78 FR 79363 - Hazardous Materials: Adoption of ASME Code Section XII and the National Board Inspection Code

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

... Rulemaking Division, (202) 366-8553, or Stanley Staniszewski, Engineering and Research [[Page 79364... increased capacity to transport product. A review of previous research by PHMSA's Engineering and Research..., knowledge-sharing, and skill development across all engineering disciplines. ASME is recognized globally for...

Accelerator System Model (ASM) user manual with physics and engineering model documentation. ASM version 1.0

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

NONE

1993-07-01

The Accelerator System Model (ASM) is a computer program developed to model proton radiofrequency accelerators and to carry out system level trade studies. The ASM FORTRAN subroutines are incorporated into an intuitive graphical user interface which provides for the {open_quotes}construction{close_quotes} of the accelerator in a window on the computer screen. The interface is based on the Shell for Particle Accelerator Related Codes (SPARC) software technology written for the Macintosh operating system in the C programming language. This User Manual describes the operation and use of the ASM application within the SPARC interface. The Appendix provides a detailed description of themore » physics and engineering models used in ASM. ASM Version 1.0 is joint project of G. H. Gillespie Associates, Inc. and the Accelerator Technology (AT) Division of the Los Alamos National Laboratory. Neither the ASM Version 1.0 software nor this ASM Documentation may be reproduced without the expressed written consent of both the Los Alamos National Laboratory and G. H. Gillespie Associates, Inc.« less

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

Development of a Pebble-Bed Liquid-Nitrogen Evaporator and Superheater for the Scaled Large Blast/Thermal Simulator Facility

DTIC Science & Technology

1991-04-01

Boiler and Pressure Vessel Code . Other design requirements are developed from standard safe... Boiler and Pressure Vessel Code . The following three condi- tions constitute the primary design parameters for pressure vessels: (a) Design Working...rules and practices of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code . Section VIII, Division 1 of the ASME

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.

Mechanical Design and Analysis of LCLS II 2 K Cold Box

NASA Astrophysics Data System (ADS)

Yang, S.; Dixon, K.; Laverdure, N.; Rath, D.; Bevins, M.; Bai, H.; Kaminski, S.; Ravindranath, V.

2017-12-01

The mechanical design and analysis of the LCLS II 2 K cold box are presented. Its feature and functionality are discussed. ASME B31.3 was used to design its internal piping, and compliance of the piping code was ensured through flexibility analysis. The 2 K cold box was analyzed using ANSYS 17.2; the requirements of the applicable codes—ASME Section VIII Division 2 and ASCE 7-10—were satisfied. Seismic load was explicitly considered in both analyses.

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

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.

FY16 ASME High Temperature Code Activities

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

Swindeman, M. J.; Jetter, R. I.; Sham, T. -L.

2016-09-01

One of the objectives of the ASME high temperature Code activities is to develop and validate both improvements and the basic features of Section III, Division 5, Subsection HB, Subpart B (HBB). The overall scope of this task is to develop a computer program to be used to assess whether or not a specific component under specified loading conditions will satisfy the elevated temperature design requirements for Class A components in Section III, Division 5, Subsection HB, Subpart B (HBB). There are many features and alternative paths of varying complexity in HBB. The initial focus of this task is amore » basic path through the various options for a single reference material, 316H stainless steel. However, the program will be structured for eventual incorporation all the features and permitted materials of HBB. Since this task has recently been initiated, this report focuses on the description of the initial path forward and an overall description of the approach to computer program development.« 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.

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

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

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.

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

78 FR 20141 - Notice Pursuant to the National Cooperative Research and Production Act of 1993 -- American...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-03

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993 -- American Society of Mechanical Engineers Notice is hereby given that, on March 5....C. 4301 et seq. (``the Act''), the American Society of Mechanical Engineers (``ASME'') has filed...

78 FR 58558 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on August 20....C. 4301 et seq. (``the Act''), the American Society of Mechanical Engineers (``ASME'') has filed...

76 FR 80406 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on December 6....C. 4301 et seq. (``the Act''), American Society of Mechanical Engineers (``ASME'') has filed written...

76 FR 27351 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on April 12....C. 4301 et seq. (``the Act''), American Society Of Mechanical Engineers (``ASME'') has filed written...

75 FR 70031 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on October 14....C. 4301 et seq. (``the Act''), American Society of Mechanical Engineers (``ASME'') has filed written...

76 FR 52014 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-19

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on July 25....C. 4301 et seq. (``the Act''), American Society of Mechanical Engineers (``ASME'') has filed written...

76 FR 6497 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-04

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on January 10....C. 4301 et seq. (``the Act''), American Society of Mechanical Engineers (``ASME'') has filed written...

75 FR 45156 - Notice Pursuant to the National Cooperative Research and Production Act of 1993; American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993; American Society of Mechanical Engineers Notice is hereby given that, on June 28....C. 4301 et seq. (``the Act''), the American Society of Mechanical Engineers (``ASME'') has filed...

77 FR 31041 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on April 27....C. 4301 et seq. (``the Act''), the American Society of Mechanical Engineers (``ASME'') has filed...

75 FR 14191 - Notice Pursuant to The National Cooperative Research and Production Act of 1993-American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-24

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to The National Cooperative Research and Production Act of 1993--American Society of Mechanical Engineers Notice is hereby given that, on February 25....C. 4301 et seq.. (``the Act''), the American Society of Mechanical Engineers (``ASME'') has filed...

77 FR 58412 - Notice Pursuant to the National Cooperative Research and Production Act of 1993; American Society...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... DEPARTMENT OF JUSTICE Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993; American Society of Mechanical Engineers Notice is hereby given that, on August 27....C. 4301 et seq. (``the Act''), the American Society of Mechanical Engineers (``ASME'') has filed...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

46 CFR 64.13 - Allowable stress; tank.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Allowable stress; tank. 64.13 Section 64.13 Shipping... CARGO HANDLING SYSTEMS Standards for an MPT § 64.13 Allowable stress; tank. (a) The calculated stress in... not exceed the allowable stress listed in Division 1 of section VIII of the ASME Code, for a design...

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...

Report on the FY17 Development of Computer Program for ASME Section III, Division 5, Subsection HB, Subpart B Rules

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

Swindeman, M. J.; Jetter, R. I.; Sham, T. -L.

One of the objectives of the high temperature design methodology activities is to develop and validate both improvements and the basic features of ASME Boiler and Pressure Vessel Code, Section III, Rules for Construction of Nuclear Facility Components, Division 5, High Temperature Reactors, Subsection HB, Subpart B (HBB). The overall scope of this task is to develop a computer program to aid assessment procedures of components under specified loading conditions in accordance with the elevated temperature design requirements for Division 5 Class A components. There are many features and alternative paths of varying complexity in HBB. The initial focus ofmore » this computer program is a basic path through the various options for a single reference material, 316H stainless steel. However, the computer program is being structured for eventual incorporation all of the features and permitted materials of HBB. This report will first provide a description of the overall computer program, particular challenges in developing numerical procedures for the assessment, and an overall approach to computer program development. This is followed by a more comprehensive appendix, which is the draft computer program manual for the program development. The strain limits rules have been implemented in the computer program. The evaluation of creep-fatigue damage will be implemented in future work scope.« less

30 CFR 250.198 - Documents incorporated by reference.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., and all Section I Interpretations Volume 55, incorporated by reference at § 250.803 and § 250.1629; (2... Interpretations Volume 55, incorporated by reference at §§ 250.803 and 250.1629; (3) ANSI/ASME Boiler and Pressure...; July 1, 2005 Addenda, Divisions 1 and 2, and all Section VIII Interpretations Volumes 54 and 55...

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.

ARC Researchers at ASME 2015 Internal Combustion Engine Division Fall

Science.gov Websites

-sense. Therefore, the focus of this paper is on the various methods of computing CA50 for analysing and classifying cycle-to-cycle variability. The assumptions made to establish fast and possibly on-line methods SI engine. Then the various fast methods for computing CA50 feed the two statistical methods

NREL's National Wind Technology Center Director Named ASME Fellow

Science.gov Websites

Division before becoming founding director of the NWTC. He joined NREL in 1984 following a 14-year stint as members with at least 10 years of engineering practice who have made "significant contributions" Monrad, (303) 275-4096 Golden, Colo., January 25, 1996 -- Dr. Robert W. Thresher, director of the

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

Implementation of ASME Code, Section XI, Code Case N-770, on Alternative Examination Requirements for Class 1 Butt Welds Fabricated with Alloy 82/182

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

Sullivan, Edmund J.; Anderson, Michael T.

In May 2010, the NRC issued a proposed notice of rulemaking that includes a provision to add a new section to its rules to require licensees to implement ASME Code Case N-770, ‘‘Alternative Examination Requirements and Acceptance Standards for Class 1 PWR Piping and Vessel Nozzle Butt Welds Fabricated with UNS N06082 or UNS W86182 Weld Filler Material With or Without the Application of Listed Mitigation Activities, Section XI, Division 1,’’ with 15 conditions. Code Case N-770 contains baseline and inservice inspection (ISI) requirements for unmitigated butt welds fabricated with Alloy 82/182 material and preservice and ISI requirements for mitigatedmore » butt welds. The NRC stated that application of ASME Code Case N-770 is necessary because the inspections currently required by the ASME Code, Section XI, were not written to address stress corrosion cracking Alloy 82/182 butt welds, and the safety consequences of inadequate inspections can be significant. The NRC expects to issue the final rule incorporating this code case into its regulations in the spring 2011 time frame. This paper discusses the new examination requirements, the conditions that NRC is imposing , and the major concerns with implementation of the new Code Case.« less

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

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

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

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

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

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.

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

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.

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.

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.

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

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

Stress analysis and evaluation of a rectangular pressure vessel

NASA Astrophysics Data System (ADS)

Rezvani, M. A.; Ziada, H. H.; Shurrab, M. S.

1992-10-01

This study addresses structural analysis and evaluation of an abnormal rectangular pressure vessel, designed to house equipment for drilling and collecting samples from Hanford radioactive waste storage tanks. It had to be qualified according to ASME boiler and pressure vessel code, section 8; however, it had the cover plate bolted along the long face, a configuration not addressed by the code. Finite element method was used to calculate stresses resulting from internal pressure; these stresses were then used to evaluate and qualify the vessel. Fatigue is not a concern; thus, it can be built according to section 8, division 1 instead of division 2. Stress analysis was checked against the code. A stayed plate was added to stiffen the long side of the vessel.

Traditional engineering in the biological century: the biotraditional engineer.

PubMed

Friedman, M H

2001-12-01

The increasing importance of life science in all engineering is prompting departments in the traditional engineering disciplines to offer life science as part of their curricula. Students who take advantage of this opportunity--"biotraditional engineers"--will be well positioned for careers in their discipline and in related areas of bioengineering. The founder engineering societies, such as the Bioengineering Division of ASME, are responding to this trend by broadening their scope and working increasingly across interdisciplinary borders.

Model of Transition from Laminar to Turbulent Flow

NASA Astrophysics Data System (ADS)

Kanda, Hidesada

2001-11-01

For circular pipe flows, a model of transition from laminar to turbulent flow has already been proposed and the minimum critical Reynolds number of approximately 2040 was obtained (Kanda, 1999). In order to prove the validity of the model, another verification is required. Thus, for plane Poiseuille flow, results of previous investigations were studied, focusing on experimental data on the critical Reynolds number Rc, the entrance length, and the transition length. Consequently, concerning the natural transition, it was confirmed from the experimental data that (i) the transition occurs in the entrance region, (ii) Rc increases as the contraction ratio in the inlet section increases, and (iii) the minimum Rc is obtained when the contraction ratio is the smallest or one, and there is no-bellshaped entrance or straight parallel plates. Its value exists in the neighborhood of 1300, based on the channel height and the average velocity. Although, for Hagen-Poiseuille flow, the minimum Rc is approximately 2000, based on the pipe diameter and the average velocity, there seems to be no significant difference in the transition from laminar to turbulent flow between Hagen-Poiseuille flow and plane Poiseuille flow (Kanda, 2001). Rc is determined by the shape of the inlet. Kanda, H., 1999, Proc. of ASME Fluids Engineering Division - 1999, FED-Vol. 250, pp. 197-204. Kanda, H., 2001, Proc. of ASME Fluids Engineering Division - 2001.

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.

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

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.

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.

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

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

Dual arm master controller development

NASA Technical Reports Server (NTRS)

Kuban, D. P.; Perkins, G. S.

1985-01-01

The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape driven manipulators. Studies were performed which addressed to human factor design and performance tradeoffs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented.

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.

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.

Special Section on InterPACK 2017—Part 1

DOE PAGES

Mysore, Kaushik; Narumanchi, Sreekant; Dede, Ercan; ...

2018-03-02

InterPACK is a premier international forum for exchange of state-of-the-art knowledge in research, development, manufacturing, and applications of micro-electronics packaging. It is the flagship conference of the ASME Electronic and Photonic Packaging Division (EPPD) founded in 1992 as an ASME-JSME joint biannual conference. Rapid changes in the semiconductor landscape together with findings from InterPACK Pathfinding workshop (IPW) in 2016 led to a significant reset of InterPACK conference priorities and focus to comprehensively address needs of the InterPACK community. As a result, starting in 2017, InterPACK has become an annual conference and the scope of the conference has increased significantly togethermore » with a systems-focus to include some of the most cutting-edge topics in electronics packaging, device integration, and reliability. These topics are organized across five different tracks: (1) heterogeneous integration: microsystems with diverse functionality, (2) servers of the future, (3) structural and physical health monitoring, (4) energy conversion and storage, and (5) transportation: autonomous and electric vehicles.« less

Special Section on InterPACK 2017—Part 1

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

Mysore, Kaushik; Narumanchi, Sreekant; Dede, Ercan

InterPACK is a premier international forum for exchange of state-of-the-art knowledge in research, development, manufacturing, and applications of micro-electronics packaging. It is the flagship conference of the ASME Electronic and Photonic Packaging Division (EPPD) founded in 1992 as an ASME-JSME joint biannual conference. Rapid changes in the semiconductor landscape together with findings from InterPACK Pathfinding workshop (IPW) in 2016 led to a significant reset of InterPACK conference priorities and focus to comprehensively address needs of the InterPACK community. As a result, starting in 2017, InterPACK has become an annual conference and the scope of the conference has increased significantly togethermore » with a systems-focus to include some of the most cutting-edge topics in electronics packaging, device integration, and reliability. These topics are organized across five different tracks: (1) heterogeneous integration: microsystems with diverse functionality, (2) servers of the future, (3) structural and physical health monitoring, (4) energy conversion and storage, and (5) transportation: autonomous and electric vehicles.« less

Guest Editorial: Special Section on InterPACK 2017 - Part 2

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

Narumanchi, Sreekant V; Mysore, Kaushik; Dede, Ercan

InterPACK is a premier international forum for exchange of state-of-the-art knowledge in research, development, manufacturing, and applications of micro-electronics packaging. It is the flagship conference of the ASME Electronic and Photonic Packaging Division (EPPD) founded in 1992 as an ASME-JSME joint biannual conference. Rapid changes in the semiconductor landscape together with findings from InterPACK Pathfinding workshop (IPW) in 2016 led to a significant reset of InterPACK conference priorities and focus to comprehensively address needs of the InterPACK community. As a result, starting in 2017, InterPACK has become an annual conference and the scope of the conference has increased significantly togethermore » with a systems-focus to include some of the most cutting-edge topics in electronics packaging, device integration, and reliability. These topics are organized across five different tracks: (1) heterogeneous integration: microsystems with diverse functionality, (2) servers of the future, (3) structural and physical health monitoring, (4) energy conversion and storage, and (5) transportation: autonomous and electric vehicles.« less

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.

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.

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.

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.

Focus on Advancing High Performance Mass Spectrometry, Honoring Dr. Richard D. Smith, Recipient of the 2013 Award for a Distinguished Contribution in Mass Spectrometry

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

Baker, Erin Shammel; Muddiman, David C.; Loo, Joseph

This special focus issue of the Journal of the American Society for Mass Spectrometry celebrates the accomplishments of Dr. Richard D. Smith, the recipient of the 2013ASMS Award for a Distinguished Contribution in Mass Spectrometry, and who serves as a Battelle Fellow, Chief Scientist in the Biological Sciences Division, and Director of Proteomics Research at Pacific Northwest National Laboratory (PNNL) in Richland, WA. The award is for his development of the electrodynamic ion funnel.

Tribology symposium -- 1994. PD-Volume 61

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

Masudi, H.

This year marks the first Tribology Symposium within the Energy-Sources Technology Conference, sponsored by the ASME Petroleum Division. The program was divided into five sessions: Tribology in High Technology, a historical discussion of some watershed events in tribology; Research/Development, design, research and development on modern manufacturing; Tribology in Manufacturing, the impact of tribology on modern manufacturing; Design/Design Representation, aspects of design related to tribological systems; and Failure Analysis, an analysis of failure, failure detection, and failure monitoring as relating to manufacturing processes. Eleven papers have been processed separately for inclusion on the data base.

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.

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.

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

Type 2 diabetes is associated with low muscle mass in older adults.

PubMed

Kim, Kyung-Soo; Park, Kyung-Sun; Kim, Moon-Jong; Kim, Soo-Kyung; Cho, Yong-Wook; Park, Seok Won

2014-02-01

Our aim was to clarify the association between type 2 diabetes and the risk of low muscle mass in older adults. In the present study, 414 adults aged 65 years or older (144 patients with type 2 diabetes and 270 control participants) were included. Body composition was measured by dual-energy X-ray absorptiometry. Low muscle mass was defined as the appendicular skeletal muscle mass/height(2) (ASM/Ht(2)) or appendicular skeletal muscle mass/weight (ASM/Wt) of <2 SD below the sex-specific normal mean of the young reference group, or

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

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.

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.

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

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.

Association of Bacillus anthracis Capsule with Lethal Toxin during Experimental Infection

DTIC Science & Technology

2009-02-01

interacts with a specific receptor on the surface of CHO- K1 cells. Infect. Immun. 59:3381– 3386. 6. Ezzell, J. W., B. E . Ivins, and S. H. Leppla. 1984...Abshire,1 R. Panchal,3 D. Chabot,2 S. Bavari,2 E . K. Leffel,4 B. Purcell,2 A. M. Friedlander,5 and W. J. Ribot2* Diagnostic Systems Division,1 Bacteriology...2153. E -mail: Wilson.ribot@amedd.army.mil. Published ahead of print on 8 December 2008. 749 by on A ugust 27, 2009 iai.asm .org D ow nloaded from

Human factors in telemanipulation: Perspectives from the Oak Ridge National Laboratory experience

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

Draper, J.V.

1994-01-01

Personnel at the Robotics and Process Systems Division (RPSD) of the Oak Ridge National Laboratory (ORNL) have extensive experience designing, building, and operating teleoperators for a variety of settings, including space, battlefields, nuclear fuel reprocessing plants, and hazardous waste retrieval. In the course of the last decade and a half, the RPSD designed, built, and operated 4 telemanipulators (M-2, ASM, LTM, CESAR arm) and operated another half dozen (M-8, Model 50, TOS SM-229, RM-10, PaR 5000, BilArm 83A). During this period, human factors professionals have been closely integrated with RPSD design teams, investigating telemanipulator feedback and feed forward, designing cockpitsmore » and control rooms, training users and designers, and helping to develop performance specifications for telemanipulators. This paper presents a brief review of this and other work, with an aim towards providing perspectives on some of the human factors aspects of telemanipulation. The first section of the paper examines user tasks during supervisory control and discusses how telemanipulator responsiveness determines the appropriate control metaphor for continuous manual control. The second section provides an ecological perspective on telemanipulator feedback and feed-forward. The third section briefly describes the RPSD control room design approach and how design projects often serve as systems integrators.« less

Preparing Technical Requirements for Third Party Contracting of Army Facilities

DTIC Science & Technology

1993-06-01

Boiler and Pressure Vessel Code Sec 9 Welding and Brazing Qualifications B 16.1 Cast Iron Pipe Flanges and Flanged...Control Terminology for Heating, Ventilating, Air Conditioning American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code B40.1...American National Standards Institute (ANSI) Boiler and Pressure Vessel Code (ASME) 125 Boilers and Pressure Vessels Code (ASTM) B31 Power

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.

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.

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.

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.

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.

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

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.

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

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.

Evaluation of the Efficacy, Potential for Vector Transmission, and Duration of Immunity of MP-12, an Attenuated Rift Valley Fever Virus Vaccine Candidate, in Sheep

DTIC Science & Technology

2015-08-01

testing by virus isolation (VI). Positive-control mosquitoes were sampled whole on the day of the spiked blood meal. b NA, not applicable. Miller et al ...percent inhibition of the negative control, calculated as 1 (test serum OD/negative serum OD) 100. Miller et al . 934 cvi.asm.org August 2015 Volume 22...Trop Med Hyg 44:278 –282. 34. Morrill JC, Mebus CA, Peters CJ. 1997. Safety of a mutagen-attenuated Miller et al . 936 cvi.asm.org August 2015 Volume 22

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.

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...

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.

Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses.

PubMed

Chevigny, Mylène; Guérin-Montpetit, Karine; Vargas, Amandine; Lefebvre-Lavoie, Josiane; Lavoie, Jean-Pierre

2015-07-01

Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, a spontaneously occurring asthma-like disease of horses, and in controls. Six horses with heaves and five aged-matched controls kept in the same environment were studied. Nuclear protein expression of SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial biopsies obtained during disease remission and after 1 and 30 days of naturally occurring antigenic exposure using immunohistochemistry and immunofluorescence techniques. Nuclear expression of SRF (P = 0.03, remission vs. 30 days) and MYOCD (P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of horses with heaves during disease exacerbation, while MYOCD (P = 0.04, remission vs. 30 days) decreased in the central airways of control horses. No changes were observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM observed in equine asthmatic airways, while the remodeling of the central airways is more static or involves different transcription factors. Copyright © 2015 the American Physiological Society.

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.

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

Draft ASME Boiler and Pressure Vessel Code Section III, Division 5, Section HB, Subsection B, Code Case for Alloy 617 and Background Documentation

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

Wright, Julie Knibloe

2015-08-01

Alloy 617 is the leading candidate material for an intermediate heat exchanger for the very high temperature reactor. To evaluate the behavior of this material in the expected service conditions, strain controlled cyclic tests that include long hold times up to 240 minutes at maximum tensile strain were conducted at 850°C. In terms of the total number of cycles to failure, the fatigue resistance decreased when a hold time was added at peak tensile strain. Increases in the tensile hold duration degraded the creep fatigue resistance, at least to the investigated strain controlled hold time of up to 60 minutesmore » at the 0.3% strain range and 240 minutes at the 1.0% strain range. The creep fatigue deformation mode is considered relative to the lack of saturation, or continually decreasing number of cycles to failure with increasing hold times. Additionally, preliminary values from the 850°C creep fatigue data are calculated for the creep fatigue damage diagram and have higher values of creep damage than those from tests at 950°C.« less

A shifting mosaic of scholarly publishing, scientific delivery, and future impact changing the face of learned societies

USGS Publications Warehouse

Leslie, David M.

2007-01-01

Nonprofit scientific societies hope that their activities advance their particular mission and impact their profession and, in the broadest sense, humanity in positive ways. The digital age has provided unprecedented mechanisms to enhance the delivery of science to the world. The marketplace of scientific publishing is a rapidly shifting mosaic of challenges and opportunities, and the responses of nonprofit and commercial publishers vary widely, but their outcomes are still uncertain. The response of the American Society of Mammalogists (ASM) provides an example of how a relatively small society has altered its scientific delivery to enhance member benefits while attempting to sustain its economic viability. Since 2000, ASM has moved from a self-publishing, break-even, print-only model to a copublishing agreement with a commercial publisher (Alliance Communications Group, a division of Allen Press, Inc., Lawrence, Kansas), which now offers members various print and electronic options and generates a shared royalty. Although it is too early to gauge the economic impact of these changes, the ASM leadership clearly attempted to signal its desire for members to view their society as a package of opportunities for edification and involvement rather than just a provider of serial subscriptions. Future challenges facing nonprofit scientific societies include open access, fiscal realities, archiving of publications, and scientific and societal impact; future opportunities include a strengthening of member responsibilities and professionalism, development of data registries to enhance scientific progress, and bundling of like societies. The manner in which nonprofit scientific societies respond to these challenges and opportunities will no doubt affect their sustainability and future impact. ?? 2007 American Society of Mammalogists.

Gender difference in association between appendicular skeletal muscle mass and cardiometabolic abnormalities in normal-weight and obese adults: Korea National Health and Nutrition Examination Survey (KNHANES) IV-3 and V-1.

PubMed

Kim, Jaehee

2015-03-01

The objective of this study was to investigate whether the relationships of appendicular muscle mass (ASM) with insulin resistance (IR) and metabolic syndrome (MS) vary by gender or obesity. Data of 10 146 normal-weight and obese men and women aged 19 to 93 years from the Korea National Health and Nutrition Examination Survey in 2009 and 2010 were analyzed. In normal-weight men and women, unadjusted odds ratio (OR) of being MS and IR significantly increased with lower ASM/wt. After adjusting for lifestyle factors, these ORs were still significant in normal-weight men but not in women. After controlling for other covariates, lower ASM/wt was related to higher risk for IR but not to MS in obese men. In obese women, relationship of lower ASM/wt with higher risk for MS disappeared after adjusting for covariates. Association between skeletal muscle mass and cardiometabolic abnormalities is dependent on gender and obesity in Korean adults. © 2012 APJPH.

Knee cartilage segmentation using active shape models and local binary patterns

NASA Astrophysics Data System (ADS)

González, Germán.; Escalante-Ramírez, Boris

2014-05-01

Segmentation of knee cartilage has been useful for opportune diagnosis and treatment of osteoarthritis (OA). This paper presents a semiautomatic segmentation technique based on Active Shape Models (ASM) combined with Local Binary Patterns (LBP) and its approaches to describe the surrounding texture of femoral cartilage. The proposed technique is tested on a 16-image database of different patients and it is validated through Leave- One-Out method. We compare different segmentation techniques: ASM-LBP, ASM-medianLBP, and ASM proposed by Cootes. The ASM-LBP approaches are tested with different ratios to decide which of them describes the cartilage texture better. The results show that ASM-medianLBP has better performance than ASM-LBP and ASM. Furthermore, we add a routine which improves the robustness versus two principal problems: oversegmentation and initialization.

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

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

Development of Standard Methods of Testing and Analyzing Fatigue Crack Growth Rate Data

DTIC Science & Technology

1978-05-01

nitrogen cooled cryostat; high temperature tests were conducted using resistance heating tapes . An automatic controller maintained test temperatures...Cracking," Int. J. Fracture, Vol. 9, 1973, pp. 63-74. 87. P. Paris and F. Erdogan , "A Critical Analysis of Crack Propagation Laws," Trans. ASME, Ser. D: J...requirements of Sec. 7.2 and Appendix B. 200 REFERENCES 1. P. C. Paris and F. Erdogan , "A Critical Analysis of Crack Propagation Laws", Trans. ASME, Ser. D: 3

Performance, Life, and Operability Trade-Offs in VCE Control Logic Design.

DTIC Science & Technology

1981-08-01

primarily USAF Actuarial Reports), including all engine returns to the intermediate or depot shop - scheduled and unscheduled - engine and non-engine...Length (Min) Training * Air to Air (ATA) 30 576 87 e Air to Ground (ATG) 30 363 128 Combat e Air Superiority ( ASM ) 13 75 228 e Intercept 2 31 94... ASME , 16th Joint Propulsion Conference, Paper No. ALAA-80-1115, June 30 - July 2, 1980. 2. Akimov, V.M., Starik, D.E., et al., The Economic Efficiency

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.

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.

Oxidative stress–induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease

PubMed Central

Wiegman, Coen H.; Michaeloudes, Charalambos; Haji, Gulammehdi; Narang, Priyanka; Clarke, Colin J.; Russell, Kirsty E.; Bao, Wuping; Pavlidis, Stelios; Barnes, Peter J.; Kanerva, Justin; Bittner, Anton; Rao, Navin; Murphy, Michael P.; Kirkham, Paul A.; Chung, Kian Fan; Adcock, Ian M.; Brightling, Christopher E.; Davies, Donna E.; Finch, Donna K.; Fisher, Andrew J.; Gaw, Alasdair; Knox, Alan J.; Mayer, Ruth J.; Polkey, Michael; Salmon, Michael; Singh, David

2015-01-01

Background Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress–induced pathology. Objective We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells. Methods Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ. Results Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β–induced ASM cell proliferation and CXCL8 release. Conclusions Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation. Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD. PMID:25828268

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.

Overexpression of human Hsp27 inhibits serum-induced proliferation in airway smooth muscle myocytes and confers resistance to hydrogen peroxide cytotoxicity.

PubMed

Salinthone, Sonemany; Ba, Mariam; Hanson, Lisa; Martin, Jody L; Halayko, Andrew J; Gerthoffer, William T

2007-11-01

Airway smooth muscle (ASM) hypertrophy and hyperplasia are characteristics of asthma that lead to thickening of the airway wall and obstruction of airflow. Very little is known about mechanisms underlying ASM remodeling, but in vascular smooth muscle, it is known that progression of atherosclerosis depends on the balance of myocyte proliferation and cell death. Small heat shock protein 27 (Hsp27) is antiapoptotic in nonmuscle cells, but its role in ASM cell survival is unknown. Our hypothesis was that phosphorylation of Hsp27 may regulate airway remodeling by modifying proliferation, cell survival, or both. To test this hypothesis, adenoviral vectors were used to overexpress human Hsp27 in ASM cells. Cells were infected with empty vector (Ad5) or wild-type Hsp27 (AdHsp27 WT), and proliferation and death were assessed. Overexpressing Hsp27 WT caused a 50% reduction in serum-induced proliferation and increased cell survival after exposure to 100 microM hydrogen peroxide (H(2)O(2)) compared with mock-infected controls. Overexpression studies utilizing an S15A, S78A, and S82A non-phosphorylation mutant (AdHsp27 3A) and an S15D, S78D, and S82D pseudo-phosphorylation mutant (AdHsp27 3D) showed phosphorylation of Hsp27 was necessary for regulation of ASM proliferation, but not survival. Hsp27 provided protection against H(2)O(2)-induced cytotoxicity by upregulating cellular glutathione levels and preventing necrotic cell death, but not apoptotic cell death. The results support the notion that ASM cells can be stimulated to undergo proliferation and death and that Hsp27 may regulate these processes, thereby contributing to airway remodeling in asthmatics.

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.

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

GC-ASM: Synergistic Integration of Graph-Cut and Active Shape Model Strategies for Medical Image Segmentation

PubMed Central

Chen, Xinjian; Udupa, Jayaram K.; Alavi, Abass; Torigian, Drew A.

2013-01-01

Image segmentation methods may be classified into two categories: purely image based and model based. Each of these two classes has its own advantages and disadvantages. In this paper, we propose a novel synergistic combination of the image based graph-cut (GC) method with the model based ASM method to arrive at the GC-ASM method for medical image segmentation. A multi-object GC cost function is proposed which effectively integrates the ASM shape information into the GC framework. The proposed method consists of two phases: model building and segmentation. In the model building phase, the ASM model is built and the parameters of the GC are estimated. The segmentation phase consists of two main steps: initialization (recognition) and delineation. For initialization, an automatic method is proposed which estimates the pose (translation, orientation, and scale) of the model, and obtains a rough segmentation result which also provides the shape information for the GC method. For delineation, an iterative GC-ASM algorithm is proposed which performs finer delineation based on the initialization results. The proposed methods are implemented to operate on 2D images and evaluated on clinical chest CT, abdominal CT, and foot MRI data sets. The results show the following: (a) An overall delineation accuracy of TPVF > 96%, FPVF < 0.6% can be achieved via GC-ASM for different objects, modalities, and body regions. (b) GC-ASM improves over ASM in its accuracy and precision to search region. (c) GC-ASM requires far fewer landmarks (about 1/3 of ASM) than ASM. (d) GC-ASM achieves full automation in the segmentation step compared to GC which requires seed specification and improves on the accuracy of GC. (e) One disadvantage of GC-ASM is its increased computational expense owing to the iterative nature of the algorithm. PMID:23585712

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.

GC-ASM: Synergistic Integration of Graph-Cut and Active Shape Model Strategies for Medical Image Segmentation.

PubMed

Chen, Xinjian; Udupa, Jayaram K; Alavi, Abass; Torigian, Drew A

2013-05-01

Image segmentation methods may be classified into two categories: purely image based and model based. Each of these two classes has its own advantages and disadvantages. In this paper, we propose a novel synergistic combination of the image based graph-cut (GC) method with the model based ASM method to arrive at the GC-ASM method for medical image segmentation. A multi-object GC cost function is proposed which effectively integrates the ASM shape information into the GC framework. The proposed method consists of two phases: model building and segmentation. In the model building phase, the ASM model is built and the parameters of the GC are estimated. The segmentation phase consists of two main steps: initialization (recognition) and delineation. For initialization, an automatic method is proposed which estimates the pose (translation, orientation, and scale) of the model, and obtains a rough segmentation result which also provides the shape information for the GC method. For delineation, an iterative GC-ASM algorithm is proposed which performs finer delineation based on the initialization results. The proposed methods are implemented to operate on 2D images and evaluated on clinical chest CT, abdominal CT, and foot MRI data sets. The results show the following: (a) An overall delineation accuracy of TPVF > 96%, FPVF < 0.6% can be achieved via GC-ASM for different objects, modalities, and body regions. (b) GC-ASM improves over ASM in its accuracy and precision to search region. (c) GC-ASM requires far fewer landmarks (about 1/3 of ASM) than ASM. (d) GC-ASM achieves full automation in the segmentation step compared to GC which requires seed specification and improves on the accuracy of GC. (e) One disadvantage of GC-ASM is its increased computational expense owing to the iterative nature of the algorithm.

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.

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.

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...

ASME Section VIII Recertification of a 33,000 Gallon Vacuum-jacketed LH2 Storage Vessel for Densified Hydrogen Testing at NASA Kennedy Space Center

NASA Technical Reports Server (NTRS)

Swanger, Adam M.; Notardonato, William U.; Jumper, Kevin M.

2015-01-01

The Ground Operations Demonstration Unit for Liquid Hydrogen (GODU-LH2) has been developed at NASA Kennedy Space Center in Florida. GODU-LH2 has three main objectives: zero-loss storage and transfer, liquefaction, and densification of liquid hydrogen. A cryogenic refrigerator has been integrated into an existing, previously certified, 33,000 gallon vacuum-jacketed storage vessel built by Minnesota Valley Engineering in 1991 for the Titan program. The dewar has an inner diameter of 9.5 and a length of 71.5; original design temperature and pressure ranges are -423 F to 100 F and 0 to 95 psig respectively. During densification operations the liquid temperature will be decreased below the normal boiling point by the refrigerator, and consequently the pressure inside the inner vessel will be sub-atmospheric. These new operational conditions rendered the original certification invalid, so an effort was undertaken to recertify the tank to the new pressure and temperature requirements (-12.7 to 95 psig and -433 F to 100 F respectively) per ASME Boiler and Pressure Vessel Code, Section VIII, Division 1. This paper will discuss the unique design, analysis and implementation issues encountered during the vessel recertification process.

The Unconventional Role of Acid Sphingomyelinase in Regulation of Retinal Microangiopathy in Diabetic Human and Animal Models

PubMed Central

Opreanu, Madalina; Tikhonenko, Maria; Bozack, Svetlana; Lydic, Todd A.; Reid, Gavin E.; McSorley, Kelly M.; Sochacki, Andrew; Perez, Gloria I.; Esselman, Walter J.; Kern, Timothy; Kolesnick, Richard; Grant, Maria B.; Busik, Julia V.

2011-01-01

OBJECTIVE Acid sphingomyelinase (ASM) is an important early responder in inflammatory cytokine signaling. The role of ASM in retinal vascular inflammation and vessel loss associated with diabetic retinopathy is not known and represents the goal of this study. RESEARCH DESIGN AND METHODS Protein and gene expression profiles were determined by quantitative RT-PCR and Western blot. ASM activity was determined using Amplex Red sphingomyelinase assay. Caveolar lipid composition was analyzed by nano-electrospray ionization tandem mass spectrometry. Streptozotocin-induced diabetes and retinal ischemia-reperfusion models were used in in vivo studies. RESULTS We identify endothelial caveolae-associated ASM as an essential component in mediating inflammation and vascular pathology in in vivo and in vitro models of diabetic retinopathy. Human retinal endothelial cells (HREC), in contrast with glial and epithelial cells, express the plasma membrane form of ASM that overlaps with caveolin-1. Treatment of HREC with docosahexaenoic acid (DHA) specifically reduces expression of the caveolae-associated ASM, prevents a tumor necrosis factor-α–induced increase in the ceramide-to-sphingomyelin ratio in the caveolae, and inhibits cytokine-induced inflammatory signaling. ASM is expressed in both vascular and neuroretina; however, only vascular ASM is specifically increased in the retinas of animal models at the vasodegenerative phase of diabetic retinopathy. The absence of ASM in ASM−/− mice or inhibition of ASM activity by DHA prevents acellular capillary formation. CONCLUSIONS This is the first study demonstrating activation of ASM in the retinal vasculature of diabetic retinopathy animal models. Inhibition of ASM could be further explored as a potential therapeutic strategy in treating diabetic retinopathy. PMID:21771974

Weld Repair of a Stamped Pressure Vessel in a Radiologically Controlled Zone

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

Cannell, Gary L.; Huth, Ralph J.; Hallum, Randall T.

2013-08-26

In September 2012 an ASME B&PVC Section VIII stamped pressure vessel located at the DOE Hanford Site Effluent Treatment Facility (ETF) developed a through-wall leak. The vessel, a steam/brine heat exchanger, operated in a radiologically controlled zone (by the CH2MHill PRC or CHPRC), had been in service for approximately 17 years. The heat exchanger is part of a single train evaporator process and its failure caused the entire system to be shut down, significantly impacting facility operations. This paper describes the activities associated with failure characterization, technical decision making/planning for repair by welding, logistical challenges associated with performing work inmore » a radiologically controlled zone, performing the repair, and administrative considerations related to ASME code requirements.« less

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.

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.

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...

[Effect of moxa-burning heat stimulating Liangmen (ST 21) and Zusanli (ST 36) on proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer].

PubMed

Peng, Li; Wang, Yadong; Chang, Xiaorong; Wu, Huangan; Liu, Mi; Wang, Hong; Chen, Jiaolong; Wang Chao; Quan, Renfu; Yang, Zongbao

2016-06-01

To observe the effect of moxa-burning heat stimulating acupoints of Liangmen (ST 21) and Zusanli (ST 36) on the proliferation and apoptosis signaling proteins in rats with stress-induced gastric ulcer. Forty rats were randomly divided into four groups: negative control (NC), ulcer control (UC), acupoints of stomach meridian (ASM), and acupoints control (AC). The acute gastric ulcer model was established by bound and water immersion. Rats in NC and UC groups didn't receive any moxa-burning heat stimulating treatment, while rats in ASM and AC groups were treated with buringmoxa heat stimulating the acupoints of Liangmen (ST 21) and Zusanli (ST 36) and their controlled points, respectively. Rats in all groups were sacrificed after 12 consecutive days treatment. The ulcer index was evaluated by using Guth's method. The expression of tumor necrosis factor-alpha (TNF-α), apoptotic protease activating facter-1 (Apaf-1), Caspase-3, p21 activated kinase 1 (PAK1), extracellular regulated protein kinases 2 (ERK2), phosphorylated ERK2 (pERK2), phosphoinositide 3-kinase (PI3K) and RAC-alpha serine/threonine-protein kinase (Akt) in gastric mucosa was detected by enzyme linked immunosorbent assay (ELISA). Compared with UC group, the ulcer index of ASM and AC groups decreased, and the injured gastric mucosa was improved, the expression of TNF-α, Apaf-1 and Caspase-3 in gastric mucosa was significantly reduced (P < 0.05), while the expression of PAK1, ERK2, pERK2, PI3K and Akt in gastric mucosa was significantly increased (P < 0.05). And ASM showed better effect than AC group (P < 0.05). Moxa-burning Heat stimulating of Liangmen (ST 21) and Zusanli (ST 36) could promote the recovery of gastric mucosal lesion probably by inhibiting cell apoptosis and promoting cell proliferation in stress-induced gastric ulcer.

A review of biotransport education in the 21st century: lessons learned from experts.

PubMed

Banerjee, Rupak K; D'Souza, Gavin A; Rylander, Christopher; Devireddy, Ram

2014-11-01

The field of bioengineering is relatively new and complex including multiple disciplines encompassing areas in science and engineering. Efforts including the National Science Foundation (NSF) sponsored Integrative Graduate Education and Research Traineeship (IGERT) and VaNTH Engineering Research Center in Bioengineering Educational Technologies have been made to establish and disseminate knowledge and proven methods for teaching bioengineering concepts. Further, the summer bioengineering conference (SBC), sponsored by the American Society of Mechanical Engineers' (ASME) Bioengineering Division, was established to provide a meeting place for engineering educators and students having common interests in biological systems. Of the many subdisciplines of bioengineering, biotransport is a key subject that has wide applicability to many issues in engineering, biology, medicine, pharmacology, and environmental science, among others. The absence of standard content, guidelines, and texts needed for teaching biotransport courses to students motivated the Biotransport committee of ASME's Bioengineering Division to establish a biotransport education initiative. Biotransport education workshop sessions were conducted during the SBC 2011, 2012, and 2013 as part of this initiative. The workshop sessions included presentations from experienced faculty covering a spectrum of information from general descriptions of undergraduate biotransport courses to very detailed outlines of graduate courses to successful teaching techniques. A list of texts and references available for teaching biotransport courses at undergraduate and graduate levels has been collated and documented based on the workshop presentations. Further, based on individual teaching experiences and methodologies shared by the presenters, it was noted that active learning techniques, including cooperative and collaborative learning, can be useful for teaching undergraduate courses while problem based learning (PBL) can be a beneficial method for graduate courses. The outcomes of the education initiative will help produce students who are knowledgeable in the subject of biotransport, facile in applying biotransport concepts for solving problems in various application areas, and comfortable with their own abilities as life-long learners.

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

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.

Expression Profiling Identifies Klf15 as a Glucocorticoid Target That Regulates Airway Hyperresponsiveness

PubMed Central

Masuno, Kiriko; Haldar, Saptarsi M.; Jeyaraj, Darwin; Mailloux, Christina M.; Huang, Xiaozhu; Panettieri, Rey A.; Jain, Mukesh K.

2011-01-01

Glucocorticoids (GCs), which activate GC receptor (GR) signaling and thus modulate gene expression, are widely used to treat asthma. GCs exert their therapeutic effects in part through modulating airway smooth muscle (ASM) structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. We therefore used transcription profiling to study the effects of a potent GC, dexamethasone, on human ASM (HASM) gene expression at 4 and 24 hours. After 24 hours of dexamethasone treatment, nearly 7,500 genes had statistically distinguishable changes in expression; quantitative PCR validation of a 40-gene subset of putative GR-regulated genes in 6 HASM cell lines suggested that the early transcriptional targets of GR signaling are similar in independent HASM lines. Gene ontology analysis implicated GR targets in controlling multiple aspects of ASM function. One GR-regulated gene, the transcription factor, Kruppel-like factor 15 (Klf15), was already known to modulate vascular smooth and cardiac muscle function, but had no known role in the lung. We therefore analyzed the pulmonary phenotype of Klf15−/− mice after ovalbumin sensitization and challenge. We found diminished airway responses to acetylcholine in ovalbumin-challenged Klf15−/− mice without a significant change in the induction of asthmatic inflammation. In cultured cells, overexpression of Klf15 reduced proliferation of HASM cells, whereas apoptosis in Klf15−/− murine ASM cells was increased. Together, these results further characterize the GR-regulated gene network in ASM and establish a novel role for the GR target, Klf15, in modulating airway function. PMID:21257922

Active State Model for Autonomous Systems

NASA Technical Reports Server (NTRS)

Park, Han; Chien, Steve; Zak, Michail; James, Mark; Mackey, Ryan; Fisher, Forest

2003-01-01

The concept of the active state model (ASM) is an architecture for the development of advanced integrated fault-detection-and-isolation (FDI) systems for robotic land vehicles, pilotless aircraft, exploratory spacecraft, or other complex engineering systems that will be capable of autonomous operation. An FDI system based on the ASM concept would not only provide traditional diagnostic capabilities, but also integrate the FDI system under a unified framework and provide mechanism for sharing of information between FDI subsystems to fully assess the overall health of the system. The ASM concept begins with definitions borrowed from psychology, wherein a system is regarded as active when it possesses self-image, self-awareness, and an ability to make decisions itself, such that it is able to perform purposeful motions and other transitions with some degree of autonomy from the environment. For an engineering system, self-image would manifest itself as the ability to determine nominal values of sensor data by use of a mathematical model of itself, and selfawareness would manifest itself as the ability to relate sensor data to their nominal values. The ASM for such a system may start with the closed-loop control dynamics that describe the evolution of state variables. As soon as this model was supplemented with nominal values of sensor data, it would possess self-image. The ability to process the current sensor data and compare them with the nominal values would represent self-awareness. On the basis of self-image and self-awareness, the ASM provides the capability for self-identification, detection of abnormalities, and self-diagnosis.

Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease.

PubMed

Wiegman, Coen H; Michaeloudes, Charalambos; Haji, Gulammehdi; Narang, Priyanka; Clarke, Colin J; Russell, Kirsty E; Bao, Wuping; Pavlidis, Stelios; Barnes, Peter J; Kanerva, Justin; Bittner, Anton; Rao, Navin; Murphy, Michael P; Kirkham, Paul A; Chung, Kian Fan; Adcock, Ian M

2015-09-01

Inflammation and oxidative stress play critical roles in patients with chronic obstructive pulmonary disease (COPD). Mitochondrial oxidative stress might be involved in driving the oxidative stress-induced pathology. We sought to determine the effects of oxidative stress on mitochondrial function in the pathophysiology of airway inflammation in ozone-exposed mice and human airway smooth muscle (ASM) cells. Mice were exposed to ozone, and lung inflammation, airway hyperresponsiveness (AHR), and mitochondrial function were determined. Human ASM cells were isolated from bronchial biopsy specimens from healthy subjects, smokers, and patients with COPD. Inflammation and mitochondrial function in mice and human ASM cells were measured with and without the presence of the mitochondria-targeted antioxidant MitoQ. Mice exposed to ozone, a source of oxidative stress, had lung inflammation and AHR associated with mitochondrial dysfunction and reflected by decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial oxidative stress, and reduced mitochondrial complex I, III, and V expression. Reversal of mitochondrial dysfunction by the mitochondria-targeted antioxidant MitoQ reduced inflammation and AHR. ASM cells from patients with COPD have reduced ΔΨm, adenosine triphosphate content, complex expression, basal and maximum respiration levels, and respiratory reserve capacity compared with those from healthy control subjects, whereas mitochondrial reactive oxygen species (ROS) levels were increased. Healthy smokers were intermediate between healthy nonsmokers and patients with COPD. Hydrogen peroxide induced mitochondrial dysfunction in ASM cells from healthy subjects. MitoQ and Tiron inhibited TGF-β-induced ASM cell proliferation and CXCL8 release. Mitochondrial dysfunction in patients with COPD is associated with excessive mitochondrial ROS levels, which contribute to enhanced inflammation and cell hyperproliferation. Targeting mitochondrial ROS represents a promising therapeutic approach in patients with COPD. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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.

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 ...

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.

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.

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.

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.

46 CFR 111.91-1 - Power, control, and interlock circuits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 111.91-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Elevators and Dumbwaiters § 111.91-1 Power, control, and interlock circuits. Each electric power, control, and interlock circuit of an elevator or dumbwaiter must meet ASME...

46 CFR 111.91-1 - Power, control, and interlock circuits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 111.91-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Elevators and Dumbwaiters § 111.91-1 Power, control, and interlock circuits. Each electric power, control, and interlock circuit of an elevator or dumbwaiter must meet ASME...

46 CFR 111.91-1 - Power, control, and interlock circuits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 111.91-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Elevators and Dumbwaiters § 111.91-1 Power, control, and interlock circuits. Each electric power, control, and interlock circuit of an elevator or dumbwaiter must meet ASME...

46 CFR 111.91-1 - Power, control, and interlock circuits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 111.91-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Elevators and Dumbwaiters § 111.91-1 Power, control, and interlock circuits. Each electric power, control, and interlock circuit of an elevator or dumbwaiter must meet ASME...

46 CFR 111.91-1 - Power, control, and interlock circuits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 111.91-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS Elevators and Dumbwaiters § 111.91-1 Power, control, and interlock circuits. Each electric power, control, and interlock circuit of an elevator or dumbwaiter must meet ASME...

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

Control of fire blight (Erwinia amylovora) on apple trees with trunk-injected plant resistance inducers and antibiotics and assessment of induction of pathogenesis-related protein genes

PubMed Central

Aćimović, Srđan G.; Zeng, Quan; McGhee, Gayle C.; Sundin, George W.; Wise, John C.

2015-01-01

Management of fire blight is complicated by limitations on use of antibiotics in agriculture, antibiotic resistance development, and limited efficacy of alternative control agents. Even though successful in control, preventive antibiotic sprays also affect non-target bacteria, aiding the selection for resistance which could ultimately be transferred to the pathogen Erwinia amylovora. Trunk injection is a target-precise pesticide delivery method that utilizes tree xylem to distribute injected compounds. Trunk injection could decrease antibiotic usage in the open environment and increase the effectiveness of compounds in fire blight control. In field experiments, after 1–2 apple tree injections of either streptomycin, potassium phosphites (PH), or acibenzolar-S-methyl (ASM), significant reduction of blossom and shoot blight symptoms was observed compared to water injected control trees. Overall disease suppression with streptomycin was lower than typically observed following spray applications to flowers. Trunk injection of oxytetracycline resulted in excellent control of shoot blight severity, suggesting that injection is a superior delivery method for this antibiotic. Injection of both ASM and PH resulted in the significant induction of PR-1, PR-2, and PR-8 protein genes in apple leaves indicating induction of systemic acquired resistance (SAR) under field conditions. The time separating SAR induction and fire blight symptom suppression indicated that various defensive compounds within the SAR response were synthesized and accumulated in the canopy. ASM and PH suppressed fire blight even after cessation of induced gene expression. With the development of injectable formulations and optimization of doses and injection schedules, the injection of protective compounds could serve as an effective option for fire blight control. PMID:25717330

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.

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.

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

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.

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.

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

NASA Astrophysics Data System (ADS)

Chen, Xinjian; Udupa, Jayaram K.; Bagci, Ulas; Alavi, Abass; Torigian, Drew A.

2010-02-01

We call the computerized assistive process of recognizing, delineating, and quantifying organs and tissue regions in medical imaging, occurring automatically during clinical image interpretation, automatic anatomy recognition (AAR). The AAR system we are developing includes five main parts: model building, object recognition, object delineation, pathology detection, and organ system quantification. In this paper, we focus on the delineation part. For the modeling part, we employ the active shape model (ASM) strategy. For recognition and delineation, we integrate several hybrid strategies of combining purely image based methods with ASM. In this paper, an iterative Graph-Cut ASM (IGCASM) method is proposed for object delineation. An algorithm called GC-ASM was presented at this symposium last year for object delineation in 2D images which attempted to combine synergistically ASM and GC. Here, we extend this method to 3D medical image delineation. The IGCASM method effectively combines the rich statistical shape information embodied in ASM with the globally optimal delineation capability of the GC method. We propose a new GC cost function, which effectively integrates the specific image information with the ASM shape model information. The proposed methods are tested on a clinical abdominal CT data set. The preliminary results show that: (a) it is feasible to explicitly bring prior 3D statistical shape information into the GC framework; (b) the 3D IGCASM delineation method improves on ASM and GC and can provide practical operational time on clinical images.

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

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

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.

A Minimal Path Searching Approach for Active Shape Model (ASM)-based Segmentation of the Lung.

PubMed

Guo, Shengwen; Fei, Baowei

2009-03-27

We are developing a minimal path searching method for active shape model (ASM)-based segmentation for detection of lung boundaries on digital radiographs. With the conventional ASM method, the position and shape parameters of the model points are iteratively refined and the target points are updated by the least Mahalanobis distance criterion. We propose an improved searching strategy that extends the searching points in a fan-shape region instead of along the normal direction. A minimal path (MP) deformable model is applied to drive the searching procedure. A statistical shape prior model is incorporated into the segmentation. In order to keep the smoothness of the shape, a smooth constraint is employed to the deformable model. To quantitatively assess the ASM-MP segmentation, we compare the automatic segmentation with manual segmentation for 72 lung digitized radiographs. The distance error between the ASM-MP and manual segmentation is 1.75 ± 0.33 pixels, while the error is 1.99 ± 0.45 pixels for the ASM. Our results demonstrate that our ASM-MP method can accurately segment the lung on digital radiographs.

A minimal path searching approach for active shape model (ASM)-based segmentation of the lung

NASA Astrophysics Data System (ADS)

Guo, Shengwen; Fei, Baowei

2009-02-01

We are developing a minimal path searching method for active shape model (ASM)-based segmentation for detection of lung boundaries on digital radiographs. With the conventional ASM method, the position and shape parameters of the model points are iteratively refined and the target points are updated by the least Mahalanobis distance criterion. We propose an improved searching strategy that extends the searching points in a fan-shape region instead of along the normal direction. A minimal path (MP) deformable model is applied to drive the searching procedure. A statistical shape prior model is incorporated into the segmentation. In order to keep the smoothness of the shape, a smooth constraint is employed to the deformable model. To quantitatively assess the ASM-MP segmentation, we compare the automatic segmentation with manual segmentation for 72 lung digitized radiographs. The distance error between the ASM-MP and manual segmentation is 1.75 +/- 0.33 pixels, while the error is 1.99 +/- 0.45 pixels for the ASM. Our results demonstrate that our ASM-MP method can accurately segment the lung on digital radiographs.

Modelling High-temperature EBPR by Incorporating Glycogen and GAOs: Challenges from a Preliminary Study.

PubMed

Liau, Kee Fui; Yeoh, Hak Koon; Shoji, Tadashi; Chua, Adeline Seak May; Ho, Pei Yee

2017-01-01

  Recently reported kinetic and stoichiometric parameters of the Activated Sludge Model no. 2d (ASM2d) for high-temperature EBPR processes suggested that the absence of glycogen in the model contributed to underestimation of PHA accumulation at 32 °C. Here, two modified ASM2d models were used to further explore the contribution of glycogen in the process. The ASM2d-1G model incorporated glycogen metabolism by PAOs (polyphosphate-accumulating organisms), while the ASM2d-2G model further included processes by GAOs (glycogen-accumulating organisms). These models were calibrated and validated using experimental data at 32 °C. The ASM2d-1G model supported the hypothesis that the excess PHA was attributed to glycogen, but remained inadequate to capture the dynamics of glycogen without considering GAOs activities. The ASM2d-2G model performed better, but it was challenging to calibrate as it often led to wash-out of either PAOs or GAOs. Associated hurdles are highlighted and additional efforts in calibrating ASM2d-2G more effectively are proposed.

A Minimal Path Searching Approach for Active Shape Model (ASM)-based Segmentation of the Lung

PubMed Central

Guo, Shengwen; Fei, Baowei

2013-01-01

We are developing a minimal path searching method for active shape model (ASM)-based segmentation for detection of lung boundaries on digital radiographs. With the conventional ASM method, the position and shape parameters of the model points are iteratively refined and the target points are updated by the least Mahalanobis distance criterion. We propose an improved searching strategy that extends the searching points in a fan-shape region instead of along the normal direction. A minimal path (MP) deformable model is applied to drive the searching procedure. A statistical shape prior model is incorporated into the segmentation. In order to keep the smoothness of the shape, a smooth constraint is employed to the deformable model. To quantitatively assess the ASM-MP segmentation, we compare the automatic segmentation with manual segmentation for 72 lung digitized radiographs. The distance error between the ASM-MP and manual segmentation is 1.75 ± 0.33 pixels, while the error is 1.99 ± 0.45 pixels for the ASM. Our results demonstrate that our ASM-MP method can accurately segment the lung on digital radiographs. PMID:24386531

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

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

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

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

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.

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.

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.

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

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.

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.

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...

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

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.

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.

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.

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

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.

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

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.

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.

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

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...

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.

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

D0 Silicon Upgrade: ASME Code and Pressure Calculations for Liquid Nitrogen Subcooler

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

Kuwazaki, Andrew; Leicht, Todd; /Fermilab

1995-10-04

Included in this engineering note are three separate calculation divisions. The first calculations are the determination of the required thickness of the LN{sub 2} subcooler flat head according to ASME code. This section includes Appendix A-C. The minimum plate thickness determined was 0.563 in. The actual thickness chosen in fabrication was a 3/4-inch plate milled to 0.594-inch at the bolt circle. Along with the plate thickness, this section calculates the required reinforcement area at the top plate penetrations. It was found that a 1/4-inch fillet weld at each penetration was adequate. The next set of calculations were done to provemore » that the subcooler internal pressure will always be less than 15 psig and therefore will not be classified as a pressure vessel. The subcooler is always open to a vent pipe. Appendix D calculations show that the vent pipe has a capacity of 1042 lbs/hr if 15 psig is present at the subcooler. It goes on to show that the inlet piping would at that flow rate, see a pressure drop of 104 psig. The maximum supply pressure of the LN{sub 2} storage dewar is 50 psig. Appendix E addresses required flow rates for steady state, loss of vacuum, or fire conditions. Page E9 shows a summary which states the maximum pressure would be 1.50 psig at fire conditions and internal pressure.« less

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

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.

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.

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

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

What's an Asthma Flare-Up?

MedlinePlus

... Staying Safe Videos for Educators Search English Español Asthma Flare-Ups KidsHealth / For Parents / Asthma Flare-Ups Print en español Crisis asmáticas What Are Asthma Flare-Ups? Keeping asthma under control helps kids ...

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...

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

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

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.

Free Radical Scavenging Properties of Annona squamosa

PubMed

Vikas, Biba; Akhil B, S; P, Remani; Sujathan, K

2017-10-26

Annona squamosa has extensively been used in the traditional and folkloric medicine and found to possess many biological activities. Different solvents, petroleum ether, chloroform, ethyl acetate and methanol extracts of Annona squamosa seeds (ASPE, ASCH, ASEA, ASME) have been used to prepare plant extracts. The present investigations dealt with the free radical scavenging activity of four extracts using various techniques such as total reducing power estimation, total phenolic count, 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging effect, evaluation of ABTS cation decolorisation capacity, FRAP assay, hdroxyl radical scavenging assay, super oxide assay and Nitric oxide radical scavenging assay of the extracts. The results showed that the four extracts of Annona squamosa showed significant reducing power in four extracts. The total phenolic contents in petroleum ether, chloroform, ethyl acetate, methanol extracts and positive control were 0.64±0.17, 0.54±0.27, 0.49±0.24, 0.57±0.22 and 0.66±0.33. The antioxidant capacity by ABTS assay of ASPE, ASCH, ASEA, ASME and positive control, trolox showed 77.75±0.5,73.25±1.7,78.5± 1.2 , 80 ± 0.8 μg/ml and 94.2 ± 0.9 respectively. The (50 % scavenging activity) SA50 of ASPE and ASCH, ASEA and ASME was found to be 34.4 μg/ml, 43.8 μg/ml 34.7 μg/m and 28.8 μg/ml respectively by DPPH assay. The percentage of hydroxyl radical scavenging increased with the increasing concentration of the extracts. ASPE, ASCH, ASEA and ASME showed superoxide radical scavenging activity, as indicated by their values 66 ± 0.5, 68 ± 1 ,63 ± 1 and 70 ± 0.5 μg/ml respectively compared to gallic acid which was 97 ± 0.5 μg/ml. The values for scavenging of nitric oxide for ASPE, ASCH, ASEA and ASME were 91.0 ± 1.0, 66.75 ± 0.5, 71.75 ± 1.1 and 75.75 ± 1.15 μg/ml while value for standard ascorbic acid was 91.0 ± 1.0 μg/ml. The results revealed strong antioxidants in four extracts may lead to the development of potent antioxidant agents from Annona squamosa seeds. Creative Commons Attribution License

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.

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

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.

Approximate Linear Regulator and Kalman Filter

DTIC Science & Technology

1980-09-01

of Equivalent Dominant Poles and Zeros Using Industrial Specifications," IEEE Trans. on Industrial Electronics and Control Instrumentation, Vol. IECI...true. In recent years, the rapid development of powerful minicomputers and microprocessors makes the industrial applications of optimal control...1976, pp. 677-687. [21] Y. Takahashi, M. Tomizuka and D. I. Auslander, Simple discrete control of industrial processes, Trans. on ASME J. of Dynamic

[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.

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.

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

Vertical-angle control system in the LLMC

NASA Astrophysics Data System (ADS)

Li, Binhua; Yang, Lei; Tie, Qiongxian; Mao, Wei

2000-10-01

A control system of the vertical angle transmission used in the Lower Latitude Meridian Circle (LLMC) is described in this paper. The transmission system can change the zenith distance of the tube quickly and precisely. It works in three modes: fast motion, slow motion and lock mode. The fast motion mode and the slow motion mode are that the tube of the instrument is driven by a fast motion stepper motor and a slow motion one separately. The lock mode is running for lock mechanism that is driven by a lock stepper motor. These three motors are controlled together by a single chip microcontroller, which is controlled in turn by a host personal computer. The slow motion mechanism and its rotational step angle are fully discussed because the mechanism is not used before. Then the hardware structure of this control system based on a microcontroller is described. Control process of the system is introduced during a normal observation, which is divided into eleven steps. All the steps are programmed in our control software in C++ and/or in ASM. The C++ control program is set up in the host PC, while the ASM control program is in the microcontroller system. Structures and functions of these rprograms are presented. Some details and skills for programming are discussed in the paper too.

Development of a security vulnerability assessment process for the RAMCAP chemical sector.

PubMed

Moore, David A; Fuller, Brad; Hazzan, Michael; Jones, J William

2007-04-11

The Department of Homeland Security (DHS), Directorate of Information Analysis & Infrastructure Protection (IAIP), Protective Services Division (PSD), contracted the American Society of Mechanical Engineers Innovative Technologies Institute, LLC (ASME ITI, LLC) to develop guidance on Risk Analysis and Management for Critical Asset Protection (RAMCAP). AcuTech Consulting Group (AcuTech) has been contracted by ASME ITI, LLC, to provide assistance by facilitating the development of sector-specific guidance on vulnerability analysis and management for critical asset protection for the chemical manufacturing, petroleum refining, and liquefied natural gas (LNG) sectors. This activity involves two key tasks for these three sectors: Development of a screening to supplement DHS understanding of the assets that are important to protect against terrorist attack and to prioritize the activities. Development of a standard security vulnerability analysis (SVA) framework for the analysis of consequences, vulnerabilities, and threats. This project involves the cooperative effort of numerous leading industrial companies, industry trade associations, professional societies, and security and safety consultants representative of those sectors. Since RAMCAP is a voluntary program for ongoing risk management for homeland security, sector coordinating councils are being asked to assist in communicating the goals of the program and in encouraging participation. The RAMCAP project will have a profound and positive impact on all sectors as it is fully developed, rolled-out and implemented. It will help define the facilities and operations of national and regional interest for the threat of terrorism, define standardized methods for analyzing consequences, vulnerabilities, and threats, and describe best security practices of the industry. This paper will describe the results of the security vulnerability analysis process that was developed and field tested for the chemical manufacturing sector. This method was developed through the cooperation of the many organizations and the individuals involved from the chemical sector RAMCAP development activities. The RAMCAP SVA method is intended to provide a common basis for making vulnerability assessments and risk-based decisions for homeland security. Mr. Moore serves as the coordinator for the chemical manufacturing, petroleum refining, and LNG sectors for the RAMCAP project and Dr. Jones is the chief technology officer for ASME-ITI, LLC for RAMCAP.

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.

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

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

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.

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

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).

High Level Analysis, Design and Validation of Distributed Mobile Systems with CoreASM

NASA Astrophysics Data System (ADS)

Farahbod, R.; Glässer, U.; Jackson, P. J.; Vajihollahi, M.

System design is a creative activity calling for abstract models that facilitate reasoning about the key system attributes (desired requirements and resulting properties) so as to ensure these attributes are properly established prior to actually building a system. We explore here the practical side of using the abstract state machine (ASM) formalism in combination with the CoreASM open source tool environment for high-level design and experimental validation of complex distributed systems. Emphasizing the early phases of the design process, a guiding principle is to support freedom of experimentation by minimizing the need for encoding. CoreASM has been developed and tested building on a broad scope of applications, spanning computational criminology, maritime surveillance and situation analysis. We critically reexamine here the CoreASM project in light of three different application scenarios.

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.

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

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...

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

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.

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.

Guidelines for the Design, Fabrication, Testing, Installation and Operation of Srf Cavities

NASA Astrophysics Data System (ADS)

Theilacker, J.; Carter, H.; Foley, M.; Hurh, P.; Klebaner, A.; Krempetz, K.; Nicol, T.; Olis, D.; Page, T.; Peterson, T.; Pfund, P.; Pushka, D.; Schmitt, R.; Wands, R.

2010-04-01

Superconducting Radio-Frequency (SRF) cavities containing cryogens under pressure pose a potential rupture hazard to equipment and personnel. Generally, pressure vessels fall within the scope of the ASME Boiler and Pressure Vessel Code however, the use of niobium as a material for the SRF cavities is beyond the applicability of the Code. Fermilab developed a guideline to ensure sound engineering practices governing the design, fabrication, testing, installation and operation of SRF cavities. The objective of the guideline is to reduce hazards and to achieve an equivalent level of safety afforded by the ASME Code. The guideline addresses concerns specific to SRF cavities in the areas of materials, design and analysis, welding and brazing, pressure relieving requirements, pressure testing and quality control.

Marketable job skills for high school students: what we learned from an evaluation of After School Matters.

PubMed

Alexander, Kendra P; Hirsch, Barton J

2012-01-01

This article summarizes findings from an experimental evaluation of After School Matters (ASM), a paid, apprenticeship-based, after-school program in Chicago for high school students. Analysis of quantitative data from a mock job interview revealed that ASM participants did not demonstrate more marketable job skills than youth in the control group. Qualitative data suggested that the nature of interpersonal interactions and the degree of professional orientation in apprenticeships contributed to variation in marketable job skills across apprenticeships. The article considers the perspective of human resource professionals who participated in the evaluation and describes an interviewing skills curriculum developed in response to the evaluation findings. Copyright © 2012 Wiley Periodicals, Inc., A Wiley Company.

49 CFR 192.112 - Additional design requirements for steel pipe using alternative maximum allowable operating...

Code of Federal Regulations, 2011 CFR

2011-10-01

..., fully killed, continuously cast steel with calcium treatment. (2) The carbon equivalents of the steel... under this section. (b) Fracture control (1) The toughness properties for pipe must address the... specification level 2 or ASME B31.8 (incorporated by reference, see § 192.7). (2) Fracture control must: (i...

49 CFR 192.112 - Additional design requirements for steel pipe using alternative maximum allowable operating...

Code of Federal Regulations, 2012 CFR

2012-10-01

..., fully killed, continuously cast steel with calcium treatment. (2) The carbon equivalents of the steel... under this section. (b) Fracture control (1) The toughness properties for pipe must address the... specification level 2 or ASME B31.8 (incorporated by reference, see § 192.7). (2) Fracture control must: (i...

49 CFR 192.112 - Additional design requirements for steel pipe using alternative maximum allowable operating...

Code of Federal Regulations, 2013 CFR

2013-10-01

..., fully killed, continuously cast steel with calcium treatment. (2) The carbon equivalents of the steel... under this section. (b) Fracture control (1) The toughness properties for pipe must address the... specification level 2 or ASME B31.8 (incorporated by reference, see § 192.7). (2) Fracture control must: (i...

49 CFR 192.112 - Additional design requirements for steel pipe using alternative maximum allowable operating...

Code of Federal Regulations, 2010 CFR

2010-10-01

..., fully killed, continuously cast steel with calcium treatment. (2) The carbon equivalents of the steel... under this section. (b) Fracture control (1) The toughness properties for pipe must address the... specification level 2 or ASME B31.8 (incorporated by reference, see § 192.7). (2) Fracture control must: (i...

49 CFR 192.112 - Additional design requirements for steel pipe using alternative maximum allowable operating...

Code of Federal Regulations, 2014 CFR

2014-10-01

..., fully killed, continuously cast steel with calcium treatment. (2) The carbon equivalents of the steel... under this section. (b) Fracture control (1) The toughness properties for pipe must address the... specification level 2 or ASME B31.8 (incorporated by reference, see § 192.7). (2) Fracture control must: (i...

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.

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...

49 CFR 222.53 - What are the requirements for supplementary and alternative safety measures?

Code of Federal Regulations, 2010 CFR

2010-10-01

..., constitute SSMs or ASMs: Standard traffic control device arrangements such as reflectorized crossbucks, STOP signs, flashing lights, or flashing lights with gates that do not completely block travel over the line of railroad, or traffic signals. ...

49 CFR 222.53 - What are the requirements for supplementary and alternative safety measures?

Code of Federal Regulations, 2011 CFR

2011-10-01

..., constitute SSMs or ASMs: Standard traffic control device arrangements such as reflectorized crossbucks, STOP signs, flashing lights, or flashing lights with gates that do not completely block travel over the line of railroad, or traffic signals. ...

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.

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

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...

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.

Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse.

PubMed

Passini, Marco A; Bu, Jie; Fidler, Jonathan A; Ziegler, Robin J; Foley, Joseph W; Dodge, James C; Yang, Wendy W; Clarke, Jennifer; Taksir, Tatyana V; Griffiths, Denise A; Zhao, Michael A; O'Riordan, Catherine R; Schuchman, Edward H; Shihabuddin, Lamya S; Cheng, Seng H

2007-05-29

Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM) activity, which results in widespread accumulation of undegraded lipids in cells of the viscera and CNS. In this study, we tested the effect of combination brain and systemic injections of recombinant adeno-associated viral vectors encoding human ASM (hASM) in a mouse model of NPD. Animals treated by combination therapy exhibited high levels of hASM in the viscera and brain, which resulted in near-complete correction of storage throughout the body. This global reversal of pathology translated to normal weight gain and superior recovery of motor and cognitive functions compared to animals treated by either brain or systemic injection alone. Furthermore, animals in the combination group did not generate antibodies to hASM, demonstrating the first application of systemic-mediated tolerization to improve the efficacy of brain injections. All of the animals treated by combination therapy survived in good health to an investigator-selected 54 weeks, whereas the median lifespans of the systemic-alone, brain-alone, or untreated ASM knockout groups were 47, 48, and 34 weeks, respectively. These data demonstrate that combination therapy is a promising therapeutic modality for treating NPD and suggest a potential strategy for treating disease indications that cause both visceral and CNS pathologies.

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

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.

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

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).

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.

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.

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.

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.

Virtual Teleoperation for Unmanned Aerial Vehicles

DTIC Science & Technology

2012-01-24

Gilbert, S., “Wayfinder: Evaluating Multitouch Interaction in Supervisory Control of Unmanned Vehicles,” Proceedings of ASME 2nd World Conference on... interactive virtual reality environment that fuses available information into a coherent picture that can be viewed from multiple perspectives and scales...for multimodal interaction • Generally abstracted controller hardware and graphical interfaces facilitating deployment on a variety of VR platform

Bionic Running for Unilateral Transtibial Military Amputees

DTIC Science & Technology

2010-01-01

Bellman, R., 2010, “An Active Ankle-Foot Prosthesis With Biomechanical Energy Regeneration”, Transactions of the ASME Journal...Lefeber, D., 2008, “A Biomechanical Transtibial Prosthesis Powered by Pleated Pneumatic Artificial Muscles,” Model Identification and Control, 4, 394- 405. ...Inc., have designed, built, and demonstrated a first of its kind motor powered, single board computer controlled, running prosthesis for military

Changing self-reported physical activity using different types of affectively and cognitively framed health messages, in a student population.

PubMed

Morris, Benjamin; Lawton, Rebecca; McEachan, Rosemary; Hurling, Robert; Conner, Mark

2016-01-01

The present research focused upon the power of different messages to increase self-reported physical activity (PA). Five hundered and ninety six participants were randomised to one of five conditions that varied in the content of message: short-term affective, short-term cognitive, long-term affective, long-term cognitive and a no message control. PA was measured at baseline and follow-up (seven days later) was done using the Godin Leisure Time Exercise Questionnaire over the subsequent seven day period. The affective short-term message (ASM) was shown to be equally effective at increasing self-reported PA as a cognitive long-term message. Furthermore, when controlling for baseline activity levels, the ASM emerged as being the message that produced the highest levels of self-reported PA at follow-up. The findings point to the value of distinguishing between health messages in terms of the focus on affective and cognitive outcomes and the temporal nature of the outcomes (short-term or long-term).

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.

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.

Early identification of radiographic osteoarthritis of the hip using an active shape model to quantify changes in bone morphometric features: can hip shape tell us anything about the progression of osteoarthritis?

PubMed

Gregory, Jennifer S; Waarsing, Jan H; Day, Judd; Pols, Huibert A; Reijman, Max; Weinans, Harrie; Aspden, Richard M

2007-11-01

Few methods exist to measure the progression of osteoarthritis (OA) or to identify people at high risk of developing OA. Striking radiographic changes include deformation of the femoral head and osteophyte growth, which are usually measured semiquantitatively following visual assessment. In this study, an active shape model (ASM) of the proximal femur was used to determine whether morphologic changes to the bone could be quantified and used as a marker of hip OA. One hundred ten subjects who had no signs of radiographic hip OA at baseline (Kellgren/Lawrence [K/L] scores 0-1) were selected from the Rotterdam Study cohort of subjects ages > or = 55 years. To measure the progression of OA, subjects were followed up with radiographic assessment after 6 years. At the 6-year followup, 55 subjects had established OA (K/L score 3), and in 12 of these OA subjects, the progression of the disease required a total hip replacement (THR). Age- and sex-matched control subjects had a K/L score of 0 at followup. Using the ASM, subjects were assessed for shape changes in the femoral head and neck before, during, and after the development of radiographic OA. Scores of shape variance, or mode scores, were assigned for 10 modes of variation in each subject, and differences in mode scores were determined. During followup, significant changes in shape of the proximal femur occurred within the OA group from baseline to followup (P < 0.0001 for mode 1 and P = 0.002 for mode 6) but not within the control group. At baseline (all subjects having K/L scores 0-1), there were significant differences in mode 6 between the OA group and the control group (P = 0.020), and in modes 3 and 6 between the OA subjects who underwent THR and the remaining OA subjects (P = 0.012 and P = 0.019, respectively). Compared with traditional scoring methods, the ASM can be used more precisely to quantify the deforming effect of OA on the proximal femur and to identify, at an earlier stage of disease, those subjects at highest risk of developing radiographic OA or needing a THR. The ASM may therefore be useful as an imaging biomarker in the assessment of patients with hip OA.

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.

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

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.

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.

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.

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

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.

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.

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.

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

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.

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

Reaction rate constants and mean population percentage for nitrifiers in an alternating oxidation ditch system.

PubMed

Mantziaras, I D; Katsiri, A

2011-01-01

This paper presents a methodology for the determination of reaction rate constants for nitrifying bacteria and their mean population percentage in biomass in an alternating oxidation ditch system. The method used is based on the growth rate equations of the ASM1 model (IWA) (Henze et al. in Activated sludge models ASM1, ASM2, ASM2d, and ASM3. IWA Scientific and Technical Report no. 9, IWA Publishing, London, UK, 2000) and the application of mass balance equations for nitrifiers and ammonium nitrogen in an operational cycle of the ditch system. The system consists of two ditches operating in four phases. Data from a large-scale oxidation ditch pilot plant with a total volume of 120 m(3) within an experimental period of 8 months was used. Maximum specific growth rate for autotrophs (μ(A)) and the half-saturation constant for ammonium nitrogen (K(NH)) were found to be 0.36 day(-1) and 0.65 mgNH(4)-N/l, respectively. Additionally, the average population percentage of the nitrifiers in the biomass was estimated to be around 3%.

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.

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.

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.

miR-142-3p is associated with aberrant Wingless/Integrase I (WNT) signaling during airway remodeling in asthma.

PubMed

Bartel, Sabine; Carraro, Gianni; Alessandrini, Francesca; Krauss-Etschmann, Susanne; Ricciardolo, Fabio L M; Bellusci, Saverio

2018-05-03

Asthma is characterized by a chronic inflammation and remodeling of the airways. While inflammation can be controlled, therapeutic options to revert remodeling do not exist. Thus, there is a large and unmet need to understand the underlying molecular mechanisms in order to develop novel therapies. we previously identified a pivotal role for miR-142-3p in regulating airway smooth muscle precursor (ASM) cell proliferation during lung development by fine-tuning the Wingless/Integrase I (WNT) signaling. Thus, we here aimed to investigate the relevance of this interaction in asthma. We performed qRT-PCR and immune-staining in a murine model for ovalbumin-induced allergic airway inflammation and in bronchial biopsies from patients with asthma and isolated primary fibroblasts thereof. miR-142-3p was increased in hyper-proliferative regions of lung in murine and human asthma, while this miRNA was excluded from regions with differentiated ASM cells. Increases in miR-142-3p were associated with a decrease of its known target Adenomatous polyposis coli (Apc). Further, we observed a differential expression of miR-142-3p in bronchial biopsies from patients with early or late onset severe asthma, which coincided with a differential WNT signature. Our data suggest that miR-142-3p is involved in regulating the balance between proliferation and differentiation of ASM cells in asthma, possibly via controlling WNT signaling. Thus, this miRNA might be an interesting target to prevent airway smooth muscle hyper-proliferation in asthma.

Alterations of the Ceramide Metabolism in the Peri-Infarct Cortex Are Independent of the Sphingomyelinase Pathway and Not Influenced by the Acid Sphingomyelinase Inhibitor Fluoxetine.

PubMed

Brunkhorst, R; Friedlaender, F; Ferreirós, N; Schwalm, S; Koch, A; Grammatikos, G; Toennes, S; Foerch, C; Pfeilschifter, J; Pfeilschifter, W

2015-01-01

Ceramides induce important intracellular signaling pathways, modulating proliferation, migration, apoptosis, and inflammation. However, the relevance of the ceramide metabolism in the reconvalescence phase after stroke is unclear. Besides its well-known property as a selective serotonin reuptake inhibitor, fluoxetine has been reported to inhibit the acid sphingomyelinase (ASM), a key regulator of ceramide levels which derives ceramide from sphingomyelin. Furthermore, fluoxetine has shown therapeutic potential in a randomized controlled rehabilitation trial in stroke patients. Our aim was to investigate and modulate ceramide concentrations in the peri-infarct cortex, whose morphological and functional properties correlate with long-term functional outcome in stroke. We show that certain ceramide species are modulated after experimental stroke and that these changes do not result from alterations of ASM activity, but rather from nontranscriptional induction of the ceramide de novo pathway. Unexpectedly, although reducing lesion size, fluoxetine did not improve functional outcome in our model and had no significant influence on ASM activity or the concentration of ceramides. The ceramide metabolism could emerge as a potential therapeutic target in the reconvalescence phase after stroke, as its accumulation in the peri-infarct cortex potentially influences membrane functions as well as signaling events in the tissue essential for neurological recovery.

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.

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

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.

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.

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.

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.

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.

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

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.

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.

Progress Report on Alloy 617 Notched Specimen Testing

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

McMurtrey, Michael David; Wright, Richard Neil; Lillo, Thomas Martin

Creep behavior of Alloy 617 has been extensively characterized to support the development of a draft Code Case to qualify Alloy 617 in Section III division 5 of the ASME Boiler and Pressure Vessel Code. This will allow use of Alloy 617 in construction of nuclear reactor components at elevated temperatures and longer periods of time (up to 950°C and 100,000 hours). Prior to actual use, additional concerns not considered in the ASME code need to be addressed. Code Cases are based largely on uniaxial testing of smooth gage specimens. In service conditions, components will generally be under multi axialmore » loading. There is also the concern of the behavior at discontinuities, such as threaded components. To address the concerns of multi axial creep behavior and at geometric discontinuities, notched specimens have been designed to create conditions representative of the states that service components experience. Two general notch geometries have been used for these series of tests: U notch and V notch specimens. The notches produce a tri axial stress state, though not uniform across the specimen. Characterization of the creep behavior of the U notch specimens and the creep rupture behavior of the V notch specimens provides a good approximation of the behavior expected of actual components. Preliminary testing and analysis have been completed and are reported in this document. This includes results from V notch specimens tested at 900°C and 800°C. Failure occurred in the smooth gage section of the specimen rather than at the root of the notch, though some damage was present at the root of the notch, where initial stress was highest. This indicates notch strengthening behavior in this material at these temperatures.« less

76 FR 81986 - Honeywell International, Inc., Automation and Control Solutions Division, Including On-Site...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

..., Inc., Automation and Control Solutions Division, Including On-Site Leased Workers From Manpower... International, Inc., Automation and Control Solutions Division, Rock Island, Illinois. The notice was published...., Automation and Control Solutions Division. The Department has determined that these workers were sufficiently...

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

Eric Larsen; Art Watkins; Timothy R. McJunkin

The U.S. Department of Energy (DOE) created the National Spent Nuclear Fuel Program (NSNFP) to manage DOE’s spent nuclear fuel (SNF). One of the NSNFP’s tasks is to prepare spent nuclear fuel for storage, transportation, and disposal at the national repository. As part of this effort, the NSNFP developed a standardized canister for interim storage and transportation of SNF. These canisters will be built and sealed to American Society of Mechanical Engineers (ASME) Section III, Division 3 requirements. Packaging SNF usually is a three-step process: canister loading, closure welding, and closure weld verification. After loading SNF into the canisters, themore » canisters must be seal welded and the welds verified using a combination of visual, surface eddy current, and ultrasonic inspection or examination techniques. If unacceptable defects in the weld are detected, the defective sections of weld must be removed, re-welded, and re-inspected. Due to the high contamination and/or radiation fields involved with this process, all of these functions must be performed remotely in a hot cell. The prototype apparatus to perform these functions is a floor-mounted carousel that encircles the loaded canister; three stations perform the functions of welding, inspecting, and repairing the seal welds. A welding operator monitors and controls these functions remotely via a workstation located outside the hot cell. The discussion describes the hardware and software that have been developed and the results of testing that has been done to date.« less

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.

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

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.

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.

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...

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.

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.

An Experimental Study of an Ultra-Mobile Vehicle for Off-Road Transportation

DTIC Science & Technology

1984-05-01

Adaptaive Hexapod Vehicle. M.S. thesis , The &io State University, August, 1982. 7. Tsai, C.K., Computer Control Design of an Energy-Efficient Leg, M.S...Applications, ASME, 1982. 9. Kao, M.L., A Reliable Multi-Microcomputer System for Real Time Control , M.S. thesis , The Ohio State University, December...13. Broerman, K.R., Development of a Proximity Sensor System for Foot Altitude Control of a Terrain-Adaptive Hexapod Robot, M.S. thesis , The Ohio State

The Performance of Five Bioelectrical Impedance Analysis Prediction Equations against Dual X-ray Absorptiometry in Estimating Appendicular Skeletal Muscle Mass in an Adult Australian Population

PubMed Central

Yu, Solomon C. Y.; Powell, Alice; Khow, Kareeann S. F.; Visvanathan, Renuka

2016-01-01

Appendicular skeletal muscle mass (ASM) is a diagnostic criterion for sarcopenia. Bioelectrical impedance analysis (BIA) offers a bedside approach to measure ASM but the performance of BIA prediction equations (PE) varies with ethnicities and body composition. We aim to validate the performance of five PEs in estimating ASM against estimation by dual-energy X-ray absorptiometry (DXA). We recruited 195 healthy adult Australians and ASM was measured using single-frequency BIA. Bland-Altman analysis was used to assess the predictive accuracy of ASM as determined by BIA against DXA. Precision (root mean square error (RMSE)) and bias (mean error (ME)) were calculated according to the method of Sheiner and Beal. Four PEs (except that by Kim) showed ASM values that correlated strongly with ASMDXA (r ranging from 0.96 to 0.97, p < 0.001). The Sergi equation performed the best with the lowest ME of −1.09 kg (CI: −0.84–−1.34, p < 0.001) and the RMSE was 2.09 kg (CI: 1.72–2.47). In men, the Kyle equation performed better with the lowest ME (−0.32 kg (CI: −0.66–0.02) and RMSE (1.54 kg (CI: 1.14–1.93)). The Sergi equation is applicable in adult Australians (Caucasian) whereas the Kyle equation can be considered in males. The need remains to validate PEs in other ethnicities and to develop equations suitable for multi-frequency BIA. PMID:27043617

Comparison of gel contraction mediated by airway smooth muscle cells from patients with and without asthma.

PubMed

Matsumoto, Hisako; Moir, Lyn M; Oliver, Brian G G; Burgess, Janette K; Roth, Michael; Black, Judith L; McParland, Brent E

2007-10-01

Exaggerated bronchial constriction is the most significant and life threatening response of patients with asthma to inhaled stimuli. However, few studies have investigated the contractility of airway smooth muscle (ASM) from these patients. The purpose of this study was to establish a method to measure contraction of ASM cells by embedding them into a collagen gel, and to compare the contraction between subjects with and without asthma. Gel contraction to histamine was examined in floating gels containing cultured ASM cells from subjects with and without asthma following overnight incubation while unattached (method 1) or attached (method 2) to casting plates. Smooth muscle myosin light chain kinase protein levels were also examined. Collagen gels containing ASM cells reduced in size when stimulated with histamine in a concentration-dependent manner and reached a maximum at a mean (SE) of 15.7 (1.2) min. This gel contraction was decreased by inhibitors for phospholipase C (U73122), myosin light chain kinase (ML-7) and Rho kinase (Y27632). When comparing the two patient groups, the maximal decreased area of gels containing ASM cells from patients with asthma was 19 (2)% (n = 8) using method 1 and 22 (3)% (n = 6) using method 2, both of which were greater than that of cells from patients without asthma: 13 (2)% (n = 9, p = 0.05) and 10 (4)% (n = 5, p = 0.024), respectively. Smooth muscle myosin light chain kinase levels were not different between the two groups. The increased contraction of asthmatic ASM cells may be responsible for exaggerated bronchial constriction in asthma.

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.

Vertical patterns and controls of soil nutrients in alpine grassland: Implications for nutrient uptake.

PubMed

Tian, Liming; Zhao, Lin; Wu, Xiaodong; Fang, Hongbing; Zhao, Yonghua; Yue, Guangyang; Liu, Guimin; Chen, Hao

2017-12-31

Vertical patterns and determinants of soil nutrients are critical to understand nutrient cycling in high-altitude ecosystems; however, they remain poorly understood in the alpine grassland due to lack of systematic field observations. In this study, we examined vertical distributions of soil nutrients and their influencing factors within the upper 1m of soil, using data of 68 soil profiles surveyed in the alpine grassland of the eastern Qinghai-Tibet Plateau. Soil organic carbon (SOC) and total nitrogen (TN) stocks decreased with depth in both alpine meadow (AM) and alpine steppe (AS), but remain constant along the soil profile in alpine swamp meadow (ASM). Total phosphorus, Ca 2+ , and Mg 2+ stocks slightly increased with depth in ASM. K + stock decreased with depth, while Na + stock increased slightly with depth among different vegetation types; however, SO 4 2- and Cl - stocks remained relatively uniform throughout different depth intervals in the alpine grassland. Except for SOC and TN, soil nutrient stocks in the top 20cm soils were significantly lower in ASM compared to those in AM and AS. Correlation analyses showed that SOC and TN stocks in the alpine grassland positively correlated with vegetation coverage, soil moisture, clay content, and silt content, while they negatively related to sand content and soil pH. However, base cation stocks revealed contrary relationships with those environmental variables compared to SOC and TN stocks. These correlations varied between vegetation types. In addition, no significant relationship was detected between topographic factors and soil nutrients. Our findings suggest that plant cycling and soil moisture primarily control vertical distributions of soil nutrients (e.g. K) in the alpine grassland and highlight that vegetation types in high-altitude permafrost regions significantly affect soil nutrients. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Training Auditory Sequential Memory and Attention on Reading.

ERIC Educational Resources Information Center

Klein, Pnina S.; Schwartz, Allen A.

1979-01-01

The study, involving 92 second and third graders with deficits in reading and auditory sequential memory (ASM), examined the possibility of improving ASM through training and the relationship between this training and reading ability. (Author/CL)

Concerted control of Escherichia coli cell division

PubMed Central

Osella, Matteo; Nugent, Eileen; Cosentino Lagomarsino, Marco

2014-01-01

The coordination of cell growth and division is a long-standing problem in biology. Focusing on Escherichia coli in steady growth, we quantify cell division control using a stochastic model, by inferring the division rate as a function of the observable parameters from large empirical datasets of dividing cells. We find that (i) cells have mechanisms to control their size, (ii) size control is effected by changes in the doubling time, rather than in the single-cell elongation rate, (iii) the division rate increases steeply with cell size for small cells, and saturates for larger cells. Importantly, (iv) the current size is not the only variable controlling cell division, but the time spent in the cell cycle appears to play a role, and (v) common tests of cell size control may fail when such concerted control is in place. Our analysis illustrates the mechanisms of cell division control in E. coli. The phenomenological framework presented is sufficiently general to be widely applicable and opens the way for rigorous tests of molecular cell-cycle models. PMID:24550446

Engineering and Design: Adsorption Design Guide

DTIC Science & Technology

2001-03-01

tested, and marked (or stamped) in accordance with the standards of the applicable Boiler and Pressure Vessel Code (ASME, 1992), and must incorporate...Boiler and Pressure Vessel Committee, Subcommittee on Pressure Vessels, 1992. ASME Boiler and Pressure Vessel Code , Section VIII, Rules for

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.

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.

Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion

PubMed Central

Fernandes, Maria Cecilia; Cortez, Mauro; Flannery, Andrew R.; Tam, Christina; Mortara, Renato A.

2011-01-01

Upon host cell contact, the protozoan parasite Trypanosoma cruzi triggers cytosolic Ca2+ transients that induce exocytosis of lysosomes, a process required for cell invasion. However, the exact mechanism by which lysosomal exocytosis mediates T. cruzi internalization remains unclear. We show that host cell entry by T. cruzi mimics a process of plasma membrane injury and repair that involves Ca2+-dependent exocytosis of lysosomes, delivery of acid sphingomyelinase (ASM) to the outer leaflet of the plasma membrane, and a rapid form of endocytosis that internalizes membrane lesions. Host cells incubated with T. cruzi trypomastigotes are transiently wounded, show increased levels of endocytosis, and become more susceptible to infection when injured with pore-forming toxins. Inhibition or depletion of lysosomal ASM, which blocks plasma membrane repair, markedly reduces the susceptibility of host cells to T. cruzi invasion. Notably, extracellular addition of sphingomyelinase stimulates host cell endocytosis, enhances T. cruzi invasion, and restores normal invasion levels in ASM-depleted cells. Ceramide, the product of sphingomyelin hydrolysis, is detected in newly formed parasitophorous vacuoles containing trypomastigotes but not in the few parasite-containing vacuoles formed in ASM-depleted cells. Thus, T. cruzi subverts the ASM-dependent ceramide-enriched endosomes that function in plasma membrane repair to infect host cells. PMID:21536739

A high-resolved record of the Asian Summer Monsoon from Dongge Cave, China for the past 1200 years

NASA Astrophysics Data System (ADS)

Zhao, Kan; Wang, Yongjin; Edwards, R. Lawrence; Cheng, Hai; Liu, Dianbing; Kong, Xinggong

2015-08-01

Two annually-laminated and 230Th-dated stalagmite oxygen isotope (δ18O) records from Dongge Cave, China, provided a high-resolution Asian Summer Monsoon (ASM) history for the past 1200 years. A close similarity between annual band thickness and stable isotope analyses (δ13C and δ18O) suggests the calcite δ18O is most likely a proxy associated with ASM precipitation. The two duplicated stalagmite δ18O records show that the ASM varies at a periodicity of ∼220 years, concordant with a dominant cycle of solar activity. A period of strong ASM activity occurred during the Spörer Minimum (1450-1550 A.D.), followed by a striking drop circa 1580 A.D., potentially consistent with the social unrest in the final decades of China's Ming Dynasty (1368-1644 A.D.). Centennial-scale changes in ASM precipitation over the last millennium match well with changes in tropical Atlantic sea surface temperatures (SSTs) and South American summer monsoon precipitation. Our findings suggest that variations in low-latitude monsoon precipitation are probably driven by shifts in the mean position of the intertropical convergence zone (ITCZ), which is further mediated by solar activity and tropical SSTs.

Chemical composition, antioxidant, anticholinesterase, antimicrobial and antibiofilm activities of essential oil and methanolic extract of Anthemis stiparum subsp. sabulicola (Pomel) Oberpr.

PubMed

Chemsa, Ahmed Elkhalifa; Zellagui, Amar; Öztürk, Mehmet; Erol, Ebru; Ceylan, Ozgür; Duru, Mehmet Emin; Lahouel, Mesbah

2018-06-01

Anthemis species are traditionally used to treat infectious and inflammatory processes, among others clinical disturbances. In the current study, the chemical composition, the total phenolic and flavonoid contents, the antioxidant, anticholinesterase, antimicrobial, and antibiofilm activities of Anthemis stiparum subsp. sabulicola aerial parts methanolic extract (As-ME) and essential oil (As-EO) were investigated. The chemical composition of As-EO was established by GC-MS and GC-FID. Total phenolic and flavonoid contents of As-ME were spectrophotometrically determined. Diphenyl-1-picrylhydrazyl (DPPH ● ) radical scavenging, cupric reducing antioxidant capacity (CUPRAC) and β-carotene bleaching assays were applied to evaluate the antioxidant potential. The anticholinesterase activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were carried out spectrophotometrically. The antimicrobial activity was assessed by Minimal Inhibitory Concentration (MIC) using broth microdilution method against 7 ATCC ® bacterial and one ATCC ® yeast reference strains. The antibiofilm effect was determined quantifying the percentage of adhesion inhibition. GC-MS and GC-FID identified 72 compounds (99.02%), being As-EO predominantly constituted by germacrene D (11.13%), t-cadinol (11.01%), camphor (6.73%), spathulenol (6.50%) and isoamyl salicylate (6.45%). The total phenolic and flavonoid contents of As-ME were 13.6 ± 0.03 and 5.9 ± 0.04 pyrocatechol equivalents and quercetin equivalents, respectively. In β-carotene-linoleic acid assay, As-ME showed the best lipid peroxidation inhibition activity with an IC 50  = 9.96 μg/mL followed by As-EO with an IC 50  = 619.98 μg/mL. In contrast, in DPPH assay, As-ME and As-EO showed moderate to low activity with an IC 50  = 92.69 μg/mL for As-ME and 917.69 μg/mL for As-EO. While in CUPRAC assay, As-EO and As-ME indicated a less to moderate reducing activity. As-ME inhibited AChE (IC 50  = 490.46 μg/mL) and BChE (IC 50  = 142.07 μg/mL), while As-EO was inactive against AChE and revealed a discreet inhibitory action against BChE (IC 50  = 212.14 μg/mL). As-ME displayed better antimicrobial activity than As-EO, being active against Staphylococcus aureus (ATCC ® 25923) and Bacillus subtilis (ATCC ® 6633), with MIC of 1.56 mg/mL. An expressive fungal adhesion inhibition (80.02%) on Candida albicans (ATCC ® 10239) was detected with As-ME at 6.25 mg/mL. These results showed that A. stiparum subsp. sabulicola is a natural source of active compounds with antibiotic and antibiofilm effects against S. aureus and B. subtilis, and C. albicans, respectively, and also presents antioxidant and anticholinesterase properties. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Generic Structural Integrity Assurance Technology Program for the Army

DTIC Science & Technology

1989-11-01

and Pressure Vessel Code , American Society of Mechanical Engineers, 1986. DEFINITIONS AND ACRONYMS Definitions A-Basis: At least 99 percent of the...Aluminum Bridge and Other Highway Structures, 1976. Aluminum Association Specifications for Aluminum Structures, Third Edition, 1976. ASME ASME Boiler

Responses of Soil Microbial Communities to Experimental Warming in Alpine Grasslands on the Qinghai-Tibet Plateau

PubMed Central

He, Xingyuan; Liu, Wenjie; Zhao, Qian; Zhao, Lin; Tian, Chunjie

2014-01-01

Global surface temperature is predicted to increase by at least 1.5°C by the end of this century. However, the response of soil microbial communities to global warming is still poorly understood, especially in high-elevation grasslands. We therefore conducted an experiment on three types of alpine grasslands on the Qinghai-Tibet Plateau to study the effect of experimental warming on abundance and composition of soil microbial communities at 0–10 and 10–20 cm depths. Plots were passively warmed for 3 years using open-top chambers and compared to adjacent control plots at ambient temperature. Soil microbial communities were assessed using phospholipid fatty acid (PLFA) analysis. We found that 3 years of experimental warming consistently and significantly increased microbial biomass at the 0–10 cm soil depth of alpine swamp meadow (ASM) and alpine steppe (AS) grasslands, and at both the 0–10 and 10–20 cm soil depths of alpine meadow (AM) grasslands, due primarily to the changes in soil temperature, moisture, and plant coverage. Soil microbial community composition was also significantly affected by warming at the 0–10 cm soil depth of ASM and AM and at the 10–20 cm soil depth of AM. Warming significantly decreased the ratio of fungi to bacteria and thus induced a community shift towards bacteria at the 0–10 cm soil depth of ASM and AM. While the ratio of arbuscular mycorrhizal fungi to saprotrophic fungi (AMF/SF) was significantly decreased by warming at the 0–10 cm soil depth of ASM, it was increased at the 0–10 cm soil depth of AM. These results indicate that warming had a strong influence on soil microbial communities in the studied high-elevation grasslands and that the effect was dependent on grassland type. PMID:25083904

Impact of typhoons on the composition of the upper troposphere within the Asian summer monsoon anticyclone: the SWOP campaign in Lhasa 2013

NASA Astrophysics Data System (ADS)

Li, Dan; Vogel, Bärbel; Bian, Jianchun; Müller, Rolf; Pan, Laura L.; Günther, Gebhard; Bai, Zhixuan; Li, Qian; Zhang, Jinqiang; Fan, Qiujun; Vömel, Holger

2017-04-01

In the frame of the SWOP (sounding water vapour, ozone, and particle) campaign during the Asian summer monsoon (ASM), ozone and water vapour profiles were measured by balloon-borne sensors launched from Lhasa (29.66° N, 91.14° E, elevation 3650 m), China, in August 2013. In total, 24 soundings were launched, nearly half of which show strong variations in the relationship between ozone and water vapour in the tracer-tracer correlation in the upper troposphere and lower stratosphere (UTLS). For each sounding, 20-day backward trajectories were calculated using the trajectory module of the Chemical Lagrangian Model of the Stratosphere (CLaMS) to analyse these variations. The trajectory calculations demonstrate that three tropical cyclones (tropical storm Jebi, typhoons Utor and Trami), which occurred over the western Pacific Ocean during August 2013, had a considerable impact on the vertical distribution of ozone and water vapour by uplifting marine air masses to altitudes of the ASM anticyclone. Air parcels subsequently arrived at the observation site via two primary pathways: firstly via direct horizontal transport from the location of the typhoon to the station within approximately 3 days, and secondly via transport following the clockwise wind flow of the ASM within a timescale of 1 week. Furthermore, the interplay between the spatial position of the ASM anticyclone and tropical cyclones plays a key role in controlling the transport pathways of air parcels from the boundary layer of the western Pacific to Lhasa in horizontal and vertical transport. Moreover, the statistical analysis shows that the strongest impact by typhoons is found at altitudes between 14.5 and 17 km (365-375 K). Low ozone values (50-80 ppbv) were observed between 370 and 380 K due to the strong vertical transport within tropical cyclones.

DiffSplice: the genome-wide detection of differential splicing events with RNA-seq

PubMed Central

Hu, Yin; Huang, Yan; Du, Ying; Orellana, Christian F.; Singh, Darshan; Johnson, Amy R.; Monroy, Anaïs; Kuan, Pei-Fen; Hammond, Scott M.; Makowski, Liza; Randell, Scott H.; Chiang, Derek Y.; Hayes, D. Neil; Jones, Corbin; Liu, Yufeng; Prins, Jan F.; Liu, Jinze

2013-01-01

The RNA transcriptome varies in response to cellular differentiation as well as environmental factors, and can be characterized by the diversity and abundance of transcript isoforms. Differential transcription analysis, the detection of differences between the transcriptomes of different cells, may improve understanding of cell differentiation and development and enable the identification of biomarkers that classify disease types. The availability of high-throughput short-read RNA sequencing technologies provides in-depth sampling of the transcriptome, making it possible to accurately detect the differences between transcriptomes. In this article, we present a new method for the detection and visualization of differential transcription. Our approach does not depend on transcript or gene annotations. It also circumvents the need for full transcript inference and quantification, which is a challenging problem because of short read lengths, as well as various sampling biases. Instead, our method takes a divide-and-conquer approach to localize the difference between transcriptomes in the form of alternative splicing modules (ASMs), where transcript isoforms diverge. Our approach starts with the identification of ASMs from the splice graph, constructed directly from the exons and introns predicted from RNA-seq read alignments. The abundance of alternative splicing isoforms residing in each ASM is estimated for each sample and is compared across sample groups. A non-parametric statistical test is applied to each ASM to detect significant differential transcription with a controlled false discovery rate. The sensitivity and specificity of the method have been assessed using simulated data sets and compared with other state-of-the-art approaches. Experimental validation using qRT-PCR confirmed a selected set of genes that are differentially expressed in a lung differentiation study and a breast cancer data set, demonstrating the utility of the approach applied on experimental biological data sets. The software of DiffSplice is available at http://www.netlab.uky.edu/p/bioinfo/DiffSplice. PMID:23155066

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

Precipitation and ice core isotopes from the Asian Summer Monsoon region reflect coherent ENSO variability

NASA Astrophysics Data System (ADS)

Cai, Z.; Tian, L.; Bowen, G. J.

2017-12-01

Oxygen isotope signals (δ18O) from paleo-archives are important proxies for past Asian Summer Monsoon (ASM) climate reconstruction. However, causes of interannual variation in the δ18O values of modern precipitation across the ASM region remain in argument. We report interannual δ18O variation in southern Tibetan Plateau precipitation based on long-term observations at Lhasa. These data, together with precipitation δ18O records from five Global Network of Isotopes in Precipitation (GNIP) stations and two ice core δ18O records, were used to define a regional metric of ASM precipitation δ18O (ASMOI). Back-trajectory analyses for rainy season precipitation events indicate that moisture sources vary little between years with relatively high and low δ18O values, a result that is consistent for the south (Lhasa), southeast (Bangkok), and east ASM regions (Hong Kong). In contrast, δ18O values at these three locations are significantly correlated with convection in the estimated source regions and along transport paths. These results suggest that upstream convection, rather than moisture source change, causes interannual variation in ASM precipitation δ18O values. Contrasting values of the ASMOI in El Niño and La Niña years reveal a positive isotope-El Niño Southern Oscillation (ENSO) response (e.g., high values corresponding to warm phases), which we interpret as a response to changes in regional convection. We show that the isotope-ENSO response is amplified at high elevation sites and during La Niña years. These findings should improve interpretations of paleo-δ18O data as a proxy for past ASM variation and provide new opportunities to use data from this region to study paleo-ENSO activity.

Interpreting ASME limits and philosophy in FEA of pressure vessel parts

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

Bezerra, L.M.; Cruz, J.R.B.; Miranda, C.A.J.

1995-12-01

In recent years there has been an effort to interpret finite element (FE) stress results on the light of the ASME B and PV rules and philosophy. Many task groups have issued guidelines on stress linearization and classifications. All those attempts have come up trying to cope modern FE techniques with the rules imposed by the ASME Code. This paper is an independent contribution to the Pressure Vessel Research Council (PVRC) groups which are studying the stress classification and the failure mechanism in a FE framework. This work tries to complement the interesting work by Hollinger and Hechmer presented inmore » the PVP-94 in Minneapolis. In that paper, the authors examined a typical support skirt and showed relations between the skirt collapse load obtained by finite element analysis and the loads allowed from the ASME stress limits. To complement such paper, in the present article, different skirt geometry configurations are analyzed. The configurations here investigated consist of similar support skirts but with different angles of attachments between cylinder and cone parts. It will be possible to observe the influence of the bending stress in the collapse load and its relation to the allowable loads inferred from the ASME limits. A pressure vessel with torispherical head under internal pressure is also examined. Using elastic and limit load FEA, the present paper determines the collapse loads of the configurations. It sets up the relations between these collapse loads, stress categories, and limits dictated by the ASME Code Subsection NB. On the light of NB rules and philosophy, this paper shows how different methods of stress assessment, classification, and limits may influence in the design of a pressure vessel.« less

Predictors of effective therapeutic relationships between pharmacists and patients with type 2 diabetes: Comparison between Arabic-speaking and Caucasian English-speaking patients.

PubMed

Alzubaidi, H; Mc Namara, K; Versace, V L

2017-11-23

The benefits of pharmacist-led interventions in achieving desired patient outcomes have been well established. Effective patient-pharmacist relationships are required to provide high-quality pharmacy care. Limited information is available about how Arabic-speaking migrants with diabetes, in Australia, perceive patient-pharmacist relationship and how these perspectives differ from the mainstream society (represented by Caucasian English-speaking people). To examine and compare the patient-pharmacist relationship, medication underuse and adherence levels among Arabic-speaking and Caucasian English-speaking patients with type 2 diabetes. A 98-item survey incorporating several previously-validated measurements was completed by Arabic-speaking migrants (ASMs) and Caucasian English-speaking patients (ESPs) with type 2 diabetes. Participants were recruited from various healthcare settings in the Melbourne metropolitan area and rural Victoria, Australia. This survey-based, cross-sectional study was designed to explore patients' perceptions of the patient-pharmacist relationship. A descriptive analysis of responses was undertaken, and binary logistic regression was used to explore patient-pharmacist relationships. A total of 701 participants were recruited; 392 ASMs and 309 ESPs. Of ASMs, 88.3% were non-adherent to their prescribed medication, compared with 45.1% of ESPs. The degree of relationship with community pharmacists differed significantly between ASMs and ESPs. Compared with ASMs, significantly more ESPs reported that they have thought about consulting a pharmacist when they had health problems (P = 0.002). Compared with ESPs, significantly fewer ASMs reported always following pharmacist recommendations (32% versus 61.9% respectively). Arabic-speaking migrants had less-effective relationships with community pharmacists when having their prescriptions filled. Community pharmacists' expertise appeared to be underused. These minimal relationships represent missed opportunities to improve health outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Late Cenozoic genus Fupingopollenites development and its implications for the Asian summer monsoon (ASM) evolution

NASA Astrophysics Data System (ADS)

Miao, Y.; Song, C.; Fang, X.; Meng, Q.; Zhang, P.; Wu, F.; Yan, X.

2015-12-01

An extinct palynomorph, Fupingopollenites, was used as the basis for a discussion of the late Cenozoic Asian summer monsoon (ASM) evolution and its possible driving forces. Based on the spatial and temporal variations in its percentages across Inner and East Asia, we found that Fupingopollenites mainly occurred in East Asia, with boundaries to the NE of ca. 42°N, 135°E and NW of ca. 36°N, 103°E during the Early Miocene (ca. 23-17 Ma). This region enlarged westwards, reaching the eastern Qaidam Basin (ca. 36°N, 97.5°E) during the Middle Miocene (ca. 17-11 Ma), before noticeably retreating to a region bounded to the NW at ca. 33°N, 105°E during ca. 11-5.3 Ma. The region then shrank further in the Pliocene, with the NE boundary shrinking southwards to about 35°N, 120°E; the area then almost disappeared during the Pleistocene (2.6-0 Ma). The flourishing and subsequent extinction of Fupingopollenites is indicative of a narrow ecological amplitude with a critical dependence on habitat humidity and temperature (most likely mean annual precipitation (MAP) >1000 mm and mean annual temperature (MAT) >10°C). Therefore, the Fupingopollenites geographic distribution can indicate the humid ASM evolution during the late Cenozoic, revealing that the strongest ASM period occurred during the Middle Miocene Climate Optimum (MMCO, ~17-14 Ma), after which the ASM weakened coincident with global cooling. We argue that the global cooling played a critical role in the ASM evolution, while the Tibetan Plateau uplifts made a relatively small contribution. This result was supported by a Miocene pollen record at the Qaidam Basin, inner Asia and the contemporaneously compiled pollen records across the Eurasia.

ENSO variability reflected in precipitation oxygen isotopes across the Asian Summer Monsoon region

NASA Astrophysics Data System (ADS)

Cai, Zhongyin; Tian, Lide; Bowen, Gabriel J.

2017-10-01

Oxygen isotope signals (δ18O) from paleo-archives are important proxies for past Asian Summer Monsoon (ASM) climate reconstruction. However, causes of interannual variation in the δ18O values of modern precipitation across the ASM region remain in argument. We report interannual δ18O variation in southern Tibetan Plateau precipitation based on long-term observations at Lhasa. These data, together with precipitation δ18O records from five Global Network of Isotopes in Precipitation (GNIP) stations and two ice core δ18O records, were used to define a regional metric of ASM precipitation δ18O (ASMOI). Back-trajectory analyses for rainy season precipitation events indicate that moisture sources vary little between years with relatively high and low δ18O values, a result that is consistent for the south (Lhasa), southeast (Bangkok), and east ASM regions (Hong Kong). In contrast, δ18O values at these three locations are significantly correlated with convection in the estimated source regions and along transport paths. These results suggest that upstream convection, rather than moisture source change, causes interannual variation in ASM precipitation δ18O values. Contrasting values of the ASMOI in El Niño and La Niña years reveal a positive isotope-El Niño Southern Oscillation (ENSO) response (e.g., high values corresponding to warm phases), which we interpret as a response to changes in regional convection. We show that the isotope-ENSO response is amplified at high elevation sites and during La Niña years. These findings should improve interpretations of paleo-δ18O data as a proxy for past ASM variation and provide new opportunities to use data from this region to study paleo-ENSO activity.

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.

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.

Sarcopenia associated with renal function in the patients with type 2 diabetes.

PubMed

Yang, Rongrong; Zhang, Yongze; Shen, Ximei; Yan, Sunjie

2016-08-01

Studies have suggested that low muscle mass is associated with declining renal function in healthy populations, whether the association is relevant to patients with type 2 diabetes is not well understood. This study investigates the association between sarcopenia and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratios (UACR) in the patients with type 2 diabetes. Two recruited groups consisted of 793 persons without diabetes (males/females=550/243) and 762 persons with type 2 diabetes (males/females=501/261). The non-sarcopenia population demonstrated higher ASM/HT(2), GFR (P<0.001) and lower UACR (P＜0.05) than the sarcopenia population. In studied men, the association between ASM/HT(2) and eGFR was statistically significant in the group without diabetes (OR=0.580, P=0.020), a trend which persisted in women (OR=0.491, P=0.014). The association between ASM/HT(2) and UACR persisted in studied women of two groups (OR=0.269, P=0.005; OR=0.405, P=0.008, respectively). The highest quartile of ASM/HT(2) in the non-sarcopenia population exhibited a 3.753-fold risk of abnormal eGFR within the diabetes group (OR=3.753, P=0.020). The cutoff point of ASM/HT(2) to indicate abnormal renal function for population with non-sarcopenia was 6.32kg/m(2) in the group without diabetes and 6.31kg/m(2) in diabetes group. Sarcopenia is associated with declining renal function, which induces lower eGFR and higher UACR. In the non-sarcopenia population, ASM/HT(2) presents as renal function risk factor, which perhaps associated with higher muscle mass to induce a greater underestimation for creatinine and urinary albumin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A probabilistic analysis of the implications of instrument failures on ESA's Swarm mission for its individual satellite orbit deployments

NASA Astrophysics Data System (ADS)

Jackson, Andrew

2015-07-01

On launch, one of Swarm's absolute scalar magnetometers (ASMs) failed to function, leaving an asymmetrical arrangement of redundant spares on different spacecrafts. A decision was required concerning the deployment of individual satellites into the low-orbit pair or the higher "lonely" orbit. I analyse the probabilities for successful operation of two of the science components of the Swarm mission in terms of a classical probabilistic failure analysis, with a view to concluding a favourable assignment for the satellite with the single working ASM. I concentrate on the following two science aspects: the east-west gradiometer aspect of the lower pair of satellites and the constellation aspect, which requires a working ASM in each of the two orbital planes. I use the so-called "expert solicitation" probabilities for instrument failure solicited from Mission Advisory Group (MAG) members. My conclusion from the analysis is that it is better to have redundancy of ASMs in the lonely satellite orbit. Although the opposite scenario, having redundancy (and thus four ASMs) in the lower orbit, increases the chance of a working gradiometer late in the mission; it does so at the expense of a likely constellation. Although the results are presented based on actual MAG members' probabilities, the results are rather generic, excepting the case when the probability of individual ASM failure is very small; in this case, any arrangement will ensure a successful mission since there is essentially no failure expected at all. Since the very design of the lower pair is to enable common mode rejection of external signals, it is likely that its work can be successfully achieved during the first 5 years of the mission.

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.

Effects of Ginger and Its Constituents on Airway Smooth Muscle Relaxation and Calcium Regulation

PubMed Central

Siviski, Matthew E.; Zhang, Yi; Xu, Carrie; Hoonjan, Bhupinder; Emala, Charles W.

2013-01-01

The prevalence of asthma has increased in recent years, and is characterized by airway hyperresponsiveness and inflammation. Many patients report using alternative therapies to self-treat asthma symptoms as adjuncts to short-acting and long-acting β-agonists and inhaled corticosteroids (ICS). As many as 40% of patients with asthma use herbal therapies to manage asthma symptoms, often without proven efficacy or known mechanisms of action. Therefore, investigations of both the therapeutic and possible detrimental effects of isolated components of herbal treatments on the airway are important. We hypothesized that ginger and its active components induce bronchodilation by modulating intracellular calcium ([Ca2+]i) in airway smooth muscle (ASM). In isolated human ASM, ginger caused significant and rapid relaxation. Four purified constituents of ginger were subsequently tested for ASM relaxant properties in both guinea pig and human tracheas: [6]-gingerol, [8]-gingerol, and [6]-shogaol induced rapid relaxation of precontracted ASM (100–300 μM), whereas [10]-gingerol failed to induce relaxation. In human ASM cells, exposure to [6]-gingerol, [8]-gingerol, and [6]-shogaol, but not [10]-gingerol (100 μM), blunted subsequent Ca2+ responses to bradykinin (10 μM) and S-(−)-Bay K 8644 (10 μM). In A/J mice, the nebulization of [8]-gingerol (100 μM), 15 minutes before methacholine challenge, significantly attenuated airway resistance, compared with vehicle. Taken together, these novel data show that ginger and its isolated active components, [6]-gingerol, [8]-gingerol, and [6]-shogaol, relax ASM, and [8]-gingerol attenuates airway hyperresponsiveness, in part by altering [Ca2+]i regulation. These purified compounds may provide a therapeutic option alone or in combination with accepted therapeutics, including β2-agonists, in airway diseases such as asthma. PMID:23065130

Soil microbial communities of three grassland ecosystems in the Bayinbuluke, China.

PubMed

Shao, Keqiang; Gao, Guang

2018-03-01

The microbial community plays an important role in soil nutrient cycles and energy transformations in alpine grassland. In this study, we investigated the composition of the soil microbial community collected from alpine cold swamp meadow (ASM), alpine cold meadow (AM), and alpine cold desert steppe (ADS) within the Bayinbuluke alpine grassland, China, using Illumina amplicon sequencing. Of the 147 271 sequences obtained, 36 microbial phyla or groups were detected. The results showed that the ADS had lower microbial diversity than the ASM and AM, as estimated by the Shannon index. The Verrucomicrobia, Chloroflexi, Planctomycetes, Proteobacteria, and Actinobacteria were the predominant phyla in all 3 ecosystems. Particularly, Thaumarchaeota was only abundant in ASM, Bacteroidetes in AM, and Acidobacteria in ADS. Additionally, the predominant genus also differed with each ecosystem. Candidatus Nitrososphaera was predominant in ADS, the Pir4 lineage in ASM, and Sphingomonas in AM. Our results indicated that the soil microbial community structure was different for each grassland ecosystem in the Bayinbuluke.

Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

PubMed Central

2016-01-01

Airway structure and function are key aspects of normal lung development, growth, and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, chronic obstructive pulmonary disease, and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and, finally, interactions with other airway cell types such as epithelium, fibroblasts, and nerves. These ASM contributions are now found to be critical in airway hyperresponsiveness and remodeling that occur in lung diseases. This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease. PMID:27742732

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

Nelumbo nucifera leaves extracts inhibit mouse airway smooth muscle contraction.

PubMed

Yang, Xiao; Xue, Lu; Zhao, Qingyang; Cai, Congli; Liu, Qing-Hua; Shen, Jinhua

2017-03-20

Alkaloids extracted from lotus leaves (AELL) can relax vascular smooth muscle. However, whether AELL has a similar relaxant role on airway smooth muscle (ASM) remains unknown. This study aimed to explore the relaxant property of AELL on ASM and the underlying mechanism. Alkaloids were extracted from dried lotus leaves using the high temperature rotary evaporation extraction method. The effects of AELL on mouse ASM tension were studied using force measuring and patch-clamp techniques. It was found that AELL inhibited the high K + or acetylcholine chloride (ACh)-induced precontraction of mouse tracheal rings by 64.8 ± 2.9%, or 48.8 ± 4.7%, respectively. The inhibition was statistically significant and performed in a dose-dependent manner. Furthermore, AELL-induced smooth muscle relaxation was partially mediated by blocking voltage-dependent Ca 2+ channels (VDCC) and non-selective cation channels (NSCC). AELL, which plays a relaxant role in ASM, might be a new complementary treatment to treat abnormal contractions of the trachea and asthma.

Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.

PubMed

Huang, Fen; Zhang, Hongkang; Wu, Meng; Yang, Huanghe; Kudo, Makoto; Peters, Christian J; Woodruff, Prescott G; Solberg, Owen D; Donne, Matthew L; Huang, Xiaozhu; Sheppard, Dean; Fahy, John V; Wolters, Paul J; Hogan, Brigid L M; Finkbeiner, Walter E; Li, Min; Jan, Yuh-Nung; Jan, Lily Yeh; Rock, Jason R

2012-10-02

Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in the adult airway surface epithelium and ASM. The epithelial expression is increased in asthmatics, particularly in secretory cells. Based on this and the proposed functions of CaCC, we hypothesized that TMEM16A inhibitors would negatively regulate both epithelial mucin secretion and ASM contraction. We used a high-throughput screen to identify small-molecule blockers of TMEM16A-CaCC channels. We show that inhibition of TMEM16A-CaCC significantly impairs mucus secretion in primary human airway surface epithelial cells. Furthermore, inhibition of TMEM16A-CaCC significantly reduces mouse and human ASM contraction in response to cholinergic agonists. TMEM16A-CaCC blockers, including those identified here, may positively impact multiple causes of asthma symptoms.

The effects of pulsed auditory stimulation on various gait measurements in persons with Parkinson's Disease.

PubMed

Freedland, Robert L; Festa, Carmel; Sealy, Marita; McBean, Andrew; Elghazaly, Paul; Capan, Ariel; Brozycki, Lori; Nelson, Arthur J; Rothman, Jeffrey

2002-01-01

The purpose of this study was to examine the Functional Ambulation Performance Score (FAP; a quantitative gait measure) in persons with Parkinson's Disease (PD) using the auditory stimulation of a metronome (ASM). Participants (n = 16; 5F/11M; range 60--84 yrs.) had a primary diagnosis of PD and were all independent ambulators. Footfall data were collected while participants walked multiple times on an electronic walkway under the following conditions: 1) PRETEST: establishing baseline cadence, 2) ASM: metronome set to baseline cadence, 3) 10ASM: metronome set to 10% FAP scores increased between PRETEST and POSTTEST. PRE/POSTTEST comparisons also indicated decreases in cycle time and double support and increases in step length and step-extremity ratio (step length/leg length). The results confirm prior findings that auditory stimulation can be used to positively influence the gait of persons with PD and suggest beneficial effects of ASM as an adjunct to dopaminergic therapy to treat gait dysfunctions in PD.

Feature extraction for face recognition via Active Shape Model (ASM) and Active Appearance Model (AAM)

NASA Astrophysics Data System (ADS)

Iqtait, M.; Mohamad, F. S.; Mamat, M.

2018-03-01

Biometric is a pattern recognition system which is used for automatic recognition of persons based on characteristics and features of an individual. Face recognition with high recognition rate is still a challenging task and usually accomplished in three phases consisting of face detection, feature extraction, and expression classification. Precise and strong location of trait point is a complicated and difficult issue in face recognition. Cootes proposed a Multi Resolution Active Shape Models (ASM) algorithm, which could extract specified shape accurately and efficiently. Furthermore, as the improvement of ASM, Active Appearance Models algorithm (AAM) is proposed to extracts both shape and texture of specified object simultaneously. In this paper we give more details about the two algorithms and give the results of experiments, testing their performance on one dataset of faces. We found that the ASM is faster and gains more accurate trait point location than the AAM, but the AAM gains a better match to the texture.

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.

Low appendicular skeletal muscle mass (ASM) with limited mobility and poor health outcomes in middle-aged African Americans.

PubMed

Malmstrom, Theodore K; Miller, Douglas K; Herning, Margaret M; Morley, John E

2013-09-01

Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical syndrome associated with the loss of both skeletal muscle mass and muscle function that occurs with aging. Validation of sarcopenia definitions that include both low muscle mass and poor muscle function is needed. In the population-based African American Health (AAH) study (N = 998 at baseline/wave 1), muscle mass and mobility were evaluated in a clinical testing center in a subsample of N = 319 persons (ages 52-68) at wave 4 (2004). Muscle mass was measured using dual energy x-ray absorptiometry and mobility by a 6-min walk test and 4-m gait walk test. Height corrected appendicular skeletal mass (ASM; 9.0 ± 1.5 in n = 124 males, 8.3 ± 2.2 in n = 195 females) was computed as total lean muscle mass in arms and legs (kilograms) divided by the square of height (meters). Cross-sectional and longitudinal (6-year) associations of low ASM (bottom 25 % AAH sample; <7.96 males and <7.06 females) and low ASM with limited mobility (4-m gait walk ≤1 m/s or 6-min walk <400 m) were examined for basic activities of daily living (ADL) difficulties, instrumental activities of daily living (IADL) difficulties, frailty, falls, and mortality (longitudinal only). Low ASM with limited mobility was associated with IADL difficulties (p = .008) and frailty (p = .040) but not with ADL difficulties or falls in cross-sectional analyses; and with ADL difficulties (p = .022), IADL difficulties (p = .006), frailty (p = .039), and mortality (p = .003) but not with falls in longitudinal analyses adjusted for age and gender. Low ASM alone was marginally associated with mortality (p = .085) but not with other outcomes in cross-sectional or longitudinal analyses. Low ASM with limited mobility is associated with poor health outcomes among late middle-aged African Americans.

Arachidonate-Regulated Ca2+ Influx in Human Airway Smooth Muscle

PubMed Central

Thompson, Michael A.; Prakash, Y. S.

2014-01-01

Plasma membrane Ca2+ influx, especially store-operated Ca2+ entry triggered by sarcoplasmic reticulum (SR) Ca2+ release, is a key component of intracellular calcium concentration ([Ca2+]i) regulation in airway smooth muscle (ASM). Agonist-induced Ca2+ oscillations in ASM that involve both influx and SR mechanisms have been previously demonstrated. In nonexcitable cells, [Ca2+]i oscillations involve Ca2+ influx via arachidonic acid (AA) –stimulated channels, which show similarities to store-operated Ca2+ entry, although their molecular identity remains undetermined. Little is known about AA-regulated Ca2+ channels or their regulation in ASM. In enzymatically dissociated human ASM cells loaded with the Ca2+ indicator, fura-2, AA (1–10 μM) triggered [Ca2+]i oscillations that were inhibited by removal of extracellular Ca2+. Other fatty acids, such as the diacylglycerol analog, 1-oleoyl-2-acetyl-SN-glycerol, oleic acid, and palmitic acid (10 μM each), failed to elicit similar [Ca2+]i responses. Preincubation with LaCl3 (1 μM or 1 mM) inhibited AA-induced oscillations. Inhibition of receptor-operated channels (SKF96,365 [10 μM]), lipoxygenase (zileuton [10 μM]), or cyclooxygenase (indomethacin [10 μM]) did not affect oscillation parameters. Inhibition of SR Ca2+ release (ryanodine [10 μM] or inositol 1,4,5-trisphosphate receptor inhibitor, xestospongin C [1 μM]) decreased [Ca2+]i oscillation frequency and amplitude. Small interfering RNA against caveolin-1, stromal interaction molecule 1, or Orai3 (20 nM each) reduced the frequency and amplitude of AA-induced [Ca2+]i oscillations. In ASM cells derived from individuals with asthma, AA increased oscillation amplitude, but not frequency. These results are highly suggestive of a novel AA-mediated Ca2+–regulatory mechanism in human ASM, reminiscent of agonist-induced oscillations. Given the role of AA in ASM intracellular signaling, especially with inflammation, AA-regulated Ca2+ channels could potentially contribute to increased [Ca2+]i in diseases such asthma. PMID:24471656

Incidence, mechanisms, predictors, and clinical impact of acute and late stent malapposition after primary intervention in patients with acute myocardial infarction: an intravascular ultrasound substudy of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.

PubMed

Guo, Ning; Maehara, Akiko; Mintz, Gary S; He, Yong; Xu, Kai; Wu, Xiaofan; Lansky, Alexandra J; Witzenbichler, Bernhard; Guagliumi, Giulio; Brodie, Bruce; Kellett, Mirle A; Dressler, Ovidiu; Parise, Helen; Mehran, Roxana; Stone, Gregg W

2010-09-14

The incidence and mechanisms of acute and late stent malapposition after primary stent implantation in ST-segment elevation myocardial infarction remain unclear. The Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial comparing paclitaxel-eluting stents (PES) and otherwise equivalent bare metal stents (BMS) in ST-segment elevation myocardial infarction patients. The intravascular ultrasound substudy enrolled 241 patients with 263 native coronary lesions (201 PES, 62 BMS) with baseline and 13-month follow-up imaging. Postintervention acute stent malapposition (ASM) occurred in 34.3% PES- and 40.3% BMS-treated lesions. Of these, 39.1% PES- and 40.0% BMS-treated lesions resolved at follow-up, especially within the stent body (66.7%); complete resolution was accompanied by a reduction in external elastic membrane area. An ASM area >1.2 mm(2) best separated persistent from resolved ASM. At follow-up, a higher frequency of late stent malapposition was detected in PES-treated lesions (46.8%) mainly because of more late acquired stent malapposition (30.8%) compared with BMS-treated lesions. Late acquired stent malapposition area correlated to the decrease of peri-stent plaque in the subset of lesions without positive remodeling and only to change in external elastic membrane in the group with positive remodeling. Independent predictors of late acquired stent malapposition were plaque/thrombus protrusion (odds ratio, 5.60; 95% confidence interval [CI], 2.32 to 13.54) and PES use (odds ratio, 6.32; 95% CI, 2.15 to 18.62). The incidence of ASM was similar in PES- and BMS-treated lesions, but late acquired stent malapposition was more common in PES-treated lesions. The reason for resolved ASM was negative remodeling, with larger ASM areas separating persistent from resolved ASM. Late acquired stent malapposition was due mainly to positive remodeling and plaque/thrombus resolution. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

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.

46 CFR 64.2 - Incorporation by reference.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Incorporation by reference. 64.2 Section 64.2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND... Mechanical Engineers (ASME) International Three Park Avenue, New York, NY 10016-5990. ASME Boiler and...

46 CFR 64.2 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Incorporation by reference. 64.2 Section 64.2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND... Mechanical Engineers (ASME) International Three Park Avenue, New York, NY 10016-5990. ASME Boiler and...

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.

Leishmania mexicana: promastigotes and amastigotes secrete protein phosphatases and this correlates with the production of inflammatory cytokines in macrophages.

PubMed

Escalona-Montaño, A R; Ortiz-Lozano, D M; Rojas-Bernabé, A; Wilkins-Rodriguez, A A; Torres-Guerrero, H; Mondragón-Flores, R; Mondragón-Gonzalez, R; Becker, I; Gutiérrez-Kobeh, L; Aguirre-Garcia, M M

2016-09-01

Phosphatase activity of Leishmania spp. has been shown to deregulate the signalling pathways of the host cell. We here show that Leishmania mexicana promastigotes and amastigotes secrete proteins with phosphatase activity to the culture medium, which was higher in the Promastigote Secretion Medium (PSM) as compared with the Amastigote Secretion Medium (ASM) and was not due to cell lysis, since parasite viability was not affected by the secretion process. The biochemical characterization showed that the phosphatase activity present in PSM was higher in dephosphorylating the peptide END (pY) INASL as compared with the peptide RRA (pT)VA. In contrast, the phosphatase activity in ASM showed little dephosphorylating capacity for both peptides. Inhibition assays demonstrated that the phosphatase activity of both PSM and ASM was sensible only to protein tyrosine phosphatases inhibitors. An antibody against a protein phosphatase 2C (PP2C) of Leishmania major cross-reacted with a 44·9 kDa molecule in different cellular fractions of L. mexicana promastigotes and amastigotes, however, in PSM and ASM, the antibody recognized a protein about 70 kDa. By electron microscopy, the PP2C was localized in the flagellar pocket of amastigotes. PSM and ASM induced the production of tumor necrosis factor alpha, IL-1β, IL-12p70 and IL-10 in human macrophages.

Autoantibodies in chronic hepatitis C virus infection and their association with disease profile.

PubMed

Williams, M J; Lawson, A; Neal, K R; Ryder, S D; Irving, W L

2009-05-01

Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.

77 FR 40638 - Alternative Staffing, Formerly Known as First Choice Staffing, Working On-Site at Ametek...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

..., Instrumentation and Speciality Controls Division, West Chicago, IL; Amended Certification Regarding Eligibility To... Nationals Controls Corporation, Instrumentation and Specialty Control Division, West Chicago, Illinois. The... Corporation, Instrumentation and Specialty Control Division, West Chicago, Illinois, separated from employment...

24 CFR 3280.703 - Minimum standards.

Code of Federal Regulations, 2012 CFR

2012-04-01

.../ASME B1.20.1-1983. Welding and Seamless Wrought Steel Pipe—ANSI/ASME B36.10-1979. Nonferrous Pipe... 1997 revisions. Ferrous Pipe and Fittings Standard Specification for Pipe, Steel, Black and Hot-Dipped, Zinc-Coated, Welded and Seamless—ASTM A53-93. Standard Specification for Electric-Resistance-Welded...

24 CFR 3280.703 - Minimum standards.

Code of Federal Regulations, 2010 CFR

2010-04-01

.../ASME B1.20.1-1983. Welding and Seamless Wrought Steel Pipe—ANSI/ASME B36.10-1979. Nonferrous Pipe... 1997 revisions. Ferrous Pipe and Fittings Standard Specification for Pipe, Steel, Black and Hot-Dipped, Zinc-Coated, Welded and Seamless—ASTM A53-93. Standard Specification for Electric-Resistance-Welded...

24 CFR 3280.703 - Minimum standards.

Code of Federal Regulations, 2011 CFR

2011-04-01

.../ASME B1.20.1-1983. Welding and Seamless Wrought Steel Pipe—ANSI/ASME B36.10-1979. Nonferrous Pipe... 1997 revisions. Ferrous Pipe and Fittings Standard Specification for Pipe, Steel, Black and Hot-Dipped, Zinc-Coated, Welded and Seamless—ASTM A53-93. Standard Specification for Electric-Resistance-Welded...

24 CFR 3280.703 - Minimum standards.

Code of Federal Regulations, 2013 CFR

2013-04-01

.../ASME B1.20.1-1983. Welding and Seamless Wrought Steel Pipe—ANSI/ASME B36.10-1979. Nonferrous Pipe... 1997 revisions. Ferrous Pipe and Fittings Standard Specification for Pipe, Steel, Black and Hot-Dipped, Zinc-Coated, Welded and Seamless—ASTM A53-93. Standard Specification for Electric-Resistance-Welded...

10 CFR 851.27 - Reference sources.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) American Society of Mechanical Engineers (ASME), P.O. Box 2300 Fairfield, NJ 07007. Telephone: 800-843-2763... Electrical Code,” (2005). (5) NFPA 70E, “Standard for Electrical Safety in the Workplace,” (2004). (6... Engineers (ASME) Boilers and Pressure Vessel Code, sections I through XII including applicable Code Cases...

10 CFR 851.27 - Reference sources.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) American Society of Mechanical Engineers (ASME), P.O. Box 2300 Fairfield, NJ 07007. Telephone: 800-843-2763... Electrical Code,” (2005). (5) NFPA 70E, “Standard for Electrical Safety in the Workplace,” (2004). (6... Engineers (ASME) Boilers and Pressure Vessel Code, sections I through XII including applicable Code Cases...

78 FR 14015 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Powered Patient Transport

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

... for Safety--Collateral Standard: Electromagnetic Compatibility--Requirements and Tests,'' and ASME A18.1 ``Safety Standard for Platform Lifts and Stairway Chair Lifts'') must validate electromagnetic...: Electromagnetic Compatibility--Requirements and Tests,'' and ASME A18.1 ``Safety Standard for Platform Lifts and...

Improving Shipbuilding Productivity Through Use of Standards

DTIC Science & Technology

1978-06-01

ship- building industry. In addition to the more familiar standards (e.g. ASME Boiler and Pressure Vessel Code , IEEE-45, etc.) this will include an...will simply refer- ence valid standards as appropriate (e.g. ASME Boiler and Pressure Vessel Code ), and will hopefully work hand in hand with the

46 CFR 56.01-2 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) American Society of Mechanical Engineers (ASME) International, Three Park Avenue, New York, NY 10016-5990... (“ASME SA-675”), 56.60-2. (e) ASTM International (formerly American Society for Testing and Materials... 15540 Ships and Marine Technology-Fire Resistance of Hose Assemblies-Test Methods, First Edition (Aug. 1...

49 CFR 178.337-3 - Structural integrity.

Code of Federal Regulations, 2011 CFR

2011-10-01

... stress at any point in the cargo tank may not exceed the maximum allowable stress value prescribed in... ASME Code or the ASTM standard to which the material is manufactured. (3) The maximum design stress at... ASME Code. The cargo tank design must include calculation of stresses generated by design pressure, the...

Revisiting Professional Teacher Standards

ERIC Educational Resources Information Center

Watson, Amanda

2016-01-01

The Australian Society for Music Education's (ASME) involvement in the development of professional standards for music educators was a significant and active research time in the history of the Society. As ASME celebrates its golden jubilee, it is appropriate to revisit that history and consider the future prospects of subject-specific standards.…

Altitude Ignition/Lean Decel Study.

DTIC Science & Technology

1985-11-01

Pittsburgh 1977. 26. Moses C. A. and Naegeli D. W., "Fuel Property Effects on Combustor Performance," ASME 79-GT-178, Presented at the Gas Turbine...29. Naegeli , D. W., Moses, C. A. and Mellor, A. M., "Preliminary Correlation of Fuel Effects on Ignitability for Gas Turbine Engines," ASME Paper No

40 CFR 63.4362 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., carbon dioxide, and carbon monoxide content of exhaust gas in ANSI/ASME, PTC 19.10-1981, “Flue and Exhaust Gas Analyses [Part 10, Instruments and Apparatus]” (incorporated by reference, see § 63.14). (4... applicable, during each test run. (b) Measure the volatile organic matter concentration as carbon at the...

Advanced systems demonstration for utilization of biomass as an energy source. Volume 3: Equipment specifications

NASA Astrophysics Data System (ADS)

1980-10-01

Specifications are given for the shipping, marking, inspection, testing, and start up of equipment to be used in a proposed wood fuel cogeneration system in Maine. Couplings, mechanical drives, electric motors, spare parts, coatings, assembling, and materials handling and packaging are covered. Both OSHA and noise control regulations are included along with the ASME code.

Mid-Miocene C4 expansion on the Chinese Loess Plateau under an enhanced Asian summer monsoon

NASA Astrophysics Data System (ADS)

Dong, Jibao; Liu, Zhonghui; An, Zhisheng; Liu, Weiguo; Zhou, Weijian; Qiang, Xiaoke; Lu, Fengyan

2018-06-01

Atmospheric CO2 starvation, aridity, fire and warm season precipitation have all been proposed as major contributors to C4 plant expansion during the Late Miocene. However, the driving factors responsible for the distribution of C4 plants in the early and mid-Miocene still remain enigmatic. Here we report pedogenic carbon and oxygen isotope data (δ13Cpedo, δ18Opedo), along with magnetic susceptibility (MS) results, from the Zhuang Lang drilling core on the Chinese Loess Plateau (CLP). Elevated δ13Cpedo values (>-5‰) signal a prominent C4 expansion and substantially increased δ18Opedo and MS values indicate enhanced Asian summer monsoon (ASM) precipitation. Both of these conditions are observed during the Mid-Miocene Climatic Optimum (MMCO), 14.5-17 million years ago. The marked increase in C4 plants, associated with warm temperatures and increased precipitation, strongly suggests the control of an enhanced ASM on C4 expansion on the CLP during the MMCO. This finding contrasts with the late-Miocene C4 expansion associated with cooling and drying conditions observed in low latitudes and argues for regionally specific control of C4 plant distribution/expansion.

Results from Evaluation of Proposed ASME AG-1 Section FI Metal Media Filters - 13063

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

Wilson, John A.; Giffin, Paxton K.; Parsons, Michael S.

High efficiency particulate air (HEPA) filtration technology is commonly used in Department of Energy (DOE) facilities that require control of radioactive particulate matter (PM) emissions due to treatment or management of radioactive materials. Although HEPA technology typically makes use of glass fiber media, metal and ceramic media filters are also capable of filtering efficiencies beyond the required 99.97%. Sintered metal fiber filters are good candidates for use in DOE facilities due to their resistance to corrosive environments and resilience at high temperature and elevated levels of relative humidity. Their strength can protect them from high differential pressure or pressure spikesmore » and allow for back pulse cleaning, extending filter lifetime. Use of these filters has the potential to reduce the cost of filtration in DOE facilities due to life cycle cost savings. ASME AG-1 section FI has not been approved due to a lack of protocols and performance criteria for qualifying section FI filters. The Institute for Clean Energy Technology (ICET) with the aid of the FI project team has developed a Section FI test stand and test plan capable of assisting in the qualification ASME AG-1 section FI filters. Testing done at ICET using the FI test stand evaluates resistance to rated air flow, test aerosol penetration and resistance to heated air of the section FI filters. Data collected during this testing consists of temperature, relative humidity, differential pressure, flow rate, upstream particle concentration, and downstream particle concentration. (authors)« less

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

33 CFR 274.6 - Division/district pest control programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Division/district pest control..., DEPARTMENT OF DEFENSE PEST CONTROL PROGRAM FOR CIVIL WORKS PROJECTS Project Operation § 274.6 Division/district pest control programs. (a) Guides. Referenced technical manuals, and Engineer Circulars issued...

75 FR 77664 - Honeywell International, Inc., Automation and Control Solutions Division, Including On-Site...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-13

..., Inc., Automation and Control Solutions Division, Including On-Site Leased Workers From Manpower...., Automation and Control Solutions Division, Rock Island, Illinois. The notice was published in the Federal...-site at the Rock Island, Illinois location of Honeywell International, Inc., Automation and Control...

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.

Internationalizing professional codes in engineering.

PubMed

Harris, Charles E

2004-07-01

Professional engineering societies which are based in the United States, such as the American Society of Mechanical Engineers (ASME, now ASME International) are recognizing that their codes of ethics must apply to engineers working throughout the world. An examination of the ethical code of the ASME International shows that its provisions pose many problems of application, especially in societies outside the United States. In applying the codes effectively in the international environment, two principal issues must be addressed. First, some Culture Transcending Guidelines must be identified and justified. Nine such guidelines are identified Second, some methods for applying the codes to particular situations must be identified Three such methods are specification, balancing, and finding a creative middle way.

Alternate Design of ITER Cryostat Skirt Support System

NASA Astrophysics Data System (ADS)

Pandey, Manish Kumar; Jha, Saroj Kumar; Gupta, Girish Kumar; Bhattacharya, Avik; Jogi, Gaurav; Bhardwaj, Anil Kumar

2017-04-01

The skirt support of ITER cryostat is a support system which takes all the load of cryostat cylinder and dome during normal and operational condition. The present design of skirt support has full penetration weld joints at the bottom (shell to horizontal plate joint). To fulfil the requirements of tolerances and control the welding distortions, we have proposed to change the full penetration weld into fillet weld. A detail calculation is done to check the feasibility and structural impact due to proposed design. The calculations provide the size requirements of fillet weld. To verify the structural integrity during most severe load case, finite element analysis (FEA) has been done in line with ASME section VIII division 2 [1]. By FEA ‘Plastic Collapse’ and ‘Local Failure’ modes has been assessed. 5° sector of skirt clamp has been modelled in CATIA V5 R21 and used in FEA. Fillet weld at shell to horizontal plate joint has been modelled and symmetry boundary condition at ± 2.5° applied. ‘Elastic Plastic Analysis’ has been performed for the most severe loading case i.e. Category IV loading. The alternate design of Cryostat Skirt support system has been found safe by analysis against Plastic collapse and Local Failure Modes with load proportionality factor 2.3. Alternate design of Cryostat skirt support system has been done and validated by FEA. As per alternate design, the proposal of fillet weld has been implemented in manufacturing.

24 CFR 3280.604 - Materials.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... Material and Property Standard for Special Cast Iron Fittings—IAPMO PS 5-84. Welding and Seamless Wrought Steel Pipe—ANSI/ASME B36.10-1979. Standard Specification for Pipe, Steel, Black and Hot-Dipped, Zinc-Coated, Welded and Seamless—ASTM A53-93. Pipe Threads, General Purpose (Inch)—ANSI/ASME B1.20.1-1983...

49 CFR Appendix C to Part 222 - Guide to Establishing Quiet Zones

Code of Federal Regulations, 2011 CFR

2011-10-01

... Horns will not be subject to annual reviews. (5) The use of FRA's web-based Quiet Zone Calculator is... appendix A (e.g., shorter than required traffic channelization devices), non-engineering ASMs (e.g., programmed law enforcement), and engineering ASMs (i.e., engineering improvements other than modified SSMs...

46 CFR 56.60-2 - Limitations on materials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Boiler and Pressure Vessel Code * ASTM specifications Source of allowable stress Notes Ferrous Materials...-5. 2 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME.... 4 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME Boiler...

46 CFR 56.60-2 - Limitations on materials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Boiler and Pressure Vessel Code * ASTM specifications Source of allowable stress Notes Ferrous Materials...-5. 2 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME.... 4 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME Boiler...

A Comparison of Fatigue Design Methods

DTIC Science & Technology

2001-04-05

Boiler and Pressure Vessel Code does not...Engineers, "ASME Boiler and Pressure Vessel Code ," ASME, 3 Park Ave., New York, NY 10016-5990. [4] Langer, B. F., "Design of Pressure Vessels Involving... and Pressure Vessel Code [3] presents these methods and has expanded the procedures to other pressure vessels besides nuclear pressure vessels. B.

29 CFR 1926.6 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-mail: [email protected]; Web site: http://www.asme.org/: (1) ASME B30.2-2005, Overhead and Gantry....1501(a). (2) ANSI B30.2.0-1967, Safety Code for Overhead and Gantry Cranes, approved May 4, 1967, IBR..., Washington, DC 20210. (2) The Regional and Field Offices of the Occupational Safety and Health Administration...

After-School Math PLUS (ASM+) Final Evaluation Report

ERIC Educational Resources Information Center

Academy for Educational Development, 2007

2007-01-01

This report summarizes findings from the Academy for Educational Development's (AED's) evaluation of After-School Math PLUS (ASM+). This program was designed to help students find the math in everyday experiences and create awareness about the importance of math skills for future career options. The evaluation was conducted by AED's Center for…

Swift/BAT and RXTE Observations of the Peculiar X-ray Binary 4U 2206+54 - Disappearance of the 9.6 Day Modulation

NASA Technical Reports Server (NTRS)

Corbet, R. H. D.; Markwardt, C.; Tueller, J.

2007-01-01

Observations of the high-mass X-ray binary 4U 2206+54 with the Swift Burst Alert Telescope (BAT) do not show modulation at the previously reported period of 9.6 days found from observations made with the Rossi X-ray Timing Explorer (RXTE) All-Sky Monitor (ASM). Instead, the strongest peak in the power spectrum of the BAT light curve occurs at a period of 19.25+/-0.08 days, twice the period found with the RXTE ASM. The maximum of the folded BAT light curve is also delayed compared to the maximum of the folded ASM light curve. The most recent ASM data folded on twice the 9.6 day period show 'similar morphology to the folded BAT light curve. This suggests that the apparent period doubling is a recent secular change rather than an energy-dependent effect. The 9.6 day period is thus not a permanent strong feature of the light curve. We suggest that the orbital period of 4U 2206+54 may be twice the previously proposed value.

Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma

PubMed Central

Yarova, Polina L.; Stewart, Alecia L.; Sathish, Venkatachalem; Britt, Rodney D; Thompson, Michael A.; Lowe, Alexander P. P.; Freeman, Michelle; Aravamudan, Bharathi; Kita, Hirohito; Brennan, Sarah C.; Schepelmann, Martin; Davies, Thomas; Yung, Sun; Cholisoh, Zakky; Kidd, Emma J.; Ford, William R.; Broadley, Kenneth J.; Rietdorf, Katja; Chang, Wenhan; Khayat, Mohd E. Bin; Ward, Donald T.; Corrigan, Christopher J.; Ward, Jeremy P. T.; Kemp, Paul J.; Pabelick, Christina M.; Prakash, Y. S.; Riccardi, Daniela

2016-01-01

Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyper-reactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics. PMID:25904744

A Retrospective Look at 20 Years of ASM Education Programs (1990-2010) and a Prospective Look at the Next 20 Years (2011-2030).

PubMed

Chang, Amy

2011-01-01

Professional societies provide visibility and legitimacy to the work of their post secondary educator members, advocate best practices in courses and sponsored student research, and establish deep networks and communities that catalyze members to collectively engage in undergraduate teaching and learning scholarship. Within the American Society for Microbiology (ASM), the Education Board, established in the mid-1970s, assumes this role. I have been fortunate enough to watch several pivotal programs support our growth and change the status quo by providing opportunities for biology educators to flourish. In this retrospective review, the background and details I offer about each initiative help explain ASM Education offerings, how our growth has been supported and how the status quo has changed. In this prospective look, I offer my vision of the future in post secondary education where classroom learning is student-centered and focused on global problems affecting our health and environment. For the profession to proliferate, the ASM must provide members as many opportunities in learning biology as they do with advancing biology to new frontiers.

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.

Tweeting the meeting: A comparative analysis of an Australian emergency medicine conference over four years.

PubMed

Udovicich, Cristian; Barberi, Anthony; Perera, Kalpa

2016-01-01

Social media allows user-generated content and dialog between users and has also entered into the domain of healthcare. The purpose of this study was to compare the use of Twitter at the Australasian College of Emergency Medicine Annual Scientific Meeting (ACEM ASM) from 2011 to 2014 and analyze its ability to spread emergency medicine education. Retrospectively, TweetReach was utilized to analyze relevant tweets. Each Annual Scientific Meeting (ASM) had an associated Twitter account/s from, which data were collected. Duplicate tweets were excluded from the analysis. Information on the number of total tweets (regular tweets, retweets, and replies) and contributors was gathered. The potential audience, the reach, was calculated. From 2011 to 2014 the number of tweets rose from 460 to 4694, a 920% increase. Only 54 Twitter users contributed to the 2011 ASM. This rose to 252 (2012), 291 (2013) and 572 (2014). The average number of tweets per contributor ranged from 8.2 to 10.9. The reach, the potential number of Twitter users exposed to posts, rose >30 times from 2011 (15,502 users) to 2014 (471,166). The use of Twitter at the ACEM ASM rose significantly from 2011 to 2014. It is a highly useful tool for the dissemination of emergency medicine education. Twitter has been harnessed by the ASM to enhance the conference experience by further generating interaction between delegates as well as those worldwide.

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

Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons

PubMed Central

Beckmann, Nadine; Sharma, Deepa; Gulbins, Erich; Becker, Katrin Anne; Edelmann, Bärbel

2014-01-01

Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM) was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer's disease, and major depression, as well as viral (e.g., measles virus) and bacterial (e.g., Staphylococcus aureus, Pseudomonas aeruginosa) infections. Ceramide molecules may act in these diseases by the alteration of membrane biophysics, the self-association of ceramide molecules within the cell membrane and the ultimate formation of larger ceramide-enriched membrane domains/platforms. These domains were shown to serve the clustering of certain receptors such as CD95 and may also act in the above named diseases. The potential to block the generation of ceramide by inhibiting the ASM has opened up new therapeutic approaches for the treatment of these conditions. Since amitriptyline is one of the longest used clinical drugs and side effects are well studied, it could potentially become a cheap and easily accessible medication for patients suffering from these diseases. In this review, we aim to provide an overview of current in vitro and in vivo studies and clinical trials utilizing amitriptyline to inhibit ASM and contemplate possible future applications of the drug. PMID:25228885

Deterministic Local Sensitivity Analysis of Augmented Systems - II: Applications to the QUENCH-04 Experiment Using the RELAP5/MOD3.2 Code System

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

Ionescu-Bujor, Mihaela; Jin Xuezhou; Cacuci, Dan G.

2005-09-15

The adjoint sensitivity analysis procedure for augmented systems for application to the RELAP5/MOD3.2 code system is illustrated. Specifically, the adjoint sensitivity model corresponding to the heat structure models in RELAP5/MOD3.2 is derived and subsequently augmented to the two-fluid adjoint sensitivity model (ASM-REL/TF). The end product, called ASM-REL/TFH, comprises the complete adjoint sensitivity model for the coupled fluid dynamics/heat structure packages of the large-scale simulation code RELAP5/MOD3.2. The ASM-REL/TFH model is validated by computing sensitivities to the initial conditions for various time-dependent temperatures in the test bundle of the Quench-04 reactor safety experiment. This experiment simulates the reflooding with water ofmore » uncovered, degraded fuel rods, clad with material (Zircaloy-4) that has the same composition and size as that used in typical pressurized water reactors. The most important response for the Quench-04 experiment is the time evolution of the cladding temperature of heated fuel rods. The ASM-REL/TFH model is subsequently used to perform an illustrative sensitivity analysis of this and other time-dependent temperatures within the bundle. The results computed by using the augmented adjoint sensitivity system, ASM-REL/TFH, highlight the reliability, efficiency, and usefulness of the adjoint sensitivity analysis procedure for computing time-dependent sensitivities.« less

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

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.

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.

Biomass characterization by dielectric monitoring of viability and oxygen uptake rate measurements in a novel membrane bioreactor.

PubMed

Shariati, Farshid Pajoum; Heran, Marc; Sarrafzadeh, Mohammad Hossein; Mehrnia, Mohammad Reza; Sarzana, Gabriele; Ghommidh, Charles; Grasmick, Alain

2013-07-01

The application of permittivity and oxygen uptake rate (OUR) as biological process control parameters in a wastewater treatment system was evaluated. Experiments were carried out in a novel airlift oxidation ditch membrane bioreactor under different organic loading rates (OLR). Permittivity as representative of activated sludge viability was measured by a capacitive on-line sensor. OUR was also measured as a representative for respirometric activity. Results showed that the biomass concentration increases with OLR and all biomass related measurements and simulators such as MLSS, permittivity, OUR, ASM1 and ASM3 almost follow the same increasing trends. The viability of biomass decreased when the OLR was reduced from 5 to 4 kg COD m(-3)d(-1). During decreasing of OLR, biomass related parameters generally decreased but not in a similar manner. Also, protein concentration in the system during OLR decreasing changed inversely with the activated sludge viability. Copyright © 2013 Elsevier Ltd. All rights reserved.

Gap Analysis of Material Properties Data for Ferritic/Martensitic HT-9 Steel

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

Brown, Neil R.; Serrano De Caro, Magdalena; Rodriguez, Edward A.

2012-08-28

The US Department of Energy (DOE), Office of Nuclear Energy (NE), is supporting the development of an ASME Code Case for adoption of 12Cr-1Mo-VW ferritic/martensitic (F/M) steel, commonly known as HT-9, primarily for use in elevated temperature design of liquid-metal fast reactors (LMFR) and components. In 2011, Los Alamos National Laboratory (LANL) nuclear engineering staff began assisting in the development of a small modular reactor (SMR) design concept, previously known as the Hyperion Module, now called the Gen4 Module. LANL staff immediately proposed HT-9 for the reactor vessel and components, as well as fuel clad and ducting, due to itsmore » superior thermal qualities. Although the ASME material Code Case, for adoption of HT-9 as an approved elevated temperature material for LMFR service, is the ultimate goal of this project, there are several key deliverables that must first be successfully accomplished. The most important key deliverable is the research, accumulation, and documentation of specific material parameters; physical, mechanical, and environmental, which becomes the basis for an ASME Code Case. Time-independent tensile and ductility data and time-dependent creep and creep-rupture behavior are some of the material properties required for a successful ASME Code case. Although this report provides a cursory review of the available data, a much more comprehensive study of open-source data would be necessary. This report serves three purposes: (a) provides a list of already existing material data information that could ultimately be made available to the ASME Code, (b) determines the HT-9 material properties data missing from available sources that would be required and (c) estimates the necessary material testing required to close the gap. Ultimately, the gap analysis demonstrates that certain material properties testing will be required to fulfill the necessary information package for an ASME Code Case.« less

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.

TRAIL death receptor 4 signaling via lysosome fusion and membrane raft clustering in coronary arterial endothelial cells: evidence from ASM knockout mice.

PubMed

Li, Xiang; Han, Wei-Qing; Boini, Krishna M; Xia, Min; Zhang, Yang; Li, Pin-Lan

2013-01-01

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor, death receptor 4 (DR4), have been implicated in the development of endothelial dysfunction and atherosclerosis. However, the signaling mechanism mediating DR4 activation leading to endothelial injury remains unclear. We recently demonstrated that ceramide production via hydrolysis of membrane sphingomyelin by acid sphingomyelinase (ASM) results in membrane raft (MR) clustering and the formation of important redox signaling platforms, which play a crucial role in amplifying redox signaling in endothelial cells leading to endothelial dysfunction. The present study aims to investigate whether TRAIL triggers MR clustering via lysosome fusion and ASM activation, thereby conducting transmembrane redox signaling and changing endothelial function. Using confocal microscopy, we found that TRAIL induced MR clustering and co-localized with DR4 in coronary arterial endothelial cells (CAECs) isolated from wild-type (Smpd1 (+/+)) mice. Furthermore, TRAIL triggered ASM translocation, ceramide production, and NADPH oxidase aggregation in MR clusters in Smpd1 ( +/+ ) CAECs, whereas these observations were not found in Smpd1 (-/-) CAECs. Moreover, ASM deficiency reduced TRAIL-induced O(2) (-[Symbol: see text]) production in CAECs and abolished TRAIL-induced impairment on endothelium-dependent vasodilation in small resistance arteries. By measuring fluorescence resonance energy transfer, we found that Lamp-1 (lysosome membrane marker protein) and ganglioside G(M1) (MR marker) were trafficking together in Smpd1 (+/+) CAECs, which was absent in Smpd1 (-/-) CAECs. Consistently, fluorescence imaging of living cells with specific lysosome probes demonstrated that TRAIL-induced lysosome fusion with membrane was also absent in Smpd1 (-/-) CAECs. Taken together, these results suggest that ASM is essential for TRAIL-induced lysosomal trafficking, membrane fusion and formation of MR redox signaling platforms, which may play an important role in DR4-mediated redox signaling in CAECs and consequently endothelial dysfunction.

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.

Divergent modulation of Rho‐kinase and Ca2+ influx pathways by Src family kinases and focal adhesion kinase in airway smooth muscle

PubMed Central

Shaifta, Yasin; Irechukwu, Nneka; Prieto‐Lloret, Jesus; MacKay, Charles E; Marchon, Keisha A; Ward, Jeremy P T

2015-01-01

Background and Purpose The importance of tyrosine kinases in airway smooth muscle (ASM) contraction is not fully understood. The aim of this study was to investigate the role of Src‐family kinases (SrcFK) and focal adhesion kinase (FAK) in GPCR‐mediated ASM contraction and associated signalling events. Experimental Approach Contraction was recorded in intact or α‐toxin permeabilized rat bronchioles. Phosphorylation of SrcFK, FAK, myosin light‐chain‐20 (MLC20) and myosin phosphatase targeting subunit‐1 (MYPT‐1) was evaluated in cultured human ASM cells (hASMC). [Ca2+]i was evaluated in Fura‐2 loaded hASMC. Responses to carbachol (CCh) and bradykinin (BK) and the contribution of SrcFK and FAK to these responses were determined. Key Results Contractile responses in intact bronchioles were inhibited by antagonists of SrcFK, FAK and Rho‐kinase, while after α‐toxin permeabilization, they were sensitive to inhibition of SrcFK and Rho‐kinase, but not FAK. CCh and BK increased phosphorylation of MYPT‐1 and MLC20 and auto‐phosphorylation of SrcFK and FAK. MYPT‐1 phosphorylation was sensitive to inhibition of Rho‐kinase and SrcFK, but not FAK. Contraction induced by SR Ca2+ depletion and equivalent [Ca2+]i responses in hASMC were sensitive to inhibition of both SrcFK and FAK, while depolarization‐induced contraction was sensitive to FAK inhibition only. SrcFK auto‐phosphorylation was partially FAK‐dependent, while FAK auto‐phosphorylation was SrcFK‐independent. Conclusions and Implications SrcFK mediates Ca2+‐sensitization in ASM, while SrcFK and FAK together and individually influence multiple Ca2+ influx pathways. Tyrosine phosphorylation is therefore a key upstream signalling event in ASM contraction and may be a viable target for modulating ASM tone in respiratory disease. PMID:26294392

Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating lysosomal acid sphingomyelinase.

PubMed

Zhu, Hong; Yoshimoto, Tanihiro; Yamashima, Tetsumori

2014-10-03

The inducible expression of heat shock protein 70.1 (Hsp70.1) plays cytoprotective roles in its molecular chaperone function. Binding of Hsp70 to an endolysosomal phospholipid, bis(monoacylglycero)phosphate (BMP), has been recently shown to stabilize lysosomal membranes by enhancing acid sphingomyelinase (ASM) activity in cancer cells. Using the monkey experimental paradigm, we have reported that calpain-mediated cleavage of oxidized Hsp70.1 causes neurodegeneration in the hippocampal cornu ammonis 1 (CA1), whereas expression of Hsp70.1 in the motor cortex without calpain activation contributes to neuroprotection. However, the molecular mechanisms of the lysosomal destabilization/stabilization determining neuronal cell fate have not been elucidated. To elucidate whether regulation of lysosomal ASM could affect the neuronal fate, we analyzed Hsp70.1-BMP binding and ASM activity by comparing the motor cortex and the CA1. We show that Hsp70.1 being localized at the lysosomal membrane, lysosomal lipid BMP levels, and the lipid binding domain of Hsp70.1 are crucial for Hsp70.1-BMP binding. In the postischemic motor cortex, Hsp70.1 being localized at the lysosomal membrane could bind to BMP without calpain activation and decreased BMP levels, resulting in increasing ASM activity and lysosomal stability. However, in the postischemic CA1, calpain activation and a concomitant decrease in the lysosomal membrane localization of Hsp70.1 and BMP levels may diminish Hsp70.1-BMP binding, resulting in decreased ASM activity and lysosomal rupture with leakage of cathepsin B into the cytosol. A TUNEL assay revealed the differential neuronal vulnerability between the CA1 and the motor cortex. These results suggest that regulation of ASM activation in vivo by Hsp70.1-BMP affects lysosomal stability and neuronal survival or death after ischemia/reperfusion. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Defining sarcopenia in terms of risk of physical limitations: a 5-year follow-up study of 3,153 chinese men and women.

PubMed

Woo, Jean; Leung, Jason; Sham, Aprille; Kwok, Timothy

2009-12-01

To examine the definition of sarcopenia in Chinese subjects by relating the value of appendicular skeletal muscle mass (ASM) divided by height squared to physical functional outcomes after 4 years. Four-year prospective study. A Chinese community in Hong Kong SAR China. Three thousand one hundred fifty-three community-living men and women aged 65 and older. Information collected by questionnaire included demographics, health limitation on activities of daily living (ADLs), self-care, physical activity level, dietary intake, and psychosocial functioning. Measurements included height, weight, grip strength, step length in a 6-minute walk, and body composition. Four-year outcomes for those with ASM in kg per height in meters squared (ASM/ht(2)) less than 2 standard deviations (SDs) and 2 SDs or more below the young adult mean value were compared using analysis of variance and logistic regression, adjusting for potential confounding factors such as age, fat mass, presence or absence of malnutrition, dietary protein and vitamin D intake, comorbidity, and cognitive impairment. Participants with ASM/ht(2) 2 SDs or more below the young adult mean had lower grip strength and greater limitation in climbing stairs and general ADLs after adjusting for confounding factors. A U-shaped relationship was observed between physical limitation and ASM/ht(2), with increasing physical limitation below or above a range of 7.25 to 6.75 kg/m(2) in men and 6.00 to 6.25 kg/m(2) in women. Values of 5.25 to 6.74 kg/m(2) in women were associated with approximately 30% less risk of functional limitation after 5 years. No clear cutoff was found in men. Sarcopenia may be defined in terms of a range of values for ASM/ht(2) associated with the lowest risk of future physical limitations. The importance of establishing a quantitative value for the definition of sarcopenia may facilitate future interventional studies using pharmacological or nonpharmacological strategies.

Active Components of Ginger Potentiate β-Agonist–Induced Relaxation of Airway Smooth Muscle by Modulating Cytoskeletal Regulatory Proteins

PubMed Central

Zhang, Yi; Xu, Carrie; Wakita, Ryo; Emala, Charles W.

2014-01-01

β-Agonists are the first-line therapy to alleviate asthma symptoms by acutely relaxing the airway. Purified components of ginger relax airway smooth muscle (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can explore the use of phytotherapeutics in combination with traditional asthma therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8-gingerol, or 6-shogaol potentiate β-agonist–induced ASM relaxation; and (2) define the mechanism(s) of action responsible for this potentiation. Human ASM was contracted in organ baths. Tissues were relaxed dose dependently with β-agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 μM). Primary human ASM cells were used for cellular experiments. Purified phosphodiesterase (PDE) 4D or phospholipase C β enzyme was used to assess inhibitory activity of ginger components using fluorescent assays. A G-LISA assay was used to determine the effects of ginger constituents on Ras homolog gene family member A activation. Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C β activity. 6-Shogaol alone inhibited Ras homolog gene family member A activation. In human ASM cells, these constituents decreased phosphorylation of 17-kD protein kinase C–potentiated inhibitory protein of type 1 protein phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated components of ginger potentiate β-agonist–induced relaxation in human ASM. This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins. Together with β-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, resulting in relief of symptoms through complementary intracellular pathways. PMID:23962082

40 CFR 63.4766 - How do I determine the add-on control device emission destruction or removal efficiency?

Code of Federal Regulations, 2010 CFR

2010-07-01

... also use as an alternative to Method 3B, the manual method for measuring the oxygen, carbon dioxide, and carbon monoxide content of exhaust gas in ANSI/ASME PTC 19.10-1981, “Flue and Exhaust Gas Analyses [Part 10, Instruments and Apparatus]” (incorporated by reference, see § 63.14). (4) Use Method 4 of...

Quantum Multicriticality near the Dirac-Semimetal to Band-Insulator Critical Point in Two Dimensions: A Controlled Ascent from One Dimension

NASA Astrophysics Data System (ADS)

Roy, Bitan; Foster, Matthew S.

2018-01-01

We compute the effects of generic short-range interactions on gapless electrons residing at the quantum critical point separating a two-dimensional Dirac semimetal and a symmetry-preserving band insulator. The electronic dispersion at this critical point is anisotropic (Ek=±√{v2kx2+b2ky2 n } with n =2 ), which results in unconventional scaling of thermodynamic and transport quantities. Because of the vanishing density of states [ϱ (E )˜|E |1 /n ], this anisotropic semimetal (ASM) is stable against weak short-range interactions. However, for stronger interactions, the direct Dirac-semimetal to band-insulator transition can either (i) become a fluctuation-driven first-order transition (although unlikely in a particular microscopic model considered here, the anisotropic honeycomb lattice extended Hubbard model) or (ii) get avoided by an intervening broken-symmetry phase. We perform a controlled renormalization group analysis with the small parameter ɛ =1 /n , augmented with a 1 /n expansion (parametrically suppressing quantum fluctuations in the higher dimension) by perturbing away from the one-dimensional limit, realized by setting ɛ =0 and n →∞ . We identify charge density wave (CDW), antiferromagnet (AFM), and singlet s -wave superconductivity as the three dominant candidates for broken symmetry. The onset of any such order at strong coupling (˜ɛ ) takes place through a continuous quantum phase transition across an interacting multicritical point, where the ordered phase, band insulator, Dirac, and anisotropic semimetals meet. We also present the phase diagram of an extended Hubbard model for the ASM, obtained via the controlled deformation of its counterpart in one dimension. The latter displays spin-charge separation and instabilities to CDW, spin density wave, and Luther-Emery liquid phases at arbitrarily weak coupling. The spin density wave and Luther-Emery liquid phases deform into pseudospin SU(2)-symmetric quantum critical points separating the ASM from the AFM and superconducting orders, respectively. Our phase diagram shows an intriguing interplay among CDW, AFM, and s -wave paired states that can be germane for a uniaxially strained optical honeycomb lattice for ultracold fermion atoms, or the organic compound α -(BEDT -TTF )2I3 .

A single-arm trial indirect comparison investigation: a proof-of-concept method to predict venous leg ulcer healing time for a new acellular synthetic matrix matched to standard care control.

PubMed

Shannon, Ronald; Nelson, Andrea

2017-08-01

To compare data on time to healing from two separate cohorts: one treated with a new acellular synthetic matrix plus standard care (SC) and one matched from four large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence network, propensity score matching and sensitivity analysis to predict the feasibility of the new acellular synthetic matrix plus SC for success in future randomised, controlled clinical trials. Prospective data on chronic VLUs from a safety and effectiveness study on an acellular synthetic matrix conducted in one wound centre in the UK (17 patients) and three wound centres in Australia (36 patients) were compared retrospectively to propensity score-matched data from patients with comparable leg ulcer disease aetiology, age, baseline ulcer area, ulcer duration, multi-layer compression bandaging and majority of care completed in specialist wound centres (average of 1 visit per week), with the outcome measures at comparable follow-up periods from patients enrolled in four prospective, multicentre, pragmatic, randomised studies of venous ulcers in the UK (the comparison group; VLU evidence network). Analysis using Kaplan-Meier survival curves showed a mean healing time of 73·1 days for ASM plus SC (ASM) treated ulcers in comparison with 83·5 days for comparison group ulcers treated with SC alone (Log rank test, χ 2 5·779, P = 0·016) within 12 weeks. Sensitivity analysis indicates that an unobserved covariate would have to change the odds of healing for SC by a factor of 1·1 to impact the baseline results. Results from this study predict a significant effect on healing time when using a new ASM as an adjunct to SC in the treatment of non-healing venous ulcers in the UK, but results are sensitive to unobserved covariates that may be important in healing time comparison. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Theophylline Represses IL-8 Secretion from Airway Smooth Muscle Cells Independently of Phosphodiesterase Inhibition. Novel Role as a Protein Phosphatase 2A Activator.

PubMed

Patel, Brijeshkumar S; Rahman, Md Mostafizur; Rumzhum, Nowshin N; Oliver, Brian G; Verrills, Nicole M; Ammit, Alaina J

2016-06-01

Theophylline is an old drug experiencing a renaissance owing to its beneficial antiinflammatory effects in chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Multiple modes of antiinflammatory action have been reported, including inhibition of the enzymes that degrade cAMP-phosphodiesterase (PDE). Using primary cultures of airway smooth muscle (ASM) cells, we recently revealed that PDE4 inhibitors can potentiate the antiinflammatory action of β2-agonists by augmenting cAMP-dependent expression of the phosphatase that deactivates mitogen-activated protein kinase (MAPK)-MAPK phosphatase (MKP)-1. Therefore, the aim of this study was to address whether theophylline repressed cytokine production in a similar, PDE-dependent, MKP-1-mediated manner. Notably, theophylline did not potentiate cAMP release from ASM cells treated with the long-acting β2-agonist formoterol. Moreover, theophylline (0.1-10 μM) did not increase formoterol-induced MKP-1 messenger RNA expression nor protein up-regulation, consistent with the lack of cAMP generation. However, theophylline (at 10 μM) was antiinflammatory and repressed secretion of the neutrophil chemoattractant cytokine IL-8, which is produced in response to TNF-α. Because theophylline's effects were independent of PDE4 inhibition or antiinflammatory MKP-1, we then wished to elucidate the novel mechanisms responsible. We investigated the impact of theophylline on protein phosphatase (PP) 2A, a master controller of multiple inflammatory signaling pathways, and show that theophylline increases TNF-α-induced PP2A activity in ASM cells. Confirmatory results were obtained in A549 lung epithelial cells. PP2A activators have beneficial effects in ex vivo and in vivo models of respiratory disease. Thus, our study is the first to link theophylline with PP2A activation as a novel mechanism to control respiratory inflammation.

76 FR 36231 - American Society of Mechanical Engineers (ASME) Codes and New and Revised ASME Code Cases

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-21

... exceed the test facility limits and reduces the number of functional tests for specific valve designs... addresses reducing the number of functional tests for specific valve designs. The NRC has identified no... the required test pressure for the new Class 1 incompressible-fluid, pressure-relief valve designs...

77 FR 46385 - Certain Small Diameter Seamless Carbon and Alloy Standard, Line, and Pressure Pipe From Germany...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-03

...: Seamless pressure pipes are intended for the conveyance of water, steam, petrochemicals, chemicals, oil... Mechanical Engineers (ASME) code stress levels. Alloy pipes made to ASTM standard A-335 must be used if temperatures and stress levels exceed those allowed for A-106 and the ASME codes. Seamless pressure pipes sold...

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

46 CFR 52.01-135 - Inspection and tests (modifies PG-90 through PG-100).

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (a) Requirements. Inspection and test of boilers and boiler pressure parts shall be as indicated in PG-90 through PG-100 of section I of the ASME Boiler and Pressure Vessel Code (incorporated by...-91 of section I of the ASME Boiler and Pressure Vessel Code (incorporated by reference; see 46 CFR 52...

Feasibility Study of Coal Gasification/Fuel Cell/Cogeneration Project, Fort Greely, Alaska Site. Preliminary Survey,

DTIC Science & Technology

1985-04-02

sothat oilconsumptior ASME Boiler and Pressure Vessel Code . can be measured. Hot water boiler plants with out- U1I Shell-and-tube type exchangers are...slopes possible to VIII of the ASME Boiler and Pressure Vessel Code . prevent rain or melting snow from penetrating into (2? Water will flow through the

Ultrasonic Inspection and Fatigue Evaluation of Critical Pore Size in Welds.

DTIC Science & Technology

1981-09-01

Boiler and Pressure Vessel Code ) 20...Five porosity levels were produced that parallelled ASME boiler and pressure vessel code specification (Section VIII). Appendix IV of the pressure...Figure 2 shows porosity charts (ASME Boiler and Pressure Vessel Code ) which classify and designate the number and size of pores in any six inch length

Status of Metric Conversion A Survey of U.S. Standards Writing Organizations.

DTIC Science & Technology

1982-05-01

Boiler and Pressure Vessel Code . 7...to and consistent with metrication of the ASME Boiler and Pressure Vessel Code . The Electrical Apparatus Service Association is a trade asso- ciation...metrication of TEMA Standards will be compatible to and consistent with metrication of the ASME Boiler and Pressure Vessel Code . TEMA’s metrication

Supercritical and Transcritical Shear Flows in Microgravity: Experiments and Direct Numerical Simulations

DTIC Science & Technology

2006-08-01

Boiler and Pressure Vessel Code were con...GRC, and to specifically state a general operating requirement. 1.1. The entire apparatus will be designed to ASME Boiler and Pressure Vessel Code , whenever...calculations, including a finite element analysis (FEA) will be inspected to verify the ASME Boiler and Pressure Vessel Code has been me, whenever

Computer-Aided Thermohydraulic Design of TEMA Type E Shell and Tube Heat Exchangers for Use in Low Pressure, Liquid-to-Liquid, Single Phase Applications.

DTIC Science & Technology

1985-04-01

and Standards .. ... ....... ....... 9 A. General . ... .. .. ... ..... .. .. ... 9 B. ASME Boiler and Pressure Vessel Code .. .. ......9 C. Foreign...several different sources. B. American Society of Mechanial Engineers (ASME) Boiler and Pressure Vessel Code A shell and tube heat exchanger is indeed a

The Development of Auditory Sequential Memory in Young Black and White Children.

ERIC Educational Resources Information Center

Hurley, Oliver L.; And Others

The question of whether Black children "peak" earlier than White children in auditory sequential memory (ASM) was investigated in 122 Black children and 120 White children in grades k-3 in two racially mixed schools in a large southern community. Each S was given the ASM subtest of the Illinois Test of Psycholinguistic Abilities. Results…

Bronchoprotection and bronchorelaxation in asthma: New targets, and new ways to target the old ones.

PubMed

Pera, Tonio; Penn, Raymond B

2016-08-01

Despite over 50years of inhaled beta-agonists and corticosteroids as the default management or rescue drugs for asthma, recent research suggests that new therapeutic options are likely to emerge. This belief stems from both an improved understanding of what causes and regulates airway smooth muscle (ASM) contraction, and the identification of new targets whose inhibition or activation can relax ASM. In this review we discuss the recent findings that provide new insight into ASM contractile regulation, a revolution in pharmacology that identifies new ways to "tune" G protein-coupled receptors to improve therapeutic efficacy, and the discovery of several novel targets/approaches capable of effecting bronchoprotection or bronchodilation. Copyright © 2016 Elsevier Inc. All rights reserved.

Accumulation of neutral mutations in growing cell colonies with competition.

PubMed

Sorace, Ron; Komarova, Natalia L

2012-12-07

Neutral mutations play an important role in many biological processes including cancer initiation and progression, the generation of drug resistance in bacterial and viral diseases as well as cancers, and the development of organs in multicellular organisms. In this paper we study how neutral mutants are accumulated in nonlinearly growing colonies of cells subject to growth constraints such as crowding or lack of resources. We investigate different types of growth control which range from "division-controlled" to "death-controlled" growth (and various mixtures of both). In division-controlled growth, the burden of handling overcrowding lies with the process of cell-divisions, the divisions slow down as the carrying capacity is approached. In death-controlled growth, it is death rate that increases to slow down expansion. We show that division-controlled growth minimizes the number of accumulated mutations, and death-controlled growth corresponds to the maximum number of mutants. We check that these results hold in both deterministic and stochastic settings. We further develop a general (deterministic) theory of neutral mutations and achieve an analytical understanding of the mutant accumulation in colonies of a given size in the absence of back-mutations. The long-term dynamics of mutants in the presence of back-mutations is also addressed. In particular, with equal forward- and back-mutation rates, if division-controlled and a death-controlled types are competing for space and nutrients, cells obeying division-controlled growth will dominate the population. Copyright © 2012 Elsevier Ltd. All rights reserved.

Time on androgen deprivation therapy and adaptations to exercise: secondary analysis from a 12-month randomized controlled trial in men with prostate cancer.

PubMed

Taaffe, Dennis R; Buffart, Laurien M; Newton, Robert U; Spry, Nigel; Denham, James; Joseph, David; Lamb, David; Chambers, Suzanne K; Galvão, Daniel A

2018-02-01

To explore if duration of previous exposure to androgen deprivation therapy (ADT) in men with prostate cancer (PCa) undertaking a year-long exercise programme moderates the exercise response with regard to body composition and muscle performance, and also to explore the moderator effects of baseline testosterone, time since ADT, and baseline value of the outcome. In a multicentre randomized controlled trial, 100 men who had previously undergone either 6 months (short-term) or 18 months (long-term) of ADT in combination with radiotherapy, as part of the TROG 03.04 RADAR trial, were randomized to 6 months supervised exercise, followed by a 6-month home-based maintenance programme, or to printed physical activity educational material for 12 months across 13 university-affiliated exercise clinics in Australia and New Zealand. The participants were long-term survivors of PCa with a mean age of 71.7 ± 6.4 years, and were assessed for lower extremity performance (repeated chair rise), with a subset of men (n = 57) undergoing additional measures for upper and lower body muscle strength and body composition (lean mass, fat mass, appendicular skeletal muscle [ASM]) by dual X-ray absorptiometry. Data were analysed using generalized estimating equations. Time on ADT significantly moderated the exercise effects on chair rise (β interaction = -1.3 s, 95% confidence interval [CI] -2.6 to 0.0), whole-body lean mass (β interaction = 1194 g, 95% CI 234 to 2153) and ASM mass (β interaction = 562 g, 95% CI 49 to 1075), and approached significance for fat mass (β interaction = -1107 g, 95% CI -2346 to 132), with greater benefits for men previously on long-term ADT. At 6 months, the intervention effects on chair rise time -1.5 s (95% CI -2.5 to -0.5), whole-body lean mass 824 g (95% CI 8 to 1640), ASM mass 709 g (95% CI 260 to 1158), and fat mass -1377 g (95% CI -2156 to -598) were significant for men previously on long-term ADT, but not for men on short-term ADT. At 12 months, the intervention effects for men on long-term ADT remained significant for the chair rise, with improved performance (-2.0 s, 95% CI -3.0 to -1.0) and increased ASM (537 g, 95% CI 153 to 921). Time on ADT did not moderate the exercise effects on muscle strength, nor did time since ADT cessation moderate any intervention effects. Similarly, testosterone and baseline values of the outcome had negligible moderator effects. Men with PCa previously treated long-term with ADT respond more favourably to exercise in terms of lower body muscle performance and body composition (lean and fat mass, and ASM) than those with short-term ADT exposure. As a result, men who were formerly on long-term androgen suppression regimens should be especially prescribed exercise medicine interventions to alleviate residual treatment-related adverse effects. © 2017 The Authors. BJU International.

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 Central

Taniguchi, M; Ogiso, H; Takeuchi, T; Kitatani, K; Umehara, H; Okazaki, T

2015-01-01

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. PMID:25855965