Sample records for efficiency acee program

  1. A qualitative evaluation of the 2005-2011 National Academic Centers of Excellence in Youth Violence Prevention Program.

    PubMed

    Holland, Kristin M; Vivolo-Kantor, Alana M; Dela Cruz, Jason; Massetti, Greta M; Mahendra, Reshma

    2015-12-01

    The Centers for Disease Control and Prevention's Division of Violence Prevention (DVP) funded eight National Academic Centers of Excellence (ACEs) in Youth Violence Prevention from 2005 to 2010 and two Urban Partnership Academic Centers of Excellence (UPACEs) in Youth Violence Prevention from 2006 to 2011. The ACEs and UPACEs constitute DVP's 2005-2011 ACE Program. ACE Program goals include partnering with communities to promote youth violence (YV) prevention and fostering connections between research and community practice. This article describes a qualitative evaluation of the 2005-2011 ACE Program using an innovative approach for collecting and analyzing data from multiple large research centers via a web-based Information System (ACE-IS). The ACE-IS was established as an efficient mechanism to collect and document ACE research and programmatic activities. Performance indicators for the ACE Program were established in an ACE Program logic model. Data on performance indicators were collected through the ACE-IS biannually. Data assessed Centers' ability to develop, implement, and evaluate YV prevention activities. Performance indicator data demonstrate substantial progress on Centers' research in YV risk and protective factors, community partnerships, and other accomplishments. Findings provide important lessons learned, illustrate progress made by the Centers, and point to new directions for YV prevention research and programmatic efforts. Published by Elsevier Ltd.

  2. A qualitative evaluation of the 2005–2011 National Academic Centers of Excellence in Youth Violence Prevention Program☆

    PubMed Central

    Holland, Kristin M.; Vivolo-Kantor, Alana M.; Cruz, Jason Dela; Massetti, Greta M.; Mahendra, Reshma

    2018-01-01

    The Centers for Disease Control and Prevention’s Division of Violence Prevention (DVP) funded eight National Academic Centers of Excellence (ACEs) in Youth Violence Prevention from 2005 to 2010 and two Urban Partnership Academic Centers of Excellence (UPACEs) in Youth Violence Prevention from 2006 to 2011. The ACEs and UPACEs constitute DVP’s 2005–2011 ACE Program. ACE Program goals include partnering with communities to promote youth violence (YV) prevention and fostering connections between research and community practice. This article describes a qualitative evaluation of the 2005–2011 ACE Program using an innovative approach for collecting and analyzing data from multiple large research centers via a web-based Information System (ACE-IS). The ACE-IS was established as an efficient mechanism to collect and document ACE research and programmatic activities. Performance indicators for the ACE Program were established in an ACE Program logic model. Data on performance indicators were collected through the ACE-IS biannually. Data assessed Centers’ ability to develop, implement, and evaluate YV prevention activities. Performance indicator data demonstrate substantial progress on Centers’ research in YV risk and protective factors, community partnerships, and other accomplishments. Findings provide important lessons learned, illustrate progress made by the Centers, and point to new directions for YV prevention research and programmatic efforts. PMID:26319174

  3. Synthesis and toughness properties of resins and composites

    NASA Technical Reports Server (NTRS)

    Johnston, N. J.

    1984-01-01

    Tensile and shear moduli of four ACEE (Aircraft Energy Efficiency Program) resins are presented along with ACEE composite material modulus predictions based on micromechanics. Compressive strength and fracture toughness of the resins and composites were discussed. In addition, several resin synthesis techniques are reviewed.

  4. The ACEE program and basic composites research at Langley Research Center (1975 to 1986): Summary and bibliography

    NASA Technical Reports Server (NTRS)

    Dow, Marvin B.

    1987-01-01

    Composites research conducted at the Langley Research Center during the period from 1975 to 1986 is described, and an annotated bibliography of over 600 documents (with their abstracts) is presented. The research includes Langley basic technology and the composite primary structures element of the NASA Aircraft Energy Efficiency (ACEE) Program. The basic technology documents cited in the bibliography are grouped according to the research activity such as design and analysis, fatigue and fracture, and damage tolerance. The ACEE documents cover development of composite structures for transport aircraft.

  5. Abstracts of ARI Research Publications FY 1983

    DTIC Science & Technology

    1983-10-01

    and the relationship between SM usage and the soldier’s ability to perform his or her job skills , as measured by 2 SQT scores. Questionnaire data were...System (ACES) on soldier performance. Four -’ ACES programs were selected for evaluation: Basic Skills Education Program I, Literacy Phase (BSEP I...the prototype system was operated at Fort Carson, CO, the relationships among maintenance workload, efficiency, and skill were studied. As workload

  6. ACEE composite structures technology

    NASA Technical Reports Server (NTRS)

    Klotzsche, M. (Compiler)

    1984-01-01

    The NASA Aircraft Energy Efficiency (ACEE) Composite Primary Aircraft Structures Program has made significant progress in the development of technology for advanced composites in commercial aircraft. Commercial airframe manufacturers have demonstrated technology readiness and cost effectiveness of advanced composites for secondary and medium primary components and have initiated a concerted program to develop the data base required for efficient application to safety-of-flight wing and fuselage structures. Oral presentations were compiled into five papers. Topics addressed include: damage tolerance and failsafe testing of composite vertical stabilizer; optimization of composite multi-row bolted joints; large wing joint demonstation components; and joints and cutouts in fuselage structure.

  7. Airframe technology for aircraft energy efficiency. [economic factors

    NASA Technical Reports Server (NTRS)

    James, R. L., Jr.; Maddalon, D. V.

    1984-01-01

    The economic factors that resulted in the implementation of the aircraft energy efficiency program (ACEE) are reviewed and airframe technology elements including content, progress, applications, and future direction are discussed. The program includes the development of laminar flow systems, advanced aerodynamics, active controls, and composite structures.

  8. ACEE Composite Structures Technology: Review of selected NASA research on composite materials and structures

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The NASA Aircraft Energy Efficiency (ACEE) Composite Primary Aircraft Structures Program was designed to develop technology for advanced composites in commercial aircraft. Research on composite materials, aircraft structures, and aircraft design is presented herein. The following parameters of composite materials were addressed: residual strength, damage tolerance, toughness, tensile strength, impact resistance, buckling, and noise transmission within composite materials structures.

  9. Propulsion/ACEE

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The research objectives of the NASA aircraft energy efficiency program are summarized. Engine component improvements for turbofan engines, diagnostics, the development of advanced turboprop engines, and propeller noise analysis are discussed.

  10. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity.

    PubMed

    Woodman, Zenda L; Schwager, Sylva L U; Redelinghuys, Pierre; Carmona, Adriana K; Ehlers, Mario R W; Sturrock, Edward D

    2005-08-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the k(cat) for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates.

  11. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity

    PubMed Central

    Woodman, Zenda L.; Schwager, Sylva L. U.; Redelinghuys, Pierre; Carmona, Adriana K.; Ehlers, Mario R. W.; Sturrock, Edward D.

    2005-01-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the kcat for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates. PMID:15813703

  12. 77 FR 48527 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... Program (NCAP) Test Concerning Automated Commercial Environment (ACE) Simplified Entry: Modification of... Automated Commercial Environment (ACE). The test's participant selection criteria are modified to reflect... (NCAP) test concerning Automated Commercial Environment (ACE) Simplified Entry functionality (Simplified...

  13. Materials and structures/ACEE

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Light weight composites made from graphite fibers, glass, or man made materials held in an epoxy matrix, and their application to airframe design are reviewed. The Aircraft Energy Efficiency program is discussed. Characteristics of composites, acceptable risks, building parts and confidence, and aeroelastic tailoring are considered.

  14. 7 CFR 2502.1 - Applicability of regulations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM General Information § 2502.1 Applicability of regulations. (a) This part contains program-specific definitions for the ACE Grants Program. (b) Subpart B establishes the criteria to be used in determining eligibility for an ACE...

  15. 7 CFR 2502.1 - Applicability of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM General Information § 2502.1 Applicability of regulations. (a) This part contains program-specific definitions for the ACE Grants Program. (b) Subpart B establishes the criteria to be used in determining eligibility for an ACE...

  16. 7 CFR 2502.1 - Applicability of regulations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM General Information § 2502.1 Applicability of regulations. (a) This part contains program-specific definitions for the ACE Grants Program. (b) Subpart B establishes the criteria to be used in determining eligibility for an ACE...

  17. Daughter-Specific Transcription Factors Regulate Cell Size Control in Budding Yeast

    PubMed Central

    Di Talia, Stefano; Wang, Hongyin; Skotheim, Jan M.; Rosebrock, Adam P.; Futcher, Bruce; Cross, Frederick R.

    2009-01-01

    In budding yeast, asymmetric cell division yields a larger mother and a smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint has long been considered to be a main regulator of the length of the G1 phase of the cell cycle, resulting in longer G1 in the smaller daughter cells. Our recent data confirmed this concept using quantitative time-lapse microscopy. However, it has been proposed that daughter-specific, Ace2-dependent repression of expression of the G1 cyclin CLN3 had a dominant role in delaying daughters in G1. We wanted to reconcile these two divergent perspectives on the origin of long daughter G1 times. We quantified size control using single-cell time-lapse imaging of fluorescently labeled budding yeast, in the presence or absence of the daughter-specific transcriptional regulators Ace2 and Ash1. Ace2 and Ash1 are not required for efficient size control, but they shift the domain of efficient size control to larger cell size, thus increasing cell size requirement for Start in daughters. Microarray and chromatin immunoprecipitation experiments show that Ace2 and Ash1 are direct transcriptional regulators of the G1 cyclin gene CLN3. Quantification of cell size control in cells expressing titrated levels of Cln3 from ectopic promoters, and from cells with mutated Ace2 and Ash1 sites in the CLN3 promoter, showed that regulation of CLN3 expression by Ace2 and Ash1 can account for the differential regulation of Start in response to cell size in mothers and daughters. We show how daughter-specific transcriptional programs can interact with intrinsic cell size control to differentially regulate Start in mother and daughter cells. This work demonstrates mechanistically how asymmetric localization of cell fate determinants results in cell-type-specific regulation of the cell cycle. PMID:19841732

  18. ACE Inhibitor and ARB utilization and expenditures in the Medicaid fee-for-service program from 1991 to 2008.

    PubMed

    Bian, Boyang; Kelton, Christina M L; Guo, Jeff J; Wigle, Patricia R

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely prescribed for the treatment of hypertension and heart failure, as well as for kidney disease prevention in patients with diabetes mellitus and the management of patients after myocardial infarction. To (a) describe ACE inhibitor and ARB utilization and spending in the Medicaid fee-for-service program from 1991 through 2008, and (b) estimate the potential cost savings for the collective Medicaid programs from a higher ratio of generic ACE inhibitor utilization. A retrospective, descriptive analysis was performed using the National Summary Files from the Medicaid State Drug Utilization Data, which are composed of pharmacy claims that are subject to federally mandated rebates from pharmaceutical manufacturers. For the years 1991-2008, quarterly claim counts and expenditures were calculated by summing data for individual ACE inhibitors and ARBs. Quarterly per-claim expenditure as a proxy for drug price was computed for all brand and generic drugs. Market shares were calculated based on the number of pharmacy claims and Medicaid expenditures. In the Medicaid fee-for-service program, ACE inhibitors accounted for 100% of the claims in the combined market for ACE inhibitors and ARBs in 1991, 80.6% in 2000, and 64.7% in 2008. The Medicaid expenditure per ACE inhibitor claim dropped from $37.24 in 1991 to $24.03 in 2008 when generics accounted for 92.5% of ACE inhibitor claims; after adjusting for inflation for the period from 1991 to 2008, the real price drop was 59.2%. Brand ACE inhibitors accounted for only 7.5% of the claims in 2008 for all ACE inhibitors but 32.1% of spending; excluding the effects of manufacturer rebates, Medicaid spending would have been reduced by $28.7 million (9%) in 2008 if all ACE inhibitor claims were generic. The average price per ACE inhibitor claim in 2008 was $24.03 ($17.64 per generic claim vs. $103.45 per brand claim) versus $81.98 per ARB claim. If the ACE inhibitor ratio had been 75% in 2008 rather than 64.7%, the Medicaid program would have saved approximately 13% or about $41.8 million, again excluding the effects of manufacturer rebates. If the ACE inhibitor ratio had been 90% in 2008, the cost savings for the combined Medicaid fee-forservice programs would have been about 33% or about $102.3 million. The total cost savings opportunity with 100% generic ACE inhibitor utilization in 2008 and an ACE inhibitor ratio of 75% was $75.1 million (24%) or $142.3M (46%) with a 90% ACE inhibitor ratio. Factors that affect Medicaid spending by contributing to increased utilization of ACE inhibitors and ARBs, such as the rising prevalence of hypertension, heart disease, and diabetes, can be offset by reduction in the average price attained through a higher proportion of ACE inhibitors and a higher percentage of generic versus brand ACE inhibitors.

  19. The Case for Including Adverse Childhood Experiences in Child Maltreatment Education: A Path Analysis.

    PubMed

    Bachmann, Michael; Bachmann, Brittany A

    2018-03-16

    The lifelong, negative consequences of exposure to adverse childhood experiences (ACEs) for individuals and their families are well established. To demonstrate the importance of including ACE information in child maltreatment education curricula using path analysis. Survey data examined the impact of child maltreatment education programs and knowledge about ACEs on medical practitioners' reporting habits and ability to detect maltreatment. A path diagram distinguished between the direct impact of education programs on outcome measures and the indirect effect that is mediated through knowledge of ACEs. Medical practitioners' ability to detect child maltreatment and their number of referrals to Child Protective Services (CPS). The optimized path diagram (χ 2 SB(3) = 3.9, p = 0.27; RMSEA-SB = 0.017; R 2 = 0.21, where SB is Satorra-Bentler coefficient and RMSEA is root-mean-square error of approximation) revealed the mediating variable "knowledge about ACEs" as the strongest structural effect (SB-β = 0.34) on the number of CPS referrals. It was almost twice as high as the second strongest effect of formal education programs (SB-β = 0.19). For workplace training programs, the total effect when including knowledge of ACEs was almost double as strong as the direct effect alone. Even when previous child maltreatment education was controlled for, practitioners familiar with the consequences of ACEs were significantly more likely to recognize and to report abuse to CPS. This study documented the importance of specialized training programs on ACEs, and the essential role ACE knowledge plays in the effectiveness of provider education programs.

  20. 7 CFR 2502.4. - Program eligibility.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM Program Eligibility...) The capacity to effectively administer a program of services and benefits authorized by the ACE...

  1. 7 CFR 2502.4. - Program eligibility.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM Program Eligibility...) The capacity to effectively administer a program of services and benefits authorized by the ACE...

  2. 7 CFR 2502.4. - Program eligibility.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM Program Eligibility...) The capacity to effectively administer a program of services and benefits authorized by the ACE...

  3. 7 CFR 2502.6 - Recipients of program benefits or services.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OUTREACH, DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM Program... receive program services or benefits under the ACE program are farmworkers who meet the definition of...

  4. 7 CFR 2502.6 - Recipients of program benefits or services.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OUTREACH, DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM Program... receive program services or benefits under the ACE program are farmworkers who meet the definition of...

  5. 7 CFR 2502.6 - Recipients of program benefits or services.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OUTREACH, DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM Program... receive program services or benefits under the ACE program are farmworkers who meet the definition of...

  6. Distinct EUV minimum of the solar irradiance (16-40 nm) observed by SolACES spectrometers onboard the International Space Station (ISS) in August/September 2009

    NASA Astrophysics Data System (ADS)

    Nikutowski, B.; Brunner, R.; Erhardt, Ch.; Knecht, St.; Schmidtke, G.

    2011-09-01

    In the field of terrestrial climatology the continuous monitoring of the solar irradiance with highest possible accuracy is an important goal. SolACES as a part of the ESA mission SOLAR on the ISS is measuring the short-wavelength solar EUV irradiance from 16-150 nm. This data will be made available to the scientific community to investigate the impact of the solar irradiance variability on the Earth's climate as well as the thermospheric/ionospheric interactions that are pursued in the TIGER program. Since the successful launch with the shuttle mission STS-122 on February 7th, 2008, SolACES initially recorded the low EUV irradiance during the extended solar activity minimum. Thereafter it has been observing the EUV irradiance during the increasing solar activity with enhanced intensity and changing spectral composition. SolACES consists of three grazing incidence planar grating spectrometers. In addition there are two three-signal ionisation chambers, each with exchangeable band-pass filters to determine the absolute EUV fluxes repeatedly during the mission. One important problem of space-borne instrumentation recording the solar EUV irradiance is the degradation of the spectrometer sensitivity. The two double ionisation chambers of SolACES, which could be re-filled with three different gases for each recording, allow the recalibration of the efficiencies of the three SolACES spectrometers from time to time.

  7. Formative Evaluation of ACES Program: Findings from Surveys and Interviews Year One, Grades 11 and 12

    ERIC Educational Resources Information Center

    Wolanin, Natalie; Modarresi, Shahpar

    2015-01-01

    The Office of Shared Accountability (OSA) in Montgomery County (Maryland) Public Schools (MCPS) is conducting a multiyear evaluation of the Achieving Collegiate Excellence and Success (ACES) program. The ACES program is a collaboration between MCPS, Montgomery College (MC), and the Universities at Shady Grove (USG) to create a seamless pathway…

  8. Evaluation of organic-vapor respirator cartridge efficiency for toluene diisocyanate vapor in the presence of methylenechloride or acetone solvent.

    PubMed

    Dharmarajan, Venkatram; Cummings, Barbara; Lingg, Robert D

    2003-08-01

    Toluene diisocyanate (TDI) is a widely used raw material in the manufacture of flexible polyurethane foams. Acetone (ACE) and/or methylenechloride (MECL) solvents are the most commonly used solvent-based blowing agents for TDI foams. ACGIH has recommended a TWA exposure limit of 5 ppb for TDI and 500 ppm for ACE. For MECL, OSHA mandates a TWA-exposure limit of 25 ppm. This study evaluated the ability of the organic-vapor respirator cartridges (OVC) to block TDI, as well as the effect of airborne MECL or ACE on the OVCs' efficiency to capture TDI. An aluminum/stainless steel exposure chamber was constructed for simultaneously challenging OVCs in triplicate with a dynamic atmosphere of TDI and ACE or MECL vapor. The challenge atmosphere was generated by combining a TDI-laden nitrogen stream from the headspace of a heated impinger with a humidified stream of the indicated solvent in air. The average challenge concentration for TDI was 275 ppb. The average MECL or ACE concentrations were 547 and 581 ppm, respectively. The challenge atmosphere at room temperature (approximately 24 degrees C) and at 25 or 80 percent relative humidity was drawn through each cartridge at 32 L/min for 40+ hours. During the last 8 hours of the challenge, the atmosphere had only TDI vapor. The pre- and post-cartridge atmospheres were periodically sampled for TDI and solvent. Five tests were conducted--two with MSA and three with North OVCs. Under these extreme test conditions no TDI breakthrough was detected from any OVC. The average-calculated efficiency of the OVCs for TDI was >99.9+ percent. Within the first 6 hours of the challenge the cartridges were saturated with ACE or MECL; nevertheless, continued challenging with TDI and solvents did not cause any TDI breakthrough. The study demonstrates that with an OSHA-compliant respiratory protection program, an OVC can safely be used for 40 hours in most polyurethane foam operations. In typical occupational environments using TDI and solvents, the solvent breakthrough, rather than TDI breakthrough, would be the determining factor for the calculation of respirator cartridge change-out schedules.

  9. 78 FR 66039 - Modification of National Customs Automation Program Test Concerning Automated Commercial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ... Customs Automation Program Test Concerning Automated Commercial Environment (ACE) Cargo Release (Formerly... Simplified Entry functionality in the Automated Commercial Environment (ACE). Originally, the test was known...) test concerning Automated Commercial Environment (ACE) Simplified Entry (SE test) functionality is...

  10. Aircraft Energy Efficiency (ACEE) status report

    NASA Technical Reports Server (NTRS)

    Nored, D. L.; Dugan, J. F., Jr.; Saunders, N. T.; Ziemianski, J. A.

    1979-01-01

    Fuel efficiency in aeronautics, for fuel conservation in general as well as for its effect on commercial aircraft operating economics is considered. Projects of the Aircraft Energy Efficiency Program related to propulsion are emphasized. These include: (1) engine component improvement, directed at performance improvement and engine diagnostics for prolonged service life; (2) energy efficient engine, directed at proving the technology base for the next generation of turbofan engines; and (3) advanced turboprop, directed at advancing the technology of turboprop powered aircraft to a point suitable for commercial airline service. Progress in these technology areas is reported.

  11. ACE: A Collaborative School Consultation Program for Secondary School Teachers

    ERIC Educational Resources Information Center

    Couture, Caroline; Massé, Line

    2014-01-01

    This article presents a description of ACE (Accompagnement collaboratif des enseignants (Collaborative teacher accompaniment)), a new program designed to guide secondary school teachers in integrating students with behavioral problems in their classrooms. ACE proposes collaborative accompaniment inspired by behavioral and mental health…

  12. Academic Success of Montgomery College Students in the Achieving Collegiate Excellence and Success (ACES) Program: 2014-2015

    ERIC Educational Resources Information Center

    Cooper-Martin, Elizabeth; Wolanin, Natalie

    2016-01-01

    The Office of Shared Accountability in Montgomery County Public Schools (MCPS) is conducting a multiyear evaluation of the Achieving Collegiate Excellence and Success (ACES) program. The ACES program is a collaboration between MCPS, Montgomery College (MC) and the Universities at Shady Grove to create a seamless pathway from high school to college…

  13. Adult and Community Education: An Overview. Australian Vocational Education and Training Statistics, 2001.

    ERIC Educational Resources Information Center

    Australian National Training Authority, Melbourne.

    In 2001, around 1,200 of 6,700 providers in the Australian public vocational education and training (VET) system delivered adult and community education (ACE) programs, which attracted 497,500 people. ACE programs accounted for 20.7 million hours of training and 972,500 subject enrolments. Vocational ACE programs accounted for 238,700 students,…

  14. The Case for Including Adverse Childhood Experiences in Child Maltreatment Education: A Path Analysis

    PubMed Central

    Bachmann, Michael; Bachmann, Brittany A

    2018-01-01

    Context The lifelong, negative consequences of exposure to adverse childhood experiences (ACEs) for individuals and their families are well established. Objective To demonstrate the importance of including ACE information in child maltreatment education curricula using path analysis. Design Survey data examined the impact of child maltreatment education programs and knowledge about ACEs on medical practitioners’ reporting habits and ability to detect maltreatment. A path diagram distinguished between the direct impact of education programs on outcome measures and the indirect effect that is mediated through knowledge of ACEs. Main Outcome Measures Medical practitioners’ ability to detect child maltreatment and their number of referrals to Child Protective Services (CPS). Results The optimized path diagram (χ2SB(3) = 3.9, p = 0.27; RMSEA-SB = 0.017; R2 = 0.21, where SB is Satorra-Bentler coefficient and RMSEA is root-mean-square error of approximation) revealed the mediating variable “knowledge about ACEs” as the strongest structural effect (SB-β = 0.34) on the number of CPS referrals. It was almost twice as high as the second strongest effect of formal education programs (SB-β = 0.19). For workplace training programs, the total effect when including knowledge of ACEs was almost double as strong as the direct effect alone. Even when previous child maltreatment education was controlled for, practitioners familiar with the consequences of ACEs were significantly more likely to recognize and to report abuse to CPS. Conclusion This study documented the importance of specialized training programs on ACEs, and the essential role ACE knowledge plays in the effectiveness of provider education programs. PMID:29616910

  15. Mentoring Functions within the American Council on Education (ACE) Fellows Leadership Development Program: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Grotrian-Ryan, Sheri A.

    2012-01-01

    The purpose of this study was to examine and better comprehend the concept of mentoring within the American Council on Education (ACE) Fellows Program. This study addressed the functions of mentoring and how they applied to those participating in the ACE Fellows Program--from the Fellows' (or protégés') perspectives. A sequential…

  16. Factors Affecting the Corporate Decision-Making Process of Air Transport Manufacturers

    NASA Technical Reports Server (NTRS)

    Ollila, R. G.; Hill, J. D.; Noton, B. R.; Duffy, M. A.; Epstein, M. M.

    1976-01-01

    Fuel economy is a pivotal question influencing the future sale and utilization of commercial aircraft. The NASA Aircraft Energy Efficiency (ACEE) Program Office has a program intended to accelerate the readiness of advanced technologies for energy efficient aircraft. Because the decision to develop a new airframe or engine is a major financial hazard for manufacturers, it is important to know what factors influence the decision making process. A method is described for identifying and ranking individuals and organizations involved at each stage of commercial air transport development, and the barriers that must be overcome in adopting new technologies.

  17. Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD.

    PubMed

    Zhang, Xiaolei; Wang, Chen; Dai, Huaping; Lin, Yingxiang; Zhang, Jun

    2008-09-01

    Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD. Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification. Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O(2) uptake, maximal O(2) pulse, maximal dyspnoea index, ventilatory response (DeltaVE/DeltaVCO(2)), O(2) cost of ventilation (VO(2)/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO(2) among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups. The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.

  18. The drive for Aircraft Energy Efficiency

    NASA Technical Reports Server (NTRS)

    James, R. L., Jr.; Maddalon, D. V.

    1984-01-01

    NASA's Aircraft Energy Efficiency (ACEE) program, which began in 1976, has mounted a development effort in four major transport aircraft technology fields: laminar flow systems, advanced aerodynamics, flight controls, and composite structures. ACEE has explored two basic methods for achieving drag-reducing boundary layer laminarization: the use of suction through the wing structure (via slots or perforations) to remove boundary layer turbulence, and the encouragement of natural laminar flow maintenance through refined design practices. Wind tunnel tests have been conducted for wide bodied aircraft equipped with high aspect ratio supercritical wings and winglets. Maneuver load control and pitch-active stability augmentation control systems reduce fuel consumption by reducing the drag associated with high aircraft stability margins. Composite structures yield lighter airframes that in turn call for smaller wing and empennage areas, reducing induced drag for a given payload. In combination, all four areas of development are expected to yield a fuel consumption reduction of 40 percent.

  19. Architecture Adaptive Computing Environment

    NASA Technical Reports Server (NTRS)

    Dorband, John E.

    2006-01-01

    Architecture Adaptive Computing Environment (aCe) is a software system that includes a language, compiler, and run-time library for parallel computing. aCe was developed to enable programmers to write programs, more easily than was previously possible, for a variety of parallel computing architectures. Heretofore, it has been perceived to be difficult to write parallel programs for parallel computers and more difficult to port the programs to different parallel computing architectures. In contrast, aCe is supportable on all high-performance computing architectures. Currently, it is supported on LINUX clusters. aCe uses parallel programming constructs that facilitate writing of parallel programs. Such constructs were used in single-instruction/multiple-data (SIMD) programming languages of the 1980s, including Parallel Pascal, Parallel Forth, C*, *LISP, and MasPar MPL. In aCe, these constructs are extended and implemented for both SIMD and multiple- instruction/multiple-data (MIMD) architectures. Two new constructs incorporated in aCe are those of (1) scalar and virtual variables and (2) pre-computed paths. The scalar-and-virtual-variables construct increases flexibility in optimizing memory utilization in various architectures. The pre-computed-paths construct enables the compiler to pre-compute part of a communication operation once, rather than computing it every time the communication operation is performed.

  20. Advanced aerodynamics. Selected NASA research

    NASA Technical Reports Server (NTRS)

    1981-01-01

    This Conference Publication contains selected NASA papers that were presented at the Fifth Annual Status Review of the NASA Aircraft Energy Efficiency (ACEE) Energy Efficient Transport (EET) Program held at Dryden Flight Research Center in Edwards, California on September 14 to 15, 1981. These papers describe the status of several NASA in-house research activities in the areas of advanced turboprops, natural laminar flow, oscillating control surfaces, high-Reynolds-number airfoil tests, high-lift technology, and theoretical design techniques.

  1. Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

    ERIC Educational Resources Information Center

    Smith, Douglas H.

    2006-01-01

    Adult Continuing Education (ACE) and Human Resource Development (HRD) have grown tremendously in the last quarter century. ACE experienced tremendous growth in the 60s and 70s, with over 17 million attending colleges and universities, and local school and community adult education programs by the end of the 1970s. More ACE programs were started…

  2. Improving resident engagement in quality improvement and patient safety initiatives at the bedside: the Advocate for Clinical Education (ACE).

    PubMed

    Schleyer, Anneliese M; Best, Jennifer A; McIntyre, Lisa K; Ehrmantraut, Ross; Calver, Patty; Goss, J Richard

    2013-01-01

    Quality improvement (QI) and patient safety (PS) are essential competencies in residency training; however, the most effective means to engage physicians remains unclear. The authors surveyed all medicine and surgery physicians at their institution to describe QI/PS practices and concurrently implemented the Advocate for Clinical Education (ACE) program to determine if a physician-centered program in the context of educational structures and at the point of care improved performance. The ACE rounded with medicine and surgery teams and provided individual and team-level education and feedback targeting 4 domains: professionalism, infection control, interpreter use, and pain assessment. In a pilot, the ACE observed 2862 physician-patient interactions and 178 physicians. Self-reported compliance often was greater than the behaviors observed. Following ACE implementation, observed professionalism behaviors trended toward improvement; infection control also improved. Physicians were highly satisfied with the program. The ACE initiative is one coaching/feedback model for engaging residents in QI/PS that may warrant further study.

  3. Energy Modeling Capabilities in ORD's Air, Climate and ...

    EPA Pesticide Factsheets

    Presentation to ACE Centers Kick-Off Meeting highlighting energy modeling work, capabilities and tools that are under development in ORD/NRMRL under the ACE Program. Presentation to ACE Centers Kick-Off Meeting

  4. Identification and the molecular mechanism of a novel myosin-derived ACE inhibitory peptide.

    PubMed

    Yu, Zhipeng; Wu, Sijia; Zhao, Wenzhu; Ding, Long; Shiuan, David; Chen, Feng; Li, Jianrong; Liu, Jingbo

    2018-01-24

    The objective of this work was to identify a novel ACE inhibitory peptide from myosin using a number of in silico methods. Myosin was evaluated as a substrate for use in the generation of ACE inhibitory peptides using BIOPEP and ExPASy PeptideCutter. Then the ACE inhibitory activity prediction of peptides in silico was evaluated using the program peptide ranker, following the database search of known and unknown peptides using the program BIOPEP. In addition, the interaction mechanisms of the peptide and ACE were evaluated by DS. All of the tripeptides were predicted to be nontoxic. Results suggested that the tripeptide NCW exerted potent ACE inhibitory activity with an IC 50 value of 35.5 μM. Furthermore, the results suggested that the peptide NCW comes into contact with Zn 701, Tyr 523, His 383, Glu 384, Glu 411, and His 387. The potential molecular mechanism of the NCW/ACE interaction was investigated. Results confirmed that the higher inhibitory potency of NCW might be attributed to the formation of more hydrogen bonds with the ACE's active site. Therefore, the in silico method is effective to predict and identify novel ACE inhibitory peptides from protein hydrolysates.

  5. Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

    PubMed

    Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

    2014-01-01

    Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

  6. Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

    PubMed Central

    Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

    2014-01-01

    Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

  7. A perspective of laminar-flow control. [aircraft energy efficiency program

    NASA Technical Reports Server (NTRS)

    Braslow, A. L.; Muraca, R. J.

    1978-01-01

    A historical review of the development of laminar flow control technology is presented with reference to active laminar boundary-layer control through suction, the use of multiple suction slots, wind-tunnel tests, continuous suction, and spanwise contamination. The ACEE laminar flow control program is outlined noting the development of three-dimensional boundary-layer codes, cruise-noise prediction techniques, airfoil development, and leading-edge region cleaning. Attention is given to glove flight tests and the fabrication and testing of wing box designs.

  8. Accompanying coordinate expansion and recurrence relation method using a transfer relation scheme for electron repulsion integrals with high angular momenta and long contractions

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

    Hayami, Masao; Seino, Junji; Nakai, Hiromi, E-mail: nakai@waseda.jp

    An efficient algorithm for the rapid evaluation of electron repulsion integrals is proposed. The present method, denoted by accompanying coordinate expansion and transferred recurrence relation (ACE-TRR), is constructed using a transfer relation scheme based on the accompanying coordinate expansion and recurrence relation method. Furthermore, the ACE-TRR algorithm is extended for the general-contraction basis sets. Numerical assessments clarify the efficiency of the ACE-TRR method for the systems including heavy elements, whose orbitals have long contractions and high angular momenta, such as f- and g-orbitals.

  9. Mentor Program Provides STEM Options

    ERIC Educational Resources Information Center

    Abdul-alim, Jamaal

    2011-01-01

    The ACE Mentor Program provides early career exposure, mentoring, and scholarships to high school students in an attempt to encourage them to enter one of the three fields that make up the ACE acronym: (1) architecture; (2) construction; and (3) engineering. Founded in 1993 by longtime engineering consultant Charles Thornton, the program is…

  10. 76 FR 34246 - Automated Commercial Environment (ACE); Announcement of National Customs Automation Program Test...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-13

    ... CBP with authority to conduct limited test programs or procedures designed to evaluate planned... aspects of this test, including the design, conduct and implementation of the test, in order to determine... Environment (ACE); Announcement of National Customs Automation Program Test of Automated Procedures for In...

  11. Kevlar/PMR-15 polyimide matrix composite for a complex shaped DC-9 drag reduction fairing

    NASA Technical Reports Server (NTRS)

    Kawai, R. T.; Mccarthy, R. F.; Willer, M. S.; Hrach, F. J.

    1982-01-01

    The Aircraft Energy Efficiency (ACEE) Program was established by NASA to improve the fuel efficiency of commercial transport aircraft and thereby to reduce the amount of fuel consumed by the air transportation industry. One of the final items developed by the program is an improved fairing which is the aft closure for the thrust reverser actuators on the JT8D nacelles on DC-9 aircraft. The reduced-drag fairing uses, in the interest of weight savings, an advanced composite construction. The composite material contains Kevlar 49 fibers in a PMR-15 matrix. Attention is given to the aerodynamic configuration, the material system, and aspects of fabrication development.

  12. Aerodynamics/ACEE: Aircraft energy efficiency

    NASA Technical Reports Server (NTRS)

    1981-01-01

    An overview is presented of a 10 year program managed by NASA which seeks to make possible the most efficient use of energy for aircraft propulsion and lift as well as provide a technology that can be used by U.S. manufacturers of air transports and engines. Supercritical wings, winglets, vortex drag reduction, high lift, active control, laminar flow control, and aerodynamics by computer are among the topics discussed. Wind tunnel models in flight verification of advanced technology, and the design, construction and testing of various aircraft structures are also described.

  13. Meet EPA Scientist Sherri Hunt, Ph.D.

    EPA Pesticide Factsheets

    Dr. Sherri Hunt is the Assistant Center Director for the Air, Climate, and Energy (ACE) Research Program. She plays an active leadership role in the ACE program planning and coordination and was a key author for the Research Action Plan development

  14. Advanced Turboprop Project

    NASA Technical Reports Server (NTRS)

    Hager, Roy D.; Vrabel, Deborah

    1988-01-01

    At the direction of Congress, a task force headed by NASA was organized in 1975 to identify potential fuel saving concepts for aviation. The result was the Aircraft Energy Efficiency (ACEE) Program implemented in 1976. An important part of the program was the development of advanced turboprop technology for Mach 0.65 to 0.85 applications having the potential fuel saving of 30 to 50 percent relative to existing turbofan engines. A historical perspective is presented of the development and the accomplishments that brought the turboprop to successful flight tests in 1986 and 1987.

  15. Advanced turboprop project

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

    Hager, R.D.; Vrabel, D.

    1988-01-01

    At the direction of Congress, a task force headed by NASA was organized in 1975 to identify potential fuel saving concepts for aviation. The result was the Aircraft Energy Efficiency (ACEE) Program implemented in 1976. An important part of the program was the development of advanced turboprop technology for Mach 0.65 to 0.85 applications having the potential fuel saving of 30 to 50 percent relative to existing turbofan engines. A historical perspective is presented of the development and the accomplishments that brought the turboprop to successful flight tests in 1986 and 1987.

  16. 7 CFR 2502.8 - Pre-award, award, and post-award procedures and administration of grants.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (ACE) GRANTS PROGRAM Grant Applications and Administration § 2502.8 Pre-award, award, and post-award... CFR part 2500, subparts A, B, C, D, and E. (b) For purposes of the ACE Grants Program, the provisions...

  17. 7 CFR 2502.8 - Pre-award, award, and post-award procedures and administration of grants.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (ACE) GRANTS PROGRAM Grant Applications and Administration § 2502.8 Pre-award, award, and post-award... CFR part 2500, subparts A, B, C, D, and E. (b) For purposes of the ACE Grants Program, the provisions...

  18. 7 CFR 2502.8 - Pre-award, award, and post-award procedures and administration of grants.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (ACE) GRANTS PROGRAM Grant Applications and Administration § 2502.8 Pre-award, award, and post-award... CFR part 2500, subparts A, B, C, D, and E. (b) For purposes of the ACE Grants Program, the provisions...

  19. Cox report and the US-China arms control technical exchange program

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

    Di Capua, M S

    The ACE program furthered the national security interests of the US by promoting technical approaches to the implementation and verification of arms control treaties that the international community embraces. The Cox Committee report suggests that uncontrolled interactions were taking place between US and Chinese nuclear weapons scientists in the course of the ACE program. On the contrary, elaborate controls were in place at the very beginning and remained in place to control the interactions and protect US national security information. The ACE program payoff to national security was just beginning and its suspension, resulting from the Cox reports allegations, ismore » a setback to US-China progress on arms control.« less

  20. Short- and long-term effects of the modified swedish version of the Active Communication Education (ACE) program for adults with hearing loss.

    PubMed

    Oberg, Marie; Bohn, Therese; Larsson, Ulrika

    2014-10-01

    In Sweden, there is a lack of evidence-based rehabilitation programs for hearing loss. The Active Communication Education program (ACE) has successfully been used in Australia and was translated and evaluated in a Swedish pilot study. The pilot study included 23 participants (age 87 yr). No statistically significant effects were found, but the qualitative assessments indicated that this population found the program to be beneficial. The participants requested more focus on the psychosocial consequences of hearing loss, and the modules in the original ACE program were modified. The aim of this study was to explore the effects of a modified Swedish version of the ACE program in a population aged 39-82 yr old. Design was a between-group and within-group intervention study. The participants were recruited from the hearing health clinic in Linköping during 2010 and 2012. A total of 73 participants agreed to undergo the ACE, and 67 (92%) completed three or more sessions. The ACE program consists of five weekly 2 hr group sessions with 6 to 10 participants per group. The outcomes were measured before initiation of the program, 3 wk after program completion, and 6 mo after program completion and included communication strategy use, activity and participation, health-related quality of life, and anxiety and depression. In addition, outcomes were measured after program completion using the International Outcome Inventory-Alternative Interventions, a modified version of the Client Oriented Scale of Improvement, and qualitative feedback was obtained about the response to the program and actions taken as a result of participation. The treatment effects were examined using repeated-measures analyses of variance. Statistically significant effects were found for communication strategy use, activity and participation, and psychosocial well-being. Statistically significant effects were found for gender and degree of hearing loss, indicating that women and those with mild hearing loss significantly improved communication strategies. It is suggested that the program be implemented as part of regular audiological rehabilitation and offered in an early stage of rehabilitation. American Academy of Audiology.

  1. Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

    NASA Astrophysics Data System (ADS)

    Kong, Zwe-Ling; Chang, Jenq-Sheng; Chang, Ke Liang B.

    2013-09-01

    Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

  2. Identification of ace inhibitory cryptides in Tilapia protein hydrolysate by UPLC-MS/MS coupled to database analysis.

    PubMed

    Yesmine, Ben Henda; Antoine, Bonnet; da Silva Ortência Leocádia, Nunes Gonzalez; Rogério, Boscolo Wilson; Ingrid, Arnaudin; Nicolas, Bridiau; Thierry, Maugard; Jean-Marie, Piot; Frédéric, Sannier; Stéphanie, Bordenave-Juchereau

    2017-05-01

    An ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry method was developed and applied to identify short angiotensin-I-converting enzyme (ACE) inhibitory cryptides in Tilapia (Oreochromis Niloticus) protein hydrolyzate. A database was created with previously identified ACE-inhibitory di- and tripeptides and the lowest molecular weight fraction of Tilapia hydrolysate was analysed for coincidences. Only VW and VY were identified. Further analysis of collected fractions conducted to the identification of 51 different peptides in major fractions. 19 peptides selected were synthesised and tested for their ACE inhibitory potential. TL, TI, IK, LR, LD, IQ, DI, AILE, ALLE, ALIE and AIIE were identified as new ACE inhibitors. The findings from this study point UPLC-MS/MS combined with the creation of a database as an efficient technique to identify specific short peptides within a complex hydrolysate, in addition with de novo sequencing. This efficient characterisation of bioactive factors like cryptides in protein hydrolysates will extend their use as functional foods. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. N-Domain Isoform of Angiotensin I Converting Enzyme as a Marker of Hypertension: Populational Study

    PubMed Central

    Maluf-Meiken, Leila C. V.; Fernandes, Fernanda B.; Aragão, Danielle S.; Ronchi, Fernanda A.; Andrade, Maria C. C.; Franco, Maria C.; Febba, Andreia C. S.; Plavnik, Frida L.; Krieger, José E.; Mill, Jose G.; Sesso, Ricardo C. C.; Casarini, Dulce E.

    2012-01-01

    The aim of this paper was to investigate the presence of the urinary 90 kDa N-domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n = 1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n = 795), ACE 90+ (65/90) (n = 186), and ACE 90− (65/190) (n = 169) based on the presence (+) or absence (−) of the 90 kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90+ compared with the ACE 90− and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90+ group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90− group. There is a high presence of the 90 kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease. PMID:22666552

  4. Family-centered prevention ameliorates the association between adverse childhood experiences and prediabetes status in young black adults.

    PubMed

    Brody, Gene H; Yu, Tianyi; Chen, Edith; Miller, Gregory E

    2017-07-01

    Individuals exposed to adverse childhood experiences (ACEs) are vulnerable to various health problems later in life. This study was designed to determine whether participation in an efficacious program to enhance supportive parenting would ameliorate the association between ACEs and prediabetes status at age 25. Rural African American parents and their 11-year-old children (N=390) participated in the Strong African American Families (SAAF) program or a control condition. Each youth at age 25 provided a total ACEs score and a blood sample from which overnight fasting glucose was assayed. Logistic regression equations were used to test the hypotheses. The logistic regression analyses revealed a significant interaction between total ACEs and random assignment to SAAF or control, OR=0.56, 95% CI [0.36, 0.88]. Follow-up analyses indicated that, for participants in the control condition, a 1-point increase in ACEs was associated with a 37.3% increase in risk of having prediabetes. ACEs were not associated with the likelihood of having prediabetes among participants in the SAAF condition. Control participants with high total ACEs scores were 3.54 times more likely to have prediabetes than were SAAF participants with similar scores. This study indicated that participation at age 11 in a randomized controlled trial designed to enhance supportive parenting ameliorated the association of ACEs with prediabetes at age 25. If substantiated, these findings may provide a strategy for preventing negative health consequences of ACEs. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Alterations in Circulatory and Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Fetal Programmed Hypertension

    PubMed Central

    Shaltout, Hossam A.; Figueroa, Jorge P.; Rose, James C.; Diz, Debra I.; Chappell, Mark C.

    2009-01-01

    Antenatal betamethasone treatment is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. However, there are reports that infants who receive antenatal glucocorticoids exhibit higher systolic blood pressure in their early adolescent years. We have developed an experimental model of programming whereby the offspring of pregnant sheep administered clinically relevant doses of betamethasone exhibit elevated blood pressure. We tested the hypothesis as to whether alterations in angiotensin-converting enzyme (ACE), ACE2, and neprilysin in serum, urine, and proximal tubules are associated with this increase in mean arterial pressure. Male sheep were administered betamethasone (2 doses of 0.17 mg/kg, 24 hours apart) or vehicle at the 80th day of gestation and delivered at term. Sheep were instrumented at adulthood (1.8 years) for direct conscious recording of mean arterial pressure. Serum and urine were collected and proximal tubules isolated from the renal cortex. Betamethasone-treated animals had elevated mean arterial pressure (97±3 versus 83±2 mm Hg; P<0.05) and a 25% increase in serum ACE activity (48.4±7.0 versus 36.0±2.7 fmol/mL per minute) but a 40% reduction in serum ACE2 activity (18.8±1.2 versus 31.4±4.4 fmol/mL per minute). In isolated proximal tubules, ACE2 activity and expression were 50% lower in the treated sheep with no significant change in ACE or neprilysin activities. We conclude that antenatal steroid treatment results in the chronic alteration of ACE and ACE2 in the circulatory and tubular compartments, which may contribute to the higher blood pressure in this model of fetal programming-induced hypertension. PMID:19047579

  6. Application of superplastically formed and diffusion bonded aluminum to a laminar flow control leading edge

    NASA Technical Reports Server (NTRS)

    Goodyear, M. D.

    1987-01-01

    NASA sponsored the Aircraft Energy Efficiency (ACEE) program in 1976 to develop technologies to improve fuel efficiency. Laminar flow control was one such technology. Two approaches for achieving laminar flow were designed and manufactured under NASA sponsored programs: the perforated skin concept used at McDonnell Douglas and the slotted design used at Lockheed-Georgia. Both achieved laminar flow, with the slotted design to a lesser degree (JetStar flight test program). The latter design had several fabrication problems concerning springback and adhesive flow clogging the air flow passages. The Lockheed-Georgia Company accomplishments is documented in designing and fabricating a small section of a leading edge article addressing a simpler fabrication method to overcome the previous program's manufacturing problems, i.e., design and fabrication using advanced technologies such as diffusion bonding of aluminum, which has not been used on aerospace structures to date, and the superplastic forming of aluminum.

  7. Art, Chaos, Ethics, and Science (ACES): a doctoring curriculum for emergency medicine.

    PubMed

    Van Groenou, Aneema A; Bakes, Katherine Mary

    2006-11-01

    ACES (Art, Chaos, Ethics, and Science) is a curriculum developed by 2 residents and a faculty mentor at the Denver Health Medical Center Emergency Medicine Residency Program. The goal of the ACES curriculum is 2-fold: (1) to discuss areas of clinical consequence typically outside the scope of the regular academic curriculum, such as ethical dilemmas and the challenges of professionalism; and (2) to encourage reflection on our roles as caregivers on a personal, public health, and political level. Each bimonthly "doctoring roundtable" session focuses on one of these goals, bringing local and national leaders in the field to the forum to enrich discussion. Attending physicians from academic and private settings within the residency, residents at all levels, rotating medical students, and, for the past year, emergency department nurses participate in the meetings. Thus far, regular voluntary participation has been the only measure of the ongoing program's success. In this descriptive article, we discuss the aim of the program, the curriculum, and how the ACES program enriches the residency's educational goals. Recent accreditation requirements for residency training programs mandate educational experiences that allow residents to demonstrate competency in professionalism and ethical principles. The ACES curriculum developed a unique niche in our residency, creating an open forum for passionate discussion of challenging clinical encounters, unpressured reflection on ethics and decisionmaking, and constructive personal and professional development.

  8. Human Capital Development: Reforms for Adult and Community Education

    ERIC Educational Resources Information Center

    Choy, Sarojni; Haukka, Sandra

    2007-01-01

    The adult and community education (ACE) sector is consistently responsive to changing community needs and government priorities. It is this particular function that has drawn ACE into the lifelong learning debate as one model for sustaining communities. The responsiveness of ACE means that the sector and its programs continue to make valuable…

  9. Program Evaluation: A Study to Evaluate the Effectiveness of Academic and Behavioral Interventions in an Alternative to out of School Suspension Program

    ERIC Educational Resources Information Center

    Rizzi, Lorenzo

    2011-01-01

    The purpose of this study was to provide insight regarding the impact that the alternative to suspension program Achievement Character Excellence (ACE) has on the students who are placed there. The study utilized four achievement indicators to track the level of improvement of students after they were placed in the ACE program and after they were…

  10. Examining Life Course Transitions of Young People with Disabilities: The ACEE Alumni Study

    ERIC Educational Resources Information Center

    Schneider, Cornelia; Chahine, Saad; Hattie, Brenda

    2016-01-01

    This article examines the outcomes of the ACEE program, which is a one-year transition program for youth with disabilities, preparing them for the workplace and adult life. In a mixed methods approach, the investigators surveyed sixty-six youth with disabilities who were alumni of the program and followed up in depth with ten alumni in in-depth…

  11. LSS systems planning and performance program

    NASA Technical Reports Server (NTRS)

    Mckenna, Victoria Jones; Dendy, Michael J.; Naumann, Charles B.; Rice, Sally A.; Weathers, John M.

    1993-01-01

    This report describes, using viewgraphs, the Marshall Space Flight Center's Large Space Structures Ground Test Facilities located in building 4619. Major topics include the Active Control Evaluation of Systems (ACES) Laboratory; the Control-Structures Interaction/Controls, Astrophysics, and Structures Experiment in Space (CSI/CASES); Advanced Development Facility; and the ACES Guest Investigator Program.

  12. Evaluating Urban Resilience to Climate Change: A Multi-Sector Approach (Final Report)

    EPA Science Inventory

    EPA is announcing the availability of this final report prepared by the Air, Climate, and Energy (ACE) Research Program, located within the Office of Research and Development, with support from Cadmus. One of the goals of the ACE research program is to provide scientific informat...

  13. SCORE/ACE Counselor Handbook. Service Corps of Retired Executives. Active Corps of Executives.

    ERIC Educational Resources Information Center

    Landsverk, Arvel; And Others

    This counselor handbook is intended to help Service Corps of Retired Executives/Active Corps of Executives (SCORE/ACE) counselors to plan and conduct counseling services more effectively. Included in the introductory section are an overview of the SCORE/ACE counseling program, a discussion of what the counselor does, directions for completing…

  14. Operational considerations for laminar flow aircraft

    NASA Technical Reports Server (NTRS)

    Maddalon, Dal V.; Wagner, Richard D.

    1986-01-01

    Considerable progress has been made in the development of laminar flow technology for commercial transports during the NASA Aircraft Energy Efficiency (ACEE) laminar flow program. Practical, operational laminar flow control (LFC) systems have been designed, fabricated, and are undergoing flight testing. New materials, fabrication methods, analysis techniques, and design concepts were developed and show much promise. The laminar flow control systems now being flight tested on the NASA Jetstar aircraft are complemented by natural laminar flow flight tests to be accomplished with the F-14 variable-sweep transition flight experiment. An overview of some operational aspects of this exciting program is given.

  15. Stormwater Management in Response to Climate Change Impacts: Lessons from the Chesapeake Bay and Great Lakes Regions (Final Report)

    EPA Science Inventory

    This report was prepared by the U.S. Environmental Protection Agency’s (EPA) Air, Climate, and Energy (ACE) research program, located within the Office of Research and Development, with support from ICF International. One of the goals of the ACE research program is to provide sci...

  16. Stormwater Management in Response to Climate Change Impacts: Lessons from the Chesapeake Bay and Great Lakes Regions (External Review Draft)

    EPA Science Inventory

    This report was prepared by the U.S. Environmental Protection Agency’s (EPA) Air, Climate, and Energy (ACE) research program, located within the Office of Research and Development, with support from ICF International. One of the goals of the ACE research program is to provide sci...

  17. Evaluation of Achieving Collegiate Excellence and Success Program: Student Outcomes Year One, Grades 11 and 12. Evaluation Brief

    ERIC Educational Resources Information Center

    Wolanin, Natalie; Modarresi, Shahpar

    2015-01-01

    The Office of Shared Accountability in Montgomery County (Maryland) Public Schools (MCPS) is conducting a multiyear evaluation of the "Achieving Collegiate Excellence and Success" (ACES) program. ACES is a collaboration between MCPS, Montgomery College (MC), and the Universities at Shady Grove (USG) to create a seamless pathway from high…

  18. Architecture-Adaptive Computing Environment: A Tool for Teaching Parallel Programming

    NASA Technical Reports Server (NTRS)

    Dorband, John E.; Aburdene, Maurice F.

    2002-01-01

    Recently, networked and cluster computation have become very popular. This paper is an introduction to a new C based parallel language for architecture-adaptive programming, aCe C. The primary purpose of aCe (Architecture-adaptive Computing Environment) is to encourage programmers to implement applications on parallel architectures by providing them the assurance that future architectures will be able to run their applications with a minimum of modification. A secondary purpose is to encourage computer architects to develop new types of architectures by providing an easily implemented software development environment and a library of test applications. This new language should be an ideal tool to teach parallel programming. In this paper, we will focus on some fundamental features of aCe C.

  19. The ACE gene and human performance: 12 years on.

    PubMed

    Puthucheary, Zudin; Skipworth, James R A; Rawal, Jai; Loosemore, Mike; Van Someren, Ken; Montgomery, Hugh E

    2011-06-01

    Some 12 years ago, a polymorphism of the angiotensin I-converting enzyme (ACE) gene became the first genetic element shown to impact substantially on human physical performance. The renin-angiotensin system (RAS) exists not just as an endocrine regulator, but also within local tissue and cells, where it serves a variety of functions. Functional genetic polymorphic variants have been identified for most components of RAS, of which the best known and studied is a polymorphism of the ACE gene. The ACE insertion/deletion (I/D) polymorphism has been associated with improvements in performance and exercise duration in a variety of populations. The I allele has been consistently demonstrated to be associated with endurance-orientated events, notably, in triathlons. Meanwhile, the D allele is associated with strength- and power-orientated performance, and has been found in significant excess among elite swimmers. Exceptions to these associations do exist, and are discussed. In theory, associations with ACE genotype may be due to functional variants in nearby loci, and/or related genetic polymorphism such as the angiotensin receptor, growth hormone and bradykinin genes. Studies of growth hormone gene variants have not shown significant associations with performance in studies involving both triathletes and military recruits. The angiotensin type-1 receptor has two functional polymorphisms that have not been shown to be associated with performance, although studies of hypoxic ascent have yielded conflicting results. ACE genotype influences bradykinin levels, and a common gene variant in the bradykinin 2 receptor exists. The high kinin activity haplotye has been associated with increased endurance performance at an Olympic level, and similar results of metabolic efficiency have been demonstrated in triathletes. Whilst the ACE genotype is associated with overall performance ability, at a single organ level, the ACE genotype and related polymorphism have significant associations. In cardiac muscle, ACE genotype has associations with left ventricular mass changes in response to stimulus, in both the health and diseased states. The D allele is associated with an exaggerated response to training, and the I allele with the lowest cardiac growth response. In light of the I-allele association with endurance performance, it seems likely that other regulatory mechanisms exist. Similarly in skeletal muscle, the D allele is associated with greater strength gains in response to training, in both healthy individuals and chronic disease states. As in overall performance, those genetic polymorphisms related to the ACE genotype, such as the bradykinin 2 gene, also influence skeletal muscle strength. Finally, the ACE genotype may influence metabolic efficiency, and elite mountaineers have demonstrated an excess of I alleles and I/I genotype frequency in comparison to controls. Interestingly, this was not seen in amateur climbers. Corroboratory evidence exists among high-altitude settlements in both South America and India, where the I allele exists in greater frequency in those who migrated from the lowlands. Unfortunately, if the ACE genotype does influence metabolic efficiency, associations with peak maximal oxygen consumption have yet to be rigorously demonstrated. The ACE genotype is an important but single factor in the determinant of sporting phenotype. Much of the mechanisms underlying this remain unexplored despite 12 years of research.

  20. AceDRG: a stereochemical description generator for ligands

    PubMed Central

    Emsley, Paul; Gražulis, Saulius; Merkys, Andrius; Vaitkus, Antanas

    2017-01-01

    The program AceDRG is designed for the derivation of stereochemical information about small molecules. It uses local chemical and topological environment-based atom typing to derive and organize bond lengths and angles from a small-molecule database: the Crystallography Open Database (COD). Information about the hybridization states of atoms, whether they belong to small rings (up to seven-membered rings), ring aromaticity and nearest-neighbour information is encoded in the atom types. All atoms from the COD have been classified according to the generated atom types. All bonds and angles have also been classified according to the atom types and, in a certain sense, bond types. Derived data are tabulated in a machine-readable form that is freely available from CCP4. AceDRG can also generate stereochemical information, provided that the basic bonding pattern of a ligand is known. The basic bonding pattern is perceived from one of the computational chemistry file formats, including SMILES, mmCIF, SDF MOL and SYBYL MOL2 files. Using the bonding chemistry, atom types, and bond and angle tables generated from the COD, AceDRG derives the ‘ideal’ bond lengths, angles, plane groups, aromatic rings and chirality information, and writes them to an mmCIF file that can be used by the refinement program REFMAC5 and the model-building program Coot. Other refinement and model-building programs such as PHENIX and BUSTER can also use these files. AceDRG also generates one or more coordinate sets corresponding to the most favourable conformation(s) of a given ligand. AceDRG employs RDKit for chemistry perception and for initial conformation generation, as well as for the interpretation of SMILES strings, SDF MOL and SYBYL MOL2 files. PMID:28177307

  1. Graphitized Porous Carbon for Rapid Screening of Angiotensin-Converting Enzyme Inhibitory Peptide GAMVVH from Silkworm Pupa Protein and Molecular Insight into Inhibition Mechanism.

    PubMed

    Tao, Mengliang; Sun, Huaju; Liu, Long; Luo, Xuan; Lin, Guoyou; Li, Renbo; Zhao, Zhenxia; Zhao, Zhongxing

    2017-10-04

    A novel hydrophobic hexapeptide with high angiotensin-converting enzyme (ACE) inhibitory activity was screened from silkworm pupa protein (SPP) hydrolysate via graphitized porous carbon and reverse-phase high-performance liquid chromatography methods. Graphitized porous carbon derived from dopamine, possessing high surface area and high graphitic carbon, was used to rapidly screen and enrich hydrophobic peptides from SPP hydrolysate. The ACE inhibition pattern and mechanism of the purified peptide were also systematically studied by the classic Lineweaver-Burk model and by molecular docking/dynamic simulation. The novel hydrophobic hexapeptide was identified as Gly-Ala-Met-Val-Val-His (GAMVVH, IC 50 = 19.39 ± 0.21 μM) with good thermal/antidigestive stabilities. Lineweaver-Burk plots revealed that GAMVVH behaved as a competitive ACE inhibitor. It formed hydrogen bonds with S1 and S2 pockets of ACE and established competitive coordination with Zn(II) of ACE. The synergy of hydrogen bonds with active pockets and Zn(II) coordination efficiently changed the three-dimensional structure of ACE and thus inhibited bioactivity of ACE.

  2. Efficient Predictions of Excited State for Nanomaterials Using Aces 3 and 4

    DTIC Science & Technology

    2017-12-20

    by first-principle methods in the software package ACES by using large parallel computers, growing tothe exascale. 15. SUBJECT TERMS Computer...modeling, excited states, optical properties, structure, stability, activation barriers first principle methods , parallel computing 16. SECURITY...2 Progress with new density functional methods

  3. Advanced structures technology and aircraft safety

    NASA Technical Reports Server (NTRS)

    Mccomb, H. G., Jr.

    1983-01-01

    NASA research and development on advanced aeronautical structures technology related to flight safety is reviewed. The effort is categorized as research in the technology base and projects sponsored by the Aircraft Energy Efficiency (ACEE) Project Office. Base technology research includes mechanics of composite structures, crash dynamics, and landing dynamics. The ACEE projects involve development and fabrication of selected composite structural components for existing commercial transport aircraft. Technology emanating from this research is intended to result in airframe structures with improved efficiency and safety.

  4. Evaluation of a Web-Based Professional Development Program (Project ACE) for Teachers of Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rakap, Salih; Jones, Hazel A.; Emery, Alice Kaye

    2015-01-01

    This article describes the development, implementation, and second-year evaluation of Project Autism Competencies for Endorsement (ACE), a web-based professional development (PD) program that is designed to train teachers currently working in the field to meet the unique and diverse needs of children with autism spectrum disorders (ASDs). A…

  5. Outcome Evaluation of the Achieving Collegiate Excellence and Success Program at Montgomery County Public Schools: Year Two

    ERIC Educational Resources Information Center

    Wolanin, Natalie; Cooper-Martin, Elizabeth

    2016-01-01

    The ACES program is a collaboration between MCPS, Montgomery College (MC), and the Universities at Shady Grove (USG) to create a seamless pathway from high school to college completion. ACES focuses on identifying and supporting students who are underrepresented in higher education, the first in their family to attend college, or both. In…

  6. ACE2-EPC-EXs protect ageing ECs against hypoxia/reoxygenation-induced injury through the miR-18a/Nox2/ROS pathway.

    PubMed

    Zhang, Cheng; Wang, Jinju; Ma, Xiaotang; Wang, Wenjun; Zhao, Bin; Chen, Yanfang; Chen, Can; Bihl, Ji C

    2018-03-01

    Oxidative stress is one of the mechanisms of ageing-associated vascular dysfunction. Angiotensin-converting enzyme 2 (ACE2) and microRNA (miR)-18a have shown to be down-regulated in ageing cells. Our previous study has shown that ACE2-primed endothelial progenitor cells (ACE2-EPCs) have protective effects on endothelial cells (ECs), which might be due to their released exosomes (EXs). Here, we aimed to investigate whether ACE2-EPC-EXs could attenuate hypoxia/reoxygenation (H/R)-induced injury in ageing ECs through their carried miR-18a. Young and angiotensin II-induced ageing ECs were subjected to H/R and co-cultured with vehicle (medium), EPC-EXs, ACE2-EPCs-EXs, ACE2-EPCs-EXs + DX600 or ACE2-EPCs-EXs with miR-18a deficiency (ACE2-EPCs-EXs anti-miR-18a ). Results showed (1) ageing ECs displayed increased senescence, apoptosis and ROS production, but decreased ACE2 and miR-18a expressions and tube formation ability; (2) under H/R condition, ageing ECs showed higher rate of apoptosis, ROS overproduction and nitric oxide reduction, up-regulation of Nox2, down-regulation of ACE2, miR-18a and eNOS, and compromised tube formation ability; (3) compared with EPC-EXs, ACE2-EPC-EXs had better efficiencies on protecting ECs from H/R-induced changes; (4) The protective effects were less seen in ACE2-EPCs-EXs + DX600 and ACE2-EPCs-EXs anti-miR-18a groups. These data suggest that ACE-EPCs-EXs have better protective effects on H/R injury in ageing ECs which could be through their carried miR-18a and subsequently down-regulating the Nox2/ROS pathway. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  7. Implications of Advanced Crew Escape Suit Transpiration for the Orion Program

    NASA Technical Reports Server (NTRS)

    Bue, Grant; Kuznetz, Lawrence

    2009-01-01

    Human testing was conducted to more fully characterize the integrated performance of the Advanced Crew Escape Suit (ACES) with liquid cooling provide by an Individual Cooling Unit (ICU) across a broad range of environmental conditions and metabolic rates. Together with a correlation for the ACES Liquid Cooling Garment as a function of inlet temperature, metabolic rate, and crew size, a reasonably conservative correlation for core temperature was achieved for the human thermal model applied to the ACES with ICU cooling. A key observation for this correlation was accounting for transpiration of evaporated sweat through the Gortex(Registered TradeMark) liner of the ACES indicated by as much as 0.6 lbm of sweat evaporated over the course of the 1 hour test profile, most of which could not be attributed to respiration or head sweat evaporation of the crew. Historically it has been assumed that transpiration was not an important design feature of the ACES suit. The correlated human thermal model will show transpiration to be highly useful in hot survival situations for the Orion Program when adequate liquid cooling is not available.

  8. A Statistical Model for Multilingual Entity Detection and Tracking

    DTIC Science & Technology

    2004-01-01

    tomatic Content Extraction ( ACE ) evaluation achieved top-tier results in all three evaluation languages. 1 Introduction Detecting entities, whether named...of com- bining the detected mentions into groups of references to the same object. The work presented here is motivated by the ACE eval- uation...Entropy (MaxEnt henceforth) (Berger et al., 1996) and Robust Risk Minimization (RRM henceforth) 1For a description of the ACE program see http

  9. FY2014 Propulsion Materials R&D Annual Progress Report

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

    None

    The Propulsion Materials Program actively supports the energy security and reduction of greenhouse emissions goals of VTO by investigating and identifying the materials properties that are most essential for continued development of cost-effective, highly efficient, and environmentally friendly next-generation heavy and light-duty powertrains. The technical approaches available to enhance propulsion systems focus on improvements in both vehicle efficiency and fuel substitution, both of which must overcome the performance limitations of the materials currently in use. Propulsion Materials Program activities work with national laboratories, industry experts, and VTO powertrain systems (e.g., Advanced Combustion Engines [ACE], Advanced Power Electronics and Electrical Machinesmore » [APEEM], and fuels) teams to develop strategies that overcome materials limitations in future powertrain performance. The technical maturity of the portfolio of funded projects ranges from basic science to subsystem prototype validation. Projects within a Propulsion Materials Program activity address materials concerns that directly impact critical technology barriers within each of the above programs, including barriers that impact fuel efficiency, thermal management, emissions reduction, improved reliability, and reduced manufacturing costs. The program engages only the barriers that result from material property limitations and represent fundamental, high-risk materials issues.« less

  10. FY2015 Propulsion Materials Annual Report

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

    None, None

    The Propulsion Materials Program actively supports the energy security and reduction of greenhouse emissions goals of VTO by investigating and identifying the materials properties that are most essential for continued development of cost-effective, highly efficient, and environmentally friendly next-generation heavy and light-duty powertrains. The technical approaches available to enhance propulsion systems focus on improvements in both vehicle efficiency and fuel substitution, both of which must overcome the performance limitations of the materials currently in use. Propulsion Materials Program activities work with national laboratories, industry experts, and VTO powertrain systems (e.g., Advanced Combustion Engines [ACE], Advanced Power Electronics and Electrical Machinesmore » [APEEM], and fuels) teams to develop strategies that overcome materials limitations in future powertrain performance. The technical maturity of the portfolio of funded projects ranges from basic science to subsystem prototype validation. Projects within a Propulsion Materials Program activity address materials concerns that directly impact critical technology barriers within each of the above programs, including barriers that impact fuel efficiency, thermal management, emissions reduction, improved reliability, and reduced manufacturing costs. The program engages only the barriers that result from material property limitations and represent fundamental, high-risk materials issues.« less

  11. SU-F-J-72: A Clinical Usable Integrated Contouring Quality Evaluation Software for Radiotherapy

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

    Jiang, S; Dolly, S; Cai, B

    Purpose: To introduce the Auto Contour Evaluation (ACE) software, which is the clinical usable, user friendly, efficient and all-in-one toolbox for automatically identify common contouring errors in radiotherapy treatment planning using supervised machine learning techniques. Methods: ACE is developed with C# using Microsoft .Net framework and Windows Presentation Foundation (WPF) for elegant GUI design and smooth GUI transition animations through the integration of graphics engines and high dots per inch (DPI) settings on modern high resolution monitors. The industrial standard software design pattern, Model-View-ViewModel (MVVM) pattern, is chosen to be the major architecture of ACE for neat coding structure, deepmore » modularization, easy maintainability and seamless communication with other clinical software. ACE consists of 1) a patient data importing module integrated with clinical patient database server, 2) a 2D DICOM image and RT structure simultaneously displaying module, 3) a 3D RT structure visualization module using Visualization Toolkit or VTK library and 4) a contour evaluation module using supervised pattern recognition algorithms to detect contouring errors and display detection results. ACE relies on supervised learning algorithms to handle all image processing and data processing jobs. Implementations of related algorithms are powered by Accord.Net scientific computing library for better efficiency and effectiveness. Results: ACE can take patient’s CT images and RT structures from commercial treatment planning software via direct user input or from patients’ database. All functionalities including 2D and 3D image visualization and RT contours error detection have been demonstrated with real clinical patient cases. Conclusion: ACE implements supervised learning algorithms and combines image processing and graphical visualization modules for RT contours verification. ACE has great potential for automated radiotherapy contouring quality verification. Structured with MVVM pattern, it is highly maintainable and extensible, and support smooth connections with other clinical software tools.« less

  12. Validity of the T-ACE in pregnancy in predicting child outcome and risk drinking.

    PubMed

    Chiodo, Lisa M; Sokol, Robert J; Delaney-Black, Virginia; Janisse, James; Hannigan, John H

    2010-01-01

    Preventing fetal alcohol spectrum disorders (FASDs) requires detection of in-pregnancy maternal risk drinking. The widely used T-ACE screen has been applied in various ways, although the impact of those different uses on effectiveness is uncertain. We examined relations among different T-ACE scoring criteria, maternal drinking, and child outcome. Self-reported across-pregnancy maternal drinking was assessed in 75 African-American women. The different T-ACE criteria used varied the level of drinking that defined tolerance (two or three drinks) and the total T-ACE score cut-points (two or three). Receiver operator curves and regression analysis assessed the significance of relations. Increasing the total T-ACE score cut-point to 3 almost doubled specificity in detecting risk drinking whereas maintaining adequate sensitivity, equivalent to that in the original report, and identified substantially more neurobehavioral deficits in children. Redefining tolerance at three drinks did not improve T-ACE effectiveness in predicting outcomes. This study is among the first to show the ability of an in-pregnancy T-ACE assessment to predict child neurodevelopmental outcome. In addition, increasing the total T-ACE score criterion (from 2 to 3) improved identification of non-drinking mothers and unaffected children with little loss in detection of drinkers and affected children. Efficient in-pregnancy screens for risk drinking afford greater opportunities for intervention that could prevent/limit FASDs. Published by Elsevier Inc.

  13. Adverse experiences in infancy and toddlerhood: Relations to adaptive behavior and academic status in middle childhood.

    PubMed

    McKelvey, Lorraine M; Edge, Nicola Conners; Mesman, Glenn R; Whiteside-Mansell, Leanne; Bradley, Robert H

    2018-06-13

    Findings from the Adverse Childhood Experiences (ACE) study articulated the negative effects of childhood trauma on long-term well-being. The purpose of the current study is to examine the associations between ACEs experienced in infancy and toddlerhood and adaptive behavior and academic status in middle childhood. We used data collected from a sample of low-income families during the impacts study of Early Head Start (EHS). Data were collected by trained interviewers demonstrating at least 85% reliability with protocols. Data come from 1469 socio-demographically diverse mothers and children collected at or near ages 1, 2, 3, and 11. At ages 1, 2, and 3, an EHS-ACEs index was created based on interview and observation items. The EHS-ACEs indices were averaged to represent exposure across infancy and toddlerhood. At age 11, parents were asked about school outcomes and completed the Child Behavior Checklist. Across development, children were exposed to zero (19%), one (31%), two (27%), and three or more ACEs (23%). Logistic regression analyses, controlling for EHS program assignment, and parent, school, and child characteristics, showed ACEs were significantly associated with parental report of the child: having an individualized educational program since starting school and in the current school year, having been retained a grade in school, and problems with externalizing and internalizing behavior, as well as attention. Findings suggest that ACEs influence children's behavioral and academic outcomes early in development. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Identifying Sets of Maximally Efficient Items from the Academic Competence Evaluation Scales-Teacher Form

    ERIC Educational Resources Information Center

    Anthony, Christopher James; DiPerna, James Clyde

    2017-01-01

    The Academic Competence Evaluation Scales-Teacher Form (ACES-TF; DiPerna & Elliott, 2000) was developed to measure student academic skills and enablers (interpersonal skills, engagement, motivation, and study skills). Although ACES-TF scores have demonstrated psychometric adequacy, the length of the measure may be prohibitive for certain…

  15. On evaluating health centers groups in Lisbon and Tagus Valley: efficiency, equity and quality

    PubMed Central

    2013-01-01

    Background Bearing in mind the increasing health expenses and their weight in the Portuguese gross domestic product, it is of the utmost importance to evaluate the performance of Primary Health Care providers taking into account both efficiency, quality and equity. This paper aims to contribute to a better understanding of the performance of Primary Health Care by measuring it in a Portuguese region (Lisbon and Tagus Valley) and identifying best practices. It also intends to evaluate the quality and equity provided. Methods For the purpose of measuring the efficiency of the health care centers (ACES) the non-parametric full frontier technique of data envelopment analysis (DEA) was adopted. The recent partial frontier method of order-m was also used to estimate the influence of exogenous variables on the efficiency of the ACES. The horizontal equity was investigated by applying the non-parametric Kruskal-Wallis test with multiple comparisons. Moreover, the quality of service was analyzed by using the ratio between the complaints and the total activity of the ACES. Results On the whole, a significant level of inefficiency was observed, although there was a general improvement in efficiency between 2009 and 2010. It was found that nursing was the service with the lowest scores. Concerning the horizontal equity, the analysis showed that there is no evidence of relevant disparities between the different subregions(NUTS III). Concerning the exogenous variables, the purchasing power, the percentage of patients aged 65 years old or older and the population size affect the efficiency negatively. Conclusions This research shows that better usage of the available resources and the creation of a learning network and dissemination of best practices will contribute to improvements in the efficiency of the ACES while maintaining or even improving quality and equity. It was also proved that the market structure does matter when efficiency measurement is addressed. PMID:24359014

  16. Exploiting Outage and Error Probability of Cooperative Incremental Relaying in Underwater Wireless Sensor Networks

    PubMed Central

    Nasir, Hina; Javaid, Nadeem; Sher, Muhammad; Qasim, Umar; Khan, Zahoor Ali; Alrajeh, Nabil; Niaz, Iftikhar Azim

    2016-01-01

    This paper embeds a bi-fold contribution for Underwater Wireless Sensor Networks (UWSNs); performance analysis of incremental relaying in terms of outage and error probability, and based on the analysis proposition of two new cooperative routing protocols. Subject to the first contribution, a three step procedure is carried out; a system model is presented, the number of available relays are determined, and based on cooperative incremental retransmission methodology, closed-form expressions for outage and error probability are derived. Subject to the second contribution, Adaptive Cooperation in Energy (ACE) efficient depth based routing and Enhanced-ACE (E-ACE) are presented. In the proposed model, feedback mechanism indicates success or failure of data transmission. If direct transmission is successful, there is no need for relaying by cooperative relay nodes. In case of failure, all the available relays retransmit the data one by one till the desired signal quality is achieved at destination. Simulation results show that the ACE and E-ACE significantly improves network performance, i.e., throughput, when compared with other incremental relaying protocols like Cooperative Automatic Repeat reQuest (CARQ). E-ACE and ACE achieve 69% and 63% more throughput respectively as compared to CARQ in hard underwater environment. PMID:27420061

  17. Development of a Robust star identification technique for use in attitude determination of the ACE spacecraft

    NASA Technical Reports Server (NTRS)

    Woodard, Mark; Rohrbaugh, Dave

    1995-01-01

    The Advanced Composition Explorer (ACE) spacecraft is designed to fly in a spin-stabilized attitude. The spacecraft will carry two attitude sensors - a digital fine Sun sensor and a charge coupled device (CCD) star tracker - to allow ground-based determination of the spacecraft attitude and spin rate. Part of the processing that must be performed on the CCD star tracker data is the star identification. Star data received from the spacecraft must be matched with star information in the SKYMAP catalog to determine exactly which stars the sensor is tracking. This information, along with the Sun vector measured by the Sun sensor, is used to determine the spacecraft attitude. Several existing star identification (star ID) systems were examined to determine whether they could be modified for use on the ACE mission. Star ID systems which exist for three-axis stabilized spacecraft tend to be complex in nature and many require fairly good knowledge of the spacecraft attitude, making their use for ACE excessive. Star ID systems used for spinners carrying traditional slit star sensors would have to be modified to model the CCD star tracker. The ACE star ID algorithm must also be robust, in that it will be able to correctly identify stars even though the attitude is not known to a high degree of accuracy, and must be very efficient to allow real-time star identification. The paper presents the star ID algorithm that was developed for ACE. Results from prototype testing are also presented to demonstrate the efficiency, accuracy, and robustness of the algorithm.

  18. Comparative Evaluation: Participants versus Nonparticipants in the Achieving Collegiate Excellence and Success (ACES) Program at Montgomery County Public Schools in Year One and Year Two

    ERIC Educational Resources Information Center

    Modarresi, Shahpar; Wolanin, Natalie; Cooper-Martin, Elizabeth

    2016-01-01

    The Achieving Collegiate Excellence and Success (ACES) program is a collaboration between MCPS, Montgomery College, and the Universities at Shady Grove to create a seamless pathway from high school to college completion; it targets students who are underrepresented in higher education, the first in their family to attend college, or both. As one…

  19. PAPR reduction in FBMC using an ACE-based linear programming optimization

    NASA Astrophysics Data System (ADS)

    van der Neut, Nuan; Maharaj, Bodhaswar TJ; de Lange, Frederick; González, Gustavo J.; Gregorio, Fernando; Cousseau, Juan

    2014-12-01

    This paper presents four novel techniques for peak-to-average power ratio (PAPR) reduction in filter bank multicarrier (FBMC) modulation systems. The approach extends on current PAPR reduction active constellation extension (ACE) methods, as used in orthogonal frequency division multiplexing (OFDM), to an FBMC implementation as the main contribution. The four techniques introduced can be split up into two: linear programming optimization ACE-based techniques and smart gradient-project (SGP) ACE techniques. The linear programming (LP)-based techniques compensate for the symbol overlaps by utilizing a frame-based approach and provide a theoretical upper bound on achievable performance for the overlapping ACE techniques. The overlapping ACE techniques on the other hand can handle symbol by symbol processing. Furthermore, as a result of FBMC properties, the proposed techniques do not require side information transmission. The PAPR performance of the techniques is shown to match, or in some cases improve, on current PAPR techniques for FBMC. Initial analysis of the computational complexity of the SGP techniques indicates that the complexity issues with PAPR reduction in FBMC implementations can be addressed. The out-of-band interference introduced by the techniques is investigated. As a result, it is shown that the interference can be compensated for, whilst still maintaining decent PAPR performance. Additional results are also provided by means of a study of the PAPR reduction of the proposed techniques at a fixed clipping probability. The bit error rate (BER) degradation is investigated to ensure that the trade-off in terms of BER degradation is not too severe. As illustrated by exhaustive simulations, the SGP ACE-based technique proposed are ideal candidates for practical implementation in systems employing the low-complexity polyphase implementation of FBMC modulators. The methods are shown to offer significant PAPR reduction and increase the feasibility of FBMC as a replacement modulation system for OFDM.

  20. The ACEII recombinant Trichoderma reesei QM9414 strains with enhanced xylanase production and its applications in production of xylitol from tree barks.

    PubMed

    Xiong, Lili; Kameshwar, Ayyappa Kumar Sista; Chen, Xi; Guo, Zhiyun; Mao, Canquan; Chen, Sanfeng; Qin, Wensheng

    2016-12-28

    ACEII transcription factor plays a significant role in regulating the expression of cellulase and hemicellulase encoding genes. Apart from ACEII, transcription factors such as XYR1, CRE1, HAP2/3/5 complex and ACEI function in a coordinated pattern for regulating the gene expression of cellulases and hemicellulases. Studies have demonstrated that ACEII gene deletion results in decreased total cellulase and xylanase activities with reduced transcript levels of lignocellulolytic enzymes. In this study, we have successfully transformed the ACEII transcription factor encoding gene in Trichoderma reesei to significantly improve its degrading abilities. Transformation experiments on parental strain T. reesei QM9414 has resulted in five genetically engineered strains T/Ace2-2, T/Ace2-5, T/Ace2-8, T/Ace5-4 and T/Ace10-1. Among which, T/Ace2-2 has exhibited significant increase in enzyme activity by twofolds, when compared to parental strain. The T/Ace2-2 was cultured on growth substrates containing 2% bark supplemented with (a) sugar free + MA medium (b) glucose + MA medium and (c) xylose + MA medium. The bark degradation efficiency of genetically modified T/Ace2-2 strain was assessed by analyzing the xylitol production yield using HPAEC. By 6th day, about 10.52 g/l of xylitol was produced through enzymatic conversion of bark (2% bark + MA + xylose) by the T/Ace2-2 strain and by 7th day the conversion rate was found to be 0.21 g/g. Obtained results confirmed that bark growth medium supplemented with D-xylose has profoundly increased the conversion rate of bark by T/Ace2-2 strain when compared to sugar free and glucose supplemented growth media. Results obtained from scanning electron microscopy has endorsed our current results. Bark samples inoculated with T/Ace2-2 strain has showed large number of degraded cells with clearly visible cavities and fractures, by exposing the microfibrillar interwoven complex. We propose a cost effective and ecofriendly method for the degradation of lignocellulosic biomass such as bark to produce xylitol by using genetically modified T. reesei. Efficient conversion rate and production yield obtained in our current study provides a great scope for the xylitol industries, as our method bypasses the pretreatment of bark achieving clean and low-cost xylitol production.

  1. A virtual screening method for inhibitory peptides of Angiotensin I-converting enzyme.

    PubMed

    Wu, Hongxi; Liu, Yalan; Guo, Mingrong; Xie, Jingli; Jiang, XiaMin

    2014-09-01

    Natural small peptides from foods have been proven to be efficient inhibitors of Angiotensin I-converting enzyme (ACE) for the regulation of blood pressure. The traditional ACE inhibitory peptides screening method is both time consuming and money costing, to the contrary, virtual screening method by computation can break these limitations. We establish a virtual screening method to obtain ACE inhibitory peptides with the help of Libdock module of Discovery Studio 3.5 software. A significant relationship between Libdock score and experimental IC(50) was found, Libdock score = 10.063 log(1/IC(50)) + 68.08 (R(2) = 0.62). The credibility of the relationship was confirmed by testing the coincidence of the estimated log(1/IC(50)) and measured log(1/IC(50)) (IC(50) is 50% inhibitory concentration toward ACE, in μmol/L) of 5 synthetic ACE inhibitory peptides, which was virtual hydrolyzed and screened from a kind of seafood, Phascolosoma esculenta. Accordingly, Libdock method is a valid IC(50) estimation tool and virtual screening method for small ACE inhibitory peptides. © 2014 Institute of Food Technologists®

  2. Adult Continuing Education: An Integral Part of Lifelong Learning. Emerging Policies and Programs for the 21st Century in Upper and Middle Income Countries. World Bank Discussion Paper.

    ERIC Educational Resources Information Center

    Fretwell, David H.; Colombano, Joe E.

    Adult continuing education (ACE) can be a major force in human capital development and an integral part of lifelong learning. Although recognition of the importance of ACE in developed countries is increasing, the impact of ACE is not well understood in some middle-income countries (MICs), there is a lack of leadership, and the sector is somewhat…

  3. Four Different Methods Comparison for Extraction of Astaxanthin from Green Alga Haematococcus pluvialis

    PubMed Central

    Dong, Shengzhao; Huang, Yi; Zhang, Rui; Wang, Shihui; Liu, Yun

    2014-01-01

    Haematococcus pluvialis is one of the potent organisms for production of astaxanthin. Up to now, no efficient method has been achieved due to its thick cell wall hindering solvent extraction of astaxanthin. In this study, four different methods, hydrochloric acid pretreatment followed by acetone extraction (HCl-ACE), hexane/isopropanol (6 : 4, v/v) mixture solvents extraction (HEX-IPA), methanol extraction followed by acetone extraction (MET-ACE, 2-step extraction), and soy-oil extraction, were intensively evaluated for extraction of astaxanthin from H. pluvialis. Results showed that HCl-ACE method could obtain the highest oil yield (33.3 ± 1.1%) and astaxanthin content (19.8 ± 1.1%). Quantitative NMR analysis provided the fatty acid chain profiles of total lipid extracts. In all cases, oleyl chains were predominant, and high amounts of polyunsaturated fatty acid chains were observed and the major fatty acid components were oleic acid (13–35%), linoleic acid (37–43%), linolenic acid (20–31%), and total saturated acid (17–28%). DPPH radical scavenging activity of extract obtained by HCl-ACE was 73.2 ± 1.0%, which is the highest amongst the four methods. The reducing power of extract obtained by four extraction methods was also examined. It was concluded that the proposed extraction method of HCl-ACE in this work allowed efficient astaxanthin extractability with high antioxidant properties. PMID:24574909

  4. Incorporation of liposomes containing squid tunic ACE-inhibitory peptides into fish gelatin.

    PubMed

    Mosquera, Mauricio; Giménez, Begoña; Montero, Pilar; Gómez-Guillén, Maria Carmen

    2016-02-01

    Hydrolysates from collagen of jumbo squid (Dosidicus gigas) tunics have shown excellent angiotensin I-converting enzyme (ACE)-inhibitory activity. However, peptides directly included in food systems may suffer a decrease in activity, which could be minimized by loading them into nanoliposomes. A fraction of peptides with molecular weights <1 kDa obtained from hydrolyzed squid tunics, with reasonably high ACE-inhibitory activity (half-maximal inhibitory concentration IC50 = 0.096 g L(-1)), was encapsulated in phosphatidylcholine nanoliposomes. The peptide concentration affected the encapsulation efficiency and the stability of the resulting liposomes, which remained with a high zeta potential value (-54.3 mV) for at least 1 week at the most suitable peptide concentration. The optimal peptide concentration was established as 1.75 g L(-1). Liposomes obtained with this peptide concentration showed an encapsulation efficiency of 53%, a zeta potential of -59 mV, an average diameter of 70.3 nm and proved to be stable in the pH range 3-7 at 4 °C. Liposomes containing ACE-inhibitory peptides were incorporated in fish gelatin without detriment to the rheological properties and thermal stability of the resulting cold-induced gel. The ACE-inhibitory activity of the peptide fraction, which was not affected by the encapsulation process, conferred the bioactive potential to the nanoliposome-containing gelatin gel. © 2015 Society of Chemical Industry.

  5. Four different methods comparison for extraction of astaxanthin from green alga Haematococcus pluvialis.

    PubMed

    Dong, Shengzhao; Huang, Yi; Zhang, Rui; Wang, Shihui; Liu, Yun

    2014-01-01

    Haematococcus pluvialis is one of the potent organisms for production of astaxanthin. Up to now, no efficient method has been achieved due to its thick cell wall hindering solvent extraction of astaxanthin. In this study, four different methods, hydrochloric acid pretreatment followed by acetone extraction (HCl-ACE), hexane/isopropanol (6:4, v/v) mixture solvents extraction (HEX-IPA), methanol extraction followed by acetone extraction (MET-ACE, 2-step extraction), and soy-oil extraction, were intensively evaluated for extraction of astaxanthin from H. pluvialis. Results showed that HCl-ACE method could obtain the highest oil yield (33.3±1.1%) and astaxanthin content (19.8±1.1%). Quantitative NMR analysis provided the fatty acid chain profiles of total lipid extracts. In all cases, oleyl chains were predominant, and high amounts of polyunsaturated fatty acid chains were observed and the major fatty acid components were oleic acid (13-35%), linoleic acid (37-43%), linolenic acid (20-31%), and total saturated acid (17-28%). DPPH radical scavenging activity of extract obtained by HCl-ACE was 73.2±1.0%, which is the highest amongst the four methods. The reducing power of extract obtained by four extraction methods was also examined. It was concluded that the proposed extraction method of HCl-ACE in this work allowed efficient astaxanthin extractability with high antioxidant properties.

  6. A novel bedside cardiopulmonary physical diagnosis curriculum for internal medicine postgraduate training.

    PubMed

    Garibaldi, Brian Thomas; Niessen, Timothy; Gelber, Allan Charles; Clark, Bennett; Lee, Yizhen; Madrazo, Jose Alejandro; Manesh, Reza Sedighi; Apfel, Ariella; Lau, Brandyn D; Liu, Gigi; Canzoniero, Jenna VanLiere; Sperati, C John; Yeh, Hsin-Chieh; Brotman, Daniel J; Traill, Thomas A; Cayea, Danelle; Durso, Samuel C; Stewart, Rosalyn W; Corretti, Mary C; Kasper, Edward K; Desai, Sanjay V

    2017-10-06

    Physicians spend less time at the bedside in the modern hospital setting which has contributed to a decline in physical diagnosis, and in particular, cardiopulmonary examination skills. This trend may be a source of diagnostic error and threatens to erode the patient-physician relationship. We created a new bedside cardiopulmonary physical diagnosis curriculum and assessed its effects on post-graduate year-1 (PGY-1; interns) attitudes, confidence and skill. One hundred five internal medicine interns in a large U.S. internal medicine residency program participated in the Advancing Bedside Cardiopulmonary Examination Skills (ACE) curriculum while rotating on a general medicine inpatient service between 2015 and 2017. Teaching sessions included exam demonstrations using healthy volunteers and real patients, imaging didactics, computer learning/high-fidelity simulation, and bedside teaching with experienced clinicians. Primary outcomes were attitudes, confidence and skill in the cardiopulmonary physical exam as determined by a self-assessment survey, and a validated online cardiovascular examination (CE). Interns who participated in ACE (ACE interns) by mid-year more strongly agreed they had received adequate training in the cardiopulmonary exam compared with non-ACE interns. ACE interns were more confident than non-ACE interns in performing a cardiac exam, assessing the jugular venous pressure, distinguishing 'a' from 'v' waves, and classifying systolic murmurs as crescendo-decrescendo or holosystolic. Only ACE interns had a significant improvement in score on the mid-year CE. A comprehensive bedside cardiopulmonary physical diagnosis curriculum improved trainee attitudes, confidence and skill in the cardiopulmonary examination. These results provide an opportunity to re-examine the way physical examination is taught and assessed in residency training programs.

  7. Energy efficient transport technology: Program summary and bibliography

    NASA Technical Reports Server (NTRS)

    Middleton, D. B.; Bartlett, D. W.; Hood, R. V.

    1985-01-01

    The Energy Efficient Transport (EET) Program began in 1976 as an element of the NASA Aircraft Energy Efficiency (ACEE) Program. The EET Program and the results of various applications of advanced aerodynamics and active controls technology (ACT) as applicable to future subsonic transport aircraft are discussed. Advanced aerodynamics research areas included high aspect ratio supercritical wings, winglets, advanced high lift devices, natural laminar flow airfoils, hybrid laminar flow control, nacelle aerodynamic and inertial loads, propulsion/airframe integration (e.g., long duct nacelles) and wing and empennage surface coatings. In depth analytical/trade studies, numerous wind tunnel tests, and several flight tests were conducted. Improved computational methodology was also developed. The active control functions considered were maneuver load control, gust load alleviation, flutter mode control, angle of attack limiting, and pitch augmented stability. Current and advanced active control laws were synthesized and alternative control system architectures were developed and analyzed. Integrated application and fly by wire implementation of the active control functions were design requirements in one major subprogram. Additional EET research included interdisciplinary technology applications, integrated energy management, handling qualities investigations, reliability calculations, and economic evaluations related to fuel savings and cost of ownership of the selected improvements.

  8. Acute Care for Elders (ACE) Tracker and e-Geriatrician: Methods to Disseminate ACE Concepts to Hospitals with No Geriatricians on Staff

    PubMed Central

    Malone, Michael L.; Vollbrecht, Marsha; Stephenson, Jeff; Burke, Laura; Pagel, Patti; Goodwin, James S.

    2014-01-01

    This article describes an innovative method to disseminate the Acute Care for Elders (ACE) model of care for hospitalized older patients implemented at 11 community hospitals in Wisconsin. The ACE Tracker is a computer-generated checklist of all older patients in a facility that takes information from multiple areas of the electronic medical record to identify the older patients’ risk factors for functional decline and poor outcomes. The ACE Tracker report was validated against in-person observation of the older patients and found to be accurate. Interdisciplinary teams on medical–surgical units use this summary report to review each patient’s plan of care and to efficiently assess the patients who are vulnerable to poor hospital outcomes. The ACE Tracker is also used during regular consultation provided through teleconferencing between an off-site geriatrician (e-Geriatrician) and the local ACE team. The effect of the ACE Tracker and e-Geriatrician models was assessed by measuring use of urinary catheters, physical restraints, high-risk medications, and social service evaluation at a single hospital for the 6 months before and after implementation of the models. There were significant improvements in urinary catheter and physical therapy referrals but no significant changes in the other outcomes. There was no change in the length of stay or in the rate of hospital readmission within 30 days. PMID:20122048

  9. A Data Services Upgrade for Advanced Composition Explorer (ACE) Data

    NASA Astrophysics Data System (ADS)

    Davis, A. J.; Hamell, G.

    2008-12-01

    Since early in 1998, NASA's Advanced Composition Explorer (ACE) spacecraft has provided continuous measurements of solar wind, interplanetary magnetic field, and energetic particle activity from L1, located approximately 0.01 AU sunward of Earth. The spacecraft has enough fuel to stay in orbit about L1 until ~2024. The ACE Science Center (ASC) provides access to ACE data, and performs level 1 and browse data processing for the science instruments. Thanks to a NASA Data Services Upgrade grant, we have recently retooled our legacy web interface to ACE data, enhancing data subsetting capabilities and improving online plotting options. We have also integrated a new application programming interface (API) and we are working to ensure that it will be compatible with emerging Virtual Observatory (VO) data services standards. The new API makes extensive use of metadata created using the Space Physics Archive Search and Extract (SPASE) data model. We describe these recent improvements to the ACE Science Center data services, and our plans for integrating these services into the VO system.

  10. Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases.

    PubMed

    Zhuang, Xiao-Dong; Liao, Li-Zhen; Dong, Xiao-Bian; Hu, Xun; Guo, Yue; Du, Zhi-Min; Liao, Xin-Xue; Wang, Li-Chun

    2016-01-01

    This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice.

  11. Music Software for Special Needs.

    ERIC Educational Resources Information Center

    McCord, Kimberly

    2001-01-01

    Discusses the use of computer software for students with special needs in the music classroom. Focuses on software programs that are appropriate for children with special needs such as: "Musicshop,""Band-in-a-Box,""Rock Rap'n Roll,""Music Mania,""Music Ace" and "Music Ace 2," and "Children's Songbook." (CMK)

  12. ACE ID genotype and the muscle strength and size response to unilateral resistance training.

    PubMed

    Pescatello, Linda S; Kostek, Matthew A; Gordish-Dressman, Heather; Thompson, Paul D; Seip, Richard L; Price, Thomas B; Angelopoulos, Theodore J; Clarkson, Priscilla M; Gordon, Paul M; Moyna, Niall M; Visich, Paul S; Zoeller, Robert F; Devaney, Joseph M; Hoffman, Eric P

    2006-06-01

    To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d.wk) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. Subjects were 631 (mean+/-SEM, 24.2+/-0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (chi=1.688, P=0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. Baseline muscle strength and size were greater in UT than T (P<0.001) and did not differ among ACE ID genotype in either arm (P >or= 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P<0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P >or= 0.05). In UT, MVC increased among ACE II/ID (7%) (P<0.001) but was similar among ACE DD (2%) pre- to post-RT (P >or= 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P<0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P<0.05). ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.

  13. Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular System.

    PubMed

    Wang, Wang; McKinnie, Shaun M K; Farhan, Maikel; Paul, Manish; McDonald, Tyler; McLean, Brent; Llorens-Cortes, Catherine; Hazra, Saugata; Murray, Allan G; Vederas, John C; Oudit, Gavin Y

    2016-08-01

    Apelin peptides mediate beneficial effects on the cardiovascular system and are being targeted as potential new drugs. However, apelin peptides have extremely short biological half-lives, and improved understanding of apelin peptide metabolism may lead to the discovery of biologically stable analogues with therapeutic potential. We examined the ability of angiotensin-converting enzyme 2 (ACE2) to cleave and inactivate pyr-apelin 13 and apelin 17, the dominant apelin peptides. Computer-assisted modeling shows a conserved binding of pyr-apelin 13 and apelin 17 to the ACE2 catalytic site. In ACE2 knockout mice, hypotensive action of pyr-apelin 13 and apelin 17 was potentiated, with a corresponding greater elevation in plasma apelin levels. Similarly, pharmacological inhibition of ACE2 potentiated the vasodepressor action of apelin peptides. Biochemical analysis confirmed that recombinant human ACE2 can cleave pyr-apelin 13 and apelin 17 efficiently, and apelin peptides are degraded slower in ACE2-deficient plasma. The biological relevance of ACE2-mediated proteolytic processing of apelin peptides was further supported by the reduced potency of pyr-apelin 12 and apelin 16 on the activation of signaling pathways and nitric oxide production from endothelial cells. Importantly, although pyr-apelin 13 and apelin 17 rescued contractile function in a myocardial ischemia-reperfusion model, ACE2 cleavage products, pyr-apelin 12 and 16, were devoid of these cardioprotective effects. We designed and synthesized active apelin analogues that were resistant to ACE2-mediated degradation, thereby confirming that stable apelin analogues can be designed as potential drugs. We conclude that ACE2 represents a major negative regulator of apelin action in the vasculature and heart. © 2016 American Heart Association, Inc.

  14. Optimized angiotensin-converting enzyme activity assay for the accurate diagnosis of sarcoidosis.

    PubMed

    Csongrádi, Alexandra; Enyedi, Attila; Takács, István; Végh, Tamás; Mányiné, Ivetta S; Pólik, Zsófia; Altorjay, István Tibor; Balla, József; Balla, György; Édes, István; Kappelmayer, János; Tóth, Attila; Papp, Zoltán; Fagyas, Miklós

    2018-06-27

    Serum angiotensin-converting enzyme (ACE) activity determination can aid the early diagnosis of sarcoidosis. We aimed to optimize a fluorescent kinetic assay for ACE activity by screening the confounding effects of endogenous ACE inhibitors and interfering factors. Genotype-dependent and genotype-independent reference values of ACE activity were established, and their diagnostic accuracies were validated in a clinical study. Internally quenched fluorescent substrate, Abz-FRK(Dnp)P-OH was used for ACE-activity measurements. A total of 201 healthy individuals and 59 presumably sarcoidotic patients were enrolled into this study. ACE activity and insertion/deletion (I/D) genotype of the ACE gene were determined. Here we report that serum samples should be diluted at least 35-fold to eliminate the endogenous inhibitor effect of albumin. No significant interferences were detected: up to a triglyceride concentration of 16 mM, a hemoglobin concentration of 0.71 g/L and a bilirubin concentration of 150 μM. Genotype-dependent reference intervals were considered as 3.76-11.25 U/L, 5.22-11.59 U/L, 7.19-14.84 U/L for II, ID and DD genotypes, respectively. I/D genotype-independent reference interval was established as 4.85-13.79 U/L. An ACE activity value was considered positive for sarcoidosis when it exceeded the upper limit of the reference interval. The optimized assay with genotype-dependent reference ranges resulted in 42.5% sensitivity, 100% specificity, 100% positive predictive value and 32.4% negative predictive value in the clinical study, whereas the genotype-independent reference range proved to have inferior diagnostic efficiency. An optimized fluorescent kinetic assay of serum ACE activity combined with ACE I/D genotype determination is an alternative to invasive biopsy for confirming the diagnosis of sarcoidosis in a significant percentage of patients.

  15. Apolipoprotein B and angiotensin-converting enzyme polymorphisms and aerobic interval training: randomized controlled trial in coronary artery disease patients.

    PubMed

    Tamburus, N Y; Verlengia, R; Kunz, V C; César, M C; Silva, E

    2018-01-01

    Physical training has been strongly recommended as a non-pharmacological treatment for coronary artery disease (CAD). Genetic polymorphisms have been studied to understand the biological variability in response to exercise among individuals. This study aimed to verify the possible influence of apolipoprotein B (ApoB: rs1042031 and rs693) and angiotensin-converting enzyme (ACE-ID: rs1799752) genotypes on the lipid profile and functional aerobic capacity, respectively, after an aerobic interval training (AIT) program in patients with CAD and/or cardiovascular risk factors. Sixty-six men were randomized and assigned to trained group (n=32) or control group (n=34). Cardiopulmonary exercise test was performed to determine the ventilatory anaerobic threshold (VAT) from cardiorespiratory variables. The AIT program, at an intensity equivalent to %VAT (70-110%), was conducted three times a week for 16 weeks. ApoB gene polymorphisms (-12669C>T (rs1042031) and -7673G>A (rs693)) were identified by real-time polymerase chain reaction (PCR). I/D polymorphism in the ACE gene (rs1799752) was identified through PCR and fragment size analysis. After 16 weeks, low-density lipoprotein (LDL) levels increased in the trained and control groups with the GA+AA genotype (-7673G>A) of the ApoB gene. Trained groups with ACE-II and ACE-ID genotypes presented an increase in oxygen consumption (VO2VAT) and power output after the AIT program. The presence of the ACE I-allele was associated with increased aerobic functional capacity after the AIT program. Increased LDL levels were observed over time in patients with the -7673G>A polymorphism of the ApoB gene. Trial Registration Information: ClinicalTrials.gov: NCT02313831.

  16. Multiple Images, Common Threads. Case Studies of Good Practice in Adult Community Education.

    ERIC Educational Resources Information Center

    Bradshaw, Delia

    This document presents 10 case studies of adult community education programs (ACE) in the state of Victoria, Australia, in the mid 1990s, that were identified as exemplifying the following principles of good practice in ACE: expansiveness, integration, responsiveness, innovation, belonging, explicitness, autonomy, accessibility, synthesis, and…

  17. Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults.

    PubMed

    Dengel, Donald R; Brown, Michael D; Ferrell, Robert E; Reynolds, Thomas H; Supiano, Mark A

    2002-10-29

    We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 +/- 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (S(I)), assessed by the frequently sampled intravenous glucose tolerance test, was significantly (P = 0.0001) increased following AEX. In addition, there was a significant (P = 0.001) interaction between AEX and ACE genotype. S(I) increased significantly (P < 0.05) more in those with the II (2.5 +/- 0.8 microU x 10(-4) x min(-1) x ml(-1)) ACE genotype compared with both the DD and ID (0.7 +/- 0.1 and 0.7 +/- 0.2 microU x 10(-4) x min(-1) x ml(-1), respectively) ACE genotypes. Similarly, there was a significant (P = 0.036) decrease in the acute insulin response to glucose (AIR(G)) and a significant (P = 0.05) interaction between AEX and ACE genotype. AIR(G) decreased significantly (P < 0.05) more in those with the II (-17.6 +/- 5.6 mU/ml) ACE genotype compared with both the DD and ID (-1.4 +/- 6.2 and -3.6 +/- 2.5 mU/ml) ACE genotypes. In conclusion, we demonstrated that those older hypertensives with the ACE II genotype have the greatest improvement in insulin action following AEX.

  18. Association for Continuing Education, Annual Report, June 30, 1973.

    ERIC Educational Resources Information Center

    Association for Continuing Education, Stanford, CA.

    Details relevant to the operation of the Association for Continuing Education (ACE) for the year ending June 30, 1973 are presented. ACE is a non-profit corporation offering live, televised courses to employees of cooperating firms in the San Francisco area. Using the television facilities of Stanford University, instructional programs are…

  19. Genomic and physiological characterization of a laboratory-isolated Acinetobacter schindleri ACE strain that quickly and efficiently catabolizes acetate.

    PubMed

    Sigala, Juan-Carlos; Suárez, Brisa Paola; Lara, Alvaro R; Borgne, Sylvie Le; Bustos, Patricia; Santamaría, Rosa Isela; González, Víctor; Martinez, Alfredo

    2017-07-01

    An Acinetobacter strain, designated ACE, was isolated in the laboratory. Phylogenetic tests and average nucleotide identity value comparisons suggested that ACE belongs to the species Acinetobacterschindleri. We report for the first time the complete genome sequence of an A. schindleri strain, which consists of a single circular chromosome of 3 001 209 bp with an overall DNA G+C content of 42.9 mol% and six plasmids that account for 266 844 bp of extrachromosomal material. The presence or absence of genes related to carbon catabolism and antibiotic resistance were in agreement with the phenotypic characterization of ACE. This strain grew faster and with a higher biomass yield on acetate than the reference strain Acinetobacter baylyi ADP1. However, ACE did not use aromatic compounds and was unable to grow on common carbon sources, such as glucose, xylose, glycerol or citrate. The gluconeogenic and the catechol pathways are complete in ACE, but compounds that are converted to protocatechuate did not sustain growth since some genes of this pathway are missing. Likewise, this strain could not grow on glucose because it lacks the genes of the Entner-Doudoroff pathway. Minimal inhibitory concentration data showed that ACE was susceptible to most of the antimicrobial agents recommended for the clinical treatment of Acinetobacter spp. Some genes related to a possible human-microbe interaction were found in the ACE genome. ACE is likely to have a low pathogenic risk, as is the case with other A. schindleri strains. These results provide a valuable reference for broadening the knowledge of the biology of Acinetobacter.

  20. Accelerated Cartesian expansion (ACE) based framework for the rapid evaluation of diffusion, lossy wave, and Klein-Gordon potentials

    DOE PAGES

    Baczewski, Andrew David; Vikram, Melapudi; Shanker, Balasubramaniam; ...

    2010-08-27

    Diffusion, lossy wave, and Klein–Gordon equations find numerous applications in practical problems across a range of diverse disciplines. The temporal dependence of all three Green’s functions are characterized by an infinite tail. This implies that the cost complexity of the spatio-temporal convolutions, associated with evaluating the potentials, scales as O(N s 2N t 2), where N s and N t are the number of spatial and temporal degrees of freedom, respectively. In this paper, we discuss two new methods to rapidly evaluate these spatio-temporal convolutions by exploiting their block-Toeplitz nature within the framework of accelerated Cartesian expansions (ACE). The firstmore » scheme identifies a convolution relation in time amongst ACE harmonics and the fast Fourier transform (FFT) is used for efficient evaluation of these convolutions. The second method exploits the rank deficiency of the ACE translation operators with respect to time and develops a recursive numerical compression scheme for the efficient representation and evaluation of temporal convolutions. It is shown that the cost of both methods scales as O(N sN tlog 2N t). Furthermore, several numerical results are presented for the diffusion equation to validate the accuracy and efficacy of the fast algorithms developed here.« less

  1. Role of nitrification in the biodegradation of selected artificial sweetening agents in biological wastewater treatment process.

    PubMed

    Tran, N H; Nguyen, V T; Urase, T; Ngo, H H

    2014-06-01

    The biodegradation of the six artificial sweetening agents including acesulfame (ACE), aspartame (ASP), cyclamate (CYC), neohesperidindihydrochalcone (NHDC), saccharin (SAC), and sucralose (SUC) by nitrifying activated sludge was first examined. Experimental results showed that ASP and NHDC were the most easily degradable compounds even in the control tests. CYC and SAC were efficiently biodegraded by the nitrifying activated sludge, whereas ACE and SUC were poorly removed. However, the biodegradation efficiencies of the ASs were increased with the increase in initial ammonium concentrations in the bioreactors. The association between nitrification and co-metabolic degradation was investigated and a linear relationship between nitrification rate and co-metabolic biodegradation rate was observed for the target artificial sweeteners (ASs). The contribution of heterotrophic microorganisms and autotrophic ammonia oxidizers in biodegradation of the ASs was elucidated, of which autotrophic ammonia oxidizers played an important role in the biodegradation of the ASs, particularly with regards to ACE and SUC. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases

    PubMed Central

    Zhuang, Xiao-dong; Liao, Li-zhen; Dong, Xiao-bian; Hu, Xun; Guo, Yue; Du, Zhi-min; Liao, Xin-xue; Wang, Li-chun

    2016-01-01

    This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice. PMID:26792980

  3. Adverse childhood experiences and the association with ever using alcohol and initiating alcohol use during adolescence.

    PubMed

    Dube, Shanta R; Miller, Jacqueline W; Brown, David W; Giles, Wayne H; Felitti, Vincent J; Dong, Maxia; Anda, Robert F

    2006-04-01

    Alcohol is the most common and frequently used drug and has the potential to cause multiple deleterious effects throughout the lifespan. Because early age at initiation of alcohol use increases this potential and programs and laws are in place to attempt to delay the onset of alcohol use, we studied the relationship between multiple adverse childhood experiences (ACEs) and both the likelihood of ever drinking and the age at initiating alcohol use. This was a retrospective cohort study of 8417 adult health maintenance organization (HMO) members in California who completed a survey about ACEs, which included childhood abuse and neglect, growing up with various forms of household dysfunction and alcohol use in adolescence and adulthood. The main outcomes measured were ever drinking and age at initiating alcohol use among ever-drinkers for four age categories: < or = 14 years (early adolescence), 15 to 17 years (mid adolescence), and 18 to 20 years (late adolescence); age > or = 21 years was the referent. The relationship between the total number of adverse childhood experiences (ACE score) and early initiation of alcohol use (< or =14 years) among four birth cohorts dating back to 1900 was also examined. Eighty-nine percent of the cohort reported ever drinking; all individual ACEs except physical neglect increased the risk of ever using alcohol (p < .05). Among ever drinkers, initiating alcohol use by age 14 years was increased two- to threefold by individual ACEs (p < .05). ACEs also accounted for a 20% to 70% increased likelihood of alcohol use initiated during mid adolescence (15-17 years). The total number of ACEs (ACE score) had a very strong graded relationship to initiating alcohol use during early adolescence and a robust but somewhat less strong relationship to initiation during mid adolescence. For each of the four birth cohorts, the ACE score had a strong, graded relationship to initiating alcohol use by age 14 years (p < .05). Adverse childhood experiences are strongly related to ever drinking alcohol and to alcohol initiation in early and mid adolescence, and the ACE score had a graded or "dose-response" relationship to these alcohol use behaviors. The persistent graded relationship between the ACE score and initiation of alcohol use by age 14 for four successive birth cohorts dating back to 1900 suggests that the stressful effects of ACEs transcend secular changes, including the increased availability of alcohol, alcohol advertising, and the recent campaigns and health education programs to prevent alcohol use. These findings strongly suggest that efforts to delay the age of onset of drinking must recognize the contribution of multiple traumatic and stressful events to alcohol-seeking behavior among children and adolescents.

  4. Methods to Assess Adverse Childhood Experiences of Children and Families: Toward Approaches to Promote Child Well-being in Policy and Practice.

    PubMed

    Bethell, Christina D; Carle, Adam; Hudziak, James; Gombojav, Narangerel; Powers, Kathleen; Wade, Roy; Braveman, Paula

    Advances in human development sciences point to tremendous possibilities to promote healthy child development and well-being across life by proactively supporting safe, stable and nurturing family relationships (SSNRs), teaching resilience, and intervening early to promote healing the trauma and stress associated with disruptions in SSNRs. Assessing potential disruptions in SSNRs, such as adverse childhood experiences (ACEs), can contribute to assessing risk for trauma and chronic and toxic stress. Asking about ACEs can help with efforts to prevent and attenuate negative impacts on child development and both child and family well-being. Many methods to assess ACEs exist but have not been compared. The National Survey of Children's Health (NSCH) now measures ACEs for children, but requires further assessment and validation. We identified and compared methods to assess ACEs among children and families, evaluated the acceptability and validity of the new NSCH-ACEs measure, and identified implications for assessing ACEs in research and practice. Of 14 ACEs assessment methods identified, 5 have been used in clinical settings (vs public health assessment or research) and all but 1 require self or parent report (3 allow child report). Across methods, 6 to 20 constructs are assessed, 4 of which are common to all: parental incarceration, domestic violence, household mental illness/suicide, household alcohol or substance abuse. Common additional content includes assessing exposure to neighborhood violence, bullying, discrimination, or parental death. All methods use a numeric, cumulative risk scoring methodology. The NSCH-ACEs measure was acceptable to respondents as evidenced by few missing values and no reduction in response rate attributable to asking about children's ACEs. The 9 ACEs assessed in the NSCH co-occur, with most children with 1 ACE having additional ACEs. This measure showed efficiency and confirmatory factor analysis as well as latent class analysis supported a cumulative risk scoring method. Formative as well as reflective measurement models further support cumulative risk scoring and provide evidence of predictive validity of the NSCH-ACEs. Common effects of ACEs across household income groups confirm information distinct from economic status is provided and suggest use of population-wide versus high-risk approaches to assessing ACEs. Although important variations exist, available ACEs measurement methods are similar and show consistent associations with poorer health outcomes in absence of protective factors and resilience. All methods reviewed appear to coincide with broader goals to facilitate health education, promote health and, where needed, to mitigate the trauma, chronic stress, and behavioral and emotional sequelae that can arise with exposure to ACEs. Assessing ACEs appears acceptable to individuals and families when conducted in population-based and clinical research contexts. Although research to date and neurobiological findings compel early identification and health education about ACEs in clinical settings, further research to guide use in pediatric practice is required, especially as it relates to distinguishing ACEs assessment from identifying current family psychosocial risks and child abuse. The reflective as well as formative psychometric analyses conducted in this study confirm use of cumulative risk scoring for the NSCH-ACEs measure. Even if children have not been exposed to ACEs, assessing ACEs has value as an educational tool for engaging and educating families and children about the importance of SSNRs and how to recognize and manage stress and learn resilience. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  5. Comparison of In-Person vs. Digital Climate Education Program

    NASA Astrophysics Data System (ADS)

    Anderson, R. K.; Flora, J. A.; Saphir, M.

    2017-12-01

    In 2014, ACE (Alliance for Climate Education) evaluated the impact of its 45-minute live climate edutainment education program on the knowledge, attitudes and behavior of high school students with respect to climate change. The results showed gains in knowledge, increased engagement, as well as increased communication about climate change with number of students reporting talking about climate change with friends and family more than doubling. In 2016, ACE launched a digital version of its in-person edutainment education program, a 40-minute video version of the live program. This digital version, Our Climate Our Future (OCOF), has now been used by nearly 4,000 teachers nationwide and viewed by over 150,000 students. We experimentally tested the impact of the digital program (OCOF) compared to the live program and a control group. The experiment was conducted with 709 students in 27 classes at two North Carolina public high schools. Classes were assigned to one of three conditions: digital, live and control. In the digital version, students watched the 40-minute OCOF video featuring the same educator that presented the live program. In the live version, students received an identical 40-minute live presentation by an ACE staff educator The control group received neither treatment. When compared to controls, both programs were effective in positively increasing climate change knowledge, climate justice knowledge, perceived self-efficacy to make climate-friendly behavior changes, and beliefs about climate change (all statistically significant at or above P<.01). In the areas of hope that people can solve climate change and intent to change behavior, only the live program showed significant increases. In these two areas, it may be that an in-person experience is key to affecting change. In light of these positive results, ACE plans to increase the use of OCOF in schools across the country to assist teachers in their efforts to teach about climate change.

  6. Comparison of In-Person vs. Digital Climate Education Program

    NASA Astrophysics Data System (ADS)

    Anbar, A. D.; Elkins-Tanton, L. T.; Klug Boonstra, S.; Ben-Naim, D.

    2016-12-01

    In 2014, ACE (Alliance for Climate Education) evaluated the impact of its 45-minute live climate edutainment education program on the knowledge, attitudes and behavior of high school students with respect to climate change. The results showed gains in knowledge, increased engagement, as well as increased communication about climate change with number of students reporting talking about climate change with friends and family more than doubling. In 2016, ACE launched a digital version of its in-person edutainment education program, a 40-minute video version of the live program. This digital version, Our Climate Our Future (OCOF), has now been used by nearly 4,000 teachers nationwide and viewed by over 150,000 students. We experimentally tested the impact of the digital program (OCOF) compared to the live program and a control group. The experiment was conducted with 709 students in 27 classes at two North Carolina public high schools. Classes were assigned to one of three conditions: digital, live and control. In the digital version, students watched the 40-minute OCOF video featuring the same educator that presented the live program. In the live version, students received an identical 40-minute live presentation by an ACE staff educator The control group received neither treatment. When compared to controls, both programs were effective in positively increasing climate change knowledge, climate justice knowledge, perceived self-efficacy to make climate-friendly behavior changes, and beliefs about climate change (all statistically significant at or above P<.01). In the areas of hope that people can solve climate change and intent to change behavior, only the live program showed significant increases. In these two areas, it may be that an in-person experience is key to affecting change. In light of these positive results, ACE plans to increase the use of OCOF in schools across the country to assist teachers in their efforts to teach about climate change.

  7. Pharmacotherapy after myocardial infarction: disease management versus usual care.

    PubMed

    Chan, Vicky; Cooke, Catherine E

    2008-06-01

    To evaluate the effectiveness of a disease management (DM) program compared with usual care on utilization of and adherence to key evidence-based therapies (angiotensin-converting enzyme [ACE] inhibitors/angiotensin II receptor blockers [ARBs], beta-blockers, and statins) after hospital discharge for patients with myocardial infarction (MI) in a managed care organization. Retrospective case-control cohort. Members were included if they were 18 years of age or older and had any medical claims for hospitalization for MI, defined as International Classification of Diseases, Ninth Revision, Clinical Modification, codes 410.xx, from January 1, 2002, to December 31, 2002. The index date was the first date of discharge for members with an MI diagnosis. Members were categorized into the active group (automatically enrolled in the DM program) or the control group (not enrolled in the program because their employer group did not purchase the benefit). Pharmacy claims were obtained for 12 months after the index date for ACE inhibitors, ARBs, beta-blockers, and statins. The study cohort included 250 members in the active group and 137 members in the control group. There were no statistical differences in utilization or time to first prescription fill of ACE inhibitors, ARBs, beta-blockers, and statins between the DM and usual care groups. Adherence to each of these therapies, as measured by medication possession ratio, was not statistically different between the 2 groups. Compared with usual care, participation in the DM program did not improve ACE inhibitor, ARB, statin, or beta-blocker utilization or adherence in members post-MI.

  8. Children and Caregivers’ Exposure to Adverse Childhood Experiences (ACES): Association with Children’s and Caregivers’ Psychological Outcomes in a Therapeutic Preschool Program

    PubMed Central

    Ziv, Yair; Sofri, Inbar; Capps Umphlet, Kristen L.; Olarte, Stephanie; Venza, Jimmy

    2018-01-01

    Exposure to adverse childhood experiences (ACE) has been found to have a profound negative impact on multiple child outcomes, including academic achievement, social cognition patterns, and behavioral adjustment. However, these links have yet to be examined in preschool children that are already experiencing behavior or social-emotional problems. Thus, the present study examined the links between the caregiver’s and the child’s exposure to ACE and multiple child and caregiver’s outcomes in a sample of 30 preschool children enrolled in a Therapeutic Nursery Program (TNP). Children are typically referred to this TNP due to significant delays in their social emotional development that often result in difficulty functioning in typical childcare, home, and community settings. Analyses revealed some contradictory patterns that may be specific to this clinical sample. Children with higher exposure to ACE showed more biased social information processing patterns and their caregivers reported lower child social skills than caregivers of children with less exposure, however their inhibitory control levels were higher (better control) and staff reported that these children exhibited better social skills as well as better approaches to learning than children with less exposure. No such contradictions were found in relation to the caregiver’s exposure to ACE, as it was positively associated with a number of negative child and caregiver outcomes. PMID:29614735

  9. 78 FR 69434 - Post-Summary Corrections to Entry Summaries Filed in ACE Pursuant to the ESAR IV Test...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ...'s) Entry Summary, Accounts and Revenue (ESAR IV) test program concerning the processing of post... DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Post-Summary Corrections to Entry Summaries Filed in ACE Pursuant to the ESAR IV Test: Modifications and Clarifications AGENCY: U.S...

  10. Six Misconceptions about Accreditation in Higher Education: Lessons from Teacher Education

    ERIC Educational Resources Information Center

    Murray, Frank B.

    2012-01-01

    The role of accreditation is to assure that the standards that uniquely define institutions and programs are adhered to so that their increasingly high costs produce solid value. In the fall 2011 issue of "The Presidency," a publication of the American Council on Education (ACE), Terry Hartle, a senior vice-president of ACE, outlined six…

  11. Navigating Uncharted Waters: An Accelerated Content-Based English for Academic Purposes Program

    ERIC Educational Resources Information Center

    Hernandez, Kelly; Thomas, Michelle; Schuemann, Cynthia

    2012-01-01

    In 2008, Miami Dade College received a $1.9 million Title V grant from the US Department of Education to develop an Accelerated Content-Based English for Academic Purposes (EAP) track called Project ACE for ESL students. The ACE curriculum is anchored by the principles of flexibility, contextualization, and faculty buy-in--critical matters given…

  12. Effect of liposomes on the rate of alkaline hydrolysis of indomethacin and acemetacin.

    PubMed

    Matos, C; Chaimovich, H; Lima, J L; Cuccovia, I M; Reis, S

    2001-03-01

    The anti-inflammatory, analgesic, and antipyretic drugs indomethacin (INDO) and acemetacin (ACE), extensively used for the treatment of diseases of degenerative or inflammatory character, exhibit marked gastric irritant action, have low water solubility at neutral pH, and decompose in alkali. Alternative formulations are being investigated to obtain products with lower toxicity and higher stability. Here we examine the effect of liposome charge on the rate of alkaline decomposition of INDO and ACE using micelles as reference. Binding of ACE and INDO to zwitterionic hexadecylphosphocholine (HDPC) micelles and phosphatidylcholine (PC) liposomes was analyzed using a two-phase separation model to quantify the effect of these aggregates on the rate of alkaline degradation. The substrate association constants to HDPC micelles were 1335 and 2192 M(-1) for INDO and ACE, respectively, whereas the corresponding values for PC vesicles were 612 and 3050 M(-1). The difference was attributed to the additional hydrophobicity of ACE. The inhibitory effect of HDPC micelles and PC vesicles was quantified by calculating the ratio between the rate constants in water (k(w)) and in the aggregate (k(m)). The values of the k(w)/k(m) ratios for INDO and ACE in HDPC micelles were, respectively, 80 and 42, and in PC liposomes these ratios were 21 and 3.7, respectively. Positively charged micelles of hexadecyltrimethylammonium chloride (CTAC) and vesicles containing varying proportions of dioctadecyldimethylammonium chloride (DODAC) and PC increase the rate of INDO and ACE alkaline decomposition. Vesicle effects were very sensitive to the DODAC/PC ratio, with rates increasing with the proportion of DODAC. The data were analyzed quantitatively using a pseudophase model with explicit consideration of ion exchange. The calculated second-order rate constants in micelles and vesicles were lower than that in water. The charge density in the liposome necessary to increase the entrapment efficiency and decrease drug decomposition can be modulated, by judicious choice of pH and ionic strength. These manipulations can lead to more stable formulation with increased efficiency in drug entrapment and controlled effects on drug stability.

  13. Aerosol Optical Properties Measured Onboard the Ronald H. Brown During ACE Asia as a Function of Aerosol Chemical Composition and Source Region

    NASA Technical Reports Server (NTRS)

    Quinn, P. K.; Coffman, D. J.; Bates, T. S.; Welton, E. J.; Covert, D. S.; Miller, T. L.; Johnson, J. E.; Maria, S.; Russell, L.; Arimoto, R.

    2004-01-01

    During the ACE Asia intensive field campaign conducted in the spring of 2001 aerosol properties were measured onboard the R/V Ronald H. Brown to study the effects of the Asian aerosol on atmospheric chemistry and climate in downwind regions. Aerosol properties measured in the marine boundary layer included chemical composition; number size distribution; and light scattering, hemispheric backscattering, and absorption coefficients. In addition, optical depth and vertical profiles of aerosol 180 deg backscatter were measured. Aerosol within the ACE Asia study region was found to be a complex mixture resulting from marine, pollution, volcanic, and dust sources. Presented here as a function of air mass source region are the mass fractions of the dominant aerosol chemical components, the fraction of the scattering measured at the surface due to each component, mass scattering efficiencies of the individual components, aerosol scattering and absorption coefficients, single scattering albedo, Angstrom exponents, optical depth, and vertical profiles of aerosol extinction. All results except aerosol optical depth and the vertical profiles of aerosol extinction are reported at a relative humidity of 55 +/- 5%. An over-determined data set was collected so that measured and calculated aerosol properties could be compared, internal consistency in the data set could be assessed, and sources of uncertainty could be identified. By taking into account non-sphericity of the dust aerosol, calculated and measured aerosol mass and scattering coefficients agreed within overall experimental uncertainties. Differences between measured and calculated aerosol absorption coefficients were not within reasonable uncertainty limits, however, and may indicate the inability of Mie theory and the assumption of internally mixed homogeneous spheres to predict absorption by the ACE Asia aerosol. Mass scattering efficiencies of non-sea salt sulfate aerosol, sea salt, submicron particulate organic matter, and dust found for the ACE Asia aerosol are comparable to values estimated for ACE 1, Aerosols99, and INDOEX. Unique to the ACE Asia aerosol was the large mass fractions of dust, the dominance of dust in controlling the aerosol optical properties, and the interaction of dust with soot aerosol.

  14. A review of advanced turboprop transport aircraft

    NASA Astrophysics Data System (ADS)

    Lange, Roy H.

    The application of advanced technologies shows the potential for significant improvement in the fuel efficiency and operating costs of future transport aircraft envisioned for operation in the 1990s time period. One of the more promising advanced technologies is embodied in an advanced turboprop concept originated by Hamilton Standard and NASA and known as the propfan. The propfan concept features a highly loaded multibladed, variable pitch propeller geared to a high pressure ratio gas turbine engine. The blades have high sweepback and advanced airfoil sections to achieve 80 percent propulsive efficiency at M=0.80 cruise speed. Aircraft system studies have shown improvements in fuel efficiency of 15-20 percent for propfan advanced transport aircraft as compared to equivalent turbofan transports. Beginning with the Lockheed C-130 and Electra turboprop aircraft, this paper presents an overview of the evolution of propfan aircraft design concepts and system studies. These system studies include possible civil and military transport applications and data on the performance, community and far-field noise characteristics and operating costs of propfan aircraft design concepts. NASA Aircraft Energy Efficiency (ACEE) program propfan projects with industry are reviewed with respect to system studies of propfan aircraft and recommended flight development programs.

  15. Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?

    PubMed

    Wang, Pei; Fedoruk, Matthew N; Rupert, Jim L

    2008-01-01

    In the decade since the angiotensin-converting enzyme (ACE) gene was first proposed to be a 'human gene for physical performance', there have been numerous studies examining the effects of ACE genotype on physical performance phenotypes such as aerobic capacity, muscle function, trainability, and athletic status. While the results are variable and sometimes inconsistent, and corroborating phenotypic data limited, carriers of the ACE 'insertion' allele (the presence of an alu repeat element in intron 16 of the gene) have been reported to have higher maximum oxygen uptake (VO2max), greater response to training, and increased muscle efficiency when compared with individuals carrying the 'deletion' allele (absence of the alu repeat). Furthermore, the insertion allele has been reported to be over-represented in elite athletes from a variety of populations representing a number of endurance sports. The mechanism by which the ACE insertion genotype could potentiate physical performance is unknown. The presence of the ACE insertion allele has been associated with lower ACE activity (ACEplasma) in number of studies, suggesting that individuals with an innate tendency to have lower ACE levels respond better to training and are at an advantage in endurance sporting events. This could be due to lower levels of angiotensin II (the vasoconstrictor converted to active form by ACE), higher levels of bradykinin (a vasodilator degraded by ACE) or some combination of the two phenotypes. Observations that individuals carrying the ACE insertion allele (and presumably lower ACEplasma) have an enhanced response to training or are over-represented amongst elite athletes raises the intriguing question: would individuals with artificially lowered ACEplasma have similar training or performance potential? As there are a number of drugs (i.e. ACE inhibitors and angiotensin II type 1 receptor antagonists [angiotensin receptor blockers--ARBs]) that have the ability to either reduce ACEplasma activity or block the action of angiotensin II, the question is relevant to the study of ergogenic agents and to the efforts to rid sports of 'doping'. This article discusses the possibility that ACE inhibitors and ARBs, by virtue of their effects on ACE or angiotensin II function, respectively, have performance-enhancing capabilities; it also reviews the data on the effects of these medications on VO2max, muscle composition and endurance capacity in patient and non-patient populations. We conclude that, while the direct evidence supporting the hypothesis that ACE-related medications are potential doping agents is not compelling, there are insufficient data on young, athletic populations to exclude the possibility, and there is ample, albeit indirect, support from genetic studies to suggest that they should be. Unfortunately, given the history of drug experimentation in athletes and the rapid appropriation of therapeutic agents into the doping arsenal, this indirect evidence, coupled with the availability of ACE-inhibiting and ACE-receptor blocking medications may be sufficiently tempting to unscrupulous competitors looking for a shortcut to the finish line.

  16. Buildings and community systems technology transfer support: Task 8, No. 1088

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

    Not Available

    Information on items prepared for delivery by the contractor for the Industrial Energy Conservation Program are presented in this document. The information in the following brochures: Integrated Community Energy Systems (ICES); Energy Savings Through Automatic Thermostat Controls; Energy-Conserving Systems in Restaurants; Waste Heat Recovery: More Power from Fuels; and Fuel Cells: A New Kind of Power Plant is included. The Energy Efficiency Logo and 2 photographs are presented. A memo concerning ERDA energy data collection, dated November 4, 1976 and a letter about Goldmark Communications, Inc., dated August 16, 1976 are included. The Energy Efficiency Research pamphlet (EER) is reprinted.more » The following are also included: Working draft - Technology Transfer Section of Buildings Conservation Pad; Environmental Concerns/Industrial Growth - Speech to Industrial Council Workshop, Urban Land Institute, 1976 Fall Meeting, October 5, 1976; discussion on Liquid Nitrogen Freezing for Process Foods; and paper on Buildings and Community Systems Program Strategy. Information on high temperature recuperator systems; microwave/vacuum grain drying; Annual Cycle Energy Systems (ACES); Sambo's; Energy Outreach Program; and thermally activated heat pumps is also included. (MCW)« less

  17. Angiotensin-Converting Enzyme Inhibition as an Adjunct to Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Curtis, Katrina J.; Meyrick, Victoria M.; Mehta, Bhavin; Haji, Gulam S.; Li, Kawah; Montgomery, Hugh; Man, William D.-C.; Polkey, Michael I.

    2016-01-01

    Rationale: Epidemiological studies in older individuals have found an association between the use of angiotensin-converting enzyme (ACE) inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength, and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation (PR). Objectives: To investigate the hypothesis that enalapril, an ACE inhibitor, would augment the improvement in exercise capacity seen during PR. Methods: We performed a double-blind, placebo-controlled, parallel-group randomized controlled trial. Patients with chronic obstructive pulmonary disease, who had at least moderate airflow obstruction and were taking part in PR, were randomized to either 10 weeks of therapy with an ACE inhibitor (10 mg enalapril) or placebo. Measurements and Main Results: The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Eighty patients were enrolled, 78 were randomized (age 67 ± 8 years; FEV1 48 ± 21% predicted), and 65 completed the trial (34 on placebo, 31 on the ACE inhibitor). The ACE inhibitor–treated group demonstrated a significant reduction in systolic blood pressure (Δ, −16 mm Hg; 95% confidence interval [CI], −22 to −11) and serum ACE activity (Δ, −18 IU/L; 95% CI, −23 to −12) versus placebo (between-group differences, P < 0.0001). Peak power increased significantly more in the placebo group (placebo Δ, +9 W; 95% CI, 5 to 13 vs. ACE-I Δ, +1 W; 95% CI, −2 to 4; between-group difference, 8 W; 95% CI, 3 to 13; P = 0.001). There was no significant between-group difference in quadriceps strength or health-related quality of life. Conclusions: Use of the ACE inhibitor enalapril, together with a program of PR, in patients without an established indication for ACE-I, reduced the peak work rate response to exercise training in patients with chronic obstructive pulmonary disease. PMID:27248440

  18. Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study.

    PubMed

    Shafaei, Armaghan; Sultan Khan, Md Shamsuddin; F A Aisha, Abdalrahim; Abdul Majid, Amin Malik Shah; Hamdan, Mohammad Razak; Mordi, Mohd Nizam; Ismail, Zhari

    2016-11-09

    This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure-activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX : BioSolveIT's LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC 50 value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC 50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.

  19. Pressure distribution data from tests of 2.29-meter (7.5-ft.) span EET high-lift research model in Langley 4- by 7-meter tunnel

    NASA Technical Reports Server (NTRS)

    Morgan, H. L., Jr.

    1982-01-01

    A 2.29 m (7.5 ft.) span high-lift research model equipped with full-span leading-edge slat and part-span double-slotted trailing-edge flap was tested in the Langley 4- by 7-Meter Tunnel to determine the low speed performance characteristics of a representative high aspect ratio suprcritical wing. These tests were performed in support of the Energy Efficient Transport (EET) program which is one element of the Aircraft Energy Efficiency (ACEE) project. Static longitudinal forces and moments and chordwise pressure distributions at three spanwise stations were measured for cruise, climb, two take-off flap, and two landing flap wing configurations. The tabulated and plotted pressure distribution data is presented without analysis or discussion.

  20. Pressure distribution data from tests of 2.29 M (7.5 feet) span EET high-lift transport aircraft model in the Ames 12-foot pressure tunnel

    NASA Technical Reports Server (NTRS)

    Kjelgaard, S. O.; Morgan, H. L., Jr.

    1983-01-01

    A high-lift transport aircraft model equipped with full-span leading-edge slat and part-span double-slotted trailing-edge flap was tested in the Ames 12-ft pressure tunnel to determine the low-speed performance characteristics of a representative high-aspect-ratio supercritical wing. These tests were performed in support of the Energy Efficient Transport (EET) program which is one element of the Aircraft Energy Efficiency (ACEE) project. Static longitudinal forces and moments and chordwise pressure distributions at three spanwise stations were measured for cruise, climb, two take-off flap, and two landing flap wing configurations. The tabulated and plotted pressure distribution data is presented without analysis or discussion.

  1. High resolution critical habitat mapping and classification of tidal freshwater wetlands in the ACE Basin

    NASA Astrophysics Data System (ADS)

    Strickland, Melissa Anne

    In collaboration with the South Carolina Department of Natural Resources ACE Basin National Estuarine Research Reserve (ACE Basin NERR), the tidal freshwater ecosystems along the South Edisto River in the ACE Basin are being accurately mapped and classified using a LIDAR-Remote Sensing Fusion technique that integrates LAS LIDAR data into texture images and then merges the elevation textures and multispectral imagery for very high resolution mapping. This project discusses the development and refinement of an ArcGIS Toolbox capable of automating protocols and procedures for marsh delineation and microhabitat identification. The result is a high resolution habitat and land use map used for the identification of threatened habitat. Tidal freshwater wetlands are also a critical habitat for colonial wading birds and an accurate assessment of community diversity and acreage of this habitat type in the ACE Basin will support SCDNR's conservation and protection efforts. The maps developed by this study will be used to better monitor the freshwater/saltwater interface and establish a baseline for an ACE NERR monitoring program to track the rates and extent of alterations due to projected environmental stressors. Preliminary ground-truthing in the field will provide information about the accuracy of the mapping tool.

  2. Mobilizing communities and building capacity for youth violence prevention: the National Academic Centers of Excellence for Youth Violence Prevention.

    PubMed

    Vivolo, Alana M; Matjasko, Jennifer L; Massetti, Greta M

    2011-09-01

    Violence, including its occurrence among youth, results in considerable physical, emotional, social, and economic consequences in the US. Youth violence prevention work at the Division of Violence Prevention (DVP) at the Centers for Disease Control and Prevention (CDC) emphasizes preventing youth violence-related behaviors, injuries, and deaths by collaborating with academic and community partners and stakeholders. In 2000 and 2005, DVP funded the National Academic Centers of Excellence (ACE) for Youth Violence Prevention. Most ACE Centers focus on building community capacity and competence so that evidence-based programs for youth violence prevention can be successfully implemented through effective and supportive research-community partnerships. This commentary provides historical information about the ACE Program, including the development, goals, accomplishments of the Centers, and the utilization of a community-based participatory research approach to prevent youth violence.

  3. Counting down: HIV prison-based peer education programs and their connection to reduced disciplinary infractions.

    PubMed

    Collica-Cox, Kimberly

    2014-08-01

    Involvement in prosocial prison activities can ameliorate rule-breaking conduct and assist in the reinforcement of conventional behavior. Extant research shows a connection between participation in traditional educational/vocational programs and reduced prison infractions. However, studies that examine a correlation between less traditional prison programs and better institutional conduct are lacking. This study analyzed rates of disciplinary infractions among 49 female prisoners that worked in two HIV prison-based peer programs (AIDS, Counseling, and Education [ACE] and CARE [Counseling, AIDS, Resource, and Education]) as peer educators during their incarceration. These women were unlikely to jeopardize their position by engaging in unlawful or deviant behaviors. Results showed that working in programs like ACE/CARE prevented periods of maladjustment and subsequent disciplinary infractions during incarceration. © The Author(s) 2013.

  4. Rural–urban differences in exposure to adverse childhood experiences among South Carolina adults.

    PubMed

    Radcliff, Elizabeth; Crouch, Elizabeth; Strompolis, Melissa

    2018-02-01

    Adverse childhood experiences (ACEs) are traumatic events that occur in a child's life between birth and 18 years. Exposure to one or more ACE has been linked to participation in risky health behaviors and the experience of chronic health conditions in adulthood. The risk for poor outcomes increases as the number of ACEs experienced increases. This research investigates rural-urban differences in exposure to ACEs using a sample from a representative southern US state, South Carolina. Using data from the 2014-2015 South Carolina Behavioral Risk Factor Surveillance System (BRFSS) and residential rurality based on UICs, ACE exposure among South Carolina adults was tabulated by urban versus rural residence and selected other demographic characteristics. Using standard descriptive statistics, frequencies and proportions were calculated for each categorical variable. Multivariable regression modeling was used to examine the impact of residential rurality and selected sociodemographic characteristics on overall and specific types of ACE exposure. All analyses used survey sampling weights that accounted for the BRFSS sampling strategy. The analytic sample of 18 176 respondents comprised 15.9% rural residents. Top reported ACEs for both rural and urban residents were the same: parental divorce/separation, emotional abuse, and household substance use. Compared to urban residents, a higher proportion of rural respondents reported experiencing no ACEs (41.4% vs 38.3%, p<0.01). The prevalence of four or more ACEs in rural respondents was 15.0%; in comparison, 17.6% of urban respondents had four or more ACEs (p<0.01). In logistic regression predicting exposure to four or more ACEs and adjusting for sex, age, race/ethnicity, education, and income, rural respondents were less likely than urban respondents to report four or more ACEs (adjusted odds ratio 0.75, 95% confidence interval 0.74-0.75). Despite reporting less ACE exposure than urban counterparts, almost 60% of rural residents reported at least one ACE and 15% reported experiencing four or more ACEs. In contrast to urban residents, rural residents may experience more social connections within their families and communities, which may influence ACE exposure; however, care coordination, social support services, and access to health care are limited in rural areas. Thus, families in rural areas may be less equipped to mitigate and manage the effects of ACEs. Findings from this study thus suggest that interventions to prevent ACE exposure are just as needed in rural southern communities as they are in urban southern communities. Topics important for future research could include an examination of ACEs in rural communities in terms of individuals' health outcomes and their access to health care, as well as the role of protective factors. Programs and policies that assist in ACE prevention in rural areas are important to reducing these multigenerational threats to health and wellbeing.

  5. Sex and sexual orientation disparities in adverse childhood experiences and early age at sexual debut in the United States: results from a nationally representative sample.

    PubMed

    Brown, Monique J; Masho, Saba W; Perera, Robert A; Mezuk, Briana; Cohen, Steven A

    2015-08-01

    Adverse childhood experiences (ACEs) have been linked to early sexual debut, which has been found to be associated with multiple adverse health outcomes. Sexual minorities and men tend to have earlier sexual debut compared to heterosexual populations and women, respectively. However, studies examining the association between ACEs and early sexual debut among men and sexual minorities are lacking. The aim of this study was to examine the sex and sexual orientation disparities in the association between ACEs and age at sexual debut. Data were obtained from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic and linear regression models were used to obtain crude and adjusted estimates and 95% confidence intervals adjusting for age, race/ethnicity, income, education, insurance and marital status for the association between ACEs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration and psychopathology) and early sexual debut. Analyses were stratified by sex and sexual orientation. Larger effect estimates depicting the association between ACEs and sexual debut were seen for women compared to men, and among sexual minorities, particularly among men who have sex with men (MSM) and women who have sex with women (WSW), compared to heterosexuals. Sexual health education programs with a focus on delaying sexual debut among children and adolescents should also consider addressing ACEs, such as neglect, physical, psychological and sexual abuse, witnessing parental violence, and parental incarceration and psychopathology. Public health practitioners, researchers and sexual health education curriculum coordinators should consider these differences by sex and sexual orientation when designing these programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Sex and sexual orientation disparities in adverse childhood experiences and early age at sexual debut in the United States: Results from a nationally representative sample☆

    PubMed Central

    Brown, Monique J.; Masho, Saba W.; Perera, Robert A.; Mezuk, Briana; Cohen, Steven A.

    2015-01-01

    Adverse childhood experiences (ACEs) have been linked to early sexual debut, which has been found to be associated with multiple adverse health outcomes. Sexual minorities and men tend to have earlier sexual debut compared to heterosexual populations and women, respectively. However, studies examining the association between ACEs and early sexual debut among men and sexual minorities are lacking. The aim of this study was to examine the sex and sexual orientation disparities in the association between ACEs and age at sexual debut. Data were obtained from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic and linear regression model were used to obtain crude and adjusted estimates and 95% confidence intervals adjusting for age, race/ethnicity, income, education, insurance and marital status for the association between ACEs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration and psychopathology) and early sexual debut. Analyses were stratified by sex and sexual orientation. Larger effect estimates depicting the association between ACEs and sexual debut were seen for women compared to men, and among sexual minorities, particularly among men who have sex with men (MSM) and women who have sex with women (WSW), compared to heterosexuals. Sexual health education programs with a focus on delaying sexual debut among children and adolescents should also consider addressing ACEs, such as neglect, physical, psychological and sexual abuse, witnessing parental violence, and parental incarceration and psychopathology. Public health practitioners, researchers and sexual health education curriculum coordinators should consider these differences by sex and sexual orientation when designing these programs. PMID:25804435

  7. The Process of General Education Reform from a Faculty Perspective at a Research-Extensive University: A Grounded Theory Approach

    ERIC Educational Resources Information Center

    Hachtmann, Frauke

    2010-01-01

    The purpose of this study was to develop a theory for institutional change that explains the process and implementation of "Achievement-Centered Education" (ACE) from the faculty perspective. ACE is a new general education program at the University of Nebraska-Lincoln, a public, doctoral/research-extensive institution. A constant…

  8. High speed reaction wheels for satellite attitude control and energy storage

    NASA Technical Reports Server (NTRS)

    Studer, P.; Rodriguez, E.

    1985-01-01

    The combination of spacecraft attitude control and energy storage (ACES) functions in common hardware, to synergistically maintain three-axis attitude control while supplying electrical power during earth orbital eclipses, allows the generation of control torques by high rotating speed wheels that react against the spacecraft structure via a high efficiency bidirectional energy conversion motor/generator. An ACES system encompasses a minimum of four wheels, controlling power and the three torque vectors. Attention is given to the realization of such a system with composite flywheel rotors that yield high energy density, magnetic suspension technology yielding low losses at high rotational speeds, and an ironless armature permanent magnet motor/generator yielding high energy conversion efficiency.

  9. Minority Engineering Program Pipeline: A Proposal to Increase Minority Student Enrollment and Retention in Engineering

    NASA Technical Reports Server (NTRS)

    Charity, Pamela C.; Klein, Paul B.; Wadhwa, Bhushan

    1995-01-01

    The Cleveland State University Minority Engineering Program Pipeline consist of programs which foster engineering career awareness, academic enrichment, and professional development for historically underrepresented minority studies. The programs involved are the Access to Careers in Engineering (ACE) Program for high school pre-engineering students: the LINK Program for undergraduate students pursuing degree which include engineering; and the PEP (Pre-calculus Enrichment Program) and EPIC (Enrichment Program in Calculus) mathematics programs for undergraduate academic enrichment. The pipeline is such that high school graduates from the ACE Program who enroll at Cleveland State University in pursuit of engineering degrees are admitted to the LINK Program for undergraduate level support. LINK Program students are among the minority participants who receive mathematics enrichment through the PEP and EPIC Programs for successful completion of their engineering required math courses. THese programs are interdependent and share the goal of preparing minority students for engineering careers by enabling them to achieve academically and obtain college degree and career related experience.

  10. Adverse childhood experiences and risk for suicidal behavior in male Iraq and Afghanistan veterans seeking PTSD treatment.

    PubMed

    Carroll, Timothy D; Currier, Joseph M; McCormick, Wesley H; Drescher, Kent D

    2017-09-01

    Adverse childhood experiences (ACEs) are associated with increased risk for suicide and appear to occur in disproportionately high rates among men who served in the U.S. military. However, research has yet to examine a comprehensive range of ACEs among Iraq/Afghanistan veterans with combat-related posttraumatic stress disorder (PTSD) or whether these premilitary stressors may contribute to suicidal behavior in this highly vulnerable population. A sample of 217 men entering a residential program for combat-related PTSD completed measures for ACEs, combat exposure, and lifetime suicidal ideation and attempts. The majority of patients had experienced multiple types of adversity or traumas during childhood/adolescence. In particular, 83.4% endorsed at least 1 ACE category and 41.5% reported experiencing 4 or more ACEs. When accounting for effects of deployment-related stressors, we further found that accumulation of ACEs was uniquely linked with thoughts of suicide or attempts among these patients. Namely, for every 1-point increase on the ACE Questionnaire, veterans' risk of suicidal ideation and attempts increased by 23% and 24%, respectively. This brief report provides initial evidence that veterans seeking treatment for combat-related PTSD often have extensive histories of premilitary stressors that may increase suicide risk beyond probable deployment-related traumas. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. The Relationship of Adverse Childhood Events to Smoking, Overweight, Obesity and Binge Drinking Among Women in Hawaii.

    PubMed

    Remigio-Baker, Rosemay A; Hayes, Donald K; Reyes-Salvail, Florentina

    2017-02-01

    To evaluate how the associations of adverse childhood events (ACEs) with smoking, overweight, obesity and binge drinking differ by race/ethnicity among women, including a large, understudied cohort of Asians and Native Hawaiians/Pacific Islanders (NHOPIs). The number and type (household dysfunction, and physical, verbal and sexual abuse) of ACEs were examined in relation to adulthood smoking, overweight, obesity and binge drinking among 3354 women in Hawaii using the 2010 Behavioral Risk Factor Surveillance System data using Poisson regression with robust error variance. We additionally investigated for interaction by race/ethnicity. Covariates included age, race/ethnicity, education, emotional support, healthcare coverage, and the other health outcomes. Overall, 54.9 % reported at least 1 ACE. The prevalence of smoking (PR = 1.40 (1 ACE) to PR = 2.55 [5+ ACEs]), overweight (PR = 1.22 [1 ACE] to PR = 1.31 [5+ ACEs]) and obesity (PR = 1.00 [1 ACE] to PR = 1.85 [5+ ACEs]) increased with increasing ACE count. Smoking was associated with household dysfunction (PR = 1.67, CI = 1.26-2.22), and physical (PR = 2.04, CI = 1.50-2.78) and verbal (PR = 1.62, CI = 1.25-2.10) abuse. Obesity was also significantly related to household dysfunction (PR = 1.22, CI = 1.01-1.48), and physical (PR = 1.36, CI = 1.10-1.70), verbal (PR = 1.35, CI = 1.11-1.64) and sexual (PR = 1.53, CI = 1.25-1.88) abuse. Among Asians, sexual abuse was associated with a lower prevalence of binge drinking (PR = 0.26, CI = 0.07-0.93), which was significantly different from the null association among Whites (interaction p = 0.02). Preventing/addressing ACEs may help optimize childhood health, and reduce the likelihood of smoking/obesity among women including Asians/NHOPIs. Further studies are warranted to evaluate the sexual abuse-binge drinking association among Asians, which may support the need for culturally-tailored programs to address ACEs.

  12. The Relationship of Adverse Childhood Events To Smoking, Overweight, Obesity and Binge Drinking Among Women In Hawaii

    PubMed Central

    Remigio-Baker, Rosemay A.; Hayes, Donald K.; Reyes-Salvail, Florentina

    2016-01-01

    OBJECTIVES To evaluate how the associations of adverse childhood events (ACEs) with smoking, overweight, obesity and binge drinking differ by race/ethnicity among women, including a large, understudied cohort of Asians and Native Hawaiians/Pacific Islanders (NHOPIs). METHODS The number and type (household dysfunction, and physical, verbal and sexual abuse) of ACEs were examined in relation to adulthood smoking, overweight, obesity and binge drinking among 3,354 women in Hawaii using the 2010 Behavioral Risk Factor Surveillance System data using Poisson regression. We additionally investigated for interaction by race/ethnicity. Covariates included age, race/ethnicity, education, emotional support, healthcare coverage, and the other health outcomes. RESULTS Overall, 54.9% reported at least 1 ACE. The prevalence of smoking (Prevalence Ratio [PR]=1.40 [1 ACE] to PR=2.55 [5+ ACEs]), overweight (PR=1.22 [1 ACE] to PR=1.31 [5+ ACEs]) and obesity (PR=1.00 [1 ACE] to PR=1.85 [5+ ACEs]) increased with increasing ACE count. Smoking was associated with household dysfunction (PR=1.67, CI=1.26–2.22), and physical (PR=2.04, CI=1.50–2.78) and verbal (PR=1.62, CI=1.25–2.10) abuse. Obesity was also significantly related to household dysfunction (PR=1.22, CI=1.01–1.48), and physical (PR=1.36, CI=1.10–1.70), verbal (PR=1.35, CI=1.11–1.64) and sexual (PR=1.53, CI=1.25–1.88) abuse. Among Asians, sexual abuse was associated with a lower prevalence of binge drinking (PR=0.26, CI=0.07, 0.93), which was significantly different from the null association among Whites (interaction p=0.02). CONCLUSION Preventing/addressing ACEs may help optimize childhood health, and reduce the likelihood of smoking/obesity among women including Asians/NHOPIs. Further studies are warranted to evaluate the sexual abuse-binge drinking association among Asians, which may support the need for culturally-tailored programs to address ACEs. PMID:27449778

  13. Effects of artificial sweeteners on metal bioconcentration and toxicity on a green algae Scenedesmus obliquus.

    PubMed

    Hu, Hongwei; Deng, Yuanyuan; Fan, Yunfei; Zhang, Pengfei; Sun, Hongwen; Gan, Zhiwei; Zhu, Hongkai; Yao, Yiming

    2016-05-01

    The ecotoxicity of heavy metals depends much on their speciation, which is influenced by other co-existing substances having chelating capacity. In the present study, the toxic effects of Cd(2+) and Cu(2+) on a green algae Scenedesmus obliquus were examined in the presence of two artificial sweeteners (ASs), acesulfame (ACE) and sucralose (SUC) by comparing the cell specific growth rate μ and pulse-amplitude-modulated (PAM) parameters (maximal photosystem II photochemical efficiency Fv/Fm, actual photochemical efficiency Yield, and non-photochemical quenching NPQ) of the algae over a 96-h period. Simultaneously, the bioconcentration of the metals by the algal cells in the presence of the ASs was measured. The presence of ACE enhanced the growth of S. obliquus and promoted the bioconcentration of Cd(2+) in S. obliquus, while the impacts of SUC were not significant. Meanwhile, EC50 values of Cd(2+) on the growth of S. obliquus increased from 0.42 mg/L to 0.54 mg/L and 0.48 mg/L with the addition of 1.0 mg/L ACE and SUC, respectively. As for Cu(2+), EC50 values increased from 0.13 mg/L to 0.17 mg/L and 0.15 mg/L with the addition of 1.0 mg/L ACE and SUC, respectively. In summary, the two ASs reduced the toxicity of the metals on the algae, with ACE showing greater effect than SUC. Although not as sensitive as the cell specific growth rate, PAM parameters could disclose the mechanisms involved in metal toxicity at subcellular levels. This study provides the first evidence for the possible impact of ASs on the ecotoxicity of heavy metals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Analysis of WakeVAS Benefits Using ACES Build 3.2.1

    NASA Technical Reports Server (NTRS)

    Smith, Jeremy C.

    2005-01-01

    The FAA and NASA are currently engaged in a Wake Turbulence Research Program to revise wake turbulence separation standards, procedures, and criteria to increase airport capacity while maintaining or increasing safety. The research program is divided into three phases: Phase I near term procedural enhancements; Phase II wind dependent Wake Vortex Advisory System (WakeVAS) Concepts of Operations (ConOps); and Phase III farther term ConOps based on wake prediction and sensing. This report contains an analysis that evaluates the benefits of a closely spaced parallel runway (CSPR) Phase I ConOps, a single runway and CSPR Phase II ConOps and a single runway Phase III ConOps. A series of simulation runs were performed using the Airspace Concepts Evaluation System (ACES) Build 3.21 air traffic simulator to provide an initial assessment of the reduction in delay and cost savings obtained by the use of a WakeVAS at selected U.S. airports. The ACES simulator is being developed by NASA Ames Research Center as part of the Virtual Airspace Modelling and Simulation (VAMS) program.

  15. ACE: an efficient and sensitive tool to detect insecticide resistance-associated mutations in insect acetylcholinesterase from RNA-Seq data.

    PubMed

    Guo, Dianhao; Luo, Jiapeng; Zhou, Yuenan; Xiao, Huamei; He, Kang; Yin, Chuanlin; Xu, Jianhua; Li, Fei

    2017-07-10

    Insecticide resistance is a substantial problem in controlling agricultural and medical pests. Detecting target site mutations is crucial to manage insecticide resistance. Though PCR-based methods have been widely used in this field, they are time-consuming and inefficient, and typically have a high false positive rate. Acetylcholinesterases (Ace) is the neural target of the widely used organophosphate (OP) and carbamate insecticides. However, there is not any software available to detect insecticide resistance associated mutations in RNA-Seq data at present. A computational pipeline ACE was developed to detect resistance mutations of ace in insect RNA-Seq data. Known ace resistance mutations were collected and used as a reference. We constructed a Web server for ACE, and the standalone software in both Linux and Windows versions is available for download. ACE was used to analyse 971 RNA-Seq data from 136 studies in 7 insect pests. The mutation frequency of each RNA-Seq dataset was calculated. The results indicated that the resistance frequency was 30%-44% in an eastern Ugandan Anopheles population, thus suggesting this resistance-conferring mutation has reached high frequency in these mosquitoes in Uganda. Analyses of RNA-Seq data from the diamondback moth Plutella xylostella indicated that the G227A mutation was positively related with resistance levels to organophosphate or carbamate insecticides. The wasp Nasonia vitripennis had a low frequency of resistant reads (<5%), but the agricultural pests Chilo suppressalis and Bemisia tabaci had a high resistance frequency. All ace reads in the 30 B. tabaci RNA-Seq data were resistant reads, suggesting that insecticide resistance has spread to very high frequency in B. tabaci. To the best of our knowledge, the ACE pipeline is the first tool to detect resistance mutations from RNA-Seq data, and it facilitates the full utilization of large-scale genetic data obtained by using next-generation sequencing.

  16. Vapor compression heat pump system field tests at the TECH complex

    NASA Astrophysics Data System (ADS)

    Baxter, V. D.

    1985-07-01

    The Tennessee Energy Conservation In Housing (TECH) complex has been utilized since 1977 as a field test site for several novel and conventional heat pump systems for space conditioning and water heating. Systems tested include the Annual Cycle Energy System (ACES), solar assisted heat pumps (SAHP) both parallel and series, two conventional air-to-air heat pumps, an air-to-air heat pump with desuperheater water heater, and horizontal coil and multiple shallow vertical coil ground-coupled heat pumps (GCHP). A direct comparison of the measured annual performance of the test systems was not possible. However, a cursory examination revealed that the ACES had the best performance. However, its high cost makes it unlikely that it will achieve widespread use. Costs for the SAHP systems are similar to those of the ACES but their performance is not as good. Integration of water heating and space conditioning functions with a desuperheater yielded significant efficiency improvement at modest cost. The GCHP systems performed much better for heating than for cooling and may well be the most efficient alternative for residences in cold climates.

  17. Vapor compression heat pump system field tests at the tech complex

    NASA Astrophysics Data System (ADS)

    Baxter, Van D.

    1985-11-01

    The Tennessee Energy Conservation In Housing (TECH) complex has been utilized since 1977 as a field test site for several novel and conventional heat pump systems for space conditioning and water heating. Systems tested include the Annual Cycle Energy System (ACES), solar assisted heat pumps (SAHP) both parallel and series, two conventional air-to-air heat pumps, an air-to-air heat pump with desuperheater water heater, and horizontal coil and multiple shallow vertical coil ground-coupled heat pumps (GCHP). A direct comparison of the measured annual performance of the test systems was not possible. However, a cursory examination revealed that the ACES had the best performance, however, its high cost makes it unlikely that it will achieve wide-spread use. Costs for the SAHP systems are similar to those of the ACES but their performance is not as good. Integration of water heating and space conditioning functions with a desuperheater yielded significant efficiency improvement at modest cost. The GCHP systems performed much better for heating than for cooling and may well be the most efficient alternative for residences in cold climates.

  18. Computer codes for thermal analysis of a solid rocket motor nozzle

    NASA Technical Reports Server (NTRS)

    Chauhan, Rajinder Singh

    1988-01-01

    A number of computer codes are available for performing thermal analysis of solid rocket motor nozzles. Aerotherm Chemical Equilibrium (ACE) computer program can be used to perform one-dimensional gas expansion to determine the state of the gas at each location of a nozzle. The ACE outputs can be used as input to a computer program called Momentum/Energy Integral Technique (MEIT) for predicting boundary layer development development, shear, and heating on the surface of the nozzle. The output from MEIT can be used as input to another computer program called Aerotherm Charring Material Thermal Response and Ablation Program (CMA). This program is used to calculate oblation or decomposition response of the nozzle material. A code called Failure Analysis Nonlinear Thermal and Structural Integrated Code (FANTASTIC) is also likely to be used for performing thermal analysis of solid rocket motor nozzles after the program is duly verified. A part of the verification work on FANTASTIC was done by using one and two dimension heat transfer examples with known answers. An attempt was made to prepare input for performing thermal analysis of the CCT nozzle using the FANTASTIC computer code. The CCT nozzle problem will first be solved by using ACE, MEIT, and CMA. The same problem will then be solved using FANTASTIC. These results will then be compared for verification of FANTASTIC.

  19. The Altus Cumulus Electrification Study (ACES): A UAV-based Investigation of Thunderstorms

    NASA Technical Reports Server (NTRS)

    Blakeslee, Richard; Arnold, James E. (Technical Monitor)

    2001-01-01

    The Altus Cumulus Electrification Study (ACES) is a NASA-sponsored and -led science investigation that utilizes an uninhabited aerial vehicle (UAV) to investigate thunderstorms in the vicinity of the NASA Kennedy Space Center, Florida. As part of NASA's UAV-based science demonstration program, ACES will provide a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. ACES will employ the Altus 11 aircraft, built by General Atomics-Aeronautical Systems, Inc. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high-altitude flight (up to 55,000 feet), the Altus will be flown near, and when possible, above (but never into) thunderstorms for long periods of time, allowing investigations to be conducted over entire storm life cycles. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and (3) provide Lightning Imaging Sensor validation. The ACES payload, already developed and flown on Altus, includes electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. The ACES field campaign will be conducted during July 2002 with a goal of performing 8 to 10 UAV flights. Each flight will require about 4 to 5 hours on station at altitudes from 40,000 ft to 55,000 ft. The ACES team is comprised of scientists from the NASA Marshall Space Flight Center and NASA Goddard Space Flight Centers partnered with General Atomics and IDEA, LLC.

  20. Modification of Epigenetic Patterns in Low Birth Weight Children: Importance of Hypomethylation of the ACE Gene Promoter

    PubMed Central

    Rangel, Marina; dos Santos, Jéssica Cassilla; Ortiz, Paula Helena Lima; Hirata, Mario; Jasiulionis, Miriam Galvonas; Araujo, Ronaldo C.; Ierardi, Daniela Filippini; Franco, Maria do Carmo

    2014-01-01

    There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels. PMID:25170764

  1. Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.

    PubMed

    Rangel, Marina; dos Santos, Jéssica Cassilla; Ortiz, Paula Helena Lima; Hirata, Mario; Jasiulionis, Miriam Galvonas; Araujo, Ronaldo C; Ierardi, Daniela Filippini; Franco, Maria do Carmo

    2014-01-01

    There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.

  2. Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states.

    PubMed

    Cunningham, Timothy J; Ford, Earl S; Croft, Janet B; Merrick, Melissa T; Rolle, Italia V; Giles, Wayne H

    2014-01-01

    Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population. Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only. ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

  3. Parallel Signal Processing and System Simulation using aCe

    NASA Technical Reports Server (NTRS)

    Dorband, John E.; Aburdene, Maurice F.

    2003-01-01

    Recently, networked and cluster computation have become very popular for both signal processing and system simulation. A new language is ideally suited for parallel signal processing applications and system simulation since it allows the programmer to explicitly express the computations that can be performed concurrently. In addition, the new C based parallel language (ace C) for architecture-adaptive programming allows programmers to implement algorithms and system simulation applications on parallel architectures by providing them with the assurance that future parallel architectures will be able to run their applications with a minimum of modification. In this paper, we will focus on some fundamental features of ace C and present a signal processing application (FFT).

  4. Relative lipophilicities and structural-pharmacological considerations of various angiotensin-converting enzyme (ACE) inhibitors.

    PubMed

    Ranadive, S A; Chen, A X; Serajuddin, A T

    1992-11-01

    Lipophilicities of seven structurally diverse angiotensin-converting enzyme (ACE) inhibitors, viz., captopril, zofenoprilat, enalaprilat, ramiprilat, lisinopril, fosinoprilat, and ceronapril (SQ29852), were compared by determining their octanol-water distribution coefficients (D) under physiological pH conditions. The distribution co-efficients of zofenopril, enalapril, ramipril and fosinopril, which are the prodrug forms of zofenoprilat, enalaprilat, ramiprilat, and fosinoprilat, respectively, were also determined. Attempts were made to correlate lipophilicities with the reported data for oral absorption, protein binding, ACE inhibitory activity, propensity for biliary excretion, and penetration across the blood-brain barrier for these therapeutic entities. Better absorption of prodrugs compared to their respective active forms is in agreement with their greater lipophilicities. Captopril, lisinopril, and ceronapril are orally well absorbed despite their low lipophilicities, suggesting involvement of other factors such as a carrier-mediated transport process. Of all the compounds studied, the two most lipophilic ACE inhibitors, fosinoprilat and zofenoprilat, exhibit a rank-order correlation with respect to biliary excretion. This may explain the dual routes of elimination (renal and hepatic) observed with fosinoprilat in humans. The more lipophilic compounds also exhibit higher protein binding. Both the lipophilicity and a carrier-mediated process may be involved in penetration of some of these drugs into brain. For structurally similar compounds, in vitro ACE inhibitory activity increased with the increase in lipophilicity. However, no clear correlation between lipophilicity and ACE inhibitory activity emerged when different types of inhibitors are compared, possibly because their interactions with enzymes are primarily ionic in nature.

  5. Effect of fed-batch vs. continuous mode of operation on microbial fuel cell performance treating biorefinery wastewater

    DOE PAGES

    Pannell, Tyler C.; Goud, R. Kannaiah; Schell, Daniel J.; ...

    2016-05-01

    Bioelectrochemical systems have been shown to treat low-value biorefinery streams while recovering energy, however, low current densities and anode conversion efficiencies (ACE) limit their application. A bioanode was developed via enrichment of electroactive biofilm under fed-batch and continuous feeding conditions using corn stover-derived waste stream. The continuously-fed MFC exhibited a current density of 5.8±0.06 A/m 2 and an ACE of 39%±4. The fed-batch MFC achieved a similar current density and an ACE of 19.2%, however, its performance dropped after 36 days of operation to 1.1 A/m 2 and 0.5%, respectively. In comparison, the ACE of the continuously-fed MFC remained stablemore » achieving an ACE of 30% ± 3 after 48 days of operation. An MFC treating a biorefinery stream post fuel separation achieved a current density of 10.7±0.1 A/m 2 and an ACE of 57% ± 9 at an organic loading of 12.5 g COD/L-day. Characterization of the microbial communities indicate higher abundance of Firmicutes and Proteobacteria and lower abundance of Bacteriodetes and a higher level of Geobacter spp. (1.4% vs. 0.2%) in continuously-fed MFC vs. fed-batch MFC. Finally, the results demonstrate that limiting substrate to the equivalent maximum current that the anode can generate, maintains MFC performance over a long term for high strength wastewaters, such as those generated in the biorefinery.« less

  6. Effect of fed-batch vs. continuous mode of operation on microbial fuel cell performance treating biorefinery wastewater

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

    Pannell, Tyler C.; Goud, R. Kannaiah; Schell, Daniel J.

    Bioelectrochemical systems have been shown to treat low-value biorefinery streams while recovering energy, however, low current densities and anode conversion efficiencies (ACE) limit their application. A bioanode was developed via enrichment of electroactive biofilm under fed-batch and continuous feeding conditions using corn stover-derived waste stream. The continuously-fed MFC exhibited a current density of 5.8±0.06 A/m 2 and an ACE of 39%±4. The fed-batch MFC achieved a similar current density and an ACE of 19.2%, however, its performance dropped after 36 days of operation to 1.1 A/m 2 and 0.5%, respectively. In comparison, the ACE of the continuously-fed MFC remained stablemore » achieving an ACE of 30% ± 3 after 48 days of operation. An MFC treating a biorefinery stream post fuel separation achieved a current density of 10.7±0.1 A/m 2 and an ACE of 57% ± 9 at an organic loading of 12.5 g COD/L-day. Characterization of the microbial communities indicate higher abundance of Firmicutes and Proteobacteria and lower abundance of Bacteriodetes and a higher level of Geobacter spp. (1.4% vs. 0.2%) in continuously-fed MFC vs. fed-batch MFC. Finally, the results demonstrate that limiting substrate to the equivalent maximum current that the anode can generate, maintains MFC performance over a long term for high strength wastewaters, such as those generated in the biorefinery.« less

  7. The Association of ACE Genotypes on Cardiorespiratory Variables Related to Physical Fitness in Healthy Men

    PubMed Central

    Bueno, Salomão; Pasqua, Leonardo A.; de Araújo, Gustavo; Eduardo Lima-Silva, Adriano; Bertuzzi, Rômulo

    2016-01-01

    Aerobic power (VO2max), aerobic capacity (RCP), and running efficiency (RE) are important markers of aerobic fitness. However, the influence of the angiotensin converting enzyme (ACE) polymorphism on these markers has not been investigated in healthy individuals. One hundred and fifty physically active young men (age 25 ± 3 years; height 1.77 ± 0.06 m; body mass 76.6 ± 0.9 kg; VO2max 47.7 ± 5.5 ml·kg-1·min-1) visited the laboratory on two separate occasions, and performed the following tests: a) a maximal incremental treadmill test to determine VO2max and RCP, and b) two constant-speed running tests (10 km·h-1 and 12 km·h-1) to determine RE. The genotype frequency was II = 21%; ID = 52%; and DD = 27%. There was a tendency for higher VO2max with the ACE II genotype (p = 0.08) compared to DD and ID genotypes. Magnitude based inferences suggested a likely beneficial effect on VO2max with the ACE II genotype. There was no association between genotypes for other variable. These findings suggest that individuals with the ACE II genotype have a tendency towards better values in aerobic power, but not with aerobic capacity or running economy. PMID:27861507

  8. What are the ideal properties for functional food peptides with antihypertensive effect? A computational peptidology approach.

    PubMed

    Zhou, Peng; Yang, Chao; Ren, Yanrong; Wang, Congcong; Tian, Feifei

    2013-12-01

    Peptides with antihypertensive potency have long been attractive to the medical and food communities. However, serving as food additives, rather than therapeutic agents, peptides should have a good taste. In the present study, we explore the intrinsic relationship between the angiotensin I-converting enzyme (ACE) inhibition and bitterness of short peptides in the framework of computational peptidology, attempting to find out the appropriate properties for functional food peptides with satisfactory bioactivities. As might be expected, quantitative structure-activity relationship modeling reveals a significant positive correlation between the ACE inhibition and bitterness of dipeptides, but this correlation is quite modest for tripeptides and, particularly, tetrapeptides. Moreover, quantum mechanics/molecular mechanics analysis of the structural basis and energetic profile involved in ACE-peptide complexes unravels that peptides of up to 4 amino acids long are sufficient to have efficient binding to ACE, and more additional residues do not bring with substantial enhance in their ACE-binding affinity and, thus, antihypertensive capability. All of above, it is coming together to suggest that the tripeptides and tetrapeptides could be considered as ideal candidates for seeking potential functional food additives with both high antihypertensive activity and low bitterness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Direct large volume injection ultra-high performance liquid chromatography-tandem mass spectrometry determination of artificial sweeteners sucralose and acesulfame in well water.

    PubMed

    Wu, Minghuo; Qian, Yichao; Boyd, Jessica M; Hrudey, Steve E; Le, X Chris; Li, Xing-Fang

    2014-09-12

    Acesulfame (ACE) and sucralose (SUC) have become recognized as ideal domestic wastewater contamination indicators. Liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) analysis is commonly used; however, the sensitivity of SUC is more than two orders of magnitude lower than that of ACE, limiting the routine monitoring of SUC. To address this issue, we examined the ESI behavior of both ACE and SUC under various conditions. ACE is ionic in aqueous solution and efficiently produces simple [M-H](-) ions, but SUC produces multiple adduct ions, limiting its sensitivity. The formic acid (FA) adducts of SUC [M+HCOO](-) are sensitively and reproducibly generated under the LC-MS conditions. When [M+HCOO](-) is used as the precursor ion for SUC detection, the sensitivity increases approximately 20-fold compared to when [M-H](-) is the precursor ion. To further improve the limit of detection (LOD), we integrated the large volume injection approach (500μL injection) with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), which reduced the method detection limit (MDL) to 0.2ng/L for ACE and 5ng/L for SUC. To demonstrate the applicability of this method, we analyzed 100 well water samples collected in Alberta. ACE was detected in 24 wells at concentrations of 1-1534ng/L and SUC in 8 wells at concentrations of 65-541ng/L. These results suggest that wastewater is the most likely source of ACE and SUC impacts in these wells, suggesting the need for monitoring the quality of domestic well water. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Efficiency of the Penumbra 5MAX ACE Reperfusion Catheter in Acute Ischemic Stroke Patients.

    PubMed

    Suzuki, Kentaro; Aoki, Junya; Sakamoto, Yuki; Kanamaru, Takuya; Abe, Arata; Suda, Satoshi; Okubo, Seiji; Kimura, Kazumi

    2016-12-01

    This study was performed to investigate whether the Penumbra 5MAX ACE is superior to other Penumbra systems. We performed a retrospective, single center analysis of patients with acute ischemic stroke with occlusion of the internal carotid artery or middle cerebral artery (M1 segment) who underwent endovascular therapy using a Penumbra system. The reperfusion success rate, puncture-to-revascularization time, and number of passes were assessed. Multivariate regression analysis was conducted to evaluate independent factors related to revascularization within 60 minutes. Successful revascularization was defined by a thrombolysis in cerebral infarction score ≥2b. The Penumbra 5MAX ACE was used in 24 of the 40 patients (60%). Although the revascularization success rate was similar between patient groups (P = .229), the number of passes was significantly lower (1.5 ± .8 versus 2.6 ± 1.3, P = .006) and the puncture-to-revascularization time was shorter (50 ± 26 minutes versus 116 ± 69 minutes, P = .002) in patients treated with the Penumbra 5MAX ACE. The Penumbra 5MAX ACE was identified as an independent factor for early revascularization (odds ratio, 5.80; P = .041). Among patients with a premorbid modified Rankin Scale score of 0-1, a modified Rankin Scale score of 0-2 at 3 months was observed in 15 of the 19 patients (79%) treated with the Penumbra 5MAX ACE and in 8 of the 16 (50%) who were not (P = .072). Acute revascularization therapy using the Penumbra 5MAX ACE can achieve rapid successful recanalization and tend to improve clinical outcomes. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Cooling Properties of the Shuttle Advanced Crew Escape Spacesuit: Results of an Environmental Chamber Experiment

    NASA Technical Reports Server (NTRS)

    Hamilton, Douglas; Gillis, David; Bue, Grant; Son, Chan; Norcross, Jason; Kuznetz, Larry; Chapman, Kirt; Chhipwadia, Ketan; McBride, Tim

    2008-01-01

    The shuttle crew wears the Advanced Crew Escape Spacesuit (ACES) to protect themselves from cabin decompression and to support bail out during landing. ACES is cooled by a liquid-cooled garment (LCG) that interfaces to a heat exchanger that dumps heat into the cabin. The ACES outer layer is made of Gore-Tex(Registered TradeMark), permitting water vapor to escape while containing oxygen. The crew can only lose heat via insensible water losses and the LCG. Under nominal landing operations, the average cabin temperature rarely exceeds 75 F, which is adequate for the ACES to function. Problem A rescue shuttle will need to return 11 crew members if the previous mission suffers a thermal protection system failure, preventing it from returning safely to Earth. Initial analysis revealed that 11 crew members in the shuttle will increase cabin temperature at wheel stop above 80 F, which decreases the ACES ability to keep crew members cool. Air flow in the middeck of the shuttle is inhomogeneous and some ACES may experience much higher temperatures that could cause excessive thermal stress to crew members. Methods A ground study was conducted to measure the cooling efficiency of the ACES at 75 F, 85 F, and 95 F at 50% relative humidity. Test subjects representing 5, 50, and 95 percentile body habitus of the astronaut corps performed hand ergometry keeping their metabolic rate at 400, 600, and 800 BTU/hr for one hour. Core temperature was measured by rectal probe and skin, while inside and outside the suit. Environmental chamber wall and cooling unit inlet and outlet temperatures were measured using high-resolution thermistors ( 0.2 C). Conclusions Under these test conditions, the ACES was able to protect the core temperature of all test subjects, however thermal stress due to high insensible losses and skin temperature and skin heat flow may impact crew performance. Further research should be performed to understand the impact on cognitive performance.

  12. The Impact of DNA Topology and Guide Length on Target Selection by a Cytosine-Specific Cas9.

    PubMed

    Tsui, Tsz Kin Martin; Hand, Travis H; Duboy, Emily C; Li, Hong

    2017-06-16

    Cas9 is an RNA-guided DNA cleavage enzyme being actively developed for genome editing and gene regulation. To be cleaved by Cas9, a double stranded DNA, or the protospacer, must be complementary to the guide region, typically 20-nucleotides in length, of the Cas9-bound guide RNA, and adjacent to a short Cas9-specific element called Protospacer Adjacent Motif (PAM). Understanding the correct juxtaposition of the protospacer- and PAM-interaction with Cas9 will enable development of versatile and safe Cas9-based technology. We report identification and biochemical characterization of Cas9 from Acidothermus cellulolyticus (AceCas9). AceCas9 depends on a 5'-NNNCC-3' PAM and is more efficient in cleaving negative supercoils than relaxed DNA. Kinetic as well as in vivo activity assays reveal that AceCas9 achieves optimal activity when combined with a guide RNA containing a 24-nucleotide complementarity region. The cytosine-specific, DNA topology-sensitive, and extended guide-dependent properties of AceCas9 may be explored for specific genome editing applications.

  13. Accelerated Cartesian expansions for the rapid solution of periodic multiscale problems

    DOE PAGES

    Baczewski, Andrew David; Dault, Daniel L.; Shanker, Balasubramaniam

    2012-07-03

    We present an algorithm for the fast and efficient solution of integral equations that arise in the analysis of scattering from periodic arrays of PEC objects, such as multiband frequency selective surfaces (FSS) or metamaterial structures. Our approach relies upon the method of Accelerated Cartesian Expansions (ACE) to rapidly evaluate the requisite potential integrals. ACE is analogous to FMM in that it can be used to accelerate the matrix vector product used in the solution of systems discretized using MoM. Here, ACE provides linear scaling in both CPU time and memory. Details regarding the implementation of this method within themore » context of periodic systems are provided, as well as results that establish error convergence and scalability. In addition, we also demonstrate the applicability of this algorithm by studying several exemplary electrically dense systems.« less

  14. Rhodium-catalyzed Intra- and Intermolecular [5+2] Cycloaddition of 3-Acyloxy-1,4-enyne and Alkyne with Concomitant 1,2-Acyloxy Migration

    PubMed Central

    Shu, Xing-Zhong; Li, Xiaoxun; Shu, Dongxu; Huang, Suyu; Schienebeck, Casi M.; Zhou, Xin; Robichaux, Patrick J.; Tang, Weiping

    2012-01-01

    A new type of rhodium-catalyzed [5+2] cycloaddition was developed for the synthesis of seven-membered rings with diverse functionalities. The ring formation was accompanied by a 1,2-acyloxy migration event. The 5- and 2-carbon components of the cycloaddition are 3-acyloxy-1,4-enynes (ACEs) and alkynes respectively. Cationic rhodium (I) catalysts worked most efficiently for the intramolecular cycloaddition, while only neutral rhodium (I) complexes could facilitate the intermolecular reaction. In both cases, electron-poor phosphite or phosphine ligands often improved the efficiency of the cycloadditions. The scope of ACEs and alkynes was investigated in both intra- and intermolecular reactions. The resulting seven-membered ring products have three double bonds that could be selectively functionalized. PMID:22364320

  15. Structural tests and development of a laminar flow control wing surface composite chordwise joint

    NASA Technical Reports Server (NTRS)

    Lineberger, L. B.

    1984-01-01

    The dramatic increases in fuel costs and the potential for periods of limited fuel availability provided the impetus to explore technologies to reduce transport aircraft fuel consumption. NASA sponsored the Aircraft Energy Efficiency (ACEE) program beginning in 1976 to develop technologies to improve fuel efficiency. The Lockheed-Georgia Company accomplished under NAS1-16235 Laminar-Flow-Control (LFC) Wing Panel Structural Design and Development (WSSD); design, manufacturing, and testing activities. An in-depth preliminary design of the baseline 1993 LFC wing was accomplished. A surface panel using the Lockheed graphite/epoxy integrated LFC wing box structural concept was designed. The concept was shown by analysis to be structurally efficient and cost effective. Critical details of the surface and surface joint was demonstrated by fabricating and testing complex, concept selection specimens. The Lockheed-Georgia Company accomplishments, Development of LFC Wind Surface Composite Structures (WSCS), are documented. Tests were conducted on two CV2 panels to verify the static tension and fatigue strength of LFC wing surface chordwise joints.

  16. Kinetic and structural characterization of amyloid-β peptide hydrolysis by human angiotensin-1-converting enzyme.

    PubMed

    Larmuth, Kate M; Masuyer, Geoffrey; Douglas, Ross G; Schwager, Sylva L; Acharya, K Ravi; Sturrock, Edward D

    2016-03-01

    Angiotensin-1-converting enzyme (ACE), a zinc metallopeptidase, consists of two homologous catalytic domains (N and C) with different substrate specificities. Here we report kinetic parameters of five different forms of human ACE with various amyloid beta (Aβ) substrates together with high resolution crystal structures of the N-domain in complex with Aβ fragments. For the physiological Aβ(1-16) peptide, a novel ACE cleavage site was found at His14-Gln15. Furthermore, Aβ(1-16) was preferentially cleaved by the individual N-domain; however, the presence of an inactive C-domain in full-length somatic ACE (sACE) greatly reduced enzyme activity and affected apparent selectivity. Two fluorogenic substrates, Aβ(4-10)Q and Aβ(4-10)Y, underwent endoproteolytic cleavage at the Asp7-Ser8 bond with all ACE constructs showing greater catalytic efficiency for Aβ(4-10)Y. Surprisingly, in contrast to Aβ(1-16) and Aβ(4-10)Q, sACE showed positive domain cooperativity and the double C-domain (CC-sACE) construct no cooperativity towards Aβ(4-10)Y. The structures of the Aβ peptide-ACE complexes revealed a common mode of peptide binding for both domains which principally targets the C-terminal P2' position to the S2' pocket and recognizes the main chain of the P1' peptide. It is likely that N-domain selectivity for the amyloid peptide is conferred through the N-domain specific S2' residue Thr358. Additionally, the N-domain can accommodate larger substrates through movement of the N-terminal helices, as suggested by the disorder of the hinge region in the crystal structures. Our findings are important for the design of domain selective inhibitors as the differences in domain selectivity are more pronounced with the truncated domains compared to the more physiological full-length forms. The atomic coordinates and structure factors for N-domain ACE with Aβ peptides 4-10 (5AM8), 10-16 (5AM9), 1-16 (5AMA), 35-42 (5AMB) and (4-10)Y (5AMC) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/). © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  17. Airborne Solar Radiant Flux Measurements During ACE-2

    NASA Technical Reports Server (NTRS)

    Bergstrom, Robert W.; Russell, Philip B.; Jonsson, Haflidi

    2000-01-01

    Aerosol effects on atmospheric radiative fluxes provide a forcing function that can change the climate in potentially significant ways. This aerosol radiative forcing is a major source of uncertainty in understanding the climate change of the past century and predicting future climate. To help reduce this uncertainty, the 1996 Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the 1997 Aerosol Characterization Experiment (ACE-2) measured the properties and radiative effects of aerosols over the Atlantic Ocean. In the ACE 2 program the solar radiant fluxes were measured on the Pelican aircraft and the UK Met Office C130. This poster will show results from the measurements for the aerosol effects during the clear column days. We will compare the results with calculations of the radiant fluxes.

  18. ACES: An Enabling Technology for Next Generation Space Transportation

    NASA Astrophysics Data System (ADS)

    Crocker, Andrew M.; Wuerl, Adam M.; Andrews, Jason E.; Andrews, Dana G.

    2004-02-01

    Andrews Space has developed the ``Alchemist'' Air Collection and Enrichment System (ACES), a dual-mode propulsion system that enables safe, economical launch systems that take off and land horizontally. Alchemist generates liquid oxygen through separation of atmospheric air using the refrigeration capacity of liquid hydrogen. The key benefit of Alchemist is that it minimizes vehicle takeoff weight. All internal and NASA-funded activities have shown that ACES, previously proposed for hypersonic combined cycle RLVs, is a higher payoff, lower-risk technology if LOX generation is performed while the vehicle cruises subsonically. Andrews Space has developed the Alchemist concept from a small system study to viable Next Generation launch system technology, conducting not only feasibility studies but also related hardware tests, and it has planned a detailed risk reduction program which employs an experienced, proven contractor team. Andrews also has participated in preliminary studies of an evolvable Next Generation vehicle architecture-enabled by Alchemist ACES-which could meet civil, military, and commercial space requirements within two decades.

  19. High-ACE Low Wage Workers: Occupational Health Nursing Research and Praxis Through a Trauma-Informed Lens.

    PubMed

    Rosemberg, Marie-Anne; Gultekin, Laura; Pardee, Michelle

    2018-05-01

    Individuals with a history of adverse childhood experiences (ACEs) disproportionately have poor mental and physical health outcomes. These experiences affect individuals across the life span extending beyond health with deleterious impact on work-related outcomes. Low-wage workers are particularly at risk. Social service and health organizations are becoming aware of the extent to which the populations they serve have been affected by these experiences. Employment support programs may serve high-ACE individuals but likely are unaware of their histories and the developmental or health deficits that result and can impinge on successful employment. Occupational health nurses may be well-positioned not only to implement trauma-informed care in workplaces but also to influence the ways in which employment services for this vulnerable group are delivered. The purpose of this article is to consider how ACEs could affect vulnerable workers. The need for trauma-informed research and praxis to advance occupational health nursing is discussed.

  20. Biodegradation of the artificial sweetener acesulfame in biological wastewater treatment and sandfilters.

    PubMed

    Castronovo, Sandro; Wick, Arne; Scheurer, Marco; Nödler, Karsten; Schulz, Manoj; Ternes, Thomas A

    2017-03-01

    A considerable removal of the artificial sweetener acesulfame (ACE) was observed during activated sludge processes at 13 wastewater treatment plants (WWTPs) as well as in a full-scale sand filter of a water works. A long-term sampling campaign over a period of almost two years revealed that ACE removal in WWTPs can be highly variable over time. Nitrifying/denitrifying sequencing batch reactors (SBR) as well as aerobic batch experiments with activated sludge and filter sand from a water works confirmed that both activated sludge as well as filter sand can efficiently remove ACE and that the removal can be attributed to biologically mediated degradation processes. The lab results strongly indicated that varying ACE removal in WWTPs is not associated with nitrification processes. Neither an enhancement of the nitrification rate nor the availability of ammonium or the inhibition of ammonium monooxygenase by N-allylthiourea (ATU) affected the degradation. Moreover, ACE was found to be also degradable by activated sludge under denitrifying conditions, while being persistent in the absence of both dissolved oxygen and nitrate. Using ion chromatography coupled with high resolution mass spectrometry, sulfamic acid (SA) was identified as the predominant transformation product (TP). Quantitative analysis of ACE and SA revealed a closed mass balance during the entire test period and confirmed that ACE was quantitatively transformed to SA. Measurements of dissolved organic carbon (DOC) revealed an almost complete removal of the carbon originating from ACE, thereby further confirming that SA is the only relevant final TP in the assumed degradation pathway of ACE. A first analysis of SA in three municipal WWTP revealed similar concentrations in influents and effluents with maximum concentrations of up to 2.3 mg/L. The high concentrations of SA in wastewater are in accordance with the extensive use of SA in acid cleaners, while the degradation of ACE in WWTPs adds only a very small portion of the total load of SA discharged into surface waters. No removal of SA was observed by the biological treatment applied at these WWTPs. Moreover, SA was also stable in the aerobic batch experiments conducted with the filter sand from a water works. Hence, SA might be a more appropriate wastewater tracer than ACE due to its chemical and microbiological persistence, the negligible sorbing affinity (high negative charge density) and its elevated concentrations in WWTP effluents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. New frontiers in sport training: genetics and artistic gymnastics.

    PubMed

    Morucci, Gabriele; Punzi, Tiziana; Innocenti, Giovanni; Gulisano, Massimo; Ceroti, Marco; Pacini, Stefania

    2014-02-01

    The increasing understanding of the genetic influences in sport has prompted an association study between the athletic performances and the polymorphisms of the angiotensin-converting enzyme (ACE), the α-actinin-3 (ACTN3), and the vitamin D receptor genes. The details of these gene polymorphisms can provide useful information to improve and plan new modern training programs for elite athletes. Eighty Italian male high level gymnasts were trained and tested for gymnastic-specific exercises and tested in all the men's artistic gymnastic apparatus (floor, pommel horse, rings, vault, parallel bars, and horizontal bar), and then genotyped. The training parameters of volume, intensity, and density of each gymnast were periodically measured during the season in each apparatus from the tests performed, and the seasonal average values were calculated. Gene polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism assay and studied in association with the performance results. The performances of ACE II gymnasts were significantly lower than that of the ACE ID/DD gymnasts in the apparatus expressing power features, confirming the predisposition of these athletes toward power-oriented sport. Gymnasts with ACTN3 RR/RX genotypes did not show a predisposition to the power-oriented apparatus, having worse performances compared with that of the ACTN3 XX gymnasts. Similarly, gymnasts with ACE II + ACTN3 RR/RX combined genotypes showed lower performances in comparison with that of the other gymnasts. Vitamin D receptor polymorphisms showed no significant association with the athletic performances. Because ACE insertion/deletion (I/D) and ACTN3 R577X polymorphisms heavily affect the physical performance of elite male gymnasts, the Italian Gymnastic Federation trainers have started to customize the current high-level training programs.

  2. Analysis of Wake VAS Benefits Using ACES Build 3.2.1: VAMS Type 1 Assessment

    NASA Technical Reports Server (NTRS)

    Smith, Jeremy C.

    2005-01-01

    The FAA and NASA are currently engaged in a Wake Turbulence Research Program to revise wake turbulence separation standards, procedures, and criteria to increase airport capacity while maintaining or increasing safety. The research program is divided into three phases: Phase I near term procedural enhancements; Phase II wind dependent Wake Vortex Advisory System (WakeVAS) Concepts of Operations (ConOps); and Phase III farther term ConOps based on wake prediction and sensing. The Phase III Wake VAS ConOps is one element of the Virtual Airspace Modelling and Simulation (VAMS) program blended concepts for enhancing the total system wide capacity of the National Airspace System (NAS). This report contains a VAMS Program Type 1 (stand-alone) assessment of the expected capacity benefits of Wake VAS at the 35 FAA Benchmark Airports and determines the consequent reduction in delay using the Airspace Concepts Evaluation System (ACES) Build 3.2.1 simulator.

  3. A simulation and video-based training program to address adverse childhood experiences.

    PubMed

    Wen, Frances K; Miller-Cribbs, Julie E; Coon, Kim A; Jelley, Martina J; Foulks-Rodriguez, Kristin A

    2017-05-01

    Adverse childhood experiences (ACEs) are 10 categories of childhood abuse and maltreatment, which have a dose-response relationship with common adult health concerns seen in primary care including health risk behaviors, chronic disease, and mental illness. Many of the ACEs-associated biopsychosocial risk factors are modifiable. However, physicians may not address these issues for fear of opening "Pandora's Box", that is, a source of extensive problems for which they are not sufficiently prepared with training, resources, or time. Residents need training in how to conduct trauma-focused conversations within the limited scope of an office visit. To address this need, a 4-hour simulation and video-based training program was developed for primary care residents about how to conduct brief interventions connecting their patients' current health concerns with their experiences of ACEs. Resident participants have evaluated this program as preparatory for real-life encounters and as being designed to allow for educational mastery. This article describes a workshop presenting this training program which was given at the 37th Annual Behavioral Science Forum in Family Medicine. Five skills targeted in the program were presented and a demonstration was made of the components, that is, didactics, provider and patient videos, simulated patient encounters, trainee feedback, and facilitated discussion that encompasses targeted skills, clinical implementation, and self-care. Companion tools were shared, including the syllabus, evaluation rubric, and provider and patient resources. Participants practiced trainee feedback and discussed the challenges in implementation.

  4. Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial.

    PubMed

    De Greef, Yves; Dekker, Lukas; Boersma, Lucas; Murray, Stephen; Wieczorek, Marcus; Spitzer, Stefan G; Davidson, Neil; Furniss, Steve; Hocini, Mélèze; Geller, J Christoph; Csanádi, Zoltan

    2016-05-01

    This prospective, multicentre study (PRECISION GOLD) evaluated the incidence of asymptomatic cerebral embolism (ACE) after pulmonary vein isolation (PVI) using a new gold multi-electrode radiofrequency (RF) ablation catheter, pulmonary vein ablation catheter (PVAC) GOLD. Also, procedural efficiency of PVAC GOLD was compared with ERACE. The ERACE study demonstrated that a low incidence of ACE can be achieved with a platinum multi-electrode RF catheter (PVAC) combined with procedural manoeuvres to reduce emboli. A total of 51 patients with paroxysmal atrial fibrillation (AF) (age 57 ± 9 years, CHA2DS2-VASc score 1.4 ± 1.4) underwent AF ablation with PVAC GOLD. Continuous oral anticoagulation using vitamin K antagonists, submerged catheter introduction, and heparinization (ACT ≥ 350 s prior to ablation) were applied. Cerebral magnetic resonance imaging (MRI) scans were performed within 48 h before and 16-72 h post-ablation. Cognitive function assessed by the Mini-Mental State Exam at baseline and 30 days post-ablation. New post-procedural ACE occurred in only 1 of 48 patients (2.1%) and was not detectable on MRI after 30 days. The average number of RF applications per patient to achieve PVI was lower in PRECISION GOLD (20.3 ± 10.0) than in ERACE (28.8 ± 16.1; P = 0.001). Further, PVAC GOLD ablations resulted in significantly fewer low-power (<3 W) ablations (15 vs. 23%, 5 vs. 10% and 2 vs. 7% in 4:1, 2:1, and 1:1 bipolar:unipolar energy modes, respectively). Mini-Mental State Exam was unchanged in all patients. Atrial fibrillation ablation with PVAC GOLD in combination with established embolic lowering manoeuvres results in a low incidence of ACE. Pulmonary vein ablation catheter GOLD demonstrates improved biophysical efficiency compared with platinum PVAC. ClinicalTrials.gov NCT01767558. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

  5. Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial

    PubMed Central

    De Greef, Yves; Dekker, Lukas; Boersma, Lucas; Murray, Stephen; Wieczorek, Marcus; Spitzer, Stefan G.; Davidson, Neil; Furniss, Steve; Hocini, Mélèze; Geller, J. Christoph; Csanádi, Zoltan

    2016-01-01

    Abstract Aims This prospective, multicentre study (PRECISION GOLD) evaluated the incidence of asymptomatic cerebral embolism (ACE) after pulmonary vein isolation (PVI) using a new gold multi-electrode radiofrequency (RF) ablation catheter, pulmonary vein ablation catheter (PVAC) GOLD. Also, procedural efficiency of PVAC GOLD was compared with ERACE. The ERACE study demonstrated that a low incidence of ACE can be achieved with a platinum multi-electrode RF catheter (PVAC) combined with procedural manoeuvres to reduce emboli. Methods and results A total of 51 patients with paroxysmal atrial fibrillation (AF) (age 57 ± 9 years, CHA2DS2-VASc score 1.4 ± 1.4) underwent AF ablation with PVAC GOLD. Continuous oral anticoagulation using vitamin K antagonists, submerged catheter introduction, and heparinization (ACT ≥ 350 s prior to ablation) were applied. Cerebral magnetic resonance imaging (MRI) scans were performed within 48 h before and 16–72 h post-ablation. Cognitive function assessed by the Mini-Mental State Exam at baseline and 30 days post-ablation. New post-procedural ACE occurred in only 1 of 48 patients (2.1%) and was not detectable on MRI after 30 days. The average number of RF applications per patient to achieve PVI was lower in PRECISION GOLD (20.3 ± 10.0) than in ERACE (28.8 ± 16.1; P = 0.001). Further, PVAC GOLD ablations resulted in significantly fewer low-power (<3 W) ablations (15 vs. 23%, 5 vs. 10% and 2 vs. 7% in 4:1, 2:1, and 1:1 bipolar:unipolar energy modes, respectively). Mini-Mental State Exam was unchanged in all patients. Conclusion Atrial fibrillation ablation with PVAC GOLD in combination with established embolic lowering manoeuvres results in a low incidence of ACE. Pulmonary vein ablation catheter GOLD demonstrates improved biophysical efficiency compared with platinum PVAC. Trial registration ClinicalTrials.gov NCT01767558. PMID:26826134

  6. Performance and economics of the ACES and alternative residential heating and air conditioning systems in 115 US cities

    NASA Astrophysics Data System (ADS)

    Abbatiello, L. A.; Nephew, E. A.; Ballou, M. L.

    1981-03-01

    The efficiency and life cycle costs of the brine chiller minimal annual cycle energy system (ACES) for residential space heating, air conditioning, and water heating requirements are compared with three conventional systems. The conventional systems evaluated are a high performance air-to-air heat pump with an electric resistance water heater, an electric furnace with a central air conditioner and an electric resistance water heater, and a high performance air-to-air heat pump with a superheater unit for hot water production. Monthly energy requirements for a reference single family house are calculated, and the initial cost and annual energy consumption of the systems, providing identical energy services, are computed and compared. The ACES consumes one third to one half ot the electrical energy required by the conventional systems and delivers the same annual loads at comparable costs.

  7. AceTree: a tool for visual analysis of Caenorhabditis elegans embryogenesis

    PubMed Central

    Boyle, Thomas J; Bao, Zhirong; Murray, John I; Araya, Carlos L; Waterston, Robert H

    2006-01-01

    Background The invariant lineage of the nematode Caenorhabditis elegans has potential as a powerful tool for the description of mutant phenotypes and gene expression patterns. We previously described procedures for the imaging and automatic extraction of the cell lineage from C. elegans embryos. That method uses time-lapse confocal imaging of a strain expressing histone-GFP fusions and a software package, StarryNite, processes the thousands of images and produces output files that describe the location and lineage relationship of each nucleus at each time point. Results We have developed a companion software package, AceTree, which links the images and the annotations using tree representations of the lineage. This facilitates curation and editing of the lineage. AceTree also contains powerful visualization and interpretive tools, such as space filling models and tree-based expression patterning, that can be used to extract biological significance from the data. Conclusion By pairing a fast lineaging program written in C with a user interface program written in Java we have produced a powerful software suite for exploring embryonic development. PMID:16740163

  8. AceTree: a tool for visual analysis of Caenorhabditis elegans embryogenesis.

    PubMed

    Boyle, Thomas J; Bao, Zhirong; Murray, John I; Araya, Carlos L; Waterston, Robert H

    2006-06-01

    The invariant lineage of the nematode Caenorhabditis elegans has potential as a powerful tool for the description of mutant phenotypes and gene expression patterns. We previously described procedures for the imaging and automatic extraction of the cell lineage from C. elegans embryos. That method uses time-lapse confocal imaging of a strain expressing histone-GFP fusions and a software package, StarryNite, processes the thousands of images and produces output files that describe the location and lineage relationship of each nucleus at each time point. We have developed a companion software package, AceTree, which links the images and the annotations using tree representations of the lineage. This facilitates curation and editing of the lineage. AceTree also contains powerful visualization and interpretive tools, such as space filling models and tree-based expression patterning, that can be used to extract biological significance from the data. By pairing a fast lineaging program written in C with a user interface program written in Java we have produced a powerful software suite for exploring embryonic development.

  9. ALTUS Cumulus Electrification Study (ACES)

    NASA Technical Reports Server (NTRS)

    Kim, Tony; Blakeslee, Richard; Russell, Larry W. (Technical Monitor)

    2002-01-01

    The ALTUS Cumulus Electrification Study (ACES) is an uninhabited aerial vehicle (UAV)-based project that will investigate thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES is being conducted to both investigate storm electrical activity and its relationship to storm morphology, and validate Tropical Rainfall Measurement Mission (TRMM) satellite measurements. In addition, as part of NASA's UAV-based science demonstration program, this project will provide a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. Part of the demonstration involves getting approvals from the Federal Aviation Administration and the NASA airworthiness flight safety review board. ACES will employ the ALTUS II aircraft, built by General Atomics - Aeronautical Systems, Inc. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and (3) provide Lightning Imaging Sensor validation. The ACES payload, already developed and flown on ALTUS, includes electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. ACES will contribute important electrical and optical measurements not available from other sources. Also, the high altitude vantage point of the UAV observing platform (up to 55,000 feet) offers a useful 'cloud-top' perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, the ALTUS will be flown near, and when possible, above (but never into) thunderstorms for long periods of time, allowing investigations to be conducted over entire storm life cycles. In addition, concurrent ground-based observations will enable the UAV measurements to be more completely interpreted and evaluated in the context of the thunderstorm structure, evolution, and environment.

  10. Cielo Computational Environment Usage Model With Mappings to ACE Requirements for the General Availability User Environment Capabilities Release Version 1.1

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

    Vigil,Benny Manuel; Ballance, Robert; Haskell, Karen

    Cielo is a massively parallel supercomputer funded by the DOE/NNSA Advanced Simulation and Computing (ASC) program, and operated by the Alliance for Computing at Extreme Scale (ACES), a partnership between Los Alamos National Laboratory (LANL) and Sandia National Laboratories (SNL). The primary Cielo compute platform is physically located at Los Alamos National Laboratory. This Cielo Computational Environment Usage Model documents the capabilities and the environment to be provided for the Q1 FY12 Level 2 Cielo Capability Computing (CCC) Platform Production Readiness Milestone. This document describes specific capabilities, tools, and procedures to support both local and remote users. The model ismore » focused on the needs of the ASC user working in the secure computing environments at Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory, or Sandia National Laboratories, but also addresses the needs of users working in the unclassified environment. The Cielo Computational Environment Usage Model maps the provided capabilities to the tri-Lab ASC Computing Environment (ACE) Version 8.0 requirements. The ACE requirements reflect the high performance computing requirements for the Production Readiness Milestone user environment capabilities of the ASC community. A description of ACE requirements met, and those requirements that are not met, are included in each section of this document. The Cielo Computing Environment, along with the ACE mappings, has been issued and reviewed throughout the tri-Lab community.« less

  11. Adverse childhood experiences and intimate partner aggression in the US: sex differences and similarities in psychosocial mediation.

    PubMed

    Brown, Monique J; Perera, Robert A; Masho, Saba W; Mezuk, Briana; Cohen, Steven A

    2015-04-01

    Six in ten people in the general population have been exposed to adverse childhood experiences (ACEs). Intimate partner violence (IPV) is a major public health problem in the US. The main objective of this study was to assess sex differences in the role of posttraumatic stress disorder (PTSD), substance abuse, and depression as mediators in the association between ACEs and intimate partner aggression. Data were obtained from Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Structural equation modeling was used to determine the mediational role of PTSD, substance abuse and depression in the association between ACE constructs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration/psychopathology) and intimate partner aggression. Among men, PTSD mediated the relationship between sexual abuse and intimate partner aggression. However, among men and women, substance abuse mediated the relationship between physical and psychological abuse and intimate partner aggression. IPV programs geared towards aggressors should address abuse (sexual, physical and psychological), which occurred during childhood and recent substance abuse and PTSD. These programs should be implemented for men and women. Programs aimed at preventing abuse of children may help to reduce rates of depression and PTSD in adulthood, and subsequent intimate partner aggression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Adverse childhood experiences and intimate partner aggression in the US: Sex differences and similarities in psychosocial mediation

    PubMed Central

    Brown, Monique J.; Perera, Robert A.; Masho, Saba W.; Mezuk, Briana; Cohen, Steven A.

    2015-01-01

    Six in ten people in the general population have been exposed to adverse childhood experiences (ACEs). Intimate partner violence (IPV) is a major public health problem in the US. The main objective of this study was to assess sex differences in the role of posttraumatic stress disorder (PTSD), substance abuse, and depression as mediators in the association between ACEs and intimate partner aggression. Data were obtained from Wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Structural equation modeling was used to determine the mediational role of PTSD, substance abuse and depression in the association between ACE constructs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration/psychopathology) and intimate partner aggression. Among men, PTSD mediated the relationship between sexual abuse and intimate partner aggression. However, among men and women, substance abuse mediated the relationship between physical and psychological abuse and intimate partner aggression. IPV programs geared towards aggressors should address abuse (sexual, physical and psychological), which occurred during childhood and recent substance abuse and PTSD. These programs should be implemented for men and women. Programs aimed at preventing abuse of children may help to reduce rates of depression and PTSD in adulthood, and subsequent intimate partner aggression. PMID:25753285

  13. ACE I/D and ACTN3 R/X polymorphisms as potential factors in modulating exercise-related phenotypes in older women in response to a muscle power training stimuli.

    PubMed

    Pereira, Ana; Costa, Aldo M; Izquierdo, Mikel; Silva, António J; Bastos, Estela; Marques, Mário C

    2013-10-01

    Genetic variation of the human ACE I/D and ACTN3 R577X polymorphisms subsequent to 12 weeks of high-speed power training on maximal strength (1RM) of the arm and leg muscles, muscle power performance (counter-movement jump), and functional capacity (sit-to-stand test) was examined in older Caucasian women [n = 139; mean age 65.5 (8.2) years; 67.0 (10.0) kg and 1.57 (0.06) m]. Chelex 100 was used for DNA extraction, and genotype was determined by PCR-RFLP methods. Muscular strength, power, and functional testing were conducted at baseline (T1) and after 12 weeks (T2) of high-speed power training. At baseline, the ACE I/D and ACTN3 R/X polymorphisms were not associated with muscle function or muscularity phenotypes in older Caucasian women. After the 12-week high-speed training program, subjects significantly increased their muscular and functional capacity performance (p < 0.05). For both polymorphisms, significant genotype-training interaction (p < 0.05) was found in all muscular performance indices, except for 1RM leg extension in the ACE I/D (p = 0.187). Analyses of the combined effects between genotypes showed significant differences in all parameters (p < 0.05) in response to high-speed power training between the power (ACTN3 RR + RX & ACE DD) versus "non-power" muscularity-oriented genotypes (ACTN3 XX & ACE II + ID)]. Our data suggest that the ACE and ACTN3 genotypes (single or combined) exert a significant influence in the muscle phenotypes of older Caucasian women in response to high-speed power training. Thus, the ACE I/D and ACTN3 R/X polymorphisms are likely factors in modulating exercise-related phenotypes in older women, particularly in response to a resistance training stimuli.

  14. Advanced Crew Escape Suit.

    PubMed

    1995-09-01

    Design of the S1032 Launch Entry Suit (LES) began following the Challenger loss and NASA's decision to incorporate a Shuttle crew escape system. The LES (see Figure 1) has successfully supported Shuttle missions since NASA's Return to Flight with STS-26 in September 1988. In 1990, engineers began developing the S1035 Advanced Crew Escape Suit (ACES) to serve as a replacement for the LES. The ACES was designed to be a simplified, lightweight, low-bulk pressure suit which aided self donning/doffing, provided improved comfort, and enhanced overall performance to reduce crew member stress and fatigue. Favorable crew member evaluations of a prototype led to full-scale development and qualification of the S1035 ACES between 1990 and 1992. Production of the S1035 ACES began in February 1993, with the first unit delivered to NASA in May 1994. The S1035 ACES first flew aboard STS-68 in August 1994 and will become the primary crew escape suit when the S1032 LES ends its service life in late 1995. The primary goal of the S1035 development program was to provide improved performance over that of the S1032 to minimize the stress and fatigue typically experienced by crew members. To achieve this, five fundamental design objectives were established, resulting in various material/configuration changes.

  15. A novel design of combining the angiotensin converting enzyme (ACE) inhibitor captopril with the angiotensin receptor blocker (ARB) losartan using homo coupling via PEG diacid linker.

    PubMed

    Hashemzadeh, Mehrnoosh; Park, Shery; Ju, Hee; Movahed, Mohammad R

    2013-12-01

    Cardiovascular disease is the leading cause of death in American adults. Furthermore, the incidence of congestive heart failure is on the rise as a major cause of hospitalization and mortality in this population. Angiotensin Converting Enzyme (ACE) inhibitors prevent the production of angiotensin II, which has been shown to reduce mortality in patients with congestive heart failure. Angiotensin II receptor blockers (ARB) were developed as a direct inhibitor of angiotensin II. ARBs have been shown to be effective in the treatment of patients with systolic heart failure but do not cause chronic coughing which is a common side effect of ACE inhibitors. In theory, a compound that has the combined effect of an ACE inhibitor and an ARB should be more effective in treating heart failure patients than either agents alone. Therefore, the purpose of this manuscript is to design and discuss the benefits of a new molecule, which combines captopril, an ACE inhibitor, with losartan, an ARB. In this experiment Captopril and Losartan were modified and synthesized separately and combined by homo or mono coupling. This was achieved by taking advantage of PEG (Polyethylene glycol) as a linker. It is expected that this molecule will have the combined modes of action of both ACEs and ARBs. Benefits from combination therapy include; increased efficacy, reduced adverse effects, convenience, compliance, and prolonged duration. Consequently, this combined molecule is expected to block the production of angiotensin II more efficiently and effectively. Although captopril and losartan work in the same system by blocking the effect of angiotensin II they have different action sites and mechanisms some patents are also discussed. Losartan blocks the AT1 receptor which is expressed on the cell surface, while captopril inhibits ACE, preventing production of angiotensin II, which is present in both the plasma and on the cell surface, especially on endothelial and smooth muscle cells.

  16. Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin.

    PubMed

    Ren, Wuze; Qu, Xiuxia; Li, Wendong; Han, Zhenggang; Yu, Meng; Zhou, Peng; Zhang, Shu-Yi; Wang, Lin-Fa; Deng, Hongkui; Shi, Zhengli

    2008-02-01

    Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed.

  17. LFC leading edge glove flight: Aircraft modification design, test article development and systems integration

    NASA Technical Reports Server (NTRS)

    Etchberger, F. R.

    1983-01-01

    Reduction of skin friction drag by suction of boundary layer air to maintain laminar flow has been known since Prandtl's published work in 1904. The dramatic increases in fuel costs and the potential for periods of limited fuel availability provided the impetus to explore technologies to reduce transport aircraft fuel consumption. NASA sponsored the Aircraft Energy Efficiency (ACEE) program in 1976 to develop technologies to improve fuel efficiency. This report documents the Lockheed-Georgia Company accomplishments in designing and fabricating a leading-edge flight test article incorporating boundary layer suction slots to be flown by NASA on their modified JetStar aircraft. Lockheed-Georgia Company performed as the integration contractor to design the JetStar aircraft modification to accept both a Lockheed and a McDonnell Douglas flight test article. McDonnell Douglas uses a porous skin concept. The report describes aerodynamic analyses, fabrication techniques, JetStar modifications, instrumentation requirements, and structural analyses and testing for the Lockheed test article. NASA will flight test the two LFC leading-edge test articles in a simulated commercial environment over a 6 to 8 month period in 1984. The objective of the flight test program is to evaluate the effectiveness of LFC leading-edge systems in reducing skin friction drag and consequently improving fuel efficiency.

  18. Efficiency of butyl rubber sorbent to remove the PAH toxicity.

    PubMed

    Okay, O S; Özdemir, P; Yakan, S D

    2011-01-01

    Large amounts of polycyclic aromatic hydrocarbons (PAHs) have been released to the marine environment as a result of oil spills and from other sources including wastewaters, surface runoff, industrial processes, atmospheric deposition, biosynthesis, and natural events such as forest fires. PAHs have been known to affect a variety of biological processes and can be potent cell mutagens/carcinogens and toxic. In this study, PAH toxicity removal was investigated by using a novel macroporous butyl rubber (BR) sorbent. To find out the toxicity removal efficiency of the sorbents, the toxicity tests with Vibrio fisheri (luminescence bacteria) and Phaeodactylum tricornutum (marine algae) were applied to the acenaphthene (Ace) and phenanthrene (Phen) solutions in seawater (Ace: 500- 1000 μg/L; Phen; 100-1000 μg/L) before and after sorbent applications. Additionally, lysosomal stability and filtration rate biomarker techniques were applied to the mussels (Mytilus galloprovincialis) exposed to 1000 μg/L Phen solution and bioaccumulation was measured. The results showed that the toxicity of the PAH solutions decreased 50-100 percent depending on the concentration of the solutions and organisms. Phaeodactylum was found as the most sensitive organism to Phen and Ace. Since the application of BR sorbent removed the Phen from the solution, the bioaccumulated Phen amount in the mussels decreased accordingly.

  19. Fate of artificial sweeteners through wastewater treatment plants and water treatment processes

    PubMed Central

    Li, Shaoli; Ren, Yuhang; Fu, Yingying; Gao, Xingsheng; Jiang, Cong; Wu, Gang; Ren, Hongqiang

    2018-01-01

    Five full-scale wastewater treatment plants (WWTPs) in China using typical biodegradation processes (SBR, oxidation ditch, A2/O) were selected to assess the removal of four popular artificial sweeteners (ASs). All four ASs (acesulfame (ACE), sucralose (SUC), cyclamate (CYC) and saccharin (SAC)) were detected, ranging from 0.43 to 27.34μg/L in the influent. Higher concentrations of ASs were measured in winter. ACE could be partly removed by 7.11–50.76% through biodegradation and especially through the denitrifying process. The A2/O process was the most efficient at biodegrading ASs. Adsorption (by granular activated carbon (GAC) and magnetic resin) and ultraviolet radiation-based advanced oxidation processes (UV/AOPs) were evaluated to remove ASs in laboratory-scale tests. The amounts of resin adsorbed were 3.33–18.51 times more than those of GAC except for SUC. The adsorption ability of resin decreased in the order of SAC > ACE > CYC > SUC in accordance with the pKa. Degradation of ASs followed pseudo-first-order kinetics in UV/H2O2 and UV/PDS. When applied to the secondary effluent, ASs could be degraded from 30.87 to 99.93% using UV/PDS in 30 minutes and UV/PDS was more efficient and economic. PMID:29293534

  20. Fate of artificial sweeteners through wastewater treatment plants and water treatment processes.

    PubMed

    Li, Shaoli; Ren, Yuhang; Fu, Yingying; Gao, Xingsheng; Jiang, Cong; Wu, Gang; Ren, Hongqiang; Geng, Jinju

    2018-01-01

    Five full-scale wastewater treatment plants (WWTPs) in China using typical biodegradation processes (SBR, oxidation ditch, A2/O) were selected to assess the removal of four popular artificial sweeteners (ASs). All four ASs (acesulfame (ACE), sucralose (SUC), cyclamate (CYC) and saccharin (SAC)) were detected, ranging from 0.43 to 27.34μg/L in the influent. Higher concentrations of ASs were measured in winter. ACE could be partly removed by 7.11-50.76% through biodegradation and especially through the denitrifying process. The A2/O process was the most efficient at biodegrading ASs. Adsorption (by granular activated carbon (GAC) and magnetic resin) and ultraviolet radiation-based advanced oxidation processes (UV/AOPs) were evaluated to remove ASs in laboratory-scale tests. The amounts of resin adsorbed were 3.33-18.51 times more than those of GAC except for SUC. The adsorption ability of resin decreased in the order of SAC > ACE > CYC > SUC in accordance with the pKa. Degradation of ASs followed pseudo-first-order kinetics in UV/H2O2 and UV/PDS. When applied to the secondary effluent, ASs could be degraded from 30.87 to 99.93% using UV/PDS in 30 minutes and UV/PDS was more efficient and economic.

  1. Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides from a cholecystokinin/gastrin and a LH-RH peptide extended at the C-terminus with gly-Arg/Lys-arg, but not from diarginyl insulin.

    PubMed

    Isaac, R E; Michaud, A; Keen, J N; Williams, T A; Coates, D; Wetsel, W C; Corvol, P

    1999-06-01

    Endoproteolytic cleavage of protein prohormones often generates intermediates extended at the C-terminus by Arg-Arg or Lys-Arg, the removal of which by a carboxypeptidase (CPE) is normally an important step in the maturation of many peptide hormones. Recent studies in mice that lack CP activity indicate the existence of alternative tissue or plasma enzymes capable of removing C-terminal basic residues from prohormone intermediates. Using inhibitors of angiotensin I-converting enzyme (ACE) and CP, we show that both these enzymes in mouse serum can remove the basic amino acids from the C-terminus of CCK5-GRR and LH-RH-GKR, but only CP is responsible for converting diarginyl insulin to insulin. ACE activity removes C-terminal dipeptides to generate the Gly-extended peptides, whereas CP hydrolysis gives rise to CCK5-GR and LH-RH-GK, both of which are susceptible to the dipeptidyl carboxypeptidase activity of ACE. Somatic ACE has two similar protein domains (the N-domain and the C-domain), each with an active site that can display different substrate specificities. CCK5-GRR is a high-affinity substrate for both the N-domain and C-domain active sites of human sACE (Km of 9.4 microm and 9.0 microm, respectively) with the N-domain showing greater efficiency (kcat : Km ratio of 2.6 in favour of the N-domain). We conclude that somatic forms of ACE should be considered as alternatives to CPs for the removal of basic residues from some Arg/Lys-extended peptides.

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

    Phillips, Laurence R.; Jordan, Danyelle N.; Bauer, Travis L.

    The large number of government and industry activities supporting the Unit of Action (UA), with attendant documents, reports and briefings, can overwhelm decision-makers with an overabundance of information that hampers the ability to make quick decisions often resulting in a form of gridlock. In particular, the large and rapidly increasing amounts of data and data formats stored on UA Advanced Collaborative Environment (ACE) servers has led to the realization that it has become impractical and even impossible to perform manual analysis leading to timely decisions. UA Program Management (PM UA) has recognized the need to implement a Decision Support Systemmore » (DSS) on UA ACE. The objective of this document is to research the commercial Knowledge Discovery and Data Mining (KDDM) market and publish the results in a survey. Furthermore, a ranking mechanism based on UA ACE-specific criteria has been developed and applied to a representative set of commercially available KDDM solutions. In addition, an overview of four R&D areas identified as critical to the implementation of DSS on ACE is provided. Finally, a comprehensive database containing detailed information on surveyed KDDM tools has been developed and is available upon customer request.« less

  3. Implementation of the agmatine-controlled expression system for inducible gene expression in Lactococcus lactis.

    PubMed

    Linares, Daniel M; Alvarez-Sieiro, Patricia; del Rio, Beatriz; Ladero, Victor; Redruello, Begoña; Martin, Ma Cruz; Fernandez, Maria; Alvarez, Miguel A

    2015-12-30

    Lactococcus lactis has been safely consumed in fermented foods for millennia. This Gram-positive bacterium has now become of industrial importance as an expression host for the overproduction of lipopolysaccharide-free recombinant proteins used as food ingredients, therapeutic proteins and biotechnological enzymes. This paper reports an agmatine-controlled expression (ACE) system for L. lactis, comprising the lactococcal agmatine-sensor/transcriptional activator AguR and its target promoter P(aguB). The usefulness and efficiency of this system was checked via the reporter gene gfp and by producing PEP (Myxococcus xanthus prolyl-endopeptidase), an enzyme of biomedical interest able to degrade the immunotoxic peptides produced during the gastrointestinal breakdown of gluten. The ACE system developed in this work was suitable for the efficient expression of the functional recombinant proteins GFP and PEP. The expression system was tightly regulated by the agmatine concentration and allowed high protein production without leakiness.

  4. Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

    PubMed Central

    Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

    2016-01-01

    Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

  5. Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.

    PubMed

    Danilov, Sergei M; Lünsdorf, Heinrich; Akinbi, Henry T; Nesterovitch, Andrew B; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V; Piegeler, Tobias; Golukhova, Elena Z; Schwartz, David E; Dull, Randal O; Minshall, Richard D; Kost, Olga A; Garcia, Joe G N

    2016-10-13

    Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.

  6. Evaluation of Achieving a College Education Plus: A Credit-Based Transition Program

    ERIC Educational Resources Information Center

    Luna, Gaye; Fowler, Michael

    2011-01-01

    This ex post facto study evaluated Achieving a College Education (ACE) Plus program, a credit-based transition program between a high school district and a community college. Achieving a College Education Plus is an early outreach program. It is designed to aid at-risk students in graduating from high school and making a smooth transition to…

  7. Natural Ventilation of Buildings through Light Shafts. Design-Based Solution Proposals

    NASA Astrophysics Data System (ADS)

    Ángel Padilla-Marcos, Miguel; Meiss, Alberto; Feijó-Muñoz, Jesús

    2017-10-01

    This work analyses how the built environment affects the quality of the air to be introduced into buildings from light shafts. Several factors such as urban environment and building design intervene in the ability of the light shaft to produce its air change process. Urban areas continuously pollute the air in cities which affects the human health and the environment sustainability. Poor air quality outside buildings supposes a big energy waste to promote an acceptable air quality inside buildings. That requires a large flow rate to maintain the indoor air quality which is translated to an energy efficiency term. The main objective focuses on the impact of standardized architecture design in the quality of the indoor air dependent on the air change in the light shaft. The air change capacity of the outdoor space is numbered analysed using the concept of air change efficiency (ACE). ACE is determined by the built environment, the wind conditions and the design of the building containing light shafts. This concept is comparatively evaluated inside a control domain virtually defined to obtain the mean age of the air for a known air volume. The longer the light shaft in the wind direction is, the better the ACE is compared with other options. Light shafts up to 12 metres high are the most suitable in order to obtain acceptable efficiency results. Other studied cases verify that assumption. Different simplified tools for the technicians to evaluate the design of buildings containing light shafts are proposed. Some strategies of architectural design of buildings with light shafts to be used for ventilation are presented.

  8. Synthesis of a new (1R)-(-)-myrtenal-derived dioxadithiadodecacycle and its use as an efficient chiral auxiliary.

    PubMed

    Vargas-Díaz, M Elena; Joseph-Nathan, Pedro; Tamariz, Joaquín; Zepeda, L Gerardo

    2007-01-04

    [reaction: see text] The new macrocycle 9 (>70% yield from hydroxythiol 10) was treated with several nucleophilic reagents (RMgX, RLi, and LiAlH4) affording carbinols 12a-j (80-96% yield, >99:1 dr). Oxidative hydrolysis of 12a,c,e, followed by LiAlH4 reduction of the resulting mixture, gave 16a,c,e in >95% ee,16c being a key precursor for the preparation of fungicide 17. The absolute configuration of 9 and 12j (Nu = H) was established by single-crystal X-ray diffraction analyses and chemical correlation.

  9. Mass loading of typical artificial sweeteners in a pig farm and their dissipation and uptake by plants in neighboring farmland.

    PubMed

    Ma, Ling; Liu, Yarui; Xu, Jiayao; Sun, Hongwen; Chen, Hao; Yao, Yiming; Zhang, Peng; Shen, Fengju; Alder, Aldredo C

    2017-12-15

    Pig farm is an important potential source for artificial sweeteners (ASs) in the environment due to their wide use as additives in pig feed. The objective of this study was to evaluate the fate of typical ASs in pig farm and neighboring farmland. For this purpose, the levels of four typical artificial ASs, i.e. saccharin (SAC), cyclamate (CYC), acesulfame (ACE) and sucralose (SUC), in pig feed and manure from a pig farm and water samples from an on-farm wastewater treatment plant (WWTP) in Tianjin, China were measured and the mass loadings and removal efficiencies were assessed. Moreover, the levels of ASs in different layers of soil and vegetables in neighboring farmland that received manure fertilizers and wastewater from the farm were consecutively monitored for 60-80days. The SAC, CYC and ACE were widely determined in all kinds of the samples, while SUC was only found in few soil samples. The mass loadings of the ASs in pig feed were estimated up to 311kg/year for SAC, 59.1kg/year for CYC, and 17.1kg/year for ACE, respectively. The fractions of the total mass of ASs excreted via manure were estimated to be 36.0% for SAC, 59.4% for CYC, and 36.7% for ACE as compared to those in pig feed. High removal efficiencies (>90%) of ASs in the on-farm WWTP was achieved. In greenhouse soils, CYC, SAC, ACE, and SUC were degraded quickly, with half-lives of 4.3-5.9 d, 2.7-4.2 d, 8.4-12.3 d, and 7.3-10.8 d, respectively. Lower levels of ASs were found in deeper soil layer (20-30cm). The ASs were considerably absorbed by plants when the ASs' concentrations were high in soil. This study presents the first comprehensive overview of ASs fate from a pig farm to the neighboring agricultural ecosystem. Copyright © 2017. Published by Elsevier B.V.

  10. Investigating the Gap Between Estimated and Actual Energy Efficiency and Conservation Savings for Public Buildings Projects & Programs in United States

    NASA Astrophysics Data System (ADS)

    Qaddus, Muhammad Kamil

    The gap between estimated and actual savings in energy efficiency and conservation (EE&C) projects or programs forms the problem statement for the scope of public and government buildings. This gap has been analyzed first on impact and then on process-level. On the impact-level, the methodology leads to categorization of the gap as 'Realization Gap'. It then views the categorization of gap within the context of past and current narratives linked to realization gap. On process-level, the methodology leads to further analysis of realization gap on process evaluation basis. The process evaluation criterion, a product of this basis is then applied to two different programs (DESEU and NYC ACE) linked to the scope of this thesis. Utilizing the synergies of impact and process level analysis, it offers proposals on program development and its structure using our process evaluation criterion. Innovative financing and benefits distribution structure is thus developed and will remain part of the proposal. Restricted Stakeholder Crowd Financing and Risk-Free Incentivized return are the products of proposed financing and benefit distribution structure respectively. These products are then complimented by proposing an alternative approach in estimating EE&C savings. The approach advocates estimation based on range-allocation rather than currently utilized unique estimated savings approach. The Way Ahead section thus explores synergy between financial and engineering ranges of energy savings as a multi-discipline approach for future research. Moreover, it provides the proposed program structure with risk aversion and incentive allocation while dealing with uncertainty. This set of new approaches are believed to better fill the realization gap between estimated and actual energy efficiency savings.

  11. Structural Sizing of a Horizontal Take-Off Launch Vehicle with an Air Collection and Enrichment System

    NASA Technical Reports Server (NTRS)

    McCurdy, David R.; Roche, Joseph M.

    2004-01-01

    In support of NASA's Next Generation Launch Technology (NGLT) program, the Andrews Gryphon booster was studied. The Andrews Gryphon concept is a horizontal lift-off, two-stage-to-orbit, reusable launch vehicle that uses an air collection and enrichment system (ACES). The purpose of the ACES is to collect atmospheric oxygen during a subsonic flight loiter phase and cool it to cryogenic temperature, ultimately resulting in a reduced initial take-off weight To study the performance and size of an air-collection based booster, an initial airplane like shape was established as a baseline and modeled in a vehicle sizing code. The code, SIZER, contains a general series of volume, surface area, and fuel fraction relationships that tie engine and ACES performance with propellant requirements and volumetric constraints in order to establish vehicle closure for the given mission. A key element of system level weight optimization is the use of the SIZER program that provides rapid convergence and a great deal of flexibility for different tank architectures and material suites in order to study their impact on gross lift-off weight. This paper discusses important elements of the sizing code architecture followed by highlights of the baseline booster study.

  12. ACE phenotyping in human heart.

    PubMed

    Tikhomirova, Victoria E; Kost, Olga A; Kryukova, Olga V; Golukhova, Elena Z; Bulaeva, Naida I; Zholbaeva, Aigerim Z; Bokeria, Leo A; Garcia, Joe G N; Danilov, Sergei M

    2017-01-01

    Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.

  13. Adverse Childhood Experiences (ACEs) Study

    MedlinePlus

    ... Data & Statistics (WISQARS) Funded Programs Press Room Social Media Publications ... experiences, both positive and negative, have a tremendous impact on future violence victimization and perpetration, and lifelong health and opportunity. ...

  14. Egg-yolk protein by-product as a source of ACE-inhibitory peptides obtained with using unconventional proteinase from Asian pumpkin (Cucurbita ficifolia).

    PubMed

    Eckert, Ewelina; Zambrowicz, Aleksandra; Pokora, Marta; Setner, Bartosz; Dąbrowska, Anna; Szołtysik, Marek; Szewczuk, Zbigniew; Polanowski, Antoni; Trziszka, Tadeusz; Chrzanowska, Józefa

    2014-10-14

    In the present study angiotensin I-converting enzyme (ACE) inhibitory peptides were isolated from egg-yolk protein preparation (YP). Enzymatic hydrolysis conducted using unconventional enzyme from Cucurbita ficifolia (dose: 1000 U/mg of hydrolyzed YP (E/S (w/w)=1:7.52)) was employed to obtain protein hydrolysates. The 4-h hydrolysate exhibited a significant (IC₅₀=482.5 μg/mL) ACE inhibitory activity. Moreover, hydrolysate showed no cytotoxic activity on human and animal cell lines which makes it a very useful multifunctional method for peptide preparation. The compiled isolation procedure (ultrafiltration, size-exclusion chromatography and RP-HPLC) of bioactive peptides from YP hydrolysate resulted in obtaining peptides with the strong ACE inhibitory activity. One homogeneous and three heterogeneous peptide fractions were identified. The peptides were composed of 9-18 amino-acid residues, including mainly arginine and leucine at the N-terminal positions. To confirm the selected bioactive peptide sequences their analogs were chemically synthesized and tested. Peptide LAPSLPGKPKPD showed the strongest ACE inhibitory activity, with IC₅₀ value of 1.97 μmol/L. Peptides with specific biological activity can be used in pharmaceutical, cosmetic or food industries. Because of their potential role as physiological modulators, as well as theirhigh safety profile, they can be used as natural pharmacological compounds or functional food ingredients. The development of biotechnological solutions to obtain peptides with desired biological activity is already in progress. Studies in this area are focused on using unconventional highly specific enzymes and more efficient methods developed to conduct food process technologies. Natural peptides have many advantages. They are mainly toxicologically safe, have wide spectra of therapeutic actions, exhibit less side effects compared to synthetic drugs and are more efficiently absorbed in the intestinal tract. The complexity of operation of large scale technologies and high cost of purification techniques are limiting factors to the commercialization of food-derived bioactive peptides. Research on the isolation of bioactive peptides in order to reduce the processing time and costs is continuously developing. Bioactive peptides can also be released from protein by-products of the food industry, which reduce the substrate expense and production cost as well as provide the added advantage of an efficient waste disposal. Moreover, proteins as precursors of food-derived peptides are well-tolerated by the human body and therefore their application in drug development may reduce costs and duration of toxicological studies during research, development and clinical trials. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. 78 FR 53466 - Modification of Two National Customs Automation Program (NCAP) Tests Concerning Automated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-29

    ... DEPARTMENT OF HOMELAND SECURITY U.S. Customs and Border Protection Modification of Two National Customs Automation Program (NCAP) Tests Concerning Automated Commercial Environment (ACE) Document Image System (DIS) and Simplified Entry (SE); Correction AGENCY: U.S. Customs and Border Protection, Department...

  16. Optimization of the Enzymatic Hydrolysis of Lupin (Lupinus) Proteins for Producing ACE-Inhibitory Peptides.

    PubMed

    Boschin, Giovanna; Scigliuolo, Graziana Maria; Resta, Donatella; Arnoldi, Anna

    2014-02-26

    Recently, the enzymatic hydrolysis of Lupinus albus and Lupinus angustifolius proteins with pepsin was showed to produce peptides able to inhibit the angiotensin-converting enzyme (ACE). The objective of the present work was to test different hydrolytic enzymes and to investigate three lupin species (L. albus, L. angustifolius, Lupinus luteus) with the final goal of selecting the best enzyme/species combination for an efficient production of ACE-inhibitory peptide mixtures. Pepsin gave peptides with the best IC50 values (mean value on three species 186 ± 10 μg/mL), followed by pepsin + trypsin (198 ± 16 μg/mL), chymotrypsin (213 ± 83 μg/mL), trypsin (405 ± 54 μg/mL), corolase PP (497 ± 32 μg/mL), umamizyme (865 ± 230 μg/mL), and flavourzyme (922 ± 91 μg/mL). The three species showed similar activity scales, but after pepsin + trypsin and chymotrypsin treatments, L. luteus peptide mixtures resulted to be significantly the most active. This investigation indicates that lupin proteins may be a valuable source of ACE-inhibitory peptides, which may explain the activity observed in experimental and clinical studies and foresee the application of lupin proteins into functional foods or dietary supplements.

  17. ACE phenotyping in human heart

    PubMed Central

    Tikhomirova, Victoria E.; Kost, Olga A.; Kryukova, Olga V.; Golukhova, Elena Z.; Bulaeva, Naida I.; Zholbaeva, Aigerim Z.; Bokeria, Leo A.; Garcia, Joe G. N.

    2017-01-01

    Aims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10–15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. “Conformational fingerprint” of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk. PMID:28771512

  18. An Angiotensin I-Converting Enzyme Mutation (Y465D) Causes a Dramatic Increase in Blood ACE via Accelerated ACE Shedding

    PubMed Central

    Gordon, Kerry; Nesterovitch, Andrew B.; Lünsdorf, Heinrich; Chen, Zhenlong; Castellon, Maricela; Popova, Isolda A.; Kalinin, Sergey; Mendonca, Emma; Petukhov, Pavel A.; Schwartz, David E.

    2011-01-01

    Background Angiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE. Methodology/Principal Findings HEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE - between Arg1203 and Ser1204 - was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another. Conclusions/Significance The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase). PMID:21998728

  19. 13 CFR 130.450 - Matching funds.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Matching Funds of the recipient organization: (1) Uncompensated student labor; (2) SCORE, ACE, or SBI volunteers; (3) Program income or fees collected from small businesses receiving assistance; (4) Funds or...

  20. 13 CFR 130.450 - Matching funds.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Matching Funds of the recipient organization: (1) Uncompensated student labor; (2) SCORE, ACE, or SBI volunteers; (3) Program income or fees collected from small businesses receiving assistance; (4) Funds or...

  1. 13 CFR 130.450 - Matching funds.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Matching Funds of the recipient organization: (1) Uncompensated student labor; (2) SCORE, ACE, or SBI volunteers; (3) Program income or fees collected from small businesses receiving assistance; (4) Funds or...

  2. 13 CFR 130.450 - Matching funds.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Matching Funds of the recipient organization: (1) Uncompensated student labor; (2) SCORE, ACE, or SBI volunteers; (3) Program income or fees collected from small businesses receiving assistance; (4) Funds or...

  3. Evaluation of the Alliance for Climate Education's national high school edutainment program (Invited)

    NASA Astrophysics Data System (ADS)

    Lappe, M.; Flora, J.; Saphir, M.; Roser-Renouf, C.; Maibach, E.; Leiserowitz, A.

    2013-12-01

    The Alliance for Climate Education educates high school students on the science of climate change and inspires them to create effective solutions. Since 2009, ACE has reached over 1.6 million students nationwide with its multi media assembly presentation. In this paper, we evaluate the climate science knowledge, beliefs, attitudes, behavior and communication impact of the ACE Assembly program in a random sample of 49 schools (from population of 779) and a panel of 1,241 high school students. Pre and post assembly surveys composed of questions from the Global Warming Six Americas segmentation and intervention specific questions were administered in classrooms. We demonstrate that exposure to climate science in an engaging edutainment format changes youths' beliefs, involvement, and behavior positively and moves them to more climate science literate audience segments. The net impact of scaled and engaging programs for youth could be a population shift in climate science literacy and positive engagement in the issue of climate change. In addition, such programs can empower youth for deeper engagement in school programs, personal action, political and consumer advocacy.

  4. The Altus Cumulus Electrification Study (ACES): A UAV-Based Science Demonstration

    NASA Technical Reports Server (NTRS)

    Blakeslee, R. J.; Croskey, C. L.; Desch, M. D.; Farrell, W. M.; Goldberg, R. A.; Houser, J. G.; Kim, H. S.; Mach, D. M.; Mitchell, J. D.; Stoneburner, J. C.

    2003-01-01

    The Altus Cumulus Electrification Study (ACES) is an unmanned aerial vehicle (UAV)- based project that investigated thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES was conducted to investigate storm electrical activity and its relationship to storm morphology, and to validate satellite-based lightning measurements. In addition, as part of the NASA sponsored UAV-based science demonstration program, this project provided a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. ACES employed the Altus II aircraft, built by General Atomics - Aeronautical Systems, Inc. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and provide Lightning Imaging Sensor validation. The ACES payload included electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. ACES contributed important electrical and optical measurements not available from other sources. Also, the high altitude vantage point of the UAV observing platform (up to 55,000 feet) provided cloud-top perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, the Altus was flown near, and when possible, over (but never into) thunderstorms for long periods of time that allowed investigations to be conducted over entire storm life cycles. An innovative real time weather system was used to identify and vector the aircraft to selected thunderstorms and safely fly around these storms, while, at the same time monitor the weather near our base of operations. In addition, concurrent ground-based observations that included radar (Miami and Key West WSRBD, NASA NPOL), satellite imagery, and lightning (NALDN and Los Alamos EDOT) enable the UAV measurements to be more completely interpreted and evaluated in the context of the thunderstorm structure, evolution, and environment.

  5. Covariate selection with group lasso and doubly robust estimation of causal effects

    PubMed Central

    Koch, Brandon; Vock, David M.; Wolfson, Julian

    2017-01-01

    Summary The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this paper, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry. PMID:28636276

  6. Covariate selection with group lasso and doubly robust estimation of causal effects.

    PubMed

    Koch, Brandon; Vock, David M; Wolfson, Julian

    2018-03-01

    The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this article, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry. © 2017, The International Biometric Society.

  7. Using the Light Microscopy Module (LMM) on the International Space Station (ISS), The Advanced Colloids Experiment (ACE) and MacroMolecular Biophysics (MMB)

    NASA Technical Reports Server (NTRS)

    Meyer, William; Foster, William M.; Motil, Brian J.; Sicker, Ronald; Abbott-Hearn, Amber; Chao, David; Chiaramonte, Fran; Atherton, Arthur; Beltram, Alexander; Bodzioney, Christopher M.; hide

    2016-01-01

    The Light Microscopy Module (LMM) was launched to the International Space Station (ISS) in 2009 and began science operations in 2010. It continues to support Physical and Biological scientific research on ISS. During 2016, if all goes as planned, three experiments will be completed: [1] Advanced Colloids Experiments with Heated base-2 (ACE-H2) and [2] Advanced Colloids Experiments with Temperature control (ACE-T1). Preliminary results, along with an overview of present and future LMM capabilities will be presented; this includes details on the planned data imaging processing and storage system, along with the confocal upgrade to the core microscope. [1] a consortium of universities from the State of Kentucky working through the Experimental Program to Stimulate Competitive Research (EPSCoR): Stuart Williams, Gerold Willing, Hemali Rathnayake, et al. and [2] from Chungnam National University, Daejeon, S. Korea: Chang-Soo Lee, et al.

  8. Single-domain angiotensin I converting enzyme (kininase II): characterization and properties.

    PubMed

    Deddish, P A; Wang, L X; Jackman, H L; Michel, B; Wang, J; Skidgel, R A; Erdös, E G

    1996-12-01

    Somatic angiotensin I converting enzyme (ACE; kininase II) has two active sites, in two (N and C) domains. We studied the active centers with separate N-domain ACE (N-ACE), testicular C-domain ACE (germinal ACE) and, as control, renal somatic ACE. Germinal ACE cleaved the nonapeptide bradykinin about two times faster than N-ACE in 20 mM Cl-. Bradykinin1-7 was hydrolyzed further to bradykinin1-5 by N-ACE four times faster in the absence of Cl-, but at 300 mM Cl- the C-domain hydrolyzed it twice as fast. The hematopoietic system regulatory peptide acetyl-Ser-Asp-Lys-Pro was split to two dipeptides by N-ACE, depending on the chloride concentration, 8 to 24 times faster than by germinal ACE; at 100 mM Cl-, the Kcat with N-ACE was eight times higher. One millimolar 1-fluoro-2,4-dinitrobenzene inhibited germinal ACE 96% but it inhibited N-ACE by only 31%. [3H]Ramiprilat was displaced by other unlabeled ACE inhibitors to establish their relative affinities. Captopril had the lowest IC50 (0.5 nM) with N-ACE and the highest IC50 (8.3 nM) with the germinal ACE. The IC50 values of ramiprilat and quinaprilat were about the same with both active sites. The association and dissociation constants of [3H]ramiprilat indicated faster association with and faster dissociation from N-ACE than from germinal ACE. After exposure to alkali or moderate heat, somatic ACE was cleaved by plasmin and kallikrein, releasing N-ACE and apparently inactivating the C-domain. These studies affirm the differences in the activity, stability and inhibition of the two active sites of ACE.

  9. Pharmacokinetic evaluation of lisinopril-tryptophan, a novel C-domain ACE inhibitor.

    PubMed

    Denti, Paolo; Sharp, Sarah-Kate; Kröger, Wendy L; Schwager, Sylva L; Mahajan, Aman; Njoroge, Mathew; Gibhard, Liezl; Smit, Ian; Chibale, Kelly; Wiesner, Lubbe; Sturrock, Edward D; Davies, Neil H

    2014-06-02

    Angiotensin-converting enzyme (ACE, EC 3.4.15.1) is a metallopeptidase comprised of two homologous catalytic domains (N- and C-domains). The C-domain cleaves the vasoactive angiotensin II precursor, angiotensin I, more efficiently than the N-domain. Thus, C-domain-selective ACE inhibitors have been designed to investigate the pharmacological effects of blocking the C-terminal catalytic site of the enzyme and improve the side effect profile of current ACE inhibitors. Lisinopril-tryptophan (LisW-S), an analogue of the ACE inhibitor lisinopril, is highly selective for the C-domain. In this study, we have analysed the ex vivo domain selectivity and pharmacokinetic profile of LisW-S. The IC50 value of LisW-S was 38.5 nM in rat plasma using the fluorogenic substrate Abz-FRKP(Dnp)P-OH. For the pharmacokinetics analysis of LisW-S, a sensitive and selective LC-MS/MS method was developed and validated to determine the concentration of LisW-S in rat plasma. LisW-S was administered to Wistar rats at a dose of 1 mg/kg bodyweight intravenously, 5 mg/kg bodyweight orally. The Cmax obtained following oral administration of the drug was 0.082 μM and LisW-S had an apparent terminal elimination half-life of around 3.1 h. The pharmacokinetic data indicate that the oral bioavailability of LisW-S was approximately 5.4%. These data provide a basis for better understanding the absorption mechanism of LisW-S and evaluating its clinical application. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. What follow-up care and self-management support do patients with type 2 diabetes want after their first acute coronary event? A qualitative study.

    PubMed

    Kasteleyn, Marise J; Gorter, Kees J; van Puffelen, Anne L; Heijmans, Monique; Vos, Rimke C; Jansen, Hanneke; Rutten, Guy E H M

    2014-10-01

    Despite diabetes patients' efforts to control their disease, many of them are confronted with an acute coronary event. This may evoke depressive feelings and self-management may be complicated. According to the American Diabetes Association, the transition from hospital to home after an acute coronary event (ACE) is a high-risk time for diabetes patients; it should be improved. Before developing an intervention for diabetes patients with an ACE in the period after discharge from hospital, we want to gain a detailed understanding of patients' views, perceptions and feelings in this respect. Qualitative design. Two semi-structured focus groups were conducted with 14 T2DM patients (71% male, aged 61-77 years) with a recent ACE. One focus group with partners (67% male, aged 64-75 years) was held. All interviews were transcribed verbatim and analyzed by two independent researchers. Patients believed that coping with an ACE differs between patients with and without T2DM. They had problems with physical exercise, sexuality and pharmacotherapy. Patients and partners were neither satisfied with the amount of information, especially on the combination of T2DM and ACE, nor with the support offered by healthcare professionals after discharge. Participants would appreciate tailored self-management support after discharge from hospital. Patients with T2DM and their partners lack tailored support after a first ACE. Our findings underpin the ADA recommendations to improve the transition from hospital to home. The results of our study will help to determine the exact content of a self-management support program delivered at home to help this specific group of patients to cope with both conditions. Copyright © 2013 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  11. Effects of aerobic exercise training on ACE and ADRB2 gene expression, plasma angiotensin II level, and flow-mediated dilation: a study on obese postmenopausal women with prehypertension.

    PubMed

    Azadpour, Noushin; Tartibian, Bakhtyar; Koşar, Şükran Nazan

    2017-03-01

    The purpose of this study is to determine the effect of 10 weeks of moderate-intensity aerobic exercise training (MIET) on blood pressure (BP), angiotensin-converting enzyme (ACE) and β2-adrenergic receptor (ADRB2) gene expression in leukocytes, plasma angiotensin II (Ang II), and flow-mediated dilation (FMD) in obese postmenopausal women (PMW) with prehypertension. Twenty-four obese prehypertensive PMW (aged 50-70 y; body mass index ≥30 kg/m) randomly assigned to control (n = 12) and exercise (n = 12) groups. Exercise group performed MIET (25-40 min/d, 3 d/wk at 50%-70% of heart rate reserve) for 10 weeks. Control group maintained their normal daily physical activity level. Body composition, VO2max, BP, ACE and ADRB2 gene expression, plasma Ang II, and FMD were measured before and after the training program. After MIET, systolic and diastolic BPs decreased by 4.6% and 2.4%, respectively (P < 0.001). Plasma Ang II level decreased by 45.7%, whereas FMD increased by 86% in the exercise group (P < 0.001). Exercise training resulted in a threefold increase in ADRB2 and a fourfold decrease in ACE gene expressions (P < 0.05). Training-induced changes in BP inversely associated with the changes in FMD and ADRB2 (r values range -0.55 to -0.78), and positively associated with Ang II and ACE (r values range 0.68-0.86) (P < 0.001). Ten weeks of MIET modulates ACE and ADRB2 gene expression, decreases Ang II plasma levels, and improves endothelial function in obese PMW, and these alterations are associated with reduction in BP.

  12. The Transcriptome Analysis and Comparison Explorer--T-ACE: a platform-independent, graphical tool to process large RNAseq datasets of non-model organisms.

    PubMed

    Philipp, E E R; Kraemer, L; Mountfort, D; Schilhabel, M; Schreiber, S; Rosenstiel, P

    2012-03-15

    Next generation sequencing (NGS) technologies allow a rapid and cost-effective compilation of large RNA sequence datasets in model and non-model organisms. However, the storage and analysis of transcriptome information from different NGS platforms is still a significant bottleneck, leading to a delay in data dissemination and subsequent biological understanding. Especially database interfaces with transcriptome analysis modules going beyond mere read counts are missing. Here, we present the Transcriptome Analysis and Comparison Explorer (T-ACE), a tool designed for the organization and analysis of large sequence datasets, and especially suited for transcriptome projects of non-model organisms with little or no a priori sequence information. T-ACE offers a TCL-based interface, which accesses a PostgreSQL database via a php-script. Within T-ACE, information belonging to single sequences or contigs, such as annotation or read coverage, is linked to the respective sequence and immediately accessible. Sequences and assigned information can be searched via keyword- or BLAST-search. Additionally, T-ACE provides within and between transcriptome analysis modules on the level of expression, GO terms, KEGG pathways and protein domains. Results are visualized and can be easily exported for external analysis. We developed T-ACE for laboratory environments, which have only a limited amount of bioinformatics support, and for collaborative projects in which different partners work on the same dataset from different locations or platforms (Windows/Linux/MacOS). For laboratories with some experience in bioinformatics and programming, the low complexity of the database structure and open-source code provides a framework that can be customized according to the different needs of the user and transcriptome project.

  13. Polymorphism of angiotensin-converting enzyme gene in sarcoidosis.

    PubMed

    Arbustini, E; Grasso, M; Leo, G; Tinelli, C; Fasani, R; Diegoli, M; Banchieri, N; Cipriani, A; Gorrini, M; Semenzato, G; Luisetti, M

    1996-02-01

    Sarcoidosis is the disease in which increased levels of serum Angiotensin-converting enzyme (sACE) are most often detected. It has recently been shown that the deletion (D) or the insertion (I) of a 250bp-DNA fragment in the ACE gene accounts for three main ACE genotypes (i.e., II, ID, and DD) and for 47% of total phenotypic variance in sACE level. The aim of our work was to investigate whether or not patients with sarcoidosis have an increased incidence of those ACE genotypes coding for highest sACE levels and to investigate whether or not sACE level in sarcoidosis is related to ACE genotypes. We studied 61 unrelated patients with sarcoidosis (test group) and 80 unrelated healthy control subjects (control group). The ACE I and D alleles were detected with polymerase chain reaction on genomic DNA. In the control group we found an ACE genotype distribution that agreed with the Hardy-Weinberg proportion. The ACE genotype distribution was not significantly different in the test group. There was no correlation between ACE genotype and roentgenologic stage of sarcoidosis. Plotting the sACE level in the control group against ACE genotype, we found a trend of increasing mean sACE value according to the order II < ID < DD. The same trend for ACE genotype was found in the test group, in which it also paralleled the trend of sACE values plotted against roentgenologic stage, according to the order Stage I < Stage II < Stage III. We conclude that in sarcoidosis the ACE genotype distribution is not altered. The trends for increasing sACE values in sarcoidosis according to both ACE genotype and roentgenologic stage would suggest that both mechanisms play a role in determining sACE level.

  14. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex

    PubMed Central

    Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

    2016-01-01

    Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy. PMID:27601681

  15. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.

    PubMed

    Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

    2016-09-20

    Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy.

  16. Apoptosis of Hepatocellular Carcinoma Cells Induced by Nanoencapsulated Polysaccharides Extracted from Antrodia Camphorata

    PubMed Central

    Chang, Ke Liang B.; Kong, Zwe-Ling

    2015-01-01

    Antrodia camphorata is a well-known medicinal mushroom in Taiwan and has been studied for decades, especially with focus on anti-cancer activity. Polysaccharides are the major bioactive compounds reported with anti-cancer activity, but the debates on how they target cells still remain. Research addressing the encapsulation of polysaccharides from A. camphorata extract (ACE) to enhance anti-cancer activity is rare. In this study, ACE polysaccharides were nano-encapsulated in chitosan-silica and silica (expressed as ACE/CS and ACE/S, respectively) to evaluate the apoptosis effect on a hepatoma cell line (Hep G2). The results showed that ACE polysaccharides, ACE/CS and ACE/S all could damage the Hep G2 cell membrane and cause cell death, especially in the ACE/CS group. In apoptosis assays, DNA fragmentation and sub-G1 phase populations were increased, and the mitochondrial membrane potential decreased significantly after treatments. ACE/CS and ACE/S could also increase reactive oxygen species (ROS) generation, induce Fas/APO-1 (apoptosis antigen 1) expression and elevate the proteolytic activities of caspase-3, caspase-8 and caspase-9 in Hep G2 cells. Unsurprisingly, ACE/CS induced a similar apoptosis mechanism at a lower dosage (ACE polysaccharides = 13.2 μg/mL) than those of ACE/S (ACE polysaccharides = 21.2 μg/mL) and ACE polysaccharides (25 μg/mL). Therefore, the encapsulation of ACE polysaccharides by chitosan-silica nanoparticles may provide a viable approach for enhancing anti-tumor efficacy in liver cancer cells. PMID:26327534

  17. Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy.

    PubMed

    Eriguchi, Masahiro; Lin, Mercury; Yamashita, Michifumi; Zhao, Tuantuan V; Khan, Zakir; Bernstein, Ellen A; Gurley, Susan B; Gonzalez-Villalobos, Romer A; Bernstein, Kenneth E; Giani, Jorge F

    2018-04-01

    Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.

  18. ACE Action Fellowship Bridges Climate Education into Action for Young People

    NASA Astrophysics Data System (ADS)

    Anderson, R. K.

    2016-12-01

    Alliance for Climate Education educates young people on the science of climate change and empowers them to take action. Since 2009, ACE has educated over two million students and trained more than 4,000 young leaders. The ACE Action Fellowship is a yearlong training program that gives young people the knowledge, skills and confidence to be strong climate leaders. Here, we present the results of the first year of evaluation of the Fellowship program in the 2014-15 school year. Sixty high school students completed matched surveys before and after completing the program. Students were evaluated on skills learned, actions taken, confidence gained, civic engagement, and plans to continue action on climate in the future. Results show that the Fellowship increases young people's confidence: 52% of Fellows report an increase in confidence in leading a group of peers on a climate-related campaign. Fellows also gained leadership skills. More than half of Fellows say they improved in the areas of recruitment, interpersonal communication skills, campaign planning, and public speaking. 50% of Fellows reported an increase in their likelihood of seeking elected office when of age. The Fellowship positively influences young people's intent to study a climate, energy or sustainability-related field. 63% of Fellows identify as people of color. Notably, despite entering the Fellowship with significantly lower self-ratings than white students in experience and skill sets, young people of color reported greater improvement in the areas of public speaking (25% improvement vs. 6% improvement) and petitioning (27% improvement vs. 1% improvement). These results show that the ACE Fellowship gives young people tangible skills and confidence that puts them on a path of climate leadership. Further evaluation will be done to expand the dataset, but early indications show that these young people are poised to make valuable contributions and bring a much needed diverse youth perspective to the climate fight.

  19. SP.ACE: taking secondary school students' hearts and minds "up, up and away"

    NASA Astrophysics Data System (ADS)

    de Schrijver, Erik

    2005-08-01

    Secondary school students were given the opportunity to build and fly "pongsats" (small experiments weighing under 100 grams each, and packed inside a ping pong ball) on high-altitude balloons bound for 100000 feet, or 30 km: the edge of space. The need to acquire the knowledge and know-how to build successful experiments gave birth to the SP.ACE project. Over their last 3 years of secondary education, students are now learning about flight vehicles, the physical conditions in space, microcontrollers, sensors, programming, data logging, flight path analysis, and much more.

  20. ACE Phenotyping as a Guide Toward Personalized Therapy With ACE Inhibitors.

    PubMed

    Danilov, Sergei M; Tovsky, Stan I; Schwartz, David E; Dull, Randal O

    2017-07-01

    Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient's blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. Due to the fact that "20% of patients do not respond to ACEI by blood pressure drop," the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.

  1. Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session.

    PubMed

    Yang, Chung-Wei; Lu, Li-Che; Chang, Chia-Chu; Cho, Ching-Chang; Hsieh, Wen-Yeh; Tsai, Chin-Hung; Lin, Yi-Chang; Lin, Chih-Sheng

    2017-11-01

    The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1-7) (Ang-(1-7))/Mas axis, respectively. There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119 HD patients with cardiovascular diseases (CVD) and 241 HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1-7) levels of the HD patients were determined. We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1-7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1-7) levels were lower than those in the healthy controls. Therefore, imbalanced ACE/ACE2 was observed in the HD patients with CVD. In the course of a single HD session, the plasma ACE, ACE/ACE2 and Ang II levels in the HD patients with CVD were increased from pre-HD to post-HD. On the contrary, ACE2 levels were decreased after the HD session. These changes were not detected in the HD patients without CVD. Pathogenically imbalanced circulating ACE/ACE2 was detected in the HD patients, particularly those with CVD. HD session could increase ACE/Ang II/AT1R axis and decrease ACE2/Ang-(1-7)/Mas axis activity in the circulation of HD patients with CVD.

  2. Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.

    PubMed

    Zou, Honghong; Wu, Guoqing; Lv, Jinlei; Xu, Gaosi

    2017-06-01

    To determine whether ACE 2 I/D and BDKRB2 3 +9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R 4 +9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp. We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Sex dimorphism in ANGII-mediated crosstalk between ACE2 and ACE in diabetic nephropathy.

    PubMed

    Clotet-Freixas, Sergi; Soler, Maria Jose; Palau, Vanesa; Anguiano, Lidia; Gimeno, Javier; Konvalinka, Ana; Pascual, Julio; Riera, Marta

    2018-06-08

    Angiotensin-converting enzyme (ACE) and ACE2 play a critical role in the renin-angiotensin system (RAS) by altering angiotensin II (ANGII) levels, thus governing its deleterious effects. Both enzymes are altered by sex and diabetes, and play an important role in the development of diabetic nephropathy (DN). Importantly, previous evidence in diabetic and ACE2-deficient (ACE2KO) males suggest a sex-dependent crosstalk between renal ACE and ACE2. In the present work, we aimed to study the sex-specific susceptibility to diabetes and direct infusion of ANGII in kidney disease progression, with a special focus on its link to ACE2 and ACE. In our mouse model, ANGII promoted hypertension, albuminuria, reduced glomerular filtration, and glomerular histological alterations. ANGII adverse effects were accentuated by diabetes and ACE2 deficiency, in a sex-dependent fashion: ACE2 deficiency accentuated ANGII-induced hypertension, albuminuria, and glomerular hypertrophy in diabetic females, whereas in diabetic males exacerbated ANGII-mediated glomerular hypertrophy, mesangial expansion, and podocyte loss. At the molecular level, ANGII downregulated renal ACE gene and enzymatic activity levels, as well as renin gene expression in ACE2KO mice. Interestingly, male sex and diabetes accentuated this effect. Here we show sex dimorphism in the severity of diabetes- and ANGII-related renal lesions, and demonstrate that ACE2- and ACE-related compensatory mechanisms are sex-specific. Supporting our previous findings, the modulation and ANGII-mediated crosstalk between ACE2 and ACE in DN progression was more evident in males. This work increases the understanding of the sex-specific role of ACE2 and ACE in DN, reinforcing the necessity of more personalized treatments targeting RAS.

  4. ACE: AMY CDC (central drift chamber) fast track finder

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

    Mori, T.

    1988-01-01

    The central drift chamber (CDC) of the AMY detector at the TRISTAN e/sup /+//e/sup /-// collider features its fine granularity and multi-band structure. The tracking software named ACE which makes the most of these features shows an excellent performance for reconstruction of high multiplicity events with highly collimated jets. The obtained reconstruction efficiency is 97% for the particles coming from within 5 cm of the primary vertex with p/sub t/ /approx gt/ 500 MeVc in the simulated hadronic events. The processing time is on average less than 300 ms per hadronic event (simulated or real) on a FACOM M-382 computer.more » 3 refs., 5 figs.« less

  5. Regulation of the aceI multidrug efflux pump gene in Acinetobacter baumannii.

    PubMed

    Liu, Qi; Hassan, Karl A; Ashwood, Heather E; Gamage, Hasinika K A H; Li, Liping; Mabbutt, Bridget C; Paulsen, Ian T

    2018-06-01

    To investigate the function of AceR, a putative transcriptional regulator of the chlorhexidine efflux pump gene aceI in Acinetobacter baumannii. Chlorhexidine susceptibility and chlorhexidine induction of aceI gene expression were determined by MIC and quantitative real-time PCR, respectively, in A. baumannii WT and ΔaceR mutant strains. Recombinant AceR was prepared as both a full-length protein and as a truncated protein, AceR (86-299), i.e. AceRt, which has the DNA-binding domain deleted. The binding interaction of the purified AceR protein and its putative operator region was investigated by electrophoretic mobility shift assays and DNase I footprinting assays. The binding of AceRt with its putative ligand chlorhexidine was examined using surface plasmon resonance and tryptophan fluorescence quenching assays. MIC determination assays indicated that the ΔaceI and ΔaceR mutant strains both showed lower resistance to chlorhexidine than the parental strain. Chlorhexidine-induced expression of aceI was abolished in a ΔaceR background. Electrophoretic mobility shift assays and DNase I footprinting assays demonstrated chlorhexidine-stimulated binding of AceR with two sites upstream of the putative aceI promoter. Surface plasmon resonance and tryptophan fluorescence quenching assays suggested that the purified ligand-binding domain of the AceR protein was able to bind with chlorhexidine with high affinity. This study provides strong evidence that AceR is an activator of aceI gene expression when challenged with chlorhexidine. This study is the first characterization, to our knowledge, of a regulator controlling expression of a PACE family multidrug efflux pump.

  6. Tissue Specificity of Human Angiotensin I-Converting Enzyme

    PubMed Central

    Kryukova, Olga V.; Tikhomirova, Victoria E.; Golukhova, Elena Z.; Evdokimov, Valery V.; Kalantarov, Gavreel F.; Trakht, Ilya N.; Schwartz, David E.; Dull, Randal O.; Gusakov, Alexander V.; Uporov, Igor V.; Kost, Olga A.; Danilov, Sergei M.

    2015-01-01

    Background Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood. Methods/Principal Findings We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests. Conclusions Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs. PMID:26600189

  7. Gender difference of serum angiotensin-converting enzyme (ACE) activity in DD genotype of ACE insertion/deletion polymorphism in elderly Chinese.

    PubMed

    Zhang, Ya-Feng; Cheng, Qiong; Tang, Nelson L S; Chu, Tanya T W; Tomlinson, Brian; Liu, Fan; Kwok, Timothy C Y

    2014-12-01

    In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t-test. No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. © The Author(s) 2013.

  8. ACE as a Mechanosensor to Shear Stress Influences the Control of Its Own Regulation via Phosphorylation of Cytoplasmic Ser1270

    PubMed Central

    Barauna, Valerio Garrone; Campos, Luciene Cristina Gastalho; Miyakawa, Ayumi Aurea; Krieger, Jose Eduardo

    2011-01-01

    Objectives We tested whether angiotensin converting enzyme (ACE) and phosphorylation of Ser1270 are involved in shear-stress (SS)-induced downregulation of the enzyme. Methods and Results Western blotting analysis showed that SS (18 h, 15 dyn/cm2) decreases ACE expression and phosphorylation as well as p-JNK inhibition in human primary endothelial cells (EC). CHO cells expressing wild-type ACE (wt-ACE) also displayed SS-induced decrease in ACE and p-JNK. Moreover, SS decreased ACE promoter activity in wt-ACE, but had no effect in wild type CHO or CHO expressing ACE without either the extra- or the intracellular domains, and decreased less in CHO expressing a mutated ACE at Ser1270 compared to wt-ACE (13 vs. 40%, respectively). The JNK inhibitor (SP600125, 18 h), in absence of SS, also decreased ACE promoter activity in wt-ACE. Finally, SS-induced inhibition of ACE expression and phosphorylation in EC was counteracted by simultaneous exposure to an ACE inhibitor. Conclusions ACE displays a key role on its own downregulation in response to SS. This response requires both the extra- and the intracellular domains and ACE Ser1270, consistent with the idea that the extracellular domain behaves as a mechanosensor while the cytoplasmic domain elicits the downstream intracellular signaling by phosphorylation on Ser1270. PMID:21901117

  9. Outcomes of a National Environmental Edutainment Program in High Schools

    NASA Astrophysics Data System (ADS)

    Lappe, M. D.

    2012-12-01

    We present results of the first longitudinal evaluation of a nation-wide environmental edutainment program. There has recently been rapid growth in curricula on the environment and climate change, yet few reach large and diverse audiences, and fewer still are evaluated. These results are from high schools participating in the Alliance for Climate Education (ACE) program. ACE is a 3 year-old program that has reached 1.2 million students with an edutainment presentation incorporating music, multi-media, animation, and documentary footage (www.acespace.org). A projected 850 schools across 23 states will see the presentation this year; 6% of schools (3 classes each) are randomly selected to be evaluated. The data described here were collected in Fall 2011 from 1,270 students in 21 schools; the full evaluation will be complete in May 2012. The sample is ethnically and socio-economically diverse — 29% are white, and 46% receive free/reduced lunches (a proxy for socio-economic status). Outcome measures included a test of climate knowledge and intentions to take (and to ask others to take) climate-related actions. The analyses examined direct effects of the ACE program on climate knowledge and intentions, as well as the moderating effects of student gender and age on learning. Before the ACE presentation, boys had significantly higher knowledge scores than girls (54% vs. 48% correct, respectively, p < .001). Afterward, boys and girls both had significantly higher knowledge scores (64% and 63% correct, respectively) and no longer differed from each other in this respect. Before the presentation, girls expressed significantly greater intentions to take climate-related actions than did boys. Afterward, intentions increased significantly in both groups, but the gap between girls and boys remained. The gap-closing pattern was somewhat different for the moderating variable of age. Before the presentation, knowledge and intentions were significantly higher among older students (11th- and 12th-graders) than among younger students (9th- and 10th-graders). Afterward, knowledge and intentions increased significantly in both groups, but the gap between them remained for knowledge and closed for intentions. These promising early results demonstrate how a single well-designed edutaiment presentation can appeal broadly to students and advance environmental education on a large scale.

  10. OLYMPEX Counterflow Spectrometer and Impactor Field Campaign Report

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

    Poellot, Michael

    The U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s ARM Aerial Facility (AAF) Counterflow Spectrometer and Impactor (CSI) probe was flown on the University of North Dakota Cessna Citation research aircraft during the Olympic Mountain Experiment (OLYMPEX). The field campaign took place from November 12 through December 19, 2015, over the Olympic Mountains and coastal waters of Washington State as part of a National Aeronautics and Space Administration (NASA) Global Precipitation Measurement (GPM) validation campaign. The CSI was added to the Citation instrument suite to support the NASA Aerosol-Cloud Ecosystem (ACE) satellite program and flights ofmore » the NASA Lockheed Earth Resources (ER-2) aircraft. ACE funded extra ER-2 flights to focus on clouds that are weakly precipitating, which are also of interest to the DOE Atmospheric System Research (ASR) program.« less

  11. Conformational Changes of Blood ACE in Chronic Uremia

    PubMed Central

    Petrov, Maxim N.; Shilo, Valery Y.; Tarasov, Alexandr V.; Schwartz, David E.; Garcia, Joe G. N.; Kost, Olga A.; Danilov, Sergei M.

    2012-01-01

    Background The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The “short” ACE inhibitor enalaprilat (tripeptide analog) and “long” inhibitor teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon anti-hypertensive therapy. PMID:23166630

  12. Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE

    PubMed Central

    Rella, Monika; Elliot, Joann L; Revett, Timothy J; Lanfear, Jerry; Phelan, Anne; Jackson, Richard M; Turner, Anthony J; Hooper, Nigel M

    2007-01-01

    Background Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. Conclusion In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene. PMID:17597519

  13. Precipitation and Hydrology Experiment Counter-Flow Spectrometer and Impactor Field Campaign Report

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

    Poellot, Michael

    The U.S. Department of Energy (DOE)’s Atmospheric Radiation Measurement (ARM) Climate Research Facility Aerial Facility (ARM AAF) counter-flow spectrometer and impactor (CSI) probe was flown on the University of North Dakota Cessna Citation research aircraft during the Integrated Precipitation and Hydrology Experiment (IPHEX). The field campaign took place during May and June of 2014 over North Carolina and its coastal waters as part of a National Aeronautics and Space Administration (NASA) Global Precipitation Measurement validation campaign. The CSI was added to the Citation instrument suite to support the involvement of Jay Mace through the NASA Advanced Composition Explorer (ACE) satellitemore » program and flights of the NASA ER-2 aircraft, which is a civilian version of the Air Force’s U2-S reconnaissance platform. The ACE program funded extra ER-2 flights to focus on clouds that are weakly precipitating, which are also of interest to the Atmospheric System Research program sponsored by DOE.« less

  14. Potential Savings of Harmonising Hospital and Community Formularies for Chronic Disease Medications Initiated in Hospital

    PubMed Central

    Lapointe-Shaw, Lauren; Fischer, Hadas D.; Newman, Alice; John-Baptiste, Ava; Anderson, Geoffrey M.; Rochon, Paula A.; Bell, Chaim M.

    2012-01-01

    Background Hospitals in Canada manage their formularies independently, yet many inpatients are discharged on medications which will be purchased through publicly-funded programs. We sought to determine how much public money could be saved on chronic medications if hospitals promoted the initiation of agents with the lowest outpatient formulary prices. Methods We used administrative databases for the province of Ontario to identify patients initiated on a proton pump inhibitor (PPI), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) following hospital admission from April 1st 2008-March 31st 2009. We assessed the cost to the Ontario Drug Benefit Program (ODB) over the year following initiation and determined the cost savings if prescriptions were substituted with the least expensive agent in each class. Results The cost for filling all PPI, ACE inhibitor and ARB prescriptions was $ 2.48 million, $968 thousand and $325 thousand respectively. Substituting the least expensive agent could have saved $1.16 million (47%) for PPIs, $162 thousand (17%) for ACE inhibitors and $14 thousand (4%) for ARBs over the year following discharge. Interpretation In a setting where outpatient prescriptions are publicly funded, harmonising outpatient formularies with inpatient therapeutic substitution resulted in modest cost savings and may be one way to control rising pharmaceutical costs. PMID:22761882

  15. Potential savings of harmonising hospital and community formularies for chronic disease medications initiated in hospital.

    PubMed

    Lapointe-Shaw, Lauren; Fischer, Hadas D; Newman, Alice; John-Baptiste, Ava; Anderson, Geoffrey M; Rochon, Paula A; Bell, Chaim M

    2012-01-01

    Hospitals in Canada manage their formularies independently, yet many inpatients are discharged on medications which will be purchased through publicly-funded programs. We sought to determine how much public money could be saved on chronic medications if hospitals promoted the initiation of agents with the lowest outpatient formulary prices. We used administrative databases for the province of Ontario to identify patients initiated on a proton pump inhibitor (PPI), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) following hospital admission from April 1(st) 2008-March 31(st) 2009. We assessed the cost to the Ontario Drug Benefit Program (ODB) over the year following initiation and determined the cost savings if prescriptions were substituted with the least expensive agent in each class. The cost for filling all PPI, ACE inhibitor and ARB prescriptions was $ 2.48 million, $968 thousand and $325 thousand respectively. Substituting the least expensive agent could have saved $1.16 million (47%) for PPIs, $162 thousand (17%) for ACE inhibitors and $14 thousand (4%) for ARBs over the year following discharge. In a setting where outpatient prescriptions are publicly funded, harmonising outpatient formularies with inpatient therapeutic substitution resulted in modest cost savings and may be one way to control rising pharmaceutical costs.

  16. The Atmospheric Chemistry Experiment (ACE): Mission Overview

    NASA Astrophysics Data System (ADS)

    Bernath, P. F.; Boone, C.; Walker, K.; McLeod, S.; Nassar, R.

    2003-12-01

    The ACE mission goals are: (1) to measure and to understand the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere, with a particular emphasis on the Arctic region; (2) to explore the relationship between atmospheric chemistry and climate change; (3) to study the effects of biomass burning in the free troposphere; (4) to measure aerosol number density, size distribution and composition in order to reduce the uncertainties in their effects on the global energy balance. ACE will make a comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols, and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) gives ACE coverage of tropical, mid-latitudes and polar regions. The solar occultation advantages are high sensitivity and self-calibration. A high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4100 cm-1) will measure the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. The ACE concept is derived from the now-retired ATMOS FTS instrument, which flew on the Space Shuttle in 1985, 1992, 1993, 1994. Climate-chemistry coupling may lead to the formation of an Arctic ozone hole. ACE will provide high quality data to confront these model predictions and will monitor polar chemistry as chlorine levels decline. The ACE-FTS can measure water vapor and HDO in the tropical tropopause region to study dehydration and strat-trop exchange. The molecular signatures of massive forest fires will evident in the ACE infrared spectra. The CO2 in our spectra can be used to either retrieve atmospheric pressure or (if the instrument pointing knowledge proves to be satisfactory) for an independent retrieval of a CO2 profile for carbon cycle science. Aerosols and clouds will be monitored using the extinction of solar radiation at 0.525 and 1.02 microns as measured by two filtered imagers as well as by their infrared spectra. A dual spectrograph called MAESTRO has been added to the mission to extend the wavelength coverage to the 280-1000 nm spectral region. The broad-band atmospheric extinction measured with high signal-to-noise ratio by MAESTRO is particularly useful for the derivation of aerosol and cloud physical properties. The PI for the MAESTRO instrument is T. McElroy from the Meteorological Service of Canada (MSC). ACE is unique in that MAESTRO, the ACE-FTS and the imagers all share the same suntracker and make simultaneous measurements of the same scene. The FTS and imagers have been built by ABB-Bomem in Quebec City, while the satellite bus has been made by Bristol Aerospace in Winnipeg. ACE was selected in the Canadian Space Agency's SCISAT-1 program, and was successfully launched by NASA on August 12, 2003 for a 2 year mission. The main international partners for ACE are NASA, for the launch and algorithm work at NASA-Langley, and Belgium/ESA, for the CMOS imaging arrays and scientific support.

  17. The Atmospheric Chemistry Experiment (ACE): Mission Overview

    NASA Astrophysics Data System (ADS)

    Bernath, P.

    2003-04-01

    The ACE mission goals are: (1) to measure and to understand the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere, with a particular emphasis on the Arctic region; (2) to explore the relationship between atmospheric chemistry and climate change; (3) to study the effects of biomass burning in the free troposphere; (4) to measure aerosol number density, size distribution and composition in order to reduce the uncertainties in their effects on the global energy balance. ACE will make a comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols, and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) will give ACE coverage of tropical, mid-latitudes and polar regions. The solar occultation advantages are high sensitivity and self-calibration. A high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4100 cm-1) will measure the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. The ACE concept is derived from the now-retired ATMOS FTS instrument, which flew on the Space Shuttle in 1985, 1992, 1993, 1994. Climate-chemistry coupling may lead to the formation of an Arctic ozone hole. ACE will provide high quality data to confront these model predictions and will monitor polar chemistry as chlorine levels decline. The ACE-FTS can measure water vapor and HDO in the tropical tropopause region to study dehydration and strat-trop exchange. The molecular signatures of massive forest fires will evident in the ACE infrared spectra. The CO_2 in our spectra can be used to either retrieve atmospheric pressure or (if the instrument pointing knowledge proves to be satisfactory) for an independent retrieval of a CO_2 profile for carbon cycle science. Aerosols and clouds will be monitored using the extinction of solar radiation at 0.525 and 1.02 microns as measured by two filtered imagers as well as by their infrared spectra. A dual spectrograph called MAESTRO has been added to the mission to extend the wavelength coverage to the 280-1000 nm spectral region. The broad-band atmospheric extinction measured with high signal-to-noise ratio by MAESTRO is particularly useful for the derivation of aerosol and cloud physical properties. The PI for the MAESTRO instrument is T. McElroy from the Meteorological Service of Canada. ACE is unique in that MAESTRO, the ACE-FTS and the imagers all share the same suntracker and make simultaneous measurements of the same scene. The FTS and imagers have been built by ABB-Bomem in Quebec City, while the satellite bus has been made by Bristol Aerospace in Winnipeg. ACE has been selected in the Canadian Space Agency's SCISAT-1 program for a planned launch by NASA in May 2003 for a 2 year mission. The main international partners for ACE are NASA, for the launch and algorithm work at NASA-Langley, and Belgium/ESA, for the CMOS imaging arrays and scientific support.

  18. Hydronephrosis alters cardiac ACE2 and Mas receptor expression in mice.

    PubMed

    Zhang, Yanling; Ma, Lulu; Wu, Junyan; Chen, Tingting

    2015-06-01

    Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin-converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. The levels of cardiac ACE, ACE2 and Mas receptor were measured after treatment of losartan or enalapril. Hydronephrosis led to an increase of ACE level and a decrease of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (p < 0.01). Enalapril increased ACE2 levels (p < 0.01), but did not affect Mas receptor in the heart. Plasma renin activity (PRA) and Ang II decreased in hydronephrotic mice, but significantly increased after treatment with losartan or enalapril. Hydronephrosis increased cardiac ACE and suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. © The Author(s) 2015.

  19. Advanced Collaborative Emissions Study (ACES)

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

    Greenbaum, Daniel; Costantini, Maria; Van Erp, Annemoon

    2013-12-31

    The objective of the Advanced Collaborative Emissions Study (ACES) was to determine before widespread commercial deployment whether or not the new, energy-efficient, heavy duty diesel engines (2007 and 2010 EPA Emissions Standards Compliant) may generate anticipated toxic emissions that could adversely affect the environment and human health. ACES was planned to take place in three phases. In Phase 1, extensive emissions characterization of four production-intent prototype engine and control systems designed to meet 2007 standards for nitrogen oxides (NOx) and particulate matter (PM) was conducted at an existing emissions characterization facility: Southwest Research Institute (SwRI). One of the tested enginesmore » was selected (at random, after careful comparison of results) for health testing in Phase 3. In Phase 2, extensive emission characterization of three production-intent prototype engine and control systems meeting the 2010 standards (including more advanced NOx controls to meet the more stringent 2010 NOx standards) was conducted at the same test facility. In Phase 3, one engine/aftertreatment system selected from Phase 1 was further characterized during health effects studies (at an existing inhalation toxicology laboratory: Lovelace Respiratory Research Institute, [LRRI]) to form the basis of the ACES safety assessment. The Department of Energy (DOE) award provided funding for emissions characterization in Phases 1 and 2 as well as exposure characterization in Phase 3. The main health analyses in Phase 3 were funded separately and are not reported here.« less

  20. Surface topography, nano-mechanics and secondary structure of wheat gluten pretreated by alternate dual-frequency ultrasound and the correlation to enzymolysis.

    PubMed

    Zhang, Yanyan; Wang, Bei; Zhou, Cunshan; Atungulu, Griffiths G; Xu, Kangkang; Ma, Haile; Ye, Xiaofei; Abdualrahman, Mohammed A Y

    2016-07-01

    The effects of alternate dual-frequency ultrasound (ADFU) pretreatment on the degree of hydrolysis (DH) of wheat gluten (WG) and angiotensin I-converting enzyme (ACE) inhibitory activity were investigated in this research. The surface topography, nano-mechanics and secondary structure of WG were also determined using atomic force microscope (AFM) and circular dichroism (CD). The correlations of ACE inhibitory activity and DH with surface topography, nano-mechanics and secondary structure of WG were determined using Pearson's correlation analysis. The results showed that with an increase in either pretreatment duration or power, the ACE inhibitory activity of the hydrolysate also increases, reaching maximum at 10 min and 150 W/L, respectively, and then decreases thereafter. Similarly, AFM analysis showed that as the pretreatment duration or power increases, the surface roughness also increase and again a decrease occurs thereafter. As the pretreatment duration or power increased, the Young's modulus and adhesion of WG also increased and then declined. Young's modulus and adhesions average values were compared with ACE inhibitory activity reversely. The result of the CD spectra analysis exhibited losses in the relative percentage of α-helix of WG. Pearson's correlation analysis showed that the average values of Young's modulus and the relative percentage of α-helix correlated with ACE inhibitory activity of the hydrolysates linearly and significantly (P<0.05); the relative percentage of β-sheet correlated linearly with DH of WG significantly (P<0.05). In conclusion, ADFU pretreatment is an efficient method in proteolysis due to its physical and chemical effect on the Young's modulus, α-helix and β-sheet of WG. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells.

    PubMed

    Mei Wang, Pamella Huey; Andrade, Maria Claudina; Quinto, Beata Marie Redublo; Di Marco, Giovana; Mortara, Renato Arruda; Vio, Carlos P; Casarini, Dulce Elena

    2015-01-01

    Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE). We focused on N-domain ACE purification and characterization from LLC-PK1. Total LLC-PK1 N-domain ACE purification was achieved by ion-exchange chromatography, which presented only one peak with ACE activity, denominated ACE(int2A). ACE(int2A) activity was influenced by pH, NaCl and temperature. The purified enzyme was inhibited by Captopril and hydrolyzed AngI, Ang1-7 and AcSDKP. Its ability to hydrolyze AcSDKP characterized it as an N-domain ACE. ACE(int2A) also presented high amino acid sequence homology with the N-terminal part of sACE from mouse, rat, human and rabbit. The presence of secreted and intracellular N-domain ACE and sACE in IMC, LLC-PK1 and IMCD cells confirmed our studies along the nephron. We identified, purified and characterized N-domain ACE from LLC-PK1. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Aviation Capacity Enhancement (ACE) Plan

    DOT National Transportation Integrated Search

    1996-12-31

    A comprehensive review of Federal Aviation Administration programs intended to improve the capacity of the National Air Transportation System. The Plan describes the extent of capacity and delay problems currently associated with air travel in the U....

  3. 1995 Aviation Capacity Enhancement (ACE) Plan

    DOT National Transportation Integrated Search

    1995-12-31

    A comprehensive review of Federal Aviation Administration programs intended to improve : the capacity of the National Air Transportation System. The Plan describes the extent of capacity : and delay problems currently associated with air travel in th...

  4. [Effect of altitude chronic hypoxia on liver enzymes and its correlation with ACE/ACE2 in yak and migrated cattle].

    PubMed

    Liu, Feng-yun; Hu, Lin; Li, Yu-xian; Liu, Shi-ming; Tang, Yong-ping; Qi, Sheng-gui; Yang, Lei; Wu, Tian-yi

    2015-05-01

    To investigate the difference of liver enzyme levels and its correlation with serum ACE/ACE2 among yak and cattle on Qinghai-Tibetan plateau, and to further explore the biochemical mechanism of their liver of altitude adaptation. The serum samples of yak were collected at 3,000 m, 3,500 m, 4,000 m and 4,300 m respectively, meanwhile the serum samples of migrated cattle on plateau (2,500 m) and lowland cattle (1,300 m) were also collected. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), serum lipase (LPS), angiotensin converting enzyme(ACE), angiotensin converting enzyme-2 (ACE2) in serum were measured by using fully automatic blood biochemcal analyzer. We analysed the differences of the above enzymes and its correlation with ACE/ACE2. We used one way analysis of variance (ANOVA). The levels of ALT in 4,000 m group and 4,300 m group of yak increased significantly compared with other groups, there were no statistically significant differences in AST, CHE, GGT, ACE/ACE2 levels of yaks at different altitudes. As compared to lowland cattle, the serum levels of AST and CHE were increased, the level of LPS and ACE was decreased significantly, respectively, and especially, the ratio of ACE/ACE2 of migranted cattle reduced nearly two times. The levels of LPS were significantly correlated to the ratio of ACE/ACE2 in yak (r = 0.357, P < 0.01), and a high correlation between ALP and ACE/ACE2 in lowland cattle( r = 0.418, P < 0.05), But the biggest contribution rate of the ratio of ACE/ACE2 was only 17.5% for the changes of the levels of liver enzyme. The results indicated that with the altitude increased did not significantly influence the changes of liver enzymes' activities in mountainous yaks but not in cattle. However, all above these changes weren't actually correlated to the ratio of ACE/ACE2.

  5. ACE phenotyping in Gaucher disease.

    PubMed

    Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

    2018-04-01

    Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Overview of ACE-Asia Spring 2001 Investigations on Aerosol Radiative Effects and Related Aerosol Properties

    NASA Technical Reports Server (NTRS)

    Russell, Philip B.; Valero, F. P. J.; Flatau, P. J.; Bergin, M.; Holben, B.; Nakajima, T.; Pilewskie, P.; Bergstrom, R.; Hipskind, R. Stephen (Technical Monitor)

    2001-01-01

    A primary, ACE-Asia objective was to quantify the interactions between aerosols and radiation in the Asia-Pacific region. Toward this end, radiometric and related aerosol measurements were made from ocean, land, air and space platforms. Models that predict aerosol fields guided the measurements and are helping integrate and interpret results. Companion overview's survey these measurement and modeling components. Here we illustrate how these components were combined to determine aerosol radiative. impacts and their relation to aerosol properties. Because clouds can obscure or change aerosol direct radiative effects, aircraft and ship sorties to measure these effects depended on predicting and finding cloud-free areas and times with interesting aerosols present. Pre-experiment satellite cloud climatologies, pre-flight aerosol and cloud forecasts, and in-flight guidance from satellite imagery all helped achieve this. Assessments of aerosol regional radiative impacts benefit from the spatiotemporal coverage of satellites, provided satellite-retrieved aerosol properties are accurate. Therefore, ACE-Asia included satellite retrieval tests, as part of many comparisons to judge the consistency (closure) among, diverse measurements. Early results include: (1) Solar spectrally resolved and broadband irradiances and optical depth measurements from the C-130 aircraft and at Kosan, Korea yielded aerosol radiative forcing efficiencies, permitting comparisons between efficiencies of ACE-Asia and INDOEX aerosols, and between dust and "pollution" aerosols. Detailed results will be presented in separate papers. (2) Based on measurements of wavelength dependent aerosol optical depth (AOD) and single scattering albedo the estimated 24-h a average aerosol radiative forcing efficiency at the surface for photosynthetically active radiation (400 - 700 nm) in Yulin, China is approx. 30 W sq m per AOD(500 nm). (3) The R/V Brown cruise from Honolulu to Sea of Japan sampled an aerosol optical depth gradient, with AOD(500 nm) extremes from 0.1 to 1.1. On the Pacific transit from Honolulu to Hachijo AOD(500 nm) averaged 0.2, including increases to 0.4 after several storms, suggesting the strong impact of wind-generated seasalt. The AOD maximum, found in the Sea of Japan, was influenced by dust and anthropogenic sources. (4) In Beijing, single scattering albedo retrieved from AERONET sun-sky radiometry yielded midvisible SSA=0.88 with strong wavelength dependence, suggesting a significant black carbon component. SSA retrieved during dust episodes was approx. 0.90 and variable but wavelength neutral reflecting the presence of urban haze with the dust. Downwind at Anmyon Island SSA was considerably higher, approx. 0.94, but wavelength neutral for dust episodes and spectrally dependent during non dust periods. (5) Satellite retrievals show major aerosol features moving from Asia over the Pacific; however, determining seasonal-average aerosol effects is hampered by sampling frequency and large-scale cloud systems that obscure key parts of aerosol patterns. Preliminary calculations using, satellite-retrieved AOD fields and initial ACE-Asia aerosol properties (including sulfates, soot, and dust) yield clear-sky aerosol radiative effects in the seasonal-average ACE-Asia plume exceeding those of manmade greenhouse gases. Quantifying all-sky direct aerosol radiative effects is complicated by the need to define the height of absorbing aerosols with respect to cloud decks.

  7. Evaluation of an intervention promoting emotion regulation skills for adults with persisting distress due to adverse childhood experiences.

    PubMed

    Cameron, Linda D; Carroll, Paul; Hamilton, W Kyle

    2018-05-01

    This phase II trial evaluated psychosocial and health outcomes of an intervention designed to improve emotion regulation skills in adults suffering from Adverse Childhood Experiences (ACEs). The study utilized a pretest-posttest design in which 92 adults enrolled in the community-based program completed pretest measures, attended either a faith-based or secular version of the 12-week ACE Overcomers program, and then completed posttest measures. The theory-guided program involved group sessions providing education and skills training to improve emotion regulation, self-awareness, resilience, and social functioning. Pretest and posttest surveys included measures of emotional regulation (suppression, rumination, cognitive reappraisal, and mindfulness), resilience (ego resilience and general self-efficacy), emotional experiences (perceived stress, moods, and depressive symptoms), quality of life (the SF-36 domains), and physical symptoms and illness (symptom load and sick days). Analyses revealed significant improvements from pretest to posttest in all facets of emotion regulation (p < .01), psychological resilience (p < .001), mental well-being (p < .001) and physical symptoms and illness (p < .001), and in specific facets of quality of life (p < .001). The faith-based and secular versions of the program yielded comparable improvements in well-being. Improvements were comparable for older versus younger participants, except that younger participants reported greater improvements in perceived stress (p < .05). These preliminary findings support the application of an emotion regulation perspective to interventions for adults with high ACEs. The study, with its single-group design, represents a promising step in the translational research pathway and provides support for further studies utilizing comparison groups. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

    PubMed Central

    He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

    2013-01-01

    Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written informed consent was obtained prior to the investigation. 221 hypertensives (cases) and 221 normotensives (controls) were interviewed, subjected to a physical examination, and provided blood for biochemical and genetic tests. The ACE mRNA expression was analyzed by real time fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed logistic regression to assess associations of ACE I/D genotypes, ACE activity, and ACE mRNA expression levels with hypertension. Results The results of the multivariate logistic regression analysis showed that the additive model (ID, DD versus II) of the ACE genotype revealed an association with hypertension with adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of 1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73), respectively. In addition, our data also indicate that plasma ACE activity (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to hypertension. However, the plasma ACE mRNA expressions were not different between the cases and controls. Conclusion ACE I/D polymorphism and ACE activity revealed significant influence on hypertension, while circulating ACE mRNA expression was not important factors associated with hypertension in this Chinese population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might be a useful method for early screening and monitoring of EH. PMID:24098401

  9. Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

    PubMed Central

    Roca-Ho, Heleia; Riera, Marta; Palau, Vanesa; Pascual, Julio; Soler, Maria Jose

    2017-01-01

    Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS. PMID:28273875

  10. The relationship between angiotensin-converting enzyme (ACE) insertion (I) / deletion (D) polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese.

    PubMed

    Zhang, Ya-Feng; Wang, Hong; Cheng, Qiong; Qin, Ling; Tang, Nelson Ls; Leung, Ping-Chong; Kwok, Timothy Cy

    2017-01-01

    In this study, we set out to investigate the relationship between angiotensin-converting enzyme ( ACE) I/D polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese. A standardized, structured, face-to-face interview was performed to collect demographic information. BMD was measured using dual-energy X-ray absorptiometry (DXA). I/D genotypes of ACE were determined by polymerase chain reaction (PCR) amplification. Serum ACE activity was determined photometrically by a commercially available kinetic kit. Multiple linear regression analysis was used to examine the relationship between ACE I/D polymorphism, serum ACE activity and BMD. A total of 1567 males and 1760 females were selected for analyzing the relationship between ACE I/D polymorphism and BMD. There was no significant difference in spine BMD, total hip BMD and femur neck BMD among different ACE I/D genotypes both in males and females. A total of 1699 males and 1739 females were selected for analyzing the relationship between serum ACE activity and BMD. There was also no significant difference in spine BMD, total hip BMD and femur neck BMD among different serum ACE activity groups both in males and females. There was no relationship between ACE I/D polymorphism, serum ACE activity and BMD in older Chinese.

  11. Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse.

    PubMed

    Roca-Ho, Heleia; Riera, Marta; Palau, Vanesa; Pascual, Julio; Soler, Maria Jose

    2017-03-05

    Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.

  12. An initial study of voice characteristics of children using two different sound coding strategies in comparison to normal hearing children.

    PubMed

    Coelho, Ana Cristina; Brasolotto, Alcione Ghedini; Bevilacqua, Maria Cecília

    2015-06-01

    To compare some perceptual and acoustic characteristics of the voices of children who use the advanced combination encoder (ACE) or fine structure processing (FSP) speech coding strategies, and to investigate whether these characteristics differ from children with normal hearing. Acoustic analysis of the sustained vowel /a/ was performed using the multi-dimensional voice program (MDVP). Analyses of sequential and spontaneous speech were performed using the real time pitch. Perceptual analyses of these samples were performed using visual-analogic scales of pre-selected parameters. Seventy-six children from three years to five years and 11 months of age participated. Twenty-eight were users of ACE, 23 were users of FSP, and 25 were children with normal hearing. Although both groups with CI presented with some deviated vocal features, the users of ACE presented with voice quality more like children with normal hearing than the users of FSP. Sound processing of ACE appeared to provide better conditions for auditory monitoring of the voice, and consequently, for better control of the voice production. However, these findings need to be further investigated due to the lack of comparative studies published to understand exactly which attributes of sound processing are responsible for differences in performance.

  13. Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

    PubMed

    Meurs, Kathryn M; Olsen, Lisbeth H; Reimann, Maria J; Keene, Bruce W; Atkins, Clarke E; Adin, Darcy; Aona, Brent; Condit, Julia; DeFrancesco, Teresa; Reina-Doreste, Yamir; Stern, Joshua A; Tou, Sandra; Ward, Jessica; Woodruff, Kathleen

    2018-02-01

    Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

  14. Estradiol, acting through ERα, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1-7 production.

    PubMed

    Mompeón, Ana; Lázaro-Franco, Macarena; Bueno-Betí, Carlos; Pérez-Cremades, Daniel; Vidal-Gómez, Xavier; Monsalve, Elena; Gironacci, Mariela M; Hermenegildo, Carlos; Novella, Susana

    2016-02-15

    Intracellular renin-angiotensin system (RAS) can operate independently of the circulating RAS. Estrogens provide protective effects by modulating the RAS. Our aim was to investigate the effect of estradiol (E2) on angiotensin converting enzymes (ACE) 1 and ACE2 expression and activities in human endothelial cells (HUVEC), and the role of estrogen receptors (ER). The results confirmed the presence of active intracellular RAS in HUVEC. Physiological concentrations of E2 induced a concentration-dependent increase of ACE1 and ACE2 mRNA expression and ACE1, but not ACE2, protein levels. ACE1 and ACE2 enzymatic activities were also induced with E2. These effects were mediated through ERα activation, since ER antagonists ICI 182780 and MPP completely abolished the effect of E2. Moreover, the ERα agonist PPT mirrored the E2 effects on ACE1 and ACE2 protein expression and activity. Exposure of endothelial cells to E2 significantly increased Ang-(1-7) production. In conclusion, E2 increases Ang-(1-7) production, through ERα, involving increased ACE1 and ACE2 mRNA expression and activity and ACE1 protein levels. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. America's Children and the Environment

    MedlinePlus

    ... Labs and Research Centers America's Children and the Environment (ACE) Contact Us Share ACE presents key information ... of updates to ACE . America's Children and the Environment (ACE) America's Children and the Environment (ACE) is ...

  16. 75 FR 64737 - Automated Commercial Environment (ACE): Announcement of a National Customs Automation Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ... Commissioner of CBP with authority to conduct limited test programs or procedures designed to evaluate planned.... Specifically, CBP is looking for test participants to include: 2-3 Ocean Carriers. At least one must be filing... their software ready to test with CBP once CBP begins the certification process. CBP will post the...

  17. Visions and Revisions. Annual Alliance/ACE Conference (16th, St. Pete Beach, Florida, October 3-5, 1996).

    ERIC Educational Resources Information Center

    Alliance, an Association for Alternative Degree Programs.

    These proceedings consist of 20 presentations made during 5 sessions at a conference dealing with alternative degree programs for adults. The following papers are included: "Narrative Reasoning as Assessment" (Richard M. Ashbrook); "Political and Administrative Issues in Developing a Distance Learning Based Program" (Margaret Foss, Conni R.…

  18. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitor-Based Treatment on Cardiovascular Outcomes in Hypertensive Blacks versus Whites

    PubMed Central

    Ogedegbe, Gbenga; Shah, Nirav R.; Phillips, Christopher; Goldfeld, Keith; Roy, Jason; Guo, Yu; Gyamfi, Joyce; Torgersen, Christopher; Capponi, Louis; Bangalore, Sripal

    2015-01-01

    BACKGROUND Clinical trial evidence suggests poorer outcomes in blacks compared to whites when treated with angiotensin-converting enzyme (ACE) inhibitor-based regimen, but this has not been evaluated in clinical practice. OBJECTIVES We evaluated the comparative effectiveness of an ACE inhibitor-based regimen on a composite outcome of all-cause mortality, stroke, and acute myocardial infarction (AMI) in hypertensive blacks compared to whites. METHODS We conducted a retrospective cohort study of 434,646 patients in a municipal health care system. Four exposure groups (Black-ACE, Black-NoACE, White-ACE, White-NoACE) were created based on race and treatment exposure (ACE or NoACE). Risk of the composite outcome and its components was compared across treatment groups and race using weighted Cox proportional hazard models. RESULTS Our analysis included 59,316 new users of ACE inhibitors, 47% of whom were black. Baseline characteristics were comparable for all groups after inverse probability weighting adjustment. For the composite outcome, the race treatment interaction was significant (p = 0.04); ACE use in blacks was associated with poorer cardiovascular outcomes (ACE vs. NoACE: 8.69% vs. 7.74%; p = 0.05) but not in whites (6.40% vs. 6.74%; p = 0.37). Similarly, the Black-ACE group had higher rates of AMI (0.46% vs. 0.26%; p = 0.04), stroke (2.43% vs. 1.93%; p = 0.05) and chronic heart failure (3.75% vs. 2.25%; p < 0.0001) than the Black-NoACE group. However, the Black-ACE group was no more likely to develop adverse effects than the White-ACE group. CONCLUSIONS ACE inhibitor-based therapy was associated with poorer cardiovascular outcomes in hypertensive blacks but not in whites. These findings confirm clinical trial evidence that hypertensive blacks have poorer outcomes than whites when treated with an ACE inhibitor-based regimen. PMID:26361152

  19. ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.

    PubMed

    Rahimi, Zohreh

    2012-10-01

    Angiotensin converting enzyme (ACE) gene encodes ACE, a key component of renin angiotensin system (RAS), plays an important role in blood pressure homeostasis by generating the vasoconstrictor peptide angiotensin II. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.

  20. Environmental Assessment: Improvements to Silver Flag Training Area at Tyndall Air Force Base, Florida

    DTIC Science & Technology

    2013-01-01

    moderate in magnitude on air quality, noise, Air Installation Compatible Use Zone program soils , wetlands, surface water, floodplains, vegetation, fish...magnitude, on air quality, noise, Air Installation Compatible Use Zone program, soils , wetlands, smf ace water, floodplains, vegetation, fish and wildlife...range from negligible to moderate in magnitude on air quality, noise, Air Installation Compatible Use Zone program, soils , wetlands, surface water

  1. Investigation into the Mechanism of Homo- and Heterodimerization of Angiotensin-Converting Enzyme.

    PubMed

    Abrie, J Albert; Moolman, Wessel J A; Cozier, Gyles E; Schwager, Sylva L; Acharya, K Ravi; Sturrock, Edward D

    2018-04-01

    Angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system (RAS), which is primarily responsible for blood pressure homeostasis. Studies have shown that ACE inhibitors yield cardiovascular benefits that cannot be entirely attributed to the inhibition of ACE catalytic activity. It is possible that these benefits are due to interactions between ACE and RAS receptors that mediate the protective arm of the RAS, such as angiotensin II receptor type 2 (AT 2 R) and the receptor MAS. Therefore, in this study, we investigated the molecular interactions of ACE, including ACE homodimerization and heterodimerization with AT 2 R and MAS, respectively. Molecular interactions were assessed by fluorescence resonance energy transfer and bimolecular fluorescence complementation in human embryonic kidney 293 cells and Chinese hamster ovary-K1 cells transfected with vectors encoding fluorophore-tagged proteins. The specificity of dimerization was verified by competition experiments using untagged proteins. These techniques were used to study several potential requirements for the germinal isoform of angiotensin-converting enzyme expressed in the testes (tACE) dimerization as well as the effect of ACE inhibitors on both somatic isoforms of angiotensin-converting enzyme expressed in the testes (sACE) and tACE dimerization. We demonstrated constitutive homodimerization of sACE and of both of its domains separately, as well as heterodimerization of both sACE and tACE with AT 2 R, but not MAS. In addition, we investigated both soluble sACE and the sACE N domain using size-exclusion chromatography-coupled small-angle X-ray scattering and we observed dimers in solution for both forms of the enzyme. Our results suggest that ACE homo- and heterodimerization does occur under physiologic conditions. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Profiles of childhood adversities in pathological gamblers - A latent class analysis.

    PubMed

    Lotzin, Annett; Ulas, Mehmet; Buth, Sven; Milin, Sascha; Kalke, Jens; Schäfer, Ingo

    2018-06-01

    Despite of high rates of adverse childhood experiences (ACEs) in pathological gamblers, researchers have rarely studied which types of ACEs often co-occur and how these profiles of ACEs are related to current psychopathology. We aimed to identify profiles of ACEs in pathological gamblers and examined how these profiles were related to gambling-related characteristics and current general psychopathology. In 329 current or lifetime pathological gamblers, diagnosed with the Composite Diagnostic Interview for DSM-IV, 10 types of ACEs were measured using the Adverse Childhood Experiences Questionnaire. Global psychopathology was assessed using the Symptom Checklist SCL-27. ACE profiles were identified using latent class analysis. Differences between ACE profiles in gambling-related characteristics and global psychopathology were analyzed using MANOVA. We found that four out of five gamblers (n=257, 78.1%) reported at least one ACE. Four distinct ACE profiles were identified: 'Low ACE', 'High ACE', 'Physical and emotional abuse', and 'Neglect'. The number of the fulfilled pathological gambling criteria and the severity of current global psychopathology differed between the ACE profiles: Gamblers with a 'High ACE' profile fulfilled more pathological gambling criteria and showed a more severe current psychopathology than gamblers of the 'Low ACE' profile. Gamblers with a 'Physical and emotional abuse' or an 'Emotion neglect' profile showed an intermediate severity of psychopathology. Our findings indicate that four different ACE profiles can be distinguished in pathological gamblers that differed in their gambling-related characteristics and current psychopathology. Systematic assessment of profiles of ACEs in pathological gamblers may inform about the severity of current global psychopathology that might be important to be addressed in addition to gambling-specific treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Inter-Agency Consultative Group for Space Science (IACG): Handbook of Missions and Payloads

    NASA Technical Reports Server (NTRS)

    1994-01-01

    The ACE spacecraft design is based on the Charge Composition Explorer (CCE) built by Johns Hopkins University (JHU) and the Applied Physics Lab (APL) for the AMPTE program. ACE is designed as a spinning spacecraft with its spin axis aligned to the Earth-Sun axis. The ACE launch weight will be approx. 633 kg, including 105 kg of scientific instruments and 184 kg of propellant. Using a Delta-class expendable launch vehicle, ACE will be launched into an L1 libration point (240 R(sub e)) orbit. Telemetry will be 6.7 kbps average, using tape recorder storage with daily readout to DSN. The experiment power requirement is approximately 76 W nominal and 96 W peak. The prime objective of the ACE mission is: (1) to determine accurate elemental and isotropic abundances including solar matter, local interstellar matter and local galactic matter; (2) to study the origin of elements and evolutionary processing in galactic nucleosynthesis, galactic evolution, origin and evolution of the solar system; (3) to study coronal formation and solar-wind acceleration processes; and (4) to study particle acceleration and transport, including coronal shock acceleration, stochastic flare acceleration, interplanetary shock acceleration, and interstellar acceleration and propagation. To accomplish this objective, ACE will perform comprehensive and coordinated determinations of the elemental and isotopic composition of energetic nuclei accelerated on the Sun, in interplanetary space, and from galactic sources. These observations will span five decades in energy, from solar wind to galactic cosmic ray energies, and will cover the element range from H-1 to Zr-40. Comparison of these samples of matter will be used to study the origin and subsequent evolution of both solar system and galactic material by isolating the effects of fundamental processes that include nucleosynthesis, charged and neutral particle separation, bulk plasma acceleration, and the acceleration of suprathermal and high-energy particles.

  4. Gestational Protein Restriction Increases Angiotensin II Production in Rat Lung1

    PubMed Central

    Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

    2013-01-01

    ABSTRACT Gestational protein restriction (PR) alters the renin-angiotensin system in uterine arteries and placentas and elevates plasma levels of angiotensin II in pregnant rats. To date, how PR increases maternal plasma levels of angiotensin II remains unknown. In this study, we hypothesize that the expression and/or the activity of angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE) in lungs, but not kidneys and blood, largely contribute to elevated plasma angiotensin II levels in pregnant rats subject to gestational PR. Time-scheduled pregnant Sprague-Dawley rats were fed a normal or low-protein diet from Day 3 of pregnancy until euthanized at Day 19 or 22. Expressions of Ace and Ace2 (angiotens in I converting enzyme [peptidyl-dipeptidase A] 2) in lungs and kidneys from pregnant rats by quantitative real-time PCR and Western blotting, and the activities of these proteins in lungs, kidneys, and plasma, were measured. The mRNA levels of Ace and Ace2 in lungs were elevated by PR at both Days 19 and 22 of pregnancy. The abundance of ACE protein in lungs was increased, but ACE2 protein was decreased, by PR. The activities of ACE, but not ACE2, in lungs were increased by PR. PR did not change expressions of Ace and Ace2, the activities of both ACE and ACE2 in kidneys, and the abundance and activity of plasma ACE. These findings suggest that maternal lungs contribute to the elevated plasma levels of angiotensin II by increasing both the expression and the activity of ACE in response to gestational PR. PMID:23365412

  5. A Novel Angiotensin I-Converting Enzyme Mutation (S333W) Impairs N-Domain Enzymatic Cleavage of the Anti-Fibrotic Peptide, AcSDKP

    PubMed Central

    Danilov, Sergei M.; Wade, Michael S.; Schwager, Sylva L.; Douglas, Ross G.; Nesterovitch, Andrew B.; Popova, Isolda A.; Hogarth, Kyle D.; Bhardwaj, Nakul; Schwartz, David E.; Sturrock, Edward D.; Garcia, Joe G. N.

    2014-01-01

    Background Angiotensin I-converting enzyme (ACE) has two functional N- and C-domain active centers that display differences in the metabolism of biologically-active peptides including the hemoregulatory tetrapeptide, Ac-SDKP, hydrolysed preferentially by the N domain active center. Elevated Ac-SDKP concentrations are associated with reduced tissue fibrosis. Results We identified a patient of African descent exhibiting unusual blood ACE kinetics with reduced relative hydrolysis of two synthetic ACE substrates (ZPHL/HHL ratio) suggestive of the ACE N domain center inactivation. Inhibition of blood ACE activity by anti-catalytic mAbs and ACE inhibitors and conformational fingerprint of blood ACE suggested overall conformational changes in the ACE molecule and sequencing identified Ser333Trp substitution in the N domain of ACE. In silico analysis demonstrated S333W localized in the S1 pocket of the active site of the N domain with the bulky Trp adversely affecting binding of ACE substrates due to steric hindrance. Expression of mutant ACE (S333W) in CHO cells confirmed altered kinetic properties of mutant ACE and conformational changes in the N domain. Further, the S333W mutant displayed decreased ability (5-fold) to cleave the physiological substrate AcSDKP compared to wild-type ACE. Conclusions and Significance A novel Ser333Trp ACE mutation results in dramatic changes in ACE kinetic properties and lowered clearance of Ac-SDKP. Individuals with this mutation (likely with significantly increased levels of the hemoregulatory tetrapeptide in blood and tissues), may confer protection against fibrosis. PMID:24505347

  6. Up-Regulation of Angiotensin-Converting Enzyme (ACE) Enhances Cell Proliferation and Predicts Poor Prognosis in Laryngeal Cancer.

    PubMed

    Han, Chao-Dong; Ge, Wen-Sheng

    2016-11-01

    BACKGROUND The angiotensin-converting enzyme (ACE, CD143) gene plays a crucial role in the pathology of many cancers. Previous studies mostly focused on the gene polymorphism, but the other functions of ACE have rarely been reported. The purpose of this study was to investigate the expression of ACE and its biological function, as well as its prognostic value, in laryngeal cancer. MATERIAL AND METHODS The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in 106 patients with laryngeal cancer and 85 healthy people. Then the cell proliferation was estimated after the cell lines Hep-2 were transfected with pGL3-ACE and empty vector, respectively. In addition, the relationship between ACE expression and clinicopathologic characteristics was analyzed. Finally, Kaplan-Meier analysis was used to evaluate the overall survival of patients with different ACE expression, while Cox regression analysis was conducted to reveal the prognostic value of ACE in laryngeal cancer. RESULTS Our results demonstrate that ACE is over-expressed in laryngeal cancer and thus promotes cell proliferation. The up-regulation of ACE was significantly influenced by tumor stage and lymph node metastasis. Patients with high ACE expression had a shorter overall survival compared with those with low ACE expression according to Kaplan-Meier analysis. The ACE gene was also found to be an important factor in the prognosis of laryngeal cancer. CONCLUSIONS Our study shows that the ACE gene was up-regulated, which promoted the cell proliferation, and it could be an independent prognostic marker in laryngeal cancer.

  7. Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita.

    PubMed

    Cui, Ruqiang; Zhang, Lei; Chen, Yuyan; Huang, Wenkun; Fan, Chengming; Wu, Qingsong; Peng, Deliang; da Silva, Washington; Sun, Xiaotang

    2017-05-01

    The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant. Copyright © 2017. Published by Elsevier Inc.

  8. Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity

    PubMed Central

    Giani, Jorge F.; Eriguchi, Masahiro; Bernstein, Ellen A.; Katsumata, Makoto; Shen, Xiao Z.; Li, Liang; McDonough, Alicia A.; Fuchs, Sebastien; Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.

    2017-01-01

    Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension. PMID:27988209

  9. Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease.

    PubMed

    Wang, Wang; Patel, Vaibhav B; Parajuli, Nirmal; Fan, Dong; Basu, Ratnadeep; Wang, Zuocheng; Ramprasath, Tharmarajan; Kassiri, Zamaneh; Penninger, Josef M; Oudit, Gavin Y

    2014-08-01

    Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion. Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to heart disease.

  10. Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

    PubMed

    Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

    2008-12-01

    Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

  11. Air, Climate and Energy (ACE) Centers: Supporting Air Quality and Climate Solutions

    EPA Pesticide Factsheets

    EPA through its Science to Achieve Results (STAR) program, is providing $30 million in funding for three university-based research centers to investigate regional differences in air pollution and the effects of global climate change.

  12. Angiotensin-I-converting enzyme and its relatives

    PubMed Central

    Riordan, James F

    2003-01-01

    Angiotensin-I-converting enzyme (ACE) is a monomeric, membrane-bound, zinc- and chloride-dependent peptidyl dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a carboxy-terminal dipeptide. ACE has long been known to be a key part of the renin angiotensin system that regulates blood pressure, and ACE inhibitors are important for the treatment of hypertension. There are two forms of the enzyme in humans, the ubiquitous somatic ACE and the sperm-specific germinal ACE, both encoded by the same gene through transcription from alternative promoters. Somatic ACE has two tandem active sites with distinct catalytic properties, whereas germinal ACE, the function of which is largely unknown, has just a single active site. Recently, an ACE homolog, ACE2, has been identified in humans that differs from ACE in being a carboxypeptidase that preferentially removes carboxy-terminal hydrophobic or basic amino acids; it appears to be important in cardiac function. ACE homologs (also known as members of the M2 gluzincin family) have been found in a wide variety of species, even in those that neither have a cardiovascular system nor synthesize angiotensin. X-ray structures of a truncated, deglycosylated form of germinal ACE and a related enzyme from Drosophila have been reported, and these show that the active site is deep within a central cavity. Structure-based drug design targeting the individual active sites of somatic ACE may lead to a new generation of ACE inhibitors, with fewer side-effects than currently available inhibitors. PMID:12914653

  13. Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation.

    PubMed

    Rivière, Guillaume; Lienhard, Daniel; Andrieu, Thomas; Vieau, Didier; Frey, Brigitte M; Frey, Felix J

    2011-04-01

    Somatic angiotensin-converting enzyme (sACE) is crucial in cardiovascular homeostasis and displays a tissue-specific profile. Epigenetic patterns modulate genes expression and their alterations were implied in pathologies including hypertension. However, the influence of DNA methylation and chromatin condensation state on the expression of sACE is unknown. We examined whether such epigenetic mechanisms could participate in the control of sACE expression in vitro and in vivo. We identified two CpG islands in the human ace-1 gene 3 kb proximal promoter region. Their methylation abolished the luciferase activity of ace-1 promoter/reporter constructs transfected into human liver (HepG2), colon (HT29), microvascular endothelial (HMEC-1) and lung (SUT) cell lines (p < 0.001). Bisulphite sequencing revealed a cell-type specific basal methylation pattern of the ace-1 gene -1,466/+25 region. As assessed by RT-qPCR, inhibition of DNA methylation by 5-aza-2'-deoxycytidine and/or of histone deacetylation by trichostatin A highly stimulated sACE mRNA expression cell-type specifically (p < 0.001 vs. vehicle treated cells). In the rat, in vivo 5-aza-cytidine injections demethylated the ace-1 promoter and increased sACE mRNA expression in the lungs and liver (p = 0.05), but not in the kidney. In conclusion, the expression level of somatic ACE is modulated by CpG-methylation and histone deacetylases inhibition. The basal methylation pattern of the promoter of the ace-1 gene is cell-type specific and correlates to sACE transcription. DNMT inhibition is associated with altered methylation of the ace-1 promoter and a cell-type and tissue-specific increase of sACE mRNA levels. This study indicates a strong influence of epigenetic mechanisms on sACE expression.

  14. ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone.

    PubMed

    Gadelha, Ary; Yonamine, Camila M; Ota, Vanessa K; Oliveira, Vitor; Sato, João Ricardo; Belangero, Sintia I; Bressan, Rodrigo A; Hayashi, Mirian A F

    2015-05-01

    Angiotensin-I converting enzyme (ACE) is a key component of the renin-angiotensin system (RAS). Although the several contradictory data, ACE has been associated with schizophrenia (SCZ) pathophysiology. Here the ACE activity of SCZ patients and healthy controls (HCs), and its possible correlations with the ACE polymorphism genotype and symptomatic dimensions, was investigated. ACE activity of 86 SCZ patients and 100 HCs paired by age, gender and educational level was measured, using the FRET peptide substrate and the specific inhibitor lisinopril. The ACE insertion/deletion (I/D) genotypes were assessed by the restriction fragment length polymorphism (RFLP) technique. Significantly higher ACE activity was observed in SCZ patients compared to HCs (t=-5.09; p<0.001). The area under the receiver operating characteristic (ROC) curve was 0.701. Mean ACE activity levels were higher for the D-allele carriers (F=5.570; p=0.005), but no significant difference was found among SCZ patients and HCs for genotypes frequencies (Chi-squared=2.08; df=2; p=0.35). Interestingly, we found that the difference between the measured ACE activity for each SCZ patient and the expected average mean value for each respective genotype group (for control subjects) was a better predictor of SCZ than the ACE dichotomized values (high/low) or ACE I/D. Our results suggest that higher levels of ACE activity are associated with SCZ with stronger impact when the genetic background of each individual is considered. This may explain the heterogeneity of the results on ACE previously reported. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

    PubMed

    Gao, Tingting; Zhao, Xin; Liu, Chenchen; Shao, Binbin; Zhang, Xi; Li, Kai; Cai, Jinyang; Wang, Su; Huang, Xiaoyan

    2018-05-24

    Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. KEGG pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and cell cycle. sACE was found to play an important role in SSC self-renewal via the regulation of MAPK-dependent cell proliferation.

  16. Angiotensin converting enzyme immobilized on magnetic beads as a tool for ligand fishing.

    PubMed

    de Almeida, Fernando G; Vanzolini, Kenia L; Cass, Quezia B

    2017-01-05

    Angiotensin converting enzyme (ACE) presents an important role in blood pressure regulation, since that converts angiotensin I to the vasoconstrictor angiotensin II. Some commercially available ACE inhibitors are captopril, lisinopril and enalapril; due to their side effects, naturally occurring inhibitors have been prospected. In order to endorse this research field we have developed a new tool for ACE ligand screening. To this end, ACE was extracted from bovine lung, purified and chemically immobilized in modified ferrite magnetic beads (ACE-MBs). The ACE-MBs have shown a Michaelian kinetic behavior towards hippuryl-histidyl-leucine. Moreover, as proof of concept, the ACE-MBs was inhibited by lisinopril with a half maximal inhibitory concentration (IC 50 ) of 10nM. At the fishing assay, ACE-MBs were able not only to fish out the reference inhibitor, but also one peptide from a pool of tryptic digested BSA. In conclusion, ACE-MBs emerge as new straightforward tool for ACE kinetics determination, inhibition and binder screening. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Serine proteases as candidates for proteolytic processing of angiotensin-I converting enzyme.

    PubMed

    Aragão, Danielle S; de Andrade, Maria Claudina C; Ebihara, Fabiana; Watanabe, Ingrid K M; Magalhães, Dayane C B P; Juliano, Maria Aparecida; Hirata, Izaura Yoshico; Casarini, Dulce Elena

    2015-01-01

    Somatic angiotensin-I converting enzyme (sACE) is a broadly distributed peptidase which plays a role in blood pressure and electrolyte homeostasis by the conversion of angiotensin I into angiotensin II. N-domain isoforms (nACE) with 65 and 90 kDa have been described in body fluids, tissues and mesangial cells (MC), and a 90 kDa nACE has been described only in spontaneously hypertensive rats. The aim of this study was to investigate the existence of proteolytic enzymes that may act in the hydrolysis of sACE generating nACEs in MC. After the confirmation of the presence of ACE sheddases in Immortalized MC (IMC), we purified and characterized these enzymes using fluorogenic substrates specifically designed for ACE sheddases. Purified enzyme identified as a serine protease by N-terminal sequence was able to generate nACE. In the present study, we described for the first time the presence of ACE sheddases in IMC, identified as serine proteases able to hydrolyze sACE in vitro. Further investigations are necessary to elucidate the mechanisms responsible for the expression and regulation of ACE sheddases in MC and their roles in the generation of nACEs, especially the 90 kDa form possibly related to hypertension. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

    PubMed Central

    Ong, Frank S.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Giani, Jorge F.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien

    2013-01-01

    Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of ACE is that it is composed of two homologous and independently catalytic domains, the result of an ancient gene duplication, and ACE-like genes are widely distributed in nature. The two ACE catalytic domains contribute to the wide substrate diversity of ACE and, by extension, the physiologic impact of the enzyme. Several studies suggest that the two catalytic domains have different biologic functions. Recently, the X-ray crystal structure of ACE has elucidated some of the structural differences between the two ACE domains. This is important now that ACE domain-specific inhibitors have been synthesized and characterized. Once widely available, these reagents will undoubtedly be powerful tools for probing the physiologic actions of each ACE domain. In turn, this knowledge should allow clinicians to envision new therapies for diseases not currently treated with ACE inhibitors. PMID:23257181

  19. Unpacking the impact of adverse childhood experiences on adult mental health.

    PubMed

    Merrick, Melissa T; Ports, Katie A; Ford, Derek C; Afifi, Tracie O; Gershoff, Elizabeth T; Grogan-Kaylor, Andrew

    2017-07-01

    Exposure to childhood adversity has an impact on adult mental health, increasing the risk for depression and suicide. Associations between Adverse Childhood Experiences (ACEs) and several adult mental and behavioral health outcomes are well documented in the literature, establishing the need for prevention. The current study analyzes the relationship between an expanded ACE score that includes being spanked as a child and adult mental health outcomes by examining each ACE separately to determine the contribution of each ACE. Data were drawn from Wave II of the CDC-Kaiser ACE Study, consisting of 7465 adult members of Kaiser Permanente in southern California. Dichotomous variables corresponding to each of the 11 ACE categories were created, with ACE score ranging from 0 to 11 corresponding to the total number of ACEs experienced. Multiple logistic regression modeling was used to examine the relationship between ACEs and adult mental health outcomes adjusting for sociodemographic covariates. Results indicated a graded dose-response relationship between the expanded ACE score and the likelihood of moderate to heavy drinking, drug use, depressed affect, and suicide attempts in adulthood. In the adjusted models, being spanked as a child was significantly associated with all self-reported mental health outcomes. Over 80% of the sample reported exposure to at least one ACE, signifying the potential to capture experiences not previously considered by traditional ACE indices. The findings highlight the importance of examining both cumulative ACE scores and individual ACEs on adult health outcomes to better understand key risk and protective factors for future prevention efforts. Copyright © 2017. Published by Elsevier Ltd.

  20. Acetylcholinesterase genes within the Diptera: takeover and loss in true flies

    PubMed Central

    Huchard, Elise; Martinez, Michel; Alout, Haoues; Douzery, Emmanuel J.P; Lutfalla, Georges; Berthomieu, Arnaud; Berticat, Claire; Raymond, Michel; Weill, Mylène

    2006-01-01

    It has recently been reported that the synaptic acetylcholinesterase (AChE) in mosquitoes is encoded by the ace-1 gene, distinct and divergent from the ace-2 gene, which performs this function in Drosophila. This is an unprecedented situation within the Diptera order because both ace genes derive from an old duplication and are present in most insects and arthropods. Nevertheless, Drosophila possesses only the ace-2 gene. Thus, a secondary loss occurred during the evolution of Diptera, implying a vital function switch from one gene (ace-1) to the other (ace-2). We sampled 78 species, representing 50 families (27% of the Dipteran families) spread over all major subdivisions of the Diptera, and looked for ace-1 and ace-2 by systematic PCR screening to determine which taxonomic groups within the Diptera have this gene change. We show that this loss probably extends to all true flies (or Cyclorrhapha), a large monophyletic group of the Diptera. We also show that ace-2 plays a non-detectable role in the synaptic AChE in a lower Diptera species, suggesting that it has non-synaptic functions. A relative molecular evolution rate test showed that the intensity of purifying selection on ace-2 sequences is constant across the Diptera, irrespective of the presence or absence of ace-1, confirming the evolutionary importance of non-synaptic functions for this gene. We discuss the evolutionary scenarios for the takeover of ace-2 and the loss of ace-1, taking into account our limited knowledge of non-synaptic functions of ace genes and some specific adaptations of true flies. PMID:17002944

  1. Molecular Probes in Marine Ecology: Concepts, Techniques and Applications.

    DTIC Science & Technology

    1991-08-16

    AD-A240 938 FINAL TECNCAL REPORT Title: Molecular Probes In Marine Ecology: Concepts, Techniques and Applications Office of Naval Research Program ...Contact: Leslie D. Garrick, Office of Sponsored Programs (508) 548-3705, ext. 218 Date: August 16, 1991 91-11818 DISCLAIMER NOTICE THIS DOCUMENT IS BEST...disguise, embi-aces the many questions and seeks workable solutions. The 1990 MBL marine ecology course, entered into its second year of a program in

  2. Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development.

    PubMed

    Heisenberg, C P; Brennan, C; Wilson, S W

    1999-05-01

    During the development of the zebrafish nervous system both noi, a zebrafish pax2 homolog, and ace, a zebrafish fgf8 homolog, are required for development of the midbrain and cerebellum. Here we describe a dominant mutation, aussicht (aus), in which the expression of noi and ace is upregulated. In aus mutant embryos, ace is upregulated at many sites in the embryo, while noi expression is only upregulated in regions of the forebrain and midbrain which also express ace. Subsequent to the alterations in noi and ace expression, aus mutants exhibit defects in the differentiation of the forebrain, midbrain and eyes. Within the forebrain, the formation of the anterior and postoptic commissures is delayed and the expression of markers within the pretectal area is reduced. Within the midbrain, En and wnt1 expression is expanded. In heterozygous aus embryos, there is ectopic outgrowth of neural retina in the temporal half of the eyes, whereas in putative homozygous aus embryos, the ventral retina is reduced and the pigmented retinal epithelium is expanded towards the midline. The observation that aus mutant embryos exhibit widespread upregulation of ace raised the possibility that aus might represent an allele of the ace gene itself. However, by crossing carriers for both aus and ace, we were able to generate homozygous ace mutant embryos that also exhibited the aus phenotype. This indicated that aus is not tightly linked to ace and is unlikely to be a mutation directly affecting the ace locus. However, increased Ace activity may underly many aspects of the aus phenotype and we show that the upregulation of noi in the forebrain of aus mutants is partially dependent upon functional Ace activity. Conversely, increased ace expression in the forebrain of aus mutants is not dependent upon functional Noi activity. We conclude that aus represents a mutation involving a locus normally required for the regulation of ace expression during embryogenesis.

  3. Association of Urinary N-Domain Angiotensin I-Converting Enzyme with Plasma Inflammatory Markers and Endothelial Function

    PubMed Central

    Fernandes, Fernanda B; Plavnik, Frida L; Teixeira, Andressa MS; Christofalo, Dejaldo MJ; Ajzen, Sergio A; Higa, Elisa MS; Ronchi, Fernanda A; Sesso, Ricardo CC; Casarini, Dulce E

    2008-01-01

    The aim of this study was to investigate the association between urinary 90 kDa N-domain Angiotensin I-converting enzyme (ACE) form with C-reactive protein (CRP) and homocysteine plasma levels (Hcy), urinary nitric oxide (NOu), and endothelial function (EF) in normotensive subjects. Forty healthy subjects were evaluated through brachial Doppler US to test the response to reactive hyperemia and a panel of blood tests to determine CRP and Hcy levels, NOu, and urinary ACE. They were divided into groups according to the presence (ACE90+) or absence (ACE90–) of the 90 kDa ACE, the presence (FH+) or absence (FH–) of family history of hypertension, and the presence or absence of these two variables FH+/ACE90+ and FH–/ACE90–. We found an impaired endothelial dilatation in subjects who presented the 90 kDa N-domain ACE as follows: 11.4% ± 5.3% in ACE90+ compared with 17.6% ± 7.1% in ACE90– group and 12.4% ± 5.6% in FH+/ACE90+ compared with 17.7% ± 6.2% in FH–/ACE90– group, P < 0.05. Hcy and CRP levels were statistically significantly lower in FH+/ACE90+ than in FH–/ACE90– group, as follows: 10.0 ± 2.3 μM compared with 12.7 ± 1.5 μM, and 1.3 ± 1.8 mg/L compared with 3.6 ± 2.0 mg/L, respectively. A correlation between flow-mediated dilatation (FMD) and CRP, Hcy, and NOu levels was not found. Our study suggests a reduction in the basal NO production confirmed by NOu analysis in subjects with the 90 kDa N-domain ACE isoform alone or associated with a family history of hypertension. Our data suggest that the presence of the 90 kDa N-domain ACE itself may have a negative impact on flow-mediated dilatation stimulated by reactive hyperemia. PMID:18475311

  4. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) III: Endogenous Inhibition of Angiotensin Converting Enzyme (ACE) Provides Protection against Cardiovascular Diseases

    PubMed Central

    Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Édes, István; Papp, Zoltán; Tóth, Attila

    2014-01-01

    ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151). ACE concentration was found to be in a wide range (47–288 ng/mL). ACE activity decreased with the increasing concentration of the serum albumin (HSA): ACE activity was 56±1 U/L in the presence of 2.4±0.3 mg/mL HSA, compared to 39±1 U/L in the presence of 12±1 mg/mL HSA (values are mean±SEM). Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74–288 ng/mL, median, 155.2 ng/mL, n = 52) compared to patients with II genotype (range, 47–194 ng/mL, median, 94.5 ng/mL, n = 28) while the difference in ACE activities was only 32% (range, 27.3–59.8 U/L, median, 43.11 U/L, and range 15.6–55.4 U/L, median, 32.74 U/L, respectively) in the presence of 12±1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype) and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5±0.5 mg/mL) or other endogenous inhibitors. Main implications are that (1) physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2) angiotensin II elimination may have a significant role in angiotensin II related pathologies. PMID:24690767

  5. Angiotensin I-converting enzyme Gln1069Arg mutation impairs trafficking to the cell surface resulting in selective denaturation of the C-domain.

    PubMed

    Danilov, Sergei M; Kalinin, Sergey; Chen, Zhenlong; Vinokour, Elena I; Nesterovitch, Andrew B; Schwartz, David E; Gribouval, Olivier; Gubler, Marie-Claire; Minshall, Richard D

    2010-05-03

    Angiotensin-converting enzyme (ACE; Kininase II; CD143) hydrolyzes small peptides such as angiotensin I, bradykinin, substance P, LH-RH and several others and thus plays a key role in blood pressure regulation and vascular remodeling. Complete absence of ACE in humans leads to renal tubular dysgenesis (RTD), a severe disorder of renal tubule development characterized by persistent fetal anuria and perinatal death. Patient with RTD in Lisbon, Portugal, maintained by peritoneal dialysis since birth, was found to have a homozygous substitution of Arg for Glu at position 1069 in the C-terminal domain of ACE (Q1069R) resulting in absence of plasma ACE activity; both parents and a brother who are heterozygous carriers of this mutation had exactly half-normal plasma ACE activity compared to healthy individuals. We hypothesized that the Q1069R substitution impaired ACE trafficking to the cell surface and led to accumulation of catalytically inactive ACE in the cell cytoplasm. CHO cells expressing wild-type (WT) vs. Q1069R-ACE demonstrated the mutant accumulates intracellularly and also that it is significantly degraded by intracellular proteases. Q1069R-ACE retained catalytic and immunological characteristics of WT-ACE N domain whereas it had 10-20% of the nativity of the WT-ACE C domain. A combination of chemical (sodium butyrate) or pharmacological (ACE inhibitor) chaperones with proteasome inhibitors (MG 132 or bortezomib) significantly restored trafficking of Q1069R-ACE to the cell surface and increased ACE activity in the cell culture media 4-fold. Homozygous Q1069R substitution results in an ACE trafficking and processing defect which can be rescued, at least in cell culture, by a combination of chaperones and proteasome inhibitors. Further studies are required to determine whether similar treatment of individuals with this ACE mutation would provide therapeutic benefits such as concentration of primary urine.

  6. Air, Climate And Energy (ACE) Centers: Supporting Air Quality And Climate Solutions

    EPA Pesticide Factsheets

    EPA, through its Science to Achieve Results program, is funding three university-based research centers to investigate regional differences in air pollution and effects of climate change, technology, and societal choices on local air quality and health.

  7. The replication of a mouse adapted SARS-CoV in a mouse cell line stably expressing the murine SARS-CoV receptor mACE2 efficiently induces the expression of proinflammatory cytokines

    PubMed Central

    Regla-Nava, Jose A.; Jimenez-Guardeño, Jose M.; Nieto-Torres, Jose L.; Gallagher, Thomas M.; Enjuanes, Luis; DeDiego, Marta L.

    2013-01-01

    Infection of conventional mice with a mouse adapted (MA15) severe acute respiratory syndrome (SARS) coronavirus (CoV) reproduces many aspects of human SARS such as pathological changes in lung, viremia, neutrophilia, and lethality. However, established mouse cell lines highly susceptible to mouse-adapted SARS-CoV infection are not available. In this work, efficiently transfectable mouse cell lines stably expressing the murine SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) have been generated. These cells yielded high SARS-CoV-MA15 titers and also served as excellent tools for plaque assays. In addition, in these cell lines, SARS-CoV-MA15 induced the expression of proinflammatory cytokines and IFN-β, mimicking what has been observed in experimental animal models infected with SARS-CoV and SARS patients. These cell lines are valuable tools to perform in vitro studies in a mouse cell system that reflects the species used for in vivo studies of SARS-CoV-MA15 pathogenesis. PMID:23911968

  8. Presence of angiotensin converting enzyme isoforms in larval lepidoptera (Spodoptera littoralis).

    PubMed

    Lemeire, E; Van Camp, J; Smagghe, G

    2007-01-01

    In this research the presence of angiotensin converting enzyme (ACE) in larvae of the lepidopteran Spodoptera littoralis was evaluated. Making use of the substrate Abz-FRK-(Dnp)P-OH and the specific inhibitor captopril at 10 microM, ACE activity was determined in a fluorescence assay for intact larvae, hemolymph, head, midgut and dorsal tissue. In dorsal tissue and hemolymph, ACE activity was highest. These data are consistent with a possible role for ACE in contractions of the dorsal vessel and metabolism of circulating peptide hormones in the hemolymph. After the presence of ACE was confirmed, a sequential procedure of anion exchange and size exclusion chromatography was applied to purify ACE from whole wandering larvae (last stage). With this procedure, three different ACE pools were collected that cleaved the fluorogenic substrate Abz-FRK-(Dnp)P-OH. Activity could be inhibited by a final concentration of 2.5 microM captopril. In addition, two out of three samples eluted at different salt concentration and thus ACE 1, 2 and 3 represent at least two different ACE isoforms. These data reveal that ACE is present in S. littoralis and that at least two out of three isolated ACE forms are truly isoforms.

  9. ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in postmenopausal women.

    PubMed

    Hagberg, James M; McCole, Steve D; Brown, Michael D; Ferrell, Robert E; Wilund, Kenneth R; Huberty, Andrea; Douglass, Larry W; Moore, Geoffrey E

    2002-03-01

    We sought to determine whether the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism is associated with submaximal exercise cardiovascular hemodynamics. Postmenopausal healthy women (20 sedentary, 20 physically active, 22 endurance athletes) had cardiac output (acetylene rebreathing) measured during 40, 60, and 80% VO(2 max) exercise. The interaction of ACE genotype and habitual physical activity (PA) level was significantly associated with submaximal exercise systolic blood pressure, with only sedentary women exhibiting differences among genotypes. No significant effects of ACE genotype or its interaction with PA levels was observed for submaximal exercise diastolic blood pressure. ACE genotype was significantly associated with submaximal exercise heart rate (HR) with ACE II having approximately 10 beats/min higher HR than ACE ID/DD genotype women. ACE genotype did not interact significantly with habitual PA level to associate with submaximal exercise HR. ACE genotype was not independently, but was interactively with habitual PA levels, associated with differences in submaximal exercise cardiac output and stroke volume. For cardiac output, ACE II genotype women athletes had ~25% greater cardiac output than ACE DD genotype women athletes, whereas for stroke volume genotype-dependent differences were observed in both the physically active and athletic women. ACE genotype was not significantly associated, either independently or interactively with habitual PA levels, with submaximal exercise total peripheral resistance or arteriovenous O(2) difference. Thus the common ACE locus polymorphic variation is associated with many submaximal exercise cardiovascular hemodynamic responses.

  10. How long will I have my ACE? The natural history of the antegrade continence enema stoma in idiopathic constipation.

    PubMed

    Khoo, A Kate; Askouni, Evita; Basson, Sonia; Ng, Jessica; Cleeve, Stewart

    2017-11-01

    We aim to determine the natural history of the ACE in idiopathic constipation and factors predictive of closure. A retrospective case-note review of all patients undergo ACE formation for idiopathic constipation Jan 2003-Mar 2016. Kaplan-Meier analysis was used to determine ACE survival and Cox's proportional hazard models to examine potential predictors of closure. 29/84 (35%) ACEs were closed: 21/84 due to success and 8/84 due to failure. Median age of closure was 15.5 years (3.5-23.6). Median ACE survival was 77.0 months (95% CI 58.0-96.0). An ACE survival curve was derived from which we estimate that 5-year post-ACE, one-third of patients can expect to have had their ACE closed. Younger age at ACE was predictive of earlier closure (p = 0.023) and closure for success (p < 0.001). Neither patient sex (p = 0.546) nor presence of psychological comorbidities (p = 0.769) predicted likelihood of closure. Incontinence 6-week post-ACE was also associated with increased likelihood of closure (p = 0.042). The ACE survival curve estimates the proportion of patients with idiopathic constipation who can expect closure (either due to success or failure) at certain timepoints. This may be useful for patient counseling. Younger age at ACE was associated with earlier closure (for success).

  11. Crystal structures of sampatrilat and sampatrilat-Asp in complex with human ACE - a molecular basis for domain selectivity.

    PubMed

    Cozier, Gyles E; Schwager, Sylva L; Sharma, Rajni K; Chibale, Kelly; Sturrock, Edward D; Acharya, K Ravi

    2018-04-01

    Angiotensin-1-converting enzyme (ACE) is a zinc metallopeptidase that consists of two homologous catalytic domains (known as nACE and cACE) with different substrate specificities. Based on kinetic studies it was previously reported that sampatrilat, a tight-binding inhibitor of ACE, K i = 13.8 nm and 171.9 nm for cACE and nACE respectively [Sharma et al., Journal of Chemical Information and Modeling (2016), 56, 2486-2494], was 12.4-fold more selective for cACE. In addition, samAsp, in which an aspartate group replaces the sampatrilat lysine, was found to be a nonspecific and lower micromolar affinity inhibitor. Here, we report a detailed three-dimensional structural analysis of sampatrilat and samAsp binding to ACE using high-resolution crystal structures elucidated by X-ray crystallography, which provides a molecular basis for differences in inhibitor affinity and selectivity for nACE and cACE. The structures show that the specificity of sampatrilat can be explained by increased hydrophobic interactions and a H-bond from Glu403 of cACE with the lysine side chain of sampatrilat that are not observed in nACE. In addition, the structures clearly show a significantly greater number of hydrophilic and hydrophobic interactions with sampatrilat compared to samAsp in both cACE and nACE consistent with the difference in affinities. Our findings provide new experimental insights into ligand binding at the active site pockets that are important for the design of highly specific domain selective inhibitors of ACE. The atomic coordinates and structure factors for N- and C-domains of ACE bound to sampatrilat and sampatrilat-Asp complexes (6F9V, 6F9R, 6F9T and 6F9U respectively) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/). © 2018 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  12. [Conformational Fingerprinting Using Monoclonal Antibodies
    (on the Example of Angiotensin I-Converting Enzyme-ACE)].

    PubMed

    Danilov, S M

    2017-01-01

    During the past 30 years my laboratory has generated 40+ monoclonal antibodies (mAbs) directed to structural and conformational epitopes on human ACE as well as ACE from rats, mice and other species. These mAbs were successfully used for detection and quantification of ACE by ELISA, Western blotting, flow cytometry and immunohistochemistry. In all these applications mainly single mAbs were used. We hypothesized that we can obtain a completely new kind of information about ACE structure and function if we use the whole set of mAbs directed to different epitopes on the ACE molecule. When we finished epitope mapping of all mAbs to ACE (and especially, those recognizing conformational epitopes), we realized that we had obtained a new tool to study ACE. First, we demonstrated that binding of some mAbs is very sensitive to local conformational changes on the ACE surface-due to local denaturation, inactivation, ACE inhibitor or mAbs binding or due to diseases. Second, we were able to detect, localize and characterize several human ACE mutations. And, finally, we established a new concept - conformational fingerprinting of ACE using mAbs that in turn allowed us to obtain evidence for tissue specificity of ACE, which has promising scientific and diagnostic perspectives. The initial goal for the generation of mAbs to ACE 30 years ago was obtaining mAbs to organ-specific endothelial cells, which could be used for organ-specific drug delivery. Our systematic work on characterization of mAbs to numerous epitopes on ACE during these years has lead not only to the generation of the most effective mAbs for specific drug/gene delivery into the lung capillaries, but also to the establishment of the concept of conformational fingerprinting of ACE, which in turn gives a theoretical base for the generation of mAbs, specific for ACE from different organs. We believe that this concept could be applicable for any glycoprotein against which there is a set of mAbs to different epitopes.

  13. Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health.

    PubMed

    Reuben, Aaron; Moffitt, Terrie E; Caspi, Avshalom; Belsky, Daniel W; Harrington, Honalee; Schroeder, Felix; Hogan, Sean; Ramrakha, Sandhya; Poulton, Richie; Danese, Andrea

    2016-10-01

    Adverse childhood experiences (ACEs; e.g. abuse, neglect, and parental loss) have been associated with increased risk for later-life disease and dysfunction using adults' retrospective self-reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures. We estimated agreement between ACEs prospectively recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively recalled in adulthood (by Study members when they reached age 38), in the population-representative Dunedin cohort (N = 1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g. biomarkers and neuropsychological tests) and subjective (e.g. self-reported) means. Dunedin and U.S. Centers for Disease Control ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r = .47, p < .001; weighted Kappa = .31, 95% CI: .27-.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable. Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may, respectively, bias retrospective ACE measures toward underestimating the impact of adversity on objectively measured life outcomes and overestimating the impact of adversity on self-reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted. © 2016 Association for Child and Adolescent Mental Health.

  14. Lest we forget: Comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health

    PubMed Central

    Reuben, Aaron; Moffitt, Terrie E.; Caspi, Avshalom; Belsky, Daniel W.; Harrington, Honalee; Schroeder, Felix; Hogan, Sean; Ramrakha, Sandhya; Poulton, Richie; Danese, Andrea

    2017-01-01

    Background Adverse childhood experiences (ACEs; e.g., abuse, neglect, parental loss, etc.) have been associated with increased risk for later-life disease and dysfunction using adults’ retrospective self-reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures. Methods We estimated agreement between ACEs prospectively-recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively-recalled in adulthood (by Study members when they reached age 38), in the population-representative Dunedin cohort (N=1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g., biomarkers and neuropsychological tests) and subjective (e.g., self-reported) means. Results Dunedin and CDC ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r=.47, p<.001; weighted Kappa = .31, 95% CI: .27–.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively-recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable. Conclusions Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may respectively bias retrospective ACE measures toward underestimating the impact of adversity on objectively-measured life outcomes and overestimating the impact of adversity on self-reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted. PMID:27647050

  15. Adverse Childhood Experiences and Health in Adulthood in a Rural Population-Based Sample

    PubMed Central

    Iniguez, Kristen C.; Stankowski, Rachel V.

    2016-01-01

    Background Adverse childhood experiences (ACEs), including emotional abuse, substance abuse in the household, separation or divorce, physical abuse, violence between adults, mental illness in the household, sexual abuse, or incarceration of a household member, have the potential to profoundly impact health and well-being in adulthood. To assess whether previously reported relationships between ACEs and health outcomes withstand validation, we conducted a community-based ACE study with the unique capacity to link self-reported ACEs and other survey results to validated health data in an electronic medical record (EMR). Methods Information regarding ACEs and health outcomes was captured from 2013–2014 via a telephone survey of residents of the predominantly rural northern and central regions of Wisconsin and electronic abstraction of EMR data. ACE score was calculated by counting each exposure as one point. We examined the relationship between ACE score, type, and self-reported and validated health outcomes. Results A total of 800 participants completed the telephone survey. Overall, 62% reported at least one ACE and 15% reported experiencing four or more. All self-reported measures of poor health were associated with increased ACE score. EMR data were positively correlated with ACE score for increased body mass index and diagnoses of depression, anxiety, and asthma. In contrast, diagnoses of hypertension, hypercholesterolemia, myocardial infarction, and skin and other cancers were inversely related to ACE score. Emotional abuse was the most common ACE reported followed by substance abuse in the household. ACEs tended to cluster so that people who reported at least one ACE were likely to have experienced multiple ACEs. There was no clear correlation between abuse type (e.g., direct abuse vs. household dysfunction) and health outcomes. Conclusions In the first community-based study to link self-reported ACEs to comprehensive health measures documented in the medical record, we observed previously reported associations between childhood adversity and poor outcomes in adulthood, but also noted an inverse relationship between ACE score and certain medical diagnoses. Potential explanations for this finding warrant further investigation. PMID:27503793

  16. Adverse childhood experiences of referred children exposed to intimate partner violence: consequences for their wellbeing.

    PubMed

    Lamers-Winkelman, Francien; Willemen, Agnes M; Visser, Margreet

    2012-02-01

    This study investigated the relationships among Adverse Childhood Experiences (ACEs) in a high risk clinical sample of Dutch children whose mothers were abused by an intimate partner, and the severity of behavioral and emotional problems and trauma symptoms. The study population comprised 208 children (M=7.81 years, SD=2.39, range 2-12) who were referred to mental health and welfare institutions after reported Intimate Partner Violence (IPV). At intake, caregivers, children, and teachers completed questionnaires on Adverse Childhood Experiences, behavior and emotional problems, and trauma symptoms. The results showed that child witnesses of IPV were also exposed to other adverse experiences, such as abuse, household dysfunction and neglect. The mean number of ACEs was 5.08 (range 2-9). Twenty percent of the children in this sample experienced seven ACEs or more. The number of ACEs children were exposed to was unrelated to the level of emotional and behavioral problems, except for trauma related symptoms reported by parents. This study shows that children who witnessed Intimate Partner Violence were also exposed to other adverse experiences. The results of this study may imply that in this high-risk clinical sample of children exposed to IPV, additional adverse experiences have a limited relationship to psychological outcomes. A thorough assessment and inclusion of all Adverse Childhood Experiences is necessary for a comprehensive treatment program. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. G119S ace-1 mutation conferring insecticide resistance detected in the Culex pipiens complex in Morocco.

    PubMed

    Bkhache, Meriem; Tmimi, Fatim-Zohra; Charafeddine, Omar; Benabdelkrim Filali, Oumama; Lemrani, Meryem; Labbé, Pierrick; Sarih, M'hammed

    2018-06-09

    Arboviruses are controlled through insecticide control of their mosquito vector. However, inconsiderate use of insecticides often results in the selection of resistance in treated populations, so that monitoring is required to optimize their usage. Here, Culex pipiens (West Nile and Rift Valley Fever virus vector) specimens were collected from four Moroccan cities. Levels of susceptibility to the organophosphate (OP) insecticide malathion were assessed using WHO-recommended bioassays. Individual mosquitoes were tested for the presence of the G119S mutation in the ace-1 gene, the main OP-target resistance mutation. Bioassays showed that mosquitoes from Mohammedia were significantly more resistant to malathion than those from Marrakech. Analyzing the ace-1 genotypes in dead and surviving individuals suggested that other resistance mechanisms may be present in Mohammedia. The ace-1 resistance allele frequencies were relatively moderate (<0.4). Their analyses in three Moroccan cities (Tangier, Casablanca and Marrakech) however showed disparities between two coexisting Cx. pipiens forms and revealed that the G119S mutation tends to be more frequent in urban than in rural collections sites. These findings provide a reference assessment of OP resistance in Morocco and should help the health authorities to develop informed and sustainable vector control programs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) I: Endogenous Angiotensin Converting Enzyme (ACE) Inhibition

    PubMed Central

    Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Édes, István; Papp, Zoltán; Tóth, Attila

    2014-01-01

    Angiotensin-converting enzyme (ACE) inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected) enzyme activities significantly increased by dilution of human serum samples (23.2±0.7 U/L at 4-fold dilution, 51.4±0.3 U/L at 32-fold dilution, n = 3, p = 0.001), suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655±145 U/L, 605±42 U/L, n = 3, p = 0.715, respectively). FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa) and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after <100 kDa filtering: 56.4±2.4 U/L, n = 4, control: 26.4±0.7 U/L, n = 4, p<0.001). Lineweaver-Burk plot indicated non-competitive inhibition of ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity from 4-fold to 32-fold dilution: 2.8-fold, 1.7-fold, 1.5-fold, 1.8-fold, 2.6-fold, respectively). We report here the existence of an evolutionary conserved mechanism suppressing circulating ACE activity, in vivo, similarly to ACE inhibitory drugs. PMID:24691160

  19. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

    PubMed Central

    Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Fülöp, Gábor Á.; Csató, Viktória; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Szentkirályi, István Elek; Maros, Tamás Miklós; Szerafin, Tamás; Édes, István; Papp, Zoltán; Tóth, Attila

    2014-01-01

    About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo. PMID:24691203

  20. Associations Between Adverse Childhood Experiences and ADHD Diagnosis and Severity.

    PubMed

    Brown, Nicole M; Brown, Suzette N; Briggs, Rahil D; Germán, Miguelina; Belamarich, Peter F; Oyeku, Suzette O

    Although identifying adverse childhood experiences (ACEs) among children with behavioral disorders is an important step in providing targeted therapy and support, little is known about the burden of ACEs among children with attention deficit-hyperactivity disorder (ADHD). We described the prevalence of ACEs in children with and without ADHD, and examined associations between ACE type, ACE score, and ADHD diagnosis and severity. Using the 2011 to 2012 National Survey of Children's Health, we identified children aged 4 to 17 years whose parents indicated presence and severity of ADHD, and their child's exposure to 9 ACEs. Multivariate logistic regression was used to estimate associations between ACEs, ACE score, and parent-reported ADHD and ADHD severity, adjusted for sociodemographic characteristics. In our sample (N = 76,227, representing 58,029,495 children), children with ADHD had a higher prevalence of each ACE compared with children without ADHD. Children who experienced socioeconomic hardship (adjusted odds ratio [aOR], 1.39; 95% confidence interval [CI], 1.21-1.59), divorce (aOR, 1.34; 95% CI, 1.16-1.55), familial mental illness (aOR, 1.55; 95% CI, 1.26-1.90), neighborhood violence (aOR, 1.47; 95% CI, 1.23-1.75), and incarceration (aOR, 1.39; 95% CI, 1.12-1.72) were more likely to have ADHD. A graded relationship was observed between ACE score and ADHD. Children with ACE scores of 2, 3, and ≥4 were significantly more likely to have moderate to severe ADHD. Children with ADHD have higher ACE exposure compared with children without ADHD. There was a significant association between ACE score, ADHD, and moderate to severe ADHD. Efforts to improve ADHD assessment and management should consider routinely evaluating for ACEs. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  1. The ACE2 gene: its potential as a functional candidate for cardiovascular disease.

    PubMed

    Burrell, Louise M; Harrap, Stephen B; Velkoska, Elena; Patel, Sheila K

    2013-01-01

    The RAS (renin-angiotensin system) plays an important role in the pathophysiology of CVD (cardiovascular disease), and RAS blockade is an important therapeutic strategy in the management of CVD. A new counterbalancing arm of the RAS is now known to exist in which ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Altered ACE2 expression is associated with cardiac and vascular disease in experimental models of CVD, and ACE2 is increased in failing human hearts and atherosclerotic vessels. In man, circulating ACE2 activity increases with coronary heart disease, as well as heart failure, and a large proportion of the variation in plasma ACE2 levels has been attributed to hereditary factors. The ACE2 gene maps to chromosome Xp22 and this paper reviews the evidence associating ACE2 gene variation with CVD and considers clues to potential functional ACE2 variants that may alter gene expression or transcriptional activity. Studies to date have investigated ACE2 gene associations in hypertension, left ventricular hypertrophy and coronary artery disease, but the results have been inconsistent. The discrepancies may reflect the sample size of the studies, the gender or ethnicity of subjects, the cardiovascular phenotype or the ACE2 SNP investigated. The frequent observation of apparent sex-dependence might be of special importance, if confirmed. As yet, there are no studies to concurrently assess ACE2 gene polymorphisms and circulating ACE2 activity. Large-scale carefully conducted clinical studies are urgently needed to clarify more precisely the potential role of ACE2 in the CVD continuum.

  2. Gonadectomy prevents the increase in blood pressure and glomerular injury in angiotensin-converting enzyme 2 knockout diabetic male mice. Effects on renin-angiotensin system.

    PubMed

    Clotet, Sergi; Soler, María José; Rebull, Marta; Gimeno, Javier; Gurley, Susan B; Pascual, Julio; Riera, Marta

    2016-09-01

    Angiotensin-converting enzyme 2 (ACE2) deletion worsens kidney injury, and its amplification ameliorates diabetic nephropathy. Male sex increases the incidence, prevalence, and progression of chronic kidney disease in our environment. Here, we studied the effect of ACE2 deficiency and gonadectomy (GDX) on diabetic nephropathy and its relationship with fibrosis, protein kinase B (Akt) activation, and the expression of several components of the renin-angiotensin system (RAS).Mice were injected with streptozotocin to induce diabetes and followed for 19 weeks. Physiological and renal parameters were studied in wild-type and ACE2 knockout (ACE2KO) male mice with and without GDX. Diabetic ACE2KO showed increased blood pressure (BP), glomerular injury, and renal fibrosis compared with diabetic wild-type. Gonadectomized diabetic ACE2KO presented a decrease in BP. In the absence of ACE2, GDX attenuated albuminuria and renal lesions, such as mesangial matrix expansion and podocyte loss. Both, α-smooth muscle actin accumulation and collagen deposition were significantly decreased in renal cortex of gonadectomized diabetic ACE2KO but not diabetic wild-type mice. GDX also reduced circulating ACE activity in ACE2KO mice. Loss of ACE2 modified the effect of GDX on cortical gene expression of RAS in diabetic mice. Akt phosphorylation in renal cortex was increased by diabetes and loss of ACE2 and decreased by GDX in control and diabetic ACE2KO but not in wild-type mice. Our results suggest that GDX may exert a protective effect within the kidney under pathological conditions of diabetes and ACE2 deficiency. This renoprotection may be ascribed to different mechanisms such as decrease in BP, modulation of RAS, and downregulation of Akt-related pathways.

  3. Angiotensin I-converting enzyme insertion/deletion polymorphism and adrenergic response to exercise in hypertensive patients.

    PubMed

    Jalil, Jorge E; Córdova, Samuel; Ocaranza, Marí a; Schumacher, Erwin; Braun, Sandra; Chamorro, Gastón; Fardella, Carlos; Lavandero, Sergio

    2002-08-01

    The insertion/deletion ACE polymorphism (ACE I/D) regulates different levels of circulating and tissue ACE activities, which may induce diverse adrenergic responses to physiological stimuli. The aim of this study was to evaluate the influence of the ACE I/D polymorphism on the adrenergic response to isotonic exercise in middle-aged hypertensive patients. Submaximal exercise (on a treadmill, using the Naughton protocol at 75% of maximal heart rate) was performed in 34 patients homozygous for the ACE I/D polymorphism (ACE II and ACE DD) with untreated essential hypertension (II = 19, DD = 15). Plasma venous adrenaline and noradrenaline were measured at rest and at submaximal exercise. Plasma ACE activity was significantly higher in the hypertensive patients carrying the ACE DD genotype compared with the ACE II group. Left atrium size, as well as LV dimensions, mass, and function, were similar in both groups. Total exercise time, baseline and 75% maximal heart rate (MHR) and blood pressure were similar in both groups. Baseline plasma adrenaline and noradrenaline levels were similar in both groups and increased significantly (p<0.05) by ca. 300% at submaximal exercise without differences between groups. The presence of the D allele on the ACE gene in middle-aged hypertensive patients determines higher circulating ACE activity but not increased sympathetic activity in response to submaximal exercise.

  4. Ancylostoma ceylanicum Excretory-Secretory Protein 2 Adopts a Netrin-Like Fold and Defines a Novel Family of Nematode Proteins

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

    K Kucera; L Harrison; M Cappello

    2011-12-31

    Hookworms are human parasites that have devastating effects on global health, particularly in underdeveloped countries. Ancylostoma ceylanicum infects humans and animals, making it a useful model organism to study disease pathogenesis. A. ceylanicum excretory-secretory protein 2 (AceES-2), a highly immunoreactive molecule secreted by adult worms at the site of intestinal attachment, is partially protective when administered as a mucosal vaccine against hookworm anemia. The crystal structure of AceES-2 determined at 1.75 {angstrom} resolution shows that it adopts a netrin-like fold similar to that found in tissue inhibitors of matrix metalloproteases (TIMPs) and in complement factors C3 and C5. However, recombinantmore » AceES-2 does not significantly inhibit the 10 most abundant human matrix metalloproteases or complement-mediated cell lysis. The presence of a highly acidic surface on AceES-2 suggests that it may function as a cytokine decoy receptor. Several small nematode proteins that have been annotated as TIMPs or netrin-domain-containing proteins display sequence homology in structurally important regions of AceES-2's netrin-likefold. Together, our results suggest that AceES-2 defines a novel family of nematode netrin-like proteins, which may function to modulate the host immune response to hookworm and other parasites.« less

  5. High-Throughput and Rapid Screening of Novel ACE Inhibitory Peptides from Sericin Source and Inhibition Mechanism by Using in Silico and in Vitro Prescriptions.

    PubMed

    Sun, Huaju; Chang, Qing; Liu, Long; Chai, Kungang; Lin, Guangyan; Huo, Qingling; Zhao, Zhenxia; Zhao, Zhongxing

    2017-11-22

    Several novel peptides with high ACE-I inhibitory activity were successfully screened from sericin hydrolysate (SH) by coupling in silico and in vitro approaches for the first time. Most screening processes for ACE-I inhibitory peptides were achieved through high-throughput in silico simulation followed by in vitro verification. QSAR model based predicted results indicated that the ACE-I inhibitory activity of these SH peptides and six chosen peptides exhibited moderate high ACE-I inhibitory activities (log IC 50 values: 1.63-2.34). Moreover, two tripeptides among the chosen six peptides were selected for ACE-I inhibition mechanism analysis which based on Lineweaver-Burk plots indicated that they behave as competitive ACE-I inhibitors. The C-terminal residues of short-chain peptides that contain more H-bond acceptor groups could easily form hydrogen bonds with ACE-I and have higher ACE-I inhibitory activity. Overall, sericin protein as a strong ACE-I inhibition source could be deemed a promising agent for antihypertension applications.

  6. Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity.

    PubMed

    Taddei, Stefano; Bortolotto, L

    2016-10-01

    Historically, the first described effect of an angiotensin converting enzyme (ACE) inhibitor was an increased activity of bradykinin, one of the substrates of ACE. However, in the subsequent years, molecular models describing the mechanism of action of ACE inhibitors in decreasing blood pressure and cardiovascular risk have focused mostly on the renin-angiotensin system. Nonetheless, over the last 20 years, the importance of bradykinin in regulating vasodilation, natriuresis, oxidative stress, fibrinolysis, inflammation, and apoptosis has become clearer. The affinity of ACE appears to be higher for bradykinin than for angiotensin I, thereby suggesting that ACE inhibitors may be more effective inhibitors of bradykinin degradation than of angiotensin II production. Data describing the effect of ACE inhibition on bradykinin signaling support the hypothesis that the most cardioprotective benefits attributed to ACE inhibition may be due to increased bradykinin signaling rather than to decreased angiotensin II signaling, especially when high dosages of ACE inhibitors are considered. In particular, modulation of bradykinin in the endothelium appears to be a major target of ACE inhibition. These new mechanistic concepts may lead to further development of strategies enhancing the bradykinin signaling.

  7. Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors

    PubMed Central

    Wang, Lei; de Kloet, Annette D.; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A.; Pioquinto, David J.; Ludin, Jacob A.; Oh, S. Paul; Katovich, Michael J.; Frazier, Charles J.; Raizada, Mohan K.; Krause, Eric G.

    2016-01-01

    Over-activation of brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme (ACE2) inhibits RAS activity by converting angiotensin II, the effector peptide of RAS, to angiotensin-(1-7), which activates Mas receptors (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ~62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the BLA. PMID:26767952

  8. Angiotensin converting enzyme over expression in myelocytes enhances the immune response

    PubMed Central

    Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.; Giani, Jorge F.; Shah, Kandarp; Bernstein, Ellen; Janjulia, Tea; Koronyo, Yosef; Shi, Peng D.; Koronyo-Hamaoui, Maya; Fuchs, Sebastien; Shen, Xiao Z.

    2015-01-01

    Angiotensin converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis and several aspects of the immune response. ACE 10/10 mice over express ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization towards a proinflammatory phenotype. As a result, ACE 10/10 mice have a highly effective immune response following challenge with either melanoma, bacterial infection or Alzheimer’s disease. The ACE 10/10 mice suggest that enhanced monocytic function greatly contributes to the ability of the immune response to defend against a wide variety of antigenic and non-antigenic challenges. PMID:24633750

  9. 7 CFR 2502.3 - Deviations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Deviations. 2502.3 Section 2502.3 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ADVOCACY AND OUTREACH, DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM General Information § 2502.3 Deviations...

  10. 7 CFR 2502.3 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Deviations. 2502.3 Section 2502.3 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ADVOCACY AND OUTREACH, DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM General Information § 2502.3 Deviations...

  11. 7 CFR 2502.3 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Deviations. 2502.3 Section 2502.3 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF ADVOCACY AND OUTREACH, DEPARTMENT OF AGRICULTURE AGRICULTURAL CAREER AND EMPLOYMENT (ACE) GRANTS PROGRAM General Information § 2502.3 Deviations...

  12. Just Out of Reach: On the Reliability of the Action-Sentence Compatibility Effect

    PubMed Central

    Papesh, Megan H.

    2015-01-01

    The action-sentence compatibility effect (ACE; Glenberg & Kaschak, 2002), a hallmark finding in Embodied Cognition, implicates the motor system in language comprehension. In the ACE, people process sentences implying movement toward or away from themselves, responding with actions toward or away from their bodies. These processes interact, implying a linkage between linguistic and motor systems. From a theoretical perspective, the ACE has been extremely influential, being widely-cited evidence in favor of embodied cognition. The present study began as an attempt to extend the ACE in a new direction, but eventually became a series of attempts to simply replicate the effect. Across eight experiments, I tested whether the ACE extends to a novel mouse-tracking method and/or is susceptible to higher-order cognitive influences. In three experiments, attempts were made to “disembody” the ACE by presenting participants' names on the computer screen (as in Markman & Brendl, 2005). In each experiment, the ACE could not be disembodied, because the ACE did not occur. In further experiments, the ACE was not observed in reading times, regardless of response mode (mouse movements versus button-presses) or stimuli, including those from the original research. Similarly, no ACE was observed in physical movement times. Bayes Factor analyses of the current experiments, and the previous ACE literature, suggest that the evidence for the ACE is generally weak: Many studies considered as positive evidence actually support the null hypothesis, and very few published results offer strong evidence for the ACE. Implications for the embodiment hypothesis are discussed. PMID:26595844

  13. Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

    PubMed Central

    Carvalho, Clarissa Coelho; Florentino, Rodrigo Machado; França, Andressa; Matias, Eveline; Guimarães, Paola Bianchi; Batista, Carolina; Freire, Valder; Carmona, Adriana Karaoglanovic; Pesquero, João Bosco; de Paula, Ana Maria; Foureaux, Giselle; Leite, Maria de Fatima

    2016-01-01

    Background The angiotensin-I converting enzyme (ACE) plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II). More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet. Aim Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration. Results We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC), and experimental results in CHO cells, demonstrated that the β3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5) showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril) or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein. Conclusion ACE activation regulates melanoma cell proliferation and migration. PMID:27992423

  14. The Pharmacogenetic Footprint of ACE Inhibition: A Population-Based Metabolomics Study.

    PubMed

    Altmaier, Elisabeth; Menni, Cristina; Heier, Margit; Meisinger, Christa; Thorand, Barbara; Quell, Jan; Kobl, Michael; Römisch-Margl, Werner; Valdes, Ana M; Mangino, Massimo; Waldenberger, Melanie; Strauch, Konstantin; Illig, Thomas; Adamski, Jerzy; Spector, Tim; Gieger, Christian; Suhre, Karsten; Kastenmüller, Gabi

    2016-01-01

    Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of ACE inhibitors, effects of genetic variation on metabolism need to be considered since genetic variance in the ACE gene locus was found to be associated with ACE-concentration in blood as well as with changes in the metabolic profiles of a general population. To investigate the interactions between genetic variance at the ACE-locus and the influence of ACE-therapy on the metabolic status we analyzed 517 metabolites in 1,361 participants from the KORA F4 study. We replicated our results in 1,964 individuals from TwinsUK. We observed differences in the concentration of five dipeptides and three ratios of di- and oligopeptides between ACE inhibitor users and non-users that were genotype dependent. Such changes in the concentration affected major homozygotes, and to a lesser extent heterozygotes, while minor homozygotes showed no or only small changes in the metabolite status. Two of these resulting dipeptides, namely aspartylphenylalanine and phenylalanylserine, showed significant associations with blood pressure which qualifies them-and perhaps also the other dipeptides-as readouts of ACE-activity. Since so far ACE activity measurement is substrate specific due to the usage of only one oligopeptide, taking several dipeptides as potential products of ACE into account may provide a broader picture of the ACE activity.

  15. Brain ACE2 shedding contributes to the development of neurogenic hypertension

    PubMed Central

    Chhabra, Kavaljit H.; Lazartigues, Eric

    2015-01-01

    Rationale Over-activity of the brain Renin Angiotensin System (RAS) is a major contributor to neurogenic hypertension. While over-expression of Angiotensin-Converting Enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming Angiotensin (Ang)-II into Ang-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension. Objective We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. Methods and Results To test this hypothesis, we used the DOCA-salt model of neurogenic hypertension in non-transgenic (NT) and syn-hACE2 mice over-expressing ACE2 in neurons. DOCA-salt treatment in NT mice led to significant increases in blood pressure, hypothalamic Ang-II levels, inflammation, impaired baroreflex sensitivity, autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, while these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled a rise in ACE2 activity in the cerebrospinal fluid of NT mice following DOCA-salt treatment and was accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function. Conclusions Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension. PMID:24014829

  16. Scientific Discovery through Advanced Computing (SciDAC-3) Partnership Project Annual Report

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

    Hoffman, Forest M.; Bochev, Pavel B.; Cameron-Smith, Philip J..

    The Applying Computationally Efficient Schemes for BioGeochemical Cycles ACES4BGC Project is advancing the predictive capabilities of Earth System Models (ESMs) by reducing two of the largest sources of uncertainty, aerosols and biospheric feedbacks, with a highly efficient computational approach. In particular, this project is implementing and optimizing new computationally efficient tracer advection algorithms for large numbers of tracer species; adding important biogeochemical interactions between the atmosphere, land, and ocean models; and applying uncertainty quanti cation (UQ) techniques to constrain process parameters and evaluate uncertainties in feedbacks between biogeochemical cycles and the climate system.

  17. Adverse childhood experiences (ACE) and adult attachment interview (AAI) in a non-clinical population.

    PubMed

    Thomson, Paula; Jaque, S Victoria

    2017-08-01

    Adverse childhood experiences (ACE) tend to be interrelated rather than independently occurring. There is a graded effect associated with ACE exposure and pathology, with an increase when ACE exposure is four or more. This study examined a sample of active individuals (n=129) to determine distribution patterns and relationships between ACEs, attachment classification, unresolved mourning (U), and disclosure difficulty. The results of this study demonstrated a strong relationship between increased ACEs and greater unresolved mourning. Specifically, the group differences for individuals who experienced no ACE (n=42, 33%), those with 1-3 ACEs (n=48, 37.8%), and those with ≥4 ACEs (n=37, 29.1%) revealed a pattern in which increased group ACE exposure was associated with greater lack of resolution for past trauma/loss experiences, more adult traumatic events, and more difficulty disclosing past trauma. Despite ≥4 ACEs, 51.4% of highly exposed individuals were classified as secure in the Adult Attachment Interview. Resilience in this group may be related to a combination of attachment security, college education, and engagement in meaningful activities. Likewise, adversity may actually encourage the cultivation of more social support, goal efficacy, and planning behaviors; factors that augment resilience to adversity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Comparative Study of Three Methods for Affinity Measurements: Capillary Electrophoresis Coupled with UV Detection and Mass Spectrometry, and Direct Infusion Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mironov, Gleb G.; Logie, Jennifer; Okhonin, Victor; Renaud, Justin B.; Mayer, Paul M.; Berezovski, Maxim V.

    2012-07-01

    We present affinity capillary electrophoresis and mass spectrometry (ACE-MS) as a comprehensive separation technique for label-free solution-based affinity analysis. The application of ACE-MS for measuring affinity constants between eight small molecule drugs [ibuprofen, s-flurbiprofen, diclofenac, phenylbutazone, naproxen, folic acid, resveratrol, and 4,4'-(propane-1,3-diyl) dibenzoic acid] and β-cyclodextrin is described. We couple on-line ACE with MS to combine the separation and kinetic capability of ACE together with the molecular weight and structural elucidation of MS in one system. To understand the full potential of ACE-MS, we compare it with two other methods: Direct infusion mass spectrometry (DIMS) and ACE with UV detection (ACE-UV). After the evaluation, DIMS provides less reliable equilibrium dissociation constants than separation-based ACE-UV and ACE-MS, and cannot be used solely for the study of noncovalent interactions. ACE-MS determines apparent dissociation constants for all reacting small molecules in a mixture, even in cases when drugs overlap with each other during separation. The ability of ACE-MS to interact, separate, and rapidly scan through m/z can facilitate the simultaneous affinity analysis of multiple interacting pairs, potentially leading to the high-throughput screening of drug candidates.

  19. Adverse childhood experiences (ACEs) and later-life depression: perceived social support as a potential protective factor.

    PubMed

    Cheong, E Von; Sinnott, Carol; Dahly, Darren; Kearney, Patricia M

    2017-09-01

    To investigate associations between adverse childhood experiences (ACEs) and later-life depressive symptoms; and to explore whether perceived social support (PSS) moderates these. We analysed baseline data from the Mitchelstown (Ireland) 2010-2011 cohort of 2047 men and women aged 50-69 years. Self-reported measures included ACEs (Centre for Disease Control ACE questionnaire), PSS (Oslo Social Support Scale) and depressive symptoms (CES-D). The primary exposure was self-report of at least one ACE. We also investigated the effects of ACE exposure by ACE scores and ACE subtypes abuse, neglect and household dysfunction. Associations between each of these exposures and depressive symptoms were estimated using logistic regression, adjusted for socio-demographic factors. We tested whether the estimated associations varied across levels of PSS (poor, moderate and strong). 23.7% of participants reported at least one ACE (95% CI 21.9% to 25.6%). ACE exposures (overall, subtype or ACE scores) were associated with a higher odds of depressive symptoms, but only among individuals with poor PSS. Exposure to any ACE (vs none) was associated with almost three times the odds of depressive symptoms (adjusted OR 2.85; 95% CI 1.64 to 4.95) among individuals reporting poor PSS, while among those reporting moderate and strong PSS, the adjusted ORs were 2.21 (95% CI 1.52 to 3.22) and 1.39 (95% CI 0.85 to 2.29), respectively. This pattern of results was similar when exposures were based on ACE subtype and ACE scores, though the interaction was clearly strongest among those reporting abuse. ACEs are common among older adults in Ireland and are associated with higher odds of later-life depressive symptoms, particularly among those with poor PSS. Interventions that enhance social support, or possibly perceptions of social support, may help reduce the burden of depression in older populations with ACE exposure, particularly in those reporting abuse. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  20. An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito.

    PubMed

    Assogba, Benoît S; Djogbénou, Luc S; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

    2015-10-05

    Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1(R) allele), is already present. Furthermore, a duplicated allele (ace-1(D)) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1(D) confers less resistance than ace-1(R), the high fitness cost associated with ace-1(R) is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management.

  1. An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito

    PubMed Central

    Assogba, Benoît S.; Djogbénou, Luc S.; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

    2015-01-01

    Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1R allele), is already present. Furthermore, a duplicated allele (ace-1D) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1D confers less resistance than ace-1R, the high fitness cost associated with ace-1R is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management. PMID:26434951

  2. ACE blood test

    MedlinePlus

    ... to help diagnose and monitor a disorder called sarcoidosis . People with sarcoidosis may have their ACE level tested regularly to ... normal ACE level may be a sign of sarcoidosis. ACE levels may rise or fall as sarcoidosis ...

  3. Affinity capillary electrophoresis for studying interactions in life sciences.

    PubMed

    Olabi, Mais; Stein, Matthias; Wätzig, Hermann

    2018-05-10

    Affinity capillary electrophoresis (ACE) analyzes noncovalent interactions between ligands and analytes based on changes in their electrophoretic mobility. This technique has been widely used to investigate various biomolecules, mainly proteins, polysaccharides and hormones. ACE is becoming a technique of choice to validate high throughput screening results, since it is very predictively working in realistic and relevant media, e.g. in body fluids. It is highly recommended to incorporate ACE as a powerful analytical tool to properly prepare animal testing and preclinical studies. The interacting molecules can be found free in solution or can be immobilized to a solid support. Thus, ACE is classified in two modes, free solution ACE and immobilized ACE. Every ACE mode has advantages and disadvantages. Each can be used for a variety of applications. This review covers literature of scopus and SciFinder data base in the period from 2016 until beginning 2018, including the keywords "affinity capillary electrophoresis", "immunoaffinity capillary electrophoresis", "immunoassay capillary electrophoresis" and "immunosorbent capillary electrophoresis". More than 200 articles have been found and 112 have been selected and thoroughly discussed. During this period, the data processing and the underlying calculations in mobility shift ACE (ms ACE), frontal analysis ACE (FA ACE) and plug-plug kinetic capillary electrophoresis (ppKCE) as mostly applied free solution techniques have substantially improved. The range of applications in diverse free solution and immobilized ACE techniques has been considerably broadened. Copyright © 2018. Published by Elsevier Inc.

  4. Patterns of adverse childhood experiences and substance use among young adults: A latent class analysis.

    PubMed

    Shin, Sunny H; McDonald, Shelby Elaine; Conley, David

    2018-03-01

    Adverse childhood experiences (ACEs) have been strongly linked with subsequent substance use. The aim of this study was to investigate how different patterns of ACEs influence substance use in young adulthood. Using a community sample of young individuals (N=336; ages 18-25), we performed latent class analyses (LCA) to identify homogenous groups of young people with similar patterns of ACEs. Exposure to ACEs incorporates 13 childhood adversities including childhood maltreatment, household dysfunction, and community violence. Multiple linear and logistic regression models were used in an effort to examine the associations between ACEs classes and four young adult outcomes such as alcohol-related problems, current tobacco use, drug dependence symptoms, and psychological distress. LCA identified four heterogeneous classes of young people distinguished by different patterns of ACEs exposure: Low ACEs (56%), Household Dysfunction/Community Violence (14%), Emotional ACEs (14%), and High/Multiple ACEs (16%). Multiple regression analyses found that compared to those in the Low ACEs class, young adults in the High/Multiple ACEs class reported more alcohol-related problems, current tobacco use, and psychological symptoms, controlling for sociodemographic characteristics and common risk factors for substance use such as peer substance use. Our findings confirm that for many young people, ACEs occur as multiple rather than single experiences. The results of this research suggest that exposure to poly-victimization during childhood is particularly related to substance use during young adulthood. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Maternal adverse childhood experiences and antepartum risks: the moderating role of social support.

    PubMed

    Racine, Nicole; Madigan, Sheri; Plamondon, Andre; Hetherington, Erin; McDonald, Sheila; Tough, Suzanne

    2018-03-28

    The aims of the current study were to examine the association between maternal adverse childhood experiences (ACEs) and antepartum health risks, and to investigate whether social support moderated this association. It was hypothesized that ACEs would be associated with antepartum health risks; however, social support in the prenatal period would buffer mothers from the deleterious consequences of ACEs. Data from 1994 women (mean age = 31 years) and their infants were collected from a longitudinal cohort recruited in health care offices in Alberta, Canada. Pregnant women completed questionnaires related to ACEs prior to the age of 18 and prenatal social support, and a health care professional assessed the mother's antepartum health risk. ACEs included physical, emotional, and sexual abuse, exposure to domestic violence, as well as exposure to household dysfunction such as parental substance use, mental illness, or incarceration. Regression analyses demonstrated a positive association between ACEs and antepartum health risks. However, a significant interaction between maternal ACEs and social support was also observed. Specifically, women exposed to high ACEs and low social support in pregnancy had high antepartum health risks. However, among mothers who had high ACEs but also high levels of social support, there was no association between ACEs and antepartum health risk. A history of ACEs can place mothers at risk of antepartum health complications. However, a resiliency effect was observed: women with a history of ACEs were buffered from experiencing antepartum health risks if they reported high levels of social support in pregnancy.

  6. Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans.

    PubMed

    Pedersen-Bjergaard, Ulrik; Thomsen, Carsten E; Høgenhaven, Hans; Smed, Annelise; Kjaer, Troels W; Holst, Jens J; Dela, Flemming; Hilsted, Linda; Frandsen, Erik; Pramming, Stig; Thorsteinsson, Birger

    2008-03-01

    In type 1 diabetes increased risk of severe hypoglycaemia is associated with high angiotensin-converting enzyme (ACE) activity. We tested in healthy humans the hypothesis that this association is explained by the reduced ability of subjects with high ACE activity to maintain normal cognitive function during hypoglycaemia. Sixteen healthy volunteers selected by either particularly high or low serum ACE activity were subjected to hypoglycaemia (plasma glucose 2.7 mmol/L). Cognitive function was assessed by choice reaction tests. Despite a similar hypoglycaemic stimulus in the two groups, only the group with high ACE activity showed significant deterioration in cognitive performance during hypoglycaemia. In the high ACE group mean reaction time (MRT) in the most complex choice reaction task was prolonged and error rate (ER) was increased in contrast to the low ACE group. The total hypoglycaemic symptom response was greater in the high ACE group than in the low ACE group (p=0.031). There were no differences in responses of counterregulatory hormones or in concentrations of substrates between the groups. Healthy humans with high ACE activity are more susceptible to cognitive dysfunction and report higher symptom scores during mild hypoglycaemia than subjects with low ACE activity.

  7. Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

    PubMed Central

    Chung, Chia-Min; Wang, Ruey-Yun; Fann, Cathy S. J.; Chen, Jaw-Wen; Jong, Yuh-Shiun; Jou, Yuh-Shan; Yang, Hsin-Chou; Kang, Chih-Sen; Chen, Chien-Chung; Chang, Huan-Cheng; Pan, Wen-Harn

    2013-01-01

    Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10–16 to <10–33). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3′UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects. PMID:23469169

  8. Association of Angiotensin-Converting Enzyme ACE Gene Polymorphism with ACE Activity and Susceptibility to Vitiligo in Egyptian Population.

    PubMed

    Badran, Dahlia I; Nada, Hesham; Hassan, Ranya

    2015-05-01

    The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with vitiligo in the Indians and Koreans, but not in those of English or Turkish background. We investigated the ACE (I/D) polymorphism in vitiligo patients for the first time in Egypt and compared serum ACE levels between vitiligo patients and controls. The present study was carried out in 100 vitiligo patients (40 males and 60 females) and in 100 healthy controls of an Egyptian population using the polymerase chain reaction genotyping method. The ACE genotype and allele frequency was significantly different between vitiligo patients and controls. Our results revealed a significant increase in the frequency of the ACE I allele (p=0.002; odds ratio: 1.99; 95% confidence intervals: 1.207-3.284) with an overrepresentation of I/D genotype in the vitiligo patient group. Furthermore, there was a significant difference between the segmental, nonsegmental, and focal vitiligo in ACE gene genotype distribution. Serum ACE levels were significantly increased in vitiligo patients compared to controls (p=0.034). This study suggests that, for the first time, ACE gene polymorphism confers susceptibility to vitiligo in the Egyptian population.

  9. A novel acetylcholinesterase gene in mosquitoes codes for the insecticide target and is non-homologous to the ace gene in Drosophila.

    PubMed Central

    Weill, Mylène; Fort, Philippe; Berthomieu, Arnaud; Dubois, Marie Pierre; Pasteur, Nicole; Raymond, Michel

    2002-01-01

    Acetylcholinesterase (AChE) is the target of two major insecticide families, organophosphates (OPs) and carbamates. AChE insensitivity is a frequent resistance mechanism in insects and responsible mutations in the ace gene were identified in two Diptera, Drosophila melanogaster and Musca domestica. However, for other insects, the ace gene cloned by homology with Drosophila does not code for the insensitive AChE in resistant individuals, indicating the existence of a second ace locus. We identified two AChE loci in the genome of Anopheles gambiae, one (ace-1) being a new locus and the other (ace-2) being homologous to the gene previously described in Drosophila. The gene ace-1 has no obvious homologue in the Drosophila genome and was found in 15 mosquito species investigated. In An. gambiae, ace-1 and ace-2 display 53% similarity at the amino acid level and an overall phylogeny indicates that they probably diverged before the differentiation of insects. Thus, both genes are likely to be present in the majority of insects and the absence of ace-1 in Drosophila is probably due to a secondary loss. In one mosquito (Culex pipiens), ace-1 was found to be tightly linked with insecticide resistance and probably encodes the AChE OP target. These results have important implications for the design of new insecticides, as the target AChE is thus encoded by distinct genes in different insect groups, even within the Diptera: ace-2 in at least the Drosophilidae and Muscidae and ace-1 in at least the Culicidae. Evolutionary scenarios leading to such a peculiar situation are discussed. PMID:12396499

  10. Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

    PubMed Central

    Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

    2016-01-01

    Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration. PMID:28066203

  11. A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

    PubMed Central

    Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

    2013-01-01

    Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

  12. Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment.

    PubMed

    Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

    2016-01-01

    Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients ( p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) ( p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score ( p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups ( p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

  13. Functional characterisation of a cyst nematode acetylcholinesterase gene using Caenorhabditis elegans as a heterologous system.

    PubMed

    Costa, Joana C; Lilley, Catherine J; Atkinson, Howard J; Urwin, Peter E

    2009-06-01

    Migration of plant-parasitic nematode infective larval stages through soil and invasion of roots requires perception and integration of sensory cues culminating in particular responses that lead to root penetration and parasite establishment. Components of the chemoreceptive neuronal circuitry involved in these responses are targets for control measures aimed at preventing infection. Here we report, to our knowledge, the first isolation of cyst nematode ace-2 genes encoding acetylcholinesterase (AChE). The ace-2 genes from Globodera pallida (Gp-ace-2) and Heterodera glycines (Hg-ace-2) show homology to ace-2 of Caenorhabditis elegans (Ce-ace-2). Gp-ace-2 is expressed most highly in the infective J2 stage with lowest expression in the early parasitic stages. Expression and functional analysis of the Globodera gene were carried out using the free-living nematode C. elegans in order to overcome the refractory nature of the obligate parasite G. pallida to many biological studies. Caenorhabditis elegans transformed with a GFP reporter construct under the control of the Gp-ace-2 promoter exhibited specific and restricted GFP expression in neuronal cells in the head ganglia. Gp-ACE-2 protein can functionally complement its C. elegans homologue. A chimeric construct containing the Ce-ace-2 promoter region and the Gp-ace-2 coding region and 3' untranslated region was able to restore a normal phenotype to the uncoordinated C. elegans double mutant ace-1;ace-2. This study demonstrates conservation of AChE function and expression between free-living and plant-parasitic nematode species, and highlights the utility of C. elegans as a heterologous system to study neuronal aspects of plant-parasitic nematode biology.

  14. Adult and Continuing Education in Kenya: The Need for Transformative Leadership

    ERIC Educational Resources Information Center

    Nyatuka, Benard O.; Ndiku, Judah M.

    2015-01-01

    As a multidisciplinary process, Adult and Continuing Education (ACE) is meant to foster efficient lifelong learning throughout life. To achieve this, it should be geared towards providing knowledge, skills as well as attitudes that ensure equal opportunities to life, meeting the needs of individuals of all ages so as to understand the world and…

  15. Adverse Childhood Experiences, Support, and the Perception of Ability to Work in Adults with Disability.

    PubMed

    Schüssler-Fiorenza Rose, Sophia Miryam; Eslinger, Jessica G; Zimmerman, Lindsey; Scaccia, Jamie; Lai, Betty S; Lewis, Catrin; Alisic, Eva

    2016-01-01

    To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability. Adults (ages 18-64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009). The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was used to adjust for potential confounders (age, sex and race) and to evaluate whether there was an independent effect of ACEs on work inability after adding other important predictors (support, education, health) to the model. ACEs were highly prevalent with almost 75% of the sample reporting at least one ACE category and over 25% having a high ACE burden (4 or more categories). ACEs were strongly associated with functional support. Participants experiencing a high ACE burden had a higher adjusted odds ratio (OR) [95% confidence interval] of 1.9 [1.5-2.4] of work inability (reference: zero ACEs). Good functional support (adjusted OR 0.52 [0.42-0.63]) and structural support (adjusted OR 0.48 [0.41-0.56]) were protective against work inability. After adding education and health to the model, ACEs no longer appeared to have an independent effect. Structural support remained highly protective, but functional support only appeared to be protective in those with good physical health. ACEs are highly prevalent in working-age US adults with a disability, particularly young adults. ACEs are associated with decreased support, lower educational attainment and worse adult health. Health care providers are encouraged to screen for ACEs. Addressing the effects of ACEs on health and support, in addition to education and retraining, may increase ability to work in those with a disability.

  16. Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial

    PubMed Central

    Bhatnagar, Vibha; O’Connor, Daniel T.; Schork, Nicholas J.; Salem, Rany M.; Nievergelt, Caroline M.; Rana, Brinda K.; Smith, Douglas W.; Bakris, George L.; Middleton, John P.; Norris, Keith C.; Wright, Jackson T.; Cheek, Deanna; Hiremath, Leena; Contreras, Gabriel; Appel, Lawrence J.; Lipkowitz, Michael S.

    2009-01-01

    Objective It has yet to be determined whether genotyping at the angiotensin-converting enzyme (ACE) locus is predictive of blood pressure response to an ACE inhibitor. Methods Participants from the African American Study of Kidney Disease and Hypertension trial randomized to the ACE inhibitor ramipril (n = 347) were genotyped at three polymorphisms on ACE, just downstream from the ACE insertion/deletion polymorphism (Ins/Del): G12269A, C17888T, and G20037A. Time to reach target mean arterial pressure (≤ 107 mmHg) was analyzed by genotype and ACE haplotype using Kaplan–Meier survival curves and Cox proportional hazard models. Results Individuals with a homozygous genotype at G12269A responded significantly faster than those with a heterozygous genotype; the adjusted (average number of medications and baseline mean arterial pressure) hazard ratio (homozygous compared to heterozygous genotype) was 1.86 (95% confidence limits 1.32–3.23; P < 0.001 for G12269A genotype). The adjusted hazard ratio for participants with homozygous ACE haplotypes compared to those heterozygous ACE haplotypes was 1.40 (1.13–1.75; P = 0.003 for haplotype). The ACE genotype effects were specific for ACE inhibition (i.e., not seen among those randomized to a calcium channel blocker), and were independent of population stratification. Conclusions African-Americans with a homozygous genotype at G12269A or homozygous ACE haplotypes responded to ramipril significantly faster than those with a heterozygous genotype or heterozygous haplotypes, suggesting that heterosis may be an important determinant of responsiveness to an ACE inhibitor. These associations may be a result of biological activity of this polymorphism, or of linkage disequilibrium with nearby variants such as the ACE Ins/Del, perhaps in the regulation of ACE splicing. PMID:17885551

  17. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease.

    PubMed

    Tekatas, Demet D; Bahcecioglu, Ibrahim H; Ispiroglu, Murat; Sahin, Abdurrahman; Ilhan, Necip; Yalniz, Mehmet; Demirel, Ulvi

    2016-01-01

    In this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease. Liver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification. A total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92). In this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD. Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.

  18. Blood type gene locus has no influence on ACE association with Alzheimer's disease.

    PubMed

    Braae, Anne; Medway, Christopher; Carrasquillo, Minerva; Younkin, Steven; Kehoe, Patrick G; Morgan, Kevin

    2015-04-01

    The ABO blood group locus was recently found to contribute independently and via interactions with angiotensin-converting enzyme (ACE) gene variation to plasma levels of ACE. Variation in ACE has previously been not only implicated as individually conferring susceptibility for Alzheimer's disease (AD) but also proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, whereas the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variations in the genetic susceptibility of 2067 AD cases compared with 1376 nondemented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Reporting of the translation and cultural adaptation procedures of the Addenbrooke's Cognitive Examination version III (ACE-III) and its predecessors: a systematic review.

    PubMed

    Mirza, Nadine; Panagioti, Maria; Waheed, Muhammad Wali; Waheed, Waquas

    2017-09-13

    The ACE-III, a gold standard for screening cognitive impairment, is restricted by language and culture, with no uniform set of guidelines for its adaptation. To develop guidelines a compilation of all the adaptation procedures undertaken by adapters of the ACE-III and its predecessors is needed. We searched EMBASE, Medline and PsychINFO and screened publications from a previous review. We included publications on adapted versions of the ACE-III and its predecessors, extracting translation and cultural adaptation procedures and assessing their quality. We deemed 32 papers suitable for analysis. 7 translation steps were identified and we determined which items of the ACE-III are culturally dependent. This review lists all adaptations of the ACE, ACE-R and ACE-III, rates the reporting of their adaptation procedures and summarises adaptation procedures into steps that can be undertaken by adapters.

  20. Adverse childhood events and current depressive symptoms among women in Hawaii: 2010 BRFSS, Hawaii.

    PubMed

    Remigio-Baker, Rosemay A; Hayes, Donald K; Reyes-Salvail, Florentina

    2014-12-01

    Research on the association between adverse childhood events (ACEs) and depression among women in Hawaii is scarce. ACEs have been linked to unfavorable health behaviors such as smoking and binge drinking which are more prevalent in the state compared to the US overall. The concomitant presence of ACEs with smoking or binge drinking may explain the excess depression prevalence in Hawaii compared to the national average. Using data of women residing in the state (2010 Hawaii Behavioral Risk Factor Surveillance System Survey), we examined the association between ACEs count or type (household dysfunction and physical, verbal and sexual abuse) and current depressive symptoms (CDS), in addition to modification by current smoking status (smoked >100 cigarettes in a lifetime and currently smoke) and binge drinking (consumed ≥4 alcoholic beverage within the past month and in ≥1 occasion(s)). Evaluation of ACEs before age 18 consisted of 11 indicators. Eight indicators of the Patient Health Questionnaire (PHQ-8) were used to assess CDS. All analyses utilized logistic regression taking into account sampling design. The odds ratio of having CDS between those with versus without ACEs increased per increasing number of ACEs (1 ACE: OR = 2.11, CI = 1.16-3.81; 2 ACEs: OR = 2.90, CI = 1.51-5.58; 3 or 4 ACEs: OR = 3.94, CI = 2.13-7.32; 5+ ACEs: OR = 4.04, CI = 2.26-7.22). Household dysfunction (OR = 2.10, CI = 1.37-3.23), physical abuse (OR = 1.67, CI = 1.08-2.59), verbal abuse (OR = 3.21, CI = 2.03-5.09) and sexual abuse (OR = 1.68, CI = 1.04-2.71) were all positively associated with CDS. Verbal abuse had the strongest magnitude of association. Neither current smoking status nor binge drinking modified the relationship between ACEs count (or type) and CDS. In conclusion, the presence of ACEs among women in Hawaii was indicative of CDS in adulthood, notably verbal abuse. Further, a dose response existed between the number of ACEs and the odds for CDS. The concomitant exposure to ACEs and current smoking status or binge drinking did not elevate odds for CDS.

  1. Adverse Childhood Experiences (ACEs) questionnaire and Adult Attachment Interview (AAI): implications for parent child relationships.

    PubMed

    Murphy, Anne; Steele, Miriam; Dube, Shanta Rishi; Bate, Jordan; Bonuck, Karen; Meissner, Paul; Goldman, Hannah; Steele, Howard

    2014-02-01

    Although Adverse Childhood Experiences (ACEs) are linked to increased health problems and risk behaviors in adulthood, there are no studies on the association between ACEs and adults' states of mind regarding their early childhood attachments, loss, and trauma experiences. To validate the ACEs questions, we analyzed the association between ACEs and emotional support indicators and Adult Attachment Interview (AAI) classifications in terms of unresolved mourning regarding past loss or trauma and discordant states of mind in cannot classify (U/CC) interviews. Seventy-five urban women (41 clinical and 34 community) completed a questionnaire on ACEs, which included 10 categories of abuse, neglect, and household dysfunction, in addition to emotional support. Internal psychological processes or states of mind concerning attachment were assessed using the AAI. ACE responses were internally consistent (Cronbach's α=.88). In the clinical sample, 84% reported≥4 ACEs compared to 27% among the community sample. AAIs judged U/CC occurred in 76% of the clinical sample compared to 9% in the community sample. When ACEs were≥4, 65% of AAIs were classified U/CC. Absence of emotional support in the ACEs questionnaire was associated with 72% of AAIs being classified U/CC. As the number of ACEs and the lack of emotional support increases so too does the probability of AAIs being classified as U/CC. Findings provide rationale for including ACEs questions in pediatric screening protocols to identify and offer treatment reducing the intergenerational transmission of risk associated with problematic parenting. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Identification and in silico characterization of a novel peptide inhibitor of angiotensin converting enzyme from pigeon pea (Cajanus cajan).

    PubMed

    Nawaz, K A Ayub; David, Swapna Merlin; Murugesh, Easwaran; Thandeeswaran, Murugesan; Kiran, Kalarikkal Gopikrishnan; Mahendran, Ramasamy; Palaniswamy, Muthusamy; Angayarkanni, Jayaraman

    2017-12-01

    Plants are important sources of bioactive peptides. Among these, angiotensin converting enzyme (ACE) inhibitory peptides have a major focus on their ability to prevent hypertension. Inhibition of ACE has been established as an effective approach for the treatment of ACE associated diseases. Some synthetic ACE inhibitory drugs cause side effects and hence there is a constant interest in natural compounds as alternatives. The study was designed to identify and characterize a peptide molecule from pigeon pea which has the biological property to inhibit ACE and can be developed as a therapeutic approach towards hypertension. Seeds of pigeon pea (Cajanus cajan (L.) Millsp.) was fermented with Aspergillus niger, a proteolytic fungus isolated from spoiled milk sweet. The extract was purified by size exclusion chromatography by FPLC system. The fractions that showed ACE inhibition was subjected to LC-MS/MS for sequence identification. The stability of the peptide was analyzed by molecular dynamic simulations and the interaction sites with ACE were identified by molecular docking. The study report a novel ACE inhibitory octapeptide Val-Val-Ser-Leu-Ser-Ile-Pro-Arg with a molecular mass of 869.53 Da. The Lineweaver-Burk plot indicated that the inhibition of ACE by this peptide is in competitive mode. Also, molecular docking and simulation studies showed a strong and stable interaction of the peptide with ACE. The results clearly show the inhibitory property of the peptide against ACE and hence it can be explored as a therapeutic strategy towards hypertension and other ACE associated diseases. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. DNA Methylation Analysis of the Angiotensin Converting Enzyme (ACE) Gene in Major Depression

    PubMed Central

    Zill, Peter; Baghai, Thomas C.; Schüle, Cornelius; Born, Christoph; Früstück, Clemens; Büttner, Andreas; Eisenmenger, Wolfgang; Varallo-Bedarida, Gabriella; Rupprecht, Rainer; Möller, Hans-Jürgen; Bondy, Brigitta

    2012-01-01

    Background The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ∼40%–50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. Materials and Methods The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. Results We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04). Conclusion The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders. PMID:22808171

  4. The two-component system GrvRS (EtaRS) regulates ace expression in Enterococcus faecalis OG1RF.

    PubMed

    Roh, Jung Hyeob; Singh, Kavindra V; La Rosa, Sabina Leanti; Cohen, Ana Luisa V; Murray, Barbara E

    2015-01-01

    Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46 °C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. Pharmacologic modulation of ACE2 expression.

    PubMed

    Soler, María José; Barrios, Clara; Oliva, Raymond; Batlle, Daniel

    2008-10-01

    Angiotensin-converting enzyme 2 (ACE2) is an enzymatically active homologue of angiotensin-converting enzyme that degrades angiotensin I, angiotensin II, and other peptides. Recent studies have shown that under pathologic conditions, ACE2 expression in the kidney is altered. In this review, we briefly summarize recent studies dealing with pharmacologic interventions that modulate ACE2 expression. ACE2 amplification may have a potential therapeutic role for kidney disease and hypertension.

  6. A Discussion of Aerodynamic Control Effectors (ACEs) for Unmanned Air Vehicles (UAVs)

    NASA Technical Reports Server (NTRS)

    Wood, Richard M.

    2002-01-01

    A Reynolds number based, unmanned air vehicle classification structure has been developed which identifies four classes of unmanned air vehicle concepts. The four unmanned air vehicle (UAV) classes are; Micro UAV, Meso UAV, Macro UAV, and Mega UAV. In a similar fashion a labeling scheme for aerodynamic control effectors (ACE) was developed and eleven types of ACE concepts were identified. These eleven types of ACEs were laid out in a five (5) layer scheme. The final section of the paper correlated the various ACE concepts to the four UAV classes and ACE recommendations are offered for future design activities.

  7. A Low-Protein Diet Enhances Angiotensin II Production in the Lung of Pregnant Rats but Not Nonpregnant Rats

    PubMed Central

    Gao, Haijun; Tanchico, Daren Tubianosa; Yallampalli, Uma; Yallampalli, Chandrasekhar

    2016-01-01

    Pulmonary angiotensin II production is enhanced in pregnant rats fed a low-protein (LP) diet. Here we assessed if LP diet induces elevations in angiotensin II production in nonpregnant rats and whether Ace expression and ACE activity in lungs are increased. Nonpregnant rats were fed a normal (CT) or LP diet for 8, 12, or 17 days and timed pregnant rats fed for 17 days from Day 3 of pregnancy. Plasma angiotensin II, expressions of Ace and Ace2, and activities of these proteins in lungs, kidneys, and plasma were measured. These parameters were compared among nonpregnant rats or between nonpregnant and pregnant rats fed different diets. Major findings are as follows: (1) plasma angiotensin II levels were slightly higher in the LP than CT group on Days 8 and 12 in nonpregnant rats; (2) expression of Ace and Ace2 and abundance and activities of ACE and ACE2 in lungs, kidneys, and plasma of nonpregnant rats were unchanged by LP diet except for minor changes; (3) the abundance and activities of ACE in lungs of pregnant rats fed LP diet were greater than nonpregnant rats, while those of ACE2 were decreased. These results indicate that LP diet-induced increase in pulmonary angiotensin II production depends on pregnancy. PMID:27195150

  8. Associations between ACE-Inhibitors, Angiotensin Receptor Blockers, and Lean Body Mass in Community Dwelling Older Women.

    PubMed

    Bea, Jennifer W; Wassertheil-Smoller, Sylvia; Wertheim, Betsy C; Klimentidis, Yann; Chen, Zhao; Zaslavsky, Oleg; Manini, Todd M; Womack, Catherine R; Kroenke, Candyce H; LaCroix, Andrea Z; Thomson, Cynthia A

    2018-01-01

    Studies suggest that ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM) among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women's Health Initiative participants that received dual energy X-ray absorptiometry scans to estimate body composition ( n =10,635) at baseline and at years 3 and 6 of follow-up. Of those, 2642 were treated for hypertension at baseline. Multivariate linear regression models, adjusted for relevant demographics, behaviors, and medications, assessed ACE-I/ARB use/nonuse and LBM associations at baseline, as well as change in LBM over 3 and 6 years. Although BMI did not differ by ACE-I/ARB use, LBM (%) was significantly higher in ACE-I/ARB users versus nonusers at baseline (52.2% versus 51.3%, resp., p =0.001). There was no association between ACE-I/ARB usage and change in LBM over time. Reasons for higher LBM with ACE-I/ARB use cross sectionally, but not longitundinally, are unclear and may reflect a threshold effect of these medications on LBM that is attenuated over time. Nevertheless, ACE-I/ARB use does not appear to negatively impact LBM in the long term.

  9. Adverse Childhood Experiences and Disordered Gambling: Assessing the Mediating Role of Emotion Dysregulation.

    PubMed

    Poole, Julia C; Kim, Hyoun S; Dobson, Keith S; Hodgins, David C

    2017-12-01

    Adverse childhood experiences (ACEs), such as sexual and physical abuse, have been established as risk factors for the development of disordered gambling. The underlying mechanism by which ACEs influence disordered gambling, however, remains unknown. The aims of the present research were to comprehensively investigate ten types of childhood adversity and their relationships to disordered gambling in adulthood, and to test whether emotion dysregulation mediated the relationship between ACEs and disordered gambling. A sample of community gamblers (N = 414) completed self-report measures of ACEs, emotion dysregulation, and gambling severity. Results revealed a significant association between all but one type (physical abuse) of ACEs and disordered gambling. Further, the results highlighted the cumulative impact of ACEs on gambling. Specifically, individuals who experienced three or more types of ACEs were more than three times as likely to report disordered gambling as compared to individuals with no history of childhood adversity. Importantly, as hypothesized, emotion dysregulation mediated the relationship between ACEs and disordered gambling. Findings from this research describe the association between ACEs and gambling and indicate a causal link between childhood adversity and disordered gambling. Results suggest that treatment initiatives may do well to address both ACEs and emotion dysregulation in the treatment of problem gambling.

  10. Influence of Alternative Engine Concepts on LCTR2 Sizing and Mission Profile

    NASA Technical Reports Server (NTRS)

    Acree, C. W., Jr.; Snyder, Christopher A.

    2012-01-01

    The Large Civil Tiltrotor (LCTR) was developed as part of the NASA Heavy Lift Rotorcraft Systems Investigation in order to establish a consistent basis for evaluating the benefits of advanced technology for large tiltrotors. The concept has since evolved into the second-generation LCTR2, designed to carry 90 passengers for 1,000 nm at 300 knots, with vertical takeoff and landing. This paper examines the impact of advanced propulsion system concepts on LCTR2 sizing. Two concepts were studied: an advanced, single-speed engine with a conventional power turbine layout (Advanced Conventional Engine, or ACE), and a variable-speed power turbine engine (VSPT). The ACE is the lighter engine, but requires a multi-speed (shifting) gearbox, whereas the VSPT uses a lighter, fixed-ratio gearbox. The NASA Design and Analysis of Rotorcraft (NDARC) design code was used to study the trades between rotor and engine efficiency and weight. Rotor performance was determined by Comprehensive Analytical Model of Rotorcraft Aerodynamics and Dynamics (CAMRAD II), and engine performance was estimated with the Numerical Propulsion System Simulation (NPSS). Design trades for the ACE vs. VSPT are presented in terms of vehicle weight empty for variations in mission altitude and range; the effect of different One Engine Inoperative (OEI) criteria are also examined. Because of its strong effect on gearbox weight and on both rotor and engine efficiency, rotor speed was chosen as the reference design variable for comparing design trades. The two propulsion concepts had nearly identical vehicle weights and mission fuel consumption, and their relative advantages varied little with cruise altitude, mission range, or OEI criteria; high cruise altitude and low cruise tip speed were beneficial for both concepts.

  11. RNA interference targeting the ACE gene reduced blood pressure and improved myocardial remodelling in SHRs.

    PubMed

    He, Junhua; Bian, Yunfei; Gao, Fen; Li, Maolian; Qiu, Ling; Wu, Weidong; Zhou, Hua; Liu, Gaizhen; Xiao, Chuanshi

    2009-02-01

    The purpose of the present study was to investigate the effects on blood pressure and myocardial hypertrophy in SHRs (spontaneously hypertensive rats) of RNAi (RNA interference) targeting ACE (angiotensin-converting enzyme). SHRs were treated with normal saline as vehicle controls, with Ad5-EGFP as vector controls, and with recombinant adenoviral vectors Ad5-EGFP-ACE-shRNA, carrying shRNA (small hairpin RNA) for ACE as ACE-RNAi. WKY (Wistar-Kyoto) rats were used as normotensive controls treated with normal saline. The systolic blood pressure of the caudal artery was recorded. Serum levels of ACE and AngII (angiotensin II) were determined using ELISA. ACE mRNA and protein levels were determined in aorta, myocardium, kidney and lung. On day 32 of the experiment, the heart was pathologically examined. The ratios of heart weight/body weight and left ventricular weight/body weight were calculated. The serum concentration of ACE was lower in ACE-RNAi rats (16.37+/-3.90 ng/ml) compared with vehicle controls and vector controls (48.26+/-1.50 ng/ml and 46.67+/-2.82 ng/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (14.88+/-3.15 ng/ml; P>0.05). The serum concentration of AngII was also significantly lower in ACE-RNAi rats (18.24+/-3.69 pg/ml) compared with vehicle controls and vector controls (46.21+/-5.06 pg/ml and 44.93+/-4.12 pg/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (16.06+/-3.11 pg/ml; P>0.05). The expression of ACE mRNA and ACE protein were significantly reduced in the myocardium, aorta, kidney and lung in ACE-RNAi rats compared with that in vehicle controls and in vector controls (all P<0.05). ACE-RNAi treatment resulted in a reduction in systolic blood pressure by 22+/-3 mmHg and the ACE-RNAi-induced reduction lasted for more than 14 days. In contrast, blood pressure was continuously increased in the vehicle controls as well as in the vector controls. The ratios of heart weight/body weight and left ventricular weight/body weight were significantly lower in ACE-RNAi rats (3.12+/-0.23 mg/g and 2.24+/-0.19 mg/g) compared with the vehicle controls (4.29+/-0.24 mg/g and 3.21+/-0.13 mg/g; P<0.05) and the vector controls (4.43+/-0.19 mg/g and 3.13+/-0.12 mg/g; P<0.05). The conclusion of the present study is that ACE-silencing had significant antihypertensive effects and reversed hypertensive-induced cardiac hypertrophy in SHRs, and therefore RNAi might be a new strategy in controlling hypertension.

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

    Daud, A.I.; Bumpus, F.M.; Husain, A.

    Ovarian angiotensin I (Ang I)-converting enzyme (ACE), estimated by the specific binding of the ACE inhibitor (125I)iodo-MK-351A, is localized on multiple ovarian structures, including follicular granulosa cells, corpora lutea, terminal epithelium, and ovarian blood vessels, but total ovarian ACE does not display a cyclic pattern of variation during the rat estrous cycle. We have previously shown that ACE is localized on the granulosa cell layer of a subpopulation of rat ovarian follicles. Our present study shows that ovarian granulosa cells contain high affinity (binding site affinity (Kd), approximately 90 pM) and low capacity (binding site density (Bmax), approximately 12 fmol/2.5more » X 10(5) cells) (125I)iodo-MK-351A-binding sites and convert (125I)iodo-Ang I to (125I)iodo-Ang II (greater than 85% of this conversion was inhibited by the ACE inhibitor captopril). Throughout the rat estrous cycle, 94-100% of developing follicles and 89-96% of atretic follicles contained high levels of ACE; however, ACE was either not observed or its levels were very low in preovulatory follicles. These findings indicate the presence of high levels of biologically active ACE on the surface of granulosa cells and suggest a potential role for follicular ACE in early stages of follicular maturation and atresia. Although ACE is known to process a variety of peptides found within the ovary, and these peptides may have opposing effects on follicular maturation, we attempted to define the cumulative effect of ACE inhibition on follicular maturation.« less

  13. ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes.

    PubMed

    Færch, Louise H; Sejling, Anne-Sophie; Lajer, Maria; Tarnow, Lise; Thorsteinsson, Birger; Pedersen-Bjergaard, Ulrik

    2015-06-01

    Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all-cause mortality in three single-institution outpatient cohorts. Genotype-based analyses were performed in 269 patients from Hillerød Hospital (HIH) (follow-up: 12 years) and in 439 patients with diabetic nephropathy and 437 patients with persistent normoalbuminuria from the Steno Diabetes Center (SDC) (follow-up: 9.5 years). Patients not on renin-angiotensin system (RAS)-blocking treatment were included in analyses of serum ACE activity (HIH: n = 208) and plasma ACE concentration (SDC: n=269). In the HIH cohort, carrying a D-allele was associated with excess mortality (hazard ratio (HR) = 4.0 (95% confidence interval (CI) 1.0-16)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.0-1.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not. In unselected patients with type 1 diabetes, carrying the ACE D-allele and high spontaneous serum ACE activity were associated with 12-year excess mortality. These findings could not be reproduced in two other cohorts with persistent normoalbuminuria or diabetic nephropathy. © The Author(s) 2013.

  14. Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress.

    PubMed

    Rabelo, Luiza A; Todiras, Mihail; Nunes-Souza, Valéria; Qadri, Fatimunnisa; Szijártó, István András; Gollasch, Maik; Penninger, Josef M; Bader, Michael; Santos, Robson A; Alenina, Natalia

    2016-01-01

    Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20-22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.

  15. ACE2 alterations in kidney disease.

    PubMed

    Soler, María José; Wysocki, Jan; Batlle, Daniel

    2013-11-01

    Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1-7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance.

  16. ACE2 alterations in kidney disease

    PubMed Central

    Soler, María José; Wysocki, Jan; Batlle, Daniel

    2013-01-01

    Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1–7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance. PMID:23956234

  17. Chronic School Absenteeism and the Role of Adverse Childhood Experiences.

    PubMed

    Stempel, Hilary; Cox-Martin, Matthew; Bronsert, Michael; Dickinson, L Miriam; Allison, Mandy A

    To examine the association between chronic school absenteeism and adverse childhood experiences (ACEs) among school-age children. We conducted a secondary analysis of data from the 2011-2012 National Survey of Children's Health including children 6 to 17 years old. The primary outcome variable was chronic school absenteeism (≥15 days absent in the past year). We examined the association between chronic school absenteeism and ACEs by logistic regression with weighting for individual ACEs, summed ACE score, and latent class analysis of ACEs. Among the 58,765 school-age children in the study sample, 2416 (4.1%) experienced chronic school absenteeism. Witnessing or experiencing neighborhood violence was the only individual ACE significantly associated with chronic absenteeism (adjusted odds ratio [aOR] 1.55, 95% confidence interval [CI] 1.20-2.01). Having 1 or more ACE was significantly associated with chronic absenteeism: 1 ACE (aOR 1.35, 95% CI 1.02-1.79), 2 to 3 ACEs (aOR 1.81, 95% CI 1.39-2.36), and ≥4 ACEs (aOR 1.79, 95% CI 1.32-2.43). Three of the latent classes were also associated with chronic absenteeism, and children in these classes had a high probability of endorsing neighborhood violence, family substance use, or having multiple ACEs. ACE exposure was associated with chronic school absenteeism in school-age children. To improve school attendance, along with future graduation rates and long-term health, these findings highlight the need for an interdisciplinary approach to address child adversity that involves pediatricians, mental health providers, schools, and public health partners. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  18. Poster - 07: Investigations of the Advanced Collapsed-cone Engine for HDR Brachytherapy Scalp Treatments

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

    Cawston-Grant, Brie; Morrison, Hali; Sloboda, Ron

    Purpose: To present an investigation of the Advanced Collapsed-cone Engine (ACE) in Oncentraê Brachy (OcB) v4.5 using a tissue equivalent phantom modeling scalp brachytherapy (BT) treatments. Methods: A slab phantom modeling the skin, skull, brain and mold was used. A dose of 400cGy was prescribed to just above the skull layer using TG-43 and was delivered using an HDR afterloader. Measurements were made using Gafchromic™ EBT3 film at four depths within the phantom. The TG-43 planned and film measured doses were compared to the standard (sACE) and high (hACE) accuracy ACE options in OcB between the surface and below themore » skull. Results: The average difference between the TG-43 calculated and film measured doses was −11.25±3.38% when there was no air gap between the mold and skin; sACE and hACE doses were on average lower than TG-43 calculated doses by 3.41±0.03% and 2.45±0.03%, respectively. With a 3mm air gap between the mold and skin, the difference between the TG-43 calculated and measured doses was −8.28±5.76%; sACE and hACE calculations yielded average doses 1.87±0.03% and 1.78±0.04% greater than TG-43, respectively. Conclusions: TG-43, sACE, and hACE were found to overestimate doses below the skull layer compared to film. With a 3mm air gap between the mold and skin, sACE and hACE more accurately predicted the film dose to the skin surface than TG-43. More clinical variations and their implications are currently being investigated.« less

  19. Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus

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

    Wu, Kailang; Peng, Guiqing; Wilken, Matthew

    The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional,more » and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.« less

  20. Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus*

    PubMed Central

    Wu, Kailang; Peng, Guiqing; Wilken, Matthew; Geraghty, Robert J.; Li, Fang

    2012-01-01

    The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals. PMID:22291007

  1. Sexual Identity, Adverse Childhood Experiences, and Suicidal Behaviors.

    PubMed

    Clements-Nolle, Kristen; Lensch, Taylor; Baxa, Amberlee; Gay, Christopher; Larson, Sandra; Yang, Wei

    2018-02-01

    The objective of this study was to examine the influence of sexual identity and adverse childhood experiences (ACEs) on suicidal behaviors in a population-based sample of high school students. A two-stage cluster random sampling design was used to recruit 5,108 students from 97 high schools. A total of 4,955 students (97%) provided information that allowed for classification of sexual identity into three groups: (1) lesbian, gay, or bisexual (LGB) (10%); (2) not sure (4.6%); and (3) heterosexual (85.4%). Five measures of childhood abuse and household dysfunction were summed, and the ACE score was categorized as 0, 1, 2, and 3-5 ACEs. Weighted logistic regression was used to assess the influence of sexual identity, ACEs, and their interaction on suicide ideation and attempts in the past 12 months. Compared with heterosexual students, those who were LGB and were not sure had higher odds of suicide ideation and attempts. There was also a graded relationship between cumulative ACE exposure and suicidal behaviors. Although sexual identity/ACE interaction was not observed, LGB/not sure students who experienced a high number of ACEs were disproportionately affected. Compared with heterosexual students with 0 ACE, LGB/not sure students with 0 ACE (adjusted odds ratio [AOR] = 3.32, 95% confidence interval [CI] = 1.96-5.61), 1 ACE (AOR = 6.58, 95% CI = 4.05-10.71), 2 ACEs (AOR 13.50, 95% CI = 8.45-21.58), and 3-5 ACEs (AOR = 14.04, 95% CI = 8.72, 22.62) had higher odds of suicide ideation. A similar pattern was observed for suicide attempts. LGB and students not sure of their sexual identity with greater exposure to ACEs have disproportionately high levels of suicide ideation and attempts. Trauma-informed interventions for these populations are warranted. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  2. Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model

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

    Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao

    Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2 weeks. 48 h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocytemore » count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. - Highlights: • Diminazene aceturate (DIZE), an ACE2 activator prevents ovalbumin-induced asthma. • DIZE acted by upregulating ACE2, downregulating ACE1, MAPKs, markers of inflammation, apoptosis. • DIZE reduced airway inflammation, fibrosis, right ventricular hypertrophy and restored airway responsiveness.« less

  3. [Angiotensin converting enzyme: the antigenic properties of the domain, role in Alzheimer's disease and tumor progression].

    PubMed

    Kugaevskaya, E V; Timoshenko, O S; Solovyeva, N I

    2015-01-01

    Angiotensin converting enzyme (ACE, EC 3.4.15.1) was discovered and characterized in the Laboratory of biochemistry and chemical pathology of proteins under the direction of academician V.N. Orekhovich, where its physiological function, associated with a key role in the regulation of the renin-angiotensin (RAS) and the kallikrein-kinin systems that control blood flow in the body and homeostasis was first deciphered. We carried out a search for structural differences between the two highly homologous domains (N- and C-domains) of somatic ACE (sACE); it was based on a comparative analysis of antigenic determinants (or B-epitopes) of both domains. The revealed epitopes were classified with variable and conserved regions and functionally important sites of the molecule ACE. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. These data indicate the existence of structural differences between the domains of sACE. We studied the role of the domains of ACE in the metabolism of human amyloid beta peptide (Ab) - the main component of senile plaques, found in the brains of patients with Alzheimer's disease (AD). Our results demonstrated that only N-domain ACE cleaved the Ab between residues R5-H6, while, the C-domain of ACE failed to hydrolyze this region. In addition, the effect of post-translational modifications of Ab on its hydrolysis by the ACE was investigated. We show that isomerization of residue D7, a common non-enzymatic age-related modification found in AD-associated species, does not reduce the affinity of the peptide to the N-domain of ACE, and conversely, it increases. According to our data, the role of ACE in the metabolism of Ab becomes more significant in the development of AD. RAS is involved in malignant transformation and tumor progression. RAS components, including ACE and angiotensin II receptors type 1 (AT1R) are expressed in various human tumors. We found a significant increase in the level of ACE activity in the tumor tissue of squamous cell carcinoma of the cervix. In our viewpoint, the increase in ACE activity may be a marker of poor clinical prognosis.

  4. Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

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

    Villard, E.; Soubrier, F.; Tiret, L.

    1996-06-01

    Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms couldmore » be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.« less

  5. The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism

    PubMed Central

    Vaughan, David; Brogioli, Michael; Maier, Thomas; White, Andy; Waldron, Sarah; Rittweger, Jörn; Toigo, Marco; Wettstein, Jessica; Laczko, Endre; Flück, Martin

    2016-01-01

    Objective A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle. Methods Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc. Results Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon. Conclusion The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism. PMID:26982073

  6. Exploration of the molecular interactions between angiotensin-I-converting enzyme (ACE) and the inhibitory peptides derived from hazelnut (Corylus heterophylla Fisch.).

    PubMed

    Liu, Chunlei; Fang, Li; Min, Weihong; Liu, Jingsheng; Li, Hongmei

    2018-04-15

    The mechanism of action of food-derived angiotensin-I-converting enzyme (ACE) inhibitory peptides has not been completely elucidated. In the present study, ion-exchange chromatography, gel filtration chromatography, reverse phase-high performance liquid chromatography, and liquid chromatography-electrospray ionization-tandem mass (LC-ESI-MS/MS) were employed for purifying and identifying the ACE inhibitory peptides from hazelnut. To understand the mode of action of these peptides, ACE inhibition kinetics, in vitro and in vivo bioavailability assays, active site analysis, and interaction between the inhibitory peptides and ACE were investigated. The results identified novel ACE inhibitory peptides Ala-Val-Lys-Val-Leu (AVKVL), Tyr-Leu-Val-Arg (YLVR), and Thr-Leu-Val-Gly-Arg (TLVGR) with IC 50 values of 73.06, 15.42, and 249.3 μM, respectively. All peptides inhibited the ACE activity via a non-competitive mode. The binding free energies of AVKVL, YLVR, and TLVGR for ACE were -3.46, -6.48, and -7.37 kcal/mol, respectively. The strong inhibition of ACE by YLVR may be attributed to the formation of cation-pi interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Activation pattern of ACE2/Ang-(1-7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice.

    PubMed

    Tyrankiewicz, Urszula; Olkowicz, Mariola; Skórka, Tomasz; Jablonska, Magdalena; Orzylowska, Anna; Bar, Anna; Gonet, Michal; Berkowicz, Piotr; Jasinski, Krzysztof; Zoladz, Jerzy A; Smolenski, Ryszard T; Chlopicki, Stefan

    2018-01-01

    Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1-7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1-10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1-7) pathway, whereas the end-stage HF was associated with downregulation of ACE2/angiotensin-(1-7) and upregulation of the ACE/Ang II pathway. ACE/ACE-2 balance seems to determine the decompensation of HF in this model.

  8. ACES--Today and Tomorrow.

    ERIC Educational Resources Information Center

    Hackney, Harold

    1991-01-01

    Presents text of Presidential Address delivered March 24, 1991, at the Association for Counselor Education and Supervision (ACES) luncheon, part of the American Association for Counseling and Development Convention held in Reno, Nevada. Comments on past, present, and future of ACES, particularly on future challenges and role of ACES. (ABL)

  9. Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

    PubMed

    Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

    2015-07-01

    Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  10. The replication of a mouse adapted SARS-CoV in a mouse cell line stably expressing the murine SARS-CoV receptor mACE2 efficiently induces the expression of proinflammatory cytokines.

    PubMed

    Regla-Nava, Jose A; Jimenez-Guardeño, Jose M; Nieto-Torres, Jose L; Gallagher, Thomas M; Enjuanes, Luis; DeDiego, Marta L

    2013-11-01

    Infection of conventional mice with a mouse adapted (MA15) severe acute respiratory syndrome (SARS) coronavirus (CoV) reproduces many aspects of human SARS such as pathological changes in lung, viremia, neutrophilia, and lethality. However, established mouse cell lines highly susceptible to mouse-adapted SARS-CoV infection are not available. In this work, efficiently transfectable mouse cell lines stably expressing the murine SARS-CoV receptor angiotensin converting enzyme 2 (ACE2) have been generated. These cells yielded high SARS-CoV-MA15 titers and also served as excellent tools for plaque assays. In addition, in these cell lines, SARS-CoV-MA15 induced the expression of proinflammatory cytokines and IFN-β, mimicking what has been observed in experimental animal models infected with SARS-CoV and SARS patients. These cell lines are valuable tools to perform in vitro studies in a mouse cell system that reflects the species used for in vivo studies of SARS-CoV-MA15 pathogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Hypertension. Part 2: The Role of Medication.

    ERIC Educational Resources Information Center

    Tanji, Jeffrey L.

    1990-01-01

    Discusses the differences between exercise alone and exercise with medication (e.g., diuretics, beta blockers, and ACE inhibitors) for treating hypertensive patients. Guidelines are presented for physicians wanting to change the therapeutic regimen or to step down from medical therapy, noting exercise must always be part of the program. (SM)

  12. Building Tomorrow's Higher Education: Leadership, Partnerships, and Communities

    ERIC Educational Resources Information Center

    Haynes, Sandra; Krebs, Paula M.; Buehler, Julie; Phillips, Clarenda M.

    2012-01-01

    Four members of the ACE Fellows Program class of 2010-2011 share the results of their fellowship projects, all of which were based at urban universities. The projects addressed partnerships between the universities and their urban communities in different contexts, including the creation of college-town developments, establishing a center for…

  13. Adverse Outcome Pathways (AOPs) in Human Systems Biology: Gas-Phase Probes for Assessing In Vitro Enzyme System Perturbations

    EPA Science Inventory

    The Air, Climate, and Energy (ACE) and Chemical Safety for Sustainability (CSS) programs at the U.S. EnvironmentalProtection Agency (EPA) encompass broad-based research that includes assessment of the health and environmentalimpacts of anthropogenic and manufactured chemicals. On...

  14. Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

    PubMed

    Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

    2004-11-01

    The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P < .05). However, predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup. ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage. Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

  15. CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice

    PubMed Central

    Qadri, Fatimunnisa; Penninger, Josef M.; Santos, Robson Augusto S.; Bader, Michael

    2016-01-01

    Background and Aims. Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system. Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2-deficient (ACE2−/y) mice. Methods. Male C57BL/6 and ACE2−/y mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis. Results. ACE2−/y mice showed lower body weight and white adipose tissue at all ages investigated. Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma. Strikingly, ACE2−/y mice showed high deposition of lipids in the liver. Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE2−/y mice. Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1. ACE2−/y mice also showed impairments in glucose metabolism and insulin signaling in the liver. Conclusions. Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis. PMID:28101297

  16. Emerging Biodegradation of the Previously Persistent Artificial Sweetener Acesulfame in Biological Wastewater Treatment.

    PubMed

    Kahl, Stefanie; Kleinsteuber, Sabine; Nivala, Jaime; van Afferden, Manfred; Reemtsma, Thorsten

    2018-03-06

    The persistence of acesulfame (ACE) in wastewater treatment (and subsequently the aquatic environment) has led to its use as a marker substance for wastewater input into surface water and groundwater. However, ACE degradation of >85% during summer and autumn was observed in nine German wastewater treatment plants (WWTPs). Annual removal performance was more stable in larger plants, enhanced by low biological oxygen demand and impeded by water temperatures below 10 °C. Literature data suggest that the potential to degrade ACE emerged in WWTPs around the year 2010. This development is ongoing, as illustrated by ACE content in the German rivers Elbe and Mulde: Between 2013 and 2016 the ACE mass load decreased by 70-80%. In enrichment cultures with ACE as sole carbon source the carbonaceous fraction of ACE was removed completely, indicating catabolic biotransformation and the inorganic compound sulfamic acid formed in quantitative amounts. Sequencing of bacterial 16S rRNA genes suggests that several species are involved in ACE degradation, with proteobacterial species affiliated to Phyllobacteriaceae, Methylophilaceae, Bradyrhizobiaceae, and Pseudomonas becoming specifically enriched. ACE appears to be the first micropollutant for which the evolution of a catabolic pathway in WWTPs has been witnessed. It can yet only be speculated whether the emergence of ACE removal in WWTPs in different regions of the world is due to independent evolution or to global spreading of genes or adapted microorganisms.

  17. Activation of renin-angiotensin-aldosterone system (RAAS) in the lung of smoking-induced pulmonary arterial hypertension (PAH) rats.

    PubMed

    Yuan, Yi-Ming; Luo, Li; Guo, Zhen; Yang, Ming; Ye, Ren-Song; Luo, Chuan

    2015-06-01

    To explore the role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of pulmonary arterial hypertension (PAH) induced by chronic exposure to cigarette smoke. 48 healthy male SD rats were randomly divided into four groups (12/group): control group (group A); inhibitor alone group (group B); cigarette induction group (group C); cigarette induction + inhibitor group (group D). After the establishment of smoking-induced PAH rat model, the right ventricular systolic pressure (RVSP) was detected using an inserted catheter; western blotting was used to detect the protein expression of angiotensin-converting enzyme-2 (ACE2) and angiotensin-converting enzyme (ACE); expression levels of angiotensin II (AngII) in lung tissue were measured by radioimmunoassay. After six months of cigarette exposure, the RVSP of chronic cigarette induction group was significantly higher than that of the control group; expression levels of AngII and ACE increased in lung tissues, but ACE2 expression levels reduced. Compared with cigarette exposure group, after losartan treatment, RVSP, ACE and AngII obviously decreased (P<0.05), and ACE2 expression levels significantly increased. Chronic cigarette exposure may result in PAH and affect the protein expression of ACE2 and ACE in lung tissue, suggesting that ACE2 and ACE play an important role in the pathogenesis of smoking-induced PAH. © The Author(s) 2015.

  18. ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

    PubMed

    Zhang, Yue Hui; Hao, Qing Qing; Wang, Xiao Yu; Chen, Xu; Wang, Nan; Zhu, Li; Li, Shu Ying; Yu, Qing Tao; Dong, Bo

    2015-06-01

    Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway. © The Author(s) 2014.

  19. Clinical and biochemical presentation of sarcoidosis with high and normal serum angiotensin-converting enzyme.

    PubMed

    Sejdic, A; Graudal, N; Baslund, B

    2018-06-22

    The presentation of sarcoidosis can involve symptoms from all organs and the diagnosis is therefore often difficult. A raised serum level of serum angiotensin-converting enzyme (sACE) can be detected in 41-58% of patients. However, whether the sACE level per se reflects the severity of the sarcoid inflammation at the onset of the disease is not well described. The purpose of this study was to investigate the clinical and laboratory significance of high versus normal sACE levels in sarcoidosis. Journal data were retrospectively extracted from 101 patients from our clinic. Clinical and biochemical data were compared between patients with high sACE levels (> 115 U/L) on at least one occasion and normal sACE levels (< 115 U/L). In total, 48% (n = 48) of the patients had high ACE and 52% (n = 53) had normal ACE. The most common extrapulmonary manifestation for both groups was arthritis, followed by skin and eye involvement, but none of these differed between the two groups. Serum ionized calcium was significantly higher in the high sACE group, with a correlation coefficient of 0.112 (p = 0.460). Our study demonstrates that serum ionized calcium is significantly higher in the high sACE group but there was no statistical correlation to sACE. No other clinical or biochemical differences were observed.

  20. Onset Time of Inhibition of Return is a Promising Index for Assessing Cognitive Functions in Older Adults.

    PubMed

    Li, Tingni; Wang, Lei; Huang, Wanyi; Zhen, Yanfen; Zhong, Chupeng; Qu, Zhe; Ding, Yulong

    2018-06-06

    Developing efficient tools for assessing general cognitive functions in older adults is essential. Previous studies found that inhibition of return (IOR) occurred later in the older adults than in the younger (e.g., Castel, Chasteen, Scialfa, & Pratt, 2003). However, little is known about the relationship between the onset time of IOR (IOR-OT) and cognitive functions in the aging population. The present study examined this issue and investigated the potential of using IOR-OT as an index of cognitive functioning in older adults. In two studies, the IOR-OT of healthy younger and older adults was measured by a modified Posner peripheral cueing task, and cognitive functions of the older adults were evaluated with the Addenbrooke's Cognitive Examination Revised (ACE-R). Both studies showed a significant correlation (r = ~0.5) between IOR-OT and cognitive functions as assessed by ACE-R in older individuals: later IOR-OT was accompanied by a lower ACE-R score. To our knowledge, the present studies are the first to discover a relatively strong correlation between IOR-OT and cognitive functions in older adults. These findings provide new evidence supporting the inhibition deficit theory of aging and lay the foundation of using IOR-OT as an objective measure of cognitive functions in the aging population.

  1. Exogenous ACE2 Expression Allows Refractory Cell Lines To Support Severe Acute Respiratory Syndrome Coronavirus Replication

    PubMed Central

    Mossel, Eric C.; Huang, Cheng; Narayanan, Krishna; Makino, Shinji; Tesh, Robert B.; Peters, C. J.

    2005-01-01

    Of 30 cell lines and primary cells examined, productive severe acute respiratory syndrome coronavirus (Urbani strain) (SARS-CoV) infection after low-multiplicity inoculation was detected in only six: three African green monkey kidney epithelial cell lines (Vero, Vero E6, and MA104), a human colon epithelial line (CaCo-2), a porcine kidney epithelial line [PK(15)], and mink lung epithelial cells (Mv 1 Lu). SARS-CoV produced a lytic infection in Vero, Vero E6, and MA104 cells, but there was no visible cytopathic effect in Caco-2, Mv 1 Lu, or PK(15) cells. Multistep growth kinetics were identical in Vero E6 and MA104 cells, with maximum titer reached 24 h postinoculation (hpi). Virus titer was maximal 96 hpi in CaCo-2 cells, and virus was continually produced from infected CaCo-2 cells for at least 6 weeks after infection. CaCo-2 was the only human cell type of 13 tested that supported efficient SARS-CoV replication. Expression of the SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), resulted in SARS-CoV replication in all refractory cell lines examined. Titers achieved were variable and dependent upon the method of ACE2 expression. PMID:15731278

  2. [Angiotensin converting enzyme 2 and its emerging role in the regulation of the renin angiotensin system].

    PubMed

    Soler, María José; Lloveras, Josep; Batlle, Daniel

    2008-07-12

    The renin-angiotensin system (RAS) plays a key role in the regulation of cardiovascular and renal function. Thus, RAS blockade with an angiotensin-converting enzyme (ACE) and/or angiotensin receptor blocker decreases blood pressure, cardiovascular events, and delays the progression of kidney disease. The discovery of ACE2, a homologue of ACE, capable of degrading angiotensin II to angiotensin 1-7, may offer new insights into the RAS. In this review we discuss the possible protective role of ACE2 in different organs, namely heart, lungs and kidneys. The role of this enzyme is inferred from recent studies performed using genetically manipulated mice that lack the ACE2 gene and also mice treated with pharmacological ACE2 inhibitors. These results suggest that ACE2 might be a new therapeutic target within the RAS.

  3. Adverse childhood experiences and association with health, mental health, and risky behavior in the kingdom of Saudi Arabia.

    PubMed

    Almuneef, Maha; Hollinshead, Dana; Saleheen, Hassan; AlMadani, Sereen; Derkash, Bridget; AlBuhairan, Fadia; Al-Eissa, Majid; Fluke, John

    2016-10-01

    The aim of this study is to determine if ACEs impact the health and risk behavior burden among Kingdom of Saudi Arabia (KSA) adults. In 2013, a cross-sectional study was conducted across KSA to identify the retrospective prevalence of ACEs and their association with high risk behaviors and chronic diseases. Surveys from 10,156 adults in all 13 Saudi regions were obtained using an Arabic version of the WHO ACE-IQ (KSA ACE-IQ). Compared to respondents reporting no ACEs, even just one ACE contributed significantly to the odds of experiencing diabetes mellitus (OR=1.3), depression (OR=1.32), or anxiety (OR=1.79) outcomes. Two ACEs were necessary for statistically significant, higher odds to emerge for hypertension (OR=1.46), mental illness (OR=1.93), smoking (OR=1.17), alcohol use (OR=1.75), and drug use (OR=1.45). Respondents who reported four or more ACEs had greater odds of coronary heart disease (OR=1.94), and obesity (OR=2.25). Compared to those reporting no ACEs, respondents reporting four or more ACEs had over four times the odds of Alcohol or Drug Use, Mental Illness, Depression, and/or Anxiety outcomes and more than twice the odds of diabetes, hypertension, obesity, and/or smoking outcomes. Findings from this analysis underscore the potential benefit of providing focused preventative approaches to mitigating ACEs in KSA in relation to both the specific and cumulative burden of health and risky behavior outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Adverse childhood experiences and blood pressure trajectories from childhood to young adulthood: the Georgia stress and Heart study.

    PubMed

    Su, Shaoyong; Wang, Xiaoling; Pollock, Jennifer S; Treiber, Frank A; Xu, Xiaojing; Snieder, Harold; McCall, W Vaughn; Stefanek, Michael; Harshfield, Gregory A

    2015-05-12

    The purposes of this study were to assess the long-term effect of adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from childhood to young adulthood and to examine whether this relation is explained by childhood socioeconomic status (SES) or risk behaviors that are associated with ACEs. Systolic and diastolic BPs were measured up to 16 times (13 times on average) over a 23-year period in 213 African Americans and 181 European Americans 5 to 38 years of age. Retrospective data on traumatic experiences before 18 years of age were collected, including abuse, neglect, and household dysfunction. Individual growth curve modeling within a multilevel framework was used to examine the relation between exposure to ACEs and BP development. No main effect of ACEs on average BP levels was found. However, a significant interaction of ACE score with age(3) was observed (systolic BP, P=0.033; diastolic BP, P=0.017). Subjects who experienced multiple traumatic events during childhood showed a faster rise in BP levels after 30 years of age than those without ACEs. As expected, a graded association of ACEs with childhood socioeconomic status and negative health behaviors was observed (P<0.001). The ACE-systolic BP relation was not explained by these factors, whereas the ACE-diastolic BP relation was partially mediated by illicit drug use. In this novel longitudinal study, we observed that participants who were exposed to multiple ACEs displayed a greater increase in BP levels in young adulthood compared with their counterparts without ACEs. © 2015 American Heart Association, Inc.

  5. Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae

    PubMed Central

    Chatterjee, Tanaya; Sheikh, Irshad Ali; Chakravarty, Devlina; Chakrabarti, Pinak; Sarkar, Paramita; Saha, Tultul; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

    2015-01-01

    Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders. PMID:26540279

  6. Our ACE in the HOLE: Justifying the Use of Angiotensin-converting Enzyme Inhibitors as Adjuvants to Standard Chemotherapy.

    PubMed

    Radin, Daniel P; Krebs, Austin; Maqsudlu, Arman; Patel, Parth

    2018-01-01

    Angiotensin-I-converting enzyme (ACE) inhibitors have been very effective in treating cardiac hypertension since their clinical inception over four decades ago. Since then, it has been established that angiotensin II, the product of ACE, has oncogenic and pro-proliferative qualities, which begs the question as to whether ACE inhibitors may have oncolytic characteristics. In fact, scattered reports suggest that ACE inhibitors are oncolytic and oncopreventive, but the available literature has yet to be thoroughly examined. In the present review, we examine the available literature and determine that ACE inhibitors would have great utility in the prevention and treatment of cancer. At the same time, they would augment the efficacy of chemo- and radiotherapy as well as mitigating damage to healthy tissue by standard chemotherapeutic regimens. We review some of the mounting clinical evidence and show that ACE inhibitors have oncolytic activity in multiple types of cancer and discuss the ability of ACE inhibitors to prevent cardiotoxicity of multiple chemotherapies. Our analysis demonstrates that the actions of ACE inhibitors converge on vascular endolthelial growth factor to reduce its levels in tumors and prevent construction of blood vessels to masses, leaving them nutrient-depleted and subsequently hindering their growth. Given that ACE inhibitors are approved by the Federal Drug Administration and the therapeutic dose for hypertension treatment also slows the growth of multiple cancers types, ACE inhibitors are in a perfect position to be repurposed as oncolytic agents, that would widely increase their utility in the clinic. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Adverse Childhood Experiences and Blood Pressure Trajectories from Childhood to Young Adulthood: The Georgia Stress and Heart Study

    PubMed Central

    Su, Shaoyong; Wang, Xiaoling; Pollock, Jennifer S.; Treiber, Frank A.; Xu, Xiaojing; Snieder, Harold; McCall, W. Vaughn; Stefanek, Michael; Harshfield, Gregory A.

    2015-01-01

    Background The purpose of this study was to assess the long-term effect of adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from childhood to young adulthood and to examine whether this relation is explained by childhood socioeconomic status (SES) and/or risk behaviors that are associated with ACEs. Methods and Results Systolic and diastolic blood pressure (SBP and DBP) were measured up to 16 times (13 times on average) over a 23-year period in 213 African Americans (AAs) and 181 European Americans (EAs) aged 5 to 38 years. Retrospective data on traumatic experiences prior to age 18 were collected, including abuse, neglect and household dysfunction. Individual growth curve modeling within a multilevel framework was used to examine the relation between exposure to ACEs and BP development. No main effect of ACEs on average BP levels was found. However, a significant interaction of ACE score with age3 was observed (SBP: p=0.033; DBP: p=0.017). Subjects who experienced multiple traumatic events during childhood showed a faster rise of BP levels after age of 30 years than those without ACEs. As expected, a graded association of ACEs with childhood SES and negative health behaviors was observed (p<0.001). The ACE-SBP relation was not explained by these factors, while the ACE-DBP relation was partially mediated by illicit drug use. Conclusions In this novel longitudinal study, we observed that participants who were exposed to multiple ACEs displayed a greater increase of BP levels in young adulthood compared to their counterparts without ACEs. PMID:25858196

  8. Adverse childhood experiences, gender, and HIV risk behaviors: Results from a population-based sample.

    PubMed

    Fang, Lin; Chuang, Deng-Min; Lee, Yookyong

    2016-12-01

    Recent HIV research suggested assessing adverse childhood experiences (ACEs) as contributing factors of HIV risk behaviors. However, studies often focused on a single type of adverse experience and very few utilized population-based data. This population study examined the associations between ACE (individual and cumulative ACE score) and HIV risk behaviors. We analyzed the 2012 Behavioral Risk Factor Surveillance Survey (BRFSS) from 5 states. The sample consisted of 39,434 adults. Eight types of ACEs that included different types of child abuse and household dysfunctions before the age of 18 were measured. A cumulative score of ACEs was also computed. Logistic regression estimated of the association between ACEs and HIV risk behaviors using odds ratio (OR) with 95% confidence intervals (CIs) for males and females separately. We found that ACEs were positively associated with HIV risk behaviors overall, but the associations differed between males and females in a few instances. While the cumulative ACE score was associated with HIV risk behaviors in a stepwise manner, the pattern varied by gender. For males, the odds of HIV risk increased at a significant level as long as they experienced one ACE, whereas for females, the odds did not increase until they experienced three or more ACEs. Future research should further investigate the gender-specific associations between ACEs and HIV risk behaviors. As childhood adversities are prevalent among general population, and such experiences are associated with increased risk behaviors for HIV transmission, service providers can benefit from the principles of trauma-informed practice.

  9. Do Pediatricians Ask About Adverse Childhood Experiences in Pediatric Primary Care?

    PubMed

    Kerker, Bonnie D; Storfer-Isser, Amy; Szilagyi, Moira; Stein, Ruth E K; Garner, Andrew S; O'Connor, Karen G; Hoagwood, Kimberly E; Horwitz, Sarah M

    2016-03-01

    The stress associated with adverse childhood experiences (ACEs) has immediate and long-lasting effects. The objectives of this study were to examine 1) how often pediatricians ask patients' families about ACEs, 2) how familiar pediatricians are with the original ACE study, and 3) physician/practice characteristics, physicians' mental health training, and physicians' attitudes/beliefs that are associated with asking about ACEs. Data were collected from 302 nontrainee pediatricians exclusively practicing general pediatrics who completed the 2013 American Academy of Pediatrics Periodic Survey. Pediatricians indicated whether they usually, sometimes, or never inquired about or screened for 7 ACEs. Sample weights were used to reduce nonresponse bias. Weighted descriptive and logistic regression analyses were conducted. Only 4% of pediatricians usually asked about all 7 ACEs; 32% did not usually ask about any. Less than 11% of pediatricians reported being very or somewhat familiar with the ACE study. Pediatricians who screened/inquired about ACEs usually asked about maternal depression (46%) and parental separation/divorce (42%). Multivariable analyses showed that pediatricians had more than twice the odds of usually asking about ACEs if they disagreed that they have little effect on influencing positive parenting skills, disagreed that screening for social emotional risk factors within the family is beyond the scope of pediatricians, or were very interested in receiving further education on managing/treating mental health problems in children and adolescents. Few pediatricians ask about all ACEs. Pediatric training that emphasizes the importance of social/emotional risk factors may increase the identification of ACEs in pediatric primary care. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  10. FIRE III ACE

    Atmospheric Science Data Center

    2013-01-23

    FIRE III ACE Data Sets The First International Satellite Cloud ... Regional Experiment (FIRE) - Arctic Cloud Experiment (ACE) was conducted April through July of 1998. It was held in conjunction with ... Heat Budget of the Arctic Ocean (SHEBA) Experiment. The FIRE-ACE focused on all aspects of Arctic cloud systems. The main facility was ...

  11. National Dam Inspection Program. Laurel Run Dam. NDI ID Number PA-00380. DER ID Number 35-6, Pennsylvania Gas and Water Company. Susquehanna River Basin, Laurel Run, Lackawanna County, Pennsylvania Phase I Inspection Report,

    DTIC Science & Technology

    1980-04-01

    Supply. g. Design and Construction History. Laurel Run Dam was constructed in 1594 by Martin Cawley, a contractor from Archbald. The construction was...1T6Ace joly PHASE I INSPECTION REPORT -4 NATIONAL DAM INSPECTION PROGRAM Lime LAUREL RUN DAM PENNSYLVANIA GAS AND WATER COMPANY RESERVOIR AREA

  12. Extensions and Adjuncts to the BRL-COMGEOM Program

    DTIC Science & Technology

    1974-08-01

    m MAGIC Code, GIFT Code, Computer Simulation, Target Description, Geometric Modeling Techniques, Vulnerability Analysis 20...Arbitrary Quadric Surf ace.. 0Oo „<>. 7 III. BRITL: A GEOMETRY PREPROCESSOR PROGRAM FOR INPUT TO THE GIFT SYSTEM „ 0 18 A. Introduction <, „. ° 18 B...the BRL- GIFT code. The tasks completed under this contract and described in the report are: Ao The addition to the list of available body types

  13. Light Microsopy Module, International Space Station Premier Automated Microscope

    NASA Technical Reports Server (NTRS)

    Meyer, William V.; Sicker, Ronald J.; Chiaramonte, Francis P.; Brown, Daniel F.; O'Toole, Martin A.; Foster, William M.; Motil, Brian J.; Abbot-Hearn, Amber Ashley; Atherton, Arthur Johnson; Beltram, Alexander; hide

    2015-01-01

    The Light Microscopy Module (LMM) was launched to the International Space Station (ISS) in 2009 and began science operations in 2010. It continues to support Physical and Biological scientific research on ISS. During 2015, if all goes as planned, five experiments will be completed: [1] Advanced Colloids Experiments with a manual sample base -3 (ACE-M-3), [2] the Advanced Colloids Experiment with a Heated Base -1 (ACE-H-1), [3] (ACE-H-2), [4] the Advanced Plant Experiment -03 (APEX-03), and [5] the Microchannel Diffusion Experiment (MDE). Preliminary results, along with an overview of present and future LMM capabilities will be presented; this includes details on the planned data imaging processing and storage system, along with the confocal upgrade to the core microscope. [1] New York University: Paul Chaikin, Andrew Hollingsworth, and Stefano Sacanna, [2] University of Pennsylvania: Arjun Yodh and Matthew Gratale, [3] a consortium of universities from the State of Kentucky working through the Experimental Program to Stimulate Competitive Research (EPSCoR): Stuart Williams, Gerold Willing, Hemali Rathnayake, et al., [4] from the University of Florida and CASIS: Anna-Lisa Paul and Rob Ferl, and [5] from the Methodist Hospital Research Institute from CASIS: Alessandro Grattoni and Giancarlo Canavese.

  14. Wave Refraction During the May 2002 Rarefaction Event

    NASA Astrophysics Data System (ADS)

    Smith, C. W.; Mullan, D. J.; Ness, N. F.; Skoug, R. M.

    2002-12-01

    In previous work [Smith et al., 2001] we examined IMF wave refraction during the May 1999 rarefaction interval known as ``The Day The Solar Wind Disappeared.'' On that day, Alfvén speeds remained elevated over an extended region. Analysis of the recorded ACE fields and plasma data revealed depressed magnetic fluctuation levels, reduced compression in the fluctuations, and a reduced wave-like component within the region of elevated Alfvén speed, all consistent with wave refraction. The May 2002 event provides a third such period (the second identified event occured 2 weeks prior to the May 1999 period) and it again demonstrates properties which are consistent with refraction. Smith, C.~W., D.~J. Mullan, N.~F. Ness, R.~M. Skoug, and J.~Steinberg, Day the solar wind almost disappeared: Magnetic field fluctuations, wave refraction and dissipation, J. Geophys. Res., A106, 18,625--18,634, 2001. Efforts at the Bartol Research Institute were supported by CIT subcontract PC251439 under NASA grant NAG5-6912 for support of the ACE magnetic field experiment and by the NASA Delaware Space College Grant. Work at Los Alamos was performed under the auspices of the U.S. Department of Energy with financial support from the NASA ACE program.

  15. WarpEngine, a Flexible Platform for Distributed Computing Implemented in the VEGA Program and Specially Targeted for Virtual Screening Studies.

    PubMed

    Pedretti, Alessandro; Mazzolari, Angelica; Vistoli, Giulio

    2018-05-21

    The manuscript describes WarpEngine, a novel platform implemented within the VEGA ZZ suite of software for performing distributed simulations both in local and wide area networks. Despite being tailored for structure-based virtual screening campaigns, WarpEngine possesses the required flexibility to carry out distributed calculations utilizing various pieces of software, which can be easily encapsulated within this platform without changing their source codes. WarpEngine takes advantages of all cheminformatics features implemented in the VEGA ZZ program as well as of its largely customizable scripting architecture thus allowing an efficient distribution of various time-demanding simulations. To offer an example of the WarpEngine potentials, the manuscript includes a set of virtual screening campaigns based on the ACE data set of the DUD-E collections using PLANTS as the docking application. Benchmarking analyses revealed a satisfactory linearity of the WarpEngine performances, the speed-up values being roughly equal to the number of utilized cores. Again, the computed scalability values emphasized that a vast majority (i.e., >90%) of the performed simulations benefit from the distributed platform presented here. WarpEngine can be freely downloaded along with the VEGA ZZ program at www.vegazz.net .

  16. Economic evaluation of the Annual Cycle Energy System (ACES). Volume 1: Executive summary

    NASA Astrophysics Data System (ADS)

    1980-05-01

    Three different classes of building are investigated, namely: single family residence; multifamily residence; and commercial office building. For each building type in each geographic location, the economic evaluation of the annual cycle energy system (ACES) is based on a comparison of the present worth of the ACES to the present worth of a number of conventional systems. The results of this analysis indicate that the economic viability of the ACES is very sensitive to the assumed value of the property tax, maintenance cost, and fuel escalation rates, while it is relatively insensitive to the assumed values of other parameters. Fortunately, any conceivable change in the fuel escalation rates would tend to increase the viability of the ACES concept. An increase in the assumed value of the maintenance cost or property tax would tend to make the ACES concept less viable; a decrease in either would tend to make the ACES concept more viable.

  17. ACE Over Expression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer's Disease

    PubMed Central

    Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F.; Janjulia, Tea; Black, Keith L.; Shi, Peng D.; Gonzalez-Villalobos, Romer A.; Fuchs, Sebastien; Shen, Xiao Z.; Bernstein, Kenneth E.

    2014-01-01

    While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice over express ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD. PMID:24792094

  18. Identification of an ACE-Inhibitory Peptide from Walnut Protein and Its Evaluation of the Inhibitory Mechanism.

    PubMed

    Wang, Cong; Tu, Maolin; Wu, Di; Chen, Hui; Chen, Cheng; Wang, Zhenyu; Jiang, Lianzhou

    2018-04-11

    In the present study, a novel angiotensin I-converting enzyme inhibitory (ACE inhibitory) peptide, EPNGLLLPQY, derived from walnut seed storage protein, fragment residues 80-89, was identified by ultra-high performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) from walnut protein hydrolysate. The IC 50 value of the peptide was 233.178 μM, which was determined by the high performance liquid chromatography method by measuring the amount of hippuric acid (HA) generated from the ACE decomposition substrate (hippuryl-l-histidyl-l-leucine (HHL) to assess the ACE activity. Enzyme inhibitory kinetics of the peptide against ACE were also conducted, by which the inhibitory mechanism of ACE-inhibitory peptide was confirmed. Moreover, molecular docking was simulated by Discovery Studio 2017 R2 software to provide the potential mechanisms underlying the ACE-inhibitory activity of EPNGLLLPQY.

  19. Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants

    PubMed Central

    Daskaya-Dikmen, Ceren; Yucetepe, Aysun; Karbancioglu-Guler, Funda; Daskaya, Hayrettin; Ozcelik, Beraat

    2017-01-01

    Hypertension is an important factor in cardiovascular diseases. Angiotensin-I-converting enzyme (ACE) inhibitors like synthetic drugs are widely used to control hypertension. ACE-inhibitory peptides from food origins could be a good alternative to synthetic drugs. A number of plant-based peptides have been investigated for their potential ACE inhibitor activities by using in vitro and in vivo assays. These plant-based peptides can be obtained by solvent extraction, enzymatic hydrolysis with or without novel food processing methods, and fermentation. ACE-inhibitory activities of peptides can be affected by their structural characteristics such as chain length, composition and sequence. ACE-inhibitory peptides should have gastrointestinal stability and reach the cardiovascular system to show their bioactivity. This paper reviews the current literature on plant-derived ACE-inhibitory peptides including their sources, production and structure, as well as their activity by in vitro and in vivo studies and their bioavailability. PMID:28333109

  20. Ultrasound-assisted synthesis of curcumin analogs promoted by activated chicken eggshells

    NASA Astrophysics Data System (ADS)

    Mardiana, L.; Ardiansah, B.; Septiarti, A.; Bakri, R.; Kosamagi, G.

    2017-07-01

    Curcumin has been widely known as a multifunctional natural product which has many biological activities. However, the biggest limitation for the large scale application of curcumin is its poor bioavailability. This research presented a cheap, mild and efficient solvent-free synthesis of monocarbonyl analogs of curcumin via Aldol condensation using activated chicken eggshells (ACE). Dibenzalpropanone as a product of Aldol condensation was prepared by mixing benzaldehyde and acetone using a simple glass tube in the presence of ACE under ultrasound irradiation (78 % yield), while dibenzalcyclohexanone was produced from the reaction of benzaldehyde with cyclohenxanone (81 %). The products have been characterized by FTIR, UV-Vis spectrophotometer and GC-MS instruments. The FTIR spectra show a significant absorption of carbonyl group that attached to the double bond in α,β-position at 1630-1660 cm-1. The molecular cation of m/z of 234 and 274 is in agreement with the products structures.

  1. ACE

    NASA Technical Reports Server (NTRS)

    Lumia, R.

    1999-01-01

    This document describes the progress made during the fourth year of the Center for Autonomous Control Engineering (ACE). We currently support 30 graduate students, 52 undergraduate students, 9 faculty members, and 4 staff members. Progress will be divided into two categories. The first category explores progress for ACE in general. The second describes the results of each specific project supported within ACE.

  2. Trauma-Sensitive Schools: An Evidence-Based Approach

    ERIC Educational Resources Information Center

    Plumb, Jacqui L.; Bush, Kelly A.; Kersevich, Sonia E.

    2016-01-01

    Adverse childhood experiences (ACEs) are a common and pervasive problem. There is a positive correlation between ACEs and difficulties across the lifespan. Unlike healthy forms of stress, ACEs have a detrimental impact on the developing brain. There are three types of trauma: acute, chronic, and complex. Most ACEs are considered complex trauma,…

  3. Adverse childhood experiences, family functioning and adolescent health and emotional well-being.

    PubMed

    Balistreri, K S; Alvira-Hammond, M

    2016-03-01

    Adverse childhood experiences (ACEs) have been consistently linked in a strong and graded fashion to a host of health problems in later adulthood but few studies have examined the more proximate effect of ACEs on health and emotional well-being in adolescence. Nationally representative cross-sectional study. Using logistic regression on the 2011/12 National Survey of Children's Health, we examined the cumulative effect of total ACE score on the health and emotional well-being of US adolescents aged 12 to 17 years. We investigated the moderating effect of family functioning on the impact of ACE on adolescent health and emotional well-being. Adolescents with higher ACE scores had worse reported physical and emotional well-being than adolescents with fewer ACEs net of key demographic and socio-economic characteristics. Family functioning moderated the negative impact of cumulative ACE on adolescent health and emotional well-being. Adolescent well-being has enduring consequences; identifying children with ACE exposure who also have lower-functioning family could also help identify those families at particular risk. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  4. ACE2 activation by xanthenone prevents leptin-induced increases in blood pressure and proteinuria during pregnancy in Sprague-Dawley rats.

    PubMed

    Ibrahim, Hisham Saleh; Froemming, Gabrielle Ruth Anisah; Omar, Effat; Singh, Harbindar Jeet

    2014-11-01

    This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure (SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injection of either saline, or leptin, or leptin plus xanthenone (ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; also their gene expressions were determined in the kidney and aorta respectively. Compared to control, SBP was higher in the leptin-only treated group (P<0.001) and lower in rats treated with xanthenone alone (P<0.01). Proteinuria, markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P<0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P<0.05). It seems, leptin administration during pregnancy significantly increases SBP, proteinuria, endothelial activation, but decreases ACE2 level and expression. These effects are prevented by concurrent administration of xanthenone. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Does acute care for the elderly (ACE) unit decrease the incidence of falls?

    PubMed

    Abdalla, Ahmed; Adhaduk, Mehul; Haddad, Raad A; Alnimer, Yanal; Ríos-Bedoya, Carlos F; Bachuwa, Ghassan

    2017-11-11

    To determine whether acute care for the elderly (ACE) units decrease the incidence of patient falls compared to general medical and surgical (GMS) units, a non-concurrent prospective study included individuals aged 65 and older admitted to ACE or GMS units over a 2-year span was done. There were 7069 admissions corresponded to 28,401 patient-days. A total of 149 falls were reported for an overall incidence rate (IR) of 5.2 falls per 1000 patient-days, 95% CI, 4.4/1000-6.1/1000 patient-days. The falls IR ratio for patients in ACE unit compared to those in non-ACE units after adjusting for age, sex, prescribed psychotropics and hypnotics, and Morse Fall Score was 0.27/1000 patient-days; 95% CI, 0.13-0.54; p < 0.001. So, an estimated 73% reduction in patient falls between ACE unit and non-ACE units. Hospitals may consider investing in ACE units to decrease the risk of falls and the associated medical and financial costs. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Bioavailability of angiotensin I-converting enzyme (ACE) inhibitory peptides derived from Virgibacillus halodenitrificans SK1-3-7 proteinases hydrolyzed tilapia muscle proteins.

    PubMed

    Toopcham, Tidarat; Mes, Jurriaan J; Wichers, Harry J; Roytrakul, Sittiruk; Yongsawatdigul, Jirawat

    2017-04-01

    The angiotensin I-converting enzyme (ACE) inhibitory activity of protein hydrolysates from tilapia muscle fractions, namely mince (M), washed mince (WM), and sarcoplasmic protein (SP), were investigated. Each fraction was hydrolyzed by Virgibacillus halodenitrificans SK1-3-7 proteinases for up to 24h. After 8h of hydrolysis, the M hydrolysate (48% degree of hydrolysis (DH)) showed the highest ACE inhibitory activity, with an IC 50 value of 0.54mg/ml, while the SP hydrolysate exhibited the lowest DH and ACE inhibition. In vitro gastrointestinal digestion reduced the ACE inhibitory activity of the M hydrolysate but enhanced its transport across Caco-2 cell monolayers. The transported peptides were found to contain 3-4 amino acid residues showing strong ACE inhibition. The novel ACE inhibitory peptide with the highest inhibition was found to be MCS, with an IC 50 value of 0.29μM. Therefore, tilapia mince hydrolyzed by V. halodenitrificans proteinases contained ACE inhibitory peptides that are potentially bioavailable. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. ADVERSE CHILDHOOD EXPERIENCES, FAMILY FUNCTIONING AND ADOLESCENT HEALTH AND EMOTIONAL WELL-BEING

    PubMed Central

    Balistreri, Kelly Stamper; Alvira-Hammond, Marta

    2015-01-01

    Objectives Adverse childhood experiences (ACE) have been consistently linked in a strong and graded fashion to a host of health problems in later adulthood but few studies have examined the more proximate effect of ACE on health and emotional well-being in adolescence. Study Design Nationally representative cross-sectional study. Methods Using logistic regression on the 2011/12 National Survey of Children’s Health, we examined the cumulative effect of total ACE score on the health and emotional well-being of US adolescents ages 12 through 17. We investigated the moderating effect of family functioning on the impact of ACE on adolescent health and emotional well-being. Results Adolescents with higher ACE scores had worse reported physical and emotional well-being than adolescents with fewer ACEs net of key demographic and socioeconomic characteristics. Family functioning moderated the negative impact of cumulative ACE on adolescent health and emotional well-being. Conclusions Adolescent well-being has enduring consequences; identifying children with ACE exposure who also have lower-functioning family could also help identify those families at particular risk. PMID:26718424

  8. Adverse Childhood Experiences (ACEs), Stress and Mental Health in College Students.

    PubMed

    Karatekin, Canan

    2018-02-01

    The goal of this short-term longitudinal study was to examine whether adverse childhood experiences (ACEs) could be used to identify college students at risk for mental health problems and whether current level of stress mediates the relationship between ACEs and mental health. Data on ACEs and mental health (depression, anxiety and suicidality) were collected at the beginning of the semester, and data on current stressors and mental health were collected toward the end of the semester (n = 239). Findings indicated that ACEs predicted worsening of mental health over the course of a semester and suggested current number of stressors as a mediator of the relationship between ACEs and mental health. Results suggest that screening for ACEs might be useful to identify students at high risk for deterioration in mental health. Results further suggest that stress-related interventions would be beneficial for students with high levels of ACEs and point to the need for more research and strategies to increase help-seeking in college students. Copyright © 2017 John Wiley & Sons, Ltd.

  9. Greater than the sum of their parts: the benefits of Youth Violence Prevention Centers.

    PubMed

    Azrael, Deborah; Hemenway, David

    2011-09-01

    Academic Centers for Excellence on Youth Violence Prevention (ACE), which support a broad range of activities over and above RO1-type research projects, can add significantly to a community's capacity to respond to youth violence. We use the example of the Harvard Youth Violence Prevention Center to describe the types of research-practice collaborations these centers can promote, as well as the ways in which these collaborations can foster adoption of program planning, development, implementation and evaluation practices consistent with evidence-based approaches to youth violence prevention. Throughout, we describe the ways in which the existence of a center led, under the ACE format, to research, policy and practice opportunities that would not have existed in the absence of a center.

  10. The role of glycosylation and domain interactions in the thermal stability of human angiotensin-converting enzyme.

    PubMed

    O'Neill, Hester G; Redelinghuys, Pierre; Schwager, Sylva L U; Sturrock, Edward D

    2008-09-01

    The N and C domains of somatic angiotensin-converting enzyme (sACE) differ in terms of their substrate specificity, inhibitor profiling, chloride dependency and thermal stability. The C domain is thermally less stable than sACE or the N domain. Since both domains are heavily glycosylated, the effect of glycosylation on their thermal stability was investigated by assessing their catalytic and physicochemical properties. Testis ACE (tACE) expressed in mammalian cells, mammalian cells in the presence of a glucosidase inhibitor and insect cells yielded proteins with altered catalytic and physicochemical properties, indicating that the more complex glycans confer greater thermal stabilization. Furthermore, a decrease in tACE and N-domain N-glycans using site-directed mutagenesis decreased their thermal stability, suggesting that certain N-glycans have an important effect on the protein's thermodynamic properties. Evaluation of the thermal stability of sACE domain swopover and domain duplication mutants, together with sACE expressed in insect cells, showed that the C domain contained in sACE is less dependent on glycosylation for thermal stabilization than a single C domain, indicating that stabilizing interactions between the two domains contribute to the thermal stability of sACE and are decreased in a C-domain-duplicating mutant.

  11. Small-angle neutron scattering study of specific interaction and coordination structure formed by mono-acetyl-substituted dibenzo-20-crown-6-ether and cesium ions

    DOE PAGES

    Motokawa, Ryuhei; Kobayashi, Tohru; Endo, Hitoshi; ...

    2015-10-26

    This study uses small-angle neutron scattering (SANS) to elucidate the coordination structure of the complex of mono-acetyl-substituted dibenzo-20-crown-6-ether (ace-DB20C6) with cesium ions (Cs +). SANS profiles obtained for the complex of ace-DB20C6 and Cs + (ace-DB20C6/Cs) in deuterated dimethyl sulfoxide indicated that Cs + coordination resulted in a more compact structure than the free ace-DB20C6. The data were fitted well with SANS profiles calculated using Debye function for scattering on an absolute scattering intensity scale. For this theoretical calculation of the scattering profiles, the coordination structure proposed based on density functional theory calculation was used. Furthermore, we conclude that themore » SANS analysis experimentally supports the proposed coordination structure of ace-DB20C6/Cs and suggests the following: (1) the complex of ace-DB20C6 and Cs + is formed with an ace-DB20C6/Cs molar ratio of 1/1 and (2) the two benzene rings of ace-DB20C6 fold around Cs + above the center of the crown ether ring of ace-DB20C6.« less

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

    Strittmatter, S.M.

    (/sup 3/H)Captopril binds to angiotensin converting enzyme (ACE) in rat tissue homogenates. The pharmacology, regional distribution and copurification of (/sup 3/H)captopril binding with enzymatic activity demonstrate the selectivity of (/sup 3/H)captopril labeling of ACE. (/sup 3/H)Captopril binding to purified ACE reveals differences in cationic dependence and anionic regulation between substrate catalysis and inhibitor recognition. (/sup 3/H)Captopril association with ACE is entropically driven. The selectivity of (/sup 3/H)captopril binding permits autoradiographic localization of the ACE in the brain, male reproductive system, pituitary gland and adrenal gland. In the brain, ACE is visualized in a striatonigral neuronal pathway which develops between 1more » and 7 d after birth. In the male reproductive system, (/sup 3/H)captopril associated silver grains are found over spermatid heads and in the lumen of seminiferous tubules in stages I-VIII and XII-XIV. In the pituitary gland, ACE is localized to the posterior lobe and patches of the anterior lobe. The adrenal medulla contains moderate ACE levels while low levels are found in the adrenal cortex. Adrenal medullary ACE is increased after hypophysectomy and after reserpine treatment. The general of ligand binding techniques for the study of enzymes is demonstrated by the specific labeling of another enzyme, enkephaline convertase, in crude tissue homogenates by the inhibitor (/sup 3/H)GEMSA.« less

  13. Small-angle neutron scattering study of specific interaction and coordination structure formed by mono-acetyl-substituted dibenzo-20-crown-6-ether and cesium ions

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

    Motokawa, Ryuhei; Kobayashi, Tohru; Endo, Hitoshi

    This study uses small-angle neutron scattering (SANS) to elucidate the coordination structure of the complex of mono-acetyl-substituted dibenzo-20-crown-6-ether (ace-DB20C6) with cesium ions (Cs +). SANS profiles obtained for the complex of ace-DB20C6 and Cs + (ace-DB20C6/Cs) in deuterated dimethyl sulfoxide indicated that Cs + coordination resulted in a more compact structure than the free ace-DB20C6. The data were fitted well with SANS profiles calculated using Debye function for scattering on an absolute scattering intensity scale. For this theoretical calculation of the scattering profiles, the coordination structure proposed based on density functional theory calculation was used. Furthermore, we conclude that themore » SANS analysis experimentally supports the proposed coordination structure of ace-DB20C6/Cs and suggests the following: (1) the complex of ace-DB20C6 and Cs + is formed with an ace-DB20C6/Cs molar ratio of 1/1 and (2) the two benzene rings of ace-DB20C6 fold around Cs + above the center of the crown ether ring of ace-DB20C6.« less

  14. The Atmospheric Chemistry Experiment (ACE): Status and Latest Results

    NASA Astrophysics Data System (ADS)

    Bernath, P. F.; Boone, C. D.; McElroy, C. T.

    2017-12-01

    ACE (also known as SCISAT) is making a comprehensive set of simultaneous measurements of numerous trace gases, thin clouds, aerosols and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74°) orbit gives ACE coverage of tropical, mid-latitudes and polar regions. The primary instrument is a high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating in the 750-4400 cm-1 region, which provides the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. A second instrument, a dual spectrophotometer called MAESTRO, extends the wavelength coverage to the 400-1000 nm spectral region. Aerosols and clouds are being monitored through the extinction of solar radiation using two filtered imagers and by MAESTRO as well as by their infrared spectra. After 14 years in orbit, the ACE is still operating well. A short overview of the ACE mission will be presented (see http://www.ace.uwaterloo.ca for more information). The current version (v. 3.5/3.6) of ACE-FTS processing includes more than 30 molecules and twenty isotopologues; v.3.5/3.6 is now available in near-real time. This talk will focus on recent ACE results and the new version 4.0 of ACE-FTS processing.

  15. Angiotensin-converting enzyme in Spodoptera littoralis: molecular characterization, expression and activity profile during development.

    PubMed

    Lemeire, Els; Vanholme, Bartel; Van Leeuwen, Thomas; Van Camp, John; Smagghe, Guy

    2008-02-01

    The characterization of the full-length angiotensin-converting enzyme (ACE) cDNA sequence of the lepidopteran Spodoptera littoralis is reported in this study. The predicted open reading frame encodes a 647 amino acids long protein (SlACE) and shows 63.6% identity with the Bombyx mori ACE sequence. A 3D-model, consisting of 26 alpha-helices and three beta-sheets, was predicted for the sequence. SlACE expression was studied in the embryonic, larval and pupal stages of S. littoralis and in different tissues of the last larval stage by reverse-transcribed PCR. This revealed that the gene is expressed throughout the life cycle and especially in brain, gut and fat body tissue of the last stage. These results are in agreement with a role of ACE in the metabolism of neuropeptides and gut hormones. In addition, ACE activity has been studied in more detail during development, making use of a fluorescent assay. High ACE peptidase activity coincides with every transition state, from embryo to larva, from larva to larva and from larva to pupa. A peak value in activity occurs during the early pupal stage. These results indicate the importance of SlACE during metamorphosis and reveal the high correlation of ACE activity with the insect's development, which is regulated by growth and developmental hormones.

  16. Comparative Diagnostic Accuracy of the ACE-III, MIS, MMSE, MoCA, and RUDAS for Screening of Alzheimer Disease.

    PubMed

    Matías-Guiu, Jordi A; Valles-Salgado, María; Rognoni, Teresa; Hamre-Gil, Frank; Moreno-Ramos, Teresa; Matías-Guiu, Jorge

    2017-01-01

    Our aim was to evaluate and compare the diagnostic properties of 5 screening tests for the diagnosis of mild Alzheimer disease (AD). We conducted a prospective and cross-sectional study of 92 patients with mild AD and of 68 healthy controls from our Department of Neurology. The diagnostic properties of the following tests were compared: Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination III (ACE-III), Memory Impairment Screen (MIS), Montreal Cognitive Assessment (MoCA), and Rowland Universal Dementia Assessment Scale (RUDAS). All tests yielded high diagnostic accuracy, with the ACE-III achieving the best diagnostic properties. The area under the curve was 0.897 for the ACE-III, 0.889 for the RUDAS, 0.874 for the MMSE, 0.866 for the MIS, and 0.856 for the MoCA. The Mini-ACE score from the ACE-III showed the highest diagnostic capacity (area under the curve 0.939). Memory scores of the ACE-III and of the RUDAS showed a better diagnostic accuracy than those of the MMSE and of the MoCA. All tests, especially the ACE-III, conveyed a higher diagnostic accuracy in patients with full primary education than in the less educated group. Implementing normative data improved the diagnostic accuracy of the ACE-III but not that of the other tests. The ACE-III achieved the highest diagnostic accuracy. This better discrimination was more evident in the more educated group. © 2017 S. Karger AG, Basel.

  17. Adverse Childhood Experiences among Veterinary Medical Students: A Multi-Site Study.

    PubMed

    Strand, Elizabeth B; Brandt, Jennifer; Rogers, Kenita; Fonken, Laurie; Chun, Ruthanne; Conlon, Peter; Lord, Linda

    This research explores Adverse Childhood Experiences (ACEs) among veterinary medical students across six academic institutions of veterinary medicine, and their relationship with depression, stress, and desire to become a veterinarian. Between April 1, 2016, and May 23, 2016, 1,118 veterinary medical students in all 4 years of the curriculum (39% response rate) completed an anonymous web-based questionnaire about ACEs, depression using the Center for Epidemiological Studies Depression scale (CESD), stress using the Perceived Stress Scale (PSS), and the age at which they wanted to become a veterinarian. Sixty-one percent (677) of respondents reported having at least one ACE. The most prevalent ACE reported was living with a household member with a mental illness (31%). Students who had experienced four or more ACEs had an approximately threefold increase in signs of clinical depression and higher than average stress when compared to students who had experienced no ACEs. The number of ACEs showed an overall graded relationship to signs of clinical depression and higher than average stress. There was no statistically significant relationship between age at which a student wanted to become a veterinarian and exposure to ACEs. Veterinary students report being exposed to ACEs before age 18 at a rate similar to that of other population-based studies. These findings do not suggest that veterinary students enter the veterinary medical education system more at risk for poor mental health due to ACEs than the general population.

  18. Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.

    PubMed

    Shahmoradi, Somayeh; Ahmadalipour, Ali; Salehi, Mansoor

    2014-01-01

    Angiotensin converting enzyme (ACE) is an important gene, which is associated with the successful physical activity. The ACE gene has a major polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In this study, we aimed to determine whether there is an association between this polymorphism and sports performance in our studied population including elite athletes of different sports disciplines. We investigated allele frequency and genotype distribution of the ACE gene in 156 Iranian elite athletes compared to 163 healthy individuals. We also investigated this allele frequency between elite athletes in three functional groups of endurance, power, and mixed sports performances. DNA was extracted from peripheral blood, and polymerase chain reaction (PCR) method was performed on intron 16 of the ACE gene. The ACE genotype was determined for each subject. Statistical analysis was performed by SPSS 15, and results were analyzed by Chi-Square test. There was a significant difference in genotype distribution and allele frequency of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively). There was also a significant difference in allele frequency of the ACE gene in 3 groups of athletes with different sports disciplines (P = 0.045). Proportion of the ACE gene D allele was greater in elite endurance athletes (37 high-distance cyclists) than two other groups. Findings of the present study demonstrated that there is an association between the ACE gene I/D polymorphism and sports performance in Iranian elite athletes.

  19. Income Inequality and the Differential Effect of Adverse Childhood Experiences in US Children.

    PubMed

    Halfon, Neal; Larson, Kandyce; Son, John; Lu, Michael; Bethell, Christina

    Adverse childhood experiences (ACEs) can affect health and development across the life course. Despite a general understanding that adversity is associated with lower income, we know less about how ACEs manifest at different income levels and how these income-related patterns affect children's health and development. Data from the 2011 to 2012 National Survey of Children's Health were used to examine the prevalence of 9 ACEs in US children, across 4 levels of household income, and in relationship to 5 parent-reported measures of child health. Bivariate analyses and multivariable logistic regression models were used to examine the associations between number of ACEs and children's health outcomes on the basis of the 4 income groups. When partitioned according to income strata, the proportion of children who experienced ACEs showed a steep income gradient, particularly for children who experienced ≥4 ACEs. The linear gradient across income groups was less pronounced for each specific ACE, with several ACEs (experience of divorce, drug and alcohol exposure, parental mental illness) showing high reported prevalence in all but the highest income group. Multivariate analysis showed a consistent income-related gradient for each of the health outcomes. However, higher income was not necessarily found to be a protective factor against ACEs. ACEs are distributed across the income ladder and not just concentrated below the poverty level. This suggests that a more comprehensive policy strategy that includes targeted as well as universal interventions is warranted. Copyright © 2016 Academic Pediatric Association. All rights reserved.

  20. Coupling corticotropin-releasing-hormone and angiotensin converting enzyme 2 dampens stress responsiveness in male mice.

    PubMed

    Wang, Lei A; de Kloet, Annette D; Smeltzer, Michael D; Cahill, Karlena M; Hiller, Helmut; Bruce, Erin B; Pioquinto, David J; Ludin, Jacob A; Katovich, Michael J; Raizada, Mohan K; Krause, Eric G

    2018-05-01

    This study used mice to evaluate whether coupling expression of corticotropin-releasing hormone (CRH) and angiotensin converting enzyme 2 (ACE2) creates central interactions that blunt endocrine and behavioral responses to psychogenic stress. Central administration of diminazene aceturate, an ACE2 activator, had no effect on restraint-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis; however, mice that ubiquitously overexpress ACE2 had reduced plasma corticosterone (CORT) and pituitary expression of POMC mRNA. The Cre-LoxP system was used to restrict ACE2 overexpression to CRH synthesizing cells and probe whether HPA axis suppression was the result of central ACE2 and CRH interactions. Within the paraventricular nucleus of the hypothalamus (PVN), mice with ACE2 overexpression directed to CRH had a ≈2.5 fold increase in ACE2 mRNA, which co-localized with CRH mRNA. Relative to controls, mice overexpressing ACE2 in CRH cells had a decreased CORT response to restraint as well as decreased CRH mRNA in the PVN and CEA and POMC mRNA in the pituitary. Administration of ACTH similarly increased plasma CORT, indicating that the blunted HPA axis activation that accompanies ACE2 overexpression in CRH cells is centrally mediated. Anxiety-like behavior was assessed to determine whether the decreased HPA axis activation was predictive of anxiolysis. Mice with ACE2 overexpression directed to CRH cells displayed decreased anxiety-like behavior in the elevated plus maze and open field when compared to that of controls. Collectively, these results suggest that exogenous ACE2 suppresses CRH synthesis, which alters the central processing of psychogenic stress, thereby blunting HPA axis activation and attenuating anxiety-like behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats.

    PubMed

    Yang, Cui; Liu, Xiuxia; Li, Shengnan

    2010-02-01

    Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway.

  2. High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs.

    PubMed

    Akif, Mohd; Georgiadis, Dimitris; Mahajan, Aman; Dive, Vincent; Sturrock, Edward D; Isaac, R Elwyn; Acharya, K Ravi

    2010-07-16

    Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE. 2010 Elsevier Ltd. All rights reserved.

  3. Expression of Magnaporthe grisea Avirulence Gene ACE1 Is Connected to the Initiation of Appressorium-Mediated Penetration▿

    PubMed Central

    Fudal, Isabelle; Collemare, Jérôme; Böhnert, Heidi U.; Melayah, Delphine; Lebrun, Marc-Henri

    2007-01-01

    Magnaporthe grisea is responsible for a devastating fungal disease of rice called blast. Current control of this disease relies on resistant rice cultivars that recognize M. grisea signals corresponding to specific secreted proteins encoded by avirulence genes. The M. grisea ACE1 avirulence gene differs from others, since it controls the biosynthesis of a secondary metabolite likely recognized by rice cultivars carrying the Pi33 resistance gene. Using a transcriptional fusion between ACE1 promoter and eGFP, we showed that ACE1 is only expressed in appressoria during fungal penetration into rice and barley leaves, onion skin, and cellophane membranes. ACE1 is almost not expressed in appressoria differentiated on Teflon and Mylar artificial membranes. ACE1 expression is not induced by cellophane and plant cell wall components, demonstrating that it does not require typical host plant compounds. Cyclic AMP (cAMP) signaling mutants ΔcpkA and Δmac1 sum1-99 and tetraspanin mutant Δpls1::hph differentiate melanized appressoria with normal turgor but are unable to penetrate host plant leaves. ACE1 is normally expressed in these mutants, suggesting that it does not require cAMP signaling or a successful penetration event. ACE1 is not expressed in appressoria of the buf1::hph mutant defective for melanin biosynthesis and appressorial turgor. The addition of hyperosmotic solutes to buf1::hph appressoria restores appressorial development and ACE1 expression. Treatments of young wild-type appressoria with actin and tubulin inhibitors reduce both fungal penetration and ACE1 expression. These experiments suggest that ACE1 appressorium-specific expression does not depend on host plant signals but is connected to the onset of appressorium-mediated penetration. PMID:17142568

  4. Isolation, Purification and Molecular Mechanism of a Peanut Protein-Derived ACE-Inhibitory Peptide

    PubMed Central

    Shi, Aimin; Liu, Hongzhi; Liu, Li; Hu, Hui; Wang, Qiang; Adhikari, Benu

    2014-01-01

    Although a number of bioactive peptides are capable of angiotensin I-converting enzyme (ACE) inhibitory effects, little is known regarding the mechanism of peanut peptides using molecular simulation. The aim of this study was to obtain ACE inhibiting peptide from peanut protein and provide insight on the molecular mechanism of its ACE inhibiting action. Peanut peptides having ACE inhibitory activity were isolated through enzymatic hydrolysis and ultrafiltration. Further chromatographic fractionation was conducted to isolate a more potent peanut peptide and its antihypertensive activity was analyzed through in vitro ACE inhibitory tests and in vivo animal experiments. MALDI-TOF/TOF-MS was used to identify its amino acid sequence. Mechanism of ACE inhibition of P8 was analyzed using molecular docking and molecular dynamics simulation. A peanut peptide (P8) having Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence was obtained which had the highest ACE inhibiting activity of 85.77% (half maximal inhibitory concentration (IC50): 0.0052 mg/ml). This peanut peptide is a competitive inhibitor and show significant short term (12 h) and long term (28 days) antihypertensive activity. Dynamic tests illustrated that P8 can be successfully docked into the active pocket of ACE and can be combined with several amino acid residues. Hydrogen bond, electrostatic bond and Pi-bond were found to be the three main interaction contributing to the structural stability of ACE-peptide complex. In addition, zinc atom could form metal-carboxylic coordination bond with Tyr, Met residues of P8, resulting into its high ACE inhibiting activity. Our finding indicated that the peanut peptide (P8) having a Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence can be a promising candidate for functional foods and prescription drug aimed at control of hypertension. PMID:25347076

  5. Angiotensin Converting Enzyme Inhibitors and the Reduced Risk of Alzheimer’s Disease in the Absence of Apolipoprotein E4 Allele

    PubMed Central

    Qiu, Wei Qiao; Mwamburi, Mkaya; Besser, Lilah M.; Zhu, Haihao; Li, Huajie; Wallack, Max; Phillips, Leslie; Qiao, Liyan; Budson, Andrew E.; Stern, Robert; Kowall, Neil

    2014-01-01

    Our cross-sectional study showed that the interaction between apolipoprotein E4 (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with Alzheimer’s disease (AD). The aim of this longitudinal study was to differentiate whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE alleles. Using the longitudinal data from the National Alzheimer’s Coordinating Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we found that in the absence of ApoE4, subjects who had been taking central ACE inhibitor use (χ2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor use (χ2 test: 13% versus 27%, p < 0.0001) had lower incidence of AD compared with those who had not been taking an ACE inhibitor. In contrast, in the presence of ApoE4, there was no such association between ACE inhibitor use and the risk of AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68, 95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95% CI = 0.33, 0.68, p < 0.0001) still remained inversely associated with a risk of developing AD in ApoE4 non-carriers. In conclusion, ACE inhibitors, especially peripherally acting ones, were associated with a reduced risk of AD in the absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A double-blind clinical trial should be considered to determine the effect of ACE inhibitors on prevention of AD in the context of ApoE genotype. PMID:23948883

  6. An investigation of the concomitant use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs and diuretics.

    PubMed

    Bucsa, C; Moga, D C; Farcas, A; Mogosan, C; Dumitrascu, D L

    2015-08-01

    To determine in retrospective data the prevalence at hospital discharge of co-prescribing angiotensin-converting enzyme inhibitors (ACE-I) and non-steroidal anti-inflammatory drugs (NSAIDs) and ACE-I/NSAIDs and diuretics and to identify factors associated with the co-prescription. Secondary, we evaluated the extent of serum creatinine and potassium monitoring in patients treated with ACE-I and these associations and determined the prevalence of values above the upper normal limit (UNL) in monitored patients. Hospitalized patients with ACE-I in their therapy at discharge were included in 3 groups as follows: ACE-I, DT (double therapy with ACE-I and NSAIDs) and TT (triple therapy with ACE-I, NSAIDs and diuretics) groups. We evaluated differences on demographic characteristics, co-morbidities, medications, laboratory monitoring and quantified the patients with serum creatinine and potassium levels above the UNL using descriptive statistics. Logistic regression analysis with backward elimination was performed to identify significant predictors of combination therapy. Of 9960 admitted patients, 1214 were prescribed ACE-I, 40 were prescribed ACE-I/NSAIDs and 22 were prescribed ACE-I/NSAIDs/diuretics (3.13% and 1.72%, respectively, of the patients prescribed with ACE-I). Serum creatinine and potassium were monitored for the great majority of patients from all groups. The highest percentage of hyperkalemia was found in the DT group (10% of the patients) and of serum creatinine above UNL in the TT group (45.45%). The logistic regression final model showed that younger patients and monitoring for potassium were significantly associated with combination therapy. The prevalence of patients receiving DT/TT was relatively low and their monitoring during hospitalization was high. Factors associated with the combinations were younger patients and patients not tested for serum potassium.

  7. ACE-FTS ozone, water vapour, nitrous oxide, nitric acid, and carbon monoxide profile comparisons with MIPAS and MLS

    NASA Astrophysics Data System (ADS)

    Sheese, Patrick E.; Walker, Kaley A.; Boone, Chris D.; Bernath, Peter F.; Froidevaux, Lucien; Funke, Bernd; Raspollini, Piera; von Clarmann, Thomas

    2017-01-01

    The atmospheric limb sounders, ACE-FTS on the SCISAT satellite, MIPAS on ESA's Envisat satellite, and MLS on NASA's Aura satellite, take measurements used to retrieve atmospheric profiles of O3, N2O, H2O, HNO3, and CO. Each was taking measurements between February 2004 and April 2012 (ACE-FTS and MLS are currently operational), providing hundreds of profile coincidences in the Northern and Southern hemispheres, and during local morning and evening. Focusing on determining diurnal and hemispheric biases in the ACE-FTS data, this study compares ACE-FTS version 3.5 profiles that are collocated with MIPAS and MLS, and analyzes the differences between instrument retrievals for Northern and Southern hemispheres and for local morning and evening data. For O3, ACE-FTS is typically within ±5% of mid-stratospheric MIPAS and MLS data and exhibits a positive bias of 10 to 20% in the upper stratosphere - lower mesosphere. For H2O, ACE-FTS exhibits an average bias of -5% between 20 and 60 km. For N2O, ACE-FTS agrees with MIPAS and MLS within -20 to +10% up to 45 km and 35 km, respectively. For HNO3, ACE-FTS typically agrees within ±10% below 30 km, and exhibits a positive bias of 10 to 20% above 30 km. With respect to MIPAS CO, ACE-FTS exhibits an average -11% bias between 28 and 50 km, and at higher altitudes a positive bias on the order of 10% (>100%) in the winter (summer). With respect to winter MLS CO, ACE-FTS is typically within ±10% between 25 and 40 km, and has an average bias of -11% above 40 km.

  8. Adverse Childhood Experiences and School-Based Victimization and Perpetration.

    PubMed

    Forster, Myriam; Gower, Amy L; McMorris, Barbara J; Borowsky, Iris W

    2017-01-01

    Retrospective studies using adult self-report data have demonstrated that adverse childhood experiences (ACEs) increase risk of violence perpetration and victimization. However, research examining the associations between adolescent reports of ACE and school violence involvement is sparse. The present study examines the relationship between adolescent reported ACE and multiple types of on-campus violence (bringing a weapon to campus, being threatened with a weapon, bullying, fighting, vandalism) for boys and girls as well as the risk of membership in victim, perpetrator, and victim-perpetrator groups. The analytic sample was comprised of ninth graders who participated in the 2013 Minnesota Student Survey ( n ~ 37,000). Multinomial logistic regression models calculated the risk of membership for victim only, perpetrator only, and victim-perpetrator subgroups, relative to no violence involvement, for students with ACE as compared with those with no ACE. Separate logistic regression models assessed the association between cumulative ACE and school-based violence, adjusting for age, ethnicity, family structure, poverty status, internalizing symptoms, and school district size. Nearly 30% of students were exposed to at least one ACE. Students with ACE represent 19% of no violence, 38% of victim only, 40% of perpetrator only, and 63% of victim-perpetrator groups. There was a strong, graded relationship between ACE and the probability of school-based victimization: physical bullying for boys but not girls, being threatened with a weapon, and theft or property destruction ( ps < .001) and perpetration: bullying and bringing a weapon to campus ( ps < .001), with boys especially vulnerable to the negative effects of cumulative ACE. We recommend that schools systematically screen for ACE, particularly among younger adolescents involved in victimization and perpetration, and develop the infrastructure to increase access to trauma-informed intervention services. Future research priorities and implications are discussed.

  9. Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan.

    PubMed

    Hsieh, M C; Lin, S R; Hsieh, T J; Hsu, C H; Chen, H C; Shin, S J; Tsai, J H

    2000-07-01

    Diabetes is one of the major causes of end-stage renal failure in the Taiwanese population. Previous studies have shown that angiotensin-converting enzyme (ACE) inhibitor can improve glucose utilization and suppress hepatic glucose production and the renin-angiotensin system may play an important role in the initiation and progression of diabetic nephropathy. Thus, ACE gene polymorphism may be associated with type 2 diabetes and diabetic nephropathy. To investigate the distribution of ACE-I/D genotype in type 2 diabetes and diabetic nephropathy, we examined 336 patients with type 2 diabetes (157 without nephropathy and 179 with nephropathy) and 263 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. ACE gene polymorphism was analysed by use of polymerase chain reaction. Our study revealed that the frequency of the D allele of the ACE gene was 29.3% in normal controls. The frequency of ACE DD genotype was significantly higher in type 2 diabetics compared with normal controls (18.2 vs 9.1%, P<0.01). The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05). To determine whether ACE gene polymorphism was associated with the severity of diabetic nephropathy, we divided patients with diabetic nephropathy into dialysis and non-dialysis groups. The frequency of ACE DD genotype in the dialysis group was significantly higher than in non-dialysis group (28.7 vs 15.3%, P<0.05). Our results indicate that the frequency of ACE DD genotype is markedly higher in patients with type 2 diabetes, and the ACE DD genotype is significantly associated with diabetic nephropathy.

  10. High frequency of DD polymorphism of the angiotensin-converting enzyme gene in Turkish asthmatic patients.

    PubMed

    Urhan, Meral; Degirmenci, Irfan; Harmanci, Emel; Gunes, Hasan V; Metintas, Muzaffer; Basaran, Ayse

    2004-01-01

    The aim of this study is to detect the incidence of the angiotensin-converting enzyme (ACE) gene polymorphism in Turkish asthmatic patients and to examine whether there is an association between the disease and ACE gene polymorphism. In our study, the genomic DNA of 100 asthmatic patients and 88 healthy subjects was analyzed Genomic DNA was isolated from peripheral blood by using standard methods. The intron 16 of the ACE gene was amplified by the polymerase chain reaction (PCR) method using primers ACE and ACEX to examine the presence and absence of a 287-base pair (bp) DNA fragment that showed I/D polymorphism genotypes. PCR products were separated by agarose gel electrophoresis and were visualized by a charge-coupled device camera. Serum ACE activities were measured using an ACE kit. The results were evaluated statistically using the chi-square test and one-way analysis of variance. Although the population of patients with asthma was characterized by a higher frequency (30%) of the DD genotype of ACE, they were characterized by lower frequency (48%) of the ID genotype of ACE (DD, 16%, and ID, 64%, in healthy control subjects). The frequency of the I and D alleles of the ACE gene was not significantly different between asthmatic patients (0.46/0.54) and healthy controls (0.52/ 0.48). In addition, in both asthmatic patients and controls, there was a significant decrease of the levels of ACE activity in individuals that have II genotypes when compared with individuals that have DD genotypes. ACE activities were increased significantly in all asthmatic patients (67.20 +/- 1.95 IU/L) compared with all healthy controls (60.90 +/- 2.12 IU/L).

  11. Association of Angiotensin-Converting Enzyme (ACE) Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

    PubMed

    Rashed, Laila; Abdel Hay, Rania; Mahmoud, Rania; Hasan, Nermeen; Zahra, Amr; Fayez, Salwa

    2015-01-01

    Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE) plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D) polymorphism of the ACE gene was reported be associated with the development of vitiligo. Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL)-6) and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide) in vitiligo patients. This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively. The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026). However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115). There were statistically significant higher VIDA score (P = 0.007), and serum IL-6 (P < 0.001) in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007) when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls. As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

  12. Screening for Adverse Childhood Experiences in a Family Medicine Setting: A Feasibility Study.

    PubMed

    Glowa, Patricia T; Olson, Ardis L; Johnson, Deborah J

    2016-01-01

    The role of adverse childhood experiences (ACEs) in predicting later adverse adult health outcomes is being widely recognized by makers of public policy. ACE questionnaires have the potential to identify in clinical practice unaddressed key social issues that can influence current health risks, morbidity, and early mortality. This study seeks to explore the feasibility of implementing the ACE screening of adults during routine family medicine office visits. At 3 rural clinical practices, the 10-question ACE screen was used before visits with 111 consecutive patients of 7 clinicians. Clinician surveys about the use of the results and the effect on the visits were completed immediately after the visits. The presence of any ACE risk and "high-risk" ACE scores (≥4) were compared with clinician survey responses. A risk of ACEs was present in 62% of patients; 22% had scores ≥4. Clinicians were more likely to have discussed ACE issues for high-risk patients (score 0-3, 36.8%; score ≥4, 83.3%; P =. 00). Clinicians also perceived that they gained new information (score 0-3, 35.6%; score ≥4, 83.3%; P = .00). Clinical care changed for a small proportion of high-risk patients, with no change in immediate referrals or plan for follow-up. In 91% of visits where a risk of ACEs was present, visit length increased by ≤5 minutes. Incorporation of ACE screening during routine care is feasible and merits further study. ACE screening offers clinicians a more complete picture of important social determinants of health. Primary care-specific interventions that incorporate treatment of early life trauma are needed. © Copyright 2016 by the American Board of Family Medicine.

  13. Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia.

    PubMed

    Gadelha, A; Vendramini, A M; Yonamine, C M; Nering, M; Berberian, A; Suiama, M A; Oliveira, V; Lima-Landman, M T; Breen, G; Bressan, R A; Abílio, V; Hayashi, M A F

    2015-12-08

    In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=-5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=-0.247; P=0.004) and Hopkins total (r=-0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations.

  14. Production of the angiotensin I converting enzyme inhibitory peptides and isolation of four novel peptides from jellyfish (Rhopilema esculentum) protein hydrolysate.

    PubMed

    Liu, Xin; Zhang, Miansong; Shi, Yaping; Qiao, Ruojin; Tang, Wei; Sun, Zhenliang

    2016-07-01

    Angiotensin I converting enzyme (ACE) plays an important role in regulating blood pressure in the human body. ACE inhibitory peptides derived from food proteins could exert antihypertensive effects without side effects. Jellyfish (Rhopilema esculentum) is an important fishery resource suitable for production of ACE inhibitory peptides. The objective of this study was to optimize the hydrolysis conditions for production of protein hydrolysate from R. esculentum (RPH) with ACE inhibitory activity, and to isolate and identify the ACE inhibitory peptides from RPH. Rhopilema esculentum protein was hydrolyzed with Compound proteinase AQ to produce protein hydrolysate with ACE inhibitory activity, and the hydrolysis conditions were optimized using response surface methodology. The optimum parameters for producing peptides with the highest ACE inhibitory activity were as follows: hydrolysis time 3.90 h, hydrolysis temperature 58 °C, enzyme:substrate ratio 2.8% and pH 7.60. Under these conditions, the ACE inhibitory rate reached 32.21%. In addition, four novel ACE inhibitory peptides were isolated, and their amino acids sequences were identified as Val-Gly-Pro-Tyr, Phe-Thr-Tyr-Val-Pro-Gly, Phe-Thr-Tyr-Val-Pro-Gly-Ala and Phe-Gln-Ala-Val-Trp-Ala-Gly, respectively. The IC50 value of the purified peptides for ACE inhibitory activity was 8.40, 23.42, 21.15 and 19.11 µmol L(-1) . These results indicate that the protein hydrolysate prepared from R. esculentum might be a commercial competitive source of ACE inhibitory ingredients to be used in functional foods. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  15. Adverse childhood experiences and frequent insufficient sleep in 5 U.S. States, 2009: a retrospective cohort study.

    PubMed

    Chapman, Daniel P; Liu, Yong; Presley-Cantrell, Letitia R; Edwards, Valerie J; Wheaton, Anne G; Perry, Geraldine S; Croft, Janet B

    2013-01-03

    Although adverse childhood experiences (ACEs) have previously been demonstrated to be adversely associated with a variety of health outcomes in adulthood, their specific association with sleep among adults has not been examined. To better address this issue, this study examines the relationship between eight self-reported ACEs and frequent insufficient sleep among community-dwelling adults residing in 5 U.S. states in 2009. To assess whether ACEs were associated with frequent insufficient sleep (respondent did not get sufficient rest or sleep ≥ 14 days in past 30 days) in adulthood, we analyzed ACE data collected in the 2009 Behavioral Risk Factor Surveillance System, a random-digit-dialed telephone survey in Arkansas, Louisiana, New Mexico, Tennessee, and Washington. ACEs included physical abuse, sexual abuse, verbal abuse, household mental illness, incarcerated household members, household substance abuse, parental separation/divorce, and witnessing domestic violence before age 18. Smoking status and frequent mental distress (FMD) (≥ 14 days in past 30 days when self-perceived mental health was not good) were assessed as potential mediators in multivariate logistic regression analyses of frequent insufficient sleep by ACEs adjusted for race/ethnicity, gender, education, and body mass index. Overall, 28.8% of 25,810 respondents reported frequent insufficient sleep, 18.8% were current smokers, 10.8% reported frequent mental distress, 59.5% percent reported ≥ 1 ACE, and 8.7% reported ≥ 5 ACEs. Each ACE was associated with frequent insufficient sleep in multivariate analyses. Odds of frequent insufficient sleep were 2.5 (95% CI, 2.1-3.1) times higher in persons with ≥ 5 ACEs compared to those with no ACEs. Most relationships were modestly attenuated by smoking and FMD, but remained significant. Childhood exposures to eight indicators of child maltreatment and household dysfunction were significantly associated with frequent insufficient sleep during adulthood in this population. ACEs could be potential indicators promoting further investigation of sleep insufficiency, along with consideration of FMD and smoking.

  16. Angiotensin converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy

    PubMed Central

    Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M.; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

    2016-01-01

    Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II(1-8) that could also be effective involves fostering its degradation. Angiotensin converting enzyme 2 (ACE2) is a monocarboxypeptidase than cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity and glomerular size, were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic nephropathy. PMID:27927599

  17. Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy.

    PubMed

    Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

    2017-06-01

    Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II (1-8) that could also be effective involves fostering its degradation. Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity, and glomerular size were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic nephropathy. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Angiotensin converting enzyme genotype and chronic allograft nephropathy in protocol biopsies.

    PubMed

    Hueso, Miguel; Alía, Pedro; Moreso, Francesc; Beltrán-Sastre, Violeta; Riera, Luis; González, Carlota; Navarro, Miguel Angel; Grinyó, Josep Maria; Navarro, Estanis; Serón, Daniel

    2004-08-01

    Genotype DD of the angiotensin-converting enzyme (ACE) is not associated with an increased incidence of native renal diseases, although it could modulate progression to renal failure in patients who already display chronic lesions. Because its role in renal allograft degeneration is not well characterized, whether ACE genotype was associated with the prevalence of chronic allograft nephropathy (CAN) was studied, in a group of protocol biopsies from 180 patients, or with the incidence of CAN in 152 patients with at least two sequential biopsies. As a control group, ACE genotype was also studied in 41 donors and 72 healthy subjects. For analyzing the influence of ACE genotype in graft survival, patients were grouped into six categories (II-normal biopsy, ID-normal, DD-normal, II-CAN, ID-CAN and DD-CAN). Finally, relative renal ACE mRNA levels were measured in 67 cases by real-time PCR using the delta threshold cycle method. ACE-DD genotype was more frequent in patients who received a transplant than in control subjects (43.3% versus 30.1%, P = 0.026), but prevalence (DD = 42.7% versus non-DD = 42.2%) or incidence (DD = 24.6% versus non-DD = 29.9%) of CAN was not different regarding recipient ACE genotype. Furthermore, patients with the ACE-DD genotype and CAN had the poorest graft survival (II-normal = 100%, ID-normal = 91%, DD-normal = 84%, II-CAN = 100%, ID-CAN = 66%, and DD-CAN = 36%; P = 0.034) and higher ACE mRNA levels than non-DD and CAN (DD = -3.36 +/- 2.35 versus non-DD = -5.65 +/- 1.72-fold in ACE copies; P = 0.012). It is concluded that ACE-DD genotype is not associated with an increased prevalence or incidence of CAN but is actually associated with higher ACE mRNA levels and poorer graft survival in patients who already display CAN.

  19. Circulating angiotensin-converting enzyme 2 activity in kidney transplantation: a longitudinal pilot study.

    PubMed

    Soler, María José; Riera, Marta; Crespo, Marta; Mir, Marisa; Márquez, Eva; Pascual, María José; Puig, Josep M; Pascual, Julio

    2012-01-01

    Angiotensin-converting enzyme 2 (ACE2) is the only known active homologue of ACE, and degrades angiotensin (Ang) II and Ang I to Ang(1-7) and Ang(1-9), respectively. The role of ACE2 in kidney transplant (KT) is unknown. Our objective was to investigate circulating ACE2 activity in KT patients, and the relationship between serum ACE2 activity and age, gender, graft function and cardiovascular risk markers in KT patients. 113 KT patients with stable graft function were included in this cross-sectional study. Circulating ACE2 activity was assessed using a fluorescent assay. Circulating ACE2 activity was detectable in KT patients and was increased in KT with ischemic heart disease as compared to KT without ischemic heart disease (105.9 ± 8.7 vs. 97.1 ± 7.05 relative fluorescence units (RFU)/µl/h, p < 0.05). ACE2 activity was increased in male KT as compared to females (105.2 ± 9.1 vs. 84.7 ± 6.9 RFU/µl/h, p = 0.05). ACE2 activity correlated positively with serum creatinine (r = 0.27), serum urea (r = 0.29), age (r = 0.24), aspartate transaminase (r = 0.39), alanine transaminase (r = 0.48), γ-glutamyl transferase (γ-GT) (r = 0.52), age (r = 0.24), and glycosylated hemoglobin (r = 0.19) (p < 0.05). By multiple regression analysis, age, serum creatinine, and serum γ-GT were independent predictors of serum ACE2 activity (r = 0.66, p < 0.001). Circulating ACE2 activity is measurable in KT patients and directly correlates with age, renal allograft and liver function parameters. These findings suggest that measurement of serum ACE2 may be used as a non-invasive marker to understand the role of the renin-angiotensin system in KT patients. Copyright © 2012 S. Karger AG, Basel.

  20. A Single Nucleotide Polymorphism Uncovers a Novel Function for the Transcription Factor Ace2 during Candida albicans Hyphal Development

    PubMed Central

    Orellana-Muñoz, Sara; Gutiérrez-Escribano, Pilar; Arnáiz-Pita, Yolanda; Dueñas-Santero, Encarnación; Suárez, M. Belén; Bougnoux, Marie-Elisabeth; del Rey, Francisco; Sherlock, Gavin; d’Enfert, Christophe; Correa-Bordes, Jaime; de Aldana, Carlos R. Vázquez

    2015-01-01

    Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages. PMID:25875512

  1. Technology Development for 3-D Wide Swath Imaging Supporting ACE

    NASA Technical Reports Server (NTRS)

    Racette, Paul; Heymsfield, Gerry; Li, Lihua; Mclinden, Matthew; Park, Richard; Cooley, Michael; Stenger, Pete; Hand, Thomas

    2014-01-01

    The National Academy of Sciences Decadal Survey (DS) Aerosol-Cloud-Ecosystems Mission (ACE) aims to advance our ability to observe and predict changes to the Earth's hydrological cycle and energy balance in response to climate forcing, especially those changes associated with the effects of aerosol on clouds and precipitation. ACE is focused on obtaining measurements to reduce the uncertainties in current climate models arising from the lack in understanding of aerosol-cloud interactions. As part of the mission instrument suite, a dual-frequency radar comprised of a fixed-beam 94 gigahertz (W-band) radar and a wide-swath 35 gigahertz (Ka-band) imaging radar has been recommended by the ACE Science Working Group.In our 2010 Instrument Incubator Program project, we've developed a radar architecture that addresses the challenge associated with achieving the measurement objectives through an innovative, shared aperture antenna that allows dual-frequency radar operation while achieving wide-swath (100 kilometers) imaging at Ka-band. The antenna system incorporates 2 key technologies; a) a novel dual-band reflectorreflectarray and b) a Ka-band Active Electronically Scanned Array (AESA) feed module. The dual-band antenna is comprised of a primary cylindrical reflectorreflectarray surface illuminated by a point-focus W-band feed (compatible with a quasi-optical beam waveguide feed, such as that employed on CloudSat); the Ka-band AESA line feed provides wide-swath across-track scanning. The benefits of this shared-aperture approach include significant reductions in ACE satellite payload size, weight, and cost, as compared to a two aperture approach. Four objectives were addressed in our project. The first entailed developing the tools for the analysis and design of reflectarray antennas, assessment of candidate reflectarray elements, and validation using test coupons. The second objective was to develop a full-scale aperture design utilizing the reflectarray surface and to detail specific requirements and trades for the Ka-band AESA line feed. As part of the third objective a subscale antenna, similar to the full-scale aperture design, was developed, integrated, and flown with the Cloud Radar System during the 2014 Integrated Precipitation and Hydrology Experiment. The fourth and ongoing objective entails developing a GaN MMIC (Gallium Nitride Monolithic Microwave Integrated Circuits) power amplifier for use in the Ka-band AESA. An overview of the progress made on this project and a look ahead at the 2013 IIP (Instrument Incubator Program) award selection will be presented.

  2. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Angiotensin converting enzyme (A.C.E.) test system... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of angiotensin...

  3. Leadership Development Program Final Project

    NASA Technical Reports Server (NTRS)

    Parrish, Teresa C.

    2016-01-01

    TOSC is NASA's prime contractor tasked to successfully assemble, test, and launch the EM1 spacecraft. TOSC success is highly dependent on design products from the other NASA Programs manufacturing and delivering the flight hardware; Space Launch System(SLS) and Multi-Purpose Crew Vehicle(MPCV). Design products directly feed into TOSC's: Procedures, Personnel training, Hardware assembly, Software development, Integrated vehicle test and checkout, Launch. TOSC senior management recognized a significant schedule risk as these products are still being developed by the other two (2) programs; SVE and ACE positions were created.

  4. System looks outside its own walls to find innovative way to cut kids' asthma admissions.

    PubMed

    1999-10-01

    Atlanta children's hospital system initiates outpatient pediatric asthma disease management program to reduce inpatient admissions and ER visits while reducing costs. Children's Healthcare of Atlanta turned to the primary care physician community for front-line support in keeping mild asthma cases out of the hospital. By offering evidence-based practice guidelines, training for staff, and educational materials for patients and their families, the Partnership to ACE Asthma program is off to a running start. Learn how to set up a similar program.

  5. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY PROTOCOL FOR STANDARDIZED PRODUCTION OF CLINICAL PRACTICE GUIDELINES, ALGORITHMS, AND CHECKLISTS - 2017 UPDATE.

    PubMed

    Mechanick, Jeffrey I; Pessah-Pollack, Rachel; Camacho, Pauline; Correa, Ricardo; Figaro, M Kathleen; Garber, Jeffrey R; Jasim, Sina; Pantalone, Kevin M; Trence, Dace; Upala, Sikarin

    2017-08-01

    Clinical practice guideline (CPG), clinical practice algorithm (CPA), and clinical checklist (CC, collectively CPGAC) development is a high priority of the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE). This 2017 update in CPG development consists of (1) a paradigm change wherein first, environmental scans identify important clinical issues and needs, second, CPA construction focuses on these clinical issues and needs, and third, CPG provide CPA node/edge-specific scientific substantiation and appended CC; (2) inclusion of new technical semantic and numerical descriptors for evidence types, subjective factors, and qualifiers; and (3) incorporation of patient-centered care components such as economics and transcultural adaptations, as well as implementation, validation, and evaluation strategies. This third point highlights the dominating factors of personal finances, governmental influences, and third-party payer dictates on CPGAC implementation, which ultimately impact CPGAC development. The AACE/ACE guidelines for the CPGAC program is a successful and ongoing iterative exercise to optimize endocrine care in a changing and challenging healthcare environment. AACE = American Association of Clinical Endocrinologists ACC = American College of Cardiology ACE = American College of Endocrinology ASeRT = ACE Scientific Referencing Team BEL = best evidence level CC = clinical checklist CPA = clinical practice algorithm CPG = clinical practice guideline CPGAC = clinical practice guideline, algorithm, and checklist EBM = evidence-based medicine EHR = electronic health record EL = evidence level G4GAC = Guidelines for Guidelines, Algorithms, and Checklists GAC = guidelines, algorithms, and checklists HCP = healthcare professional(s) POEMS = patient-oriented evidence that matters PRCT = prospective randomized controlled trial.

  6. Advancements for Active Remote Sensing of Carbon Dioxide from Space using the ASCENDS CarbonHawk Experiment Simulator: First Results

    NASA Astrophysics Data System (ADS)

    Obland, M. D.; Nehrir, A. R.; Lin, B.; Harrison, F. W.; Kooi, S. A.; Choi, Y.; Plant, J.; Yang, M. M.; Antill, C.; Campbell, J. F.; Ismail, S.; Browell, E. V.; Meadows, B.; Dobler, J. T.; Zaccheo, T. S.; Moore, B., III; Crowell, S.

    2014-12-01

    The ASCENDS CarbonHawk Experiment Simulator (ACES) is an Intensity-Modulated Continuous-Wave lidar system recently developed at NASA Langley Research Center that seeks to advance technologies and techniques critical to measuring atmospheric column carbon dioxide (CO2) mixing ratios in support of the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. These advancements include: (1) increasing the power-aperture product to approach ASCENDS mission requirements by implementing multi-aperture telescopes and multiple co-aligned laser transmitters; (2) incorporating high-efficiency, high-power Erbium-Doped Fiber Amplifiers (EDFAs); (3) developing and incorporating a high-bandwidth, low-noise HgCdTe detector and transimpedence amplifier (TIA) subsystem capable of long-duration operation on Global Hawk aircraft, and (4) advancing algorithms for cloud and aerosol discrimination. The ACES instrument architecture is being developed for operation on high-altitude aircraft and will be directly scalable to meet the ASCENDS mission requirements. ACES simultaneously transmits five laser beams: three from commercial EDFAs operating near 1571 nm, and two from the Exelis oxygen (O2) Raman fiber laser amplifier system operating near 1260 nm. The Integrated-Path Differential Absorption (IPDA) lidar approach is used at both wavelengths to independently measure the CO2 and O2 column number densities and retrieve the average column CO2 mixing ratio. The outgoing laser beams are aligned to the field of view of ACES' three fiber-coupled 17.8-cm diameter athermal telescopes. The backscattered light collected by the three telescopes is sent to the detector/TIA subsystem, which has a bandwidth of 4.7 MHz and operates service-free using a tactical dewar and cryocooler. Two key laser modulation approaches are being tested to significantly mitigate the effects of thin clouds on the retrieved CO2 column amounts. Full instrument development concluded in the spring of 2014. After ground range tests of the instrument, ACES successfully completed six test flights on the Langley Hu-25 aircraft in July, 2014, and recorded data at multiple altitudes over land and ocean surfaces with and without intervening clouds. Preliminary results from these flights will be presented in this paper.

  7. The Changing Face of Adult Learning. Adult Higher Education Alliance/ACE Conference Proceedings (Austin, TX, October 10-13, 2001).

    ERIC Educational Resources Information Center

    Adult Higher Education Alliance.

    These proceedings included the following papers: "The Language of Interdisciplinary Programs or 'What Do You Mean By That?'" (Ezzell, Turner); "When Mothers Become Students: Impact on Children and the Family System" (Burns, Gabrick); "Multi-Discipline Theorizing Meets the Blackboard: The Evolving Discourse Community"…

  8. 78 FR 44142 - Modification of Two National Customs Automation Program (NCAP) Tests Concerning Automated...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... efforts are accomplished through phased releases of ACE component functionality designed to introduce new... designed to evaluate planned components of the NCAP. This test is authorized pursuant to Sec. 101.9(b) of... import meat, poultry, or egg products or ``Samples for Laboratory Examination, Research, Evaluative...

  9. 76 FR 69755 - National Customs Automation Program Test Concerning Automated Commercial Environment (ACE...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-09

    ... include functionality specific to the filing of entry data for formal and informal consumption entries... three (3) optional data elements to CBP at any time prior to the arrival of the merchandise on the conveyance transporting the cargo to the United States. This data will fulfill merchandise entry requirements...

  10. The Impact of In-Service Technology Training Programmes on Technology Teachers

    ERIC Educational Resources Information Center

    Gumbo, Mishack; Makgato, Moses; Muller, Helene

    2012-01-01

    The aim of this paper is to assess the impact the Advanced Certificate in Education (ACE) in-service technology training program has on technology teachers' knowledge and understanding of technology. The training of technology teachers is an initiative toward teachers' professional development within the mathematics, science, and technology sphere…

  11. National Service Programs and Their Effects on Military Manpower and Civilian Youth Problems. Budget Issue Paper for Fiscal Year 1979.

    DTIC Science & Technology

    1978-01-01

    advent of the All-Volunteer Force (AVF), military salaries have risen substantially; working conditions have improved; recruiting and advertising ...to be second-class citizens. 14/ Alienation among disavantaged youth—for example, black teenagers in urban ghettos—is particularly high. 13/ ACE

  12. New Directions for Higher Education: Q&A with ACE's Molly Corbett Broad on Attainment

    ERIC Educational Resources Information Center

    DiSalvio, Philip

    2013-01-01

    In April 2013, the "New England Journal of Higher Education" ("NEJHE") launched its "New Directions for Higher Education" series to examine emerging issues, trends, and ideas that have an impact on higher education policies, programs and practices. In this installment of the series, DiSalvio speaks with American…

  13. Ace: Action-Communication-Expression. IMPACT II: Houston's Teacher-to-Teacher Network.

    ERIC Educational Resources Information Center

    McIntyre, Margie

    The Action-Communication-Expression program, an extension of a speech communication class in a Houston (Texas) high school, involves visual and concrete communication, such as photography, script writing, and filmmaking. Students in two speech classes work in small groups of four or five, independently of the teacher, after receiving initial…

  14. Worldwide flight and ground-based exposure of composite materials

    NASA Technical Reports Server (NTRS)

    Dexter, H. B.; Baker, D. J.

    1984-01-01

    The long-term durability of those advanced composite materials which are applicable to aircraft structures was discussed. The composite components of various military and commercial aircraft and helicopters were reviewed. Both ground exposure and flight service were assessed in terms of their impact upon composite structure durability. The ACEE Program is mentioned briefly.

  15. 75 FR 67083 - Magnuson-Stevens Act Provisions; General Provisions for Domestic Fisheries; Application for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-01

    ... Research program. The primary objective of this study is to assess the effects of different stressors on... Reflex Action Mortality Predictors (RAMP) under different stressors to assess the discard mortality rates... research landings from the VTRs in their ACE accounting, in addition to the vessel's dealer-recorded...

  16. A Partnership Training Program in Breast Cancer Research Using Molecular Imaging Techniques

    DTIC Science & Technology

    2006-07-01

    Laurence GG, Teos L, Haddad GE. Effects of ACE- Inhibition on ANG II and IGF-1 signaling during development and regression of eccentric cardiac...2274. [33] Morawski AM, Winter PM, Crowder KC , Caruthers SD, Fuhrhop RW, Scott MJ, Robertson JD, Abendschein DR, Lanza GM, Wickline SA (2004). Targeted

  17. On Preparing Moral Educators: A Reply to Commentators

    ERIC Educational Resources Information Center

    Woodbury, Ryan; Lapsley, Daniel

    2016-01-01

    Ryan Woodbury, doctoral student in the developmental psychology program at the University of Notre Dame, and Daniel Lapsley, ACE Collegiate Professor of Psychology and Senior Academic Advisor for the Alliance for Catholic Education at the University of Notre Dame, advance further conversation on how best to prepare educators for the moral work of…

  18. An application of high authority/low authority control and positivity

    NASA Technical Reports Server (NTRS)

    Seltzer, S. M.; Irwin, D.; Tollison, D.; Waites, H. B.

    1988-01-01

    Control Dynamics Company (CDy), in conjunction with NASA Marshall Space Flight Center (MSFC), has supported the U.S. Air Force Wright Aeronautical Laboratory (AFWAL) in conducting an investigation of the implementation of several DOD controls techniques. These techniques are to provide vibration suppression and precise attitude control for flexible space structures. AFWAL issued a contract to Control Dynamics to perform this work under the Active Control Technique Evaluation for Spacecraft (ACES) Program. The High Authority Control/Low Authority Control (HAC/LAC) and Positivity controls techniques, which were cultivated under the DARPA Active Control of Space Structures (ACOSS) Program, were applied to a structural model of the NASA/MSFC Ground Test Facility ACES configuration. The control systems design were accomplished and linear post-analyses of the closed-loop systems are provided. The control system designs take into account effects of sampling and delay in the control computer. Nonlinear simulation runs were used to verify the control system designs and implementations in the facility control computers. Finally, test results are given to verify operations of the control systems in the test facility.

  19. Buffering of blood pressure variability by the renin-angiotensin system in the conscious dog

    PubMed Central

    Just, Armin; Kirchheim, Hartmut R; Ehmke, Heimo

    1998-01-01

    The renin-angiotensin system (RAS) participates in the compensation of major blood pressure disturbances such as haemorrhage and is involved in the tonic long-term (> 1 day) maintenance of mean arterial blood pressure (MABP). Since its contribution to the short-term (< 1 h) buffering of normal blood pressure variability is not known, this was investigated in resting conscious dogs.The regulatory efficiency and the response time of the RAS were studied by an acute step reduction of renal artery pressure to 70 mmHg for 1 h using a suprarenal aortic cuff. After a delay of at least 100 s, MABP rose exponentially by 22 ± 5 mmHg in normal dogs (n = 4), by 6 ± 3 mmHg after angiotensin converting enzyme (ACE) inhibition (n = 4), and by 25 ± 5 mmHg after ganglionic blockade (n = 4). MABP returned to control after release of the cuff with similar time courses. The time constants of the MABP responses were in the range of 20 min. Thus, possible feedback oscillations of the RAS would be expected around 0.0025 Hz (1/(4 × 100 s)); a buffering effect would be possible below this frequency.Blood pressure variability was investigated by spectral analysis of MABP from 3.75 h recordings in the frequency ranges of 0.002–0.003 Hz (feedback oscillations) and below 0.002 Hz (buffering effect).ACE inhibition (n = 7) decreased MABP by 11 ± 2 mmHg (P < 0.05), but in both frequency ranges integrated spectral density was not affected. ACE inhibition also failed to significantly change spectral density in either of the two frequency ranges under the following conditions: (1) during ganglionic blockade (n = 7), (2) during a low-sodium diet (except for a very slight elevation below 0.002 Hz) (n = 7), and (3) when the fall of MABP induced by ACE inhibition was compensated by an angiotensin II infusion (n = 7).It is concluded that in spite of its high regulatory efficiency with an adequate response time the RAS does not directly contribute to the short-term buffering of blood pressure variability, nor does it give rise to feedback oscillations under normal resting conditions. Even if the RAS is stimulated by sodium restriction its contribution to short-term blood pressure buffering is only marginal. PMID:9763646

  20. Acetone fraction from Sechium edule (Jacq.) S.w. edible roots exhibits anti-endothelial dysfunction activity.

    PubMed

    Trejo-Moreno, Celeste; Castro-Martínez, Gabriela; Méndez-Martínez, Marisol; Jiménez-Ferrer, Jesús Enrique; Pedraza-Chaverri, José; Arrellín, Gerardo; Zamilpa, Alejandro; Medina-Campos, Omar Noel; Lombardo-Earl, Galia; Barrita-Cruz, Gerardo Joel; Hernández, Beatriz; Ramírez, Christian Carlos; Santana, María Angélica; Fragoso, Gladis; Rosas, Gabriela

    2018-06-28

    A recent ethnomedical survey on medicinal plants grown in Mexico revealed that Sechium edule (Jacq.) Sw. (Cucurbitaceae) is one of the most valued plant species to treat cardiovascular diseases, including hypertension. Fruits, young leaves, buds, stems, and tuberous roots of the plant are edible. Considering that endothelial dysfunction induced by Angiotensin II plays an important role in the pathogenesis of hypertension and is accompanied by a prooxidative condition, which in turn induces an inflammatory state, vascular remodeling, and tissue damage, and that S. edule has been reported to possess antioxidant, anti-inflammatory and antihypertensive activity, its capability to control endothelial dysfunction was also assessed. To assess in vivo the anti-endothelial dysfunction activity of the acetone fraction (rSe-ACE) of the hydroalcoholic extract from S. edule roots. Endothelial dysfunction was induced in female C57BL/6 J mice by a daily intraperitoneal injection of angiotensin II for 10 weeks. Either rSe-ACE or losartan (as a control) were co-administered with angiotensin II for the same period. Blood pressure was measured at weeks 0, 5, and 10. Kidney extracts were prepared to determine IL1β, IL4, IL6, IL10, IL17, IFNγ, TNFα, and TGFβ levels by ELISA, along with the prooxidative status as assessed by the activity of antioxidant enzymes. The expression of ICAM-1 was evaluated by immunohistochemistry in kidney histological sections. Kidney and hepatic damage, as well as vascular tissue remodeling, were studied. The rSe-ACE fraction administered at a dose of 10 mg/kg was able to control hypertension, as well as the prooxidative and proinflammatory status in kidney as efficiently as losartan, returning mice to normotensive levels. Additionally, the fraction was more efficient than losartan to prevent liver and kidney damage. Phytochemical characterization identified cinnamic acid as a major compound, and linoleic, palmitic, and myristic acids as the most abundant non-polar components in the mixture, previously reported to aid in the control of hypertension, inflammation, and oxidative stress, three important components of endothelial dysfunction. this study demonstrated that rSe-ACE has anti-endothelial dysfunction activity in an experimental model and highlights the role of cinnamic acid and fatty acids in the observed effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Evaluation of the Functional Pre-Basic-Training English-as-a-Second- Language Course

    DTIC Science & Technology

    1985-02-01

    orientation materials, two training video tapes have been recently prepared by the University of South Carolina under the direction of the ACES staff at Fort...most programs. Installations should receive guidelines describing an orientation program for new teachers. The video tapes developed by the University...should be instructed to increase their use of military training aids and be provided information and examples of how to do this. A video tape showing

  2. Fostering Hope and Closing the Academic Gap: An Examination of College Retention for African-American and Latino Students Who Participate in the Louis Stokes Alliance Minority Participation Program (Learning Community) While Enrolled in a Predominately White Institution

    ERIC Educational Resources Information Center

    Hollands, Aisha La'Chae

    2012-01-01

    Colleges are struggling to retain students of color at four-year academic institutions (Kuh, 2005). The result is that while African-American and Latino students are entering college, fewer successfully complete their programs of study and obtain an undergraduate degree (ACE, 2006). For this reason, institutions are establishing supportive…

  3. ACE2 Therapy Using Adeno-associated Viral Vector Inhibits Liver Fibrosis in Mice

    PubMed Central

    Mak, Kai Y; Chin, Ruth; Cunningham, Sharon C; Habib, Miriam R; Torresi, Joseph; Sharland, Alexandra F; Alexander, Ian E; Angus, Peter W; Herath, Chandana B

    2015-01-01

    Angiotensin converting enzyme 2 (ACE2) which breaks down profibrotic peptide angiotensin II to antifibrotic peptide angiotensin-(1–7) is a potential therapeutic target in liver fibrosis. We therefore investigated the long-term therapeutic effect of recombinant ACE2 using a liver-specific adeno-associated viral genome 2 serotype 8 vector (rAAV2/8-ACE2) with a liver-specific promoter in three murine models of chronic liver disease, including carbon tetrachloride-induced toxic injury, bile duct ligation-induced cholestatic injury, and methionine- and choline-deficient diet-induced steatotic injury. A single injection of rAAV2/8-ACE2 was administered after liver disease has established. Hepatic fibrosis, gene and protein expression, and the mechanisms that rAAV2/8-ACE2 therapy associated reduction in liver fibrosis were analyzed. Compared with control group, rAAV2/8-ACE2 therapy produced rapid and sustained upregulation of hepatic ACE2, resulting in a profound reduction in fibrosis and profibrotic markers in all diseased models. These changes were accompanied by reduction in hepatic angiotensin II levels with concomitant increases in hepatic angiotensin-(1–7) levels, resulting in significant reductions of NADPH oxidase assembly, oxidative stress and ERK1/2 and p38 phosphorylation. Moreover, rAAV2/8-ACE2 therapy normalized increased intrahepatic vascular tone in fibrotic livers. We conclude that rAAV2/8-ACE2 is an effective liver-targeted, long-term therapy for liver fibrosis and its complications without producing unwanted systemic effects. PMID:25997428

  4. Murine recombinant angiotensin-converting enzyme 2 attenuates kidney injury in experimental Alport syndrome.

    PubMed

    Bae, Eun Hui; Fang, Fei; Williams, Vanessa R; Konvalinka, Ana; Zhou, Xiaohua; Patel, Vaibhav B; Song, Xuewen; John, Rohan; Oudit, Gavin Y; Pei, York; Scholey, James W

    2017-06-01

    Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase in the renin-angiotensin system that catalyzes the breakdown of angiotensin II to angiotensin 1-7. We have reported that ACE2 expression in the kidney is reduced in experimental Alport syndrome but the impact of this finding on disease progression has not been studied. Accordingly, we evaluated effects of murine recombinant ACE2 treatment in Col4a3 knockout mice, a model of Alport syndrome characterized by proteinuria and progressive renal injury. Murine recombinant ACE2 (0.5 mg/kg/day) was administered from four to seven weeks of age via osmotic mini-pump. Pathological changes were attenuated by murine recombinant ACE2 treatment which ameliorated kidney fibrosis as shown by decreased expression of COL1α1 mRNA, less accumulation of extracellular matrix proteins, and inhibition of transforming growth factor-β signaling. Further, increases in proinflammatory cytokine expression, macrophage infiltration, inflammatory signaling pathway activation, and heme oxygenase-1 levels in Col4a3 knockout mice were also reduced by murine recombinant ACE2 treatment. Lastly, murine recombinant ACE2 influenced the turnover of renal ACE2, as it suppressed the expression of tumor necrosis factor-α converting enzyme, a negative regulator of ACE2. Thus, treatment with exogenous ACE2 alters angiotensin peptide metabolism in the kidneys of Col4a3 knockout mice and attenuates the progression of Alport syndrome nephropathy. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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

    Ryan, J.W.; Anderson, D.R.

    Eye tissues contain kininase activities, including an angiotensin converting enzyme (ACE)-like activity. The authors have begun further to characterize the ACE-like activity and to examine for another reputed kininase, carboxypeptidase N (CPN). Homogenates of tissues of 6 cat eyes and paired plasmas were assayed for ACE using 3 acyl-tripeptide substrates, /sup 3/H-benzoylated F-A-P, F-G-P and A-G-P (respectively, BFAP, BFGP and BAGP). CPN was assayed using /sup 3/H-benzoyl-A-R. All eye tissues and fluids contained ACE- and CPN-like activities. The ACE activity was clearly owing to ACE: relative values of Kc/Km for BFAP, BFGP and BAGP were those for pure ACE (2.213,more » 1.751 and 1.0); reactivities with inhibitors were as expected (Ki for captopril, MK 422 and RAC-X-65: 2.7, 0.62 and 0.31 nM). EDTA inhibited both ACE and CPN (I/sub 50/'s: 43 and 47 ..mu..M). CPN activity was inhibited by 2-mercaptomethyl-3-guanidinoethylthiopropionate (Ki 2.4 nM). However, distributions of the two enzymes differed markedly. Virtually all tissues contained ACE at specific activities higher than that of plasma. Specific activities appeared to be a function of tissue vascularity (for choroid, ciliary body, iris, retina and plasma: 7.31, 2.57, 1.98, 1.53 and 0.21 pmol/mg protein). Only iris contained more CPN that did plasma (23.0 v. 7.21 pmol/mg protein). The tissue distribution of ACE is that expected for an endothelial-associated enzyme. Plasma may be the major source of CPN in eye tissues other than iris.« less

  6. On Becoming Trauma-Informed: Role of the Adverse Childhood Experiences Survey in Tertiary Child and Adolescent Mental Health Services and the Association with Standard Measures of Impairment and Severity.

    PubMed

    Rahman, Abdul; Perri, Andrea; Deegan, Avril; Kuntz, Jennifer; Cawthorpe, David

    2018-01-01

    There is a movement toward trauma-informed, trauma-focused psychiatric treatment. To examine Adverse Childhood Experiences (ACE) survey items by sex and by total scores by sex vs clinical measures of impairment to examine the clinical utility of the ACE survey as an index of trauma in a child and adolescent mental health care setting. Descriptive, polychoric factor analysis and regression analyses were employed to analyze cross-sectional ACE surveys (N = 2833) and registration-linked data using past admissions (N = 10,400) collected from November 2016 to March 2017 related to clinical data (28 independent variables), taking into account multicollinearity. Distinct ACE items emerged for males, females, and those with self-identified sex and for ACE total scores in regression analysis. In hierarchical regression analysis, the final models consisting of standard clinical measures and demographic and system variables (eg, repeated admissions) were associated with substantial ACE total score variance for females (44%) and males (38%). Inadequate sample size foreclosed on developing a reduced multivariable model for the self-identified sex group. The ACE scores relate to independent clinical measures and system and demographic variables. There are implications for clinical practice. For example, a child presenting with anxiety and a high ACE score likely requires treatment that is different from a child presenting with anxiety and an ACE score of zero. The ACE survey score is an important index of presenting clinical status that guides patient care planning and intervention in the progress toward a trauma-focused system of care.

  7. ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

    PubMed

    Patel, Vaibhav B; Mori, Jun; McLean, Brent A; Basu, Ratnadeep; Das, Subhash K; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M; Grant, Maria B; Lopaschuk, Gary D; Oudit, Gavin Y

    2016-01-01

    Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. MSCs with ACE II gene affect apoptosis pathway of acute lung injury induced by bleomycin.

    PubMed

    Zhang, Xiaomiao; Gao, Fengying; Li, Qian; Dong, Zhixia; Sun, Bo; Hou, Lili; Li, Zhuozhe; Liu, Zhenwei

    2015-02-01

    The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI). MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II. The apoptotic index (AI) was calculated using TUNEL, and the detection of protein and mRNA of Bax, Bak and p53, Bcl-2, Grp78, CHOP and Caspase 12 were used by western-blot and RT-PCR, respectively. The umbilical cord cells differentiated into stable MSCs about 14 days, and ACE II transfection reached a peak at the 5th day after transfection. ACE II silence did not affect the phenotype of MSCs. All the proteins and mRNAs expression except Bcl-2 in the stem and stem + ACE II were significantly lower than those in control from 8 h (p < 0.05, p < 0.01), while Bcl-2 exhibited an opposite trend. Stem + ACE II performed a better effect than single stem in most indexes, including AI (p < 0.05, p < 0.01). The co-administration of MSCs and ACE II can significantly suppress apoptosis in ALI mice, and may be an effective clinical treatment for ALI.

  9. In vitro autoradiographic localization of angiotensin-converting enzyme in sarcoid lymph nodes

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

    Allen, R.K.; Chai, S.Y.; Dunbar, M.S.

    1986-09-01

    Angiotensin-converting enzyme (ACE) was localized in sarcoid lymph nodes by an in vitro autoradiographic technique using a synthetic ACE inhibitor of high affinity, /sup 125/I-labelled 351A. The lymph nodes were from seven patients with active sarcoidosis who underwent mediastinoscopy and from six control subjects who had nodes resected at either mediastinoscopy or laparotomy. Angiotensin-converting enzyme was localized in the epithelioid cells of sarcoid granulomata in markedly increased amounts compared with control nodes, where it was restricted to vessels and some histiocytes. In sarcoid lymph nodes, there was little ACE present in lymphocytes or fibrous tissue. Sarcoid nodes with considerable fibrosismore » had much less intense ACE activity than the nonfibrotic nodes. The specific activity of ACE measured by an enzymatic assay in both the control and sarcoid lymph nodes closely reflected the ACE activity demonstrated by autoradiography. Sarcoid lymph nodes with fibrosis had an ACE specific activity of half that of nonfibrotic nodes (p less than 0.05). There was a 15-fold increase in specific ACE activity in sarcoid nodes (p less than 0.05) compared to normal. Serum ACE was significantly higher in those sarcoid patients whose lymph nodes were not fibrosed compared with those with fibrosis (p less than 0.01). This technique offers many advantages over the use of polyclonal antibodies. The 351A is a highly specific ACE inhibitor, chemically defined and in limitless supply. This method enables the quantitation of results, and autoradiographs may be stored indefinitely for later comparison.« less

  10. Absence of cell surface expression of human ACE leads to perinatal death

    PubMed Central

    Michaud, Annie; Acharya, K. Ravi; Masuyer, Geoffrey; Quenech'du, Nicole; Gribouval, Olivier; Morinière, Vincent; Gubler, Marie-Claire; Corvol, Pierre

    2014-01-01

    Renal tubular dysgenesis (RTD) is a recessive autosomal disease characterized most often by perinatal death. It is due to the inactivation of any of the major genes of the renin-angiotensin system (RAS), one of which is the angiotensin I-converting enzyme (ACE). ACE is present as a tissue-bound enzyme and circulates in plasma after its solubilization. In this report, we present the effect of different ACE mutations associated with RTD on ACE intracellular trafficking, secretion and enzymatic activity. One truncated mutant, R762X, responsible for neonatal death was found to be an enzymatically active, secreted form, not inserted in the plasma membrane. In contrast, another mutant, R1180P, was compatible with life after transient neonatal renal insufficiency. This mutant was located at the plasma membrane and rapidly secreted. These results highlight the importance of tissue-bound ACE versus circulating ACE and show that the total absence of cell surface expression of ACE is incompatible with life. In addition, two missense mutants (W594R and R828H) and two truncated mutants (Q1136X and G1145AX) were also studied. These mutants were neither inserted in the plasma membrane nor secreted. Finally, the structural implications of these ACE mutations were examined by molecular modelling, which suggested some important structural alterations such as disruption of intra-molecular non-covalent interactions (e.g. salt bridges). PMID:24163131

  11. Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

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

    Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko

    Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recoverymore » of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.« less

  12. Preparing GMAT for Operational Maneuver Planning of the Advanced Composition Explorer (ACE)

    NASA Technical Reports Server (NTRS)

    Qureshi, Rizwan Hamid; Hughes, Steven P.

    2014-01-01

    The General Mission Analysis Tool (GMAT) is an open-source space mission design, analysis and trajectory optimization tool. GMAT is developed by a team of NASA, private industry, public and private contributors. GMAT is designed to model, optimize and estimate spacecraft trajectories in flight regimes ranging from low Earth orbit to lunar applications, interplanetary trajectories and other deep space missions. GMAT has also been flight qualified to support operational maneuver planning for the Advanced Composition Explorer (ACE) mission. ACE was launched in August, 1997 and is orbiting the Sun-Earth L1 libration point. The primary science objective of ACE is to study the composition of both the solar wind and the galactic cosmic rays. Operational orbit determination, maneuver operations and product generation for ACE are conducted by NASA Goddard Space Flight Center (GSFC) Flight Dynamics Facility (FDF). This paper discusses the entire engineering lifecycle and major operational certification milestones that GMAT successfully completed to obtain operational certification for the ACE mission. Operational certification milestones such as gathering of the requirements for ACE operational maneuver planning, gap analysis, test plans and procedures development, system design, pre-shadow operations, training to FDF ACE maneuver planners, shadow operations, Test Readiness Review (TRR) and finally Operational Readiness Review (ORR) are discussed. These efforts have demonstrated that GMAT is flight quality software ready to support ACE mission operations in the FDF.

  13. Effect of protease inhibitors on angiotensin-converting enzyme activity in human T-lymphocytes.

    PubMed

    Petrov, V; Fagard, R; Lijnen, P

    2000-05-01

    The purpose of these investigations was to determine whether the aminopeptidase B and leucine aminopeptidase inhibitor bestatin, the chymase inhibitor chymostatin, the calpain inhibitor E-64, and the neutral serine protease inhibitor leupeptin affect the angiotensin converting enzyme (ACE) activity in T-lymphocytes. ACE activity in homogenates of T-lymphocytes or in intact T-lymphocytes in suspension was measured by determining fluorimetrically histidyl-leucine, formed from the conversion of hippuryl-histidyl-leucine, coupled with ophtaldialdehyde. The effect of various concentrations (10(-9) to 10(-3) mol/L) of the angiotensin-converting enzyme inhibitors lisinopril and captopril and of the various protease inhibitors on ACE activity was studied. Lisinopril and captopril reduced the ACE activity in homogenates of T-lymphocytes in a concentration-dependent manner. Lisinopril exhibited a more pronounced inhibition of ACE in T-lymphocytes than did captopril. Chymostatin and E-64 had no effect on the ACE activity in T-lymphocytes, whereas leupeptin inhibited its activity in a dose-dependent fashion. Bestatin, on the contrary, increased the ACE activity in homogenates of T-lymphocytes as well as in intact T-lymphocytes in proportion to the concentration. Our data showed that the ACE activity in T-lymphocytes was stimulated by bestatin and inhibited by leupeptin, whereas chymostatin and E-64 did not affect the ACE activity in T-lymphocytes.

  14. ACE [Adult and Community Education] into the 21st Century: A Vision.

    ERIC Educational Resources Information Center

    Adult, Community, and Further Education Board, Melbourne (Australia).

    This document outlines a vision for adult and community education (ACE) in Victoria for the next 3 years and provides a broad map of how to reach that vision. A description of the context is followed by the ACE vision statement: ACE delivers accessible, quality, and timely learning in autonomous, community settings as a valued and essential…

  15. Vibrio cholerae ACE stimulates Ca(2+)-dependent Cl(-)/HCO(3)(-) secretion in T84 cells in vitro.

    PubMed

    Trucksis, M; Conn, T L; Wasserman, S S; Sears, C L

    2000-09-01

    ACE, accessory cholera enterotoxin, the third enterotoxin in Vibrio cholerae, has been reported to increase short-circuit current (I(sc)) in rabbit ileum and to cause fluid secretion in ligated rabbit ileal loops. We studied the ACE-induced change in I(sc) and potential difference (PD) in T84 monolayers mounted in modified Ussing chambers, an in vitro model of a Cl(-) secretory cell. ACE added to the apical surface alone stimulated a rapid increase in I(sc) and PD that was concentration dependent and immediately reversed when the toxin was removed. Ion replacement studies established that the current was dependent on Cl(-) and HCO(3)(-). ACE acted synergistically with the Ca(2+)-dependent acetylcholine analog, carbachol, to stimulate secretion in T84 monolayers. In contrast, the secretory response to cAMP or cGMP agonists was not enhanced by ACE. The ACE-stimulated secretion was dependent on extracellular and intracellular Ca(2+) but was not associated with an increase in intracellular cyclic nucleotides. We conclude that the mechanism of secretion by ACE involves Ca(2+) as a second messenger and that this toxin stimulates a novel Ca(2+)-dependent synergy.

  16. ACE Gene I/D Polymorphism and Obesity in 1,574 Patients with Type 2 Diabetes Mellitus.

    PubMed

    Pan, Yan-Hong; Wang, Min; Huang, Yan-Mei; Wang, Ying-Hui; Chen, Yin-Ling; Geng, Li-Jun; Zhang, Xiao-Xi; Zhao, Hai-Lu

    2016-01-01

    Association between ACE gene I/D polymorphism and the risk of overweight/obesity remains controversial. We investigated the possible relationship between ACE gene I/D polymorphism and obesity in Chinese type 2 diabetes mellitus (T2DM) patients. In this study, obesity was defined as a body mass index (BMI) value ≥ 25 kg/m 2 and subjects were classified into 4 groups (lean, normal, overweight, and obese). PCR (polymerase chain reaction) was used to detect the ACE gene I/D polymorphism in T2DM patients. Metabolic measurements including blood glucose, lipid profile, and blood pressure were obtained. Frequencies of the ACE genotypes (DD, ID, and II) were not significant among the 4 groups of BMI-defined patients ( P = 0.679) while ACE II carriers showed higher systolic blood pressure (SBP) and pulse pressure (PP) (all P < 0.050). Hyperglycemia, hypertension, and dyslipidemia in these T2DM patients were found to be significantly associated with BMI. In conclusion, the relationship of ACE gene I/D polymorphism with obesity is insignificant in Chinese patients with T2DM. SBP and PP might be higher in the ACE II carriers than in the DD and ID carriers.

  17. Production of angiotensin I converting enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in reducing hypertension.

    PubMed

    Rai, Amit Kumar; Sanjukta, Samurailatpam; Jeyaram, Kumaraswamy

    2017-09-02

    Fermented milk is a potential source of various biologically active peptides with specific health benefits. Angiotensin converting enzyme inhibitory (ACE-I) peptides are one of the most studied bioactive peptides produced during milk fermentation. The presence of these peptides is reported in various fermented milk products such as, yoghurt, cheese, sour milk, etc., which are also available as commercial products. Many of the ACE-I peptides formed during milk fermentation are resistant to gastrointestinal digestion and inhibit angiotensin converting enzyme (ACE) in the rennin angiotension system (RAS). There are various factors, which affect the formation ACE-I peptides and their ability to reach the target tissue in active form, which includes type of starters (lactic acid bacteria (LAB), yeast, etc.), substrate composition (casein type, whey protein, etc.), composition of ACE-I peptide, pre and post-fermentation treatments, and its stability during gastrointestinal digestion. The antihypertensive effect of fermented milk products has also been proved by various in vitro and in vivo (animal and human trials) experiments. This paper reviews the literature on fermented milk products as a source of ACE-I peptides and various factors affecting the production and activity of ACE-I peptides.

  18. Focus on increased serum angiotensin-converting enzyme level: From granulomatous diseases to genetic mutations.

    PubMed

    Lopez-Sublet, Marilucy; di Lanzacco, Lorenzo Caratti; Jan Danser, A H; Lambert, Michel; Elourimi, Ghassan; Persu, Alexandre

    2018-06-18

    Angiotensin I-converting enzyme (ACE) is a well-known zinc-metallopeptidase that converts angiotensin I to the potent vasoconstrictor angiotensin II and degrades bradykinin, a powerful vasodilator, and as such plays a key role in the regulation of vascular tone and cardiac function. Increased circulating ACE (cACE) activity has been reported in multiple diseases, including but not limited to granulomatous disorders. Since 2001, genetic mutations leading to cACE elevation have also been described. This review takes advantage of the identification of a novel ACE mutation (25-IVS25 + 1G > A) in two Belgian pedigrees to summarize current knowledge about the differential diagnosis of cACE elevation, based on literature review and the experience of our centre. Furthermore, we propose a practical approach for the evaluation and management of patients with elevated cACE and discuss in which cases search for genetic mutations should be considered. Copyright © 2018. Published by Elsevier Inc.

  19. Occurrence and fate of ACE-inhibitor peptides in cheeses and in their digestates following in vitro static gastrointestinal digestion.

    PubMed

    Stuknytė, Milda; Cattaneo, Stefano; Masotti, Fabio; De Noni, Ivano

    2015-02-01

    The occurrence of the casein-derived angiotensin converting enzyme-inhibitor (ACE-I) peptides VPP, IPP, RYLGY, RYLG, AYFYPEL, AYFYPE, LHLPLP and HLPLP were investigated in 12 different cheese samples by Ultra Performance Liquid Chromatography/High-Resolution Mass Spectrometry. The total amount of ACE-I peptides was in the range 0.87-331mgkg(-1). VPP and IPP largely prevailed in almost all cheeses. Following in vitro static gastrointestinal digestion of Cheddar, Gorgonzola, Maasdam and Grana Padano cheeses, type and amount of ACE-I peptides changed, and only VPP, IPP, HLPLP and LHLPLP were detected in the intestinal digestates. The results evidenced that the degree of proteolysis itself cannot be regarded as a promoting or hindering factor for ACE-I peptide release during cheese digestion. Moreover, the data indicated that the ACE-I potential of cheeses cannot be inferred based on the type and amount of ACE-I peptides present in undigested samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Assessment of the rs4340 ACE gene polymorphism in acute coronary syndrome in a Western Mexican population.

    PubMed

    Valdez-Haro, A; Valle, Y; Valdes-Alvarado, E; Casillas-Muñoz, F; Muñoz-Valle, J F; Reynoso-Villalpando, G L; Flores-Salinas, H E; Padilla-Gutiérrez, J R

    2017-09-27

    Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P < 0.0021) in the CG. The D/D genotype of the rs4340 polymorphism is associated with higher ACE concentration levels; however, the polymorphism was not associated with ACS.

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