Application of the International Water Association activated sludge models to describe aerobic sludge digestion.

PubMed

Ghorbani, M; Eskicioglu, C

2011-12-01

Batch and semi-continuous flow aerobic digesters were used to stabilize thickened waste-activated sludge at different initial conditions and mean solids retention times. Under dynamic conditions, total suspended solids, volatile suspended solids (VSS) and total and particulate chemical oxygen demand (COD and PCOD) were monitored in the batch reactors and effluent from the semi-continuous flow reactors. Activated Sludge Model (ASM) no. 1 and ASM no. 3 were applied to measured data (calibration data set) to evaluate the consistency and performances of models at different flow regimes for digester COD and VSS modelling. The results indicated that both ASM1 and ASM3 predicted digester COD, VSS and PCOD concentrations well (R2, Ra2 > or = 0.93). Parameter estimation concluded that compared to ASM1, ASM3 parameters were more consistent across different batch and semi-continuous flow runs with different operating conditions. Model validation on a data set independent from the calibration data successfully predicted digester COD (R2 = 0.88) and VSS (R2 = 0.94) concentrations by ASM3, while ASM1 overestimated both reactor COD (R2 = 0.74) and VSS concentrations (R2 = 0.79) after 15 days of aerobic batch digestion.

Alternative splicing of SMPD1 coding for acid sphingomyelinase in major depression.

PubMed

Rhein, Cosima; Reichel, Martin; Kramer, Marcel; Rotter, Andrea; Lenz, Bernd; Mühle, Christiane; Gulbins, Erich; Kornhuber, Johannes

2017-02-01

Major depressive disorder (MDD) is a psychiatric disorder characterized by key symptoms that include depressed mood and a loss of interest and pleasure. A recently developed pathogenic model of MDD involves disturbed neurogenesis in the hippocampus, where the acid sphingomyelinase (ASM)/ceramide system plays an important role and is proposed as a molecular target for antidepressant action. Because alternative splicing of SMPD1 mRNA, coding for ASM, is relevant for the regulation of ASM enzymatic activity, we investigated the frequency of alternatively spliced ASM isoforms in peripheral blood cells of MDD patients versus healthy controls. Because the full-length transcript variant 1 of SMPD1 (termed ASM-1) is the only known form within the splicing pattern that encodes an enzymatically fully active ASM, we determined a fraction of splice isoforms deviating from ASM-1 using PCR amplification and capillary electrophoresis with laser-induced fluorescence analysis. ASM alternative splicing events occurred significantly less frequently in MDD patients compared to healthy subjects. After 5 days of antidepressant treatment, the frequency of alternatively spliced ASM isoforms decreased in those patients who were treated with a functional inhibitor of ASM activity (FIASMA) but remained constant in MDD patients treated with other antidepressant drugs. This effect was more pronounced when healthy male volunteers were treated with the FIASMAs fluoxetine or paroxetine, in contrast to a placebo group. Patients were treated with different antidepressant drugs, depending on individual parameters and disease courses. This study shows that the ASM alternative splicing pattern could be a biological target with diagnostic relevance and could serve as a novel biomarker for MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

Activated sludge model (ASM) based modelling of membrane bioreactor (MBR) processes: a critical review with special regard to MBR specificities.

PubMed

Fenu, A; Guglielmi, G; Jimenez, J; Spèrandio, M; Saroj, D; Lesjean, B; Brepols, C; Thoeye, C; Nopens, I

2010-08-01

Membrane bioreactors (MBRs) have been increasingly employed for municipal and industrial wastewater treatment in the last decade. The efforts for modelling of such wastewater treatment systems have always targeted either the biological processes (treatment quality target) as well as the various aspects of engineering (cost effective design and operation). The development of Activated Sludge Models (ASM) was an important evolution in the modelling of Conventional Activated Sludge (CAS) processes and their use is now very well established. However, although they were initially developed to describe CAS processes, they have simply been transferred and applied to MBR processes. Recent studies on MBR biological processes have reported several crucial specificities: medium to very high sludge retention times, high mixed liquor concentration, accumulation of soluble microbial products (SMP) rejected by the membrane filtration step, and high aeration rates for scouring purposes. These aspects raise the question as to what extent the ASM framework is applicable to MBR processes. Several studies highlighting some of the aforementioned issues are scattered through the literature. Hence, through a concise and structured overview of the past developments and current state-of-the-art in biological modelling of MBR, this review explores ASM-based modelling applied to MBR processes. The work aims to synthesize previous studies and differentiates between unmodified and modified applications of ASM to MBR. Particular emphasis is placed on influent fractionation, biokinetics, and soluble microbial products (SMPs)/exo-polymeric substances (EPS) modelling, and suggestions are put forward as to good modelling practice with regard to MBR modelling both for end-users and academia. A last section highlights shortcomings and future needs for improved biological modelling of MBR processes. (c) 2010 Elsevier Ltd. All rights reserved.

A Novel Protocol for Model Calibration in Biological Wastewater Treatment

PubMed Central

Zhu, Ao; Guo, Jianhua; Ni, Bing-Jie; Wang, Shuying; Yang, Qing; Peng, Yongzhen

2015-01-01

Activated sludge models (ASMs) have been widely used for process design, operation and optimization in wastewater treatment plants. However, it is still a challenge to achieve an efficient calibration for reliable application by using the conventional approaches. Hereby, we propose a novel calibration protocol, i.e. Numerical Optimal Approaching Procedure (NOAP), for the systematic calibration of ASMs. The NOAP consists of three key steps in an iterative scheme flow: i) global factors sensitivity analysis for factors fixing; ii) pseudo-global parameter correlation analysis for non-identifiable factors detection; and iii) formation of a parameter subset through an estimation by using genetic algorithm. The validity and applicability are confirmed using experimental data obtained from two independent wastewater treatment systems, including a sequencing batch reactor and a continuous stirred-tank reactor. The results indicate that the NOAP can effectively determine the optimal parameter subset and successfully perform model calibration and validation for these two different systems. The proposed NOAP is expected to use for automatic calibration of ASMs and be applied potentially to other ordinary differential equations models. PMID:25682959

c-Abl Is an Upstream Regulator of Acid Sphingomyelinase in Apoptosis Induced by Inhibition of Integrins αvβ3 and αvβ5

PubMed Central

Cooper, Jason P.; Kang, Min H.; Erdreich-Epstein, Anat

2012-01-01

Inhibition of integrins αvβ3/αvβ5 by the cyclic function-blocking peptide, RGDfV (Arg-Gly-Asp-Phe-Val) can induce apoptosis in both normal cells and tumor cells. We show that RGDfV induced apoptosis in ECV-304 carcinoma cells, increased activity and mRNA expression of acid sphingomyelinase (ASM), and increased ceramides C16, C18∶0, C24∶0 and C24∶1 while decreasing the corresponding sphingomyelins. siRNA to ASM decreased RGDfV-induced apoptosis as measured by TUNEL, PARP cleavage, mitochondrial depolarization, and caspase-3 and caspase-8 activities, as well as by annexinV in a 3D collagen model. These findings indicate a causal role for ASM in RGDfV-induced apoptosis in ECV-304. We have shown that c-Abl, a non-receptor tyrosine kinase, also mediates RGDfV-induced apoptosis. However, c-Abl, has not been previously linked to ASM in any system. Here we show that STI-571 (imatinib, inhibitor of c-Abl) inhibited RGDfV-induced ASM activity. Furthermore, STI-571 and c-Abl-siRNA both inhibited RGDfV-induced increase in ASM mRNA, but ASM-siRNA did not affect c-Abl phosphorylation or expression, supporting that c-Abl regulates the RGDfV-induced increase in ASM expression. These studies implicate ASM as a mediator of apoptosis induced by inhibition of integrins αvβ3/αvβ5, and for the first time place c-Abl as an upstream regulator of ASM expression and activity. PMID:22879933

A Probabilistic Approach to Zhang's Sandpile Model

NASA Astrophysics Data System (ADS)

Boer, Anne Fey-Den; Meester, Ronald; Quant, Corrie; Redig, Frank

2008-06-01

The current literature on sandpile models mainly deals with the abelian sandpile model (ASM) and its variants. We treat a less known - but equally interesting - model, namely Zhang’s sandpile. This model differs in two aspects from the ASM. First, additions are not discrete, but random amounts with a uniform distribution on an interval [ a, b]. Second, if a site topples - which happens if the amount at that site is larger than a threshold value E c (which is a model parameter), then it divides its entire content in equal amounts among its neighbors. Zhang conjectured that in the infinite volume limit, this model tends to behave like the ASM in the sense that the stationary measure for the system in large volumes tends to be peaked narrowly around a finite set. This belief is supported by simulations, but so far not by analytical investigations. We study the stationary distribution of this model in one dimension, for several values of a and b. When there is only one site, exact computations are possible. Our main result concerns the limit as the number of sites tends to infinity. We find that the stationary distribution, in the case a ≥ E c /2, indeed tends to that of the ASM (up to a scaling factor), in agreement with Zhang’s conjecture. For the case a = 0, b = 1 we provide strong evidence that the stationary expectation tends to sqrt{1/2}.

An extension of ASM2d including pH calculation.

PubMed

Serralta, J; Ferrer, J; Borrás, L; Seco, A

2004-11-01

This paper presents an extension of the Activated Sludge Model No. 2d (ASM2d) including a chemical model able to calculate the pH value in biological processes. The developed chemical model incorporates the complete set of chemical species affecting the pH value to ASM2d describing non-equilibrium biochemical processes. It considers the system formed by one aqueous phase, in which biochemical processes take place, and one gaseous phase, and is based on the assumptions of instantaneous chemical equilibrium under liquid phase and kinetically governed mass transport between the liquid and gas phase. The ASM2d enlargement comprises the addition of every component affecting the pH value and an ion-balance for the calculation of the pH value and the dissociation species. The significant pH variations observed in a sequencing batch reactor operated for enhanced biological phosphorus removal were used to verify the capability of the extended model for predicting the dynamics of pH jointly with concentrations of acetic acid and phosphate. A pH inhibition function for polyphosphate accumulating bacteria has also been included in the model to simulate the behaviour observed. Experimental data obtained in four different experiments (with different sludge retention time and influent phosphorus concentrations) were accurately reproduced.

Establishment and characterization of an angiosarcoma-derived cell line, AS-M.

PubMed

Krump-Konvalinkova, Vera; Bittinger, Fernando; Olert, Jürgen; Bräuninger, Wolfgang; Brunner, Joachim; Kirkpatrick, C James

2003-01-01

A novel human endothelial cell line, AS-M, has been established from a cutaneous angiosarcoma on the scalp. The cells expressing platelet endothelial cell adhesion molecule-1 (CD31) were isolated using magnetic beads and subsequently cultured for a year. To date, the cells have undergone more than 100 population doublings (PDs). The AS-M cells manifested endothelial characteristics, such as active uptake of acetylated low-density lipoprotein labeled with 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil-Ac-LDL), capacity to bind the Ulex europeaus agglutin-I (UEA-I), and expression of von Willebrand factor (vWF) and CD31. The single cell-derived clone, AS-M.5, showed a constitutive expression of CD31, vWF, angiotensin-converting enzyme (ACE), endoglin (CD105), and the endothelial cell receptor tyrosine kinases KDR and Tie-1. Similarly to freshly isolated endothelial cells, the AS-M.5 responded to induction by bacterial lipopolysaccharide (LPS) by increased transcription of cell adhesion molecules and cytokines. The AS-M.5 cultures required endothelial growth supplements for optimal growth and long-term propagation in vitro. However, in contrast to normal endothelial cells, p53 gene products were detected in nuclei of AS-M.5 cells. Cytogenetic analyses consistently revealed a hypodiploid karyotype with complete loss of one homologue of several chromosomes and a homogeneous pattern of distinct karyotypic changes. Although the AS-M.5 presented characteristics suggestive of tumor cells, they did not develop into tumors when inoculated subcutaneously into nude mice. The cell line AS-M.5 could be a useful model system to study endothelial pathobiology in vitro.

Biological phosphorus removal in an extended ASM2 model: Roles of extracellular polymeric substances and kinetic modeling.

PubMed

Yang, Shan-Shan; Pang, Ji-Wei; Guo, Wan-Qian; Yang, Xiao-Yin; Wu, Zhong-Yang; Ren, Nan-Qi; Zhao, Zhi-Qing

2017-05-01

This paper presents the results of an extended ASM2 model for the modeling and calibration of the role of extracellular polymeric substances (EPS) in phosphorus (P) removal in an anaerobic-aerobic process. In this extended ASM2 model, two new components, the bound EPS (X EPS ) and the soluble EPS (S EPS ), are introduced. Compared with the ASM2, 7.71, 8.53, and 9.28% decreases in polyphosphate (polyP) were observed in the extended ASM2 in three sequencing batch reactors feeding with different COD/P ratios, indicating that 7.71-9.28% of P in the liquid was adsorbed by EPS. Sensitive analysis indicated that, five parameters were the significant influential parameters and had been chosen for further model calibration by using the least square method to simulate by MATLAB. This extended ASM2 has been successfully established to simulate the output variables and provides a useful reference for the mathematic simulations of the role of EPS in biological phosphorus removal process. Copyright © 2017. Published by Elsevier Ltd.

Characterization of Acid Sphingomyelinase Activity in Human Cerebrospinal Fluid

PubMed Central

Mühle, Christiane; Huttner, Hagen B.; Walter, Silke; Reichel, Martin; Canneva, Fabio; Lewczuk, Piotr; Gulbins, Erich; Kornhuber, Johannes

2013-01-01

Background As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM) is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum. Methods An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF) collected from mice and from 42 patients who were classified as controls based on normal routine CSF values. Results We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme’s properties. The enzyme resembles plasmatic ASM including protein stability and Zn2+-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters. Conclusions Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success. PMID:23658784

Modelling carbon oxidation in pulp mill activated sludge systems: calibration of Activated Sludge Model No 3.

PubMed

Barañao, P A; Hall, E R

2004-01-01

Activated Sludge Model No 3 (ASM3) was chosen to model an activated sludge system treating effluents from a mechanical pulp and paper mill. The high COD concentration and the high content of readily biodegradable substrates of the wastewater make this model appropriate for this system. ASM3 was calibrated based on batch respirometric tests using fresh wastewater and sludge from the treatment plant, and on analytical measurements of COD, TSS and VSS. The model, developed for municipal wastewater, was found suitable for fitting a variety of respirometric batch tests, performed at different temperatures and food to microorganism ratios (F/M). Therefore, a set of calibrated parameters, as well as the wastewater COD fractions, was estimated for this industrial wastewater. The majority of the calibrated parameters were in the range of those found in the literature.

Acid sphingomyelinase serum activity predicts mortality in intensive care unit patients after systemic inflammation: a prospective cohort study.

PubMed

Kott, Matthias; Elke, Gunnar; Reinicke, Maike; Winoto-Morbach, Supandi; Schädler, Dirk; Zick, Günther; Frerichs, Inéz; Weiler, Norbert; Schütze, Stefan

2014-01-01

Acid sphingomyelinase is involved in lipid signalling pathways and regulation of apoptosis by the generation of ceramide and plays an important role during the host response to infectious stimuli. It thus has the potential to be used as a novel diagnostic marker in the management of critically ill patients. The objective of our study was to evaluate acid sphingomyelinase serum activity (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit population before, during, and after systemic inflammation. 40 patients admitted to the intensive care unit at risk for developing systemic inflammation (defined as systemic inflammatory response syndrome plus a significant procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission, before (PCT before), during (PCT peak) and after (PCT low) onset of SIRS. Patients undergoing elective surgery served as control (N = 8). Receiver-operating characteristics curves were computed. ASM significantly increased after surgery in the eight control patients. Patients from the intensive care unit had significantly higher ASM on admission than control patients after surgery. 19 out of 40 patients admitted to the intensive care unit developed systemic inflammation and 21 did not, with no differences in ASM between these two groups on admission. In patients with SIRS and PCT peak, ASM between admission and PCT before was not different, but further increased at PCT peak in non-survivors and was significantly higher at PCT low compared to survivors. Survivors exhibited decreased ASM at PCT peak and PCT low. Receiver operating curve analysis on discrimination of ICU mortality showed an area under the curve of 0.79 for ASM at PCT low. In summary, ASM was generally higher in patients admitted to the intensive care unit compared to patients undergoing uncomplicated surgery. ASM did not indicate onset of systemic inflammation. In contrast to PCT however, it remained high in non-surviving ICU patients after systemic inflammation.

Acid Sphingomyelinase Serum Activity Predicts Mortality in Intensive Care Unit Patients after Systemic Inflammation: A Prospective Cohort Study

PubMed Central

Reinicke, Maike; Winoto-Morbach, Supandi; Schädler, Dirk; Zick, Günther; Frerichs, Inéz; Weiler, Norbert; Schütze, Stefan

2014-01-01

Introduction Acid sphingomyelinase is involved in lipid signalling pathways and regulation of apoptosis by the generation of ceramide and plays an important role during the host response to infectious stimuli. It thus has the potential to be used as a novel diagnostic marker in the management of critically ill patients. The objective of our study was to evaluate acid sphingomyelinase serum activity (ASM) as a diagnostic and prognostic marker in a mixed intensive care unit population before, during, and after systemic inflammation. Methods 40 patients admitted to the intensive care unit at risk for developing systemic inflammation (defined as systemic inflammatory response syndrome plus a significant procalcitonin [PCT] increase) were included. ASM was analysed on ICU admission, before (PCTbefore), during (PCTpeak) and after (PCTlow) onset of SIRS. Patients undergoing elective surgery served as control (N = 8). Receiver-operating characteristics curves were computed. Results ASM significantly increased after surgery in the eight control patients. Patients from the intensive care unit had significantly higher ASM on admission than control patients after surgery. 19 out of 40 patients admitted to the intensive care unit developed systemic inflammation and 21 did not, with no differences in ASM between these two groups on admission. In patients with SIRS and PCT peak, ASM between admission and PCTbefore was not different, but further increased at PCTpeak in non-survivors and was significantly higher at PCTlow compared to survivors. Survivors exhibited decreased ASM at PCTpeak and PCTlow. Receiver operating curve analysis on discrimination of ICU mortality showed an area under the curve of 0.79 for ASM at PCTlow. Conclusions In summary, ASM was generally higher in patients admitted to the intensive care unit compared to patients undergoing uncomplicated surgery. ASM did not indicate onset of systemic inflammation. In contrast to PCT however, it remained high in non-surviving ICU patients after systemic inflammation. PMID:25384060

The Role of Inflammation Resolution Speed in Airway Smooth Muscle Mass Accumulation in Asthma: Insight from a Theoretical Model

PubMed Central

Chernyavsky, Igor L.; Croisier, Huguette; Chapman, Lloyd A. C.; Kimpton, Laura S.; Hiorns, Jonathan E.; Brook, Bindi S.; Jensen, Oliver E.; Billington, Charlotte K.; Hall, Ian P.; Johnson, Simon R.

2014-01-01

Despite a large amount of in vitro data, the dynamics of airway smooth muscle (ASM) mass increase in the airways of patients with asthma is not well understood. Here, we present a novel mathematical model that describes qualitatively the growth dynamics of ASM cells over short and long terms in the normal and inflammatory environments typically observed in asthma. The degree of ASM accumulation can be explained by an increase in the rate at which ASM cells switch between non-proliferative and proliferative states, driven by episodic inflammatory events. Our model explores the idea that remodelling due to ASM hyperplasia increases with the frequency and magnitude of these inflammatory events, relative to certain sensitivity thresholds. It highlights the importance of inflammation resolution speed by showing that when resolution is slow, even a series of small exacerbation events can result in significant remodelling, which persists after the inflammatory episodes. In addition, we demonstrate how the uncertainty in long-term outcome may be quantified and used to design an optimal low-risk individual anti-proliferative treatment strategy. The model shows that the rate of clearance of ASM proliferation and recruitment factors after an acute inflammatory event is a potentially important, and hitherto unrecognised, target for anti-remodelling therapy in asthma. It also suggests new ways of quantifying inflammation severity that could improve prediction of the extent of ASM accumulation. This ASM growth model should prove useful for designing new experiments or as a building block of more detailed multi-cellular tissue-level models. PMID:24632688

Functional Implications of Novel Human Acid Sphingomyelinase Splice Variants

PubMed Central

Rhein, Cosima; Tripal, Philipp; Seebahn, Angela; Konrad, Alice; Kramer, Marcel; Nagel, Christine; Kemper, Jonas; Bode, Jens; Mühle, Christiane; Gulbins, Erich; Reichel, Martin; Becker, Cord-Michael; Kornhuber, Johannes

2012-01-01

Background Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity. Methodology/Principal Findings We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models. Conclusions/Significance These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity. PMID:22558155

Development and characterization of a 3D multicell microtissue culture model of airway smooth muscle.

PubMed

West, Adrian R; Zaman, Nishat; Cole, Darren J; Walker, Matthew J; Legant, Wesley R; Boudou, Thomas; Chen, Christopher S; Favreau, John T; Gaudette, Glenn R; Cowley, Elizabeth A; Maksym, Geoffrey N

2013-01-01

Airway smooth muscle (ASM) cellular and molecular biology is typically studied with single-cell cultures grown on flat 2D substrates. However, cells in vivo exist as part of complex 3D structures, and it is well established in other cell types that altering substrate geometry exerts potent effects on phenotype and function. These factors may be especially relevant to asthma, a disease characterized by structural remodeling of the airway wall, and highlights a need for more physiologically relevant models of ASM function. We utilized a tissue engineering platform known as microfabricated tissue gauges to develop a 3D culture model of ASM featuring arrays of ∼0.4 mm long, ∼350 cell "microtissues" capable of simultaneous contractile force measurement and cell-level microscopy. ASM-only microtissues generated baseline tension, exhibited strong cellular organization, and developed actin stress fibers, but lost structural integrity and dissociated from the cantilevers within 3 days. Addition of 3T3-fibroblasts dramatically improved survival times without affecting tension development or morphology. ASM-3T3 microtissues contracted similarly to ex vivo ASM, exhibiting reproducible responses to a range of contractile and relaxant agents. Compared with 2D cultures, microtissues demonstrated identical responses to acetylcholine and KCl, but not histamine, forskolin, or cytochalasin D, suggesting that contractility is regulated by substrate geometry. Microtissues represent a novel model for studying ASM, incorporating a physiological 3D structure, realistic mechanical environment, coculture of multiple cells types, and comparable contractile properties to existing models. This new model allows for rapid screening of biochemical and mechanical factors to provide insight into ASM dysfunction in asthma.

A beamline systems model for Accelerator-Driven Transmutation Technology (ADTT) facilities

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

Todd, A.M.M.; Paulson, C.C.; Peacock, M.A.

1995-10-01

A beamline systems code, that is being developed for Accelerator-Driven Transmutation Technology (ADTT) facility trade studies, is described. The overall program is a joint Grumman, G.H. Gillespie Associates (GHGA) and Los Alamos National Laboratory effort. The GHGA Accelerator Systems Model (ASM) has been adopted as the framework on which this effort is based. Relevant accelerator and beam transport models from earlier Grumman systems codes are being adapted to this framework. Preliminary physics and engineering models for each ADTT beamline component have been constructed. Examples noted include a Bridge Coupled Drift Tube Linac (BCDTL) and the accelerator thermal system. A decisionmore » has been made to confine the ASM framework principally to beamline modeling, while detailed target/blanket, balance-of-plant and facility costing analysis will be performed externally. An interfacing external balance-of-plant and facility costing model, which will permit the performance of iterative facility trade studies, is under separate development. An ABC (Accelerator Based Conversion) example is used to highlight the present models and capabilities.« less

A beamline systems model for Accelerator-Driven Transmutation Technology (ADTT) facilities

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

Todd, Alan M. M.; Paulson, C. C.; Peacock, M. A.

1995-09-15

A beamline systems code, that is being developed for Accelerator-Driven Transmutation Technology (ADTT) facility trade studies, is described. The overall program is a joint Grumman, G. H. Gillespie Associates (GHGA) and Los Alamos National Laboratory effort. The GHGA Accelerator Systems Model (ASM) has been adopted as the framework on which this effort is based. Relevant accelerator and beam transport models from earlier Grumman systems codes are being adapted to this framework. Preliminary physics and engineering models for each ADTT beamline component have been constructed. Examples noted include a Bridge Coupled Drift Tube Linac (BCDTL) and the accelerator thermal system. Amore » decision has been made to confine the ASM framework principally to beamline modeling, while detailed target/blanket, balance-of-plant and facility costing analysis will be performed externally. An interfacing external balance-of-plant and facility costing model, which will permit the performance of iterative facility trade studies, is under separate development. An ABC (Accelerator Based Conversion) example is used to highlight the present models and capabilities.« less

Adapting Active Shape Models for 3D segmentation of tubular structures in medical images.

PubMed

de Bruijne, Marleen; van Ginneken, Bram; Viergever, Max A; Niessen, Wiro J

2003-07-01

Active Shape Models (ASM) have proven to be an effective approach for image segmentation. In some applications, however, the linear model of gray level appearance around a contour that is used in ASM is not sufficient for accurate boundary localization. Furthermore, the statistical shape model may be too restricted if the training set is limited. This paper describes modifications to both the shape and the appearance model of the original ASM formulation. Shape model flexibility is increased, for tubular objects, by modeling the axis deformation independent of the cross-sectional deformation, and by adding supplementary cylindrical deformation modes. Furthermore, a novel appearance modeling scheme that effectively deals with a highly varying background is developed. In contrast with the conventional ASM approach, the new appearance model is trained on both boundary and non-boundary points, and the probability that a given point belongs to the boundary is estimated non-parametrically. The methods are evaluated on the complex task of segmenting thrombus in abdominal aortic aneurysms (AAA). Shape approximation errors were successfully reduced using the two shape model extensions. Segmentation using the new appearance model significantly outperformed the original ASM scheme; average volume errors are 5.1% and 45% respectively.

Kinetics of autothermal thermophilic aerobic digestion - application and extension of Activated Sludge Model No 1 at thermophilic temperatures.

PubMed

Kovács, R; Miháltz, P; Csikor, Zs

2007-01-01

The application of an ASM1-based mathematical model for the modeling of autothermal thermophilic aerobic digestion is demonstrated. Based on former experimental results the original ASM1 was extended by the activation of facultative thermophiles from the feed sludge and a new component, the thermophilic biomass was introduced. The resulting model was calibrated in the temperature range of 20-60 degrees C. The temperature dependence of the growth and decay rates in the model is given in terms of the slightly modified Arrhenius and Topiwala-Sinclair equations. The capabilities of the calibrated model in realistic ATAD scenarios are demonstrated with a focus on autothermal properties of ATAD systems at different conditions.

Influences of volcano eruptions on Asian Summer Monsoon over the last 110 years.

PubMed

Ning, Liang; Liu, Jian; Sun, Weiyi

2017-02-16

Asian summer monsoon (ASM) precipitation is the primary water resource for agriculture in many Asian countries that have experienced rapid economic growth in recent decades, thus implying the necessity for further investigations on both the internal variability of the ASM and the influence of external factors on the ASM. Using long-term high-resolution (0.5° × 0.5°) observed precipitation data, contrary to previous studies on inter-annual timescale, we showed that over the last 110 years, volcanic eruptions have influenced ASM variations on an inter-decadal timescale via teleconnections with the Atlantic Multi-decadal Oscillation (AMO). This relationship was also confirmed by Coupled Model Intercomparison Program Phase 5 (CMIP5) model simulations. During the active volcanic eruption periods (1901-1935 and 1963-1993), significantly lower ASM precipitation was observed compared with that during the inactive volcanic eruption period (1936-1962). We found that during active volcanic eruption periods, which correspond to a negative AMO state, there is an anomalously weakened Walker circulation over the tropical Pacific that transports less moisture to the ASM region and subsequently reduces ASM precipitation. This new finding may help improve decadal predictions of future changes in the ASM.

Influences of volcano eruptions on Asian Summer Monsoon over the last 110 years

NASA Astrophysics Data System (ADS)

Ning, Liang; Liu, Jian; Sun, Weiyi

2017-02-01

Asian summer monsoon (ASM) precipitation is the primary water resource for agriculture in many Asian countries that have experienced rapid economic growth in recent decades, thus implying the necessity for further investigations on both the internal variability of the ASM and the influence of external factors on the ASM. Using long-term high-resolution (0.5° × 0.5°) observed precipitation data, contrary to previous studies on inter-annual timescale, we showed that over the last 110 years, volcanic eruptions have influenced ASM variations on an inter-decadal timescale via teleconnections with the Atlantic Multi-decadal Oscillation (AMO). This relationship was also confirmed by Coupled Model Intercomparison Program Phase 5 (CMIP5) model simulations. During the active volcanic eruption periods (1901-1935 and 1963-1993), significantly lower ASM precipitation was observed compared with that during the inactive volcanic eruption period (1936-1962). We found that during active volcanic eruption periods, which correspond to a negative AMO state, there is an anomalously weakened Walker circulation over the tropical Pacific that transports less moisture to the ASM region and subsequently reduces ASM precipitation. This new finding may help improve decadal predictions of future changes in the ASM.

Airway smooth muscle contraction - perspectives on past, present and future.

PubMed

Mitchell, H W

2009-10-01

Past and contemporary views of airway smooth muscle (ASM) have led to a high level of understanding of the control and intracellular regulation of force or shortening of ASM and of its possible role in airway disease. As well as the multitude of cellular mechanisms that regulate ASM contraction, a number of structural and mechanical factors, which are only present at the airway and lung level, provide overriding control over ASM. With new knowledge about the cellular physiology and biology of ASM, there is increasing need to understand how ASM contraction is regulated and expressed at these airway and system levels.

Simulation and optimization of a coking wastewater biological treatment process by activated sludge models (ASM).

PubMed

Wu, Xiaohui; Yang, Yang; Wu, Gaoming; Mao, Juan; Zhou, Tao

2016-01-01

Applications of activated sludge models (ASM) in simulating industrial biological wastewater treatment plants (WWTPs) are still difficult due to refractory and complex components in influents as well as diversity in activated sludges. In this study, an ASM3 modeling study was conducted to simulate and optimize a practical coking wastewater treatment plant (CWTP). First, respirometric characterizations of the coking wastewater and CWTP biomasses were conducted to determine the specific kinetic and stoichiometric model parameters for the consecutive aeration-anoxic-aeration (O-A/O) biological process. All ASM3 parameters have been further estimated and calibrated, through cross validation by the model dynamic simulation procedure. Consequently, an ASM3 model was successfully established to accurately simulate the CWTP performances in removing COD and NH4-N. An optimized CWTP operation condition could be proposed reducing the operation cost from 6.2 to 5.5 €/m(3) wastewater. This study is expected to provide a useful reference for mathematic simulations of practical industrial WWTPs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Towards a consensus-based biokinetic model for green microalgae - The ASM-A.

PubMed

Wágner, Dorottya S; Valverde-Pérez, Borja; Sæbø, Mariann; Bregua de la Sotilla, Marta; Van Wagenen, Jonathan; Smets, Barth F; Plósz, Benedek Gy

2016-10-15

Cultivation of microalgae in open ponds and closed photobioreactors (PBRs) using wastewater resources offers an opportunity for biochemical nutrient recovery. Effective reactor system design and process control of PBRs requires process models. Several models with different complexities have been developed to predict microalgal growth. However, none of these models can effectively describe all the relevant processes when microalgal growth is coupled with nutrient removal and recovery from wastewaters. Here, we present a mathematical model developed to simulate green microalgal growth (ASM-A) using the systematic approach of the activated sludge modelling (ASM) framework. The process model - identified based on a literature review and using new experimental data - accounts for factors influencing photoautotrophic and heterotrophic microalgal growth, nutrient uptake and storage (i.e. Droop model) and decay of microalgae. Model parameters were estimated using laboratory-scale batch and sequenced batch experiments using the novel Latin Hypercube Sampling based Simplex (LHSS) method. The model was evaluated using independent data obtained in a 24-L PBR operated in sequenced batch mode. Identifiability of the model was assessed. The model can effectively describe microalgal biomass growth, ammonia and phosphate concentrations as well as the phosphorus storage using a set of average parameter values estimated with the experimental data. A statistical analysis of simulation and measured data suggests that culture history and substrate availability can introduce significant variability on parameter values for predicting the reaction rates for bulk nitrate and the intracellularly stored nitrogen state-variables, thereby requiring scenario specific model calibration. ASM-A was identified using standard cultivation medium and it can provide a platform for extensions accounting for factors influencing algal growth and nutrient storage using wastewater resources. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computation of turbulent reacting flow in a solid-propellant ducted rocket

NASA Astrophysics Data System (ADS)

Chao, Yei-Chin; Chou, Wen-Fuh; Liu, Sheng-Shyang

1995-05-01

A mathematical model for computation of turbulent reacting flows is developed under general curvilinear coordinate systems. An adaptive, streamline grid system is generated to deal with the complex flow structures in a multiple-inlet solid-propellant ducted rocket (SDR) combustor. General tensor representations of the k-epsilon and algebraic stress (ASM) turbulence models are derived in terms of contravariant velocity components, and modification caused by the effects of compressible turbulence is also included in the modeling. The clipped Gaussian probability density function is incorporated in the combustion model to account for fluctuations of properties. Validation of the above modeling is first examined by studying mixing and reacting characteristics in a confined coaxial-jet problem. This is followed by study of nonreacting and reacting SDR combustor flows. The results show that Gibson and Launder's ASM incorporated with Sarkar's modification for compressible turbulence effects based on the general curvilinear coordinate systems yields the most satisfactory prediction for this complicated SDR flowfield.

Computation of turbulent reacting flow in a solid-propellant ducted rocket

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

Chao, Y.; Chou, W.; Liu, S.

1995-05-01

A mathematical model for computation of turbulent reacting flows is developed under general curvilinear coordinate systems. An adaptive, streamline grid system is generated to deal with the complex flow structures in a multiple-inlet solid-propellant ducted rocket (SDR) combustor. General tensor representations of the k-epsilon and algebraic stress (ASM) turbulence models are derived in terms of contravariant velocity components, and modification caused by the effects of compressible turbulence is also included in the modeling. The clipped Gaussian probability density function is incorporated in the combustion model to account for fluctuations of properties. Validation of the above modeling is first examined bymore » studying mixing and reacting characteristics in a confined coaxial-jet problem. This is followed by study of nonreacting and reacting SDR combustor flows. The results show that Gibson and Launder`s ASM incorporated with Sarkar`s modification for compressible turbulence effects based on the general curvilinear coordinate systems yields the most satisfactory prediction for this complicated SDR flowfield. 36 refs.« less

Roles of the outer membrane protein AsmA of Salmonella enterica in the control of marRAB expression and invasion of epithelial cells.

PubMed

Prieto, Ana I; Hernández, Sara B; Cota, Ignacio; Pucciarelli, M Graciela; Orlov, Yuri; Ramos-Morales, Francisco; García-del Portillo, Francisco; Casadesús, Josep

2009-06-01

A genetic screen for suppressors of bile sensitivity in DNA adenine methylase (dam) mutants of Salmonella enterica serovar Typhimurium yielded insertions in an uncharacterized locus homologous to the Escherichia coli asmA gene. Disruption of asmA suppressed bile sensitivity also in phoP and wec mutants of S. enterica and increased the MIC of sodium deoxycholate for the parental strain ATCC 14028. Increased levels of marA mRNA were found in asmA, asmA dam, asmA phoP, and asmA wec strains of S. enterica, suggesting that lack of AsmA activates expression of the marRAB operon. Hence, asmA mutations may enhance bile resistance by inducing gene expression changes in the marRAB-controlled Mar regulon. In silico analysis of AsmA structure predicted the existence of one transmembrane domain. Biochemical analysis of subcellular fractions revealed that the asmA gene of S. enterica encodes a protein of approximately 70 kDa located in the outer membrane. Because AsmA is unrelated to known transport and/or efflux systems, we propose that activation of marRAB in asmA mutants may be a consequence of envelope reorganization. Competitive infection of BALB/c mice with asmA(+) and asmA isogenic strains indicated that lack of AsmA attenuates Salmonella virulence by the oral route but not by the intraperitoneal route. Furthermore, asmA mutants showed a reduced ability to invade epithelial cells in vitro.

Transport of chemical tracers from the boundary layer to stratosphere associated with the dynamics of the Asian summer monsoon

NASA Astrophysics Data System (ADS)

Pan, Laura L.; Honomichl, Shawn B.; Kinnison, Douglas E.; Abalos, Marta; Randel, William J.; Bergman, John W.; Bian, Jianchun

2016-12-01

Chemical transport associated with the dynamics of the Asian summer monsoon (ASM) system is investigated using model output from the National Center for Atmospheric Research (NCAR) Whole Atmosphere Community Climate Model run in specified dynamics mode. The 3-D day-to-day behavior of modeled carbon monoxide is analyzed together with dynamical fields and transport boundaries to identify preferred locations of uplifting from the boundary layer, the role of subseasonal-scale dynamics in the upper troposphere and lower stratosphere (UTLS), and the relationship of ASM transport and the stratospheric residual circulation. The model simulation of CO shows the intraseasonal east-west oscillation of the anticyclone may play an essential role in transporting convectively pumped boundary layer pollutants in the UTLS. A statistical analysis of 11 year CO also shows that the southern flank of the Tibetan plateau is a preferred location for boundary layer tracers to be lofted to the tropopause region. The vertical structure of a model tracer (E90) further shows that the rapid ASM vertical transport is only effective up to the tropopause level (around 400 K). The efficiency of continued vertical transport into the deep stratosphere is limited by the slow ascent associated with the zonal-mean residual circulation in the lower stratosphere during northern summer. Quasi-isentropic transport near the 400 K potential temperature level is likely the most effective process for ASM anticyclone air to enter the stratosphere.

Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

PubMed

Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

2015-10-01

Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD.

Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors.

PubMed

Burgess, J K; Ketheson, A; Faiz, A; Limbert Rempel, K A; Oliver, B G; Ward, J P T; Halayko, A J

2018-01-16

Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research.

Induced Pluripotent Stem Cells for Disease Modeling and Evaluation of Therapeutics for Niemann-Pick Disease Type A.

PubMed

Long, Yan; Xu, Miao; Li, Rong; Dai, Sheng; Beers, Jeanette; Chen, Guokai; Soheilian, Ferri; Baxa, Ulrich; Wang, Mengqiao; Marugan, Juan J; Muro, Silvia; Li, Zhiyuan; Brady, Roscoe; Zheng, Wei

2016-12-01

: Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes. By using this disease model, we also evaluated three compounds that reportedly reduced lysosomal lipid accumulation in Niemann-Pick disease type C as well as enzyme replacement therapy with ASM. We found that α-tocopherol, δ-tocopherol, hydroxypropyl-β-cyclodextrin, and ASM reduced sphingomyelin accumulation and enlarged lysosomes in NPA neural stem cells. Therefore, the NPA neural stem cells possess the characteristic NPA disease phenotype that can be ameliorated by tocopherols, cyclodextrin, and ASM. Our results demonstrate the efficacies of cyclodextrin and tocopherols in the NPA cell-based model. Our data also indicate that the NPA neural stem cells can be used as a new cell-based disease model for further study of disease pathophysiology and for high-throughput screening to identify new lead compounds for drug development. Currently, there is no effective treatment for Niemann-Pick disease type A (NPA). To accelerate drug discovery for treatment of NPA, NPA-induced pluripotent stem cells were generated from patient dermal fibroblasts and differentiated into neural stem cells. By using the differentiated NPA neuronal cells as a cell-based disease model system, α-tocopherol, δ-tocopherol, and hydroxypropyl-β-cyclodextrin significantly reduced sphingomyelin accumulation in these NPA neuronal cells. Therefore, this cell-based NPA model can be used for further study of disease pathophysiology and for high-throughput screening of compound libraries to identify lead compounds for drug development. ©AlphaMed Press.

Application of adjusted subpixel method (ASM) in HRCT measurements of the bronchi in bronchial asthma patients and healthy individuals.

PubMed

Mincewicz, Grzegorz; Rumiński, Jacek; Krzykowski, Grzegorz

2012-02-01

Recently, we described a model system which included corrections of high-resolution computed tomography (HRCT) bronchial measurements based on the adjusted subpixel method (ASM). To verify the clinical application of ASM by comparing bronchial measurements obtained by means of the traditional eye-driven method, subpixel method alone and ASM in a group comprised of bronchial asthma patients and healthy individuals. The study included 30 bronchial asthma patients and the control group comprised of 20 volunteers with no symptoms of asthma. The lowest internal and external diameters of the bronchial cross-sections (ID and ED) and their derivative parameters were determined in HRCT scans using: (1) traditional eye-driven method, (2) subpixel technique, and (3) ASM. In the case of the eye-driven method, lower ID values along with lower bronchial lumen area and its percentage ratio to total bronchial area were basic parameters that differed between asthma patients and healthy controls. In the case of the subpixel method and ASM, both groups were not significantly different in terms of ID. Significant differences were observed in values of ED and total bronchial area with both parameters being significantly higher in asthma patients. Compared to ASM, the eye-driven method overstated the values of ID and ED by about 30% and 10% respectively, while understating bronchial wall thickness by about 18%. Results obtained in this study suggest that the traditional eye-driven method of HRCT-based measurement of bronchial tree components probably overstates the degree of bronchial patency in asthma patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Influences of volcano eruptions on Asian Summer Monsoon over the last 110 years

PubMed Central

Ning, Liang; Liu, Jian; Sun, Weiyi

2017-01-01

Asian summer monsoon (ASM) precipitation is the primary water resource for agriculture in many Asian countries that have experienced rapid economic growth in recent decades, thus implying the necessity for further investigations on both the internal variability of the ASM and the influence of external factors on the ASM. Using long-term high-resolution (0.5° × 0.5°) observed precipitation data, contrary to previous studies on inter-annual timescale, we showed that over the last 110 years, volcanic eruptions have influenced ASM variations on an inter-decadal timescale via teleconnections with the Atlantic Multi-decadal Oscillation (AMO). This relationship was also confirmed by Coupled Model Intercomparison Program Phase 5 (CMIP5) model simulations. During the active volcanic eruption periods (1901–1935 and 1963–1993), significantly lower ASM precipitation was observed compared with that during the inactive volcanic eruption period (1936–1962). We found that during active volcanic eruption periods, which correspond to a negative AMO state, there is an anomalously weakened Walker circulation over the tropical Pacific that transports less moisture to the ASM region and subsequently reduces ASM precipitation. This new finding may help improve decadal predictions of future changes in the ASM. PMID:28205603

Characterization and machine learning prediction of allele-specific DNA methylation.

PubMed

He, Jianlin; Sun, Ming-an; Wang, Zhong; Wang, Qianfei; Li, Qing; Xie, Hehuang

2015-12-01

A large collection of Single Nucleotide Polymorphisms (SNPs) has been identified in the human genome. Currently, the epigenetic influences of SNPs on their neighboring CpG sites remain elusive. A growing body of evidence suggests that locus-specific information, including genomic features and local epigenetic state, may play important roles in the epigenetic readout of SNPs. In this study, we made use of mouse methylomes with known SNPs to develop statistical models for the prediction of SNP associated allele-specific DNA methylation (ASM). ASM has been classified into parent-of-origin dependent ASM (P-ASM) and sequence-dependent ASM (S-ASM), which comprises scattered-S-ASM (sS-ASM) and clustered-S-ASM (cS-ASM). We found that P-ASM and cS-ASM CpG sites are both enriched in CpG rich regions, promoters and exons, while sS-ASM CpG sites are enriched in simple repeat and regions with high frequent SNP occurrence. Using Lasso-grouped Logistic Regression (LGLR), we selected 21 out of 282 genomic and methylation related features that are powerful in distinguishing cS-ASM CpG sites and trained the classifiers with machine learning techniques. Based on 5-fold cross-validation, the logistic regression classifier was found to be the best for cS-ASM prediction with an ACC of 0.77, an AUC of 0.84 and an MCC of 0.54. Lastly, we applied the logistic regression classifier on human brain methylome and predicted 608 genes associated with cS-ASM. Gene ontology term enrichment analysis indicated that these cS-ASM associated genes are significantly enriched in the category coding for transcripts with alternative splicing forms. In summary, this study provided an analytical procedure for cS-ASM prediction and shed new light on the understanding of different types of ASM events. Published by Elsevier Inc.

Beneficial Effects of Prebiotic Saccharomyces cerevisiae Mannan on Allergic Asthma Mouse Models.

PubMed

Lew, D Betty; Michael, Christie F; Overbeck, Tracie; Robinson, W Scout; Rohman, Erin L; Lehman, Jeffrey M; Patel, Jennifer K; Eiseman, Brandi; LeMessurier, Kim S; Samarasinghe, Amali E; Gaber, M Waleed

2017-01-01

One of the unmet needs for asthma management is a new therapeutic agent with both anti-inflammatory and anti-smooth muscle (ASM) remodeling effects. The mannose receptor (MR) family plays an important role in allergen uptake and processing of major allergens Der p 1 and Fel d 1. We have previously reported that ASM cells express a mannose receptor (ASM-MR) and that mannan derived from Saccharomyces cerevisiae (SC-MN) inhibits mannosyl-rich lysosomal hydrolase-induced bovine ASM cell proliferation. Using a humanized transgenic mouse strain (huASM-MRC2) expressing the human MRC2 receptor in a SM tissue-specific manner, we have demonstrated that ASM hyperplasia/hypertrophy can occur as early as 15 days after allergen challenge in this mouse model and this phenomenon is preventable with SC-MN treatment. This proof-of-concept study would facilitate future development of a potential asthma therapeutic agent with dual function of anti-inflammatory and anti-smooth muscle remodeling effects.

People detection in crowded scenes using active contour models

NASA Astrophysics Data System (ADS)

Sidla, Oliver

2009-01-01

The detection of pedestrians in real-world scenes is a daunting task, especially in crowded situations. Our experience over the last years has shown that active shape models (ASM) can contribute significantly to a robust pedestrian detection system. The paper starts with an overview of shape model approaches, it then explains our approach which builds on top of Eigenshape models which have been trained using real-world data. These models are placed over candidate regions and matched to image gradients using a scoring function which integrates i) point distribution, ii) local gradient orientations iii) local image gradient strengths. A matching and shape model update process is iteratively applied in order to fit the flexible models to the local image content. The weights of the scoring function have a significant impact on the ASM performance. We analyze different settings of scoring weights for gradient magnitude, relative orientation differences, distance between model and gradient in an experiment which uses real-world data. Although for only one pedestrian model in an image computation time is low, the number of necessary processing cycles which is needed to track many people in crowded scenes can become the bottleneck in a real-time application. We describe the measures which have been taken in order to improve the speed of the ASM implementation and make it real-time capable.

Assessment of the long-lead probabilistic prediction for the Asian summer monsoon precipitation (1983-2011) based on the APCC multimodel system and a statistical model

NASA Astrophysics Data System (ADS)

Sohn, Soo-Jin; Min, Young-Mi; Lee, June-Yi; Tam, Chi-Yung; Kang, In-Sik; Wang, Bin; Ahn, Joong-Bae; Yamagata, Toshio

2012-02-01

The performance of the probabilistic multimodel prediction (PMMP) system of the APEC Climate Center (APCC) in predicting the Asian summer monsoon (ASM) precipitation at a four-month lead (with February initial condition) was compared with that of a statistical model using hindcast data for 1983-2005 and real-time forecasts for 2006-2011. Particular attention was paid to probabilistic precipitation forecasts for the boreal summer after the mature phase of El Niño and Southern Oscillation (ENSO). Taking into account the fact that coupled models' skill for boreal spring and summer precipitation mainly comes from their ability to capture ENSO teleconnection, we developed the statistical model using linear regression with the preceding winter ENSO condition as the predictor. Our results reveal several advantages and disadvantages in both forecast systems. First, the PMMP appears to have higher skills for both above- and below-normal categories in the six-year real-time forecast period, whereas the cross-validated statistical model has higher skills during the 23-year hindcast period. This implies that the cross-validated statistical skill may be overestimated. Second, the PMMP is the better tool for capturing atypical ENSO (or non-canonical ENSO related) teleconnection, which has affected the ASM precipitation during the early 1990s and in the recent decade. Third, the statistical model is more sensitive to the ENSO phase and has an advantage in predicting the ASM precipitation after the mature phase of La Niña.

Optimization of A(2)O BNR processes using ASM and EAWAG Bio-P models: model performance.

PubMed

El Shorbagy, Walid E; Radif, Nawras N; Droste, Ronald L

2013-12-01

This paper presents the performance of an optimization model for a biological nutrient removal (BNR) system using the anaerobic-anoxic-oxic (A(2)O) process. The formulated model simulates removal of organics, nitrogen, and phosphorus using a reduced International Water Association (IWA) Activated Sludge Model #3 (ASM3) model and a Swiss Federal Institute for Environmental Science and Technology (EAWAG) Bio-P module. Optimal sizing is attained considering capital and operational costs. Process performance is evaluated against the effect of influent conditions, effluent limits, and selected parameters of various optimal solutions with the following results: an increase of influent temperature from 10 degrees C to 25 degrees C decreases the annual cost by about 8.5%, an increase of influent flow from 500 to 2500 m(3)/h triples the annual cost, the A(2)O BNR system is more sensitive to variations in influent ammonia than phosphorus concentration and the maximum growth rate of autotrophic biomass was the most sensitive kinetic parameter in the optimization model.

Structural and functional analysis of the ASM p.Ala359Asp mutant that causes acid sphingomyelinase deficiency.

PubMed

Acuña, Mariana; Castro-Fernández, Víctor; Latorre, Mauricio; Castro, Juan; Schuchman, Edward H; Guixé, Victoria; González, Mauricio; Zanlungo, Silvana

2016-10-21

Niemann-Pick disease (NPD) type A and B are recessive hereditary disorders caused by deficiency in acid sphingomyelinase (ASM). The p.Ala359Asp mutation has been described in several patients but its functional and structural effects in the protein are unknown. In order to characterize this mutation, we modeled the three-dimensional ASM structure using the recent available crystal of the mammalian ASM as a template. We found that the p.Ala359Asp mutation is localized in the hydrophobic core and far from the sphingomyelin binding site. However, energy function calculations using statistical potentials indicate that the mutation causes a decrease in ASM stability. Therefore, we investigated the functional effect of the p.Ala359Asp mutation in ASM expression, secretion, localization and activity in human fibroblasts. We found a 3.8% residual ASM activity compared to the wild-type enzyme, without changes in the other parameters evaluated. These results support the hypothesis that the p.Ala359Asp mutation causes structural alterations in the hydrophobic environment where ASM is located, decreasing its enzymatic activity. A similar effect was observed in other previously described NPDB mutations located outside the active site of the enzyme. This work shows the first full size ASM mutant model describe at date, providing a complete analysis of the structural and functional effects of the p.Ala359Asp mutation over the stability and activity of the enzyme. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of numerical predictions of horizontal nonisothermal jet in a room with three turbulence models -- {kappa}-{epsilon} EVM, ASM, and DSM

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

Murakami, Shuzo; Kato, Shinsuke; Ooka, Ryozo

1994-12-31

A three-dimensional nonisothermal jet in a room is analyzed numerically by the standard {kappa}-{epsilon} eddy viscosity model (EVM) and two second-moment closure models-the algebraic stress model (ASM) (Hossain and Rodi 1982) and the differential stress model (DSM) (Launder et al. 1975). Numerical results given by these turbulence models are compared with experimental results, and the prediction errors existing in the results are examined, thus clarifying the relative structural differences between the {kappa}-{epsilon} EVM and the second-moment closure models. Since the second moment closure models clearly manifest the turbulence structures of the flow field, they are more accurate than the {kappa}-{epsilon}more » EVM. A small difference between the DSM and the ASM -- one based on an inappropriate approximation of the convection and diffusion terms in the Reynolds stress transport equations in the ASM -- is also observed.« less

Interplay between the Westerlies and Asian monsoon recorded in Lake Qinghai sediments since 32 ka

PubMed Central

An, Zhisheng; Colman, Steven M.; Zhou, Weijian; Li, Xiaoqiang; Brown, Eric T.; Jull, A. J. Timothy; Cai, Yanjun; Huang, Yongsong; Lu, Xuefeng; Chang, Hong; Song, Yougui; Sun, Youbin; Xu, Hai; Liu, Weiguo; Jin, Zhangdong; Liu, Xiaodong; Cheng, Peng; Liu, Yu; Ai, Li; Li, Xiangzhong; Liu, Xiuju; Yan, Libin; Shi, Zhengguo; Wang, Xulong; Wu, Feng; Qiang, Xiaoke; Dong, Jibao; Lu, Fengyan; Xu, Xinwen

2012-01-01

Two atmospheric circulation systems, the mid-latitude Westerlies and the Asian summer monsoon (ASM), play key roles in northern-hemisphere climatic changes. However, the variability of the Westerlies in Asia and their relationship to the ASM remain unclear. Here, we present the longest and highest-resolution drill core from Lake Qinghai on the northeastern Tibetan Plateau (TP), which uniquely records the variability of both the Westerlies and the ASM since 32 ka, reflecting the interplay of these two systems. These records document the anti-phase relationship of the Westerlies and the ASM for both glacial-interglacial and glacial millennial timescales. During the last glaciation, the influence of the Westerlies dominated; prominent dust-rich intervals, correlated with Heinrich events, reflect intensified Westerlies linked to northern high-latitude climate. During the Holocene, the dominant ASM circulation, punctuated by weak events, indicates linkages of the ASM to orbital forcing, North Atlantic abrupt events, and perhaps solar activity changes. PMID:22943005

Autonomous spacecraft maintenance study group

NASA Technical Reports Server (NTRS)

Marshall, M. H.; Low, G. D.

1981-01-01

A plan to incorporate autonomous spacecraft maintenance (ASM) capabilities into Air Force spacecraft by 1989 is outlined. It includes the successful operation of the spacecraft without ground operator intervention for extended periods of time. Mechanisms, along with a fault tolerant data processing system (including a nonvolatile backup memory) and an autonomous navigation capability, are needed to replace the routine servicing that is presently performed by the ground system. The state of the art fault handling capabilities of various spacecraft and computers are described, and a set conceptual design requirements needed to achieve ASM is established. Implementations for near term technology development needed for an ASM proof of concept demonstration by 1985, and a research agenda addressing long range academic research for an advanced ASM system for 1990s are established.

ASME Material Challenges for Advanced Reactor Concepts

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

Piyush Sabharwall; Ali Siahpush

2013-07-01

This study presents the material Challenges associated with Advanced Reactor Concept (ARC) such as the Advanced High Temperature Reactor (AHTR). ACR are the next generation concepts focusing on power production and providing thermal energy for industrial applications. The efficient transfer of energy for industrial applications depends on the ability to incorporate cost-effective heat exchangers between the nuclear heat transport system and industrial process heat transport system. The heat exchanger required for AHTR is subjected to a unique set of conditions that bring with them several design challenges not encountered in standard heat exchangers. The corrosive molten salts, especially at highermore » temperatures, require materials throughout the system to avoid corrosion, and adverse high-temperature effects such as creep. Given the very high steam generator pressure of the supercritical steam cycle, it is anticipated that water tube and molten salt shell steam generators heat exchanger will be used. In this paper, the ASME Section III and the American Society of Mechanical Engineers (ASME) Section VIII requirements (acceptance criteria) are discussed. Also, the ASME material acceptance criteria (ASME Section II, Part D) for high temperature environment are presented. Finally, lack of ASME acceptance criteria for thermal design and analysis are discussed.« less

A Simple Model to Identify Risk of Sarcopenia and Physical Disability in HIV-Infected Patients.

PubMed

Farinatti, Paulo; Paes, Lorena; Harris, Elizabeth A; Lopes, Gabriella O; Borges, Juliana P

2017-09-01

Farinatti, P, Paes, L, Harris, EA, Lopes, GO, and Borges, JP. A simple model to identify risk of sarcopenia and physical disability in HIV-infected patients. J Strength Cond Res 31(9): 2542-2551, 2017-Early detection of sarcopenia might help preventing muscle loss and disability in HIV-infected patients. This study proposed a model for estimating appendicular skeletal muscle mass (ASM) to calculate indices to identify "sarcopenia" (SA) and "risk for disability due to sarcopenia" (RSA) in patients with HIV. An equation to estimate ASM was developed in 56 patients (47.2 ± 6.9 years), with a cross-validation sample of 24 patients (48.1 ± 6.6 years). The model validity was determined by calculating, in both samples: (a) Concordance between actual vs. estimated ASM; (b) Correlations between actual/estimated ASM vs. peak torque (PT) and total work (TW) during isokinetic knee extension/flexion; (c) Agreement of patients classified with SA and RSA. The predictive equation was ASM (kg) = 7.77 (sex; F = 0/M = 1) + 0.26 (arm circumference; cm) + 0.38 (thigh circumference; cm) + 0.03 (Body Mass Index; kg·m) - 8.94 (R = 0.74; Radj = 0.72; SEE = 3.13 kg). Agreement between actual vs. estimated ASM was confirmed in validation (t = 0.081/p = 0.94; R = 0.86/p < 0.0001) and cross-validation (t = 0.12/p = 0.92; R = 0.87/p < 0.0001) samples. Regression characteristics in cross-validation sample (Radj = 0.80; SEE = 3.65) and PRESS (RPRESS = 0.69; SEEPRESS = 3.35) were compatible with the original model. Percent agreements for the classification of SA and RSA from indices calculated using actual and estimated ASM were of 87.5% and 77.2% (gamma correlations 0.72-1.0; p < 0.04) in validation, and 95.8% and 75.0% (gamma correlations 0.98-0.97; p < 0.001) in cross-validation sample, respectively. Correlations between actual/estimated ASM vs. PT (range 0.50-0.73, p ≤ 0.05) and TW (range 0.59-0.74, p ≤ 0.05) were similar in both samples. In conclusion, our model correctly estimated ASM to determine indices for identifying SA and RSA in HIV-infected patients.

Clinical predictors of advanced sellar masses.

PubMed

Rambaldini, Gloria M; Butalia, Sonia; Ezzat, Shereen; Kucharczyk, Walter; Sawka, Anna M

2007-10-01

To identify clinical variables associated with the presence of a structurally advanced sellar mass (ASM). We performed a retrospective study of patients referred for evaluation of suspected new pituitary disease or sellar mass to the Endocrine Oncology Unit of Mount Sinai Hospital in Toronto, Ontario, Canada. By multivariate analysis, we examined predictors of a structurally ASM (a sellar lesion with any of the following characteristics: diameter of >or=1 cm on magnetic resonance imaging [MRI], optic chiasmal compression on MRI, or clinical or biochemical evidence of hypopituitarism). Data from 152 patients were analyzed. Of the 152 sellar masses, 142 (93%) were pituitary adenomas. An ASM was noted in 85 of the 152 patients (56%). In the final multivariate model, male sex (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.84 to 13.56; P<0.001) and self-reported visual field defect (OR, 3.62; 95% CI, 1.07 to 12.25; P = 0.039) were significantly independently associated with the presence of an ASM. The presence of new or changed headaches also tended to be associated with an ASM (OR, 2.11; 95% CI, 0.96 to 4.64; P = 0.063). Age and self-reported galactorrhea were not independently associated with the presence of an ASM and were conditionally removed from the final model. In patients with suspected sellar or pituitary disease, male sex and self-reported visual field defects independently predict the presence of an ASM. New or changed headaches also tend to be related to the presence of an ASM. The presence of predictors of an ASM should prompt expedited sellar MRI and biochemical evaluation.

ASM Conference on Prokaryotic Development

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

Kaplan, H. B.

2005-07-13

Support was provided by DOE for the 2nd ASM Conference on Prokaryotic Development. The final conference program and abstracts book is attached. The conference presentations are organized around topics that are central to the current research areas in prokaryotic development. The program starts with topics that involve relatively simple models systems and ends with systems that are more complex. The topics are: i) the cell cycle, ii) the cytoskeleton, iii) morphogenesis, iv) developmental transcription, v) signaling, vi) multicellularity, and vii) developmental diversity and symbiosis. The best-studied prokaryotic development model systems will be highlighted at the conference through research presentations bymore » leaders in the field. Many of these systems are also model systems of relevance to the DOE mission including carbon sequestration (Bradyrizobium, Synechococcus), energy production (Anabaena, Rhodobacter) and bioremediation (Caulobacter, Mesorhizobium). In addition, many of the highlighted organisms have important practical applications; the actinomycetes and myxobacteria produce antimicrobials that are of commercial interest. It is certain that the cutting-edge science presented at the conference will be applicable to the large group of bacteria relevant to the DOE mission.« less

Discriminating sarcopenia in community-dwelling older women with high frequency of overweight/obesity: the São Paulo Ageing & Health Study (SPAH).

PubMed

Domiciano, D S; Figueiredo, C P; Lopes, J B; Caparbo, V F; Takayama, L; Menezes, P R; Bonfa, E; Pereira, R M R

2013-02-01

The criteria most used for the definition of sarcopenia, those based on the ratio between the appendicular skeletal muscle mass (ASM) and the square of the height (h(2)) underestimate prevalence in overweight/obese people whereas another criteria consider ASM adjusted for total fat mass. We have shown that ASM adjusted for fat seems to be more appropriate for sarcopenia diagnosis. Since the prevalence of overweight and obesity is a growing public health issue, the aim of this study was to evaluate the prevalence and risk factors associated with sarcopenia, based on these two criteria, among older women. Six hundred eleven community-dwelling women were evaluated by specific questionnaire including clinical data. Body composition and bone mineral density were evaluated by dual X-ray absorptiometry. Logistic regression models were used to identify factors independently related to sarcopenia by ASM/h(2) and ASM adjusted for total fat mass criteria. The prevalence of overweight/obesity was high (74.3 %). The frequency of sarcopenia was lower using the criteria of ASM/h(2) (3.7 %) than ASM adjusted for fat (19.9 %) (P < 0.0001). We also note that less than 5 %(1/23) of sarcopenic women, according to ASM/h(2), had overweight/obesity, whereas 60 % (74/122) of sarcopenic women by ASM adjusted for fat had this complication. Using ASM/h(2), the associated factors observed in regression models were femoral neck T-score (OR = 1.90; 95 % CI 1.06-3.41; P = 0.03) and current alcohol intake (OR = 4.13, 95 % CI 1.18-14.45, P = 0.03). In contrast, we have identified that creatinine (OR = 0.21; 95 % CI 0.07-0.63; P = 0.005) and the White race (OR = 1.81; 95 % CI 1.15-2.84; P = 0.01) showed a significant association with sarcopenia using ASM adjusted for fat. In women with overweight/obesity, ASM adjusted for fat seems to be the more appropriate criteria for sarcopenia diagnosis. This finding has relevant public health implications, considering the high prevalence of overweight/obesity in older women.

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease.

PubMed

Martin, J G; Duguet, A; Eidelman, D H

2000-08-01

Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass. Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASM, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM. Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin light chain kinase activity. Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined.

ARC Software and Models

Science.gov Websites

produce software code and methodologies that are transferred to TARDEC and industry partners. These constraints", ASME Dynamic Systems and Control Conference, 2013, DOI:10.1115/DSCC2013-3935 Software Monitoring",IEEE Transactions on Control Systems Technology, DOI:10.1109/TCST.2012.2217143 Fast

Effect of Biological and Mass Transfer Parameter Uncertainty on N₂O Emission Estimates from WRRFs.

PubMed

Song, Kang; Harper, Willie F; Takeuchi, Yuki; Hosomi, Masaaki; Terada, Akihiko

2017-07-01

  This research used the detailed activated sludge model (ASM) to investigate the effect of parameter uncertainty on nitrous oxide (N2O) emissions from biological wastewater treatment systems. Monte Carlo simulations accounted for uncertainty in the values of the microbial growth parameters and in the volumetric mass transfer coefficient for dissolved oxygen (kLaDO), and the results show that the detailed ASM predicted N2O emission of less than 4% (typically 1%) of the total influent loading. Uncertainties in kLaDO were further investigated in experiments, which showed that lower values of kLaDO generated higher soluble N2O levels. The detailed ASM likely requires revision to account for abiotic reactions and other factors that cause higher levels of N2O emission.

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

PubMed

Yoshida, Shuichiro; Noguchi, Atsuko; Kikuchi, Wataru; Fukaya, Hiroshi; Igarashi, Kiyoshi; Takahashi, Tsutomu

2017-12-01

Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p < 0.05). In the other illness groups, the serum S-ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

PubMed

Wang, Lu; Chitano, Pasquale; Murphy, Thomas M

2005-10-01

It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

AIS ASM Operational Integration Plan

DTIC Science & Technology

2013-08-01

al. | Public August 2013 This page intentionally left blank. AIS ASM Operational Integration Plan v ...that supply AIS Routers as part of their AIS shoreside network software : Kongsberg C-Scope, Gatehouse AIS, Transas AIS Network, and CNS DataSwitch...commercial systems would be suitable for the current USCG traffic conditions. The ASM Manager is software that adds the required queuing and

The Bauschinger Effect in Autofrettaged Tubes- A Comparison of Models Including the ASME Code

DTIC Science & Technology

1998-06-01

possible error in Division 3 of Section Vm of the ASME Boiler and Pressure Vessel Code . They show that the empirical method used in the code to...Discussion presented by DP Kendall We appreciate the acknowledgement in the Kendall discussion that Division 3 of Section VIII of the ASME Boiler and Pressure Vessel Code may

Specificity of arrestin subtypes in regulating airway smooth muscle G protein-coupled receptor signaling and function.

PubMed

Pera, Tonio; Hegde, Akhil; Deshpande, Deepak A; Morgan, Sarah J; Tiegs, Brian C; Theriot, Barbara S; Choi, Yeon H; Walker, Julia K L; Penn, Raymond B

2015-10-01

Arrestins have been shown to regulate numerous G protein-coupled receptors (GPCRs) in studies employing receptor/arrestin overexpression in artificial cell systems. Which arrestin isoforms regulate which GPCRs in primary cell types is poorly understood. We sought to determine the effect of β-arrestin-1 or β-arrestin-2 inhibition or gene ablation on signaling and function of multiple GPCRs endogenously expressed in airway smooth muscle (ASM). In vitro [second messenger (calcium, cAMP generation)], ex vivo (ASM tension generation in suspended airway), and in vivo (invasive airway resistance) analyses were performed on human ASM cells and murine airways/whole animal subject to β-arrestin-1 or -2 knockdown or knockout (KO). In both human and murine model systems, knockdown or KO of β-arrestin-2 relative to control missense small interfering RNA or wild-type mice selectively increased (40-60%) β2-adrenoceptor signaling and function. β-arrestin-1 knockdown or KO had no effect on signaling and function of β2-adrenoceptor or numerous procontractile GPCRs, but selectively inhibited M3 muscarinic acetylcholine receptor signaling (∼50%) and function (∼25% ex vivo, >50% in vivo) without affecting EC50 values. Arrestin subtypes differentially regulate ASM GPCRs and β-arrestin-1 inhibition represents a novel approach to managing bronchospasm in obstructive lung diseases. © FASEB.

Predictors and Long-Term Clinical Impact of Acute Stent Malapposition: An Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) Intravascular Ultrasound Substudy.

PubMed

Wang, Bin; Mintz, Gary S; Witzenbichler, Bernhard; Souza, Cristiano F; Metzger, D Christopher; Rinaldi, Michael J; Duffy, Peter L; Weisz, Giora; Stuckey, Thomas D; Brodie, Bruce R; Matsumura, Mitsuaki; Yamamoto, Myong-Hwa; Parvataneni, Rupa; Kirtane, Ajay J; Stone, Gregg W; Maehara, Akiko

2016-12-22

The impact of acute stent malapposition (ASM) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention is still controversial. We sought to evaluate predictors and long-term clinical outcomes of ASM. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective multicenter study of 8663 patients undergoing percutaneous coronary intervention using drug-eluting stents. In a prespecified intravascular ultrasound-guided substudy, 2072 patients with 2446 culprit lesions had post-percutaneous coronary intervention intravascular ultrasound and were classified according to the presence or absence of ASM. After intravascular ultrasound-guided percutaneous coronary intervention, the overall prevalence of ASM after successful drug-eluting stents implantation was 14.4% per patient and 12.6% per lesion. Compared to lesions without ASM, lesions with ASM had larger in-stent lumen areas, larger stent areas, and larger in-stent vessel areas. A larger mean plaque area along with more attenuated plaque was observed in lesions with ASM versus lesions without ASM. Lesions with ASM had greater proximal and distal reference lumen areas and more distal, but not proximal, reference calcium compared to lesions without ASM. At 2-year follow-up, there was no significant difference in the incidence of cardiac death; myocardial infarction; early, late, or very late stent thrombosis; or clinically driven target lesion revascularization in patients with ASM versus those without ASM. Furthermore, ASM was not an independent predictor of 2-year major adverse cardiac events or target lesion revascularization even when forced into the multivariate model. In patients treated with intravascular ultrasound-guided drug-eluting stents implantation, ASM was not associated with adverse clinical events during long-term follow-up including, but not limited to, stent thrombosis. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Risk of cardiac events in Long QT syndrome patients when taking antiseizure medications.

PubMed

Auerbach, David S; Biton, Yitschak; Polonsky, Bronislava; McNitt, Scott; Gross, Robert A; Dirksen, Robert T; Moss, Arthur J

2018-01-01

Many antiseizure medications (ASMs) affect ion channel function. We investigated whether ASMs alter the risk of cardiac events in patients with corrected QT (QT c ) prolongation. The study included people from the Rochester-based Long QT syndrome (LQTS) Registry with baseline QT c prolongation and history of ASM therapy (n = 296). Using multivariate Anderson-Gill models, we assessed the risk of recurrent cardiac events associated with ASM therapy. We stratified by LQTS genotype and predominant mechanism of ASM action (Na + channel blocker and gamma-aminobutyric acid modifier.) There was an increased risk of cardiac events when participants with QT c prolongation were taking vs off ASMs (HR 1.65, 95% confidence interval [CI] 1.36-2.00, P < 0.001). There was an increased risk of cardiac events when LQTS2 (HR 1.49, 95% CI 1.03-2.15, P = 0.036) but not LQTS1 participants were taking ASMs (interaction, P = 0.016). Na + channel blocker ASMs were associated with an increased risk of cardiac events in participants with QT c prolongation, specifically LQTS2, but decreased risk in LQTS1. The increased risk when taking all ASMs and Na + channel blocker ASMs was attenuated by concurrent beta-adrenergic blocker therapy (interaction, P < 0.001). Gamma-aminobutyric acid modifier ASMs were associated with an increased risk of events in patients not concurrently treated with beta-adrenergic blockers. Female participants were at an increased risk of cardiac events while taking all ASMs and each class of ASMs. Despite no change in overall QT c duration, pharmacogenomic analyses set the stage for future prospective clinical and mechanistic studies to validate that ASMs with predominantly Na + channel blocking actions are deleterious in LQTS2, but protective in LQTS1. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of turbulent models for scramjet flowfields

NASA Technical Reports Server (NTRS)

Sindir, M. M.; Harsha, P. T.

1982-01-01

The behavior of several turbulence models applied to the prediction of scramjet combustor flows is described. These models include the basic two equation model, the multiple dissipation length scale variant of the two equation model, and the algebraic stress model (ASM). Predictions were made of planar backward facing step flows and axisymmetric sudden expansion flows using each of these approaches. The formulation of each of these models are discussed, and the application of the different approaches to supersonic flows is described. A modified version of the ASM is found to provide the best prediction of the planar backward facing step flow in the region near the recirculation zone, while the basic ASM provides the best results downstream of the recirculation. Aspects of the interaction of numerica modeling and turbulences modeling as they affect the assessment of turbulence models are discussed.

Three-Dimensional modelling of the long-term variability of tracer transport in the Asian Summer Monsoon anticyclone

NASA Astrophysics Data System (ADS)

Taverna, Giorgio; Chipperfield, Martyn; Feng, Wuhu; Pope, Richard; Hossaini, Ryan; Forster, Piers

2017-04-01

The Asian Monsoon is an important region for the transport of gases from the troposphere to the stratosphere. Recent work by many groups has focused on quantifying processes which contribute to coupling in the upper troposphere - lower stratosphere (UTLS), including transport during the Asian Summer Monsoon (ASM). Troposphere-to-stratosphere transport in this region has been the focus of a number of recent campaigns, including the EU "StratoClim campaign" in Kalamata, Greece, 2016. Anthropogenic compounds such as CO Very Short-Lived Substances (VSLS), which destroy stratospheric ozone, and sulphur compounds, which maintain the stratospheric aerosol layer, are among the important species involved in large convective systems transport such as the ASM. An important question for halogenated VSLS is whether ASM-associated transport can take place on timescales which are short relative to their chemical lifetimes of days to months. This talk will present results of the TOMCAT/SLIMCAT off-line 3-D chemical transport model to investigate these issues using moderate-resolution simulations (2.8°x2.8°, 60 levels from surface to 60 km). The model is forced by ECMWF ERA-Interim reanalyses. A 1979-2016 simulation was run using artificial and idealized tracers with parametrized loss rates, lifetimes and emissions. These types of tracer have already been successfully used to study the transport of VSLS from surface through the TTL. The interannual variability of the transport inside and through the ASM anticyclone and related confinement will be shown and quantified. Comparisons will be made with in-situ and remote satellite data, where possible.

Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer's disease.

PubMed

Lee, Jong Kil; Jin, Hee Kyung; Park, Min Hee; Kim, Bo-ra; Lee, Phil Hyu; Nakauchi, Hiromitsu; Carter, Janet E; He, Xingxuan; Schuchman, Edward H; Bae, Jae-sung

2014-07-28

In Alzheimer's disease (AD), abnormal sphingolipid metabolism has been reported, although the pathogenic consequences of these changes have not been fully characterized. We show that acid sphingomyelinase (ASM) is increased in fibroblasts, brain, and/or plasma from patients with AD and in AD mice, leading to defective autophagic degradation due to lysosomal depletion. Partial genetic inhibition of ASM (ASM(+/-)) in a mouse model of familial AD (FAD; amyloid precursor protein [APP]/presenilin 1 [PS1]) ameliorated the autophagocytic defect by restoring lysosomal biogenesis, resulting in improved AD clinical and pathological findings, including reduction of amyloid-β (Aβ) deposition and improvement of memory impairment. Similar effects were noted after pharmacologic restoration of ASM to the normal range in APP/PS1 mice. Autophagic dysfunction in neurons derived from FAD patient induced pluripotent stem cells (iPSCs) was restored by partial ASM inhibition. Overall, these results reveal a novel mechanism of ASM pathogenesis in AD that leads to defective autophagy due to impaired lysosomal biogenesis and suggests that partial ASM inhibition is a potential new therapeutic intervention for the disease. © 2014 Lee et al.

Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer’s disease

PubMed Central

Lee, Jong Kil; Jin, Hee Kyung; Park, Min Hee; Kim, Bo-ra; Lee, Phil Hyu; Nakauchi, Hiromitsu; Carter, Janet E.; He, Xingxuan; Schuchman, Edward H.

2014-01-01

In Alzheimer’s disease (AD), abnormal sphingolipid metabolism has been reported, although the pathogenic consequences of these changes have not been fully characterized. We show that acid sphingomyelinase (ASM) is increased in fibroblasts, brain, and/or plasma from patients with AD and in AD mice, leading to defective autophagic degradation due to lysosomal depletion. Partial genetic inhibition of ASM (ASM+/−) in a mouse model of familial AD (FAD; amyloid precursor protein [APP]/presenilin 1 [PS1]) ameliorated the autophagocytic defect by restoring lysosomal biogenesis, resulting in improved AD clinical and pathological findings, including reduction of amyloid-β (Aβ) deposition and improvement of memory impairment. Similar effects were noted after pharmacologic restoration of ASM to the normal range in APP/PS1 mice. Autophagic dysfunction in neurons derived from FAD patient induced pluripotent stem cells (iPSCs) was restored by partial ASM inhibition. Overall, these results reveal a novel mechanism of ASM pathogenesis in AD that leads to defective autophagy due to impaired lysosomal biogenesis and suggests that partial ASM inhibition is a potential new therapeutic intervention for the disease. PMID:25049335

SDZ ASM 981: an emerging safe and effective treatment for atopic dermatitis.

PubMed

Luger, T; Van Leent, E J; Graeber, M; Hedgecock, S; Thurston, M; Kandra, A; Berth-Jones, J; Bjerke, J; Christophers, E; Knop, J; Knulst, A C; Morren, M; Morris, A; Reitamo, S; Roed-Petersen, J; Schoepf, E; Thestrup-Pedersen, K; Van Der Valk, P G; Bos, J D

2001-04-01

SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6% and 1.0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0.05%, 0.2%, 0.6%, or 1.0%, matching vehicle cream, or the internal control 0.1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. A clear dose-response relationship for SDZ ASM 981 was evident, with 0.2%, 0.6% and 1.0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0.041, 0.001 and 0.008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1.0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0.6% and 1.0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42.9%, 48.9% and 34.9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1.0% cream was similar to that of the lower concentrations. 1.0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

Comparison of liver volumetry on contrast-enhanced CT images: one semiautomatic and two automatic approaches.

PubMed

Cai, Wei; He, Baochun; Fan, Yingfang; Fang, Chihua; Jia, Fucang

2016-11-08

This study was to evaluate the accuracy, consistency, and efficiency of three liver volumetry methods- one interactive method, an in-house-developed 3D medical Image Analysis (3DMIA) system, one automatic active shape model (ASM)-based segmentation, and one automatic probabilistic atlas (PA)-guided segmentation method on clinical contrast-enhanced CT images. Forty-two datasets, including 27 normal liver and 15 space-occupying liver lesion patients, were retrospectively included in this study. The three methods - one semiautomatic 3DMIA, one automatic ASM-based, and one automatic PA-based liver volumetry - achieved an accuracy with VD (volume difference) of -1.69%, -2.75%, and 3.06% in the normal group, respectively, and with VD of -3.20%, -3.35%, and 4.14% in the space-occupying lesion group, respectively. However, the three methods achieved an efficiency of 27.63 mins, 1.26 mins, 1.18 mins on average, respectively, compared with the manual volumetry, which took 43.98 mins. The high intraclass correlation coefficient between the three methods and the manual method indicated an excel-lent agreement on liver volumetry. Significant differences in segmentation time were observed between the three methods (3DMIA, ASM, and PA) and the manual volumetry (p < 0.001), as well as between the automatic volumetries (ASM and PA) and the semiautomatic volumetry (3DMIA) (p < 0.001). The semiautomatic interactive 3DMIA, automatic ASM-based, and automatic PA-based liver volum-etry agreed well with manual gold standard in both the normal liver group and the space-occupying lesion group. The ASM- and PA-based automatic segmentation have better efficiency in clinical use. © 2016 The Authors.

Impact of East Asian Winter and Australian Summer Monsoons on the Enhanced Surface Westerlies over the Western Tropical Pacific Ocean Preceding the El Niño Onset

NASA Astrophysics Data System (ADS)

Zheng, Y.; Zhang, R.; Bourassa, M. A.

2014-12-01

Composite analysis from NCEP-NCAR reanalysis datasets over the period 1948-2007 indicates that stronger East Asian winter monsoons (EAWM) and stronger Australian summer monsoons (ASM) generally co-exist in boreal winters preceding the onset of El Niño, although the EAWM tend to be weak after 1990, probably because of the decadal shift of EAWM and the change in El Niño events from cold-tongue type to warm-pool type. The anomalous EAWM and ASM enhance surface westerlies over the western tropical Pacific Ocean (WTP). It is proposed that the enhanced surface westerlies over the WTP prior to El Niño onset are generally associated with the concurrent anomalous EAWM and ASM. A simple analytical atmospheric model is constructed to test the hypothesis that the emergence of enhanced surface westerlies over the WTP can be linked to concurrent EAWM and ASM anomalies. Model results indicate that when anomalous northerlies from the EAWM converge with anomalous southerlies from the ASM, westerly anomalies over the WTP are enhanced. This result provides a possible explanation of the co-impact of the EAWM and the ASM on the onset of El Niño through enhancing the surface westerly over the WTP.

Decreased muscle mass is not an independent risk factor for metabolic syndrome in Korean population aged 70 or older.

PubMed

Koo, Hyung Suk; Kim, Moon Jong; Kim, Kwang-Min; Kim, Young-Sang

2015-04-01

The association of low muscle mass with cardiometabolic risks is still controversial. The aim of this study was to investigate the relationship between low muscle mass and metabolic syndrome (MetS) according to the various muscle mass indices and to evaluate the influence of muscle mass on MetS independent of fat mass. Cross-sectional study About 841 men and 1106 women aged 70 or older from Korea National Health and Nutrition Examination Survey 2008-2010 MEASUREMENTS: We used various muscle mass indices: appendicular skeletal muscle mass (ASM) divided by height squared (ASM/Ht(2) ), ASM divided by body weight (ASM/Wt) and ASM adjusted for height and fat mass (residual). Low muscle mass is defined as ASM/Ht(2) and ASM/Wt below 2 SD of the sex-specific mean for healthy young adults. The sex-specific lowest quintile of the distribution of the residual was regarded as low muscle mass. The prevalence of MetS was higher in the population with low muscle mass defined by ASM/Wt, but lower in those defined by ASM/Ht(2) . However, after stratification according to the central obesity, low muscle mass was barely related with MetS. Meanwhile, when both ASM and fat mass were included in a logistic regression model, the odds ratios of 1 SD change of ASM for MetS were 1·07 (0·85-1·34) for men and 1·24 (1·04-1·47) for women, respectively. The relationship between low muscle mass and MetS was different according to the various muscle mass indices. After controlling the influence of fat mass, decreased muscle mass was not an independent risk factor for MetS. © 2014 John Wiley & Sons Ltd.

Requirements for construction of nuclear system components at elevated temperatures (supplement to ASME Code Cases 1592, 1593, 1594, 1595, and 1596)

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

Not Available

This standard provides rules for the construction of Class 1 nuclear components, parts, and appurtenances for use at elevated temperatures. This standard is a complete set of requirements only when used in conjunction with Section III of the ASME Boiler and Pressure Vessel Code (ASME Code) and addenda, ASME Code Cases 1592, 1593, 1594, 1595, and 1596, and RDT E 15-2NB. Unmodified paragraphs of the referenced Code Cases are not repeated in this standard but are a part of the requirements of this standard.

Regulation of hematogenous tumor metastasis by acid sphingomyelinase

PubMed Central

Carpinteiro, Alexander; Becker, Katrin Anne; Japtok, Lukasz; Hessler, Gabriele; Keitsch, Simone; Požgajovà, Miroslava; Schmid, Kurt W; Adams, Constantin; Müller, Stefan; Kleuser, Burkhard; Edwards, Michael J; Grassmé, Heike; Helfrich, Iris; Gulbins, Erich

2015-01-01

Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy and accounts for approximately 90% of human cancer deaths. We investigated the role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma cells. Intravenous injection of B16F10 melanoma cells into wild-type mice resulted in multiple lung metastases, while Asm-deficient mice (Smpd1−/− mice) were protected from pulmonary tumor spread. Transplanting wild-type platelets into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice were protected from hematogenous MT/ret melanoma metastasis to the spleen in a mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells triggered activation and release of platelet secretory Asm, in turn leading to ceramide formation, clustering, and activation of α5β1 integrins on melanoma cells finally leading to adhesion of the tumor cells. Clustering of integrins by applying purified Asm or C16 ceramide to B16F10 melanoma cells before intravenous injection restored trapping of tumor cells in the lung in Asm-deficient mice. This effect was revertable by arginine-glycine-aspartic acid peptides, which are known inhibitors of integrins, and by antibodies neutralizing β1 integrins. These findings indicate that melanoma cells employ platelet-derived Asm for adhesion and metastasis. PMID:25851537

Model-based segmentation of abdominal aortic aneurysms in CTA images

NASA Astrophysics Data System (ADS)

de Bruijne, Marleen; van Ginneken, Bram; Niessen, Wiro J.; Loog, Marco; Viergever, Max A.

2003-05-01

Segmentation of thrombus in abdominal aortic aneurysms is complicated by regions of low boundary contrast and by the presence of many neighboring structures in close proximity to the aneurysm wall. We present an automated method that is similar to the well known Active Shape Models (ASM), combining a three-dimensional shape model with a one-dimensional boundary appearance model. Our contribution is twofold: we developed a non-parametric appearance modeling scheme that effectively deals with a highly varying background, and we propose a way of generalizing models of curvilinear structures from small training sets. In contrast with the conventional ASM approach, the new appearance model trains on both true and false examples of boundary profiles. The probability that a given image profile belongs to the boundary is obtained using k nearest neighbor (kNN) probability density estimation. The performance of this scheme is compared to that of original ASMs, which minimize the Mahalanobis distance to the average true profile in the training set. The generalizability of the shape model is improved by modeling the objects axis deformation independent of its cross-sectional deformation. A leave-one-out experiment was performed on 23 datasets. Segmentation using the kNN appearance model significantly outperformed the original ASM scheme; average volume errors were 5.9% and 46% respectively.

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

PubMed Central

Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.; Edmunds, Tim; Qiu, Huawei; Wei, Ronnie R.

2016-01-01

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients. PMID:27725636

Management Sciences Division Annual Report (9th)

DTIC Science & Technology

1992-01-01

41 Actuarial Process Consolidation and Review ....................................... 43 How M alfunction Code Reduction...47 Sun W ork Stations ............................................................................... 48 Actuarial Process Consolidation and...Information System (WSMIS). Dyna-METRIC is used for wartime supply support capability assessments. The Aircraft Sustainability Model ( ASM ) is the

A Summary of the Foundation Research Program, Fiscal Year 1985.

DTIC Science & Technology

1986-05-12

system in the domain of actuarial science. Publication: T. R. Sivasankaran and M. Jarke, "Coupling Expert .z- Systems and Actuarial Pricing Models... Actuarial Pricing Models," Workshop on Coupling Symbolic and Numerical Computing in Expert Systems, Bellevue, Washington, August 1985. 16 Title: Application...Ramjets", AIAA-85-1177, AIAA/SAE/ ASME /ASEE 21st Joint Propulsion Conference, July 8-10, 1985. A. Gany and D. W. Netzer, "Fuel Performance Evaluation

Continuous Abelian Sandpile Model in Two Dimensional Lattice

NASA Astrophysics Data System (ADS)

Azimi-Tafreshi, N.; Lotfi, E.; Moghimi-Araghi, S.

We investigate a new version of sandpile model which is very similar to Abelian Sandpile Model (ASM), but the height variables are continuous ones. With the toppling rule we define in our model, we show that the model can be mapped to ASM, so the general properties of the two models are identical. Yet the new model allows us to investigate some problems such as the effect of very small mass on the height probabilities, different boundary conditions, etc.

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data.

PubMed

Hu, Bo; Ji, Yuan; Xu, Yaomin; Ting, Angela H

2013-05-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach.

Multifactor analysis and simulation of the surface runoff and soil infiltration at different slope gradients

NASA Astrophysics Data System (ADS)

Huang, J.; Kang, Q.; Yang, J. X.; Jin, P. W.

2017-08-01

The surface runoff and soil infiltration exert significant influence on soil erosion. The effects of slope gradient/length (SG/SL), individual rainfall amount/intensity (IRA/IRI), vegetation cover (VC) and antecedent soil moisture (ASM) on the runoff depth (RD) and soil infiltration (INF) were evaluated in a series of natural rainfall experiments in the South of China. RD is found to correlate positively with IRA, IRI, and ASM factors and negatively with SG and VC. RD decreased followed by its increase with SG and ASM, it increased with a further decrease with SL, exhibited a linear growth with IRA and IRI, and exponential drop with VC. Meanwhile, INF exhibits a positive correlation with SL, IRA and IRI and VC, and a negative one with SG and ASM. INF was going up and then down with SG, linearly rising with SL, IRA and IRI, increasing by a logit function with VC, and linearly falling with ASM. The VC level above 60% can effectively lower the surface runoff and significantly enhance soil infiltration. Two RD and INF prediction models, accounting for the above six factors, were constructed using the multiple nonlinear regression method. The verification of those models disclosed a high Nash-Sutcliffe coefficient and low root-mean-square error, demonstrating good predictability of both models.

Strengthened African summer monsoon in the mid-Piacenzian

NASA Astrophysics Data System (ADS)

Zhang, Ran; Zhang, Zhongshi; Jiang, Dabang; Yan, Qing; Zhou, Xin; Cheng, Zhigang

2016-09-01

Using model results from the first phase of the Pliocene Model Intercomparison Project (PlioMIP) and four experiments with CAM4, the intensified African summer monsoon (ASM) in the mid-Piacenzian and corresponding mechanisms are analyzed. The results from PlioMIP show that the ASM intensified and summer precipitation increased in North Africa during the mid-Piacenzian, which can be explained by the increased net energy in the atmospheric column above North Africa. Further experiments with CAM4 indicated that the combined changes in the mid-Piacenzian of atmospheric CO2 concentration and SST, as well as the vegetation change, could have substantially increased the net energy in the atmospheric column over North Africa and further intensified the ASM. The experiments also demonstrated that topography change had a weak effect. Overall, the combined changes of atmospheric CO2 concentration and SST were the most important factor that brought about the intensified ASM in the mid-Piacenzian.

Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner.

PubMed

Hultsch, T; Müller, K D; Meingassner, J G; Grassberger, M; Schopf, R E; Knop, J

1998-09-01

Mast cells play an important role in the pathological development of many inflammatory and allergic diseases and inhibition of mast cell activation is a potential target for therapeutic intervention. Therefore, the effect of the novel ascomycin macrolactam derivative SDZ ASM 981 on Fc epsilonRI-mediated activation of rat basophilic leukemia (RBL) cells, as a model for mast cell activation, was investigated. First, the ability to inhibit different mast cell immunophilins in vitro was tested. Using recombinant macrophilin-12 (FKBP-12), inhibition of rotamase activity with an IC50 of approximately 6 nM was observed. The rotamase activity of cyclophilin A (18 kDa) was not affected. Secondly, the effect of SDZ ASM 981 on Fc epsilonRI-mediated mast cell activation was investigated in the RBL cell model. SDZ ASM 981 inhibited exocytosis of preformed mediators (e.g. serotonin) with an IC50 of approximately 30 nM. Transcription and release of newly synthesized mediators (e.g. TNF-alpha) was inhibited with an IC50 of approximately 100 nM. The inhibitory effect of SDZ ASM 981 was antagonized by rapamycin. We conclude that SDZ ASM 981 is a potent inhibitor of Fc epsilonRI-mediated activation of mast cells in vitro. The mechanism of action involves formation of (calcineurin) inhibitory complexes with macrophilins. We suggest that this inhibitory action on mast cells might contribute to the antiinflammatory effect of SDZ ASM 981 observed in vivo (e.g. in aptopic dermatitis and psoriasis).

46 CFR 56.01-5 - Adoption of ASME B31.1 for power piping, and other standards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENGINEERING PIPING SYSTEMS AND APPURTENANCES General § 56.01-5 Adoption of ASME B31.1 for power piping, and other standards. (a) Piping systems for ships and barges must be designed, constructed, and inspected in... subchapter. See 46 CFR 56.60-1(b) for the other adopted commercial standards applicable to piping systems...

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data

PubMed Central

Hu, Bo; Xu, Yaomin

2013-01-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach. PMID:23710259

77 FR 19413 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-30

...-0023. UP seeks to use an automated sound measurement system (ASMS) to test locomotive horns as required in 49 CFR 229.129(b). The ASMS uses a Class 1 sound-level measuring instrument that is permanently...

Numerical prediction of an axisymmetric turbulent mixing layer using two turbulence models

NASA Astrophysics Data System (ADS)

Johnson, Richard W.

1992-01-01

Nuclear power, once considered and then rejected (in the U. S.) for application to space vehicle propulsion, is being reconsidered for powering space rockets, especially for interplanetary travel. The gas core reactor, a high risk, high payoff nuclear engine concept, is one that was considered in the 1960s and 70s. As envisioned then, the gas core reactor would consist of a heavy, slow moving core of fissioning uranium vapor surrounded by a fast moving outer stream of hydrogen propellant. Satisfactory operation of such a configuration would require stable nuclear reaction kinetics to occur simultaneously with a stable, coflowing, probably turbulent fluid system having a dense inner stream and a light outer stream. The present study examines the behavior of two turbulence models in numerically simulating an idealized version of the above coflowing fluid system. The two models are the standard k˜ɛ model and a thin shear algebraic stress model (ASM). The idealized flow system can be described as an axisymmetric mixing layer of constant density. Predictions for the radial distribution of the mean streamwise velocity and shear stress for several axial stations are compared with experiment. Results for the k˜ɛe predictions are broadly satisfactory while those for the ASM are distinctly poorer.

Is the apical soft tissue margin a better predictor of biochemical recurrence than the surgical specimen?

PubMed

Godoy, Guilherme; Tareen, Basir U; Lepor, Herbert

2011-01-01

To identify predictors of apical surgical margin (ASM) and apical soft tissue margin (ASTM), determine if the ASTM is a better predictor of biochemical recurrence (BR) than the ASM, and ascertain the impact of apical biopsies on BR rates. One thousand three hundred eight consecutive men underwent open radical retropubic prostatectomy (RP) between October 2000 and December 2006. Circumferential biopsies of the ASTM were obtained intraoperatively and submitted for frozen section analysis. Logistic regression models were utilized to identify the factors associated with the presence of positive ASMs and ASTMs. The estimated 5-year risk of BR was calculated by the Kaplan-Meier method. Overall, 43 (3.3%) and 86 (6.6%) of cases exhibited positive ASM and ASTM, respectively. ASM was significantly associated with higher mean serum prostate-specific antigen levels, presence of perineural invasion, and greater volume of tumor in the biopsy specimen. None of these factors were observed to be associated with the presence of cancer in the ASTMs. In the multivariate analysis, only the presence of perineural invasion was a significant independent predictor of ASMs. The estimated 5-year BR rates in the positive ASMs only, ASTMs only, and both positive ASMs and ASTMs groups were 48.6%, 4.7%, and 38.8%, respectively. A positive ASM was associated with a significantly greater risk of BR compared with a positive ASTM. The very low estimated risk of BR at 5 years in cases with ASTM suggests that performing the ASTM biopsies may increase the cure rates achieved with RP. Copyright © 2011 Elsevier Inc. All rights reserved.

Endocrine regulation of airway contractility is overlooked.

PubMed

Bossé, Ynuk

2014-08-01

Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked. © 2014 Society for Endocrinology.

Human acid sphingomyelinase structures provide insight to molecular basis of Niemann–Pick disease

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

Zhou, Yan-Feng; Metcalf, Matthew C.; Garman, Scott C.

Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann–Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures revealmore » the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients.« less

Exploiting the relationship between birefringence and force to measure airway smooth muscle contraction with PS-OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Adams, David C.; Hariri, Lida P.; Holz, Jasmin A.; Szabari, Margit V.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

2016-03-01

The ability to observe airway dynamics is fundamental to forming a complete understanding of pulmonary diseases such as asthma. We have previously demonstrated that Optical Coherence Tomography (OCT) can be used to observe structural changes in the airway during bronchoconstriction, but standard OCT lacks the contrast to discriminate airway smooth muscle (ASM) bands- ASM being responsible for generating the force that drives airway constriction- from the surrounding tissue. Since ASM in general exhibits a greater degree of birefringence than the surrounding tissue, a potential solution to this problem lies in the implementation of polarization sensitivity (PS) to the OCT system. By modifying the OCT system so that it is sensitive to the birefringence of tissue under inspection, we can visualize the ASM with much greater clarity and definition. In this presentation we show that the force of contraction can be indirectly measured by an associated increase in the birefringence signal of the ASM. We validate this approach by attaching segments of swine trachea to an isometric force transducer and stimulating contraction, while simultaneously measuring the exerted force and imaging the segment with PS-OCT. We then show how our results may be used to extrapolate the force of contraction of closed airways in absence of additional measurement devices. We apply this technique to assess ASM contractility volumetrically and in vivo, in both asthmatic and non-asthmatic human volunteers.

Segmentation of multiple heart cavities in 3-D transesophageal ultrasound images.

PubMed

Haak, Alexander; Vegas-Sánchez-Ferrero, Gonzalo; Mulder, Harriët W; Ren, Ben; Kirişli, Hortense A; Metz, Coert; van Burken, Gerard; van Stralen, Marijn; Pluim, Josien P W; van der Steen, Antonius F W; van Walsum, Theo; Bosch, Johannes G

2015-06-01

Three-dimensional transesophageal echocardiography (TEE) is an excellent modality for real-time visualization of the heart and monitoring of interventions. To improve the usability of 3-D TEE for intervention monitoring and catheter guidance, automated segmentation is desired. However, 3-D TEE segmentation is still a challenging task due to the complex anatomy with multiple cavities, the limited TEE field of view, and typical ultrasound artifacts. We propose to segment all cavities within the TEE view with a multi-cavity active shape model (ASM) in conjunction with a tissue/blood classification based on a gamma mixture model (GMM). 3-D TEE image data of twenty patients were acquired with a Philips X7-2t matrix TEE probe. Tissue probability maps were estimated by a two-class (blood/tissue) GMM. A statistical shape model containing the left ventricle, right ventricle, left atrium, right atrium, and aorta was derived from computed tomography angiography (CTA) segmentations by principal component analysis. ASMs of the whole heart and individual cavities were generated and consecutively fitted to tissue probability maps. First, an average whole-heart model was aligned with the 3-D TEE based on three manually indicated anatomical landmarks. Second, pose and shape of the whole-heart ASM were fitted by a weighted update scheme excluding parts outside of the image sector. Third, pose and shape of ASM for individual heart cavities were initialized by the previous whole heart ASM and updated in a regularized manner to fit the tissue probability maps. The ASM segmentations were validated against manual outlines by two observers and CTA derived segmentations. Dice coefficients and point-to-surface distances were used to determine segmentation accuracy. ASM segmentations were successful in 19 of 20 cases. The median Dice coefficient for all successful segmentations versus the average observer ranged from 90% to 71% compared with an inter-observer range of 95% to 84%. The agreement against the CTA segmentations was slightly lower with a median Dice coefficient between 85% and 57%. In this work, we successfully showed the accuracy and robustness of the proposed multi-cavity segmentation scheme. This is a promising development for intraoperative procedure guidance, e.g., in cardiac electrophysiology.

Prevalence of sarcopenia and associated risk factors by two diagnostic criteria in community-dwelling older men: the São Paulo Ageing & Health Study (SPAH).

PubMed

Figueiredo, C P; Domiciano, D S; Lopes, J B; Caparbo, V F; Scazufca, M; Bonfá, E; Pereira, R M R

2014-02-01

Sarcopenia is an aging syndrome that can be characterized by many criteria adjusted or not by fat mass. This study suggested that the optimal criteria should be selected according to body mass index (BMI) in older men and identified age, BMI, race, smoking, physical activity, hip bone mineral density (BMD) as risk factors for this syndrome. This study aims to analyze the prevalence of sarcopenia and associated risk factors using appendicular skeletal mass (ASM)/height(2) and ASM adjusted for total fat mass criteria in older men from community. Three hundred ninety-nine men were included and answered a questionnaire about lifestyle and medical history. Individuals were classified by their BMI using the classification adjusted by age. Body composition and bone mineral density were measured by dual X-ray absorptiometry. Sarcopenia was classified according to both criteria. Logistic regression models were used to analyze risk factors associated with sarcopenia. The mean BMI was 26.46 kg/m(2): 12.5 % underweight, 43.6 % normal, and 43.9 % overweight/obese. Fifty-four (13.5 %) were considered sarcopenic by ASM/height(2) and 79 (19.8 %) by ASM adjusted for fat (p = 0.001). Fifty-one (12.8 %) individuals had discordant sarcopenia classification: 13 were classified only by ASM/height(2) and 38 only by ASM adjusted for fat. Of the 13 subjects classified as sarcopenic only by ASM/height(2), 84.6 % (11/13) were underweight and solely one (7.7 %) was considered overweight/obese. In contrast, of those 38 older men classified as sarcopenic only by ASM adjusted for fat, none were underweight and 53 % (20/38) were overweight/obese. Subjects classified as sarcopenic according to both criteria had the same risk factors in the final model analyses (age, BMI, race, smoking, physical activity, hip BMD; p < 0.05). This study suggested that the optimal criteria for sarcopenia should be selected according to BMI in community-dwelling older men.

TH-A-9A-01: Active Optical Flow Model: Predicting Voxel-Level Dose Prediction in Spine SBRT

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

Liu, J; Wu, Q.J.; Yin, F

2014-06-15

Purpose: To predict voxel-level dose distribution and enable effective evaluation of cord dose sparing in spine SBRT. Methods: We present an active optical flow model (AOFM) to statistically describe cord dose variations and train a predictive model to represent correlations between AOFM and PTV contours. Thirty clinically accepted spine SBRT plans are evenly divided into training and testing datasets. The development of predictive model consists of 1) collecting a sequence of dose maps including PTV and OAR (spinal cord) as well as a set of associated PTV contours adjacent to OAR from the training dataset, 2) classifying data into fivemore » groups based on PTV's locations relative to OAR, two “Top”s, “Left”, “Right”, and “Bottom”, 3) randomly selecting a dose map as the reference in each group and applying rigid registration and optical flow deformation to match all other maps to the reference, 4) building AOFM by importing optical flow vectors and dose values into the principal component analysis (PCA), 5) applying another PCA to features of PTV and OAR contours to generate an active shape model (ASM), and 6) computing a linear regression model of correlations between AOFM and ASM.When predicting dose distribution of a new case in the testing dataset, the PTV is first assigned to a group based on its contour characteristics. Contour features are then transformed into ASM's principal coordinates of the selected group. Finally, voxel-level dose distribution is determined by mapping from the ASM space to the AOFM space using the predictive model. Results: The DVHs predicted by the AOFM-based model and those in clinical plans are comparable in training and testing datasets. At 2% volume the dose difference between predicted and clinical plans is 4.2±4.4% and 3.3±3.5% in the training and testing datasets, respectively. Conclusion: The AOFM is effective in predicting voxel-level dose distribution for spine SBRT. Partially supported by NIH/NCI under grant #R21CA161389 and a master research grant by Varian Medical System.« less

A 'Good' muscle in a 'Bad' environment: the importance of airway smooth muscle force adaptation to airway hyperresponsiveness.

PubMed

Bossé, Ynuk; Chapman, David G; Paré, Peter D; King, Gregory G; Salome, Cheryl M

2011-12-15

Asthma is characterized by airway inflammation, with a consequent increase in spasmogens, and exaggerated airway narrowing in response to stimuli, termed airway hyperresponsiveness (AHR). The nature of any relationship between inflammation and AHR is less clear. Recent ex vivo data has suggested a novel mechanism by which inflammation may lead to AHR, in which increased basal ASM-tone, due to the presence of spasmogens in the airways, may "strengthen" the ASM and ultimately lead to exaggerated airway narrowing. This phenomenon was termed "force adaptation" [Bossé, Y., Chin, L.Y., Paré, P.D., Seow, C.Y., 2009. Adaptation of airway smooth muscle to basal tone: relevance to airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 40, 13-18]. However, it is unknown whether the magnitude of the effect of force adaptation ex vivo could contribute to exaggerated airway narrowing in vivo. Our aim was to utilize a computational model of ASM shortening in order to quantify the potential effect of force adaptation on airway narrowing when all other mechanical factors were kept constant. The shortening in the model is dictated by a balance between physiological loads and ASM force-generating capacity at different lengths. The results suggest that the magnitude of the effect of force adaptation on ASM shortening would lead to substantially more airway narrowing during bronchial challenge at any given airway generation. We speculate that the increased basal ASM-tone in asthma, due to the presence of inflammation-derived spasmogens, produces an increase in the force-generating capacity of ASM, predisposing to AHR during subsequent challenge. Copyright © 2011 Elsevier B.V. All rights reserved.

Visceral adiposity and skeletal muscle mass are independently and synergistically associated with left ventricular structure and function: the Korean Genome and Epidemiology Study.

PubMed

Park, Juri; Kim, Nan Hee; Kim, Seong Hwan; Kim, Jin-Seok; Kim, Yong Hyun; Lim, Hong Euy; Kim, Eung Ju; Na, Jin Oh; Cho, Goo-Yeong; Baik, Inkyung; Kim, Doo Man; Choi, Dong Seop; Lee, Seung Ku; Shin, Chol

2014-10-20

Obesity and low muscle mass may coexist as age-related changes in body composition. We aimed to investigate the effect of visceral adiposity and skeletal muscle mass on left ventricular (LV) structure and function in the general population. A total of 1941 participants without known cardiovascular disease were enrolled from the Korean Genome and Epidemiology Study. Visceral fat area (VFA) was assessed by computed tomography. Appendicular skeletal muscle mass (ASM) was estimated by dual-energy X-ray absorptiometry and was used as a percentage of body weight (ASM/Wt). LV structure and function were assessed by tissue Doppler imaging (TDI) echocardiography. Across VFA tertiles, ASM increased, but ASM/Wt decreased (all P<0.001). In multivariate models adjusted for conventional cardiovascular risk factors, LV mass index and LV diastolic parameters, such as left atrial dimension, TDI Ea velocity, and E/Ea ratio, were significantly impaired as VFA increased. On the other hand, an increase in ASM/Wt was associated with a decrease in LV mass index and improvement of LV diastolic parameters. With regard to LV mass index and TDI Ea velocity, VFA and ASM/Wt showed synergistic effects (all P interaction<0.05). When both VFA and ASM/Wt were simultaneously included in the same model, both remained independent predictors of LV mass index and TDI Ea velocity. More visceral fat and less muscle mass are independently and synergistically associated with an increase in LV mass index and impairment of LV diastolic parameters. Further research is needed to explore the complex mechanisms underlying these associations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Coherent Phase Wide Band Demodulation Technique for Turbomachinery Cavitation Detection and Monitoring

DTIC Science & Technology

1996-04-01

levels were high a strong modulating frequency was recovered at the periodic vortex shedding rate. Experimental study of cavitation in hydroturbines ...of a Francis Model and Prototype Hydroturbine ," ASME Winter Annual Meeting, International Symposium on Bubble Noise Cavitation Erosion in Fluid Systems

ASM LabCap's contributions to disease surveillance and the International Health Regulations (2005).

PubMed

Specter, Steven; Schuermann, Lily; Hakiruwizera, Celestin; Sow, Mah-Séré Keita

2010-12-03

The revised International Health Regulations [IHR(2005)], which requires the Member States of the World Health Organization (WHO) to develop core capacities to detect, assess, report, and respond to public health threats, is bringing new challenges for national and international surveillance systems. As more countries move toward implementation and/or strengthening of their infectious disease surveillance programs, the strengthening of clinical microbiology laboratories becomes increasingly important because they serve as the first line responders to detect new and emerging microbial threats, re-emerging infectious diseases, the spread of antibiotic resistance, and the possibility of bioterrorism. In fact, IHR(2005) Core Capacity #8, "Laboratory", requires that laboratory services be a part of every phase of alert and response.Public health laboratories in many resource-constrained countries require financial and technical assistance to build their capacity. In recognition of this, in 2006, the American Society for Microbiology (ASM) established an International Laboratory Capacity Building Program, LabCap, housed under the ASM International Board. ASM LabCap utilizes ASM's vast resources and its membership's expertise-40,000 microbiologists worldwide-to strengthen clinical and public health laboratory systems in low and low-middle income countries. ASM LabCap's program activities align with HR(2005) by building the capability of resource-constrained countries to develop quality-assured, laboratory-based information which is critical to disease surveillance and the rapid detection of disease outbreaks, whether they stem from natural, deliberate or accidental causes.ASM LabCap helps build laboratory capacity under a cooperative agreement with the U.S. Centers for Disease Control and Prevention (CDC) and under a sub-contract with the Program for Appropriate Technology in Health (PATH) funded by the United States Agency for International Development (USAID). Successful activities of ASM LabCap have occurred throughout Africa, Asia, Central America and the Caribbean. In addition, ASM LabCap coordinates efforts with international agencies such as the WHO in order to maximize resources and ensure a unified response, with the intended goal to help build integrated disease surveillance and response capabilities worldwide in compliance with HR(2005)'s requirements.

Future changes of interannual variation of the Asian summer monsoon precipitation using the CMIP5

NASA Astrophysics Data System (ADS)

Kamizawa, Nozomi; Takahashi, Hiroshi G.

2015-04-01

The Asian summer monsoon (ASM) region is one of the most populated areas in the world. Since the life of people who live in the region and the industry are strongly dependent on the ASM precipitation, it is interested that how it would change under the circumstance of global warming. Many studies have reported that the mean ASM precipitation would increase by comparing the CMIP models' climatology. Although the changes in mean climate are important, the long-term changes of interannual variability in precipitation are also significant. This study investigated the long-term trend of interannual precipitation variation over the ASM region by using 22 CMIP5 models. The RCP4.5 scenario was used. To investigate the long-term trend of the interannual variation of the ASM precipitation, each model data was recreated to 2.5 degree resolution and a running standard deviation for 21 years of June-July-August (JJA) precipitation were calculated. Next, we created the coefficient variation (CV) by dividing the running standard deviation by the mean JJA precipitation. Then we run a Mann-Kendall test for the CV at each grid. There were more areas which were indicated a statistically significant increasing trend than a decreasing trend in the ASM region. 40.6% of the region indicated an increasing trend in the future. On the other hand, 16.8% of the area was indicated to have a decreasing trend. It was also common in the global scale that the there were more areas that indicated an increasing trend than a decreasing trend. We also divided the area into three groups: land, shore and open ocean. In the ASM region, the shore areas particularly had an increasing CV trend. To investigate the long-term changes of the interannual variability of the precipitation and the atmospheric circulation over the ASM region, we conducted a composite analysis for the five wettest and driest years for two periods: the early 21st century (2007-2031) and the late 21st century (2076-2100). The special patterns of the interannual variation of the precipitation and the atmospheric circulation between the two periods had differed only slightly. A positive deviation precipitation band with a cyclonic circulation was recognized from across the Bay of Bengal to the equatorial Northwest Pacific. The none-big-difference of the patterns may suggest that interannual variation in the ASM region would increase not because the pattern changes, but because the pattern's strength gets stronger or its frequency gets higher.

Exploiting graph kernels for high performance biomedical relation extraction.

PubMed

Panyam, Nagesh C; Verspoor, Karin; Cohn, Trevor; Ramamohanarao, Kotagiri

2018-01-30

Relation extraction from biomedical publications is an important task in the area of semantic mining of text. Kernel methods for supervised relation extraction are often preferred over manual feature engineering methods, when classifying highly ordered structures such as trees and graphs obtained from syntactic parsing of a sentence. Tree kernels such as the Subset Tree Kernel and Partial Tree Kernel have been shown to be effective for classifying constituency parse trees and basic dependency parse graphs of a sentence. Graph kernels such as the All Path Graph kernel (APG) and Approximate Subgraph Matching (ASM) kernel have been shown to be suitable for classifying general graphs with cycles, such as the enhanced dependency parse graph of a sentence. In this work, we present a high performance Chemical-Induced Disease (CID) relation extraction system. We present a comparative study of kernel methods for the CID task and also extend our study to the Protein-Protein Interaction (PPI) extraction task, an important biomedical relation extraction task. We discuss novel modifications to the ASM kernel to boost its performance and a method to apply graph kernels for extracting relations expressed in multiple sentences. Our system for CID relation extraction attains an F-score of 60%, without using external knowledge sources or task specific heuristic or rules. In comparison, the state of the art Chemical-Disease Relation Extraction system achieves an F-score of 56% using an ensemble of multiple machine learning methods, which is then boosted to 61% with a rule based system employing task specific post processing rules. For the CID task, graph kernels outperform tree kernels substantially, and the best performance is obtained with APG kernel that attains an F-score of 60%, followed by the ASM kernel at 57%. The performance difference between the ASM and APG kernels for CID sentence level relation extraction is not significant. In our evaluation of ASM for the PPI task, ASM performed better than APG kernel for the BioInfer dataset, in the Area Under Curve (AUC) measure (74% vs 69%). However, for all the other PPI datasets, namely AIMed, HPRD50, IEPA and LLL, ASM is substantially outperformed by the APG kernel in F-score and AUC measures. We demonstrate a high performance Chemical Induced Disease relation extraction, without employing external knowledge sources or task specific heuristics. Our work shows that graph kernels are effective in extracting relations that are expressed in multiple sentences. We also show that the graph kernels, namely the ASM and APG kernels, substantially outperform the tree kernels. Among the graph kernels, we showed the ASM kernel as effective for biomedical relation extraction, with comparable performance to the APG kernel for datasets such as the CID-sentence level relation extraction and BioInfer in PPI. Overall, the APG kernel is shown to be significantly more accurate than the ASM kernel, achieving better performance on most datasets.

Genetic trend in economic traits in Iranian native fowl.

PubMed

Ghorbani, S H; Kamali, M A

2007-09-15

Genetic parameters were estimated in base population of a closed experimental strain fowl, from data issued from 13 successive generations of selection. This population had been selected for body weight at 12 weeks of age (BW12) and egg number during the first 12 weeks of laying period (EN), mean egg weight at 28th, 30th, 32nd weeks and Age at Sexual Maturity (ASM). Data were obtained on 35461 Iranian native hens belonging to breeding center for Fars province in Iran. The method of multi-traits restricted maximum likelihood with an animal model was used to estimate genetic parameters. Resulting heritabilities for BW12, EN, EW and ASM were 0.58, 0.34, 0.62 and 0.49, respectively. Genetic correlations between BW12 and EN, EW and ASM were -0.06, 0.49 and 0.02, respectively. Genetic correlations between EN and EW and ASM were -0.26 and-0.77, respectively, while between EW and ASM, it was 0.20. The overall predicted genetic gains, after 13 generations of selection, estimated by the regression coefficients of the breeding value on generation number were equal to 9.55, 0.99, 0.05 and -1.66, for BW12, EN, EW and ASM, respectively.

Modelling airway smooth muscle passive length adaptation via thick filament length distributions

PubMed Central

Donovan, Graham M.

2013-01-01

We present a new model of airway smooth muscle (ASM), which surrounds and constricts every airway in the lung and thus plays a central role in the airway constriction associated with asthma. This new model of ASM is based on an extension of sliding filament/crossbridge theory, which explicitly incorporates the length distribution of thick sliding filaments to account for a phenomenon known as dynamic passive length adaptation; the model exhibits good agreement with experimental data for ASM force–length behaviour across multiple scales. Principally these are (nonlinear) force–length loops at short timescales (seconds), parabolic force–length curves at medium timescales (minutes) and length adaptation at longer timescales. This represents a significant improvement on the widely-used cross-bridge models which work so well in or near the isometric regime, and may have significant implications for studies which rely on crossbridge or other dynamic airway smooth muscle models, and thus both airway and lung dynamics. PMID:23721681

Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma.

PubMed

Patel, Kruti R; Bai, Yan; Trieu, Kenneth G; Barrios, Juliana; Ai, Xingbin

2017-10-01

Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation. We found that allergen exposure in neonatal mice, but not in adult mice, elevated the level and activity of cholinergic nerves (termed neuroplasticity). We demonstrated that cholinergic neuroplasticity is necessary for the induction of persistent AHR after neonatal exposure during rescue assays in mice deficient in neuroplasticity. In addition, early intervention with cholinergic receptor muscarinic (ChRM)-3 blocker reversed the progression of AHR in the neonatal exposure model, whereas β2-adrenoceptor agonists had no such effect. Together, our findings demonstrate a functional relationship between cholinergic neuroplasticity and ASM contractile phenotypes that operates uniquely in early life to induce persistent AHR after allergen exposure. Targeting ChRM3 may have disease-modifying benefits in childhood asthma.-Patel, K. R., Bai, Y., Trieu, K. G., Barrios, J., Ai, X. Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma. © FASEB.

Preoperative preparation. Value, perspective, and practice in patient care.

PubMed

Kopp, V J

2000-09-01

Preanesthesia preparation will continue to stimulate creativity and debate. Strategies for process improvement will take various shapes and require tools previously unfamiliar to many medical managers. At UNC Health System, anesthesiologists currently are committed to the centralized preanesthesia clinic approach used in PreCare. To date, their strategies have been validated by their institutional measures of success: a 0.7% first-case AM work-up rate, a 5% no PreCare visit rate, a 5% consent problem rate, and a 0% rejected specimen rate, with a 43% blood-draw rate for all patients. As their health system expands, however, other strategies and preparation modalities may become necessary. Telemedicine and Internet-dependent processes are appealing in the highly educated and technologically sophisticated marketplace. As the region becomes increasingly urbanized, local employment patterns prevent easy access to services, and functional compromises, such as bypassing PreCare or reliance on telephone or on-line interviews for preparation, may become necessary. The need to expand PreCare in the near future is already evident. As was found during initial planning, process improvement and space planning are enhanced by computer modeling. UNC Health System employed a proprietary animated simulation modeling (ASM) tool, MedModel, (ProModel, Orem, UT), although other techniques exist for the same purpose. Use of ASM as a strategy management tool allowed generation of ideal space-time-personnel scenarios that could expose potential problems before resources and physical restructuring occurred. ASM also can be used to compare data obtained from real-time observations to any reference scenario, including any that looks at economic measures of process, to help refine strategic visions before instituting tactical solutions. Used in this manner, ASM can reveal physical, temporal, personnel, and policy-related factors not otherwise seen as exerting effects on overall preprocedural preparation processes. Coupled with other classic planning techniques, such as time-motion studies, modified Delphi techniques, customer satisfaction surveys, benchmarking studies, and financial analysis and growth projections, ASM has helped enhance total quality management efforts in PreCare and other planning projects at UNC Health System. Other researchers have used other simulation techniques to assess clinic functions. Operational challenges that exist in preanesthesia preparation clinics place these clinics on the same level as other kinds of medical service clinics. The lessons learned in most clinic settings may be applied in a cross-wise manner to the preanesthesia clinic. Dexter contends that efficient delivery of care that respects patients' time and needs does more than assist the procedural preparation process; it also supports the physician's ethical obligation to the patient to give the best possible care. Documenting patient medical information, education efforts, and maintaining the medical-legal integrity of the preanesthesia preparation materials is another area of increasing concern and research. When hand-held computers capable of linking by way of infrared technologies or that use rented downloadable software to run specific applications become commonly used, the complexity of ensuring privacy will grow. The complexity, however, will not be insurmountable. Privacy problems exist in any information management system, whether paper-based (i.e., reducing redundant forms, eliminating indiscriminant photocopying of records), electronic-based (i.e., encryption, server access, system failure), or both. Electronic conveyance of medical information faces more legal and economic than technical hurdles. The penetration in US households of Internet services presently is less than 40%, whereas the penetration of personal computers is just over 50%. These figures are compared with penetration of corded telephones, televisions, and radios at levels greater tha

PHASE I MATERIALS PROPERTY DATABASE DEVELOPMENT FOR ASME CODES AND STANDARDS

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

Ren, Weiju; Lin, Lianshan

2013-01-01

To support the ASME Boiler and Pressure Vessel Codes and Standard (BPVC) in modern information era, development of a web-based materials property database is initiated under the supervision of ASME Committee on Materials. To achieve efficiency, the project heavily draws upon experience from development of the Gen IV Materials Handbook and the Nuclear System Materials Handbook. The effort is divided into two phases. Phase I is planned to deliver a materials data file warehouse that offers a depository for various files containing raw data and background information, and Phase II will provide a relational digital database that provides advanced featuresmore » facilitating digital data processing and management. Population of the database will start with materials property data for nuclear applications and expand to data covering the entire ASME Code and Standards including the piping codes as the database structure is continuously optimized. The ultimate goal of the effort is to establish a sound cyber infrastructure that support ASME Codes and Standards development and maintenance.« less

The ASM-NSF Biology Scholars Program: An Evidence-Based Model for Faculty Development.

PubMed

Chang, Amy L; Pribbenow, Christine M

2016-05-01

The American Society for Microbiology (ASM) established its ASM-NSF (National Science Foundation) Biology Scholars Program (BSP) to promote undergraduate education reform by 1) supporting biologists to implement evidence-based teaching practices, 2) engaging life science professional societies to facilitate biologists' leadership in scholarly teaching within the discipline, and 3) participating in a teaching community that fosters disciplinary-level science, technology, engineering, and mathematics (STEM) reform. Since 2005, the program has utilized year-long residency training to provide a continuum of learning and practice centered on principles from the scholarship of teaching and learning (SoTL) to more than 270 participants ("scholars") from biology and multiple other disciplines. Additionally, the program has recruited 11 life science professional societies to support faculty development in SoTL and discipline-based education research (DBER). To identify the BSP's long-term outcomes and impacts, ASM engaged an external evaluator to conduct a study of the program's 2010-2014 scholars (n = 127) and society partners. The study methods included online surveys, focus groups, participant observation, and analysis of various documents. Study participants indicate that the program achieved its proposed goals relative to scholarship, professional society impact, leadership, community, and faculty professional development. Although participants also identified barriers that hindered elements of their BSP participation, findings suggest that the program was essential to their development as faculty and provides evidence of the BSP as a model for other societies seeking to advance undergraduate science education reform. The BSP is the longest-standing faculty development program sponsored by a collective group of life science societies. This collaboration promotes success across a fragmented system of more than 80 societies representing the life sciences and helps catalyze biology education reform efforts.

The ASM-NSF Biology Scholars Program: An Evidence-Based Model for Faculty Development

PubMed Central

Chang, Amy L.; Pribbenow, Christine M.

2016-01-01

The American Society for Microbiology (ASM) established its ASM-NSF (National Science Foundation) Biology Scholars Program (BSP) to promote undergraduate education reform by 1) supporting biologists to implement evidence-based teaching practices, 2) engaging life science professional societies to facilitate biologists’ leadership in scholarly teaching within the discipline, and 3) participating in a teaching community that fosters disciplinary-level science, technology, engineering, and mathematics (STEM) reform. Since 2005, the program has utilized year-long residency training to provide a continuum of learning and practice centered on principles from the scholarship of teaching and learning (SoTL) to more than 270 participants (“scholars”) from biology and multiple other disciplines. Additionally, the program has recruited 11 life science professional societies to support faculty development in SoTL and discipline-based education research (DBER). To identify the BSP’s long-term outcomes and impacts, ASM engaged an external evaluator to conduct a study of the program’s 2010–2014 scholars (n = 127) and society partners. The study methods included online surveys, focus groups, participant observation, and analysis of various documents. Study participants indicate that the program achieved its proposed goals relative to scholarship, professional society impact, leadership, community, and faculty professional development. Although participants also identified barriers that hindered elements of their BSP participation, findings suggest that the program was essential to their development as faculty and provides evidence of the BSP as a model for other societies seeking to advance undergraduate science education reform. The BSP is the longest-standing faculty development program sponsored by a collective group of life science societies. This collaboration promotes success across a fragmented system of more than 80 societies representing the life sciences and helps catalyze biology education reform efforts. PMID:27158300

USAF Hyperbaric Animal Transfer Chamber System.

DTIC Science & Technology

1988-01-01

in full accordance with the requirements of the ASME Boiler and Pressure Vessel Code , Section VIII, Division 2, including provisions for lethal and...possible application to military and aviation medicine. REFERENCES 1. ASME Boiler and Pressure Vessel Code , Sec III, Div 2, para AD-160, AF-402, . and

Oriented active shape models.

PubMed

Liu, Jiamin; Udupa, Jayaram K

2009-04-01

Active shape models (ASM) are widely employed for recognizing anatomic structures and for delineating them in medical images. In this paper, a novel strategy called oriented active shape models (OASM) is presented in an attempt to overcome the following five limitations of ASM: 1) lower delineation accuracy, 2) the requirement of a large number of landmarks, 3) sensitivity to search range, 4) sensitivity to initialization, and 5) inability to fully exploit the specific information present in the given image to be segmented. OASM effectively combines the rich statistical shape information embodied in ASM with the boundary orientedness property and the globally optimal delineation capability of the live wire methodology of boundary segmentation. The latter characteristics allow live wire to effectively separate an object boundary from other nonobject boundaries with similar properties especially when they come very close in the image domain. The approach leads to a two-level dynamic programming method, wherein the first level corresponds to boundary recognition and the second level corresponds to boundary delineation, and to an effective automatic initialization method. The method outputs a globally optimal boundary that agrees with the shape model if the recognition step is successful in bringing the model close to the boundary in the image. Extensive evaluation experiments have been conducted by utilizing 40 image (magnetic resonance and computed tomography) data sets in each of five different application areas for segmenting breast, liver, bones of the foot, and cervical vertebrae of the spine. Comparisons are made between OASM and ASM based on precision, accuracy, and efficiency of segmentation. Accuracy is assessed using both region-based false positive and false negative measures and boundary-based distance measures. The results indicate the following: 1) The accuracy of segmentation via OASM is considerably better than that of ASM; 2) The number of landmarks can be reduced by a factor of 3 in OASM over that in ASM; 3) OASM becomes largely independent of search range and initialization becomes automatic. All three benefits of OASM ensue mainly from the severe constraints brought in by the boundary-orientedness property of live wire and the globally optimal solution found by the 2-level dynamic programming algorithm.

A biomechanical model of agonist-initiated contraction in the asthmatic airway.

PubMed

Brook, B S; Peel, S E; Hall, I P; Politi, A Z; Sneyd, J; Bai, Y; Sanderson, M J; Jensen, O E

2010-01-31

This paper presents a modelling framework in which the local stress environment of airway smooth muscle (ASM) cells may be predicted and cellular responses to local stress may be investigated. We consider an elastic axisymmetric model of a layer of connective tissue and circumferential ASM fibres embedded in parenchymal tissue and model the active contractile force generated by ASM via a stress acting along the fibres. A constitutive law is proposed that accounts for active and passive material properties as well as the proportion of muscle to connective tissue. The model predicts significantly different contractile responses depending on the proportion of muscle to connective tissue in the remodelled airway. We find that radial and hoop-stress distributions in remodelled muscle layers are highly heterogenous with distinct regions of compression and tension. Such patterns of stress are likely to have important implications, from a mechano-transduction perspective, on contractility, short-term cytoskeletal adaptation and long-term airway remodelling in asthma. Copyright 2009 Elsevier B.V. All rights reserved.

Active shape models unleashed

NASA Astrophysics Data System (ADS)

Kirschner, Matthias; Wesarg, Stefan

2011-03-01

Active Shape Models (ASMs) are a popular family of segmentation algorithms which combine local appearance models for boundary detection with a statistical shape model (SSM). They are especially popular in medical imaging due to their ability for fast and accurate segmentation of anatomical structures even in large and noisy 3D images. A well-known limitation of ASMs is that the shape constraints are over-restrictive, because the segmentations are bounded by the Principal Component Analysis (PCA) subspace learned from the training data. To overcome this limitation, we propose a new energy minimization approach which combines an external image energy with an internal shape model energy. Our shape energy uses the Distance From Feature Space (DFFS) concept to allow deviations from the PCA subspace in a theoretically sound and computationally fast way. In contrast to previous approaches, our model does not rely on post-processing with constrained free-form deformation or additional complex local energy models. In addition to the energy minimization approach, we propose a new method for liver detection, a new method for initializing an SSM and an improved k-Nearest Neighbour (kNN)-classifier for boundary detection. Our ASM is evaluated with leave-one-out tests on a data set with 34 tomographic CT scans of the liver and is compared to an ASM with standard shape constraints. The quantitative results of our experiments show that we achieve higher segmentation accuracy with our energy minimization approach than with standard shape constraints.nym

Use of artificial sputum medium to test antibiotic efficacy against Pseudomonas aeruginosa in conditions more relevant to the cystic fibrosis lung.

PubMed

Kirchner, Sebastian; Fothergill, Joanne L; Wright, Elli A; James, Chloe E; Mowat, Eilidh; Winstanley, Craig

2012-06-05

There is growing concern about the relevance of in vitro antimicrobial susceptibility tests when applied to isolates of P. aeruginosa from cystic fibrosis (CF) patients. Existing methods rely on single or a few isolates grown aerobically and planktonically. Predetermined cut-offs are used to define whether the bacteria are sensitive or resistant to any given antibiotic. However, during chronic lung infections in CF, P. aeruginosa populations exist in biofilms and there is evidence that the environment is largely microaerophilic. The stark difference in conditions between bacteria in the lung and those during diagnostic testing has called into question the reliability and even relevance of these tests. Artificial sputum medium (ASM) is a culture medium containing the components of CF patient sputum, including amino acids, mucin and free DNA. P. aeruginosa growth in ASM mimics growth during CF infections, with the formation of self-aggregating biofilm structures and population divergence. The aim of this study was to develop a microtitre-plate assay to study antimicrobial susceptibility of P. aeruginosa based on growth in ASM, which is applicable to both microaerophilic and aerobic conditions. An ASM assay was developed in a microtitre plate format. P. aeruginosa biofilms were allowed to develop for 3 days prior to incubation with antimicrobial agents at different concentrations for 24 hours. After biofilm disruption, cell viability was measured by staining with resazurin. This assay was used to ascertain the sessile cell minimum inhibitory concentration (SMIC) of tobramycin for 15 different P. aeruginosa isolates under aerobic and microaerophilic conditions and SMIC values were compared to those obtained with standard broth growth. Whilst there was some evidence for increased MIC values for isolates grown in ASM when compared to their planktonic counterparts, the biggest differences were found with bacteria tested in microaerophilic conditions, which showed a much increased resistance up to a > 128 fold, towards tobramycin in the ASM system when compared to assays carried out in aerobic conditions. The lack of association between current susceptibility testing methods and clinical outcome has questioned the validity of current methods. Several in vitro models have been used previously to study P. aeruginosa biofilms. However, these methods rely on surface attached biofilms, whereas the ASM biofilms resemble those observed in the CF lung. In addition, reduced oxygen concentration in the mucus has been shown to alter the behavior of P. aeruginosa and affect antibiotic susceptibility. Therefore using ASM under microaerophilic conditions may provide a more realistic environment in which to study antimicrobial susceptibility.

ASME B89.4.19 Performance Evaluation Tests and Geometric Misalignments in Laser Trackers

PubMed Central

Muralikrishnan, B.; Sawyer, D.; Blackburn, C.; Phillips, S.; Borchardt, B.; Estler, W. T.

2009-01-01

Small and unintended offsets, tilts, and eccentricity of the mechanical and optical components in laser trackers introduce systematic errors in the measured spherical coordinates (angles and range readings) and possibly in the calculated lengths of reference artifacts. It is desirable that the tests described in the ASME B89.4.19 Standard [1] be sensitive to these geometric misalignments so that any resulting systematic errors are identified during performance evaluation. In this paper, we present some analysis, using error models and numerical simulation, of the sensitivity of the length measurement system tests and two-face system tests in the B89.4.19 Standard to misalignments in laser trackers. We highlight key attributes of the testing strategy adopted in the Standard and propose new length measurement system tests that demonstrate improved sensitivity to some misalignments. Experimental results with a tracker that is not properly error corrected for the effects of the misalignments validate claims regarding the proposed new length tests. PMID:27504211

An adaptive sampling method for variable-fidelity surrogate models using improved hierarchical kriging

NASA Astrophysics Data System (ADS)

Hu, Jiexiang; Zhou, Qi; Jiang, Ping; Shao, Xinyu; Xie, Tingli

2018-01-01

Variable-fidelity (VF) modelling methods have been widely used in complex engineering system design to mitigate the computational burden. Building a VF model generally includes two parts: design of experiments and metamodel construction. In this article, an adaptive sampling method based on improved hierarchical kriging (ASM-IHK) is proposed to refine the improved VF model. First, an improved hierarchical kriging model is developed as the metamodel, in which the low-fidelity model is varied through a polynomial response surface function to capture the characteristics of a high-fidelity model. Secondly, to reduce local approximation errors, an active learning strategy based on a sequential sampling method is introduced to make full use of the already required information on the current sampling points and to guide the sampling process of the high-fidelity model. Finally, two numerical examples and the modelling of the aerodynamic coefficient for an aircraft are provided to demonstrate the approximation capability of the proposed approach, as well as three other metamodelling methods and two sequential sampling methods. The results show that ASM-IHK provides a more accurate metamodel at the same simulation cost, which is very important in metamodel-based engineering design problems.

Accomplishments of the NASA Johnson Space Center portion of the soil moisture project in fiscal year 1981

NASA Technical Reports Server (NTRS)

Paris, J. F.; Arya, L. M.; Davidson, S. A.; Hildreth, W. W.; Richter, J. C.; Rosenkranz, W. A.

1982-01-01

The NASA/JSC ground scatterometer system was used in a row structure and row direction effects experiment to understand these effects on radar remote sensing of soil moisture. Also, a modification of the scatterometer system was begun and is continuing, to allow cross-polarization experiments to be conducted in fiscal years 1982 and 1983. Preprocessing of the 1978 agricultural soil moisture experiment (ASME) data was completed. Preparations for analysis of the ASME data is fiscal year 1982 were completed. A radar image simulation procedure developed by the University of Kansas is being improved. Profile soil moisture model outputs were compared quantitatively for the same soil and climate conditions. A new model was developed and tested to predict the soil moisture characteristic (water tension versus volumetric soil moisture content) from particle-size distribution and bulk density data. Relationships between surface-zone soil moisture, surface flux, and subsurface moisture conditions are being studied as well as the ways in which measured soil moisture (as obtained from remote sensing) can be used for agricultural applications.

Asian Summer Monsoon Pollutes the Northern Hemispheric Stratosphere

NASA Astrophysics Data System (ADS)

Yu, P.; Gao, R. S.; Rosenlof, K. H.; Telg, H.; Liu, S.; Zhixuan, B.; Bian, J.

2016-12-01

An enhanced aerosol layer near the tropopause over Asia during the period of the Asian summer monsoon (ASM) was recently identified by satellites. Previous modeling studies suggest the layer is largely composed of organics and sulfate. However its source, detailed distribution, and climate implications are presently not well understood. To address this issue, in-situ measurements of aerosol size distribution during the 2015 ASM were made from Kunming, China. These showed a robust aerosol enhancement up to 2 km above the tropopause. We use a global climate model coupled with the Community Aerosol and Radiation Model for Atmospheres (CARMA) to show that these aerosol particles are transported to the entire 10°N - 50°N latitude band in the lower stratosphere. These transported particles, originally formed in the region of the ASM anticyclone, account for a significant fraction of total aerosol mass in the 10°N - 50°N latitude band between 16 to 20 km.

Changing circulation structure and precipitation characteristics in Asian monsoon regions: greenhouse warming vs. aerosol effects

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

Lau, William K. M.; Kim, Kyu-Myong; Ruby Leung, L.

Using model outputs from CMIP5 historical integrations, we have investigated the relative roles of anthropogenic emissions of greenhouse gases (GHG) and aerosols in changing the characteristics of the large-scale circulation and rainfall in Asian summer monsoon (ASM) regions. Under GHG warming, a strong positive trend in low-level moist static energy (MSE) is found over ASM regions, associated with increasing large-scale land–sea thermal contrast from 1870s to present. During the same period, a mid-tropospheric convective barrier (MCB) due to widespread reduction in relative humidity in the mid- and lower troposphere is strengthening over the ASM regions, in conjunction with expanding areasmore » of anomalous subsidence associated with the Deep Tropical Squeeze (Lau and Kim in Proc Natl Acad Sci 12:3630–3635, 2015). The opposing effects of MSE and MCB lead to enhanced total ASM rainfall, but only a partial strengthening of the southern portion of the monsoon meridional circulation, coupled to anomalous multi-cellular overturning motions over ASM land. Including anthropogenic aerosol emissions strongly masks MSE but enhances MCB via increased stability in the lower troposphere, resulting in an overall weakened ASM circulation with suppressed rainfall. Analyses of rainfall characteristics indicate that under GHG, overall precipitation efficiency over the ASM region is reduced, manifesting in less moderate but more extreme heavy rain events. Under combined effects of GHG and aerosols, precipitation efficiency is unchanged, with more moderate, but less extreme rainfall.« less

Changing circulation structure and precipitation characteristics in Asian monsoon regions: greenhouse warming vs. aerosol effects

NASA Astrophysics Data System (ADS)

Lau, William K. M.; Kim, Kyu-Myong; Ruby Leung, L.

2017-12-01

Using model outputs from CMIP5 historical integrations, we have investigated the relative roles of anthropogenic emissions of greenhouse gases (GHG) and aerosols in changing the characteristics of the large-scale circulation and rainfall in Asian summer monsoon (ASM) regions. Under GHG warming, a strong positive trend in low-level moist static energy (MSE) is found over ASM regions, associated with increasing large-scale land-sea thermal contrast from 1870s to present. During the same period, a mid-tropospheric convective barrier (MCB) due to widespread reduction in relative humidity in the mid- and lower troposphere is strengthening over the ASM regions, in conjunction with expanding areas of anomalous subsidence associated with the Deep Tropical Squeeze (Lau and Kim in Proc Natl Acad Sci 12:3630-3635, 2015). The opposing effects of MSE and MCB lead to enhanced total ASM rainfall, but only a partial strengthening of the southern portion of the monsoon meridional circulation, coupled to anomalous multi-cellular overturning motions over ASM land. Including anthropogenic aerosol emissions strongly masks MSE but enhances MCB via increased stability in the lower troposphere, resulting in an overall weakened ASM circulation with suppressed rainfall. Analyses of rainfall characteristics indicate that under GHG, overall precipitation efficiency over the ASM region is reduced, manifesting in less moderate but more extreme heavy rain events. Under combined effects of GHG and aerosols, precipitation efficiency is unchanged, with more moderate, but less extreme rainfall.

Parameter estimation procedure for complex non-linear systems: calibration of ASM No. 1 for N-removal in a full-scale oxidation ditch.

PubMed

Abusam, A; Keesman, K J; van Straten, G; Spanjers, H; Meinema, K

2001-01-01

When applied to large simulation models, the process of parameter estimation is also called calibration. Calibration of complex non-linear systems, such as activated sludge plants, is often not an easy task. On the one hand, manual calibration of such complex systems is usually time-consuming, and its results are often not reproducible. On the other hand, conventional automatic calibration methods are not always straightforward and often hampered by local minima problems. In this paper a new straightforward and automatic procedure, which is based on the response surface method (RSM) for selecting the best identifiable parameters, is proposed. In RSM, the process response (output) is related to the levels of the input variables in terms of a first- or second-order regression model. Usually, RSM is used to relate measured process output quantities to process conditions. However, in this paper RSM is used for selecting the dominant parameters, by evaluating parameters sensitivity in a predefined region. Good results obtained in calibration of ASM No. 1 for N-removal in a full-scale oxidation ditch proved that the proposed procedure is successful and reliable.

Could an increase in airway smooth muscle shortening velocity cause airway hyperresponsiveness?

PubMed Central

Bullimore, Sharon R.; Siddiqui, Sana; Donovan, Graham M.; Martin, James G.; Sneyd, James; Bates, Jason H. T.

2011-01-01

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma. It has been proposed that an increase in the shortening velocity of airway smooth muscle (ASM) could contribute to AHR. To address this possibility, we tested whether an increase in the isotonic shortening velocity of ASM is associated with an increase in the rate and total amount of shortening when ASM is subjected to an oscillating load, as occurs during breathing. Experiments were performed in vitro using 27 rat tracheal ASM strips supramaximally stimulated with methacholine. Isotonic velocity at 20% isometric force (Fiso) was measured, and then the load on the muscle was varied sinusoidally (0.33 ± 0.25 Fiso, 1.2 Hz) for 20 min, while muscle length was measured. A large amplitude oscillation was applied every 4 min to simulate a deep breath. We found that: 1) ASM strips with a higher isotonic velocity shortened more quickly during the force oscillations, both initially (P < 0.001) and after the simulated deep breaths (P = 0.002); 2) ASM strips with a higher isotonic velocity exhibited a greater total shortening during the force oscillation protocol (P < 0.005); and 3) the effect of an increase in isotonic velocity was at least comparable in magnitude to the effect of a proportional increase in ASM force-generating capacity. A cross-bridge model showed that an increase in the total amount of shortening with increased isotonic velocity could be explained by a change in either the cycling rate of phosphorylated cross bridges or the rate of myosin light chain phosphorylation. We conclude that, if asthma involves an increase in ASM velocity, this could be an important factor in the associated AHR. PMID:20971805

Shortage of Appendicular Skeletal Muscle Is an Independent Risk Factor for Mortality in Peritoneal Dialysis Patients.

PubMed

Jin, Sanli; Lu, Qian; Su, Chunyan; Pang, Dong; Wang, Tao

♦ BACKGROUND: Limited data are available on clinical outcomes among peritoneal dialysis patients with shortage of appendicular skeletal muscle (ASM). In this study, we tested the hypothesis that the shortage of ASM is an independent risk factor for mortality in continuous ambulatory peritoneal dialysis (CAPD) patients. ♦ METHODS: Adult patients undergoing CAPD between March and August 2007 in a single center in China were recruited in this prospective cohort study. Body composition, protein/energy intake, clinical, and biochemical data were collected at baseline, 6 months, and 12 months. End points were all-cause mortality by 12 September 2014. The mean follow-up time was 60.21 (± 24.45) months (11.00 - 89.00). ♦ RESULTS: Compared with the baseline, the mean value of ASM in CAPD patients decreased at 12 months (19.40 ± 5.60 vs 21.85 ± 6.14, p < 0.001). According to the estimation of patient survival by Kaplan-Meier, patients with a shortage of ASM had a worse survival rate than those with normal ASM (χ 2 = 16.588, p < 0.001). In the Cox's proportional hazards model, patients' survival was independently associated with a shortage of ASM (hazard ratio [HR] = 2.318, p = 0.024, 95% confidence interval [CI] = 1.116 - 4.812). Standard daily protein intake (stDPI) and standard daily energy intake (stDEI) in patients with a shortage of ASM were significantly lower than those in patients with normal ASM in the first follow-up year (t = 2.067, p = 0.041; t = 3.673, p = 0.001). ♦ CONCLUSIONS: A shortage of ASM is an independent risk factor for mortality in CAPD patients. Further studies are needed to demonstrate that nutritional intervention helps with improving muscle mass and, consequently, the survival of CAPD patients. Copyright © 2017 International Society for Peritoneal Dialysis.

Statistical analysis of geomagnetic field intensity differences between ASM and VFM instruments onboard Swarm constellation

NASA Astrophysics Data System (ADS)

De Michelis, Paola; Tozzi, Roberta; Consolini, Giuseppe

2017-02-01

From the very first measurements made by the magnetometers onboard Swarm satellites launched by European Space Agency (ESA) in late 2013, it emerged a discrepancy between scalar and vector measurements. An accurate analysis of this phenomenon brought to build an empirical model of the disturbance, highly correlated with the Sun incidence angle, and to correct vector data accordingly. The empirical model adopted by ESA results in a significant decrease in the amplitude of the disturbance affecting VFM measurements so greatly improving the vector magnetic data quality. This study is focused on the characterization of the difference between magnetic field intensity measured by the absolute scalar magnetometer (ASM) and that reconstructed using the vector field magnetometer (VFM) installed on Swarm constellation. Applying empirical mode decomposition method, we find the intrinsic mode functions (IMFs) associated with ASM-VFM total intensity differences obtained with data both uncorrected and corrected for the disturbance correlated with the Sun incidence angle. Surprisingly, no differences are found in the nature of the IMFs embedded in the analyzed signals, being these IMFs characterized by the same dominant periodicities before and after correction. The effect of correction manifests in the decrease in the energy associated with some IMFs contributing to corrected data. Some IMFs identified by analyzing the ASM-VFM intensity discrepancy are characterized by the same dominant periodicities of those obtained by analyzing the temperature fluctuations of the VFM electronic unit. Thus, the disturbance correlated with the Sun incidence angle could be still present in the corrected magnetic data. Furthermore, the ASM-VFM total intensity difference and the VFM electronic unit temperature display a maximal shared information with a time delay that depends on local time. Taken together, these findings may help to relate the features of the observed VFM-ASM total intensity difference to the physical characteristics of the real disturbance thus contributing to improve the empirical model proposed for the correction of data.[Figure not available: see fulltext.

A Comparison of the Variability of the Symbiotic X-ray Binaries GX 1+4, 4U 1954+31, and 4U 1700+24 from Swift/BAT and RXTE/ASM Observations

NASA Technical Reports Server (NTRS)

Corbet, R. H. D.; Sokoloski, J. L.; Mukai, K.; Markwardt, C. B.; Tueller, J.

2007-01-01

We present an analysis of the X-ray variability of three symbiotic X-ray binaries, GX 1+4, 4U 1700+24, and 4U 1954+31, using observations made with the Swift Burst Alert Telescope (BAT) and the Rossi X-ray Timing Explorer (RXTE) All-Sky Monitor (ASM). Observations of 4U 1954+31 with the Swift BAT show modulation at a period near 5 hours. Models to explain this modulation are discussed including the presence of an exceptionally slow X-ray pulsar in the system and accretion instabilities. We conclude that the most likely interpretation is that 4U 1954+31 contains one of the slowest known X-ray pulsars. Unlike 4U 1954+31, neither GX 1+4 nor 4U 1700+24 show any evidence for modulation on a timescale of hours. An analysis of the RXTE ASM light curves of GX l+4, 4U 1700+24, and 4U 1954+31 does not show the presence of periodic modulation in any source, although there is considerable variability on long timescales for all three sources. There is no modulation in GX 1+4 on either the optical 1161 day orbital period or a previously reported 304 day X-ray period. For 4U 1700+24 we do not confirm the 404 day period previously proposed for this source from a shorter duration ASM light curve.

Probabilistic parameter estimation of activated sludge processes using Markov Chain Monte Carlo.

PubMed

Sharifi, Soroosh; Murthy, Sudhir; Takács, Imre; Massoudieh, Arash

2014-03-01

One of the most important challenges in making activated sludge models (ASMs) applicable to design problems is identifying the values of its many stoichiometric and kinetic parameters. When wastewater characteristics data from full-scale biological treatment systems are used for parameter estimation, several sources of uncertainty, including uncertainty in measured data, external forcing (e.g. influent characteristics), and model structural errors influence the value of the estimated parameters. This paper presents a Bayesian hierarchical modeling framework for the probabilistic estimation of activated sludge process parameters. The method provides the joint probability density functions (JPDFs) of stoichiometric and kinetic parameters by updating prior information regarding the parameters obtained from expert knowledge and literature. The method also provides the posterior correlations between the parameters, as well as a measure of sensitivity of the different constituents with respect to the parameters. This information can be used to design experiments to provide higher information content regarding certain parameters. The method is illustrated using the ASM1 model to describe synthetically generated data from a hypothetical biological treatment system. The results indicate that data from full-scale systems can narrow down the ranges of some parameters substantially whereas the amount of information they provide regarding other parameters is small, due to either large correlations between some of the parameters or a lack of sensitivity with respect to the parameters. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modeling and parameter estimation of two-phase endogenous respirograms and COD measurements during aerobic digestion of biological sludge.

PubMed

Fall, C; Rogel-Dorantes, J A; Millán-Lagunas, E L; Martínez-García, C G; Silva-Hernández, B C; Silva-Trejo, F S

2014-12-01

Long-term aerobic digestion batch tests were performed on a sludge that contained mainly two fractions, a heterotrophic biomass XH and its endogenous residues XP, which were cultivated in conditions known to favor bio-storage (XSto). The objective was to model the stabilization of the sludge and determine the parameters of the endogenous decay processes, based on simultaneous measurements of the chemical oxygen demand (COD) and oxygen uptake rates (OUR). The respirograms were shown to have a two-phase structure that was describable with activated sludge model 3 (ASM3), but not with ASM1. Comparing the information from the COD and OUR data suggested the presence of two different groups of heterotrophs (XHa and XHb), one that decays with oxygen consumption and another without using O2. A modified ASM3 model was proposed, which was able to fit the OUR and COD data from the digesters, as well as cases from the literature. Copyright © 2014 Elsevier Ltd. All rights reserved.

Application of materials database (MAT.DB.) to materials education

NASA Technical Reports Server (NTRS)

Liu, Ping; Waskom, Tommy L.

1994-01-01

Finding the right material for the job is an important aspect of engineering. Sometimes the choice is as fundamental as selecting between steel and aluminum. Other times, the choice may be between different compositions in an alloy. Discovering and compiling materials data is a demanding task, but it leads to accurate models for analysis and successful materials application. Mat. DB. is a database management system designed for maintaining information on the properties and processing of engineered materials, including metals, plastics, composites, and ceramics. It was developed by the Center for Materials Data of American Society for Metals (ASM) International. The ASM Center for Materials Data collects and reviews material property data for publication in books, reports, and electronic database. Mat. DB was developed to aid the data management and material applications.

Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.

PubMed

Ranganath, Prajnya; Matta, Divya; Bhavani, Gandham SriLakshmi; Wangnekar, Savita; Jain, Jamal Mohammed Nurul; Verma, Ishwar C; Kabra, Madhulika; Puri, Ratna Dua; Danda, Sumita; Gupta, Neerja; Girisha, Katta M; Sankar, Vaikom H; Patil, Siddaramappa J; Ramadevi, Akella Radha; Bhat, Meenakshi; Gowrishankar, Kalpana; Mandal, Kausik; Aggarwal, Shagun; Tamhankar, Parag Mohan; Tilak, Preetha; Phadke, Shubha R; Dalal, Ashwin

2016-10-01

Acid sphingomyelinase (ASM)-deficient Niemann-Pick disease is an autosomal recessive lysosomal storage disorder caused by biallelic mutations in the SMPD1 gene. To date, around 185 mutations have been reported in patients with ASM-deficient NPD world-wide, but the mutation spectrum of this disease in India has not yet been reported. The aim of this study was to ascertain the mutation profile in Indian patients with ASM-deficient NPD. We sequenced SMPD1 in 60 unrelated families affected with ASM-deficient NPD. A total of 45 distinct pathogenic sequence variants were found, of which 14 were known and 31 were novel. The variants included 30 missense, 4 nonsense, and 9 frameshift (7 single base deletions and 2 single base insertions) mutations, 1 indel, and 1 intronic duplication. The pathogenicity of the novel mutations was inferred with the help of the mutation prediction software MutationTaster, SIFT, Polyphen-2, PROVEAN, and HANSA. The effects of the identified sequence variants on the protein structure were studied using the structure modeled with the help of the SWISS-MODEL workspace program. The p. (Arg542*) (c.1624C>T) mutation was the most commonly identified mutation, found in 22% (26 out of 120) of the alleles tested, but haplotype analysis for this mutation did not identify a founder effect for the Indian population. To the best of our knowledge, this is the largest study on mutation analysis of patients with ASM-deficient Niemann-Pick disease reported in literature and also the first study on the SMPD1 gene mutation spectrum in India. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Diagnostic delay in psychogenic seizures and the association with anti-seizure medication trials.

PubMed

Kerr, Wesley T; Janio, Emily A; Le, Justine M; Hori, Jessica M; Patel, Akash B; Gallardo, Norma L; Bauirjan, Janar; Chau, Andrea M; D'Ambrosio, Shannon R; Cho, Andrew Y; Engel, Jerome; Cohen, Mark S; Stern, John M

2016-08-01

The average delay from first seizure to diagnosis of psychogenic non-epileptic seizures (PNES) is over 7 years. The reason for this delay is not well understood. We hypothesized that a perceived decrease in seizure frequency after starting an anti-seizure medication (ASM) may contribute to longer delays, but the frequency of such a response has not been well established. Time from onset to diagnosis, medication history and associated seizure frequency was acquired from the medical records of 297 consecutive patients with PNES diagnosed using video-electroencephalographic monitoring. Exponential regression was used to model the effect of medication trials and response on diagnostic delay. Mean diagnostic delay was 8.4 years (min 1 day, max 52 years). The robust average diagnostic delay was 2.8 years (95% CI: 2.2-3.5 years) based on an exponential model as 10 to the mean of log10 delay. Each ASM trial increased the robust average delay exponentially by at least one third of a year (Wald t=3.6, p=0.004). Response to ASM trials did not significantly change diagnostic delay (Wald t=-0.9, p=0.38). Although a response to ASMs was observed commonly in these patients with PNES, the presence of a response was not associated with longer time until definitive diagnosis. Instead, the number of ASMs tried was associated with a longer delay until diagnosis, suggesting that ASM trials were continued despite lack of response. These data support the guideline that patients with seizures should be referred to epilepsy care centers after failure of two medication trials. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

FY17 Status Report on the Initial Development of a Constitutive Model for Grade 91 Steel

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

Messner, M. C.; Phan, V. -T.; Sham, T. -L.

Grade 91 is a candidate structural material for high temperature advanced reactor applications. Existing ASME Section III, Subsection HB, Subpart B simplified design rules based on elastic analysis are setup as conservative screening tools with the intent to supplement these screening rules with full inelastic analysis when required. The Code provides general guidelines for suitable inelastic models but does not provide constitutive model implementations. This report describes the development of an inelastic constitutive model for Gr. 91 steel aimed at fulfilling the ASME Code requirements and being included into a new Section III Code appendix, HBB-Z. A large database ofmore » over 300 experiments on Gr. 91 was collected and converted to a standard XML form. Five families of Gr. 91 material models were identified in the literature. Of these five, two are potentially suitable for use in the ASME code. These two models were implemented and evaluated against the experimental database. Both models have deficiencies so the report develops a framework for developing and calibrating an improved model. This required creating a new modeling method for representing changes in material rate sensitivity across the full ASME allowable temperature range for Gr. 91 structural components: room temperature to 650° C. On top of this framework for rate sensitivity the report describes calibrating a model for work hardening and softening in the material using genetic algorithm optimization. Future work will focus on improving this trial model by including tension/compression asymmetry observed in experiments and necessary to capture material ratcheting under zero mean stress and by improving the optimization and analysis framework.« less

The multiaxial fatigue response of cylindrical geometry under proportional loading subject to fluctuating tractions

NASA Astrophysics Data System (ADS)

Martinez, Rudy D.

A multiaxial fatigue model is proposed, as it would apply to cylindrical geometry in the form of industrial sized pressure vessels. The main focus of the multiaxial fatigue model will be based on using energy methods with the loading states confined to fluctuating tractions under proportional loading. The proposed fatigue model is an effort to support and enhance existing fatigue life predicting methods for pressure vessel design, beyond the ASME Boiler and Pressure Vessel codes, ASME Section VIII Division 2 and 3, which is currently used in industrial engineering practice for pressure vessel design. Both uniaxial and biaxial low alloy pearlittic-ferritic steel cylindrical cyclic test data are utilized to substantiate the proposed fatigue model. Approximate material hardening and softening aspects from applied load cycling states and the Bauschinger effect are accounted for by adjusting strain control generated hysteresis loops and the cyclic stress strain curve. The proposed fatigue energy model and the current ASME fatigue model are then compared with regards to the accuracy of predicting fatigue life cycle consistencies.

Equatorward dispersion of the Sarychev volcanic plume and the relation to the Asian summer monsoon

NASA Astrophysics Data System (ADS)

Wu, Xue; Griessbach, Sabine; Hoffmann, Lars

2017-04-01

Sulfur dioxide emissions and subsequent sulfate aerosols from strong volcanic eruptions have large impact on global climate. Although most of previous studies attribute the global influence to volcanic eruptions in the tropics, high-latitude volcanic eruptions are also an important cause for global climate variations. In fact, the potential climate impact of volcanic also largely depends on the season when eruptions occur, the erupted plume height and the surrounding meteorological conditions. This work focuses on the eruption of a high-latitude volcano Sarychev, and the role of Asian summer monsoon (ASM) during the transport and dispersion of the erupted plumes. First, the sulfur dioxide emission rate and height of emission of the Sarychev eruption in June 2009 are modelled using a Lagrangian particle dispersion model named Massive-Parallel Trajectory Calculations (MPTRAC), together with sulfur dioxide observations of the Atmospheric Infrared Sounder (AIRS/Aqua) and a backward trajectory approach. Then, the transport and dispersion of the plumes are modelled with MPTRAC and validated with sulfur dioxide observations from AIRS and aerosol observations from the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS). The modelled trajectories and the MIPAS data both show the plumes are transported towards the tropics from the southeast edge of the ASM (in the vertical range of 340-400K) controlled by the clockwise winds of ASM, and from above the ASM (above 400K) in form of in-mixing process. Especially, in the vertical range around 340-400K, a transport barrier based on potential vorticity (PV) gradients separates the 'aerosol hole' inside of the ASM circulation and the aerosol-rich surrounding area, which shows the PV gradients based barrier may be more practical than the barrier based on the geopotential height. With help of ASM circulation, the aerosol transported to the tropics and stayed in the tropical lower stratosphere for about eight months, which were the main aerosol sources during that time. This enables the Sarychev eruption to have potential impact on global radiative budget similar to a tropical volcanic eruption.

Active shape modeling of the hip in the prediction of incident hip fracture.

PubMed

Baker-LePain, Julie C; Luker, Kali R; Lynch, John A; Parimi, Neeta; Nevitt, Michael C; Lane, Nancy E

2011-03-01

The objective of this study was to evaluate right proximal femur shape as a risk factor for incident hip fracture using active shape modeling (ASM). A nested case-control study of white women 65 years of age and older enrolled in the Study of Osteoporotic Fractures (SOF) was performed. Subjects (n = 168) were randomly selected from study participants who experienced hip fracture during the follow-up period (mean 8.3 years). Controls (n = 231) had no fracture during follow-up. Subjects with baseline radiographic hip osteoarthritis were excluded. ASM of digitized right hip radiographs generated 10 independent modes of variation in proximal femur shape that together accounted for 95% of the variance in proximal femur shape. The association of ASM modes with incident hip fracture was analyzed by logistic regression. Together, the 10 ASM modes demonstrated good discrimination of incident hip fracture. In models controlling for age and body mass index (BMI), the area under receiver operating characteristic (AUROC) curve for hip shape was 0.813, 95% confidence interval (CI) 0.771-0.854 compared with models containing femoral neck bone mineral density (AUROC = 0.675, 95% CI 0.620-0.730), intertrochanteric bone mineral density (AUROC = 0.645, 95% CI 0.589-0.701), femoral neck length (AUROC = 0.631, 95% CI 0.573-0.690), or femoral neck width (AUROC = 0.633, 95% CI 0.574-0.691). The accuracy of fracture discrimination was improved by combining ASM modes with femoral neck bone mineral density (AUROC = 0.835, 95% CI 0.795-0.875) or with intertrochanteric bone mineral density (AUROC = 0.834, 95% CI 0.794-0.875). Hips with positive standard deviations of ASM mode 4 had the highest risk of incident hip fracture (odds ratio = 2.48, 95% CI 1.68-3.31, p < .001). We conclude that variations in the relative size of the femoral head and neck are important determinants of incident hip fracture. The addition of hip shape to fracture-prediction tools may improve the risk assessment for osteoporotic hip fractures. Copyright © 2011 American Society for Bone and Mineral Research.

ASM Based Synthesis of Handwritten Arabic Text Pages

PubMed Central

Al-Hamadi, Ayoub; Elzobi, Moftah; El-etriby, Sherif; Ghoneim, Ahmed

2015-01-01

Document analysis tasks, as text recognition, word spotting, or segmentation, are highly dependent on comprehensive and suitable databases for training and validation. However their generation is expensive in sense of labor and time. As a matter of fact, there is a lack of such databases, which complicates research and development. This is especially true for the case of Arabic handwriting recognition, that involves different preprocessing, segmentation, and recognition methods, which have individual demands on samples and ground truth. To bypass this problem, we present an efficient system that automatically turns Arabic Unicode text into synthetic images of handwritten documents and detailed ground truth. Active Shape Models (ASMs) based on 28046 online samples were used for character synthesis and statistical properties were extracted from the IESK-arDB database to simulate baselines and word slant or skew. In the synthesis step ASM based representations are composed to words and text pages, smoothed by B-Spline interpolation and rendered considering writing speed and pen characteristics. Finally, we use the synthetic data to validate a segmentation method. An experimental comparison with the IESK-arDB database encourages to train and test document analysis related methods on synthetic samples, whenever no sufficient natural ground truthed data is available. PMID:26295059

A Multi-Year Light Curve of Scorpius X-1 Based on CGRO BATSE Spectroscopy Detector Observations

NASA Technical Reports Server (NTRS)

McNamara, B. J.; Harrison, T. E.; Mason, P. A.; Templeton, M.; Heikkila, C. W.; Buckley, T.; Galvan, E.; Silva, A.; Harmon, B. A.

1998-01-01

A multi-year light curve of the low mass X-ray binary, Scorpius X-1, is constructed based on the Compton Gamma-ray Observatory (CGRO) Burst and Transient Source Experiment (BATSE) Spectroscopy Detector (SD) data in the nominal energy range of 10-20 keV. A detailed discussion is given of the reduction process of the BATSE/SD data. Corrections to the SD measurements are made for off-axis pointings, spectral and bandpass changes, and differences in the eight SD sensitivities. The resulting 4.4 year Sco X-1 SD light curve is characterized in terms of the time scales over which various types of emission changes occur. This light curve is then compared with Sco X-1 light curves obtained by Axiel 5, the BATSE Large Area Detectors (LADs), and the RXTE all-sky monitor (ASM). Coincident temporal coverage by the BATSE/SD and RXTE/ASM allows a direct comparison of the behavior of Sco X-1 over a range of high energies to be made. These ASM light curves are then used to discuss model constraints on the Sco X-1 system.

ASM Based Synthesis of Handwritten Arabic Text Pages.

PubMed

Dinges, Laslo; Al-Hamadi, Ayoub; Elzobi, Moftah; El-Etriby, Sherif; Ghoneim, Ahmed

2015-01-01

Document analysis tasks, as text recognition, word spotting, or segmentation, are highly dependent on comprehensive and suitable databases for training and validation. However their generation is expensive in sense of labor and time. As a matter of fact, there is a lack of such databases, which complicates research and development. This is especially true for the case of Arabic handwriting recognition, that involves different preprocessing, segmentation, and recognition methods, which have individual demands on samples and ground truth. To bypass this problem, we present an efficient system that automatically turns Arabic Unicode text into synthetic images of handwritten documents and detailed ground truth. Active Shape Models (ASMs) based on 28046 online samples were used for character synthesis and statistical properties were extracted from the IESK-arDB database to simulate baselines and word slant or skew. In the synthesis step ASM based representations are composed to words and text pages, smoothed by B-Spline interpolation and rendered considering writing speed and pen characteristics. Finally, we use the synthetic data to validate a segmentation method. An experimental comparison with the IESK-arDB database encourages to train and test document analysis related methods on synthetic samples, whenever no sufficient natural ground truthed data is available.

3D automatic anatomy segmentation based on iterative graph-cut-ASM.

PubMed

Chen, Xinjian; Bagci, Ulas

2011-08-01

This paper studies the feasibility of developing an automatic anatomy segmentation (AAS) system in clinical radiology and demonstrates its operation on clinical 3D images. The AAS system, the authors are developing consists of two main parts: object recognition and object delineation. As for recognition, a hierarchical 3D scale-based multiobject method is used for the multiobject recognition task, which incorporates intensity weighted ball-scale (b-scale) information into the active shape model (ASM). For object delineation, an iterative graph-cut-ASM (IGCASM) algorithm is proposed, which effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. The presented IGCASM algorithm is a 3D generalization of the 2D GC-ASM method that they proposed previously in Chen et al. [Proc. SPIE, 7259, 72590C1-72590C-8 (2009)]. The proposed methods are tested on two datasets comprised of images obtained from 20 patients (10 male and 10 female) of clinical abdominal CT scans, and 11 foot magnetic resonance imaging (MRI) scans. The test is for four organs (liver, left and right kidneys, and spleen) segmentation, five foot bones (calcaneus, tibia, cuboid, talus, and navicular). The recognition and delineation accuracies were evaluated separately. The recognition accuracy was evaluated in terms of translation, rotation, and scale (size) error. The delineation accuracy was evaluated in terms of true and false positive volume fractions (TPVF, FPVF). The efficiency of the delineation method was also evaluated on an Intel Pentium IV PC with a 3.4 GHZ CPU machine. The recognition accuracies in terms of translation, rotation, and scale error over all organs are about 8 mm, 10 degrees and 0.03, and over all foot bones are about 3.5709 mm, 0.35 degrees and 0.025, respectively. The accuracy of delineation over all organs for all subjects as expressed in TPVF and FPVF is 93.01% and 0.22%, and all foot bones for all subjects are 93.75% and 0.28%, respectively. While the delineations for the four organs can be accomplished quite rapidly with average of 78 s, the delineations for the five foot bones can be accomplished with average of 70 s. The experimental results showed the feasibility and efficacy of the proposed automatic anatomy segmentation system: (a) the incorporation of shape priors into the GC framework is feasible in 3D as demonstrated previously for 2D images; (b) our results in 3D confirm the accuracy behavior observed in 2D. The hybrid strategy IGCASM seems to be more robust and accurate than ASM and GC individually; and (c) delineations within body regions and foot bones of clinical importance can be accomplished quite rapidly within 1.5 min.

Shuttle Systems 3-D Applications: Application of 3-D Graphics in Engineering Training for Shuttle Ground Processing

NASA Technical Reports Server (NTRS)

Godfrey, Gary S.

2003-01-01

This project illustrates an animation of the orbiter mate to the external tank, an animation of the OMS POD installation to the orbiter, and a simulation of the landing gear mechanism at the Kennedy Space Center. A detailed storyboard was created to reflect each animation or simulation. Solid models were collected and translated into Pro/Engineer's prt and asm formats. These solid models included computer files of the: orbiter, external tank, solid rocket booster, mobile launch platform, transporter, vehicle assembly building, OMS POD fixture, and landing gear. A depository of the above solid models was established. These solid models were translated into several formats. This depository contained the following files: stl for sterolithography, stp for neutral file work, shrinkwrap for compression, tiff for photoshop work, jpeg for Internet use, and prt and asm for Pro/Engineer use. Solid models were created of the material handling sling, bay 3 platforms, and orbiter contact points. Animations were developed using mechanisms to reflect each storyboard. Every effort was made to build all models technically correct for engineering use. The result was an animated routine that could be used by NASA for training material handlers and uncovering engineering safety issues.

Lawriter - OAC

Science.gov Websites

authorized by section 3709.05 of the Revised Code. (C) "Circulation system" means an arrangement of transferred and does not mean the person who formerly operated or maintained the public swimming pool. (J ://catalog.asme.org/. ASME documents are also generally available at the state library of Ohio. (c) American national

When a Plant Resistance Inducer Leaves the Lab for the Field: Integrating ASM into Routine Apple Protection Practices.

PubMed

Marolleau, Brice; Gaucher, Matthieu; Heintz, Christelle; Degrave, Alexandre; Warneys, Romain; Orain, Gilles; Lemarquand, Arnaud; Brisset, Marie-Noëlle

2017-01-01

Plant resistance inducers, also called elicitors, could be useful to reduce the use of pesticides. However, their performance in controlling diseases in the field remains unsatisfactory due to lack of specific knowledge of how they can integrate crop protection practices. In this work, we focused on apple crop and acibenzolar- S -methyl (ASM), a well-known SAR (systemic acquired resistance) inducer of numerous plant species. We provide a protocol for orchard-effective control of apple scab due to the ascomycete fungus Venturia inaequalis , by applying ASM in combination with a light integrated pest management program. Besides we pave the way for future optimization levers by demonstrating in controlled conditions (i) the high influence of apple genotypes, (ii) the ability of ASM to prime defenses in newly formed leaves, (iii) the positive effect of repeated elicitor applications, (iv) the additive effect of a thinning fruit agent.

When a Plant Resistance Inducer Leaves the Lab for the Field: Integrating ASM into Routine Apple Protection Practices

PubMed Central

Marolleau, Brice; Gaucher, Matthieu; Heintz, Christelle; Degrave, Alexandre; Warneys, Romain; Orain, Gilles; Lemarquand, Arnaud; Brisset, Marie-Noëlle

2017-01-01

Plant resistance inducers, also called elicitors, could be useful to reduce the use of pesticides. However, their performance in controlling diseases in the field remains unsatisfactory due to lack of specific knowledge of how they can integrate crop protection practices. In this work, we focused on apple crop and acibenzolar-S-methyl (ASM), a well-known SAR (systemic acquired resistance) inducer of numerous plant species. We provide a protocol for orchard-effective control of apple scab due to the ascomycete fungus Venturia inaequalis, by applying ASM in combination with a light integrated pest management program. Besides we pave the way for future optimization levers by demonstrating in controlled conditions (i) the high influence of apple genotypes, (ii) the ability of ASM to prime defenses in newly formed leaves, (iii) the positive effect of repeated elicitor applications, (iv) the additive effect of a thinning fruit agent. PMID:29255473

Nonclinical safety assessment of recombinant human acid sphingomyelinase (rhASM) for the treatment of acid sphingomyelinase deficiency:the utility of animal models of disease in the toxicological evaluation of potential therapeutics.

PubMed

Murray, James M; Thompson, Anne Marie; Vitsky, Allison; Hawes, Michael; Chuang, Wei-Lien; Pacheco, Joshua; Wilson, Stephen; McPherson, John M; Thurberg, Beth L; Karey, Kenneth P; Andrews, Laura

2015-02-01

Recombinant human acid sphingomyelinase (rhASM) is being developed as an enzyme replacement therapy for patients with acid sphingomyelinase deficiency (Niemann-Pick disease types A and B), which causes sphingomyelin to accumulate in lysosomes. In the acid sphingomyelinase knock-out (ASMKO) mouse, intravenously administered rhASM reduced tissue sphingomyelin levels in a dose-dependent manner. When rhASM was administered to normal rats, mice, and dogs, no toxicity was observed up to a dose of 30mg/kg. However, high doses of rhASM≥10mg/kg administered to ASMKO mice resulted in unexpected toxicity characterized by cardiovascular shock, hepatic inflammation, adrenal hemorrhage, elevations in ceramide and cytokines (especially IL-6, G-CSF, and keratinocyte chemoattractant [KC]), and death. The toxicity could be completely prevented by the administration of several low doses (3mg/kg) of rhASM prior to single or repeated high doses (≥20mg/kg). These results suggest that the observed toxicity involves the rapid breakdown of large amounts of sphingomyelin into ceramide and/or other toxic downstream metabolites, which are known signaling molecules with cardiovascular and pro-inflammatory effects. Our results suggest that the nonclinical safety assessment of novel therapeutics should include the use of specific animal models of disease whenever feasible. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Rotating Detonation Engine Research at NRL

DTIC Science & Technology

2013-07-01

Bykovskii, Wolanski, Falempin, Hayashi, Schauer, Yi, Wang, Brophy, Wu, Clafin, Smith, Tsuboi, Frolov, et al.) Recant RDE Studies at NRL Flow-field...Symposium) Injection/inflow effects (JPC 2011~044; ASM 2012-0617, ASM 2013-1178) the expansion region change RDE performance. Can this model be...Efficient Complex Configuration Simulation Capability 158 BASELINE SOLUTION • Basetine configUration Stoichiometric hydrogen-air RDE of Wolanski

TOWARD THE DEVELOPMENT OF A CONSENSUS MATERIALS DATABASE FOR PRESSURE TECHNOLGY APPLICATIONS

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

Swindeman, Robert W; Ren, Weiju

The ASME construction code books specify materials and fabrication procedures that are acceptable for pressure technology applications. However, with few exceptions, the materials properties provided in the ASME code books provide no statistics or other information pertaining to material variability. Such information is central to the prediction and prevention of failure events. Many sources of materials data exist that provide variability information but such sources do not necessarily represent a consensus of experts with respect to the reported trends that are represented. Such a need has been identified by the ASME Standards Technology, LLC and initial steps have been takenmore » to address these needs: however, these steps are limited to project-specific applications only, such as the joint DOE-ASME project on materials for Generation IV nuclear reactors. In contrast to light-water reactor technology, the experience base for the Generation IV nuclear reactors is somewhat lacking and heavy reliance must be placed on model development and predictive capability. The database for model development is being assembled and includes existing code alloys such as alloy 800H and 9Cr-1Mo-V steel. Ownership and use rights are potential barriers that must be addressed.« less

Metabolic Effects of Acibenzolar-S-Methyl for Improving Heat or Drought Stress in Creeping Bentgrass

PubMed Central

Jespersen, David; Yu, Jingjin; Huang, Bingru

2017-01-01

Acibenzolar-S-methyl (ASM) is a synthetic functional analog of salicylic acid which can induce systemic acquired resistance in plants, but its effects on abiotic stress tolerance is not well known. The objectives of this study were to examine effects of acibenzolar-S-methyl on heat or drought tolerance in creeping bentgrass (Agrostis stolonifera) and to determine major ASM-responsive metabolites and proteins associated with enhanced abiotic stress tolerance. Creeping bentgrass plants (cv. ‘Penncross’) were foliarly sprayed with ASM and were exposed to non-stress (20/15°C day/night), heat stress (35/30°C), or drought conditions (by withholding irrigation) in controlled-environment growth chambers. Exogenous ASM treatment resulted in improved heat or drought tolerance, as demonstrated by higher overall turf quality, relative water content, and chlorophyll content compared to the untreated control. Western blotting revealed that ASM application resulted in up-regulation of ATP synthase, HSP-20, PR-3, and Rubisco in plants exposed to heat stress, and greater accumulation of dehydrin in plants exposed to drought stress. Metabolite profiling identified a number of amino acids, organic acids, and sugars which were differentially accumulated between ASM treated and untreated plants under heat or drought stress, including aspartic acid, glycine, citric acid, malic acid, and the sugars glucose, and fructose. Our results suggested that ASM was effective in improving heat or drought tolerance in creeping bentgrass, mainly through enhancing protein synthesis and metabolite accumulation involved in osmotic adjustment, energy metabolism, and stress signaling. PMID:28744300

Image segmentation using local shape and gray-level appearance models

NASA Astrophysics Data System (ADS)

Seghers, Dieter; Loeckx, Dirk; Maes, Frederik; Suetens, Paul

2006-03-01

A new generic model-based segmentation scheme is presented, which can be trained from examples akin to the Active Shape Model (ASM) approach in order to acquire knowledge about the shape to be segmented and about the gray-level appearance of the object in the image. Because in the ASM approach the intensity and shape models are typically applied alternately during optimizing as first an optimal target location is selected for each landmark separately based on local gray-level appearance information only to which the shape model is fitted subsequently, the ASM may be misled in case of wrongly selected landmark locations. Instead, the proposed approach optimizes for shape and intensity characteristics simultaneously. Local gray-level appearance information at the landmark points extracted from feature images is used to automatically detect a number of plausible candidate locations for each landmark. The shape information is described by multiple landmark-specific statistical models that capture local dependencies between adjacent landmarks on the shape. The shape and intensity models are combined in a single cost function that is optimized non-iteratively using dynamic programming which allows to find the optimal landmark positions using combined shape and intensity information, without the need for initialization.

Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics

PubMed Central

Sutcliffe, A; Kaur, D; Page, S; Woodman, L; Armour, C L; Baraket, M; Bradding, P; Hughes, J M; Brightling, C E

2006-01-01

Background Mast cell microlocalisation within the airway smooth muscle (ASM) bundle is an important determinant of the asthmatic phenotype. We hypothesised that mast cells migrate towards ASM in response to ASM derived chemokines. Methods Primary ASM cultures from subjects with and without asthma were stimulated with interleukin (IL)‐1β, IL‐4, and IL‐13 alone and in combination. Mast cell chemotaxis towards these ASM supernatants was investigated, and the chemotaxins mediating migration by using specific blocking antibodies for stem cell factor (SCF) and the chemokine receptors CCR3, CXCR1, 3 and 4 as well as the Gi inhibitor pertussis toxin and the tyrosine kinase inhibitor genistein were defined. The concentrations of CCL11, CXCL8, CXCL10, TGF‐β, and SCF in the supernatants were measured and the effect of non‐asthmatic ASM supernatants on the mast cell chemotactic activity of asthmatic ASM was examined. Results Human lung mast cells and HMC‐1 cells migrated towards Th2 stimulated ASM from asthmatics but not non‐asthmatics. Mast cell migration was mediated through the combined activation of CCR3 and CXCR1. CCL11 and CXCL8 expression by ASM increased markedly after stimulation, but was similar in those with and without asthma. ASM supernatants from non‐asthmatics inhibited mast cell migration towards the asthmatic ASM supernatant. Conclusion Th2 stimulated ASM from asthmatics is chemotactic for mast cells. Non‐asthmatic ASM releases a mediator or mediators that inhibit mast cell migration towards stimulated asthmatic ASM. Specifically targeting mast cell migration into the ASM bundle may provide a novel treatment for asthma. PMID:16601090

Review and Application of ASME NOG-1 and ASME NUM-1-2000

NASA Technical Reports Server (NTRS)

Lytle, Bradford P.; Delgado, H. (Technical Monitor)

2002-01-01

The intent of the workshop is to review the application of the ASME Nuclear Crane Standards ASME NOG-1 and ASME NUM-1-2000. The ASME Nuclear Crane standards provide a basis for purchasing overhead handling equipment with enhanced safety features, based upon accepted engineering principles, and including performance and environmental parameters specific to nuclear facilities.

Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction.

PubMed

Deshpande, Deepak A; Wang, Wayne C H; McIlmoyle, Elizabeth L; Robinett, Kathryn S; Schillinger, Rachel M; An, Steven S; Sham, James S K; Liggett, Stephen B

2010-11-01

Bitter taste receptors (TAS2Rs) on the tongue probably evolved to evoke signals for avoiding ingestion of plant toxins. We found expression of TAS2Rs on human airway smooth muscle (ASM) and considered these to be avoidance receptors for inhalants that, when activated, lead to ASM contraction and bronchospasm. TAS2R agonists such as saccharin, chloroquine and denatonium evoked increased intracellular calcium ([Ca²(+)](i)) in ASM in a Gβγ-, phospholipase Cβ (PLCβ)- and inositol trisphosphate (IP₃) receptor-dependent manner, which would be expected to evoke contraction. Paradoxically, bitter tastants caused relaxation of isolated ASM and dilation of airways that was threefold greater than that elicited by β-adrenergic receptor agonists. The relaxation induced by TAS2Rs is associated with a localized [Ca²(+)](i) response at the cell membrane, which opens large-conductance Ca²(+)-activated K(+) (BK(Ca)) channels, leading to ASM membrane hyperpolarization. Inhaled bitter tastants decreased airway obstruction in a mouse model of asthma. Given the need for efficacious bronchodilators for treating obstructive lung diseases, this pathway can be exploited for therapy with the thousands of known synthetic and naturally occurring bitter tastants.

Sarcopenic obesity: prevalence and association with metabolic syndrome in the Korean Longitudinal Study on Health and Aging (KLoSHA).

PubMed

Lim, Soo; Kim, Jung Hee; Yoon, Ji Won; Kang, Seon Mee; Choi, Sung Hee; Park, Young Joo; Kim, Ki Woong; Lim, Jae Young; Park, Kyong Soo; Jang, Hak Chul

2010-07-01

We investigated the prevalence of sarcopenic obesity (SO) and its relationship with metabolic syndrome in a community-based elderly cohort in Korea. In this study, 287 men and 278 women aged 65 or older were recruited. Sarcopenia was defined as the appendicular skeletal muscle mass (ASM) divided by height squared (Ht(2)) (kg/m(2)) or by weight (Wt) (%) of <1 SD below the sex-specific mean for young adults. Obesity was defined as a visceral fat area >or=100 cm(2). The prevalence of SO was 16.7% in men and 5.7% in women with sarcopenia defined by ASM/Ht(2); however, it was 35.1% in men and 48.1% in women by ASM/Wt. Using ASM/Wt, the homeostasis model assessment of insulin resistance of subjects with SO was higher and they were at higher risk for metabolic syndrome (odds ratio [OR] 8.28 [95% CI 4.45-15.40]) than the obese (5.51 [2.81-10.80]) or sarcopenic group (2.64 [1.08-6.44]). SO defined by ASM/Wt was more closely associated with metabolic syndrome than either sarcopenia or obesity alone.

Evaluation of the information content of long-term wastewater characteristics data in relation to activated sludge model parameters.

PubMed

Alikhani, Jamal; Takacs, Imre; Al-Omari, Ahmed; Murthy, Sudhir; Massoudieh, Arash

2017-03-01

A parameter estimation framework was used to evaluate the ability of observed data from a full-scale nitrification-denitrification bioreactor to reduce the uncertainty associated with the bio-kinetic and stoichiometric parameters of an activated sludge model (ASM). Samples collected over a period of 150 days from the effluent as well as from the reactor tanks were used. A hybrid genetic algorithm and Bayesian inference were used to perform deterministic and parameter estimations, respectively. The main goal was to assess the ability of the data to obtain reliable parameter estimates for a modified version of the ASM. The modified ASM model includes methylotrophic processes which play the main role in methanol-fed denitrification. Sensitivity analysis was also used to explain the ability of the data to provide information about each of the parameters. The results showed that the uncertainty in the estimates of the most sensitive parameters (including growth rate, decay rate, and yield coefficients) decreased with respect to the prior information.

Improved Problem Formulation in Engineering Systems Design

DTIC Science & Technology

1990-05-01

Journal model is ASME Journal of Mechanical Design. 2 1.1 Research Objective and Methods The objective of this research project was to improve...Methods and Theories, Journal of Design Methods Group, Vol. 20, No. 2, 1986, p. 410. 19 Nadler, G., Smith, J. M. and Frey, C. E., "Problem...sources do you routinely use to gather the information you need to develop a packaging system? 26 Trade journals 6 Consultants 21 Reference books 26

Colour Constancy Beyond the Classical Receptive Field.

PubMed

Akbarinia, Arash; Parraga, C Alejandro

2017-09-18

The problem of removing illuminant variations to preserve the colours of objects (colour constancy) has already been solved by the human brain using mechanisms that rely largely on centre-surround computations of local contrast. In this paper we adopt some of these biological solutions described by long known physiological findings into a simple, fully automatic, functional model (termed Adaptive Surround Modulation or ASM). In ASM, the size of a visual neuron's receptive field (RF) as well as the relationship with its surround varies according to the local contrast within the stimulus, which in turn determines the nature of the centre-surround normalisation of cortical neurons higher up in the processing chain. We modelled colour constancy by means of two overlapping asymmetric Gaussian kernels whose sizes are adapted based on the contrast of the surround pixels, resembling the change of RF size. We simulated the contrast-dependent surround modulation by weighting the contribution of each Gaussian according to the centre-surround contrast. In the end, we obtained an estimation of the illuminant from the set of the most activated RFs' outputs. Our results on three single-illuminant and one multi-illuminant benchmark datasets show that ASM is highly competitive against the state-of-the-art and it even outperforms learning-based algorithms in one case. Moreover, the robustness of our model is more tangible if we consider that our results were obtained using the same parameters for all datasets, that is, mimicking how the human visual system operates. These results might provide an insight on how dynamical adaptation mechanisms contribute to make object's colours appear constant to us.

Targeting Phosphoinositide 3-Kinase γ in Airway Smooth Muscle Cells to Suppress Interleukin-13-Induced Mouse Airway Hyperresponsiveness

PubMed Central

Jiang, Haihong; Xie, Yan; Abel, Peter W.; Toews, Myron L.; Townley, Robert G.; Casale, Thomas B.

2012-01-01

We recently reported that phosphoinositide 3-kinase γ (PI3Kγ) directly regulates airway smooth muscle (ASM) contraction by modulating Ca2+ oscillations. Because ASM contraction plays a critical role in airway hyperresponsiveness (AHR) of asthma, the aim of the present study was to determine whether targeting PI3Kγ in ASM cells could suppress AHR in vitro and in vivo. Intranasal administration into mice of interleukin-13 (IL-13; 10 μg per mouse), a key pathophysiologic cytokine in asthma, induced AHR after 48 h, as assessed by invasive tracheostomy. Intranasal administration of a broad-spectrum PI3K inhibitor or a PI3Kγ-specific inhibitor 1 h before AHR assessment attenuated IL-13 effects. Airway responsiveness to bronchoconstrictor agonists was also examined in precision-cut mouse lung slices pretreated without or with IL-13 for 24 h. Acetylcholine and serotonin dose-response curves indicated that IL-13-treated lung slices had a 40 to 50% larger maximal airway constriction compared with controls. Furthermore, acetylcholine induced a larger initial Ca2+ transient and increased Ca2+ oscillations in IL-13-treated primary mouse ASM cells compared with control cells, correlating with increased cell contraction. As expected, PI3Kγ inhibitor treatment attenuated IL-13-augmented airway contractility of lung slices and ASM cell contraction. In both control and IL-13-treated ASM cells, small interfering RNA-mediated knockdown of PI3Kγ by 70% only reduced the initial Ca2+ transient by 20 to 30% but markedly attenuated Ca2+ oscillations and contractility of ASM cells by 50 to 60%. This report is the first to demonstrate that PI3Kγ in ASM cells is important for IL-13-induced AHR and that acute treatment with a PI3Kγ inhibitor can ameliorate AHR in a murine model of asthma. PMID:22543031

The Role of TNF Family Molecules Light in Cellular Interaction Between Airway Smooth Muscle Cells and T Cells During Chronic Allergic Inflammation.

PubMed

Shi, Fei; Xiong, Yi; Zhang, Yarui; Qiu, Chen; Li, Manhui; Shan, Aijun; Yang, Ying; Li, Binbin

2018-06-01

Interaction between T cells and airway smooth muscle (ASM) cells has been identified as an important factor in the development of asthma. LIGHT (known as TNFSF14) -mediated signaling likely contributes to various inflammatory disorders and airway remodeling. The objective of this study was to investigate the roles of LIGHT-mediated pathways in the interaction between ASM cells and T cells during chronic allergic inflammation. Mice were sensitized and challenged by ovalbumin (OVA) to induce chronic airway allergic inflammation. The control group received PBS only. The histological features and LIGHT expressions in lungs were assessed in vivo. Furthermore, T cells and ASM cells derived from the model mice were co-cultured both in the presence and absence of anti-LIGHT Ab for 72 h. The effects of LIGHT blockade on expressions of downstream signaling molecules, proliferation, and apoptosis of ASM cells, differentiation of T cells, and inflammatory cytokines release were evaluated. We demonstrated that LIGHT blockade strikingly inhibited the mRNA and protein expressions of HVEM, c-JUN, and NFκB. Additionally, LIGHT blockade resulted in decreased proliferation and increased apoptosis of ASM cells. Moreover, depletion of LIGHT dramatically reduced the differentiation of CD4 + T cells into Th1, Th2, and Th17 cells, as well as inhibited inflammatory cytokines release including IL-13, TGF-β, and IFN-γ, which are associated with CD4 + T cell differentiation and ASM cell proliferation. LIGHT plays an important role in the interaction between T cells and ASM cells in chronic allergic asthma. Blockade of LIGHT markedly suppressed ASM hyperplasia and inflammatory responses, which might be modulated through HVEM-NFκB or c-JUN pathways. Therefore, targeting LIGHT is a promising therapeutic strategy for airway inflammation and remodeling in chronic allergic asthma.

Static and Wind Tunnel Aero-Performance Tests of NASA AST Separate Flow Nozzle Noise Reduction Configurations

NASA Technical Reports Server (NTRS)

Mikkelsen, Kevin L.; McDonald, Timothy J.; Saiyed, Naseem (Technical Monitor)

2001-01-01

This report presents the results of cold flow model tests to determine the static and wind tunnel performance of several NASA AST separate flow nozzle noise reduction configurations. The tests were conducted by Aero Systems Engineering, Inc., for NASA Glenn Research Center. The tests were performed in the Channels 14 and 6 static thrust stands and the Channel 10 transonic wind tunnel at the FluiDyne Aerodynamics Laboratory in Plymouth, Minnesota. Facility checkout tests were made using standard ASME long-radius metering nozzles. These tests demonstrated facility data accuracy at flow conditions similar to the model tests. Channel 14 static tests reported here consisted of 21 ASME nozzle facility checkout tests and 57 static model performance tests (including 22 at no charge). Fan nozzle pressure ratio varied from 1.4 to 2.0, and fan to core total pressure ratio varied from 1.0 to 1.19. Core to fan total temperature ratio was 1.0. Channel 10 wind tunnel tests consisted of 15 tests at Mach number 0.28 and 31 tests at Mach 0.8. The sting was checked out statically in Channel 6 before the wind tunnel tests. In the Channel 6 facility, 12 ASME nozzle data points were taken and 7 model data points were taken. In the wind tunnel, fan nozzle pressure ratio varied from 1.73 to 2.8, and fan to core total pressure ratio varied from 1.0 to 1.19. Core to fan total temperature ratio was 1.0. Test results include thrust coefficients, thrust vector angle, core and fan nozzle discharge coefficients, total pressure and temperature charging station profiles, and boat-tail static pressure distributions in the wind tunnel.

PROPERTIES OF THE 24 DAY MODULATION IN GX 13+1 FROM NEAR-INFRARED AND X-RAY OBSERVATIONS

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

Corbet, Robin H. D.; Pearlman, Aaron B.; Buxton, Michelle

2010-08-10

A 24 day period for the low-mass X-ray binary (LMXB) GX 13+1 was previously proposed on the basis of seven years of RXTE All-Sky Monitor (ASM) observations and it was suggested that this was the orbital period of the system. This would make it one of the longest known orbital periods for a Galactic LMXB powered by Roche lobe overflow. We present here the results of (1) K-band photometry obtained with the SMARTS Consortium CTIO 1.3 m telescope on 68 nights over a 10 month interval; (2) continued monitoring with the RXTE ASM, analyzed using a semi-weighted power spectrum insteadmore » of the data filtering technique previously used; and (3) Swift Burst Alert Telescope (BAT) hard X-ray observations. Modulation near 24 days is seen in both the K band and additional statistically independent ASM X-ray observations. However, the modulation in the ASM is not strictly periodic. The periodicity is also not detected in the Swift BAT observations, but modulation at the same relative level as seen with the ASM cannot be ruled out. If the 24 day period is the orbital period of system, this implies that the X-ray modulation is caused by structure that is not fixed in location. A possible mechanism for the X-ray modulation is the dipping behavior recently reported from XMM-Newton observations.« less

W-320 Department of Health documentation

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

Bailey, J.W.

1998-08-07

The purpose of this document is to gather information required to show that Project W-320 is in compliance with Washington State Department of Health requirements as specified in Radioactive Air Emissions Notice of Construction Project W-320, Tank 241-C-106 Sluicing, DOE/RL-95-45. Specifically, that W-320 is in compliance with ASME N509-1989 (Nuclear Power Plant Air-Cleaning Units and Components) and ASME N5 10-1989 (Testing of Nuclear Air Treatment Systems) for the 296-C-006 exhaust system.

Orosomucoid-like 3 (ORMDL3) upregulates airway smooth muscle proliferation, contraction, and Ca2+ oscillations in asthma.

PubMed

Chen, Jun; Miller, Marina; Unno, Hirotoshi; Rosenthal, Peter; Sanderson, Michael J; Broide, David H

2017-09-07

Airway hyperresponsiveness is a major feature of asthma attributed predominantly to an extrinsic immune/inflammatory response increasing airway smooth muscle (ASM) contractility. We investigated whether increased ASM expression of orosomucoid-like 3 (ORMDL3), a gene on chromosome 17q21 highly linked to asthma, induced increased ASM proliferation and contractility in vitro and influenced airway contractility and calcium flux in ASM in precision-cut lung slices (PCLSs) from wild-type and hORMDL3 Zp3-Cre mice (which express increased levels of human ORMDL3 [hORMDL3]). Levels of ASM proliferation and contraction were assessed in ASM cells transfected with ORMDL3 in vitro. In addition, airway contractility and calcium oscillations were quantitated in ASM cells in PCLSs derived from naive wild-type and naive hORMDL3 Zp3-Cre mice, which do not have a blood supply. Increased ASM expression of ORMDL3 in vitro resulted in increased ASM proliferation and contractility. PCLSs derived from naive hORMDL3 Zp3-Cre mice, which do not have airway inflammation, exhibit increased airway contractility with increased calcium oscillations in ASM cells. Increased ASM ORMDL3 expression increases levels of ASM sarcoplasmic reticulum Ca 2+ ATPase 2b (SERCA2b), which increases ASM proliferation and contractility. Overall, these studies provide evidence that an intrinsic increase in ORMDL3 expression in ASM can induce increased ASM proliferation and contractility, which might contribute to increased airway hyperresponsiveness in the absence of airway inflammation in asthmatic patients. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

β2-Agonist Induced cAMP Is Decreased in Asthmatic Airway Smooth Muscle Due to Increased PDE4D

PubMed Central

Trian, Thomas; Burgess, Janette K.; Niimi, Kyoko; Moir, Lyn M.; Ge, Qi; Berger, Patrick; Liggett, Stephen B.; Black, Judith L.; Oliver, Brian G.

2011-01-01

Background and Objective Asthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known. Objective To characterize the potential defect in β-agonist induced cAMP in ASM derived from asthmatic in comparison to non-asthmatic subjects and to investigate its mechanism. Methods We examined β2-adrenergic (β2AR) receptor expression and basal β-agonist and forskolin (direct activator of adenylyl cyclase) stimulated cAMP production in asthmatic cultured ASM (n = 15) and non-asthmatic ASM (n = 22). Based on these results, PDE activity, PDE4D expression and cell proliferation were determined. Results In the presence of IBMX, a pan PDE inhibitor, asthmatic ASM had ∼50% lower cAMP production in response to isoproterenol, albuterol, formoterol, and forskolin compared to non-asthmatic ASM. However when PDE4 was specifically inhibited, cAMP production by the agonists and forskolin was normalized in asthmatic ASM. We then measured the amount and activity of PDE4, and found ∼2-fold greater expression and activity in asthmatic ASM compared to non-asthmatic ASM. Furthermore, inhibition of PDE4 reduced asthmatic ASM proliferation but not that of non-asthmatic ASM. Conclusion Decreased β-agonist induced cAMP in ASM from asthmatics results from enhanced degradation due to increased PDE4D expression. Clinical manifestations of this dysregulation would be suboptimal β-agonist-mediated bronchodilation and possibly reduced control over increasing ASM mass. These phenotypes appear to be “hard-wired” into ASM from asthmatics, as they do not require an inflammatory environment in culture to be observed. PMID:21611147

Acid sphingomyelinase-deficient macrophages have defective cholesterol trafficking and efflux.

PubMed

Leventhal, A R; Chen, W; Tall, A R; Tabas, I

2001-11-30

Cholesterol efflux from macrophage foam cells, a key step in reverse cholesterol transport, requires trafficking of cholesterol from intracellular sites to the plasma membrane. Sphingomyelin is a cholesterol-binding molecule that transiently exists with cholesterol in endosomes and lysosomes but is rapidly hydrolyzed by lysosomal sphingomyelinase (L-SMase), a product of the acid sphingomyelinase (ASM) gene. We therefore hypothesized that sphingomyelin hydrolysis by L-SMase enables cholesterol efflux by preventing cholesterol sequestration by sphingomyelin. Macrophages from wild-type and ASM knockout mice were incubated with [(3)H]cholesteryl ester-labeled acetyl-LDL and then exposed to apolipoprotein A-I or high density lipoprotein. In both cases, [(3)H]cholesterol efflux was decreased substantially in the ASM knockout macrophages. Similar results were shown for ASM knockout macrophages labeled long-term with [(3)H]cholesterol added directly to medium, but not for those labeled for a short period, suggesting defective efflux from intracellular stores but not from the plasma membrane. Cholesterol trafficking to acyl-coenzyme A:cholesterol acyltransferase (ACAT) was also defective in ASM knockout macrophages. Using filipin to probe cholesterol in macrophages incubated with acetyl-LDL, we found there was modest staining in the plasma membrane of wild-type macrophages but bright, perinuclear fluorescence in ASM knockout macrophages. Last, when wild-type macrophages were incubated with excess sphingomyelin to "saturate" L-SMase, [(3)H]cholesterol efflux was decreased. Thus, sphingomyelin accumulation due to L-SMase deficiency leads to defective cholesterol trafficking and efflux, which we propose is due to sequestration of cholesterol by sphingomyelin and possibly other mechanisms. This model may explain the low plasma high density lipoprotein found in ASM-deficient humans and may implicate L-SMase deficiency and/or sphingomyelin enrichment of lipoproteins as novel atherosclerosis risk factors.

In situ water vapor and ozone measurements in Lhasa and Kunming during the Asian summer monsoon

NASA Astrophysics Data System (ADS)

Bian, Jianchun; Pan, Laura L.; Paulik, Laura; Vömel, Holger; Chen, Hongbin; Lu, Daren

2012-10-01

The Asian summer monsoon (ASM) anticyclone circulation system is recognized to be a significant transport pathway for water vapor and pollutants to enter the stratosphere. The observational evidence, however, is largely based on satellite retrievals. We report the first coincident in situ measurements of water vapor and ozone within the ASM anticyclone. The combined water vapor and ozonesondes were launched from Kunming, China in August 2009 and Lhasa, China in August 2010. In total, 11 and 12 sondes were launched in Kunming and Lhasa, respectively. We present the key characteristics of these measurements, and provide a comparison to similar measurements from an equatorial tropical location, during the Tropical Composition, Cloud and Climate Coupling (TC4) campaign in July and August of 2007. Results show that the ASM anticyclone region has higher water vapor and lower ozone concentrations in the upper troposphere and lower stratosphere than the TC4 observations. The results also show that the cold point tropopause in the ASM region has a higher average height and potential temperature. The in situ observations therefore support the satellite-based conclusion that the ASM is an effective transport pathway for water vapor to enter stratosphere.

Simultaneous Vibration Suppression and Energy Harvesting

DTIC Science & Technology

2013-08-15

D.J., 2011. “Modeling and Analysis of Piezoelectric Energy Harvesting from Aeroelastic Vibrations Using the Doublet-Lattice Method,” ASME Journal...Friswell, M. I., and Inman, D. J., 2009, “ Piezoelectric Energy Harvesting from Broadband Random Vibrations ,” Smart Materials and Structures, Vol. 18...and Electrode Configuration on Piezoelectric Energy Harvesting from Cantilevered Beams,” ASME Journal of Vibration and Acoustics, Vol. 131, No. 1, pp

14 CFR 330.45 - What is the basis on which air carriers will be compensated under the set-aside?

Code of Federal Regulations, 2010 CFR

2010-01-01

... be calculated using a fixed ASM rate equivalent to the mean losses per ASM for all Class I carriers... graduated ASM rate equivalent to— (i) The mean loss per ASM for all Class I carriers applying for compensation, for each of the first 75,000 ASMs reported; and (ii) The mean remaining loss per ASM for all...

Allele-Skewed DNA Modification in the Brain: Relevance to a Schizophrenia GWAS

PubMed Central

Gagliano, Sarah A.; Ptak, Carolyn; Mak, Denise Y.F.; Shamsi, Mehrdad; Oh, Gabriel; Knight, Joanne; Boutros, Paul C.; Petronis, Arturas

2016-01-01

Numerous recent studies have suggested that phenotypic effects of DNA sequence variants can be mediated or modulated by their epigenetic marks, such as allele-skewed DNA modification (ASM). Using Affymetrix SNP microarrays, we performed a comprehensive search of ASM effects in human post-mortem brain and sperm samples (total n = 256) from individuals with major psychosis and control individuals. Depending on the phenotypic category of the brain samples, 1.4%–7.5% of interrogated SNPs exhibited ASM effects. Next, we investigated ASM in the context of genetic studies of schizophrenia and detected that brain ASM SNPs were significantly overrepresented among sub-threshold SNPs from a schizophrenia genome-wide association study (GWAS). Brain ASM SNPs showed a much stronger enrichment in a schizophrenia GWAS than in 17 large GWASs of non-psychiatric diseases and traits, arguing that ASM effects are at least partially tissue specific. Studies of germline and control brain ASM SNPs supported a causal association between ASM and schizophrenia. Finally, significantly higher proportions of ASM SNPs than of non-ASM SNPs were detected at loci exhibiting epigenetic signatures of enhancers and promoters, and they were overrepresented within transcription factor binding regions and DNase I hypersensitive sites. All of these findings collectively indicate that ASM SNPs should be prioritized in follow-up GWASs. PMID:27087318

A novel high-throughput screening format to identify inhibitors of secreted acid sphingomyelinase.

PubMed

Mintzer, Robert J; Appell, Kenneth C; Cole, Andrew; Johns, Anthony; Pagila, Rene; Polokoff, Mark A; Tabas, Ira; Snider, R Michael; Meurer-Ogden, Janet A

2005-04-01

Secreted extracellular acid sphingomyelinase (sASM) activity has been suggested to promote atherosclerosis by enhancing subendothelial aggregation and retention of low-density lipoprotein (LDL) with resultant foam cell formation. Compounds that inhibit sASM activity, at neutral pH, may prevent lipid retention and thus would be expected to be anti-atherosclerotic. With the goal of identifying novel compounds that inhibit sASM at pH 7.4, a high-throughput screen was performed. Initial screening was run using a modification of a proven system that measures the hydrolysis of radiolabeled sphingomyelin presented in detergent micelles in a 96-well format. Separation of the radiolabeled aqueous phosphorylcholine reaction product from uncleaved sphingomyelin lipid substrate was achieved by chloroform/methanol extraction. During the screening campaign, a novel extraction procedure was developed to eliminate the use of the hazardous organic reagents. This new procedure exploited the ability of uncleaved, radiolabeled lipid substrate to interact with hydrophobic phenyl-sepharose beads. A comparison of the organic-based and the bead-based extraction sASM screening assays revealed Z' factor values ranging from 0.7 to 0.95 for both formats. In addition, both assay formats led to the identification of sub- to low micromolar inhibitors of sASM at pH 7.4 with similar IC(50) values. Subsequent studies demonstrated that both methods were also adaptable to run in a 384-well format. In contrast to the results observed at neutral pH, however, only the organic extraction assay was capable of accurately measuring sASM activity at its pH optimum of 5.0. The advantages and disadvantages of both sASM assay formats are discussed.

Bayesian segregation analysis of production traits in two strains of laying chickens.

PubMed

Szydłowski, M; Szwaczkowski, T

2001-02-01

A bayesian marker-free segregation analysis was applied to search for evidence of segregating genes affecting production traits in two strains of laying hens under long-term selection. The study used data from 6 generations of Leghorn (H77) and New Hampshire (N88) breeding nuclei. Estimation of marginal posterior means of variance components and parameters of a single autosomal locus was performed by use of the Gibbs sampler. The results showed evidence for a mixed major gene: -polygenic inheritance of BW and age at sexual maturity (ASM) in both strains. Single genes affecting BW and ASM explained one-third of the genetic variance. For ASM large overdominance effect at single locus was estimated. Initial egg production (IEP) and average egg weight (EW) showed a polygenic model of inheritance. The polygenic heritability estimates for BW, ASM, IEP, and EW were 0.32, 0.25, 0.23, and 0.08 in Strain H77 and 0.25, 0.24, 0.11, and 0.38 in Strain N88, respectively.

Laminated Composite Shell Element Using Absolute Nodal Coordinate Formulation and Its Application to ANCF Tire Model

DTIC Science & Technology

2015-04-24

Paramsothy Jayakumar US Army TARDEC 6501 E. 11 Mile Road Warren, MI 48397-5000 Hiroyuki Sugiyama Department of Mechanical and Industrial...Part 2: Development of a Physical Tyre Model", Vehicle System Dynamics, vol. 50, pp. 339-356. [4] Sugiyama, H., Yamashita, H. and Jayakumar , P., 2014... Jayakumar , P. and Sugiyama, H., "Continuum Mechanics Based Bi-Linear Shear Deformable Shell Element using Absolute Nodal Coordinate Formulation", ASME

A Survey of Variable Extragalactic Sources with XTE's All Sky Monitor (ASM)

NASA Technical Reports Server (NTRS)

Jernigan, Garrett

1998-01-01

The original goal of the project was the near real-time detection of AGN utilizing the SSC 3 of the ASM on XTE which does a deep integration on one 100 square degree region of the sky. While the SSC never performed sufficiently well to allow the success of this goal, the work on the project has led to the development of a new analysis method for coded aperture systems which has now been applied to ASM data for mapping regions near clusters of galaxies such as the Perseus Cluster and the Coma Cluster. Publications are in preparation that describe both the new method and the results from mapping clusters of galaxies.

Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma.

PubMed

Moore, Brian D; Hyde, Dallas; Miller, Lisa; Wong, Emily; Frelinger, Jessica; Schelegle, Edward S

2012-01-01

Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O(3)) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity. In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O(3) and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction. Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O(3) or in combination (HDMA+O(3)). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS). 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT(2), 5-HT(3) and 5-HT(4) receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT(2), 5-HT(3) and 5-HT(4) receptors. Conversely, a 5-HT(1) receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine. HDMA, O(3) and HDMA+O(3) exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT(2), 5-HT(3) and 5-HT(4) receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT(1) receptors located on ASM. Copyright © 2012 S. Karger AG, Basel.

Development of a Pebble-Bed Liquid-Nitrogen Evaporator/Superheater for the BRL 1/6th Scale Large Blast/Thermal Simulator Test Bed. Phase 1. Prototype Design and Analysis

DTIC Science & Technology

1991-08-01

specifications are taken primarily from the 1983 version of the ASME Boiler and Pressure Vessel Code . Other design requirements were developea from standard safe...rules and practices of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code to provide a safe and reliable system

3D automatic anatomy segmentation based on iterative graph-cut-ASM

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

Chen, Xinjian; Bagci, Ulas; Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Building 10 Room 1C515, Bethesda, Maryland 20892-1182

2011-08-15

Purpose: This paper studies the feasibility of developing an automatic anatomy segmentation (AAS) system in clinical radiology and demonstrates its operation on clinical 3D images. Methods: The AAS system, the authors are developing consists of two main parts: object recognition and object delineation. As for recognition, a hierarchical 3D scale-based multiobject method is used for the multiobject recognition task, which incorporates intensity weighted ball-scale (b-scale) information into the active shape model (ASM). For object delineation, an iterative graph-cut-ASM (IGCASM) algorithm is proposed, which effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability ofmore » the GC method. The presented IGCASM algorithm is a 3D generalization of the 2D GC-ASM method that they proposed previously in Chen et al.[Proc. SPIE, 7259, 72590C1-72590C-8 (2009)]. The proposed methods are tested on two datasets comprised of images obtained from 20 patients (10 male and 10 female) of clinical abdominal CT scans, and 11 foot magnetic resonance imaging (MRI) scans. The test is for four organs (liver, left and right kidneys, and spleen) segmentation, five foot bones (calcaneus, tibia, cuboid, talus, and navicular). The recognition and delineation accuracies were evaluated separately. The recognition accuracy was evaluated in terms of translation, rotation, and scale (size) error. The delineation accuracy was evaluated in terms of true and false positive volume fractions (TPVF, FPVF). The efficiency of the delineation method was also evaluated on an Intel Pentium IV PC with a 3.4 GHZ CPU machine. Results: The recognition accuracies in terms of translation, rotation, and scale error over all organs are about 8 mm, 10 deg. and 0.03, and over all foot bones are about 3.5709 mm, 0.35 deg. and 0.025, respectively. The accuracy of delineation over all organs for all subjects as expressed in TPVF and FPVF is 93.01% and 0.22%, and all foot bones for all subjects are 93.75% and 0.28%, respectively. While the delineations for the four organs can be accomplished quite rapidly with average of 78 s, the delineations for the five foot bones can be accomplished with average of 70 s. Conclusions: The experimental results showed the feasibility and efficacy of the proposed automatic anatomy segmentation system: (a) the incorporation of shape priors into the GC framework is feasible in 3D as demonstrated previously for 2D images; (b) our results in 3D confirm the accuracy behavior observed in 2D. The hybrid strategy IGCASM seems to be more robust and accurate than ASM and GC individually; and (c) delineations within body regions and foot bones of clinical importance can be accomplished quite rapidly within 1.5 min.« less

3D automatic anatomy segmentation based on iterative graph-cut-ASM

PubMed Central

Chen, Xinjian; Bagci, Ulas

2011-01-01

Purpose: This paper studies the feasibility of developing an automatic anatomy segmentation (AAS) system in clinical radiology and demonstrates its operation on clinical 3D images.Methods: The AAS system, the authors are developing consists of two main parts: object recognition and object delineation. As for recognition, a hierarchical 3D scale-based multiobject method is used for the multiobject recognition task, which incorporates intensity weighted ball-scale (b-scale) information into the active shape model (ASM). For object delineation, an iterative graph-cut-ASM (IGCASM) algorithm is proposed, which effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. The presented IGCASM algorithm is a 3D generalization of the 2D GC-ASM method that they proposed previously in Chen et al. [Proc. SPIE, 7259, 72590C1–72590C-8 (2009)]. The proposed methods are tested on two datasets comprised of images obtained from 20 patients (10 male and 10 female) of clinical abdominal CT scans, and 11 foot magnetic resonance imaging (MRI) scans. The test is for four organs (liver, left and right kidneys, and spleen) segmentation, five foot bones (calcaneus, tibia, cuboid, talus, and navicular). The recognition and delineation accuracies were evaluated separately. The recognition accuracy was evaluated in terms of translation, rotation, and scale (size) error. The delineation accuracy was evaluated in terms of true and false positive volume fractions (TPVF, FPVF). The efficiency of the delineation method was also evaluated on an Intel Pentium IV PC with a 3.4 GHZ CPU machine.Results: The recognition accuracies in terms of translation, rotation, and scale error over all organs are about 8 mm, 10° and 0.03, and over all foot bones are about 3.5709 mm, 0.35° and 0.025, respectively. The accuracy of delineation over all organs for all subjects as expressed in TPVF and FPVF is 93.01% and 0.22%, and all foot bones for all subjects are 93.75% and 0.28%, respectively. While the delineations for the four organs can be accomplished quite rapidly with average of 78 s, the delineations for the five foot bones can be accomplished with average of 70 s.Conclusions: The experimental results showed the feasibility and efficacy of the proposed automatic anatomy segmentation system: (a) the incorporation of shape priors into the GC framework is feasible in 3D as demonstrated previously for 2D images; (b) our results in 3D confirm the accuracy behavior observed in 2D. The hybrid strategy IGCASM seems to be more robust and accurate than ASM and GC individually; and (c) delineations within body regions and foot bones of clinical importance can be accomplished quite rapidly within 1.5 min. PMID:21928634

Acid Sphingomyelinase Gene Knockout Ameliorates Hyperhomocysteinemic Glomerular Injury in Mice Lacking Cystathionine-β-Synthase

PubMed Central

Boini, Krishna M.; Xia, Min; Abais, Justine M.; Xu, Ming; Li, Cai-xia; Li, Pin-Lan

2012-01-01

Acid sphingomyelinase (ASM) has been implicated in the development of hyperhomocysteinemia (hHcys)-induced glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and characterized the mice lacking cystathionine β-synthase (Cbs) and Asm mouse gene by cross breeding Cbs+/− and Asm+/− mice. Given that the homozygotes of Cbs−/−/Asm−/− mice could not survive for 3 weeks. Cbs+/−/Asm+/+, Cbs+/−/Asm+/− and Cbs+/−/Asm−/− as well as their Cbs wild type littermates were used to study the role of Asm−/− under a background of Cbs+/− with hHcys. HPLC analysis revealed that plasma Hcys level was significantly elevated in Cbs heterozygous (Cbs+/−) mice with different copies of Asm gene compared to Cbs+/+ mice with different Asm gene copies. Cbs+/−/Asm+/+ mice had significantly increased renal Asm activity, ceramide production and O2.− level compared to Cbs+/+/Asm+/+, while Cbs+/−/Asm−/− mice showed significantly reduced renal Asm activity, ceramide production and O2.− level due to increased plasma Hcys levels. Confocal microscopy demonstrated that colocalization of podocin with ceramide was much lower in Cbs+/−/Asm−/− mice compared to Cbs+/−/Asm+/+ mice, which was accompanied by a reduced glomerular damage index, albuminuria and proteinuria in Cbs+/−/Asm−/− mice. Immunofluorescent analyses of the podocin, nephrin and desmin expression also illustrated less podocyte damages in the glomeruli from Cbs+/−/Asm−/− mice compared to Cbs+/−/Asm+/+ mice. In in vitro studies of podocytes, hHcys-enhanced O2.− production, desmin expression, and ceramide production as well as decreases in VEGF level and podocin expression in podocytes were substantially attenuated by prior treatment with amitriptyline, an Asm inhibitor. In conclusion, Asm gene knockout or corresponding enzyme inhibition protects the podocytes and glomeruli from hHcys-induced oxidative stress and injury. PMID:23024785

Ceramide and Its Related Neurochemical Networks as Targets for Some Brain Disorder Therapies.

PubMed

Brodowicz, Justyna; Przegaliński, Edmund; Müller, Christian P; Filip, Malgorzata

2018-02-01

Correlational and causal comparative research link ceramide (Cer), the precursor of complex sphingolipids, to some psychiatric (e.g., depression, schizophrenia (SZ), alcohol use disorder, and morphine antinociceptive tolerance) and neurological (e.g., Alzheimer's disease (AD), Parkinson disease (PD)) disorders. Cer generation can occur through the de novo synthesis pathway, the sphingomyelinase pathways, and the salvage pathway. The discoveries that plasma Cer concentration increase during depressive episodes in patients and that tricyclic and tetracyclic antidepressants functionally inhibit acid sphingomyelinase (ASM), the enzyme that catalyzes the degradation of sphingomyelin to Cer, have initiated a series of studies on the role of the ASM-Cer system in depressive disorder. Disturbances in the metabolism of Cer or SM are associated with the occurrence of SZ and PD. In both PD and SZ patients, the elevated levels of Cer or SM in the brain regions were associated with the disease. AD patients showed also an abnormal metabolism of brain Cer at early stages of the disease which may suggest Cer as an AD biomarker. In plasma of AD patients and in AD transgenic mice, ASM activity was increased. In contrast, partial ASM inhibition of Aβ deposition improved memory deficits. Furthermore, in clinical and preclinical research, ethanol enhanced activation of ASM followed by Cer production. Limited data have shown that Cer plays an important role in the development of morphine antinociceptive tolerance. In summary, clinical and preclinical findings provide evidence that targeting the Cer system should be considered as an innovative translational strategy for some brain disorders.

University NanoSat Program: AggieSat3

DTIC Science & Technology

2009-06-01

commercially available product for stereo machine vision developed by Point Grey Research. The current binocular BumbleBee2® system incorporates two...and Fellow of the American Society of Mechanical Engineers (ASME) in 1997. She was awarded the 2007 J. Leland "Lee" Atwood Award from the ASEE...AggieSat2 satellite programs. Additional experience gained in the area of drawing standards, machining capabilities, solid modeling, safety

[Anthropometric model for the prediction of appendicular skeletal muscle mass in Chilean older adults].

PubMed

Lera, Lydia; Albala, Cecilia; Ángel, Bárbara; Sánchez, Hugo; Picrin, Yaisy; Hormazabal, María José; Quiero, Andrea

2014-03-01

To develop a predictive model of appendicular skeletal muscle mass (ASM) based on anthropometric measurements in elderly from Santiago, Chile. 616 community dwelling, non-disabled subjects ≥ 60 years (mean 69.9 ± 5.2 years) living in Santiago, 64.6% female, participating in ALEXANDROS study. Anthropometric measurements, handgrip strength, mobility tests and DEXA were performed. Step by step linear regression models were used to associate ASM from DEXA with anthropometric variables, age and sex. The sample was divided at random into two to obtain prediction equations for both subsamples, which were mutually validated by double cross-validation. The high correlation between the values of observed and predicted MMAE in both sub-samples and the low degree of shrinkage allowed developing the final prediction equation with the total sample. The cross-validity coefficient between prediction models from the subsamples (0.941 and 0.9409) and the shrinkage (0.004 and 0.006) were similar in both equations. The final prediction model obtained from the total sample was: ASM (kg) = 0.107(weight in kg) + 0.251( knee height in cm) + 0.197 (Calf Circumference in cm) +0.047 (dynamometry in kg) - 0.034 (Hip Circumference in cm) + 3.417 (Man) - 0.020 (age years) - 7.646 (R2 = 0.89). The mean ASM obtained by the prediction equation and the DEXA measurement were similar (16.8 ± 4.0 vs 16.9 ± 3.7) and highly concordant according Bland and Altman (95% CI: -2.6 -2.7) and Lin (concordance correlation coefficient = 0.94) methods. We obtained a low cost anthropometric equation to determine the appendicular skeletal muscle mass useful for the screening of sarcopenia in older adults. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

A Multi-Scale Approach to Airway Hyperresponsiveness: From Molecule to Organ

PubMed Central

Lauzon, Anne-Marie; Bates, Jason H. T.; Donovan, Graham; Tawhai, Merryn; Sneyd, James; Sanderson, Michael J.

2012-01-01

Airway hyperresponsiveness (AHR), a characteristic of asthma that involves an excessive reduction in airway caliber, is a complex mechanism reflecting multiple processes that manifest over a large range of length and time scales. At one extreme, molecular interactions determine the force generated by airway smooth muscle (ASM). At the other, the spatially distributed constriction of the branching airways leads to breathing difficulties. Similarly, asthma therapies act at the molecular scale while clinical outcomes are determined by lung function. These extremes are linked by events operating over intermediate scales of length and time. Thus, AHR is an emergent phenomenon that limits our understanding of asthma and confounds the interpretation of studies that address physiological mechanisms over a limited range of scales. A solution is a modular computational model that integrates experimental and mathematical data from multiple scales. This includes, at the molecular scale, kinetics, and force production of actin-myosin contractile proteins during cross-bridge and latch-state cycling; at the cellular scale, Ca2+ signaling mechanisms that regulate ASM force production; at the tissue scale, forces acting between contracting ASM and opposing viscoelastic tissue that determine airway narrowing; at the organ scale, the topographic distribution of ASM contraction dynamics that determine mechanical impedance of the lung. At each scale, models are constructed with iterations between theory and experimentation to identify the parameters that link adjacent scales. This modular model establishes algorithms for modeling over a wide range of scales and provides a framework for the inclusion of other responses such as inflammation or therapeutic regimes. The goal is to develop this lung model so that it can make predictions about bronchoconstriction and identify the pathophysiologic mechanisms having the greatest impact on AHR and its therapy. PMID:22701430

Delivery of acid sphingomyelinase in normal and niemann-pick disease mice using intercellular adhesion molecule-1-targeted polymer nanocarriers.

PubMed

Garnacho, Carmen; Dhami, Rajwinder; Simone, Eric; Dziubla, Thomas; Leferovich, John; Schuchman, Edward H; Muzykantov, Vladimir; Muro, Silvia

2008-05-01

Type B Niemann-Pick disease (NPD) is a multiorgan system disorder caused by a genetic deficiency of acid sphingomyelinase (ASM), for which lung is an important and challenging therapeutic target. In this study, we designed and evaluated new delivery vehicles for enzyme replacement therapy of type B NPD, consisting of polystyrene and poly(lactic-coglycolic) acid polymer nanocarriers targeted to intercellular adhesion molecule (ICAM)-1, an endothelial surface protein up-regulated in many pathologies, including type B NPD. Real-time vascular imaging using intravital microscopy and postmortem imaging of mouse organs showed rapid, uniform, and efficient binding of fluorescently labeled ICAM-1-targeted ASM nanocarriers (anti-ICAM/ASM nanocarriers) to endothelium after i.v. injection in mice. Fluorescence microscopy of lung alveoli actin, tissue histology, and 125I-albumin blood-to-lung transport showed that anti-ICAM nanocarriers cause neither detectable lung injury, nor abnormal vascular permeability in animals. Radioisotope tracing showed rapid disappearance from the circulation and enhanced accumulation of anti-ICAM/125I-ASM nanocarriers over the nontargeted naked enzyme in kidney, heart, liver, spleen, and primarily lung, both in wild-type and ASM knockout mice. These data demonstrate that ICAM-1-targeted nanocarriers may enhance enzyme replacement therapy for type B NPD and perhaps other lysosomal storage disorders.

A novel anti-inflammatory drug, SDZ ASM 981, for the treatment of skin diseases: in vitro pharmacology.

PubMed

Grassberger, M; Baumruker, T; Enz, A; Hiestand, P; Hultsch, T; Kalthoff, F; Schuler, W; Schulz, M; Werner, F J; Winiski, A; Wolff, B; Zenke, G

1999-08-01

SDZ ASM 981, a novel ascomycin macrolactam derivative, has high anti-inflammatory activity in animal models of allergic contact dermatitis and shows clinical efficacy in atopic dermatitis, allergic contact dermatitis and psoriasis, after topical application. Here we report on the in vitro activities of this promising new drug. SDZ ASM 981 inhibits the proliferation of human T cells after antigen-specific or non-specific stimulation. It downregulates the production of Th1 [interleukin (IL)-2, interferon-gamma] and Th2 (IL-4, IL-10) type cytokines after antigen-specific stimulation of a human T-helper cell clone isolated from the skin of an atopic dermatitis patient. SDZ ASM 981 inhibits the phorbol myristate acetate/phytohaemagglutinin-stimulated transcription of a reporter gene coupled to the human IL-2 promoter in the human T-cell line Jurkat and the IgE/antigen-mediated transcription of a reporter gene coupled to the human tumour necrosis factor (TNF)-alpha promoter in the murine mast-cell line CPII. It does not, however, affect the human TNF-alpha promoter controlled transcription of a reporter gene in a murine dendritic cell line (DC18 RGA) after stimulation via the FcgammaRIII receptor. SDZ ASM 981 also prevents the release of preformed pro-inflammatory mediators from mast cells, as shown in the murine cell line CPII after stimulation with IgE/antigen. In summary, these results demonstrate that SDZ ASM 981 is a specific inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro.

Millennial-scale Asian summer monsoon variations in South China since the last deglaciation

NASA Astrophysics Data System (ADS)

Wang, Xisheng; Chu, Guoqiang; Sheng, Mei; Zhang, Shuqin; Li, Jinhua; Chen, Yun; Tang, Ling; Su, Youliang; Pei, Junling; Yang, Zhenyu

2016-10-01

Characterizing spatiotemporal variability of the Asian summer monsoon (ASM) is critical for full understanding of its behavior, dynamics, and future impacts. The present knowledge about ASM variations since the last glaciation in South China largely relies on several precisely-dated speleothem stable oxygen isotope (δ18 O) records. Although these speleothem δ18 O signals provide useful evidence for regional past environmental changes, their validity for denoting ASM intensity remains a great controversy. The Huguangyan Maar Lake (HML) provides one of the most complete archives of environmental and climatic changes in the tropical-subtropical South and East Asia since the last glaciation. Here we document a continuous centennial- to millennial-scale ASM record over the past 16 ky BP from the high-sedimentation-rate HML sediments. In contrast with the low-amplitude variations of Chinese speleothem-derived δ18 O signals and the Chinese loess-based monsoon precipitation proxy indexes, our multi-proxy records reveal a pattern of high-amplitude regional climatic fluctuations, including fine-scale oscillations during the Bølling-Allerød warming, the 8.2 ka cooling event, and an abrupt climate shift from 6.5-5.9 ka. The existence of Bond-like cold/dry events indicates a distinct influence of the North Atlantic circulation on low-latitude monsoon changes. The broad comparability between the HML paleo-proxies, Chinese speleothem δ18 O records, and the northern hemisphere summer insolation throughout the Holocene, suggests that solar insolation exerts a profound influence on ASM changes. These findings reinforce a model of combined insolation and glacial forcing of the ASM.

ASM-3 Acid Sphingomyelinase Functions as a Positive Regulator of the DAF-2/AGE-1 Signaling Pathway and Serves as a Novel Anti-Aging Target

PubMed Central

Kim, Yongsoon; Sun, Hong

2012-01-01

In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals. PMID:23049887

ASM-3 acid sphingomyelinase functions as a positive regulator of the DAF-2/AGE-1 signaling pathway and serves as a novel anti-aging target.

PubMed

Kim, Yongsoon; Sun, Hong

2012-01-01

In C. elegans, the highly conserved DAF-2/insulin/insulin-like growth factor 1 receptor signaling (IIS) pathway regulates longevity, metabolism, reproduction and development. In mammals, acid sphingomyelinase (ASM) is an enzyme that hydrolyzes sphingomyelin to produce ceramide. ASM has been implicated in CD95 death receptor signaling under certain stress conditions. However, the involvement of ASM in growth factor receptor signaling under physiological conditions is not known. Here, we report that in vivo ASM functions as a positive regulator of the DAF-2/IIS pathway in C. elegans. We have shown that inactivation of asm-3 extends animal lifespan and promotes dauer arrest, an alternative developmental process. A significant cooperative effect on lifespan is observed between asm-3 deficiency and loss-of-function alleles of the age-1/PI 3-kinase, with the asm-3; age-1 double mutant animals having a mean lifespan 259% greater than that of the wild-type animals. The lifespan extension phenotypes caused by the loss of asm-3 are dependent on the functions of daf-16/FOXO and daf-18/PTEN. We have demonstrated that inactivation of asm-3 causes nuclear translocation of DAF-16::GFP protein, up-regulates endogenous DAF-16 protein levels and activates the downstream targeting genes of DAF-16. Together, our findings reveal a novel role of asm-3 in regulation of lifespan and diapause by modulating IIS pathway. Importantly, we have found that two drugs known to inhibit mammalian ASM activities, desipramine and clomipramine, markedly extend the lifespan of wild-type animals, in a manner similar to that achieved by genetic inactivation of the asm genes. Our studies illustrate a novel strategy of anti-aging by targeting ASM, which may potentially be extended to mammals.

Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

PubMed Central

Januskevicius, Andrius; Gosens, Reinoud; Sakalauskas, Raimundas; Vaitkiene, Simona; Janulaityte, Ieva; Halayko, Andrew J.; Hoppenot, Deimante; Malakauskas, Kestutis

2017-01-01

Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact through integrin–ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell–cell and cell–extracellular matrix interactions. In our previous study we demonstrated that asthmatic eosinophils show increased adhesion to ASM cells and it may be important factor contributing to ASM remodeling in asthma. According to these findings, in the present study we investigated the effects of suppression of eosinophil integrin on eosinophil-induced ASM remodeling in asthma. Materials and Methods: Individual combined cell cultures of immortalized human ASM cells and eosinophils from peripheral blood of 22 asthmatic patients and 17 healthy controls were prepared. Eosinophil adhesion was evaluated using eosinophil peroxidase activity assay. Genes expression levels in ASM cells and eosinophils were measured using quantitative real-time PCR. ASM cell proliferation was measured using alamarBlue® solution. Eosinophil integrins were blocked by incubating with Arg-Gly-Asp-Ser peptide. Results: Eosinophils from the asthma group showed increased outer membrane α4β1 and αMβ2 integrin expression, increased adhesion to ASM cells, and overexpression of TGF-β1 compared with eosinophils from the healthy control group. Blockade of eosinophil RGD-binding integrins by Arg-Gly-Asp-Ser peptide significantly reduced adhesion of eosinophils to ASM cells in both groups. Integrin-blocking decreased the effects of eosinophils on TGF-β1, WNT-5a, and extracellular matrix protein gene expression in ASM cells and ASM cell proliferation in both groups. These effects were more pronounced in the asthma group compared with the control group. Conclusion: Suppression of eosinophil-ASM interaction via RGD-binding integrins attenuates eosinophil-induced ASM remodeling in asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT02648074. PMID:28119625

Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase.

PubMed

Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya

2017-05-31

Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact. SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila , Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Copyright © 2017 the authors 0270-6474/17/375496-•$15.00/0.

Estimation of parameter uncertainty for an activated sludge model using Bayesian inference: a comparison with the frequentist method.

PubMed

Zonta, Zivko J; Flotats, Xavier; Magrí, Albert

2014-08-01

The procedure commonly used for the assessment of the parameters included in activated sludge models (ASMs) relies on the estimation of their optimal value within a confidence region (i.e. frequentist inference). Once optimal values are estimated, parameter uncertainty is computed through the covariance matrix. However, alternative approaches based on the consideration of the model parameters as probability distributions (i.e. Bayesian inference), may be of interest. The aim of this work is to apply (and compare) both Bayesian and frequentist inference methods when assessing uncertainty for an ASM-type model, which considers intracellular storage and biomass growth, simultaneously. Practical identifiability was addressed exclusively considering respirometric profiles based on the oxygen uptake rate and with the aid of probabilistic global sensitivity analysis. Parameter uncertainty was thus estimated according to both the Bayesian and frequentist inferential procedures. Results were compared in order to evidence the strengths and weaknesses of both approaches. Since it was demonstrated that Bayesian inference could be reduced to a frequentist approach under particular hypotheses, the former can be considered as a more generalist methodology. Hence, the use of Bayesian inference is encouraged for tackling inferential issues in ASM environments.

A Proposal for the Maximum KIC for Use in ASME Code Flaw and Fracture Toughness Evaluations

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

Kirk, Mark; Stevens, Gary; Erickson, Marjorie A

2011-01-01

Nonmandatory Appendices A [1] and G [2] of Section XI of the ASME Code use the KIc curve (indexed to the material reference transition temperature, RTNDT) in reactor pressure vessel (RPV) flaw evaluations, and for the purpose of establishing RPV pressure-temperature (P-T) limits. Neither of these appendices places an upper-limit on the KIc value that may be used in these assessments. Over the years, it has often been suggested by some of the members of the ASME Section XI Code committees that are responsible for maintaining Appendices A and G that there is a practical upper limit of 200 ksimore » in (220 MPa m) [4]. This upper limit is not well recognized by all users of the ASME Code, is not explicitly documented within the Code itself, and the one source known to the authors where it is defended [4] relies on data that is either in error, or is less than 220 MPa m. However, as part of the NRC/industry pressurized thermal shock (PTS) re-evaluation effort, empirical models were developed that propose common temperature dependencies for all ferritic steels operating on the upper shelf. These models relate the fracture toughness properties in the transition regime to those on the upper shelf and, combined with data for a wide variety of RPV steels and welds on which they are based, suggest that the practical upper limit of 220 MPa m exceeds the upper shelf fracture toughness of most RPV steels by a considerable amount, especially for irradiated steels. In this paper, available models and data are used to propose upper bound limits of applicability on the KIc curve for use in ASME Code, Section XI, Nonmandatory Appendices A and G evaluations that are consistent with available data for RPV steels.« less

Combining registration and active shape models for the automatic segmentation of the lymph node regions in head and neck CT images

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

Chen Antong; Deeley, Matthew A.; Niermann, Kenneth J.

2010-12-15

Purpose: Intensity-modulated radiation therapy (IMRT) is the state of the art technique for head and neck cancer treatment. It requires precise delineation of the target to be treated and structures to be spared, which is currently done manually. The process is a time-consuming task of which the delineation of lymph node regions is often the longest step. Atlas-based delineation has been proposed as an alternative, but, in the authors' experience, this approach is not accurate enough for routine clinical use. Here, the authors improve atlas-based segmentation results obtained for level II-IV lymph node regions using an active shape model (ASM)more » approach. Methods: An average image volume was first created from a set of head and neck patient images with minimally enlarged nodes. The average image volume was then registered using affine, global, and local nonrigid transformations to the other volumes to establish a correspondence between surface points in the atlas and surface points in each of the other volumes. Once the correspondence was established, the ASMs were created for each node level. The models were then used to first constrain the results obtained with an atlas-based approach and then to iteratively refine the solution. Results: The method was evaluated through a leave-one-out experiment. The ASM- and atlas-based segmentations were compared to manual delineations via the Dice similarity coefficient (DSC) for volume overlap and the Euclidean distance between manual and automatic 3D surfaces. The mean DSC value obtained with the ASM-based approach is 10.7% higher than with the atlas-based approach; the mean and median surface errors were decreased by 13.6% and 12.0%, respectively. Conclusions: The ASM approach is effective in reducing segmentation errors in areas of low CT contrast where purely atlas-based methods are challenged. Statistical analysis shows that the improvements brought by this approach are significant.« less

The ASM Curriculum Guidelines for Undergraduate Microbiology: A Case Study of the Advocacy Role of Societies in Reform Efforts

PubMed Central

Horak, Rachel E. A.; Merkel, Susan; Chang, Amy

2015-01-01

A number of national reports, including Vision and Change in Undergraduate Biology Education: A Call to Action, have called for drastic changes in how undergraduate biology is taught. To that end, the American Society for Microbiology (ASM) has developed new Curriculum Guidelines for undergraduate microbiology that outline a comprehensive curriculum for any undergraduate introductory microbiology course or program of study. Designed to foster enduring understanding of core microbiology concepts, the Guidelines work synergistically with backwards course design to focus teaching on student-centered goals and priorities. In order to qualitatively assess how the ASM Curriculum Guidelines are used by educators and learn more about the needs of microbiology educators, the ASM Education Board distributed two surveys to the ASM education community. In this report, we discuss the results of these surveys (353 responses). We found that the ASM Curriculum Guidelines are being implemented in many different types of courses at all undergraduate levels. Educators indicated that the ASM Curriculum Guidelines were very helpful when planning courses and assessments. We discuss some specific ways in which the ASM Curriculum Guidelines have been used in undergraduate classrooms. The survey identified some barriers that microbiology educators faced when trying to adopt the ASM Curriculum Guidelines, including lack of time, lack of financial resources, and lack of supporting resources. Given the self-reported challenges to implementing the ASM Curriculum Guidelines in undergraduate classrooms, we identify here some activities related to the ASM Curriculum Guidelines that the ASM Education Board has initiated to assist educators in the implementation process. PMID:25949769

The ASM Curriculum Guidelines for Undergraduate Microbiology: A Case Study of the Advocacy Role of Societies in Reform Efforts.

PubMed

Horak, Rachel E A; Merkel, Susan; Chang, Amy

2015-05-01

A number of national reports, including Vision and Change in Undergraduate Biology Education: A Call to Action, have called for drastic changes in how undergraduate biology is taught. To that end, the American Society for Microbiology (ASM) has developed new Curriculum Guidelines for undergraduate microbiology that outline a comprehensive curriculum for any undergraduate introductory microbiology course or program of study. Designed to foster enduring understanding of core microbiology concepts, the Guidelines work synergistically with backwards course design to focus teaching on student-centered goals and priorities. In order to qualitatively assess how the ASM Curriculum Guidelines are used by educators and learn more about the needs of microbiology educators, the ASM Education Board distributed two surveys to the ASM education community. In this report, we discuss the results of these surveys (353 responses). We found that the ASM Curriculum Guidelines are being implemented in many different types of courses at all undergraduate levels. Educators indicated that the ASM Curriculum Guidelines were very helpful when planning courses and assessments. We discuss some specific ways in which the ASM Curriculum Guidelines have been used in undergraduate classrooms. The survey identified some barriers that microbiology educators faced when trying to adopt the ASM Curriculum Guidelines, including lack of time, lack of financial resources, and lack of supporting resources. Given the self-reported challenges to implementing the ASM Curriculum Guidelines in undergraduate classrooms, we identify here some activities related to the ASM Curriculum Guidelines that the ASM Education Board has initiated to assist educators in the implementation process.

Predicting OA progression to total hip replacement: can we do better than risk factors alone using active shape modelling as an imaging biomarker?

PubMed

Barr, Rebecca J; Gregory, Jennifer S; Reid, David M; Aspden, Richard M; Yoshida, Kanako; Hosie, Gillian; Silman, Alan J; Alesci, Salvatore; Macfarlane, Gary J

2012-03-01

Previously, active shape modelling (ASM) of the proximal femur was shown to identify those individuals at highest risk of developing radiographic OA. Here we determine whether ASM predicts the need for total hip replacement (THR) independent of Kellgren-Lawrence grade (KLG) and other known risk factors. A retrospective cohort study of 141 subjects consulting primary care with new hip pain was conducted. Pelvic radiographs taken on recruitment were assessed for KLG, centre-edge angle, acetabular depth and femoral head migration. Clinical factors (duration of pain, use of a stick and physical function) were collected by self-completed questionnaires. ASM differences between shape mode scores at baseline for individuals who underwent THR during the 5-year follow-up (n = 27) and those whose OA did not progress radiographically (n = 75) were compared. A 1 s.d. reduction in baseline ASM mode 2 score was associated with an 81% reduction in odds of THR (OR = 0.19, 95% CI 0.52, 0.70) after adjustment for KLG, radiographic and clinical factors. A similar reduction in odds of THR was associated with a 1 s.d. reduction in mode 3 (OR = 0.45, 95% CI 0.28, 0.71) and a 1 s.d. increase in mode 4 score (OR = 2.8, 95% CI 1.7, 4.7), although these associations were no longer significant after adjustment for KLG and clinical factors. ASM of the hip joint is a reliable early biomarker of radiographic OA severity, which can improve the ability to identify patients at higher risk of rapid progression and poor outcome even when KLG and clinical risk factors are taken into account.

Modeling nitrous oxide production during biological nitrogen removal via nitrification and denitrification: extensions to the general ASM models.

PubMed

Ni, Bing-Jie; Ruscalleda, Maël; Pellicer-Nàcher, Carles; Smets, Barth F

2011-09-15

Nitrous oxide (N(2)O) can be formed during biological nitrogen (N) removal processes. In this work, a mathematical model is developed that describes N(2)O production and consumption during activated sludge nitrification and denitrification. The well-known ASM process models are extended to capture N(2)O dynamics during both nitrification and denitrification in biological N removal. Six additional processes and three additional reactants, all involved in known biochemical reactions, have been added. The validity and applicability of the model is demonstrated by comparing simulations with experimental data on N(2)O production from four different mixed culture nitrification and denitrification reactor study reports. Modeling results confirm that hydroxylamine oxidation by ammonium oxidizers (AOB) occurs 10 times slower when NO(2)(-) participates as final electron acceptor compared to the oxic pathway. Among the four denitrification steps, the last one (N(2)O reduction to N(2)) seems to be inhibited first when O(2) is present. Overall, N(2)O production can account for 0.1-25% of the consumed N in different nitrification and denitrification systems, which can be well simulated by the proposed model. In conclusion, we provide a modeling structure, which adequately captures N(2)O dynamics in autotrophic nitrification and heterotrophic denitrification driven biological N removal processes and which can form the basis for ongoing refinements.

Effects of Php Gene-Associated versus Induced Resistance to Tobacco Cyst Nematode in Flue-Cured Tobacco

PubMed Central

Johnson, Charles S.; Eisenback, Jon D.

2009-01-01

Effects of the systemic acquired resistance (SAR)-inducing compound acibenzolar-S-methyl (ASM) and the plant-growth promoting rhizobacterial mixture Bacillus subtilis A13 and B. amyloliquefaciens IN937a (GB99+GB122) were assessed on the reproduction of a tobacco cyst nematode (TCN- Globodera tabacum solanacearum) under greenhouse conditions. Two sets of two independent experiments were conducted, each involving soil or root sampling. Soil sample experiments included flue-cured tobacco cultivars with (Php+: NC71 and NC102) and without (Php-: K326 and K346) a gene (Php) suppressing TCN parasitism. Root sample experiments examined TCN root parasitism of NC71 and K326. Cultivars possessing the Php gene (Php+) were compared with Php- cultivars to assess the effects of resistance mediated via Php gene vs. induced resistance to TCN. GB99+GB122 consistently reduced nematode reproductive ratio on both Php+ and Php- cultivars, but similar effects of ASM across Php- cultivars were less consistent. In addition, ASM application resulted in leaf yellowing and reduced root weight. GB99+GB122 consistently reduced nematode development in roots of both Php+ and Php- cultivars, while similar effects of ASM were frequently less consistent. The results of this study indicate that GB99+GB122 consistently reduced TCN reproduction in all flue-cured tobacco cultivars tested, while the effects of ASM were only consistent in Php+ cultivars. Under most circumstances, GB99+GB122 suppressed nematode reproduction more consistently than ASM compared to the untreated control. PMID:22736824

46 CFR 56.60-1 - Acceptable materials and specifications (replaces 123 and Table 126.1 in ASME B31.1).

Code of Federal Regulations, 2014 CFR

2014-10-01

... standards ASME standards Notes Pipe, seamless: A 106 Carbon steel ASME B31.1 A 335 Ferritic alloys ASME B31.1 A 376 Austenitic alloys ASME B31.1 (1). Pipe, seamless and welded: A 53 Types S, F, and E steel... cast: (None applicable) (1 9) Tube, seamless: A 179 Carbon steel heat exchanger and condenser tubes...

46 CFR 56.60-1 - Acceptable materials and specifications (replaces 123 and Table 126.1 in ASME B31.1).

Code of Federal Regulations, 2013 CFR

2013-10-01

... standards ASME standards Notes Pipe, seamless: A 106 Carbon steel ASME B31.1 A 335 Ferritic alloys ASME B31.1 A 376 Austenitic alloys ASME B31.1 (1). Pipe, seamless and welded: A 53 Types S, F, and E steel... cast: (None applicable) (1 9) Tube, seamless: A 179 Carbon steel heat exchanger and condenser tubes...

46 CFR 56.60-1 - Acceptable materials and specifications (replaces 123 and Table 126.1 in ASME B31.1).

Code of Federal Regulations, 2012 CFR

2012-10-01

... standards ASME standards Notes Pipe, seamless: A 106 Carbon steel ASME B31.1 A 335 Ferritic alloys ASME B31.1 A 376 Austenitic alloys ASME B31.1 (1). Pipe, seamless and welded: A 53 Types S, F, and E steel... cast: (None applicable) (1,9) Tube, seamless: A 179 Carbon steel heat exchanger and condenser tubes...

Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells.

PubMed

Sharma, Pawan; Panebra, Alfredo; Pera, Tonio; Tiegs, Brian C; Hershfeld, Alena; Kenyon, Lawrence C; Deshpande, Deepak A

2016-02-15

Airway remodeling is a hallmark feature of asthma and chronic obstructive pulmonary disease. Clinical studies and animal models have demonstrated increased airway smooth muscle (ASM) mass, and ASM thickness is correlated with severity of the disease. Current medications control inflammation and reverse airway obstruction effectively but have limited effect on remodeling. Recently we identified the expression of bitter taste receptors (TAS2R) on ASM cells, and activation with known TAS2R agonists resulted in ASM relaxation and bronchodilation. These studies suggest that TAS2R can be used as new therapeutic targets in the treatment of obstructive lung diseases. To further establish their effectiveness, in this study we aimed to determine the effects of TAS2R agonists on ASM growth and promitogenic signaling. Pretreatment of healthy and asthmatic human ASM cells with TAS2R agonists resulted in a dose-dependent inhibition of ASM proliferation. The antimitogenic effect of TAS2R ligands was not dependent on activation of protein kinase A, protein kinase C, or high/intermediate-conductance calcium-activated K(+) channels. Immunoblot analyses revealed that TAS2R agonists inhibit growth factor-activated protein kinase B phosphorylation without affecting the availability of phosphatidylinositol 3,4,5-trisphosphate, suggesting TAS2R agonists block signaling downstream of phosphatidylinositol 3-kinase. Furthermore, the antimitogenic effect of TAS2R agonists involved inhibition of induced transcription factors (activator protein-1, signal transducer and activator of transcription-3, E2 factor, nuclear factor of activated T cells) and inhibition of expression of multiple cell cycle regulatory genes, suggesting a direct inhibition of cell cycle progression. Collectively, these findings establish the antimitogenic effect of TAS2R agonists and identify a novel class of receptors and signaling pathways that can be targeted to reduce or prevent airway remodeling as well as bronchoconstriction in obstructive airway disease. Copyright © 2016 the American Physiological Society.

Antimitogenic effect of bitter taste receptor agonists on airway smooth muscle cells

PubMed Central

Sharma, Pawan; Panebra, Alfredo; Pera, Tonio; Tiegs, Brian C.; Hershfeld, Alena; Kenyon, Lawrence C.

2015-01-01

Airway remodeling is a hallmark feature of asthma and chronic obstructive pulmonary disease. Clinical studies and animal models have demonstrated increased airway smooth muscle (ASM) mass, and ASM thickness is correlated with severity of the disease. Current medications control inflammation and reverse airway obstruction effectively but have limited effect on remodeling. Recently we identified the expression of bitter taste receptors (TAS2R) on ASM cells, and activation with known TAS2R agonists resulted in ASM relaxation and bronchodilation. These studies suggest that TAS2R can be used as new therapeutic targets in the treatment of obstructive lung diseases. To further establish their effectiveness, in this study we aimed to determine the effects of TAS2R agonists on ASM growth and promitogenic signaling. Pretreatment of healthy and asthmatic human ASM cells with TAS2R agonists resulted in a dose-dependent inhibition of ASM proliferation. The antimitogenic effect of TAS2R ligands was not dependent on activation of protein kinase A, protein kinase C, or high/intermediate-conductance calcium-activated K+ channels. Immunoblot analyses revealed that TAS2R agonists inhibit growth factor-activated protein kinase B phosphorylation without affecting the availability of phosphatidylinositol 3,4,5-trisphosphate, suggesting TAS2R agonists block signaling downstream of phosphatidylinositol 3-kinase. Furthermore, the antimitogenic effect of TAS2R agonists involved inhibition of induced transcription factors (activator protein-1, signal transducer and activator of transcription-3, E2 factor, nuclear factor of activated T cells) and inhibition of expression of multiple cell cycle regulatory genes, suggesting a direct inhibition of cell cycle progression. Collectively, these findings establish the antimitogenic effect of TAS2R agonists and identify a novel class of receptors and signaling pathways that can be targeted to reduce or prevent airway remodeling as well as bronchoconstriction in obstructive airway disease. PMID:26684251

Heritabilities and genetic correlations of economic traits in Iranian native fowl and estimated genetic trend and inbreeding coefficients.

PubMed

Kamali, M A; Ghorbani, S H; Sharbabak, M Moradi; Zamiri, M J

2007-08-01

1. Genetic parameters were estimated in a base population of a closed experimental strain of fowl. Data were obtained on 21 245 Iranian native hens (breeding centre for Fars province) subject to 8 successive generations of selection. This population had been selected for body weight at 12 weeks of age (BW12) and egg number during the first 12 weeks of the laying period (EN), mean egg weight (EW) at weeks 28, 30 and 32, and age at sexual maturity (ASM). 2. The method of multi-traits restricted maximum likelihood with an animal model was used to estimate genetic parameters. Resulting heritabilities for BW12, EN, EW and ASM were 0.68 +/- 0.02, 0.40 +/- 0.02, 0.64 +/- 0.02 and 0.49 +/- 0.02, respectively. 3. Genetic correlations between BW12 and EN, EW and ASM were 0.11 +/- 0.33, 0.54 +/- 0.21 and -0.12 +/- 0.03, respectively. Genetic correlations between EN and EW and ASM were -0.09 +/- 0.03 and -0.85 +/- 0.01, respectively, while between EW and ASM, it was 0.05 +/- 0.03. 4. The overall predicted genetic gains, after 7 generations of selection, estimated by the regression coefficients of the breeding value on generation number were equal to 22.7, 0.17, 0.04 and -1.38, for BW12, EN, EW and ASM, respectively. 5. A pedigree file of 21 245 female and male birds was used to calculate inbreeding coefficients and their influence on production and reproduction traits. Average inbreeding coefficients for all birds, inbred birds, female birds and male birds were 0.048, 0.673, 0.055 and 0.047%, respectively. Regression coefficients of BW12, ASM, EN and EW on inbreeding coefficient for all birds were equal to 0.51 +/- 0.001, 0.31 +/- 0.003, -0.51 +/- 0.003 and 0.03 +/- 0.001, respectively.

Bitter taste receptors in the wrong place: novel airway smooth muscle targets for treating asthma.

PubMed

Liggett, Stephen B

2014-01-01

There is a need to expand the classes of drugs used to treat obstructive lung diseases to achieve better outcomes. With only one class of direct bronchodilators (β-agonists), we sought to find receptors on human airway smooth muscle (ASM) that act via a unique mechanism to relax the muscle, have a diverse agonist binding profile to enhance the probability of finding new therapeutics, and relax ASM with equal or greater efficacy than β-agonists. We have found that human and mouse ASM express six bitter taste receptor (TAS2R) subtypes, previously thought only to exist in taste buds of the tongue. Agonists acting at TAS2Rs evoke profound bronchodilation via a Ca(2+)-dependent mechanism. TAS2R function is not altered in asthma models, undergoes minimal tachyphylaxis upon repetitive dosing, and relaxes even under extreme desensitization of relaxation by β-agonists. Taken together, TAS2Rs on ASM represent a novel pathway to consider for development of agonists in the treatment of asthma and chronic obstructive lung disease.

Removal of Antibiotics in Biological Wastewater Treatment Systems-A Critical Assessment Using the Activated Sludge Modeling Framework for Xenobiotics (ASM-X).

PubMed

Polesel, Fabio; Andersen, Henrik R; Trapp, Stefan; Plósz, Benedek Gy

2016-10-04

Many scientific studies present removal efficiencies for pharmaceuticals in laboratory-, pilot-, and full-scale wastewater treatment plants, based on observations that may be impacted by theoretical and methodological approaches used. In this Critical Review, we evaluated factors influencing observed removal efficiencies of three antibiotics (sulfamethoxazole, ciprofloxacin, tetracycline) in pilot- and full-scale biological treatment systems. Factors assessed include (i) retransformation to parent pharmaceuticals from e.g., conjugated metabolites and analogues, (ii) solid retention time (SRT), (iii) fractions sorbed onto solids, and (iv) dynamics in influent and effluent loading. A recently developed methodology was used, relying on the comparison of removal efficiency predictions (obtained with the Activated Sludge Model for Xenobiotics (ASM-X)) with representative measured data from literature. By applying this methodology, we demonstrated that (a) the elimination of sulfamethoxazole may be significantly underestimated when not considering retransformation from conjugated metabolites, depending on the type (urban or hospital) and size of upstream catchments; (b) operation at extended SRT may enhance antibiotic removal, as shown for sulfamethoxazole; (c) not accounting for fractions sorbed in influent and effluent solids may cause slight underestimation of ciprofloxacin removal efficiency. Using tetracycline as example substance, we ultimately evaluated implications of effluent dynamics and retransformation on environmental exposure and risk prediction.

On two-point boundary correlations in the six-vertex model with domain wall boundary conditions

NASA Astrophysics Data System (ADS)

Colomo, F.; Pronko, A. G.

2005-05-01

The six-vertex model with domain wall boundary conditions on an N × N square lattice is considered. The two-point correlation function describing the probability of having two vertices in a given state at opposite (top and bottom) boundaries of the lattice is calculated. It is shown that this two-point boundary correlator is expressible in a very simple way in terms of the one-point boundary correlators of the model on N × N and (N - 1) × (N - 1) lattices. In alternating sign matrix (ASM) language this result implies that the doubly refined x-enumerations of ASMs are just appropriate combinations of the singly refined ones.

DOD Residential Proton Exchange Membrane (PEM) Fuel Cell Demonstration Program. Volume 1. Summary of the Fiscal Year 2001 Program

DTIC Science & Technology

2004-02-01

Potential new stan- dard ASME Boiler and Pressure Vessel Code, Section VIII ( BPVC -VIII), Division 1 Rules for Construction of Pressure Vessels...Published and avail- able for sale. ASME BPVC -VIII Division 2 Rules for Construction of Pressure Vessels, Division 2, Gerry Eisenberg, ASME ...Vessels, Division 3, Alternate ASME BPVC -VIII Division 3 Gerry Eisenberg, ASME Published and avail- able for sale. Rules High

ASM-024, a Piperazinium Compound, Promotes the In Vitro Relaxation of β2-Adrenoreceptor Desensitized Tracheas

PubMed Central

Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon

2015-01-01

Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short—acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024 could potentially provide clinical benefit when used adjunctively with inhaled β2-adrenoreceptor agonists in those patients exhibiting a reduced response to their chronic use. PMID:25799096

ASM-024, a piperazinium compound, promotes the in vitro relaxation of β2-adrenoreceptor desensitized tracheas.

PubMed

Israël-Assayag, Evelyne; Beaulieu, Marie-Josée; Cormier, Yvon

2015-01-01

Inhaled β2-adrenoreceptor agonists are widely used in asthma and chronic obstructive pulmonary disease (COPD) for bronchoconstriction relief. β2-Adrenoreceptor agonists relax airway smooth muscle cells via cyclic adenosine monophosphate (cAMP) mediated pathways. However, prolonged stimulation induces functional desensitization of the β2-adrenoreceptors (β2-AR), potentially leading to reduced clinical efficacy with chronic or prolonged administration. ASM-024, a small synthetic molecule in clinical stage development, has shown activity at the level of nicotinic receptors and possibly at the muscarinic level and presents anti-inflammatory and bronchodilator properties. Aerosolized ASM-024 reduces airway resistance in mice and promotes in-vitro relaxation of tracheal and bronchial preparations from animal and human tissues. ASM-024 increased in vitro relaxation response to maximally effective concentration of short-acting beta-2 agonists in dog and human bronchi. Although the precise mechanisms by which ASM-024 promotes airway smooth muscle (ASM) relaxation remain unclear, we hypothesized that ASM-024 will attenuate and/or abrogate agonist-induced contraction and remain effective despite β2-AR tachyphylaxis. β2-AR tachyphylaxis was induced with salbutamol, salmeterol and formoterol on guinea pig tracheas. The addition of ASM-024 relaxed concentration-dependently intact or β2-AR desensitized tracheal rings precontracted with methacholine. ASM-024 did not induce any elevation of intracellular cAMP in isolated smooth muscle cells; moreover, blockade of the cAMP pathway with an adenylate cyclase inhibitor had no significant effect on ASM-024-induced guinea pig trachea relaxation. Collectively, these findings show that ASM-024 elicits relaxation of β2-AR desensitized tracheal preparations and suggest that ASM-024 mediates smooth muscle relaxation through a different target and signaling pathway than β2-adrenergic receptor agonists. These findings suggest ASM-024 could potentially provide clinical benefit when used adjunctively with inhaled β2-adrenoreceptor agonists in those patients exhibiting a reduced response to their chronic use.

Systemic mastocytosis: A rare cause of non-cirrhotic portal hypertension.

PubMed

Martins, Cláudio; Teixeira, Cristina; Ribeiro, Suzane; Trabulo, Daniel; Cardoso, Cláudia; Mangualde, João; Freire, Ricardo; Gamito, Élia; Alves, Ana Luísa; Cremers, Isabelle; Alves, Cecília; Neves, Anabela; Oliveira, Ana Paula

2016-07-28

Mastocytosis is a clonal neoplastic disorder of the mast cells (MC) that can be limited to the skin (cutaneous mastocytosis) or involve one or more extracutaneous organs (systemic mastocytosis). The clinical manifestations of mastocytosis are heterogeneous ranging from indolent disease with a long-term survival to a highly aggressive neoplasm with survival of about 6 mo. Although liver involvement in aggressive systemic mastocytosis (ASM) is relatively common, the development of portal hypertension with or without cirrhosis is rare. We report a case of ASM without skin involvement in a 72-year-old caucasian male who presented with non-cirrhotic portal hypertension based on clinical, analytical, imagiological and endoscopic findings. Given the hematological picture, the correct diagnosis was established based on ancillary tests for MC using bone marrow aspirates and biopsy. Extensive involvement of the liver and gastrointestinal tract was histologically documented. The disease progressed rapidly and severe pancytopenia and recurrent upper gastrointestinal bleeding became the dominant problem. This case illustrates the challenge in establishing a diagnosis of ASM especially when the clinical picture is atypical and without skin involvement. Gastroenterologists should consider infiltrative disease, particularly systemic mastocytosis, as a differential diagnosis in a clinical case of portal hypertension of unknown etiology.

Parametric Sensitivity Analysis for the Asian Summer Monsoon Precipitation Simulation in the Beijing Climate Center AGCM Version 2.1

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

Yang, Ben; Zhang, Yaocun; Qian, Yun

In this study, we apply an efficient sampling approach and conduct a large number of simulations to explore the sensitivity of the simulated Asian summer monsoon (ASM) precipitation, including the climatological state and interannual variability, to eight parameters related to the cloud and precipitation processes in the Beijing Climate Center AGCM version 2.1 (BCC_AGCM2.1). Our results show that BCC_AGCM2.1 has large biases in simulating the ASM precipitation. The precipitation efficiency and evaporation coefficient for deep convection are the most sensitive parameters in simulating the ASM precipitation. With optimal parameter values, the simulated precipitation climatology could be remarkably improved, e.g. increasedmore » precipitation over the equator Indian Ocean, suppressed precipitation over the Philippine Sea, and more realistic Meiyu distribution over Eastern China. The ASM precipitation interannual variability is further analyzed, with a focus on the ENSO impacts. It shows the simulations with better ASM precipitation climatology can also produce more realistic precipitation anomalies during El Niño decaying summer. In the low-skill experiments for precipitation climatology, the ENSO-induced precipitation anomalies are most significant over continents (vs. over ocean in observation) in the South Asian monsoon region. More realistic results are derived from the higher-skill experiments with stronger anomalies over the Indian Ocean and weaker anomalies over India and the western Pacific, favoring more evident easterly anomalies forced by the tropical Indian Ocean warming and stronger Indian Ocean-western Pacific tele-connection as observed. Our model results reveal a strong connection between the simulated ASM precipitation climatological state and interannual variability in BCC_AGCM2.1 when key parameters are perturbed.« less

Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells.

PubMed

Prabhala, Pavan; Bunge, Kristin; Ge, Qi; Ammit, Alaina J

2016-10-01

Exaggerated cytokine secretion drives pathogenesis of a number of chronic inflammatory diseases, including asthma. Anti-inflammatory pharmacotherapies, including corticosteroids, are front-line therapies and although they have proven clinical utility, the molecular mechanisms responsible for their actions are not fully understood. The corticosteroid-inducible gene, mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1, DUSP1) has emerged as a key molecule responsible for the repressive effects of steroids. MKP-1 is known to deactivate p38 MAPK phosphorylation and can control the expression and activity of the mRNA destabilizing protein-tristetraprolin (TTP). But whether corticosteroid-induced MKP-1 acts via p38 MAPK-mediated modulation of TTP function in a pivotal airway cell type, airway smooth muscle (ASM), was unknown. While pretreatment of ASM cells with the corticosteroid dexamethasone (preventative protocol) is known to reduce ASM synthetic function in vitro, the impact of adding dexamethasone after stimulation (therapeutic protocol) had not been explored. Whether dexamethasone modulates TTP in a p38 MAPK-dependent manner in this cell type was also unknown. We address this herein and utilize an in vitro model of asthmatic inflammation where ASM cells were stimulated with the pro-asthmatic cytokine tumor necrosis factor (TNF) and the impact of adding dexamethasone 1 h after stimulation assessed. IL-6 mRNA expression and protein secretion was significantly repressed by dexamethasone acting in a temporally distinct manner to increase MKP-1, deactivate p38 MAPK, and modulate TTP phosphorylation status. In this way, dexamethasone-induced MKP-1 acts via p38 MAPK to switch on the mRNA destabilizing function of TTP to repress pro-inflammatory cytokine secretion from ASM cells. J. Cell. Physiol. 231: 2153-2158, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Doxofylline does not increase formoterol-induced cAMP nor MKP-1 expression in ASM cells resulting in lack of anti-inflammatory effect.

PubMed

Patel, Brijeshkumar S; Kugel, Michael J; Baehring, Gina; Ammit, Alaina J

2017-08-01

The xanthine doxofylline has been examined in clinical trials and shown to have efficacy and greater tolerability than theophylline in asthma and chronic obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental models of respiratory disease. However, there are limited studies in vitro. We address this herein and examine whether doxofylline has anti-inflammatory impact on primary cultures of airway smooth muscle (ASM) cells. We conduct a series of investigations comparing and contrasting doxofylline with the archetypal xanthine, theophylline, and the specific phosphodiesterase (PDE) 4 inhibitor, cilomilast. We confirm that the xanthine drugs do not have action as PDE inhibitors in ASM cells. Unlike cilomilast, doxofylline (and theophylline) do not increase cAMP production in ASM cells induced by long-acting β 2 -agonist formoterol. Similar to theophylline, and consistent with the lack of cAMP potentiation, doxofylline does not augment formoterol-induced upregulation of the anti-inflammatory protein mitogen-activated protein kinase phosphatase 1 (MKP-1). However, when we examine the effect of doxofylline on secretion of the interleukin 8 from ASM cells stimulated by tumour necrosis factor (an in vitro surrogate measure of inflammation), there was no repression of inflammation. This is in contrast to the anti-inflammatory impact exerted by theophylline and cilomilast in confirmatory experiments. In summary, our study is the first to examine the effect of doxofylline on ASM cells in vitro and highlights some distinct differences between two key members of xanthine drug family, doxofylline and theophylline. Copyright © 2017 Elsevier Ltd. All rights reserved.

The anti-proliferative and anti-inflammatory response of COPD airway smooth muscle cells to hydrogen sulfide.

PubMed

Perry, Mark M; Tildy, Bernadett; Papi, Alberto; Casolari, Paolo; Caramori, Gaetano; Rempel, Karen Limbert; Halayko, Andrew J; Adcock, Ian; Chung, Kian Fan

2018-05-09

COPD is a common, highly debilitating disease of the airways, primarily caused by smoking. Chronic inflammation and structural remodelling are key pathological features of this disease caused, in part, by the aberrant function of airway smooth muscle (ASM). We have previously demonstrated that hydrogen sulfide (H 2 S) can inhibit ASM cell proliferation and CXCL8 release, from cells isolated from non-smokers. We examined the effect of H 2 S upon ASM cells from COPD patients. ASM cells were isolated from non-smokers, smokers and patients with COPD (n = 9). Proliferation and cytokine release (IL-6 and CXCL8) of ASM was induced by FCS, and measured by bromodeoxyuridine incorporation and ELISA, respectively. Exposure of ASM to H 2 S donors inhibited FCS-induced proliferation and cytokine release, but was less effective upon COPD ASM cells compared to the non-smokers and smokers. The mRNA and protein expression of the enzymes responsible for endogenous H 2 S production (cystathionine-β-synthase [CBS] and 3-mercaptopyruvate sulphur transferase [MPST]) were inhibited by H 2 S donors. Finally, we report that exogenous H 2 S inhibited FCS-stimulated phosphorylation of ERK-1/2 and p38 mitogen activated protein kinases (MAPKs), in the non-smoker and smoker ASM cells, with little effect in COPD cells. H 2 S production provides a novel mechanism for the repression of ASM proliferation and cytokine release. The ability of COPD ASM cells to respond to H 2 S is attenuated in COPD ASM cells despite the presence of the enzymes responsible for H 2 S production.

Model building techniques for analysis.

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

Walther, Howard P.; McDaniel, Karen Lynn; Keener, Donald

2009-09-01

The practice of mechanical engineering for product development has evolved into a complex activity that requires a team of specialists for success. Sandia National Laboratories (SNL) has product engineers, mechanical designers, design engineers, manufacturing engineers, mechanical analysts and experimentalists, qualification engineers, and others that contribute through product realization teams to develop new mechanical hardware. The goal of SNL's Design Group is to change product development by enabling design teams to collaborate within a virtual model-based environment whereby analysis is used to guide design decisions. Computer-aided design (CAD) models using PTC's Pro/ENGINEER software tools are heavily relied upon in the productmore » definition stage of parts and assemblies at SNL. The three-dimensional CAD solid model acts as the design solid model that is filled with all of the detailed design definition needed to manufacture the parts. Analysis is an important part of the product development process. The CAD design solid model (DSM) is the foundation for the creation of the analysis solid model (ASM). Creating an ASM from the DSM currently is a time-consuming effort; the turnaround time for results of a design needs to be decreased to have an impact on the overall product development. This effort can be decreased immensely through simple Pro/ENGINEER modeling techniques that summarize to the method features are created in a part model. This document contains recommended modeling techniques that increase the efficiency of the creation of the ASM from the DSM.« less

49 CFR Appendix B to Part 222 - Alternative Safety Measures

Code of Federal Regulations, 2010 CFR

2010-10-01

...-Engineering ASMs, and Engineering ASMs. Modified SSMs are SSMs that do not fully comply with the provisions... reduction credit for pre-existing modified SSMs under the final rule. Non-engineering ASMs consist of... reduce risk within a quiet zone. Engineering ASMs consist of engineering improvements that address...

49 CFR Appendix B to Part 222 - Alternative Safety Measures

Code of Federal Regulations, 2011 CFR

2011-10-01

...-Engineering ASMs, and Engineering ASMs. Modified SSMs are SSMs that do not fully comply with the provisions... reduction credit for pre-existing modified SSMs under the final rule. Non-engineering ASMs consist of... reduce risk within a quiet zone. Engineering ASMs consist of engineering improvements that address...

An ASM/ADM model interface for dynamic plant-wide simulation.

PubMed

Nopens, Ingmar; Batstone, Damien J; Copp, John B; Jeppsson, Ulf; Volcke, Eveline; Alex, Jens; Vanrolleghem, Peter A

2009-04-01

Mathematical modelling has proven to be very useful in process design, operation and optimisation. A recent trend in WWTP modelling is to include the different subunits in so-called plant-wide models rather than focusing on parts of the entire process. One example of a typical plant-wide model is the coupling of an upstream activated sludge plant (including primary settler, and secondary clarifier) to an anaerobic digester for sludge digestion. One of the key challenges when coupling these processes has been the definition of an interface between the well accepted activated sludge model (ASM1) and anaerobic digestion model (ADM1). Current characterisation and interface models have key limitations, the most critical of which is the over-use of X(c) (or lumped complex) variable as a main input to the ADM1. Over-use of X(c) does not allow for variation of degradability, carbon oxidation state or nitrogen content. In addition, achieving a target influent pH through the proper definition of the ionic system can be difficult. In this paper, we define an interface and characterisation model that maps degradable components directly to carbohydrates, proteins and lipids (and their soluble analogues), as well as organic acids, rather than using X(c). While this interface has been designed for use with the Benchmark Simulation Model No. 2 (BSM2), it is widely applicable to ADM1 input characterisation in general. We have demonstrated the model both hypothetically (BSM2), and practically on a full-scale anaerobic digester treating sewage sludge.

Patient-Reported Outcome Questionnaire for Systemic Mastocytosis

ClinicalTrials.gov

2017-01-06

Aggressive Systemic Mastocytosis (ASM); SM w Assoc Clonal Hema Non-mast Cell Lineage Disease (SM-AHNMD); Mast Cell Leukemia (MCL); Smoldering Systemic Mastocytosis (SSM); Indolent Systemic Mastocytosis (ISM) ISM Subgroup Fully Recruited

Chromatin remodeling by rosuvastatin normalizes TSC2-/meth cell phenotype through the expression of tuberin.

PubMed

Lesma, Elena; Ancona, Silvia; Orpianesi, Emanuela; Grande, Vera; Di Giulio, Anna Maria; Gorio, Alfredo

2013-05-01

Tuberous sclerosis complex (TSC) is a multi-systemic syndrome caused by mutations in TSC1 or TSC2 gene. In TSC2-null cells, Rheb, a member of the Ras family of GTPases, is constitutively activated. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase and block the synthesis of isoprenoid lipids with inhibition of Rheb farnesylation and RhoA geranylgeranylation. The effects of rosuvastatin on the function of human TSC2(-/-) and TSC2(-/meth) α-actin smooth muscle (ASM) cells have been investigated. The TSC2(-/-) and TSC2(-/meth) ASM cells, previously isolated in our laboratory from the renal angiomyolipoma of two TSC patients, do not express tuberin and bear loss of heterozigosity caused by a double hit on TSC2 and methylation of TSC2 promoter, respectively. Exposure to rosuvastatin affected TSC2(-/meth) ASM cell growth and promoted tuberin expression by acting as a demethylating agent. This occurred without changes in interleukin release. Rosuvastatin also reduced RhoA activation in TSC2(-/meth) ASM cells, and it required coadministration with the specific mTOR (mammalian target of rapamycin) inhibitor rapamycin to be effective in TSC2(-/-) ASM cells. Rapamycin enhanced rosuvastatin effect in inhibiting cell proliferation in TSC2(-/-) and TSC2(-/meth) ASM cells. Rosuvastatin alone did not alter phosphorylation of S6 and extracellular signal-regulated kinase (ERK), and at the higher concentration, rosuvastatin and rapamycin slightly decreased ERK phosphorylation. These results suggest that rosuvastatin may potentially represent a treatment adjunct to the therapy with mTOR inhibitors now in clinical development for TSC. In particular, rosuvastatin appears useful when the disease is originated by epigenetic defects.

Cod Fractions In Mechanical-Biological Wastewater Treatment Plant

NASA Astrophysics Data System (ADS)

Płuciennik-Koropczuk, Ewelina; Jakubaszek, Anita; Myszograj, Sylwia; Uszakiewicz, Sylwia

2017-03-01

The paper presents results of studies concerning the designation of COD fraction in the raw, mechanically treated and biologically treated wastewater. The test object was a wastewater treatment plant with the output of over 20,000 PE. The results were compared with data received in the ASM models. During investigation following fractions of COD were determined: dissolved non-biodegradable SI, dissolved easily biodegradable SS, in organic suspension slowly degradable XS and in organic suspension non-biodegradable XI. Methodology for determining the COD fraction was based on the guidelines ATV-A 131. The real percentage of each fraction in total COD in raw wastewater are different from data received in ASM models.

Abdomen and spinal cord segmentation with augmented active shape models.

PubMed

Xu, Zhoubing; Conrad, Benjamin N; Baucom, Rebeccah B; Smith, Seth A; Poulose, Benjamin K; Landman, Bennett A

2016-07-01

Active shape models (ASMs) have been widely used for extracting human anatomies in medical images given their capability for shape regularization of topology preservation. However, sensitivity to model initialization and local correspondence search often undermines their performances, especially around highly variable contexts in computed-tomography (CT) and magnetic resonance (MR) images. In this study, we propose an augmented ASM (AASM) by integrating the multiatlas label fusion (MALF) and level set (LS) techniques into the traditional ASM framework. Using AASM, landmark updates are optimized globally via a region-based LS evolution applied on the probability map generated from MALF. This augmentation effectively extends the searching range of correspondent landmarks while reducing sensitivity to the image contexts and improves the segmentation robustness. We propose the AASM framework as a two-dimensional segmentation technique targeting structures with one axis of regularity. We apply AASM approach to abdomen CT and spinal cord (SC) MR segmentation challenges. On 20 CT scans, the AASM segmentation of the whole abdominal wall enables the subcutaneous/visceral fat measurement, with high correlation to the measurement derived from manual segmentation. On 28 3T MR scans, AASM yields better performances than other state-of-the-art approaches in segmenting white/gray matter in SC.

The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

PubMed Central

Ozier, Annaïg; Allard, Benoit; Bara, Imane; Girodet, Pierre-Olivier; Trian, Thomas; Marthan, Roger; Berger, Patrick

2011-01-01

Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR. The mechanisms of AHR in asthma may involve a larger release of contractile mediators and/or a lower release of relaxant mediators, an improved ASM cell excitation/contraction coupling, and/or an alteration in the contraction/load coupling. Beyond its contractile function, ASM is also involved in bronchial inflammation and remodelling. Whereas ASM is a target of the inflammatory process, it can also display proinflammatory and immunomodulatory functions, through its synthetic properties and the expression of a wide range of cell surface molecules. ASM remodelling represents a key feature of asthmatic bronchial remodelling. ASM also plays a role in promoting complementary airway structural alterations, in particular by its synthetic function. PMID:22220184

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.

PubMed

Yim, Peter D; Gallos, George; Perez-Zoghbi, Jose F; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W

2013-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Acid sphingomyelinase mediates human CD4+ T-cell signaling: potential roles in T-cell responses and diseases

PubMed Central

Bai, Aiping; Guo, Yuan

2017-01-01

Acid sphingomyelinase (ASM) is a lipid hydrolase. By generating ceramide, ASM had been reported to have an important role in regulating immune cell functions inclusive of macrophages, NK cells, and CD8+ T cells, whereas the role of ASM bioactivity in regulation of human CD4+ T-cell functions remained uncertain. Recent studies have provided novel findings in this field. Upon stimulation of CD3 and/or CD28, ASM-dependent ceramide signaling mediates intracellular downstream signal cascades of CD3 and CD28, and regulates CD4+ T-cell activation and proliferation. Meanwhile, CD39 and CD161 have direct interactions with ASM, which mediates downstream signals inclusive of STAT3 and mTOR and thus defines human Th17 cells. Intriguingly, ASM mediates Th1 responses, but negatively regulates Treg functions. In this review, we summarized the pivotal roles of ASM in regulation of human CD4+ T-cell activation and responses. ASM/sphingolipid signaling may be a novel target for the therapy of human autoimmune diseases. PMID:28749465

Acid Sphingomyelinase Gene Deficiency Ameliorates the Hyperhomocysteinemia-Induced Glomerular Injury in Mice

PubMed Central

Boini, Krishna M.; Xia, Min; Li, Caixia; Zhang, Chun; Payne, Lori P.; Abais, Justine M.; Poklis, Justin L.; Hylemon, Philip B.; Li, Pin-Lan

2011-01-01

Hyperhomocysteinemia (hHcys) enhances ceramide production, leading to the activation of NADPH oxidase and consequent glomerular oxidative stress and sclerosis. The present study was performed to determine whether acid sphingomyelinase (Asm), a ceramide-producing enzyme, is implicated in the development of hHcys-induced glomerular oxidative stress and injury. Uninephrectomized Asm-knockout (Asm−/−) and wild-type (Asm+/+) mice, with or without Asm short hairpin RNA (shRNA) transfection, were fed a folate-free (FF) diet for 8 weeks, which significantly elevated the plasma Hcys level compared with mice fed normal chow. By using in vivo molecular imaging, we found that transfected shRNAs were expressed in the renal cortex starting on day 3 and continued for 24 days. The FF diet significantly increased renal ceramide production, Asm mRNA and activity, urinary total protein and albumin excretion, glomerular damage index, and NADPH-dependent superoxide production in the renal cortex from Asm+/+ mice compared with that from Asm−/− or Asm shRNA-transfected wild-type mice. Immunofluorescence analysis showed that the FF diet decreased the expression of podocin but increased desmin and ceramide levels in glomeruli from Asm+/+ mice but not in those from Asm−/− and Asm shRNA-transfected wild-type mice. In conclusion, our observations reveal that Asm plays a pivotal role in mediating podocyte injury and glomerular sclerosis associated with NADPH oxidase–associated local oxidative stress during hHcys. PMID:21893018

Instigation of NLRP3 inflammasome activation and glomerular injury in mice on the high fat diet: role of acid sphingomyelinase gene

PubMed Central

Boini, Krishna M.; Xia, Min; Koka, Saisudha; Gehr, Todd W.; Li, Pin-Lan

2016-01-01

Ceramide has been reported to initiate inflammasome formation and activation in obesity and different pathological conditions. The present study was performed to explore the role of acid sphingomyelinase (Asm) in the development of high fat diet (HFD)-induced inflammasome and activation and consequent glomerular injury. Asm knockout (Asm−/−) and wild type (Asm+/+) mice with or without Asm short hairpin RNA (shRNA) transfection were fed a HFD or normal chow for 12 weeks to produce obesity and associated glomerular injury. HFD significantly enhanced the Asm activity, ceramide production, colocalization of Nlrp3 (Nod-like receptor protein 3) with ASC (apoptosis-associated speck-like protein) or Caspase-1, NADPH-dependent superoxide (O2•−) production in glomeruli of Asm+/+mice than in control diet-fed mice. However, such HFD-induced increases in Asm activity, ceramide production, colocalization of Nlrp3 with ASC or Caspase-1, superoxide (O2•−) production was attenuated in Asm−/− or Asm shRNA-transfected wild-type mice. In consistency with decreased inflammasome formation, the caspase-1 activity and IL-1β production was significantly attenuated in Asm−/− or Asm shRNA-transfected wild-type mice fed a HFD. Morphological examinations showed that HFD-induced profound injury in glomeruli of Asm+/+ mice which was markedly attenuated in Asm−/− mice. The decreased glomerular damage index in Asm−/− mice was accompanied by attenuated proteinuria. Fluorescent immunohistochemical examinations using podocin as a podocyte marker showed that inflammasome formation induced by the HFD were mostly located in podocytes as demonstrated by co-localization of podocin with Nlrp3. In conclusion, these observations disclose a pivotal role of Asm in the HFD-induced inflammasome formation and consequent glomerular inflammation and injury. PMID:26980705

Robot Path Planning in Uncertain Environments: A Language Measure-theoretic Approach

DTIC Science & Technology

2014-01-01

Paper DS-14-1028 to appear in the Special Issue on Stochastic Models, Control and Algorithms in Robotics, ASME Journal of Dynamic Systems...Measurement and Control Robot Path Planning in Uncertain Environments: A Language Measure-theoretic Approach⋆ Devesh K. Jha† Yue Li† Thomas A. Wettergren‡† Asok...algorithm, called ν⋆, that was formulated in the framework of probabilistic finite state automata (PFSA) and language measure from a control -theoretic

77 FR 3073 - American Society of Mechanical Engineers (ASME) Codes and New and Revised ASME Code Cases...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

... NUCLEAR REGULATORY COMMISSION 10 CFR Part 50 [NRC-2008-0554] RIN 3150-AI35 American Society of Mechanical Engineers (ASME) Codes and New and Revised ASME Code Cases; Corrections AGENCY: Nuclear Regulatory... the American Society of Mechanical Engineers, Three Park Avenue, New York, NY 10016, phone (800) 843...

Central Heat Plant Modernization: FY98 Update and Recommendations.

DTIC Science & Technology

1999-12-01

Boiler and Pressure Vessel Code suggests an inspection frequency of 12 months for...28 April 1997). ASME International, Boiler and Pressure Vessel Code (ASME International, New York, NY, 1995). Bloomquist, R.G., J.D. Nimmons, and K...Services (HQDA, 28 April 1997). ASME International, Boiler and Pressure Vessel Code (ASME International, New York, NY, 1995). Bloomquist, R.G.,

75 FR 40026 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

...) and Alternative Safety Measures (ASM) as follows: 1 crossing closure (SSM), 1 crossing with gates and... channelization (ASM). The 2 SSMs will be completed by June 24, 2010, and the ASM will be completed within 45 working days of receipt of the ASM approval from FRA. In the future, 2 other crossings will be modified as...

Airway mechanics and methods used to visualize smooth muscle dynamics in vitro.

PubMed

Cooper, P R; McParland, B E; Mitchell, H W; Noble, P B; Politi, A Z; Ressmeyer, A R; West, A R

2009-10-01

Contraction of airway smooth muscle (ASM) is regulated by the physiological, structural and mechanical environment in the lung. We review two in vitro techniques, lung slices and airway segment preparations, that enable in situ ASM contraction and airway narrowing to be visualized. Lung slices and airway segment approaches bridge a gap between cell culture and isolated ASM, and whole animal studies. Imaging techniques enable key upstream events involved in airway narrowing, such as ASM cell signalling and structural and mechanical events impinging on ASM, to be investigated.

Fast automated segmentation of multiple objects via spatially weighted shape learning

NASA Astrophysics Data System (ADS)

Chandra, Shekhar S.; Dowling, Jason A.; Greer, Peter B.; Martin, Jarad; Wratten, Chris; Pichler, Peter; Fripp, Jurgen; Crozier, Stuart

2016-11-01

Active shape models (ASMs) have proved successful in automatic segmentation by using shape and appearance priors in a number of areas such as prostate segmentation, where accurate contouring is important in treatment planning for prostate cancer. The ASM approach however, is heavily reliant on a good initialisation for achieving high segmentation quality. This initialisation often requires algorithms with high computational complexity, such as three dimensional (3D) image registration. In this work, we present a fast, self-initialised ASM approach that simultaneously fits multiple objects hierarchically controlled by spatially weighted shape learning. Prominent objects are targeted initially and spatial weights are progressively adjusted so that the next (more difficult, less visible) object is simultaneously initialised using a series of weighted shape models. The scheme was validated and compared to a multi-atlas approach on 3D magnetic resonance (MR) images of 38 cancer patients and had the same (mean, median, inter-rater) Dice’s similarity coefficients of (0.79, 0.81, 0.85), while having no registration error and a computational time of 12-15 min, nearly an order of magnitude faster than the multi-atlas approach.

Fast automated segmentation of multiple objects via spatially weighted shape learning.

PubMed

Chandra, Shekhar S; Dowling, Jason A; Greer, Peter B; Martin, Jarad; Wratten, Chris; Pichler, Peter; Fripp, Jurgen; Crozier, Stuart

2016-11-21

Active shape models (ASMs) have proved successful in automatic segmentation by using shape and appearance priors in a number of areas such as prostate segmentation, where accurate contouring is important in treatment planning for prostate cancer. The ASM approach however, is heavily reliant on a good initialisation for achieving high segmentation quality. This initialisation often requires algorithms with high computational complexity, such as three dimensional (3D) image registration. In this work, we present a fast, self-initialised ASM approach that simultaneously fits multiple objects hierarchically controlled by spatially weighted shape learning. Prominent objects are targeted initially and spatial weights are progressively adjusted so that the next (more difficult, less visible) object is simultaneously initialised using a series of weighted shape models. The scheme was validated and compared to a multi-atlas approach on 3D magnetic resonance (MR) images of 38 cancer patients and had the same (mean, median, inter-rater) Dice's similarity coefficients of (0.79, 0.81, 0.85), while having no registration error and a computational time of 12-15 min, nearly an order of magnitude faster than the multi-atlas approach.

Development of an algebraic stress/two-layer model for calculating thrust chamber flow fields

NASA Technical Reports Server (NTRS)

Chen, C. P.; Shang, H. M.; Huang, J.

1993-01-01

Following the consensus of a workshop in Turbulence Modeling for Liquid Rocket Thrust Chambers, the current effort was undertaken to study the effects of second-order closure on the predictions of thermochemical flow fields. To reduce the instability and computational intensity of the full second-order Reynolds Stress Model, an Algebraic Stress Model (ASM) coupled with a two-layer near wall treatment was developed. Various test problems, including the compressible boundary layer with adiabatic and cooled walls, recirculating flows, swirling flows and the entire SSME nozzle flow were studied to assess the performance of the current model. Detailed calculations for the SSME exit wall flow around the nozzle manifold were executed. As to the overall flow predictions, the ASM removes another assumption for appropriate comparison with experimental data, to account for the non-isotropic turbulence effects.

Turbulence modelling of flow fields in thrust chambers

NASA Technical Reports Server (NTRS)

Chen, C. P.; Kim, Y. M.; Shang, H. M.

1993-01-01

Following the consensus of a workshop in Turbulence Modelling for Liquid Rocket Thrust Chambers, the current effort was undertaken to study the effects of second-order closure on the predictions of thermochemical flow fields. To reduce the instability and computational intensity of the full second-order Reynolds Stress Model, an Algebraic Stress Model (ASM) coupled with a two-layer near wall treatment was developed. Various test problems, including the compressible boundary layer with adiabatic and cooled walls, recirculating flows, swirling flows, and the entire SSME nozzle flow were studied to assess the performance of the current model. Detailed calculations for the SSME exit wall flow around the nozzle manifold were executed. As to the overall flow predictions, the ASM removes another assumption for appropriate comparison with experimental data to account for the non-isotropic turbulence effects.

Maintenance treatment for GERD: residual symptoms are associated with psychological distress.

PubMed

van der Velden, A W; de Wit, N J; Quartero, A O; Grobbee, D E; Numans, M E

2008-01-01

The aim of this study was to explore determinants of residual reflux symptoms among patients with gastroesophageal reflux disease (GERD) despite maintenance treatment with acid suppressive medication (ASM). Primary care GERD patients on chronic ASM were classified as symptom-free (55%) or symptomatic (45%) according to the impact of their residual reflux symptoms (QolRad). They were compared with respect to lifestyle (BMI, alcohol, smoking, physical exercise), compliance (daily ASM dosage), disease history, psychological factors (SCL-90) and quality of life (SF-36). None of the investigated lifestyle factors, nor dosage and disease history were related to residual symptoms. However, symptomatic patients differed from patients with relief on all psychological and quality of life dimensions. In a multiple logistic regression model somatization, hostility, mental health, body pain, as well as gender were independently associated with residual symptoms; the derived ROC curve had an AUC of 0.78. The majority of GERD patients is symptom-free on chronic ASM; they display a healthy psychological state and high quality of life. Residual symptoms however, are associated with psychological distress and lower quality of life. Recognition of this subgroup might hold the key to improving long-term management of gastroesophageal reflux. Copyright 2008 S. Karger AG, Basel.

[Quantitative analysis of the structure of neuronal dendritic spines in the striatum using the Leitz-ASM system].

PubMed

Leontovich, T A; Zvegintseva, E G

1985-10-01

Two principal classes of striatum long axonal neurons (sparsely ramified reticular cells and densely ramified dendritic cells) were analyzed quantitatively in four animal species: hedgehog, rabbit, dog and monkey. The cross section area, total dendritic length and the area of dendritic field were measured using "LEITZ-ASM" system. Classes of neurons studied were significantly different in dogs and monkeys, while no differences were noted between hedgehog and rabbit. Reticular neurons of different species varied much more than dendritic ones. Quantitative analysis has revealed the progressive increase in the complexity of dendritic tree in mammals from rabbit to monkey.

Types A and B Niemann-Pick disease.

PubMed

Schuchman, Edward H; Wasserstein, Melissa P

2015-03-01

Two distinct metabolic abnormalities are encompassed under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly in infancy and profound central nervous system involvement. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no central nervous system signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second NPD category are designated as having types C and D NPD. These patients may have mild hepatosplenomegaly, but the central nervous system is profoundly affected. Impaired intracellular trafficking of cholesterol causes types C and D NPD, and two distinct gene defects have been found. In this chapter only types A and B NPD will be discussed. Copyright © 2014. Published by Elsevier Ltd.

The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD

PubMed Central

2016-01-01

Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor β (TGF-β) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-β, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF-β in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF-β signaling in the pathogenesis of COPD, which warrants further investigation. PMID:27656649

Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca(2+) regulation in airway smooth muscle (ASM).

PubMed

Delmotte, Philippe; Sieck, Gary C

2015-02-01

Airway inflammation is a key aspect of diseases such as asthma. Several inflammatory cytokines (e.g., TNFα and IL-13) increase cytosolic Ca(2+) ([Ca(2+)]cyt) responses to agonist stimulation and Ca(2+) sensitivity of force generation, thereby enhancing airway smooth muscle (ASM) contractility (hyper-reactive state). Inflammation also induces ASM proliferation and remodeling (synthetic state). In normal ASM, the transient elevation of [Ca(2+)]cyt induced by agonists leads to a transient increase in mitochondrial Ca(2+) ([Ca(2+)]mito) that may be important in matching ATP production with ATP consumption. In human ASM (hASM) exposed to TNFα and IL-13, the transient increase in [Ca(2+)]mito is blunted despite enhanced [Ca(2+)]cyt responses. We also found that TNFα and IL-13 induce reactive oxidant species (ROS) formation and endoplasmic/sarcoplasmic reticulum (ER/SR) stress (unfolded protein response) in hASM. ER/SR stress in hASM is associated with disruption of mitochondrial coupling with the ER/SR membrane, which relates to reduced mitofusin 2 (Mfn2) expression. Thus, in hASM it appears that TNFα and IL-13 result in ROS formation leading to ER/SR stress, reduced Mfn2 expression, disruption of mitochondrion-ER/SR coupling, decreased mitochondrial Ca(2+) buffering, mitochondrial fragmentation, and increased cell proliferation.

Smooth muscle in human bronchi is disposed to resist airway distension.

PubMed

Gazzola, Morgan; Henry, Cyndi; Couture, Christian; Marsolais, David; King, Gregory G; Fredberg, Jeffrey J; Bossé, Ynuk

2016-07-15

Studying airway smooth muscle (ASM) in conditions that emulate the in vivo environment within which the bronchi normally operate may provide important clues regarding its elusive physiological function. The present study examines the effect of lengthening and shortening of ASM on tension development in human bronchial segments. ASM from each bronchial segment was set at a length approximating in situ length (Linsitu). Bronchial tension was then measured during a slow cyclical strain (0.004Hz, from 0.7Linsitu to 1.3Linsitu) in the relaxed state and at graded levels of activation by methacholine. In all cases, tension was greater at longer ASM lengths, and greater during lengthening than shortening. The threshold of methacholine concentration that was required for ASM to account for bronchial tension across the entire range of ASM lengths tested was on average smaller by 2.8 logs during lengthening than during shortening. The length-dependency of ASM tension, together with this lower threshold of methacholine concentration during lengthening versus shortening, suggest that ASM has a greater ability to resist airway dilation during lung inflation than to narrow the airways during lung deflation. More than serving to narrow the airway, as has long been thought, these data suggest that the main function of ASM contraction is to limit airway wall distension during lung inflation. Copyright © 2016 Elsevier B.V. All rights reserved.

Interaction between endoplasmic/sarcoplasmic reticulum stress (ER/SR stress), mitochondrial signaling and Ca2+ regulation in airway smooth muscle (ASM)1

PubMed Central

Delmotte, Philippe; Sieck, Gary C.

2015-01-01

Airway inflammation is a key aspect of diseases such as asthma. Several inflammatory cytokines (e.g., TNFα and IL-13) increase cytosolic Ca2+ ([Ca2+]cyt) responses to agonist stimulation and Ca2+ sensitivity of force generation, thereby enhancing airway smooth muscle (ASM) contractility (hyper-reactive state). Inflammation also induces ASM proliferation and remodeling (synthetic state). In normal ASM, the transient elevation of [Ca2+]cyt induced by agonists leads to a transient increase in mitochondrial Ca2+ ([Ca2+]mito) that may be important in matching ATP production with ATP consumption. In human ASM (hASM) exposed to TNFα and IL-13, the transient increase in [Ca2+]mito is blunted despite enhanced [Ca2+]cyt responses. We also found that TNFα and IL-13 induce reactive oxidant species (ROS) formation and endoplasmic/sarcoplasmic reticulum (ER/SR) stress (unfolded protein response) in hASM. ER/SR stress in hASM is associated with disruption of mitochondrial coupling with the ER/SR membrane, which relates to reduced mitofusin 2 (Mfn2) expression. Thus, in hASM it appears that TNFα and IL-13 result in ROS formation leading to ER/SR stress, reduced Mfn2 expression, disruption of mitochondrion–ER/SR coupling, decreased mitochondrial Ca2+ buffering, mitochondrial fragmentation, and increased cell proliferation. PMID:25506723

Pesticides

MedlinePlus

... Satellite Session 2018 ASM Agenda 2018 ASM Faculty Bios 2018 ASM Events for Residents and Students 2018 ... Purchase CME Board Review Course Overview Agenda Faculty Bios Fees and Registration Course Materials Continuing Ed Hotel ...

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle

PubMed Central

Yim, Peter D.; Gallos, George; Perez-zoghbi, Jose F.; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W.

2014-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K+ channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders. PMID:24662476

Stalagmite-inferred centennial variability of the Asian summer monsoon in southwest China between 58 and 79 ka BP

NASA Astrophysics Data System (ADS)

Zhang, Tao-Tao; Li, Ting-Yong; Cheng, Hai; Edwards, R. Lawrence; Shen, Chuan-Chou; Spötl, Christoph; Li, Hong-Chun; Han, Li-Yin; Li, Jun-Yun; Huang, Chun-Xia; Zhao, Xin

2017-03-01

We use a new spliced stalagmite oxygen isotope record from Yangkou Cave and Xinya Cave, Chongqing, southwest China, to reconstruct the centennial-millennial-scale changes in Asian Summer Monsoon (ASM) intensity between 58.0 and 79.3 thousand years before present (ka BP, before AD 1950). This multidecadally resolved record shows four strong ASM periods, corresponding to Greenland Interstadials (GIS) 17-20, and three weak ASM episodes, among which, the one starting at 61.5 ± 0.2 ka BP and ending at 59.4 ± 0.2 ka BP that may correlate with Heinrich Event 6. The close agreement of climate events between China and Greenland supports the notion that the ASM is dominantly governed by high-latitude forcings in the Northern Hemisphere. The short-lived interstadial GIS 18, however, lasted for over 3 kyr in the records derived from ASM region, reflecting a gradual decline of ASM intensity, which coincides with a millennial-scale warming trend in Antarctica. This suggests an additional forcing of the ASM by the Southern Hemisphere, which also affected GIS 8-12, H4 and H5, as shown by previous speleothem studies from the ASM region.

Regulation of dynein-mediated autophagosomes trafficking by ASM in CASMCs.

PubMed

Xu, Ming; Zhang, Qiufang; Li, Pin-Lan; Nguyen, Thaison; Li, Xiang; Zhang, Yang

2016-01-01

Acid sphingomyelinase (ASM; gene symbol Smpd1) has been shown to play a crucial role in autophagy maturation by controlling lysosomal fusion with autophagosomes in coronary arterial smooth muscle cells (CASMCs). However, the underlying molecular mechanism by which ASM controls autophagolysosomal fusion remains unknown. In primary cultured CASMCs, lysosomal Ca2+ induced by 7-ketocholesterol (7-Ket, an atherogenic stimulus and autophagy inducer) was markedly attenuated by ASM deficiency or TRPML1 gene silencing suggesting that ASM signaling is required for TRPML1 channel activity and subsequent lysosomal Ca(2+) release. In these CASMCs, ASM deficiency or TRPML1 gene silencing markedly inhibited 7-Ket-induced dynein activation. In addition, 7-Ket-induced autophagosome trafficking, an event associated with lysosomal Ca(2+) release and dynein activity, was significantly inhibited in ASM-deficient (Smpd1(-/-)) CASMCs compared to that in Smpd1(+/+) CASMCs. Finally, overexpression of TRPML1 proteins restored 7-Ket-induced lysosomal Ca(2+) release and autophagosome trafficking in Smpd1-/- CASMCs. Collectively, these results suggest that ASM plays a critical role in regulating lysosomal TRPML1-Ca(2+) signaling and subsequent dynein-mediated autophagosome trafficking, which leads its role in controlling autophagy maturation in CASMCs under atherogenic stimulation.

Dynamic fracture toughness of ASME SA508 Class 2a ASME SA533 grade A Class 2 base and heat affected zone material and applicable weld metals

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

Logsdon, W.A.; Begley, J.A.; Gottshall, C.L.

1978-03-01

The ASME Boiler and Pressure Vessel Code, Section III, Article G-2000, requires that dynamic fracture toughness data be developed for materials with specified minimum yield strengths greater than 50 ksi to provide verification and utilization of the ASME specified minimum reference toughness K/sub IR/ curve. In order to qualify ASME SA508 Class 2a and ASME SA533 Grade A Class 2 pressure vessel steels (minimum yield strengths equal 65 kip/in./sup 2/ and 70 kip/in./sup 2/, respectively) per this requirement, dynamic fracture toughness tests were performed on these materials. All dynamic fracture toughness values of SA508 Class 2a base and HAZ material,more » SA533 Grade A Class 2 base and HAZ material, and applicable weld metals exceeded the ASME specified minimum reference toughness K/sub IR/ curve.« less

Body composition indices of a load-capacity model: gender- and BMI-specific reference curves.

PubMed

Siervo, Mario; Prado, Carla M; Mire, Emily; Broyles, Stephanie; Wells, Jonathan C K; Heymsfield, Steven; Katzmarzyk, Peter T

2015-05-01

Fat mass (FM) and fat-free mass (FFM) are frequently measured to define body composition phenotypes. The load-capacity model integrates the effects of both FM and FFM to improve disease-risk prediction. We aimed to derive age-, gender- and BMI-specific reference curves of load-capacity model indices in an adult population (≥18 years). Cross-sectional study. Dual-energy X-ray absorptiometry was used to measure FM, FFM, appendicular skeletal muscle mass (ASM) and truncal fat mass (TrFM). Two metabolic load-capacity indices were calculated: ratio of FM (kg) to FFM (kg) and ratio of TrFM (kg) to ASM (kg). Age-standardised reference curves, stratified by gender and BMI (<25.0 kg/m2, 25.0-29.9 kg/m2, ≥30.0 kg/m2), were constructed using an LMS approach. Percentiles of the reference curves were 5th, 15th, 25th, 50th, 75th, 85th and 95th. Secondary analysis of data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES). The population included 6580 females and 6656 males. The unweighted proportions of obesity in males and females were 25.5 % and 34.7 %, respectively. The average values of both FM:FFM and TrFM:ASM were greater in female and obese subjects. Gender and BMI influenced the shape of the association of age with FM:FFM and TrFM:ASM, as a curvilinear relationship was observed in female and obese subjects. Menopause appeared to modify the steepness of the reference curves of both indices. This is a novel risk-stratification approach integrating the effects of high adiposity and low muscle mass which may be particularly useful to identify cases of sarcopenic obesity and improve disease-risk prediction.

Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2[S

PubMed Central

Oninla, Vincent O.; Breiden, Bernadette; Babalola, Jonathan O.; Sandhoff, Konrad

2014-01-01

During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747–1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion. PMID:25339683

An FGF-driven feed-forward circuit patterns the cardiopharyngeal mesoderm in space and time

PubMed Central

Razy-Krajka, Florian; Gravez, Basile; Kaplan, Nicole; Racioppi, Claudia; Wang, Wei

2018-01-01

In embryos, multipotent progenitors divide to produce distinct progeny and express their full potential. In vertebrates, multipotent cardiopharyngeal progenitors produce second-heart-field-derived cardiomyocytes, and branchiomeric skeletal head muscles. However, the mechanisms underlying these early fate choices remain largely elusive. The tunicate Ciona emerged as an attractive model to study early cardiopharyngeal development at high resolution: through two asymmetric and oriented divisions, defined cardiopharyngeal progenitors produce distinct first and second heart precursors, and pharyngeal muscle (aka atrial siphon muscle, ASM) precursors. Here, we demonstrate that differential FGF-MAPK signaling distinguishes between heart and ASM precursors. We characterize a feed-forward circuit that promotes the successive activations of essential ASM determinants, Hand-related, Tbx1/10 and Ebf. Finally, we show that coupling FGF-MAPK restriction and cardiopharyngeal network deployment with cell divisions defines the timing of gene expression and permits the emergence of diverse cell types from multipotent progenitors. PMID:29431097

Types A and B Niemann-Pick Disease.

PubMed

Schuchman, Edward H; Wasserstein, Melissa P

2016-06-01

Two distinct metabolic abnormalities are included under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly, frequent pulmonary infections, and profound central nervous system involvement in infancy. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and progressive alterations of their lungs, but there are usually no central nervous system signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second category are designated as having type C NPD. Impaired intracellular trafficking of cholesterol causes type C NPD, and two distinct gene defects have been found. In this chapter only types A and B NPD will be discussed.

EDITORIAL: Adaptive and Active Materials: Selected Papers from the ASME 2008 Conference on Smart Materials, Adaptive Structures and Intelligent Systems (SMASIS 08) (Maryland, USA, 28-30 October 2008) Adaptive and Active Materials: Selected Papers from the ASME 2008 Conference on Smart Materials, Adaptive Structures and Intelligent Systems (SMASIS 08) (Maryland, USA, 28-30 October 2008)

NASA Astrophysics Data System (ADS)

Lynch, Christopher

2009-10-01

The rapid development of the field of Smart Materials, Adaptive Structures, and Materials Systems led the Aerospace Division ASMS TC to launch the new annual SMASIS conference in 2008. The conference focuses on the multi-disciplinary challenges of developing new multifunctional materials and implementing them in advanced systems. The research spans length scales from nano-structured materials to civil, air, and space structures. The first conference consisted of six symposia, each focusing on a different research area. This special issue of Smart Materials and Structures summarizes some of the top research presented at the 2008 SMASIS conference in the materials-focused symposia. These symposia focused on the behavior and mechanics of active materials, on multifunctional materials, and on bio-inspired materials. The behavior and mechanics of active materials is an approach that combines observed material behavior with mechanism-based models that not only give insight into the observed behavior, but guide the development of new materials. This approach has been applied to shape memory metals and polymers, ferroelectrics, ferromagnetics, and recently to multiferroic materials, and has led to considerable improvements in our understanding of multi-field phenomena. Multifunctional materials are the next generation of active materials. These materials include structural, sensing, and actuation components integrated into a material system. A natural extension of multifunctional materials is a new class of bio-inspired materials. Bio-inspired materials range from detailed bio-mimicry of sensing and self healing materials to nano and microstructures that take advantage of features observed in biological systems. The Editors would like to express their sincere thanks to all of the authors for their contributions to this special issue on 'Adaptive and Active Materials' for Smart Materials and Structures. We convey our gratitude to all of the reviewers for their time and dedication. We thank IOP Publishing for their support and encouragement of this special issue and the staff for their special attention and timely response.

Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice.

PubMed

Abu-Taweel, Gasem M; A, Zyadah M; Ajarem, Jamaan S; Ahmad, Mohammad

2014-01-01

The present study was designed to investigate the in vivo effects of monosodium glutamate (MSG) and aspartame (ASM) individually and in combination on the cognitive behavior and biochemical parameters like neurotransmitters and oxidative stress indices in the brain tissue of mice. Forty male Swiss albino mice were randomly divided into four groups of ten each and were exposed to MSG and ASM through drinking water for one month. Group I was the control and was given normal tap water. Groups II and III received MSG (8 mg/kg) and ASM (32 mg/kg) respectively dissolved in tap water. Group IV received MSG and ASM together in the same doses. After the exposure period, the animals were subjected to cognitive behavioral tests in a shuttle box and a water maze. Thereafter, the animals were sacrificed and the neurotransmitters and oxidative stress indices were estimated in their forebrain tissue. Both MSG and ASM individually as well as in combination had significant disruptive effects on the cognitive responses, memory retention and learning capabilities of the mice in the order (MSG+ASM)>ASM>MSG. Furthermore, while MSG and ASM individually were unable to alter the brain neurotransmitters and the oxidative stress indices, their combination dose (MSG+ASM) decreased significantly the levels of neurotransmitters (dopamine and serotonin) and it also caused oxidative stress by increasing the lipid peroxides measured in the form of thiobarbituric acid-reactive substances (TBARS) and decreasing the level of total glutathione (GSH). Further studies are required to evaluate the synergistic effects of MSG and ASM on the neurotransmitters and oxidative stress indices and their involvement in cognitive dysfunctions. Copyright © 2014 Elsevier Inc. All rights reserved.

Defining a Role for Acid Sphingomyelinase in the p38/Interleukin-6 Pathway*

PubMed Central

Perry, David M.; Newcomb, Benjamin; Adada, Mohamad; Wu, Bill X.; Roddy, Patrick; Kitatani, Kazuyuki; Siskind, Leah; Obeid, Lina M.; Hannun, Yusuf A.

2014-01-01

Acid sphingomyelinase (ASM) is one of the key enzymes involved in regulating the metabolism of the bioactive sphingolipid ceramide in the sphingolipid salvage pathway, yet defining signaling pathways by which ASM exerts its effects has proven difficult. Previous literature has implicated sphingolipids in the regulation of cytokines such as interleukin-6 (IL-6), but the specific sphingolipid pathways and mechanisms involved in inflammatory signaling need to be further elucidated. In this work, we sought to define the role of ASM in IL-6 production because our previous work showed that a parallel pathway of ceramide metabolism, acid β-glucosidase 1, negatively regulates IL-6. First, silencing ASM with siRNA abrogated IL-6 production in response to the tumor promoter, 4β-phorbol 12-myristate 13-acetate (PMA), in MCF-7 cells, in distinction to acid β-glucosidase 1 and acid ceramidase, suggesting specialization of the pathways. Moreover, treating cells with siRNA to ASM or with the indirect pharmacologic inhibitor desipramine resulted in significant inhibition of TNFα- and PMA-induced IL-6 production in MDA-MB-231 and HeLa cells. Knockdown of ASM was found to significantly inhibit PMA-dependent IL-6 induction at the mRNA level, probably ruling out mechanisms of translation or secretion of IL-6. Further, ASM knockdown or desipramine blunted p38 MAPK activation in response to TNFα, revealing a key role for ASM in activating p38, a signaling pathway known to regulate IL-6 induction. Last, knockdown of ASM dramatically blunted invasion of HeLa and MDA-MB-231 cells through Matrigel. Taken together, these results demonstrate that ASM plays a critical role in p38 signaling and IL-6 synthesis with implications for tumor pathobiology. PMID:24951586

Overexpression of microRNA-375 impedes platelet-derived growth factor-induced proliferation and migration of human fetal airway smooth muscle cells by targeting Janus kinase 2.

PubMed

Ji, Yamei; Yang, Xin; Su, Huixia

2018-02-01

The abnormal proliferation and migration of airway smooth muscle (ASM) cells play a critical role in airway remodeling during the development of asthma. MicroRNAs (miRNAs) have emerged as critical regulators of ASM cell proliferation and migration in airway remodeling. In this study, we aimed to investigate the potential role of miR-375 in the regulation of platelet-derived growth factor (PDGF)-induced fetal ASM cell proliferation and migration. Our results showed that miR-375 expression was significantly decreased in fetal ASM cells that were treated with PDGF. Functional data showed that overexpression of miR-375 inhibited the proliferation and migration of fetal ASM cells, whereas inhibition of miR-375 enhanced the proliferation and migration of fetal ASM cells. The results of bioinformatics analysis and a dual-luciferase reporter assay showed that miR-375 binds directly to the 3'-untranslated region of Janus kinase 2 (JAK2). Further data confirmed that miR-375 negatively regulates the expression of JAK2 in fetal ASM cells. Moreover, miR-375 also impeded the PDGF-induced activation of signal transducer and activator of transcription 3 (STAT3) in fetal ASM cells. However, restoration of JAK2 expression partially reversed the inhibitory effect of miR-375 on fetal ASM cell proliferation and migration. Overall, our results demonstrate that miR-375 inhibits fetal ASM cell proliferation and migration by targeting JAK2/STAT3 signaling. Our study provides a potential therapeutic target for the development of novel treatment strategies for pediatric asthma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Probing the Mysteries of the X-Ray Binary 4U 1210-64 with ASM, MAXI and Suzaku

NASA Astrophysics Data System (ADS)

Coley, Joel B.; Corbet, R.; Mukai, K.; Pottschmidt, K.

2013-01-01

Optical and X-ray observations of 4U 1210-64 (1ES 1210-646) suggest that the source is a High Mass X-ray Binary (HMXB) probably powered by the Be mechanism. Data acquired by the RXTE All Sky Monitor (ASM), the ISS Monitor of All-sky X-ray Image (MAXI) and Suzaku provide a detailed temporal and spectral description of this poorly understood source. Long-term data produced by ASM and MAXI indicate that the source shows two distinct high and low states. A 6.7-day orbital period of the system was found in folded light curves produced by both ASM and MAXI. A two day Suzaku observation in Dec. 2010 took place during a transition from the minimum to the maximum of the folded light curve. The two day Suzaku observation reveals large variations in flux indicative of strong orbit to orbit variability. Flares in the Suzaku light curve can reach nearly 1.4 times the mean count rate. From a spectral analysis of the Suzaku data, emission lines in the Fe K alpha region were detected at 6.4 keV, 6.7 keV and 6.97 keV interpreted as FeI, FeXXV and FeXXVI. In addition, emission lines were observed at approximately 1.0 and 2.6 keV, corresponding to NeX and SXVI respectively. Thermal bremsstrahlung or power law models both modified by interstellar and partially covering absorption provide a good fit to the continuum data. This source is intriguing for these reasons: i) No pulse period was observed; ii) 6.7 day orbital period is much less than typical orbital periods seen in Be/X-ray Binaries; iii) The optical companion is a B5V--an unusual spectral class for an HMXB; iv) There are extended high and low X-ray states.

ASME Nuclear Crane Standards for Enhanced Crane Safety and Increased Profit

NASA Astrophysics Data System (ADS)

Parkhurst, Stephen N.

2000-01-01

The ASME NOG-1 standard, 'Rules for Construction of Overhead and Gantry Cranes', covers top running cranes for nuclear facilities; with the ASME NUM-1 standard, 'Rules for Construction of Cranes, Monorails, and Hoists', covering the single girder, underhung, wall and jib cranes, as well as the monorails and hoists. These two ASME nuclear crane standards provide criteria for designing, inspecting and testing overhead handling equipment with enhanced safety to meet the 'defense-in-depth' approach of the United States Nuclear Regulatory Commission (USNRC) documents NUREG 0554 and NUREG 0612. In addition to providing designs for enhanced safety, the ASME nuclear crane standards provide a basis for purchasing overhead handling equipment with standard safety features, based upon accepted engineering principles, and including performance and environmental parameters specific to nuclear facilities. The ASME NOG-1 and ASME NUM-1 standards not only provide enhanced safety for handling a critical load, but also increase profit by minimizing the possibility of load drops, by reducing cumbersome operating restrictions, and by providing the foundation for a sound licensing position. The ASME nuclear crane standards can also increase profit by providing the designs and information to help ensure that the right standard equipment is purchased. Additionally, the ASME nuclear crane standards can increase profit by providing designs and information to help address current issues, such as the qualification of nuclear plant cranes for making 'planned engineered lifts' for steam generator replacement and decommissioning.

An RGS4-mediated phenotypic switch of bronchial smooth muscle cells promotes fixed airway obstruction in asthma.

PubMed

Damera, Gautam; Druey, Kirk M; Cooper, Philip R; Krymskaya, Vera P; Soberman, Roy J; Amrani, Yassine; Hoshi, Toshinori; Brightling, Christopher E; Panettieri, Reynold A

2012-01-01

In severe asthma, bronchodilator- and steroid-insensitive airflow obstruction develops through unknown mechanisms characterized by increased lung airway smooth muscle (ASM) mass and stiffness. We explored the role of a Regulator of G-protein Signaling protein (RGS4) in the ASM hyperplasia and reduced contractile capacity characteristic of advanced asthma. Using immunocytochemical staining, ASM expression of RGS4 was determined in endobronchial biopsies from healthy subjects and those from subjects with mild, moderate and severe asthma. Cell proliferation assays, agonist-induced calcium mobilization and bronchoconstriction were determined in cultured human ASM cells and in human precision cut lung slices. Using gain- and loss-of-function approaches, the precise role of RGS proteins was determined in stimulating human ASM proliferation and inhibiting bronchoconstriction. RGS4 expression was restricted to a subpopulation of ASM and was specifically upregulated by mitogens, which induced a hyperproliferative and hypocontractile ASM phenotype similar to that observed in recalcitrant asthma. RGS4 expression was markedly increased in bronchial smooth muscle of patients with severe asthma, and expression correlated significantly with reduced pulmonary function. Whereas RGS4 inhibited G protein-coupled receptor (GPCR)-mediated bronchoconstriction, unexpectedly RGS4 was required for PDGF-induced proliferation and sustained activation of PI3K, a mitogenic signaling molecule that regulates ASM proliferation. These studies indicate that increased RGS4 expression promotes a phenotypic switch of ASM, evoking irreversible airway obstruction in subjects with severe asthma.

Understanding the Long-Term Spectral Variability of Cygnus X-1 from BATSE and ASM Observations

NASA Technical Reports Server (NTRS)

Zdziarski, Andrzej A.; Poutanen, Juri; Paciesas, William S.; Wen, Linqing; Six, N. Frank (Technical Monitor)

2002-01-01

We present a spectral analysis of observations of Cygnus X-1 by the RXTE/ASM (1.5-12 keV) and CGRO/BATSE (20-300 keV), including about 1200 days of simultaneous data. We find a number of correlations between intensities and hardnesses in different energy bands from 1.5 keV to 300 keV. In the hard (low) spectral state, there is a negative correlation between the ASM 1.5-12 keV flux and the hardness at any energy. In the soft (high) spectral state, the ASM flux is positively correlated with the ASM hardness (as previously reported) but uncorrelated with the BATSE hardness. In both spectral states, the BATSE hardness correlates with the flux above 100 keV, while it shows no correlation with the flux in the 20-100 keV range. At the same time, there is clear correlation between the BATSE fluxes below and above 100 keV. In the hard state, most of the variability can be explained by softening the overall spectrum with a pivot at approximately 50 keV. The observations show that there has to be another, independent variability pattern of lower amplitude where the spectral shape does not change when the luminosity changes. In the soft state, the variability is mostly caused by a variable hard (Comptonized) spectral component of a constant shape superimposed on a constant soft blackbody component. These variability patterns are in agreement with the dependence of the rms variability on the photon energy in the two states. We interpret the observed correlations in terms of theoretical Comptonization models. In the hard state, the variability appears to be driven mostly by changing flux in seed photons Comptonized in a hot thermal plasma cloud with an approximately constant power supply. In the soft state, the variability is consistent with flares of hybrid, thermal/nonthermal, plasma with variable power above a stable cold disk. Also, based on broadband pointed observations simultaneous with those of the ASM and BATSE, we find the intrinsic bolometric luminosity increases by a factor of approximately 3-4 from the hard state to the soft one, which supports models of the state transition based on a change of the accretion rate.

Effect of Loading History on Airway Smooth Muscle Cell-Matrix Adhesions.

PubMed

Irons, Linda; Owen, Markus R; O'Dea, Reuben D; Brook, Bindi S

2018-06-05

Integrin-mediated adhesions between airway smooth muscle (ASM) cells and the extracellular matrix (ECM) regulate how contractile forces generated within the cell are transmitted to its external environment. Environmental cues are known to influence the formation, size, and survival of cell-matrix adhesions, but it is not yet known how they are affected by dynamic fluctuations associated with tidal breathing in the intact airway. Here, we develop two closely related theoretical models to study adhesion dynamics in response to oscillatory loading of the ECM, representing the dynamic environment of ASM cells in vivo. Using a discrete stochastic-elastic model, we simulate individual integrin binding and rupture events and observe two stable regimes in which either bond formation or bond rupture dominate, depending on the amplitude of the oscillatory loading. These regimes have either a high or low fraction of persistent adhesions, which could affect the level of strain transmission between contracted ASM cells and the airway tissue. For intermediate loading, we observe a region of bistability and hysteresis due to shared loading between existing bonds; the level of adhesion depends on the loading history. These findings are replicated in a related continuum model, which we use to investigate the effect of perturbations mimicking deep inspirations (DIs). Because of the bistability, a DI applied to the high adhesion state could either induce a permanent switch to a lower adhesion state or allow a return of the system to the high adhesion state. Transitions between states are further influenced by the frequency of oscillations, cytoskeletal or ECM stiffnesses, and binding affinities, which modify the magnitudes of the stable adhesion states as well as the region of bistability. These findings could explain (in part) the transient bronchodilatory effect of a DI observed in asthmatics compared to a more sustained effect in normal subjects. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Abdomen and spinal cord segmentation with augmented active shape models

PubMed Central

Xu, Zhoubing; Conrad, Benjamin N.; Baucom, Rebeccah B.; Smith, Seth A.; Poulose, Benjamin K.; Landman, Bennett A.

2016-01-01

Abstract. Active shape models (ASMs) have been widely used for extracting human anatomies in medical images given their capability for shape regularization of topology preservation. However, sensitivity to model initialization and local correspondence search often undermines their performances, especially around highly variable contexts in computed-tomography (CT) and magnetic resonance (MR) images. In this study, we propose an augmented ASM (AASM) by integrating the multiatlas label fusion (MALF) and level set (LS) techniques into the traditional ASM framework. Using AASM, landmark updates are optimized globally via a region-based LS evolution applied on the probability map generated from MALF. This augmentation effectively extends the searching range of correspondent landmarks while reducing sensitivity to the image contexts and improves the segmentation robustness. We propose the AASM framework as a two-dimensional segmentation technique targeting structures with one axis of regularity. We apply AASM approach to abdomen CT and spinal cord (SC) MR segmentation challenges. On 20 CT scans, the AASM segmentation of the whole abdominal wall enables the subcutaneous/visceral fat measurement, with high correlation to the measurement derived from manual segmentation. On 28 3T MR scans, AASM yields better performances than other state-of-the-art approaches in segmenting white/gray matter in SC. PMID:27610400

Molecular mechanisms underlying airway smooth muscle contraction and proliferation: implications for asthma.

PubMed

Pelaia, Girolamo; Renda, Teresa; Gallelli, Luca; Vatrella, Alessandro; Busceti, Maria Teresa; Agati, Sergio; Caputi, Mario; Cazzola, Mario; Maselli, Rosario; Marsico, Serafino A

2008-08-01

Airway smooth muscle (ASM) plays a key role in bronchomotor tone, as well as in structural remodeling of the bronchial wall. Therefore, ASM contraction and proliferation significantly participate in the development and progression of asthma. Many contractile agonists also behave as mitogenic stimuli, thus contributing to frame a hyperresponsive and hyperplastic ASM phenotype. In this review, the molecular mechanisms and signaling pathways involved in excitation-contraction coupling and ASM cell growth will be outlined. Indeed, the recent advances in understanding the basic aspects of ASM biology are disclosing important cellular targets, currently explored for the implementation of new, more effective anti-asthma therapies.

Report on FY15 alloy 617 code rules development

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

Sham, Sam; Jetter, Robert I; Hollinger, Greg

2015-09-01

Due to its strength at very high temperatures, up to 950°C (1742°F), Alloy 617 is the reference construction material for structural components that operate at or near the outlet temperature of the very high temperature gas-cooled reactors. However, the current rules in the ASME Section III, Division 5 Subsection HB, Subpart B for the evaluation of strain limits and creep-fatigue damage using simplified methods based on elastic analysis have been deemed inappropriate for Alloy 617 at temperatures above 650°C (1200°F) (Corum and Brass, Proceedings of ASME 1991 Pressure Vessels and Piping Conference, PVP-Vol. 215, p.147, ASME, NY, 1991). The rationalemore » for this exclusion is that at higher temperatures it is not feasible to decouple plasticity and creep, which is the basis for the current simplified rules. This temperature, 650°C (1200°F), is well below the temperature range of interest for this material for the high temperature gas-cooled reactors and the very high temperature gas-cooled reactors. The only current alternative is, thus, a full inelastic analysis requiring sophisticated material models that have not yet been formulated and verified. To address these issues, proposed code rules have been developed which are based on the use of elastic-perfectly plastic (EPP) analysis methods applicable to very high temperatures. The proposed rules for strain limits and creep-fatigue evaluation were initially documented in the technical literature (Carter, Jetter and Sham, Proceedings of ASME 2012 Pressure Vessels and Piping Conference, papers PVP 2012 28082 and PVP 2012 28083, ASME, NY, 2012), and have been recently revised to incorporate comments and simplify their application. Background documents have been developed for these two code cases to support the ASME Code committee approval process. These background documents for the EPP strain limits and creep-fatigue code cases are documented in this report.« less

A method for assessment of the shape of the proximal femur and its relationship to osteoporotic hip fracture.

PubMed

Gregory, J S; Testi, D; Stewart, A; Undrill, P E; Reid, D M; Aspden, R M

2004-01-01

The shape of the proximal femur has been demonstrated to be important in the occurrence of fractures of the femoral neck. Unfortunately, multiple geometric measurements frequently used to describe this shape are highly correlated. A new method, active shape modeling (ASM) has been developed to quantify the morphology of the femur. This describes the shape in terms of orthogonal modes of variation that, consequently, are all independent. To test this method, digitized standard pelvic radiographs were obtained from 26 women who had suffered a hip fracture and compared with images from 24 age-matched controls with no fracture. All subjects also had their bone mineral density (BMD) measured at five sites using dual-energy X-ray absorptiometry. An ASM was developed and principal components analysis used to identify the modes which best described the shape. Discriminant analysis was used to determine which variable, or combination of variables, was best able to discriminate between the groups. ASM alone correctly identified 74% of the individuals and placed them in the appropriate group. Only one of the BMD values (Ward's triangle) achieved a higher value (82%). A combination of Ward's triangle BMD and ASM improved the accuracy to 90%. Geometric variables used in this study were weaker, correctly classifying less than 60% of the study group. Logistic regression showed that after adjustment for age, body mass index, and BMD, the ASM data was still independently associated with hip fracture (odds ratio (OR)=1.83, 95% confidence interval 1.08 to 3.11). The odds ratio was calculated relative to a 10% increase in the probability of belonging to the fracture group. Though these initial results were obtained from a limited data set, this study shows that ASM may be a powerful method to help identify individuals at risk of a hip fracture in the future.

S100A8 protein attenuates airway hyperresponsiveness by suppressing the contraction of airway smooth muscle.

PubMed

Xu, Yu-Dong; Wang, Yu; Yin, Lei-Miao; Park, Gyoung-Hee; Ulloa, Luis; Yang, Yong-Qing

2017-02-26

Airway hyperresponsiveness (AHR) is a major clinical problem in allergic asthma mainly caused by the hypercontractility of airway smooth muscles (ASM). S100A8 is an important member of the S100 calcium-binding protein family with a potential to regulate cell contractility. Here, we analyze the potential of S100A8 to regulate allergen-induced AHR and ASM contraction. Treatment with recombinant S100A8 (rS100A8) diminished airway hyperresponsiveness in OVA-sensitized rats. ASM contraction assays showed that rS100A8 reduced hypercontractility in both isolated tracheal rings and primary ASM cells treated by acetylcholine. rS100A8 markedly rescued the phosphorylation level of myosin light chain induced by acetylcholine in ASM cells. These results show that rS100A8 plays a protective role in regulating AHR in asthma by inhibiting ASM contraction. These results support S100A8 as a novel therapeutic target to control ASM contraction in asthma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A Review & Assessment of Current Operating Conditions Allowable Stresses in ASME Section III Subsection NH

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

R. W. Swindeman

2009-12-14

The current operating condition allowable stresses provided in ASME Section III, Subsection NH were reviewed for consistency with the criteria used to establish the stress allowables and with the allowable stresses provided in ASME Section II, Part D. It was found that the S{sub o} values in ASME III-NH were consistent with the S values in ASME IID for the five materials of interest. However, it was found that 0.80 S{sub r} was less than S{sub o} for some temperatures for four of the materials. Only values for alloy 800H appeared to be consistent with the criteria on which S{submore » o} values are established. With the intent of undertaking a more detailed evaluation of issues related to the allowable stresses in ASME III-NH, the availabilities of databases for the five materials were reviewed and augmented databases were assembled.« less

Integrin and GPCR Crosstalk in the Regulation of ASM Contraction Signaling in Asthma.

PubMed

Teoh, Chun Ming; Tam, John Kit Chung; Tran, Thai

2012-01-01

Airway hyperresponsiveness (AHR) is one of the cardinal features of asthma. Contraction of airway smooth muscle (ASM) cells that line the airway wall is thought to influence aspects of AHR, resulting in excessive narrowing or occlusion of the airway. ASM contraction is primarily controlled by agonists that bind G protein-coupled receptor (GPCR), which are expressed on ASM. Integrins also play a role in regulating ASM contraction signaling. As therapies for asthma are based on symptom relief, better understanding of the crosstalk between GPCRs and integrins holds good promise for the design of more effective therapies that target the underlying cellular and molecular mechanism that governs AHR. In this paper, we will review current knowledge about integrins and GPCRs in their regulation of ASM contraction signaling and discuss the emerging concept of crosstalk between the two and the implication of this crosstalk on the development of agents that target AHR.

Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.

PubMed

Matusovsky, Oleg S; Kachmar, Linda; Ijpma, Gijs; Bates, Genevieve; Zitouni, Nedjma; Benedetti, Andrea; Lavoie, Jean-Pierre; Lauzon, Anne-Marie

2016-05-01

Heaves is a naturally occurring equine disease that shares many similarities with human asthma, including reversible antigen-induced bronchoconstriction, airway inflammation, and remodeling. The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth muscle (ASM) in an equine model of asthma. Tracheal and peripheral ASM of heaves-affected horses under exacerbation, or under clinical remission of the disease, and control horses were dissected and freed of epithelium to measure unloaded shortening velocity (Vmax), stress (force/cross-sectional area), methacholine effective concentration at which 50% of the maximum response is obtained, and stiffness. Myofibrillar Mg(2+)-ATPase activity, actomyosin in vitro motility, and contractile protein expression were also measured. Horses with heaves had significantly greater Vmax and Mg(2+)-ATPase activity in peripheral airway but not in tracheal smooth muscle. In addition, a significant correlation was found between Vmax and the time elapsed since the end of the corticosteroid treatment for the peripheral airways in horses with heaves. Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared with controls and the horses under exacerbation, potentially due to remodeling. Actomyosin in vitro motility was not different between controls and horses with heaves. These data demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses. It is therefore conceivable that the trachealis muscle may not be representative of the peripheral ASM in human asthma either, but this will require further investigation.

Efficient transport of tropospheric aerosol into the stratosphere via the Asian summer monsoon anticyclone

NASA Astrophysics Data System (ADS)

Yu, Pengfei; Rosenlof, Karen H.; Liu, Shang; Telg, Hagen; Thornberry, Troy D.; Rollins, Andrew W.; Portmann, Robert W.; Bai, Zhixuan; Ray, Eric A.; Duan, Yunjun; Pan, Laura L.; Toon, Owen B.; Bian, Jianchun; Gao, Ru-Shan

2017-07-01

An enhanced aerosol layer near the tropopause over Asia during the June-September period of the Asian summer monsoon (ASM) was recently identified using satellite observations. Its sources and climate impact are presently not well-characterized. To improve understanding of this phenomenon, we made in situ aerosol measurements during summer 2015 from Kunming, China, then followed with a modeling study to assess the global significance. The in situ measurements revealed a robust enhancement in aerosol concentration that extended up to 2 km above the tropopause. A climate model simulation demonstrates that the abundant anthropogenic aerosol precursor emissions from Asia coupled with rapid vertical transport associated with monsoon convection leads to significant particle formation in the upper troposphere within the ASM anticyclone. These particles subsequently spread throughout the entire Northern Hemispheric (NH) lower stratosphere and contribute significantly (˜15%) to the NH stratospheric column aerosol surface area on an annual basis. This contribution is comparable to that from the sum of small volcanic eruptions in the period between 2000 and 2015. Although the ASM contribution is smaller than that from tropical upwelling (˜35%), we find that this region is about three times as efficient per unit area and time in populating the NH stratosphere with aerosol. With a substantial amount of organic and sulfur emissions in Asia, the ASM anticyclone serves as an efficient smokestack venting aerosols to the upper troposphere and lower stratosphere. As economic growth continues in Asia, the relative importance of Asian emissions to stratospheric aerosol is likely to increase.

Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ

PubMed Central

Brown, Amy; Danielsson, Jennifer; Townsend, Elizabeth A.; Zhang, Yi; Perez-Zoghbi, Jose F.; Emala, Charles W.

2016-01-01

Enhanced contractility of airway smooth muscle (ASM) is a major pathophysiological characteristic of asthma. Expanding the therapeutic armamentarium beyond β-agonists that target ASM hypercontractility would substantially improve treatment options. Recent studies have identified naturally occurring phytochemicals as candidates for acute ASM relaxation. Several flavonoids were evaluated for their ability to acutely relax human and murine ASM ex vivo and murine airways in vivo and were evaluated for their ability to inhibit procontractile signaling pathways in human ASM (hASM) cells. Two members of the flavonol subfamily, galangin and fisetin, significantly relaxed acetylcholine-precontracted murine tracheal rings ex vivo (n = 4 and n = 5, respectively, P < 0.001). Galangin and fisetin also relaxed acetylcholine-precontracted hASM strips ex vivo (n = 6–8, P < 0.001). Functional respiratory in vivo murine studies demonstrated that inhaled galangin attenuated the increase in lung resistance induced by inhaled methacholine (n = 6, P < 0.01). Both flavonols, galangin and fisetin, significantly inhibited purified phosphodiesterase-4 (PDE4) (n = 7, P < 0.05; n = 7, P < 0.05, respectively), and PLCβ enzymes (n = 6, P < 0.001 and n = 6, P < 0.001, respectively) attenuated procontractile Gq agonists' increase in intracellular calcium (n = 11, P < 0.001), acetylcholine-induced increases in inositol phosphates, and CPI-17 phosphorylation (n = 9, P < 0.01) in hASM cells. The prorelaxant effect retained in these structurally similar flavonols provides a novel pharmacological method for dual inhibition of PLCβ and PDE4 and therefore may serve as a potential treatment option for acute ASM constriction. PMID:26773068

Attenuation of airway smooth muscle contractility via flavonol-mediated inhibition of phospholipase-Cβ.

PubMed

Brown, Amy; Danielsson, Jennifer; Townsend, Elizabeth A; Zhang, Yi; Perez-Zoghbi, Jose F; Emala, Charles W; Gallos, George

2016-04-15

Enhanced contractility of airway smooth muscle (ASM) is a major pathophysiological characteristic of asthma. Expanding the therapeutic armamentarium beyond β-agonists that target ASM hypercontractility would substantially improve treatment options. Recent studies have identified naturally occurring phytochemicals as candidates for acute ASM relaxation. Several flavonoids were evaluated for their ability to acutely relax human and murine ASM ex vivo and murine airways in vivo and were evaluated for their ability to inhibit procontractile signaling pathways in human ASM (hASM) cells. Two members of the flavonol subfamily, galangin and fisetin, significantly relaxed acetylcholine-precontracted murine tracheal rings ex vivo (n = 4 and n = 5, respectively, P < 0.001). Galangin and fisetin also relaxed acetylcholine-precontracted hASM strips ex vivo (n = 6-8, P < 0.001). Functional respiratory in vivo murine studies demonstrated that inhaled galangin attenuated the increase in lung resistance induced by inhaled methacholine (n = 6, P < 0.01). Both flavonols, galangin and fisetin, significantly inhibited purified phosphodiesterase-4 (PDE4) (n = 7, P < 0.05; n = 7, P < 0.05, respectively), and PLCβ enzymes (n = 6, P < 0.001 and n = 6, P < 0.001, respectively) attenuated procontractile Gq agonists' increase in intracellular calcium (n = 11, P < 0.001), acetylcholine-induced increases in inositol phosphates, and CPI-17 phosphorylation (n = 9, P < 0.01) in hASM cells. The prorelaxant effect retained in these structurally similar flavonols provides a novel pharmacological method for dual inhibition of PLCβ and PDE4 and therefore may serve as a potential treatment option for acute ASM constriction. Copyright © 2016 the American Physiological Society.

Airway hyperresponsiveness; smooth muscle as the principal actor

PubMed Central

Lauzon, Anne-Marie; Martin, James G.

2016-01-01

Airway hyperresponsiveness (AHR) is a defining characteristic of asthma that refers to the capacity of the airways to undergo exaggerated narrowing in response to stimuli that do not result in comparable degrees of airway narrowing in healthy subjects. Airway smooth muscle (ASM) contraction mediates airway narrowing, but it remains uncertain as to whether the smooth muscle is intrinsically altered in asthmatic subjects or is responding abnormally as a result of the milieu in which it sits. ASM in the trachea or major bronchi does not differ in its contractile characteristics in asthmatics, but the more pertinent peripheral airways await complete exploration. The mass of ASM is increased in many but not all asthmatics and therefore cannot be a unifying hypothesis for AHR, although when increased in mass it may contribute to AHR. The inability of a deep breath to reverse or prevent bronchial narrowing in asthma may reflect an intrinsic difference in the mechanisms that lead to softening of contracted ASM when subjected to stretch. Cytokines such as interleukin-13 and tumor necrosis factor-α promote a more contractile ASM phenotype. The composition and increased stiffness of the matrix in which ASM is embedded promotes a more proliferative and pro-inflammatory ASM phenotype, but the expected dedifferentiation and loss of contractility have not been shown. Airway epithelium may drive ASM proliferation and/or molecular remodeling in ways that may lead to AHR. In conclusion, AHR is likely multifactorial in origin, reflecting the plasticity of ASM properties in the inflammatory environment of the asthmatic airway. PMID:26998246

Recent antiseizure medications in the Intensive Care Unit.

PubMed

Orinx, Cindy; Legros, Benjamin; Gaspard, Nicolas

2017-08-01

Seizures and status epilepticus (SE), both clinical and subclinical, are frequent in critically ill patients. The list of available antiseizure medications (ASMs) is expanding and now includes older and widely used drugs as well as more recent medications with a better safety and pharmacokinetics profile. We review a selection of recent publications about the indications and administration of ASMs in critical care for the prophylaxis and treatment of seizures and SE, focusing on recent ASMs available as intravenous formulation and emphasizing pharmacokinetics and safety issues in relation to several aspects of critical illness. Levetiracetam, lacosamide and more recently brivaracetam, represent interesting alternatives to older ASMs, mostly due to a more favorable safety and pharmacokinetic profile. Low-quality studies suggest that this profile results in better tolerability in treated patients. Ketamine might represent a useful addition in our anesthetic armamentarium for refractory SE, due to its different mechanism of action and cardiovascular properties. Little evidence is available however to support the prophylactic use of ASMs in critically ill patients, except in specific settings (traumatic brain injury and subarachnoid hemorrhage). Head-to-head studies comparing recent and older ASMs in the treatment of acute seizures and SE are ongoing or awaiting publication. Administration of ASMs to critically ill patients needs to be adapted to organ dysfunction, and especially to renal dysfunction for recent drugs. Recent ASMs and could represent better treatment choices in critically ill patients than older ones but this needs to be confirmed in randomized controlled studies. In general, further studies are required to clarify the indications and optimal use of ASMs in the critical care setting.

Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2.

PubMed

Oninla, Vincent O; Breiden, Bernadette; Babalola, Jonathan O; Sandhoff, Konrad

2014-12-01

During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747-1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Active Solvent Modulation: A Valve-Based Approach To Improve Separation Compatibility in Two-Dimensional Liquid Chromatography.

PubMed

Stoll, Dwight R; Shoykhet, Konstantin; Petersson, Patrik; Buckenmaier, Stephan

2017-09-05

Two-dimensional liquid chromatography (2D-LC) is increasingly being viewed as a viable tool for solving difficult separation problems, ranging from targeted separations of structurally similar molecules to untargeted separations of highly complex mixtures. In spite of this performance potential, though, many users find method development challenging and most frequently cite the "incompatibility" between the solvent systems used in the first and second dimensions as a major obstacle. This solvent strength related incompatibility can lead to severe peak distortion and loss of resolution and sensitivity in the second dimension. In this paper, we describe a novel approach to address the incompatibility problem, which we refer to as Active Solvent Modulation (ASM). This valve-based approach enables dilution of 1 D effluent with weak solvent prior to transfer to the 2 D column but without the need for additional instrument hardware. ASM is related to the concept we refer to as Fixed Solvent Modulation (FSM), with the important difference being that ASM allows toggling of the diluent stream during each 2 D separation cycle. In this work, we show that ASM eliminates the major drawbacks of FSM including complex elution solvent profiles, baseline disturbances, and slow 2 D re-equilibration and demonstrate improvements in 2 D separation quality using both simple small molecule probes and degradants of heat-treated bovine insulin as case studies. We believe that ASM will significantly ease method development for 2D-LC, providing a path to practical methods that involve both highly complementary 1 D and 2 D separations and sensitive detection.

An Intercomparison of Tropospheric Ozone Retrievals Derived from Two Aura Instruments and Measurements in Western North America in 2006

NASA Technical Reports Server (NTRS)

Doughty, D. C.; Thompson, A. M.; Schoeberl, M. R.; Stajner, I.; Wargan, K.; Hui, W. C. J.

2011-01-01

Two recently developed methods for quantifying tropospheric ozone abundances based on Aura data, the Trajectory-enhanced Tropospheric Ozone Residual (TTOR) and an assimilation of Aura data into Goddard Earth Observing System Version 4 (ASM), are compared to ozone measurements from ozonesonde data collected in April-May 2006 during the INTEX Ozonesonde Network Study 2006 (IONS-06) campaign. Both techniques use Ozone Monitoring Instrument (OMI) and Microwave Limb Sounder (MLS) observations. Statistics on column ozone amounts for both products are presented. In general, the assimilation compares better to sonde integrated ozone to 200 hPa (28.6% difference for TTOR versus 2.7% difference for ASM), and both products are biased low. To better characterize the performance of ASM, ozone profiles based on the assimilation are compared to those from ozonesondes. We noted slight negative biases in the lower troposphere, and slight positive biases in the upper troposphere/lower stratosphere (UT/ LS), where we observed the greatest variability. Case studies were used to further understand ASM performance. We examine one case from 17 April 2006 at Bratt's Lake, Saskatchewan, where geopotential height gradients appear to be related to an underestimation in the ASM in the UT/LS region. A second case, from 21 April 2006 at Trinidad Head, California, is a situation where the overprediction of ozone in the UT/LS region does not appear to be due to current dynamic conditions but seems to be related to uncertainty in the flow pattern and large differences in MLS observations upstream.

Changes in the Long-Term Intensity Variations in Cygnus X-2 and LMC X-3

NASA Astrophysics Data System (ADS)

Paul, B.; Kitamoto, S.; Makino, F.

2000-01-01

We report the detection of changes in the long-term intensity variations in two X-ray binaries, Cyg X-2 and LMC X-3. In this work, we have used the long-term light curves obtained with the All-Sky Monitors (ASMs) of the Rossi X-Ray Timing Explorer (RXTE), Ginga, Ariel 5, and Vela 5B and the scanning modulation collimator of HEAO 1. It is found that in the light curves of both the sources, obtained with these instruments at various times over the last 30 years, more than one periodic or quasi-periodic component is always present. The multiple prominent peaks in the periodograms have frequencies unrelated to each other. In Cyg X-2, RXTE-ASM data show strong peaks at 40.4 and 68.8 days, and Ginga-ASM data show strong peaks at 53.7 and 61.3 days. Multiple peaks are also observed in LMC X-3. The various strong peaks in the periodograms of LMC X-3 appear at 104, 169, and 216 days (observed with RXTE-ASM) and 105, 214, and 328 days (observed with Ginga-ASM). The present results, when compared with the earlier observations of periodicities in these two systems, demonstrate the absence of any stable long period. The 78 day periodicity detected earlier in Cyg X-2 was probably due to the short time base in the RXTE data that were used, and the periodicity of 198 days in LMC X-3 was due to a relatively short duration of observation with HEAO 1.

Whole abdominal wall segmentation using augmented active shape models (AASM) with multi-atlas label fusion and level set

NASA Astrophysics Data System (ADS)

Xu, Zhoubing; Baucom, Rebeccah B.; Abramson, Richard G.; Poulose, Benjamin K.; Landman, Bennett A.

2016-03-01

The abdominal wall is an important structure differentiating subcutaneous and visceral compartments and intimately involved with maintaining abdominal structure. Segmentation of the whole abdominal wall on routinely acquired computed tomography (CT) scans remains challenging due to variations and complexities of the wall and surrounding tissues. In this study, we propose a slice-wise augmented active shape model (AASM) approach to robustly segment both the outer and inner surfaces of the abdominal wall. Multi-atlas label fusion (MALF) and level set (LS) techniques are integrated into the traditional ASM framework. The AASM approach globally optimizes the landmark updates in the presence of complicated underlying local anatomical contexts. The proposed approach was validated on 184 axial slices of 20 CT scans. The Hausdorff distance against the manual segmentation was significantly reduced using proposed approach compared to that using ASM, MALF, and LS individually. Our segmentation of the whole abdominal wall enables the subcutaneous and visceral fat measurement, with high correlation to the measurement derived from manual segmentation. This study presents the first generic algorithm that combines ASM, MALF, and LS, and demonstrates practical application for automatically capturing visceral and subcutaneous fat volumes.

National Manpower Inventory. Volume 3. Technical Documentation for Software for the Model

DTIC Science & Technology

1985-09-01

Technician APS-96 Search Radar IMA Technician USM-449 (V) & AAI 5500 Series ATE Int Maintenance Level Tech. CO CP-413/ASA-27A SACE TesI Bench IMA...MATE) Test Console IMA Technician ALQ-91/108 DECM IMA Technician ALQ-99 ECM Jammer/Tmilter & ALM-107 TesI Console IMA Technician ALQ-99 ECM Track...Receivers & ALM-109 TesI Console IMA Technician ECM Systems Intermediate Maintenance Technician ASM-347 (GT-1) SACE Programmer/Mainlenanca IMA

Longitudinal structure in temperate stream fish communities: evaluating conceptual models with temporal data

USGS Publications Warehouse

Roberts, James H.; Hitt, Nathaniel P.

2010-01-01

Five conceptual models of longitudinal fish community organization in streams were examined: (1) niche diversity model (NDM), (2) stream continuum model (SCM), (3) immigrant accessibility model (IAM), (4) environmental stability model (ESM), and (5) adventitious stream model (ASM). We used differences among models in their predictions about temporal species turnover, along with five spatiotemporal fish community data sets, to evaluate model applicability. Models were similar in predicting a positive species richness–stream size relationship and longitudinal species nestedness, but differed in predicting either similar temporal species turnover throughout the stream continuum (NDM, SCM), higher turnover upstream (IAM, ESM), or higher turnover downstream (ASM). We calculated measures of spatial and temporal variation from spatiotemporal fish data in five wadeable streams in central and eastern North America spanning 34–68 years (French Creek [New York], Piasa Creek [Illinois], Spruce Run [Virginia], Little Stony Creek [Virginia], and Sinking Creek [Virginia]). All streams exhibited substantial species turnover (i.e., at least 27% turnover in stream-scale species pools), in contrast to the predictions of the SCM. Furthermore, community change was greater in downstream than upstream reaches in four of five streams. This result is most consistent with the ASM and suggests that downstream communities are strongly influenced by migrants to and from species pools outside the focal stream. In Sinking Creek, which is isolated from external species pools, temporal species turnover (via increased richness) was higher upstream than downstream, which is a pattern most consistent with the IAM or ESM. These results corroborate the hypothesis that temperate stream habitats and fish communities are temporally dynamic and that fish migration and environmental disturbances play fundamental roles in stream fish community organization.

SLATE: scanning laser automatic threat extraction

NASA Astrophysics Data System (ADS)

Clark, David J.; Prickett, Shaun L.; Napier, Ashley A.; Mellor, Matthew P.

2016-10-01

SLATE is an Autonomous Sensor Module (ASM) designed to work with the SAPIENT system providing accurate location tracking and classifications of targets that pass through its field of view. The concept behind the SLATE ASM is to produce a sensor module that provides a complementary view of the world to the camera-based systems that are usually used for wide area surveillance. Cameras provide a hi-fidelity, human understandable view of the world with which tracking and identification algorithms can be used. Unfortunately, positioning and tracking in a 3D environment is difficult to implement robustly, making location-based threat assessment challenging. SLATE uses a Scanning Laser Rangefinder (SLR) that provides precise (<1cm) positions, sizes, shapes and velocities of targets within its field-of-view (FoV). In this paper we will discuss the development of the SLATE ASM including the techniques used to track and classify detections that move through the field of view of the sensor providing the accurate tracking information to the SAPIENT system. SLATE's ability to locate targets precisely allows subtle boundary-crossing judgements, e.g. on which side of a chain-link fence a target is. SLATE's ability to track targets in 3D throughout its FoV enables behavior classification such as running and walking which can provide an indication of intent and help reduce false alarm rates.

Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

PubMed

Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

2015-12-01

Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone

PubMed Central

Pearson, Helen; Britt, Rodney D.; Pabelick, Christine M.; Prakash, Y.S.; Amrani, Yassine; Pandya, Hitesh C.

2016-01-01

Background Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Methods Cultured fetal human ASM cells stimulated with TNF-α (0–20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. Results CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Conclusion Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases. PMID:26331770

MicroRNA-20b-5p inhibits platelet-derived growth factor-induced proliferation of human fetal airway smooth muscle cells by targeting signal transducer and activator of transcription 3.

PubMed

Tang, Jin; Luo, Lingying

2018-06-01

Pediatric asthma is still a health threat to the pediatric population in recent years. The airway remodeling induced by abnormal airway smooth muscle (ASM) cell proliferation is an important cause of asthma. MicroRNAs (miRNAs) are important regulators of ASM cell proliferation. Numerous studies have reported that miR-20b-5p is a critical regulator for cell proliferation. However, whether miR-20b-5p is involved in regulating ASM cell proliferation remains unknown. In this study, we aimed to investigate the potential role of miR-20b-5p in regulating the proliferation of fetal ASM cell induced by platelet-derived growth factor (PDGF). Here, we showed that miR-20b-5p was significantly decreased in fetal ASM cells treated with PDGF. Biological experiments showed that the overexpression of miR-20b-5p inhibited the proliferation while miR-20b-5p inhibition markedly promoted the proliferation of fetal ASM cells. Bioinformatics analysis and luciferase reporter assay showed that miR-20b-5p directly targeted the 3'-UTR of signal transducer and activator of transcription 3 (STAT3). Further data showed that miR-20b-5p negatively regulated the expression of STAT3 in fetal ASM cells. Moreover, miR-20b-5p regulates the transcriptional activity of STAT3 in fetal ASM cells. Overexpression of STAT3 reversed the inhibitory effect of miR-20b-5p overexpression on fetal ASM cell proliferation while the knockdown of STAT3 abrogated the promoted effect of miR-20b-5p inhibition on fetal ASM cell proliferation. Overall, our results show that miR-20b-5p impedes PDGF-induced proliferation of fetal ASM cells through targeting STAT3. Our study suggests that miR-20b-5p may play an important role in airway remodeling during asthma and suggests that miR-20b-5p may serve as a potential therapeutic target for pediatric asthma. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

14 CFR 330.31 - What data must air carriers submit concerning ASMs or RTMs?

Code of Federal Regulations, 2010 CFR

2010-01-01

... combination passenger/cargo carrier, you must have submitted your August 2001 total completed ASM report to... correct an error that you document to the Department, you must not alter the ASM or RTM reports you...

Rapid equilibrium sampling initiated from nonequilibrium data.

PubMed

Huang, Xuhui; Bowman, Gregory R; Bacallado, Sergio; Pande, Vijay S

2009-11-24

Simulating the conformational dynamics of biomolecules is extremely difficult due to the rugged nature of their free energy landscapes and multiple long-lived, or metastable, states. Generalized ensemble (GE) algorithms, which have become popular in recent years, attempt to facilitate crossing between states at low temperatures by inducing a random walk in temperature space. Enthalpic barriers may be crossed more easily at high temperatures; however, entropic barriers will become more significant. This poses a problem because the dominant barriers to conformational change are entropic for many biological systems, such as the short RNA hairpin studied here. We present a new efficient algorithm for conformational sampling, called the adaptive seeding method (ASM), which uses nonequilibrium GE simulations to identify the metastable states, and seeds short simulations at constant temperature from each of them to quantitatively determine their equilibrium populations. Thus, the ASM takes advantage of the broad sampling possible with GE algorithms but generally crosses entropic barriers more efficiently during the seeding simulations at low temperature. We show that only local equilibrium is necessary for ASM, so very short seeding simulations may be used. Moreover, the ASM may be used to recover equilibrium properties from existing datasets that failed to converge, and is well suited to running on modern computer clusters.

Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation.

PubMed

Ambhore, Nilesh Sudhakar; Katragadda, Rathnavali; Raju Kalidhindi, Rama Satyanarayana; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S; Sathish, Venkatachalem

2018-04-20

Airway smooth muscle (ASM) cell hyperplasia driven by persistent inflammation is a hallmark feature of remodeling in asthma. Sex steroid signaling in the lungs is of considerable interest, given epidemiological data showing more asthma in pre-menopausal women and aging men. Our previous studies demonstrated that estrogen receptor (ER) expression increases in asthmatic human ASM; however, very limited data are available regarding differential roles of ERα vs. ERβ isoforms in human ASM cell proliferation. In this study, we evaluated the effect of selective ERα and ERβ modulators on platelet-derived growth factor (PDGF)-stimulated ASM proliferation and the mechanisms involved. Asthmatic and non-asthmatic primary human ASM cells were treated with PDGF, 17β-estradiol, ERα-agonist and/or ERβ-agonist and/or G-protein-coupled estrogen receptor 30 (GPR30/GPER) agonist and proliferation was measured using MTT and CyQuant assays followed by cell cycle analysis. Transfection of small interfering RNA (siRNA) ERα and ERβ significantly altered the human ASM proliferation. The specificity of siRNA transfection was confirmed by Western blot analysis. Gene and protein expression of cell cycle-related antigens (PCNA and Ki67) and C/EBP were measured by RT-PCR and Western analysis, along with cell signaling proteins. PDGF significantly increased ASM proliferation in non-asthmatic and asthmatic cells. Treatment with PPT showed no significant effect on PDGF-induced proliferation, whereas WAY interestingly suppressed proliferation via inhibition of ERK1/2, Akt, and p38 signaling. PDGF-induced gene expression of PCNA, Ki67 and C/EBP in human ASM was significantly lower in cells pre-treated with WAY. Furthermore, WAY also inhibited PDGF-activated PCNA, C/EBP, cyclin-D1, and cyclin-E. Overall, we demonstrate ER isoform-specific signaling in the context of ASM proliferation. Activation of ERβ can diminish remodeling in human ASM by inhibiting pro-proliferative signaling pathways, and may point to a novel perception for blunting airway remodeling. Copyright © 2018 Elsevier B.V. All rights reserved.

Globalization of ASME Nuclear Codes and Standards

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

Swayne, Rick; Erler, Bryan A.

2006-07-01

With the globalization of the nuclear industry, it is clear that the reactor suppliers are based in many countries around the world (such as United States, France, Japan, Canada, South Korea, South Africa) and they will be marketing their reactors to many countries around the world (such as US, China, South Korea, France, Canada, Finland, Taiwan). They will also be fabricating their components in many different countries around the world. With this situation, it is clear that the requirements of ASME Nuclear Codes and Standards need to be adjusted to accommodate the regulations, fabricating processes, and technology of various countriesmore » around the world. It is also very important for the American Society of Mechanical Engineers (ASME) to be able to assure that products meeting the applicable ASME Code requirements will provide the same level of safety and quality assurance as those products currently fabricated under the ASME accreditation process. To do this, many countries are in the process of establishing or changing their regulations, and it is important for ASME to interface with the appropriate organizations in those countries, in order to ensure there is effective use of ASME Codes and standards around the world. (authors)« less

Observations of Near-Bottom Flow in a Wave-Dominated Nearshore Environment.

DTIC Science & Technology

1994-02-01

E 0 0 0 ~- X : (- 1.. pI m~ ffm ~o .pcr onf> ..... X • -- E X/• x,. "£ "*.. . .. . 0o 0 0 a c c ,(s0wO) (S/PH w) (SlUwo) . 7109 I 3 I Mean of LDV...1 I 8250 ASM X,ANDA #&HBF :REM 0000 OXXX ACCA 8260 ASM X,ANDB #&HBF :REM 0000 1XXX ACCB 8270 ASM X,STAB &H17 :REM /CS=0 3 8280 ASM X,STAA &H17 :REM

49 CFR 230.8 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... American National Standards Institute. API. American Petroleum Institute. ASME. American Society of... metropolitan areas, without regard to whether those systems use new technologies not associated with...

49 CFR 230.8 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... American National Standards Institute. API. American Petroleum Institute. ASME. American Society of... metropolitan areas, without regard to whether those systems use new technologies not associated with...

Glucocorticoid- and Protein Kinase A–Dependent Transcriptome Regulation in Airway Smooth Muscle

PubMed Central

Misior, Anna M.; Deshpande, Deepak A.; Loza, Matthew J.; Pascual, Rodolfo M.; Hipp, Jason D.; Penn, Raymond B.

2009-01-01

Glucocorticoids (GCs) and protein kinase A (PKA)–activating agents (β-adrenergic receptor agonists) are mainstream asthma therapies based on their ability to prevent or reverse excessive airway smooth muscle (ASM) constriction. Their abilities to regulate another important feature of asthma—excessive ASM growth—are poorly understood. Recent studies have suggested that GCs render agents of inflammation such as IL-1β and TNF-α mitogenic to ASM, via suppression of (antimitogenic) induced cyclooxygenase-2–dependent PKA activity. To further explore the mechanistic basis of these observations, we assessed the effects of epidermal growth factor and IL-1β stimulation, and the modulatory effects of GC treatment and PKA inhibition, on the ASM transcriptome by microarray analysis. Results demonstrate that ASM stimulated with IL-1β, in a manner that is often cooperative with stimulation with epidermal growth factor, exhibit a profound capacity to function as immunomodulatory cells. Moreover, results implicate an important role for induced autocrine/paracrine factors (many whose regulation was minimally affected by GCs or PKA inhibition) as regulators of both airway inflammation and ASM growth. Induction of numerous chemokines, in conjunction with regulation of proteases and agents of extracellular matrix remodeling, is suggested as an important mechanism promoting upregulated G protein–coupled receptor signaling capable of stimulating ASM growth. Additional functional assays suggest that intracellular PKA plays a critical role in suppressing the promitogenic effects of induced autocrine factors in ASM. Finally, identification and comparison of GC- and PKA-sensitive genes in ASM provide insight into the complementary effects of β-agonist/GC combination therapies, and suggest specific genes as important targets for guiding the development of new generations of GCs and adjunct asthma therapies. PMID:19059887

Inhibition of allergen-induced basophil activation by ASM-024, a nicotinic receptor ligand.

PubMed

Watson, Brittany M; Oliveria, John Paul; Nusca, Graeme M; Smith, Steven G; Beaudin, Sue; Dua, Benny; Watson, Rick M; Assayag, Evelynne Israël; Cormier, Yvon F; Sehmi, Roma; Gauvreau, Gail M

2014-01-01

Nicotinic acetylcholine receptors (nAChRs) were identified on eosinophils and shown to regulate inflammatory responses, but nAChR expression on basophils has not been explored yet. We investigated surface receptor expression of nAChR α4, α7 and α1/α3/α5 subunits on basophils. Furthermore, we examined the effects of ASM-024, a synthetic nicotinic ligand, on in vitro anti-IgE and in vivo allergen-induced basophil activation. Basophils were enriched from the peripheral blood of allergic donors and the expression of nAChR subunits and muscarinic receptors was determined. Purified basophils were stimulated with anti-IgE in the presence of ASM-024 with or without muscarinic or nicotinic antagonists for the measurement of CD203c expression and histamine release. The effect of 9 days of treatment with 50 and 200 mg ASM-024 on basophil CD203c expression was examined in the blood of mild allergic asthmatics before and after allergen inhalation challenge. nAChR α4, α7 and α1/α3/α5 receptor subunit expression was detected on basophils. Stimulation of basophils with anti-IgE increased CD203c expression and histamine release, which was inhibited by ASM-024 (10(-5) to 10(-)(3) M, p < 0.05). The effect of ASM-024 was reversed in the presence of muscarinic and nicotinic antagonists. In subjects with mild asthma, ASM-024 inhalation significantly inhibited basophil CD203c expression measured 24 h after allergen challenge (p = 0.03). This study shows that ASM-024 inhibits IgE- and allergen-induced basophil activation through both nicotinic and muscarinic receptors, and suggests that ASM-024 may be an efficacious agent for modulating allergic asthma responses. © 2015 S. Karger AG, Basel.

Acid Sphingomyelinase (ASM) is a Negative Regulator of Regulatory T Cell (Treg) Development.

PubMed

Zhou, Yuetao; Salker, Madhuri S; Walker, Britta; Münzer, Patrick; Borst, Oliver; Gawaz, Meinrad; Gulbins, Erich; Singh, Yogesh; Lang, Florian

2016-01-01

Regulatory T cell (Treg) is required for the maintenance of tolerance to various tissue antigens and to protect the host from autoimmune disorders. However, Treg may, indirectly, support cancer progression and bacterial infections. Therefore, a balance of Treg function is pivotal for adequate immune responses. Acid sphingomyelinase (ASM) is a rate limiting enzyme involved in the production of ceramide by breaking down sphingomyelin. Previous studies in T-cells have suggested that ASM is involved in CD28 signalling, T lymphocyte granule secretion, degranulation, and vesicle shedding similar to the formation of phosphatidylserine-exposing microparticles from glial cells. However, whether ASM affects the development of Treg has not yet been described. Splenocytes, isolated Naive T lymphocytes and cultured T cells were characterized for various immune T cell markers by flow cytometery. Cell proliferation was measured by Carboxyfluorescein succinimidyl ester (CFSE) dye, cell cycle analysis by Propidium Iodide (PI), mRNA transcripts by q-RT PCR and protein expression by Western Blotting respectively. ASM deficient mice have higher number of Treg compared with littermate control mice. In vitro induction of ASM deficient T cells in the presence of TGF-β and IL-2 lead to a significantly higher number of Foxp3+ induced Treg (iTreg) compared with control T-cells. Further, ASM deficient iTreg has less AKT (serine 473) phosphorylation and Rictor levels compared with control iTreg. Ceramide C6 led to significant reduction of iTreg in both ASM deficient and WT mice. The reduction in iTreg leads to induction of IL-1β, IL-6 and IL-17 but not IFN-γ mRNA levels. ASM is a negative regulator of natural and iTreg. © 2016 The Author(s) Published by S. Karger AG, Basel.

ASM observations of X-ray flares from 4U 0115+63 and ASM 1354-64.

NASA Astrophysics Data System (ADS)

Tsunemi, H.; Kitamoto, S.

The authors report two X-ray flares detected with the All Sky Monitor (ASM) on board the GINGA satellite. One is from the recurrent X-ray pulsar 4U 0115+63 and the other is from the probable recurrent X-ray nova named ASM 1354-64. The maximum intensity for 4U 0115+63 was 180 mCrab and its duration was at least 22 days. Its spectrum was hard and resembled those of X-ray pulsars. The maximum intensity of ASM 1354-64 was 300 mCrab. It faded down below the detection limit at the end of August 1987. Its spectrum was soft and was similar to those of black hole candidates.

Threat assessment and sensor management in a modular architecture

NASA Astrophysics Data System (ADS)

Page, S. F.; Oldfield, J. P.; Islip, S.; Benfold, B.; Brandon, R.; Thomas, P. A.; Stubbins, D. J.

2016-10-01

Many existing asset/area protection systems, for example those deployed to protect critical national infrastructure, are comprised of multiple sensors such as EO/IR, radar, and Perimeter Intrusion Detection Systems (PIDS), loosely integrated with a central Command and Control (C2) system. Whilst some sensors provide automatic event detection and C2 systems commonly provide rudimentary multi-sensor rule based alerting, the performance of such systems is limited by the lack of deep integration and autonomy. As a result, these systems have a high degree of operator burden. To address these challenges, an architectural concept termed "SAPIENT" was conceived. SAPIENT is based on multiple Autonomous Sensor Modules (ASMs) connected to a High-Level Decision Making Module (HLDMM) that provides data fusion, situational awareness, alerting, and sensor management capability. The aim of the SAPIENT concept is to allow for the creation of a surveillance system, in a modular plug-and-play manner, that provides high levels of autonomy, threat detection performance, and reduced operator burden. This paper considers the challenges associated with developing an HLDMM aligned with the SAPIENT concept, through the discussion of the design of a realised HLDMM. Particular focus is drawn to how high levels of system level performance can be achieved whilst retaining modularity and flexibility. A number of key aspects of our HLDMM are presented, including an integrated threat assessment and sensor management framework, threat sequence matching, and ASM trust modelling. The results of real-world testing of the HLDMM, in conjunction with multiple Laser, Radar, and EO/IR sensors, in representative semi-urban environments, are discussed.

Vehicle Exhaust Waste Heat Recovery Model with Integrated Thermal Load Leveling

DTIC Science & Technology

2015-08-01

recovery from automobile engine. Energy. 2010;35:1447–1454. 14 12. Ceraianu MO, Gontean A. Parasitic elements modelling in thermoelectric...JP, Sampath S. Heat transfer modeling and geometry optimization of TEG for automobile applications. Proceedings of the ASME Summer Heat Transfer

Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

PubMed

Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

2006-01-01

Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

Penetration of ASM 981 in canine skin: a comparative study.

PubMed

Gutzwiller, Meret E Ricklin; Reist, Martin; Persohn, Elke; Peel, John E; Roosje, Petra J

2006-01-01

ASM 981 has been developed for topical treatment of inflammatory skin diseases. It specifically inhibits the production and release of pro-inflammatory cytokines. We measured the skin penetration of ASM 981 in canine skin and compared penetration in living and frozen skin. To make penetration of ASM 981 visible in dog skin, tritium labelled ASM 981 was applied to a living dog and to defrosted skin of the same dog. Using qualitative autoradiography the radioactive molecules were detected in the lumen of the hair follicles until the infundibulum, around the superficial parts of the hair follicles and into a depth of the dermis of 200 to 500 microm. Activity could not be found in deeper parts of the hair follicles, the dermis or in the sebaceous glands. Penetration of ASM 981 is low in canine skin and is only equally spread in the upper third of the dermis 24 hours after application. Penetration in frozen skin takes even longer than in living canine skin but shows the same distribution.

Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF‐β expression in the lungs of female BALB/c mice

PubMed Central

Foong, Rachel E.; Shaw, Nicole C.; Berry, Luke J.; Hart, Prue H.; Gorman, Shelley; Zosky, Graeme R.

2014-01-01

Abstract Vitamin D deficiency is associated with disease severity in asthma. We tested whether there is a causal association between vitamin D deficiency, airway smooth muscle (ASM) mass, and the development of airway hyperresponsiveness (AHR). A physiologically relevant mouse model of vitamin D deficiency was developed by raising BALB/c mice on vitamin D‐deficient or ‐replete diets. AHR was assessed by measuring lung function responses to increasing doses of inhaled methacholine. Five‐micron sections from formalin‐fixed lungs were used for ASM measurement and assessment of lung structure using stereological methods. Transforming growth factor (TGF)‐β levels were measured in bronchoalveolar lavage fluid (BALF). Lungs were dissected from embryonic day (E) 17.5 vitamin D‐deficient and ‐replete fetal mice for quantification of ASM density and relative gene expression of TGF‐β signaling pathway molecules. Eight‐week‐old adult vitamin D‐deficient female mice had significantly increased airway resistance and ASM in the large airways compared with controls. Vitamin D‐deficient female mice had a smaller lung volume, volume of parenchyma, and alveolar septa. Both vitamin D‐deficient male and female mice had reduced TGF‐β levels in BALF. Vitamin D deficiency did not have an effect on ASM density in E17.5 mice, however, expression of TGF‐β1 and TGF‐β receptor I was downregulated in vitamin D‐deficient female fetal mice. Decreased expression of TGF‐β1 and TGF‐β receptor I during early lung development in vitamin D‐deficient mice may contribute to airway remodeling and AHR in vitamin D‐deficient adult female mice. This study provides a link between vitamin D deficiency and respiratory symptoms in chronic lung disease. PMID:24760528

Appendicular Skeletal Muscle Mass Reference Values and the Peak Muscle Mass to Identify Sarcopenia among Iranian Healthy Population.

PubMed

Shafiee, Gita; Ostovar, Afshin; Heshmat, Ramin; Keshtkar, Abbas Ali; Sharifi, Farshad; Shadman, Zhaleh; Nabipour, Iraj; Soltani, Akbar; Larijani, Bagher

2018-01-01

Sacopenia is a common problem in elderly with the adverse outcomes. The objective of this study was to estimate the peak appendicular skeletal muscle mass (ASM) and age of its attainment by sex among the Iranian population. A total of 691 men and women aged 18-94 years participated in this cross-sectional, population-based study in Bushehr, Iran. ASM was measured by dual X-ray absorptiometry. Cutoff points for men and women were established considering two standard deviations (SDs) below the mean values of the skeletal muscle index (SMI) for young reference groups. The relationship between ASM and age was described by the second-degree regression models. Two SDs below the mean SMIs of reference groups were as cutoff values of low muscle mass in Iranian population. The peak ASM values were 21.35 ± 0.12 Kg and 13.68 ± 0.10 Kg, and the age at peak ASM were 26 (24-28) years and 34 (33-35) years for men and women, respectively. Mean and SD of SMI in those ages were 7.01 ± 0.02 Kg/m 2 and 5.44 ± 0.02 Kg/m 2 among men and women, respectively. Calculated cutoff values of low muscle mass among the Iranian population were 7.0 Kg/m 2 and 5.4 Kg/m 2 among men and women, respectively. Iranian reference values of SMI for both genders were similar to Asia Working Group for Sarcopenia recommendation and lower than the United States and European values. Further studies from different nations and the Middle East countries are needed to obtain reference values for populations, enabling the researchers for comparison and also more valid reports on sarcopenia prevalence.

Role of non-coding RNAs in maintaining primary airway smooth muscle cells

PubMed Central

2014-01-01

Background The airway smooth muscle (ASM) cell maintains its own proliferative rate and contributes to the inflammatory response in the airways, effects that are inhibited by corticosteroids, used in the treatment of airways diseases. Objective We determined the differential expression of mRNAs, microRNAs (miRNAs) and long noncoding RNA species (lncRNAs) in primary ASM cells following treatment with a corticosteroid, dexamethasone, and fetal calf serum (FCS). Methods mRNA, miRNA and lncRNA expression was measured by microarray and quantitative real-time PCR. Results A small number of miRNAs (including miR-150, −371-5p, −718, −940, −1181, −1207-5p, −1915, and −3663-3p) were decreased following exposure to dexamethasone and FCS. The mRNA targets of these miRNAs were increased in expression. The changes in mRNA expression were associated with regulation of ASM actin cytoskeleton. We also observed changes in expression of lncRNAs, including natural antisense, pseudogenes, intronic lncRNAs, and intergenic lncRNAs following dexamethasone and FCS. We confirmed the change in expression of three of these, LINC00882, LINC00883, PVT1, and its transcriptional activator, c-MYC. We propose that four of these lincRNAs (RP11-46A10.4, LINC00883, BCYRN1, and LINC00882) act as miRNA ‘sponges’ for 4 miRNAs (miR-150, −371-5p, −940, −1207-5p). Conclusion This in-vitro model of primary ASM cell phenotype was associated with the regulation of several ncRNAs. Their identification allows for in-vitro functional experimentation to establish causality with the primary ASM phenotype, and in airway diseases such as asthma and chronic obstructive pulmonary disease (COPD). PMID:24886442

Neurospora crassa ASM-1 complements the conidiation defect in a stuA mutant of Aspergillus nidulans.

PubMed

Chung, Dawoon; Upadhyay, Srijana; Bomer, Brigitte; Wilkinson, Heather H; Ebbole, Daniel J; Shaw, Brian D

2015-01-01

Aspergillus nidulans StuA and Neurospora crassa ASM-1 are orthologous APSES (ASM-1, PHD1, SOK2, Efg1, StuA) transcription factors conserved across a diverse group of fungi. StuA and ASM-1 have roles in asexual (conidiation) and sexual (ascospore formation) development in both organisms. To address the hypothesis that the last common ancestor of these diverse fungi regulated conidiation with similar genes, asm-1 was introduced into the stuA1 mutant of A. nidulans. Expression of asm-1 complemented defective conidiophore morphology and restored conidia production to wild type levels in stuA1. Expression of asm-1 in the stuA1 strain did not rescue the defect in sexual development. When the conidiation regulator AbaA was tagged at its C-terminus with GFP in A. nidulans, it localized to nuclei in phialides. When expressed in the stuA1 mutant, AbaA::GFP localized to nuclei in conidiophores but no longer was confined to phialides, suggesting that expression of AbaA in specific cell types of the conidiophore was conditioned by StuA. Our data suggest that the function in conidiation of StuA and ASM-1 is conserved and support the view that, despite the great morphological and ontogenic diversity of their condiphores, the last common ancestor of A. nidulans and N. crassa produced an ortholog of StuA that was involved in conidiophore development. © 2015 by The Mycological Society of America.

Early discontinuation of antiseizure medications in neonates with hypoxic-ischemic encephalopathy.

PubMed

Fitzgerald, Mark P; Kessler, Sudha Kilaru; Abend, Nicholas S

2017-06-01

Neonates with hypoxic-ischemic encephalopathy (HIE) managed with therapeutic hypothermia (TH) often experience acute symptomatic seizures, prompting treatment with antiseizure medications (ASMs). Because the risk of seizure occurrence after hospital discharge is unknown, the optimal ASM treatment duration is unclear. We aimed to determine the risk of seizure occurrence after hospital discharge and the impact of ASM treatment duration on this outcome. We performed a single-center, retrospective study of consecutive neonates with HIE managed with TH who received ASMs for acute symptomatic seizures from June 2010 through December 2014. Neonates were monitored with continuous electroencephalography (EEG) during TH. Follow-up data were available for 59 (82%) of 72 neonates who survived to discharge, with a median follow-up period of 19 months (interquartile range [IQR] 11-25). Acute symptomatic seizures occurred in 35 neonates (59%), including electrographic seizures in 21 neonates (36%). ASMs were continued upon discharge in 17 (49%) of 35 neonates. Seizures occurred in follow-up in four neonates (11%). No patient for whom ASMs were discontinued prior to discharge experienced seizures during the follow-up period. Among neonates with HIE, seizures after hospital discharge were rare in those with acute symptomatic seizures and did not occur in neonates without acute symptomatic seizures. ASM discontinuation prior to discharge did not increase the risk of seizures during the follow-up period, suggesting that ASMs may be discontinued in many neonates prior to discharge. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Acid Sphingomyelinase Mediates Oxidized-LDL Induced Apoptosis in Macrophage via Endoplasmic Reticulum Stress

PubMed Central

Zhao, Min; Pan, Wei; Shi, Rui-zheng; Bai, Yong-ping; You, Bo-yang; Zhang, Kai; Fu, Qiong-mei; Schuchman, Edward H.

2016-01-01

Aim: Macrophage apoptosis is a vital event in advanced atherosclerosis, and oxidized low-density lipoprotein (ox-LDL) is a major contributor to this process. Acid sphingomyelinase (ASM) and ceramide are also involved in the induction of apoptosis, particularly in macrophages. Our current study focuses on ASM and investigates its role in ox-LDL-induced macrophage apoptosis. Methods: Human THP-1 and mouse peritoneal macrophages were cultured in vitro and treated with ox-LDL. ASM activity and ceramide levels were quantified using ultra performance liquid chromatography. Protein and mRNA levels were analyzed using Western blot analysis and quantitative realtime PCR, respectively. Cell apoptosis was determined using Hoechst staining and flow cytometry. Results: Ox-LDL-induced macrophage apoptosis was triggered by profound endoplasmic reticulum (ER) stress, leading to an upregulation of ASM activity and ceramide levels at an early stage. ASM was inhibited by siRNA or desipramine (DES), and/or ceramide was degraded by recombinant acid ceramidase (AC). These events attenuated the effect of ox-LDL on ER stress. In contrast, recombinant ASM upregulated ceramide and ER stress. ASM siRNA, DES, recombinant AC, and ER stress inhibitor 4-phenylbutyric acid were blocked by elevated levels of C/EBP homologous protein (CHOP); ox-LDL induced elevated levels of CHOP. These events attenuated macrophage apoptosis. Conclusion: These results indicate that ASM/ceramide signaling pathway is involved in ox-LDL-induced macrophage apoptosis via ER stress pathway. PMID:26923251

AIAA/ASME/ASCE/AHS/ASC Structures, Structural Dynamics, and Materials Conference, 34th and AIAA/ASME Adaptive Structures Forum, La Jolla, CA, Apr. 19-22, 1993, Technical Papers. Pts. 1-6

NASA Astrophysics Data System (ADS)

Topics addressed include the prediction of helicopter component loads using neural networks, spacecraft on-orbit coupled loads analysis, hypersonic flutter of a curved shallow panel with aerodynamic heating, thermal-acoustic fatigue of ceramic matrix composite materials, transition elements based on transfinite interpolation, damage progression in stiffened composite panels, a direct treatment of min-max dynamic response optimization problems, and sources of helicopter rotor hub inplane shears. Also discussed are dynamics of a layered elastic system, confidence bounds on structural reliability, mixed triangular space-time finite elements, advanced transparency development for USAF aircraft, a low-velocity impact on a graphite/PEEK, an automated mode-tracking strategy, transonic flutter suppression by a passive flap, a nonlinear response of composite panels to random excitation, an optimal placement of elastic supports on a simply supported plate, a probabilistic assessment of composite structures, a model for mode I failure of laminated composites, a residual flexibility approach to multibody dynamics,and multilayer piezoelectric actuators.

Next-generation sequencing in systemic mastocytosis: Derivation of a mutation-augmented clinical prognostic model for survival.

PubMed

Pardanani, Animesh; Lasho, Terra; Elala, Yoseph; Wassie, Emnet; Finke, Christy; Reichard, Kaaren K; Chen, Dong; Hanson, Curtis A; Ketterling, Rhett P; Tefferi, Ayalew

2016-09-01

In routine practice, the World Health Organization classification of systemic mastocytosis (SM) is also the de facto prognostic system; a core value is distinguishing indolent (ISM) from advanced SM (includes aggressive SM [ASM], SM with associated hematological neoplasm [SM-AHN] and mast cell leukemia [MCL]). We sequenced 27 genes in 150 SM patients to identify mutations that could be integrated into a clinical-molecular prognostic model for survival. Forty four patients (29%) had ISM, 25 (17%) ASM, 80 (53%) SM-AHN and 1 (0.7%) MCL; overall KITD816V prevalence was 75%. In 87 patients, 148 non-KIT mutations were detected; the most frequently mutated genes were TET2 (29%), ASXL1 (17%), and CBL (11%), with significantly higher mutation frequency in SM-AHN > ASM > ISM (P < 0.0001). In advanced SM, ASXL1 and RUNX1 mutations were associated with inferior survival. In multivariate analysis, age > 60 years (HR = 2.4), hemoglobin < 10 g/dL or transfusion-dependence (HR = 1.7), platelet count < 150 × 10(9) /L (HR = 3.2), serum albumin < 3.5 g/dL (HR = 2.6), and ASXL1 mutation (HR = 2.3) were associated with inferior survival. A mutation-augmented prognostic scoring system (MAPSS) based on these parameters stratified advanced SM patients into high-, intermediate-, and low-risk groups with median survival of 5, 21 and 86 months, respectively (P < 0.0001). These data should optimize risk-stratification and treatment selection for advanced SM patients. Am. J. Hematol. 91:888-893, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Engineering studies of vectorcardiographs in blood pressure measuring systems, appendix 3

NASA Technical Reports Server (NTRS)

Mark, R. G.

1975-01-01

The following subjects were covered: (1) ASM80 manual, (2) signal preprocessing as an aid to on-line EKG analysis, and (3) high speed evaluation of magnetic tape recordings of electrocardiograms. A description of the ASM80 symbolic assembly program for the INTEL 8080 microprocessor and a user's manual were presented. The capability of three redundancy reduction algorithms to produce adequate representations of electrocardiographic data was examined. A hardware device was constructed which carried out zero order interpolation on a signal. Examination of the zero order interpolators reconstructed signal indicated that this representation was adequate for analysis of rhythm. A system to analyze magnetic tapes of electrocardiograms recorded over 24 hour intervals was designed. The recordings are sampled 200 times per second using a Nova computer and a special interface system. This system was tested on several recordings of clinical data, containing over 75 premature ventricular contractions, each one of which was flagged.

XTE Observations of PSR 1259-63 and a Test of Spin Orbit Coupling in the 4U0115+63 System

NASA Technical Reports Server (NTRS)

Cominsky, Lynn R.

1999-01-01

During this report period, Mallory Roberts went to GSFC to analyze the data from two minor outbursts, which occurred from 4UO115+63. Unfortunately, the outbursts were not of sufficient duration to do a unique orbital determination (which was the scientific goal of the experiment). As this report is being written, 4UO115+63 is undergoing its first major outburst in four years. We are planning on adding our RXTE PCA data to any public ASM or PCA data that is obtained through the duration of this outburst, and combining it with our BATSE data from 1994 and 1995 outbursts in order to learn something about the orbital evolution in this system. We have formed a collaboration with colleagues at MIT who are working on the ASM data for this outburst. Thus, work on the original data will continue, with no further funding, and we are hopeful that some important questions with regard to the orbital timing will finally be resolved. The PSR 1259-63 data were originally analyzed by Barry Giles, who reported that no pulsations or flux were seen from this source near apastron. Recently, a new background model for low-count rate sources has been developed for the PCA. We intend to use this new background model to reanalyze these data to see if we can improve the upper limit to the flux. This work will also continue with no further funding.

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Institute “Code for Pressure Piping, Power Piping.” ASME Code means the American Society of Mechanical Engineers “Boiler and Pressure Vessel Code.” ASME PVHO-1 means the ANSI/ASME standard “Safety Standard for Pressure Vessels for Human Occupancy.” ATA means a measure of pressure expressed in terms of atmosphere...

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Institute “Code for Pressure Piping, Power Piping.” ASME Code means the American Society of Mechanical Engineers “Boiler and Pressure Vessel Code.” ASME PVHO-1 means the ANSI/ASME standard “Safety Standard for Pressure Vessels for Human Occupancy.” ATA means a measure of pressure expressed in terms of atmosphere...

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Institute “Code for Pressure Piping, Power Piping.” ASME Code means the American Society of Mechanical Engineers “Boiler and Pressure Vessel Code.” ASME PVHO-1 means the ANSI/ASME standard “Safety Standard for Pressure Vessels for Human Occupancy.” ATA means a measure of pressure expressed in terms of atmosphere...

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Institute “Code for Pressure Piping, Power Piping.” ASME Code means the American Society of Mechanical Engineers “Boiler and Pressure Vessel Code.” ASME PVHO-1 means the ANSI/ASME standard “Safety Standard for Pressure Vessels for Human Occupancy.” ATA means a measure of pressure expressed in terms of atmosphere...

The LBT experience of adaptive secondary mirror operations for routine seeing- and diffraction-limited science operations

NASA Astrophysics Data System (ADS)

Guerra, J. C.; Brusa, G.; Christou, J.; Miller, D.; Ricardi, A.; Xompero, M.; Briguglio, R.; Wagner, M.; Lefebvre, M.; Sosa, R.

2013-09-01

The Large Binocular Telescope (LBT) is unique in that it is currently the only large telescope (2 x 8.4m primary mirrors) with permanently mounted adaptive secondary mirrors (ASMs). These ASMs have been used for regular observing since early 2010 on the right side and since late 2011 on the left side. They are currently regularly used for seeing-limited observing as well as for selective diffraction-limited observing and are required to be fully operational every observing night. By comparison the other telescopes using ASMs, the Multi Mirrot Telescope (MMT) and more recently Magellan, use fixed secondaries of seeing-limited observing and switch in the ASMs for diffraction-limited observing. We will discuss the night-to-night operational requirements for ASMs specifically for seeing-limited but also for diffraction-limited observations based on the LBT experience. These will include preparation procedures for observing (mirror flattening and resting as examples); hardware failure statistics and how to deal with them such as for the actuators; observing protocols for; and current limitations of use due to the ASM technology such as the minimum elevation limit (25 degrees) and the hysteresis of the gravity-vector induced astigmatism. We will also discuss the impact of ASM maintenance and preparation

Tissue-specific patterns of allelically-skewed DNA methylation

PubMed Central

Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan

2016-01-01

ABSTRACT While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood. PMID:26786711

Soluble guanylyl cyclase-activated cyclic GMP-dependent protein kinase inhibits arterial smooth muscle cell migration independent of VASP-serine 239 phosphorylation.

PubMed

Holt, Andrew W; Martin, Danielle N; Shaver, Patti R; Adderley, Shaquria P; Stone, Joshua D; Joshi, Chintamani N; Francisco, Jake T; Lust, Robert M; Weidner, Douglas A; Shewchuk, Brian M; Tulis, David A

2016-09-01

Coronary artery disease (CAD) accounts for over half of all cardiovascular disease-related deaths. Uncontrolled arterial smooth muscle (ASM) cell migration is a major component of CAD pathogenesis and efforts aimed at attenuating its progression are clinically essential. Cyclic nucleotide signaling has long been studied for its growth-mitigating properties in the setting of CAD and other vascular disorders. Heme-containing soluble guanylyl cyclase (sGC) synthesizes cyclic guanosine monophosphate (cGMP) and maintains vascular homeostasis predominantly through cGMP-dependent protein kinase (PKG) signaling. Considering that reactive oxygen species (ROS) can interfere with appropriate sGC signaling by oxidizing the cyclase heme moiety and so are associated with several CVD pathologies, the current study was designed to test the hypothesis that heme-independent sGC activation by BAY 60-2770 (BAY60) maintains cGMP levels despite heme oxidation and inhibits ASM cell migration through phosphorylation of the PKG target and actin-binding vasodilator-stimulated phosphoprotein (VASP). First, using the heme oxidant ODQ, cGMP content was potentiated in the presence of BAY60. Using a rat model of arterial growth, BAY60 significantly reduced neointima formation and luminal narrowing compared to vehicle (VEH)-treated controls. In rat ASM cells BAY60 significantly attenuated cell migration, reduced G:F actin, and increased PKG activity and VASP Ser239 phosphorylation (pVASP·S239) compared to VEH controls. Site-directed mutagenesis was then used to generate overexpressing full-length wild type VASP (FL-VASP/WT), VASP Ser239 phosphorylation-mimetic (FL-VASP/239D) and VASP Ser239 phosphorylation-resistant (FL-VASP/239A) ASM cell mutants. Surprisingly, FL-VASP/239D negated the inhibitory effects of FL-VASP/WT and FL-VASP/239A cells on migration. Furthermore, when FL-VASP mutants were treated with BAY60, only the FL-VASP/239D group showed reduced migration compared to its VEH controls. Intriguingly, FL-VASP/239D abrogated the stimulatory effects of FL-VASP/WT and FL-VASP/239A cells on PKG activity. In turn, pharmacologic blockade of PKG in the presence of BAY60 reversed the inhibitory effect of BAY60 on naïve ASM cell migration. Taken together, we demonstrate for the first time that BAY60 inhibits ASM cell migration through cGMP/PKG/VASP signaling yet through mechanisms independent of pVASP·S239 and that FL-VASP overexpression regulates PKG activity in rat ASM cells. These findings implicate BAY60 as a potential pharmacotherapeutic agent against aberrant ASM growth disorders such as CAD and also establish a unique mechanism through which VASP controls PKG activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of operational cycle time length on nitrogen removal in an alternating oxidation ditch system.

PubMed

Mantziaras, I D; Stamou, A; Katsiri, A

2011-06-01

This paper refers to nitrogen removal optimization of an alternating oxidation ditch system through the use of a mathematical model and pilot testing. The pilot system where measurements have been made has a total volume of 120 m(3) and consists of two ditches operating in four phases during one cycle and performs carbon oxidation, nitrification, denitrification and settling. The mathematical model consists of one-dimensional mass balance (convection-dispersion) equations based on the IAWPRC ASM 1 model. After the calibration and verification of the model, simulation system performance was made. Optimization is achieved by testing operational cycles and phases with different time lengths. The limits of EU directive 91/271 for nitrogen removal have been used for comparison. The findings show that operational cycles with smaller time lengths can achieve higher nitrogen removals and that an "equilibrium" between phase time percentages in the whole cycle, for a given inflow, must be achieved.

Sarcopenic obesity and overall mortality: Results from the application of novel models of body composition phenotypes to the National Health and Nutrition Examination Survey 1999-2004.

PubMed

Van Aller, Carla; Lara, Jose; Stephan, Blossom C M; Donini, Lorenzo Maria; Heymsfield, Steven; Katzmarzyk, Peter T; Wells, Jonathan C K; Prado, Carla M; Siervo, Mario

2018-02-15

There is no consensus on the definition of sarcopenic obesity (SO), resulting in inconsistent associations of SO with mortality risk. We aim to evaluate association of dual energy x-ray absorptiometry (DXA) SO models with mortality risk in a US adult population (≥50 years). The study population consisted of 3577 participants aged 50 years and older from the 1999-2004 National Health and Nutrition and Examination Survey with mortality follow-up data through December 31, 2011. Difference in survival time in people with and without SO defined by three body composition DXA models (Model 1: body composition phenotype model; Model 2: Truncal Fat Mass (TrFM)/Appendicular Skeletal Muscle Mass (ASM) ratio model; Model 3: Fat Mass (FM)/Fat Free Mass (FFM) ratio). The differences between the models were assessed by the acceleration failure time model, and expressed as time ratios (TR). Participants age 50-70 years with SO had a significantly decreased survival time, according to the body composition phenotype model (TR: 0.92; 95% CI: 0.87-0.97), and TrFM/ASM ratio model (TR: 0.88; 95% CI: 0.81-0.95). The FM/FFM ratio model did not detect significant differences in survival time. Participants with SO aged 70 years and older did not have a significantly decreased survival time, according to all three models. A SO phenotype increases mortality risk in people of age 50-70 years, but not in people aged 70 years and older. The application of the body composition phenotype and the TrFM/ASM ratio models may represent useful diagnostic approaches to improve the prediction of disease and mortality risk. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Anti-EGFR Antibody Efficiently and Specifically Inhibits Human TSC2−/− Smooth Muscle Cell Proliferation. Possible Treatment Options for TSC and LAM

PubMed Central

Lesma, Elena; Grande, Vera; Ancona, Silvia; Carelli, Stephana; Di Giulio, Anna Maria; Gorio, Alfredo

2008-01-01

Background Tuberous sclerosis complex (TSC), a tumor syndrome caused by mutations in TSC1 or TSC2 genes, is characterized by the development of hamartomas. We previously isolated, from an angiomyolipoma of a TSC2 patient, a homogenous population of smooth muscle-like cells (TSC2−/− ASM cells) that have a mutation in the TSC2 gene as well as TSC2 loss of heterozygosity (LOH) and consequently, do not produce the TSC2 gene product, tuberin. TSC2−/− ASM cell proliferation is EGF-dependent. Methods and Findings Effects of EGF on proliferation of TSC2−/− ASM cells and TSC2−/− ASM cells transfected with TSC2 gene were determined. In contrast to TSC2−/− ASM cells, growth of TSC2-transfected cells was not dependent on EGF. Moreover, phosphorylation of Akt, PTEN, Erk and S6 was significantly decreased. EGF is a proliferative factor of TSC2−/− ASM cells. Exposure of TSC2−/− ASM cells to anti-EGFR antibodies significantly inhibited their proliferation, reverted reactivity to HMB45 antibody, a marker of TSC2−/− cell phenotype, and inhibited constitutive phosphorylation of S6 and ERK. Exposure of TSC2−/− ASM cells to rapamycin reduced the proliferation rate, but only when added at plating time. Although rapamycin efficiently inhibited S6 phosphorylation, it was less efficient than anti-EGFR antibody in reverting HMB45 reactivity and blocking ERK phosphorylation. In TSC2−/− ASM cells specific PI3K inhibitors (e.g. LY294002, wortmannin) and Akt1 siRNA had little effect on S6 and ERK phosphorylation. Following TSC2-gene transfection, Akt inhibitor sensitivity was observed. Conclusion Our results show that an EGF independent pathway is more important than that involving IGF-I for growth and survival of TSC−/− ASM cells, and such EGF-dependency is the result of the lack of tuberin. PMID:18958173

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease.

PubMed

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score ([Formula: see text]) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing [Formula: see text] >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of [Formula: see text] (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 ([Formula: see text] = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility.

Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

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

Pei, Qing-Mei, E-mail: 34713316@qq.com; Jiang, Ping, E-mail: jiangping@163.com; Yang, Min, E-mail: YangMin@163.com

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferationmore » and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation of caveolin-1. • RXM inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. • Our findings expand our knowledge of the role of RXM in airway remodelling.« less

Allele-specific DNA methylation of disease susceptibility genes in Japanese patients with inflammatory bowel disease

PubMed Central

Chiba, Hirofumi; Kakuta, Yoichi; Kinouchi, Yoshitaka; Kawai, Yosuke; Watanabe, Kazuhiro; Nagao, Munenori; Naito, Takeo; Onodera, Motoyuki; Moroi, Rintaro; Kuroha, Masatake; Kanazawa, Yoshitake; Kimura, Tomoya; Shiga, Hisashi; Endo, Katsuya; Negoro, Kenichi; Nagasaki, Masao; Unno, Michiaki; Shimosegawa, Tooru

2018-01-01

Background Inflammatory bowel disease (IBD) has an unknown etiology; however, accumulating evidence suggests that IBD is a multifactorial disease influenced by a combination of genetic and environmental factors. The influence of genetic variants on DNA methylation in cis and cis effects on expression have been demonstrated. We hypothesized that IBD susceptibility single-nucleotide polymorphisms (SNPs) regulate susceptibility gene expressions in cis by regulating DNA methylation around SNPs. For this, we determined cis-regulated allele-specific DNA methylation (ASM) around IBD susceptibility genes in CD4+ effector/memory T cells (Tem) in lamina propria mononuclear cells (LPMCs) in patients with IBD and examined the association between the ASM SNP genotype and neighboring susceptibility gene expressions. Methods CD4+ effector/memory T cells (Tem) were isolated from LPMCs in 15 Japanese IBD patients (ten Crohn's disease [CD] and five ulcerative colitis [UC] patients). ASM analysis was performed by methylation-sensitive SNP array analysis. We defined ASM as a changing average relative allele score (ΔRAS¯) >0.1 after digestion by methylation-sensitive restriction enzymes. Among SNPs showing ΔRAS¯ >0.1, we extracted the probes located on tag-SNPs of 200 IBD susceptibility loci and around IBD susceptibility genes as candidate ASM SNPs. To validate ASM, bisulfite-pyrosequencing was performed. Transcriptome analysis was examined in 11 IBD patients (seven CD and four UC patients). The relation between rs36221701 genotype and neighboring gene expressions were analyzed. Results We extracted six candidate ASM SNPs around IBD susceptibility genes. The top of ΔRAS¯ (0.23) was rs1130368 located on HLA-DQB1. ASM around rs36221701 (ΔRAS¯ = 0.14) located near SMAD3 was validated using bisulfite pyrosequencing. The SMAD3 expression was significantly associated with the rs36221701 genotype (p = 0.016). Conclusions We confirmed the existence of cis-regulated ASM around IBD susceptibility genes and the association between ASM SNP (rs36221701) genotype and SMAD3 expression, a susceptibility gene for IBD. These results give us supporting evidence that DNA methylation mediates genetic effects on disease susceptibility. PMID:29547621

Activation of human acid sphingomyelinase through modification or deletion of C-terminal cysteine.

PubMed

Qiu, Huawei; Edmunds, Tim; Baker-Malcolm, Jennifer; Karey, Kenneth P; Estes, Scott; Schwarz, Cordula; Hughes, Heather; Van Patten, Scott M

2003-08-29

One form of Niemann-Pick disease is caused by a deficiency in the enzymatic activity of acid sphingomyelinase. During efforts to develop an enzyme replacement therapy based on a recombinant form of human acid sphingomyelinase (rhASM), purified preparations of the recombinant enzyme were found to have substantially increased specific activity if cell harvest media were stored for several weeks at -20 degrees C prior to purification. This increase in activity was found to correlate with the loss of the single free thiol on rhASM, suggesting the involvement of a cysteine residue. It was demonstrated that a variety of chemical modifications of the free cysteine on rhASM all result in substantial activation of the enzyme, and the modified cysteine responsible for this activation was shown to be the C-terminal residue (Cys629). Activation was also achieved by copper-promoted dimerization of rhASM (via cysteine) and by C-terminal truncation using carboxypeptidase Y. The role of the C-terminal cysteine in activation was confirmed by creating mutant forms of rhASM in which this residue was either deleted or replaced by a serine, with both forms having substantially higher specific activity than wild-type rhASM. These results indicate that purified rhASM can be activated in vitro by loss of the free thiol on the C-terminal cysteine via chemical modification, dimerization, or deletion of this amino acid residue. This method of activation is similar to the cysteine switch mechanism described previously for matrix metalloproteinases and could represent a means of posttranslational regulation of ASM activity in vivo.

IL-17A Mediates a Selective Gene Expression Profile in Asthmatic Human Airway Smooth Muscle Cells

PubMed Central

Dragon, Stéphane; Hirst, Stuart J.; Lee, Tak H.

2014-01-01

Airway smooth muscle (ASM) cells are thought to contribute to the pathogenesis of allergic asthma by orchestrating and perpetuating airway inflammation and remodeling responses. In this study, we evaluated the IL-17RA signal transduction and gene expression profile in ASM cells from subjects with mild asthma and healthy individuals. Human primary ASM cells were treated with IL-17A and probed by the Affymetrix GeneChip array, and gene targets were validated by real-time quantitative RT-PCR. Genomic analysis underlined the proinflammatory nature of IL-17A, as multiple NF-κB regulatory factors and chemokines were induced in ASM cells. Transcriptional regulators consisting of primary response genes were overrepresented and displayed dynamic expression profiles. IL-17A poorly enhanced IL-1β or IL-22 gene responses in ASM cells from both subjects with mild asthma and healthy donors. Interestingly, protein modifications to the NF-κB regulatory network were not observed after IL-17A stimulation, although oscillations in IκBε expression were detected. ASM cells from subjects with mild asthma up-regulated more genes with greater overall variability in response to IL-17A than from healthy donors. Finally, in response to IL-17A, ASM cells displayed rapid activation of the extracellular signal–regulated kinase/ribosomal S6 kinase signaling pathway and increased nuclear levels of phosphorylated extracellular signal–regulated kinase. Taken together, our results suggest that IL-17A mediated modest gene expression response, which, in cooperation with the NF-κB signaling network, may regulate the gene expression profile in ASM cells. PMID:24393021

Stress and strain in the contractile and cytoskeletal filaments of airway smooth muscle.

PubMed

Deng, Linhong; Bosse, Ynuk; Brown, Nathan; Chin, Leslie Y M; Connolly, Sarah C; Fairbank, Nigel J; King, Greg G; Maksym, Geoffrey N; Paré, Peter D; Seow, Chun Y; Stephen, Newman L

2009-10-01

Stress and strain are omnipresent in the lung due to constant lung volume fluctuation associated with respiration, and they modulate the phenotype and function of all cells residing in the airways including the airway smooth muscle (ASM) cell. There is ample evidence that the ASM cell is very sensitive to its physical environment, and can alter its structure and/or function accordingly, resulting in either desired or undesired consequences. The forces that are either conferred to the ASM cell due to external stretching or generated inside the cell must be borne and transmitted inside the cytoskeleton (CSK). Thus, maintaining appropriate levels of stress and strain within the CSK is essential for maintaining normal function. Despite the importance, the mechanisms regulating/dysregulating ASM cytoskeletal filaments in response to stress and strain remained poorly understood until only recently. For example, it is now understood that ASM length and force are dynamically regulated, and both can adapt over a wide range of length, rendering ASM one of the most malleable living tissues. The malleability reflects the CSK's dynamic mechanical properties and plasticity, both of which strongly interact with the loading on the CSK, and all together ultimately determines airway narrowing in pathology. Here we review the latest advances in our understanding of stress and strain in ASM cells, including the organization of contractile and cytoskeletal filaments, range and adaptation of functional length, structural and functional changes of the cell in response to mechanical perturbation, ASM tone as a mediator of strain-induced responses, and the novel glassy dynamic behaviors of the CSK in relation to asthma pathophysiology.

Mechanisms of Cigarette Smoke Effects on Human Airway Smooth Muscle.

PubMed

Wylam, Mark E; Sathish, Venkatachalem; VanOosten, Sarah Kay; Freeman, Michelle; Burkholder, David; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S

2015-01-01

Cigarette smoke contributes to or exacerbates airway diseases such as asthma and COPD, where airway hyperresponsiveness and airway smooth muscle (ASM) proliferation are key features. While factors such as inflammation contribute to asthma in part by enhancing agonist-induced intracellular Ca(2+) ([Ca(2+)]i) responses of ASM, the mechanisms by which cigarette smoke affect ASM are still under investigation. In the present study, we tested the hypothesis that cigarette smoke enhances the expression and function of Ca(2+) regulatory proteins leading to increased store operated Ca(2+) entry (SOCE) and cell proliferation. Using isolated human ASM (hASM) cells, incubated in the presence and absence cigarette smoke extract (CSE) we determined ([Ca(2+)]i) responses and expression of relevant proteins as well as ASM proliferation, reactive oxidant species (ROS) and cytokine generation. CSE enhanced [Ca(2+)]i responses to agonist and SOCE: effects mediated by increased expression of TRPC3, CD38, STIM1, and/or Orai1, evident by attenuation of CSE effects when siRNAs against these proteins were used, particularly Orai1. CSE also increased hASM ROS generation and cytokine secretion. In addition, we found in the airways of patients with long-term smoking history, TRPC3 and CD38 expression were significantly increased compared to life-long never-smokers, supporting the role of these proteins in smoking effects. Finally, CSE enhanced hASM proliferation, an effect confirmed by upregulation of PCNA and Cyclin E. These results support a critical role for Ca(2+) regulatory proteins and enhanced SOCE to alter airway structure and function in smoking-related airway disease.

Oxygen dose responsiveness of human fetal airway smooth muscle cells.

PubMed

Hartman, William R; Smelter, Dan F; Sathish, Venkatachalem; Karass, Michael; Kim, Sunchin; Aravamudan, Bharathi; Thompson, Michael A; Amrani, Yassine; Pandya, Hitesh C; Martin, Richard J; Prakash, Y S; Pabelick, Christina M

2012-10-15

Maintenance of blood oxygen saturation dictates supplemental oxygen administration to premature infants, but hyperoxia predisposes survivors to respiratory diseases such as asthma. Although much research has focused on oxygen effects on alveoli in the setting of bronchopulmonary dysplasia, the mechanisms by which oxygen affects airway structure or function relevant to asthma are still under investigation. We used isolated human fetal airway smooth muscle (fASM) cells from 18-20 postconceptual age lungs (canalicular stage) to examine oxygen effects on intracellular Ca(2+) ([Ca(2+)](i)) and cellular proliferation. fASM cells expressed substantial smooth muscle actin and myosin and several Ca(2+) regulatory proteins but not fibroblast or epithelial markers, profiles qualitatively comparable to adult human ASM. Fluorescence Ca(2+) imaging showed robust [Ca(2+)](i) responses to 1 μM acetylcholine (ACh) and 10 μM histamine (albeit smaller and slower than adult ASM), partly sensitive to zero extracellular Ca(2+). Compared with adult, fASM showed greater baseline proliferation. Based on this validation, we assessed fASM responses to 10% hypoxia through 90% hyperoxia and found enhanced proliferation at <60% oxygen but increased apoptosis at >60%, effects accompanied by appropriate changes in proliferative vs. apoptotic markers and enhanced mitochondrial fission at >60% oxygen. [Ca(2+)](i) responses to ACh were enhanced for <60% but blunted at >60% oxygen. These results suggest that hyperoxia has dose-dependent effects on structure and function of developing ASM, which could have consequences for airway diseases of childhood. Thus detrimental effects on ASM should be an additional consideration in assessing risks of supplemental oxygen in prematurity.

Oxygen dose responsiveness of human fetal airway smooth muscle cells

PubMed Central

Hartman, William R.; Smelter, Dan F.; Sathish, Venkatachalem; Karass, Michael; Kim, Sunchin; Aravamudan, Bharathi; Thompson, Michael A.; Amrani, Yassine; Pandya, Hitesh C.; Martin, Richard J.; Prakash, Y. S.

2012-01-01

Maintenance of blood oxygen saturation dictates supplemental oxygen administration to premature infants, but hyperoxia predisposes survivors to respiratory diseases such as asthma. Although much research has focused on oxygen effects on alveoli in the setting of bronchopulmonary dysplasia, the mechanisms by which oxygen affects airway structure or function relevant to asthma are still under investigation. We used isolated human fetal airway smooth muscle (fASM) cells from 18–20 postconceptual age lungs (canalicular stage) to examine oxygen effects on intracellular Ca2+ ([Ca2+]i) and cellular proliferation. fASM cells expressed substantial smooth muscle actin and myosin and several Ca2+ regulatory proteins but not fibroblast or epithelial markers, profiles qualitatively comparable to adult human ASM. Fluorescence Ca2+ imaging showed robust [Ca2+]i responses to 1 μM acetylcholine (ACh) and 10 μM histamine (albeit smaller and slower than adult ASM), partly sensitive to zero extracellular Ca2+. Compared with adult, fASM showed greater baseline proliferation. Based on this validation, we assessed fASM responses to 10% hypoxia through 90% hyperoxia and found enhanced proliferation at <60% oxygen but increased apoptosis at >60%, effects accompanied by appropriate changes in proliferative vs. apoptotic markers and enhanced mitochondrial fission at >60% oxygen. [Ca2+]i responses to ACh were enhanced for <60% but blunted at >60% oxygen. These results suggest that hyperoxia has dose-dependent effects on structure and function of developing ASM, which could have consequences for airway diseases of childhood. Thus detrimental effects on ASM should be an additional consideration in assessing risks of supplemental oxygen in prematurity. PMID:22923637

49 CFR 222.57 - Can parties seek review of the Associate Administrator's actions?

Code of Federal Regulations, 2013 CFR

2013-10-01

... the Associate Administrator granting or denying an application for approval of a new SSM or ASM under... demonstration of the proposed new SSM or ASM , the highway or traffic control authority or law enforcement authority having control over vehicular traffic at the crossings affected by the new SSM/ASM demonstration...

49 CFR 222.57 - Can parties seek review of the Associate Administrator's actions?

Code of Federal Regulations, 2012 CFR

2012-10-01

... the Associate Administrator granting or denying an application for approval of a new SSM or ASM under... demonstration of the proposed new SSM or ASM , the highway or traffic control authority or law enforcement authority having control over vehicular traffic at the crossings affected by the new SSM/ASM demonstration...

49 CFR 222.57 - Can parties seek review of the Associate Administrator's actions?

Code of Federal Regulations, 2014 CFR

2014-10-01

... the Associate Administrator granting or denying an application for approval of a new SSM or ASM under... demonstration of the proposed new SSM or ASM , the highway or traffic control authority or law enforcement authority having control over vehicular traffic at the crossings affected by the new SSM/ASM demonstration...

78 FR 37848 - ASME Code Cases Not Approved for Use

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-1233, ``ASME Code Cases not Approved for Use.'' This regulatory guide lists the American Society of Mechanical Engineers (ASME) Code Cases that the NRC has determined not to be acceptable for use on a generic basis.

75 FR 24323 - American Society of Mechanical Engineers (ASME) Codes and New and Revised ASME Code Cases

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-04

... Approved for Incorporation by Reference Introductory text to paragraph Introductory text Revise to title... reference. ASME B&PV Code, Section III Introductory text to paragraph Introductory text Revise to clarify... editorial corrections and additions. Introductory text to paragraph Introductory text Revise to include the...

Differential Activation of Acid Sphingomyelinase and Ceramide Release Determines Invasiveness of Neisseria meningitidis into Brain Endothelial Cells

PubMed Central

Simonis, Alexander; Hebling, Sabrina; Gulbins, Erich; Schneider-Schaulies, Sibylle; Schubert-Unkmeir, Alexandra

2014-01-01

The interaction with brain endothelial cells is central to the pathogenicity of Neisseria meningitidis infections. Here, we show that N. meningitidis causes transient activation of acid sphingomyelinase (ASM) followed by ceramide release in brain endothelial cells. In response to N. meningitidis infection, ASM and ceramide are displayed at the outer leaflet of the cell membrane and condense into large membrane platforms which also concentrate the ErbB2 receptor. The outer membrane protein Opc and phosphatidylcholine-specific phospholipase C that is activated upon binding of the pathogen to heparan sulfate proteoglycans, are required for N. meningitidis-mediated ASM activation. Pharmacologic or genetic ablation of ASM abrogated meningococcal internalization without affecting bacterial adherence. In accordance, the restricted invasiveness of a defined set of pathogenic isolates of the ST-11/ST-8 clonal complex into brain endothelial cells directly correlated with their restricted ability to induce ASM and ceramide release. In conclusion, ASM activation and ceramide release are essential for internalization of Opc-expressing meningococci into brain endothelial cells, and this segregates with invasiveness of N. meningitidis strains. PMID:24945304

Implementing ADM1 for plant-wide benchmark simulations in Matlab/Simulink.

PubMed

Rosen, C; Vrecko, D; Gernaey, K V; Pons, M N; Jeppsson, U

2006-01-01

The IWA Anaerobic Digestion Model No.1 (ADM1) was presented in 2002 and is expected to represent the state-of-the-art model within this field in the future. Due to its complexity the implementation of the model is not a simple task and several computational aspects need to be considered, in particular if the ADM1 is to be included in dynamic simulations of plant-wide or even integrated systems. In this paper, the experiences gained from a Matlab/Simulink implementation of ADM1 into the extended COST/IWA Benchmark Simulation Model (BSM2) are presented. Aspects related to system stiffness, model interfacing with the ASM family, mass balances, acid-base equilibrium and algebraic solvers for pH and other troublesome state variables, numerical solvers and simulation time are discussed. The main conclusion is that if implemented properly, the ADM1 will also produce high-quality results in dynamic plant-wide simulations including noise, discrete sub-systems, etc. without imposing any major restrictions due to extensive computational efforts.

Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall

PubMed Central

Hiorns, J. E.

2016-01-01

Airway hyperresponsiveness (AHR) is a key characteristic of asthma that remains poorly understood. Tidal breathing and deep inspiration ordinarily cause rapid relaxation of airway smooth muscle (ASM) (as demonstrated via application of length fluctuations to tissue strips) and are therefore implicated in modulation of AHR, but in some cases (such as application of transmural pressure oscillations to isolated intact airways) this mechanism fails. Here we use a multiscale biomechanical model for intact airways that incorporates strain stiffening due to collagen recruitment and dynamic force generation by ASM cells to show that the geometry of the airway, together with interplay between dynamic active and passive forces, gives rise to large stress and compliance heterogeneities across the airway wall that are absent in tissue strips. We show further that these stress heterogeneities result in auxotonic loading conditions that are currently not replicated in tissue-strip experiments; stresses in the strip are similar to hoop stress only at the outer airway wall and are under- or overestimates of stresses at the lumen. Taken together these results suggest that a previously underappreciated factor, stress heterogeneities within the airway wall and consequent ASM cellular response to this micromechanical environment, could contribute to AHR and should be explored further both theoretically and experimentally. PMID:27197860

Left-ventricle segmentation in real-time 3D echocardiography using a hybrid active shape model and optimal graph search approach

NASA Astrophysics Data System (ADS)

Zhang, Honghai; Abiose, Ademola K.; Campbell, Dwayne N.; Sonka, Milan; Martins, James B.; Wahle, Andreas

2010-03-01

Quantitative analysis of the left ventricular shape and motion patterns associated with left ventricular mechanical dyssynchrony (LVMD) is essential for diagnosis and treatment planning in congestive heart failure. Real-time 3D echocardiography (RT3DE) used for LVMD analysis is frequently limited by heavy speckle noise or partially incomplete data, thus a segmentation method utilizing learned global shape knowledge is beneficial. In this study, the endocardial surface of the left ventricle (LV) is segmented using a hybrid approach combining active shape model (ASM) with optimal graph search. The latter is used to achieve landmark refinement in the ASM framework. Optimal graph search translates the 3D segmentation into the detection of a minimum-cost closed set in a graph and can produce a globally optimal result. Various information-gradient, intensity distributions, and regional-property terms-are used to define the costs for the graph search. The developed method was tested on 44 RT3DE datasets acquired from 26 LVMD patients. The segmentation accuracy was assessed by surface positioning error and volume overlap measured for the whole LV as well as 16 standard LV regions. The segmentation produced very good results that were not achievable using ASM or graph search alone.

Robust boundary detection of left ventricles on ultrasound images using ASM-level set method.

PubMed

Zhang, Yaonan; Gao, Yuan; Li, Hong; Teng, Yueyang; Kang, Yan

2015-01-01

Level set method has been widely used in medical image analysis, but it has difficulties when being used in the segmentation of left ventricular (LV) boundaries on echocardiography images because the boundaries are not very distinguish, and the signal-to-noise ratio of echocardiography images is not very high. In this paper, we introduce the Active Shape Model (ASM) into the traditional level set method to enforce shape constraints. It improves the accuracy of boundary detection and makes the evolution more efficient. The experiments conducted on the real cardiac ultrasound image sequences show a positive and promising result.

Asian Summer Monsoon Rainfall associated with ENSO and its Predictability

NASA Astrophysics Data System (ADS)

Shin, C. S.; Huang, B.; Zhu, J.; Marx, L.; Kinter, J. L.; Shukla, J.

2015-12-01

The leading modes of the Asian summer monsoon (ASM) rainfall variability and their seasonal predictability are investigated using the CFSv2 hindcasts initialized from multiple ocean analyses over the period of 1979-2008 and observation-based analyses. It is shown that the two leading empirical orthogonal function (EOF) modes of the observed ASM rainfall anomalies, which together account for about 34% of total variance, largely correspond to the ASM responses to the ENSO influences during the summers of the developing and decaying years of a Pacific anomalous event, respectively. These two ASM modes are then designated as the contemporary and delayed ENSO responses, respectively. It is demonstrated that the CFSv2 is capable of predicting these two dominant ASM modes up to the lead of 5 months. More importantly, the predictability of the ASM rainfall are much higher with respect to the delayed ENSO mode than the contemporary one, with the predicted principal component time series of the former maintaining high correlation skill and small ensemble spread with all lead months whereas the latter shows significant degradation in both measures with lead-time. A composite analysis for the ASM rainfall anomalies of all warm ENSO events in this period substantiates the finding that the ASM is more predictable following an ENSO event. The enhanced predictability mainly comes from the evolution of the warm SST anomalies over the Indian Ocean in the spring of the ENSO maturing phases and the persistence of the anomalous high sea surface pressure over the western Pacific in the subsequent summer, which the hindcasts are able to capture reasonably well. The results also show that the ensemble initialization with multiple ocean analyses improves the CFSv2's prediction skill of both ENSO and ASM rainfall. In fact, the skills of the ensemble mean hindcasts initialized from the four different ocean analyses are always equivalent to the best ones initialized from any individual ocean analysis, although the best performer varies with lead-time and starting calendar month.

Comparative anatomy of chromosomal domains with imprinted and non-imprinted allele-specific DNA methylation.

PubMed

Paliwal, Anupam; Temkin, Alexis M; Kerkel, Kristi; Yale, Alexander; Yotova, Iveta; Drost, Natalia; Lax, Simon; Nhan-Chang, Chia-Ling; Powell, Charles; Borczuk, Alain; Aviv, Abraham; Wapner, Ronald; Chen, Xiaowei; Nagy, Peter L; Schork, Nicholas; Do, Catherine; Torkamani, Ali; Tycko, Benjamin

2013-08-01

Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM.

Bitter taste receptor agonists alter mitochondrial function and induce autophagy in airway smooth muscle cells.

PubMed

Pan, Shi; Sharma, Pawan; Shah, Sushrut D; Deshpande, Deepak A

2017-07-01

Airway remodeling, including increased airway smooth muscle (ASM) mass, is a hallmark feature of asthma and COPD. We previously identified the expression of bitter taste receptors (TAS2Rs) on human ASM cells and demonstrated that known TAS2R agonists could promote ASM relaxation and bronchodilation and inhibit mitogen-induced ASM growth. In this study, we explored cellular mechanisms mediating the antimitogenic effect of TAS2R agonists on human ASM cells. Pretreatment of ASM cells with TAS2R agonists chloroquine and quinine resulted in inhibition of cell survival, which was largely reversed by bafilomycin A1, an autophagy inhibitor. Transmission electron microscope studies demonstrated the presence of double-membrane autophagosomes and deformed mitochondria. In ASM cells, TAS2R agonists decreased mitochondrial membrane potential and increased mitochondrial ROS and mitochondrial fragmentation. Inhibiting dynamin-like protein 1 (DLP1) reversed TAS2R agonist-induced mitochondrial membrane potential change and attenuated mitochondrial fragmentation and cell death. Furthermore, the expression of mitochondrial protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) and mitochondrial localization of DLP1 were significantly upregulated by TAS2R agonists. More importantly, inhibiting Bnip3 mitochondrial localization by dominant-negative Bnip3 significantly attenuated cell death induced by TAS2R agonist. Collectively the TAS2R agonists chloroquine and quinine modulate mitochondrial structure and function, resulting in ASM cell death. Furthermore, Bnip3 plays a central role in TAS2R agonist-induced ASM functional changes via a mitochondrial pathway. These findings further establish the cellular mechanisms of antimitogenic effects of TAS2R agonists and identify a novel class of receptors and pathways that can be targeted to mitigate airway remodeling as well as bronchoconstriction in obstructive airway diseases. Copyright © 2017 the American Physiological Society.

Comparative Anatomy of Chromosomal Domains with Imprinted and Non-Imprinted Allele-Specific DNA Methylation

PubMed Central

Kerkel, Kristi; Yale, Alexander; Yotova, Iveta; Drost, Natalia; Lax, Simon; Nhan-Chang, Chia-Ling; Powell, Charles; Borczuk, Alain; Aviv, Abraham; Wapner, Ronald; Chen, Xiaowei; Nagy, Peter L.; Schork, Nicholas; Do, Catherine; Torkamani, Ali; Tycko, Benjamin

2013-01-01

Allele-specific DNA methylation (ASM) is well studied in imprinted domains, but this type of epigenetic asymmetry is actually found more commonly at non-imprinted loci, where the ASM is dictated not by parent-of-origin but instead by the local haplotype. We identified loci with strong ASM in human tissues from methylation-sensitive SNP array data. Two index regions (bisulfite PCR amplicons), one between the C3orf27 and RPN1 genes in chromosome band 3q21 and the other near the VTRNA2-1 vault RNA in band 5q31, proved to be new examples of imprinted DMRs (maternal alleles methylated) while a third, between STEAP3 and C2orf76 in chromosome band 2q14, showed non-imprinted haplotype-dependent ASM. Using long-read bisulfite sequencing (bis-seq) in 8 human tissues we found that in all 3 domains the ASM is restricted to single differentially methylated regions (DMRs), each less than 2kb. The ASM in the C3orf27-RPN1 intergenic region was placenta-specific and associated with allele-specific expression of a long non-coding RNA. Strikingly, the discrete DMRs in all 3 regions overlap with binding sites for the insulator protein CTCF, which we found selectively bound to the unmethylated allele of the STEAP3-C2orf76 DMR. Methylation mapping in two additional genes with non-imprinted haplotype-dependent ASM, ELK3 and CYP2A7, showed that the CYP2A7 DMR also overlaps a CTCF site. Thus, two features of imprinted domains, highly localized DMRs and allele-specific insulator occupancy by CTCF, can also be found in chromosomal domains with non-imprinted ASM. Arguing for biological importance, our analysis of published whole genome bis-seq data from hES cells revealed multiple genome-wide association study (GWAS) peaks near CTCF binding sites with ASM. PMID:24009515

[Ca2+]i oscillations in ASM: relationship with persistent airflow obstruction in asthma.

PubMed

Sweeney, David; Hollins, Fay; Gomez, Edith; Saunders, Ruth; Challiss, R A John; Brightling, Christopher E

2014-07-01

The cause of airway smooth muscle (ASM) hypercontractility in asthma is not fully understood. The relationship of spontaneous intracellular calcium oscillation frequency in ASM to asthma severity was investigated. Oscillations were increased in subjects with impaired lung function abolished by extracellular calcium removal, attenuated by caffeine and unaffected by verapamil or nitrendipine. Whether modulation of increased spontaneous intracellular calcium oscillations in ASM from patients with impaired lung function represents a therapeutic target warrants further investigation. © 2014 The Authors. Respirology published by Wiley Publishing Asia Pty Ltd on behalf of Asian Pacific Society of Respirology.

Full-scale 3-D finite element modeling of a two-loop pressurized water reactor for heat transfer, thermal–mechanical cyclic stress analysis, and environmental fatigue life estimation

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

Mohanty, Subhasish; Soppet, William K.; Majumdar, Saurindranath

This paper discusses a system-level finite element model of a two-loop pressurized water reactor (PWR). Based on this model, system-level heat transfer analysis and subsequent sequentially coupled thermal-mechanical stress analysis were performed for typical thermal-mechanical fatigue cycles. The in-air fatigue lives of example components, such as the hot and cold legs, were estimated on the basis of stress analysis results, ASME in-air fatigue life estimation criteria, and fatigue design curves. Furthermore, environmental correction factors and associated PWR environment fatigue lives for the hot and cold legs were estimated by using estimated stress and strain histories and the approach described inmore » US-NRC report: NUREG-6909.« less

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

PubMed Central

2013-01-01

It is now established that airway smooth muscle (ASM) has roles in determining airway structure and function, well beyond that as the major contractile element. Indeed, changes in ASM function are central to the manifestation of allergic, inflammatory, and fibrotic airway diseases in both children and adults, as well as to airway responses to local and environmental exposures. Emerging evidence points to novel signaling mechanisms within ASM cells of different species that serve to control diverse features, including 1) [Ca2+]i contractility and relaxation, 2) cell proliferation and apoptosis, 3) production and modulation of extracellular components, and 4) release of pro- vs. anti-inflammatory mediators and factors that regulate immunity as well as the function of other airway cell types, such as epithelium, fibroblasts, and nerves. These diverse effects of ASM “activity” result in modulation of bronchoconstriction vs. bronchodilation relevant to airway hyperresponsiveness, airway thickening, and fibrosis that influence compliance. This perspective highlights recent discoveries that reveal the central role of ASM in this regard and helps set the stage for future research toward understanding the pathways regulating ASM and, in turn, the influence of ASM on airway structure and function. Such exploration is key to development of novel therapeutic strategies that influence the pathophysiology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. PMID:24142517

Airway structural alterations selectively associated with severe asthma.

PubMed

Benayoun, Laurent; Druilhe, Anne; Dombret, Marie-Christine; Aubier, Michel; Pretolani, Marina

2003-05-15

To identify airway pathologic abnormalities selectively associated with severe asthma, we examined 10 control subjects, 10 patients with intermittent asthma, 15 patients with mild-to-moderate persistent asthma, 15 patients with severe persistent asthma, and 10 patients with chronic obstructive pulmonary disease. Bronchial biopsies were assessed for epithelial integrity; subepithelial basement membrane (SBM) thickness; collagen type III deposition; eosinophil, neutrophil, and fibroblast numbers; mucous gland and airway smooth muscle (ASM) areas; SBM-ASM distance; ASM hypertrophy (increased cell size); and the expression of the contractile proteins alpha-actin, smooth muscle myosin heavy-chain isoforms, myosin light-chain kinase, and the phosphorylated form of the regulatory light chain of myosin. Neither mucosal eosinophilia nor neutrophilia, epithelial damage, or SBM thickness reflected asthma severity. In contrast, higher numbers of fibroblasts (p < 0.001), an increase in collagen type III deposition (p < 0.020), larger mucous gland (p < 0.040) and ASM (p < 0.001) areas, augmented ASM cell size (p < 0.001), and myosin light-chain kinase expression (p < 0.005) distinguished patients with severe persistent asthma from patients with milder disease or with chronic obstructive pulmonary disease. Stepwise multivariate regression analysis established that fibroblast numbers and ASM cell size were negatively associated with prebronchodilator and postbronchodilator FEV1 values in patients with asthma. We conclude that fibroblast accumulation and ASM hypertrophy in proximal airways are selective determinants of severe persistent asthma.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle.

PubMed

Mizuta, Kentaro; Zhang, Yi; Xu, Dingbang; Mizuta, Fumiko; D'Ovidio, Frank; Masaki, Eiji; Emala, Charles W

2013-09-02

Dopamine signaling is mediated by Gs protein-coupled "D1-like" receptors (D1 and D5) and Gi-coupled "D2-like" receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D1-like receptor antagonists SCH23390 or SCH39166. A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. These results demonstrate that the dopamine D1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM.

The dopamine D1 receptor is expressed and facilitates relaxation in airway smooth muscle

PubMed Central

2013-01-01

Background Dopamine signaling is mediated by Gs protein-coupled “D1-like” receptors (D1 and D5) and Gi-coupled “D2-like” receptors (D2-4). In asthmatic patients, inhaled dopamine induces bronchodilation. Although the Gi-coupled dopamine D2 receptor is expressed and sensitizes adenylyl cyclase activity in airway smooth muscle (ASM) cells, the Gs-coupled dopamine D1-like receptor subtypes have never been identified on these cells. Activation of Gs-coupled receptors stimulates cyclic AMP (cAMP) production through the stimulation of adenylyl cyclase, which promotes ASM relaxation. We questioned whether the dopamine D1-like receptor is expressed on ASM, and modulates its function through Gs-coupling. Methods The mRNA and protein expression of dopamine D1-like receptor subtypes in both native human and guinea pig ASM tissue and cultured human ASM (HASM) cells was measured. To characterize the stimulation of cAMP through the dopamine D1 receptor, HASM cells were treated with dopamine or the dopamine D1-like receptor agonists (A68930 or SKF38393) before cAMP measurements. To evaluate whether the activation of dopamine D1 receptor induces ASM relaxation, guinea pig tracheal rings suspended under isometric tension in organ baths were treated with cumulatively increasing concentrations of dopamine or A68930, following an acetylcholine-induced contraction with or without the cAMP-dependent protein kinase (PKA) inhibitor Rp-cAMPS, the large-conductance calcium-activated potassium (BKCa) channel blocker iberiotoxin, or the exchange proteins directly activated by cAMP (Epac) antagonist NSC45576. Results Messenger RNA encoding the dopamine D1 and D5 receptors were detected in native human ASM tissue and cultured HASM cells. Immunoblots confirmed the protein expression of the dopamine D1 receptor in both native human and guinea pig ASM tissue and cultured HASM cells. The dopamine D1 receptor was also immunohistochemically localized to both human and guinea pig ASM. The dopamine D1-like receptor agonists stimulated cAMP production in HASM cells, which was reversed by the selective dopamine D1-like receptor antagonists SCH23390 or SCH39166. A68930 relaxed acetylcholine-contracted guinea pig tracheal rings, which was attenuated by Rp-cAMPS but not by iberiotoxin or NSC45576. Conclusions These results demonstrate that the dopamine D1 receptors are expressed on ASM and regulate smooth muscle force via cAMP activation of PKA, and offer a novel target for therapeutic relaxation of ASM. PMID:24004608

Bronchodilatory and Anti-Inflammatory Effects of ASM-024, a Nicotinic Receptor Ligand, Developed for the Treatment of Asthma

PubMed Central

Assayag, Evelyne Israël; Beaulieu, Marie-Josée; Cormier, Yvon

2014-01-01

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145±0.032 mg/kg for ASM 024-treated group as compared to 0.088±0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD. PMID:24465890

Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma

PubMed Central

Johnson, Martin; Nikolos, Christina; Jester, William; Klanderman, Barbara; Litonjua, Augusto A.; Tantisira, Kelan G.; Truskowski, Kevin; MacDonald, Kevin; Panettieri, Reynold A.; Weiss, Scott T.

2015-01-01

Globally, asthma is a chronic inflammatory respiratory disease affecting over 300 million people. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. Vitamin D, as an adjunct therapy, may improve disease control in severe asthma patients since vitamin D enhances glucocorticoid responsiveness and mitigates airway smooth muscle (ASM) hyperplasia. We sought to characterize differences in transcriptome responsiveness to vitamin D between fatal asthma- and non-asthma-derived ASM by using RNA-Seq to measure ASM transcript expression in five donors with fatal asthma and ten non-asthma-derived donors at baseline and with vitamin D treatment. Based on a Benjamini-Hochberg corrected p-value <0.05, 838 genes were differentially expressed in fatal asthma vs. non-asthma-derived ASM at baseline, and vitamin D treatment compared to baseline conditions induced differential expression of 711 and 867 genes in fatal asthma- and non-asthma-derived ASM, respectively. Functional gene categories that were highly represented in all groups included extracellular matrix, and responses to steroid hormone stimuli and wounding. Genes differentially expressed by vitamin D also included cytokine and chemokine activity categories. Follow-up qPCR and individual analyte ELISA experiments were conducted for four cytokines (i.e. CCL2, CCL13, CXCL12, IL8) to measure TNFα-induced changes by asthma status and vitamin D treatment. Vitamin D inhibited TNFα-induced IL8 protein secretion levels to a comparable degree in fatal asthma- and non-asthma-derived ASM even though IL8 had significantly higher baseline levels in fatal asthma-derived ASM. Our findings identify vitamin D-specific gene targets and provide transcriptomic data to explore differences in the ASM of fatal asthma- and non-asthma-derived donors. PMID:26207385

Bronchodilatory and anti-inflammatory effects of ASM-024, a nicotinic receptor ligand, developed for the treatment of asthma.

PubMed

Assayag, Evelyne Israël; Beaulieu, Marie-Josée; Cormier, Yvon

2014-01-01

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145 ± 0.032 mg/kg for ASM 024-treated group as compared to 0.088 ± 0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD.

Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation

PubMed Central

Do, Catherine; Lang, Charles F.; Lin, John; Darbary, Huferesh; Krupska, Izabela; Gaba, Aulona; Petukhova, Lynn; Vonsattel, Jean-Paul; Gallagher, Mary P.; Goland, Robin S.; Clynes, Raphael A.; Dwork, Andrew; Kral, John G.; Monk, Catherine; Christiano, Angela M.; Tycko, Benjamin

2016-01-01

Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-Seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A∗-ILF2, associated with immune phenotypes, MYT1L, PTPRN2, CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites were over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to macaques, indicated that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; and variation in CTCF and TF binding sites is an underlying mechanism, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supra- and sub-threshold GWAS peaks in immunological and neurological disorders. PMID:27153397

PRA and Risk Informed Analysis

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

Bernsen, Sidney A.; Simonen, Fredric A.; Balkey, Kenneth R.

2006-01-01

The Boiler and Pressure Vessel Code (BPVC) of the American Society of Mechanical Engineers (ASME) has introduced a risk based approach into Section XI that covers Rules for Inservice Inspection of Nuclear Power Plant Components. The risk based approach requires application of the probabilistic risk assessments (PRA). Because no industry consensus standard existed for PRAs, ASME has developed a standard to evaluate the quality level of an available PRA needed to support a given risk based application. The paper describes the PRA standard, Section XI application of PRAs, and plans for broader applications of PRAs to other ASME nuclear codesmore » and standards. The paper addresses several specific topics of interest to Section XI. Important consideration are special methods (surrogate components) used to overcome the lack of PRA treatments of passive components in PRAs. The approach allows calculations of conditional core damage probabilities both for component failures that cause initiating events and failures in standby systems that decrease the availability of these systems. The paper relates the explicit risk based methods of the new Section XI code cases to the implicit consideration of risk used in the development of Section XI. Other topics include the needed interactions of ISI engineers, plant operating staff, PRA specialists, and members of expert panels that review the risk based programs.« less

Frame Synchronization Without Attached Sync Markers

NASA Technical Reports Server (NTRS)

Hamkins, Jon

2011-01-01

We describe a method to synchronize codeword frames without making use of attached synchronization markers (ASMs). Instead, the synchronizer identifies the code structure present in the received symbols, by operating the decoder for a handful of iterations at each possible symbol offset and forming an appropriate metric. This method is computationally more complex and doesn't perform as well as frame synchronizers that utilize an ASM; nevertheless, the new synchronizer acquires frame synchronization in about two seconds when using a 600 kbps software decoder, and would take about 15 milliseconds on prototype hardware. It also eliminates the need for the ASMs, which is an attractive feature for short uplink codes whose coding gain would be diminished by the overheard of ASM bits. The lack of ASMs also would simplify clock distribution for the AR4JA low-density parity-check (LDPC) codes and adds a small amount to the coding gain as well (up to 0.2 dB).

115-year-old society knows how to reach young scientists: ASM Young Ambassador Program.

PubMed

Karczewska-Golec, Joanna

2015-12-25

With around 40,000 members in more than 150 countries, American Society for Microbiology (ASM) faces the challenge of meeting very diverse needs of its increasingly international members base. The newly launched ASM Young Ambassador Program seeks to aid the Society in this effort. Equipped with ASM conceptual support and financing, Young Ambassadors (YAs) design and pursue country-tailored approaches to strengthen the Society's ties with local microbiological communities. In a trans-national setting, the active presence of YAs at important scientific events, such as 16th European Congress on Biotechnology, forges new interactions between ASM and sister societies. The paper presents an overview of the Young Ambassadors-driven initiatives at both global and country levels, and explores the topic of how early-career scientists can contribute to science diplomacy and international relations. Copyright © 2014 Elsevier B.V. All rights reserved.

Emergence of airway smooth muscle mechanical behavior through dynamic reorganization of contractile units and force transmission pathways

PubMed Central

2014-01-01

Airway hyperresponsiveness (AHR) in asthma remains poorly understood despite significant research effort to elucidate relevant underlying mechanisms. In particular, a significant body of experimental work has focused on the effect of tidal fluctuations on airway smooth muscle (ASM) cells, tissues, lung slices, and whole airways to understand the bronchodilating effect of tidal breathing and deep inspirations. These studies have motivated conceptual models that involve dynamic reorganization of both cytoskeletal components as well as contractile machinery. In this article, a biophysical model of the whole ASM cell is presented that combines 1) crossbridge cycling between actin and myosin; 2) actin-myosin disconnectivity, under imposed length changes, to allow dynamic reconfiguration of “force transmission pathways”; and 3) dynamic parallel-to-serial transitions of contractile units within these pathways that occur through a length fluctuation. Results of this theoretical model suggest that behavior characteristic of experimentally observed force-length loops of maximally activated ASM strips can be explained by interactions among the three mechanisms. Crucially, both sustained disconnectivity and parallel-to-serial transitions are necessary to explain the nature of hysteresis and strain stiffening observed experimentally. The results provide strong evidence that dynamic rearrangement of contractile machinery is a likely mechanism underlying many of the phenomena observed at timescales associated with tidal breathing. This theoretical cell-level model captures many of the salient features of mechanical behavior observed experimentally and should provide a useful starting block for a bottom-up approach to understanding tissue-level mechanical behavior. PMID:24481961

33 CFR 127.1101 - Piping systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Waterfront Facilities Handling Liquefied Hazardous Gas Design and Construction § 127.1101 Piping systems... following criteria: (a) Each system must be designed and constructed in accordance with ASME B31.3. (b) Each... the line or equipment. Unless the layout of the piping allows the isolation valve at the transfer...

33 CFR 127.1101 - Piping systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Waterfront Facilities Handling Liquefied Hazardous Gas Design and Construction § 127.1101 Piping systems... following criteria: (a) Each system must be designed and constructed in accordance with ASME B31.3. (b) Each... the line or equipment. Unless the layout of the piping allows the isolation valve at the transfer...

33 CFR 127.1101 - Piping systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Waterfront Facilities Handling Liquefied Hazardous Gas Design and Construction § 127.1101 Piping systems... following criteria: (a) Each system must be designed and constructed in accordance with ASME B31.3. (b) Each... the line or equipment. Unless the layout of the piping allows the isolation valve at the transfer...

33 CFR 127.1101 - Piping systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Waterfront Facilities Handling Liquefied Hazardous Gas Design and Construction § 127.1101 Piping systems... following criteria: (a) Each system must be designed and constructed in accordance with ASME B31.3. (b) Each... the line or equipment. Unless the layout of the piping allows the isolation valve at the transfer...

33 CFR 127.1101 - Piping systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Waterfront Facilities Handling Liquefied Hazardous Gas Design and Construction § 127.1101 Piping systems... following criteria: (a) Each system must be designed and constructed in accordance with ASME B31.3. (b) Each... the line or equipment. Unless the layout of the piping allows the isolation valve at the transfer...

49 CFR 178.345-10 - Pressure relief.

Code of Federal Regulations, 2010 CFR

2010-10-01

... applicable individual specification. The pressure and vacuum relief system must be designed to operate and... resulting from loading, unloading, or from heating and cooling of lading. Pressure relief systems are not required to conform to the ASME Code. (b) Type and construction of relief systems and devices. (1) Each...

Fault imprint in clay units: magnetic fabric, structural and mineralogical signature

NASA Astrophysics Data System (ADS)

Moreno, Eva; Homberg, Catherine; Schnyder, Johann; Person, Alain; du Peloux1, Arthur; Dick, Pierre

2014-05-01

Fault-induced deformations in clay units can be difficult to decipher because strain markers are not always visible at outcrop scale or using geophysical methods. Previous studies have indicated that the anisotropy of magnetic susceptibility (ASM) provides a powerful and rapid technique to investigate tectonic deformation in clay units even when they appear quite homogenous and undeformed at the outcrop scale (Lee et al. 1990, Mattei et al. 1997). We report here a study based on ASM, structural analysis and magnetic and clay mineralogy from two boreholes (TF1 and ASM1)drilled horizontally in the Experimental Station of Tournemire of the Institute for Radiological Protection and Nuclear Safety (IRSN) in Aveyron (France). The boreholes intersect a N-S trending strike-slip fault from west to east. The ASM study indicates the evolution of the magnetic fabric from the undeformed host rock to the fault core. Also, all the fractures cutting the studied interval of the core have been measured as well as the slip vectors which are generally well preserved. In the two boreholes, the undeformed sediments outside the fault zone are characterized by an oblate fabric, a sub-vertical minimum susceptibility axis (k3) perpendicular to the bedding plane and without magnetic lineation. Within the fault zone, a tilt in the bedding plane has been observed in two boreholes TF1 and ASM1. In addition, in the TF1 core, the fault area presents a tectonic fabric characterized by a triaxial AMS ellipsoid. Moreover, the magnetic lineation increases and k3 switches from a vertical to a sub-horizontal plane. This kind of fabric has not been observed in borehole ASM1. The structural analysis of the individual fractures making the fault zone indicates a complex tectonic history with different imprint in the two fault segments cut by the two boreholes. The large majority of fractures correspond to dextral strike-slip faults but normal and reverse movements were observed and are more or less frequent depending on the borehole. Notably, many fractures are low angle faults (dip<45°) and may bear both strike-slip or normal striae. The mineralogical study based on X-ray diffraction analysis, have pointed out some variations in clay minerals associations nearby the deformed zones that may be the result of fluid circulation along the fault system which is in agreement with the presence of goethite determined by low magnetic temperature measurements. This multi-proxi study, combining ASM, petrostructural and mineralogical approaches has highlighted the heterogeneity of the fault, but also its past role as a drain to fluid circulation.

A Guide for Recertification of Ground Based Pressure Vessels and Liquid Holding Tanks

DTIC Science & Technology

1987-12-15

Boiler and Pressure Vessel Code , Section...Requirements 202 Calculate Vessel MAWP Using ASME Boiler and Pressure Vessel Code Section VUI, Division 1. 203 Assess Vessel MAWP Using ASME Boiler and Pressure Vessel Code Section...Engineers (ASME) Boiler and Pressure Vessel Code (B&PV) Section VIll, Division 1, or other applicable standard. This activity involves the

49 CFR 222.55 - How are new supplementary or alternative safety measures approved?

Code of Federal Regulations, 2010 CFR

2010-10-01

... applicant; (2) A description and design of the proposed new SSM or ASM; (3) A description and results of the... SSM or ASM; and (5) Any other information deemed necessary. (e) If the Associate Administrator is... an ASM to be used in the same manner as the measures listed in appendix B of this part. The Associate...

Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling.

PubMed

Noble, Peter B; Pascoe, Chris D; Lan, Bo; Ito, Satoru; Kistemaker, Loes E M; Tatler, Amanda L; Pera, Tonio; Brook, Bindi S; Gosens, Reinoud; West, Adrian R

2014-12-01

Asthma is an obstructive airway disease, with a heterogeneous and multifactorial pathogenesis. Although generally considered to be a disease principally driven by chronic inflammation, it is becoming increasingly recognised that the immune component of the pathology poorly correlates with the clinical symptoms of asthma, thus highlighting a potentially central role for non-immune cells. In this context airway smooth muscle (ASM) may be a key player, as it comprises a significant proportion of the airway wall and is the ultimate effector of acute airway narrowing. Historically, the contribution of ASM to asthma pathogenesis has been contentious, yet emerging evidence suggests that ASM contractile activation imparts chronic effects that extend well beyond the temporary effects of bronchoconstriction. In this review article we describe the effects that ASM contraction, in combination with cellular mechanotransduction and novel contraction-inflammation synergies, contribute to asthma pathogenesis. Specific emphasis will be placed on the effects that ASM contraction exerts on the mechanical properties of the airway wall, as well as novel mechanisms by which ASM contraction may contribute to more established features of asthma such as airway wall remodelling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibition of acid sphingomyelinase disrupts LYNUS signaling and triggers autophagy.

PubMed

Justice, Matthew J; Bronova, Irina; Schweitzer, Kelly S; Poirier, Christophe; Blum, Janice S; Berdyshev, Evgeny V; Petrache, Irina

2018-04-01

Activation of the lysosomal ceramide-producing enzyme, acid sphingomyelinase (ASM), by various stresses is centrally involved in cell death and has been implicated in autophagy. We set out to investigate the role of the baseline ASM activity in maintaining physiological functions of lysosomes, focusing on the lysosomal nutrient-sensing complex (LYNUS), a lysosomal membrane-anchored multiprotein complex that includes mammalian target of rapamycin (mTOR) and transcription factor EB (TFEB). ASM inhibition with imipramine or sphingomyelin phosphodiesterase 1 ( SMPD1 ) siRNA in human lung cells, or by transgenic Smpd1 +/- haploinsufficiency of mouse lungs, markedly reduced mTOR- and P70-S6 kinase (Thr 389)-phosphorylation and modified TFEB in a pattern consistent with its activation. Inhibition of baseline ASM activity significantly increased autophagy with preserved degradative potential. Pulse labeling of sphingolipid metabolites revealed that ASM inhibition markedly decreased sphingosine (Sph) and Sph-1-phosphate (S1P) levels at the level of ceramide hydrolysis. These findings suggest that ASM functions to maintain physiological mTOR signaling and inhibit autophagy and implicate Sph and/or S1P in the control of lysosomal function. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

Activated sludge pilot plant: comparison between experimental and predicted concentration profiles using three different modelling approaches.

PubMed

Le Moullec, Y; Potier, O; Gentric, C; Leclerc, J P

2011-05-01

This paper presents an experimental and numerical study of an activated sludge channel pilot plant. Concentration profiles of oxygen, COD, NO(3) and NH(4) have been measured for several operating conditions. These profiles have been compared to the simulated ones with three different modelling approaches, namely a systemic approach, CFD and compartmental modelling. For these three approaches, the kinetics model was the ASM-1 model (Henze et al., 2001). The three approaches allowed a reasonable simulation of all the concentration profiles except for ammonium for which the simulations results were far from the experimental ones. The analysis of the results showed that the role of the kinetics model is of primary importance for the prediction of activated sludge reactors performance. The fact that existing kinetics parameters in the literature have been determined by parametric optimisation using a systemic model limits the reliability of the prediction of local concentrations and of the local design of activated sludge reactors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Airway compliance and dynamics explain the apparent discrepancy in length adaptation between intact airways and smooth muscle strips.

PubMed

Dowie, Jackson; Ansell, Thomas K; Noble, Peter B; Donovan, Graham M

2016-01-01

Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyper-responsiveness in asthma. Recent results by Ansell et al., 2015 (JAP 2014 10.1152/japplphysiol.00724.2014) have cast doubt on this role by testing for length adaptation using an intact airway preparation, rather than strips of ASM. Using this technique they found no evidence for length adaptation in intact airways. Here we attempt to resolve this apparent discrepancy by constructing a minimal mathematical model of the intact airway, including ASM which follows the classic length-tension curve and undergoes length adaptation. This allows us to show that (1) no evidence of length adaptation should be expected in large, cartilaginous, intact airways; (2) even in highly compliant peripheral airways, or at more compliant regions of the pressure-volume curve of large airways, the effect of length adaptation would be modest and at best marginally detectable in intact airways; (3) the key parameters which control the appearance of length adaptation in intact airways are airway compliance and the relaxation timescale. The results of this mathematical simulation suggest that length adaptation observed at the level of the isolated ASM may not clearly manifest in the normal intact airway. Copyright © 2015 Elsevier B.V. All rights reserved.

The vertical structure of ozone and water vapor profiles in Lhasa within Asia summer monsoon anticyclone during the stratospheric intrusion

NASA Astrophysics Data System (ADS)

Li, Dan; Vogel, Bärbel; Bian, Jianchun; Müller, Rolf; Günther, Gebhard; Bai, Zhixuan; Li, Qian; Fan, Qiujun; Zhang, Jinqiang

2017-04-01

A stratospheric intrusion process occurred over the southeastern side of the Asia summer monsoon (ASM) region is investigated using the balloon-borne measurements of ozone and water vapor during 18-20 August 2013. Data from Lhasa (29.66° N, 91.14° E, above sea level (asl.) 3,650 m) show that the positive relative change of the ozone mixing ratios in the tropopause layer attained to 90 % on 19 and 20 August. The backward trajectory calculation from CLaMS model and the satellite data from the ozone monitoring instrument (OMI) and the atmospheric infrared sounder (AIRS) indicate that the (stratospheric) air parcels intruded (originated) from the Northeast Asia to the southeastern edge of the ASM anticyclone. Meanwhile, typhoon Utor occurred over the sourtheastern edge of the ASM and lasted from 8 to 18 August 2013. The convection associated with Utor uplifted air with low ozone from the Western Pacific to the middle/upper troposphere. Air parcels with high ozone from the high latitude and with low ozone from the Western Pacific met at the sourtheastern side of the ASM and then transported westward to Lhasa over long-distances (˜2,000 km). In addition, the laminated identification method is used to identify the laminae structure of the ozone and water vapor profiles from the middle troposphere to the lower stratosphere in Lhasa, confirming the role of the dynamic disturbance (e.g., Rossby and gravity wave)

ITER's Tokamak Cooling Water System and the the Use of ASME Codes to Comply with French Regulations of Nuclear Pressure Equipment

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

Berry, Jan; Ferrada, Juan J; Curd, Warren

During inductive plasma operation of ITER, fusion power will reach 500 MW with an energy multiplication factor of 10. The heat will be transferred by the Tokamak Cooling Water System (TCWS) to the environment using the secondary cooling system. Plasma operations are inherently safe even under the most severe postulated accident condition a large, in-vessel break that results in a loss-of-coolant accident. A functioning cooling water system is not required to ensure safe shutdown. Even though ITER is inherently safe, TCWS equipment (e.g., heat exchangers, piping, pressurizers) are classified as safety important components. This is because the water is predictedmore » to contain low-levels of radionuclides (e.g., activated corrosion products, tritium) with activity levels high enough to require the design of components to be in accordance with French regulations for nuclear pressure equipment, i.e., the French Order dated 12 December 2005 (ESPN). ESPN has extended the practical application of the methodology established by the Pressure Equipment Directive (97/23/EC) to nuclear pressure equipment, under French Decree 99-1046 dated 13 December 1999, and Order dated 21 December 1999 (ESP). ASME codes and supplementary analyses (e.g., Failure Modes and Effects Analysis) will be used to demonstrate that the TCWS equipment meets these essential safety requirements. TCWS is being designed to provide not only cooling, with a capacity of approximately 1 GW energy removal, but also elevated temperature baking of first-wall/blanket, vacuum vessel, and divertor. Additional TCWS functions include chemical control of water, draining and drying for maintenance, and facilitation of leak detection/localization. The TCWS interfaces with the majority of ITER systems, including the secondary cooling system. U.S. ITER is responsible for design, engineering, and procurement of the TCWS with industry support from an Engineering Services Organization (ESO) (AREVA Federal Services, with support from Northrop Grumman, and OneCIS). ITER International Organization (ITER-IO) is responsible for design oversight and equipment installation in Cadarache, France. TCWS equipment will be fabricated using ASME design codes with quality assurance and oversight by an Agreed Notified Body (approved by the French regulator) that will ensure regulatory compliance. This paper describes the TCWS design and how U.S. ITER and fabricators will use ASME codes to comply with EU Directives and French Orders and Decrees.« less

Comparison of liver volumetry on contrast‐enhanced CT images: one semiautomatic and two automatic approaches

PubMed Central

Cai, Wei; He, Baochun; Fang, Chihua

2016-01-01

This study was to evaluate the accuracy, consistency, and efficiency of three liver volumetry methods— one interactive method, an in‐house‐developed 3D medical Image Analysis (3DMIA) system, one automatic active shape model (ASM)‐based segmentation, and one automatic probabilistic atlas (PA)‐guided segmentation method on clinical contrast‐enhanced CT images. Forty‐two datasets, including 27 normal liver and 15 space‐occupying liver lesion patients, were retrospectively included in this study. The three methods — one semiautomatic 3DMIA, one automatic ASM‐based, and one automatic PA‐based liver volumetry — achieved an accuracy with VD (volume difference) of −1.69%,−2.75%, and 3.06% in the normal group, respectively, and with VD of −3.20%,−3.35%, and 4.14% in the space‐occupying lesion group, respectively. However, the three methods achieved an efficiency of 27.63 mins, 1.26 mins, 1.18 mins on average, respectively, compared with the manual volumetry, which took 43.98 mins. The high intraclass correlation coefficient between the three methods and the manual method indicated an excellent agreement on liver volumetry. Significant differences in segmentation time were observed between the three methods (3DMIA, ASM, and PA) and the manual volumetry (p<0.001), as well as between the automatic volumetries (ASM and PA) and the semiautomatic volumetry (3DMIA) (p<0.001). The semiautomatic interactive 3DMIA, automatic ASM‐based, and automatic PA‐based liver volumetry agreed well with manual gold standard in both the normal liver group and the space‐occupying lesion group. The ASM‐ and PA‐based automatic segmentation have better efficiency in clinical use. PACS number(s): 87.55.‐x PMID:27929487

Similar speleothem δ18O signals indicating diverging climate variations in inland central Asia and monsoonal south Asia during the Holocene

NASA Astrophysics Data System (ADS)

Jin, Liya; Zhang, Xiaojian

2017-04-01

High-resolution and precisely dated speleothem oxygen isotope (δ18O) records from Asia have provided key evidence for past monsoonal changes. It is found that δ18O records of stalagmites from Kesang Cave (42°52'N, 81°45'E, Xinjiang, China) in inland central Asia were very similar to those from Qunf Cave (17°10'N, 54°18'E, southern Oman) in South Asia, shifting from light to heavy throughout the Holocene, which was regarded as a signal that strong Asian summer monsoon (ASM) may have intruded into the Kesang Cave site and/or adjacent areas in inland central Asia to produce heavy rainfall during the high insolation times (e.g. the early Holocene). However, this is in contrast to conclusions based on other Holocene proxy records and modeling simulations, showing a persistent wetting trend in arid central Asia during the Holocene with a dryer condition in the early Holocene and the wettest condition in the late Holocene. With an analysis of model-proxy data comparison, we revealed a possible physical mechanism responsible for the Holocene evolution of moisture/precipitation in Asian summer monsoon (ASM)-dominated regions and that in the inland central Asia. It is revealed that a recurrent circumglobal teleconnection (CGT) pattern in the summertime mid-latitude circulation of the Northern Hemisphere was closely related to the ASM and the climate of inland central Asia, acting as a bridge linking the ASM to insolation, high-latitude forcing (North Atlantic sea surface temperature (SST)), and low-latitude forcing (tropical Ocean SST). Also, the CGT influence speleothem δ18O values in South Asia via its effect on the amount of precipitation. In addition, the moisture source from the Indian Ocean is associated with relatively high δ18O values compared with that from the North Atlantic Ocean, leading to increased precipitation δ18O values. Hence, the CGT has probably been the key factor responsible for the in-phase relationship in speleothem δ18O values (Kesang Cave and Qunf Cave), but out-of-phase relationship in moisture/precipitation evolutions between inland central Asia and the ASM region during the Holocene. In addition, since boreal winter (December-January-February, DJF) precipitation in northwestern China (a part of the core zone in inland central Asia) during the Holocene has been revealed to contribute a great deal to moisture evolution in inland central Asia, and the changes in the seasonal cycle of incoming solar radiation driven by Earth's orbital changes have probably played an important role in the out-of-phase relationship in the moisture evolution between the inland central Asia and ASM regions during the Holocene.

46 CFR 56.60-1 - Acceptable materials and specifications (replaces 123 and Table 126.1 in ASME B31.1).

Code of Federal Regulations, 2010 CFR

2010-10-01

... Low temperature steel pipe Sec. VIII of the ASME Boiler and Pressure Vessel Code (5). Pipe, welded: A... only, fusion welded steel pipe ASME B31.1 (8). A 358 Electric fusion welded pipe, high temperature... Seamless and welded (no added filler metal) carbon and low alloy tubing for low temperature UCS23, Sec...

Turbulent Transport at High Reynolds Numbers in an Inertial Confinement Fusion Context

DTIC Science & Technology

2014-09-01

Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794 P . Rao1 Department of Applied Mathematics and Statistics...scales, 1Corresponding author. Contributed by the Fluids Engineering Division of ASME for publication in the JOURNAL OF FLUIDS ENGINEERING...Engineering SEPTEMBER 2014, Vol. 136 / 091206-1Copyright VC 2014 by ASME Downloaded From: http://fluidsengineering.asmedigitalcollection.asme.org/ on

A Population Pharmacokinetic Modeling Approach Shows that Serum Penicillin G Concentrations Are Below Inhibitory Concentrations by Two Weeks after Benzathine Penicillin G Injection in the Majority of Young Adults

DTIC Science & Technology

2014-11-01

H , El-Kholy AG, Madkour AA, Kaplan EL. 1996. Rheumatic fever prophylaxis using benzathine...by N A V A L H E A LT H R E S E A R C H C T R http://aac.asm .org/ D ow nloaded from received in the study. On day 1, which was sample 1, we...2015 by N A V A L H E A LT H R E S E A R C H C T R http://aac.asm .org/ D ow nloaded from mean of 0.006 g/ml for the other subjects.

Asm-Triggered too Observations of Z Sources at Low Accretion Rate

NASA Astrophysics Data System (ADS)

van der Klis, Michiel

We propose to perform a pointed observation if the ASM shows that a Z source has entered a state of low accretion rate. This would provide a unique opportunity to detect millisecond pulsations. In Sco X-1 we would expect to discover beat-frequency QPO, and could perform a unique high count rate study of them. At sufficiently low accretion rate it would be possible to study the accretion flow when the magnetospheric radius approaches the corotation radius. The frequency of the horizontal branch QPO should go to zero here, and centrifugal inhibition of the accretion should set in, providing direct tests of the magnetospheric model of Z sources.

The Chaotic Long-term X-ray Variability of 4U 1705-44

NASA Astrophysics Data System (ADS)

Phillipson, R. A.; Boyd, P. T.; Smale, A. P.

2018-04-01

The low-mass X-ray binary 4U1705-44 exhibits dramatic long-term X-ray time variability with a timescale of several hundred days. The All-Sky Monitor (ASM) aboard the Rossi X-ray Timing Explorer (RXTE) and the Japanese Monitor of All-sky X-ray Image (MAXI) aboard the International Space Station together have continuously observed the source from December 1995 through May 2014. The combined ASM-MAXI data provide a continuous time series over fifty times the length of the timescale of interest. Topological analysis can help us identify 'fingerprints' in the phase-space of a system unique to its equations of motion. The Birman-Williams theorem postulates that if such fingerprints are the same between two systems, then their equations of motion must be closely related. The phase-space embedding of the source light curve shows a strong resemblance to the double-welled nonlinear Duffing oscillator. We explore a range of parameters for which the Duffing oscillator closely mirrors the time evolution of 4U1705-44. We extract low period, unstable periodic orbits from the 4U1705-44 and Duffing time series and compare their topological information. The Duffing and 4U1705-44 topological properties are identical, providing strong evidence that they share the same underlying template. This suggests that we can look to the Duffing equation to help guide the development of a physical model to describe the long-term X-ray variability of this and other similarly behaved X-ray binary systems.

Automated bone segmentation from large field of view 3D MR images of the hip joint

NASA Astrophysics Data System (ADS)

Xia, Ying; Fripp, Jurgen; Chandra, Shekhar S.; Schwarz, Raphael; Engstrom, Craig; Crozier, Stuart

2013-10-01

Accurate bone segmentation in the hip joint region from magnetic resonance (MR) images can provide quantitative data for examining pathoanatomical conditions such as femoroacetabular impingement through to varying stages of osteoarthritis to monitor bone and associated cartilage morphometry. We evaluate two state-of-the-art methods (multi-atlas and active shape model (ASM) approaches) on bilateral MR images for automatic 3D bone segmentation in the hip region (proximal femur and innominate bone). Bilateral MR images of the hip joints were acquired at 3T from 30 volunteers. Image sequences included water-excitation dual echo stead state (FOV 38.6 × 24.1 cm, matrix 576 × 360, thickness 0.61 mm) in all subjects and multi-echo data image combination (FOV 37.6 × 23.5 cm, matrix 576 × 360, thickness 0.70 mm) for a subset of eight subjects. Following manual segmentation of femoral (head-neck, proximal-shaft) and innominate (ilium+ischium+pubis) bone, automated bone segmentation proceeded via two approaches: (1) multi-atlas segmentation incorporating non-rigid registration and (2) an advanced ASM-based scheme. Mean inter- and intra-rater reliability Dice's similarity coefficients (DSC) for manual segmentation of femoral and innominate bone were (0.970, 0.963) and (0.971, 0.965). Compared with manual data, mean DSC values for femoral and innominate bone volumes using automated multi-atlas and ASM-based methods were (0.950, 0.922) and (0.946, 0.917), respectively. Both approaches delivered accurate (high DSC values) segmentation results; notably, ASM data were generated in substantially less computational time (12 min versus 10 h). Both automated algorithms provided accurate 3D bone volumetric descriptions for MR-based measures in the hip region. The highly computational efficient ASM-based approach is more likely suitable for future clinical applications such as extracting bone-cartilage interfaces for potential cartilage segmentation.

Automated bone segmentation from large field of view 3D MR images of the hip joint.

PubMed

Xia, Ying; Fripp, Jurgen; Chandra, Shekhar S; Schwarz, Raphael; Engstrom, Craig; Crozier, Stuart

2013-10-21

Accurate bone segmentation in the hip joint region from magnetic resonance (MR) images can provide quantitative data for examining pathoanatomical conditions such as femoroacetabular impingement through to varying stages of osteoarthritis to monitor bone and associated cartilage morphometry. We evaluate two state-of-the-art methods (multi-atlas and active shape model (ASM) approaches) on bilateral MR images for automatic 3D bone segmentation in the hip region (proximal femur and innominate bone). Bilateral MR images of the hip joints were acquired at 3T from 30 volunteers. Image sequences included water-excitation dual echo stead state (FOV 38.6 × 24.1 cm, matrix 576 × 360, thickness 0.61 mm) in all subjects and multi-echo data image combination (FOV 37.6 × 23.5 cm, matrix 576 × 360, thickness 0.70 mm) for a subset of eight subjects. Following manual segmentation of femoral (head-neck, proximal-shaft) and innominate (ilium+ischium+pubis) bone, automated bone segmentation proceeded via two approaches: (1) multi-atlas segmentation incorporating non-rigid registration and (2) an advanced ASM-based scheme. Mean inter- and intra-rater reliability Dice's similarity coefficients (DSC) for manual segmentation of femoral and innominate bone were (0.970, 0.963) and (0.971, 0.965). Compared with manual data, mean DSC values for femoral and innominate bone volumes using automated multi-atlas and ASM-based methods were (0.950, 0.922) and (0.946, 0.917), respectively. Both approaches delivered accurate (high DSC values) segmentation results; notably, ASM data were generated in substantially less computational time (12 min versus 10 h). Both automated algorithms provided accurate 3D bone volumetric descriptions for MR-based measures in the hip region. The highly computational efficient ASM-based approach is more likely suitable for future clinical applications such as extracting bone-cartilage interfaces for potential cartilage segmentation.

Association between visceral obesity and sarcopenia and vitamin D deficiency in older Koreans: the Ansan Geriatric Study.

PubMed

Seo, Ji A; Cho, Hyunjoo; Eun, Chai R; Yoo, Hye J; Kim, Sin G; Choi, Kyung M; Baik, Sei H; Choi, Dong S; Park, Moon H; Han, Changsu; Kim, Nan H

2012-04-01

To investigate whether vitamin D levels are independently associated with visceral obesity, sarcopenia, or sarcopenic obesity. Cross-sectional. Population-based sample of elderly adults living in Ansan, Korea. Two hundred sixteen men and 268 women aged 65 and older. Serum 25-hydroxyvitamin D (25(OH)D) levels, visceral fat area (VFA) according to abdominal computed tomography scanning, and body composition (body fat percentage, appendicular skeletal muscle mass (ASM)) using dual-energy X-ray absorptiometry. Visceral obesity was defined as VFA of 100 cm(2) or greater and sarcopenia as ASM/height(2) more than 1 standard deviation (SD) below the sex-specific mean of a young reference group. The adjusted 25(OH)D level for men was negatively associated with systolic blood pressure, VFA, and body fat percentage but positively associated with ASM. In women, waist circumference, triglyceride levels, and VFA were negatively correlated with 25(OH)D levels. In the joint regression model, VFA and ASM were independently associated with 25(OH)D levels (β = -0.078, P = .01 and β = 0.087, P = .02, respectively) per 1SD difference in VFA and ASM in men but not women. When participants were categorized according to four visceral obesity and sarcopenia categories, adjusted mean 25(OH)D level was lower in men with visceral obesity than in men without but was not affected by the presence or absence of sarcopenia. Greater visceral fat and lower muscle mass were associated with lower 25(OH)D levels in elderly Korean men, suggesting that screening for vitamin D deficiency may be appropriate in older Koreans with visceral obesity or sarcopenia. Sarcopenic obesity as defined according to prespecified criteria did not have an additive association with 25(OH)D levels. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

49 CFR 195.110 - External loads.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., vibration, thermal expansion, and contraction must be provided for in designing a pipeline system. In providing for expansion and flexibility, section 419 of ASME/ANSI B31.4 must be followed. (b) The pipe and...

49 CFR 195.110 - External loads.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., vibration, thermal expansion, and contraction must be provided for in designing a pipeline system. In providing for expansion and flexibility, section 419 of ASME/ANSI B31.4 must be followed. (b) The pipe and...

RXTE and BeppoSAX Observations of the Transient X-ray Pulsar XTE J 18591+083

NASA Technical Reports Server (NTRS)

Corbet, R. H. D.; intZand, J. J. M.; Levine, A. M.; Marshall, F. E.

2008-01-01

We present observations of the 9.8 s X-ray pulsar XTE J159+083 made with the All-Sky Monitor (ASM) and Proportional Counter Array (PCA) on board the Rossi X-ray Timing Explorer (RXTE), and the Wide Field Cameras (WFC) on board BeppoSAX. The ASM data cover a 12 year time interval and show that an extended outburst occurred between approximately MJD50, 250, and 50, 460 (1996 June 16 to 1997 January 12). The ASM data excluding this outburst interval suggest a possible 61 day modulation. Eighteen sets of PCA observations were obtained over an approx. one month interval in 1999. The flux variability measured with the PCA appears consistent with the possible period found with the ASM. The PCA measurements of the pulse period showed it to decrease non-monotonically and then to increase significantly. Doppler shifts due to orbital motion rather than accretion torques appear to be better able to explain the pulse period changes. Observations with the WFC during the extended outburst give an error box which is consistent with a previously determined PCA error box but is significantly smaller. The transient nature of XTE J1859+083 and the length of its pulse period are consistent with it being a Be/neutral star binary. The possible 61 day orbital period would be of the expected length for a Be star system with a 9.8 s pulse period.

Application of as-synthesised MCM-41 and MCM-41 wrapped with reduced graphene oxide/graphene oxide in the remediation of acetaminophen and aspirin from aqueous system.

PubMed

Akpotu, Samson O; Moodley, Brenda

2018-03-01

In this study, ASM41 (as-synthesised MCM-41), MCM-41, MCM-41 encapsulated with graphene oxide (MCM-41-GO) and reduced graphene oxide (MCM-41-G) were fabricated and utilized in the remediation of acetaminophen and aspirin from water. A surfactant template (cetyltrimethylammonium bromide) was added to ASM41 to make it more hydrophobic and its effects on the remediation of acetaminophen and aspirin from wastewater was studied. To further improve the adsorption capacity of the adsorbent, MCM-41 was encapsulated with GO and G which also aided in easy separation of the adsorbent from the aqueous solution. Comparative studies of the adsorption of acetaminophen and aspirin on all four adsorbents were investigated. Batch adsorption studies of acetaminophen and aspirin were carried out to determine the effects of pH, initial concentration, time and adsorbent dose. Adsorption mechanism was through EDA, π-π interactions, and hydrophobic effects. Data from sorption kinetics showed ASM41 had the highest q m value for aspirin (909.1 mg/g) and MCM-41-G had the highest q m value for acetaminophen (555.6 mg/g). The significant adsorption by ASM41 can be attributed to increased hydrophobicity due to the retention of the surfactant template. Thermodynamic studies revealed the adsorption process as spontaneous and exothermic. Desorption studies revealed that adsorbents could be regenerated and reused for adsorption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Orbitally-paced variations of water availability in the SE Asian Monsoon region following the Miocene Climate Transition

NASA Astrophysics Data System (ADS)

Heitmann, Emma O.; Ji, Shunchuan; Nie, Junsheng; Breecker, Daniel O.

2017-09-01

Middle Miocene Earth had several boundary conditions similar to those predicted for future Earth including similar atmospheric pCO2 and substantial Antarctic ice cover but no northern hemisphere ice sheets. We describe a 12 m outcrop of the terrestrial Yanwan Section in the Tianshui Basin, Gansu, China, following the Miocene Climate Transition (13.9-13.7 Ma). It consists of ∼25 cm thick CaCO3-cemented horizons that overprint siltstones every ∼1 m. We suggest that stacked soils developed in siltstones under a seasonal climate with a fluctuating water table, evidenced by roots, clay films, mottling, presence of CaCO3 nodules, and stacked carbonate nodule δ13 C and δ18 O profiles that mimic modern soils. We suggest that the CaCO3-cemented horizons are capillary-fringe carbonates that formed in an arid climate with a steady water table and high potential evapotranspiration rates (PET), evidenced by sharp upper and basal contacts, micrite, sparite, and root-pore cements. The CaCO3 of the cemented horizons and the carbonate nodules have similar mean δ18 O and δ13 C values but the cements have significantly smaller variance in δ13 C and δ18 O values and a different δ18 O versus δ13 C slope, supporting the conclusion that these carbonates are from different populations. The magneto-stratigraphic age model indicates obliquity pacing of the arid conditions required to form the CaCO3-cemented horizons suggesting an orbital control on water availability. We suggest two possible drivers for the obliquity pacing of arid conditions: 1) variability in the cross-equatorial pressure gradient that controls summer monsoon (ASM) strength and is influenced by obliquity-paced variations of Antarctic ice volume and 2) variability in Western Pacific Ocean-East Asian continent pressure gradient controlled by the 25-45°N meridional insolation gradient. We also suggest that variations in aridity were influenced by variations in PET and sensible heating of the regional land surface which are both influenced by precession-controlled 35°N summer insolation. We then use orbital configurations to predict lithology. Coincidence of obliquity minima (strong ASM) and 35°N summer insolation maxima (strong ASM) drives strong ASM and high PET, resulting in soil formation in an environment with relatively large seasonal changes in water availability. Coincidence of obliquity maxima (weak ASM) and 35°N summer insolation maxima (strong ASM) moderates the ASM, results in high PET, and thus drives overprinting of soils by capillary fringe carbonates above a deepened and relatively stable water table. Coincidence of obliquity and insolation minima also moderates the ASM but results in low PET and thus a high water table, which explains the previously documented occurrence of aquatic plants in this section. This context allows us to assign an orbital configuration to atmospheric pCO2 determined from the paleosols. Our best estimate of pCO2 during the times of intermediate ice volume is 475 + 650 / - 230 ppmV (median value with error reported as 84th-16th percentile values). Southern hemisphere control of ASM variability during the Middle Miocene may have resulted in larger orbital scale water availability variations compared with the Pleistocene.

Alloy-steel nuts for bolting for high-pressure and high-temperature service (ASME SA-194 with additional requirements)

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

Not Available

This standard covers alloy steel nuts for bolting for high-pressure and high-temperature service in nuclear and associated applications. This standard does not cover bar or other starting materials. The only implied special considerations for starting materials are that they be capable of passing the required tests when processed into finished products in accordance with this standard. Material shall conform to the requirements of ASME SA-194; to the requirements of the ASME Boiler and Pressure Vessel Code (ASME Code), Section III, Article NB-2000; to the requirements of NE E 8-18; and to the additional requirements of this standard.

Development of the Artistic Supervision Model Scale (ASMS)

ERIC Educational Resources Information Center

Kapusuzoglu, Saduman; Dilekci, Umit

2017-01-01

The purpose of the study is to develop the Artistic Supervision Model Scale in accordance with the perception of inspectors and the elementary and secondary school teachers on artistic supervision. The lack of a measuring instrument related to the model of artistic supervision in the field of literature reveals the necessity of such study. 290…

46 CFR 53.01-3 - Adoption of section IV of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Adoption of section IV of the ASME Boiler and Pressure Vessel Code. 53.01-3 Section 53.01-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING HEATING BOILERS General Requirements § 53.01-3 Adoption of section IV of the ASME Boiler and Pressure Vessel Code. (a) Heating...

46 CFR 53.01-3 - Adoption of section IV of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Adoption of section IV of the ASME Boiler and Pressure Vessel Code. 53.01-3 Section 53.01-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING HEATING BOILERS General Requirements § 53.01-3 Adoption of section IV of the ASME Boiler and Pressure Vessel Code. (a) Heating...

46 CFR 52.01-2 - Adoption of section I of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Adoption of section I of the ASME Boiler and Pressure Vessel Code. 52.01-2 Section 52.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-2 Adoption of section I of the ASME Boiler and Pressure Vessel Code. (a) Main power...

46 CFR 52.01-2 - Adoption of section I of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of section I of the ASME Boiler and Pressure Vessel Code. 52.01-2 Section 52.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-2 Adoption of section I of the ASME Boiler and Pressure Vessel Code. (a) Main power...

46 CFR 53.01-3 - Adoption of section IV of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of section IV of the ASME Boiler and Pressure Vessel Code. 53.01-3 Section 53.01-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING HEATING BOILERS General Requirements § 53.01-3 Adoption of section IV of the ASME Boiler and Pressure Vessel Code. (a) Heating...

46 CFR 52.01-2 - Adoption of section I of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Adoption of section I of the ASME Boiler and Pressure Vessel Code. 52.01-2 Section 52.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-2 Adoption of section I of the ASME Boiler and Pressure Vessel Code. (a) Main power...

46 CFR 53.01-3 - Adoption of section IV of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Adoption of section IV of the ASME Boiler and Pressure Vessel Code. 53.01-3 Section 53.01-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING HEATING BOILERS General Requirements § 53.01-3 Adoption of section IV of the ASME Boiler and Pressure Vessel Code. (a) Heating...

46 CFR 52.01-2 - Adoption of section I of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Adoption of section I of the ASME Boiler and Pressure Vessel Code. 52.01-2 Section 52.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-2 Adoption of section I of the ASME Boiler and Pressure Vessel Code. (a) Main power...

46 CFR 52.01-2 - Adoption of section I of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Adoption of section I of the ASME Boiler and Pressure Vessel Code. 52.01-2 Section 52.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-2 Adoption of section I of the ASME Boiler and Pressure Vessel Code. (a) Main power...

46 CFR 53.01-3 - Adoption of section IV of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Adoption of section IV of the ASME Boiler and Pressure Vessel Code. 53.01-3 Section 53.01-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING HEATING BOILERS General Requirements § 53.01-3 Adoption of section IV of the ASME Boiler and Pressure Vessel Code. (a) Heating...

Identification of Novel Functional Inhibitors of Acid Sphingomyelinase

PubMed Central

Trapp, Stefan; Pechmann, Stefanie; Friedl, Astrid; Reichel, Martin; Mühle, Christiane; Terfloth, Lothar; Groemer, Teja W.; Spitzer, Gudrun M.; Liedl, Klaus R.; Gulbins, Erich; Tripal, Philipp

2011-01-01

We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 µM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans. PMID:21909365

cAMP Regulation of Airway Smooth Muscle Function

PubMed Central

Billington, Charlotte K.; Ojo, Oluwaseun O.; Penn, Raymond B.; Ito, Satoru

2013-01-01

Agonists activating β2-adrenoceptors (β2ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E2 and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β2ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β2AR desensitization, and recent findings regarding the manner in which β2ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β2ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD. PMID:22634112

Histidine pKa shifts and changes of tautomeric states induced by the binding of gallium-protoporphyrin IX in the hemophore HasASM

PubMed Central

Wolff, Nicolas; Deniau, Clarisse; Létoffé, Sylvie; Simenel, Catherine; Kumar, Veena; Stojiljkovic, Igor; Wandersman, Cécile; Delepierre, Muriel; Lecroisey, Anne

2002-01-01

The HasASM hemophore, secreted by Serratia marcescens, binds free or hemoprotein bound heme with high affinity and delivers it to a specific outer membrane receptor, HasR. In HasASM, heme is held by two loops and coordinated to iron by two residues, His 32 and Tyr 75. A third residue His 83 was shown recently to play a crucial role in heme ligation. To address the mechanistic issues of the heme capture and release processes, the histidine protonation states were studied in both apo- and holo-forms of HasASM in solution. Holo-HasASM was formed with gallium-protoporphyrin IX (GaPPIX), giving rise to a diamagnetic protein. By use of heteronuclear correlation NMR spectroscopy, the imidazole side-chain 15N and 1H resonances of the six HasASM histidines were assigned and their pKa values and predominant tautomeric states according to pH were determined. We show that protonation states of the heme pocket histidines can modulate the nucleophilic character of the two axial ligands and, consequently, control the heme binding. In particular, the essential role of the His 83 is emphasized according to its direct interaction with Tyr 75. PMID:11910020

Change in the relationship between the Australian summer monsoon circulation and boreal summer precipitation over Central China in the late 1990s

NASA Astrophysics Data System (ADS)

Yang, Ruowen; Wang, Jian; Zhang, Tianyu; He, Shengping

2017-09-01

Recent study revealed a close connection between the Australian summer monsoon (ASM) and boreal summer precipitation over Central China (SPCC). This study further revealed a strengthening of the ASM-SPCC relationship around the late 1990s. It is found that the relationship between the ASM and the SPCC during 1979-1997 (1998-2014) relationship is statistically insignificant (significant). Further analysis indicated that during 1998-2014, the weakened ASM is concurrent with significant positive sea surface temperature (SST) in the Indian Ocean and South China Sea, which could persist into the following boreal summer and further lead to intensified East Asian summer monsoon, strengthened western North Pacific subtropical high, and anomalous ascending motion over Central China. Consequently, more moisture is transported from the western Pacific northward to Central China where significant anomalous convergence appears. Therefore, the ASM could potentially influence the SPCC during 1998-2014. By contrast, the ASM-related SST and atmospheric circulation anomalies in boreal winter are statistically insignificant during 1979-1997. Such an interdecadal change might be attributed to the interdecadal warming that occurred in the Indian Ocean and South China Sea around the late 1990s. This study might be useful for the prediction of the SPCC.

10 CFR Appendix K to Part 50 - ECCS Evaluation Models

Code of Federal Regulations, 2012 CFR

2012-01-01

... stated circumstances shall be justified by comparative analyses or by experimental data. 4. Critical Heat..., ASME, New York, 1969. (3) Hench-Levy. J. M. Healzer, J. E. Hench, E. Janssen, S. Levy, “Design Basis...

10 CFR Appendix K to Part 50 - ECCS Evaluation Models

Code of Federal Regulations, 2013 CFR

2013-01-01

... stated circumstances shall be justified by comparative analyses or by experimental data. 4. Critical Heat..., ASME, New York, 1969. (3) Hench-Levy. J. M. Healzer, J. E. Hench, E. Janssen, S. Levy, “Design Basis...

10 CFR Appendix K to Part 50 - ECCS Evaluation Models

Code of Federal Regulations, 2014 CFR

2014-01-01

... stated circumstances shall be justified by comparative analyses or by experimental data. 4. Critical Heat..., ASME, New York, 1969. (3) Hench-Levy. J. M. Healzer, J. E. Hench, E. Janssen, S. Levy, “Design Basis...

Sphingosine-1-phosphate induces pro-remodelling response in airway smooth muscle cells

PubMed Central

Fuerst, E; Foster, H R; Ward, J P T; Corrigan, C J; Cousins, D J; Woszczek, G

2014-01-01

Background Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one of the most characteristic features of airway remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested to affect airway remodelling by stimulation of human ASM cell proliferation. Objective To investigate the effect of S1P on signalling and regulation of gene expression in ASM cells from healthy and asthmatic individuals. Methods Airway smooth muscle cells grown from bronchial biopsies of healthy and asthmatic individuals were exposed to S1P. Gene expression was analysed using microarray, real-time PCR and Western blotting. Receptor signalling and function were determined by mRNA knockdown and intracellular calcium mobilization experiments. Results S1P potently regulated the expression of more than 80 genes in human ASM cells, including several genes known to be involved in the regulation of cell proliferation and airway remodelling (HBEGF, TGFB3, TXNIP, PLAUR, SERPINE1, RGS4). S1P acting through S1P2 and S1P3 receptors activated intracellular calcium mobilization and extracellular signal-regulated and Rho-associated kinases to regulate gene expression. S1P-induced responses were not inhibited by corticosteroids and did not differ significantly between ASM cells from healthy and asthmatic individuals. Conclusion S1P induces a steroid-resistant, pro-remodelling pathway in ASM cells. Targeting S1P or its receptors could be a novel treatment strategy for inhibiting airway remodelling in asthma. PMID:25041788

Lysosomal ceramide generated by acid sphingomyelinase triggers cytosolic cathepsin B-mediated degradation of X-linked inhibitor of apoptosis protein in natural killer/T lymphoma cell apoptosis.

PubMed

Taniguchi, M; Ogiso, H; Takeuchi, T; Kitatani, K; Umehara, H; Okazaki, T

2015-04-09

We previously reported that IL-2 deprivation induced acid sphingomyelinase-mediated (ASM-mediated) ceramide elevation and apoptosis in an NK/T lymphoma cell line KHYG-1. However, the molecular mechanism of ASM-ceramide-mediated apoptosis during IL-2 deprivation is poorly understood. Here, we showed that IL-2 deprivation induces caspase-dependent apoptosis characterized by phosphatidylserine externalization, caspase-8, -9, and -3 cleavage, and degradation of X-linked inhibitor of apoptosis protein (XIAP). IL-2 re-supplementation rescued apoptosis via inhibition of XIAP degradation without affecting caspase cleavage. However, IL-2 deprivation induced ceramide elevation via ASM in lysosomes and activated lysosomal cathepsin B (CTSB) but not cathepsin D. A CTSB inhibitor CA-074 Me and knockdown of CTSB inhibited ceramide-mediated XIAP degradation and apoptosis. Inhibition of ceramide accumulation in lysosomes using an ASM inhibitor, desipramine, decreased cytosolic activation of CTSB by inhibiting its transfer into cytosol from the lysosome. Knockdown of ASM also inhibited XIAP degradation and apoptosis. Furthermore, cell permeable N-acetyl sphingosine (C2-ceramide), which increases mainly endogenous d18:1/16:0 and d18:1/24:1 ceramide-like IL-2 deprivation, induced caspase-dependent apoptosis with XIAP degradation through CTSB. These findings suggest that lysosomal ceramide produced by ASM mediates XIAP degradation by activation of cytosolic CTSB and caspase-dependent apoptosis. The ASM-ceramide-CTSB signaling axis is a novel pathway of ceramide-mediated apoptosis in IL-2-deprived NK/T lymphoma cells.

Sarcopenia: an independent predictor of mortality in community-dwelling older Korean men.

PubMed

Kim, Jung Hee; Lim, Soo; Choi, Sung Hee; Kim, Kyoung Min; Yoon, Ji Won; Kim, Ki Woong; Lim, Jae-Young; Park, Kyong Soo; Jang, Hak Chul

2014-10-01

The concept of sarcopenia has expanded recently to include muscle strength or physical performance. We investigated whether the Europe Working Group on Sarcopenia in Older People (EWGSOP) definition of sarcopenia predicts the risk of all-cause mortality in community-dwelling older adults. This study included 284 men and 272 women aged 65 and older. The outcome was all-cause mortality during the 6-year follow-up period. We defined sarcopenia based on the EWGSOP definitions of sarcopenia: height (ht)- or weight (wt)-adjusted appendicular skeletal muscle mass (ASM/ht(2) or ASM/wt) assessed by dual-energy x-ray absorptiometry, leg muscle strength, and short physical performance battery test score. During the 6-year follow-up, 40 men and 19 women died. The risk of death was 2.99 times and 3.22 times higher in men with sarcopenia identified by ASM/ht(2) and ASM/wt, respectively, compared with nonsarcopenic men. The hazard ratio for death was 5.37 for men with weak leg muscle strength. Men with a low short physical performance battery score had a 3.15 times higher risk of death compared with those with high short physical performance battery scores, even after adjusting for all covariates. The adjusted hazard ratios for EWGSOP-defined sarcopenia were 4.00 for ASM/ht(2) and 6.89 for ASM/wt in men. By contrast, sarcopenia defined by these criteria was not associated with a higher risk of death in women. Our data suggest that, in older men, EWGSOP-defined sarcopenia is related to higher mortality compared with nonsarcopenia regardless of the ASM/ht(2) or ASM/wt index. In older women, further studies with large sample sizes are needed to assess whether EWGSOP-defined sarcopenia increases the mortality risk. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of ASM-024, a modulator of acetylcholine receptor function, on airway responsiveness and allergen-induced responses in patients with mild asthma.

PubMed

Boulet, Louis-Philippe; Gauvreau, Gail M; Cockcroft, Donald W; Davis, Beth; Vachon, Luc; Cormier, Yvon; O'Byrne, Paul M

2015-01-01

To evaluate the safety, tolerability and clinical activity of ASM-024, a new cholinergic compound with dual nicotinic and muscarinic activity, in mild allergic asthma. The present study involved 24 stable, mild allergic asthmatic subjects. In a cross-over design, ASM-024 (50 mg or 200 mg) or placebo were administered once daily by nebulization over three periods of nine consecutive days separated by a three-week washout. The effect of each treatment on the forced expiratory volume in 1 s (FEV1), provocative concentration of methacholine causing a 20% decline in FEV1 (PC20), early and late asthmatic responses, and allergen-induced inflammation were measured. Seventeen subjects completed the study. During treatment with ASM-024 at 50 mg or 200 mg, the PC20 value increased respectively from a mean (± SD) 2.56±3.86 mg/mL to 4.11 mg/mL (P=0.007), and from 3.12±4.37 mg/mL to 5.23 mg/mL (P=0.005) (no change with placebo). On day 7 (day preceding allergen challenge), postdosing FEV1 increased by 2.0% with 50 mg (P=0.005) and 1.9% with 200 mg (P=0.008) (placebo -1.1%). ASM-24 had no inhibitory effect on early and late asthmatic responses, nor on sputum eosinophil or neutrophil levels. ASM-024 induced no serious adverse events, but caused cough in 22% and 48% of the subjects with 50 mg and 200 mg, respectively, compared with 10% who were on placebo. ASM-024 did not inhibit allergen-induced asthmatic response and related airway inflammation, but reduced methacholine airway responsiveness and slightly improved lung function. The mechanism by which ASM-024 improves these outcomes requires further study.

Influence of enhanced Asian NOx emissions on ozone in the upper troposphere and lower stratosphere in chemistry-climate model simulations

NASA Astrophysics Data System (ADS)

Roy, Chaitri; Fadnavis, Suvarna; Müller, Rolf; Ayantika, D. C.; Ploeger, Felix; Rap, Alexandru

2017-01-01

The Asian summer monsoon (ASM) anticyclone is the most pronounced circulation pattern in the upper troposphere and lower stratosphere (UTLS) during northern hemispheric summer. ASM convection plays an important role in efficient vertical transport from the surface to the upper-level anticyclone. In this paper we investigate the potential impact of enhanced anthropogenic nitrogen oxide (NOx) emissions on the distribution of ozone in the UTLS using the fully coupled aerosol-chemistry-climate model, ECHAM5-HAMMOZ. Ozone in the UTLS is influenced both by the convective uplift of ozone precursors and by the uplift of enhanced-NOx-induced tropospheric ozone anomalies. We performed anthropogenic NOx emission sensitivity experiments over India and China. In these simulations, covering the years 2000-2010, anthropogenic NOx emissions have been increased by 38 % over India and by 73 % over China with respect to the emission base year 2000. These emission increases are comparable to the observed linear trends of 3.8 % per year over India and 7.3 % per year over China during the period 2000 to 2010. Enhanced NOx emissions over India by 38 % and China by 73 % increase the ozone radiative forcing in the ASM anticyclone (15-40° N, 60-120° E) by 16.3 and 78.5 mW m-2 respectively. These elevated NOx emissions produce significant warming over the Tibetan Plateau and increase precipitation over India due to a strengthening of the monsoon Hadley circulation. However, increase in NOx emissions over India by 73 % (similar to the observed increase over China) results in large ozone production over the Indo-Gangetic Plain and Tibetan Plateau. The higher ozone concentrations, in turn, induce a reversed monsoon Hadley circulation and negative precipitation anomalies over India. The associated subsidence suppresses vertical transport of NOx and ozone into the ASM anticyclone.

Computational mechanics - Advances and trends; Proceedings of the Session - Future directions of Computational Mechanics of the ASME Winter Annual Meeting, Anaheim, CA, Dec. 7-12, 1986

NASA Technical Reports Server (NTRS)

Noor, Ahmed K. (Editor)

1986-01-01

The papers contained in this volume provide an overview of the advances made in a number of aspects of computational mechanics, identify some of the anticipated industry needs in this area, discuss the opportunities provided by new hardware and parallel algorithms, and outline some of the current government programs in computational mechanics. Papers are included on advances and trends in parallel algorithms, supercomputers for engineering analysis, material modeling in nonlinear finite-element analysis, the Navier-Stokes computer, and future finite-element software systems.

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

Optical alignment using a CGH and an autostigmatic microscope

NASA Astrophysics Data System (ADS)

Parks, Robert E.

2017-08-01

We show how custom computer generated holograms (CGH) are used along with an autostigmatic microscope (ASM) to align both optical and mechanical components relative to the CGH. The patterns in the CGHs define points and lines in space when interrogated with the focus of the ASM. Once the ASM is aligned to the CGH, an optical or mechanical component such as a lens, a well-polished ball or a cylinder can be aligned to the ASM in 3 or 4 degrees of freedom and thus to the CGH. In this case we show how a CGH is used to make a fixture for cementing a doublet lens without the need for a rotary table or a precision vertical stage.

Development of an Automated Seed Sowing and Induced Germination System for Space Flight Application

NASA Technical Reports Server (NTRS)

Heyenga, A. G.; Kliss, Mark

1995-01-01

The successful utilization of higher plants in space flight is likely to require the effective transition of plants through all phases of growth and development. A particularly sensitive and critical stage in this cycle is seed germination. The present inflight capability to manipulate seed from a state of dormancy to germination and the performance of such activity under aseptic conditions is extremely limited. An Automated Sowing Mechanism (ASM) has been designed to address this area of science and technology. The self-contained system is readily compatible with the existing Shuttle middeck locker Plant Growth Unit (PGU) and planned Plant Growth Facility (PGF), presenting an opportunity to extend the experimental capability of these systems. The ASM design encompasses the controlled transition of seed from a dry to hydrated state utilizing solid media substrate as the source of water and nutrient support. System activation has been achieved with both photo and timing mechanisms. Controlled induced germination and development of various plant species has been achieved in ground-based trials. The system is presently being prepared for a KC-135 flight test.

Systemic Mastocytosis with Smoldering Multiple Myeloma: Report of a Case

PubMed Central

Garcia, Gwenalyn; Ying, Liu; Hurford, Matthew; Odaimi, Marcel

2016-01-01

Systemic mastocytosis (SM) is a disease characterized by a clonal infiltration of mast cells affecting various tissues of the body. It is grouped into six different subtypes according to the World Health Organization classification. It is called indolent systemic mastocytosis (ISM) when there is no evidence of end organ dysfunction, while the presence of end organ dysfunction defines aggressive systemic mastocytosis (ASM). When SM coexists with a clonal hematological disorder, it is classified as systemic mastocytosis with associated clonal hematological nonmast cell lineage disease (SM-AHNMD). Over 80% of SM-AHNMD cases involve disorders of the myeloid cell lines. To our knowledge, there are only 8 reported cases to date of SM associated with a plasma cell disorder. We report a patient with ISM who was found to have concomitant smoldering multiple myeloma. His disease later progressed to ASM. We discuss this rare association between SM and a plasma cell disorder, and potential common pathophysiologic mechanisms linking the two disorders will be reviewed. We also discuss prognostic factors in SM as well as the management options considered during the evolution of the patient's disease. PMID:27293930

Biphasic force response to iso-velocity stretch in airway smooth muscle.

PubMed

Norris, Brandon A; Lan, Bo; Wang, Lu; Pascoe, Christopher D; Swyngedouw, Nicholas E; Paré, Peter D; Seow, Chun Y

2015-10-01

Airway smooth muscle (ASM) in vivo is constantly subjected to oscillatory strain due to tidal breathing and deep inspirations. ASM contractility is known to be adversely affected by strains, especially those of large amplitudes. Based on the cross-bridge model of contraction, it is likely that strain impairs force generation by disrupting actomyosin cross-bridge interaction. There is also evidence that strain modulates muscle stiffness and force through induction of cytoskeletal remodeling. However, the molecular mechanism by which strain alters smooth muscle function is not entirely clear. Here, we examine the response of ASM to iso-velocity stretches to probe the components within the muscle preparation that give rise to different features in the force response. We found in ASM that force response to a ramp stretch showed a biphasic feature, with the initial phase associated with greater muscle stiffness compared with that in the later phase, and that the transition between the phases occurred at a critical strain of ∼3.3%. Only strains with amplitudes greater than the critical strain could lead to reduction in force and stiffness of the muscle in the subsequent stretches. The initial-phase stiffness was found to be linearly related to the degree of muscle activation, suggesting that the stiffness stems mainly from attached cross bridges. Both phases were affected by the degree of muscle activation and by inhibitors of myosin light-chain kinase, PKC, and Rho-kinase. Different responses due to different interventions suggest that cross-bridge and cytoskeletal stiffness is regulated differently by the kinases. Copyright © 2015 the American Physiological Society.

PAB3D Simulations for the CAWAPI F-16XL

NASA Technical Reports Server (NTRS)

Elmiligui, Alaa; Abdol-Hamid, K. S.; Massey, Steven J.

2007-01-01

Numerical simulations of the flow around F-16XL are performed as a contribution to the Cranked Arrow Wing Aerodynamic Project International (CAWAPI) using the PAB3D CFD code. Two turbulence models are used in the calculations: a standard k-! model, and the Shih-Zhu-Lumley (SZL) algebraic stress model. Seven flight conditions are simulated for the flow around the F-16XL where the free stream Mach number varies from 0.242 to 0.97. The range of angles of attack varies from 0deg to 20deg. Computational results, surface static pressure, boundary layer velocity profiles, and skin friction are presented and compared with flight data. Numerical results are generally in good agreement with flight data, considering that only one grid resolution is utilized for the different flight conditions simulated in this study. The ASM results are closer to the flight data than the k-! model results. The ASM predicted a stronger primary vortex, however, the origin of the vortex and footprint is approximately the same as in the k-! predictions.

Implementation of algebraic stress models in a general 3-D Navier-Stokes method (PAB3D)

NASA Technical Reports Server (NTRS)

Abdol-Hamid, Khaled S.

1995-01-01

A three-dimensional multiblock Navier-Stokes code, PAB3D, which was developed for propulsion integration and general aerodynamic analysis, has been used extensively by NASA Langley and other organizations to perform both internal (exhaust) and external flow analysis of complex aircraft configurations. This code was designed to solve the simplified Reynolds Averaged Navier-Stokes equations. A two-equation k-epsilon turbulence model has been used with considerable success, especially for attached flows. Accurate predicting of transonic shock wave location and pressure recovery in separated flow regions has been more difficult. Two algebraic Reynolds stress models (ASM) have been recently implemented in the code that greatly improved the code's ability to predict these difficult flow conditions. Good agreement with Direct Numerical Simulation (DNS) for a subsonic flat plate was achieved with ASM's developed by Shih, Zhu, and Lumley and Gatski and Speziale. Good predictions were also achieved at subsonic and transonic Mach numbers for shock location and trailing edge boattail pressure recovery on a single-engine afterbody/nozzle model.

Increase in acid sphingomyelinase level in human retinal endothelial cells and CD34+ circulating angiogenic cells isolated from diabetic individuals is associated with dysfunctional retinal vasculature and vascular repair process in diabetes

PubMed Central

Kady, Nermin; Yan, Yuanqing; Salazar, Tatiana; Wang, Qi; Chakravarthy, Harshini; Huang, Chao; Beli, Eleni; Navitskaya, Svetlana; Grant, Maria; Busik, Julia

2017-01-01

Background Diabetic retinopathy (DR) is a microvascular disease that results from retinal vascular degeneration and defective repair due to diabetes induced endothelial progenitor dysfunction. Objective Understanding key molecular factors involved in vascular degeneration and repair is paramount for developing effective DR treatment strategies. We propose that diabetes-induced activation of acid sphingomyelinase (ASM) plays essential role in retinal endothelial and CD34+ circulating angiogenic cell (CAC) dysfunction in diabetes. Methods Human retinal endothelial cells (HRECs) isolated from control and diabetic donor tissue and human CD34+ CACs from control and diabetic patients were used in this study. ASM mRNA and protein expression was assessed by quantitative PCR and ELISA, respectively. To evaluate the effect of diabetes-induced ASM on HRECs and CD34+ CACs function, tube formation, CAC incorporation into endothelial tubes, and diurnal release of CD34+ CACs in diabetic individuals was determined. Results ASM expression level was significantly increased in HRECs isolated from diabetic compared to control donor tissue, as well as CD34+CACs and plasma of diabetic patients. A significant decrease in tube area was observed in HRECs from diabetic donors as compared to control HRECs. The tube formation deficiency was associated with increased expression of ASM in diabetic HRECs. Moreover, diabetic CD34+ CACs with high ASM showed defective incorporation into endothelial tubes. Diurnal release of CD34+ CACs was disrupted with the rhythmicity lost in diabetic patients. Conclusion Collectively, these findings support that diabetes-induced ASM upregulation has a marked detrimental effect on both retinal endothelial cells and CACs. PMID:28457994

Acid Sphingomyelinase-Derived Ceramide Regulates ICAM-1 Function during T Cell Transmigration across Brain Endothelial Cells.

PubMed

Lopes Pinheiro, Melissa A; Kroon, Jeffrey; Hoogenboezem, Mark; Geerts, Dirk; van Het Hof, Bert; van der Pol, Susanne M A; van Buul, Jaap D; de Vries, Helga E

2016-01-01

Multiple sclerosis (MS) is a chronic demyelinating disorder of the CNS characterized by immune cell infiltration across the brain vasculature into the brain, a process not yet fully understood. We previously demonstrated that the sphingolipid metabolism is altered in MS lesions. In particular, acid sphingomyelinase (ASM), a critical enzyme in the production of the bioactive lipid ceramide, is involved in the pathogenesis of MS; however, its role in the brain vasculature remains unknown. Transmigration of T lymphocytes is highly dependent on adhesion molecules in the vasculature such as intercellular adhesion molecule-1 (ICAM-1). In this article, we hypothesize that ASM controls T cell migration by regulating ICAM-1 function. To study the role of endothelial ASM in transmigration, we generated brain endothelial cells lacking ASM activity using a lentiviral shRNA approach. Interestingly, although ICAM-1 expression was increased in cells lacking ASM activity, we measured a significant decrease in T lymphocyte adhesion and consequently transmigration both in static and under flow conditions. As an underlying mechanism, we revealed that upon lack of endothelial ASM activity, the phosphorylation of ezrin was perturbed as well as the interaction between filamin and ICAM-1 upon ICAM-1 clustering. Functionally this resulted in reduced microvilli formation and impaired transendothelial migration of T cells. In conclusion, in this article, we show that ASM coordinates ICAM-1 function in brain endothelial cells by regulating its interaction with filamin and phosphorylation of ezrin. The understanding of these underlying mechanisms of T lymphocyte transmigration is of great value to develop new strategies against MS lesion formation. Copyright © 2015 by The American Association of Immunologists, Inc.

Does smooth muscle in an intact airway undergo length adaptation during a sustained change in transmural pressure?

PubMed

Ansell, Thomas K; McFawn, Peter K; McLaughlin, Robert A; Sampson, David D; Eastwood, Peter R; Hillman, David R; Mitchell, Howard W; Noble, Peter B

2015-03-01

In isolated airway smooth muscle (ASM) strips, an increase or decrease in ASM length away from its current optimum length causes an immediate reduction in force production followed by a gradual time-dependent recovery in force, a phenomenon termed length adaptation. In situ, length adaptation may be initiated by a change in transmural pressure (Ptm), which is a primary physiological determinant of ASM length. The present study sought to determine the effect of sustained changes in Ptm and therefore, ASM perimeter, on airway function. We measured contractile responses in whole porcine bronchial segments in vitro before and after a sustained inflation from a baseline Ptm of 5 cmH2O to 25 cmH2O, or deflation to -5 cmH2O, for ∼50 min in each case. In one group of airways, lumen narrowing and stiffening in response to electrical field stimulation (EFS) were assessed from volume and pressure signals using a servo-controlled syringe pump with pressure feedback. In a second group of airways, lumen narrowing and the perimeter of the ASM in situ were determined by anatomical optical coherence tomography. In a third group of airways, active tension was determined under isovolumic conditions. Both inflation and deflation reduced the contractile response to EFS. Sustained Ptm change resulted in a further decrease in contractile response, which returned to baseline levels upon return to the baseline Ptm. These findings reaffirm the importance of Ptm in regulating airway narrowing. However, they do not support a role for ASM length adaptation in situ under physiological levels of ASM lengthening and shortening. Copyright © 2015 the American Physiological Society.

TNFα enhances force generation in airway smooth muscle

PubMed Central

Han, Young-Soo; Delmotte, Philippe

2017-01-01

Airway inflammation is a hallmark of asthma, triggering airway smooth muscle (ASM) hyperreactivity and airway remodeling. TNFα increases both agonist-induced cytosolic Ca2+ concentration ([Ca2+]cyt) and force in ASM. The effects of TNFα on ASM force may also be due to an increase in Ca2+ sensitivity, cytoskeletal remodeling, and/or changes in contractile protein content. We hypothesized that 24 h of exposure to TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization. Porcine ASM strips were permeabilized with 10% Triton X-100, and force was measured in response to increasing concentrations of Ca2+ (pCa 9.0 to 4.0) in control and TNFα-treated groups. Relative phosphorylation of the regulatory myosin light chain (p-MLC) and total actin, MLC, and MyHC concentrations were quantified at pCa 9.0, 6.1, and 4.0. Actin polymerization was quantified by the ratio of filamentous to globular actin at pCa 9.0 and 4.0. For determination of total cross-bridge formation, isometric ATP hydrolysis rate at pCa 4.0 was measured using an enzyme-coupled NADH-linked fluorometric technique. Exposure to TNFα significantly increased force across the range of Ca2+ activation but did not affect the intrinsic Ca2+ sensitivity of force generation. The TNFα-induced increase in ASM force was associated with an increase in total actin, MLC, and MyHC content, as well as an increase in actin polymerization and an increase in maximum isometric ATP hydrolysis rate. The results of this study support our hypothesis that TNFα increases force generation in ASM by increasing the number of contractile units (actin-myosin content) contributing to force generation. PMID:28385814

Phosphoinositide 3-kinase gamma regulates airway smooth muscle contraction by modulating calcium oscillations.

PubMed

Jiang, Haihong; Abel, Peter W; Toews, Myron L; Deng, Caishu; Casale, Thomas B; Xie, Yan; Tu, Yaping

2010-09-01

Phosphoinositide 3-kinase gamma (PI3Kgamma) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kgamma can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kgamma protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kgamma inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 muM. In contrast, inhibitors of PI3Kalpha, PI3Kbeta, or PI3Kdelta, at concentrations 40-fold higher than their reported IC(50) values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kgamma inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kgamma-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca(2+) transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca(2+) oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kgamma directly controls contractility of airways through regulation of Ca(2+) oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kgamma inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness.

Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement.

PubMed

Alrashdan, Yazan A; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E; Burgess, Janette K; Armour, Carol L; Ammit, Alaina J; Hughes, J Margaret

2012-05-15

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma.

Glioma Cell Death Induced by Irradiation or Alkylating Agent Chemotherapy Is Independent of the Intrinsic Ceramide Pathway

PubMed Central

Gramatzki, Dorothee; Herrmann, Caroline; Happold, Caroline; Becker, Katrin Anne; Gulbins, Erich; Weller, Michael; Tabatabai, Ghazaleh

2013-01-01

Background/Aims Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS) catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells. Methods Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II–IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA) was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ)-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations. Results Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation. Conclusion Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PMID:23667632

Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity

PubMed Central

Tan, Xiahui; Sanderson, Michael J

2014-01-01

Background and Purpose While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca2+ signalling and Ca2+ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinine and denotonium regulate contractile agonist-induced Ca2+ signalling and sensitivity. Experimental Approach Airways in mouse lung slices were contracted with either methacholine (MCh) or 5HT and bronchodilation assessed using phase-contrast microscopy. Ca2+ signalling was measured with 2-photon fluorescence microscopy of ASM cells loaded with Oregon Green, a Ca2+-sensitive indicator (with or without caged-IP3). Effects on Ca2+ sensitivity were assessed on lung slices treated with caffeine and ryanodine to permeabilize ASM cells to Ca2+. Key Results The TAS2R10 agonists dilated airways constricted by either MCh or 5HT, accompanied by inhibition of agonist-induced Ca2+ oscillations. However, in non-contracted airways, TAS2R10 agonists, at concentrations that maximally dilated constricted airways, did not evoke Ca2+ signals in ASM cells. Ca2+ increases mediated by the photolysis of caged-IP3 were also attenuated by chloroquine, quinine and denotonium. In Ca2+-permeabilized ASM cells, the TAS2R10 agonists dilated MCh- and 5HT-constricted airways. Conclusions and Implications TAS2R10 agonists reversed bronchoconstriction by inhibiting agonist-induced Ca2+ oscillations while simultaneously reducing the Ca2+ sensitivity of ASM cells. Reduction of Ca2+ oscillations may be due to inhibition of Ca2+ release through IP3 receptors. Further characterization of bronchodilatory TAS2R agonists may lead to the development of novel therapies for the treatment of bronchoconstrictive conditions. PMID:24117140

Phosphoinositide 3-Kinase γ Regulates Airway Smooth Muscle Contraction by Modulating Calcium Oscillations

PubMed Central

Jiang, Haihong; Abel, Peter W.; Toews, Myron L.; Deng, Caishu; Casale, Thomas B.; Xie, Yan

2010-01-01

Phosphoinositide 3-kinase γ (PI3Kγ) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kγ can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kγ protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kγ inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 μM. In contrast, inhibitors of PI3Kα, PI3Kβ, or PI3Kδ, at concentrations 40-fold higher than their reported IC50 values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kγ inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kγ-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca2+ transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca2+ oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kγ directly controls contractility of airways through regulation of Ca2+ oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kγ inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness. PMID:20501633

Development of prediction equations for estimating appendicular skeletal muscle mass in Japanese men and women.

PubMed

Furushima, Taishi; Miyachi, Motohiko; Iemitsu, Motoyuki; Murakami, Haruka; Kawano, Hiroshi; Gando, Yuko; Kawakami, Ryoko; Sanada, Kiyoshi

2017-08-29

This study aimed to develop and cross-validate prediction equations for estimating appendicular skeletal muscle mass (ASM) and to examine the relationship between sarcopenia defined by the prediction equations and risk factors for cardiovascular diseases (CVD) or osteoporosis in Japanese men and women. Subjects were healthy men and women aged 20-90 years, who were randomly allocated to the following two groups: the development group (D group; 257 men, 913 women) and the cross-validation group (V group; 119 men, 112 women). To develop prediction equations, stepwise multiple regression analyses were performed on data obtained from the D group, using ASM measured by dual-energy X-ray absorptiometry (DXA) as a dependent variable and five easily obtainable measures (age, height, weight, waist circumference, and handgrip strength) as independent variables. When the prediction equations for ASM estimation were applied to the V group, a significant correlation was found between DXA-measured ASM and predicted ASM in both men and women (R 2  = 0.81 and R 2  = 0.72). Our prediction equations had higher R 2 values compared to previously developed equations (R 2  = 0.75-0.59 and R 2  = 0.69-0.40) in both men and women. Moreover, sarcopenia defined by predicted ASM was related to risk factors for osteoporosis and CVD, as well as sarcopenia defined by DXA-measured ASM. In this study, novel prediction equations were developed and cross-validated in Japanese men and women. Our analyses validated the clinical significance of these prediction equations and showed that previously reported equations were not applicable in a Japanese population.

Mechanical Failure Prognosis Through Oil Debris Monitoring

DTIC Science & Technology

1975-01-01

laboratories. The writer first heard of it from Hakkenburg of the Caterpillar Tractor Company at the ASLE/ ASME 16 Chiu, Y. P., et al, "Refinement...34Examination of Abrasion Resistance Criteria for Some Ductile Metals," ASME Jour, of Lubr. Tech. 96F, 210-214 and 246 (1974). 21 Leonard, L...failures during five months in 1970. 28 Littmann, W. E., et al, "The role of Lubrication in Propagation of Con- tact Fatigue Cracks," Trans. ASME

A study of airway smooth muscle in asthmatic and non-asthmatic airways using PS-OCT (Conference Presentation)

NASA Astrophysics Data System (ADS)

Adams, David C.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

2016-03-01

Present understanding of the pathophysiological mechanisms of asthma has been severely limited by the lack of an imaging modality capable of assessing airway conditions of asthma patients in vivo. Of particular interest is the role that airway smooth muscle (ASM) plays in the development of asthma and asthma related symptoms. With standard Optical Coherence Tomography (OCT), imaging ASM is often not possible due to poor structural contrast between the muscle and surrounding tissues. A potential solution to this problem is to utilize additional optical contrast factors intrinsic to the tissue, such as birefringence. Due to its highly ordered structure, ASM is strongly birefringent. Previously, we demonstrated that Polarization Sensitive OCT(PS-OCT) has the potential to be used to visualize ASM as well as easily segment it from the surrounding (weakly) birefringent tissue by exploiting a property which allows it to discriminate the orientation of birefringent fibers. We have already validated our technology with a substantial set of histological comparisons made against data obtained ex vivo. In this work we present a comprehensive comparison of ASM distributions in asthmatic and non-asthmatic human volunteers. By isolating the ASM we parameterize its distribution in terms of both thickness and band width, calculated volumetrically over centimeters of airway. Using this data we perform analyses of the asthmatic and non-asthmatic airways using a broad number and variety and subjects.

cAMP regulation of airway smooth muscle function.

PubMed

Billington, Charlotte K; Ojo, Oluwaseun O; Penn, Raymond B; Ito, Satoru

2013-02-01

Agonists activating β(2)-adrenoceptors (β(2)ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting β-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. β-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E(2) and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, β(2)ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of β-agonist therapy due to drug tachyphylaxis related to β(2)AR desensitization, and recent findings regarding the manner in which β(2)ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding β(2)ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Acid sphingomyelinase is required for cell surface presentation of Met receptor tyrosine kinase in cancer cells

PubMed Central

Zhu, Linyu; Xiong, Xiahui; Kim, Yongsoon; Okada, Naomi; Lu, Fei; Zhang, Hui

2016-01-01

ABSTRACT Receptor tyrosine kinases (RTKs) are embedded in the lipid bilayer of the plasma membrane, but the specific roles of various lipids in cell signaling remain largely uncharacterized. We have previously found that acid sphingomyelinase (ASM; also known as SMPD1) regulates the conserved DAF-2 (the ortholog IGF-1R in mammals) RTK signaling pathway in Caenorhabditis elegans. How ASM and its catalytic products, ceramides, control RTK signaling pathways remain unclear. Here, we report that ASM regulates the homeostasis of Met, an RTK that is frequently overexpressed in various cancers. Inactivation of ASM led to a rapid loss of Met from the plasma membrane, reduced Met phosphorylation and activation, and induced Met accumulation in the trans-Golgi network (TGN). However, trafficking of integrin β3 and vesicular stomatitis virus glycoprotein (VSVG) was largely unaffected. Knockdown of syntaxin 6 (STX6) also blocked the Golgi exit of Met. Depletion of either ASM or STX6 led to aberrant trafficking of Met to lysosomes, promoting its degradation. Our studies reveal that ASM and ceramides, together with STX6 and cholesterol, constitute a new regulatory mechanism for the exit of Met from the Golgi during its biosynthetic route, which is used to rapidly replenish and regulate the plasma membrane levels of Met in various cancer cells. PMID:27802163

Allele-Specific Methylation Occurs at Genetic Variants Associated with Complex Disease

PubMed Central

Hutchinson, John N.; Raj, Towfique; Fagerness, Jes; Stahl, Eli; Viloria, Fernando T.; Gimelbrant, Alexander; Seddon, Johanna; Daly, Mark; Chess, Andrew; Plenge, Robert

2014-01-01

We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results. PMID:24911414

Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.

PubMed

Muro, Silvia; Schuchman, Edward H; Muzykantov, Vladimir R

2006-01-01

Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.

A numerical identifiability test for state-space models--application to optimal experimental design.

PubMed

Hidalgo, M E; Ayesa, E

2001-01-01

This paper describes a mathematical tool for identifiability analysis, easily applicable to high order non-linear systems modelled in state-space and implementable in simulators with a time-discrete approach. This procedure also permits a rigorous analysis of the expected estimation errors (average and maximum) in calibration experiments. The methodology is based on the recursive numerical evaluation of the information matrix during the simulation of a calibration experiment and in the setting-up of a group of information parameters based on geometric interpretations of this matrix. As an example of the utility of the proposed test, the paper presents its application to an optimal experimental design of ASM Model No. 1 calibration, in order to estimate the maximum specific growth rate microH and the concentration of heterotrophic biomass XBH.

Mechanical properties of asthmatic airway smooth muscle.

PubMed

Chin, Leslie Y M; Bossé, Ynuk; Pascoe, Chris; Hackett, Tillie L; Seow, Chun Y; Paré, Peter D

2012-07-01

Airway smooth muscle (ASM) is the major effector of excessive airway narrowing in asthma. Changes in some of the mechanical properties of ASM could contribute to excessive narrowing and have not been systematically studied in human ASM from nonasthmatic and asthmatic subjects. Human ASM strips (eight asthmatic and six nonasthmatic) were studied at in situ length and force was normalised to maximal force induced by electric field stimulation (EFS). Measurements included: passive and active force versus length before and after length adaptation, the force-velocity relationship, maximal shortening and force recovery after length oscillation. Force was converted to stress by dividing by cross-sectional area of muscle. The only functional differences were that the asthmatic tissue was stiffer at longer lengths (p<0.05) and oscillatory strain reduced isometric force in response to EFS by 19% as opposed to 36% in nonasthmatics (p<0.01). The mechanical properties of human ASM from asthmatic and nonasthmatic subjects are comparable except for increased passive stiffness and attenuated decline in force generation after an oscillatory perturbation. These data may relate to reduced bronchodilation induced by a deep inspiration in asthmatic subjects.

Smooth muscle in the maintenance of increased airway resistance elicited by methacholine in humans.

PubMed

Chapman, David G; Pascoe, Chris D; Lee-Gosselin, Audrey; Couture, Christian; Seow, Chun Y; Paré, Peter D; Salome, Cheryl M; King, Gregory G; Bossé, Ynuk

2014-10-15

Airway narrowing is maintained for a prolonged period after acute bronchoconstriction in humans in the absence of deep inspirations (DIs). To determine whether maintenance of airway smooth muscle (ASM) shortening is responsible for the persistence of airway narrowing in healthy subjects following transient methacholine (MCh)-induced bronchoconstriction. On two separate visits, five healthy subjects underwent MCh challenges until respiratory system resistance (Rrs) had increased by approximately 1.5 cm H2O/L/s. Subjects took a DI either immediately after or 30 minutes after the last dose. The extent of renarrowing following the bronchodilator effect of DI was used to assess the continued action of MCh (calculated as percent change in Rrs from the pre-DI Rrs). We then used human bronchial rings to determine whether ASM can maintain shortening during a progressive decrease of carbachol concentration. The increased Rrs induced by MCh was maintained for 30 minutes despite waning of MCh concentration over that period, measured as attenuated renarrowing when the DI was taken 30 minutes after compared with immediately after the last dose (7 min post-DI, -36.2 ± 11.8 vs. 14.4 ± 13.2%; 12 min post-DI, -39.5 ± 9.8 vs. 15.2 ± 17.8%). Ex vivo, ASM shortening was largely maintained during a progressive decrease of carbachol concentration, even down to concentrations that would not be expected to induce shortening. The maintenance of airway narrowing despite MCh clearance in humans is attributed to an intrinsic ability of ASM to maintain shortening during a progressive decrease of contractile stimulation.

Airway smooth muscle: a potential target for asthma therapy.

PubMed

Dowell, Maria L; Lavoie, Tera L; Solway, Julian; Krishnan, Ramaswamy

2014-01-01

Asthma is a major public health problem that afflicts nearly one in 20 people worldwide. Despite available treatments, asthma symptoms remain poorly controlled in a significant minority of asthma patients, especially those with severe disease. Accordingly, much ongoing effort has been directed at developing new therapeutic strategies; these efforts are described in detail below. Although mucus hypersecretion is an important component of asthma pathobiology, the primary mechanism of morbidity and mortality in asthma is excessive narrowing of the airway. The key end- effector of excessive airway narrowing is airway smooth muscle (ASM) contraction; overcoming ASM contraction is therefore a prominent therapeutic strategy. Here, we review exciting new advances aimed at ASM relaxation. Exciting advances in ASM biology have identified new therapeutic targets for the prevention or reversal of bronchoconstriction in asthma.

Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

PubMed

Allen, Jodi C; Seidel, Petra; Schlosser, Tobias; Ramsay, Emma E; Ge, Qi; Ammit, Alaina J

2012-01-01

Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

The American Society of Maxillofacial Surgery Preceptorship Program: A Product of the 2013 American Society of Maxillofacial Surgery Executive Board Strategy Session and Survey.

PubMed

Papay, Francis; Taub, Peter J; Doumit, Gaby; Flores, Roberto L; Kuang, Anna A; Mlynek, Karolina; Tadisina, Kashyap K; Gharb, Bahar Bassiri

2015-06-01

One of the main goals of the American Society of Maxillofacial Surgery (ASMS) is to develop educational programs that increase expertise in maxillofacial surgery. We describe the outline of the new ASMS Preceptorship Program, a collective effort by ASMS members to increase access to all areas of maxillofacial surgery. Furthermore, we discuss the original survey pertinent to the development of this program, the results of the survey, and specifics regarding the structure of the program. We hope for the preceptorship program to be an excellent resource for members to mentor one another, develop intellectual and academic curiosity, provide avenues for collaboration, and further the ASMS's role in shaping maxillofacial surgery into the future.

Absorbing phase transitions in deterministic fixed-energy sandpile models

NASA Astrophysics Data System (ADS)

Park, Su-Chan

2018-03-01

We investigate the origin of the difference, which was noticed by Fey et al. [Phys. Rev. Lett. 104, 145703 (2010), 10.1103/PhysRevLett.104.145703], between the steady state density of an Abelian sandpile model (ASM) and the transition point of its corresponding deterministic fixed-energy sandpile model (DFES). Being deterministic, the configuration space of a DFES can be divided into two disjoint classes such that every configuration in one class should evolve into one of absorbing states, whereas no configurations in the other class can reach an absorbing state. Since the two classes are separated in terms of toppling dynamics, the system can be made to exhibit an absorbing phase transition (APT) at various points that depend on the initial probability distribution of the configurations. Furthermore, we show that in general the transition point also depends on whether an infinite-size limit is taken before or after the infinite-time limit. To demonstrate, we numerically study the two-dimensional DFES with Bak-Tang-Wiesenfeld toppling rule (BTW-FES). We confirm that there are indeed many thresholds. Nonetheless, the critical phenomena at various transition points are found to be universal. We furthermore discuss a microscopic absorbing phase transition, or a so-called spreading dynamics, of the BTW-FES, to find that the phase transition in this setting is related to the dynamical isotropic percolation process rather than self-organized criticality. In particular, we argue that choosing recurrent configurations of the corresponding ASM as an initial configuration does not allow for a nontrivial APT in the DFES.

Absorbing phase transitions in deterministic fixed-energy sandpile models.

PubMed

Park, Su-Chan

2018-03-01

We investigate the origin of the difference, which was noticed by Fey et al. [Phys. Rev. Lett. 104, 145703 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.145703], between the steady state density of an Abelian sandpile model (ASM) and the transition point of its corresponding deterministic fixed-energy sandpile model (DFES). Being deterministic, the configuration space of a DFES can be divided into two disjoint classes such that every configuration in one class should evolve into one of absorbing states, whereas no configurations in the other class can reach an absorbing state. Since the two classes are separated in terms of toppling dynamics, the system can be made to exhibit an absorbing phase transition (APT) at various points that depend on the initial probability distribution of the configurations. Furthermore, we show that in general the transition point also depends on whether an infinite-size limit is taken before or after the infinite-time limit. To demonstrate, we numerically study the two-dimensional DFES with Bak-Tang-Wiesenfeld toppling rule (BTW-FES). We confirm that there are indeed many thresholds. Nonetheless, the critical phenomena at various transition points are found to be universal. We furthermore discuss a microscopic absorbing phase transition, or a so-called spreading dynamics, of the BTW-FES, to find that the phase transition in this setting is related to the dynamical isotropic percolation process rather than self-organized criticality. In particular, we argue that choosing recurrent configurations of the corresponding ASM as an initial configuration does not allow for a nontrivial APT in the DFES.

DICOM implementation on online tape library storage system

NASA Astrophysics Data System (ADS)

Komo, Darmadi; Dai, Hailei L.; Elghammer, David; Levine, Betty A.; Mun, Seong K.

1998-07-01

The main purpose of this project is to implement a Digital Image and Communications (DICOM) compliant online tape library system over the Internet. Once finished, the system will be used to store medical exams generated from U.S. ARMY Mobile ARMY Surgical Hospital (MASH) in Tuzla, Bosnia. A modified UC Davis implementation of DICOM storage class is used for this project. DICOM storage class user and provider are implemented as the system's interface to the Internet. The DICOM software provides flexible configuration options such as types of modalities and trusted remote DICOM hosts. Metadata is extracted from each exam and indexed in a relational database for query and retrieve purposes. The medical images are stored inside the Wolfcreek-9360 tape library system from StorageTek Corporation. The tape library system has nearline access to more than 1000 tapes. Each tape has a capacity of 800 megabytes making the total nearline tape access of around 1 terabyte. The tape library uses the Application Storage Manager (ASM) which provides cost-effective file management, storage, archival, and retrieval services. ASM automatically and transparently copies files from expensive magnetic disk to less expensive nearline tape library, and restores the files back when they are needed. The ASM also provides a crash recovery tool, which enable an entire file system restore in a short time. A graphical user interface (GUI) function is used to view the contents of the storage systems. This GUI also allows user to retrieve the stored exams and send the exams to anywhere on the Internet using DICOM protocols. With the integration of different components of the system, we have implemented a high capacity online tape library storage system that is flexible and easy to use. Using tape as an alternative storage media as opposed to the magnetic disk has the great potential of cost savings in terms of dollars per megabyte of storage. As this system matures, the Hospital Information Systems/Radiology Information Systems (HIS/RIS) or other components can be developed potentially as interfaces to the outside world thus widen the usage of the tape library system.

The Preboreal-like Asian monsoon climate in the early last interglacial period recorded from the Dark Cave, Southwest China

NASA Astrophysics Data System (ADS)

Jiang, Xiuyang; He, Yaoqi; Wang, Xiaoyan; Sun, Xiaoshuang; Hong, Hui; Liu, Juan; Yu, Tsai-Luen; Li, Zhizhong; Shen, Chuan-Chou

2017-08-01

Transitions of glacial-interglacial cycles are critical periods for Quaternary climate shifts. Here, we present new, decadal resolution Asian summer monsoon (ASM) record from three stalagmites obtained from the Dark Cave in southwestern China over 130-114 thousand years ago (ka, before CE 1950). Chronology was anchored by 28 230Th dates with typical uncertainties of ±0.3-1.0 kyr, allowing an assessment of timing and transition of climate changes during the onset and end of the last interglacial. An agreement between this new and previous stalagmite δ18O records supports that summer insolation predominates orbital-scale ASM evolution. A 2-3 kyr-long gradually increasing ASM period, analogous to the classical Preboreal episode in the early Holocene, follows the termination of a weak monsoon interval at 129.0 ± 0.8 ka. This finding suggests a strong influence of high-latitude ice-sheet dynamics on Asian monsoonal conditions during the early interglacial period. An abrupt end of the marine isotope stage 5e at 118.8 ± 0.6 ka was probably caused by the internal climate system threshold effects.

U.S. Naval Research Laboratory Final Analysis Report to NATO Above Water Warfare Capabilities Group 2016 Naval Electromagnetic Operations Trials

DTIC Science & Technology

2017-05-23

Systems and the NRL Code 5763 Radio Frequency (RF) Stimulator. It includes and covers system descriptions , setup, data collection, and test goals that...6 4. Test Asset Descriptions ...7 4.1. Description of FOXTROT Anti-ship Missile (ASM) Simulator ......................................... 7

78 FR 48727 - Proposed Revisions to Design of Structures, Components, Equipment and Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-09

... Analysis Reports for Nuclear Power Plants: LWR Edition,'' Section 3.9.3 ``ASME Code Class 1, 2, and 3...'s Agencywide Documents Access and Management System (ADAMS): You may access publicly available... operational readiness of snubbers (ADAMS Accession No. ML070720041), and review interfaces have been updated...

Intrinsic Coupled Ocean-Atmosphere Modes of the Asian Summer Monsoon: A Re-assessment of Monsoon-ENSO Relationships

NASA Technical Reports Server (NTRS)

Lau, K.-M.; Wu, H. T.

2000-01-01

Using global rainfall and sea surface temperature (SST) data for the past two decades (1979-1998), we have investigated the intrinsic modes of Asian summer monsoon (ASM) and ENSO co-variability. Three recurring ASM rainfall-SST coupled modes were identified. The first is a basin scale mode that features SST and rainfall variability over the entire tropics (including the ASM region), identifiable with those occurring during El Nino or La Nina. This mode is further characterized by a pronounced biennial variation in ASM rainfall and SST associated with fluctuations of the anomalous Walker circulation that occur during El Nino/La Nina transitions. The second mode comprises mixed regional and basin-scale rainfall and SST signals, with pronounced intraseasonal and interannual variabilities. This mode features a SST pattern associated with a developing La Nina, with a pronounced low level anticyclone in the subtropics of the western Pacific off the coast of East Asia. The third mode depicts an east-west rainfall and SST dipole across the southern equatorial Indian Ocean, most likely stemming from coupled ocean-atmosphere processes within the ASM region. This mode also possesses a decadal time scale and a linear trend, which are not associated with El Nino/La Nina variability. Possible causes of year-to-year rainfall variability over the ASM and sub-regions have been evaluated from a reconstruction of the observed rainfall from singular eigenvectors of the coupled modes. It is found that while basin-scale SST can account for portions of ASM rainfall variability during ENSO events (up to 60% in 1998), regional processes can accounts up to 20-25% of the rainfall variability in typical non-ENSO years. Stronger monsoon-ENSO relationship tends to occur in the boreal summer immediately preceding a pronounced La Nina, i.e., 1998, 1988 and 1983. Based on these results, we discuss the possible impacts of the ASM on ENSO variability via the west Pacific anticyclone and articulate a hypothesis that anomalous wind forcings derived from the anticyclone may be instrumental in inducing a strong biennial modulation to natural ENSO cycles.

Evaluation of Crossbreeding of Australian Superfine Merinos with Gansu Alpine Finewool Sheep to Improve Wool Characteristics

PubMed Central

Li, Fanwen; Niu, Chune

2016-01-01

Crossbreeding of Australian Superfine Merinos (ASMs) with Gansu Alpine Finewool (GAF) sheep and an evaluation of the potential benefits of this genetic cross has not been previously conducted. 13 ASMs were crossbred with GAF sheep over a five year period with backcrossing designed to assess heterosis. Data from 11,178 lambs sired by 189 rams were used in the study. Genotype, birth year, birth type, dam age, sex and/or management group, and record age were fitted as fixed effects and within-genotype sire fitted as a random effect. Crossbreeds of 1/2 ASM expressed the most desirable effects for improving average fiber diameter (AFD), clean fleece weight (CFW), yield, coefficient of variation of AFD (CVAFD), yearling staple length (YSL) to AFD ratio (YSL/AFD), and CFW to metabolic yearling bodyweight (YWT0.75) ratio (CFW/YWT0.75) but showed the least post-weaning average daily gain (powADG) and YWT. Genotype of backcrossing with 1/4 ASM obtained moderate improvements in AFD, CFW, CVAFD, and YSL/AFD but the highest YSL, WWT, and prwADG. Except for yield (-1.42%) and CFW/YWT0.75 (-1%), heterosis estimates were generally low and positive, and ranged from 0.1% for CVAFD to 4% for powADG, which indicates the potential to improve relevant traits through exploiting heterosis to a varying extent. The ASMs sampled in this study were found to be superior to GAFs for AFD, CFW, yield, and CVAFD by 19.82%, 11.68%, 14.47%, and 6.99%, respectively, but inferior for YSL, PowADG, and YWT by 4.36%, 50.97%, and 16.93%, respectively. ASMs also appeared to be more efficient than GAFs in clean wool production (25.34%) and staple length growth (16.17%). The results of our study strongly suggest that an infusion of ASM genes via crossbreeding is an effective and appropriate approach to improve wool microns and wool production from GAF sheep, and we make recommendations to tackle the undesirable traits of YWT and YSL from ASM introduction. PMID:27832155

The chaotic long-term X-ray variability of 4U 1705-44

NASA Astrophysics Data System (ADS)

Phillipson, R. A.; Boyd, P. T.; Smale, A. P.

2018-07-01

The low-mass X-ray binary 4U1705-44 exhibits dramatic long-term X-ray time variability with a time-scale of several hundred days. The All-Sky Monitor (ASM) aboard the Rossi X-ray Timing Explorer (RXTE) and the Japanese Monitor of All-sky X-ray Image (MAXI) aboard the International Space Station together have continuously observed the source from 1995 December through 2014 May. The combined ASM-MAXI data provide a continuous time series over 50 times the length of the time-scale of interest. Topological analysis can help us identify `fingerprints' in the phase space of a system unique to its equations of motion. The Birman-Williams theorem postulates that if such fingerprints are the same between two systems, then their equations of motion must be closely related. The phase-space embedding of the source light curve shows a strong resemblance to the double-welled non-linear Duffing oscillator. We explore a range of parameters for which the Duffing oscillator closely mirrors the time evolution of 4U1705-44. We extract low period, unstable periodic orbits from the 4U1705-44 and Duffing time series and compare their topological information. The Duffing and 4U1705-44 topological properties are identical, providing strong evidence that they share the same underlying template. This suggests that we can look to the Duffing equation to help guide the development of a physical model to describe the long-term X-ray variability of this and other similarly behaved X-ray binary systems.

Numerical Solutions for the CAWAPI Configuration on Structured Grids at NASA LaRC, United States. Chapter 7

NASA Technical Reports Server (NTRS)

Elmiligui, Alaa A.; Abdol-Hamid, Khaled S.; Massey, Steven J.

2009-01-01

In this chapter numerical simulations of the flow around F-16XL are performed as a contribution to the Cranked Arrow Wing Aerodynamic Project International (CAWAPI) using the PAB3D CFD code. Two turbulence models are used in the calculations: a standard k-epsilon model, and the Shih-Zhu-Lumley (SZL) algebraic stress model. Seven flight conditions are simulated for the flow around the F-16XL where the free stream Mach number varies from 0.242 to 0.97. The range of angles of attack varies from 0 deg to 20 deg. Computational results, surface static pressure, boundary layer velocity profiles, and skin friction are presented and compared with flight data. Numerical results are generally in good agreement with flight data, considering that only one grid resolution is utilized for the different flight conditions simulated in this study. The Algebraic Stress Model (ASM) results are closer to the flight data than the k-epsilon model results. The ASM predicted a stronger primary vortex, however, the origin of the vortex and footprint is approximately the same as in the k-epsilon predictions.

46 CFR 56.07-10 - Design conditions and criteria (modifies 101-104.7).

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENGINEERING PIPING SYSTEMS AND APPURTENANCES Design § 56.07-10 Design conditions and criteria (modifies 101... system must not be greater than the internal design pressure defined in 104.1.2 of ASME B31.1 (incorporated by reference; see 46 CFR 56.01-2). (2) Where the maximum allowable working pressure of a system...

Length adaptation of airway smooth muscle.

PubMed

Bossé, Ynuk; Sobieszek, Apolinary; Paré, Peter D; Seow, Chun Y

2008-01-01

Many types of smooth muscle, including airway smooth muscle (ASM), are capable of generating maximal force over a large length range due to length adaptation, which is a relatively rapid process in which smooth muscle regains contractility after experiencing a force decrease induced by length fluctuation. Although the underlying mechanism is unclear, it is believed that structural malleability of smooth muscle cells is essential for the adaptation to occur. The process is triggered by strain on the cell cytoskeleton that results in a series of yet undefined biochemical and biophysical events leading to restructuring of the cytoskeleton and contractile apparatus and consequently optimization of the overlap between the myosin and actin filaments. Although length adaptability is an intrinsic property of smooth muscle, maladaptation of ASM could result in excessive constriction of the airways and the inability of deep inspirations to dilate them. In this article, we describe the phenomenon of length adaptation in ASM and some possible underlying mechanisms that involve the myosin filament assembly and disassembly. We discuss a possible role of maladaptation of ASM in the pathogenesis of asthma. We believe that length adaptation in ASM is mediated by specific proteins and their posttranslational regulations involving covalent modifications, such as phosphorylation. The discovery of these molecules and the processes that regulate their activity will greatly enhance our understanding of the basic mechanisms of ASM contraction and will suggest molecular targets to alleviate asthma exacerbation related to excessive constriction of the airways.

Prestretched airway smooth muscle response to length oscillation.

PubMed

Al-Jumaily, Ahmed M; Roos, Kevin; Bessaguet, Sandy; Jo Avila, Miguel

2017-01-01

Airway smooth muscle (ASM) hyperconstriction is the cause of many respiratory diseases including asthma. In vitro testing has demonstrated that the active forces of ASM are reduced by length oscillation (LO) mimicking tidal breathing. In a previous study, we demonstrated that this force reduction can be further enhanced when superimposing oscillations (with certain frequencies and amplitudes) on this LO In contrast, it has been reported that pressurizing the lung may help in relieving asthmatic airway constrictions. Ultimately, this pressurizing stretches the ASM and may disturb the acto-myosin cross-bridges in a manner similar to LO; however, it is of a static rather than dynamic nature. This research investigates the effect of combining both prestretch- and LO-applications on contracted porcine ASM Isolated porcine ASM relaxation was tested with a 0.56%, 2%, or 4% stretch of its reference length (L ref ) in addition to LO These oscillations are composed of a main wave mimicking the normal breathing (frequency of 0.33 Hz and amplitude of 4% L ref ) and superimposed oscillations (frequencies of 20, 30, 40, 60 and 80 Hz and amplitude of 1% L ref ). The oscillations were maintained for 10 min. The results demonstrate that a prestretch of 0.56% and 2% L ref does enhance the contracted ASM relaxation at certain superimposed length oscillations frequencies while of 4% L ref does not. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Characterization of primary cilia in human airway smooth muscle cells.

PubMed

Wu, Jun; Du, Hui; Wang, Xiangling; Mei, Changlin; Sieck, Gary C; Qian, Qi

2009-08-01

Considerable evidence indicates a key role for primary cilia of mammalian cells in mechanochemical sensing. Dysfunctions of primary cilia have been linked to the pathogenesis of several human diseases. However, cilia-related research has been limited to a few cell and tissue types; to our knowledge, no literature exists on primary cilia in airway smooth muscle (ASM). The aim of this study was to characterize primary cilia in human ASM. Primary cilia of human bronchial smooth muscle cells (HBSMCs) were examined using immunofluorescence confocal microscopy, and scanning and transmission electron microscopy. HBSMC migration and injury repair were examined by scratch-wound and epidermal growth factor (EGF)-induced migration assays. Cross-sectional images of normal human bronchi revealed that primary cilia of HBSMCs within each ASM bundle aggregated at the same horizontal level, forming a "cilium layer." Individual cilia of HBSMCs projected into extracellular matrix and exhibited varying degrees of deflection. Mechanochemical sensing molecules, polycystins, and alpha2-, alpha5-, and beta1-integrins were enriched in cilia, as was EGF receptor, known to activate jointly with integrins during cell migration. Migration assays demonstrated a ciliary contribution to HBSMC migration and wound repair. The primary cilia of ASM cells exert a role in sensing and transducing extracellular mechanochemical signals and in ASM injury repair. Defects in ASM ciliary function could potentially affect airway wall maintenance and/or remodeling, possibly relating to the genesis of bronchiectasis in autosomal dominant polycystic kidney disease, a disease of ciliopathy.

Cysteinyl leukotrienes promote human airway smooth muscle migration.

PubMed

Parameswaran, Krishnan; Cox, Gerard; Radford, Katherine; Janssen, Luke J; Sehmi, Roma; O'Byrne, Paul M

2002-09-01

Cysteinyl leukotrienes promote airway smooth muscle (ASM) contraction and proliferation. Little is known about their role in ASM migration. We investigated this using cultured human ASMs (between the second and fifth passages) obtained from the large airways of resected nonasthmatic lung. Platelet-derived growth factor-BB (1 ng/ml) promoted significant (3.5-fold) ASM migration of myocytes across collagen-coated 8- micro m polycarbonate membranes in Transwell culture plates. Leukotriene E(4) (10(-7), 10(-8), 10(-9) M) did not demonstrate a chemotactic effect; it did promote chemokinesis. Priming by leukotriene E(4) (10(-7) M) significantly augmented the directional migratory response to platelet-derived growth factor (1.5-fold, p < 0.05). This was blocked by montelukast (10(-6) M), demonstrating the effect to be mediated by the cysteinyl leukotriene receptor. The "priming effect" was also partially attenuated by prostaglandin E(2) (10(-7) M). Whereas both the chemokinetic and the chemotactic "primed" responses were equally attenuated by a p38 mitogen-activated protein kinase inhibitor (SB203580, 25 micro M) and by a Rho-kinase inhibitor (Y27632, 10 micro M), the chemotactic response showed greater inhibition than chemokinesis by a phosphatidylinositol-3 kinase inhibitor (LY294002, 50 micro M). These experiments suggest that cysteinyl leukotrienes play an augmentary role in human ASM migration. The phosphatidylinositol-3 kinase pathway is a key signaling mechanism in the chemotactic migration of ASM cells in response to cysteinyl leukotrienes.

49 CFR 222.9 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... part, a State agency, responsible for highway-rail grade crossing safety or highway and road safety... Administrator's delegate. Alternative safety measures (ASM) means a safety system or procedure, other than an.... Associate Administrator means the Associate Administrator for Safety of the Federal Railroad Administration...

Variability in age and size at maturation, reproductive longevity, and long-term growth dynamics for Kemp's ridley sea turtles in the Gulf of Mexico

PubMed Central

Goshe, Lisa R.; Coggins, Lewis; Shaver, Donna J.; Higgins, Ben; Landry, Andre M.; Bailey, Rhonda

2017-01-01

Effective management of protected sea turtle populations requires knowledge not only of mean values for demographic and life-history parameters, but also temporal and spatial trends, variability, and underlying causes. For endangered Kemp’s ridley sea turtles (Lepidochelys kempii), the need for baseline information of this type has been emphasized during attempts to understand causes underlying the recent truncation in the recovery trajectory for nesting females. To provide insight into variability in age and size at sexual maturation (ASM and SSM) and long-term growth patterns likely to influence population trends, we conducted skeletochronological analysis of humerus bones from 333 Kemp’s ridleys stranded throughout the Gulf of Mexico (GOM) from 1993 to 2010. Ranges of possible ASMs (6.8 to 21.8 yr) and SSMs (53.3 to 68.3 cm straightline carapace length (SCL)) estimated using the “rapprochement” skeletal growth mark associated with maturation were broad, supporting incorporation of a maturation schedule in Kemp’s ridley population models. Mean ASMs estimated from rapprochement and by fitting logistic, generalized additive mixed, and von Bertalanffy growth models to age and growth data ranged from 11 to 13 yr; confidence intervals for the logistic model predicted maturation of 95% of the population between 11.9 and 14.8 yr. Early juvenile somatic growth rates in the GOM were greater than those previously reported for the Atlantic, indicating potential for differences in maturation trajectories between regions. Finally, long-term, significant decreases in somatic growth response were found for both juveniles and adults, which could influence recruitment to the reproductive population and observed nesting population trends. PMID:28333937

Variability in age and size at maturation, reproductive longevity, and long-term growth dynamics for Kemp's ridley sea turtles in the Gulf of Mexico.

PubMed

Avens, Larisa; Goshe, Lisa R; Coggins, Lewis; Shaver, Donna J; Higgins, Ben; Landry, Andre M; Bailey, Rhonda

2017-01-01

Effective management of protected sea turtle populations requires knowledge not only of mean values for demographic and life-history parameters, but also temporal and spatial trends, variability, and underlying causes. For endangered Kemp's ridley sea turtles (Lepidochelys kempii), the need for baseline information of this type has been emphasized during attempts to understand causes underlying the recent truncation in the recovery trajectory for nesting females. To provide insight into variability in age and size at sexual maturation (ASM and SSM) and long-term growth patterns likely to influence population trends, we conducted skeletochronological analysis of humerus bones from 333 Kemp's ridleys stranded throughout the Gulf of Mexico (GOM) from 1993 to 2010. Ranges of possible ASMs (6.8 to 21.8 yr) and SSMs (53.3 to 68.3 cm straightline carapace length (SCL)) estimated using the "rapprochement" skeletal growth mark associated with maturation were broad, supporting incorporation of a maturation schedule in Kemp's ridley population models. Mean ASMs estimated from rapprochement and by fitting logistic, generalized additive mixed, and von Bertalanffy growth models to age and growth data ranged from 11 to 13 yr; confidence intervals for the logistic model predicted maturation of 95% of the population between 11.9 and 14.8 yr. Early juvenile somatic growth rates in the GOM were greater than those previously reported for the Atlantic, indicating potential for differences in maturation trajectories between regions. Finally, long-term, significant decreases in somatic growth response were found for both juveniles and adults, which could influence recruitment to the reproductive population and observed nesting population trends.

Phase behavior and characterization of heptamethyltrisiloxane-based de Vries smectic liquid crystal by electro-optics, x rays, and dielectric spectroscopy

NASA Astrophysics Data System (ADS)

Sreenilayam, S. P.; Agra-Kooijman, D. M.; Panov, V. P.; Swaminathan, V.; Vij, J. K.; Panarin, Yu. P.; Kocot, A.; Panov, A.; Rodriguez-Lojo, D.; Stevenson, P. J.; Fisch, Michael R.; Kumar, Satyendra

2017-03-01

A heptamethyltrisiloxane liquid crystal (LC) exhibiting I -Sm A*-Sm C* phases has been characterized by calorimetry, polarizing microscopy, x-ray diffraction, electro-optics, and dielectric spectroscopy. Observations of a large electroclinic effect, a large increase in the birefringence (Δ n ) with electric field, a low shrinkage in the layer thickness (˜1.75%) at 20 °C below the Sm A*-Sm C* transition, and low values of the reduction factor (˜0.40) suggest that the Sm A* phase in this material is of the de Vries type. The reduction factor is a measure of the layer shrinkage in the Sm C* phase and it should be zero for an ideal de Vries. Moreover, a decrease in the magnitude of Δ n with decreasing temperature indicates the presence of the temperature-dependent tilt angle in the Sm A* phase. The electro-optic behavior is explained by the generalized Langevin-Debye model as given by Shen et al. [Y. Shen et al., Phys. Rev. E 88, 062504 (2013), 10.1103/PhysRevE.88.062504]. The soft-mode dielectric relaxation strength shows a critical behavior when the system goes from the Sm A* to the Sm C* phase.

A comprehensive overview of the climatological composition of the Asian summer monsoon anticyclone based on 10 years of Aura Microwave Limb Sounder measurements

NASA Astrophysics Data System (ADS)

Santee, M. L.; Manney, G. L.; Livesey, N. J.; Schwartz, M. J.; Neu, J. L.; Read, W. G.

2017-05-01

Intense deep convection associated with the Asian summer monsoon (ASM) lofts surface pollutants to the upper troposphere/lower stratosphere (UTLS), where strong winds and long chemical lifetimes allow intercontinental transport, affecting atmospheric composition around the globe. The Aura Microwave Limb Sounder (MLS), launched in 2004, makes simultaneous colocated measurements of trace gases and cloud ice water content (a proxy for deep convection) in the UTLS on a daily basis. Here we exploit the dense spatial and temporal coverage, long-term data record, extensive measurement suite, and insensitivity to aerosol and most clouds of Aura MLS to characterize the climatological (2005-2014) composition of the ASM anticyclone throughout its annual life cycle. We use version 4 MLS data to quantify spatial and temporal variations in both tropospheric (H2O, CO, CH3Cl, CH3CN, CH3OH) and stratospheric (O3, HNO3, HCl) tracers on four potential temperature surfaces (350-410 K). Inside the mature anticyclone, all species exhibit substantial changes, not only from their premonsoon distributions in the ASM region but also from their summertime distributions in the rest of the hemisphere. Different tracers exhibit dissimilar seasonal evolution, and the exact location and timing of their extreme values vary. Although individual aspects of the anticyclone have been described previously, we present a uniquely comprehensive overview of the climatological seasonal evolution of the ASM and its impact on UTLS composition. This work provides valuable context for planned in situ measurements as well as a benchmark for model evaluation and future investigations of interannual variability and long-term changes in monsoon processes.

Osteoporosis and gait and balance disturbances in older sarcopenic obese New Zealanders.

PubMed

Waters, D L; Hale, L; Grant, A M; Herbison, P; Goulding, A

2010-02-01

Bone, muscle, and fat may affect gait and balance in older adults. Osteoporosis was prevalent in low muscle mass participants and related to gait and balance deficits. Low muscle combined with high fat mass had more functional deficits and poorer bone health, which has implications for falls risk and fractures. Decreasing bone density and muscle mass and increasing fat mass may act synergistically to affect gait and balance in older adults. One hundred eighty-three older adults (age 72.7 +/- 6 years, range 56-93; body mass index 28.2 +/- 4.9, range 16.6-46.0) were recruited from a New Zealand falls prevention intervention trial. Total and appendicular skeletal muscle mass (ASM), percent fat, and bone mineralization were assessed by dual energy X-ray absorptiometry and used to characterize normal lean (NL, n = 51), sarcopenic (SS, n = 18), sarcopenic obese (SO, n = 29), and obese (OO, n = 85) phenotypes. Functional performance was assessed using timed up and go, chair stand, single leg stand, and step test. Regression models were adjusted for age, sex, medications, and physical activity. Femoral neck osteoporosis was present in 22% SS, 17% SO, 12% NL, and 7% OO. Femoral neck osteoporosis with low ASM predicted poor chair stand performance (beta -3.3, standard error 1.6, p = 0.04). SO scored lowest on the chair stand (p = 0.03) and step test (p = 0.03). Higher ASM predicted faster timed up and go performance (p = 0.001). Osteoporosis was prevalent in low ASM groups (SS and SO) and related to gait and balance deficits, particularly in the SO. This has implications for falls risk, fractures, and interventions.

Nanosatellite High-Precision Magnetic Missions Enabled by Advances in a Stand-Alone Scalar/Vector Absolute Magnetometer

NASA Astrophysics Data System (ADS)

Hulot, G.; Leger, J. M.; Vigneron, P.; Jager, T.; Bertrand, F.; Coisson, P.; Deram, P.; Boness, A.; Tomasini, L.; Faure, B.

2017-12-01

Satellites of the ESA Swarm mission currently in operation carry a new generation of Absolute Scalar Magnetometers (ASM), which nominally deliver 1 Hz scalar for calibrating the relative flux gate magnetometers that complete the magnetometry payload (together with star cameras, STR, for attitude restitution) and providing extremely accurate scalar measurements of the magnetic field for science investigations. These ASM instruments, however, can also operate in two additional modes, a high-frequency 250 Hz scalar mode and a 1 Hz absolute dual-purpose scalar/vector mode. The 250 Hz scalar mode already allowed the detection of until now very poorly documented extremely low frequency whistler signals produced by lightning in the atmosphere, while the 1 Hz scalar/vector mode has provided data that, combined with attitude restitution from the STR, could be used to produce scientifically relevant core field and lithospheric field models. Both ASM modes have thus now been fully validated for science applications. Efforts towards developing an improved and miniaturized version of this instrument is now well under way with CNES support in the context of the preparation of a 12U nanosatellite mission (NanoMagSat) proposed to be launched to complement the Swarm satellite constellation. This advanced miniaturized ASM could potentially operate in an even more useful mode, simultaneously providing high frequency (possibly beyond 500 Hz) absolute scalar data and self-calibrated 1 Hz vector data, thus providing scientifically valuable data for multiple science applications. In this presentation, we will illustrate the science such an instrument taken on board a nanosatellite could enable, and report on the current status of the NanoMagSat project that intends to take advantage of it.

Identification of genes differentially regulated by vitamin D deficiency that alter lung pathophysiology and inflammation in allergic airways disease.

PubMed

Foong, Rachel E; Bosco, Anthony; Troy, Niamh M; Gorman, Shelley; Hart, Prue H; Kicic, Anthony; Zosky, Graeme R

2016-09-01

Vitamin D deficiency is associated with asthma risk. Vitamin D deficiency may enhance the inflammatory response, and we have previously shown that airway remodeling and airway hyperresponsiveness is increased in vitamin D-deficient mice. In this study, we hypothesize that vitamin D deficiency would exacerbate house dust mite (HDM)-induced inflammation and alterations in lung structure and function. A BALB/c mouse model of vitamin D deficiency was established by dietary manipulation. Responsiveness to methacholine, airway smooth muscle (ASM) mass, mucus cell metaplasia, lung and airway inflammation, and cytokines in bronchoalveolar lavage (BAL) fluid were assessed. Gene expression patterns in mouse lung samples were profiled by RNA-Seq. HDM exposure increased inflammation and inflammatory cytokines in BAL, baseline airway resistance, tissue elastance, and ASM mass. Vitamin D deficiency enhanced the HDM-induced influx of lymphocytes into BAL, ameliorated the HDM-induced increase in ASM mass, and protected against the HDM-induced increase in baseline airway resistance. RNA-Seq identified nine genes that were differentially regulated by vitamin D deficiency in the lungs of HDM-treated mice. Immunohistochemical staining confirmed that protein expression of midline 1 (MID1) and adrenomedullin was differentially regulated such that they promoted inflammation, while hypoxia-inducible lipid droplet-associated, which is associated with ASM remodeling, was downregulated. Protein expression studies in human bronchial epithelial cells also showed that addition of vitamin D decreased MID1 expression. Differential regulation of these genes by vitamin D deficiency could determine lung inflammation and pathophysiology and suggest that the effect of vitamin D deficiency on HDM-induced allergic airways disease is complex. Copyright © 2016 the American Physiological Society.

Economic Evidence for U.S. Asthma Self-Management Education and Home-Based Interventions

PubMed Central

Hsu, Joy; Wilhelm, Natalie; Lewis, Lillianne; Herman, Elizabeth

2016-01-01

The health and economic burden of asthma in the United States is substantial. Asthma self-management education (AS-ME) and home-based interventions for asthma can improve asthma control and prevent asthma exacerbations, and interest in health care-public health collaboration regarding asthma is increasing. However, outpatient AS-ME and home-based asthma intervention programs are not widely available; economic sustainability is a common concern. Thus, we conducted a narrative review of existing literature regarding economic outcomes of outpatient AS-ME and home-based intervention programs for asthma in the United States. We identified 9 outpatient AS-ME programs and 17 home-based intervention programs with return on investment (ROI) data. Most programs were associated with a positive ROI; a few programs observed positive ROIs only among selected populations (e.g., higher health care utilization). Interpretation of existing data is limited by heterogeneous ROI calculations. Nevertheless, the literature suggests promise for sustainable opportunities to expand access to outpatient AS-ME and home-based asthma intervention programs in the United States. More definitive knowledge about how to maximize program benefit and sustainability could be gained through more controlled studies of specific populations and increased uniformity in economic assessments. PMID:27658535

Physical Activity Energy Expenditure and Sarcopenia in Black South African Urban Women.

PubMed

Kruger, Herculina S; Havemann-Nel, Lize; Ravyse, Chrisna; Moss, Sarah J; Tieland, Michael

2016-03-01

Black women are believed to be genetically less predisposed to age-related sarcopenia. The objective of this study was to investigate lifestyle factors associated with sarcopenia in black South African (SA) urban women. In a cross-sectional study, 247 women (mean age 57 y) were randomly selected. Anthropometric and sociodemographic variables, dietary intakes, and physical activity were measured. Activity was also measured by combined accelerometery/heart rate monitoring (ActiHeart), and HIV status was tested. Dual energy x-ray absorptiometry was used to measure appendicular skeletal mass (ASM). Sarcopenia was defined according to a recently derived SA cutpoint of ASM index (ASM/height squared) < 4.94 kg/m(2). In total, 8.9% of the women were sarcopenic, decreasing to 8.1% after exclusion of participants who were HIV positive. In multiple regressions with ASM index, grip strength, and gait speed, respectively, as dependent variables, only activity energy expenditure (β = .27) was significantly associated with ASM index. Age (β = -.50) and activity energy expenditure (β = .17) were significantly associated with gait speed. Age (β = -.11) and lean mass (β = .21) were significantly associated with handgrip strength. Sarcopenia was prevalent among these SA women and was associated with low physical activity energy expenditure.

The Sophora flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction.

PubMed

Yang, Nan; Liang, Banghao; Srivastava, Kamal; Zeng, Jia; Zhan, Jixun; Brown, LaVerne; Sampson, Hugh; Goldfarb, Joseph; Emala, Charles; Li, Xiu-Min

2013-11-01

Asthma is a serious health problem worldwide, particularly in industrialized countries. Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for classes of drugs. ASHMI™ (Anti-asthma Herbal Medicine Intervention) is an aqueous extract of Ganoderma lucidum (Fr.) P. Karst (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao). It prevents allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice. The purpose of this research was to identify individual herb(s) and their active compound(s) that inhibit ASM contraction. It was found that S. flavescens, but not G. lucidum or G. uralensis aqueous extracts, inhibited ASM contraction in tracheal rings from asthmatic mice. Bioassay-guided isolation and identification of flavonoid fractions/compound(s) via methylene chloride extraction, preparative HPLC fractionation, and LC-MS and NMR spectroscopic analyses showed that trifolirhizin is an active constituent that inhibits acetylcholine mediated ASM contraction or directly relaxes pre-contracted ASM independent of β2-adrenoceptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Sophora Flavescens flavonoid compound trifolirhizin inhibits acetylcholine induced airway smooth muscle contraction

PubMed Central

Zeng, Jia; Zhan, Jixun; Brown, LaVerne; Sampson, Hugh; Goldfarb, Joseph; Emala, Charles; Li, Xiu-Min

2014-01-01

Asthma is a serious health problem worldwide, particularly in industrialized countries. Despite a better understanding of the pathophysiology of asthma, there are still considerable gaps in knowledge as well as a need for new classes of drugs. ASHMI™ (Anti-asthma Herbal Medicine Intervention) is an aqueous extract of Ganoderma lucidum (Fr.) P. Karst (Ling Zhi), Sophora flavescens Aiton (Ku Shen) and Glycyrrhiza uralensis Fisch. ex DC (Gan Cao). It prevents allergic asthma airway hyper-reactivity in mice and inhibits acetylcholine (ACh) induced airway smooth muscle (ASM) contraction in tracheal rings from allergic asthmatic mice. The purpose of this research was to identify individual herb(s) and their active compound(s) that inhibit ASM contraction. It was found that Sophora flavescens (S. flavescens), but not Ganoderma lucidum (G. lucidum) or Glycyrrhiza uralensis (G. uralensis) aqueous extracts, inhibited ASM contraction in tracheal rings from asthmatic mice. Bioassay-guided isolation and identification of flavonoid fractions/compound(s) via methylene chloride extraction, preparative HPLC fractionation, and LC-MS and NMR spectroscopic analyses showed that trifolirhizin is an active constituent that inhibits acetylcholine mediated ASM contraction or directly relaxes pre-contracted ASM independent of β2-adrenoceptors. PMID:23993294

Modelling energy costs for different operational strategies of a large water resource recovery facility.

PubMed

Póvoa, P; Oehmen, A; Inocêncio, P; Matos, J S; Frazão, A

2017-05-01

The main objective of this paper is to demonstrate the importance of applying dynamic modelling and real energy prices on a full scale water resource recovery facility (WRRF) for the evaluation of control strategies in terms of energy costs with aeration. The Activated Sludge Model No. 1 (ASM1) was coupled with real energy pricing and a power consumption model and applied as a dynamic simulation case study. The model calibration is based on the STOWA protocol. The case study investigates the importance of providing real energy pricing comparing (i) real energy pricing, (ii) weighted arithmetic mean energy pricing and (iii) arithmetic mean energy pricing. The operational strategies evaluated were (i) old versus new air diffusers, (ii) different DO set-points and (iii) implementation of a carbon removal controller based on nitrate sensor readings. The application in a full scale WRRF of the ASM1 model coupled with real energy costs was successful. Dynamic modelling with real energy pricing instead of constant energy pricing enables the wastewater utility to optimize energy consumption according to the real energy price structure. Specific energy cost allows the identification of time periods with potential for linking WRRF with the electric grid to optimize the treatment costs, satisfying operational goals.

Corrosion fatigue of alloys 600 and 690 in simulated LWR environments

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

Ruther, W.E.; Soppett, W.K.; Kassner, T.F.

1996-04-01

Crack growth data were obtained on fracture-mechanics specimens of Alloys 600 and 690 to investigate environmentally assisted cracking (EAC) in simulated boiling water reactor and pressurized water reactor environments at 289 and 320 C. Preliminary information was obtained on the effect of temperature, load ratio, stress intensity (K), and the dissolved-oxygen and -hydrogen concentrations of the water on EAC. Specimens of Type 316NG and sensitized Type 304 stainless steel (SS) were included in several of the experiments to assess the behavior of these materials and Alloy 600 under the same water chemistry and loading conditions. The experimental data are comparedmore » with predictions from an Argonne National Laboratory (ANL) model for crack growth rates (CGRs) of SSs in water and the ASME Code Section 11 correlation for CGRs in air at the K{sub max} and load-ratio values in the various tests. The data for all of the materials were bounded by ANL model predictions and the ASME Section 11 ``air line.``« less

A 3D global-to-local deformable mesh model based registration and anatomy-constrained segmentation method for image guided prostate radiotherapy

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

Zhou Jinghao; Kim, Sung; Jabbour, Salma

2010-03-15

Purpose: In the external beam radiation treatment of prostate cancers, successful implementation of adaptive radiotherapy and conformal radiation dose delivery is highly dependent on precise and expeditious segmentation and registration of the prostate volume between the simulation and the treatment images. The purpose of this study is to develop a novel, fast, and accurate segmentation and registration method to increase the computational efficiency to meet the restricted clinical treatment time requirement in image guided radiotherapy. Methods: The method developed in this study used soft tissues to capture the transformation between the 3D planning CT (pCT) images and 3D cone-beam CTmore » (CBCT) treatment images. The method incorporated a global-to-local deformable mesh model based registration framework as well as an automatic anatomy-constrained robust active shape model (ACRASM) based segmentation algorithm in the 3D CBCT images. The global registration was based on the mutual information method, and the local registration was to minimize the Euclidian distance of the corresponding nodal points from the global transformation of deformable mesh models, which implicitly used the information of the segmented target volume. The method was applied on six data sets of prostate cancer patients. Target volumes delineated by the same radiation oncologist on the pCT and CBCT were chosen as the benchmarks and were compared to the segmented and registered results. The distance-based and the volume-based estimators were used to quantitatively evaluate the results of segmentation and registration. Results: The ACRASM segmentation algorithm was compared to the original active shape model (ASM) algorithm by evaluating the values of the distance-based estimators. With respect to the corresponding benchmarks, the mean distance ranged from -0.85 to 0.84 mm for ACRASM and from -1.44 to 1.17 mm for ASM. The mean absolute distance ranged from 1.77 to 3.07 mm for ACRASM and from 2.45 to 6.54 mm for ASM. The volume overlap ratio ranged from 79% to 91% for ACRASM and from 44% to 80% for ASM. These data demonstrated that the segmentation results of ACRASM were in better agreement with the corresponding benchmarks than those of ASM. The developed registration algorithm was quantitatively evaluated by comparing the registered target volumes from the pCT to the benchmarks on the CBCT. The mean distance and the root mean square error ranged from 0.38 to 2.2 mm and from 0.45 to 2.36 mm, respectively, between the CBCT images and the registered pCT. The mean overlap ratio of the prostate volumes ranged from 85.2% to 95% after registration. The average time of the ACRASM-based segmentation was under 1 min. The average time of the global transformation was from 2 to 4 min on two 3D volumes and the average time of the local transformation was from 20 to 34 s on two deformable superquadrics mesh models. Conclusions: A novel and fast segmentation and deformable registration method was developed to capture the transformation between the planning and treatment images for external beam radiotherapy of prostate cancers. This method increases the computational efficiency and may provide foundation to achieve real time adaptive radiotherapy.« less

A non-isotropic multiple-scale turbulence model

NASA Technical Reports Server (NTRS)

Chen, C. P.

1990-01-01

A newly developed non-isotropic multiple scale turbulence model (MS/ASM) is described for complex flow calculations. This model focuses on the direct modeling of Reynolds stresses and utilizes split-spectrum concepts for modeling multiple scale effects in turbulence. Validation studies on free shear flows, rotating flows and recirculating flows show that the current model perform significantly better than the single scale k-epsilon model. The present model is relatively inexpensive in terms of CPU time which makes it suitable for broad engineering flow applications.

Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal

PubMed Central

Valent, P.; Sotlar, K.; Sperr, W. R.; Escribano, L.; Yavuz, S.; Reiter, A.; George, T. I.; Kluin-Nelemans, H. C.; Hermine, O.; Butterfield, J. H.; Hägglund, H.; Ustun, C.; Hornick, J. L.; Triggiani, M.; Radia, D.; Akin, C.; Hartmann, K.; Gotlib, J.; Schwartz, L. B.; Verstovsek, S.; Orfao, A.; Metcalfe, D. D.; Arock, M.; Horny, H.-P.

2014-01-01

Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011–2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%–19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials. PMID:24675021

Tidal stretches do not modulate responsiveness of intact airways in vitro

PubMed Central

Szabo, Thomas L.; Suki, Béla; Lutchen, Kenneth R.

2010-01-01

Studies on isolated tracheal airway smooth muscle (ASM) strips have shown that length/force fluctuations, similar to those likely occurring during breathing, will mitigate ASM contractility. These studies conjecture that, solely by reducing length oscillations on a healthy, intact airway, one can create airway hyperresponsiveness, but this has never been explicitly tested. The intact airway has additional complexities of geometry and structure that may impact its relevance to isolated ASM strips. We examined the role of transmural pressure (Ptm) fluctuations of physiological amplitudes on the responsiveness of an intact airway. We developed an integrated system utilizing ultrasound imaging to provide real-time measurements of luminal radius and wall thickness over the full length of an intact airway (generation 10 and below) during Ptm oscillations. First, airway constriction dynamics to cumulative acetylcholine (ACh) doses (10−7 to 10−3 M) were measured during static and dynamic Ptm protocols. Regardless of the breathing pattern, the Ptm oscillation protocols were ineffective in reducing the net level of constriction for any ACh dose, compared with the static control (P = 0.225–0.793). Next, Ptm oscillations of increasing peak-to-peak amplitude were applied subsequent to constricting intact airways under static conditions (5.0-cmH2O Ptm) with a moderate ACh dose (10−5 M). Peak-to-peak Ptm oscillations ≤5.0 cmH2O resulted in no statistically significant bronchodilatory response (P = 0.429 and 0.490). Larger oscillations (10 cmH2O, peak to peak) produced modest dilation of 4.3% (P = 0.009). The lack of modulation of airway responsiveness by Ptm oscillations in intact, healthy airways suggests that ASM level mechanisms alone may not be the sole determinant of airway responsiveness. PMID:20431023

CD28 in thymocyte development and peripheral T cell activation in mice exposed to suspended particulate matter

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

Drela, Nadzieja; Zesko, Izabela; Jakubowska, Martyna

2006-09-01

The CD28:B7 signaling pathway is very important for the activity of mature peripheral T lymphocytes and thymocyte development. The proper development of thymocytes into mature single positive CD4{sup +}and CD8{sup +} T cells is crucial for almost all immune functions. In naturally occurring conditions, T cells maturation in the thymus is influenced by environmental agents. The expression of CD28 and the distribution of CD28{sup low/high} thymocytes have been examined at various stages of thymocyte development in BALB/c mice exposed to air-suspended particulate matter (ASM). Acute exposure to ASM resulted in the decrease of CD28 expression in the total thymocyte population.more » The increase of the percentage of CD28{sup low} and the decrease of CD28{sup high} thymocytes were observed, which may account for the acceleration of thymocyte development under the conditions of elevated risk resulting from the exposure of animals to environmental xenobiotics. ASM exposure resulted in the increase of the level of proliferation of lymph node T cells induced by anti-CD3 and anti-CD28 monoclonal antibodies activation despite normal expression of CD28 molecule. In contrast, the level of proliferation of spleen T cells was lowered or normal dependently of the concentration of stimuli used for activation. Results of these studies demonstrate that acute exposure of mice to ASM can result in the progression of two contrasting processes in the immune system: upregulation of thymocyte development, which contributes to the maintenance of peripheral T cell pool, and over-activation of lymph node lymphocytes, which may lead to uncontrolled immunostimulation.« less

Vitamin D inhibits growth of human airway smooth muscle cells through growth factor-induced phosphorylation of retinoblastoma protein and checkpoint kinase 1

PubMed Central

Damera, G; Fogle, HW; Lim, P; Goncharova, EA; Zhao, H; Banerjee, A; Tliba, O; Krymskaya, VP; Panettieri, RA

2009-01-01

Background and purpose: Airway remodelling in asthma is manifested, in part, as increased airway smooth muscle (ASM) mass, reflecting myocyte proliferation. We hypothesized that calcitriol, a secosteroidal vitamin D receptor (VDR) modulator, would inhibit growth factor-induced myocyte proliferation. Experimental approach: Human ASM cell cultures were derived from bronchial samples taken during surgery. ASM cells were treated with platelet-derived growth factor (PDGF) (10 ng·mL−1) for 24 h in the presence of calcitriol, dexamethasone or a checkpoint kinase 1 (Chk1) inhibitor (SB218078). The effects of calcitriol on PDGF-mediated cell proliferation were assessed by thymidine incorporation assay, propidium iodide-based cell cycle analysis, caspase-3 assay and immunoblotting for specific cell cycle modulators. Key results: Calcitriol, but not dexamethasone, inhibited PDGF-induced ASM DNA synthesis concentration dependently (IC50= 520 ± 52 nM). These effects were associated with VDR-mediated expression of cytochrome CYP24A1 with no effects on ASM apoptosis. Calcitriol substantially inhibited (P < 0.01) PDGF-stimulated cell growth in ASM derived from both normal (59 ± 8%) and asthmatic subjects (57 ± 9%). Calcitriol inhibited PDGF-induced phosphorylation of retinoblastoma protein (Rb) and Chk1, with no effects on PDGF-mediated activation of extracellular signal-regulated kinases 1/2, PI3-kinase and S6 kinase, or expression of p21Waf/Cip-1, p27Kip1, cyclin D and E2F-1. Consistent with these observations, SB218078 also inhibited (IC50= 450 ± 100 pM) PDGF-induced cell cycle progression. Conclusions and implications: Calcitriol decreased PDGF-induced ASM cell growth by inhibiting Rb and Chk1 phosphorylation. This Research Paper is the subject of a Commentary in this issue by Clifford and Knox (pp. 1426–1428). To view this article visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009 PMID:19814732

IL-17A induces eotaxin-1/CC chemokine ligand 11 expression in human airway smooth muscle cells: role of MAPK (Erk1/2, JNK, and p38) pathways.

PubMed

Rahman, Muhammad Shahidur; Yamasaki, Akira; Yang, Jie; Shan, Lianyu; Halayko, Andrew J; Gounni, Abdelilah Soussi

2006-09-15

Recently, IL-17A has been shown to be expressed in higher levels in respiratory secretions from asthmatics and correlated with airway hyperresponsiveness. Although these studies raise the possibility that IL-17A may influence allergic disease, the mechanisms remain unknown. In this study, we investigated the molecular mechanisms involved in IL-17A-mediated CC chemokine (eotaxin-1/CCL11) production from human airway smooth muscle (ASM) cells. We found that incubation of human ASM cells with rIL-17A resulted in a significant increase of eotaxin-1/CCL11 release from ASM cells that was reduced by neutralizing anti-IL-17A mAb. Moreover, IL-17A significantly induced eotaxin-1/CCL11 release and mRNA expression, an effect that was abrogated with cycloheximide and actinomycin D treatment. Furthermore, transfection studies using a luciferase-driven reporter construct containing eotaxin-1/CCL11 proximal promoter showed that IL-17A induced eotaxin-1/CCL11 at the transcriptional level. IL-17A also enhanced significantly IL-1beta-mediated eotaxin-1/CCL11 mRNA, protein release, and promoter activity in ASM cells. Primary human ASM cells pretreated with inhibitors of MAPK p38, p42/p44 ERK, JNK, or JAK but not PI3K, showed a significant decrease in eotaxin-1/CCL11 release upon IL-17A treatment. In addition, IL-17A mediated rapid phosphorylation of MAPK (p38, JNK, and p42/44 ERK) and STAT-3 but not STAT-6 or STAT-5 in ASM cells. Taken together, our data provide the first evidence of IL-17A-induced eotaxin-1/CCL11 expression in ASM cells via MAPK (p38, p42/p44 ERK, JNK) signaling pathways. Our results raise the possibility that IL-17A may play a role in allergic asthma by inducing eotaxin-1/CCL11 production.

Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement

PubMed Central

Alrashdan, Yazan A.; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J.; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E.; Burgess, Janette K.; Armour, Carol L.; Ammit, Alaina J.

2012-01-01

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma. PMID:22387292

46 CFR 56.30-5 - Welded joints.

Code of Federal Regulations, 2010 CFR

2010-10-01

... systems and should be checked when designing for these systems. (c) Socket welds (Modifies 127.3.3A.). (1) Each socket weld must conform to ASME B16.11 (incorporated by reference; see 46 CFR 56.01-2), to... approximately one-sixteenth inch between the end of the pipe and the bottom of the socket must be provided...

46 CFR 56.30-5 - Welded joints.

Code of Federal Regulations, 2012 CFR

2012-10-01

... systems and should be checked when designing for these systems. (c) Socket welds (Modifies 127.3.3A.). (1) Each socket weld must conform to ASME B16.11 (incorporated by reference; see 46 CFR 56.01-2), to... approximately one-sixteenth inch between the end of the pipe and the bottom of the socket must be provided...

46 CFR 56.30-5 - Welded joints.

Code of Federal Regulations, 2011 CFR

2011-10-01

... systems and should be checked when designing for these systems. (c) Socket welds (Modifies 127.3.3A.). (1) Each socket weld must conform to ASME B16.11 (incorporated by reference; see 46 CFR 56.01-2), to... approximately one-sixteenth inch between the end of the pipe and the bottom of the socket must be provided...

46 CFR 56.30-5 - Welded joints.

Code of Federal Regulations, 2013 CFR

2013-10-01

... systems and should be checked when designing for these systems. (c) Socket welds (Modifies 127.3.3A.). (1) Each socket weld must conform to ASME B16.11 (incorporated by reference; see 46 CFR 56.01-2), to... approximately one-sixteenth inch between the end of the pipe and the bottom of the socket must be provided...

46 CFR 56.30-5 - Welded joints.

Code of Federal Regulations, 2014 CFR

2014-10-01

... systems and should be checked when designing for these systems. (c) Socket welds (Modifies 127.3.3A.). (1) Each socket weld must conform to ASME B16.11 (incorporated by reference; see 46 CFR 56.01-2), to... approximately one-sixteenth inch between the end of the pipe and the bottom of the socket must be provided...

Phytoremediation of arsenic in submerged soil by wetland plants.

PubMed

Jomjun, Nateewattana; Siripen, Trichaiyaporn; Maliwan, Saeouy; Jintapat, Nateewattana; Prasak, Thavornyutikarn; Somporn, Choonluchanon; Petch, Pengchai

2011-01-01

Wetland aquatic plants including Canna glauca L., Colocasia esculenta L. Schott, Cyperus papyrus L. and Typha angustifolia L. were used in the phytoremediation of submerged soil polluted by arsenic (As). Cyperus papyrus L. was noticed as the largest biomass producer which has arsenic accumulation capacity of 130-172 mg As/kg plant. In terms of arsenic removal rate, however, Colocasia esculenta L. was recognized as the largest and fastest arsenic remover in this study. Its arsenic removal rate was 68 mg As/m2/day while those rates of Canna glauca L., Cyperus papyrus L. and Typha angustifolia L. were 61 mg As/m2/day, 56 mg As/m2/day, and 56 mg As/m2/day, respectively. Although the 4 aquatic plants were inferior in arsenic accumulation, their high arsenic removal rates were observed. Phytostabilization should be probable for the application of these plants.

Optimal Regulation of Structural Systems with Uncertain Parameters.

DTIC Science & Technology

1981-02-02

been addressed, in part, by Statistical Energy Analysis . Moti- vated by a concern with high frequency vibration and acoustical- structural...Parameter Systems," AFOSR-TR-79-0753 (May, 1979). 25. R. H. Lyon, Statistical Energy Analysis of Dynamical Systems: Theory and Applications, (M.I.T...Press, Cambridge, Mass., 1975). 26. E. E. Ungar, " Statistical Energy Analysis of Vibrating Systems," Trans. ASME, J. Eng. Ind. 89, 626 (1967). 139 27

76 FR 53497 - Florida Power and Light Company; St. Lucie Plant, Units 1 and 2; Environmental Assessment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... Appendix G to the Code for calculating K IM factors, and instead applies FEM [finite element modeling..., Units 1 and 2 are calculated using the CE NSSS finite element modeling methods. The Need for the... Society of Mechanical Engineers (ASME) Code, Section XI, Appendix G) or determined by applying finite...

Groundwars Analysis of the Laser Warning Receiver (LWR). Phase 2

DTIC Science & Technology

1992-06-02

Advanced Field Artillery Systems, ATTN: SFAE-ASM-.AF, Picatinny Arsenal, NJ 07801 Future Armored Resupply Vehicle-Ammunition, ATTN: SFAE-ASM- FR , Picatinny...I I i I I uW I I D I IA ZL I I I 1 3 Tu W- WI IJJ 1 I i I li I x i l l l l I WW WW WWW LJ IzI I U- . I3 1I Z I I I I I n I IzT--:-)I I W0 1 1 1 I " I...Lfi I ll I 0 cc c) -- w z .1 00 LU I -4 , I . .. . . . IJ ’L coJ,< E ..: :.... ...... Z EDX -J - CI) zV I I S . .1 w w V OL__ z.I Lr >- 0 !- 0