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...

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

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. 54.01-2 Section 54.01-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS General Requirements § 54.01-2 Adoption of division 1 of section VIII of the ASME Boiler and...

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

DTIC Science & Technology

1998-06-01

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

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

DTIC Science & Technology

2004-02-01

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

NIST/ASME Steam Properties Database

National Institute of Standards and Technology Data Gateway

SRD 10 NIST/ASME Steam Properties Database (PC database for purchase)   Based upon the International Association for the Properties of Water and Steam (IAPWS) 1995 formulation for the thermodynamic properties of water and the most recent IAPWS formulations for transport and other properties, this updated version provides water properties over a wide range of conditions according to the accepted international standards.

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.

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...

Non Destructive Test Dye Penetrant and Ultrasonic on Welding SMAW Butt Joint with Acceptance Criteria ASME Standard

NASA Astrophysics Data System (ADS)

Endramawan, T.; Sifa, A.

2018-02-01

The purpose of this research is to know the type of discontinuity of SMAW welding result and to determine acceptance criteria based on American Society of Mechanical Engineer (ASME) standard. Material used is mild steel 98,71% Fe and 0,212% C with hardness 230 VHN with specimen diameter 20 cm and thickness 1.2 cm which is welded use SMAW butt joint with electrode for rooting LB 52U diameter 2.6 mm, current 70 Ampere and voltage 380 volt, filler used LB 5218 electrode diameter 3.2 mm with current 80 Ampere and 380 volt. The method used to analyze the welded with non destructive test dye penetrant (PT) method to see indication on the surface of the object and Ultrasonic (UT) to see indication on the sub and inner the surface of the object, the result is discontinuity recorded and analyzed and then the discontinuity is determine acceptance criteria based on the American Society of Mechanical Engineer (ASME) standards. The result show the discontinuity of porosity on the surface of the welded and inclusion on sub material used ultrasonic test, all indication on dye penetrant or ultrasonic test if there were rejected of result of welded that there must be gouging on part which rejected and then re-welding.

High Temperature Gas Reactors: Assessment of Applicable Codes and Standards

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

McDowell, Bruce K.; Nickolaus, James R.; Mitchell, Mark R.

2011-10-31

Current interest expressed by industry in HTGR plants, particularly modular plants with power up to about 600 MW(e) per unit, has prompted NRC to task PNNL with assessing the currently available literature related to codes and standards applicable to HTGR plants, the operating history of past and present HTGR plants, and with evaluating the proposed designs of RPV and associated piping for future plants. Considering these topics in the order they are arranged in the text, first the operational histories of five shut-down and two currently operating HTGR plants are reviewed, leading the authors to conclude that while small, simplemore » prototype HTGR plants operated reliably, some of the larger plants, particularly Fort St. Vrain, had poor availability. Safety and radiological performance of these plants has been considerably better than LWR plants. Petroleum processing plants provide some applicable experience with materials similar to those proposed for HTGR piping and vessels. At least one currently operating plant - HTR-10 - has performed and documented a leak before break analysis that appears to be applicable to proposed future US HTGR designs. Current codes and standards cover some HTGR materials, but not all materials are covered to the high temperatures envisioned for HTGR use. Codes and standards, particularly ASME Codes, are under development for proposed future US HTGR designs. A 'roadmap' document has been prepared for ASME Code development; a new subsection to section III of the ASME Code, ASME BPVC III-5, is scheduled to be published in October 2011. The question of terminology for the cross-duct structure between the RPV and power conversion vessel is discussed, considering the differences in regulatory requirements that apply depending on whether this structure is designated as a 'vessel' or as a 'pipe'. We conclude that designing this component as a 'pipe' is the more appropriate choice, but that the ASME BPVC allows the owner of the facility to select the preferred designation, and that either designation can be acceptable.« less

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...

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...

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

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.

Structural Integrity of Water Reactor Pressure Boundary Components.

DTIC Science & Technology

1980-08-01

Boiler and Pressure Vessel Code , Sec. Ill). Estimates of the upper shelf K level from small-specimen...from Appendix A of Section XI of the ASME Boiler and Pressure Vessel Code [11. Figure 9 shows this same data set, together with earlier data for...0969, NRL Memo- randum Report 4063, Sep. 1979. 11. Section XI - ASME Boiler and Pressure Vessel Code , Rules for Inservice Inspection of Nuclear

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

Evaluation on the Feasibility of Using Ultrasonic Testing of Reactor Pressure Vessel Welds for Assessing Flaw Density/Distribution per 10 CFR 50.61a, Alternate Fracture Toughness Requirements for Protection Against Pressurized Thermal Shock

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

Sullivan, Edmund J.; Anderson, Michael T.

2014-06-10

This technical letter report provides the status of an assessment undertaken by PNNL at the request of the NRC to verify the capability of periodic ASME-required volumetric examinations of reactor vessels to characterize the density and distribution of flaws of interest for applying §50.61a on a plant-by-plant basis. The PTS rule, described in the Code of Federal Regulations, Title 10, Section 50.61 (§50.61), "Fracture Toughness Requirements for Protection against Pressurized Thermal Shock Events," establishes screening criteria to ensure that the potential for a reactor vessel to fail due to a PTS event is deemed to be acceptably low. Recently, themore » NRC completed a research program that concluded that the risk of through-wall cracking due to a PTS event is much lower than previously estimated. The NRC subsequently developed and promulgated an alternate PTS rule, §50.61a, that can be implemented by PWR licensees. The §50.61a rule differs from §50.61 in that it requires licensees who choose to follow this alternate method to analyze the results from periodic volumetric examinations required by the ASME Code, Section XI, Rules for Inservice Inspection (ISI) of Nuclear Power Plants.« less

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.

46 CFR 54.01-1 - Incorporation by reference.

Code of Federal Regulations, 2012 CFR

2012-10-01

...://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. The material is also...) American Society of Mechanical Engineers (ASME) International, Three Park Avenue, New York, NY 10016-5990: (1) ASME Boiler and Pressure Vessel Code, Section VIII, Division 1, Rules for Construction of...

46 CFR 54.01-1 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-10-01

...://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. The material is also...) American Society of Mechanical Engineers (ASME) International, Three Park Avenue, New York, NY 10016-5990: (1) ASME Boiler and Pressure Vessel Code, Section VIII, Division 1, Rules for Construction of...

46 CFR 54.01-1 - Incorporation by reference.

Code of Federal Regulations, 2013 CFR

2013-10-01

...://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. The material is also... of Mechanical Engineers (ASME) International, Three Park Avenue, New York, NY 10016-5990: (1) ASME Boiler and Pressure Vessel Code, Section VIII, Division 1, Rules for Construction of Pressure Vessels...

46 CFR 54.01-1 - Incorporation by reference.

Code of Federal Regulations, 2014 CFR

2014-10-01

...://www.archives.gov/federal_register/code_of_federal_regulations/ibr_locations.html. The material is also... of Mechanical Engineers (ASME) International, Three Park Avenue, New York, NY 10016-5990: (1) ASME Boiler and Pressure Vessel Code, Section VIII, Division 1, Rules for Construction of Pressure Vessels...

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...

USAF Hyperbaric Animal Transfer Chamber System.

DTIC Science & Technology

1988-01-01

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

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.

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 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...

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.

ORNL Evaluation of Electrabel Safety Cases for Doel 3 / Tihange 2: Final Report

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

Bass, Bennett Richard; Dickson, Terry L.; Gorti, Sarma B.

Oak Ridge National Laboratory (ORNL) performed a detailed technical review of the 2015 Electrabel (EBL) Safety Cases prepared for the Belgium reactor pressure vessels (RPVs) at Doel 3 and Tihange 2 (D3/T2). The Federal Agency for Nuclear Control (FANC) in Belgium commissioned ORNL to provide a thorough assessment of the existing safety margins against cracking of the RPVs due to the presence of almost laminar flaws found in each RPV. Initial efforts focused on surveying relevant literature that provided necessary background knowledge on the issues related to the quasilaminar flaws observed in D3/T2 reactors. Next, ORNL proceeded to develop anmore » independent quantitative assessment of the entire flaw population in the two Belgian reactors according to the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code, Section XI, Appendix G, Fracture Toughness Criteria for Protection Against Failure, New York (1992 and 2004). That screening assessment of all EBL-characterized flaws in D3/T2 used ORNL tools, methodologies, and the ASME Code Case N-848, Alternative Characterization Rules for QuasiLaminar Flaws . Results and conclusions from the ORNL flaw acceptance assessments of D3/T2 were compared with those from the 2015 EBL Safety Cases. Specific findings of the ORNL evaluation of that part of the EBL structural integrity assessment focusing on stability of the flaw population subjected to primary design transients include the following: ORNL s analysis results were similar to those of EBL in that very few characterized flaws were found not compliant with the ASME (1992) acceptance criterion. ORNL s application of the more recent ASME Section XI (2004) produced only four noncompliant flaws, all due to LOCAs. The finding of a greater number of non-compliant flaws in the EBL screening assessment is due principally to a significantly more restrictive (conservative) criterion for flaw size acceptance used by EBL. ORNL s screening assessment results (obtained using an analysis methodology different from that of EBL) are interpreted herein as confirming the EBL screening results for D3/T2. ORNL s independent refined analysis demonstrated the EBL-characterized flaw 1660, which is non-compliant in the ORNL and EBL screening assessment, is rendered compliant when modeled as a more realistic individual quasi-laminar flaw using a 3-D XFEM analysis approach. ORNL s and EBL s refined analyses are in good agreement for the flaw 1660 close to the clad/base metal interface; ORNL is not persuaded that repeating this exercise for more than one non-compliant flaw is necessary to accept the EBL conclusions derived from the aggregate of EBL refined analysis results. ORNL General Conclusions Regarding the Structural Integrity Assessment (SIA) Conducted by EBL for D3/T2 Based on comparative evaluations of ORNL and EBL SIA analyses and on consideration of other results, ORNL is in agreement with the general conclusions reported by Electrabel in their RPV D3/T2 Technical Summary Note of April 14, 2015: More than 99 percent of flaws in D3/T2 meet the defined screening criterion, rendering them benign with respect to initiation in the event of a design transient. Refined analyses of non-compliant flaws from the screening assessment indicate that only 11 of the 16196 detected flaws have a critical reference-temperature material index (designated RTNDT) that implies the possibility of the initiation of cleavage fracture at some future time. For those 11 2 flaws, the calculated margin in RTNDT (a measure of acceptable embrittlement relative to end-ofservice-life conditions) is significant, being greater than 80 C. Fatigue crack growth is not a concern in the flaw-acceptability analyses. Primary stress re-evaluation confirms that the collapse pressure is more than 1.5 times the design pressure in the presence of defects detected in D3/T2. Sufficient conservatisms are built into the input data and into the different steps of the SIA; in some cases, those conservatisms are quantified and imply that additional margins exist in the SIA. Taken as a whole, the foregoing results and conclusions confirm the structural integrity of Doel 3 and Tihange 2 under all design transients with ample margin in the presence of the 16196 detected flaws.« less

ASME AG-1 Section FC Qualified HEPA Filters; a Particle Loading Comparison - 13435

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

Stillo, Andrew; Ricketts, Craig I.

High Efficiency Particulate Air (HEPA) Filters used to protect personnel, the public and the environment from airborne radioactive materials are designed, manufactured and qualified in accordance with ASME AG-1 Code section FC (HEPA Filters) [1]. The qualification process requires that filters manufactured in accordance with this ASME AG-1 code section must meet several performance requirements. These requirements include performance specifications for resistance to airflow, aerosol penetration, resistance to rough handling, resistance to pressure (includes high humidity and water droplet exposure), resistance to heated air, spot flame resistance and a visual/dimensional inspection. None of these requirements evaluate the particle loading capacitymore » of a HEPA filter design. Concerns, over the particle loading capacity, of the different designs included within the ASME AG-1 section FC code[1], have been voiced in the recent past. Additionally, the ability of a filter to maintain its integrity, if subjected to severe operating conditions such as elevated relative humidity, fog conditions or elevated temperature, after loading in use over long service intervals is also a major concern. Although currently qualified HEPA filter media are likely to have similar loading characteristics when evaluated independently, filter pleat geometry can have a significant impact on the in-situ particle loading capacity of filter packs. Aerosol particle characteristics, such as size and composition, may also have a significant impact on filter loading capacity. Test results comparing filter loading capacities for three different aerosol particles and three different filter pack configurations are reviewed. The information presented represents an empirical performance comparison among the filter designs tested. The results may serve as a basis for further discussion toward the possible development of a particle loading test to be included in the qualification requirements of ASME AG-1 Code sections FC and FK[1]. (authors)« less

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

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

Swindeman, Robert W; Ren, Weiju

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

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.

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

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

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

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.

PRA and Risk Informed Analysis

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

Bernsen, Sidney A.; Simonen, Fredric A.; Balkey, Kenneth R.

2006-01-01

The Boiler and Pressure Vessel Code (BPVC) of the American Society of Mechanical Engineers (ASME) has introduced a risk based approach into Section XI that covers Rules for Inservice Inspection of Nuclear Power Plant Components. The risk based approach requires application of the probabilistic risk assessments (PRA). Because no industry consensus standard existed for PRAs, ASME has developed a standard to evaluate the quality level of an available PRA needed to support a given risk based application. The paper describes the PRA standard, Section XI application of PRAs, and plans for broader applications of PRAs to other ASME nuclear codesmore » and standards. The paper addresses several specific topics of interest to Section XI. Important consideration are special methods (surrogate components) used to overcome the lack of PRA treatments of passive components in PRAs. The approach allows calculations of conditional core damage probabilities both for component failures that cause initiating events and failures in standby systems that decrease the availability of these systems. The paper relates the explicit risk based methods of the new Section XI code cases to the implicit consideration of risk used in the development of Section XI. Other topics include the needed interactions of ISI engineers, plant operating staff, PRA specialists, and members of expert panels that review the risk based programs.« less

49 CFR 178.345-2 - Material and material thickness.

Code of Federal Regulations, 2010 CFR

2010-10-01

... authorized for cargo tanks “constructed in accordance with the ASME Code”, Section VIII. ASTM A 569 ASTM A 570 ASTM A 572 ASTM A 622 ASTM A 656 ASTM A 715 ASTM A 1008/ A 1008M, ASTM A 1011/A 1011M (2) Aluminum... ASTM specifications may be used for cargo tanks “constructed in accordance with the ASME Code”: ASTM B...

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

78 FR 25591 - Magnuson-Stevens Act Provisions; Fisheries of the Northeastern United States; Northeast...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-02

... details the method for initial ACE sub-allocation to sector members. For FY 2013, each sector has proposed... for the sectors to operate. The NE Multispecies Fishery Management Plan (FMP) allows limited access... accepting additional public comment on the revised explanation of at-sea monitoring (ASM) coverage for FY...

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

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

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

2011-01-01

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

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.

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.

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.

Technical Letter Report Development of Flaw Size Distribution Tables Including Effects of Flaw Depth Sizing Errors for Draft 10CFR 50.61a (Alternate PTS Rule) JCN-N6398, Task 4

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

Simonen, Fredric A.; Gosselin, Stephen R.; Doctor, Steven R.

2013-04-22

This document describes a new method to determine whether the flaws in a particular reactor pressure vessel are consistent with the assumptions regarding the number and sizes of flaws used in the analyses that formed the technical justification basis for the new voluntary alternative Pressurized Thermal Shock (PTS) rule (Draft 10 CFR 50.61a). The new methodology addresses concerns regarding prior methodology because ASME Code Section XI examinations do not detect all fabrication flaws, they have higher detection performance for some flaw types, and there are flaw sizing errors always present (e.g., significant oversizing of small flaws and systematic under sizingmore » of larger flaws). The new methodology allows direct comparison of ASME Code Section XI examination results with values in the PTS draft rule Tables 2 and 3 in order to determine if the number and sizes of flaws detected by an ASME Code Section XI examination are consistent with those assumed in the probabilistic fracture mechanics calculations performed in support of the development of 10 CFR 50.61a.« less

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

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

Code of Federal Regulations, 2011 CFR

2011-10-01

..., and fittings when it receives certification of their mechanical properties. Without this certification... certifying that the mechanical properties at room temperature specified in ASTM A 520 (incorporated by... manufacturer certifying that the mechanical properties for A192 in ASTM A 520 have been met. Without this...

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.

Potential advantages associated with implementing a risk-based inspection program by a nuclear facility

NASA Astrophysics Data System (ADS)

McNeill, Alexander, III; Balkey, Kenneth R.

1995-05-01

The current inservice inspection activities at a U.S. nuclear facility are based upon the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code, Section XI. The Code selects examination locations based upon a sampling criteria which includes component geometry, stress, and usage among other criteria. This can result in a significant number of required examinations. As a result of regulatory action each nuclear facility has conducted probabilistic risk assessments (PRA) or individual plant examinations (IPE), producing plant specific risk-based information. Several initiatives have been introduced to apply this new plant risk information. Among these initiatives is risk-based inservice inspection. A code case has been introduced for piping inspections based upon this new risk- based technology. This effort brought forward to the ASME Section XI Code committee, has been initiated and championed by the ASME Research Task Force on Risk-Based Inspection Guidelines -- LWR Nuclear Power Plant Application. Preliminary assessments associated with the code case have revealed that potential advantages exist in a risk-based inservice inspection program with regard to a number of exams, risk, personnel exposure, and cost.

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.

β-Agonist-mediated Relaxation of Airway Smooth Muscle Is Protein Kinase A-dependent*

PubMed Central

Morgan, Sarah J.; Deshpande, Deepak A.; Tiegs, Brian C.; Misior, Anna M.; Yan, Huandong; Hershfeld, Alena V.; Rich, Thomas C.; Panettieri, Reynold A.; An, Steven S.; Penn, Raymond B.

2014-01-01

Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects. PMID:24973219

49 CFR 195.214 - Welding procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 3 2010-10-01 2010-10-01 false Welding procedures. 195.214 Section 195.214... PIPELINE Construction § 195.214 Welding procedures. (a) Welding must be performed by a qualified welder in accordance with welding procedures qualified under Section 5 of API 1104 or Section IX of the ASME Boiler and...

49 CFR 195.214 - Welding procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 3 2014-10-01 2014-10-01 false Welding procedures. 195.214 Section 195.214... PIPELINE Construction § 195.214 Welding procedures. (a) Welding must be performed by a qualified welder in accordance with welding procedures qualified under Section 5 of API 1104 or Section IX of the ASME Boiler and...

49 CFR 195.214 - Welding procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 3 2011-10-01 2011-10-01 false Welding procedures. 195.214 Section 195.214... PIPELINE Construction § 195.214 Welding procedures. (a) Welding must be performed by a qualified welder in accordance with welding procedures qualified under Section 5 of API 1104 or Section IX of the ASME Boiler and...

49 CFR 195.214 - Welding procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 3 2013-10-01 2013-10-01 false Welding procedures. 195.214 Section 195.214... PIPELINE Construction § 195.214 Welding procedures. (a) Welding must be performed by a qualified welder in accordance with welding procedures qualified under Section 5 of API 1104 or Section IX of the ASME Boiler and...

49 CFR 195.214 - Welding procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 3 2012-10-01 2012-10-01 false Welding procedures. 195.214 Section 195.214... PIPELINE Construction § 195.214 Welding procedures. (a) Welding must be performed by a qualified welder in accordance with welding procedures qualified under Section 5 of API 1104 or Section IX of the ASME Boiler and...

Compressive sensing sectional imaging for single-shot in-line self-interference incoherent holography

NASA Astrophysics Data System (ADS)

Weng, Jiawen; Clark, David C.; Kim, Myung K.

2016-05-01

A numerical reconstruction method based on compressive sensing (CS) for self-interference incoherent digital holography (SIDH) is proposed to achieve sectional imaging by single-shot in-line self-interference incoherent hologram. The sensing operator is built up based on the physical mechanism of SIDH according to CS theory, and a recovery algorithm is employed for image restoration. Numerical simulation and experimental studies employing LEDs as discrete point-sources and resolution targets as extended sources are performed to demonstrate the feasibility and validity of the method. The intensity distribution and the axial resolution along the propagation direction of SIDH by angular spectrum method (ASM) and by CS are discussed. The analysis result shows that compared to ASM the reconstruction by CS can improve the axial resolution of SIDH, and achieve sectional imaging. The proposed method may be useful to 3D analysis of dynamic systems.

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.

46 CFR 64.2 - Incorporation by reference.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Incorporation by reference. 64.2 Section 64.2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING MARINE PORTABLE TANKS AND... sections affected, are: American Society of Mechanical Engineers (ASME) International Three Park Avenue...

Assuring Structural Integrity in Army Systems

DTIC Science & Technology

1985-02-28

power plants are* I. American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code , Section III - Rules for Construction of Nuclear...Power Plant Components; 2. ASNE Boiler and Pressure Vessel Code , Section XI, Rules for In-Service Inspection of Nuclear Power Plant Components; and 3

β-Agonist-mediated relaxation of airway smooth muscle is protein kinase A-dependent.

PubMed

Morgan, Sarah J; Deshpande, Deepak A; Tiegs, Brian C; Misior, Anna M; Yan, Huandong; Hershfeld, Alena V; Rich, Thomas C; Panettieri, Reynold A; An, Steven S; Penn, Raymond B

2014-08-15

Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

Military Power of the People’s Republic of China

DTIC Science & Technology

2009-01-01

executed for taking bribes to approve fake drugs. Environment . China’s economic development has come at a significant environmental cost. Acceptable air... ASEAN : Association of Southeast Asian Nations ASEM: Asia-Europe Meeting ASBM: Anti-Ship Ballistic Missile ASCM: Anti-Ship Cruise Missile ASM: Air-to...Capability IRBM: Intermediate-Range Ballistic Missile LACM: Land Attack Cruise Missile LEO: Low Earth Orbit MaRV: Maneuvering Re- entry Vehicle MINUSTAH

Fatigue Behavior of HY-130 Steel Weldments Containing Fabrication Discontinuities.

DTIC Science & Technology

1985-04-18

discontinuities to solutions for elliptical discontinuities. One such approach has been formalized in the ASME Section XI Boiler and Pressure Vessel Code [1... Boiler and Pressure Vessel Code , Section XI, "Rules for Inservice Inspection of Nuclear Reactor Coolant Systems," American Society of Mechanical

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.

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

Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal

PubMed Central

Valent, P.; Sotlar, K.; Sperr, W. R.; Escribano, L.; Yavuz, S.; Reiter, A.; George, T. I.; Kluin-Nelemans, H. C.; Hermine, O.; Butterfield, J. H.; Hägglund, H.; Ustun, C.; Hornick, J. L.; Triggiani, M.; Radia, D.; Akin, C.; Hartmann, K.; Gotlib, J.; Schwartz, L. B.; Verstovsek, S.; Orfao, A.; Metcalfe, D. D.; Arock, M.; Horny, H.-P.

2014-01-01

Mast cell leukemia (MCL), the leukemic manifestation of systemic mastocytosis (SM), is characterized by leukemic expansion of immature mast cells (MCs) in the bone marrow (BM) and other internal organs; and a poor prognosis. In a subset of patients, circulating MCs are detectable. A major differential diagnosis to MCL is myelomastocytic leukemia (MML). Although criteria for both MCL and MML have been published, several questions remain concerning terminologies and subvariants. To discuss open issues, the EU/US-consensus group and the European Competence Network on Mastocytosis (ECNM) launched a series of meetings and workshops in 2011–2013. Resulting discussions and outcomes are provided in this article. The group recommends that MML be recognized as a distinct condition defined by mastocytic differentiation in advanced myeloid neoplasms without evidence of SM. The group also proposes that MCL be divided into acute MCL and chronic MCL, based on the presence or absence of C-Findings. In addition, a primary (de novo) form of MCL should be separated from secondary MCL that typically develops in the presence of a known antecedent MC neoplasm, usually aggressive SM (ASM) or MC sarcoma. For MCL, an imminent prephase is also proposed. This prephase represents ASM with rapid progression and 5%–19% MCs in BM smears, which is generally accepted to be of prognostic significance. We recommend that this condition be termed ASM in transformation to MCL (ASM-t). The refined classification of MCL fits within and extends the current WHO classification; and should improve prognostication and patient selection in practice as well as in clinical trials. PMID:24675021

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

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.

49 CFR 195.110 - External loads.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., vibration, thermal expansion, and contraction must be provided for in designing a pipeline system. In providing for expansion and flexibility, section 419 of ASME/ANSI B31.4 must be followed. (b) The pipe and...

49 CFR 195.110 - External loads.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., vibration, thermal expansion, and contraction must be provided for in designing a pipeline system. In providing for expansion and flexibility, section 419 of ASME/ANSI B31.4 must be followed. (b) The pipe and...

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

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

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

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

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

PubMed

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

2017-09-07

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

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

PubMed Central

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

2011-01-01

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

Model-based segmentation of abdominal aortic aneurysms in CTA images

NASA Astrophysics Data System (ADS)

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

2003-05-01

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

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.

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

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

49 CFR 179.400-3 - Type.

Code of Federal Regulations, 2010 CFR

2010-10-01

... essentially concentric within an outer jacket of circular cross section, with the out of roundness of both the inner tank and outer jacket limited in accordance with Paragraph UG-80 in Section VIII of the ASME Code (IBR, see § 171.7 of this subchapter); (2) Have the annular space evacuated after filling the annular...

49 CFR 179.400-3 - Type.

Code of Federal Regulations, 2011 CFR

2011-10-01

... essentially concentric within an outer jacket of circular cross section, with the out of roundness of both the inner tank and outer jacket limited in accordance with Paragraph UG-80 in Section VIII of the ASME Code (IBR, see § 171.7 of this subchapter); (2) Have the annular space evacuated after filling the annular...

49 CFR 179.400-3 - Type.

Code of Federal Regulations, 2012 CFR

2012-10-01

... essentially concentric within an outer jacket of circular cross section, with the out of roundness of both the inner tank and outer jacket limited in accordance with Paragraph UG-80 in Section VIII of the ASME Code (IBR, see § 171.7 of this subchapter); (2) Have the annular space evacuated after filling the annular...

49 CFR 179.400-3 - Type.

Code of Federal Regulations, 2014 CFR

2014-10-01

... essentially concentric within an outer jacket of circular cross section, with the out of roundness of both the inner tank and outer jacket limited in accordance with Paragraph UG-80 in Section VIII of the ASME Code (IBR, see § 171.7 of this subchapter); (2) Have the annular space evacuated after filling the annular...

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...

49 CFR 178.338-16 - Inspection and testing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Inspection and testing. 178.338-16 Section 178.338... PACKAGINGS Specifications for Containers for Motor Vehicle Transportation § 178.338-16 Inspection and testing... Section VIII of the ASME Code. The welder and the welding procedure must be qualified in accordance with...

49 CFR 192.939 - What are the required reassessment intervals?

Code of Federal Regulations, 2013 CFR

2013-10-01

... Transmission Pipeline Integrity Management § 192.939 What are the required reassessment intervals? An operator... stress levels of pipeline (operating at or above 30% SMYS) listed in ASME/ANSI B31.8S, section 5, Table 3... equivalent technology following the requirements in paragraph (a)(1) of this section except that the stress...

49 CFR 192.939 - What are the required reassessment intervals?

Code of Federal Regulations, 2011 CFR

2011-10-01

... Transmission Pipeline Integrity Management § 192.939 What are the required reassessment intervals? An operator... stress levels of pipeline (operating at or above 30% SMYS) listed in ASME/ANSI B31.8S, section 5, Table 3... equivalent technology following the requirements in paragraph (a)(1) of this section except that the stress...

49 CFR 192.939 - What are the required reassessment intervals?

Code of Federal Regulations, 2012 CFR

2012-10-01

... Transmission Pipeline Integrity Management § 192.939 What are the required reassessment intervals? An operator... stress levels of pipeline (operating at or above 30% SMYS) listed in ASME/ANSI B31.8S, section 5, Table 3... equivalent technology following the requirements in paragraph (a)(1) of this section except that the stress...

49 CFR 192.939 - What are the required reassessment intervals?

Code of Federal Regulations, 2014 CFR

2014-10-01

... Transmission Pipeline Integrity Management § 192.939 What are the required reassessment intervals? An operator... stress levels of pipeline (operating at or above 30% SMYS) listed in ASME/ANSI B31.8S, section 5, Table 3... equivalent technology following the requirements in paragraph (a)(1) of this section except that the stress...

46 CFR 56.70-5 - Material.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Material. 56.70-5 Section 56.70-5 Shipping COAST GUARD..., Assembly and Erection § 56.70-5 Material. (a) Filler metal. All filler metal, including consumable insert material, must comply with the requirements of section IX of the ASME Boiler and Pressure Vessel Code...

46 CFR 56.70-5 - Material.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Material. 56.70-5 Section 56.70-5 Shipping COAST GUARD..., Assembly and Erection § 56.70-5 Material. (a) Filler metal. All filler metal, including consumable insert material, must comply with the requirements of section IX of the ASME Boiler and Pressure Vessel Code...

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...

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

The role of the AWS CWI in a major power plant outage

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

Walsh, T.W.

In March of 1988, an eight-week outage began at the Keystone Electric Generating Station, 35 miles northwest of Johnstown, Pa. This outage encompassed the complete replacement of the reheat section of a 1,7000,000 kW boiler unit, as well as major repairs to the boiler itself. The author discusses how AWS (Certified Welding Inspectors) (CWl's) played a major part in the successful completion of over 7600 ASME butt joint welds during the outage. The welding on these outages is performed in strict accordance with the Pennsylvania Electric Company Quanity Assurance Specification and the applicable codes (ASME, NBIC, ANSI and AWS).

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

PubMed

Leontovich, T A; Zvegintseva, E G

1985-10-01

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

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.

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

An evaluation of human factors research for ultrasonic inservice inspection

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

Pond, D.J.; Donohoo, D.T.; Harris, R.V. Jr.

1998-03-01

This work was undertaken to determine if human factors research has yielded information applicable to upgrading requirements in ASME Boiler and Pressure Vessel Code Section XI, improving methods and techniques in Section V, and/or suggesting relevant research. A preference was established for information and recommendations which have become accepted and standard practice. Manual Ultrasonic Testing/Inservice Inspection (UT/ISI) is a complex task subject to influence by dozens of variables. This review frequently revealed equivocal findings regarding effects of environmental variables as well as repeated indications that inspection performance may be more, and more reliably, influenced by the workers` social environment, includingmore » managerial practices, than by other situational variables. Also of significance are each inspector`s relevant knowledge, skills, and abilities, and determination of these is seen as a necessary first step in upgrading requirements, methods, and techniques as well as in focusing research in support of such programs, While understanding the effects and mediating mechanisms of the variables impacting inspection performance is a worthwhile pursuit for researchers, initial improvements in industrial UTASI performance may be achieved by implementing practices already known to mitigate the effects of potentially adverse conditions. 52 refs., 2 tabs.« less

46 CFR 54.03-1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Scope. 54.03-1 Section 54.03-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Low Temperature Operation § 54.03-1 Scope. The pressure vessels for low temperature operation shall be as required by section VIII of the ASME Boiler and Pressure Vessel...

46 CFR 54.03-1 - Scope.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Scope. 54.03-1 Section 54.03-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Low Temperature Operation § 54.03-1 Scope. The pressure vessels for low temperature operation shall be as required by section VIII of the ASME Boiler and Pressure Vessel...

46 CFR 54.03-1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Scope. 54.03-1 Section 54.03-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Low Temperature Operation § 54.03-1 Scope. The pressure vessels for low temperature operation shall be as required by section VIII of the ASME Boiler and Pressure Vessel...

46 CFR 54.03-1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Scope. 54.03-1 Section 54.03-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Low Temperature Operation § 54.03-1 Scope. The pressure vessels for low temperature operation shall be as required by section VIII of the ASME Boiler and Pressure Vessel...

46 CFR 54.03-1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Scope. 54.03-1 Section 54.03-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Low Temperature Operation § 54.03-1 Scope. The pressure vessels for low temperature operation shall be as required by section VIII of the ASME Boiler and Pressure Vessel...

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...

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.

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

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

PubMed

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

2010-08-01

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

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

PubMed

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

2018-01-01

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

Fast and accurate semi-automated segmentation method of spinal cord MR images at 3T applied to the construction of a cervical spinal cord template.

PubMed

El Mendili, Mohamed-Mounir; Chen, Raphaël; Tiret, Brice; Villard, Noémie; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

2015-01-01

To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects' images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template.

46 CFR 54.10-5 - Maximum allowable working pressure (reproduces UG-98).

Code of Federal Regulations, 2010 CFR

2010-10-01

... section VIII of the ASME Boiler and Pressure Vessel Code, together with the effect of any combination of... operating temperature, using for each temperature the applicable allowable stress value. Note: Table 54.10-5...

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.

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

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.

Estimation of prevalence of sarcopenia by using a new bioelectrical impedance analysis in Chinese community-dwelling elderly people.

PubMed

Wang, Hui; Hai, Shan; Cao, Li; Zhou, Jianghua; Liu, Ping; Dong, Bi-Rong

2016-12-28

The aim of the present study was to validate the usefulness of the new octapolar multifrequency bioelectrical impedance analysis (BIA) for assessment of appendicular skeletal muscle mass (ASM) by comparing it with that of dual-energy X-ray absorptiometry (DXA) and to investigate the prevalence of sarcopenia in Chinese community-dwelling elderly according to Asian Working Group for Sarcopenia (AWGS) definition. A cross-sectional study was conducted in communities of Chengdu, China. A total of 944 community-dwelling elderly adults aged ≥60 years were included. ASM was measured by using DXA as a criterion method to validate a standing eight-electrode multifrequency BIA (InBody 720), followed by a further estimation of the prevalence of sarcopenia according the AWGS definition. In the Bland-Altman analysis, no significant difference was found between DXA and BIA based on the ASM measurements. The prevalence of AWGS-defined sarcopenia was 12.5% in the elderly women and 8.2% in the elderly men. BIA is suitable for body composition monitoring (ASM) in elderly Chinese as a fast, noninvasive, and convenient method; therefore, it may be a better choice in large epidemiological studies in the Chinese population. The prevalence of AWGS-defined sarcopenia was approximately 10.4% and increased with age in the Chinese community-dwelling elderly in this study.

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.

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

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.

76 FR 11191 - Hazardous Materials: Adoption of ASME Code Section XII and the National Board Inspection Code

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

... parts of the National Board Inspection Code at http://www.nationalboard.org . DATES: The comment period... edition of the National Board Inspection Code for public review at www.nationalboard.org . Both documents...

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

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.

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.

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.

Ratio of Dietary n-6/n-3 Polyunsaturated Fatty Acids Independently Related to Muscle Mass Decline in Hemodialysis Patients.

PubMed

Wong, Te-Chih; Chen, Yu-Tong; Wu, Pei-Yu; Chen, Tzen-Wen; Chen, Hsi-Hsien; Chen, Tso-Hsiao; Yang, Shwu-Huey

2015-01-01

n-3 polyunsaturated fatty acids (PUFAs) might be useful nutritional strategy for treating patients with sarcopenia. We evaluated the effect of the intake of dietary n-3 PUFAs on the skeletal muscle mass (SMM), appendicular skeletal muscle mass (ASM), and its determinants in patients receiving standard hemodialysis (HD) treatment for the management of end stage renal disease. In this cross-sectional study, data of 111 HD patients were analyzed. Anthropometric and bioelectrical impedance measurements used to estimate the muscle mass were performed the day of dialysis immediately after the dialysis session. Routine laboratory and 3-day dietary data were also collected. The cutoff value of adequate intake (AI) for both n-3 PUFAs and alpha-linolenic acid (ALA) was 1.6 g/day and 1.1 g/day for men and women, respectively. The mean age, mean dietary n-3 PUFAs intake, ALA intake, ratio of n-6/n-3 PUFAs intake, SMM, and ASM of patients were 61.4 ± 10.4 years, 2.0 ± 1.3 g/day, 1.5 ± 1.0 g/day, 9.5 ± 6.7 g/day, 23.9 ± 5.5 kg, and 17.5 ± 4.5 kg, respectively. A higher SMM and ASM significantly observed in patients who achieved an AI of n-3 PUFAs. Similar trends appeared to be observed among those patients who achieved the AI of ALA, but the difference was not significantly, except for ASM (P = 0.047). No relevant differences in demographics, laboratory and nutritional parameters were observed, regardless of whether the patients achieved an AI of n-3 PUFAs. Multivariate analysis showed that the BMI and equilibrated Kt/V were independent determinants of the muscle mass. Moreover, the ratio of n-6/n-3 PUFAs was an independent risk determinant of reduced ASM in HD patients. Patients with an AI of n-3 PUFAs had better total-body SMM and ASM. A higher dietary ratio of n-6/n-3 PUFAs seemed to be associated with a reduced muscle mass in HD patients.

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...

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

46 CFR 52.25-3 - Feedwater heaters (modifies PFH-1).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Feedwater heaters (modifies PFH-1). 52.25-3 Section 52.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS Other Boiler Types § 52.25-3 Feedwater heaters (modifies PFH-1). In addition to the requirements in PFH-1 of section I of the ASME Boiler and...

46 CFR 52.25-3 - Feedwater heaters (modifies PFH-1).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Feedwater heaters (modifies PFH-1). 52.25-3 Section 52.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS Other Boiler Types § 52.25-3 Feedwater heaters (modifies PFH-1). In addition to the requirements in PFH-1 of section I of the ASME Boiler and...

46 CFR 52.25-3 - Feedwater heaters (modifies PFH-1).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Feedwater heaters (modifies PFH-1). 52.25-3 Section 52.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS Other Boiler Types § 52.25-3 Feedwater heaters (modifies PFH-1). In addition to the requirements in PFH-1 of section I of the ASME Boiler and...

46 CFR 52.25-3 - Feedwater heaters (modifies PFH-1).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Feedwater heaters (modifies PFH-1). 52.25-3 Section 52.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS Other Boiler Types § 52.25-3 Feedwater heaters (modifies PFH-1). In addition to the requirements in PFH-1 of section I of the ASME Boiler and...

46 CFR 52.25-3 - Feedwater heaters (modifies PFH-1).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Feedwater heaters (modifies PFH-1). 52.25-3 Section 52.25-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS Other Boiler Types § 52.25-3 Feedwater heaters (modifies PFH-1). In addition to the requirements in PFH-1 of section I of the ASME Boiler and...

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

16 CFR 1450.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Definitions. 1450.2 Section 1450.2... GRAEME BAKER POOL AND SPA SAFETY ACT REGULATIONS § 1450.2 Definitions. (a) [Reserved] (b) Unblockable... American Society of Mechanical Engineers (ASME), ATTN: Secretary, A112 Standards Committee, Three Park...

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

Corrosion fatigue of alloys 600 and 690 in simulated LWR environments

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

Ruther, W.E.; Soppett, W.K.; Kassner, T.F.

1996-04-01

Crack growth data were obtained on fracture-mechanics specimens of Alloys 600 and 690 to investigate environmentally assisted cracking (EAC) in simulated boiling water reactor and pressurized water reactor environments at 289 and 320 C. Preliminary information was obtained on the effect of temperature, load ratio, stress intensity (K), and the dissolved-oxygen and -hydrogen concentrations of the water on EAC. Specimens of Type 316NG and sensitized Type 304 stainless steel (SS) were included in several of the experiments to assess the behavior of these materials and Alloy 600 under the same water chemistry and loading conditions. The experimental data are comparedmore » with predictions from an Argonne National Laboratory (ANL) model for crack growth rates (CGRs) of SSs in water and the ASME Code Section 11 correlation for CGRs in air at the K{sub max} and load-ratio values in the various tests. The data for all of the materials were bounded by ANL model predictions and the ASME Section 11 ``air line.``« less

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

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.

49 CFR 178.345-14 - Marking.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Specifications for Containers for Motor Vehicle Transportation § 178.345-14 Marking. (a) General. The manufacturer shall certify that each cargo tank motor vehicle has been designed, constructed and tested in....348) cargo tank requirements and, when applicable, with Section VIII of the ASME Code (IBR, see § 171...

46 CFR 38.01-3 - Incorporation by reference.

Code of Federal Regulations, 2011 CFR

2011-10-01

... incorporation by reference in this part, and the sections affected, are: American Society for Nondestructive...) American Society of Mechanical Engineers (ASME) International Three Park Avenue, New York, NY 10016-5990...) American Society for Testing and Materials (ASTM) 100 Barr Harbor Drive, West Conshohocken, PA 19428-2959...

46 CFR 38.01-3 - Incorporation by reference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... incorporation by reference in this part, and the sections affected, are: American Society for Nondestructive...) American Society of Mechanical Engineers (ASME) International Three Park Avenue, New York, NY 10016-5990...) American Society for Testing and Materials (ASTM) 100 Barr Harbor Drive, West Conshohocken, PA 19428-2959...

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.

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.

Ratio of dietary ω-3 and ω-6 fatty acids-independent determinants of muscle mass-in hemodialysis patients with diabetes.

PubMed

Wong, Te-Chih; Chen, Yu-Tong; Wu, Pei-Yu; Chen, Tzen-Wen; Chen, Hsi-Hsien; Chen, Tso-Hsiao; Hsu, Yung-Ho; Yang, Shwu-Huey

2016-09-01

ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) are essential nutrients in the human diet and possibly affect muscle mass. We evaluated the association between the dietary ratios of ω-3 and ω-6 PUFAs and muscle mass, indicated as skeletal muscle mass (SMM) and appendicular skeletal muscle mass (ASM), in patients with diabetes undergoing hemodialysis (HD). In this cross-sectional study, data on 69 patients with diabetes who underwent standard HD therapy were analyzed. For estimating muscle mass, anthropometric and bioelectrical impedance analyses were conducted following dialysis. In addition, routine laboratory and 3-d dietary data were obtained. The adequate intake (AI) cut-off for ω-3 PUFAs was 1.6 g/d and 1.1 g/d for male and female patients, respectively. The average age of the participants was 63.0 ± 10.4 y. The mean ratios of ω-3/ω-6 PUFA intake, ω-6/ω-3 PUFA intake, SMM, and ASM of the patients were 0.13 ± 0.07, 9.4 ± 6.4, 24.6 ± 5.4 kg, and 18.3 ± 4.6 kg, respectively. Patients who had AI of ω-3 PUFAs had significantly higher SMM and ASM than did their counterparts. Linear and stepwise multivariable adjustment analyses revealed that insulin resistance and the ω-6/ω-3 PUFA ratio were the independent deleterious determinants of ASM normalized to height in HD patients. Patients with AI of ω-3 PUFAs had total-body SMM and ASM that were more appropriate. A higher dietary ratio of ω-6/ω-3 PUFAs was associated with reduced muscle mass in HD patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Fast and Accurate Semi-Automated Segmentation Method of Spinal Cord MR Images at 3T Applied to the Construction of a Cervical Spinal Cord Template

PubMed Central

El Mendili, Mohamed-Mounir; Trunet, Stéphanie; Pélégrini-Issac, Mélanie; Lehéricy, Stéphane; Pradat, Pierre-François; Benali, Habib

2015-01-01

Objective To design a fast and accurate semi-automated segmentation method for spinal cord 3T MR images and to construct a template of the cervical spinal cord. Materials and Methods A semi-automated double threshold-based method (DTbM) was proposed enabling both cross-sectional and volumetric measures from 3D T2-weighted turbo spin echo MR scans of the spinal cord at 3T. Eighty-two healthy subjects, 10 patients with amyotrophic lateral sclerosis, 10 with spinal muscular atrophy and 10 with spinal cord injuries were studied. DTbM was compared with active surface method (ASM), threshold-based method (TbM) and manual outlining (ground truth). Accuracy of segmentations was scored visually by a radiologist in cervical and thoracic cord regions. Accuracy was also quantified at the cervical and thoracic levels as well as at C2 vertebral level. To construct a cervical template from healthy subjects’ images (n=59), a standardization pipeline was designed leading to well-centered straight spinal cord images and accurate probability tissue map. Results Visual scoring showed better performance for DTbM than for ASM. Mean Dice similarity coefficient (DSC) was 95.71% for DTbM and 90.78% for ASM at the cervical level and 94.27% for DTbM and 89.93% for ASM at the thoracic level. Finally, at C2 vertebral level, mean DSC was 97.98% for DTbM compared with 98.02% for TbM and 96.76% for ASM. DTbM showed similar accuracy compared with TbM, but with the advantage of limited manual interaction. Conclusion A semi-automated segmentation method with limited manual intervention was introduced and validated on 3T images, enabling the construction of a cervical spinal cord template. PMID:25816143

Association between visceral obesity and sarcopenia and vitamin D deficiency in older Koreans: the Ansan Geriatric Study.

PubMed

Seo, Ji A; Cho, Hyunjoo; Eun, Chai R; Yoo, Hye J; Kim, Sin G; Choi, Kyung M; Baik, Sei H; Choi, Dong S; Park, Moon H; Han, Changsu; Kim, Nan H

2012-04-01

To investigate whether vitamin D levels are independently associated with visceral obesity, sarcopenia, or sarcopenic obesity. Cross-sectional. Population-based sample of elderly adults living in Ansan, Korea. Two hundred sixteen men and 268 women aged 65 and older. Serum 25-hydroxyvitamin D (25(OH)D) levels, visceral fat area (VFA) according to abdominal computed tomography scanning, and body composition (body fat percentage, appendicular skeletal muscle mass (ASM)) using dual-energy X-ray absorptiometry. Visceral obesity was defined as VFA of 100 cm(2) or greater and sarcopenia as ASM/height(2) more than 1 standard deviation (SD) below the sex-specific mean of a young reference group. The adjusted 25(OH)D level for men was negatively associated with systolic blood pressure, VFA, and body fat percentage but positively associated with ASM. In women, waist circumference, triglyceride levels, and VFA were negatively correlated with 25(OH)D levels. In the joint regression model, VFA and ASM were independently associated with 25(OH)D levels (β = -0.078, P = .01 and β = 0.087, P = .02, respectively) per 1SD difference in VFA and ASM in men but not women. When participants were categorized according to four visceral obesity and sarcopenia categories, adjusted mean 25(OH)D level was lower in men with visceral obesity than in men without but was not affected by the presence or absence of sarcopenia. Greater visceral fat and lower muscle mass were associated with lower 25(OH)D levels in elderly Korean men, suggesting that screening for vitamin D deficiency may be appropriate in older Koreans with visceral obesity or sarcopenia. Sarcopenic obesity as defined according to prespecified criteria did not have an additive association with 25(OH)D levels. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

Mehanical Properties of Electron Beam Welded Joints in Thick Gage CA6NM Stainless Steel

NASA Astrophysics Data System (ADS)

Sarafan, Sheida; Wanjara, Priti; Gholipour, Javad; Champliaud, Henri; Mathieu, Louis

2017-10-01

Design of hydroelectric turbine components requires high integrity welds (without detectable volumetric defects) in heavy gage sections of stainless steel materials, such as ASTM A743 grade CA6NM—a low carbon 13% Cr-4% Ni martensitic stainless steel that is manufactured in cast form. In this work, 90-mm-thick plates of CA6NM were joined using a single-pass autogenous electron beam (EB) welding process and the mechanical properties were evaluated in the as-welded condition to characterize the performance of the joints. The static tensile properties that were evaluated in two directions—transverse and longitudinal to the EB weld seam—demonstrated conformance of the joints with the requirements of the ASME Section IX standard. The Charpy impact energies of the EB welds—measured at -18 °C on samples with V-notch roots located in the fusion and heat-affected zones—met the minimum requirements of 27 J specified in ASME Section VIII standard. In addition, bend tests that were conducted on the entire weld cross section displayed no discontinuities on the tension side of the bent joints. Hence, the developed EB welding process was demonstrated to render high-performance joints and promises key advantages for industrialization, such as cost savings through reductions in consumable material, production time and labor intensity.

Design and fabrication considerations for stainless steel liquid helium jackets surrounding SCRF cavities

NASA Astrophysics Data System (ADS)

Bonnema, E. C.; Cunningham, E. K.; Rumel, J. D.

2014-01-01

The Department of Energy requires its subcontractors to meet 10 CFR 851 Appendix A Part 4 for all new pressure vessels and pressure piping. The stainless steel pressure vessel boundaries surrounding SCRF cavities fall under this requirement. Methods for meeting this requirement include design and fabrication of the pressure vessels to meet the requirements of the ASME Boiler & Pressure Vessel Code Section VIII Division 1 or Division 2. Design considerations include determining whether the configuration of the SCRF cavity can be accommodated under the rules of Division 1 or must be analyzed under Division 2 Part 4 Design by Rule Requirements or Part 5 Design by Analysis Requirements. Regardless of the Division or Part choice, designers will find the rules of the ASME Code require thicker pressure boundary members, larger welds, and additional non-destructive testing and quality assurance requirements. These challenges must be met and overcome by the fabricator through the development of robust, detailed, and repeatable manufacturing processes. In this paper we discuss the considerations for stainless steel pressure vessels that must meet the ASME Code and illustrate the discussion with examples from direct experience fabricating such vessels.

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.

49 CFR 178.337-3 - Structural integrity.

Code of Federal Regulations, 2010 CFR

2010-10-01

... calculated design stress at any point in the cargo tank may not exceed the maximum allowable stress value... maximum design stress at any point in the cargo tank must be calculated separately for the loading... with Section VIII of the ASME Code. The cargo tank design must include calculation of stresses...

40 CFR 194.22 - Quality assurance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Quality assurance. 194.22 Section 194... General Requirements § 194.22 Quality assurance. (a)(1) As soon as practicable after April 9, 1996, the Department shall adhere to a quality assurance program that implements the requirements of ASME NQA-1-1989...

Fracture Analysis of Welded Type 304 Stainless Steel Pipe

DTIC Science & Technology

1986-11-01

American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code . In order to accomplish these objectives, a series of seven full...Mechanical Engineers Boiler and Pressure Vessel Code , Section XI IWB-3640 (Winter Addenda 1983). 5. Ranganath, S., and U.S. Mehta, "Engineering Methods for

49 CFR 178.337-16 - Testing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Specifications for Containers for Motor Vehicle Transportation § 178.337-16 Testing. (a) Inspection and tests. Inspection of materials of construction of the cargo tank and its appurtenances and original test and inspection of the finished cargo tank and its appurtenances must be as required by Section VIII of the ASME...

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

Ji, Yamei; Yang, Xin; Su, Huixia

2018-02-01

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

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

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.

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

Management Sciences Division Annual Report (10th)

DTIC Science & Technology

1993-01-01

of the Weapon System Management Information System (WSMIS). TheI Aircraft Sustainability Model ( ASM ) is the computational technique employed by...provisioning. We enhanced the capabilities of RBIRD by using the Aircraft Sustainability Model ( ASM ) for the spares calculation. ASM offers many... ASM for several years to 3 compute spares for war. It is also fully compatible with the Air Force’s peacetime spares computation system (D041). This

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

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.

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.

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.

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.

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

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

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.

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-04-15

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

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.

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.

ASTM and ASME-BPE Standards--Complying with the Needs of the Pharmaceutical Industry.

PubMed

Huitt, William M

2011-01-01

Designing and building a pharmaceutical facility requires the owner, engineer of record, and constructor to be knowledgeable with regard to the industry codes and standards that apply to this effort. Up until 1997 there were no industry standards directed at the needs and requirements of the pharmaceutical industry. Prior to that time it was a patchwork effort at resourcing and adopting nonpharmaceutical-related codes and standards and then modifying them in order to meet the more stringent requirements of the Food and Drug Administration (FDA). In 1997 the American Society of Mechanical Engineers (ASME) published the first Bioprocessing Equipment (BPE) Standard. Through harmonization efforts this relatively new standard has brought together, scrutinized, and refined industry accepted methodologies together with FDA compliance requirements, and has established an American National Standard that provides a comprehensive set of standards that are integral to the pharmaceutical industry. This article describes various American National Standards, including those developed and published by the American Society for Testing and Materials (ASTM), and how they apply to the pharmaceutical industry. It goes on to discuss the harmonization effort that takes place between the various standards developers in an attempt to prevent conflicts and omissions between the many standards. Also included are examples of tables and figures taken from the ASME-BPE Standard. These examples provide the reader with insight to the relevant content of the ASME-BPE Standard. Designing and building a pharmaceutical facility requires the owner, engineer of record, and constructor to be knowledgeable with regard to the industry codes and standards that apply to this effort. Up until 1997 there were no industry standards directed at the needs and requirements of the pharmaceutical industry. Prior to that time it was a patchwork effort at resourcing and adopting nonpharmaceutical-related codes and standards and then modifying them in order to meet the more stringent requirements of the Food and Drug Administration (FDA). In 1997 the American Society of Mechanical Engineers (ASME) published the first Bioprocessing Equipment (BPE) Standard. In its initial development and ongoing maintenance it works with other American National Standards developers to harmonize the many standards associated with the design, engineering, and construction of bioprocessing facilities. This harmonization effort has established a comprehensive set of standards for the betterment of the pharmaceutical industry at large. This effort is, and will remain, very important as technology, along with new and improved product and processes, evolve into the future.

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

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

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

2014-06-15

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

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.

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.

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.

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.

75 FR 80765 - Hazardous Materials: Adoption of ASME Code Section XII and the National Board Inspection Code

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... requirement for allowable peak secondary stresses for MC 331 cargo tanks. 4. Rational Design of Non-circular... the design, construction, and certification of cargo tank motor vehicles, cryogenic portable tanks and... CTMV: Cargo Tank Motor Vehicle DCE: Design Certifying Engineer FMCSA: Federal Motor Carrier Safety...

49 CFR 195.3 - Incorporation by reference.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Fittings Industry, Inc. (MSS), 127 Park Street, NE., Vienna, VA 22180. 5. American Society for Testing and...)) §§ 195.205(b)(1); 195.432(b). (12) API Standard 1104, “Welding of Pipelines and Related Facilities” (20th....307(e). (7) 2007 ASME Boiler & Pressure Vessel Code, Section IX: “Qualification Standard for Welding...

46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 57.02-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING... qualifications for all types of welders and brazers, the qualification of welding procedures, and the production tests for all types of manual and machine arc and gas welding and brazing processes shall be in...

77 FR 54839 - Clarification of Submission of Requests for Relief or Alternatives From the Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... the examination or testing, evaluates the susceptibility to known degradation, mechanisms or failure... and applicants have not been supported by adequate descriptive and detailed technical information... attempted. Sections 50.55a(f)(6)(i) and (g)(6)(i) state that the NRC will evaluate determinations that ASME...

The Effect of Weld Metal Strength Mismatch on the Deformation and Fracture Behavior of Steel Butt Weldments

DTIC Science & Technology

1991-01-01

Society 6 of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code [ 1980]. Their results are similar to those of Satoh and Toyoda, and are...E813-89. American Society of Mechanical Engineers, Boiler and Pressure Vessel Code , Section III, Nuclear Power Plant Components, 1980. American

75 FR 1655 - Biweekly Notice Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

... environmental impact statement or environmental assessment need be prepared for these amendments. If the... (ADAMS) Public Electronic Reading Room on the internet at the NRC Web site, http://www.nrc.gov/reading-rm... Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code, Section XI as the source of...

46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 57.02-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING... qualifications for all types of welders and brazers, the qualification of welding procedures, and the production tests for all types of manual and machine arc and gas welding and brazing processes shall be in...

46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 57.02-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING... qualifications for all types of welders and brazers, the qualification of welding procedures, and the production tests for all types of manual and machine arc and gas welding and brazing processes shall be in...

46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 57.02-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING... qualifications for all types of welders and brazers, the qualification of welding procedures, and the production tests for all types of manual and machine arc and gas welding and brazing processes shall be in...

46 CFR 57.02-2 - Adoption of section IX of the ASME Code.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 57.02-2 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING WELDING... qualifications for all types of welders and brazers, the qualification of welding procedures, and the production tests for all types of manual and machine arc and gas welding and brazing processes shall be in...

78 FR 48727 - Proposed Revisions to Design of Structures, Components, Equipment and Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-09

... Analysis Reports for Nuclear Power Plants: LWR Edition,'' Section 3.9.3 ``ASME Code Class 1, 2, and 3...'s Agencywide Documents Access and Management System (ADAMS): You may access publicly available... operational readiness of snubbers (ADAMS Accession No. ML070720041), and review interfaces have been updated...

DEVELOPMENT OF ASME SECTION X CODE RULES FOR HIGH PRESSURE COMPOSITE HYDROGEN PRESSURE VESSELS WITH NON-LOAD SHARING LINERS

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

Rawls, G.; Newhouse, N.; Rana, M.

2010-04-13

The Boiler and Pressure Vessel Project Team on Hydrogen Tanks was formed in 2004 to develop Code rules to address the various needs that had been identified for the design and construction of up to 15000 psi hydrogen storage vessel. One of these needs was the development of Code rules for high pressure composite vessels with non-load sharing liners for stationary applications. In 2009, ASME approved new Appendix 8, for Section X Code which contains the rules for these vessels. These vessels are designated as Class III vessels with design pressure ranging from 20.7 MPa (3,000 ps)i to 103.4 MPamore » (15,000 psi) and maximum allowable outside liner diameter of 2.54 m (100 inches). The maximum design life of these vessels is limited to 20 years. Design, fabrication, and examination requirements have been specified, included Acoustic Emission testing at time of manufacture. The Code rules include the design qualification testing of prototype vessels. Qualification includes proof, expansion, burst, cyclic fatigue, creep, flaw, permeability, torque, penetration, and environmental testing.« less

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.

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

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

Creep and Creep-Fatigue Crack Growth at Structural Discontinuities and Welds

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

Dr. F. W. Brust; Dr. G. M. Wilkowski; Dr. P. Krishnaswamy

2010-01-27

The subsection ASME NH high temperature design procedure does not admit crack-like defects into the structural components. The US NRC identified the lack of treatment of crack growth within NH as a limitation of the code and thus this effort was undertaken. This effort is broken into two parts. Part 1, summarized here, involved examining all high temperature creep-fatigue crack growth codes being used today and from these, the task objective was to choose a methodology that is appropriate for possible implementation within NH. The second part of this task, which has just started, is to develop design rules formore » possible implementation within NH. This second part is a challenge since all codes require step-by-step analysis procedures to be undertaken in order to assess the crack growth and life of the component. Simple rules for design do not exist in any code at present. The codes examined in this effort included R5, RCC-MR (A16), BS 7910, API 579, and ATK (and some lesser known codes). There are several reasons that the capability for assessing cracks in high temperature nuclear components is desirable. These include: (1) Some components that are part of GEN IV reactors may have geometries that have sharp corners - which are essentially cracks. Design of these components within the traditional ASME NH procedure is quite challenging. It is natural to ensure adequate life design by modeling these features as cracks within a creep-fatigue crack growth procedure. (2) Workmanship flaws in welds sometimes occur and are accepted in some ASME code sections. It can be convenient to consider these as flaws when making a design life assessment. (3) Non-destructive Evaluation (NDE) and inspection methods after fabrication are limited in the size of the crack or flaw that can be detected. It is often convenient to perform a life assessment using a flaw of a size that represents the maximum size that can elude detection. (4) Flaws that are observed using in-service detection methods often need to be addressed as plants age. Shutdown inspection intervals can only be designed using creep and creep-fatigue crack growth techniques. (5) The use of crack growth procedures can aid in examining the seriousness of creep damage in structural components. How cracks grow can be used to assess margins on components and lead to further safe operation. After examining the pros and cons of all these methods, the R5 code was chosen as the most up-to-date and validated high temperature creep and creep fatigue code currently used in the world at present. R5 is considered the leader because the code: (1) has well established and validated rules, (2) has a team of experts continually improving and updating it, (3) has software that can be used by designers, (4) extensive validation in many parts with available data from BE resources as well as input from Imperial college's database, and (5) was specifically developed for use in nuclear plants. R5 was specifically developed for use in gas cooled nuclear reactors which operate in the UK and much of the experience is based on materials and temperatures which are experienced in these reactors. If the next generation advanced reactors to be built in the US used these same materials within the same temperature ranges as these reactors, then R5 may be appropriate for consideration of direct implementation within ASME code NH or Section XI. However, until more verification and validation of these creep/fatigue crack growth rules for the specific materials and temperatures to be used in the GEN IV reactors is complete, ASME should consider delaying this implementation. With this in mind, it is this authors opinion that R5 methods are the best available for code use today. The focus of this work was to examine the literature for creep and creep-fatigue crack growth procedures that are well established in codes in other countries and choose a procedure to consider implementation into ASME NH. It is very important to recognize that all creep and creep fatigue crack growth procedures that are part of high temperature design codes are related and very similar. This effort made no attempt to develop a new creep-fatigue crack growth predictive methodology. Rather examination of current procedures was the only goal. The uncertainties in the R5 crack growth methods and recommendations for more work are summarized here also.« less

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

PubMed Central

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

2009-01-01

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

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

PubMed

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

2014-01-01

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

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

PubMed

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

2016-01-01

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

The Effect of Cold Work on Properties of Alloy 617

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

Wright, Richard

2014-08-01

Alloy 617 is approved for non-nuclear construction in the ASME Boiler and Pressure Vessel Code Section I and Section VIII, but is not currently qualified for nuclear use in ASME Code Section III. A draft Code Case was submitted in 1992 to qualify the alloy for nuclear service but efforts were stopped before the approval process was completed.1 Renewed interest in high temperature nuclear reactors has resulted in a new effort to qualify Alloy 617 for use in nuclear pressure vessels. The mechanical and physical properties of Alloy 617 were extensively characterized for the VHTR programs in the 1980’s andmore » incorporated into the 1992 draft Code Case. Recently, the properties of modern heats of the alloy that incorporate an additional processing step, electro-slag re-melting, have been characterized both to confirm that the properties of contemporary material are consistent with those in the historical record and to increase the available database. A number of potential issues that were identified as requiring further consideration prior to the withdrawal of the 1992 Code Case are also being re-examined in the current R&D program. Code Cases are again being developed to allow use of Alloy 617 for nuclear design within the rules of the ASME Boiler and Pressure Vessel Code. In general the Code defines two temperature ranges for nuclear design with austenitic and nickel based alloys. Below 427°C (800°F) time dependent behavior is not considered, while above this temperature creep and creep-fatigue are considered to be the dominant life-limiting deformation modes. There is a corresponding differentiation in the treatment of the potential for effects associated with cold work. Below 427°C the principal issue is the relationship between the level of cold work and the propensity for stress corrosion cracking and above that temperature the primary concern is the impact of cold work on creep-rupture behavior.« less

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

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

PubMed

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

2015-05-01

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

Progress Report on Alloy 617 Time Dependent Allowables

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

Wright, Julie Knibloe

2015-06-01

Time dependent allowable stresses are required in the ASME Boiler and Pressure Vessel Code for design of components in the temperature range where time dependent deformation (i.e., creep) is expected to become significant. There are time dependent allowable stresses in Section IID of the Code for use in the non-nuclear construction codes, however, there are additional criteria that must be considered in developing time dependent allowables for nuclear components. These criteria are specified in Section III NH. St is defined as the lesser of three quantities: 100% of the average stress required to obtain a total (elastic, plastic, primary andmore » secondary creep) strain of 1%; 67% of the minimum stress to cause rupture; and 80% of the minimum stress to cause the initiation of tertiary creep. The values are reported for a range of temperatures and for time increments up to 100,000 hours. These values are determined from uniaxial creep tests, which involve the elevated temperature application of a constant load which is relatively small, resulting in deformation over a long time period prior to rupture. The stress which is the minimum resulting from these criteria is the time dependent allowable stress St. In this report data from a large number of creep and creep-rupture tests on Alloy 617 are analyzed using the ASME Section III NH criteria. Data which are used in the analysis are from the ongoing DOE sponsored high temperature materials program, form Korea Atomic Energy Institute through the Generation IV VHTR Materials Program and historical data from previous HTR research and vendor data generated in developing the alloy. It is found that the tertiary creep criterion determines St at highest temperatures, while the stress to cause 1% total strain controls at low temperatures. The ASME Section III Working Group on Allowable Stress Criteria has recommended that the uncertainties associated with determining the onset of tertiary creep and the lack of significant cavitation associated with early tertiary creep strain suggest that the tertiary creep criteria is not appropriate for this material. If the tertiary creep criterion is dropped from consideration, the stress to rupture criteria determines St at all but the lowest temperatures.« less

Low skeletal muscle mass is associated with poor structural parameters of bone and impaired balance in elderly men--the MINOS study.

PubMed

Szulc, Pawel; Beck, Tom J; Marchand, François; Delmas, Pierre D

2005-05-01

In 796 men, 50-85 years of age, decreased relative skeletal muscle mass index was associated with narrower bones, thinner cortices, and a consequent decreased bending strength (lower section modulus), as well as with impaired balance and an increased risk of falls. In men, appendicular skeletal muscle mass (ASM) is correlated positively with BMC and areal BMD (aBMD). In elderly men, low muscle mass and strength (sarcopenia) is associated with difficulties in daily living activities. The aim of this study was to evaluate if ASM is correlated with bone size, mechanical properties of bones, balance, and risk of falls in elderly men. This study used 796 men, 50-85 years of age, belonging to the MINOS cohort. Lifestyle factors were evaluated by standardized questionnaires. Estimates of mechanical bone properties were derived from aBMD measured by DXA. ASM was estimated by DXA. The relative skeletal muscle mass index (RASM) was calculated as ASM/(body height)(2.3). After adjustment for age, body size, tobacco smoking, professional physical activity, and 17beta-estradiol concentration, RASM was correlated positively with BMC, aBMD, external diameter, and cortical thickness (r = 0.17-0.34, p < 0.0001) but not with volumetric BMD. Consequently, RASM was correlated with section modulus (r = 0.29-0.39, p < 0.0001). Men in the lowest quartile of RASM had section modulus of femoral neck and distal radius lower by 12-18% in comparison with men in the highest quartile of RASM. In contrast, bone width was not correlated with fat mass, reflecting the load of body weight (except for L(3)), which suggests that the muscular strain may exert a direct stimulatory effect on periosteal apposition. After adjustment for confounding variables, a decrease in RASM was associated with increased risk of falls and of inability to accomplish clinical tests of muscle strength, static balance, and dynamic balance (odds ratio per 1 SD decrease in RASM, 1.31-2.23; p < 0.05-0.001). In elderly men, decreased RASM is associated with narrower bones and thinner cortices, which results in a lower bending strength. Low RASM is associated with impaired balance and with an increased risk of falls in elderly men. It remains to be studied whether low RASM is associated with decreased periosteal apposition and with increased fracture risk in elderly men, and whether the difference in skeletal muscle mass between men and women contributes to the between-sex difference in fracture incidence.

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

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

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

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

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

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

46 CFR 197.204 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

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

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

NASA Astrophysics Data System (ADS)

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

2013-09-01

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

Tissue-specific patterns of allelically-skewed DNA methylation

PubMed Central

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

2016-01-01

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

49 CFR 178.277 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2011 CFR

2011-10-01

... design pressure in the ASME Code, Section VIII (IBR, see § 171.7 of this subchapter). Holding time is the... 49 Transportation 3 2011-10-01 2011-10-01 false Requirements for the design, construction... FOR PACKAGINGS Specifications for Portable Tanks § 178.277 Requirements for the design, construction...

49 CFR 178.277 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2012 CFR

2012-10-01

... design pressure in the ASME Code, Section VIII (IBR, see § 171.7 of this subchapter). Holding time is the... 49 Transportation 3 2012-10-01 2012-10-01 false Requirements for the design, construction... FOR PACKAGINGS Specifications for Portable Tanks § 178.277 Requirements for the design, construction...

49 CFR 178.277 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2014 CFR

2014-10-01

... design pressure in the ASME Code, Section VIII (IBR, see § 171.7 of this subchapter). Holding time is the... 49 Transportation 3 2014-10-01 2014-10-01 false Requirements for the design, construction... FOR PACKAGINGS Specifications for Portable Tanks § 178.277 Requirements for the design, construction...

49 CFR 178.277 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2010 CFR

2010-10-01

... design pressure in the ASME Code, Section VIII (IBR, see § 171.7 of this subchapter). Holding time is the... 49 Transportation 2 2010-10-01 2010-10-01 false Requirements for the design, construction... FOR PACKAGINGS Specifications for Portable Tanks § 178.277 Requirements for the design, construction...

49 CFR 178.277 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2013 CFR

2013-10-01

... design pressure in the ASME Code, Section VIII (IBR, see § 171.7 of this subchapter). Holding time is the... 49 Transportation 3 2013-10-01 2013-10-01 false Requirements for the design, construction... FOR PACKAGINGS Specifications for Portable Tanks § 178.277 Requirements for the design, construction...

46 CFR 54.30-5 - Limitations and requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... pounds per square inch, thickness of shell is not greater than 1 inch, and the design temperature is not greater than 115 °F. (3) It will carry liquids of specific gravity no greater than 1.05. (4) Design... designs involving the following types of welded connections shown in UW-16.1 of section VIII of the ASME...

46 CFR 54.30-5 - Limitations and requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pounds per square inch, thickness of shell is not greater than 1 inch, and the design temperature is not greater than 115 °F. (3) It will carry liquids of specific gravity no greater than 1.05. (4) Design... designs involving the following types of welded connections shown in UW-16.1 of section VIII of the ASME...

46 CFR 54.30-5 - Limitations and requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... pounds per square inch, thickness of shell is not greater than 1 inch, and the design temperature is not greater than 115 °F. (3) It will carry liquids of specific gravity no greater than 1.05. (4) Design... designs involving the following types of welded connections shown in UW-16.1 of section VIII of the ASME...

46 CFR 54.30-5 - Limitations and requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... pounds per square inch, thickness of shell is not greater than 1 inch, and the design temperature is not greater than 115 °F. (3) It will carry liquids of specific gravity no greater than 1.05. (4) Design... designs involving the following types of welded connections shown in UW-16.1 of section VIII of the ASME...

46 CFR 54.30-5 - Limitations and requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... pounds per square inch, thickness of shell is not greater than 1 inch, and the design temperature is not greater than 115 °F. (3) It will carry liquids of specific gravity no greater than 1.05. (4) Design... designs involving the following types of welded connections shown in UW-16.1 of section VIII of the ASME...

Effects of Cluster Porosity on the Tensile Properties of Butt-Weldments in T-1 Steel

DTIC Science & Technology

1974-11-01

i 12 Boiler and Pressure Vessel Code .19 In this code, the algebraic difference between the largest and smallest principal stresses is defined...Report U1LU- HN(J 7l-2()24 (University ot Illinois. 1971). "Nuclear Power Components.’* ASME Boiler and Pressure Vessel Code . Section HI. Subsections

49 CFR 195.587 - What methods are available to determine the strength of corroded pipe?

Code of Federal Regulations, 2011 CFR

2011-10-01

... strength of corroded pipe? 195.587 Section 195.587 Transportation Other Regulations Relating to... methods are available to determine the strength of corroded pipe? Under § 195.585, you may use the procedure in ASME B31G, “Manual for Determining the Remaining Strength of Corroded Pipelines,” or the...

49 CFR 195.587 - What methods are available to determine the strength of corroded pipe?

Code of Federal Regulations, 2010 CFR

2010-10-01

... strength of corroded pipe? 195.587 Section 195.587 Transportation Other Regulations Relating to... methods are available to determine the strength of corroded pipe? Under § 195.585, you may use the procedure in ASME B31G, “Manual for Determining the Remaining Strength of Corroded Pipelines,” or the...

Gas tungsten arc welding of aluminum alloys 6XXX. Welding procedure specification

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

Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

1985-08-01

Procedure WPS-1003 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of aluminum alloys 6061 and 6063 (P-23), in thickness range 0.035 to 0.516 in.; filler metal is ER4043 (F-23) or ER5356 (F-22); shielding gas is argon.

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...

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

PubMed Central

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

2008-01-01

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

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

PubMed

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

2018-01-01

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

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

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

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

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

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2003-08-29

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2009-10-01

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

Mechanisms of Cigarette Smoke Effects on Human Airway Smooth Muscle.

PubMed

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

2015-01-01

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

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

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...

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.

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.

[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.

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.

AIS ASM Operational Integration Plan

DTIC Science & Technology

2013-08-01

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

The 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.

Bronchodilatory and Anti-Inflammatory Effects of ASM-024, a Nicotinic Receptor Ligand, Developed for the Treatment of Asthma

PubMed Central

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

2014-01-01

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145±0.032 mg/kg for ASM 024-treated group as compared to 0.088±0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD. PMID:24465890

Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma

PubMed Central

Johnson, Martin; Nikolos, Christina; Jester, William; Klanderman, Barbara; Litonjua, Augusto A.; Tantisira, Kelan G.; Truskowski, Kevin; MacDonald, Kevin; Panettieri, Reynold A.; Weiss, Scott T.

2015-01-01

Globally, asthma is a chronic inflammatory respiratory disease affecting over 300 million people. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. Vitamin D, as an adjunct therapy, may improve disease control in severe asthma patients since vitamin D enhances glucocorticoid responsiveness and mitigates airway smooth muscle (ASM) hyperplasia. We sought to characterize differences in transcriptome responsiveness to vitamin D between fatal asthma- and non-asthma-derived ASM by using RNA-Seq to measure ASM transcript expression in five donors with fatal asthma and ten non-asthma-derived donors at baseline and with vitamin D treatment. Based on a Benjamini-Hochberg corrected p-value <0.05, 838 genes were differentially expressed in fatal asthma vs. non-asthma-derived ASM at baseline, and vitamin D treatment compared to baseline conditions induced differential expression of 711 and 867 genes in fatal asthma- and non-asthma-derived ASM, respectively. Functional gene categories that were highly represented in all groups included extracellular matrix, and responses to steroid hormone stimuli and wounding. Genes differentially expressed by vitamin D also included cytokine and chemokine activity categories. Follow-up qPCR and individual analyte ELISA experiments were conducted for four cytokines (i.e. CCL2, CCL13, CXCL12, IL8) to measure TNFα-induced changes by asthma status and vitamin D treatment. Vitamin D inhibited TNFα-induced IL8 protein secretion levels to a comparable degree in fatal asthma- and non-asthma-derived ASM even though IL8 had significantly higher baseline levels in fatal asthma-derived ASM. Our findings identify vitamin D-specific gene targets and provide transcriptomic data to explore differences in the ASM of fatal asthma- and non-asthma-derived donors. PMID:26207385

Bronchodilatory and anti-inflammatory effects of ASM-024, a nicotinic receptor ligand, developed for the treatment of asthma.

PubMed

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

2014-01-01

Conventional asthma and COPD treatments include the use of bronchodilators, mainly β2-adrenergic agonists, muscarinic receptor antagonists and corticosteroids or leukotriene antagonists as anti-inflammatory agents. These active drugs are administered either separately or given as a fixed-dose combination medication into a single inhaler. ASM-024, a homopiperazinium compound, derived from the structural modification of diphenylmethylpiperazinium (DMPP), has been developed to offer an alternative mechanism of action that could provide symptomatic control through combined anti-inflammatory and bronchodilator properties in a single entity. A dose-dependent inhibition of cellular inflammation in bronchoalveolar lavage fluid was observed in ovalbumin-sensitized mice, subsequently treated for 3 days by nose-only exposure with aerosolized ASM-024 at doses up to 3.8 mg/kg (ED50 = 0.03 mg/kg). The methacholine ED250 values indicated that airway hyperresponsivenness (AHR) to methacholine decreased following ASM-024 administration by inhalation at a dose of 1.5 mg/kg, with a value of 0.145 ± 0.032 mg/kg for ASM 024-treated group as compared to 0.088 ± 0.023 mg/kg for untreated mice. In in vitro isometric studies, ASM-024 elicited dose-dependent relaxation of isolated mouse tracheal, human, and dog bronchial preparations contracted with methacholine and guinea pig tracheas contracted with histamine. ASM-024 showed also a dose and time dependant protective effect on methacholine-induced contraction. Overall, with its combined anti-inflammatory, bronchodilating and bronchoprotective properties, ASM-024 may represent a new class of drugs with a novel pharmacological approach that could prove useful for the chronic maintenance treatment of asthma and, possibly, COPD.

Mechanisms and Disease Associations of Haplotype-Dependent Allele-Specific DNA Methylation

PubMed Central

Do, Catherine; Lang, Charles F.; Lin, John; Darbary, Huferesh; Krupska, Izabela; Gaba, Aulona; Petukhova, Lynn; Vonsattel, Jean-Paul; Gallagher, Mary P.; Goland, Robin S.; Clynes, Raphael A.; Dwork, Andrew; Kral, John G.; Monk, Catherine; Christiano, Angela M.; Tycko, Benjamin

2016-01-01

Haplotype-dependent allele-specific methylation (hap-ASM) can impact disease susceptibility, but maps of this phenomenon using stringent criteria in disease-relevant tissues remain sparse. Here we apply array-based and Methyl-Seq approaches to multiple human tissues and cell types, including brain, purified neurons and glia, T lymphocytes, and placenta, and identify 795 hap-ASM differentially methylated regions (DMRs) and 3,082 strong methylation quantitative trait loci (mQTLs), most not previously reported. More than half of these DMRs have cell type-restricted ASM, and among them are 188 hap-ASM DMRs and 933 mQTLs located near GWAS signals for immune and neurological disorders. Targeted bis-seq confirmed hap-ASM in 12/13 loci tested, including CCDC155, CD69, FRMD1, IRF1, KBTBD11, and S100A∗-ILF2, associated with immune phenotypes, MYT1L, PTPRN2, CMTM8 and CELF2, associated with neurological disorders, NGFR and HLA-DRB6, associated with both immunological and brain disorders, and ZFP57, a trans-acting regulator of genomic imprinting. Polymorphic CTCF and transcription factor (TF) binding sites were over-represented among hap-ASM DMRs and mQTLs, and analysis of the human data, supplemented by cross-species comparisons to macaques, indicated that CTCF and TF binding likelihood predicts the strength and direction of the allelic methylation asymmetry. These results show that hap-ASM is highly tissue specific; an important trans-acting regulator of genomic imprinting is regulated by this phenomenon; and variation in CTCF and TF binding sites is an underlying mechanism, and maps of hap-ASM and mQTLs reveal regulatory sequences underlying supra- and sub-threshold GWAS peaks in immunological and neurological disorders. PMID:27153397

Characterization of Nanowire Photodetectors

DTIC Science & Technology

2016-11-28

Low frequency noise measurement has been set-up using the cross correlation technique. Successful demonstration of noise measurements on the single...nanowires. Low frequency noise measurement has been set-up using the cross correlation technique. Successful demonstration of noise measurements on the...MRS/ASM/AVS North Carolina Section Meeting 2016 at Raleigh, North Carolina. Following is a brief description of the use of these equipment in our

46 CFR 54.01-5 - Scope (modifies U-1 and U-2).

Code of Federal Regulations, 2014 CFR

2014-10-01

... vessels must also comply with the requirements that are listed or prescribed in paragraphs (d) through (g... selected is Class I-L. (g) The design pressure for each interface between two chambers in a multichambered... BCategories C and D in accordance with UW-16 of section VIII of the ASME Boiler and Pressure Vessel Code Spot...

76 FR 53497 - Florida Power and Light Company; St. Lucie Plant, Units 1 and 2; Environmental Assessment and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-26

... Appendix G to the Code for calculating K IM factors, and instead applies FEM [finite element modeling..., Units 1 and 2 are calculated using the CE NSSS finite element modeling methods. The Need for the... Society of Mechanical Engineers (ASME) Code, Section XI, Appendix G) or determined by applying finite...

78 FR 6394 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... Change Relating to Fees for EdgeBook Attributed\\SM\\ January 23, 2012. Pursuant to Section 19(b)(1) of the... external distribution of EdgeBook Attributed\\SM\\, the Exchange's attributed book feed, and (ii) offer a new...-2011-19,\\4\\ the Exchange made available the EDGA Book Feed (``EdgeBook Depth A\\SM\\'') to Members and...

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

REVIEW OF PROPOSED METHODOLOGY FOR A RISK- INFORMED RELAXATION TO ASME SECTION XI APPENDIX G

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

Dickson, Terry L; Kirk, Mark

2010-01-01

The current regulations, as set forth by the United States Nuclear Regulatory Commission (NRC), to insure that light-water nuclear reactor pressure vessels (RPVs) maintain their structural integrity when subjected to planned normal reactor startup (heat-up) and shut-down (cool-down) transients are specified in Appendix G to 10 CFR Part 50, which incorporates by reference Appendix G to Section XI of the American Society of Mechanical Engineers (ASME) Code. The technical basis for these regulations are now recognized by the technical community as being conservative and some plants are finding it increasingly difficult to comply with the current regulations. Consequently, the nuclearmore » industry has developed, and submitted to the ASME Code for approval, an alternative risk-informed methodology that reduces the conservatism and is consistent with the methods previously used to develop a risk-informed revision to the regulations for accidental transients such as pressurized thermal shock (PTS). The objective of the alternative methodology is to provide a relaxation to the current regulations which will provide more operational flexibility, particularly for reactor pressure vessels with relatively high irradiation levels and radiation sensitive materials, while continuing to provide reasonable assurance of adequate protection to public health and safety. The NRC and its contractor at Oak Ridge National Laboratory (ORNL) have recently performed an independent review of the industry proposed methodology. The NRC / ORNL review consisted of performing probabilistic fracture mechanics (PFM) analyses for a matrix of cool-down and heat-up rates, permutated over various reactor geometries and characteristics, each at multiple levels of embrittlement, including 60 effective full power years (EFPY) and beyond, for various postulated flaw characterizations. The objective of this review is to quantify the risk of a reactor vessel experiencing non-ductile fracture, and possible subsequent failure, over a wide range of normal transient conditions, when the maximum allowable thermal-hydraulic boundary conditions, derived from both the current ASME code and the industry proposed methodology, are imposed on the inner surface of the reactor vessel. This paper discusses the results of the NRC/ORNL review of the industry proposal including the matrices of PFM analyses, results, insights, and conclusions derived from these analyses.« less

49 CFR 222.55 - How are new supplementary or alternative safety measures approved?

Code of Federal Regulations, 2010 CFR

2010-10-01

... applicant; (2) A description and design of the proposed new SSM or ASM; (3) A description and results of the... SSM or ASM; and (5) Any other information deemed necessary. (e) If the Associate Administrator is... an ASM to be used in the same manner as the measures listed in appendix B of this part. The Associate...

Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling.

PubMed

Noble, Peter B; Pascoe, Chris D; Lan, Bo; Ito, Satoru; Kistemaker, Loes E M; Tatler, Amanda L; Pera, Tonio; Brook, Bindi S; Gosens, Reinoud; West, Adrian R

2014-12-01

Asthma is an obstructive airway disease, with a heterogeneous and multifactorial pathogenesis. Although generally considered to be a disease principally driven by chronic inflammation, it is becoming increasingly recognised that the immune component of the pathology poorly correlates with the clinical symptoms of asthma, thus highlighting a potentially central role for non-immune cells. In this context airway smooth muscle (ASM) may be a key player, as it comprises a significant proportion of the airway wall and is the ultimate effector of acute airway narrowing. Historically, the contribution of ASM to asthma pathogenesis has been contentious, yet emerging evidence suggests that ASM contractile activation imparts chronic effects that extend well beyond the temporary effects of bronchoconstriction. In this review article we describe the effects that ASM contraction, in combination with cellular mechanotransduction and novel contraction-inflammation synergies, contribute to asthma pathogenesis. Specific emphasis will be placed on the effects that ASM contraction exerts on the mechanical properties of the airway wall, as well as novel mechanisms by which ASM contraction may contribute to more established features of asthma such as airway wall remodelling. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibition of acid sphingomyelinase disrupts LYNUS signaling and triggers autophagy.

PubMed

Justice, Matthew J; Bronova, Irina; Schweitzer, Kelly S; Poirier, Christophe; Blum, Janice S; Berdyshev, Evgeny V; Petrache, Irina

2018-04-01

Activation of the lysosomal ceramide-producing enzyme, acid sphingomyelinase (ASM), by various stresses is centrally involved in cell death and has been implicated in autophagy. We set out to investigate the role of the baseline ASM activity in maintaining physiological functions of lysosomes, focusing on the lysosomal nutrient-sensing complex (LYNUS), a lysosomal membrane-anchored multiprotein complex that includes mammalian target of rapamycin (mTOR) and transcription factor EB (TFEB). ASM inhibition with imipramine or sphingomyelin phosphodiesterase 1 ( SMPD1 ) siRNA in human lung cells, or by transgenic Smpd1 +/- haploinsufficiency of mouse lungs, markedly reduced mTOR- and P70-S6 kinase (Thr 389)-phosphorylation and modified TFEB in a pattern consistent with its activation. Inhibition of baseline ASM activity significantly increased autophagy with preserved degradative potential. Pulse labeling of sphingolipid metabolites revealed that ASM inhibition markedly decreased sphingosine (Sph) and Sph-1-phosphate (S1P) levels at the level of ceramide hydrolysis. These findings suggest that ASM functions to maintain physiological mTOR signaling and inhibit autophagy and implicate Sph and/or S1P in the control of lysosomal function. Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.

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.

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.

Methodology for the structural design of single spoke accelerating cavities at Fermilab

DOE PAGES

Passarelli, Donato; Wands, Robert H.; Merio, Margherita; ...

2016-10-01

Fermilab is planning to upgrade its accelerator complex to deliver a more powerful and intense proton-beam for neutrino experiments. In the framework of the so-called Proton Improvement Plan-II (PIP-II), we are designing and developing a cryomodule containing superconducting accelerating cavities, the Single Spoke Resonators of type 1 (SSR1). In this paper, we present the sequence of analysis and calculations performed for the structural de- sign of these cavities, using the rules of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (BPVC). The lack of an accepted procedure for addressing the design, fabrication, and inspection of suchmore » unique pressure vessels makes the task demanding and challenging every time. Several factors such as exotic materials, unqualified brazing procedures, limited nondestructive examination, and the general R&D nature of these early generations of cavity design, conspire to make it impractical to obtain full compliance with all ASME BPVC requirements. However, the presented approach allowed us to validate the design of these new generation of single spoke cavities with values of maximum allowable working pressure that exceed the safety requirements. This set of rules could be used as a starting point for the structural design and development of similar objects.« less

Methodology for the structural design of single spoke accelerating cavities at Fermilab

NASA Astrophysics Data System (ADS)

Passarelli, Donato; Wands, Robert H.; Merio, Margherita; Ristori, Leonardo

2016-10-01

Fermilab is planning to upgrade its accelerator complex to deliver a more powerful and intense proton-beam for neutrino experiments. In the framework of the so-called Proton Improvement Plan-II (PIP-II), we are designing and developing a cryomodule containing superconducting accelerating cavities, the Single Spoke Resonators of type 1 (SSR1). In this paper, we present the sequence of analysis and calculations performed for the structural design of these cavities, using the rules of the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code (BPVC). The lack of an accepted procedure for addressing the design, fabrication, and inspection of such unique pressure vessels makes the task demanding and challenging every time. Several factors such as exotic materials, unqualified brazing procedures, limited nondestructive examination, and the general R&D nature of these early generations of cavity design, conspire to make it impractical to obtain full compliance with all ASME BPVC requirements. However, the presented approach allowed us to validate the design of this new generation of single spoke cavities with values of maximum allowable working pressure that exceeds the safety requirements. This set of rules could be used as a starting point for the structural design and development of similar objects.

Turbulent Transport at High Reynolds Numbers in an Inertial Confinement Fusion Context

DTIC Science & Technology

2014-09-01

Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794 P . Rao1 Department of Applied Mathematics and Statistics...scales, 1Corresponding author. Contributed by the Fluids Engineering Division of ASME for publication in the JOURNAL OF FLUIDS ENGINEERING...Engineering SEPTEMBER 2014, Vol. 136 / 091206-1Copyright VC 2014 by ASME Downloaded From: http://fluidsengineering.asmedigitalcollection.asme.org/ on

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.

Design and Evaluation of a Chamber Capable of Containing the Detonation Effects of 40 Pounds of TNT

DTIC Science & Technology

1975-11-01

Boiler and Pressure Vessel Code , 197A. For the girth welds, short lengths of 26-in.-dia. pipe were tacked to the vessel around the...and tensile tests meet the requirements of Section IX, ASHE Boiler and Pressure Vessel Code , 1974. Weld made by W. H. Stefanov ■.^^ w-^iiMaLwärt...Macro Results Kos, No Remarl.s The results of the bond and it^nsile tests met the requirements of Section IX, ASME Boiler and Pressure

46 CFR 54.20-3 - Design (modifies UW-9, UW-11(a), UW-13, and UW-16).

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-3 Design (modifies UW-9, UW-11(a), UW-13, and UW-16). (a) Fabrication by welding shall be in accordance with the provisions of this part and with part 57 of this subchapter. (b) Welding subject to UW-11(a) of section VIII of the ASME Boiler and...

46 CFR 54.20-3 - Design (modifies UW-9, UW-11(a), UW-13, and UW-16).

Code of Federal Regulations, 2012 CFR

2012-10-01

... ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-3 Design (modifies UW-9, UW-11(a), UW-13, and UW-16). (a) Fabrication by welding shall be in accordance with the provisions of this part and with part 57 of this subchapter. (b) Welding subject to UW-11(a) of section VIII of the ASME Boiler and...

46 CFR 54.20-3 - Design (modifies UW-9, UW-11(a), UW-13, and UW-16).

Code of Federal Regulations, 2011 CFR

2011-10-01

... ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-3 Design (modifies UW-9, UW-11(a), UW-13, and UW-16). (a) Fabrication by welding shall be in accordance with the provisions of this part and with part 57 of this subchapter. (b) Welding subject to UW-11(a) of section VIII of the ASME Boiler and...

46 CFR 54.20-3 - Design (modifies UW-9, UW-11(a), UW-13, and UW-16).

Code of Federal Regulations, 2014 CFR

2014-10-01

... ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-3 Design (modifies UW-9, UW-11(a), UW-13, and UW-16). (a) Fabrication by welding shall be in accordance with the provisions of this part and with part 57 of this subchapter. (b) Welding subject to UW-11(a) of section VIII of the ASME Boiler and...

46 CFR 54.20-3 - Design (modifies UW-9, UW-11(a), UW-13, and UW-16).

Code of Federal Regulations, 2013 CFR

2013-10-01

... ENGINEERING PRESSURE VESSELS Fabrication by Welding § 54.20-3 Design (modifies UW-9, UW-11(a), UW-13, and UW-16). (a) Fabrication by welding shall be in accordance with the provisions of this part and with part 57 of this subchapter. (b) Welding subject to UW-11(a) of section VIII of the ASME Boiler and...

Advanced servomanipulator remote maintenance demonstration

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

Bradley, E.C.; Ladd, L.D.

1988-01-01

The Fuel Recycle Division (FRD) of the Oak Ridge National Laboratory (ORNL) is developing remote maintenance systems for the Consolidated Fuel Reprocessing Program for applications in future nuclear fuel cycle facilities. The most recent development is the advanced servomanipulator (ASM), a digitally controlled, force-reflecting, dual-arm, master/slave servomanipulator. A unique feature of ASM is that the slave arms are remotely maintainable. The ASM slave arms are composed of modules, each of which is capable of being removed and replaced by another manipulator system. The intent of this test was to demonstrate that the ASM slave arms could be completely disassembled andmore » reassembled remotely. This remote maintenance demonstration was performed using the Remote Operations and Maintenance Demonstration (ROMD) facility model M-2 servomanipulator maintenance system. Maintenance of ASM was successfully demonstrated using the M-2 servomanipulator and special fixtures. Recommendations, generally applicable to other remotely maintained equipment, have been made for maintainability improvements. 3 refs., 5 figs.« less

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

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

Histidine pKa shifts and changes of tautomeric states induced by the binding of gallium-protoporphyrin IX in the hemophore HasASM

PubMed Central

Wolff, Nicolas; Deniau, Clarisse; Létoffé, Sylvie; Simenel, Catherine; Kumar, Veena; Stojiljkovic, Igor; Wandersman, Cécile; Delepierre, Muriel; Lecroisey, Anne

2002-01-01

The HasASM hemophore, secreted by Serratia marcescens, binds free or hemoprotein bound heme with high affinity and delivers it to a specific outer membrane receptor, HasR. In HasASM, heme is held by two loops and coordinated to iron by two residues, His 32 and Tyr 75. A third residue His 83 was shown recently to play a crucial role in heme ligation. To address the mechanistic issues of the heme capture and release processes, the histidine protonation states were studied in both apo- and holo-forms of HasASM in solution. Holo-HasASM was formed with gallium-protoporphyrin IX (GaPPIX), giving rise to a diamagnetic protein. By use of heteronuclear correlation NMR spectroscopy, the imidazole side-chain 15N and 1H resonances of the six HasASM histidines were assigned and their pKa values and predominant tautomeric states according to pH were determined. We show that protonation states of the heme pocket histidines can modulate the nucleophilic character of the two axial ligands and, consequently, control the heme binding. In particular, the essential role of the His 83 is emphasized according to its direct interaction with Tyr 75. PMID:11910020

Change in the relationship between the Australian summer monsoon circulation and boreal summer precipitation over Central China in the late 1990s

NASA Astrophysics Data System (ADS)

Yang, Ruowen; Wang, Jian; Zhang, Tianyu; He, Shengping

2017-09-01

Recent study revealed a close connection between the Australian summer monsoon (ASM) and boreal summer precipitation over Central China (SPCC). This study further revealed a strengthening of the ASM-SPCC relationship around the late 1990s. It is found that the relationship between the ASM and the SPCC during 1979-1997 (1998-2014) relationship is statistically insignificant (significant). Further analysis indicated that during 1998-2014, the weakened ASM is concurrent with significant positive sea surface temperature (SST) in the Indian Ocean and South China Sea, which could persist into the following boreal summer and further lead to intensified East Asian summer monsoon, strengthened western North Pacific subtropical high, and anomalous ascending motion over Central China. Consequently, more moisture is transported from the western Pacific northward to Central China where significant anomalous convergence appears. Therefore, the ASM could potentially influence the SPCC during 1998-2014. By contrast, the ASM-related SST and atmospheric circulation anomalies in boreal winter are statistically insignificant during 1979-1997. Such an interdecadal change might be attributed to the interdecadal warming that occurred in the Indian Ocean and South China Sea around the late 1990s. This study might be useful for the prediction of the SPCC.

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.

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

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2018-06-01

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

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.

THE LONGEST TIMESCALE X-RAY VARIABILITY REVEALS EVIDENCE FOR ACTIVE GALACTIC NUCLEI IN THE HIGH ACCRETION STATE

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

Zhang Youhong, E-mail: youhong.zhang@mail.tsinghua.edu.cn

2011-01-01

The All Sky Monitor (ASM) on board the Rossi X-ray Timing Explorer has continuously monitored a number of active galactic nuclei (AGNs) with similar sampling rates for 14 years, from 1996 January to 2009 December. Utilizing the archival ASM data of 27 AGNs, we calculate the normalized excess variances of the 300-day binned X-ray light curves on the longest timescale (between 300 days and 14 years) explored so far. The observed variance appears to be independent of AGN black-hole mass and bolometric luminosity. According to the scaling relation of black-hole mass (and bolometric luminosity) from galactic black hole X-ray binariesmore » (GBHs) to AGNs, the break timescales that correspond to the break frequencies detected in the power spectral density (PSD) of our AGNs are larger than the binsize (300 days) of the ASM light curves. As a result, the singly broken power-law (soft-state) PSD predicts the variance to be independent of mass and luminosity. Nevertheless, the doubly broken power-law (hard-state) PSD predicts, with the widely accepted ratio of the two break frequencies, that the variance increases with increasing mass and decreases with increasing luminosity. Therefore, the independence of the observed variance on mass and luminosity suggests that AGNs should have soft-state PSDs. Taking into account the scaling of the break timescale with mass and luminosity synchronously, the observed variances are also more consistent with the soft-state than the hard-state PSD predictions. With the averaged variance of AGNs and the soft-state PSD assumption, we obtain a universal PSD amplitude of 0.030 {+-} 0.022. By analogy with the GBH PSDs in the high/soft state, the longest timescale variability supports the standpoint that AGNs are scaled-up GBHs in the high accretion state, as already implied by the direct PSD analysis.« less

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.

Experimental uncertainty and drag measurements in the national transonic facility

NASA Technical Reports Server (NTRS)

Batill, Stephen M.

1994-01-01

This report documents the results of a study which was conducted in order to establish a framework for the quantitative description of the uncertainty in measurements conducted in the National Transonic Facility (NTF). The importance of uncertainty analysis in both experiment planning and reporting results has grown significantly in the past few years. Various methodologies have been proposed and the engineering community appears to be 'converging' on certain accepted practices. The practical application of these methods to the complex wind tunnel testing environment at the NASA Langley Research Center was based upon terminology and methods established in the American National Standards Institute (ANSI) and the American Society of Mechanical Engineers (ASME) standards. The report overviews this methodology.

Sarcopenic obesity is more closely associated with knee osteoarthritis than is nonsarcopenic obesity: a cross-sectional study.

PubMed

Lee, Sunggun; Kim, Tae-Nyun; Kim, Seong-Ho

2012-12-01

Sarcopenic obesity is a body composition category in which obesity is accompanied by low skeletal muscle mass, offsetting the increase in body weight caused by increased adipose tissue. The purpose of this study was to analyze the association between knee osteoarthritis (OA) and 4 different categories of body composition: normal, sarcopenic nonobesity, nonsarcopenic obesity, and sarcopenic obesity. This was a cross-sectional study using the data from 2,893 participants in the Fifth Korean National Health and Nutrition Examination Survey. Radiographic knee OA was defined as a Kellgren/Lawrence grade of ≥2. Appendicular skeletal muscle mass (ASM) and whole-body fat mass were measured using dual x-ray absorptiometry. Sarcopenia was defined as a skeletal muscle mass index (ASM/body weight [%]) below -2SD of the value in sex-matched young reference groups. Nonsarcopenic obesity was defined as a body mass index (BMI) ≥27.5 kg/m(2) . The prevalence of each body composition category was as follows: 83.5% normal, 4.3% sarcopenic nonobesity, 9.2% nonsarcopenic obesity, and 3.0% sarcopenic obesity. Compared with nonsarcopenic obesity participants, participants with sarcopenic obesity were significantly older, had lower ASM, higher whole-body fat mass, and higher waist circumference. However, there was no significant difference in body weight or BMI. In multivariate analysis, sarcopenic obesity was more closely associated with radiographic knee OA (OR 3.51 [95% confidence interval (95% CI) 2.15-5.75]) than was nonsarcopenic obesity (OR 2.38 [95% CI 1.80-3.15]). Sarcopenic nonobesity showed no significant association with knee OA. Sarcopenic obesity was more closely associated with knee OA than was nonsarcopenic obesity, although both groups had equivalent body weight. This finding supports the importance of the systemic metabolic effect of obesity in knee OA. Copyright © 2012 by the American College of Rheumatology.

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

Evaluation of the ICET Test Stand to Assess the Performance of a Range of Ceramic Media Filter Elements in Support of ASME AG-1 Subsection FO

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

Schemmel, A.

High Efficiency Particulate Air (HEPA) filters are defined as extended-medium, dry-type filters with: (1) a minimum particle removal efficiency of no less than 99.97 percent for 0.3 micrometer particles, (2) a maximum, clean resistance of 1.0 inch water column (in. WC) when operated at 1,000 cubic feet per minute (CFM), and (3) a rigid casing that extends the full depth of the medium. Specifically, ceramic media HEPA filters provide better performance at elevated temperatures, are moisture resistant and nonflammable, can perform their function if wetted and exposed to greater pressures, and can be cleaned and reused. This paper describes themore » modification and design of a large scale test stand which properly evaluates the filtration characteristics of a range of ceramic media filters challenged with a nuclear aerosol agent in order to develop Section FO of ASME AG-1.« less

Creep-Rupture Behavior and Recrystallization in HR6W and Haynes Alloy 230 Cold-Bent Boiler Tubing for Ultrasupercritical (USC) Steam Boiler Applications

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

Shingledecker, John P

2007-01-01

Creep-rupture experiments were conducted on HR6W and Haynes 230, candidate Ultrasupercritical (USC) alloys, tubes to evaluate the effects of cold-work and recrystallization during high-temperature service. These creep tests were performed by internally pressurizing cold-bent boiler tubes at 775 C for times up to 8000 hours. The bends were fabricated with cold-work levels beyond the current ASME Boiler and Pressure Vessel (ASME B&PV) Code Section I limits for austenitic stainless steels. Destructive metallographic evaluation of the crept tube bends was used to determine the effects of cold-work and the degree of recrystallization. The metallographic analysis combined with an evaluation of themore » creep and rupture data suggest that solid-solution strengthened nickel-based alloys can be fabricated for high-temperature service at USC conditions utilizing levels of cold-work higher than the current allowed levels for austenitic stainless steels.« 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

Creep-Rupture Behavior of Ni-Based Alloy Tube Bends for A-USC Boilers

NASA Astrophysics Data System (ADS)

Shingledecker, John

Advanced ultrasupercritical (A-USC) boiler designs will require the use of nickel-based alloys for superheaters and reheaters and thus tube bending will be required. The American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel Code Section II PG-19 limits the amount of cold-strain for boiler tube bends for austenitic materials. In this summary and analysis of research conducted to date, a number of candidate nickel-based A-USC alloys were evaluated. These alloys include alloy 230, alloy 617, and Inconel 740/740H. Uniaxial creep and novel structural tests and corresponding post-test analysis, which included physical measurements, simplified analytical analysis, and detailed microscopy, showed that different damage mechanisms may operate based on test conditions, alloy, and cold-strain levels. Overall, creep strength and ductility were reduced in all the alloys, but the degree of degradation varied substantially. The results support the current cold-strain limits now incorporated in ASME for these alloys for long-term A-USC boiler service.

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.

49 CFR 178.276 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2014 CFR

2014-10-01

....): (A) Without insulation or sun shield: 60 °C (140 °F); (B) With sun shield: 55 °C (131 °F); and (C) With insulation: 50 °C (122 °F). (3) Filling density means the average mass of liquefied compressed gas... stamped in accordance with the ASME Code, Section VIII. (2) Portable tanks must be postweld heat-treated...

49 CFR 178.276 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2012 CFR

2012-10-01

....): (A) Without insulation or sun shield: 60 °C (140 °F); (B) With sun shield: 55 °C (131 °F); and (C) With insulation: 50 °C (122 °F). (3) Filling density means the average mass of liquefied compressed gas... stamped in accordance with the ASME Code, Section VIII. (2) Portable tanks must be postweld heat-treated...

49 CFR 178.276 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2013 CFR

2013-10-01

....): (A) Without insulation or sun shield: 60 °C (140 °F); (B) With sun shield: 55 °C (131 °F); and (C) With insulation: 50 °C (122 °F). (3) Filling density means the average mass of liquefied compressed gas... stamped in accordance with the ASME Code, Section VIII. (2) Portable tanks must be postweld heat-treated...

49 CFR 178.276 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2010 CFR

2010-10-01

....): (A) Without insulation or sun shield: 60 °C (140 °F); (B) With sun shield: 55 °C (131 °F); and (C) With insulation: 50 °C (122 °F). (3) Filling density means the average mass of liquefied compressed gas... stamped in accordance with the ASME Code, Section VIII. (2) Portable tanks must be postweld heat-treated...

49 CFR 178.276 - Requirements for the design, construction, inspection and testing of portable tanks intended for...

Code of Federal Regulations, 2011 CFR

2011-10-01

....): (A) Without insulation or sun shield: 60 °C (140 °F); (B) With sun shield: 55 °C (131 °F); and (C) With insulation: 50 °C (122 °F). (3) Filling density means the average mass of liquefied compressed gas... stamped in accordance with the ASME Code, Section VIII. (2) Portable tanks must be postweld heat-treated...

Gas tungsten arc welding of aluminum alloys 6XXX. Welding procedure specification. Supplement 1. Records of procedure qualification tests. [6061 and 6063

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

Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

1986-06-01

Procedure WPS-1003 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of aluminum alloys 6061 and 6063 (P-23), in thickness range 0.035 to 0.516 inch; filler metal is ER4043 (F-23) or ER5356 (F-22); shielding gas is argon.

Gas tungsten arc welding of aluminum alloys 1XXX and 3003 to 3004, 5052 and 5X54. Welding procedure specification

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

Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

1985-08-01

Procedure WPS-2201 is qualified under Section IX of the ASME Boiler and Pressure Vessel for gas tungsten arc welding of aluminum alloys 1060, 1100, and 3003 (P-21) to 3004, 5052, 5154, and 5454 (P-22), in thickness range 0.062 to 0.5 in.; filler metal is ER5356 (F-22); shielding gas is argon.

Gas tungsten arc welding of aluminum alloys 3004, 5052, and 5X54. Welding procedure specification

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

Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

1985-08-01

Procedure WPS-1002 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of aluminum alloys 3004, 5052, 5154, and 5454 (P-22), in thickness range 0.062 to 0.5 in.; filler metal is ER4043 (F-23) for 3004, and ER5356 (F-22) for other alloys; shielding gas is argon.

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.

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.

Increase in acid sphingomyelinase level in human retinal endothelial cells and CD34+ circulating angiogenic cells isolated from diabetic individuals is associated with dysfunctional retinal vasculature and vascular repair process in diabetes

PubMed Central

Kady, Nermin; Yan, Yuanqing; Salazar, Tatiana; Wang, Qi; Chakravarthy, Harshini; Huang, Chao; Beli, Eleni; Navitskaya, Svetlana; Grant, Maria; Busik, Julia

2017-01-01

Background Diabetic retinopathy (DR) is a microvascular disease that results from retinal vascular degeneration and defective repair due to diabetes induced endothelial progenitor dysfunction. Objective Understanding key molecular factors involved in vascular degeneration and repair is paramount for developing effective DR treatment strategies. We propose that diabetes-induced activation of acid sphingomyelinase (ASM) plays essential role in retinal endothelial and CD34+ circulating angiogenic cell (CAC) dysfunction in diabetes. Methods Human retinal endothelial cells (HRECs) isolated from control and diabetic donor tissue and human CD34+ CACs from control and diabetic patients were used in this study. ASM mRNA and protein expression was assessed by quantitative PCR and ELISA, respectively. To evaluate the effect of diabetes-induced ASM on HRECs and CD34+ CACs function, tube formation, CAC incorporation into endothelial tubes, and diurnal release of CD34+ CACs in diabetic individuals was determined. Results ASM expression level was significantly increased in HRECs isolated from diabetic compared to control donor tissue, as well as CD34+CACs and plasma of diabetic patients. A significant decrease in tube area was observed in HRECs from diabetic donors as compared to control HRECs. The tube formation deficiency was associated with increased expression of ASM in diabetic HRECs. Moreover, diabetic CD34+ CACs with high ASM showed defective incorporation into endothelial tubes. Diurnal release of CD34+ CACs was disrupted with the rhythmicity lost in diabetic patients. Conclusion Collectively, these findings support that diabetes-induced ASM upregulation has a marked detrimental effect on both retinal endothelial cells and CACs. PMID:28457994

Acid Sphingomyelinase-Derived Ceramide Regulates ICAM-1 Function during T Cell Transmigration across Brain Endothelial Cells.

PubMed

Lopes Pinheiro, Melissa A; Kroon, Jeffrey; Hoogenboezem, Mark; Geerts, Dirk; van Het Hof, Bert; van der Pol, Susanne M A; van Buul, Jaap D; de Vries, Helga E

2016-01-01

Multiple sclerosis (MS) is a chronic demyelinating disorder of the CNS characterized by immune cell infiltration across the brain vasculature into the brain, a process not yet fully understood. We previously demonstrated that the sphingolipid metabolism is altered in MS lesions. In particular, acid sphingomyelinase (ASM), a critical enzyme in the production of the bioactive lipid ceramide, is involved in the pathogenesis of MS; however, its role in the brain vasculature remains unknown. Transmigration of T lymphocytes is highly dependent on adhesion molecules in the vasculature such as intercellular adhesion molecule-1 (ICAM-1). In this article, we hypothesize that ASM controls T cell migration by regulating ICAM-1 function. To study the role of endothelial ASM in transmigration, we generated brain endothelial cells lacking ASM activity using a lentiviral shRNA approach. Interestingly, although ICAM-1 expression was increased in cells lacking ASM activity, we measured a significant decrease in T lymphocyte adhesion and consequently transmigration both in static and under flow conditions. As an underlying mechanism, we revealed that upon lack of endothelial ASM activity, the phosphorylation of ezrin was perturbed as well as the interaction between filamin and ICAM-1 upon ICAM-1 clustering. Functionally this resulted in reduced microvilli formation and impaired transendothelial migration of T cells. In conclusion, in this article, we show that ASM coordinates ICAM-1 function in brain endothelial cells by regulating its interaction with filamin and phosphorylation of ezrin. The understanding of these underlying mechanisms of T lymphocyte transmigration is of great value to develop new strategies against MS lesion formation. Copyright © 2015 by The American Association of Immunologists, Inc.

Does smooth muscle in an intact airway undergo length adaptation during a sustained change in transmural pressure?

PubMed

Ansell, Thomas K; McFawn, Peter K; McLaughlin, Robert A; Sampson, David D; Eastwood, Peter R; Hillman, David R; Mitchell, Howard W; Noble, Peter B

2015-03-01

In isolated airway smooth muscle (ASM) strips, an increase or decrease in ASM length away from its current optimum length causes an immediate reduction in force production followed by a gradual time-dependent recovery in force, a phenomenon termed length adaptation. In situ, length adaptation may be initiated by a change in transmural pressure (Ptm), which is a primary physiological determinant of ASM length. The present study sought to determine the effect of sustained changes in Ptm and therefore, ASM perimeter, on airway function. We measured contractile responses in whole porcine bronchial segments in vitro before and after a sustained inflation from a baseline Ptm of 5 cmH2O to 25 cmH2O, or deflation to -5 cmH2O, for ∼50 min in each case. In one group of airways, lumen narrowing and stiffening in response to electrical field stimulation (EFS) were assessed from volume and pressure signals using a servo-controlled syringe pump with pressure feedback. In a second group of airways, lumen narrowing and the perimeter of the ASM in situ were determined by anatomical optical coherence tomography. In a third group of airways, active tension was determined under isovolumic conditions. Both inflation and deflation reduced the contractile response to EFS. Sustained Ptm change resulted in a further decrease in contractile response, which returned to baseline levels upon return to the baseline Ptm. These findings reaffirm the importance of Ptm in regulating airway narrowing. However, they do not support a role for ASM length adaptation in situ under physiological levels of ASM lengthening and shortening. Copyright © 2015 the American Physiological Society.

TNFα enhances force generation in airway smooth muscle

PubMed Central

Han, Young-Soo; Delmotte, Philippe

2017-01-01

Airway inflammation is a hallmark of asthma, triggering airway smooth muscle (ASM) hyperreactivity and airway remodeling. TNFα increases both agonist-induced cytosolic Ca2+ concentration ([Ca2+]cyt) and force in ASM. The effects of TNFα on ASM force may also be due to an increase in Ca2+ sensitivity, cytoskeletal remodeling, and/or changes in contractile protein content. We hypothesized that 24 h of exposure to TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization. Porcine ASM strips were permeabilized with 10% Triton X-100, and force was measured in response to increasing concentrations of Ca2+ (pCa 9.0 to 4.0) in control and TNFα-treated groups. Relative phosphorylation of the regulatory myosin light chain (p-MLC) and total actin, MLC, and MyHC concentrations were quantified at pCa 9.0, 6.1, and 4.0. Actin polymerization was quantified by the ratio of filamentous to globular actin at pCa 9.0 and 4.0. For determination of total cross-bridge formation, isometric ATP hydrolysis rate at pCa 4.0 was measured using an enzyme-coupled NADH-linked fluorometric technique. Exposure to TNFα significantly increased force across the range of Ca2+ activation but did not affect the intrinsic Ca2+ sensitivity of force generation. The TNFα-induced increase in ASM force was associated with an increase in total actin, MLC, and MyHC content, as well as an increase in actin polymerization and an increase in maximum isometric ATP hydrolysis rate. The results of this study support our hypothesis that TNFα increases force generation in ASM by increasing the number of contractile units (actin-myosin content) contributing to force generation. PMID:28385814

Phosphoinositide 3-kinase gamma regulates airway smooth muscle contraction by modulating calcium oscillations.

PubMed

Jiang, Haihong; Abel, Peter W; Toews, Myron L; Deng, Caishu; Casale, Thomas B; Xie, Yan; Tu, Yaping

2010-09-01

Phosphoinositide 3-kinase gamma (PI3Kgamma) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kgamma can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kgamma protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kgamma inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 muM. In contrast, inhibitors of PI3Kalpha, PI3Kbeta, or PI3Kdelta, at concentrations 40-fold higher than their reported IC(50) values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kgamma inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kgamma-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca(2+) transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca(2+) oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kgamma directly controls contractility of airways through regulation of Ca(2+) oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kgamma inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness.

Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement.

PubMed

Alrashdan, Yazan A; Alkhouri, Hatem; Chen, Emily; Lalor, Daniel J; Poniris, Maree; Henness, Sheridan; Brightling, Christopher E; Burgess, Janette K; Armour, Carol L; Ammit, Alaina J; Hughes, J Margaret

2012-05-15

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma.

Glioma Cell Death Induced by Irradiation or Alkylating Agent Chemotherapy Is Independent of the Intrinsic Ceramide Pathway

PubMed Central

Gramatzki, Dorothee; Herrmann, Caroline; Happold, Caroline; Becker, Katrin Anne; Gulbins, Erich; Weller, Michael; Tabatabai, Ghazaleh

2013-01-01

Background/Aims Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS) catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells. Methods Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II–IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA) was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ)-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations. Results Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation. Conclusion Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PMID:23667632

Bitter tasting compounds dilate airways by inhibiting airway smooth muscle calcium oscillations and calcium sensitivity

PubMed Central

Tan, Xiahui; Sanderson, Michael J

2014-01-01

Background and Purpose While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca2+ signalling and Ca2+ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinine and denotonium regulate contractile agonist-induced Ca2+ signalling and sensitivity. Experimental Approach Airways in mouse lung slices were contracted with either methacholine (MCh) or 5HT and bronchodilation assessed using phase-contrast microscopy. Ca2+ signalling was measured with 2-photon fluorescence microscopy of ASM cells loaded with Oregon Green, a Ca2+-sensitive indicator (with or without caged-IP3). Effects on Ca2+ sensitivity were assessed on lung slices treated with caffeine and ryanodine to permeabilize ASM cells to Ca2+. Key Results The TAS2R10 agonists dilated airways constricted by either MCh or 5HT, accompanied by inhibition of agonist-induced Ca2+ oscillations. However, in non-contracted airways, TAS2R10 agonists, at concentrations that maximally dilated constricted airways, did not evoke Ca2+ signals in ASM cells. Ca2+ increases mediated by the photolysis of caged-IP3 were also attenuated by chloroquine, quinine and denotonium. In Ca2+-permeabilized ASM cells, the TAS2R10 agonists dilated MCh- and 5HT-constricted airways. Conclusions and Implications TAS2R10 agonists reversed bronchoconstriction by inhibiting agonist-induced Ca2+ oscillations while simultaneously reducing the Ca2+ sensitivity of ASM cells. Reduction of Ca2+ oscillations may be due to inhibition of Ca2+ release through IP3 receptors. Further characterization of bronchodilatory TAS2R agonists may lead to the development of novel therapies for the treatment of bronchoconstrictive conditions. PMID:24117140

Phosphoinositide 3-Kinase γ Regulates Airway Smooth Muscle Contraction by Modulating Calcium Oscillations

PubMed Central

Jiang, Haihong; Abel, Peter W.; Toews, Myron L.; Deng, Caishu; Casale, Thomas B.; Xie, Yan

2010-01-01

Phosphoinositide 3-kinase γ (PI3Kγ) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kγ can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kγ protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kγ inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 μM. In contrast, inhibitors of PI3Kα, PI3Kβ, or PI3Kδ, at concentrations 40-fold higher than their reported IC50 values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kγ inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kγ-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca2+ transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca2+ oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kγ directly controls contractility of airways through regulation of Ca2+ oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kγ inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness. PMID:20501633

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.

Acid sphingomyelinase is required for cell surface presentation of Met receptor tyrosine kinase in cancer cells

PubMed Central

Zhu, Linyu; Xiong, Xiahui; Kim, Yongsoon; Okada, Naomi; Lu, Fei; Zhang, Hui

2016-01-01

ABSTRACT Receptor tyrosine kinases (RTKs) are embedded in the lipid bilayer of the plasma membrane, but the specific roles of various lipids in cell signaling remain largely uncharacterized. We have previously found that acid sphingomyelinase (ASM; also known as SMPD1) regulates the conserved DAF-2 (the ortholog IGF-1R in mammals) RTK signaling pathway in Caenorhabditis elegans. How ASM and its catalytic products, ceramides, control RTK signaling pathways remain unclear. Here, we report that ASM regulates the homeostasis of Met, an RTK that is frequently overexpressed in various cancers. Inactivation of ASM led to a rapid loss of Met from the plasma membrane, reduced Met phosphorylation and activation, and induced Met accumulation in the trans-Golgi network (TGN). However, trafficking of integrin β3 and vesicular stomatitis virus glycoprotein (VSVG) was largely unaffected. Knockdown of syntaxin 6 (STX6) also blocked the Golgi exit of Met. Depletion of either ASM or STX6 led to aberrant trafficking of Met to lysosomes, promoting its degradation. Our studies reveal that ASM and ceramides, together with STX6 and cholesterol, constitute a new regulatory mechanism for the exit of Met from the Golgi during its biosynthetic route, which is used to rapidly replenish and regulate the plasma membrane levels of Met in various cancer cells. PMID:27802163

Allele-Specific Methylation Occurs at Genetic Variants Associated with Complex Disease

PubMed Central

Hutchinson, John N.; Raj, Towfique; Fagerness, Jes; Stahl, Eli; Viloria, Fernando T.; Gimelbrant, Alexander; Seddon, Johanna; Daly, Mark; Chess, Andrew; Plenge, Robert

2014-01-01

We hypothesize that the phenomenon of allele-specific methylation (ASM) may underlie the phenotypic effects of multiple variants identified by Genome-Wide Association studies (GWAS). We evaluate ASM in a human population and document its genome-wide patterns in an initial screen at up to 380,678 sites within the genome, or up to 5% of the total genomic CpGs. We show that while substantial inter-individual variation exists, 5% of assessed sites show evidence of ASM in at least six samples; the majority of these events (81%) are under genetic influence. Many of these cis-regulated ASM variants are also eQTLs in peripheral blood mononuclear cells and monocytes and/or in high linkage-disequilibrium with variants linked to complex disease. Finally, focusing on autoimmune phenotypes, we extend this initial screen to confirm the association of cis-regulated ASM with multiple complex disease-associated variants in an independent population using next-generation bisulfite sequencing. These four variants are implicated in complex phenotypes such as ulcerative colitis and AIDS progression disease (rs10491434), Celiac disease (rs2762051), Crohn's disease, IgA nephropathy and early-onset inflammatory bowel disease (rs713875) and height (rs6569648). Our results suggest cis-regulated ASM may provide a mechanistic link between the non-coding genetic changes and phenotypic variation observed in these diseases and further suggests a route to integrating DNA methylation status with GWAS results. PMID:24911414

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.

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.

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.

Airway smooth muscle: a potential target for asthma therapy.

PubMed

Dowell, Maria L; Lavoie, Tera L; Solway, Julian; Krishnan, Ramaswamy

2014-01-01

Asthma is a major public health problem that afflicts nearly one in 20 people worldwide. Despite available treatments, asthma symptoms remain poorly controlled in a significant minority of asthma patients, especially those with severe disease. Accordingly, much ongoing effort has been directed at developing new therapeutic strategies; these efforts are described in detail below. Although mucus hypersecretion is an important component of asthma pathobiology, the primary mechanism of morbidity and mortality in asthma is excessive narrowing of the airway. The key end- effector of excessive airway narrowing is airway smooth muscle (ASM) contraction; overcoming ASM contraction is therefore a prominent therapeutic strategy. Here, we review exciting new advances aimed at ASM relaxation. Exciting advances in ASM biology have identified new therapeutic targets for the prevention or reversal of bronchoconstriction in asthma.

Cyclin D1 in ASM Cells from Asthmatics Is Insensitive to Corticosteroid Inhibition.

PubMed

Allen, Jodi C; Seidel, Petra; Schlosser, Tobias; Ramsay, Emma E; Ge, Qi; Ammit, Alaina J

2012-01-01

Hyperplasia of airway smooth muscle (ASM) is a feature of the remodelled airway in asthmatics. We examined the antiproliferative effectiveness of the corticosteroid dexamethasone on expression of the key regulator of G(1) cell cycle progression-cyclin D1-in ASM cells from nonasthmatics and asthmatics stimulated with the mitogen platelet-derived growth factor BB. While cyclin D1 mRNA and protein expression were repressed in cells from nonasthmatics in contrast, cyclin D1 expression in asthmatics was resistant to inhibition by dexamethasone. This was independent of a repressive effect on glucocorticoid receptor translocation. Our results corroborate evidence demonstrating that corticosteroids inhibit mitogen-induced proliferation only in ASM cells from subjects without asthma and suggest that there are corticosteroid-insensitive proliferative pathways in asthmatics.

The American Society of Maxillofacial Surgery Preceptorship Program: A Product of the 2013 American Society of Maxillofacial Surgery Executive Board Strategy Session and Survey.

PubMed

Papay, Francis; Taub, Peter J; Doumit, Gaby; Flores, Roberto L; Kuang, Anna A; Mlynek, Karolina; Tadisina, Kashyap K; Gharb, Bahar Bassiri

2015-06-01

One of the main goals of the American Society of Maxillofacial Surgery (ASMS) is to develop educational programs that increase expertise in maxillofacial surgery. We describe the outline of the new ASMS Preceptorship Program, a collective effort by ASMS members to increase access to all areas of maxillofacial surgery. Furthermore, we discuss the original survey pertinent to the development of this program, the results of the survey, and specifics regarding the structure of the program. We hope for the preceptorship program to be an excellent resource for members to mentor one another, develop intellectual and academic curiosity, provide avenues for collaboration, and further the ASMS's role in shaping maxillofacial surgery into the future.

Transactions of the Conference of Army Mathematicians (23rd), held at U. S. Army Mobility Research and Development Laboratory, Langley Research Center, Hampton, Virginia, 11-13 May 1977

DTIC Science & Technology

1978-02-01

Trans. ASME, Vol. 81, 1959, pp. 259- 264 . 112 0 C> 0 LJj 0 CD 0 D ~) . [") r "-’ . 1’ n -- 1 . 2 0 1 . lj 0 1. :iO 1 • 13 0 ? . (JO p;a...n ntout Compute determinant elements forb n, Comoute and write backsc~tter cross-section\\ (Figure 2.2-1) 264 J. BACKSCATTER CROSS-SECTION FOR A...Overrelaxation Iteration Methods," Report WAPD -TM-1038, Bettis Atomic Power Laboratory, Westinghouse Electric Corp., Pittsburgh, Pennsylvania. 10

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

Low Cycle Fatigue and Creep-Fatigue Behavior of Alloy 617 at High Temperature

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

Cabet, Celine; Carroll, Laura; Wright, Richard

Alloy 617 is the leading candidate material for an intermediate heat exchanger (IHX) application of the Very High Temperature Nuclear Reactor (VHTR), expected to have an outlet temperature as high as 950 degrees C. Acceptance of Alloy 617 in Section III of the ASME Code for nuclear construction requires a detailed understanding of the creep-fatigue behavior. Initial creep-fatigue work on Alloy 617 suggests a more dominant role of environment with increasing temperature and/or hold times evidenced through changes in creep-fatigue crack growth mechanism/s and failure life. Continuous cycle fatigue and creep-fatigue testing of Alloy 617 was conducted at 950 degreesmore » C and 0.3% and 0.6% total strain in air to simulate damage modes expected in a VHTR application. Continuous cycle specimens exhibited transgranular cracking. Intergranular cracking was observed in the creep-fatigue specimens, although evidence of grain boundary cavitation was not observed. Despite the absence of grain boundary cavitation to accelerate crack propagation, the addition of a hold time at peak tensile strain was detrimental to cycle life. This suggests that creepfatigue interaction may occur by a different mechanism or that the environment may be partially responsible for accelerating failure.« less

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.

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.

Ocean Engineering Studies Compiled 1991. Volume 6. Acrylic Windows - Typical Applications in Pressure Housings

DTIC Science & Technology

1991-01-01

either the metallic or plastic composite pressure envelope. The ASME Boiler and Pressure Vessel Code Section 8 provides such design criteria, and the...fabricated of metallic or piastic composite materials. To preclude potential catastrophic failures of windows designed on the basis of inadequate data, in...pressure-resistant acrylic windows (reference 12). Acrylic windows are usually machined from Plexiglas G plate, which is limited in thickness to 4 inches

Potential Effects of Leak-Before-Break on Light Water Reactor Design.

DTIC Science & Technology

1985-08-26

Boiler and Pressure Vessel Code . In fact, section 3 of that code was created for nuclear applications. This... Boiler and Pressure Vessel Code . The only major change which leak-before-break would require in these analyses would be that all piping to be considered...XI of the ASME Boiler and Pressure Vessel Code , and is already required for all Class I piping systems in the plant. Class I systems are those

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.

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

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

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.

Results from Evaluation of Representative ASME AG-1 Section FK Radial Flow Dimple Pleated HEPA Filters Under Elevated Conditions - 12002

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

Giffin, Paxton K.; Parsons, Michael S.; Rickert, Jaime G.

The American Society of Mechanical Engineers (ASME) has recently added Section FK establishing requirements for radial flow HEPA filters to the Code on Nuclear Air and Gas Treatment (AG-1). Section FK filters are expected to be a major element in the HEPA filtration systems across the US Department of Energy (DOE) complex. Radial flow filters have been used in Europe for some time, however a limited amount of performance evaluation data exists with respect to these new AG-1 Section FK units. In consultation with a technical working group, the Institute for Clean Energy Technology (ICET) at Mississippi State University (MSU)hasmore » evaluated a series of representative AG-1 Section FK dimple pleated radial flow HEPA filters. The effects of elevated relative humidity and temperature conditions on these filters are particularly concerning. Results from the evaluation of Section FK filters under ambient conditions have been presented at the 2011 waste management conference. Additions to the previous test stand to enable high temperature and high humidity testing, a review of the equipment used, the steps taken to characterize the new additions, and the filter test results are presented in this study. Test filters were evaluated at a volumetric flow rate of 56.6 m{sup 3}/min (2000 cfm) and were challenged under ambient conditions with Alumina, Al(OH){sub 3}, until reaching a differential pressure of 1 kPa (4 in. w.c.), at which time the filters were tested, unchallenged with aerosol, at 54 deg. C (130 deg. F) for approximately 1 hour. At the end of that hour water was sprayed near the heat source to maximize vaporization exposing the filter to an elevated relative humidity up to 95%. Collected data include differential pressure, temperature, relative humidity, and volumetric flow rate versus time. (authors)« 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.

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.

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.

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

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.

Flaw Stability Considering Residual Stress for Aging Management of Spent Nuclear Fuel Multiple-Purpose Canisters

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

Lam, Poh-Sang; Sindelar, Robert L.

A typical multipurpose canister (MPC) is made of austenitic stainless steel and is loaded with spent nuclear fuel assemblies. Because heat treatment for stress relief is not required for the construction of the MPC, the canister is susceptible to stress corrosion cracking in the weld or heat affected zone regions under long-term storage conditions. Logic for flaw acceptance is developed should crack-like flaws be detected by Inservice Inspection. The procedure recommended by API 579-1/ASME FFS-1, Fitness-for-Service, is used to calculate the instability crack length or depth by failure assessment diagram. It is demonstrated that the welding residual stress has amore » strong influence on the results.« less

Flaw Stability Considering Residual Stress for Aging Management of Spent Nuclear Fuel Multiple-Purpose Canisters

DOE PAGES

Lam, Poh-Sang; Sindelar, Robert L.

2016-04-28

A typical multipurpose canister (MPC) is made of austenitic stainless steel and is loaded with spent nuclear fuel assemblies. Because heat treatment for stress relief is not required for the construction of the MPC, the canister is susceptible to stress corrosion cracking in the weld or heat affected zone regions under long-term storage conditions. Logic for flaw acceptance is developed should crack-like flaws be detected by Inservice Inspection. The procedure recommended by API 579-1/ASME FFS-1, Fitness-for-Service, is used to calculate the instability crack length or depth by failure assessment diagram. It is demonstrated that the welding residual stress has amore » strong influence on the results.« less

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.

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.

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.

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

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

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.

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.

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

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)

Welding procedure specification. Supplement 1. Records of procedure qualification tests. Gas tungsten arc welding of aluminum alloys 3004, 5052, and 5X54

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

Wodtke, C.H.; Frizzell, D.R.; Plunkett, W.A.

1986-06-01

Procedure WPS-1002 is qualified under Section IX of the ASME Boiler and Pressure Vessel Code for gas tungsten arc welding of aluminum alloys 3004, 5052, 5154, and 5454 (P-22), in thickness range 0.062 to 0.5 inches; filler metal is ER4043 (F-23) for 3004, and ER5356 (F-22) for other alloys; shielding gas is argon.

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

Report on FY15 Alloy 617 SMT Creep-Fatigue Test Results

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

Wang, Yanli; Jetter, Robert I.; Baird, Seth T.

For the temperature range of 990-950C, Alloy 617 is a candidate IHX structural material for high temperature gas reactors (HTGRs) because of its high temperature creep properties. Also, its superior strength over a broad temperature range also offers advantages for certain component applications. In order for the designers to be able to use Alloy 617 for these high temperature components, Alloy 617 has to be approved for use in Section III (the nuclear section) of the ASME (American Society of Mechanical Engineers) Boiler and Pressure Vessel Code. A plan has been developed to propose a Code Case for use ofmore » Alloy 617 at elevated temperature in Section III of the ASME Code by September 2015. There has not been a new high temperature material approved for use in Section III for almost 20 years. The Alloy 617 Code Case effort would lead the way to establish a path for Code qualification of new high temperature materials of interest to other advanced SMRs. Creep-fatigue at elevated temperatures is the most damaging structural failure mode. In the past 40 years significant efforts have been devoted to the elevated temperature Code rule development in Section III, Subsection NH* of the ASME Boiler and Pressure Vessel Code, to ascertain conservative structural designs to prevent creep-fatigue failure. The current Subsection NH creep-fatigue procedure was established by the steps of (1) analytically obtaining a detailed stress-strain history, (2) comparing the stress and strain components to cyclic test results deconstructed into stress and strain quantities, and (3) recombining the results to obtain a damage function in the form of the so-called creep-fatigue damage-diagram. The deconstruction and recombination present difficulties in evaluation of test data and determination of cyclic damage in design. The uncertainties in these steps lead to the use of overly conservative design factors in the current creep-fatigue procedure. In addition, and of major significance to the viability of the Alloy 617 Code Case, the use of the current elastic analysis based rules in Subsection NH for the evaluation of strain limits (a precursor for the creep-fatigue rules) and the creep-fatigue rules themselves have been deemed inappropriate for Alloy 617 at temperatures above 650C (Corum and Brass, 1991). The rationale 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, 650C, is well below the temperature range of interest for this material for the High Temperature Gas Cooled Reactor (HTGR) as well as the VHTR. The only current alternative is, thus, a full inelastic analysis which requires sophisticated material models which have not yet been formulated and verified. To address the prohibition on the use of current methods at very high temperatures, proposed Code rules have been developed which are based on the use of elastic-perfectly plastic (E-PP) analysis methods and which are expected to be applicable to very high temperatures. To provide data to implement the proposed rules and to verify their application, a series of tests have been initiated. One test concept, the Simplified Model Test (SMT), takes into account the stress and strain redistribution in real structures by including representative follow-up characteristics in the test specimen. The correlation parameter between test and design is the elastically calculated strain, and the dependent test variable is the observed cycles to failure. Although the initial priority for the SMT approach is to generate data to support validation of the E-PP Code Case for evaluation of creep-fatigue damage, the broader goal of the SMT approach is to develop a methodology for evaluation of creep fatigue damage which is simpler to implement than the current complex rules and applicable to the full temperature range from ambient conditions to the very high temperature creep regime of 900-950C. Also, guidance has been received from ASME Code committees that the proposed EPP methodology for evaluation of creep-fatigue damage should be extended to the other Subsection NH materials to the extent feasible. Thus, the scope of testing has been expanded to include SS304H and SS316H. This report describes the SMT approach and the development of testing capability to conduct SMT experiments on Alloy 617 and 304H and 316H and stainless steels. These SMT specimen data are also representative of component loading conditions and have been used as part of the verification of the proposed elastic-perfectly plastic Code Cases. Results from the SMT tests on both Alloy 617 and SS316H were compared to the predictions from the EPP Creep-Fatigue Code Case. Two different comparisons were made; one based on design life equal to the test duration and the other with an acceptable design life determined from the EPP Code Case procedure. The latter approach permits the determination of...« less

DEVELOPMENT OF AG-1 SECTION FI ON METAL MEDIA FILTERS - 9061

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

Adamson, D; Charles A. Waggoner, C

Development of a metal media standard (FI) for ASME AG-1 (Code on Nuclear Air and Gas Treatment) has been under way for almost ten years. This paper will provide a brief history of the development process of this section and a detailed overview of its current content/status. There have been at least two points when dramatic changes have been made in the scope of the document due to feedback from the full Committee on Nuclear Air and Gas Treatment (CONAGT). Development of the proposed section has required resolving several difficult issues associated with scope; namely, filtering efficiency, operating conditions (mediamore » velocity, pressure drop, etc.), qualification testing, and quality control/acceptance testing. A proposed version of Section FI is currently undergoing final revisions prior to being submitted for balloting. The section covers metal media filters of filtering efficiencies ranging from medium (less than 99.97%) to high (99.97% and greater). Two different types of high efficiency filters are addressed; those units intended to be a direct replacement of Section FC fibrous glass HEPA filters and those that will be placed into newly designed systems capable of supporting greater static pressures and differential pressures across the filter elements. Direct replacements of FC HEPA filters in existing systems will be required to meet equivalent qualification and testing requirements to those contained in Section FC. A series of qualification and quality assurance test methods have been identified for the range of filtering efficiencies covered by this proposed standard. Performance characteristics of sintered metal powder vs. sintered metal fiber media are dramatically different with respect to parameters like differential pressures and rigidity of the media. Wide latitude will be allowed for owner specification of performance criteria for filtration units that will be placed into newly designed systems. Such allowances will permit use of the most appropriate metal media for a system as specified by the owner with respect to material of manufacture, media velocity, system maximum static pressure, maximum differential pressure across the filter, and similar parameters.« less

The role of materials in global competitiveness

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

NONE

A symposium on global competitiveness was sponsored by ASM`s Advisory Technical Awareness Council during Materials Week in Cleveland last October. Carpenter Technology`s approach to internationalization and diversification involves three steps: internationalization of core businesses, diversification into engineered products, and focused research and development. Aluminum`s potential was the basis of the Audi-Alcoa relationship, and the result was a true breakthrough: a spaceframe structure designed to integrate every component surface as a structural entity, featuring straight and curved extruded sections joined by complex diecast nodes at key intersections and connection points. Through the support of research and development, many federal departments andmore » agencies have long been involved directly or indirectly in the support of civilian as well as defense industries. New copper alloys and fabrication techniques are enhancing global competitiveness, based largely on copper`s natural advantages of conductivity and corrosion resistance. The heavy equipment industry is a major transformer and user of steel, rubber, aluminum, welding consumables and equipment; glass, plastics, microprocessors and electronics; machine tools, and energy. It comprises the construction, farming, mining, and powertrain equipment manufacturers.« less

The First ASME Code Stamped Cryomodule at SNS

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

Howell, M P; Crofford, M T; Douglas, D L

The first spare cryomodule for the Spallation Neutron Source (SNS) has been designed, fabricated, and tested by SNS personnel. The approach to design for this cryomodule was to hold critical design features identical to the original design such as bayonet positions, coupler positions, cold mass assembly, and overall footprint. However, this is the first SNS cryomodule that meets the pressure requirements put forth in the 10 CFR 851: Worker Safety and Health Program. The most significant difference is that Section VIII of the ASME Boiler and Pressure Vessel Code was applied to the vacuum vessel of this cryomodule. Applying themore » pressure code to the helium vessels within the cryomodule was considered. However, it was determined to be schedule prohibitive because it required a code case for materials that are not currently covered by the code. Good engineering practice was applied to the internal components to verify the quality and integrity of the entire cryomodule. The design of the cryomodule, fabrication effort, and cryogenic test results will be reported in this paper.« less

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

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.

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

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

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.

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

PubMed

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

2016-10-01

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

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

PubMed

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

2017-08-01

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

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.

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

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.

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.

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.

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

PubMed

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

2009-04-01

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

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.