry, whereas procoagulant activity was assessed by coagulation time, purified coagulation complex assays, and fibrin formation. MP-induced fibrins were visualized by confocal microscopy. On admission, the total MP count was ∼2.5-fold higher in the ACS groups compared with the healthy controls (P<0.05), primarily originating from platelets and endothelial cells, and there were no significant differences among ACS subgroups. Specifically, leukocyte-derived and erythrocyte-derived MPs were higher in the STEMI group compared with unstable angina and non-STEMI groups (both P<0.05). Further, MPs from the ACS groups reduced coagulation time by 27.5% and induced intrinsic and extrinsic FXase, prothrombinase, and fibrin formation by 2.8-, 2.3-, 2.5-, and 1.7-fold, respectively (P<0.05 for all), whereas blocking phosphatidylserine with lactadherin inhibited ∼70% of procoagulant activity. MP number and concomitant coagulation decreased significantly by day 2 and continued to decrease gradually during the recovery period. This study shows that MP characteristics from circulating blood may be used as prognostic indicators to reflect the origin cell of activation and thrombophilic states found in ACS subgroups.

Association between vascular access failure and microparticles in hemodialysis patients

PubMed Central

Ryu, Jung-Hwa; Lim, Su-Young; Ryu, Dong-Ryeol; Kang, Duk-Hee; Choi, Kyu Bok; Kim, Seung-Jung

2012-01-01

Background Vascular access failure, a major cause of morbidity in hemodialysis (HD) patients, occurs mainly at stenotic endothelium following an acute thrombotic event. Microparticles (MPs) are fragments derived from injured cell membrane and are closely associated with coagulation and vascular inflammatory responses. Methods We investigated the relationship between levels of circulating MPs and vascular access patency in HD patients. A total of 82 HD patients and 28 healthy patients were enrolled. We used flow cytometry to measure endothelial MPs (EMPs) identified by CD31+CD42− or CD51+ and platelet-derived MPs (PMPs) identified by CD31+CD42+ in plasma samples of participants. Vascular access patency was defined as an interval from the time of access formation to the time of first access stenosis in each patient. MP counts were compared according to access patent duration. Results The levels of EMP (both CD31+CD42− and CD51+) and CD31+CD42+PMP were significantly higher in patients than in healthy participants. Levels of CD31+CD42−EMP and CD31+CD42+PMP showed a positive correlation. In non-diabetic HD patients, CD31+CD42−EMPs and CD31+CD42+PMPs were more elevated in the shorter access survival group (access survival <1 year) than in the longer survival group (access survival ≥ 4 years). Conclusion Elevated circulating EMP or PMP counts are influenced by end-stage renal disease and increased levels of EMP and PMP may be associated with vascular access failure in HD patients. PMID:26889407

Lack of TAFI increases brain damage and microparticle generation after thrombolytic therapy in ischemic stroke.

PubMed

Orbe, J; Alexandru, N; Roncal, C; Belzunce, M; Bibiot, P; Rodriguez, J A; Meijers, J C M; Georgescu, A; Paramo, J A

2015-08-01

Thrombin-activatable fibrinolysis inhibitor (TAFI) plays an important role in coagulation and fibrinolysis. Whereas TAFI deficiency may lead to a haemorrhagic tendency, data from TAFI knockout mice (TAFI-/-) are controversial and no differences have been reported in these animals after ischemic stroke. There are also no data regarding the role of circulating microparticles (MPs) in TAFI-/-. to examine the effect of tPA on the rate of intracranial haemorrhage (ICH) and on MPs generated in a model of ischemic stroke in TAFI-/- mice. Thrombin was injected into the middle cerebral artery (MCA) to analyse the effect of tPA (10mg/Kg) on the infarct size and haemorrhage in the absence of TAFI. Immunofluorescence for Fluoro-Jade C was performed on frozen brain slides to analyse neuronal degeneration after ischemia. MPs were isolated from mouse blood and their concentrations calculated by flow cytometry. Compared with saline, tPA significantly increased the infarct size in TAFI-/- mice (p<0.05). Although plasma fibrinolytic activity (fibrin plate assay) was higher in these animals, no macroscopic or microscopic ICH was detected. A positive signal for apoptosis and degenerating neurons was observed in the infarct area, being significantly higher in tPA treated TAFI-/- mice (p<0.05). Interestingly, higher numbers of MPs were found in TAFI-/- plasma as compared to wild type, after stroke (p<0.05). TAFI deficiency results in increased brain damage in a model of thrombolysis after ischemic stroke, which was not associated with bleeding but with neuronal degeneration and MP production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biophysical and X-ray crystallographic analysis of Mps1 kinase inhibitor complexes.

PubMed

Chu, Matthew L H; Lang, Zhaolei; Chavas, Leonard M G; Neres, João; Fedorova, Olga S; Tabernero, Lydia; Cherry, Mike; Williams, David H; Douglas, Kenneth T; Eyers, Patrick A

2010-03-02

The dual-specificity protein kinase monopolar spindle 1 (Mps1) is a central component of the mitotic spindle assembly checkpoint (SAC), a sensing mechanism that prevents anaphase until all chromosomes are bioriented on the metaphase plate. Partial depletion of Mps1 protein levels sensitizes transformed, but not untransformed, human cells to therapeutic doses of the anticancer agent Taxol, making it an attractive novel therapeutic cancer target. We have previously determined the X-ray structure of the catalytic domain of human Mps1 in complex with the anthrapyrazolone kinase inhibitor SP600125. In order to validate distinct inhibitors that target this enzyme and improve our understanding of nucleotide binding site architecture, we now report a biophysical and structural evaluation of the Mps1 catalytic domain in the presence of ATP and the aspecific model kinase inhibitor staurosporine. Collective in silico, enzymatic, and fluorescent screens also identified several new lead quinazoline Mps1 inhibitors, including a low-affinity compound termed Compound 4 (Cpd 4), whose interaction with the Mps1 kinase domain was further characterized by X-ray crystallography. A novel biophysical analysis demonstrated that the intrinsic fluorescence of SP600125 changed markedly upon Mps1 binding, allowing spectrophotometric displacement analysis and determination of dissociation constants for ATP-competitive Mps1 inhibitors. By illuminating the structure of the Mps1 ATP-binding site our results provide novel biophysical insights into Mps1-ligand interactions that will be useful for the development of specific Mps1 inhibitors, including those employing a therapeutically validated quinazoline template.

Overexpression of Mps1 in colon cancer cells attenuates the spindle assembly checkpoint and increases aneuploidy.

PubMed

Ling, Youguo; Zhang, Xiaojuan; Bai, Yuanyuan; Li, Ping; Wei, Congwen; Song, Ting; Zheng, Zirui; Guan, Kai; Zhang, Yanhong; Zhang, Buchang; Liu, Xuedong; Ma, Runlin Z; Cao, Cheng; Zhong, Hui; Xu, Quanbin

2014-08-08

The spindle assembly checkpoint kinase Mps1 is highly expressed in several types of cancers, but its cellular involvement in tumorigenesis is less defined. Herein, we confirm that Mps1 is overexpressed in colon cancer tissues. Further, we find that forced expression of Mps1 in the colon cancer cell line SW480 enables cells to become resistant to both Mps1 inhibition-induced checkpoint depletion and cell death. Overexpression of Mps1 also increases genome instability in tumor cells owing to a weakened spindle assembly checkpoint. Collectively, our findings suggest that high levels of Mps1 contribute to tumorigenesis by attenuating the spindle assembly checkpoint. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical characterization of cardiovascular abnormalities associated with feline mucopolysaccharidosis I and VI.

PubMed

Sleeper, M M; Kusiak, C M; Shofer, F S; O'Donnell, P; Bryan, C; Ponder, K P; Haskins, M E

2008-06-01

The purpose of this study was to define the cardiovascular abnormalities present in young and adult cats affected with the lysosomal storage diseases mucopolysaccharidosis (MPS) I and MPS VI. Eighteen cats affected with MPS I and 10 cats affected with MPS VI were evaluated by physical examination, electrocardiography and echocardiography. Electrocardiography (ECG) was performed on all MPS I and 9 of the MPS VI cats. Twelve unaffected cats underwent complete examinations for comparison purposes. No cardiovascular abnormalities were noted on physical examination. Measured ECG intervals were normal in affected cats; however, sinus arrhythmia was noted more frequently than in the unaffected cats. Significant echocardiographic abnormalities included aortic valve thickening, regurgitation and aortic root dilation. Significant mitral valve thickening was also noted. The severity of changes increased in older affected cats. As affected animals increased in age, more cardiac abnormalities were found with increasing severity. Significant lesions included the mitral and aortic valves and ascending aorta, but myocardial changes were not recognized. MPS I and MPS VI cats have similar cardiovascular findings to those seen in children and constitute important models for testing new MPS therapies.

Dynamic autophosphorylation of mps1 kinase is required for faithful mitotic progression.

PubMed

Wang, Xinghui; Yu, Huijuan; Xu, Leilei; Zhu, Tongge; Zheng, Fan; Fu, Chuanhai; Wang, Zhiyong; Dou, Zhen

2014-01-01

The spindle assembly checkpoint (SAC) is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression.

Structure-Based Design of Orally Bioavailable 1H-Pyrrolo[3,2-c]pyridine Inhibitors of Mitotic Kinase Monopolar Spindle 1 (MPS1)

PubMed Central

2013-01-01

The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly overexpressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology. We report the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition, leading to 65 (CCT251455). This potent and selective chemical tool stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP and substrate-peptide binding; it displays a favorable oral pharmacokinetic profile, shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model, and is an attractive tool compound to elucidate further the therapeutic potential of MPS1 inhibition. PMID:24256217

Structure-based design of orally bioavailable 1H-pyrrolo[3,2-c]pyridine inhibitors of mitotic kinase monopolar spindle 1 (MPS1).

PubMed

Naud, Sébastien; Westwood, Isaac M; Faisal, Amir; Sheldrake, Peter; Bavetsias, Vassilios; Atrash, Butrus; Cheung, Kwai-Ming J; Liu, Manjuan; Hayes, Angela; Schmitt, Jessica; Wood, Amy; Choi, Vanessa; Boxall, Kathy; Mak, Grace; Gurden, Mark; Valenti, Melanie; de Haven Brandon, Alexis; Henley, Alan; Baker, Ross; McAndrew, Craig; Matijssen, Berry; Burke, Rosemary; Hoelder, Swen; Eccles, Suzanne A; Raynaud, Florence I; Linardopoulos, Spiros; van Montfort, Rob L M; Blagg, Julian

2013-12-27

The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly overexpressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology. We report the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition, leading to 65 (CCT251455). This potent and selective chemical tool stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP and substrate-peptide binding; it displays a favorable oral pharmacokinetic profile, shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model, and is an attractive tool compound to elucidate further the therapeutic potential of MPS1 inhibition.

Dynamic Autophosphorylation of Mps1 Kinase Is Required for Faithful Mitotic Progression

PubMed Central

Wang, Xinghui; Yu, Huijuan; Xu, Leilei; Zhu, Tongge; Zheng, Fan; Fu, Chuanhai; Wang, Zhiyong; Dou, Zhen

2014-01-01

The spindle assembly checkpoint (SAC) is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression. PMID:25265012

Regulation of kinetochore recruitment of two essential mitotic spindle checkpoint proteins by Mps1 phosphorylation.

PubMed

Xu, Quanbin; Zhu, Songcheng; Wang, Wei; Zhang, Xiaojuan; Old, William; Ahn, Natalie; Liu, Xuedong

2009-01-01

Mps1 is a protein kinase that plays essential roles in spindle checkpoint signaling. Unattached kinetochores or lack of tension triggers recruitment of several key spindle checkpoint proteins to the kinetochore, which delays anaphase onset until proper attachment or tension is reestablished. Mps1 acts upstream in the spindle checkpoint signaling cascade, and kinetochore targeting of Mps1 is required for subsequent recruitment of Mad1 and Mad2 to the kinetochore. The mechanisms that govern recruitment of Mps1 or other checkpoint proteins to the kinetochore upon spindle checkpoint activation are incompletely understood. Here, we demonstrate that phosphorylation of Mps1 at T12 and S15 is required for Mps1 recruitment to the kinetochore. Mps1 kinetochore recruitment requires its kinase activity and autophosphorylation at T12 and S15. Mutation of T12 and S15 severely impairs its kinetochore association and markedly reduces recruitment of Mad2 to the kinetochore. Our studies underscore the importance of Mps1 autophosphorylation in kinetochore targeting and spindle checkpoint signaling.

Investigations of thermal barrier coatings of turbine parts using gas flame heating

NASA Astrophysics Data System (ADS)

Lepeshkin, A. R.; Bichkov, N. G.; Ilinskaja, O. I.; Nazarov, V. V.

2017-09-01

The development of methods for the calculated and experimental investigations thermal barrier coatings and thermal state of gas-turbine engine parts with a thermal barrier coatings is actual work. The gas flame heating was demonstrated to be effectively used during investigations of a thermal ceramic barrier coatings and thermal state of such gas-turbine engine parts with a TBC as the cooled turbine blades and vanes and combustion liner components. The gas-flame heating is considered to be preferable when investigating the gas-turbine engine parts with a TBC in the special cases when both the convective and radiant components of thermal flow are of great importance. The small-size rig with gas-flame flow made it possible to conduct the comparison investigations with the purpose of evaluating the efficiency of thermal protection of the ceramic deposited thermal barrier coatings on APS and EB techniques. The developed design-experiment method was introduced in bench tests of turbine blades and combustion liner components of gas turbine engines.

Spin-Projected Matrix Product States: Versatile Tool for Strongly Correlated Systems.

PubMed

Li, Zhendong; Chan, Garnet Kin-Lic

2017-06-13

We present a new wave function ansatz that combines the strengths of spin projection with the language of matrix product states (MPS) and matrix product operators (MPO) as used in the density matrix renormalization group (DMRG). Specifically, spin-projected matrix product states (SP-MPS) are constructed as [Formula: see text], where [Formula: see text] is the spin projector for total spin S and |Ψ MPS (N,M) ⟩ is an MPS wave function with a given particle number N and spin projection M. This new ansatz possesses several attractive features: (1) It provides a much simpler route to achieve spin adaptation (i.e., to create eigenfunctions of Ŝ 2 ) compared to explicitly incorporating the non-Abelian SU(2) symmetry into the MPS. In particular, since the underlying state |Ψ MPS (N,M) ⟩ in the SP-MPS uses only Abelian symmetries, one does not need the singlet embedding scheme for nonsinglet states, as normally employed in spin-adapted DMRG, to achieve a single consistent variationally optimized state. (2) Due to the use of |Ψ MPS (N,M) ⟩ as its underlying state, the SP-MPS can be closely connected to broken-symmetry mean-field states. This allows one to straightforwardly generate the large number of broken-symmetry guesses needed to explore complex electronic landscapes in magnetic systems. Further, this connection can be exploited in the future development of quantum embedding theories for open-shell systems. (3) The sum of MPOs representation for the Hamiltonian and spin projector [Formula: see text] naturally leads to an embarrassingly parallel algorithm for computing expectation values and optimizing SP-MPS. (4) Optimizing SP-MPS belongs to the variation-after-projection (VAP) class of spin-projected theories. Unlike usual spin-projected theories based on determinants, the SP-MPS ansatz can be made essentially exact simply by increasing the bond dimensions in |Ψ MPS (N,M) ⟩. Computing excited states is also simple by imposing orthogonality constraints, which are simple to implement with MPS. To illustrate the versatility of SP-MPS, we formulate algorithms for the optimization of ground and excited states, develop perturbation theory based on SP-MPS, and describe how to evaluate spin-independent and spin-dependent properties such as the reduced density matrices. We demonstrate the numerical performance of SP-MPS with applications to several models typical of strong correlation, including the Hubbard model, and [2Fe-2S] and [4Fe-4S] model complexes.

Going deeper into phosphorus adsorbents for lake restoration: Combined effects of magnetic particles, intraspecific competition and habitat heterogeneity pressure on Daphnia magna.

PubMed

Del Arco, Ana; Parra, Gema; de Vicente, Inmaculada

2018-02-01

Aquatic population responses to chemical exposure may be exacerbated by intraspecific competition pressures, being also shaped by habitat heterogeneity. Magnetic particles (MPs) have been recently proposed as promising phosphorus (P) adsorbents for lake restoration. This study focuses on assessing the effects of MPs on the abundance of the crustacean Daphnia magna under different levels of both intraspecific competition pressure and habitat heterogeneity. The experimental design consisted of two experiments (in homogeneous and heterogeneous habitats) done in glass jars with four concentrations of MPs: controls of 0g MPsL -1 , and treatments of 1, 1.5 and 2g MPsL -1 . In addition, competition treatments were established by using different population densities, and hence, no competition (C), low (L) and high (H) competition pressures were simulated. The experiments lasted for 7 days, with a 4-day pre-exposure period, in which competition was all allowed to take place, and a 3-day post-exposure period. Twenty-four hours after adding MPs, the MPs were removed by applying a magnetic separation technique. The results showed that competition pressures occurred and significantly reduced population abundances during the pre-exposure period. During the post-exposure period, the combined effects of competition and MPs were detected in both homogeneous (Ho-) and heterogeneous (He-) habitat experiments, showing a significantly drastic reduction in abundances. In fact, the lethal concentration for 50% of the population (LC 50 - 24h) was 0 and 0.16g MPsL -1 in the Ho- and He-experiments respectively, indicating that the addition and especially the removal of MPs cause extreme mortality. These results indicated that even though competition plays a role in shaping populations, its influence was down-weighted by the stronger pressures of MPs. In addition, as no significant differences between homogeneous and heterogeneous habitats were found, we may state that the refuge offered was not protective enough to avoid the effects of MPs. In conclusion, the removal of the MPs causes drastic effects on D. magna abundances despite the concentration of MPs, competition or habitat structure. Finally, considering the validated high efficiency of MPs for P removal, and in the context of a future whole-lake application, it is essential to restrict the use of MPs to the moments when D. magna is absent in the study site. Further research on the effects of MP removal on other organisms is required before implementing the addition of MPs as a restoration tool. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced Order Modeling of SLS Liquid Hydrogen Pre-Valve Flow Guide to Enable Rapid Transient Analysis

NASA Technical Reports Server (NTRS)

Brown, Andrew M.; Mulder, Andrew

2017-01-01

NASA is developing a new launch vehicle, called the Space Launch System (SLS), which is intended on taking humans out of low earth orbit to destinations including the moon, asteroids, and Mars. The propulsion system for the core stage of this vehicle includes four RS-25 Liquid Hydrogen/Oxygen rocket engines. These engines are upgraded versions of the Space Shuttle Main Engines (SSME); the upgrades include higher power levels and affordability enhancements. As with any new vehicle, the Main Propulsion System (MPS), which include the feedlines and ancillary hardware connecting the engines to the fuel and oxidizer tanks, had to be redesigned (figure 1 - export clearance in progress), as the previous MPS for the SSME's was inherently part of the Space Shuttle System, which had a completely different overall configuration.

VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes.

PubMed

Majumder, Shubhra; Slabodnick, Mark; Pike, Amanda; Marquardt, Joseph; Fisk, Harold A

2012-10-01

Centrioles are duplicated during S-phase to generate the two centrosomes that serve as mitotic spindle poles during mitosis. The centrosomal pool of the Mps1 kinase is important for centriole assembly, but how Mps1 is delivered to centrosomes is unknown. Here we have identified a centrosome localization domain within Mps1 and identified the mitochondrial porin VDAC3 as a protein that binds to this region of Mps1. Moreover, we show that VDAC3 is present at the mother centriole and modulates centriole assembly by recruiting Mps1 to centrosomes.

VDAC3 regulates centriole assembly by targeting Mps1 to centrosomes

PubMed Central

Majumder, Shubhra; Slabodnick, Mark; Pike, Amanda; Marquardt, Joseph; Fisk, Harold A.

2012-01-01

Centrioles are duplicated during S-phase to generate the two centrosomes that serve as mitotic spindle poles during mitosis. The centrosomal pool of the Mps1 kinase is important for centriole assembly, but how Mps1 is delivered to centrosomes is unknown. Here we have identified a centrosome localization domain within Mps1 and identified the mitochondrial porin VDAC3 as a protein that binds to this region of Mps1. Moreover, we show that VDAC3 is present at the mother centriole and modulates centriole assembly by recruiting Mps1 to centrosomes. PMID:22935710

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

PubMed Central

Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L.; Yao, Xuebiao

2015-01-01

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C–MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression. PMID:26240331

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment.

PubMed

Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L; Yao, Xuebiao

2015-08-18

The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.

Cancer cell–derived microparticles bearing P-selectin glycoprotein ligand 1 accelerate thrombus formation in vivo

PubMed Central

Thomas, Grace M.; Panicot-Dubois, Laurence; Lacroix, Romaric; Dignat-George, Françoise; Lombardo, Dominique

2009-01-01

Recent publications have demonstrated the presence of tissue factor (TF)–bearing microparticles (MPs) in the blood of patients suffering from cancer. However, whether these MPs are involved in thrombosis remains unknown. We show that pancreatic and lung cancer cells produce MPs that express active TF and P-selectin glycoprotein ligand 1 (PSGL-1). Cancer cell–derived MPs aggregate platelets via a TF-dependent pathway. In vivo, cancer cell–derived MPs, but not their parent cells, infused into a living mouse accumulate at the site of injury and reduce tail bleeding time and the time to occlusion of venules and arterioles. This thrombotic state is also observed in mice developing tumors. In such mice, the amount of circulating platelet-, endothelial cell–, and cancer cell–derived MPs is increased. Endogenous cancer cell–derived MPs shed from the growing tumor are able to accumulate at the site of injury. Infusion of a blocking P-selectin antibody abolishes the thrombotic state observed after injection of MPs or in mice developing a tumor. Collectively, our results indicate that cancer cell–derived MPs bearing PSGL-1 and TF play a key role in thrombus formation in vivo. Targeting these MPs could be of clinical interest in the prevention of thrombosis and to limit formation of metastasis in cancer patients. PMID:19667060

Sanfilippo syndrome: causes, consequences, and treatments

PubMed Central

Fedele, Anthony O

2015-01-01

Sanfilippo syndrome, or mucopolysaccharidosis (MPS) type III, refers to one of five autosomal recessive, neurodegenerative lysosomal storage disorders (MPS IIIA to MPS IIIE) whose symptoms are caused by the deficiency of enzymes involved exclusively in heparan sulfate degradation. The primary characteristic of MPS III is the degeneration of the central nervous system, resulting in mental retardation and hyperactivity, typically commencing during childhood. The significance of the order of events leading from heparan sulfate accumulation through to downstream changes in the levels of biomolecules within the cell and ultimately the (predominantly neuropathological) clinical symptoms is not well understood. The genes whose deficiencies cause the MPS III subtypes have been identified, and their gene products, as well as a selection of disease-causing mutations, have been characterized to varying degrees with respect to both frequency and direct biochemical consequences. A number of genetic and biochemical diagnostic methods have been developed and adopted by diagnostic laboratories. However, there is no effective therapy available for any form of MPS III, with treatment currently limited to clinical management of neurological symptoms. The availability of animal models for all forms of MPS III, whether spontaneous or generated via gene targeting, has contributed to improved understanding of the MPS III subtypes, and has provided and will deliver invaluable tools to appraise emerging therapies. Indeed, clinical trials to evaluate intrathecally-delivered enzyme replacement therapy in MPS IIIA patients, and gene therapy for MPS IIIA and MPS IIIB patients are planned or underway. PMID:26648750

Effects of polystyrene microplastics on the fitness of earthworms in an agricultural soil

NASA Astrophysics Data System (ADS)

Cao, Dongdong; Wang, Xiao; Luo, Xianxiang; Liu, Guocheng; Zheng, Hao

2017-04-01

Microplastics (MPs) pollution is widespread in the environment, while the effects of MPs on the soil organisms are poorly understood. In this study, we investigated the fitness of earthworms (E. Foetida) exposed to MPs (Polystyrene, 58 μm) in soils at the concentrations of 0, 0.25, 0.5, 1 and 2% (w/w). The results showed that MPs had little effects on the fitness of earthworms under low exposure concentrations (≤ 0.5 % (w/w)), while MPs exposure with high concentrations (i.e., 1% and 2%) significantly inhibited the growth and increased the mortality of earthworms. The results indicated that the MPs pollution in soils have an adverse effect on the fitness of soil organisms, and implied the ecological risk of MPs in terrestrial ecosystems.

Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII

PubMed Central

Rowan, Daniel J.; Tomatsu, Shunji; Grubb, Jeffrey H.; Montaño, Adriana M.; Sly, William S.

2012-01-01

Summary Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MPS have been described, no detailed analysis that compares GAGs levels and characteristics of bone by micro-CT has been done. The aims of this study were to assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA and VII), to determine the relationship between severity of bone dysplasia and serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models. Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone dysplasia, higher bone mineral density, narrowed spinal canal, and shorter sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT, radiographs and histopathology correlated with the level of KS elevation. We showed that elevated HS levels in MPS mouse models could inhibit N-acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS could be released from chondrocytes affected by accumulation of other GAGs and that KS could be useful as a biomarker for severity of bone dysplasia in MPS disorders. PMID:22971960

Structural and functional characterization of the protein kinase Mps1 in Arabidopsis thaliana.

PubMed

de Oliveira, Eduardo Alves Gamosa; Romeiro, Nelilma Correia; Ribeiro, Elane da Silva; Santa-Catarina, Claudete; Oliveira, Antônia Elenir Amâncio; Silveira, Vanildo; de Souza Filho, Gonçalo Apolinário; Venancio, Thiago Motta; Cruz, Marco Antônio Lopes

2012-01-01

In eukaryotes, protein kinases catalyze the transfer of a gamma-phosphate from ATP (or GTP) to specific amino acids in protein targets. In plants, protein kinases have been shown to participate in signaling cascades driving responses to environmental stimuli and developmental processes. Plant meristems are undifferentiated tissues that provide the major source of cells that will form organs throughout development. However, non-dividing specialized cells can also dedifferentiate and re-initiate cell division if exposed to appropriate conditions. Mps1 (Monopolar spindle) is a dual-specificity protein kinase that plays a critical role in monitoring the accuracy of chromosome segregation in the mitotic checkpoint mechanism. Although Mps1 functions have been clearly demonstrated in animals and fungi, its role in plants is so far unclear. Here, using structural and biochemical analyses here we show that Mps1 has highly similar homologs in many plant genomes across distinct lineages (e.g. AtMps1 in Arabidopsis thaliana). Several structural features (i.e. catalytic site, DFG motif and threonine triad) are clearly conserved in plant Mps1 kinases. Structural and sequence analysis also suggest that AtMps1 interact with other cell cycle proteins, such as Mad2 and MAPK1. By using a very specific Mps1 inhibitor (SP600125) we show that compromised AtMps1 activity hampers the development of A. thaliana seedlings in a dose-dependent manner, especially in secondary roots. Moreover, concomitant administration of the auxin IAA neutralizes the AtMps1 inhibition phenotype, allowing secondary root development. These observations let us to hypothesize that AtMps1 might be a downstream regulator of IAA signaling in the formation of secondary roots. Our results indicate that Mps1 might be a universal component of the Spindle Assembly Checkpoint machinery across very distant lineages of eukaryotes.

Contact lens care solutions downregulate membrane-associated mucins 1 and 16 in cultured human corneal epithelial cells and at the rat corneal surface in vivo.

PubMed

Tchedre, Kissaou; Imayasu, Masaki; Hori, Yuichi; Cavanagh, H Dwight

2013-11-01

The purpose of this study was first to evaluate the effect of multipurpose contact lens care solutions (MPSs) on the expression of membrane-associated mucins (MUC1 and MUC16) in SV40-transformed human corneal epithelial (HCE-T) cells and in vivo rat cornea. The second aim of this study was to determine the role of the common MPS additive boric acid in reducing mucin expression and release. The HCE-T cells were exposed to different concentrations of MPS-F, MPS-G, MPS-H, MPS-I, and MPS-J with 100% treatment for 30 minutes and 10% treatment for 24 hours. MUC1 and MUC16 expressions were subsequently analyzed by Western blotting. Wister rats were also subjected to MPS-A, MPS-B, MPS-C, MPS-D, and MPS-E and received phosphate-buffered saline exposure (1 drop in the right eye every 10 minutes for 1 hour). The left eye was used as control. Cornea sections and lysates were used for the immunohistochemical assay of MUC1 and MUC16 expressions. Conditioned media from treated HCE-T cells were also analyzed using Western blotting. The MPSs containing boric acid downregulated MUC1 and MUC16 in the rat cornea, whereas MPSs without boric acid had no effect as demonstrated by the Western blotting and immunohistochemical analysis. Conditioned media from MPS-containing boric acid revealed some trace of MUC16. The clinical use of MPSs containing boric acid that reduce MUC1 and MUC16 availability should be avoided. Additionally, the presence of MUC16 in the conditioned media suggests that boric acid may have enhanced cleavage of MUC16 at the cell membrane surface.

Cytotoxic and inflammatory effects of contact lens solutions on human corneal epithelial cells in vitro.

PubMed

Oh, Sarah; McCanna, David J; Subbaraman, Lakshman N; Jones, Lyndon W

2018-06-01

To ascertain the effect that four contact lens (CL) multipurpose solutions (MPS) have on the viability and release of pro-inflammatory cytokines from human corneal epithelial cells (HCEC). HCEC were exposed to four different MPS at various concentrations for 18 hours. The cells were also exposed to phosphate buffer, borate buffer, and PHMB. The cell viability was evaluated using the alamarBlue assay. The release of pro-inflammatory cytokines was measured using a Multiplex electrochemiluminescent assay. MPS-A, MPS-B and MPS-C all reduced cell metabolic activity p < 0.05 from control with MPS-A showing the greatest cytotoxic effect (maximum reduction, 90.6%). In contrast, MPS-D showed no significant reductions in cytotoxicity except at the highest concentration tested (19% reduction at 20% MPS concentration). Of the four cytokines evaluated MPS-C showed a substantial increase in the release of IL-1β, IL-6, IL-8, and TNF-α at higher concentrations when compared to control p < 0.05. At the 20% concentration of MPS-A and MPS-B the release of IL-1 β increased p < 0.05 but the release of IL-6, IL-8, and TNF-α decreased. MPS-D did not cause a change in the release of cytokines IL-1β, IL-6, IL-8 and TNF-α p > 0.05. Exposing the cells to borate buffer and PHMB caused an increase in the release of TNF-α p < 0.05. This investigation demonstrates that at different concentration levels, several of the MPS tested showed a decrease in viability and an increase in the release of inflammatory cytokines from HCEC. The borate buffer component as well as PHMB appears to contribute to this pro-inflammatory reaction. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Calculative techniques for transonic flows about certain classes of wing-body combinations, phase 2

NASA Technical Reports Server (NTRS)

Stahara, S. S.; Spreiter, J. R.

1972-01-01

Theoretical analysis and associated computer programs were developed for predicting properties of transonic flows about certain classes of wing-body combinations. The procedures used are based on the transonic equivalence rule and employ either an arbitrarily-specified solution or the local linerization method for determining the nonlifting transonic flow about the equivalent body. The class of wind planform shapes include wings having sweptback trailing edges and finite tip chord. Theoretical results are presented for surface and flow-field pressure distributions for both nonlifting and lifting situations at Mach number one.

Effect of MPS1 Inhibition on Genotoxic Stress Responses in Murine Tumour Cells.

PubMed

Suzuki, Motofumi; Yamamori, Tohru; Yasui, Hironobu; Inanami, Osamu

2016-06-01

The monopolar spindle 1 (MPS1) is a serine/threonine kinase that plays an important role in spindle assembly checkpoint signaling. To determine the possible relationship between MPS1 inhibition and genotoxic stress responses, herein we examined whether MPS1 inhibition influences cellular susceptibility towards two genotoxic treatments, etoposide and ionizing radiation (IR). Two murine tumour cell lines, SCCVII and EMT6, were used. The effect of genotoxic treatments with or without two novel MPS1 inhibitors, NMS-P715 and AZ3146, on cellular survival, cell-cycle distribution, centrosome status and mitotic catastrophe (MC) was evaluated. MPS1 inhibition sensitized murine tumour cells to etoposide but not to IR. In addition, MPS1 inhibition altered cell-cycle progression and exacerbated centrosome abnormalities, resulting in enhanced MC induced by etoposide but not by IR. MPS1 inhibition promotes the etoposide-induced aberrant mitosis and, consequently, the induction of tumour cell death. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The MPS1 Family of Protein Kinases

PubMed Central

Liu, Xuedong; Winey, Mark

2014-01-01

MPS1 protein kinases are found widely, but not ubiquitously, in eukaryotes. This family of potentially dual-specific protein kinases is among several that regulate a number of steps of mitosis. The most widely conserved MPS1 kinase functions involve activities at the kinetochore in both the chromosome attachment and the spindle checkpoint. MPS1 kinases also function at centrosomes. Beyond mitosis, MPS1 kinases have been implicated in development, cytokinesis, and several different signaling pathways. Family members are identified by virtue of a conserved C-terminal kinase domain, though the N-terminal domain is quite divergent. The kinase domain of the human enzyme has been crystallized, revealing an unusual ATP-binding pocket. The activity, level, and subcellular localization of Mps1 family members are tightly regulated during cell-cycle progression. The mitotic functions of Mps1 kinases and their overexpression in some tumors have prompted the identification of Mps1 inhibitors and their active development as anticancer drugs. PMID:22482908

Mps1/TTK: a novel target and biomarker for cancer.

PubMed

Xie, Yuan; Wang, Anqiang; Lin, Jianzhen; Wu, Liangcai; Zhang, Haohai; Yang, Xiaobo; Wan, Xueshuai; Miao, Ruoyu; Sang, Xinting; Zhao, Haitao

2017-02-01

Monopolar spindle1 (Mps1, also known as TTK) is the core component of the spindle assembly checkpoint, which functions to ensure proper distribution of chromosomes to daughter cells. Mps1 is hardly detectable in normal organs except the testis and placenta. However, high levels of Mps1 are found in many types of human malignancies, including glioblastoma, thyroid carcinoma, breast cancer, and other cancers. Several Mps1 inhibitors can inhibit the proliferation of cancer cells and exhibit demonstrable survival benefits. Mps1 can be utilized as a new immunogenic epitope, which is able to induce potent cytotoxic T lymphocyte activity against cancer cells while sparing normal cells. Some clinical trials have validated its safety, immunogenicity and clinical response. Thus, Mps1 may be a novel target for cancer therapy. Mps1 is differentially expressed between normal and malignant tissues, indicating its potential as a molecular biomarker for diagnosis. Meanwhile, the discovery that it clearly correlates with recurrence and survival time suggests it may serve as an independent prognostic biomarker as well.

Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function

PubMed Central

Sawant, Dwitiya B.; Majumder, Shubhra; Perkins, Jennifer L.; Yang, Ching-Hui; Eyers, Patrick A.; Fisk, Harold A.

2015-01-01

Centrins are a family of small, calcium-binding proteins with diverse cellular functions that play an important role in centrosome biology. We previously identified centrin 2 and centrin 3 (Cetn2 and Cetn3) as substrates of the protein kinase Mps1. However, although Mps1 phosphorylation sites control the function of Cetn2 in centriole assembly and promote centriole overproduction, Cetn2 and Cetn3 are not functionally interchangeable, and we show here that Cetn3 is both a biochemical inhibitor of Mps1 catalytic activity and a biological inhibitor of centrosome duplication. In vitro, Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. Finally, overexpression of Cetn3 reduces Mps1 Thr-676 phosphorylation at centrosomes, and mimicking Mps1-dependent phosphorylation of Cetn2 bypasses the inhibitory effect of Cetn3, suggesting that the biological effects of Cetn3 are due to the inhibition of Mps1 function at centrosomes. PMID:26354417

Centriole assembly and the role of Mps1: defensible or dispensable?

PubMed

Pike, Amanda N; Fisk, Harold A

2011-04-14

The Mps1 protein kinase is an intriguing and controversial player in centriole assembly. Originally shown to control duplication of the budding yeast spindle pole body, Mps1 is present in eukaryotes from yeast to humans, the nematode C. elegans being a notable exception, and has also been shown to regulate the spindle checkpoint and an increasing number of cellular functions relating to genomic stability. While its function in the spindle checkpoint appears to be both universally conserved and essential in most organisms, conservation of its originally described function in spindle pole duplication has proven controversial, and it is less clear whether Mps1 is essential for centrosome duplication outside of budding yeast. Recent studies of Mps1 have identified at least two distinct functions for Mps1 in centriole assembly, while simultaneously supporting the notion that Mps1 is dispensable for the process. However, the fact that at least one centrosomal substrate of Mps1 is conserved from yeast to humans down to the phosphorylation site, combined with evidence demonstrating the exquisite control exerted over centrosomal Mps1 levels suggest that the notion of being essential may not be the most important of distinctions.

Indazole-based potent and cell-active Mps1 kinase inhibitors: rational design from pan-kinase inhibitor anthrapyrazolone (SP600125).

PubMed

Kusakabe, Ken-ichi; Ide, Nobuyuki; Daigo, Yataro; Tachibana, Yuki; Itoh, Takeshi; Yamamoto, Takahiko; Hashizume, Hiroshi; Hato, Yoshio; Higashino, Kenichi; Okano, Yousuke; Sato, Yuji; Inoue, Makiko; Iguchi, Motofumi; Kanazawa, Takayuki; Ishioka, Yukichi; Dohi, Keiji; Kido, Yasuto; Sakamoto, Shingo; Yasuo, Kazuya; Maeda, Masahiro; Higaki, Masayo; Ueda, Kazuo; Yoshizawa, Hidenori; Baba, Yoshiyasu; Shiota, Takeshi; Murai, Hitoshi; Nakamura, Yusuke

2013-06-13

Monopolar spindle 1 (Mps1) is essential for centrosome duplication, the spindle assembly check point, and the maintenance of chromosomal instability. Mps1 is highly expressed in cancer cells, and its expression levels correlate with the histological grades of cancers. Thus, selective Mps1 inhibitors offer an attractive opportunity for the development of novel cancer therapies. To design novel Mps1 inhibitors, we utilized the pan-kinase inhibitor anthrapyrazolone (4, SP600125) and its crystal structure bound to JNK1. Our design efforts led to the identification of indazole-based lead 6 with an Mps1 IC50 value of 498 nM. Optimization of the 3- and 6-positions on the indazole core of 6 resulted in 23c with improved Mps1 activity (IC50 = 3.06 nM). Finally, application of structure-based design using the X-ray structure of 23d bound to Mps1 culminated in the discovery of 32a and 32b with improved potency for cellular Mps1 and A549 lung cancer cells. Moreover, 32a and 32b exhibited reasonable selectivities over 120 and 166 kinases, respectively.

Musculoskeletal pain symptoms among allied health professions' students: Prevalence rates and associated factors.

PubMed

Almhdawi, Khader A; Mathiowetz, Virgil; Al-Hourani, Zeid; Khader, Yousef; Kanaan, Saddam F; Alhasan, Mustafa

2017-11-06

Very few articles, comprehensively, investigated musculoskeletal pain symptoms (MPS) among wide variety of allied health professions (AHP) students. This study aimed to investigate the prevalence of MPS and their associated factors among different AHP majors' students. A cross-sectional design was conducted. A sample of AHP students from nine majors (n= 838, Mean age = 21.3 years) completed a validated structured self-administrated questionnaires including Nordic Musculoskeletal Questionnaire, Depression Anxiety Stress Scale (DASS 21), and specific questions regarding demographics and life style. MPS prevalence rate were compared between males and females and between majors. Logistic regression was conducted to identify predictors of MPS. MPS in neck, lower back, and shoulder 12-month were the most prevalent (67.1%, and 61.4%, 58.8% respectively). MPS prevalence was significantly higher in females and statistically different among majors. MPS were significantly associated with increased clinical training load, mental stress symptoms, and smartphone average use time. MPS in AHP students are prevalent and statistically higher among females. Students are advised to adhere to different conservative precautions and follow prevention programs. Future studies are needed to assess actual mechanisms causing MPS among AHP students and designing effective prevention programs specific to AHP students.

Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy.

PubMed

Kamalov, Marat I; Đặng, Trinh; Petrova, Natalia V; Laikov, Alexander V; Luong, Duong; Akhmadishina, Rezeda A; Lukashkin, Andrei N; Abdullin, Timur I

2018-04-01

A new self-assembled formulation of methylprednisolone succinate (MPS) based on a carboxylated trifunctional block copolymer of ethylene oxide and propylene oxide (TBC-COOH) was developed. TBC-COOH and MPS associated spontaneously at increased concentrations in aqueous solutions to form almost monodisperse mixed micelles (TBC-COOH/MPS) with a hydrodynamic diameter of 19.6 nm, zeta potential of -27.8 mV and optimal weight ratio ∼1:6.3. Conditions for the effective formation of TBC-COOH/MPS were elucidated by comparing copolymers and glucocorticoids with different structure. The micellar structure of TBC-COOH/MPS persisted upon dilution, temperature fluctuations and interaction with blood serum components. TBC-COOH increased antiradical activity of MPS and promoted its intrinsic cytotoxicity in vitro attributed to enhanced cellular availability of the mixed micelles. Intracellular transportation and hydrolysis of MPS were analyzed using optimized liquid chromatography tandem mass spectrometry with multiple reaction monitoring which showed increased level of both MPS and methylprednisolone in neuronal cells treated with the formulated glucocorticoid. Our results identify TBC-COOH/MPS as an advanced in situ prepared nanoformulation and encourage its further investigation for a potential local glucocorticoid therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Magnetic particles for in vitro molecular diagnosis: From sample preparation to integration into microsystems.

PubMed

Tangchaikeeree, Tienrat; Polpanich, Duangporn; Elaissari, Abdelhamid; Jangpatarapongsa, Kulachart

2017-10-01

Colloidal magnetic particles (MPs) have been developed in association with molecular diagnosis for several decades. MPs have the great advantage of easy manipulation using a magnet. In nucleic acid detection, these particles can act as a capture support for rapid and simple biomolecule separation. The surfaces of MPs can be modified by coating with various polymer materials to provide functionalization for different applications. The use of MPs enhances the sensitivity and specificity of detection due to the specific activity on the surface of the particles. Practical applications of MPs demonstrate greater efficiency than conventional methods. Beyond traditional detection, MPs have been successfully adopted as a smart carrier in microfluidic and lab-on-a-chip biosensors. The versatility of MPs has enabled their integration into small single detection units. MPs-based biosensors can facilitate rapid and highly sensitive detection of very small amounts of a sample. In this review, the application of MPs to the detection of nucleic acids, from sample preparation to analytical readout systems, is described. State-of-the-art integrated microsystems containing microfluidic and lab-on-a-chip biosensors for the nucleic acid detection are also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Towards a class library for mission planning

NASA Technical Reports Server (NTRS)

Pujo, Oliver; Smith, Simon T.; Starkey, Paul; Wolff, Thilo

1994-01-01

The PASTEL Mission Planning System (MPS) has been developed in C++ using an object-oriented (OO) methodology. While the scope and complexity of this system cannot compare to that of an MPS for a complex mission one of the main considerations of the development was to ensure that we could reuse some of the classes in future MPS. We present here PASTEL MPS classes which could be used in the foundations of a class library for MPS.

Structure and strength at the bonding interface of a titanium-segmented polyurethane composite through 3-(trimethoxysilyl) propyl methacrylate for artificial organs.

PubMed

Sakamoto, Harumi; Doi, Hisashi; Kobayashi, Equo; Yoneyama, Takayuki; Suzuki, Yoshiaki; Hanawa, Takao

2007-07-01

The objective of this study was to investigate the structure and strength at the bonding interface of a titanium (Ti)-segmented polyurethane (SPU) composite through (3-trimethoxysilyl) propyl methacrylate (gamma-MPS) for artificial organs. The effects of the thickness of the gamma-MPS layer on the shear bonding strength between Ti and SPU were investigated. Ti disks were immersed in various concentrations of gamma-MPS solutions for several immersion times. The depth profiles of elements and the thickness of the gamma-MPS layer were determined by glow discharge optical emission spectroscopy and ellipsometry, respectively. The bonding stress at the Ti/gamma-MPS/SPU interface was evaluated with a shear bonding test. Furthermore, the fractured surface of a Ti-SPU composite was observed by optical microscopy and characterized using X-ray photoelectron spectroscopy. Consequently, the thickness of the gamma-MPS layer was controlled by the concentration of the gamma-MPS solution and immersion time. The shear bonding stress at the interface increased with the increase of the thickness of the gamma-MPS layer. Therefore, the control of the thickness of the gamma-MPS layer is significant to increase the shear bonding stress at the Ti/gamma-MPS/SPU interface. These results are significant to create composites for artificial organs consisting of other metals and polymers. Copyright 2007 Wiley Periodicals, Inc.

CDK-dependent potentiation of MPS1 kinase activity is essential to the mitotic checkpoint.

PubMed

Morin, Violeta; Prieto, Susana; Melines, Sabrina; Hem, Sonia; Rossignol, Michel; Lorca, Thierry; Espeut, Julien; Morin, Nathalie; Abrieu, Ariane

2012-02-21

Accurate chromosome segregation relies upon a mitotic checkpoint that monitors kinetochore attachment toward opposite spindle poles before enabling chromosome disjunction [1]. The MPS1/TTK protein kinase is a core component of the mitotic checkpoint that lies upstream of MAD2 and BubR1 both at the kinetochore and in the cytoplasm [2, 3]. To gain insight into the mechanisms underlying the regulation of MPS1 kinase, we undertook the identification of Xenopus MPS1 phosphorylation sites by mass spectrometry. We mapped several phosphorylation sites onto MPS1 and we show that phosphorylation of S283 in the noncatalytic region of MPS1 is required for full kinase activity. This phosphorylation potentiates MPS1 catalytic efficiency without impairing its affinity for the substrates. By using Xenopus egg extracts depleted of endogenous MPS1 and reconstituted with single point mutants, we show that phosphorylation of S283 is essential to activate the mitotic checkpoint. This phosphorylation does not regulate the localization of MPS1 to the kinetochore but is required for the recruitment of MAD1/MAD2, demonstrating its role at the kinetochore. Constitutive phosphorylation of S283 lowers the number of kinetochores required to hold the checkpoint, which suggests that CDK-dependent phosphorylation of MPS1 is essential to sustain the mitotic checkpoint when few kinetochores remain unattached. Copyright © 2012 Elsevier Ltd. All rights reserved.

Active site mutant transgene confers tolerance to human β-glucuronidase without affecting the phenotype of MPS VII mice

PubMed Central

Sly, William S.; Vogler, Carole; Grubb, Jeffrey H.; Zhou, Mi; Jiang, Jinxing; Zhou, Xiao Yan; Tomatsu, Shunji; Bi, Yanhua; Snella, Elizabeth M.

2001-01-01

Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is an autosomal recessive lysosomal storage disorder due to an inherited deficiency of β-glucuronidase. A naturally occurring mouse model for this disease was discovered at The Jackson Laboratory and shown to be due to homozygosity for a 1-bp deletion in exon 10 of the gus gene. The murine model MPS VII (gusmps/mps) has been very well characterized and used extensively to evaluate experimental strategies for lysosomal storage diseases, including bone marrow transplantation, enzyme replacement therapy, and gene therapy. To enhance the value of this model for enzyme and gene therapy, we produced a transgenic mouse expressing the human β-glucuronidase cDNA with an amino acid substitution at the active site nucleophile (E540A) and bred it onto the MPS VII (gusmps/mps) background. We demonstrate here that the mutant mice bearing the active site mutant human transgene retain the clinical, morphological, biochemical, and histopathological characteristics of the original MPS VII (gusmps/mps) mouse. However, they are now tolerant to immune challenge with human β-glucuronidase. This “tolerant MPS VII mouse model” should be useful for preclinical trials evaluating the effectiveness of enzyme and/or gene therapy with the human gene products likely to be administered to human patients with MPS VII. PMID:11226217

The effects of environmental conditions on the enrichment of antibiotics on microplastics in simulated natural water column.

PubMed

Shen, Xian-Cheng; Li, De-Chang; Sima, Xiao-Feng; Cheng, Hui-Yuan; Jiang, Hong

2018-06-20

Concerns regarding the release of microplastics (MPs) into the environment led us to explore the relationship between the different environmental factors and physicochemical properties of MPs, as well as the change of interaction between MPs and organic pollutants. In this study, the effects of environmental factors (ageing conditions), such as pH, temperature, ionic strength, ageing time, and humic acid (HA) concentration, on the characteristics of MPs and their adsorption toward tetracycline (TC) were systematically investigated. The results showed that ageing factors such as pH, ionic strength, and temperature were found to have little impact on the adsorptive capacity of MPs for TC. However, MPs aged in HA solution exhibited a significant decreased adsorptive capacity for TC. HA, which has numerous functional groups, can cover the surface of MPs and change their hydrophobicity, thereby reducing the adsorption affinity to TC. The electrostatic repulsion between adsorbed HA and TC molecules may also decrease the adsorption of TC. In addition, the competing effect of HA for adsorption sites on the surface of MPs further reduces the adsorption of TC. The data presented in this work provide useful information for understanding the transfer of antibiotics by aged MPs, which is of fundamental importance to assess the environmental impact of MPs. Copyright © 2018 Elsevier Inc. All rights reserved.

Myocardial deformation in pediatric patients with mucopolysaccharidoses: A two-dimensional speckle tracking echocardiography study.

PubMed

Borgia, Francesco; Pezzullo, Enrica; Schiano Lomoriello, Vincenzo; Sorrentino, Regina; Lo Iudice, Francesco; Cocozza, Sara; Della Casa, Roberto; Parenti, Giancarlo; Strisciuglio, Pietro; Trimarco, Bruno; Galderisi, Maurizio

2017-02-01

Mucopolysaccharidoses (MPS) are inherited lysosomal storage disorders caused by deficiency of required glycosaminoglycans breakdown enzymes, inducing cardiac involvement. Little is known about myocardial deformation involvement in MPS. Our aim was to assess biventricular structure and function in asymptomatic children with MPS using standard echo Doppler and 2D speckle tracking (STE). Fifteen MPS children (one type I, six type II, three type III A, one III B, three IV A, one VI), asymptomatic for cardiac symptoms, and 15 age and sex-matched healthy controls underwent echo Doppler and STE. Left ventricular (LV) wall thicknesses, diameters, and mass were normalized by z-score. LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) at papillary muscles, LV twisting, and right ventricular (RV) GLS were measured. The two groups were comparable for body mass index, heart rate, and blood pressure. LV mass index and relative wall thickness were higher in MPS. Ejection fraction (EF), and s' velocity did not differ between the two groups. E/A ratio was lower and E/e' higher in MPS. Tricuspid annular plane systolic excursion, RV s' and e' were lower in MPS. LV GLS did not differ between the two groups, but GCS (P=.014), GRS (P=.023), twisting (P=.012), and RV GLS (P<.001) were lower in the MPS group. LV strain abnormalities are detectable in MPS pediatric patients, independently of MPS type, when EF is still normal. RV GLS is also involved consensually with TAPSE reduction. STE can be useful for detection of subclinical myocardial damage in MPS. © 2017, Wiley Periodicals, Inc.

Spray-Dried Thiolated Chitosan-Coated Sodium Alginate Multilayer Microparticles for Vaginal HIV Microbicide Delivery.

PubMed

Meng, Jianing; Agrahari, Vivek; Ezoulin, Miezan J; Purohit, Sudhaunshu S; Zhang, Tao; Molteni, Agostino; Dim, Daniel; Oyler, Nathan A; Youan, Bi-Botti C

2017-05-01

It is hypothesized that novel thiolated chitosan-coated multilayer microparticles (MPs) with enhanced drug loading are more mucoadhesive than uncoated MPs and safe in vivo for vaginal delivery of topical anti-HIV microbicide. Formulation optimization is achieved through a custom experimental design and the alginate (AG) MPs cores are prepared using the spray drying method. The optimal MPs are then coated with the thiolated chitosan (TCS) using a layer-by-layer method. The morphological analysis, in situ drug payload, in vitro drug release profile, and mucoadhesion potential of the MPs are carried out using scanning electron microscopy, solid-state 31 P NMR spectroscopy, UV spectroscopy, fluorescence imaging and periodic acid Schiff method, respectively. The cytotoxicity and preclinical safety of MPs are assessed on human vaginal (VK2/E6E7) and endocervical (End1/E6E7) epithelial cell lines and in female C57BL/6 mice, respectively. The results show that the MPs are successfully formulated with an average diameter ranging from 2 to 3 μm with a drug loading of 7-12% w/w. The drug release profile of these MPs primarily follows the Baker-Lonsdale and Korsmeyer-Peppas models. The MPs exhibit high mucoadhesion (20-50 folds) compared to native AGMPs. The multilayer MPs are noncytotoxic. Histological and immunochemical analysis of the mice genital tract shows neither signs of damage nor inflammatory cell infiltrate. These data highlight the potential use of TCS-coated AG-based multilayer MPs templates for the topical vaginal delivery of anti-HIV/AIDS microbicides.

Novel Method of Quantifying Radioactive Cesium-Rich Microparticles (CsMPs) in the Environment from the Fukushima Daiichi Nuclear Power Plant.

PubMed

Ikehara, Ryohei; Suetake, Mizuki; Komiya, Tatsuki; Furuki, Genki; Ochiai, Asumi; Yamasaki, Shinya; Bower, William R; Law, Gareth T W; Ohnuki, Toshihiko; Grambow, Bernd; Ewing, Rodney C; Utsunomiya, Satoshi

2018-06-05

Highly radioactive cesium-rich microparticles (CsMPs) were released from the Fukushima Daiichi nuclear power plant (FDNPP) to the surrounding environment at an early stage of the nuclear disaster in March of 2011; however, the quantity of released CsMPs remains undetermined. Here, we report a novel method to quantify the number of CsMPs in surface soils at or around Fukushima and the fraction of radioactivity they contribute, which we call "quantification of CsMPs" (QCP) and is based on autoradiography. Here, photostimulated luminescence (PSL) is linearly correlated to the radioactivity of various microparticles, with a regression coefficient of 0.0523 becquerel/PSL/h (Bq/PSL/h). In soil collected from Nagadoro, Fukushima, Japan, CsMPs were detected in soil sieved with a 114 μm mesh. There was no overlap between the radioactivities of CsMPs and clay particles adsorbing Cs. Based on the distribution of radioactivity of CsMPs, the threshold radioactivity of CsMPs in the size fraction of <114 μm was determined to be 0.06 Bq. Based on this method, the number and radioactivity fraction of CsMPs in four surface soils collected from the vicinity of the FDNPP were determined to be 48-318 particles per gram and 8.53-31.8%, respectively. The QCP method is applicable to soils with a total radioactivity as high as ∼10 6 Bq/kg. This novel method is critically important and can be used to quantitatively understand the distribution and migration of the highly radioactive CsMPs in near-surface environments surrounding Fukushima.

Effective professional intraoral tooth brushing instruction using the modified plaque score: a randomized clinical trial

PubMed Central

2018-01-01

Purpose The purpose of this study was to evaluate the efficacy of the modified plaque score (MPS) for assessing the oral hygiene status of periodontitis patients. Methods A total of 116 patients were included in this study. After evaluation of the Löe and Silness gingival index (GI), Silness and Löe plaque index (PlI), O'Leary plaque control record (PCR), and MPS, patients were randomly assigned to either a conventional tooth brushing instruction (C-TBI) group (n=56) or a professional intraoral tooth brushing instruction (P-TBI) group (n=60). The MPS and clinical parameters were re-evaluated after scaling and a series of root planing. The convergent validity of MPS with the PlI and PCR was assessed. The measurement time for MPS and PCR was compared according to the proficiency of the examiner. Results After root planing, the GI, PlI, PCR, and MPS improved from their respective baseline values in both groups. Three different plaque indices including the MPS, showed significant differences between the C-TBI group and the P-TBI group after root planing. The MPS showed significant concurrence with the PCR and PlI. The mean time for PCR measurement was 2.76±0.71 times longer than that for MPS measurement after 2 weeks of training. Conclusions MPS seems to be a practical plaque scoring system compared with the PlI and PCR. These findings suggest that repetitive plaque control combined with an easily applicable plaque index (MPS) may facilitate more effective oral hygiene education and improved periodontal health. PMID:29535888

Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

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

Xu, Jiajun; Yang, Ming; Kosterin, Paul

We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm formore » 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.« less

Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomas.

PubMed

Alizadeh, Darya; Zhang, Leying; Hwang, Jungyeon; Schluep, Thomas; Badie, Behnam

2010-04-01

The goal of this study was to evaluate the mechanism of cyclodextrin-based nanoparticle (CDP-NP) uptake into a murine glioma model. Using mixed in vitro culture systems, we demonstrated that CDP-NPs were preferentially taken up by BV2 and N9 microglia (MG) cells compared with GL261 glioma cells. Fluorescent microscopy and flow cytometry analysis of intracranial GL261 gliomas confirmed these findings and demonstrated a predominant CDP-NP uptake by macrophages (MPs) and MG within and around the tumor site. Notably, in mice bearing bilateral intracranial tumor, MG and MPs carrying CDP-NPs were able to migrate to the contralateral tumors. In conclusion, these studies better characterize the cellular distribution of CDP-NPs in intracranial tumors and demonstrate that MPs and MG could potentially be used as nanoparticle drug carriers into malignant brain tumors. The goal of this study was to evaluate the mechanism of cyclodextrin-based nanoparticle (CDP-NP) uptake into a murine glioma model. CDP-NP was preferentially taken up microglia (MG) cells as compared to glioma cells. A predominant CDP-NP uptake by macrophages and MG was also shown in and around the tumor site. Macrophages and MG could potentially be used as nanoparticle drug carriers into malignant brain tumors. Copyright 2010 Elsevier Inc. All rights reserved.

A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes

PubMed Central

Hansen, Maren F; Neckmann, Ulrike; Lavik, Liss A S; Vold, Trine; Gilde, Bodil; Toft, Ragnhild K; Sjursen, Wenche

2014-01-01

The purpose of this study was to develop a massive parallel sequencing (MPS) workflow for diagnostic analysis of mismatch repair (MMR) genes using the GS Junior system (Roche). A pathogenic variant in one of four MMR genes, (MLH1, PMS2, MSH6, and MSH2), is the cause of Lynch Syndrome (LS), which mainly predispose to colorectal cancer. We used an amplicon-based sequencing method allowing specific and preferential amplification of the MMR genes including PMS2, of which several pseudogenes exist. The amplicons were pooled at different ratios to obtain coverage uniformity and maximize the throughput of a single-GS Junior run. In total, 60 previously identified and distinct variants (substitutions and indels), were sequenced by MPS and successfully detected. The heterozygote detection range was from 19% to 63% and dependent on sequence context and coverage. We were able to distinguish between false-positive and true-positive calls in homopolymeric regions by cross-sample comparison and evaluation of flow signal distributions. In addition, we filtered variants according to a predefined status, which facilitated variant annotation. Our study shows that implementation of MPS in routine diagnostics of LS can accelerate sample throughput and reduce costs without compromising sensitivity, compared to Sanger sequencing. PMID:24689082

Methoxypyrazines biosynthesis and metabolism in grape: A review.

PubMed

Lei, Yujuan; Xie, Sha; Guan, Xueqiang; Song, Changzheng; Zhang, Zhenwen; Meng, Jiangfei

2018-04-15

This review summarizes research on the discovery, biosynthesis, accumulation, transport, and metabolism of 3-alkyl-2-methoxypyrazines (MPs) in grape. The MPs are a family of potent volatile compounds distributed throughout biological kingdoms. These compounds impart herbaceous/green/vegetal sensory attributes to certain varieties of wine. Generally, high levels of MPs in wine are derived mainly from the corresponding grapes. Although two pathways for MPs biosynthesis have been proposed, only the final step and the enzymes that catalyze it has been confirmed in grape, and the metabolic intermediates and key enzymes involved in other steps are still unknown. The limited understanding of MPs metabolism has restricted research on these compounds, and some empirical results cannot be explained by the current knowledge of MPs metabolism. This review provides insights into research on MPs biosynthesis and metabolism, and proposes directions for further research on this important class of flavour/odour compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells

PubMed Central

Daniel, Jewel; Coulter, Jonathan; Woo, Ju-Hyung; Wilsbach, Kathleen; Gabrielson, Edward

2011-01-01

Most human cancers are aneuploid and have chromosomal instability, which contrasts to the inability of human cells to normally tolerate aneuploidy. Noting that aneuploidy in human breast cancer correlates with increased expression levels of the Mps1 checkpoint gene, we investigated whether these high levels of Mps1 contribute to the ability of breast cancer cells to tolerate this aneuploidy. Reducing Mps1 levels in cultured human breast cancer cells by RNAi resulted in aberrant mitoses, induction of apoptosis, and decreased ability of human breast cancer cells to grow as xenografts in nude mice. Remarkably, breast cancer cells that survive reductions in levels of Mps1 have relatively less aneuploidy, as measured by copies of specific chromosomes, compared with cells that have constitutively high levels of Mps1. Thus, high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy. PMID:21402910

High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells.

PubMed

Daniel, Jewel; Coulter, Jonathan; Woo, Ju-Hyung; Wilsbach, Kathleen; Gabrielson, Edward

2011-03-29

Most human cancers are aneuploid and have chromosomal instability, which contrasts to the inability of human cells to normally tolerate aneuploidy. Noting that aneuploidy in human breast cancer correlates with increased expression levels of the Mps1 checkpoint gene, we investigated whether these high levels of Mps1 contribute to the ability of breast cancer cells to tolerate this aneuploidy. Reducing Mps1 levels in cultured human breast cancer cells by RNAi resulted in aberrant mitoses, induction of apoptosis, and decreased ability of human breast cancer cells to grow as xenografts in nude mice. Remarkably, breast cancer cells that survive reductions in levels of Mps1 have relatively less aneuploidy, as measured by copies of specific chromosomes, compared with cells that have constitutively high levels of Mps1. Thus, high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy.

77 FR 43071 - MPS Customer Group v. Maine Public Service Company; Notice of Complaint

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-23

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-84-000] MPS Customer Group v. Maine Public Service Company; Notice of Complaint Take notice that on July 13, 2012, pursuant..., MPS Customer Group (Complainant) filed a formal complaint against Maine Public Service Company (MPS or...

Circulating microparticles: square the circle

PubMed Central

2013-01-01

Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

MPS1 kinase as a potential therapeutic target in medulloblastoma

PubMed Central

Alimova, Irina; Ng, June; Harris, Peter; Birks, Diane; Donson, Andrew; Taylor, Michael D.; Foreman, Nicholas K.; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-01-01

Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. The SAC can be activated in aneuploid cancer cells and MPS1 is overexpressed in many types of cancers. A previous study has demonstrated the effectiveness of inhibiting MPS1 with small-molecule inhibitors, but the role of MPS1 in medulloblastoma is unknown. In the present study, we demonstrated that MPS1 inhibition by shRNA or with a small-molecule drug, NMS-P715, resulted in decreased cell growth, inhibition of clonogenic potential and induction of apoptosis in cells belonging to both the Shh and group 3 medulloblastoma genomic signature. These findings highlight MPS1 as a rational therapeutic target for medulloblastoma. PMID:27633003

A TPR domain–containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B

PubMed Central

Nijenhuis, Wilco; von Castelmur, Eleonore; Littler, Dene; De Marco, Valeria; Tromer, Eelco; Vleugel, Mathijs; van Osch, Maria H.J.; Snel, Berend

2013-01-01

The mitotic checkpoint ensures correct chromosome segregation by delaying cell cycle progression until all kinetochores have attached to the mitotic spindle. In this paper, we show that the mitotic checkpoint kinase MPS1 contains an N-terminal localization module, organized in an N-terminal extension (NTE) and a tetratricopeptide repeat (TPR) domain, for which we have determined the crystal structure. Although the module was necessary for kinetochore localization of MPS1 and essential for the mitotic checkpoint, the predominant kinetochore binding activity resided within the NTE. MPS1 localization further required HEC1 and Aurora B activity. We show that MPS1 localization to kinetochores depended on the calponin homology domain of HEC1 but not on Aurora B–dependent phosphorylation of the HEC1 tail. Rather, the TPR domain was the critical mediator of Aurora B control over MPS1 localization, as its deletion rendered MPS1 localization insensitive to Aurora B inhibition. These data are consistent with a model in which Aurora B activity relieves a TPR-dependent inhibitory constraint on MPS1 localization. PMID:23569217

A TPR domain-containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B.

PubMed

Nijenhuis, Wilco; von Castelmur, Eleonore; Littler, Dene; De Marco, Valeria; Tromer, Eelco; Vleugel, Mathijs; van Osch, Maria H J; Snel, Berend; Perrakis, Anastassis; Kops, Geert J P L

2013-04-15

The mitotic checkpoint ensures correct chromosome segregation by delaying cell cycle progression until all kinetochores have attached to the mitotic spindle. In this paper, we show that the mitotic checkpoint kinase MPS1 contains an N-terminal localization module, organized in an N-terminal extension (NTE) and a tetratricopeptide repeat (TPR) domain, for which we have determined the crystal structure. Although the module was necessary for kinetochore localization of MPS1 and essential for the mitotic checkpoint, the predominant kinetochore binding activity resided within the NTE. MPS1 localization further required HEC1 and Aurora B activity. We show that MPS1 localization to kinetochores depended on the calponin homology domain of HEC1 but not on Aurora B-dependent phosphorylation of the HEC1 tail. Rather, the TPR domain was the critical mediator of Aurora B control over MPS1 localization, as its deletion rendered MPS1 localization insensitive to Aurora B inhibition. These data are consistent with a model in which Aurora B activity relieves a TPR-dependent inhibitory constraint on MPS1 localization.

MPS1 kinase as a potential therapeutic target in medulloblastoma.

PubMed

Alimova, Irina; Ng, June; Harris, Peter; Birks, Diane; Donson, Andrew; Taylor, Michael D; Foreman, Nicholas K; Venkataraman, Sujatha; Vibhakar, Rajeev

2016-11-01

Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. The SAC can be activated in aneuploid cancer cells and MPS1 is overexpressed in many types of cancers. A previous study has demonstrated the effectiveness of inhibiting MPS1 with small-molecule inhibitors, but the role of MPS1 in medulloblastoma is unknown. In the present study, we demonstrated that MPS1 inhibition by shRNA or with a small-molecule drug, NMS-P715, resulted in decreased cell growth, inhibition of clonogenic potential and induction of apoptosis in cells belonging to both the Shh and group 3 medulloblastoma genomic signature. These findings highlight MPS1 as a rational therapeutic target for medulloblastoma.

Exploiting Conjugated Polyelectrolyte Photophysics toward Monitoring Real-Time Lipid Membrane-Surface Interaction Dynamics at the Single-Particle Level.

PubMed

Calver, Christina F; Liu, Hsiao-Wei; Cosa, Gonzalo

2015-11-03

Herein we report the real-time observation of the interaction dynamics between cationic liposomes flowing in solution and a surface-immobilized charged scaffolding formed by the deposition of conjugated polyanion poly[5-methoxy-2-(3-sulfopropoxy)-1,4-phenylenevinylene (MPS-PPV) onto 100-nm-diameter SiO2 nanoparticles (NPs). Contact of the freely floating liposomes with the polymer-coated surfaces led to the formation of supported lipid bilayers (SLBs). The interaction of the incoming liposomes with MPS-PPV adsorbed on individual SiO2 nanoparticles promoted the deaggregation of the polymer conformation and led to large emission intensity enhancements. Single-particle total internal reflection fluorescence microscopy studies exploited this phenomenon as a way to monitor the deformation dynamics of liposomes on surface-immobilized NPs. The MPS-PPV emission enhancement (up to 25-fold) reflected on the extent of membrane contact with the surface of the NP and was correlated with the size of the incoming liposome. The time required for the MPS-PPV emission to reach a maximum (ranging from 400 to 1000 ms) revealed the dynamics of membrane deformation and was also correlated with the liposome size. Cryo-TEM experiments complemented these results by yielding a structural view of the process. Immediately following the mixing of liposomes and NPs the majority of NPs had one or more adsorbed liposomes, yet the presence of a fully formed SLB was rare. Prolonged incubation of liposomes and NPs showed completely formed SLBs on all of the NPs, confirming that the liposomes eventually ruptured to form SLBs. We foresee that the single-particle studies we report herein may be readily extended to study membrane dynamics of other lipids including cellular membranes in live cell studies and to monitor the formation of polymer-cushioned SLBs.

Modern nuclear cardiac imaging in diagnosis and clinical management of patients with left ventricular dysfunction.

PubMed

Abidov, A; Hachamovitch, R; Berman, D S

2004-12-01

Congestive heart failure (CHF) has become a large social burden in modern Western society, with very high morbidity and mortality and extremely large financial costs. The largest cause of CHF is coronary heart disease, with ventricular dysfunction that may or may not be reversible by revascularization. Thus, evaluation of the viable myocardial tissue in patients with ischemic left ventricular (LV) dysfunction has important clinical and therapeutic implications. Furthermore, since patients with ventricular dysfunction are at higher operative risk, cardiologists and cardiac surgeons are commonly faced with issues regarding the balance between the potential risk vs benefit of revascularization procedures. Cardiac nuclear imaging [myocardial perfusion SPECT (MPS) and positron emission tomography (PET)] provide objective information that augments standard clinical and angiographic assessments of patients with ventricular dysfunction with respect to diagnosis (etiology), prognosis, and potential benefit from intervention. Development of the technology and methodology of gated MPS, now the routine method for MPS, allows assessment of the extent and severity of inducible ischemia as well as hypoperfused but viable myocardium, and also provides measurements of LV ejection fraction, regional wall motion, LV volume measurements, diastolic function and LV geometry. With PET, myocardial metabolism and blood flow reserve can be added to the measurements provided by nuclear cardiology procedures. This paper provides insight into the current evidence regarding settings in which nuclear cardiac imaging procedures are helpful in assessment of patients in the setting of coronary artery disease with severe LV dysfunction. A risk-benefit approach to MPS results is proposed, with principal focus on identifying patients at risk for major cardiac events who may benefit from myocardial revascularization.

Circulating cell membrane microparticles transfer heme to endothelial cells and trigger vasoocclusions in sickle cell disease.

PubMed

Camus, Stéphane M; De Moraes, João A; Bonnin, Philippe; Abbyad, Paul; Le Jeune, Sylvain; Lionnet, François; Loufrani, Laurent; Grimaud, Linda; Lambry, Jean-Christophe; Charue, Dominique; Kiger, Laurent; Renard, Jean-Marie; Larroque, Claire; Le Clésiau, Hervé; Tedgui, Alain; Bruneval, Patrick; Barja-Fidalgo, Christina; Alexandrou, Antigoni; Tharaux, Pierre-Louis; Boulanger, Chantal M; Blanc-Brude, Olivier P

2015-06-11

Intravascular hemolysis describes the relocalization of heme and hemoglobin (Hb) from erythrocytes to plasma. We investigated the concept that erythrocyte membrane microparticles (MPs) concentrate cell-free heme in human hemolytic diseases, and that heme-laden MPs have a physiopathological impact. Up to one-third of cell-free heme in plasma from 47 patients with sickle cell disease (SCD) was sequestered in circulating MPs. Erythrocyte vesiculation in vitro produced MPs loaded with heme. In silico analysis predicted that externalized phosphatidylserine (PS) in MPs may associate with and help retain heme at the cell surface. Immunohistology identified Hb-laden MPs adherent to capillary endothelium in kidney biopsies from hyperalbuminuric SCD patients. In addition, heme-laden erythrocyte MPs adhered and transferred heme to cultured endothelial cells, inducing oxidative stress and apoptosis. In transgenic SAD mice, infusion of heme-laden MPs triggered rapid vasoocclusions in kidneys and compromised microvascular dilation ex vivo. These vascular effects were largely blocked by heme-scavenging hemopexin and by the PS antagonist annexin-a5, in vitro and in vivo. Adversely remodeled MPs carrying heme may thus be a source of oxidant stress for the endothelium, linking hemolysis to vascular injury. This pathway might provide new targets for the therapeutic preservation of vascular function in SCD. © 2015 by The American Society of Hematology.

Mps1 (Monopolar Spindle 1) Protein Inhibition Affects Cellular Growth and Pro-Embryogenic Masses Morphology in Embryogenic Cultures of Araucaria angustifolia (Araucariaceae).

PubMed

Douétts-Peres, Jackellinne C; Cruz, Marco Antônio L; Reis, Ricardo S; Heringer, Angelo S; de Oliveira, Eduardo A G; Elbl, Paula M; Floh, Eny I S; Silveira, Vanildo; Santa-Catarina, Claudete

2016-01-01

Somatic embryogenesis has been shown to be an efficient tool for studying processes based on cell growth and development. The fine regulation of the cell cycle is essential for proper embryo formation during the process of somatic embryogenesis. The aims of the present work were to identify and perform a structural and functional characterization of Mps1 and to analyze the effects of the inhibition of this protein on cellular growth and pro-embryogenic mass (PEM) morphology in embryogenic cultures of A. angustifolia. A single-copy Mps1 gene named AaMps1 was retrieved from the A. angustifolia transcriptome database, and through a mass spectrometry approach, AaMps1 was identified and quantified in embryogenic cultures. The Mps1 inhibitor SP600125 (10 μM) inhibited cellular growth and changed PEMs, and these effects were accompanied by a reduction in AaMps1 protein levels in embryogenic cultures. Our work has identified the Mps1 protein in a gymnosperm species for the first time, and we have shown that inhibiting Mps1 affects cellular growth and PEM differentiation during A. angustifolia somatic embryogenesis. These data will be useful for better understanding cell cycle control during somatic embryogenesis in plants.

AAV Gene Therapy for MPS1-associated Corneal Blindness.

PubMed

Vance, Melisa; Llanga, Telmo; Bennett, Will; Woodard, Kenton; Murlidharan, Giridhar; Chungfat, Neil; Asokan, Aravind; Gilger, Brian; Kurtzberg, Joanne; Samulski, R Jude; Hirsch, Matthew L

2016-02-22

Although cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent, and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA, and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness.

Mps1 (Monopolar Spindle 1) Protein Inhibition Affects Cellular Growth and Pro-Embryogenic Masses Morphology in Embryogenic Cultures of Araucaria angustifolia (Araucariaceae)

PubMed Central

Douétts-Peres, Jackellinne C.; Cruz, Marco Antônio L.; Reis, Ricardo S.; Heringer, Angelo S.; de Oliveira, Eduardo A. G.; Elbl, Paula M.; Floh, Eny I. S.; Silveira, Vanildo

2016-01-01

Somatic embryogenesis has been shown to be an efficient tool for studying processes based on cell growth and development. The fine regulation of the cell cycle is essential for proper embryo formation during the process of somatic embryogenesis. The aims of the present work were to identify and perform a structural and functional characterization of Mps1 and to analyze the effects of the inhibition of this protein on cellular growth and pro-embryogenic mass (PEM) morphology in embryogenic cultures of A. angustifolia. A single-copy Mps1 gene named AaMps1 was retrieved from the A. angustifolia transcriptome database, and through a mass spectrometry approach, AaMps1 was identified and quantified in embryogenic cultures. The Mps1 inhibitor SP600125 (10 μM) inhibited cellular growth and changed PEMs, and these effects were accompanied by a reduction in AaMps1 protein levels in embryogenic cultures. Our work has identified the Mps1 protein in a gymnosperm species for the first time, and we have shown that inhibiting Mps1 affects cellular growth and PEM differentiation during A. angustifolia somatic embryogenesis. These data will be useful for better understanding cell cycle control during somatic embryogenesis in plants. PMID:27064899

AAV Gene Therapy for MPS1-associated Corneal Blindness

PubMed Central

Vance, Melisa; Llanga, Telmo; Bennett, Will; Woodard, Kenton; Murlidharan, Giridhar; Chungfat, Neil; Asokan, Aravind; Gilger, Brian; Kurtzberg, Joanne; Samulski, R. Jude; Hirsch, Matthew L.

2016-01-01

Although cord blood transplantation has significantly extended the lifespan of mucopolysaccharidosis type 1 (MPS1) patients, over 95% manifest cornea clouding with about 50% progressing to blindness. As corneal transplants are met with high rejection rates in MPS1 children, there remains no treatment to prevent blindness or restore vision in MPS1 children. Since MPS1 is caused by mutations in idua, which encodes alpha-L-iduronidase, a gene addition strategy to prevent, and potentially reverse, MPS1-associated corneal blindness was investigated. Initially, a codon optimized idua cDNA expression cassette (opt-IDUA) was validated for IDUA production and function following adeno-associated virus (AAV) vector transduction of MPS1 patient fibroblasts. Then, an AAV serotype evaluation in human cornea explants identified an AAV8 and 9 chimeric capsid (8G9) as most efficient for transduction. AAV8G9-opt-IDUA administered to human corneas via intrastromal injection demonstrated widespread transduction, which included cells that naturally produce IDUA, and resulted in a >10-fold supraphysiological increase in IDUA activity. No significant apoptosis related to AAV vectors or IDUA was observed under any conditions in both human corneas and MPS1 patient fibroblasts. The collective preclinical data demonstrate safe and efficient IDUA delivery to human corneas, which may prevent and potentially reverse MPS1-associated cornea blindness. PMID:26899286

Improving the water solubility of Monascus pigments under acidic conditions with gum arabic.

PubMed

Jian, Wenjie; Sun, Yuanming; Wu, Jian-Yong

2017-07-01

Monascus pigments (Mps) are natural food colorants and their stability in acidic solutions is important for application in the food industry. This study aimed to evaluate the use of gum arabic (GA) as a stabilizer for maintaining the solubility of Mps in an acidic aqueous solution exposed to a high temperature, and to analyze the molecular interactions between GA and Mps. Mps dispersed (0.2 g kg -1 ) in deionized water at pH 3.0-4.0 without GA formed precipitates but remained in a stable solution in the presence of GA (1 g kg -1 ). The significant improvement of Mps water solubility under acidic conditions was attributed to the formation of Mps-GA complexes, as indicated by a sharp increase in the fluorescence intensity. The results on particle size, zeta potential, and transmission electron microscopy further suggested that molecular binding of Mps to GA, electrostatic repulsion, and steric hindrance of GA were contributing factors to preventing the aggregation of Mps in acidic solutions. A mechanistic model was presented for GA-Mps interactions and complex structures. GA was proven to be an effective stabilizer of natural food colorants in acidic solutions. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Evaluation of Disease Lesions in the Developing Canine MPS IIIA Brain.

PubMed

Winner, Leanne K; Marshall, Neil R; Jolly, Robert D; Trim, Paul J; Duplock, Stephen K; Snel, Marten F; Hemsley, Kim M

2018-06-20

Mucopolysaccharidosis IIIA (MPS IIIA) is an inherited neurodegenerative disease of childhood that results in early death. Post-mortem studies have been carried out on human MPS IIIA brain, but little is known about early disease development. Here, we utilised the Huntaway dog model of MPS IIIA to evaluate disease lesion development from 2 to 24 weeks of age. A significant elevation in primarily stored heparan sulphate was observed in all brain regions assessed in MPS IIIA pups ≤9.5 weeks of age. There was a significant elevation in secondarily stored ganglioside (GM3 36:1) in ≤9.5-week-old MPS IIIA pup cerebellum, and other brain regions also exhibited accumulation of this lipid with time. The number of neural stem cells and neuronal precursor cells was essentially unchanged in MPS IIIA dog brain (c.f. unaffected) over the time course assessed, a finding corroborated by neuron cell counts. We observed early neuroinflammatory changes in young MPS IIIA pup brain, with significantly increased numbers of activated microglia recorded in all but one brain region in MPS IIIA pups ≤9.5 weeks of age (c.f. age-matched unaffected pups). In conclusion, infant-paediatric-stage MPS IIIA canine brain exhibits substantial and progressive primary and secondary substrate accumulation, coupled with early and robust microgliosis. Whilst early initiation of treatment is likely to be required to maintain optimal neurological function, the brain's neurodevelopmental potential appears largely unaffected by the disease process; further investigations confirming this are warranted.

Newborn screening for mucopolysaccharidoses: A pilot study of measurement of glycosaminoglycans by tandem mass spectrometry

PubMed Central

Kubaski, Francyne; Mason, Robert W.; Nakatomi, Akiko; Shintaku, Haruo; Xie, Li; van Vlies, Naomi N.; Church, Heather; Giugliani, Roberto; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao; Fukao, Toshiyuki; Montaño, Adriana M.; Tomatsu, Shunji

2016-01-01

BACKGROUND Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible in skeletal, visceral and/or brain damage, highlighting a need for early diagnosis. METHODS This pilot study analyzed 2,862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. RESULTS The cutoffs were as follows: HS-0S> 90ng/mL; HS-NS> 23 ng/mL, DS> 88 ng/mL; mono-sulfated KS> 445 ng/mL; di-sulfated KS> 89 ng/mL and ratio di-KS in total KS> 32%. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03% based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9% based upon a combination of HS-0S and HS-NS. CONCLUSIONS Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS. PMID:27718145

Microparticles and infectious diseases.

PubMed

Delabranche, X; Berger, A; Boisramé-Helms, J; Meziani, F

2012-08-01

Membrane shedding with microvesicle (MV) release after membrane budding due to cell stimulation is a highly conserved intercellular interplay. MV can be released by micro-organisms or by host cells in the course of infectious diseases. Host MVs are divided according to cell compartment origin in microparticles (MPs) from plasma membrane and exosomes from intracellular membranes. MPs are cell fragments resulting from plasma membrane reorganization characterized by phosphatidylserine (PhtdSer) content and parental cell antigens on membrane. The role of MPs in physiology and pathophysiology is not yet well elucidated; they are a pool of bioactive molecules able to transmit a pro-inflammatory message to neighboring or target cells. The first acknowledged function of MP was the dissemination of a procoagulant potential via PhtdSer and it is now obvious than MPs bear tissue factor (TF). Such MPs have been implicated in the coagulation disorders observed during sepsis and septic shock. MPs have been implicated in the regulation of vascular tone and cardiac dysfunction in experimental sepsis. Beside a non-specific role, pathogens such as Neisseria meningitidis and Ebola Virus can specifically activate blood coagulation after TF-bearing MPs release in the bloodstream with disseminated intravascular coagulopathy and Purpura fulminans. The role of MPs in host-pathogen interactions is also fundamental in Chagas disease, where MPs could allow immune evasion by inhibiting C3 convertase. During cerebral malaria, MPs play a complex role facilitating the activation of brain endothelium that contributes to amplify vascular obstruction by parasitized erythrocytes. Phagocytosis of HIV induced MPs expressing PhtdSer by monocytes/macrophages results in cellular infection and non-inflammatory response via up-regulation of TGF-β. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia.

PubMed

Nor, Azimah; Zabedah, Md Yunus; Norsiah, Md Desa; Ngu, Lock Hock; Suhaila, Abd Rahman

2010-06-01

Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.

Inhibition of HeLa cell growth by doxorubicin-loaded and tuftsin-conjugated arginate-PEG microparticles.

PubMed

Hu, Tianmu; Qahtan, Anwar Saeed Ahmed; Lei, Lei; Lei, Zhixin; Zhao, Dapeng; Nie, Hemin

2018-03-01

In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance, poly(ethylene glycol amine) (PEG)-modified alginate microparticles (ALG-PEG MPs) were developed then two different mechanisms were employed to load doxorubicin (Dox): 1) forming Dox/ALG-PEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG; 2) forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG, respectively. Additionally, tuftsin (TFT), a natural immunomodulation peptide, was conjugated to MPs in order to enhance the efficiency of cellular uptake. It was found that the Dox-ALG-PEG-TFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium, suggesting the role of covalent bonding in prolonging Dox retention. Besides, the release of Dox from these MPs was pH-sensitive, and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4. Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs, their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h, implying the effectiveness of TFT in enhancing cellular uptake of MPs. Over a period of 48 h, Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant ( p  > 0.05). In consideration of the prolonged and sustained release of Dox, Dox-ALG-PEG-TFT MPs possess the advantages for long-term treatment.

Newborn screening for mucopolysaccharidoses: a pilot study of measurement of glycosaminoglycans by tandem mass spectrometry.

PubMed

Kubaski, Francyne; Mason, Robert W; Nakatomi, Akiko; Shintaku, Haruo; Xie, Li; van Vlies, Naomi N; Church, Heather; Giugliani, Roberto; Kobayashi, Hironori; Yamaguchi, Seiji; Suzuki, Yasuyuki; Orii, Tadao; Fukao, Toshiyuki; Montaño, Adriana M; Tomatsu, Shunji

2017-01-01

Mucopolysaccharidoses (MPS) are a group of inborn errors of metabolism that are progressive and usually result in irreversible skeletal, visceral, and/or brain damage, highlighting a need for early diagnosis. This pilot study analyzed 2862 dried blood spots (DBS) from newborns and 14 DBS from newborn patients with MPS (MPS I, n = 7; MPS II, n = 2; MPS III, n = 5). Disaccharides were produced from polymer GAGs by digestion with chondroitinase B, heparitinase, and keratanase II. Heparan sulfate (0S, NS), dermatan sulfate (DS) and mono- and di-sulfated KS were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). Median absolute deviation (MAD) was used to determine cutoffs to distinguish patients from controls. Cutoffs were defined as median + 7× MAD from general newborns. The cutoffs were as follows: HS-0S > 90 ng/mL; HS-NS > 23 ng/mL, DS > 88 ng/mL; mono-sulfated KS > 445 ng/mL; di-sulfated KS > 89 ng/mL and ratio di-KS in total KS > 32 %. All MPS I and II samples were above the cutoffs for HS-0S, HS-NS, and DS, and all MPS III samples were above cutoffs for HS-0S and HS-NS. The rate of false positives for MPS I and II was 0.03 % based on a combination of HS-0S, HS-NS, and DS, and for MPS III was 0.9 % based upon a combination of HS-0S and HS-NS. Combination of levels of two or more different GAGs improves separation of MPS patients from unaffected controls, indicating that GAG measurements are potentially valuable biomarkers for newborn screening for MPS.

The density-matrix renormalization group: a short introduction.

PubMed

Schollwöck, Ulrich

2011-07-13

The density-matrix renormalization group (DMRG) method has established itself over the last decade as the leading method for the simulation of the statics and dynamics of one-dimensional strongly correlated quantum lattice systems. The DMRG is a method that shares features of a renormalization group procedure (which here generates a flow in the space of reduced density operators) and of a variational method that operates on a highly interesting class of quantum states, so-called matrix product states (MPSs). The DMRG method is presented here entirely in the MPS language. While the DMRG generally fails in larger two-dimensional systems, the MPS picture suggests a straightforward generalization to higher dimensions in the framework of tensor network states. The resulting algorithms, however, suffer from difficulties absent in one dimension, apart from a much more unfavourable efficiency, such that their ultimate success remains far from clear at the moment.

Lentiviral-mediated gene therapy results in sustained expression of β-glucuronidase for up to 12 months in the gus(mps/mps) and up to 18 months in the gus(tm(L175F)Sly) mouse models of mucopolysaccharidosis type VII.

PubMed

Derrick-Roberts, Ainslie L K; Pyragius, Carmen E; Kaidonis, Xenia M; Jackson, Matilda R; Anson, Donald S; Byers, Sharon

2014-09-01

A number of mucopolysaccharidosis type VII (MPS VII) mouse models with different levels of residual enzyme activity have been created replicating the range of clinical phenotypes observed in human MPS VII patients. In this study, a lentivirus encoding murine β-glucuronidase was administered intravenously at birth to both the severe (Gus(mps/mps) strain) and attenuated (Gus(tm(L175F)Sly) strain) mouse models of MPS VII. Circulating enzyme levels were normalized in the Gus(mps/mps) mice and were 3.5-fold higher than normal in the Gus(tm(L175F)Sly) mouse 12 and 18 months after administration. Tissue β-glucuronidase activity increased over untreated levels in all tissues evaluated in both strains at 12 months, and the elevated level was maintained in Gus(tm(L175F)Sly) tissues at 18 months. These elevated enzyme levels reduced glycosaminoglycan storage in the liver, spleen, kidney, and heart in both models. Bone mineral volume decreased toward normal in both models after 12 months of therapy and after 18 months in the Gus(tm(L175F)Sly) mouse. Open-field exploration was improved in 18-month-old treated Gus(tm(L175F)Sly) mice, while spatial learning improved in both 12- and 18-month-old treated Gus(tm(L175F)Sly) mice. Overall, neonatal administration of lentiviral gene therapy resulted in sustained enzyme expression for up to 18 months in murine models of MPS VII. Significant improvements in biochemistry and enzymology as well as functional improvement of bone and behavior deficits in the Gus(tm(L175F)Sly) model were observed. Therapy significantly increased the lifespan of Gus(mps/mps) mice, with 12 months being the longest reported lentiviral treatment for this strain. It is important to assess the long-term outcome on enzyme levels and effect on pathology for lentiviral gene therapy to be a potential therapy for MPS patients.

Characterization of novel MPS1 inhibitors with preclinical anticancer activity.

PubMed

Jemaà, M; Galluzzi, L; Kepp, O; Senovilla, L; Brands, M; Boemer, U; Koppitz, M; Lienau, P; Prechtl, S; Schulze, V; Siemeister, G; Wengner, A M; Mumberg, D; Ziegelbauer, K; Abrieu, A; Castedo, M; Vitale, I; Kroemer, G

2013-11-01

Monopolar spindle 1 (MPS1), a mitotic kinase that is overexpressed in several human cancers, contributes to the alignment of chromosomes to the metaphase plate as well as to the execution of the spindle assembly checkpoint (SAC). Here, we report the identification and functional characterization of three novel inhibitors of MPS1 of two independent structural classes, N-(4-{2-[(2-cyanophenyl)amino][1,2,4]triazolo[1,5-a]pyridin-6-yl}phenyl)-2-phenylacetamide (Mps-BAY1) (a triazolopyridine), N-cyclopropyl-4-{8-[(2-methylpropyl)amino]-6-(quinolin-5-yl)imidazo[1,2-a]pyrazin-3-yl}benzamide (Mps-BAY2a) and N-cyclopropyl-4-{8-(isobutylamino)imidazo[1,2-a]pyrazin-3-yl}benzamide (Mps-BAY2b) (two imidazopyrazines). By selectively inactivating MPS1, these small inhibitors can arrest the proliferation of cancer cells, causing their polyploidization and/or their demise. Cancer cells treated with Mps-BAY1 or Mps-BAY2a manifested multiple signs of mitotic perturbation including inefficient chromosomal congression during metaphase, unscheduled SAC inactivation and severe anaphase defects. Videomicroscopic cell fate profiling of histone 2B-green fluorescent protein-expressing cells revealed the capacity of MPS1 inhibitors to subvert the correct timing of mitosis as they induce a premature anaphase entry in the context of misaligned metaphase plates. Hence, in the presence of MPS1 inhibitors, cells either divided in a bipolar (but often asymmetric) manner or entered one or more rounds of abortive mitoses, generating gross aneuploidy and polyploidy, respectively. In both cases, cells ultimately succumbed to the mitotic catastrophe-induced activation of the mitochondrial pathway of apoptosis. Of note, low doses of MPS1 inhibitors and paclitaxel (a microtubular poison) synergized at increasing the frequency of chromosome misalignments and missegregations in the context of SAC inactivation. This resulted in massive polyploidization followed by the activation of mitotic catastrophe. A synergistic interaction between paclitaxel and MPS1 inhibitors could also be demonstrated in vivo, as the combination of these agents efficiently reduced the growth of tumor xenografts and exerted superior antineoplastic effects compared with either compound employed alone. Altogether, these results suggest that MPS1 inhibitors may exert robust anticancer activity, either as standalone therapeutic interventions or combined with microtubule-targeting chemicals.

Advanced Technology Components for Model GTP305-2 Aircraft Auxiliary Power System.

DTIC Science & Technology

1980-02-01

minimum specific fuel consumption o A high specific power In addition these studies indicated that a turbine rotor inlet temperature of 20506F still...skirt leading edge had pulled away from the liner in areas at high metal temperatures and then formed an aerodynamic pocket for circulation and combus...cooling is required to prevent high temperature turbine inlet flow from recirculating on the rotor disk. Magnitude of the cooling flow required to

Lessons Learned from the Space Shuttle Engine Hydrogen Flow Control Valve Poppet Breakage

NASA Technical Reports Server (NTRS)

Martinez, Hugo E.; Damico, Stephen; Brewer, John

2011-01-01

The Main Propulsion System (MPS) uses three Flow Control Valves (FCV) to modulate the flow of pressurant hydrogen gas from the Space Shuttle Main Engines (SSME) to the hydrogen External Tank (ET). This maintains pressure in the ullage volume as the liquid level drops, preserving ET structural integrity and assuring the engines receive a sufficient amount of head pressure. On Space Transportation System (STS)-126 (2009), with only a handful of International Space Station (ISS) assembly flights from the end of the Shuttle program, a portion of a single FCV?s poppet head broke off at about a minute and a half after liftoff. The risk of the poppet head failure is that the increased flow area through the FCV could result in excessive gaseous hydrogen flow back to the external tank, which could result in overboard venting of hydrogen ullage pressure. If the hydrogen venting were to occur in first stage (i.e., lower atmosphere), a flammability hazard exists that could lead to catastrophic loss of crew and vehicle. Other failure risks included particle impact damage to MPS downstream hardware. Although the FCV design had been plagued by contamination-related sluggish valve response problems prior to a redesign at STS-80 (1996), contamination was ruled out as the cause of the STS-126 failure. Employing a combination of enhanced hardware inspection and a better understanding of the consequences of a poppet failure, safe flight rationale for subsequent flights (STS-119 and later) was achieved. This paper deals with the technical lessons learned during the investigation and mitigation of this problem at a time when assembly flights were each in the critical path to Space Station success.

Longitudinal Study of Neurodegenerative Disorders

ClinicalTrials.gov

2018-01-31

MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

Mps1 as a link between centrosomes and genomic instability.

PubMed

Kasbek, Christopher; Yang, Ching-Hui; Fisk, Harold A

2009-10-01

Centrosomes are microtubule-organizing centers that must be precisely duplicated before mitosis. Centrosomes regulate mitotic spindle assembly, and the presence of excess centrosomes leads to the production of aberrant mitotic spindles which generate chromosome segregation errors. Many human tumors possess excess centrosomes that lead to the production of abnormal spindles in situ. In some tumors, these extra centrosomes appear before aneuploidy, suggesting that defects in centrosome duplication might promote genomic instability and tumorigenesis. The Mps1 protein kinase is required for centrosome duplication, and preventing the proteasome-dependent degradation of Mps1 at centrosomes increases its local concentration and causes the production of excess centrosomes during a prolonged S-phase. Here, we show that Mps1 degradation is misregulated in two tumor-derived cell lines, and that the failure to appropriately degrade Mps1 correlates with the ability of these cells to produce extra centrosomes during a prolonged S-phase. In the 21NT breast-tumor derived cell line, a mutant Mps1 protein that is normally constitutively degraded can accumulate at centrosomes and perturb centrosome duplication, suggesting that these cells have a defect in the mechanisms that target Mps1 to the proteasome. In contrast, the U2OS osteosarcoma cell line expresses a nondegradable form of Mps1, which we show causes the dose-dependent over duplication of centrioles even at very low levels of expression. Our data demonstrate that defects in Mps1 degradation can occur through multiple mechanisms, and suggest that Mps1 may provide a link between the control of centrosome duplication and genomic instability. (c) 2009 Wiley-Liss, Inc.

Exploring the Relationship Between the Misuse of Stimulant Medications and Academic Dishonesty Among a Sample of College Students.

PubMed

Gallucci, Andrew R; Martin, Ryan J; Hackman, Christine; Hutcheson, Amanda

2017-04-01

The misuse of prescription stimulant medications (MPS) and academic dishonesty (AD) are both problematic behaviors among college students. Although both behaviors are linked to a student's desire to succeed academically, little research has been conducted to examine the relationship between these behaviors. The purpose of this study was to determine if students who engaged in past-year MPS committed acts of AD more frequently than those who do not engage in MPS. We collected our data from a sample of undergraduates (n = 974) between the ages of 18 and 25 enrolled at one of three universities in the US who completed an online questionnaire to assess AD and MPS. Results indicated that 18.2 % of the sample engaged in MPS in the past year and 65 % committed one or more acts of AD during the past year. An increased frequency of AD increased the odds of reporting MPS when controlling for known covariates (e.g., gender, stimulant prescription status, and energy drink consumption). In addition, higher rates of MPS were identified in students affiliated with a Greek organization, those with a current stimulant prescription, those who consume energy drinks, and those who misuse other prescriptions. Concerning specific AD-types, misusers reported copying off someone else's homework, having someone copy of their homework, and using the internet to commit acts of dishonesty more frequently than those who do not engage in MPS. This study adds to the MPS college student literature by highlighting the relationship between MPS and AD.

Deep Coverage Proteomics Identifies More Low-Abundance Missing Proteins in Human Testis Tissue with Q-Exactive HF Mass Spectrometer.

PubMed

Wei, Wei; Luo, Weijia; Wu, Feilin; Peng, Xuehui; Zhang, Yao; Zhang, Manli; Zhao, Yan; Su, Na; Qi, YingZi; Chen, Lingsheng; Zhang, Yangjun; Wen, Bo; He, Fuchu; Xu, Ping

2016-11-04

Since 2012, missing proteins (MPs) investigation has been one of the critical missions of Chromosome-Centric Human Proteome Project (C-HPP) through various biochemical strategies. On the basis of our previous testis MPs study, faster scanning and higher resolution mass-spectrometry-based proteomics might be conducive to MPs exploration, especially for low-abundance proteins. In this study, Q-Exactive HF (HF) was used to survey proteins from the same testis tissues separated by two separating methods (tricine- and glycine-SDS-PAGE), as previously described. A total of 8526 proteins were identified, of which more low-abundance proteins were uniquely detected in HF data but not in our previous LTQ Orbitrap Velos (Velos) reanalysis data. Further transcriptomics analysis showed that these uniquely identified proteins by HF also had lower expression at the mRNA level. Of the 81 total identified MPs, 74 and 39 proteins were listed as MPs in HF and Velos data sets, respectively. Among the above MPs, 47 proteins (43 neXtProt PE2 and 4 PE3) were ranked as confirmed MPs after verifying with the stringent spectra match and isobaric and single amino acid variants filtering. Functional investigation of these 47 MPs revealed that 11 MPs were testis-specific proteins and 7 MPs were involved in spermatogenesis process. Therefore, we concluded that higher scanning speed and resolution of HF might be factors for improving the low-abundance MP identification in future C-HPP studies. All mass-spectrometry data from this study have been deposited in the ProteomeXchange with identifier PXD004092.

Quantitative evaluation improves specificity of myocardial perfusion SPECT in the assessment of functionally significant intermediate coronary artery stenoses: a comparative study with fractional flow reserve measurements.

PubMed

Sahiner, Ilgin; Akdemir, Umit O; Kocaman, Sinan A; Sahinarslan, Asife; Timurkaynak, Timur; Unlu, Mustafa

2013-02-01

Myocardial perfusion SPECT (MPS) is a noninvasive method commonly used for assessment of the hemodynamic significance of intermediate coronary stenoses. Fractional flow reserve (FFR) measurement is a well-validated invasive method used for the evaluation of intermediate stenoses. We aimed to determine the association between MPS and FFR findings in intermediate degree stenoses and evaluate the added value of quantification in MPS. Fifty-eight patients who underwent intracoronary pressure measurement in the catheterization laboratory to assess the physiological significance of intermediate (40-70%) left anterior descending (LAD) artery lesions, and who also underwent stress myocardial perfusion SPECT either for the assessment of an intermediate stenosis or for suspected coronary artery disease were analyzed retrospectively in the study. Quantitative analysis was performed using the 4DMSPECT program, with visual assessment performed by two experienced nuclear medicine physicians blinded to the angiographic findings. Summed stress scores (SSS) and summed difference scores (SDS) in the LAD artery territory according to the 20 segment model were calculated. A summed stress score of ≥ 3 and an SDS of ≥ 2 were assumed as pathologic, indicating significance of the lesion; a cutoff value of 0.75 was used to define abnormal FFR. Both visual and quantitative assessment results were compared with FFR using Chi-square (χ²) test. The mean time interval between two studies was 13 ± 11 days. FFR was normal in 45 and abnormal in 13 patients. Considering the FFR results as the gold standard method for assessing the significance of the lesion, the sensitivity and specificity of quantitative analysis determining the abnormal flow reserve were 85 and 84%, respectively, while visual analysis had a sensitivity of 77% and a specificity of 51%. There was a good agreement between the observers (κ = 0.856). Summed stress and difference scores demonstrated moderate inverse correlations with FFR values (r = -0.542, p < 0.001 and r = -0.506, p < 0.001, respectively). Quantitative analysis of the myocardial perfusion SPECT increases the specificity in evaluating the significance of intermediate degree coronary lesions.

Effects of multipurpose solutions (MPS) for hydrogel contact lenses on gap-junctional intercellular communication (GJIC) in rabbit corneal keratocytes.

PubMed

Sumide, Taizo; Tsuchiya, Toshie

2003-02-15

To ensure the effects of multipurpose solutions (MPS) for hydrogel contact lenses on the cornea, the inhibitory activity of three types of MPS on corneal cells has been evaluated with the use of scrape loading and dye transfer assay (SLDT assay) and Western blotting on rabbit corneal keratocytes (RC4). In SLDT assay, MPS-A and poloxamine showed dose-dependent inhibitory activity, suggesting the inhibitory action of MPS-A and poloxamine to gap junctional intercellular communication (GJIC) in the tested cells. Moreover, after treatment with MPS-A, the GJIC was initially inhibited within 4 h, and thereafter gradually turned to an approximately 60% level of the initial value. When MPS-A was removed from the incubation media after exposure of the cells, the recovery of GJIC was time dependent and returned to approximately initial levels at 8 h. Complete recovery was established after approximately 24 h. These findings suggested that the inhibitory action of MPS-A on corneal keratocytes was reversible. This inhibition was accompanied by a decrease in the quantity of connexin-43, which is a major protein constituting the gap junctional channel of these cells, and its change in the phosphorylation state. Taken together, it was suggested that MPS-A interacts with connexin-43, inducing an inhibitory action on GJIC. (c) 2002 Wiley Periodicals, Inc.

Characterization of Spindle Checkpoint Kinase Mps1 Reveals Domain with Functional and Structural Similarities to Tetratricopeptide Repeat Motifs of Bub1 and BubR1 Checkpoint Kinases*

PubMed Central

Lee, Semin; Thebault, Philippe; Freschi, Luca; Beaufils, Sylvie; Blundell, Tom L.; Landry, Christian R.; Bolanos-Garcia, Victor M.; Elowe, Sabine

2012-01-01

Kinetochore targeting of the mitotic kinases Bub1, BubR1, and Mps1 has been implicated in efficient execution of their functions in the spindle checkpoint, the self-monitoring system of the eukaryotic cell cycle that ensures chromosome segregation occurs with high fidelity. In all three kinases, kinetochore docking is mediated by the N-terminal region of the protein. Deletions within this region result in checkpoint failure and chromosome segregation defects. Here, we use an interdisciplinary approach that includes biophysical, biochemical, cell biological, and bioinformatics methods to study the N-terminal region of human Mps1. We report the identification of a tandem repeat of the tetratricopeptide repeat (TPR) motif in the N-terminal kinetochore binding region of Mps1, with close homology to the tandem TPR motif of Bub1 and BubR1. Phylogenetic analysis indicates that TPR Mps1 was acquired after the split between deutorostomes and protostomes, as it is distinguishable in chordates and echinoderms. Overexpression of TPR Mps1 resulted in decreased efficiency of both chromosome alignment and mitotic arrest, likely through displacement of endogenous Mps1 from the kinetochore and decreased Mps1 catalytic activity. Taken together, our multidisciplinary strategy provides new insights into the evolution, structural organization, and function of Mps1 N-terminal region. PMID:22187426

Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore

PubMed Central

Marquardt, Joseph R.; Perkins, Jennifer L.; Beuoy, Kyle J.; Fisk, Harold A.

2016-01-01

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus. PMID:27339139

Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore.

PubMed

Marquardt, Joseph R; Perkins, Jennifer L; Beuoy, Kyle J; Fisk, Harold A

2016-07-12

Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.

Characterization of spindle checkpoint kinase Mps1 reveals domain with functional and structural similarities to tetratricopeptide repeat motifs of Bub1 and BubR1 checkpoint kinases.

PubMed

Lee, Semin; Thebault, Philippe; Freschi, Luca; Beaufils, Sylvie; Blundell, Tom L; Landry, Christian R; Bolanos-Garcia, Victor M; Elowe, Sabine

2012-02-17

Kinetochore targeting of the mitotic kinases Bub1, BubR1, and Mps1 has been implicated in efficient execution of their functions in the spindle checkpoint, the self-monitoring system of the eukaryotic cell cycle that ensures chromosome segregation occurs with high fidelity. In all three kinases, kinetochore docking is mediated by the N-terminal region of the protein. Deletions within this region result in checkpoint failure and chromosome segregation defects. Here, we use an interdisciplinary approach that includes biophysical, biochemical, cell biological, and bioinformatics methods to study the N-terminal region of human Mps1. We report the identification of a tandem repeat of the tetratricopeptide repeat (TPR) motif in the N-terminal kinetochore binding region of Mps1, with close homology to the tandem TPR motif of Bub1 and BubR1. Phylogenetic analysis indicates that TPR Mps1 was acquired after the split between deutorostomes and protostomes, as it is distinguishable in chordates and echinoderms. Overexpression of TPR Mps1 resulted in decreased efficiency of both chromosome alignment and mitotic arrest, likely through displacement of endogenous Mps1 from the kinetochore and decreased Mps1 catalytic activity. Taken together, our multidisciplinary strategy provides new insights into the evolution, structural organization, and function of Mps1 N-terminal region.

Contributions of phosphatidylserine-positive platelets and leukocytes and microparticles to hypercoagulable state in gastric cancer patients.

PubMed

Yang, Chunfa; Ma, Ruishuang; Jiang, Tao; Cao, Muhua; Zhao, Liangliang; Bi, Yayan; Kou, Junjie; Shi, Jialan; Zou, Xiaoming

2016-06-01

Hypercoagulability in gastric cancer is a common complication and a major contributor to poor prognosis. This study aimed to determine procoagulant activity of blood cells and microparticles (MPs) in gastric cancer patients. Phosphatidylserine-positive blood cells and MPs, and their procoagulant properties in particular, were assessed in 48 gastric cancer patients and 35 healthy controls. Phosphatidylserine-positive platelets, leukocytes, and MPs in patients with tumor-node-metastasis stage III/IV gastric cancer were significantly higher than those in stage I/II patients or healthy controls. Moreover, procoagulant activity of platelets, leukocytes, and MPs in stage III/IV patients was significantly increased compared to the controls, as indicated by shorter clotting time, higher intrinsic and extrinsic factor tenase, and prothrombinase complex activity. Interestingly, lactadherin, which competes with factors V and VIII to bind phosphatidylserine, dramatically prolonged clotting time of the cells and MPs by inhibiting factor tenase and prothrombinase complex activity. Although anti-tissue factor antibody significantly attenuated extrinsic tenase complex activity of leukocytes and MPs, it only slightly prolonged clotting times. Meanwhile, treatment with radical resection reduced phosphatidylserine-positive platelets, leukocytes, and MPs, and prolonged the clotting times of the remaining cells and MPs. Our results suggest that phosphatidylserine-positive platelets, leukocytes, and MPs contribute to hypercoagulability and represent a potential therapeutic target to prevent coagulation in patients with stage III/IV gastric cancer.

Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling.

PubMed

Maciejowski, John; George, Kelly A; Terret, Marie-Emilie; Zhang, Chao; Shokat, Kevan M; Jallepalli, Prasad V

2010-07-12

The spindle assembly checkpoint (SAC) in mammals uses cytosolic and kinetochore-based signaling pathways to inhibit anaphase. In this study, we use chemical genetics to show that the protein kinase Mps1 regulates both aspects of the SAC. Human MPS1-null cells were generated via gene targeting and reconstituted with either the wild-type kinase (Mps1(wt)) or a mutant version (Mps1(as)) sensitized to bulky purine analogues. Mps1 inhibition sharply accelerated anaphase onset, such that cells completed mitosis in 12 min, and prevented Cdc20's association with either Mad2 or BubR1 during interphase, i.e., before the appearance of functional kinetochores. Furthermore, intramitotic Mps1 inhibition evicted Bub1 and all other known SAC transducers from the outer kinetochore, but contrary to a recent study, did not perturb aurora B-dependent phosphorylation. We conclude that Mps1 has two complementary roles in SAC regulation: (1) initial cytoplasmic activation of Cdc20 inhibitors and (2) recruitment of factors that promote sustained anaphase inhibition and chromosome biorientation to unattached kinetochores.

Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation.

PubMed

Maciejowski, John; Drechsler, Hauke; Grundner-Culemann, Kathrin; Ballister, Edward R; Rodriguez-Rodriguez, Jose-Antonio; Rodriguez-Bravo, Veronica; Jones, Mathew J K; Foley, Emily; Lampson, Michael A; Daub, Henrik; McAinsh, Andrew D; Jallepalli, Prasad V

2017-04-24

The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore. Substrate modification was microtubule sensitive and opposed by PP2A-B56 phosphatases that stabilize chromosome-spindle attachment. Consistently, Mps1 inhibition rescued K-fiber stability after depleting PP2A-B56. We also identify the Ska complex as a key effector of Mps1 at the kinetochore-microtubule interface, as mutations that mimic constitutive phosphorylation destabilized K fibers in vivo and reduced the efficiency of the Ska complex's conversion from lattice diffusion to end-coupled microtubule binding in vitro. Our results reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation. Copyright © 2017 Elsevier Inc. All rights reserved.

Spindle checkpoint–independent inhibition of mitotic chromosome segregation by Drosophila Mps1

PubMed Central

Althoff, Friederike; Karess, Roger E.; Lehner, Christian F.

2012-01-01

Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's significance for faithful mitotic chromosome segregation and emphasize the importance of its careful regulation. PMID:22553353

Mps1 Mediated Phosphorylation of Hsp90 Confers Renal Cell Carcinoma Sensitivity and Selectivity to Hsp90 Inhibitors.

PubMed

Woodford, Mark R; Truman, Andrew W; Dunn, Diana M; Jensen, Sandra M; Cotran, Richard; Bullard, Renee; Abouelleil, Mourad; Beebe, Kristin; Wolfgeher, Donald; Wierzbicki, Sara; Post, Dawn E; Caza, Tiffany; Tsutsumi, Shinji; Panaretou, Barry; Kron, Stephen J; Trepel, Jane B; Landas, Steve; Prodromou, Chrisostomos; Shapiro, Oleg; Stetler-Stevenson, William G; Bourboulia, Dimitra; Neckers, Len; Bratslavsky, Gennady; Mollapour, Mehdi

2016-02-02

The molecular chaperone Hsp90 protects deregulated signaling proteins that are vital for tumor growth and survival. Tumors generally display sensitivity and selectivity toward Hsp90 inhibitors; however, the molecular mechanism underlying this phenotype remains undefined. We report that the mitotic checkpoint kinase Mps1 phosphorylates a conserved threonine residue in the amino-domain of Hsp90. This, in turn, regulates chaperone function by reducing Hsp90 ATPase activity while fostering Hsp90 association with kinase clients, including Mps1. Phosphorylation of Hsp90 is also essential for the mitotic checkpoint because it confers Mps1 stability and activity. We identified Cdc14 as the phosphatase that dephosphorylates Hsp90 and disrupts its interaction with Mps1. This causes Mps1 degradation, thus providing a mechanism for its inactivation. Finally, Hsp90 phosphorylation sensitizes cells to its inhibitors, and elevated Mps1 levels confer renal cell carcinoma selectivity to Hsp90 drugs. Mps1 expression level can potentially serve as a predictive indicator of tumor response to Hsp90 inhibitors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Natural Loss of Mps1 Kinase in Nematodes Uncovers a Role for Polo-like Kinase 1 in Spindle Checkpoint Initiation.

PubMed

Espeut, Julien; Lara-Gonzalez, Pablo; Sassine, Mélanie; Shiau, Andrew K; Desai, Arshad; Abrieu, Ariane

2015-07-07

The spindle checkpoint safeguards against chromosome loss during cell division by preventing anaphase onset until all chromosomes are attached to spindle microtubules. Checkpoint signal is generated at kinetochores, the primary attachment site on chromosomes for spindle microtubules. Mps1 kinase initiates checkpoint signaling by phosphorylating the kinetochore-localized scaffold protein Knl1 to create phospho-docking sites for Bub1/Bub3. Mps1 is widely conserved but is surprisingly absent in many nematode species. Here, we show that PLK-1, which targets a substrate motif similar to that of Mps1, functionally substitutes for Mps1 in C. elegans by phosphorylating KNL-1 to direct BUB-1/BUB-3 kinetochore recruitment. This finding led us to re-examine checkpoint initiation in human cells, where we found that Plk1 co-inhibition significantly reduced Knl1 phosphorylation and Bub1 kinetochore recruitment relative to Mps1 inhibition alone. Thus, the finding that PLK-1 functionally substitutes for Mps1 in checkpoint initiation in C. elegans uncovered a role for Plk1 in species that have Mps1. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1.

PubMed

Althoff, Friederike; Karess, Roger E; Lehner, Christian F

2012-06-01

Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's significance for faithful mitotic chromosome segregation and emphasize the importance of its careful regulation.

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

PubMed Central

Provenzale, James M.; Nestrasil, Igor; Chen, Steven; Kan, Shih-hsin; Le, Steven Q.; Jens, Jacqueline K.; Snella, Elizabeth M.; Vondrak, Kristen N.; Yee, Jennifer K.; Vite, Charles H.; Elashoff, David; Duan, Lewei; Wang, Raymond Y.; Ellinwood, N. Matthew; Guzman, Miguel A.; Shapiro, Elsa G.; Dickson, Patricia I.

2015-01-01

Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment. PMID:26222335

Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis.

PubMed

Saurin, Adrian T; van der Waal, Maike S; Medema, René H; Lens, Susanne M A; Kops, Geert J P L

2011-01-01

The mitotic checkpoint prevents mitotic exit until all chromosomes are attached to spindle microtubules. Aurora B kinase indirectly invokes this checkpoint by destabilizing incorrect attachments; however, a more direct role remains controversial. In contrast, activity of the kinase Mps1 is indispensible for the mitotic checkpoint. Here we show that Aurora B and Hec1 are needed for efficient Mps1 recruitment to unattached kinetochores, allowing rapid Mps1 activation at the onset of mitosis. Live monitoring of cyclin B degradation reveals that this is essential to establish the mitotic checkpoint quickly at the start of mitosis. Delayed Mps1 activation and checkpoint establishment upon Aurora B inhibition or Hec1 depletion are rescued by tethering Mps1 to kinetochores, demonstrating that Mps1 recruitment is the primary role of Aurora B and Hec1 in mitotic checkpoint signalling. These data demonstrate a direct role for Aurora B in initiating the mitotic checkpoint rapidly at the onset of mitosis.

Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing.

PubMed

Moura, Margarida; Osswald, Mariana; Leça, Nelson; Barbosa, João; Pereira, António J; Maiato, Helder; Sunkel, Claudio E; Conde, Carlos

2017-05-02

Faithfull genome partitioning during cell division relies on the Spindle Assembly Checkpoint (SAC), a conserved signaling pathway that delays anaphase onset until all chromosomes are attached to spindle microtubules. Mps1 kinase is an upstream SAC regulator that promotes the assembly of an anaphase inhibitor through a sequential multi-target phosphorylation cascade. Thus, the SAC is highly responsive to Mps1, whose activity peaks in early mitosis as a result of its T-loop autophosphorylation. However, the mechanism controlling Mps1 inactivation once kinetochores attach to microtubules and the SAC is satisfied remains unknown. Here we show in vitro and in Drosophila that Protein Phosphatase 1 (PP1) inactivates Mps1 by dephosphorylating its T-loop. PP1-mediated dephosphorylation of Mps1 occurs at kinetochores and in the cytosol, and inactivation of both pools of Mps1 during metaphase is essential to ensure prompt and efficient SAC silencing. Overall, our findings uncover a mechanism of SAC inactivation required for timely mitotic exit.

Liner Optimization Studies Using the Ducted Fan Noise Prediction Code TBIEM3D

NASA Technical Reports Server (NTRS)

Dunn, M. H.; Farassat, F.

1998-01-01

In this paper we demonstrate the usefulness of the ducted fan noise prediction code TBIEM3D as a liner optimization design tool. Boundary conditions on the interior duct wall allow for hard walls or a locally reacting liner with axially segmented, circumferentially uniform impedance. Two liner optimization studies are considered in which farfield noise attenuation due to the presence of a liner is maximized by adjusting the liner impedance. In the first example, the dependence of optimal liner impedance on frequency and liner length is examined. Results show that both the optimal impedance and attenuation levels are significantly influenced by liner length and frequency. In the second example, TBIEM3D is used to compare radiated sound pressure levels between optimal and non-optimal liner cases at conditions designed to simulate take-off. It is shown that significant noise reduction is achieved for most of the sound field by selecting the optimal or near optimal liner impedance. Our results also indicate that there is relatively large region of the impedance plane over which optimal or near optimal liner behavior is attainable. This is an important conclusion for the designer since there are variations in liner characteristics due to manufacturing imprecisions.

On the Use of Experimental Methods to Improve Confidence in Educed Impedance

NASA Technical Reports Server (NTRS)

Jones, Michael G.; Watson, Willie R.

2011-01-01

Results from impedance eduction methods developed by NASA Langley Research Center are used throughout the acoustic liner community. In spite of recent enhancements, occasional anomalies persist with these methods, generally at frequencies where the liner produces minimal attenuation. This investigation demonstrates an experimental approach to educe impedance with increased confidence over a desired frequency range, by combining results from successive tests with different cavity depths. A series of tests is conducted with three wire-mesh facesheets, for which the results should be weakly dependent on source sound pressure level and mean grazing flow speed. First, a raylometer is used to measure the DC flow resistance of each facesheet. These facesheets are then mounted onto a frame and a normal incidence tube is used to determine their respective acoustic impedance spectra. A comparison of the acoustic resistance component with the DC flow resistance for each facesheet is used to validate the measurement process. Next, each facesheet is successively mounted onto three frames with different cavity depths, and a grazing flow impedance tube is used to educe their respective acoustic impedance spectra with and without mean flow. The no-flow results are compared with those measured in the normal incidence tube to validate the impedance eduction method. Since the anti-resonance frequency varies with cavity depth, each sample provides robust results over a different frequency range. Hence, a combination of results can be used to determine the facesheet acoustic resistance. When combined with the acoustic reactance, observed to be weakly dependent on the source sound pressure level and grazing flow Mach number, the acoustic impedance can be educed with increased confidence. Representative results of these tests are discussed, and the complete database is available in electronic format upon request.

Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review.

PubMed

Wolfenden, C; Wittkowski, A; Hare, D J

2017-11-01

The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD in MPS III and quality assessed a total of 16 studies. Results indicated that difficulties within speech, language and communication consistent with ASD were present in MPS III, whilst repetitive and restricted behaviours and interests were less widely reported. The presence of ASD-like symptoms can result in late diagnosis or misdiagnosis of MPS III and prevent opportunities for genetic counselling and the provision of treatments.

On modeling the sound propagation through a lined duct with a modified Ingard-Myers boundary condition

NASA Astrophysics Data System (ADS)

Yang, Cheng; Fang, Yi; Zhao, Chao; Zhang, Xin

2018-06-01

A duct acoustics model is an essential component of an impedance eduction technique and its computation cost determines the impedance measurement efficiency. In this paper, a model is developed for the sound propagation through a lined duct carrying a uniform mean flow. In contrast to many existing models, the interface between the liner and the duct field is defined with a modified Ingard-Myers boundary condition that takes account of the effect of the boundary layer above the liner. A mode-matching method is used to couple the unlined and lined duct segments for the model development. For the lined duct segment, the eigenvalue problem resulted from the modified boundary condition is solved by an integration scheme which, on the one hand, allows the lined duct modes to be computed in an efficient manner, and on the other hand, orders the modes automatically. The duct acoustics model developed from the solved lined duct modes is shown to converge more rapidly than the one developed from the rigid-walled duct modes. Validation against the experiment data in the literature shows that the proposed model is able to predict more accurately the liner performance measured by the two-source method. This, however, cannot be made by a duct acoustics model associated with the conventional Ingard-Myers boundary condition. The proposed model has the potential to be integrated into an impedance eduction technique for more reliable liner measurement.

Successful percutaneous coronary intervention with GuideLiner® catheter for subtotal occlusive lesion in the right coronary artery with anomalous origin from the left sinus of Valsalva: a case report.

PubMed

Shirota, Ayumi; Nomura, Tetsuya; Kubota, Hiroshi; Taminishi, Shunta; Urata, Ryota; Sugimoto, Takeshi; Higuchi, Yusuke; Kato, Taku; Keira, Natsuya; Tatsumi, Tetsuya

2015-07-28

Because of the unusual anatomy of an anomalous origin of the right coronary artery from the left sinus of Valsalva, selective cannulation of the guiding catheter in percutaneous coronary intervention for these cases is always challenging. A 58-year-old Japanese man was admitted to our hospital complaining of worsening exertional chest pain. He was suspected of having unstable angina pectoris and underwent cardiac catheterization. We found a subtotal occlusive lesion in the mid-portion of his right coronary artery that originated from the left sinus of Valsalva. On the previous percutaneous coronary intervention, we failed to cannulate the guiding catheter to the anomalous orifice of the right coronary artery. Therefore, we decided to use the GuideLiner catheter for stable back-up support from the beginning. A 6Fr GuideLiner catheter was introduced into the right coronary artery by anchoring it coaxially with a semi-compliant balloon catheter. And we successfully deployed two drug-eluting stents by crossing over the posterior-descending artery. Final angiography demonstrated favorable dilatation of the target lesion, and native blood flow in the right coronary artery was completely recovered. GuideLiner is a monorail-type "child" support catheter that facilitates coaxial guiding catheter engagement and an appropriate back-up force, achieving successful device delivery to target lesions in this kind of complex percutaneous coronary intervention.

Novel Mps1 kinase inhibitors: from purine to pyrrolopyrimidine and quinazoline leads.

PubMed

Bursavich, Matthew G; Dastrup, David; Shenderovich, Mark; Yager, Kraig M; Cimbora, Daniel M; Williams, Brandi; Kumar, D Vijay

2013-12-15

Mps1, also known as TTK, is a mitotic checkpoint protein kinase that has become a promising new target of cancer research. In an effort to improve the lead-likeness of our recent Mps1 purine lead compounds, a scaffold hopping exercise has been undertaken. Structure-based design, principles of conformational restriction, and subsequent scaffold hopping has led to novel pyrrolopyrimidine and quinazoline Mps1 inhibitors. These new single-digit nanomolar leads provide the basis for developing potent, novel Mps1 inhibitors with improved drug-like properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

Use of myocardial perfusion imaging and estimation of associated radiation doses in Germany from 2005 to 2012.

PubMed

Lindner, O; Bengel, F M; Hacker, M; Schäfer, W; Burchert, W

2014-05-01

For several years the Working Group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine has been performing a regular survey to obtain information on technique, utilization and development of myocardial perfusion scintigraphy (MPS). Currently, data of six surveys from 2005 to 2012 are available. The aim of this paper is to deliver a general and comprehensive overview of all surveys documenting the course of patient doses over time and the development of the method. A one-page questionnaire with number of MPS patients, number of stress and rest MPS, referral structure and several technical issues was sent to all centres performing MPS in Germany and evaluated. With the data on protocol utilization, effective MPS patient doses were estimated. MPS per million population (pmp) varied between 2,380 and 2,770. In 2012, MPS pmp showed a slight increase for the first time. From 2005 to 2009 the angiography to MPS ratio increased from 3.4 to 4.4, and the revascularization to MPS ratio decreased from 0.66 to 0.53. In 2012, both indices demonstrated an opposite trend for the first time (4.1 and 0.55). A total of 108 centres participated in all surveys. They showed an increase in MPS patients of 4.0 % over the reporting period. In 2012, more than 50 % of the centres experienced no change or an increase in MPS numbers. The leading single competitor was MRI, followed by angiography and stress echocardiography. (201)Tl studies have decreased since 2005 from 20 to 5 %. (99m)Tc MPS studies showed a mild increase in 2-day protocols. In 2012, the average effective dose per patient was estimated at 7.4 mSv. Due to the decreasing use of (201)Tl, a mild decline over the observation period can be documented. Dynamic exercise stress was the most common stress test and adenosine the leading pharmacological stress agent, with a growing percentage. In 2012, the regadenoson percentage was 9 %. Gated single photon emission computed tomography (SPECT) noted an increasing acceptance with >70 % in 2012. The segmental scoring of perfusion studies had a low acceptance. Ambulatory care cardiologists represented the major referral group. Germany has a moderate to moderate-high MPS utilization rate. Nevertheless, coronary artery disease (CAD) diagnosis and disease management are dominated by angiography. The survey data reveal a positive trend in MPS and a decrease in average patient dose reflecting good practice with guideline adherence, the implementation of technical improvements and success in training.

Microparticles Provide a Novel Biomarker To Predict Severe Clinical Outcomes of Dengue Virus Infection

PubMed Central

Punyadee, Nuntaya; Mairiang, Dumrong; Thiemmeca, Somchai; Komoltri, Chulaluk; Pan-ngum, Wirichada; Chomanee, Nusara; Charngkaew, Komgrid; Tangthawornchaikul, Nattaya; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida

2014-01-01

ABSTRACT Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1–anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. IMPORTANCE Dengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care. PMID:25410854

Microparticles provide a novel biomarker to predict severe clinical outcomes of dengue virus infection.

PubMed

Punyadee, Nuntaya; Mairiang, Dumrong; Thiemmeca, Somchai; Komoltri, Chulaluk; Pan-Ngum, Wirichada; Chomanee, Nusara; Charngkaew, Komgrid; Tangthawornchaikul, Nattaya; Limpitikul, Wannee; Vasanawathana, Sirijitt; Malasit, Prida; Avirutnan, Panisadee

2015-02-01

Shedding of microparticles (MPs) is a consequence of apoptotic cell death and cellular activation. Low levels of circulating MPs in blood help maintain homeostasis, whereas increased MP generation is linked to many pathological conditions. Herein, we investigated the role of MPs in dengue virus (DENV) infection. Infection of various susceptible cells by DENV led to apoptotic death and MP release. These MPs harbored a viral envelope protein and a nonstructural protein 1 (NS1) on their surfaces. Ex vivo analysis of clinical specimens from patients with infections of different degrees of severity at multiple time points revealed that MPs generated from erythrocytes and platelets are two major MP populations in the circulation of DENV-infected patients. Elevated levels of red blood cell-derived MPs (RMPs) directly correlated with DENV disease severity, whereas a significant decrease in platelet-derived MPs was associated with a bleeding tendency. Removal by mononuclear cells of complement-opsonized NS1-anti-NS1 immune complexes bound to erythrocytes via complement receptor type 1 triggered MP shedding in vitro, a process that could explain the increased levels of RMPs in severe dengue. These findings point to the multiple roles of MPs in dengue pathogenesis. They offer a potential novel biomarker candidate capable of differentiating dengue fever from the more serious dengue hemorrhagic fever. Dengue is the most important mosquito-transmitted viral disease in the world. No vaccines or specific treatments are available. Rapid diagnosis and immediate treatment are the keys to achieve a positive outcome. Dengue virus (DENV) infection, like some other medical conditions, changes the level and composition of microparticles (MPs), tiny bag-like structures which are normally present at low levels in the blood of healthy individuals. This study investigated how MPs in culture and patients' blood are changed in response to DENV infection. Infection of cells led to programmed cell death and MP release. In patients' blood, the majority of MPs originated from red blood cells and platelets. Decreased platelet-derived MPs were associated with a bleeding tendency, while increased levels of red blood cell-derived MPs (RMPs) correlated with more severe disease. Importantly, the level of RMPs during the early acute phase could serve as a biomarker to identify patients with potentially severe disease who require immediate care. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Comparison of experimental with theoretical total-pressure loss in parallel-walled turbojet combustors

NASA Technical Reports Server (NTRS)

Dittrich, Ralph T

1957-01-01

An experimental investigation of combustor total-pressure loss was undertaken to confirm previous theoretical analyses of effects of geometric and flow variables and of heat addition. The results indicate that a reasonable estimate of cold-flow total-pressure-loss coefficient may be obtained from the theoretical analyses. Calculated total-pressure loss due to heat addition agreed with experimental data only when there was no flame ejection from the liner at the upstream air-entry holes.

Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis.

PubMed

Deng, Guoying; Dai, Chenyun; Chen, Jinyuan; Ji, Anqi; Zhao, Jingpeng; Zhai, Yue; Kang, Yingjie; Liu, Xijian; Wang, Yin; Wang, Qiugen

2018-01-01

Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. The potential interferences Se@SiO 2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO 2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. In the present study, we found that in the rat model of ARDS, Se@SiO 2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO 2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO 2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO 2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO 2 could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO 2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Se@SiO 2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy.

Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis

PubMed Central

Chen, Jinyuan; Ji, Anqi; Zhao, Jingpeng; Zhai, Yue; Kang, Yingjie; Liu, Xijian; Wang, Yin; Wang, Qiugen

2018-01-01

Background Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. Methods The potential interferences Se@SiO2 nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO2 have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. Results In the present study, we found that in the rat model of ARDS, Se@SiO2 nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@SiO2 did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO2 also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO2 significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO2 could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO2 in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Conclusion Se@SiO2 nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy. PMID:29606872

NASA supercritical laminar flow control airfoil experiment

NASA Technical Reports Server (NTRS)

Harvey, W. D.

1982-01-01

The design and goals of experimental investigations of supercritical LFC airfoils conducted in the NASA Langley 8-ft Transonic Pressure Tunnel beginning in March 1982 are reviewed. Topics addressed include laminarization aspects; flow-quality requirements; simulation of flight parameters; the setup of screens, honeycomb, and sonic throat; the design cycle; theoretical pressure distributions and shock-free limits; drag divergence and stability analysis; and the LFC suction system. Consideration is given to the LFC airfoil model, the air-flow control system, airfoil-surface instrumentation, liner design and hardware, and test options. Extensive diagrams, drawings, graphs, photographs, and tables of numerical data are provided.

Delayed hypertrophic differentiation of epiphyseal chondrocytes contributes to failed secondary ossification in mucopolysaccharidosis VII dogs

PubMed Central

Peck, Sun H.; O'Donnell, Philip J.M.; Kang, Jennifer L.; Malhotra, Neil R.; Dodge, George R.; Pacifici, Maurizio; Shore, Eileen M.; Haskins, Mark E.; Smith, Lachlan J.

2015-01-01

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients. PMID:26422116

Gas turbine combustor

NASA Technical Reports Server (NTRS)

Burd, Steven W. (Inventor); Cheung, Albert K. (Inventor); Dempsey, Dae K. (Inventor); Hoke, James B. (Inventor); Kramer, Stephen K. (Inventor); Ols, John T. (Inventor); Smith, Reid Dyer Curtis (Inventor); Sowa, William A. (Inventor)

2011-01-01

A gas turbine engine has a combustor module including an annular combustor having a liner assembly that defines an annular combustion chamber having a length, L. The liner assembly includes a radially inner liner, a radially outer liner that circumscribes the inner liner, and a bulkhead, having a height, H1, which extends between the respective forward ends of the inner liner and the outer liner. The combustor has an exit height, H3, at the respective aft ends of the inner liner and the outer liner interior. The annular combustor has a ratio H1/H3 having a value less than or equal to 1.7. The annular combustor may also have a ration L/H3 having a value less than or equal to 6.0.

Suppression of nonlinear oscillations in combustors with partial length acoustic liners

NASA Technical Reports Server (NTRS)

Espander, W. R.; Mitchell, C. E.; Baer, M. R.

1975-01-01

An analytical model is formulated for a three-dimensional nonlinear stability problem in a rocket motor combustion chamber. The chamber is modeled as a right circular cylinder with a short (multi-orifice) nozzle, and an acoustic linear covering an arbitrary portion of the cylindrical periphery. The combustion is concentrated at the injector and the gas flow field is characterized by a mean Mach number. The unsteady combustion processes are formulated using the Crocco time lag model. The resulting equations are solved using a Green's function method combined with numerical evaluation techniques. The influence of acoustic liners on the nonlinear waveforms is predicted. Nonlinear stability limits and regions where triggering is possible are also predicted for both lined and unlined combustors in terms of the combustion parameters.

Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy

PubMed Central

Faisal, Amir; Mak, Grace W Y; Gurden, Mark D; Xavier, Cristina P R; Anderhub, Simon J; Innocenti, Paolo; Westwood, Isaac M; Naud, Sébastien; Hayes, Angela; Box, Gary; Valenti, Melanie R; De Haven Brandon, Alexis K; O'Fee, Lisa; Schmitt, Jessica; Woodward, Hannah L; Burke, Rosemary; vanMontfort, Rob L M; Blagg, Julian; Raynaud, Florence I; Eccles, Suzanne A; Hoelder, Swen; Linardopoulos, Spiros

2017-01-01

Background: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy. Therefore, MPS1 inhibition represents an attractive strategy to target cancers. Methods: To evaluate CCT271850 cellular potency, two specific antibodies that recognise the activation sites of MPS1 were used and its antiproliferative activity was determined in 91 human cancer cell lines. DLD1 cells with induced GFP-MPS1 and HCT116 cells were used in in vivo studies to directly measure MPS1 inhibition and efficacy of CCT271850 treatment. Results: CCT271850 selectively and potently inhibits MPS1 kinase activity in biochemical and cellular assays and in in vivo models. Mechanistically, tumour cells treated with CCT271850 acquire aberrant numbers of chromosomes and the majority of cells divide their chromosomes without proper alignment because of abrogation of the mitotic checkpoint, leading to cell death. We demonstrated a moderate level of efficacy of CCT271850 as a single agent in a human colorectal carcinoma xenograft model. Conclusions: CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24 h is required to achieve tumour stasis or regression by CCT271850. PMID:28334731

Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.

PubMed

Faisal, Amir; Mak, Grace W Y; Gurden, Mark D; Xavier, Cristina P R; Anderhub, Simon J; Innocenti, Paolo; Westwood, Isaac M; Naud, Sébastien; Hayes, Angela; Box, Gary; Valenti, Melanie R; De Haven Brandon, Alexis K; O'Fee, Lisa; Schmitt, Jessica; Woodward, Hannah L; Burke, Rosemary; vanMontfort, Rob L M; Blagg, Julian; Raynaud, Florence I; Eccles, Suzanne A; Hoelder, Swen; Linardopoulos, Spiros

2017-04-25

The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which prevents anaphase onset until the appropriate attachment and tension across kinetochores is achieved. MPS1 kinase activity is essential for the activation of the spindle assembly checkpoint and has been shown to be deregulated in human tumours with chromosomal instability and aneuploidy. Therefore, MPS1 inhibition represents an attractive strategy to target cancers. To evaluate CCT271850 cellular potency, two specific antibodies that recognise the activation sites of MPS1 were used and its antiproliferative activity was determined in 91 human cancer cell lines. DLD1 cells with induced GFP-MPS1 and HCT116 cells were used in in vivo studies to directly measure MPS1 inhibition and efficacy of CCT271850 treatment. CCT271850 selectively and potently inhibits MPS1 kinase activity in biochemical and cellular assays and in in vivo models. Mechanistically, tumour cells treated with CCT271850 acquire aberrant numbers of chromosomes and the majority of cells divide their chromosomes without proper alignment because of abrogation of the mitotic checkpoint, leading to cell death. We demonstrated a moderate level of efficacy of CCT271850 as a single agent in a human colorectal carcinoma xenograft model. CCT271850 is a potent, selective and orally bioavailable MPS1 kinase inhibitor. On the basis of in vivo pharmacodynamic vs efficacy relationships, we predict that more than 80% inhibition of MPS1 activity for at least 24 h is required to achieve tumour stasis or regression by CCT271850.

Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice.

PubMed

Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie; Wang, Xin-Chun; Peng, Xin-Yu

2015-01-01

This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole-chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome-Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150 mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150 mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice.

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

Cochran, C.B.

This patent describes a double nut setting tool and liner hanger assembly. It comprises a tool which is releasably coupled to the liner hanger by a nut means threadedly connected to the liner hanger: upon reaching a desired setting location, hanging the liner hanger in the well to support the weight of the liner and to permit rotation of the liner: manipulating the string of pipe to simultaneously rotate the nut means to a released condition relative to the liner hanger while rotating a lock nut in a clutch housing into a locking position in the clutch housing to engagemore » the clutch housing with the liner; and applying weight to the string of pipe to engage the clutch housing with the liner when the coupling nut is released and the lock nut is in a locking position so that the liner can be rotated by rotation of the string of pipe after the coupling nut is released.« less

Oncogenic B-Raf(V600E) abrogates the AKT/B-Raf/Mps1 interaction in melanoma cells.

PubMed

Zhang, Ling; Shi, Ruyi; He, Chanting; Cheng, Caixia; Song, Bin; Cui, Heyang; Zhang, Yanyan; Zhao, Zhiping; Bi, Yanghui; Yang, Xiaofeng; Miao, Xiaoping; Guo, Jiansheng; Chen, Xing; Wang, Jinfen; Li, Yaoping; Cheng, Xiaolong; Liu, Jing; Cui, Yongping

2013-08-28

Activating B-Raf mutations that deregulate the mitogen-activated protein kinase (MAPK) pathway commonly occur in cancer. Although B-Raf(V600E) induces increased Mps1 protein contributing to centrosome amplification and chromosome instability, the regulatory mechanisms of Mps1 in melanoma cells is not fully understood. Here, we report that Mps1/AKT and B-Raf(WT)/ERK signaling form an auto-regulatory negative feedback loop in melanoma cells; notably, oncogenic B-Raf(V600E) abrogates the negative feedback loop, contributing the aberrant Mps1 functions and tumorigenesis. Our findings raise the possibility that targeting the oncogenic B-Raf and Mps1, especially when used in combination could potentially provide great therapeutic opportunities for cancer treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Mps1 promotes rapid centromere accumulation of Aurora B.

PubMed

van der Waal, Maike S; Saurin, Adrian T; Vromans, Martijn J M; Vleugel, Mathijs; Wurzenberger, Claudia; Gerlich, Daniel W; Medema, René H; Kops, Geert J P L; Lens, Susanne M A

2012-09-01

Aurora B localization to mitotic centromeres, which is required for proper chromosome alignment during mitosis, relies on Haspin-dependent histone H3 phosphorylation and on Bub1-dependent histone H2A phosphorylation--which interacts with Borealin through a Shugoshin (Sgo) intermediate. We demonstrate that Mps1 stimulates the latter recruitment axis. Mps1 activity enhances H2A-T120ph and is critical for Sgo1 recruitment to centromeres, thereby promoting Aurora B centromere recruitment in early mitosis. Importantly, chromosome biorientation defects caused by Mps1 inhibition are improved by restoring Aurora B centromere recruitment. As Mps1 kinetochore localization reciprocally depends on Aurora B, we propose that this Aurora B-Mps1 recruitment circuitry cooperates with the Aurora B-Haspin feedback loop to ensure rapid centromere accumulation of Aurora B at the onset of mitosis.

Microparticles from splenectomized β-thalassemia/HbE patients play roles on procoagulant activities with thrombotic potential.

PubMed

Klaihmon, Phatchanat; Phongpao, Kunwadee; Kheansaard, Wasinee; Noulsri, Egarit; Khuhapinant, Archrob; Fucharoen, Suthat; Morales, Noppawan Phumala; Svasti, Saovaros; Pattanapanyasat, Kovit; Chaichompoo, Pornthip

2017-02-01

Thromboembolic events including cerebral thrombosis, deep vein thrombosis, and pulmonary embolism are major complications in β-thalassemia. Damaged red blood cells and chronic platelet activation in splenectomized β-thalassemia/HbE patients were associated with increased microparticles (MPs) releases into blood circulation. MPs are small membrane vesicles, which play important roles on coagulation. However, the role of MP in thalassemia is poorly understood. In this study, the effects of splenectomized-MPs on platelet activation and aggregation were investigated. The results showed that isolated MPs from fresh platelet-free plasma of patients and normal subjects directly induce platelet activation, platelet aggregation, and platelet-neutrophil aggregation in a dose-dependent manner. Interestingly, MPs obtained from splenectomized patients are more efficient in induction of platelet activation (P-selectin + ) when compared to MPs from normal subjects (P < 0.05), tenfold lower than pathophysiological level, at 1:0.1 platelet MP ratio. Co-incubation of splenectomized-MPs with either normal-, non-splenectomized- or splenectomized-platelets at 1:10 platelet MP ratio increased platelet activation up to 5.1 ± 2.2, 5.6 ± 3.7, and 9.5 ± 3.0%, respectively, when normalized with individual baseline. These findings suggest that splenectomized patients were proned to be activated by MPs, and splenectomized-MPs could play an important role on chronic platelet activation and aggregation, leading to thrombus formation in β-thalassemia/HbE patients.

Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function.

PubMed

Sawant, Dwitiya B; Majumder, Shubhra; Perkins, Jennifer L; Yang, Ching-Hui; Eyers, Patrick A; Fisk, Harold A

2015-11-01

Centrins are a family of small, calcium-binding proteins with diverse cellular functions that play an important role in centrosome biology. We previously identified centrin 2 and centrin 3 (Cetn2 and Cetn3) as substrates of the protein kinase Mps1. However, although Mps1 phosphorylation sites control the function of Cetn2 in centriole assembly and promote centriole overproduction, Cetn2 and Cetn3 are not functionally interchangeable, and we show here that Cetn3 is both a biochemical inhibitor of Mps1 catalytic activity and a biological inhibitor of centrosome duplication. In vitro, Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. Finally, overexpression of Cetn3 reduces Mps1 Thr-676 phosphorylation at centrosomes, and mimicking Mps1-dependent phosphorylation of Cetn2 bypasses the inhibitory effect of Cetn3, suggesting that the biological effects of Cetn3 are due to the inhibition of Mps1 function at centrosomes. © 2015 Sawant et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Altered lumbar spine structure, biochemistry and biomechanical properties in a canine model of mucopolysaccharidosis type VII

PubMed Central

Smith, Lachlan J; Martin, John T; Szczesny, Spencer E; Ponder, Katherine P; Haskins, Mark E; Elliott, Dawn M

2010-01-01

Mucopolysaccharidosis VII (MPS VII) is a lysosomal storage disorder characterized by a deficiency in β-glucuronidase activity, leading to systemic accumulation of poorly degraded glycosaminoglycans (GAG). Along with other morbidities, MPS VII is associated with paediatric spinal deformity. The objective of this study was to examine potential associations between abnormal lumbar spine matrix structure and composition in MPS VII, and spine segment and tissue-level mechanical properties, using a naturally occurring canine model with a similar clinical phenotype to the human form of the disorder. Segments from juvenile MPS VII and unaffected dogs were allocated to: radiography, gross morphology, histology, biochemistry, and mechanical testing. MPS VII spines had radiolucent lesions in the vertebral body epiphyses. Histologically, this corresponded to a GAG-rich cartilaginous region in place of bone, and elevated GAG staining was seen in the annulus fibrosus. Biochemically, MPS VII samples had elevated GAG in the outer annulus fibrosus and epiphyses, low calcium in the epiphyses, and high water content in all regions except the nucleus pulposus. MPS VII spine segments had higher range of motion and lower stiffness than controls. Endplate indentation stiffness and failure loads were significantly lower in MPS VII samples, while annulus fibrosus tensile mechanical properties were normal. Vertebral body lesions in MPS VII spines suggest a failure to convert cartilage to bone during development. Low stiffness in these regions likely contributes to mechanical weakness in motion segments and is a potential factor in the progression of spinal deformity. PMID:19918911

Preparation, characterization and in vivo assessment of the bioavailability of glycyrrhizic acid microparticles by supercritical anti-solvent process.

PubMed

Sui, Xiaoyu; Wei, Wei; Yang, Lei; Zu, Yuangang; Zhao, Chunjian; Zhang, Lin; Yang, Fengjian; Zhang, Zhonghua

2012-02-28

In this study, glycyrrhizic acid (GA) microparticles were successfully prepared using a supercritical anti-solvent (SAS) process. Carbon dioxide and ethanol were used as the anti-solvent and solvent, respectively. The influences of several process parameters on the mean particle size (MPS), particle size distribution (PSD) and total yield were investigated. Processed particle sizes gradually decreased as temperature and solution flow rate increased. In addition, processed particle sizes increased from 119 to 205 nm as GA concentration increased. However, CO(2) flow rate did not significantly affect particle size. The optimized process conditions were applied, those included temperature (65 °C), pressure (250 bar), CO(2) and drug solution flow rate (15 and 8 mL min(-1)), drug concentration in ethanol (20 mg mL(-1)). Microparticles with a span of PSD ranging from 95 and 174 nm, MPS of 128 nm were obtained, and total yield was 63.5%. The X-ray diffraction patterns of glycyrrhizic acid microparticles show apparent amorphous nature. Fourier transform infrared (FT-IR) spectroscopy results show that no chemical structural changes occurred. The in vitro dissolution tests showed that the GA microparticles exhibited great enhancement of dissolution performance when compared to GA original drug. Furthermore, the in vivo studies revealed that the microparticles provided improved pharmacokinetic parameter after oral administration to rats as compared with original drug. Copyright © 2011 Elsevier B.V. All rights reserved.

46 CFR Appendix A to Part 535 - Information Form and Instructions

Code of Federal Regulations, 2011 CFR

2011-10-01

... units] (B)Utilization [percent] Carrier A [Name] Liner Service 1 [Name] XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Carrier B Liner Service 1 XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Etc. . . . (C) Narrative statement on significant changes in vessel...

46 CFR Appendix A to Part 535 - Information Form and Instructions

Code of Federal Regulations, 2012 CFR

2012-10-01

... units] (B)Utilization [percent] Carrier A [Name] Liner Service 1 [Name] XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Carrier B Liner Service 1 XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Etc. . . . (C) Narrative statement on significant changes in vessel...

46 CFR Appendix A to Part 535 - Information Form and Instructions

Code of Federal Regulations, 2014 CFR

2014-10-01

... units] (B)Utilization [percent] Carrier A [Name] Liner Service 1 [Name] XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Carrier B Liner Service 1 XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Etc. . . . (C) Narrative statement on significant changes in vessel...

46 CFR Appendix A to Part 535 - Information Form and Instructions

Code of Federal Regulations, 2013 CFR

2013-10-01

... units] (B)Utilization [percent] Carrier A [Name] Liner Service 1 [Name] XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Carrier B Liner Service 1 XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Etc. . . . (C) Narrative statement on significant changes in vessel...

46 CFR Appendix A to Part 535 - Information Form and Instructions

Code of Federal Regulations, 2010 CFR

2010-10-01

... units] (B)Utilization [percent] Carrier A [Name] Liner Service 1 [Name] XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Carrier B Liner Service 1 XX,XXX XX Liner Service 2 XX,XXX XX Liner Service 3 XX,XXX XX Etc. . . . Etc. . . . (C) Narrative statement on significant changes in vessel...

Optimization of pore structure and particle morphology of mesoporous silica for antibody adsorption for use in affinity chromatography

NASA Astrophysics Data System (ADS)

Hikosaka, Ryouichi; Nagata, Fukue; Tomita, Masahiro; Kato, Katsuya

2016-10-01

Antibodies have received significant attention for use as antibody drugs, because they bind the objective protein (antigen) via antigen-antibody reactions. Recently, many reports have appeared on various monoclonal antibodies that recognize a single antigen. In this study, monoclonal antibodies are used as adsorbates on mesoporous silica (MPS) for affinity chromatography. MPS has high surface area and large pore volume; moreover, pore diameter, pore structure, and particle morphology are relatively easy to tune by adjusting the conditions of synthesis. The pore structure (two-dimensional (2D) hexagonal and three-dimensional cubic) and particle morphology (spherical and polyhedral) of MPS are optimized for use in a monoclonal antibody/MPS composite. When anti-IgG (one of the monoclonal antibodies) adsorbs on the MPS material and IgG (antigen) binds to anti-IgG/MPS composites, MCM-41p with a 2D-hexagonal pore structure and polyhedral particle morphology has the highest IgG binding efficiency. In addition, the antibody/MPS composites remain stable in chaotropic and low-pH solutions and can be cycled at least five times without decreasing IgG elution. In purification and removal tests, the use of the antibody/MPS composites allows only the objective protein from protein mixtures to be bound and eluted.

Structural and mechanistic insights into Mps1 kinase activation.

PubMed

Wang, Wei; Yang, Yuting; Gao, Yuefeng; Xu, Quanbin; Wang, Feng; Zhu, Songcheng; Old, William; Resing, Katheryn; Ahn, Natalie; Lei, Ming; Liu, Xuedong

2009-08-01

Mps1 is one of the several essential kinases whose activation is required for robust mitotic spindle checkpoint signalling. The activity of Mps1 is tightly regulated and increases dramatically during mitosis or in response to spindle damage. To understand the molecular mechanism underlying Mps1 regulation, we determined the crystal structure of the kinase domain of Mps1. The 2.7-A-resolution crystal structure shows that the Mps1 kinase domain adopts a unique inactive conformation. Intramolecular interactions between the key Glu residue in the C helix of the N-terminal lobe and the backbone amides in the catalytic loop lock the kinase in the inactive conformation. Autophosphorylation appears to be a priming event for kinase activation. We identified Mps1 autophosphorylation sites in the activation and the P+1 loops. Whereas activation loop autophosphorylation enhances kinase activity, autophosphorylation at the P+1 loop (T686) is associated with the active kinase. Mutation of T686 autophosphorylation site impairs both autophosphorylation and transphosphorylation. Furthermore, we demonstrated that phosphorylation of T676 may be a priming event for phosphorylation at T686. Finally, we identified two critical lysine residues in the loop between helices EF and F that are essential for substrate recruitment and maintaining high levels of kinase activity. Our studies reveal critical biochemical mechanisms for Mps1 kinase regulation.

Cleavage of the SUN-domain protein Mps3 at its N-terminus regulates centrosome disjunction in budding yeast meiosis

PubMed Central

Koch, Bailey A.; Han, Xuemei

2017-01-01

Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge. Using the unique feature in yeast meiosis that centrosomes are linked for hours before their separation, we have revealed that Mps3 is cleaved at its nucleus-localized N-terminal domain, the process of which is regulated by its phosphorylation at serine 70. Cleavage of Mps3 takes place at the yeast centrosome and requires proteasome activity. We show that noncleavable Mps3 (Mps3-nc) inhibits centrosome separation during yeast meiosis. In addition, overexpression of mps3-nc in vegetative yeast cells also inhibits centrosome separation and is lethal. Our findings provide a genetic mechanism for the regulation of SUN-domain protein-mediated activities, including centrosome separation, by irreversible protein cleavage at the nuclear periphery. PMID:28609436

Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice.

PubMed

Lau, Adeline A; Crawley, Allison C; Hopwood, John J; Hemsley, Kim M

2008-08-05

Mucopolysaccharidosis (MPS) IIIA, or Sanfilippo syndrome, is a lysosomal storage disorder characterized by severe and progressive neuropathology. Following an asymptomatic period, patients may present with sleep disturbances, cognitive decline, aggressive tendencies and hyperactivity. A naturally-occurring mouse model of MPS IIIA also exhibits many of these behavioral features and has been recently back-crossed onto a C57BL/6 genetic background. To more thoroughly characterize the behavioral phenotype of congenic MPS IIIA mice, we assessed exploratory activity and unconditioned anxiety-related behavior in the elevated plus maze (EPM) and open field locomotor activity. Although MPS IIIA male mice were less active in the EPM at 18 and 20 weeks of age, they were more likely to explore the open arms than their normal counter-parts suggesting reduced anxiety. Repeated EPM testing reduced exploration of the open arms in MPS IIIA mice. In the open field test, significant reductions in activity were evident in naïve-tested male MPS IIIA mice from 10 weeks of age. Female normal and MPS IIIA mice displayed similar exploratory activity in the open field test. These differences in anxiety and locomotor activity will allow us to evaluate the efficacy of therapeutic regimes for MPS IIIA as a forerunner to developing safe and effective therapies for Sanfilippo patients.

CO₂ sorption kinetics of scaled-up polyethylenimine-functionalized mesoporous silica sorbent.

PubMed

Al-Marri, M J; Khader, M M; Tawfik, M; Qi, G; Giannelis, E P

2015-03-31

Two CO2 solid sorbents based on polyethylenimine, PEI (M(n) ∼ 423 and 10K), impregnated into mesoporous silica (MPS) foam prepared in kilogram quantities via a scale-up process were synthesized and systematically characterized by a range of analytical and surface techniques. The mesoporous silica sorbent impregnated with lower molecular weight PEI, PEI-423/MPS, showed higher capacity toward CO2 sorption than the sorbent functionalized with the higher molecular weight PEI (PEI-10K/MPS). On the other hand, PEI-10K/MPS exhibited higher thermal stability than PEI-423/MPS. The kinetics of CO2 adsorption on both PEI/MPS fitted well with a double-exponential model. According to this model CO2 adsorption can be divided into two steps: the first is fast and is attributed to CO2 adsorption on the sorbent surface; the second is slower and can be related to the diffusion of CO2 within and between the mesoporous particles. In contrast, the desorption process obeyed first-order kinetics with activation energies of 64.3 and 140.7 kJ mol(-1) for PEI-423/MPS and PEI-10K/MPS, respectively. These studies suggest that the selection of amine is critical as it affects not only sorbent capacity and stability but also the energy penalty associated with sorbent regeneration.

Chemiluminescent labels released from long spacer arm-functionalized magnetic particles: a novel strategy for ultrasensitive and highly selective detection of pathogen infections.

PubMed

Yang, Haowen; Liang, Wenbiao; He, Nongyue; Deng, Yan; Li, Zhiyang

2015-01-14

Previously, the unique advantages provided by chemiluminescence (CL) and magnetic particles (MPs) have resulted in the development of many useful nucleic acid detection methods. CL is highly sensitive, but when applied to MPs, its intensity is limited by the inner filter-like effect arising from excess dark MPs. Herein, we describe a modified strategy whereby CL labels are released from MPs to eliminate this negative effect. This approach relies on (1) the magnetic capture of target molecules on long spacer arm-functionalized magnetic particles (LSA-MPs), (2) the conjugation of streptavidin-alkaline phosphatase (SA-AP) to biotinylated amplicons of target pathogens, (3) the release of CL labels (specifically, AP tags), and (4) the detection of the released labels. CL labels were released from LSA-MPs through LSA ultrasonication or DNA enzymolysis, which proved to be the superior method. In contrast to conventional MPs, LSA-MPs exhibited significantly improved CL detection, because of the introduction of LSA, which was made of water-soluble carboxymethylated β-1,3-glucan. Detection of hepatitis B virus with this technique revealed a low detection limit of 50 fM, high selectivity, and excellent reproducibility. Thus, this approach may hold great potential for early stage clinical diagnosis of infectious diseases.

Materials experiment carrier concepts definition study. Volume 1: Executive summary, part 2

NASA Technical Reports Server (NTRS)

1981-01-01

The materials experiment carrier (MEC) is an optimized carrier for near term and advanced materials processing in space (MPS) research and commercial payloads. When coupled with the space platform (SP), the MEC can provide the extended duration, high power and low acceleration environment the MPS payload typically requires. The lowest cost, technically reasonable first step MEC that meets the MPS program missions objectives with minimum programmatic risks is defined. The effectiveness of the initial MEC/space platform idea for accommodating high priority, multidiscipline, R&D and commercial MPS payloads, and conducting MPS payload oprations at affordable funding and acceptable productivity levels is demonstrated.

Membrane microparticles and diseases.

PubMed

Wu, Z-H; Ji, C-L; Li, H; Qiu, G-X; Gao, C-J; Weng, X-S

2013-09-01

Membrane microparticles (MPs) are plasma membrane-derived vesicles shed by various types of activated or apoptotic cells including platelets, monocytes, endothelial cells, red blood cells, and granulocytes. MPs are being increasingly recognized as important regulators of cell-to-cell interactions. Recent evidences suggest they may play important functions not only in homeostasis but also in the pathogenesis of a number of diseases such as vascular diseases, cancer, infectious diseases and diabetes mellitus. Accordingly, inhibiting the production of MPs may serve as a novel therapeutic strategy for these diseases. Here we review recent advances on the mechanism underlying the generation of MPs and the role of MPs in vascular diseases, cancer, diabetes, inflammation, and pathogen infection.

Microplastic abundances in a mussel bed and ingestion by the ribbed marsh mussel Geukensia demissa.

PubMed

Khan, Matthew B; Prezant, Robert S

2018-05-01

Human activities have generated large quantities of microplastics that can be consumed by filter-feeding organisms as potential food sources. As a result, organisms may experience marked reductions in growth and/or health. To date there has been no investigations connecting microplastics (MPs) with the critically important ribbed mussel Geukensia demissa. Here we examined MP abundances within a bed of G. demissa in New Jersey. Results indicate that MP densities ranged between 11,000-50,000 pieces/m 2 . The abundance of larger MPs (5 mm ≥ 1 mm) did not vary among sampling sites while the smaller MPs (<1 mm) abundances did vary between sampling sites. These smaller MPs also accounted for 79% of MPs recovered from these sites. Based on the higher abundance of smaller MPs, we also investigated MP ingestion/rejection in a laboratory setting. These results confirmed that ribbed mussels can ingest MPs with negative consequences for the buoyancy of plastics rejected in feces and pseudofeces. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.

PubMed

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-10

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C Cdc20 ) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1-Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

Protein Phosphatase 1 inactivates Mps1 to ensure efficient Spindle Assembly Checkpoint silencing

PubMed Central

Moura, Margarida; Osswald, Mariana; Leça, Nelson; Barbosa, João; Pereira, António J; Maiato, Helder; Sunkel, Claudio E; Conde, Carlos

2017-01-01

Faithfull genome partitioning during cell division relies on the Spindle Assembly Checkpoint (SAC), a conserved signaling pathway that delays anaphase onset until all chromosomes are attached to spindle microtubules. Mps1 kinase is an upstream SAC regulator that promotes the assembly of an anaphase inhibitor through a sequential multi-target phosphorylation cascade. Thus, the SAC is highly responsive to Mps1, whose activity peaks in early mitosis as a result of its T-loop autophosphorylation. However, the mechanism controlling Mps1 inactivation once kinetochores attach to microtubules and the SAC is satisfied remains unknown. Here we show in vitro and in Drosophila that Protein Phosphatase 1 (PP1) inactivates Mps1 by dephosphorylating its T-loop. PP1-mediated dephosphorylation of Mps1 occurs at kinetochores and in the cytosol, and inactivation of both pools of Mps1 during metaphase is essential to ensure prompt and efficient SAC silencing. Overall, our findings uncover a mechanism of SAC inactivation required for timely mitotic exit. DOI: http://dx.doi.org/10.7554/eLife.25366.001 PMID:28463114

Preliminary Study on Gene Expression of Chitinase-Like Cytokines in Human Airway Epithelial Cell Under Chitin and Chitosan Microparticles Treatment.

PubMed

Alimohammadi, Masumeh; Yeganeh, Farshid; Haji Molla Hoseini, Mostafa

2016-06-01

Small-sized chitin and chitosan microparticles (MPs) reduce allergic inflammation. We examined the capacity of these glycans to stimulate A549 human airway epithelial cells to determine the feasibility of using of these glycans as allergic therapeutic modality. A549 cells were treated with MPs and then expressions levels of chitinase domain-containing 1 (CHID1) and chitinase 3-like 1 (CHI3L1) genes were determined by quantitative real-time PCR. IL-6 production was measured by ELISA. Chitin MPs resulted in upregulation of CHI3L1 expression by 35.7-fold while mRNA expression did not change with chitosan MPs. Compared to the untreated group, production of IL-6 was significantly decreased in the chitosan MPs-treated group, but chitin MPs treatment cause elevation of IL-6 level. This study demonstrates that chitin potently induces CHI3L1 expression, but chitosan is relatively inert. This effect and inhibition of pro-inflammatory cytokine (IL-6) suggest that chitosan MPs may possess more potential for therapeutic uses in human airway allergic inflammation.

Microplastics in Sewage Sludge: Effects of Treatment.

PubMed

Mahon, A M; O'Connell, B; Healy, M G; O'Connor, I; Officer, R; Nash, R; Morrison, L

2017-01-17

Waste water treatment plants (WWTPs) are receptors for the cumulative loading of microplastics (MPs) derived from industry, landfill, domestic wastewater and stormwater. The partitioning of MPs through the settlement processes of wastewater treatment results in the majority becoming entrained in the sewage sludge. This study characterized MPs in sludge samples from seven WWTPs in Ireland which use anaerobic digestion (AD), thermal drying (TD), or lime stabilization (LS) treatment processes. Abundances ranged from 4196 to 15 385 particles kg -1 (dry weight). Results of a general linear mixed model (GLMM) showed significantly higher abundances of MPs in smaller size classes in the LS samples, suggesting that the treatment process of LS shears MP particles. In contrast, lower abundances of MPs found in the AD samples suggests that this process may reduce MP abundances. Surface morphologies examined using scanning electron microscopy (SEM) showed characteristics of melting and blistering of TD MPs and shredding and flaking of LS MPs. This study highlights the potential for sewage sludge treatment processes to affect the risk of MP pollution prior to land spreading and may have implications for legislation governing the application of biosolids to agricultural land.

Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.

PubMed

Eguchi, Akiko; Mulya, Anny; Lazic, Milos; Radhakrishnan, Deepa; Berk, Michael P; Povero, Davide; Gornicka, Agnieszka; Feldstein, Ariel E

2015-01-01

Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs) are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity.

The Importance of Detailed Component Simulations in the Feedsystem Development for a Two-Stage-to Orbit Reusable Launch Vehicle

NASA Technical Reports Server (NTRS)

Mazurkivich, Pete; Chandler, Frank; Grayson, Gary

2005-01-01

To meet the requirements for the 2nd Generation Reusable Launch Vehicle (RLV), a unique propulsion feed system concept was identified using crossfeed between the booster and orbiter stages that could reduce the Two-Stage-to-Orbit (TSTO) vehicle weight and development cost by approximately 25%. A Main Propulsion System (MPS) crossfeed water demonstration test program was configured to address all the activities required to reduce the risks for the MPS crossfeed system. A transient, one-dimensional system simulation was developed for the subscale crossfeed water flow tests. To ensure accurate representation of the crossfeed valve's dynamics in the system model, a high-fidelity, three-dimensional, computational fluid-dynamics (CFD) model was employed. The results from the CFD model were used to specify the valve's flow characteristics in the system simulation. This yielded a crossfeed system model that was anchored to the specific valve hardware and achieved good agreement with the measured test data. These results allowed the transient models to be correlated and validated and used for full scale mission predictions. The full scale model simulations indicate crossfeed is ' viable with the system pressure disturbances at the crossfeed transition being less than experienced by the propulsion system during engine start and shutdown transients.

A Networked Sensor System for the Analysis of Plot-Scale Hydrology.

PubMed

Villalba, German; Plaza, Fernando; Zhong, Xiaoyang; Davis, Tyler W; Navarro, Miguel; Li, Yimei; Slater, Thomas A; Liang, Yao; Liang, Xu

2017-03-20

This study presents the latest updates to the Audubon Society of Western Pennsylvania (ASWP) testbed, a $50,000 USD, 104-node outdoor multi-hop wireless sensor network (WSN). The network collects environmental data from over 240 sensors, including the EC-5, MPS-1 and MPS-2 soil moisture and soil water potential sensors and self-made sap flow sensors, across a heterogeneous deployment comprised of MICAz, IRIS and TelosB wireless motes. A low-cost sensor board and software driver was developed for communicating with the analog and digital sensors. Innovative techniques (e.g., balanced energy efficient routing and heterogeneous over-the-air mote reprogramming) maintained high success rates (>96%) and enabled effective software updating, throughout the large-scale heterogeneous WSN. The edaphic properties monitored by the network showed strong agreement with data logger measurements and were fitted to pedotransfer functions for estimating local soil hydraulic properties. Furthermore, sap flow measurements, scaled to tree stand transpiration, were found to be at or below potential evapotranspiration estimates. While outdoor WSNs still present numerous challenges, the ASWP testbed proves to be an effective and (relatively) low-cost environmental monitoring solution and represents a step towards developing a platform for monitoring and quantifying statistically relevant environmental parameters from large-scale network deployments.

A Networked Sensor System for the Analysis of Plot-Scale Hydrology

PubMed Central

Villalba, German; Plaza, Fernando; Zhong, Xiaoyang; Davis, Tyler W.; Navarro, Miguel; Li, Yimei; Slater, Thomas A.; Liang, Yao; Liang, Xu

2017-01-01

This study presents the latest updates to the Audubon Society of Western Pennsylvania (ASWP) testbed, a $50,000 USD, 104-node outdoor multi-hop wireless sensor network (WSN). The network collects environmental data from over 240 sensors, including the EC-5, MPS-1 and MPS-2 soil moisture and soil water potential sensors and self-made sap flow sensors, across a heterogeneous deployment comprised of MICAz, IRIS and TelosB wireless motes. A low-cost sensor board and software driver was developed for communicating with the analog and digital sensors. Innovative techniques (e.g., balanced energy efficient routing and heterogeneous over-the-air mote reprogramming) maintained high success rates (>96%) and enabled effective software updating, throughout the large-scale heterogeneous WSN. The edaphic properties monitored by the network showed strong agreement with data logger measurements and were fitted to pedotransfer functions for estimating local soil hydraulic properties. Furthermore, sap flow measurements, scaled to tree stand transpiration, were found to be at or below potential evapotranspiration estimates. While outdoor WSNs still present numerous challenges, the ASWP testbed proves to be an effective and (relatively) low-cost environmental monitoring solution and represents a step towards developing a platform for monitoring and quantifying statistically relevant environmental parameters from large-scale network deployments. PMID:28335534

Variable volume combustor with a conical liner support

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

Johnson, Thomas Edward; McConnaughhay, Johnie Franklin; Keener, Chrisophter Paul

The present application provides a variable volume combustor for use with a gas turbine engine. The variable volume combustor may include a liner, a number of micro-mixer fuel nozzles positioned within the liner, and a conical liner support supporting the liner.

Antihepatotoxic efficacy of Mangifera indica L. polysaccharides against cyclophosphamide in rats.

PubMed

Fahmy, Sohair R; Amien, Ahmed I; Abd-Elgleel, Fathi M; Elaskalany, Sara M

2016-01-25

The present study aims to evaluate the possible protective role of polysaccharides extracted from the Egyptian mango Mangifera indica L. (MPS) and/or silymarine against cyclophosphamide (CP) toxicity in male albino rats. The MPS and/or silymarin significantly decreased the activities of serum ASAT and ALAT. However, MPS (1000 mg/kg) normalized their activities towards the normal levels recording 28.75 and 78.75 U/ml respectively. The recorded data also showed the antioxidant effect of MPS by decreasing the level of malondialdehyde (MDA) and increasing the level of reduced glutathione (GSH) as well as normalized the activities of the antioxidant enzyme GST and SOD. Histopathological examinations also confirmed the protective efficacy of MPS against liver toxicity of CP. In conclusion, the recorded results of the present study support the protective role of MPS and/or silymarin against CP-induced hepatic damage. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nanotechnology applied to treatment of mucopolysaccharidoses.

PubMed

Schuh, Roselena S; Baldo, Guilherme; Teixeira, Helder F

2016-12-01

Mucopolysaccharidoses (MPS) are genetic disorders caused by the accumulation of glycosaminoglycans due to deficiencies in the lysosomal enzymes responsible for their catabolism. Current treatments are not fully effective and are not available for all MPS types. Accordingly, researchers have tested novel therapies for MPS, including nanotechnology-based enzyme delivery systems and gene therapy. In this review, we aim to analyze some of the approaches involving nanotechnology as alternative treatments for MPS. Areas covered: We analyze nanotechnology-based systems, focusing on the biomaterials, such as polymers and lipids, that comprise these nanostructures, and we have highlighted studies that describe their use as enzyme and gene delivery systems for the treatment of MPS diseases. Expert opinion: Some protocols, such as the use of polymer-based systems or nanostructured carriers associated with enzymes and nanotechnology-based carriers for gene therapy, along with combined approaches, seem to be the future of MPS therapy.

Microplastic in three urban estuaries, China.

PubMed

Zhao, Shiye; Zhu, Lixin; Li, Daoji

2015-11-01

Estuarine Microplastics (MPs) are limited to know globally. By filtering subsurface water through 330 μm nets, MPs in Jiaojiang, Oujiang Estuaries were quantified, as well as that in Minjiang Estuary responding to Typhoon Soulik. Polymer matrix was analyzed by Raman spectroscopy. MP (<5 mm) comprised more than 90% of total number plastics. The highest MPs density was found in Minjiang, following Jiaojiang and Oujiang. Fibers and granules were the primary shapes, with no pellets found. Colored MPs were the majority. The concentrations of suspended microplastics determine their bioavailability to low trophic organisms, and then possibly promoting the transfer of microplastic to higher trophic levels. Polypropylene and polyethylene were the prevalent types of MPs analyzed. Economic structures in urban estuaries influenced on MPs contamination levels. Typhoon didn't influence the suspended MP densities significantly. Our results provide basic information for better understanding suspended microplastics within urban estuaries and for managerial actions. Copyright © 2015. Published by Elsevier Ltd.

Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis.

PubMed

Kagami, Yuya; Nihira, Keishi; Wada, Shota; Ono, Masaya; Honda, Mariko; Yoshida, Kiyotsugu

2014-06-23

During mitosis, genomic DNA is condensed into chromosomes to promote its equal segregation into daughter cells. Chromosome condensation occurs during cell cycle progression from G2 phase to mitosis. Failure of chromosome compaction at prophase leads to subsequent misregulation of chromosomes. However, the molecular mechanism that controls the early phase of mitotic chromosome condensation is largely unknown. Here, we show that Mps1 regulates initial chromosome condensation during mitosis. We identify condensin II as a novel Mps1-associated protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492 during mitosis, and this phosphorylation event is required for the proper loading of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of condensin II and accurate chromosome condensation during prophase. These findings demonstrate that Mps1 governs chromosomal organization during the early stage of mitosis to facilitate proper chromosome segregation. © 2014 Kagami et al.

Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis

PubMed Central

Kagami, Yuya; Nihira, Keishi; Wada, Shota; Ono, Masaya; Honda, Mariko

2014-01-01

During mitosis, genomic DNA is condensed into chromosomes to promote its equal segregation into daughter cells. Chromosome condensation occurs during cell cycle progression from G2 phase to mitosis. Failure of chromosome compaction at prophase leads to subsequent misregulation of chromosomes. However, the molecular mechanism that controls the early phase of mitotic chromosome condensation is largely unknown. Here, we show that Mps1 regulates initial chromosome condensation during mitosis. We identify condensin II as a novel Mps1-associated protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492 during mitosis, and this phosphorylation event is required for the proper loading of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of condensin II and accurate chromosome condensation during prophase. These findings demonstrate that Mps1 governs chromosomal organization during the early stage of mitosis to facilitate proper chromosome segregation. PMID:24934155

Transformation of cell-derived microparticles into quantum-dot-labeled nanovectors for antitumor siRNA delivery.

PubMed

Chen, Gang; Zhu, Jun-Yi; Zhang, Zhi-Ling; Zhang, Wei; Ren, Jian-Gang; Wu, Min; Hong, Zheng-Yuan; Lv, Cheng; Pang, Dai-Wen; Zhao, Yi-Fang

2015-01-12

Cell-derived microparticles (MPs) have been recently recognized as critical intercellular information conveyors. However, further understanding of their biological behavior and potential application has been hampered by the limitations of current labeling techniques. Herein, a universal donor-cell-assisted membrane biotinylation strategy was proposed for labeling MPs by skillfully utilizing the natural membrane phospholipid exchange of their donor cells. This innovative strategy conveniently led to specific, efficient, reproducible, and biocompatible quantum dot (QD) labeling of MPs, thereby reliably conferring valuable traceability on MPs. By further loading with small interference RNA, QD-labeled MPs that had inherent cell-targeting and biomolecule-conveying ability were successfully employed for combined bioimaging and tumor-targeted therapy. This study provides the first reliable and biofriendly strategy for transforming biogenic MPs into functionalized nanovectors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Disabled personnel emergency-heating system. Final report

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

Van Dine, N.

1974-12-16

This progress report describes a receiving well for the operating fuel supply (two provided) designed within the unit to permit parasitic heat loss from the system to be captured by the fuel supply. The Zero can housing provides adequate volume to accommodate stowage of the fluid-flow umbilicals for connection of the heater system to the tubulated casualty bag liner.

Geosynthetic clay liners shrinkage under simulated daily thermal cycles.

PubMed

Sarabadani, Hamid; Rayhani, Mohammad T

2014-06-01

Geosynthetic clay liners are used as part of composite liner systems in municipal solid waste landfills and other applications to restrict the escape of contaminants into the surrounding environment. This is attainable provided that the geosynthetic clay liner panels continuously cover the subsoil. Previous case histories, however, have shown that some geosynthetic clay liner panels are prone to significant shrinkage and separation when an overlying geomembrane is exposed to solar radiation. Experimental models were initiated to evaluate the potential shrinkage of different geosynthetic clay liner products placed over sand and clay subsoils, subjected to simulated daily thermal cycles (60°C for 8 hours and 22°C for 16 hours) modelling field conditions in which the liner is exposed to solar radiation. The variation of geosynthetic clay liner shrinkage was evaluated at specified times by a photogrammetry technique. The manufacturing techniques, the initial moisture content, and the aspect ratio (ratio of length to width) of the geosynthetic clay liner were found to considerably affect the shrinkage of geosynthetic clay liners. The particle size distribution of the subsoil and the associated suction at the geosynthetic clay liner-subsoil interface was also found to have significant effects on the shrinkage of the geosynthetic clay liner. © The Author(s) 2014.