Science.gov

Sample records for air conditioners racs

  1. Air Conditioner/Dehumidifier

    NASA Technical Reports Server (NTRS)

    1986-01-01

    An ordinary air conditioner in a very humid environment must overcool the room air, then reheat it. Mr. Dinh, a former STAC associate, devised a heat pipe based humidifier under a NASA Contract. The system used heat pipes to precool the air; the air conditioner's cooling coil removes heat and humidity, then the heat pipes restore the overcooled air to a comfortable temperature. The heat pipes use no energy, and typical savings are from 15-20%. The Dinh Company also manufactures a "Z" coil, a retrofit cooling coil which may be installed on an existing heater/air conditioner. It will also provide free hot water. The company has also developed a photovoltaic air conditioner and solar powered water pump.

  2. Ventilating Air-Conditioner

    NASA Technical Reports Server (NTRS)

    Dinh, Khanh

    1994-01-01

    Air-conditioner provides ventilation designed to be used alone or incorporated into cooling or heating system operates efficiently only by recirculating stale air within building. Energy needed to operate overall ventilating cooling or heating system slightly greater than operating nonventilating cooling or heating system. Helps to preserve energy efficiency while satisfying need for increased forced ventilation to prevent accumulation of undesired gases like radon and formaldehyde. Provides fresh treated air to variety of confined spaces: hospital surgeries, laboratories, clean rooms, and printing shops and other places where solvents used. In mobile homes and portable classrooms, eliminates irritant chemicals exuded by carpets, panels, and other materials, ensuring healthy indoor environment for occupants.

  3. Stirling Air Conditioner for Compact Cooling

    SciTech Connect

    2010-09-01

    BEETIT Project: Infinia is developing a compact air conditioner that uses an unconventional high efficient Stirling cycle system (vs. conventional vapor compression systems) to produce cool air that is energy efficient and does not rely on polluting refrigerants. The Stirling cycle system is a type of air conditioning system that uses a motor with a piston to remove heat to the outside atmosphere using a gas refrigerant. To date, Stirling systems have been expensive and have not had the right kind of heat exchanger to help cool air efficiently. Infinia is using chip cooling technology from the computer industry to make improvements to the heat exchanger and improve system performance. Infinia’s air conditioner uses helium gas as refrigerant, an environmentally benign gas that does not react with other chemicals and does not burn. Infinia’s improvements to the Stirling cycle system will enable the cost-effective mass production of high-efficiency air conditioners that use no polluting refrigerants.

  4. High Efficiency Room Air Conditioner

    SciTech Connect

    Bansal, Pradeep

    2015-01-01

    This project was undertaken as a CRADA project between UT-Battelle and Geberal Electric Company and was funded by Department of Energy to design and develop of a high efficiency room air conditioner. A number of novel elements were investigated to improve the energy efficiency of a state-of-the-art WAC with base capacity of 10,000 BTU/h. One of the major modifications was made by downgrading its capacity from 10,000 BTU/hr to 8,000 BTU/hr by replacing the original compressor with a lower capacity (8,000 BTU/hr) but high efficiency compressor having an EER of 9.7 as compared with 9.3 of the original compressor. However, all heat exchangers from the original unit were retained to provide higher EER. The other subsequent major modifications included- (i) the AC fan motor was replaced by a brushless high efficiency ECM motor along with its fan housing, (ii) the capillary tube was replaced with a needle valve to better control the refrigerant flow and refrigerant set points, and (iii) the unit was tested with a drop-in environmentally friendly binary mixture of R32 (90% molar concentration)/R125 (10% molar concentration). The WAC was tested in the environmental chambers at ORNL as per the design rating conditions of AHAM/ASHRAE (Outdoor- 95F and 40%RH, Indoor- 80F, 51.5%RH). All these modifications resulted in enhancing the EER of the WAC by up to 25%.

  5. Switching on the Aire conditioner.

    PubMed

    Matsumoto, Mitsuru

    2015-12-01

    Aire has been cloned as the gene responsible for a hereditary type of organ-specific autoimmune disease. Aire controls the expression of a wide array of tissue-restricted Ags by medullary thymic epithelial cells (mTECs), thereby leading to clonal deletion and Treg-cell production, and ultimately to the establishment of self-tolerance. However, relatively little is known about the mechanism responsible for the control of Aire expression itself. In this issue of the European Journal of Immunology, Haljasorg et al. [Eur. J. Immunol. 2015. 45: 3246-3256] have reported the presence of an enhancer element for Aire that binds with NF-κB components downstream of the TNF receptor family member, RANK (receptor activator of NF-κB). The results suggest that RANK has a dual mode of action in Aire expression: one involving the promotion of mTEC differentiation and the other involving activation of the molecular switch for Aire within mature mTECs. PMID:26643138

  6. Switching on the Aire conditioner.

    PubMed

    Matsumoto, Mitsuru

    2015-12-01

    Aire has been cloned as the gene responsible for a hereditary type of organ-specific autoimmune disease. Aire controls the expression of a wide array of tissue-restricted Ags by medullary thymic epithelial cells (mTECs), thereby leading to clonal deletion and Treg-cell production, and ultimately to the establishment of self-tolerance. However, relatively little is known about the mechanism responsible for the control of Aire expression itself. In this issue of the European Journal of Immunology, Haljasorg et al. [Eur. J. Immunol. 2015. 45: 3246-3256] have reported the presence of an enhancer element for Aire that binds with NF-κB components downstream of the TNF receptor family member, RANK (receptor activator of NF-κB). The results suggest that RANK has a dual mode of action in Aire expression: one involving the promotion of mTEC differentiation and the other involving activation of the molecular switch for Aire within mature mTECs.

  7. Air Conditioner Compressor Performance Model

    SciTech Connect

    Lu, Ning; Xie, YuLong; Huang, Zhenyu

    2008-09-05

    During the past three years, the Western Electricity Coordinating Council (WECC) Load Modeling Task Force (LMTF) has led the effort to develop the new modeling approach. As part of this effort, the Bonneville Power Administration (BPA), Southern California Edison (SCE), and Electric Power Research Institute (EPRI) Solutions tested 27 residential air-conditioning units to assess their response to delayed voltage recovery transients. After completing these tests, different modeling approaches were proposed, among them a performance modeling approach that proved to be one of the three favored for its simplicity and ability to recreate different SVR events satisfactorily. Funded by the California Energy Commission (CEC) under its load modeling project, researchers at Pacific Northwest National Laboratory (PNNL) led the follow-on task to analyze the motor testing data to derive the parameters needed to develop a performance models for the single-phase air-conditioning (SPAC) unit. To derive the performance model, PNNL researchers first used the motor voltage and frequency ramping test data to obtain the real (P) and reactive (Q) power versus voltage (V) and frequency (f) curves. Then, curve fitting was used to develop the P-V, Q-V, P-f, and Q-f relationships for motor running and stalling states. The resulting performance model ignores the dynamic response of the air-conditioning motor. Because the inertia of the air-conditioning motor is very small (H<0.05), the motor reaches from one steady state to another in a few cycles. So, the performance model is a fair representation of the motor behaviors in both running and stalling states.

  8. 10 CFR 429.15 - Room air conditioners.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 3 2014-01-01 2014-01-01 false Room air conditioners. 429.15 Section 429.15 Energy... COMMERCIAL AND INDUSTRIAL EQUIPMENT Certification § 429.15 Room air conditioners. (a) Sampling plan for selection of units for testing. (1) The requirements of § 429.11 are applicable to room air...

  9. 10 CFR 429.15 - Room air conditioners.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Room air conditioners. 429.15 Section 429.15 Energy... COMMERCIAL AND INDUSTRIAL EQUIPMENT Certification § 429.15 Room air conditioners. (a) Sampling plan for selection of units for testing. (1) The requirements of § 429.11 are applicable to room air...

  10. 10 CFR 429.15 - Room air conditioners.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 3 2012-01-01 2012-01-01 false Room air conditioners. 429.15 Section 429.15 Energy... COMMERCIAL AND INDUSTRIAL EQUIPMENT Certification § 429.15 Room air conditioners. (a) Sampling plan for selection of units for testing. (1) The requirements of § 429.11 are applicable to room air...

  11. Low GWP Refrigerants Modelling Study for a Room Air Conditioner Having Microchannel Heat Exchangers

    SciTech Connect

    Shen, Bo; Bhandari, Mahabir S

    2016-01-01

    Microchannel heat exchangers (MHX) have found great successes in residential and commercial air conditioning applications, being compact heat exchangers, to reduce refrigerant charge and material cost. This investigation aims to extend the application of MHXs in split, room air conditioners (RAC), per fundamental heat exchanger and system modelling. For this paper, microchannel condenser and evaporator models were developed, using a segment-to-segment modelling approach. The microchannel heat exchanger models were integrated to a system design model. The system model is able to predict the performance indices, such as cooling capacity, efficiency, sensible heat ratio, etc. Using the calibrated system and heat exchanger models, we evaluated numerous low GWP (global warming potential) refrigerants. The predicted system performance indices, e.g. cooling efficiency, compressor discharge temperature, and required compressor displacement volume etc., are compared. Suitable replacements for R22 and R-410A for the room air conditioner application are recommended.

  12. 16 CFR Appendix E to Part 305 - Room Air Conditioners

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Room Air Conditioners E Appendix E to Part... PRODUCTS REQUIRED UNDER THE ENERGY POLICY AND CONSERVATION ACT (âAPPLIANCE LABELING RULEâ) Pt. 305, App. E Appendix E to Part 305—Room Air Conditioners Range Information Manufacturer's rated cooling capacity in...

  13. Energy savings potential in air conditioners and chiller systems

    DOE PAGES

    Kaya, Durmus; Alidrisi, Hisham

    2014-01-22

    In the current paper we quantified and evaluated the energy saving potential in air conditioners and chiller systems. Here, we also showed how to reduce the cost of air conditioners and chiller systems in existing facilities on the basis of payback periods. Among the measures investigated were: (1) installing higher efficiency air conditioners, (2) installing higher efficiency chillers, (3) duty cycling air conditioning units, and (4) utilizing existing economizers on air conditioning units. For each method, examples were provided from Arizona, USA. In these examples, the amount of saved energy, the financial evaluation of this energy, and the investment costmore » and pay back periods were calculated.« less

  14. Energy savings potential in air conditioners and chiller systems

    SciTech Connect

    Kaya, Durmus; Alidrisi, Hisham

    2014-01-22

    In the current paper we quantified and evaluated the energy saving potential in air conditioners and chiller systems. Here, we also showed how to reduce the cost of air conditioners and chiller systems in existing facilities on the basis of payback periods. Among the measures investigated were: (1) installing higher efficiency air conditioners, (2) installing higher efficiency chillers, (3) duty cycling air conditioning units, and (4) utilizing existing economizers on air conditioning units. For each method, examples were provided from Arizona, USA. In these examples, the amount of saved energy, the financial evaluation of this energy, and the investment cost and pay back periods were calculated.

  15. High efficiency novel window air conditioner

    SciTech Connect

    Bansal, Pradeep

    2015-01-01

    This paper presents the technical development of a high efficiency window air conditioner. In order to achieve higher energy efficiency ratio (EER), the original capacity of the R410A unit was downgraded by replacing the original compressor with a lower capacity but higher EER compressor, while all heat exchangers and the chassis from the original unit were retained. The other subsequent major modifications included – the AC fan motor being replaced with a brushless high efficiency electronically commuted motor (ECM) motor, the capillary tube being replaced with a needle valve to better control the refrigerant flow and refrigerant set points, and R410A being replaced with drop-in environmentally friendly binary mixture of R32 (85% molar concentration)/R125 (15% molar concentration). All these modifications resulted in significant EER enhancement of the modified unit.

  16. High efficiency novel window air conditioner

    DOE PAGES

    Bansal, Pradeep

    2015-01-01

    This paper presents the technical development of a high efficiency window air conditioner. In order to achieve higher energy efficiency ratio (EER), the original capacity of the R410A unit was downgraded by replacing the original compressor with a lower capacity but higher EER compressor, while all heat exchangers and the chassis from the original unit were retained. The other subsequent major modifications included – the AC fan motor being replaced with a brushless high efficiency electronically commuted motor (ECM) motor, the capillary tube being replaced with a needle valve to better control the refrigerant flow and refrigerant set points, andmore » R410A being replaced with drop-in environmentally friendly binary mixture of R32 (85% molar concentration)/R125 (15% molar concentration). All these modifications resulted in significant EER enhancement of the modified unit.« less

  17. Improving Air-Conditioner and Heat Pump Modeling

    SciTech Connect

    Winkler, Jon

    2012-03-02

    This presentation describes a new approach to modeling residential air conditioners and heat pumps, which allows users to model systems by specifying only the more readily-available SEER/EER/HSPF-type metrics. Manufacturer data was used to generate full sets of model inputs for over 450 heat pumps and air conditioners. A sensitivity analysis identified which inputs can be safely defaulted “behind-the-scenes” without negatively impacting the reliability of energy simulations.

  18. Improving Air-Conditioner and Heat Pump Modeling (Presentation)

    SciTech Connect

    Winkler, J.

    2012-03-01

    A new approach to modeling residential air conditioners and heat pumps allows users to model systems by specifying only the more readily-available SEER/EER/HSPF-type metrics. Manufacturer data was used to generate full sets of model inputs for over 450 heat pumps and air conditioners. A sensitivity analysis identified which inputs can be safely defaulted 'behind-the-scenes' without negatively impacting the reliability of energy simulations.

  19. Air-conditioner filters enriching dust mites allergen

    PubMed Central

    Zhan, Xiaodong; Li, Chaopin; Xu, Haifeng; Xu, Pengfei; Zhu, Haibin; Diao, Jidong; Li, Na; Zhao, Beibei

    2015-01-01

    We detected the concentration of dust mites allergen (Der f1 & Der p1) in the air of different places before and after the starting of air-conditioners in Wuhu City, Anhui, China, and to discuss the relation between the dust mites allergen in air-conditioner filters and the asthma attack. The dust samples were collected from the air-conditioner filters in dining rooms, shopping malls, hotels and households respectively. Concentrations of dust mites major group allergen 1 (Der f 1, Der p1) were detected with enzyme linked immunosorbent assay (ELISA), and the dust mite immune activities were determined by dot-ELISA. The concentration of Der f1 in dining rooms, shopping malls, hotels and households was 1.52 μg/g, 1.24 μg/g, 1.31 μg/g and 1.46 μg/g respectively, and the concentration of Der p1 in above-mentioned places was 1.23 μg/g, 1.12 μg/g, 1.16 μg/g and 1.18 μg/g respectively. The concentration of Der f1 & Der p1 in air was higher after the air-conditioners starting one hours later, and the difference was significant (P<0.05, respectively). Additionally, dot-ELISA findings revealed that the allergen extracted from the dust was capable of reacting with IgE from the sera of asthma mice allergic to dust mites. The study concludes that air-conditioner filters can enrich dust mites major group allergen, and the allergens can induce asthma. The air-conditioner filters shall be cleaned or replaced regularly to prevent or reduce accumulation of the dust mites and its allergens. PMID:26064381

  20. Air-conditioner filters enriching dust mites allergen.

    PubMed

    Zhan, Xiaodong; Li, Chaopin; Xu, Haifeng; Xu, Pengfei; Zhu, Haibin; Diao, Jidong; Li, Na; Zhao, Beibei

    2015-01-01

    We detected the concentration of dust mites allergen (Der f1 & Der p1) in the air of different places before and after the starting of air-conditioners in Wuhu City, Anhui, China, and to discuss the relation between the dust mites allergen in air-conditioner filters and the asthma attack. The dust samples were collected from the air-conditioner filters in dining rooms, shopping malls, hotels and households respectively. Concentrations of dust mites major group allergen 1 (Der f 1, Der p1) were detected with enzyme linked immunosorbent assay (ELISA), and the dust mite immune activities were determined by dot-ELISA. The concentration of Der f1 in dining rooms, shopping malls, hotels and households was 1.52 μg/g, 1.24 μg/g, 1.31 μg/g and 1.46 μg/g respectively, and the concentration of Der p1 in above-mentioned places was 1.23 μg/g, 1.12 μg/g, 1.16 μg/g and 1.18 μg/g respectively. The concentration of Der f1 & Der p1 in air was higher after the air-conditioners starting one hours later, and the difference was significant (P<0.05, respectively). Additionally, dot-ELISA findings revealed that the allergen extracted from the dust was capable of reacting with IgE from the sera of asthma mice allergic to dust mites. The study concludes that air-conditioner filters can enrich dust mites major group allergen, and the allergens can induce asthma. The air-conditioner filters shall be cleaned or replaced regularly to prevent or reduce accumulation of the dust mites and its allergens. PMID:26064381

  1. Rooftop Unitary Air Conditioner with Integral Dedicated Outdoor Air System

    SciTech Connect

    Tiax Llc

    2006-02-28

    Energy use of rooftop and other unitary air-conditioners in commercial applications accounts for about 1 quad (10{sup 15} Btu) of primary energy use annually in the U.S. [Reference 7]. The realization that this cooling equipment accounts for the majority of commercial building cooled floorspace and the majority also of commercial building energy use has spurred development of improved-efficiency equipment as well as development of stricter standards addressing efficiency levels. Another key market driver affecting design of rooftop air-conditioning equipment has been concern regarding comfort and the control of humidity. Trends for increases in outdoor air ventilation rates in certain applications, and the increasing concern about indoor air quality problems associated with humidity levels and moisture in buildings points to a need for improved dehumidification capability in air-conditioning equipment of all types. In many cases addressing this issue exacerbates energy efficiency, and vice versa. The integrated dedicated outdoor air system configuration developed in this project addresses both energy and comfort/humidity issues.

  2. Laboratory Performance Testing of Residential Window Air Conditioners

    SciTech Connect

    Winkler, J.; Booten, C.; Christensen, D.; Tomerlin, J.

    2013-03-01

    Window air conditioners are the dominant cooling product for residences, in terms of annual unit sales. They are inexpensive, portable and can be installed by the owner. For this reason, they are an attractive solution for supplemental cooling, for retrofitting air conditioning into a home which lacks ductwork, and for renters. Window air conditioners for sale in the United States are required to meet very modest minimum efficiency standards. Four window air conditioners' performance were tested in the Advanced HVAC Systems Laboratory on NREL's campus in Golden, CO. In order to separate and study the refrigerant system's performance, the unit's internal leakage pathways, the unit's fanforced ventilation, and the leakage around the unit resulting from installation in a window, a series of tests were devised that focused on each aspect of the unit's performance. These tests were designed to develop a detailed performance map to determine whole-house performance in different climates. Even though the test regimen deviated thoroughly from the industry-standard ratings test, the results permit simple calculation of an estimated rating for both capacity and efficiency that would result from a standard ratings test. Using this calculation method, it was found that the three new air conditioners' measured performance was consistent with their ratings. This method also permits calculation of equivalent SEER for the test articles. Performance datasets were developed across a broad range of indoor and outdoor operating conditions, and used them to generate performance maps.

  3. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... and Air Conditioners. 52.223-12 Section 52.223-12 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.223-12 Refrigeration Equipment and Air Conditioners. As prescribed in 23.804(b), insert the following clause: Refrigeration Equipment and Air Conditioners (MAY 1995) The Contractor...

  4. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... and Air Conditioners. 52.223-12 Section 52.223-12 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.223-12 Refrigeration Equipment and Air Conditioners. As prescribed in 23.804(b), insert the following clause: Refrigeration Equipment and Air Conditioners (MAY 1995) The Contractor...

  5. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and Air Conditioners. 52.223-12 Section 52.223-12 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.223-12 Refrigeration Equipment and Air Conditioners. As prescribed in 23.804(b), insert the following clause: Refrigeration Equipment and Air Conditioners (MAY 1995) The Contractor...

  6. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... and Air Conditioners. 52.223-12 Section 52.223-12 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.223-12 Refrigeration Equipment and Air Conditioners. As prescribed in 23.804(b), insert the following clause: Refrigeration Equipment and Air Conditioners (MAY 1995) The Contractor...

  7. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... and Air Conditioners. 52.223-12 Section 52.223-12 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.223-12 Refrigeration Equipment and Air Conditioners. As prescribed in 23.804(b), insert the following clause: Refrigeration Equipment and Air Conditioners (MAY 1995) The Contractor...

  8. Development of a solar-powered residential air conditioner

    NASA Technical Reports Server (NTRS)

    1975-01-01

    An extensive review of the literature was conducted which was concerned with the characterization of systems and equipment that could be applicable to the development of solar-powered air conditioners based on the Rankine cycle approach, and the establishment of baseline data defining the performance, physical characteristics, and cost of systems using the LiBr/H2O absorption cycle.

  9. Development of vehicle magnetic air conditioner (VMAC) technology. Final report

    SciTech Connect

    Gschneidner, Karl A., Jr.; Pecharsky, V.K.; Jiles, David; Zimm, Carl B.

    2001-08-28

    The objective of Phase I was to explore the feasibility of the development of a new solid state refrigeration technology - magnetic refrigeration - in order to reduce power consumption of a vehicle air conditioner by 30%. The feasibility study was performed at Iowa State University (ISU) together with Astronautics Corporation of America Technology Center (ACATC), Madison, WI, through a subcontract with ISU.

  10. Domestic Refrigeration, Freezer, and Window Air Conditioner Service. Teacher Edition.

    ERIC Educational Resources Information Center

    Clemons, Mark

    This curriculum guide contains six units of instruction for a course in domestic refrigerator, freezer, and window air conditioner service. The units cover the following topics: (1) service fundamentals; (2) mechanical components and functions; (3) electrical components and control devices; (4) refrigerator and freezer service; (5) domestic ice…

  11. Monitoring and evaluation of replacing low-efficiency air conditioners with high-efficiency air conditioners in single-family detached houses in Austin, Texas

    SciTech Connect

    Burns, R.; Hough, R.E. and Associates, Inc., Syracuse, NY )

    1991-10-01

    The US DOE initiated this project to evaluate the performance of an air conditioner retrofit program in Austin, Texas. The City's Austin's Resource Management Department pursued this project to quantify the retrofit effect of replacing low-efficiency air conditioners with high-efficiency air conditioners in single-family detached homes. If successfully implemented, this retrofit program could help defer construction of a new power plant which is a major goal of this department. The project compares data collected from 12 houses during two cooling seasons under pre-retrofit and then post-retrofit air conditioner units. The existing low-efficiency air conditioners were monitored during the 1987 cooling season, replaced during the 1987--88 heating season with new, smaller sized, high-efficiency units, and then monitored again during the 1988 cooling season. Results indicated that the air conditioner retrofits reduce the annual air conditioner electric consumption and peak electric demand by an average of 38%. When normalized to the nominal capacity of the air conditioner, average demand savings were 1.12 W/ft{sup 2} and estimated annual energy savings were 1.419 kWh/ft{sup 2}. Individual air conditioner power requirements were found to be a well defined function of outdoor temperature as expected. In the absence of detailed data, estimates of the peak demand reductions of new air conditioners can be made from the manufacturer's specifications. Air conditioner energy consumption proved to be strongly linear as a function of the outdoor temperature as expected when taken as an aggregate. No noticeable differences in the diversity factor of the air conditioner usage were found. Analysis of the retrofit effect using PRISM yields estimates of the reduction in normalized annual consumption (NAC) and annual cooling consumption of 12% and 30%. 2 refs., 11 figs., 17 tabs.

  12. Development of a solar-powered residential air conditioner

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The initial objective of the program was the optimization (in terms of cost and performance) of a Rankine cycle mechanical refrigeration system which utilizes thermal energy from a flat solar collector for air conditioning residential buildings. However, feasibility investigations of the adsorption process revealed that a dessicant-type air conditioner offers many significant advantages. As a result, limited efforts were expended toward the optimization of such a system.

  13. Assessment of Environmentally Friendly Refrigerants for Window Air Conditioners

    SciTech Connect

    Bansal, Pradeep; Shen, Bo

    2014-01-01

    This paper presents technical assessment of environmentally friendly refrigerants for window air conditioners that currently use refrigerant R410A for residential and commercial applications. The alternative refrigerants that are studied for its replacement include R32, R600a, R290, R1234yf, R1234ze and a mixture of R32 (90% molar concentration) and R125 (10% molar concentration). Baseline experiments were performed on a window unit charged with R410A. The ORNL Heat Pump Design Model was calibrated with the baseline data and was used to assess the comparative performance of the WAC with alternative refrigerants. The paper discusses the advantages and disadvantages of each refrigerants and their suitability for window air conditioners.

  14. Analysis of Environmentally Friendly Refrigerant Options for Window Air Conditioners

    DOE PAGES

    Bansal, Pradeep; Shen, Bo

    2015-03-12

    This paper presents a technical assessment of environmentally friendly refrigerants as alternatives to R410A for window air conditioners. The alternative refrigerants that are studied for its replacement include R32, a mixture of R32/R125 with 90%/10% molar concentration, R600a, R290, R1234yf, R1234ze and R134a. Baseline experiments were performed on a window unit charged with R410A. The heat pump design model (HPDM) was modified and calibrated with the baseline data and was used to evaluate the comparative performance of the WAC with alternative refrigerants. The paper discusses the advantages and disadvantages of each refrigerants and their suitability for window air conditioners. Amongmore » all the refrigerants studied, R32 offers the best efficiency and the lowest Global Warming Potential (GWP), and hence its use will result in the overall environmental friendliness.« less

  15. Analysis of Environmentally Friendly Refrigerant Options for Window Air Conditioners

    SciTech Connect

    Bansal, Pradeep; Shen, Bo

    2015-03-12

    This paper presents a technical assessment of environmentally friendly refrigerants as alternatives to R410A for window air conditioners. The alternative refrigerants that are studied for its replacement include R32, a mixture of R32/R125 with 90%/10% molar concentration, R600a, R290, R1234yf, R1234ze and R134a. Baseline experiments were performed on a window unit charged with R410A. The heat pump design model (HPDM) was modified and calibrated with the baseline data and was used to evaluate the comparative performance of the WAC with alternative refrigerants. The paper discusses the advantages and disadvantages of each refrigerants and their suitability for window air conditioners. Among all the refrigerants studied, R32 offers the best efficiency and the lowest Global Warming Potential (GWP), and hence its use will result in the overall environmental friendliness.

  16. Study on the Refrigeration Cycle of Automotive Air-Conditioner

    NASA Astrophysics Data System (ADS)

    Hara, Junichiro; Honda, Itsuro; Kanazawa, Koji; Ohba, Hideki; Uemura, Masakazu

    The steady state characteristics of a refrigeration cycle for automotive air-conditioners using Freon 12 gas is studied numerically. The numerical method for the simulation of a refrigeration cycle executed on a personal computer is presented. The model for a refrigeration cycle consists of a compressor, condenser, expansion valve and evaporator. Non linear equations for pressure, temperature and refrigerant mass are calculated by the Newton-Raphson method. In particular, experimental date are employed for calculation of compressor condition and influence of refrigerator oil is considered. From the comparison with the experiment, it is made c1ear that this simulation is useful for the prediction of the performance of a refrigeration cycle. Therefore, the optimum design and the shortening of the design process for automotive air-conditioners are possible by this simulation.

  17. Development and Analysis of Desiccant Enhanced Evaporative Air Conditioner Prototype

    SciTech Connect

    Kozubal, E.; Woods, J.; Judkoff, R.

    2012-04-01

    This report documents the design of a desiccant enhanced evaporative air conditioner (DEVAP AC) prototype and the testing to prove its performance. Previous numerical modeling and building energy simulations indicate a DEVAP AC can save significant energy compared to a conventional vapor compression AC (Kozubal et al. 2011). The purposes of this research were to build DEVAP prototypes, test them to validate the numerical model, and identify potential commercialization barriers.

  18. Determining benefits and costs of improved central air conditioner efficiencies

    SciTech Connect

    Rosenquist, G.; Levok, A.; Chan, P.; McMahon, J.

    2001-01-12

    Economic impacts on individual consumers from possible revisions to U.S. residential-type central air conditioner energy-efficiency standards are examined using a life-cycle cost (LCC) analysis. LCC is the consumer's cost of purchasing and installing a central air conditioner and operating it over its lifetime. This approach makes it possible to evaluate the economic impacts on individual consumers from the revised standards. The methodology allows an examination of groups of the population which benefit or lose from suggested efficiency standards. The results show that the economic benefits to consumers due to modest increases in efficiency are significant. For an efficiency increase of 20percent over the existing minimum standard (i.e., 12 SEER), 35percent of households with central air conditioners experience significant LCC savings, with an average savings of $453, while 25percent show significant LCC losses, with an average loss of $158 compared to apre-standard LCC average of $5,170. The remainder of the population (40percent) are largely unaffected.

  19. 16 CFR Appendix H to Part 305 - Cooling Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Conditioners (Cooling Only): All capacities 10.6 16.5 Heat Pumps (Cooling Function): All capacities 10.6 16.0 Split System Units Central Air Conditioners (Cooling Only): All capacities 10.9 23.0 Heat Pumps (Cooling... Conditioners H Appendix H to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER...

  20. 16 CFR Appendix H to Part 305 - Cooling Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Conditioners (Cooling Only): All capacities 10.6 16.5 Heat Pumps (Cooling Function): All capacities 10.6 16.0 Split System Units Central Air Conditioners (Cooling Only): All capacities 10.9 23.0 Heat Pumps (Cooling... Conditioners H Appendix H to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER...

  1. Building pressurization control with rooftop air conditioners

    SciTech Connect

    Winter, S.

    1982-10-01

    The modulated exhaust fan appears to be the most cost effective positive means to maintain close building pressure control with rooftop air conditioning, but because building construction and applications vary, every building's pressure control needs must be analyzed. Requirements will vary from no relief to barometric dampers to return fans to modulated exhaust fans. As heating and cooling costs continue to rise and tighter building codes prevail, proper selection of building pressure control is one area that must be monitored more carefully by the HVAC system designer.

  2. Zero Carryover Liquid-Desiccant Air Conditioner for Solar Applications: Preprint

    SciTech Connect

    Lowenstein, A.; Slayzak, S.; Kozubal, E.

    2006-07-01

    A novel liquid-desiccant air conditioner that dries and cools building supply air will transform the use of direct-contact liquid-desiccant systems in HVAC applications, improving comfort, air quality, and providing energy-efficient humidity control.

  3. Huffing air conditioner fluid: a cool way to die?

    PubMed

    Phatak, Darshan R; Walterscheid, Jeffrey

    2012-03-01

    "Huffing," the form of substance abuse involving inhalants, is growing in popularity because of the ease and availability of chemical inhalants in many household products. The purpose in huffing is to achieve euphoria when the chemicals in question interact with the central nervous system in combination with oxygen displacement. The abuser is lulled into a false sense of safety despite the well-documented potential for lethal cardiac arrhythmia and the effects of chronic inhalant abuse, including multisystem organ failure, and brain damage. Huffing air conditioner fluid is a growing problem given the accessibility to outdoor units and their fluid components, such as difluorochloromethane(chlorodifluoromethane, Freon), and we have classified multiple cases of accidental death due to the toxicity of difluorochloromethane. Given the ubiquity of these devices and the vast lack of gating or security devices, they make an inviting target for inhalant abusers. Acute huffing fatalities have distinct findings that are present at the scene, given the position of the decedent and proximity to the air conditioner unit. The purpose of the autopsy in these cases is to exclude other potential causes of death and to procure specimens for toxicological analysis.

  4. Huffing air conditioner fluid: a cool way to die?

    PubMed

    Phatak, Darshan R; Walterscheid, Jeffrey

    2012-03-01

    "Huffing," the form of substance abuse involving inhalants, is growing in popularity because of the ease and availability of chemical inhalants in many household products. The purpose in huffing is to achieve euphoria when the chemicals in question interact with the central nervous system in combination with oxygen displacement. The abuser is lulled into a false sense of safety despite the well-documented potential for lethal cardiac arrhythmia and the effects of chronic inhalant abuse, including multisystem organ failure, and brain damage. Huffing air conditioner fluid is a growing problem given the accessibility to outdoor units and their fluid components, such as difluorochloromethane(chlorodifluoromethane, Freon), and we have classified multiple cases of accidental death due to the toxicity of difluorochloromethane. Given the ubiquity of these devices and the vast lack of gating or security devices, they make an inviting target for inhalant abusers. Acute huffing fatalities have distinct findings that are present at the scene, given the position of the decedent and proximity to the air conditioner unit. The purpose of the autopsy in these cases is to exclude other potential causes of death and to procure specimens for toxicological analysis. PMID:22442834

  5. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... heat pumps. 431.92 Section 431.92 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Commercial Air Conditioners and Heat Pumps § 431.92 Definitions concerning commercial air conditioners and heat pumps. The following definitions...

  6. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... heat pumps. 431.92 Section 431.92 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Commercial Air Conditioners and Heat Pumps § 431.92 Definitions concerning commercial air conditioners and heat pumps. The following definitions...

  7. 16 CFR Appendix H to Part 305 - Cooling Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Manufacturer's rated cooling capacities (Btu's/hr.) Range of SEER's Low High Single Package Units Central Air Conditioners (Cooling Only): All capacities 10.6 16.5 Heat Pumps (Cooling Function): All capacities 10.6 16.0 Split System Units Central Air Conditioners (Cooling Only): All capacities 10.9 23.0 Heat Pumps...

  8. 16 CFR Appendix H to Part 305 - Cooling Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... for Central Air Conditioners Manufacturer's rated cooling capacities (Btu's/hr.) Range of SEER's Low High Single Package Units Central Air Conditioners (Cooling Only): All capacities 10.6 16.5 Heat Pumps...): All capacities 10.9 23.0 Heat Pumps (Cooling Function): All capacities 10.9 21.0...

  9. 10 CFR 431.96 - Uniform test method for the measurement of energy efficiency of commercial air conditioners and...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Air Conditioners and Heat Pumps Test Procedures § 431.96 Uniform test method for the measurement of energy efficiency of commercial air conditioners and heat pumps. (a) Scope. This section contains test... efficiency of commercial air conditioners and heat pumps. 431.96 Section 431.96 Energy DEPARTMENT OF...

  10. Dirty air conditioners: Energy implications of coil fouling

    SciTech Connect

    Siegel, Jeffrey; Walker, Iain; Sherman, Max

    2002-03-01

    Residential air conditioning is responsible for a substantial amount of peak electrical demand and energy consumption throughout most of the United States. Coil fouling, the deposition of indoor dusts and other particulate matter on evaporator heat exchangers, increases system pressure drop and, correspondingly, decreases system air flow and air conditioner performance. In this paper, we apply experimental and simulation results describing particle deposition on evaporator coils as well as research about indoor particle and dust concentrations to determine coil fouling rates. The results suggest that typical coils foul enough to double evaporator pressure drop in about 7.5 years, much sooner than the expected 15-30 year life time for an evaporator coil. The most important parameters in determining coil fouling times are the efficiency of the filter and indoor particle concentrations, although filter bypass and duct and coil design are important as well. The reduced air flows that result from coil fouling cause typical efficiency and capacity degradations of less than 5%, however they can be much greater for marginal systems or extreme conditions. These energy issues, as well as possible indoor air quality issues resulting from fouling by biological aerosols, suggest that regular coil cleaning to ameliorate low flow and the elimination of filter bypass should be an important part of residential air conditioning commissioning and maintenance practices.

  11. Greenhouse gas emissions for refrigerant choices in room air conditioner units.

    PubMed

    Galka, Michael D; Lownsbury, James M; Blowers, Paul

    2012-12-01

    In this work, potential replacement refrigerants for window-mounted room air conditioners (RACs) in the U.S. have been evaluated using a greenhouse gas (GHG) emissions analysis. CO(2)-equivalent emissions for several hydrofluoroethers (HFEs) and other potential replacements were compared to the most widely used refrigerants today. Included in this comparison are pure refrigerants that make up a number of hydrofluorocarbon (HFC) mixtures, pure hydrocarbons, and historically used refrigerants such as propane and ammonia. GHG emissions from direct and indirect sources were considered in this thermodynamic analysis. Propylene, dimethyl ether, ammonia, R-152a, propane, and HFE-152a all performed effectively in a 1 ton window unit and produced slightly lower emissions than the currently used R-22 and R-134a. The results suggest that regulation of HFCs in this application would have some effect on reducing emissions since end-of-life emissions remain at 55% of total refrigerant charge despite EPA regulations that mandate 80% recovery. Even so, offsite emissions due to energy generation dominate over direct GHG emissions and all the refrigerants perform similarly in totals of indirect GHG emissions. PMID:23136858

  12. High-Efficiency Rooftop Air Conditioners: Small Commercial ACs Could Add Up to Big Energy Savings

    SciTech Connect

    Hollomon, J Bradford; Gilbride, Theresa L.

    2003-04-01

    This paper describes a technology procurement conducted by DOE, PNNL, and the Defense Logistics Agency to increase the availability of energy-efficient, packaged, unitary ''rooftop'' air conditioners. The procurement encourages air conditioner manufacturers to produce equipment that exceeds federal energy efficiency standards by at least 25 percent at a lower first cost. Program developers have also sought to aggregate market demand by organizing groups of large-volume buyers of air conditioning equipment. A Cost Estimator tool developed by PNNL to help consumers determine the cost effectiveness, based on local climate conditions, of purchasing energy efficient air conditioners for their own facilities is also described.

  13. Shortening the Defrost Time on a Heat Pump Air Conditioner

    NASA Astrophysics Data System (ADS)

    Kuwahara, Eiji; Yamazaki, Masaya; Kawamura, Toshiaki

    Methods to shorten the defrost time have been studied on a heat pump air conditioner. The experiment has been carried out using a 0.75kW heat pump and the energy balance during defrosting has been analyzed. We have found that the following methods are effective to shorten the defrost time; (1) Increase in power inqut to the compressor during defrosting, (2) Utilization of the compressor for thermal energy storage, (3) Reduction of the water left on the outdoor heat exchanger fins. The heat pump with the new defrosting system has been made on an experimental basis. lts defrost time is 1 minute and 55 seconds under the defrost condition of the Japanese Industrial Standard. The defrost time of a conventional heat pump is about 4 or 5 minutes.

  14. Development of a solar powered residential air conditioner (General optimization)

    NASA Technical Reports Server (NTRS)

    Lowen, D. J.

    1976-01-01

    A commercially available 3-ton residential Lithium Bromide (LiBr) absorption air conditioner was modified for use with lower temperature solar heated water. The modification included removal of components such as the generator, concentration control chamber, liquid trap, and separator; and the addition of a Chrysler designed generator, an off-the-shelf LiBr-solution pump. The design goal of the modified unit was to operate with water as the heat-transfer fluid at a target temperature of 85 C (185 F), 29.4 C (85 F) cooling water inlet, producing 10.5 kW (3 tons) of cooling. Tests were performed on the system before and after modification to provide comparative data. At elevated temperatures (96 C, 205 F), the test results show that Lithium Bromide was carried into the condenser due to the extremely violent boiling and degraded the evaporator performance.

  15. High-Efficiency Rooftop Air Conditioners: Innovative Procurement to Achieve Advances in Technology

    SciTech Connect

    Hollomon, Brad

    2003-08-01

    The U.S. Department of Energy, Defense Logistics Agency, and Pacific Northwest National Laboratory recently conducted a technology procurement to increase the availability of energy-efficient, packaged unitary ''rooftop'' air conditioners. The procurement encouraged air conditioner manufacturers to produce equipment that exceeded US energy efficiency standards by at least 25% at a lower life-cycle cost. An outgrowth of the project, a web-based cost estimator tool is now available to help consumers determine the cost-effectiveness of purchasing energy-efficient air conditioners based on climate conditions and other factors at their own locations.

  16. Effect of air-conditioner on fungal contamination

    NASA Astrophysics Data System (ADS)

    Hamada, Nobuo; Fujita, Tadao

    Air-conditioners (AC) produce much dew and wet conditions inside their apparatus, when in operation. We studied the fungal contamination in AC and found that the average fungal contamination of AC filters was about 5-fold greater than that of a carpet, and Cladosporium and Penicillium were predominant in AC filters. The fungal contamination inside AC, which were used everyday, increased more markedly than those not used daily, e.g. a few days per week or rarely. Moreover, the airborne fungal contamination in rooms during air-conditioning was about 2-fold greater than one in rooms without AC, and was highest when air-conditioning started and decreased gradually with time. We recognized that the airborne fungal contamination was controlled by the environmental condition of the rooms, in which AC were used. It is suggested that AC might promote mold allergies in users via airborne fungal spores derived from the AC. On the other hand, AC was estimated to remove moisture in the room atmosphere and carpets, and reduce the relative humidity in rooms. It was found that the average fungal contamination in the house dust of carpets with AC was suppressed by two-third of that in rooms without AC. The use of AC for suppressing fungal hazards was discussed.

  17. Building America Top Innovations 2013 Profile – High-Efficiency Window Air Conditioners

    SciTech Connect

    none,

    2013-09-01

    This Top Innovation profile explains how comprehensive performance testing by the National Renewable Energy Laboratory led to simple, affordable methods that homeowners could employ for increasing the energy efficiency of window air conditioners.

  18. Improved Modeling of Residential Air Conditioners and Heat Pumps for Energy Calculations

    SciTech Connect

    Cutler, D.; Winkler, J.; Kruis, N.; Christensen, C.; Brendemuehl, M.

    2013-01-01

    This report presents improved air conditioner and heat pump modeling methods in the context of whole-building simulation tools, with the goal of enabling more accurate evaluation of cost effective equipment upgrade opportunities and efficiency improvements in residential buildings.

  19. Understanding Energy Impacts of Oversized Air Conditioners; NREL Highlights, Research & Development, NREL (National Renewable Energy Laboratory)

    SciTech Connect

    2015-06-01

    This NREL highlight describes a simulation-based study that analyzes the energy impacts of oversized residential air conditioners. Researchers found that, if parasitic power losses are minimal, there is very little increase in energy use for oversizing an air conditioner. The research demonstrates that new residential air conditioners can be sized primarily based on comfort considerations, because capacity typically has minimal impact on energy efficiency. The results of this research can be useful for contractors and homeowners when choosing a new air conditioner or heat pump during retrofits of existing homes. If the selected unit has a crankcase heater, performing proper load calculations to be sure the new unit is not oversized will help avoid excessive energy use.

  20. Development of a solar-powered residential air conditioner: System optimization preliminary specification

    NASA Technical Reports Server (NTRS)

    Rousseau, J.; Hwang, K. C.

    1975-01-01

    Investigations aimed at the optimization of a baseline Rankine cycle solar powered air conditioner and the development of a preliminary system specification were conducted. Efforts encompassed the following: (1) investigations of the use of recuperators/regenerators to enhance the performance of the baseline system, (2) development of an off-design computer program for system performance prediction, (3) optimization of the turbocompressor design to cover a broad range of conditions and permit operation at low heat source water temperatures, (4) generation of parametric data describing system performance (COP and capacity), (5) development and evaluation of candidate system augmentation concepts and selection of the optimum approach, (6) generation of auxiliary power requirement data, (7) development of a complete solar collector-thermal storage-air conditioner computer program, (8) evaluation of the baseline Rankine air conditioner over a five day period simulating the NASA solar house operation, and (9) evaluation of the air conditioner as a heat pump.

  1. A hybrid air conditioner driven by a hybrid solar collector

    NASA Astrophysics Data System (ADS)

    Al-Alili, Ali

    The objective of this thesis is to search for an efficient way of utilizing solar energy in air conditioning applications. The current solar Air Conditioners (A/C)s suffer from low Coefficient of Performance (COP) and performance degradation in hot and humid climates. By investigating the possible ways of utilizing solar energy in air conditioning applications, the bottlenecks in these approaches were identified. That resulted in proposing a novel system whose subsystem synergy led to a COP higher than unity. The proposed system was found to maintain indoor comfort at a higher COP compared to the most common solar A/Cs, especially under very hot and humid climate conditions. The novelty of the proposed A/C is to use a concentrating photovoltaic/thermal collector, which outputs thermal and electrical energy simultaneously, to drive a hybrid A/C. The performance of the hybrid A/C, which consists of a desiccant wheel, an enthalpy wheel, and a vapor compression cycle (VCC), was investigated experimentally. This work also explored the use of a new type of desiccant material, which can be regenerated with a low temperature heat source. The experimental results showed that the hybrid A/C is more effective than the standalone VCC in maintaining the indoor conditions within the comfort zone. Using the experimental data, the COP of the hybrid A/C driven by a hybrid solar collector was found to be at least double that of the current solar A/Cs. The innovative integration of its subsystems allows each subsystem to do what it can do best. That leads to lower energy consumption which helps reduce the peak electrical loads on electric utilities and reduces the consumer operating cost since less energy is purchased during the on peak periods and less solar collector area is needed. In order for the proposed A/C to become a real alternative to conventional systems, its performance and total cost were optimized using the experimentally validated model. The results showed that for an

  2. 16 CFR Appendix I to Part 305 - Heating Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Heating Performance and Cost for Central Air... CONSERVATION ACT (âENERGY LABELING RULEâ) Pt. 305, App. I Appendix I to Part 305—Heating Performance and Cost for Central Air Conditioners Manufacturer's rated heating capacity (Btu's/hr.) Range of HSPF's...

  3. 16 CFR Appendix I to Part 305 - Heating Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Heating Performance and Cost for Central Air... RULEâ) Pt. 305, App. I Appendix I to Part 305—Heating Performance and Cost for Central Air Conditioners Manufacturer's rated heating capacity (Btu's/hr.) Range of HSPF's Low High Single Package Units Heat...

  4. 16 CFR Appendix I to Part 305 - Heating Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Heating Performance and Cost for Central Air... RULEâ) Pt. 305, App. I Appendix I to Part 305—Heating Performance and Cost for Central Air Conditioners Manufacturer's rated heating capacity (Btu's/hr.) Range of HSPF's Low High Single Package Units Heat...

  5. 16 CFR Appendix I to Part 305 - Heating Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Heating Performance and Cost for Central Air... RULEâ) Pt. 305, App. I Appendix I to Part 305—Heating Performance and Cost for Central Air Conditioners Manufacturer's rated heating capacity (Btu's/hr.) Range of HSPF's Low High Single Package Units Heat...

  6. 16 CFR Appendix I to Part 305 - Heating Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Heating Performance and Cost for Central Air... RULEâ) Pt. 305, App. I Appendix I to Part 305—Heating Performance and Cost for Central Air Conditioners Manufacturer's rated heating capacity (Btu's/hr.) Range of HSPF's Low High Single Package Units Heat...

  7. 16 CFR Appendix H to Part 305 - Cooling Performance and Cost for Central Air Conditioners

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Cooling Performance and Cost for Central Air Conditioners H Appendix H to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC... RULEâ) Pt. 305, App. H Appendix H to Part 305—Cooling Performance and Cost for Central Air...

  8. Study on Actual Performance and Exhaust Heat of Air-conditioner Concerning Heat Island Problem

    NASA Astrophysics Data System (ADS)

    Shinomiya, Naruaki; Nishimura, Nobuya; Iyota, Hiroyuki; Kurata, Satoru

    A novel simple measuring method of actual performance of room air-conditioners by neural net work analysis (NNW) has been developed. The actual performance for a long term which is difficult to be measured by air enthalpy method is able to be measured easily by this method. In other words, actual performance of room air-conditioners can be measured by the proposed NNW method without measurement of air flow at indoor unit and outdoor unit which changes due to clogging of heat exchanger by dust. In order to gather data for training and testing the proposed NNW method, the room air-conditioner for experiment was set up. Inputs to NNW are outdoor temperature, indoor temperature, indoor wet-bulb temperature, inlet temperature of evaporator, outlet temperature of evaporator, condensation temperature and power consumption. The output from NNW is COP. The COP by NNW method has mean errors under 2.8% in quasi-steady operation condition and has mean errors under 4.6% in unsteady operation condition, compared to the COP of air enthalpy method. Results show that the COP of air conditioners can be measured easily for a long term using NNW within a high degree of accuracy.

  9. Swozzle based burner tube premixer including inlet air conditioner for low emissions combustion

    DOEpatents

    Tuthill, Richard Sterling; Bechtel, II, William Theodore; Benoit, Jeffrey Arthur; Black, Stephen Hugh; Bland, Robert James; DeLeonardo, Guy Wayne; Meyer, Stefan Martin; Taura, Joseph Charles; Battaglioli, John Luigi

    2002-01-01

    A burner for use in a combustion system of a heavy-duty industrial gas turbine includes a fuel/air premixer having an air inlet, a fuel inlet, and an annular mixing passage. The fuel/air premixer mixes fuel and air into a uniform mixture for injection into a combustor reaction zone. The burner also includes an inlet flow conditioner disposed at the air inlet of the fuel/air premixer for controlling a radial and circumferential distribution of incoming air. The pattern of perforations in the inlet flow conditioner is designed such that a uniform air flow distribution is produced at the swirler inlet annulus in both the radial and circumference directions. The premixer includes a swozzle assembly having a series of preferably air foil shaped turning vanes that impart swirl to the airflow entering via the inlet flow conditioner. Each air foil contains internal fuel flow passages that introduce natural gas fuel into the air stream via fuel metering holes that pass through the walls of the air foil shaped turning vanes. By injecting fuel in this manner, an aerodynamically clean flow field is maintained throughout the premixer. By injecting fuel via two separate passages, the fuel/air mixture strength distribution can be controlled in the radial direction to obtain optimum radial concentration profiles for control of emissions, lean blow outs, and combustion driven dynamic pressure activity as machine and combustor load are varied.

  10. 10 CFR 431.96 - Uniform test method for the measurement of energy efficiency of commercial air conditioners and...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... certified ratings that is required to be maintained under 10 CFR 429.71. (f) Manufacturer involvement in... efficiency of commercial air conditioners and heat pumps. 431.96 Section 431.96 Energy DEPARTMENT OF ENERGY... Air Conditioners and Heat Pumps Test Procedures § 431.96 Uniform test method for the measurement...

  11. 10 CFR Appendix M to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Central Air Conditioners and Heat Pumps

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... of Central Air Conditioners and Heat Pumps M Appendix M to Subpart B of Part 430 Energy DEPARTMENT OF... Consumption of Central Air Conditioners and Heat Pumps Note: The procedures and calculations that refer to off... determine compliance with energy conservation standards for central air conditioners and heat pumps at...

  12. 10 CFR Appendix M to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Central Air Conditioners and Heat Pumps

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... of Central Air Conditioners and Heat Pumps M Appendix M to Subpart B of Part 430 Energy DEPARTMENT OF... Consumption of Central Air Conditioners and Heat Pumps Note: The procedures and calculations that refer to off... determine compliance with energy conservation standards for central air conditioners and heat pumps at...

  13. 10 CFR Appendix M to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Central Air Conditioners and Heat Pumps

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... of Central Air Conditioners and Heat Pumps M Appendix M to Subpart B of Part 430 Energy DEPARTMENT OF... Consumption of Central Air Conditioners and Heat Pumps Note: The procedures and calculations that refer to off... determine compliance with energy conservation standards for central air conditioners and heat pumps at...

  14. Improved Modeling of Residential Air Conditioners and Heat Pumps for Energy Calculations

    SciTech Connect

    Cutler, D.; Winkler, J.; Kruis, N.; Christensen, C.; Brandemuehl, M.

    2013-01-01

    This report presents improved air conditioner and heat pump modeling methods in the context of whole-building simulation tools, with the goal of enabling more accurate evaluation of cost-effective equipment upgrade opportunities and efficiency improvements in residential buildings.

  15. 10 CFR 429.16 - Central air conditioners and heat pumps.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... more than one indoor unit, a “tested combination” as defined in 10 CFR 430.2 shall be used for tests... 10 Energy 3 2012-01-01 2012-01-01 false Central air conditioners and heat pumps. 429.16 Section... and heat pumps. (a) Sampling plan for selection of units for testing. (1) The general requirements...

  16. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... applications; rated for sensible coefficient of performance (SCOP) and tested in accordance with 10 CFR 431.96... heat pumps. 431.92 Section 431.92 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Commercial Air Conditioners and Heat Pumps §...

  17. 10 CFR 429.16 - Central air conditioners and heat pumps.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... more than one indoor unit, a “tested combination” as defined in 10 CFR 430.2 shall be used for tests... 10 Energy 3 2014-01-01 2014-01-01 false Central air conditioners and heat pumps. 429.16 Section... and heat pumps. (a) Sampling plan for selection of units for testing. (1) The general requirements...

  18. 10 CFR 429.16 - Central air conditioners and heat pumps.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... more than one indoor unit, a “tested combination” as defined in 10 CFR 430.2 shall be used for tests... 10 Energy 3 2013-01-01 2013-01-01 false Central air conditioners and heat pumps. 429.16 Section... and heat pumps. (a) Sampling plan for selection of units for testing. (1) The general requirements...

  19. Product lifetime, energy efficiency and climate change: A case study of air conditioners in Japan.

    PubMed

    Nishijima, Daisuke

    2016-10-01

    This study proposed a modelling technique for estimating life-cycle CO2 emissions of durable goods by considering changes in product lifetime and energy efficiency. The stock and flow of durable goods was modelled by Weibull lifetime distributions and the trend in annual energy efficiency (i.e., annual electricity consumption) of an "average" durable good was formulated as a reverse logistic curve including a technologically critical value (i.e., limit energy efficiency) with respect to time. I found that when the average product lifetime is reduced, there is a trade-off between the reduction in emissions during product use (use phase), due to the additional purchases of new, more energy-efficient air conditioners, and the increase in emissions arising from the additional production of new air conditioners stimulated by the reduction of the average product lifetime. A scenario analysis focused on residential air conditioners in Japan during 1972-2013 showed that for a reduction of average lifetime of 1 year, if the air conditioner energy efficiency limit can be improved by 1.4% from the estimated current efficiency level, then CO2 emissions can be reduced by approximately the same amount as for an extension of average product lifetime of 1 year. PMID:27423771

  20. Technical and economic analysis of energy efficiency of Chinese room air conditioners

    SciTech Connect

    Fridley, David G.; Rosenquist, Gregory; Jiang, Lin; Li, Aixian; Xin, Dingguo; Cheng, Jianhong

    2001-02-01

    China has experienced tremendous growth in the production and sales of room air conditioners over the last decade. Although minimum room air conditioner energy efficiency standards have been in effect since 1989, no efforts were made during most of the 1990's to update the standard to be more reflective of current market conditions. In 1999, China's State Bureau of Technical Supervision (SBTS) included in their annual plan the development and revision of the 1989 room air conditioner standard, and experts from SBTS worked together with LBNL to analyze the new standards. Based on the engineering and life cycle-cost analyses performed, the most predominant type of room air conditioner in the Chinese market (split-type with a cooling capacity between 2500 and 4500 W (8500 Btu/h and 15,300Btu/h)) can have its efficiency increased cost-effectively to an energy efficiency ratio (EER) of 2.92 W/W (9.9 Btu/hr/W). If an EER standard of 2.92 W/W became effective in 2001, Chinese consumers would be estimated to save over 3.5 billion Yuan (420 million U.S. dollars) over the period of 2001-2020. Carbon emissions over the same period would be reduced by approximately 12 million metric tonnes.

  1. Product lifetime, energy efficiency and climate change: A case study of air conditioners in Japan.

    PubMed

    Nishijima, Daisuke

    2016-10-01

    This study proposed a modelling technique for estimating life-cycle CO2 emissions of durable goods by considering changes in product lifetime and energy efficiency. The stock and flow of durable goods was modelled by Weibull lifetime distributions and the trend in annual energy efficiency (i.e., annual electricity consumption) of an "average" durable good was formulated as a reverse logistic curve including a technologically critical value (i.e., limit energy efficiency) with respect to time. I found that when the average product lifetime is reduced, there is a trade-off between the reduction in emissions during product use (use phase), due to the additional purchases of new, more energy-efficient air conditioners, and the increase in emissions arising from the additional production of new air conditioners stimulated by the reduction of the average product lifetime. A scenario analysis focused on residential air conditioners in Japan during 1972-2013 showed that for a reduction of average lifetime of 1 year, if the air conditioner energy efficiency limit can be improved by 1.4% from the estimated current efficiency level, then CO2 emissions can be reduced by approximately the same amount as for an extension of average product lifetime of 1 year.

  2. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... (ii) Each heat pump label, except as noted in paragraph (g)(4)(iii) of this section, shall contain two... only heat pump label shall contain a range of comparability consisting of the lowest and highest... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Labeling for central air conditioners,...

  3. 10 CFR Appendix M to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Central Air Conditioners and Heat Pumps

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of Central Air Conditioners and Heat Pumps M Appendix M to Subpart B of Part 430 Energy DEPARTMENT OF... Consumption of Central Air Conditioners and Heat Pumps 1. DEFINITIONS 2. TESTING CONDITIONS 2.1Test room... conditioners and heat pumps, and systems composed of multiple mini-split units (outdoor units located...

  4. Study on Variable Capacity Control Mechanism of Scroll Compressor for Automotive Air Conditioner

    NASA Astrophysics Data System (ADS)

    Hirano, Takahisa; Shigeoka, Tetsuo

    As for the automotive air conditioner, (1) to keep the automotive cabin temperature in a comfortable region, (2) to improve driving feeling, (3) to drive the air conditioning system economically through all seasons, are universally required. Recently, from these points, compressors with variable capacity control mechanism for automotive air conditioners have been remarkably requested. We have developed a scroll comoressor with variable capacity control mechanism. The capacity control mechanism, which changes the channel area of the bypass hole continuously, according to the suction gas pressure and the discharge gas pressure, has been developed. In this report, we describe the mechanism of variable capacity control and the performance simulation program that has been developed for the scroll compressor. Further, we describe the measuring results of cylinder pressure behavior, the results of energy loss analysis and the effect of comfort, drivability, power saving in the refrigerating cycle using the developed capacity control compressor.

  5. Air conditioner operation behaviour based on students' skin temperature in a classroom.

    PubMed

    Song, Gook-Sup; Lim, Jae-Han; Ahn, Tae-Kyung

    2012-01-01

    A total of 25 college students participated in a study to determine when they would use an air conditioner during a lecture in a university classroom. The ambient temperature and relative humidity were measured 75 cm above the floor every minute. Skin temperatures were measured every minute at seven points, according to the recommendation of Hardy and Dubois. The average clothing insulation value (CLO) of subjects was 0.53 ± 0.07 CLO. The mean air velocity in the classroom was 0.13 ± 0.028 m/s. When the subjects turned the air conditioner both on and off, the average ambient temperatures, relative humidity and mean skin temperatures were 27.4 and 23.7 °C (p = 0.000), 40.9 and 40.0% (p = 0.528) and 32.7 and 32.2 °C (p = 0.024), respectively. When the status of the air conditioner was changed, the differences of skin temperatures in core body parts (head, abdomen and thigh) were not statistically significant. However, in the extremities (mid-lower arm, hand, shin and instep), the differences were statistically significant. Subjects preferred a fluctuating environment to a constant temperature condition. We found that a changing environment does not affect classroom study. PMID:21665190

  6. 10 CFR Appendix F to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Room Air Conditioners

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... or without energizing active air-cleaning components or devices such as ultraviolet (UV) radiation... conditioners at 10 CFR 430.32(b). 1. Definitions. 1.1 “Active mode” means a mode in which the room...

  7. 10 CFR Appendix F to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Room Air Conditioners

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... or without energizing active air-cleaning components or devices such as ultraviolet (UV) radiation... conditioners at 10 CFR 430.32(b). 1. Definitions. 1.1“Active mode” means a mode in which the room...

  8. 10 CFR Appendix F to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Room Air Conditioners

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... or without energizing active air-cleaning components or devices such as ultraviolet (UV) radiation... conditioners at 10 CFR 430.32(b). 1. Definitions. 1.1“Active mode” means a mode in which the room...

  9. Techno-Economic Analysis of Indian Draft Standard Levels for RoomAir Conditioners

    SciTech Connect

    McNeil, Michael A.; Iyer, Maithili

    2007-03-01

    The Indian Bureau of Energy Efficiency (BEE) finalized its first set of efficiency standards and labels for room air conditioners in July of 2006. These regulations followed soon after the publication of levels for frost-free refrigerators in the same year. As in the case of refrigerators, the air conditioner program introduces Minimum Efficiency Performance Standards (MEPS) and comparative labels simultaneously, with levels for one to five stars. Also like the refrigerator program, BEE defined several successive program phases of increasing stringency. In support of BEE's refrigerator program, Lawrence Berkeley National Laboratory (LBNL) produced an analysis of national impacts of standards in collaboration with the Collaborative Labeling and Standards Program (CLASP). That analysis drew on LBNL's experience with standards programs in the United States, as well as many other countries. Subsequently, as part of the process for setting optimal levels for air conditioner regulations, CLASP commissioned LBNL to provide support to BEE in the form of a techno-economic evaluation of air conditioner efficiency technologies. This report describes the methodology and results of this techno-economic evaluation. The analysis consists of three components: (1) Cost effectiveness to consumers of efficiency technologies relative to current baseline. (2) Impacts on the current market from efficiency regulations. (3) National energy and financial impacts. The analysis relied on detailed and up-to-date technical data made available by BEE and industry representatives. Technical parameters were used in conjunction with knowledge about air conditioner use patterns in the residential and commercial sectors, and prevailing marginal electricity prices, in order to give an estimate of per-unit financial impacts. In addition, the overall impact of the program was evaluated by combining unit savings with market forecasts in order to yield national impacts. LBNL presented preliminary results

  10. The Performance of a Desiccant-Based air Conditioner on a Florida School

    SciTech Connect

    Miller, J.

    2001-08-22

    Indoor air quality has become a major public health issue in recent years. ASHRAE standard 62-1989-which is an attempt to improve indoor air quality by increasing building ventilation rates-greatly increases the latent loads on many buildings. In more humid climates, the Sensible Heat Ratio (SHR) of a building's air conditioner (which is the fraction of total delivered cooling that is sensible) is too high to meet the existing latent loads. The implementation of ASHRAE 62-1989 will only exacerbate this problem.

  11. EER, COP, and the Second Law Efficiency for Air Conditioners

    ERIC Educational Resources Information Center

    Leff, Harvey S.; Teeters, William D.

    1978-01-01

    Describes the relationship existing between coefficient of performance (COP) and energy efficiency ratio (EER) in air conditioning units and introduces new efficiency parameters measured relative to the energy extracted from the primary energy source. (SL)

  12. Room Air Conditioners; Appliance Repair--Advanced: 9027.04.

    ERIC Educational Resources Information Center

    Dade County Public Schools, Miami, FL.

    This Quinmester course includes installations, electrical and mechanical servicing, reverse cycle air conditioning, malfunctions, troubleshooting and repair, discharge, pump down, and recharging the system. The course may be taught as a two or three Quinmester credit course. In each instance the course consists of six instructional blocks:…

  13. Automotive absorption air conditioner utilizing solar and motor waste heat

    NASA Technical Reports Server (NTRS)

    Popinski, Z. (Inventor)

    1981-01-01

    In combination with the ground vehicles powered by a waste heat generating electric motor, a cooling system including a generator for driving off refrigerant vapor from a strong refrigerant absorbant solution is described. A solar collector, an air-cooled condenser connected with the generator for converting the refrigerant vapor to its liquid state, an air cooled evaporator connected with the condenser for returning the liquid refrigerant to its vapor state, and an absorber is connected to the generator and to the evaporator for dissolving the refrigerant vapor in the weak refrigerant absorbant solution, for providing a strong refrigerant solution. A pump is used to establish a pressurized flow of strong refrigerant absorbant solution from the absorber through the electric motor, and to the collector.

  14. Measure Guideline. Air Conditioner Diagnostics, Maintenance, and Replacement

    SciTech Connect

    Springer, David; Dakin, Bill

    2013-03-01

    This guideline responds to the need for an efficient means of identifying, diagnosing, and repairing faults in air conditioning systems in existing homes that are undergoing energy upgrades. Inadequate airflow due to constricted ducts or undersized filters, improper refrigerant charge, and other system defects can be corrected at a fraction of the cost of equipment replacement and can yield significant savings. The guideline presents a two-step approach to diagnostics and repair.

  15. Measure Guideline: Air Conditioner Diagnostics, Maintenance, and Replacement

    SciTech Connect

    Springer, D.; Dakin, B.

    2013-03-01

    This guideline responds to the need for an efficient means of identifying, diagnosing, and repairing faults in air conditioning systems in existing homes that are undergoing energy upgrades. Inadequate airflow due to constricted ducts or undersized filters, improper refrigerant charge, and other system defects can be corrected at a fraction of the cost of equipment replacement and can yield significant savings. The guideline presents a two-step approach to diagnostics and repair.

  16. Development of solar driven absorption air conditioners and heat pumps

    NASA Astrophysics Data System (ADS)

    Dao, K.; Wahlig, M.; Wali, E.; Rasson, J.; Molishever, E.

    1980-03-01

    The development of absorption refrigeration systems for solar active heating and cooling applications is discussed. The approaches investigated are those using air-cooled condenser-absorber and those leading to coefficient of performances (COP) that increase continuously with heat source temperature. This is primarily an experimental project, with the emphasis on designing, fabricating and testing absorption chillers in operating regimes that are particularly suited for solar energy applications. Its demonstrated that the conventional single-effect ammonia-water absorption cycle can be used (with minor modifications) for solar cooling.

  17. A liquid overfeeding military air conditioner with a quench valve

    SciTech Connect

    Mei, V.C.; Chen, F.C.; Bolton, C.W.

    1997-12-31

    A 3.3-ton rated military air-conditioning unit has been studied experimentally for baseline and liquid overfeeding (LOF) operation. The tests before any modification, using the nameplate-specified refrigerant charge, showed the measured cooling capacity to be less than 1% off the rated capacity at 95 F (35 C) ambient temperature. The test results, after modification, indicate that LOF operation outperforms the baseline case over a wide ambient temperature range in terms of cooling capacity, power consumption, and system coefficient of performance (COP). At a 95 F (35 C) test point, LOF operation has a cooling capacity of 51,100 Btu per hour, which is an 18% improvement over the baseline operation capacity of 42,500 Btu per hour. The COP for LOF at 95 F (35 C) is 2.62, which is 29% better than the baseline COP of 2.03. However, an optimal refrigerant charge is essential for LOF to work properly.

  18. Desiccant-assisted air conditioner improves IAQ and comfort

    SciTech Connect

    Meckler, M. )

    1994-10-01

    This article describes a system which offers the advantage of downsizing the evaporator coil and condensing unit capacities for comparable design loads, which in turn provides numerous benefits. Airborne microorganisms, which are responsible for many acute diseases, infections, and allergies, are well protected indoors by the moisture surrounding them. While the human body is generally the host for various bacteria and viruses, fungi can grow in moist places. It has been concluded that an optimum relative humidity (RH) range of 40 to 60 percent is necessary to minimize or eliminate the bacterial, viral, and fungal growth. In addition, humidity also has an effect on air cleanliness--it reduces the presence of dust particles--and on the deterioration of the building structure and its contents. Therefore, controlling humidity is a very important factor to human comfort in minimizing adverse health effects and maximizing the structural longevity of the building.

  19. Using Field-Metered Data to Quantify Annual Energy Use of Portable Air Conditioners

    SciTech Connect

    Burke, Thomas; Willem, Henry; Ni, Chun Chun; Stratton, Hannah; Chen, Yuting; Ganeshalingam, Mohan; Iyer, Maithili; Price, Sarah; Dunham, Camilla

    2014-12-01

    As many regions of the United States experience rising temperatures, consumers have come to rely increasingly on cooling appliances (including portable air conditioners) to provide a comfortable indoor temperature. Home occupants sometimes use a portable air conditioner (PAC) to maintain a desired indoor temperature in a single room or enclosed space. Although PACs in residential use are few compared to centrally installed and room air conditioning (AC) units, the past few years have witnessed an increase of PACs use throughout the United States. There is, however, little information and few research projects focused on the energy consumption and performance of PACs, particularly studies that collect information from field applications of PACs. The operation and energy consumption of PACs may differ among geographic locations and households, because of variations in cooling load, frequency, duration of use, and other user-selected settings. In addition, the performance of building envelope (thermal mass and air leakage) as well as inter-zonal mixing within the building would substantially influence the ability to control and maintain desirable indoor thermal conditions. Lawrence Berkeley National Laboratory (LBNL) conducted an initial field-metering study aimed at increasing the knowledge and data related to PAC operation and energy consumption in the United States.

  20. A liquid over-feeding military air conditioner

    SciTech Connect

    Mei, V.C.; Chen, F.C.

    1995-07-01

    A 3.3-ton military air conditioning unit has been studied experimentally in both baseline (as received) and as modified for liquid over-feeding (LOF) operation. Tne baseline test, using a proper refrigerant charge, showed the measured cooling capacity to be less than 1% off the rated capacity at 95{degrees}F ambient temperature. The test results indicate that LOF operation outperforms the baseline case over a wide ambient temperature range in terms of cooling capacity, power consumption, and system coefficient of performance (COP). At a 95{degrees}F test point, LOF operation has a cooling capacity of 51,100 BTU per hour, which is a 28.9% improvement over the baseline operation capacity of 39,600 BTU per hour. The COP for LOF at 95{degrees}F is 2.62, which is 29% better than the baseline COP of 2.03. However, an optimal refrigerant charge is essential for LOF to work properly.

  1. Air Sample Conditioner Helps the Waste Treatment Plant Meet Emissions Standards

    SciTech Connect

    Glissmeyer, John A.; Flaherty, Julia E.; Pekour, Mikhail S.

    2014-12-02

    The air in three of the Hanford Site Waste Treatment and Immobilization Plant (WTP) melter off-gas discharge stacks will be hot and humid after passing through the train of emission abatement equipment. The off-gas temperature and humidity levels will be incompatible with the airborne emissions monitoring equipment required for this type of stack. To facilitate sampling from these facilities, an air sample conditioner system will be installed to introduce cool, dry air into the sample stream to reduce the temperature and dew point. This will avoid thermal damage to the instrumentation and problematic condensation. The complete sample transport system must also deliver at least 50% of the particles in the sample airstream to the sample collection and on-line analysis equipment. The primary components of the sample conditioning system were tested in a laboratory setting. The sample conditioner itself is based on a commercially-available porous tube filter design. It consists of a porous sintered metal tube inside a coaxial metal jacket. The hot gas sample stream passes axially through the porous tube, and the dry, cool air is injected into the jacket and through the porous wall of the inner tube, creating an effective sample diluter. The dilution and sample air mix along the entire length of the porous tube, thereby simultaneously reducing the dew point and temperature of the mixed sample stream. Furthermore, because the dilution air enters through the porous tube wall, the sample stream does not come in contact with the porous wall and particle deposition is reduced in this part of the sampling system. Tests were performed with an environmental chamber to supply air with the temperature and humidity needed to simulate the off-gas conditions. Air from the chamber was passed through the conditioning system to test its ability to reduce the temperature and dew point of the sample stream. To measure particle deposition, oil droplets in the range of 9 to 11 micrometer

  2. Optimum dry-cooling sub-systems for a solar air conditioner

    NASA Technical Reports Server (NTRS)

    Chen, J. L. S.; Namkoong, D.

    1978-01-01

    Dry-cooling sub-systems for residential solar powered Rankine compression air conditioners were economically optimized and compared with the cost of a wet cooling tower. Results in terms of yearly incremental busbar cost due to the use of dry-cooling were presented for Philadelphia and Miami. With input data corresponding to local weather, energy rate and capital costs, condenser surface designs and performance, the computerized optimization program yields design specifications of the sub-system which has the lowest annual incremental cost.

  3. Liquid Desiccant in Air Conditioners: Nano-Engineered Porous Hollow Fiber Membrane-Based Air Conditioning System

    SciTech Connect

    2010-09-02

    BEETIT Project: UTRC is developing an air conditioning system that is optimized for use in warm and humid climates. UTRC’s air conditioning system integrates a liquid drying agent or desiccant and a traditional vapor compression system found in 90% of air conditioners. The drying agent reduces the humidity in the air before it is cooled, using less energy. The technology uses a membrane as a barrier between the air and the liquid salt stream allowing only water vapor to pass through and not the salt molecules. This solves an inherent problem with traditional liquid desiccant systems—carryover of the liquid drying agent into the conditioned air stream—which eliminates corrosion and health issues

  4. Effects of Air Conditioner Use on Real-World Fuel Economy

    SciTech Connect

    Huff, Shean P; West, Brian H; Thomas, John F

    2013-01-01

    Vehicle data were acquired on-road and on a chassis dynamometer to assess fuel consumption under several steady cruise conditions and at idle. Data were gathered for various air conditioner (A/C) settings and with the A/C off and the windows open. Two vehicles were used in the comparisonstudy: a 2009 Ford Explorer and a 2009 Toyota Corolla. At steady speeds between 64.4 and 112.7 kph (40 and 70 mph), both vehicles consumed more fuel with the A/C on at maximum cooling load (compressor at 100% duty cycle) than when driving with the windows down. The Explorer maintained this trend beyond 112.7 kph (70 mph), while the Corolla fuel consumption with the windows down matched that of running the A/C at 120.7 kph (75 mph), and exceeded it at 128.7 kph (80 mph). The largest incremental fuel consumption rate penalty due to air conditioner use occurred was nearly constant with a weakslight trend of increasing consumption with increasing compressor (and vehicle) speed. Lower consumption is seenobserved at idle for both vehicles, likely due to the low compressor speed at this operating point

  5. A Proposal for the Time Domain Modeling of Split Air Conditioners for Consumer Reimbursement Studies

    NASA Astrophysics Data System (ADS)

    Rezende, Paulo Henrique Oliveira; Almeida Junior, Afonso Bernardino; Gondim, Isaque Nogueira; Oliveira, José Carlos

    2015-04-01

    This paper deals with computer application procedures for the evaluation of the causal consistency between anomalous phenomena manifested in electrical networks, along with the physical damage associated with electrical equipment and possible reimbursement requests. The focus is on the development of an air conditioner appliance model of the type known as split founded upon a representation, in the time domain, in accordance with the Alternative Transients Program (ATP) simulator requirements. This approach permits investigations concerning the performance of the product when submitted to ideal and non-ideal supply conditions. Once the equipment model is implemented in the program, a set of investigative studies are carried out to show the device performance under specific energy quality disturbance conditions. In addition, there are still the results for the validation of the process established through the correlation between computational performance of the air conditioner with corresponding studies carried out experimentally, which are presented herein. Moreover, once the effectiveness of the developed model is verified, it is implemented into the Requests for Reimbursement Software. Investigations related to the correlation between disturbances and the levels of thermal and dielectric tolerance are then performed aiming at illustrating the use of the research results for the reimbursement analyzes purposes.

  6. Energy Impacts of Oversized Residential Air Conditioners -- Simulation Study of Retrofit Sequence Impacts

    SciTech Connect

    Booten, C.; Christensen, C.; Winkler, J.

    2014-11-01

    This research addresses the question of what are the energy consequences for oversizing of an air conditioner in a home. Conventional wisdom holds that oversizing the AC results in significant energy penalties. However, the reason for this was shown to be due to crankcase heaters and not due to cycling performance of the AC, and is only valid for a particular set of assumptions. Adding or removing individual characteristics, such as ducts or crankcase heaters, can have measurable impacts on energy use. However, with all other home characteristics held constant, oversizing the AC generally has a small effect on cooling energy use, even if the cycling performance of the unit is poor. The relevant aspects of air conditioner modeling are discussed to illustrate the effects of the cycling loss coefficient, Cd, capacity, climate, ducts and parasitic losses such as crankcase heaters. A case study of a typical 1960's vintage home demonstrates results in the context of whole building simulations using EnergyPlus.

  7. Development of a solar-powered residential air conditioner: Economic analysis

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The results of investigations aimed at the development of cost models to be used in the economic assessment of Rankine-powered air conditioning systems for residential application are summarized. The rationale used in the development of the cost model was to: (1) collect cost data on complete systems and on the major equipment used in these systems; (2) reduce these data and establish relationships between cost and other engineering parameters such as weight, size, power level, etc; and (3) derive simple correlations from which cost-to-the-user can be calculated from performance requirements. The equipment considered in the survey included heat exchangers, fans, motors, and turbocompressors. This kind of hardware represents more than 2/3 of the total cost of conventional air conditioners.

  8. [A patient with acute hypersensitivity pneumonitis with a diagnosis of air-conditioner lung, who responded to therapy].

    PubMed

    Ishikawa, Rie; Kamiya, Hiroyuki; Ikushima, Souichiro; Oristu, Masaru; Takemura, Tamiko

    2010-02-01

    The patient was a 48-year-old woman and current smoker. In May 2007, she moved to a new residence. In the middle of the following month, she developed acute respiratory distress and a fever (38 degrees C) after running her air conditioner continuously throughout the night. The chest X-ray film showed diffuse infiltrative shadows in the middle and lower lung fields. After hospital admission, her oxygenation improved without treatment and the infiltrates improved over the clinical course. As a consequence, we suspected hypersensitivity pneumonitis. The bronchoalveolar lavage showed predominant lymphocytes of 72.6%, with a low CD 4/8 ratio of 0.2. Transbronchial lung biopsy findings corresponded to acute hypersensitivity pneumonitis. The results of the environmental challenge test were positive only when her air conditioner was on, resulting, in a diagnosis of air-conditioner lung. Several microorganisms were detected in an environmental sample, but 20 kinds of serum precipitating antibodies were negative on a thorough screening, so no responsible antigen could be identified. The patient's symptoms did not recur after her air conditioner was replaced. PMID:20184245

  9. 10 CFR Appendix F to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Room Air Conditioners

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Uniform Test Method for Measuring the Energy Consumption of Room Air Conditioners F Appendix F to Subpart B of Part 430 Energy DEPARTMENT OF ENERGY ENERGY... Appendix F to Subpart B of Part 430—Uniform Test Method for Measuring the Energy Consumption of Room...

  10. 10 CFR Appendix F to Subpart B of... - Uniform Test Method for Measuring the Energy Consumption of Room Air Conditioners

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of Room Air Conditioners F Appendix F to Subpart B of Part 430 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CONSERVATION PROGRAM FOR CONSUMER PRODUCTS Test Procedures Pt. 430, Subpt. B, App. F Appendix F to Subpart B of Part 430—Uniform Test Method for Measuring the Energy Consumption of Room...

  11. Particulate matter concentrations in residences: an intervention study evaluating stand-alone filters and air conditioners

    PubMed Central

    Batterman, S.; Du, L.; Mentz, G.; Mukherjee, B.; Parker, E.; Godwin, C.; Chin, J.-Y.; O'Toole, A.; Robins, T.; Rowe, Z.; Lewis, T.

    2014-01-01

    This study, a randomized controlled trial, evaluated the effectiveness of free-standing air filters and window air conditioners (ACs) in 126 low-income households of children with asthma. Households were randomized into a control group, a group receiving a free-standing HEPA filter placed in the child's sleeping area, and a group receiving the filter and a window-mounted AC. Indoor air quality (IAQ) was monitored for week-long periods over three to four seasons. High concentrations of particulate matter (PM) and carbon dioxide were frequently seen. When IAQ was monitored, filters reduced PM levels in the child's bedroom by an average of 50%. Filter use varied greatly among households and declined over time, for example, during weeks when pollutants were monitored, filter use was initially high, averaging 84 ± 27%, but dropped to 63 ± 33% in subsequent seasons. In months when households were not visited, use averaged only 34 ± 30%. Filter effectiveness did not vary in homes with central or room ACs. The study shows that measurements over multiple seasons are needed to characterize air quality and filter performance. The effectiveness of interventions using free-standing air filters depends on occupant behavior, and strategies to ensure filter use should be an integral part of interventions. PMID:22145709

  12. Effect of central ventilation and air conditioner system on the concentration and health risk from airborne polycyclic aromatic hydrocarbons.

    PubMed

    Lv, Jinze; Zhu, Lizhong

    2013-03-01

    Central ventilation and air conditioner systems are widely utilized nowadays in public places for air exchange and temperature control, which significantly influences the transfer of pollutants between indoors and outdoors. To study the effect of central ventilation and air conditioner systems on the concentration and health risk from airborne pollutants, a spatial and temporal survey was carried out using polycyclic aromatic hydrocarbons (PAHs) as agent pollutants. During the period when the central ventilation system operated without air conditioning (AC-off period), concentrations of 2-4 ring PAHs in the model supermarket were dominated by outdoor levels, due to the good linearity between indoor air and outdoor air (r(p) > 0.769, p < 0.05), and the slopes (1.2-4.54) indicated that ventilating like the model supermarket increased the potential health risks from low molecular weight PAHs. During the period when the central ventilation and air conditioner systems were working simultaneously (AC-on period), although the total levels of PAHs were increased, the concentrations and percentage of the particulate PAHs indoors declined significantly. The BaP equivalency (BaPeq) concentration indicated that utilization of air conditioning reduced the health risks from PAHs in the model supermarket. PMID:23923426

  13. Life-cycle cost and payback period analysis for commercial unitary air conditioners

    SciTech Connect

    Rosenquist, Greg; Coughlin, Katie; Dale, Larry; McMahon, James; Meyers, Steve

    2004-03-31

    This report describes an analysis of the economic impacts of possible energy efficiency standards for commercial unitary air conditioners and heat pumps on individual customers in terms of two metrics: life-cycle cost (LCC) and payback period (PBP). For each of the two equipment classes considered, the 11.5 EER provides the largest mean LCC savings. The results show how the savings vary among customers facing different electricity prices and other conditions. At 11.5 EER, at least 80% of the users achieve a positive LCC savings. At 12.0 EER, the maximum efficiency analyzed, mean LCC savings are lower but still positive. For the {ge} $65,000 Btu/h to <135,000 Btu/h equipment class, 59% of users achieve a positive LCC savings. For the $135,000 Btu/h to <240,000 Btu/h equipment class, 91% of users achieve a positive LCC savings.

  14. Modeling of a second-generation solar-driven Rankine air conditioner. Final report

    SciTech Connect

    Denius, M.W.; Batton, W.D.

    1984-07-01

    Ten configurations of a second-generation (2G), solar-powered, Rankine-driven air conditioner were simulated and the data presented for use in companion studies. The results of the analysis show that the boiling-in-collector (BIC) configuration generates more power per collector area than the other configurations. The models used to simulate the configuration are presented in this report. The generated data are also presented. Experimental work was done under this study to both improve a novel refrigerant and oil lubrication system for the centrifugal compressor and investigate the aerodynamic unloading characteristics of the centrifugal compressor. The information generated was used to define possible turbo-gearbox configurations for use in the second generation computer simulation.

  15. Development of a solar-powered residential air conditioner: Screening analysis

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Screening analysis aimed at the definition of an optimum configuration of a Rankine cycle solar-powered air conditioner designed for residential application were conducted. Initial studies revealed that system performance and cost were extremely sensitive to condensing temperature and to the type of condenser used in the system. Consequently, the screening analyses were concerned with the generation of parametric design data for different condenser approaches; i. e., (1) an ambient air condenser, (2) a humidified ambient air condenser (3) an evaporative condenser, and (4) a water condenser (with a cooling tower). All systems feature a high performance turbocompressor and a single refrigerant (R-11) for the power and refrigeration loops. Data were obtained by computerized methods developed to permit system characterization over a broad range of operating and design conditions. The criteria used for comparison of the candidate system approaches were (1) overall system COP (refrigeration effect/solar heat input), (2) auxiliary electric power for fans and pumps, and (3) system installed cost or cost to the user.

  16. Field evaluation of advanced controls for the retrofit of packaged air conditioners and heat pumps

    SciTech Connect

    Wang, Weimin; Katipamula, Srinivas; Ngo, Hung; Underhill, Ronald M.; Taasevigen, Danny J.; Lutes, Robert G.

    2015-09-01

    This paper documents the magnitude of energy savings achievable in the field by retrofitting existing packaged rooftop units (RTUs) with advanced control strategies not ordinarily used for RTUs. A total of 66 RTUs on 8 different buildings were retrofitted with a commercially available advanced controller for improving RTU operational efficiency. The controller features enhanced air-side economizer control, multi-speed fan control, and demand controlled ventilation. Of the 66 RTUs, 18 are packaged heat pumps and the rest are packaged air conditioners with gas heat. The eight buildings cover four building types and four climate conditions. Based on the data collected for about a whole year, the advanced controller reduced the normalized annual RTU energy consumption between 22% and 90%, with an average of 57% for all RTUs. The average fractional savings uncertainty was 12% at 95% confidence level. Normalized annual electricity savings were in the range between 0.47 kWh/h (kWh per hour of RTU operation) and 7.21 kWh/h, with an average of 2.39 kWh/h. RTUs greater than 53 kW and runtime greater than 14 hours per day had payback periods less than 3 years even at $0.05/kWh.

  17. Flow control of a centrifugal fan in a commercial air conditioner

    NASA Astrophysics Data System (ADS)

    Kim, Jiyu; Bang, Kyeongtae; Choi, Haecheon; Seo, Eung Ryeol; Kang, Yonghun

    2015-11-01

    Air-conditioning fans require a low noise level to provide user comfort and quietness. The aerodynamic noise sources are generated by highly unsteady, turbulent structures near the fan blade. In this study, we investigate the flow characteristics of a centrifugal fan in an air-conditioner indoor unit and suggest control ideas to develop a low noise fan. The experiment is conducted at the operation condition where the Reynolds number is 163000 based on the blade tip velocity and chord length. Intermittent separation occurs at the blade leading edge and thus flow significantly fluctuates there, whereas vortex shedding occurs at the blade trailing edge. Furthermore, the discharge flow observed in the axial plane near the shroud shows low-frequency intermittent behaviors, resulting in high Reynolds stresses. To control these flow structures, we modify the shapes of the blade leading edge and shroud of the centrifugal fan and obtain noise reduction. The flow characteristics of the base and modified fans will be discussed. Supported by 0420-20130051.

  18. Consumer life-cycle cost impacts of energy-efficiency standards for residential-type central air conditioners and heat pumps

    SciTech Connect

    Rosenquist, Gregory; Chan, Peter; Lekov, Alex; McMahon, James; Van Buskirk, Robert

    2001-10-10

    In support of the federal government's efforts to raise the minimum energy-efficiency standards for residential-type central air conditioners and heat pumps, a consumer life-cycle cost (LCC) analysis was conducted to demonstrate the economic impacts on individual consumers from revisions to the standards. LCC is the consumer's cost of purchasing and installing an air conditioner or heat pump and operating the unit over its lifetime. The LCC analysis is conducted on a nationally representative sample of air conditioner and heat pump consumers resulting in a distribution of LCC impacts showing the percentage of consumers that are either benefiting or being burdened by increased standards. Relative to the existing minimum efficiency standard of 10 SEER, the results show that a majority of split system air conditioner and heat pump consumers will either benefit or be insignificantly impacted by increased efficiency standards of up to 13 SEER.

  19. Progress towards Managing Residential Electricity Demand: Impacts of Standards and Labeling for Refrigerators and Air Conditioners in India

    SciTech Connect

    McNeil, Michael A.; Iyer, Maithili

    2009-05-30

    The development of Energy Efficiency Standards and Labeling (EES&L) began in earnest in India in 2001 with the Energy Conservation Act and the establishment of the Indian Bureau of Energy Efficiency (BEE). The first main residential appliance to be targeted was refrigerators, soon to be followed by room air conditioners. Both of these appliances are of critical importance to India's residential electricity demand. About 15percent of Indian households own a refrigerator, and sales total about 4 million per year, but are growing. At the same time, the Indian refrigerator market has seen a strong trend towards larger and more consumptive frost-free units. Room air conditioners in India have traditionally been sold to commercial sector customers, but an increasing number are going to the residential sector. Room air conditioner sales growth in India peaked in the last few years at 20percent per year. In this paper, we perform an engineering-based analysis using data specific to Indian appliances. We evaluate costs and benefits to residential and commercial sector consumers from increased equipment costs and utility bill savings. The analysis finds that, while the BEE scheme presents net benefits to consumers, there remain opportunities for efficiency improvement that would optimize consumer benefits, according to Life Cycle Cost analysis. Due to the large and growing market for refrigerators and air conditioners in India, we forecast large impacts from the standards and labeling program as scheduled. By 2030, this program, if fully implemented would reduce Indian residential electricity consumption by 55 TWh. Overall savings through 2030 totals 385 TWh. Finally, while efficiency levels have been set for several years for refrigerators, labels and MEPS for these products remain voluntary. We therefore consider the negative impact of this delay of implementation to energy and financial savings achievable by 2030.

  20. Air Conditioner Charging. Automotive Mechanics. Air Conditioning. Instructor's Guide [and] Student Guide.

    ERIC Educational Resources Information Center

    Spignesi, B.

    This instructional package, one in a series of individualized instructional units on automobile air conditioning, consists of a student guide and an instructor guide dealing with air conditioning charging. Covered in the module are checking the air conditioning system for leaks, checking and adding refrigerant oil as needed, evacuating the system,…

  1. The System Impact of Air-Conditioner Under-voltage Protection Schemes

    SciTech Connect

    Lu, Ning; Yang, Bo; Huang, Zhenyu; Bravo, Richard

    2009-03-31

    This paper presents simulation results of evaluating an under-voltage protection scheme designed to take stalled air-conditioner (a/c) units offline such that the slow voltage recovery phenomena can be solved on areas heavily loaded with a/c motors during summer peak periods. A three feeder test-bed has been first used to quantify the effectiveness of the protection scheme and the sensitivity of the under-voltage relay settings. Then two real system events of the Western US power grid have been studied to evaluate the area impact of the protection scheme proposed by Southern California Edison. The study demonstrates that by taking all or most of the stalled a/c unit offline, the feeder voltage will recover in a few seconds, much quicker than the tens of seconds that the standard thermal relays imbedded in the motors need to trip the units. The drawback of the control scheme is that after the voltage recover, it settled at a higher voltage than before the faults because a large chuck of load has been shed.

  2. Incidence of polybrominated diphenyl ethers in central air conditioner filter dust from a new office building.

    PubMed

    Ni, Hong-Gang; Cao, Shan-Ping; Chang, Wen-Jing; Zeng, Hui

    2011-07-01

    This study examined polybrominated diphenyl ethers (PBDEs) in central air conditioner filter (CACF) dust from a new office building in Shenzhen, China. Human exposure to PBDE via dust inhalation and ingestion were also estimated. PBDEs level in CACF dust was lower than those in the other countries and regions. Approximately 0.671 pg/kg bw/day PM(2.5) (Particulate Matter up to 2.5 μm in size) bounded Σ(15)PBDEs can be inhaled deep into the lungs and 4.123 pg/kg bw/day PM(10) (Particulate Matter up to 10 μm in size) bounded Σ(15)PBDEs tend to be deposited in the upper parts of the respiratory system. The average total intake of Σ(15)PBDEs via dust inhalation and ingestion for adults reached ∼ 141 pg/kg bw/day in this building. This value was far below the reference dose (RfD) recommended by United States Environmental Protection Agency. Human exposure to PBDEs via dust inhalation and ingestion in the new building is less than the old ones. PMID:21497428

  3. Performance characteristics of a turbo expander substituted for expansion valve on air-conditioner

    SciTech Connect

    Cho, Soo-Yong; Cho, Chong-Hyun; Kim, Chaesil

    2008-09-15

    An experimental study is conducted on a small turbo expander which could be applied to the expansion process in place of expansion valves in refrigerator or air-conditioner to improve the cycle efficiency by recovering energy from the throttling process. The operating gas is HFC134a and the maximum cooling capacity of experiment apparatus is 32.7 kW. Four different turbo expanders are tested to find the performance characteristics of the turbo expander when they operate at a low partial admission rate. The partial admission rate is 1.70% or 2.37, and expanders are operated in the supersonic flow. In the experiment, pressure and temperature are measured at 10 different locations in the experimental apparatus. In addition to these measurements, output power at the turbo expander is measured through a generator installed on a rotor shaft with the rotational speed. Performance data of the turbo expander are obtained at many part load operations by adjusting the output power of the generator. A maximum of 15.8% total-to-static efficiency is obtained when the pressure ratio and the partial admission ratio are 2.37 and 1.70%, respectively. Experimental results show that the optimal velocity ratio decreases when the pressure ratio is decreased, and peak efficiencies, which are obtained at locally maximized efficiency depending on the operating condition, vary linearly against the subcooling temperature or the pressure ratio. (author)

  4. Using Field-Metered Data to Quantify Annual Energy Use of Portable Air Conditioners

    SciTech Connect

    Burke, Thomas; Willem, Henry; Ni, Chun Chun; Stratton, Hannah; Chen, Yuting; Ganeshalingam, Mohan; Iyer, Maithili; Price, Sarah; Dunham, Camilla

    2014-12-12

    As many regions of the United States experience rising temperatures, consumers have come to rely increasingly on cooling appliances (including portable air conditioners) to provide a comfortable indoor temperature. Home occupants sometimes use a portable air conditioner (PAC) to maintain a desired indoor temperature in a single room or enclosed space. Although PACs in residential use are few compared to centrally installed and room air conditioning (AC) units, the past few years have witnessed an increase of PACs use throughout the United States. There is, however, little information and few research projects focused on the energy consumption and performance of PACs, particularly studies that collect information from field applications of PACs. The operation and energy consumption of PACs may differ among geographic locations and households, because of variations in cooling load, frequency, duration of use, and other user-selected settings. In addition, the performance of building envelope (thermal mass and air leakage) as well as inter-zonal mixing within the building would substantially influence the ability to control and maintain desirable indoor thermal conditions. Lawrence Berkeley National Laboratory (LBNL) conducted an initial field-metering study aimed at increasing the knowledge and data related to PAC operation and energy consumption in the United States. LBNL performed its field-metering study from mid-April to late October 2014. The study, which monitored 19 sites in the Northeastern United States (4 in upstate New York and 15 near Philadelphia), collected real-time data on PAC energy consumption along with information regarding housing characteristics, consumer behavior, and environmental conditions that were expected to affect PAC performance. Given the limited number of test sites, this study was not intended to be statistically representative of PAC users in the United States but rather to understand the system response to the cooling demand and to

  5. China Energy Efficiency Round Robin Testing Results for Room Air Conditioners

    SciTech Connect

    Zhou, Nan; Fridley, David; Zheng, Nina; Pierrot, Andre

    2010-06-07

    of all countries energy strategies. As we all know, a very large amount of total energy consumption is due to energy consuming products and equipment, which account for about 50% of China's total energy consumption. However, the current average energy utilization efficiency of this sector is only about 60%, 10 percent lower than the international advanced level. Therefore, China's energy consuming products and equipment sector holds great energy-saving potential. On the other hand, the energy supplied to these products is mainly from fossil fuel combustion, a major source of greenhouse gas (GHG) emissions. Therefore, improving the energy efficiency and augmenting the market share of market-dominant energy consuming products is of significant importance to achieving China's energy saving and emission reduction target and is an effective means to deal with energy and environmental constraints and climate change issues. Main energy consuming products generally include widely-used home appliances, industrial equipment, office equipment, transportation vehicles, etc. China is one of the major manufacturers and exporters of energy end-using products such as air-conditioners, refrigerators, televisions, etc. Their overall energy efficiency is comparatively low and the products are poorly designed, leading to great energy-saving potential. For example, electricity consumption of air conditioners accounts for about 20% of China's total electricity consumption and 40% of the summer electricity peak load in large and medium cities. However, less than 5% of units sold in the domestic market in 2009 reached the standard's highly efficient level of grade 2 above. The electricity consumption of electric motors and their related drive systems accounts for about 60% of China's total electricity consumption; however, less than 2% of the domestic market share consists of energy-efficient electric motor products. Promoting the energy efficiency and market shares of main energy

  6. Future emissions and atmospheric fate of HFC-1234yf from mobile air conditioners in Europe.

    PubMed

    Henne, Stephan; Shallcross, Dudley E; Reimann, Stefan; Xiao, Ping; Brunner, Dominik; O'Doherty, Simon; Buchmann, Brigitte

    2012-02-01

    HFC-1234yf (2,3,3,3-tetrafluoropropene) is under discussion for replacing HFC-134a (1,1,1,2-tetrafluoroethane) as a cooling agent in mobile air conditioners (MACs) in the European vehicle fleet. Some HFC-1234yf will be released into the atmosphere, where it is almost completely transformed to the persistent trifluoroacetic acid (TFA). Future emissions of HFC-1234yf after a complete conversion of the European vehicle fleet were assessed. Taking current day leakage rates and predicted vehicle numbers for the year 2020 into account, European total HFC-1234yf emissions from MACs were predicted to range between 11.0 and 19.2 Gg yr(-1). Resulting TFA deposition rates and rainwater concentrations over Europe were assessed with two Lagrangian chemistry transport models. Mean European summer-time TFA mixing ratios of about 0.15 ppt (high emission scenario) will surpass previously measured levels in background air in Germany and Switzerland by more than a factor of 10. Mean deposition rates (wet + dry) of TFA were estimated to be 0.65-0.76 kg km(-2) yr(-1), with a maxium of ∼2.0 kg km(-2) yr(-1) occurring in Northern Italy. About 30-40% of the European HFC-1234yf emissions were deposited as TFA within Europe, while the remaining fraction was exported toward the Atlantic Ocean, Central Asia, Northern, and Tropical Africa. Largest annual mean TFA concentrations in rainwater were simulated over the Mediterranean and Northern Africa, reaching up to 2500 ng L(-1), while maxima over the continent of about 2000 ng L(-1) occurred in the Czech Republic and Southern Germany. These highest annual mean concentrations are at least 60 times lower than previously determined to be a safe level for the most sensitive aquatic life-forms. Rainwater concentrations during individual rain events would still be 1 order of magnitude lower than the no effect level. To verify these results future occasional sampling of TFA in the atmospheric environment should be considered. If future HFC-1234yf

  7. The Oklahoma Field Test: Air-Conditioning Electricity Savings from Standard Energy Conservation Measures, Radiant Barriers, and High-Efficiency Window Air Conditioners

    SciTech Connect

    Ternes, M.P.

    1992-01-01

    A field test involving 104 houses was performed in Tulsa, Oklahoma, to measure the air-conditioning electricity consumption of low-income houses equipped with window air conditioners, the reduction in this electricity consumption attributed to the installation of energy conservation measures (ECMs) as typically installed under the Oklahoma Weatherization Assistance Program (WAP), and the reduction achieved by the replacement of low-efficiency window air conditioners with high-efficiency units and the installation of attic radiant barriers. Air-conditioning electricity consumption and indoor temperature were monitored weekly during the pre-weatherization period (June to September 1988) and post-weatherization period (May to September 1989). House energy consumption models and regression analyses were used to normalize the air-conditioning electricity savings to average outdoor temperature conditions and the pre-weatherization indoor temperature of each house. The average measured pre-weatherization air-conditioning electricity consumption was 1664 kWh/year ($119/year). Ten percent of the houses used less than 250 kWh/year, while another 10% used more than 3000 kWh/year. An average reduction in air-conditioning electricity consumption of 535 kWh/year ($38/year and 28% of pre-weatherization consumption) was obtained from replacement of one low-efficiency window air conditioner (EER less than 7.0) per house with a high-efficiency unit (EER greater than 9.0). For approximately the same cost, savings tripled to 1503 kWh/year ($107/year and 41% of pre-weatherization consumption) in those houses with initial air-conditioning electricity consumption greater than 2750 kWh/year. For these houses, replacement of a low-efficiency air conditioner with a high-efficiency unit was cost effective using the incremental cost of installing a new unit now rather than later; the average installation cost for these houses under a weatherization program was estimated to be $786. The

  8. 75 FR 14368 - Energy Conservation Standards for Residential Central Air Conditioners and Heat Pumps: Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ... and the national energy savings (NES) and net present value (NPV) at various standard levels. There is... the real consumer cost of capital and puts the LCC in present-value terms. The PBP represents the... conditioners and heat pumps. 66 FR 7170. The amended standards would have increased the minimum SEER to 13...

  9. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Department of Energy for those products in 10 CFR part 430, manufacturers shall affix labels to covered... 10 CFR part 430 for non-weatherized, and mobile home furnaces and content of labels for weatherized... conditioners issued by the Department of Energy in 10 CFR part 430. (1) Headlines and texts, as illustrated...

  10. The Oklahoma Field Test: Air-conditioning electricity savings from standard energy conservation measures, radiant barriers, and high-efficiency window air conditioners

    SciTech Connect

    Ternes, M.P.; Levins, W.P.

    1992-08-01

    A field test Involving 104 houses was performed in Tulsa, Oklahoma, to measure the air-conditioning electricity consumption of low-income houses equipped with window air conditioners, the reduction in this electricity consumption attributed to the installation of energy conservation measures (ECMS) as typically installed under the Oklahoma Weatherization Assistance Program (WAP), and the reduction achieved by the replacement of low-efficiency window air conditioners with high-efficiency units and the installation of attic radiant barriers. Air-conditioning electricity consumption and indoor temperature were monitored weekly during the pre-weatherization period (June to September 1988) and post-weatherization period (May to September 1989). House energy consumption models and regression analyses were used to normalize the air-conditioning electricity savings to average outdoor temperature conditions and the pre-weatherization indoor temperature of each house. The following conclusions were drawn from the study: (1) programs directed at reducing air-conditioning electricity consumption should be targeted at clients with high consumption to improve cost effectiveness; (2) replacing low-efficiency air conditioners with high-efficiency units should be considered an option in a weatherization program directed at reducing air-conditioning electricity consumption; (3) ECMs currently being installed under the Oklahoma WAP (chosen based on effectiveness at reducing space-heating energy consumption) should continue to be justified based on their space-heating energy savings potential only; and (4) attic radiant barriers should not be included in the Oklahoma WAP if alternatives with verified savings are available or until further testing demonstrates energy savings or other benefits in this typo of housing.

  11. Phase Characteristics of 1-Monopalmitoyl-rac-glycerol Monolayers at the Air/Water Interface.

    PubMed

    Vollhardt, D; Brezesinski, G

    2016-07-26

    1-Monopalmitoyl-rac-glycerol is omnipresent in numerous biological and applied systems. Systematic GIXD measurements of 1-monopalmitoyl-rac-glycerol monolayers are carried out over a large pressure interval at 5, 10, and 15 °C to construct the phase diagram on the basis of reliable 2D lattice structures. These studies are complemented by other monolayer characteristics, such as π-A isotherms and mesoscopic domain topographies. A phase transition is found between the two orthorhombic structures with NN and NNN tilted alkyl chains at low temperatures (5 and 10 °C). It increases linearly with increasing temperature. With a further increase in temperature to 15 °C, only NN-tilted orthorhombic lattices are observed in the whole pressure region. The cross-sectional area, A0, is less affected by surface pressure and temperature and amounts to values of between 19.7 and 19.8 Å(2), as expected for a rotator phase at the lower limit. The tilt angle t with respect to the surface normal decreases with increasing pressure and is only slightly influenced by the temperature. The transition pressure to untilted alkyl chains, as determined by the extrapolation of 1/cos(t) to zero tilt angle, is >50 mN/m for all temperatures. The results of lattice distortion d versus sin 2(t) suggest for 10 and 15 °C the tilt of the aliphatic chains as the reason for the monolayer lattice distortion whereas at 5 °C the nonzero-tilt-angle intercept d0 could be an indication of the prevention of hexagonal packing. The generic π-T phase diagram of racemic monoacylglycerol monolayers is constructed on the basis of the phase diagrams of 1-monopalmitoyl-rac-glycerol and 1-monostearoyl-rac-glycerol, which shows that for 1-monopalmitoyl-rac-glycerol monolayers the oblique phase can occur only close to and below 0 °C. The possible phase behavior of other racemic monoacylglycerol monolayers with alkyl chain lengths of C14 and C20 is discussed on the basis of the generic phase diagram. PMID:27351635

  12. Measurement of Fine Particles From Mobile and Stationary Sources, and Reducing the Air Conditioner Power Consumption in Hybrid Electric Vehicles

    NASA Astrophysics Data System (ADS)

    Brewer, Eli Henry

    We study the PM2.5and ultrafine exhaust emissions from a new natural gas-fired turbine power facility to better understand air pollution in California. To characterize the emissions from new natural gas turbines, a series of tests were performed on a GE LMS100 gas turbine. These tests included PM2.5 and wet chemical tests for SO2/SO 3 and NH3, as well as ultrafine (less than 100 nm in diameter) particulate matter measurements. The turbine exhaust had an average particle number concentration that was 2.3x103 times higher than ambient air. The majority of these particles were nanoparticles; at the 100 nm size, stack particle concentrations were about 20 times higher than ambient, and increased to 3.9x104 times higher on average in the 2.5 - 3 nm particle size range. This study also found that ammonia emissions were higher than expected, but in compliance with permit conditions. This was possibly due to an ammonia imbalance entering the catalyst, some flue gas bypassing the catalyst, or not enough catalyst volume. SO3 accounted for an average of 23% of the total sulfur oxides emissions measured. Some of the SO3 is formed in the combustion process, it is likely that the majority formed as the SO2 in the combustion products passed across the oxidizing CO catalyst and SCR catalyst. The 100 MW turbine sampled in this study emitted particle loadings similar to those previously measured from turbines in the SCAQMD area, however, the turbine exhaust contained far more particles than ambient air. The power consumed by an air conditioner accounts for a significant fraction of the total power used by hybrid and electric vehicles especially during summer. This study examined the effect of recirculation of cabin air on power consumption of mobile air conditioners both in-lab and on-road. Real time power consumption and vehicle mileage were recorded by an On Board Diagnostic monitor and carbon balance method. Vehicle mileage improved with increased cabin air recirculation. The

  13. Development of a double-effect air conditioner-heater (deach) phase 2. Final report, January 1989-December 1989

    SciTech Connect

    De Vuono, A.C.; Landstrom, D.K.; Osborne, R.L.; Christensen, R.N.; Flanigan, L.

    1992-12-01

    The report describes the results of Phase II of a multi-phase project to develop a high-efficiency, gas-fired, residential size air-conditioner/heater based on a double-effect, absorption cycle using LiBr and water as working fluids. The results discussed include experimental and analytical analysis of various options for key components and subsystems including absorber, direct expansion evaporator, solution heat exchangers and burner/generator subsystem. The thermodynamic model used to evaluate various system design tradeoffs is also discussed. The results of the Phase II effort provided the basis for full-scale, integrated breadboard testing to be conducted in Phase III of the project.

  14. Influence of surrounding structures upon the aerodynamic and acoustic performance of the outdoor unit of a split air-conditioner

    NASA Astrophysics Data System (ADS)

    Wu, Chengjun; Liu, Jiang; Pan, Jie

    2014-07-01

    DC-inverter split air-conditioner is widely used in Chinese homes as a result of its high-efficiency and energy-saving. Recently, the researches on its outdoor unit have focused on the influence of surrounding structures upon the aerodynamic and acoustic performance, however they are only limited to the influence of a few parameters on the performance, and practical design of the unit requires more detailed parametric analysis. Three-dimensional computational fluid dynamics(CFD) and computational aerodynamic acoustics(CAA) simulation based on FLUENT solver is used to study the influence of surrounding structures upon the aforementioned properties of the unit. The flow rate and sound pressure level are predicted for different rotating speed, and agree well with the experimental results. The parametric influence of three main surrounding structures(i.e. the heat sink, the bell-mouth type shroud and the outlet grille) upon the aerodynamic performance of the unit is analyzed thoroughly. The results demonstrate that the tip vortex plays a major role in the flow fields near the blade tip and has a great effect on the flow field of the unit. The inlet ring's size and throat's depth of the bell-mouth type shroud, and the through-flow area and configuration of upwind and downwind sections of the outlet grille are the most important factors that affect the aerodynamic performance of the unit. Furthermore, two improved schemes against the existing prototype of the unit are developed, which both can significantly increase the flow rate more than 6 %(i.e. 100 m3·h-1) at given rotating speeds. The inevitable increase of flow noise level when flow rate is increased and the advantage of keeping a lower rotating speed are also discussed. The presented work could be a useful guideline in designing the aerodynamic and acoustic performance of the split air-conditioner in engineering practice.

  15. The use of heteroduplex analysis of polymerase chain reaction products to support the possible transmission of Legionella pneumophila from a malfunctioning automobile air conditioner.

    PubMed

    Pinar, Ahmet; Ramirez, Julio A; Schindler, Laura L; Miller, Richard D; Summersgill, James T

    2002-03-01

    Air conditioner condensates have not been previously associated with cases of Legionnaires' disease. We report the possible transmission of Legionella pneumophila serogroup 1 from a malfunctioning automobile air conditioning system's leaking water onto the floorboard of a car driven for a long distance by the patient. Heteroduplex analysis of polymerase chain reaction products was used to help establish an epidemiologic link between the water specimen and the patient. PMID:11918120

  16. Cardio-Muscular Conditioner

    NASA Technical Reports Server (NTRS)

    1993-01-01

    In the mid-sixties, Gary Graham, a Boeing designer, developed a cardiovascular conditioner for a planned Air Force orbiting laboratory. After the project was cancelled, Graham participated in space station conditioning studies for the Skylab program. Twenty years later, he used this expertise to develop the Shuttle 2000-1, a physical therapy and athletic development conditioner, available through Contemporary Designs. The machine is used by football teams, sports clinics and medical rehabilitation centers. Cardiovascular fitness and muscular strength development are promoted through both kinetic and plyometric exercises.

  17. Improving Best Air Conditioner Efficiency by 20-30% through a High Efficiency Fan and Diffuser Stage Coupled with an Evaporative Condenser Pre-Cooler

    SciTech Connect

    Parker, Danny S; Sherwin, John R; Raustad, Richard

    2014-04-10

    The Florida Solar Energy Center (FSEC) conducted a research project to improve the best residential air conditioner condenser technology currently available on the market by retrofitting a commercially-available unit with both a high efficiency fan system and an evaporative pre-cooler. The objective was to integrate these two concepts to achieve an ultra-efficient residential air conditioner design. The project produced a working prototype that was 30% more efficient compared to the best currently-available technologies; the peak the energy efficiency ratio (EER) was improved by 41%. Efficiency at the Air-Conditioning and Refrigeration Institute (ARI) standard B-condition which is used to estimate seasonal energy efficiency ratio (SEER), was raised from a nominal 21 Btu/Wh to 32 Btu/Wh.

  18. Auto-ignition of lubricating oil working at high pressures in a compressor for an air conditioner.

    PubMed

    Kim, Chul Jin; Choi, Hyo Hyun; Sohn, Chae Hoon

    2011-01-15

    Auto-ignition of lubricating oil working in a compressor for an air conditioner is studied experimentally. The adopted lubricating oil is an unknown mixture with multi-components and known to have flash point temperature of 170 °C. First, its auto-ignition temperature is measured 365 °C at atmospheric pressure. The lubricating oil works under high-pressure condition up to 30 atm and it is heated and cooled down repeatedly. Accordingly, auto-ignition temperatures or flammable limits of lubricating oil are required at high pressures with respect to fire safety. Because there is not a standard test method for the purpose, a new ignition-test method is proposed in this study and thereby, auto-ignition temperatures are measured over the pressure range below 30 atm. The measured temperatures range from 215 °C to 255 °C and they strongly depend on pressure of gas mixture consisting of oil vapor, nitrogen, and oxygen. They are close to flash point temperature and the lubricating oil can be hazardous when it works for high-pressure operating condition and abundant air flows into a compressor. PMID:20934810

  19. Alternative Refrigerant Evaluation for High-Ambient Temperature Environments: R-22 and R-410A Alternatives for Mini-Split Air Conditioners

    SciTech Connect

    Abdelaziz, Omar; Munk, Jeffrey D.; Shrestha, Som S.; Linkous, Randall Lee; Goetzler, William; Guernsey, Matt; Kassuga, Theo

    2015-08-01

    The Oak Ridge National Laboratory (ORNL) High-Ambient Temperature Testing Program for Low-GWP Refrigerants aims to develop an understanding of the performance of low-Global Warming Potential (low-GWP) alternatives to Hydrochlorofluorocarbon (HCFC) and Hydrofluorocarbon (HFC) refrigerants in mini-split air conditioners under high ambient temperature conditions. This interim working paper describes the parties involved, the alternative refrigerants selection process, the test procedures, and the preliminary results.

  20. Alternative Refrigerant Evaluation for High-Ambient-Temperature Environments: R-22 and R-410A Alternatives for Mini-Split Air Conditioners

    SciTech Connect

    Abdelaziz, Omar; Shrestha, Som S.; Munk, Jeffrey D.; Linkous, Randall Lee; Goetzler, William; Guernsey, Matt; Kassuga, Theo

    2015-10-01

    The Oak Ridge National Laboratory (ORNL) High-Ambient-Temperature Evaluation Program for low– global warming potential (Low-GWP) Refrigerants aims to develop an understanding of the performance of low-GWP alternative refrigerants to hydrochlorofluorocarbon (HCFC) and hydrofluorocarbon (HFC) refrigerants in mini-split air conditioners under high-ambient-temperature conditions. This final report describes the parties involved, the alternative refrigerant selection process, the test procedures, and the final results.

  1. Increased prevalence of IgG-induced sensitization and hypersensitivity pneumonitis (humidifier lung) in nonsmokers exposed to aerosols of a contaminated air conditioner.

    PubMed

    Baur, X; Richter, G; Pethran, A; Czuppon, A B; Schwaiblmair, M

    1992-01-01

    Specific IgG antibodies against antigens of a contaminated air conditioner were estimated in serum of 134 workers of a printing company. Altogether 64% of the workers investigated revealed significantly elevated levels (> 3 U/ml) of IgG antibodies specific to these antigens as compared to a nonexposed control group. The occurrence of IgG antibodies for microbial extracts were 25% for Fusarium, 23% for Penicillium notatum, 13% for Alternaria tenuis, 12% for Aureobasidium pullulans, 9% for Sphaeropsidales species, 3% for Micropolyspora faeni, 2% for Aspergillus fumigatus and 2% for Thermoactionomyces vulgaris. Out of the 86 workers with elevated IgG antibodies for air conditioner antigens, 59 were nonsmokers. Considering a cut-off level of 10 U/ml IgG for high values, the proportion of smokers to nonsmokers becomes even more pronounced (6 to 36 respectively, binominal test p < 0.001). This is despite the fact that the distribution of smokers and nonsmokers among the 134 workers is approximately equal (60 to 74). All 3 workers with clinical diagnosis of humidifier lung or humidifier fever belonged to the nonsmoker group. Our findings indicate that crude water extracts of contaminated air conditioners are the best choice as antigen source for the diagnosis of humidifier lung in exposed workers. Nonsmokers are shown to have a high risk for immunological sensitization. PMID:1485005

  2. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... water, or gas, but may not include reverse cycle refrigeration as a heating means. Single package... measurement. Commercial package air-conditioning and heating equipment means air-cooled, water-cooled, evaporatively-cooled, or water source (not including ground water source) electrically operated, unitary...

  3. 76 FR 19913 - Compliance Testing Procedures: Correction Factor for Room Air Conditioners

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... that as atmospheric pressure drops, so does the air density and, therefore, the mass of air in a room. As atmospheric pressure drops, the efficiency of a unit would also drop because there would be less... (Atmospheric Pressure Inputs). Condenser Inlet Pressure psia 14.695 14.204 13.713 13.222 12.731...

  4. Factors influencing on the bioaccessibility of polybrominated diphenyl ethers in size-specific dust from air conditioner filters.

    PubMed

    Yu, Yingxin; Yang, Dan; Wang, Xinxin; Huang, Ningbao; Zhang, Xinyu; Zhang, Dongping; Fu, Jiamo

    2013-11-01

    Size-specific concentrations and bioaccessibility of polybrominated diphenyl ethers (PBDEs) in dust from air conditioner filters were measured, and the factors influencing the PBDE bioaccessibility were determined. Generally, the PBDE concentrations increased with decreasing dust particle size, and BDE209 (deca-BDE) was generally the predominant congener. The bioaccessibility ranged from 20.3% to 50.8% for tri- to hepta-BDEs, and from 5.1% to 13.9% for BDE209 in dust fractions of varied particle size. The bioaccessibility of most PBDE congeners decreased with increasing dust particle size. The way of being of PBDE (adsorbed to dust surface or incorporated into polymers) in dust significantly influenced the bioaccessibility. There was a significant negative correlation between the tri- to hepta-BDE bioaccessibility and organic matter (OM) contents in dust. Furthermore, tri- to hepta-BDE bioaccessibility increased with increasing polarity of OMs, while with decreasing aromaticity of OMs. The tri- to hepta-BDE bioaccessibility significantly positively correlated with the surface areas and pore volumes of dust. Using multiple linear regression analysis, it was found that the OM contents and pore volumes of dust were the most important factors to influence the tri- to hepta-BDE bioaccessibility and they could be used to estimate the bioaccessibility of tri- to hepta-BDEs according to the following equation: bioaccessibility (%)=45.05-0.49 × OM%+1.79 × pore volume. However, BDE209 bioaccessibility did not correlate to any of these factors. PMID:24144462

  5. Preliminary design package for residential heating/cooling system: Rankine air conditioner redesign

    NASA Technical Reports Server (NTRS)

    1978-01-01

    A summary of the preliminary redesign and development of a marketable single family heating and cooling system is presented. The interim design and schedule status of the residential (3-ton) redesign, problem areas and solutions, and the definition of plans for future design and development activities were discussed. The proposed system for a single-family residential heating and cooling system is a single-loop, solar-assisted, hydronic-to-warm-air heating subsystem with solar-assisted domestic water heating and a Rankine-driven expansion air-conditioning subsystem.

  6. Gohieria fusca (Acari: Astigmata) found in the filter dusts of air conditioners in China.

    PubMed

    Li, Chaopin; Zhan, Xiaodong; Zhao, Jinhong; Wei, Guo

    2014-10-06

    Objetivo: La Gohieria fusca (Oudemans, 1902) se reproduce en la harina de trigo, arroz, maíz, piensos, salvado de trigo y los medicamentos a base de hierbas, además de en otros productos almacenados; este ácaro puede tener una reactividad cruzada de leve a moderada con alérgenos de los ácaros del polvo domésticos, una importante fuente de alérgenos de interior asociada al asma y otras afecciones alérgicas. Los sistemas de aire acondicionado son indispensables en edificios públicos y civiles, y las pantallas de estos aparatos son los lugares donde más se acumula el polvo. Se realizó este estudio con el fin de investigar si la Gohieria fusca puede reproducirse en las pantallas de los acondicionadores de aire instalados en espacios públicos o viviendas en la ciudad de Wuhu, provincia de Anhui, China. Métodos: Se recogieron 430 muestras de polvo de los filtros de los sistemas de aire acondicionado en la cafeterías de centros educativos, mercados, hoteles y edificios civiles entre junio y septiembre de 2013, y se aisló la Gohieria fusca de dichas muestras. Resultados: Los resultados indicaron que la Gohieria fusca estaba presente en 98 de las 430 muestras (22,79%), y la tasa de reproducción fue significativa en los filtros del aire acondicionado de diferentes espacios (c2=18.294, P.

  7. DEVELOPMENT OF A LINEAR COMPRESSOR FOR AIR CONDITIONERS AND HEAT PUMPS

    EPA Science Inventory

    The report discusses the design, building, testing, and delivering to the Environmental Protection Agency of a linear compressor for operation in a 3.0- ton (10.5 kW) residential air-conditioning and heat pumping system. The compressor design evolved from a linear resonant piston...

  8. Development of a solar-powered residential air conditioner. Program review

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Progress in the effort to develop a residential solar-powered air conditioning system is reported. The topics covered include the objectives, scope and status of the program. The results of state-of-art, design, and economic studies and component and system data are also presented.

  9. Fuel conditioner

    SciTech Connect

    Nelson, M.L.; Nelson, O.L. Jr.

    1988-06-28

    A fuel conditioner is described comprising 10 to 80% of a polar oxygenated hydrocarbon having an average molecular weight from about 250 to about 500, an acid acid number from about 25 to about 125, and a saponification number from about 30 to about 250; and 5 to 50% of an oxygenated compatibilizing agent having a solubility parameter of from about 8.8 to about 11.5 and moderate to strong hydrogen-bonding capacity.

  10. Local Voltage Support from Distributed Energy Resources to Prevent Air Conditioner Motor Stalling

    SciTech Connect

    Baone, Chaitanya A; Xu, Yan; Kueck, John D

    2010-01-01

    Microgrid voltage collapse often happens when there is a high percentage of low inertia air-conditioning (AC) motors in the power systems. The stalling of the AC motors results in Fault Induced Delayed Voltage Recovery (FIDVR). A hybrid load model including typical building loads, AC motor loads, and other induction motor loads is built to simulate the motoring stalling phenomena. Furthermore, distributed energy resources (DE) with local voltage support capability are utilized to boost the local bus voltage during a fault, and prevent the motor stalling. The simulation results are presented. The analysis of the simulation results show that local voltage support from multiple DEs can effectively and economically solve the microgrid voltage collapse problem.

  11. Spinning Reserves from Controllable Packaged Through the Wall Air Conditioner (PTAC) Units

    SciTech Connect

    Kirby, B.J.

    2003-04-02

    This report summarizes the feasibility of providing spinning reserves from packaged through the wall air conditioning (PTAC) units. Spinning reserves, together with non-spinning reserves, compose the contingency reserves; the essential resources that the power system operator uses to restore the generation and load balance and maintain bulk power system reliability in the event of a major generation or transmission outage. Spinning reserves are the fastest responding and most expensive reserves. Many responsive load technologies could (and we hope will) be used to provide spinning reserve. It is also easier for many loads (including air conditioning loads) to provide the relatively shorter and less frequent interruptions required to respond to contingencies than it is for them to reduce consumption for an entire peak period. Oak Ridge National Laboratory (ORNL) is conducting research on obtaining spinning reserve from large pumping loads and from residential and small commercial thermostat controlled heating, ventilation and air conditioning (HVAC) units. The technology selected for this project, Digi-Log's retrofit PTAC controller, offers significant advantages. To evaluate the availability of spinning reserve capacity from responsive heating and air conditioning loads, ORNL obtained data from a number of units operating over a year at a motel in the TVA service territory. A total of 24 PTAC units in as many rooms were fitted with Digi-Log's supervisory control unit that could be controlled from the motel front desk. Twelve of the rooms formed the group in which the controller was controlled from the hotel front desk only. The remaining twelve rooms were controlled by the occupant and formed the uncontrolled group. This enables us to evaluate the spinning reserve capacity from PTACS that were operating normally and from those under active energy management. A second generation of the Digi-Log controller that will respond quickly enough to provide spinning reserve

  12. High-Efficiency Variable Dehumidification for Air Conditioners: ClimaStat

    SciTech Connect

    West, Michael K., Ph.D. P.E.

    2006-04-30

    Advantek has successfully developed the first low-cost technology offering significant improvement in both Seasonal Energy Efficiency (SEER) and comfort & humidity control. A production prototype was constructed based on a commercial roof top package unit. The prototype was operated under a wide range of psychrometric conditions. Test data was analyzed to identify refinements, which were implemented to further improve performance in an iterative procedure that resulted in a fully optimized technology. The latest results show an increase in dehumidification capacity of 56% with ClimaStat™ in full dehumidify mode vs. with ClimaStat™ off. Dehumidification improved by a factor of 1.7 to 1.9 – meaning that the unit can provide nearly twice the water removal per unit of sensible cooling load. Performance testing results have been consistent, verifiable and repeatable. . ClimaStat™ cost-effectively controls humidity on-demand and improves indoor air quality while reducing annual energy costs. Test data clearly shows that ClimaStat™ costs 20% to 60% less to operate. ClimaStat™ is ready for market.

  13. COP improvement of refrigerator/freezers, air-conditioners, and heat pumps using nonazeotropic refrigerant mixtures

    NASA Technical Reports Server (NTRS)

    Westra, Douglas G.

    1993-01-01

    With the February, 1992 announcement by President Bush to move the deadline for outlawing CFC (chloro-fluoro-carbon) refrigerants from the year 2000 to the year 1996, the refrigeration and air-conditioning industries have been accelerating their efforts to find alternative refrigerants. Many of the alternative refrigerants being evaluated require synthetic lubricants, are less efficient, and have toxicity problems. One option to developing new, alternative refrigerants is to combine existing non-CFC refrigerants to form a nonazeotropic mixture, with the concentration optimized for the given application so that system COP (Coefficient Of Performance) may be maintained or even improved. This paper will discuss the dilemma that industry is facing regarding CFC phase-out and the problems associated with CFC alternatives presently under development. A definition of nonazeotropic mixtures will be provided, and the characteristics and COP benefits of nonazeotropic refrigerant mixtures will be explained using thermodynamic principles. Limitations and disadvantages of nonazeotropic mixtures will be discussed, and example systems using such mixtures will be reviewed.

  14. Properties and Cycle Performance of Refrigerant Blends Operating Near and Above the Refrigerant Critical Point, Task 2: Air Conditioner System Study

    SciTech Connect

    Piotr A. Domanski; W. Vance Payne

    2002-10-31

    The main goal of this project was to investigate and compare the performance of an R410A air conditioner to that of an R22 air conditioner, with specific interest in performance at high ambient temperatures at which the condenser of the R410A system may be operating above the refrigerant's critical point. Part 1 of this project consisted of conducting comprehensive measurements of thermophysical for refrigerant R125 and refrigerant blends R410A and R507A and developing new equation of state formulations and mixture models for predicting thermophysical properties of HFC refrigerant blends. Part 2 of this project conducted performance measurements of split-system, 3-ton R22 and R410A residential air conditioners in the 80 to 135 F (27.8 to 57.2 C) outdoor temperature range and development of a system performance model. The performance data was used in preparing a beta version of EVAP-COND, a windows-based simulation package for predicting performance of finned-tube evaporators and condensers. The modeling portion of this project also included the formulation of a model for an air-conditioner equipped with a thermal expansion valve (TXV). Capacity and energy efficiency ratio (EER) were measured and compared. The R22 system's performance was measured over the outdoor ambient temperature range of 80 to 135 F (27.8 to 57.2 C). The same test range was planned for the R410A system. However, the compressor's safety system cut off the compressor at the 135.0 F (57.2 C) test temperature. The highest measurement on this system was at 130.0 F (54.4 C). Subsequently, a custom-manufactured R410A compressor with a disabled safety system and a more powerful motor was installed and performance was measured at outdoor temperatures up to 155.0 F (68.3 C). Both systems had similar capacity and EER performance at 82.0 F (27.8 C). The capacity and EER degradation of both systems were nearly linearly dependent with rising ambient outdoor ambient test temperatures. The performance

  15. A Novel, Low-Cost, Reduced-Sensor Approach for Providing Smart Renote Monitoring and Diagnostics for Packaged Air Conditioners and Heat Pumps

    SciTech Connect

    Brambley, Michael R.

    2009-09-01

    This report describes conceptually an approach to providing automated remote performance and conditioning monitoring and fault detection for air conditioners and heat pumps that shows great promise to reduce the capital and installation costs of such systems from over $1000 per unit to $200 to $400 per unit. The approach relies on non-intrusive electric load monitoring (NIELM) to enable separation of the power use signals of compressors and fans in the air conditioner or heat pump. Then combining information on the power uses and one or two air temperature measurements, changes in energy efficiency and occurrence of major faults would be detected. By decreasing the number of sensors used from between ten and twenty in current diagnostic monitoring systems to three for the envisaged system, the capital cost of the monitoring system hardware and the cost of labor for installation would be decreased significantly. After describing the problem being addressed and the concept for performance monitoring and fault detection in more detail, the report identifies specific conditions and faults that the proposed method would detect, discusses specific needs for successful use of the NIELM approach, and identifies the major elements in the path from concept to a commercialized monitoring and diagnostic system.

  16. Endow My Air Conditioner!

    ERIC Educational Resources Information Center

    Simmons, Charles E. P.

    1982-01-01

    Administrators need to plan and set priorities in various energy/maintenance areas, and trustees and legislators, faculty and students have to be educated regarding maintenance and conservation. Cost of energy consumption by area and department must be worked out. (MLW)

  17. Development of a Double-Effect Air-Conditioner Heater (DEACH). Phase 3 and final report, January 1990-December 1991. Phase 3, September 1987-December 1991. Overall project

    SciTech Connect

    De Vuono, A.C.; Hanna, W.T.; Osborne, R.L.; Ball, D.A.

    1992-04-01

    The report describes development efforts on a Double-Effect Air-Conditioner Heater (DEACH). Based on a double-effect LiBr/H2O absorption cycle, the DEACH was focused on residential applications with the primary objective being a low first-cost efficient gas-fired cooling system. The concept included compact integrated heat exchangers, direct heat rejection to outdoor air (no cooling tower), and ability to self-decrystallize. The performance goals of the system were essentially demonstrated in a full-scale (3 refrigeration ton), fully integrated breadboard. However, the projected manufacturing cost was somewhat above the original target and even further above that deemed competitive at the end of the project. Therefore, technical development was stopped in late 1991.

  18. Rho/RacGAPs

    PubMed Central

    Csépányi-Kömi, Roland; Lévay, Magdolna; Ligeti, Erzsébet

    2012-01-01

    Regulatory proteins such as guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) determine the activity of small GTPases. In the Rho/Rac family, the number of GEFs and GAPs largely exceeds the number of small GTPases, raising the question of specific or overlapping functions. In our recent study we investigated the first time ARHGAP25 at the protein level, determined its activity as RacGAP and showed its involvement in phagocytosis. With the discovery of ARHGAP25, the number of RacGAPs described in phagocytes is increased to six. We provide data that indicate the specific functions of selected Rho/RacGAPs and we show an example of differential regulation of a Rho/Rac family GAP by different kinases. We propose that the abundance of Rho/Rac family GAPs is an important element of the fine spatiotemporal regulation of diverse cellular functions. PMID:22751505

  19. Solar-Powered, Liquid-Desiccant Air Conditioner for Low-Electricity Humidity Control: Report and Summary Report

    SciTech Connect

    Dean, J.; Kozubal, E.; Herrmann, L.; Miller, J.; Lowenstein, A.; Barker, G.; Slayzak, S.

    2012-11-01

    The primary objective of this project was to demonstrate the capabilities of a new high-performance, liquid-desiccant dedicated outdoor air system (DOAS) to enhance cooling efficiency and comfort in humid climates while substantially reducing electric peak demand at Tyndall Air Force Base (AFB), which is 12 miles east of Panama City, Florida.

  20. Concentrations of polybrominated diphenyl ethers (PBDEs) in central air-conditioner filter dust and relevance of non-dietary exposure in occupational indoor environments in Greece.

    PubMed

    Besis, Athanasios; Katsoyiannis, Athanasios; Botsaropoulou, Elisavet; Samara, Constantini

    2014-05-01

    Polybrominated Diphenyl Ethers (PBDEs) are ubiquitous in the indoor environment owing to their use in consumer products and various studies around the world have found higher concentrations indoors than outdoors. Central air conditioner (A/C) systems have been widely used in many workplaces, therefore, studying of PBDEs in central A/C filter dust is useful to better understand the occurrences and health implications of PBDEs in indoor environments. The present study examined the occurrence of PBDEs in central A/C filter dust collected from various workplaces (n = 20) in Thessaloniki, Greece. The sum concentrations of 21 target congeners (∑21PBDE) in A/C dust ranged between 84 and 4062 ng g(-1) with a median value of 1092 ng g(-1), while BDE-209 was found to be the most abundant BDE congener. The daily intake via dust ingestion of PBDEs estimated for the employees of the occupational settings ranged from 3 to 45 ng day(-1) (median 12 ng day(-1)). PMID:24556227

  1. Rac GTPases in Human Diseases

    PubMed Central

    Pai, Sung-Yun; Kim, Chaekyun; Williams, David A.

    2010-01-01

    Rho GTPases are members of the Ras superfamily of GTPases that regulate a wide variety of cellular functions. While Rho GTPase pathways have been implicated in various pathological conditions in humans, to date coding mutations in only the hematopoietic specific GTPase, RAC2, have been found to cause a human disease, a severe phagocytic immunodeficiency characterized by life-threatening infections in infancy. Interestingly, the phenotype was predicted by a mouse knock-out of RAC2 and resembles leukocyte adhesion deficiency (LAD). Here we review Rho GTPases with a specific focus on Rac GTPases. In particular, we discuss a new understanding of the unique and overlapping roles of Rac2 in blood cells that has developed since the generation of mice deficient in Rac1, Rac2 and Rac3 proteins. We propose that Rac2 mutations leading to disease be termed LAD type IV. PMID:21178276

  2. China Cools with Tighter RAC Standards

    SciTech Connect

    Lin, Jiang; Rosenquist, Gregory

    2006-06-01

    After boiling summer brought brown-out to most part of the country in 2004, China announced a new set of minimum energy efficiency standards for room air conditioners in September 2004, with the first tier going into effect on March 1, 2005 and the reach standard taking effect on January 1, 2009. This represents a milestone in China's standard setting process since the reach standard levels are significantly more stringent than previous standards for other appliances. This paper first analyzes cost-effectiveness of China's new standards for room air conditioners, and then attempts to evaluate the impact of the new standards on energy savings, electric generation capacity, and CO2 emissions reductions.

  3. Radiation damage on Langmuir monolayers of the anionic 1.2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt)(DPPG) phospholipid at the air-DNA solution interface.

    PubMed

    Gomes, Paulo J; Gonçalves da Silva, Amélia M P S; Ribeiro, Paulo A; Oliveira, Osvaldo N; Raposo, Maria

    2016-01-01

    The resilience of cells to ultraviolet (UV) irradiation is probably associated with the effects induced in biological molecules such as DNA and in the cell membrane. In this study, we investigated UV damage to the anionic 1.2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DPPG) phospholipid, which is an important component of cell membranes. In films cast from DPPG emulsions, UV irradiation induced cleavage of C-O, C=O and -PO(2-) bonds, while in Langmuir monolayers at the air/water interface representing the cell membrane this irradiation caused the monolayer stability to decrease. When DNA was present in the subphase, however, the effects from UV irradiation were smaller, since the ionic products from degradation of either DPPG or DNA stabilize the intact DPPG molecules. This mechanism may explain why UV irradiation does not cause immediate cell collapse, thus providing time for the cellular machinery to repair elements damaged by UV.

  4. Technical support document: Energy efficiency standards for consumer products: Room air conditioners, water heaters, direct heating equipment, mobile home furnaces, kitchen ranges and ovens, pool heaters, fluorescent lamp ballasts and television sets. Volume 1, Methodology

    SciTech Connect

    Not Available

    1993-11-01

    The Energy Policy and Conservation Act (P.L. 94-163), as amended, establishes energy conservation standards for 12 of the 13 types of consumer products specifically covered by the Act. The legislation requires the Department of Energy (DOE) to consider new or amended standards for these and other types of products at specified times. DOE is currently considering amending standards for seven types of products: water heaters, direct heating equipment, mobile home furnaces, pool heaters, room air conditioners, kitchen ranges and ovens (including microwave ovens), and fluorescent light ballasts and is considering establishing standards for television sets. This Technical Support Document presents the methodology, data, and results from the analysis of the energy and economic impacts of the proposed standards. This volume presents a general description of the analytic approach, including the structure of the major models.

  5. 75 FR 8397 - Notice of Utah's Resource Advisory Council (RAC)/Recreation RAC Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-24

    ... Bureau of Land Management Notice of Utah's Resource Advisory Council (RAC)/Recreation RAC Meeting AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Utah's Resource Advisory Council (RAC)/Recreation... Management's (BLM) Utah Resource Advisory Council (RAC)/Recreation RAC will meet as indicated below....

  6. Field performance of the Gallagher flow conditioner

    SciTech Connect

    Gallagher, J.E.; LaNasa, P.J.

    1995-12-31

    This paper contains a summary of the current {open_quotes}state of the art{close_quotes} for flow conditioners, the basis for the Gallagher Flow Conditioner (GFC), and experimental results from several evaluations. Experimental results for the GFC indicate a maximum metering uncertainty of approximately plus or minus one-tenth of one percent ({+-} 0.10%) due to upstream flow disturbances for orifice meters and virtually zero for other inferential flowmeters. Experiments have been conducted at five commercial laboratories, seven field laboratories, line sizes form 25 to 460 mm (1 to 18 inch), over a Reynolds number range of 2,000 to 3,000,000, for three inferential flowmeters -orifice, turbine and vortex. The GFC has been tested in a multitude of fluid applications --- natural gas, dry air, nine different crude oils, polymer-grade ethylene, etcetera. In these applications the flowing stream has ranged from clean to very dirty. Based on independently conducted research results, it is the authors` opinions that the GFC {open_quotes}isolates{close_quotes} flowmeters from piping-induced disturbances and, thereby, allows more accurate metering of fluids flowing in pipelines. The device achieves the optimal flow conditioner objectives and maintains pseudofully developed flow in a pipe with respect to the axial position.

  7. Hybrid respiration-signal conditioner

    NASA Technical Reports Server (NTRS)

    Rinard, G. A.; Steffen, D. A.; Sturm, R. E.

    1979-01-01

    Hybrid impedance-pneumograph and respiration-rate signal conditioner element of hand-held vital signs monitor measures changes in impedance of chest during breathing cycle and generates analog respiration signal as output along with synchronous square wave that can be monitored by breath-rate processor.

  8. Rho/RacGAPs: embarras de richesse?

    PubMed

    Csépányi-Kömi, Roland; Lévay, Magdolna; Ligeti, Erzsébet

    2012-01-01

    Regulatory proteins such as guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) determine the activity of small GTPases. In the Rho/Rac family, the number of GEFs and GAPs largely exceeds the number of small GTPases, raising the question of specific or overlapping functions. In our recent study we investigated the first time ARHGAP25 at the protein level, determined its activity as RacGAP and showed its involvement in phagocytosis. With the discovery of ARHGAP25, the number of RacGAPs described in phagocytes is increased to six. We provide data that indicate the specific functions of selected Rho/RacGAPs and we show an example of differential regulation of a Rho/Rac family GAP by different kinases. We propose that the abundance of Rho/Rac family GAPs is an important element of the fine spatiotemporal regulation of diverse cellular functions.

  9. Development of a linear compressor for air conditioners and heat pumps. Design and test report. Final report, October 1995-November 1996

    SciTech Connect

    Waldron, W.D.

    1997-09-01

    The report discusses the design, building, testing, and delivering to the Environmental Protection Agency of a linear compressor for operation in a 3.0-ton (10.5 kW) resident air-conditioning and heat pumping system. During the design work, the Resonant Piston Compression (RPC) was modified to extend its range into the heating mode, and a voltage controller was developed that could sense the proximity of the compressor plunger to the top dead center and bottom dead center stops and limit the plunger stroke. The test program that followed construction was successful, except for several minor difficulties, including a failure in the epoxy bond of the compressor plunger. The test results proved the performance advantage of the RPC in terms of a high Seasonal Energy Efficiency Rating potential and also demonstrated that the compressor can be controlled in a stable manner using low cost, commercially available motor control devices.

  10. Shampoos, conditioners, and camouflage techniques.

    PubMed

    Draelos, Zoe Diana

    2013-01-01

    This article examines hair care in persons with hair loss. The use of shampoos, conditioners, and hair styling products to camouflage hair loss is discussed. Because hair is nonliving, medical treatments are limited to only inducing change in the follicles within the scalp skin and do not improve the hair loss actually witnessed by the patient. There is therefore a need to accompany medical treatment of hair loss with cosmetic hair treatment to optimize patient satisfaction.

  11. 7 CFR 3201.92 - Fuel conditioners.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Fuel conditioners. 3201.92 Section 3201.92... Designated Items § 3201.92 Fuel conditioners. (a) Definition. Products formulated to improve the performance... fuel system. (b) Minimum biobased content. The Federal preferred procurement product must have...

  12. 7 CFR 3201.92 - Fuel conditioners.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Fuel conditioners. 3201.92 Section 3201.92... Designated Items § 3201.92 Fuel conditioners. (a) Definition. Products formulated to improve the performance... fuel system. (b) Minimum biobased content. The Federal preferred procurement product must have...

  13. Low-noise pulse conditioner

    DOEpatents

    Bird, David A.

    1983-01-01

    A low-noise pulse conditioner is provided for driving electronic digital processing circuitry directly from differentially induced input pulses. The circuit uses a unique differential-to-peak detector circuit to generate a dynamic reference signal proportional to the input peak voltage. The input pulses are compared with the reference signal in an input network which operates in full differential mode with only a passive input filter. This reduces the introduction of circuit-induced noise, or jitter, generated in ground referenced input elements normally used in pulse conditioning circuits, especially speed transducer processing circuits.

  14. Space shuttle aps propellant thermal conditioner study

    NASA Technical Reports Server (NTRS)

    Fulton, D. L.

    1973-01-01

    An analytical and experimental effort was completed to evaluate a baffle type thermal conditioner for superheating O2 and H2 at supercritical pressures. The thermal conditioner consisted of a heat exchanger and an integral reactor (gas generator) operating on O2/H2 propellants. Primary emphasis was placed on the hydrogen conditioner with some effort on the oxygen conditioner and a study completed of alternate concepts for use in conditioning oxygen. A hydrogen conditioner was hot fire tested under a range of conditions to establish ignition, heat exchange and response parameters. A parallel technology task was completed to further evaluate the integral reactor and heat exchanger with the side mounted electrical spark igniter.

  15. Conditioner for a helically transported electron beam

    SciTech Connect

    Wang, Changbiao.

    1992-05-01

    The kinetic theory is developed to investigate a conditioner for a helically transported electron beam. Linear expressions for axial velocity spread are derived. Numerical simulation is used to check the theoretical results and examine nonlinear aspects of the conditioning process. The results show that in the linear regime the action of the beam conditioner on a pulsed beam mainly depends on the phase at which the beam enters the conditioner and depends only slightly on the operating wavelength. In the nonlinear regime, however, the action of the conditioner strongly depends on the operating wavelength and only slightly upon the entrance phase. For a properly chosen operating wavelength, a little less than the electron's relativistic cyclotron wavelength, the conditioner can decrease the axial velocity spread of a pulsed beam down to less than one-third of its initial value.

  16. Conditioner for a helically transported electron beam

    SciTech Connect

    Wang, Changbiao

    1992-05-01

    The kinetic theory is developed to investigate a conditioner for a helically transported electron beam. Linear expressions for axial velocity spread are derived. Numerical simulation is used to check the theoretical results and examine nonlinear aspects of the conditioning process. The results show that in the linear regime the action of the beam conditioner on a pulsed beam mainly depends on the phase at which the beam enters the conditioner and depends only slightly on the operating wavelength. In the nonlinear regime, however, the action of the conditioner strongly depends on the operating wavelength and only slightly upon the entrance phase. For a properly chosen operating wavelength, a little less than the electron`s relativistic cyclotron wavelength, the conditioner can decrease the axial velocity spread of a pulsed beam down to less than one-third of its initial value.

  17. Conditioner for a helically transported electron beam

    SciTech Connect

    Wang, C.

    1992-05-01

    The kinetic theory is developed to investigate a conditioner for a helically imported electron beam. Linear expressions for axial velocity spread are derived. Numerical simulation is used to check the theoretical results and examine nonlinear aspects of the conditioning process. The results show that in the linear regime the action of the beam conditioner on a pulsed beam mainly depends on the phase at which the beam enters the conditioner and depends only slightly on the operating wavelength. In the nonlinear regime, however, the action of the conditioner strongly depends on the operating wavelength and only slightly upon the entrance phase. For a properly chosen operating wavelength, a little less than the electron's relativistic cyclotron wavelength, the conditioner can decrease the axial velocity spread of a pulsed beam down to less than one-third of its initial value.

  18. Conditioner for a helically transported electron beam

    SciTech Connect

    Wang, C.

    1992-05-01

    The kinetic theory is developed to investigate a conditioner for a helically imported electron beam. Linear expressions for axial velocity spread are derived. Numerical simulation is used to check the theoretical results and examine nonlinear aspects of the conditioning process. The results show that in the linear regime the action of the beam conditioner on a pulsed beam mainly depends on the phase at which the beam enters the conditioner and depends only slightly on the operating wavelength. In the nonlinear regime, however, the action of the conditioner strongly depends on the operating wavelength and only slightly upon the entrance phase. For a properly chosen operating wavelength, a little less than the electron`s relativistic cyclotron wavelength, the conditioner can decrease the axial velocity spread of a pulsed beam down to less than one-third of its initial value.

  19. Formulation of humic-based soil conditioners

    NASA Astrophysics Data System (ADS)

    Amanova, M. A.; Mamytova, G. A.; Mamytova, B. A.; Kydralieva, K. A.; Jorobekova, Sh. J.

    2009-04-01

    The goal of the study is to prepare soil conditioners (SC) able to carry out the following functions: (i) the chemical conditioning of soil mainly comprising the adjustment of pH, (ii) the balancing of inorganic nutrients, (iii) the physical conditioning of soil mainly comprising the improvement of water permeability, air permeability and water retention properties, and (iv) improvement of the ecological system concerning of useful microorganisms activity in the soil. The SC was made of a mixture of inorganic ingredients, a chemical composition and physical and chemical properties of which promoted improvement of physical characteristic of soil and enrichment by its mineral nutritious elements. In addition to aforesaid ingredients, this soil conditioner contains agronomical-valued groups of microorganisms having the function promoting the growth of the crop. As organic component of SC humic acids (HA) was used. HA serve many major functions that result in better soil and plant health. In soil, HA can increase microbial and mycorrhizal activity while enhancing nutrient uptake by plant roots. HA work as a catalyst by stimulating root and plant growth, it may enhance enzymatic activity that in turn accelerates cell division which can lead to increased yields. HA can help to increase crop yields, seed germination, and much more. In short, humic acids helps keep healthy plants health. The first stage goal was to evaluate mineral and organic ingredients for formulation of SC. Soil conditioners assessed included ash and slag. The use of slags has been largelly used in agriculture as a source of lime and phosphoric acid. The silicic acid of slags reduces Al-acitivity thus, promoting a better assimilation of P-fertilizer by plants. Additionally, silicic acid is also known to improve soil moisture capacity, thus enhancing soil water availability to plants. Physico-chemical characteristics of ash and slag were determined, as a total - about 20 samples. Results include

  20. Rac1 deletion causes thymic atrophy.

    PubMed

    Hunziker, Lukas; Benitah, Salvador Aznar; Aznar Benitah, Salvador; Braun, Kristin M; Jensen, Kim; McNulty, Katrina; Butler, Colin; Potton, Elspeth; Nye, Emma; Boyd, Richard; Laurent, Geoff; Glogauer, Michael; Wright, Nick A; Watt, Fiona M; Janes, Sam M

    2011-04-29

    The thymic stroma supports T lymphocyte development and consists of an epithelium maintained by thymic epithelial progenitors. The molecular pathways that govern epithelial homeostasis are poorly understood. Here we demonstrate that deletion of Rac1 in Keratin 5/Keratin 14 expressing embryonic and adult thymic epithelial cells leads to loss of the thymic epithelial compartment. Rac1 deletion led to an increase in c-Myc expression and a generalized increase in apoptosis associated with a decrease in thymic epithelial proliferation. Our results suggest Rac1 maintains the epithelial population, and equilibrium between Rac1 and c-Myc may control proliferation, apoptosis and maturation of the thymic epithelial compartment. Understanding thymic epithelial maintenance is a step toward the dual goals of in vitro thymic epithelial cell culture and T cell differentiation, and the clinical repair of thymic damage from graft-versus-host-disease, chemotherapy or irradiation.

  1. High efficiency laser spectrum conditioner

    DOEpatents

    Greiner, Norman R.

    1980-01-01

    A high efficiency laser spectrum conditioner for generating a collinear parallel output beam containing a predetermined set of frequencies from a multifrequency laser. A diffraction grating and spherical mirror are used in combination, to disperse the various frequencies of the input laser beam and direct these frequencies along various parallel lines spatially separated from one another to an apertured mask. Selection of the desired frequencies is accomplished by placement of apertures at locations on the mask where the desired frequencies intersect the mask. A recollimated parallel output beam with the desired set of frequencies is subsequently generated utilizing a mirror and grating matched and geometrically aligned in the same manner as the input grating and mirror.

  2. Low-noise pulse conditioner

    DOEpatents

    Bird, D.A.

    1981-06-16

    A low-noise pulse conditioner is provided for driving electronic digital processing circuitry directly from differentially induced input pulses. The circuit uses a unique differential-to-peak detector circuit to generate a dynamic reference signal proportional to the input peak voltage. The input pulses are compared with the reference signal in an input network which operates in full differential mode with only a passive input filter. This reduces the introduction of circuit-induced noise, or jitter, generated in ground referenced input elements normally used in pulse conditioning circuits, especially speed transducer processing circuits. This circuit may be used for conditioning the sensor signal from the Fidler coil in a gas centrifuge for separation of isotopic gaseous mixtures.

  3. Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration

    PubMed Central

    Marei, Hadir; Carpy, Alejandro; Woroniuk, Anna; Vennin, Claire; White, Gavin; Timpson, Paul; Macek, Boris; Malliri, Angeliki

    2016-01-01

    The small GTPase Rac1 has been implicated in the formation and dissemination of tumours. Upon activation by guanine nucleotide exchange factors (GEFs), Rac1 associates with a variety of proteins in the cell thereby regulating various functions, including cell migration. However, activation of Rac1 can lead to opposing migratory phenotypes raising the possibility of exacerbating tumour progression when targeting Rac1 in a clinical setting. This calls for the identification of factors that influence Rac1-driven cell motility. Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and pro-migratory signalling cascades, respectively, through regulating the Rac1 interactome. In particular, we demonstrate that P-Rex1 stimulates migration through enhancing the interaction between Rac1 and the actin-remodelling protein flightless-1 homologue, to modulate cell contraction in a RhoA-ROCK-independent manner. PMID:26887924

  4. Influence of storage methods on the surface roughness of tissue conditioners.

    PubMed

    Hong, Guan; Li, YingAi; Maeda, Takeshi; Mizumachi, Wataru; Sadamori, Shinsuke; Hamada, Taizo; Murata, Hiroshi

    2008-03-01

    The purpose of this study was to compare the influence of three kinds of storage methods on surface roughness of tissue conditioners. Four commercial tissue conditioners (GC Soft Liner, Softone, Fictioner, and Hydro-Cast) were used in this study. Five samples of each material were stored in distilled water, air, and a denture cleanser (Polident). Mean surface roughness (R(a)) values of dental stone casts made from the tissue conditioners were measured after 0, 1, 3, 7, and 14 days of immersion using a profilometer. Significant differences in the R(a) values of the specimens were found among the three storage methods. The values of R(a) significantly increased with increase in immersion time for each storage method, except for the materials stored in air. It was found that the materials stored in air showed the most stable and lowest values of R(a). Results obtained suggested that a tissue conditioner exhibited smooth and minimal change in surface roughness with time when stored in air than in distilled water and denture cleanser. PMID:18540387

  5. Historical and projected emissions of HCFC-22 and HFC-410A from China's room air conditioning sector

    NASA Astrophysics Data System (ADS)

    Wang, Ziyuan; Fang, Xuekun; Li, Li; Bie, Pengju; Li, Zhifang; Hu, Jianxin; Zhang, Boya; Zhang, Jianbo

    2016-05-01

    Recent decades witnessed the increase in production and uses of HCFC-22 (chlorodifluoromethane, CHClF2) and its alternative, HFC-410A (a blend of difluoromethane and pentafluoroethane), in China in response to the booming of room air conditioners (RACs) for both domestic use and exports. HCFC-22 is an ozone-depleting substance under the Montreal Protocol, while both HCFC-22 and HFC-410A are greenhouse gases (GHGs). This study provides a most comprehensive consumption and emission inventory of refrigerants emissions (HCFC-22 and HFC-410A) from RAC sector during 1995-2014, for the first time. Our estimates show that HCFC-22 emissions increased from 0.7 Gg/yr in 1995 to 48.2 Gg/yr in 2014. The accumulative emissions contributed to global total HCFCs emissions by 4.4% (3.3%-6.1%) CFC-11-equivalent (CFC-11-eq) and 5.4% (4.1%-7.5%) CO2-equivalent (CO2-eq) during 1995-2012. If left uncontrolled, accumulative emissions of HFC-410A will be12.4 (7.1-20.2) CO2-eq Pg during 2015-2050, which can offset the global climate benefits achieved by the Montreal Protocol. The HFC-410A emissions from China's RAC sector are estimated to be of importance to both global HFCs emissions and China's GHG emissions. Further, we probed the emission mitigation performances of the current 2014 North American Proposal scenario and a modified more ambitious scenario. The emissions of two mitigation scenarios are only 28% and 22% of the emissions without mitigation actions, respectively. This study is the first effort to map the transition of eliminated substance HCFC-22 and its alternative HFC-410A in RAC sector. Therefore, alternative chemicals should be scrutinized with cautions before they are promoted and applied.

  6. Rac1 mediates intestinal epithelial cell apoptosis via JNK.

    PubMed

    Jin, Shi; Ray, Ramesh M; Johnson, Leonard R

    2006-12-01

    Apoptosis plays a key role in the maintenance of a constant cell number and a low incidence of cancer in the mucosa of the intestine. Although the small GTPase Rac1 has been established as an important regulator of migration of intestinal epithelial cells, whether Rac1 is also involved in apoptosis is unclear. The present study tested the hypothesis that Rac1 mediates TNF-alpha-induced apoptosis in IEC-6 cells. Rac1 is activated during TNF-alpha-induced apoptosis as judged by the level of GTP-Rac1, the level of microsomal membrane-associated Rac1, and lamellipodia formation. Although expression of constitutively active Rac1 does not increase apoptosis in the basal condition, inhibition of Rac1 either by NSC-23766 (Rac1 inhibitor) or expression of dominant negative Rac1 protects cells from TNF-alpha-induced apoptosis by inhibiting caspase-3, -8, and -9 activities. Inhibition of Rac1 before the administration of apoptotic stimuli significantly prevents TNF-alpha-induced activation of JNK1/2, the key proapoptotic regulator in IEC-6 cells. Inhibition of Rac1 does not modulate TNF-alpha-induced ERK1/2 and Akt activation. Inhibition of ERK1/2 and Akt activity by U-0126 and LY-294002, respectively, increased TNF-alpha-induced apoptosis. However, inhibition of Rac1 significantly decreased apoptosis in the presence of ERK1/2 and Akt inhibitors, similar to the effect observed with NSC-23766 alone in response to TNF-alpha. Thus, Rac1 inhibition protects cells independently of ERK1/2 and Akt activation during TNF-alpha-induced apoptosis. Although p38 MAPK is activated in response to TNF-alpha, inhibition of p38 MAPK did not decrease apoptosis. Rac1 inhibition did not alter p38 MAPK activity. Thus, these results indicate that Rac1 mediates apoptosis via JNK and plays a key role in proapoptotic pathways in intestinal epithelial cells.

  7. Testing of a Receiver-Absorber-Converter (RAC) for the Integrated Solar Upper Stage (ISUS) program

    NASA Astrophysics Data System (ADS)

    Westerman, Kurt O.; Miles, Barry J.

    1998-01-01

    The Integrated Solar Upper Stage (ISUS) is a solar bi-modal system based on a concept developed by Babcock & Wilcox in 1992. ISUS will provide advanced power and propulsion capabilities that will enable spacecraft designers to either increase the mass to orbit or decrease the cost to orbit for their satellites. In contrast to the current practice of using chemical propulsion for orbit transfer and photovoltaic conversion/battery storage for electrical power, ISUS uses a single collection, storage, and conversion system for both the power and propulsion functions. The ISUS system is currently being developed by the Air Force's Phillips Laboratory. The ISUS program consists of a systems analysis, design, and integration (SADI) effort, and three major sub-system development efforts: the Concentrator Array and Tracking (CATS) sub-system which tracks the sun and collects/focuses the energy; the Receiver-Absorber-Converter (RAC) sub-system which receives and stores the solar energy, transfers the stored energy to the propellant during propulsion operations, and converts the stored energy to electricity during power operations; and the Cryogenic Storage and Propellant Feed Sub-system (CSPFS) which stores the liquid hydrogen propellant and provides it to the RAC during propulsion operations. This paper discuses the evolution of the RAC sub-system as a result of the component level testing, and provides the initial results of systems level ground testing. A total of 5 RACs were manufactured as part of the Phillips Laboratory ISUS Technology Development program. The first series of component tests were carried out at the Solar Rocket Propulsion Laboratory at Edwards AFB, California. These tests provided key information on the propulsion mode of operations. The second series of RAC tests were performed at the Thermionic Evaluation Facility (TEF) in Albuquerque, New Mexico and provided information on the electrical performance of the RAC. The systems level testing was

  8. Aeroacoustic Characteristics of Model Jet Test Facility Flow Conditioners

    NASA Technical Reports Server (NTRS)

    Kinzie, Kevin W.; Henderson, Brenda S.; Haskin, Harry H.

    2005-01-01

    An experimental investigation of flow conditioning devices used to suppress internal rig noise in high speed, high temperature experimental jet facilities is discussed. The aerodynamic and acoustic characteristics of a number of devices including pressure loss and extraneous noise generation are measured. Both aerodynamic and acoustic characteristics are strongly dependent on the porosity of the flow conditioner and the closure ratio of the duct system. For unchoked flow conditioners, the pressure loss follows conventional incompressible flow models. However, for choked flow conditioners, a compressible flow model where the duct and flow conditioner system is modeled as a convergent-divergent nozzle can be used to estimate pressure loss. Choked flow conditioners generate significantly more noise than unchoked conditioners. In addition, flow conditioners with small hole diameters or sintered metal felt material generate less self-noise noise compared to flow conditioners with larger holes.

  9. Coevolution of RAC Small GTPases and their Regulators GEF Proteins

    PubMed Central

    Jiménez-Sánchez, Alejandro

    2016-01-01

    RAC proteins are small GTPases involved in important cellular processes in eukaryotes, and their deregulation may contribute to cancer. Activation of RAC proteins is regulated by DOCK and DBL protein families of guanine nucleotide exchange factors (GEFs). Although DOCK and DBL proteins act as GEFs on RAC proteins, DOCK and DBL family members are evolutionarily unrelated. To understand how DBL and DOCK families perform the same function on RAC proteins despite their unrelated primary structure, phylogenetic analyses of the RAC, DBL, and DOCK families were implemented, and interaction patterns that may suggest a coevolutionary process were searched. Interestingly, while RAC and DOCK proteins are very well conserved in humans and among eukaryotes, DBL proteins are highly divergent. Moreover, correlation analyses of the phylogenetic distances of RAC and GEF proteins and covariation analyses between residues in the interacting domains showed significant coevolution rates for both RAC–DOCK and RAC–DBL interactions. PMID:27226705

  10. Photovoltaic array: Power conditioner interface characteristics

    NASA Technical Reports Server (NTRS)

    Gonzalez, C. C.; Hill, G. M.; Ross, R. G., Jr.

    1982-01-01

    The electrical output (power, current, and voltage) of flat plate solar arrays changes constantly, due primarily to changes in cell temperature and irradiance level. As a result, array loads such as dc-to-ac power conditioners must be capable of accommodating widely varying input levels while maintaining operation at or near the maximum power point of the array. The array operating characteristics and extreme output limits necessary for the systematic design of array load interfaces under a wide variety of climatic conditions are studied. A number of interface parameters are examined, including optimum operating voltage, voltage energy, maximum power and current limits, and maximum open circuit voltage. The effect of array degradation and I-V curve fill factor or the array power conditioner interface is also discussed. Results are presented as normalized ratios of power conditioner parameters to array parameters, making the results universally applicable to a wide variety of system sizes, sites, and operating modes.

  11. 46 CFR 56.15-5 - Fluid-conditioner fittings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Fluid-conditioner fittings. 56.15-5 Section 56.15-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Fittings § 56.15-5 Fluid-conditioner fittings. (a) Fluid conditioner fittings certified in accordance with subpart 50.25 of...

  12. Physiological Function of Rac Prophage During Biofilm Formation and Regulation of Rac Excision in Escherichia coli K-12.

    PubMed

    Liu, Xiaoxiao; Li, Yangmei; Guo, Yunxue; Zeng, Zhenshun; Li, Baiyuan; Wood, Thomas K; Cai, Xingsheng; Wang, Xiaoxue

    2015-11-04

    Rac or rac-like prophage harbors many genes with important physiological functions, while it remains excision-proficient in several bacterial strains including Escherichia coli, Salmonella spp. and Shigella spp. Here, we found that rac excision is induced during biofilm formation, and the isogenic stain without rac is more motile and forms more biofilms in nutrient-rich medium at early stages in E. coli K-12. Additionally, the presence of rac genes increases cell lysis during biofilm development. In most E. coli strains, rac is integrated into the ttcA gene which encodes a tRNA-thioltransferase. Rac excision in E. coli K-12 leads to a functional change of TtcA, which results in reduced fitness in the presence of carbenicillin. Additionally, we demonstrate that YdaQ (renamed as XisR) is the excisionase of rac in E. coli K-12, and that rac excision is induced by the stationary sigma factor RpoS through inducing xisR expression. Taken together, our results reveal that upon rac integration, not only are new genes introduced into the host, but also there is a functional change in a host enzyme. Hence, rac excision is tightly regulated by host factors to control its stability in the host genome under different stress conditions.

  13. Serine-71 phosphorylation of Rac1 modulates downstream signaling.

    PubMed

    Schwarz, Janett; Proff, Julia; Hävemeier, Anika; Ladwein, Markus; Rottner, Klemens; Barlag, Britta; Pich, Andreas; Tatge, Helma; Just, Ingo; Gerhard, Ralf

    2012-01-01

    The Rho GTPases Rac1 and Cdc42 regulate a variety of cellular functions by signaling to different signal pathways. It is believed that the presence of a specific effector at the location of GTPase activation determines the route of downstream signaling. We previously reported about EGF-induced Ser-71 phosphorylation of Rac1/Cdc42. By using the phosphomimetic S71E-mutants of Rac1 and Cdc42 we investigated the impact of Ser-71 phosphorylation on binding to selected effector proteins. Binding of the constitutively active (Q61L) variants of Rac1 and Cdc42 to their specific interaction partners Sra-1 and N-WASP, respectively, as well as to their common effector protein PAK was abrogated when Ser-71 was exchanged to glutamate as phosphomimetic substitution. Interaction with their common effector proteins IQGAP1/2/3 or MRCK alpha was, however, hardly affected. This ambivalent behaviour was obvious in functional assays. In contrast to Rac1 Q61L, phosphomimetic Rac1 Q61L/S71E was not able to induce increased membrane ruffling. Instead, Rac1 Q61L/S71E allowed filopodia formation, which is in accordance with abrogation of the dominant Sra-1/Wave signalling pathway. In addition, in contrast to Rac1 transfected cells Rac1 S71E failed to activate PAK1/2. On the other hand, Rac1 Q61L/S71E was as effective in activation of NF-kappaB as Rac1 Q61L, illustrating positive signal transduction of phosphorylated Rac1. Together, these data suggest that phosphorylation of Rac1 and Cdc42 at serine-71 represents a reversible mechanism to shift specificity of GTPase/effector coupling, and to preferentially address selected downstream pathways. PMID:22970203

  14. Flow conditioner location effects in orifice flowmeters

    NASA Astrophysics Data System (ADS)

    Scott, J. L.; Sindt, C. F.; Lewis, M. A.

    1993-01-01

    Tests sponsored by Gas Research Institute were conducted with orifice flowmeters of two nominal sizes: 104 mm and 52 mm. For the 104 mm orifice meter, the authors compared discharge coefficients measured in two common piping configurations used by laboratories to establish baseline flow conditions. The discharge coefficients are similar for beta ratios of 0.43, 0.55, and 0.67, but not for the 0.73 beta ratio plate. For other tests with the orifice meter, a 90 degree elbow or a reducer was located upstream of the orifice plate and flow conditioner. Two beta ratios (0.54, 0.67) were tested in the 52 mm orifice meter in baseline configuration and with an elbow at 17D and a flow conditioner at 12D. For many of the tests, differential pressures were measured at more than one flange tap location. Placing the flow conditioner too close to the orifice plate in either meter yields discharge coefficients below baseline values. The location of the flow conditioner with respect to the orifice plate appears to influence meter performance more significantly than the type or location of flow disturbance upstream of it.

  15. RAC: Repository of Antibiotic resistance Cassettes

    PubMed Central

    Tsafnat, Guy; Copty, Joseph; Partridge, Sally R.

    2011-01-01

    Antibiotic resistance in bacteria is often due to acquisition of resistance genes associated with different mobile genetic elements. In Gram-negative bacteria, many resistance genes are found as part of small mobile genetic elements called gene cassettes, generally found integrated into larger elements called integrons. Integrons carrying antibiotic resistance gene cassettes are often associated with mobile elements and here are designated ‘mobile resistance integrons’ (MRIs). More than one cassette can be inserted in the same integron to create arrays that contribute to the spread of multi-resistance. In many sequences in databases such as GenBank, only the genes within cassettes, rather than whole cassettes, are annotated and the same gene/cassette may be given different names in different entries, hampering analysis. We have developed the Repository of Antibiotic resistance Cassettes (RAC) website to provide an archive of gene cassettes that includes alternative gene names from multiple nomenclature systems and allows the community to contribute new cassettes. RAC also offers an additional function that allows users to submit sequences containing cassettes or arrays for annotation using the automatic annotation system Attacca. Attacca recognizes features (gene cassettes, integron regions) and identifies cassette arrays as patterns of features and can also distinguish minor cassette variants that may encode different resistance phenotypes (aacA4 cassettes and bla cassettes-encoding β-lactamases). Gaps in annotations are manually reviewed and those found to correspond to novel cassettes are assigned unique names. While there are other websites dedicated to integrons or antibiotic resistance genes, none includes a complete list of antibiotic resistance gene cassettes in MRI or offers consistent annotation and appropriate naming of all of these cassettes in submitted sequences. RAC thus provides a unique resource for researchers, which should reduce confusion

  16. Strategies for responding to RAC requests electronically.

    PubMed

    Schramm, Michael

    2012-04-01

    Providers that would like to respond to complex RAC reviews electronically should consider three strategies: Invest in an EHR software package or a high-powered scanner that can quickly scan large amounts of paper. Implement an audit software platform that will allow providers to manage the entire audit process in one place. Use a CONNECT-compatible gateway capable of accessing the Nationwide Health Information Network (the network on which the electronic submission of medical documentation program runs).

  17. 76 FR 2883 - Humboldt Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-18

    ... Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Adam Dellinger... Meeting. SUMMARY: The Humboldt Resource Advisory Committee (RAC) will meet in Eureka, California....

  18. 75 FR 69620 - Humboldt Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Adam Dellinger... meeting. SUMMARY: The Humboldt Resource Advisory Committee (RAC) will meet in Eureka, California....

  19. 75 FR 43140 - Humboldt Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Julie Ranieri... meeting. SUMMARY: The Humboldt Resource Advisory Committee (RAC) will meet in Eureka, California....

  20. 75 FR 54297 - Humboldt Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    ... Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Julie Ranieri... meeting. SUMMARY: The Humboldt Resource Advisory Committee (RAC) will meet in Eureka, California....

  1. Cell module and fuel conditioner

    NASA Technical Reports Server (NTRS)

    Hoover, D. Q., Jr.

    1981-01-01

    The results of the completed tests on Stack 561 and the on-going tests of 562 (23 cell stacks of the MK-1 and M-2 designs respectively) are reported and their performance is compared. Results of the on-going endurance test of Stack 560 (5 cell, MK-2) are reported. Plans for fabrication of Stacks 563 and 564 (23 cell stacks of the MK-1 and MK-2 design) are summarized. Results of the burner tests are given. Excellent performance was achieved on simulated anode exhaust gas over very wide load and air/fuel ranges.

  2. Hospital industry pushes back against the RACs.

    PubMed

    2013-01-01

    Groups ranging from the American Hospital Association to the U.S. Congress have taken up the issues posed by the Recovery Audit Contractors and other Medicare and Medicaid auditors. The high percentage of denials overturned upon appeal and large number of records requests are getting attention. Hospitals may get relief, but it's not likely to be immediate so they should continue preparing for the audits. Meanwhile, in addition to the Recovery Audit Contractors (RACs), hospitals are facing scrutiny from the Zoned Program Integrity Contractors (ZPICs), Medicare Prepayment Reviews, and Medicare Administrative Contractor (MAC) on-site audits. PMID:23339269

  3. Characterisation of the Rac/PAK pathway in Amoeba proteus.

    PubMed

    Kłopocka, W; Moraczewska, J; Redowicz, M J

    2005-04-01

    Molecular mechanisms underlying the unique locomotion of the highly motile Amoeba proteus still remain poorly understood. Recently, we have shown that blocking the endogenous amoebal Rac-like protein(s) leads to distinct and irreversible changes in the appearance of these large migrating cells as well as to a significant inhibition of their locomotion. To elucidate the mechanism of the Rac pathway in Amoeba proteus, we tested the effects of blocking the endogenous myosin I heavy chain kinase (MIHCK), one of the Rac effectors in Acanthamoeba castellanii and Dictyostelium discoideum, with anti-MIHCK antibodies in migrating amoebae, as well as the effect of inhibiting Rac and MIHCK on the actin polymerisation process. Antibodies against A. castellanii MIHCK detected an A. proteus protein with a molecular mass (ca. 95 kDa) similar to the A. castellanii kinase. The cellular distribution of MIHCK in A. proteus was very similar to those of Rac-like protein in amoebae and MIHCK in A. castellanii. Amoebae microinjected with anti-MIHCK antibodies moved slower and protruded fewer wide pseudopodia (5-6) than the control cells (9-10), resembling to some extent the phenotype of cells microinjected with anti-Rac antibodies. The in vitro studies indicate that the A. proteus Rac-like protein, but not the MIHCK isoform, is engaged in the regulation of the nucleation step of the actin polymerisation process. These observations suggest that MIHCK may be one of the effectors for Rac in these extremely large cells.

  4. Characterisation of the Rac/PAK pathway in Amoeba proteus.

    PubMed

    Kłopocka, W; Moraczewska, J; Redowicz, M J

    2005-04-01

    Molecular mechanisms underlying the unique locomotion of the highly motile Amoeba proteus still remain poorly understood. Recently, we have shown that blocking the endogenous amoebal Rac-like protein(s) leads to distinct and irreversible changes in the appearance of these large migrating cells as well as to a significant inhibition of their locomotion. To elucidate the mechanism of the Rac pathway in Amoeba proteus, we tested the effects of blocking the endogenous myosin I heavy chain kinase (MIHCK), one of the Rac effectors in Acanthamoeba castellanii and Dictyostelium discoideum, with anti-MIHCK antibodies in migrating amoebae, as well as the effect of inhibiting Rac and MIHCK on the actin polymerisation process. Antibodies against A. castellanii MIHCK detected an A. proteus protein with a molecular mass (ca. 95 kDa) similar to the A. castellanii kinase. The cellular distribution of MIHCK in A. proteus was very similar to those of Rac-like protein in amoebae and MIHCK in A. castellanii. Amoebae microinjected with anti-MIHCK antibodies moved slower and protruded fewer wide pseudopodia (5-6) than the control cells (9-10), resembling to some extent the phenotype of cells microinjected with anti-Rac antibodies. The in vitro studies indicate that the A. proteus Rac-like protein, but not the MIHCK isoform, is engaged in the regulation of the nucleation step of the actin polymerisation process. These observations suggest that MIHCK may be one of the effectors for Rac in these extremely large cells. PMID:15948264

  5. 75 FR 54846 - Hood/Willamette Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ...; ] DEPARTMENT OF AGRICULTURE Forest Service Hood/Willamette Resource Advisory Committee (RAC) AGENCY: Forest Service, USDA. ACTION: Action of meeting. SUMMARY: The Hood/Willamette Resource Advisory Committee (RAC... FURTHER INFORMATION CONTACT: For more information regarding this meeting, contact Connie Athman; Mt....

  6. 75 FR 18144 - Hood/Willamette Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ...; ] DEPARTMENT OF AGRICULTURE Hood/Willamette Resource Advisory Committee (RAC) AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Hood/Willamette Resource Advisory Committee (RAC) will meet on... INFORMATION CONTACT: For more information regarding this meeting, contact Connie Athman; Mt. Hood...

  7. 75 FR 21220 - Hood/Willamette Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... Forest Service Hood/Willamette Resource Advisory Committee (RAC) AGENCY: Forest Service, USDA. ACTION: Action of meeting. SUMMARY: The Hood/Willamette Resource Advisory Committee (RAC) will meet on Tuesday... meeting, contact Connie Athman; Mt. Hood National Forest; 16400 Champion Way; Sandy, Oregon 97055;...

  8. Roles of Rac1 and Rac3 GTPases during the development of cortical and hippocampal GABAergic interneurons.

    PubMed

    de Curtis, Ivan

    2014-01-01

    Rac GTPases are regulators of the cytoskeleton that play an important role in several aspects of neuronal and brain development. Two distinct Rac GTPases are expressed in the developing nervous system, the widely expressed Rac1 and the neural-specific Rac3 proteins. Recent experimental evidence supports a central role of these two Rac proteins in the development of inhibitory GABAergic interneurons, important modulatory elements of the brain circuitry. The combined inactivation of the genes for the two Rac proteins has profound effects on distinct aspects of interneuron development, and has highlighted a synergistic contribution of the two proteins to the postmitotic maturation of specific populations of cortical and hippocampal interneurons. Rac function is modulated by different types of regulators, and can influence the activity of specific effectors. Some of these proteins have been associated to the development and maturation of interneurons. Cortical interneuron dysfunction is implicated in several neurological and psychiatric diseases characterized by cognitive impairment. Therefore the description of the cellular processes regulated by the Rac GTPases, and the identification of the molecular networks underlying these processes during interneuron development is relevant to the understanding of the role of GABAergic interneurons in cognitive functions.

  9. Roles of Rac1 and Rac3 GTPases during the development of cortical and hippocampal GABAergic interneurons

    PubMed Central

    de Curtis, Ivan

    2014-01-01

    Rac GTPases are regulators of the cytoskeleton that play an important role in several aspects of neuronal and brain development. Two distinct Rac GTPases are expressed in the developing nervous system, the widely expressed Rac1 and the neural-specific Rac3 proteins. Recent experimental evidence supports a central role of these two Rac proteins in the development of inhibitory GABAergic interneurons, important modulatory elements of the brain circuitry. The combined inactivation of the genes for the two Rac proteins has profound effects on distinct aspects of interneuron development, and has highlighted a synergistic contribution of the two proteins to the postmitotic maturation of specific populations of cortical and hippocampal interneurons. Rac function is modulated by different types of regulators, and can influence the activity of specific effectors. Some of these proteins have been associated to the development and maturation of interneurons. Cortical interneuron dysfunction is implicated in several neurological and psychiatric diseases characterized by cognitive impairment. Therefore the description of the cellular processes regulated by the Rac GTPases, and the identification of the molecular networks underlying these processes during interneuron development is relevant to the understanding of the role of GABAergic interneurons in cognitive functions. PMID:25309333

  10. Air

    MedlinePlus

    ... do to protect yourself from dirty air . Indoor air pollution and outdoor air pollution Air can be polluted indoors and it can ... this chart to see what things cause indoor air pollution and what things cause outdoor air pollution! Indoor ...

  11. 21 CFR 870.2060 - Transducer signal amplifier and conditioner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Transducer signal amplifier and conditioner. 870.2060 Section 870.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Transducer signal amplifier and conditioner. (a) Identification. A transducer signal amplifier...

  12. 21 CFR 870.2050 - Biopotential amplifier and signal conditioner.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Biopotential amplifier and signal conditioner. 870.2050 Section 870.2050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Biopotential amplifier and signal conditioner. (a) Identification. A biopotential amplifier and...

  13. 21 CFR 870.2050 - Biopotential amplifier and signal conditioner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Biopotential amplifier and signal conditioner. 870.2050 Section 870.2050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Biopotential amplifier and signal conditioner. (a) Identification. A biopotential amplifier and...

  14. 21 CFR 870.2060 - Transducer signal amplifier and conditioner.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Transducer signal amplifier and conditioner. 870.2060 Section 870.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Transducer signal amplifier and conditioner. (a) Identification. A transducer signal amplifier...

  15. 21 CFR 870.2050 - Biopotential amplifier and signal conditioner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Biopotential amplifier and signal conditioner. 870.2050 Section 870.2050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Biopotential amplifier and signal conditioner. (a) Identification. A biopotential amplifier and...

  16. 21 CFR 870.2060 - Transducer signal amplifier and conditioner.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Transducer signal amplifier and conditioner. 870.2060 Section 870.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Transducer signal amplifier and conditioner. (a) Identification. A transducer signal amplifier...

  17. 21 CFR 870.2060 - Transducer signal amplifier and conditioner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Transducer signal amplifier and conditioner. 870.2060 Section 870.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Transducer signal amplifier and conditioner. (a) Identification. A transducer signal amplifier...

  18. 21 CFR 870.2050 - Biopotential amplifier and signal conditioner.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Biopotential amplifier and signal conditioner. 870.2050 Section 870.2050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... Biopotential amplifier and signal conditioner. (a) Identification. A biopotential amplifier and...

  19. 21 CFR 870.2050 - Biopotential amplifier and signal conditioner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Biopotential amplifier and signal conditioner. 870.2050 Section 870.2050 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... conditioner is a device used to amplify or condition an electrical signal of biologic origin....

  20. Cell module and fuel conditioner development

    NASA Technical Reports Server (NTRS)

    Hoover, D. Q., Jr.

    1981-01-01

    The test results of and post test analysis of Stack 559 are reported. The design features and construction status of Stacks 560, 561, 562 and 563 are described. The measurements of cell materials compressibility are rationalized and summarized and an explanation of their uses is given. Preliminary results of a manifold material/coating survey are given. The results of shift converter catalyst performance tests and reforming catalyst aging tests are reported. State points for full load and part load operation of the fuel conditioning subsystem tabulated. Work on the data base for the fuel conditioner ancillary subsystems is summarized.

  1. Rac1 activity regulates proliferation of aggressive metastatic melanoma

    SciTech Connect

    Bauer, Natalie N. Chen Yihwen; Samant, Rajeev S.; Shevde, Lalita A.; Fodstad, Oystein

    2007-11-01

    Molecular mechanisms underlying the different capacity of two in vivo selected human melanoma cell variants to form experimental metastases were studied. The doubling times of the FEMX-I and FEMX-V cell sublines in vitro were 15 and 25 h, respectively. The invasive capacity of FEMX-I cells was 8-fold higher than FEMX-V cells, and the time to form approximately 10 mm s.c. tumors in nude mice was 21 versus 35 days. FEMX-I displayed a spindle-like formation in vitro, whereas FEMX-V cells had a rounded shape. Hence, we examined known determinants of cell shape and proliferation, the small GTPases. The four studied showed equal expression in both cell types, but Rac1 activity was significantly decreased in FEMX-V cells. Rac1 stimulates NF{kappa}B, and we found that endogenous NF{kappa}B activity of FEMX-V cells was 2% of that of FEMX-I cells. Inhibition of Rac1 resulted in blocked NF{kappa}B activity. Specific inhibition of either Rac1 or NF{kappa}B significantly reduced proliferation and invasion of FEMX-I cells, the more pronounced effects observed with Rac1 inhibition. These data indicate that Rac1 activity in FEMX cells regulates cell proliferation and invasion, in part via its effect on NF{kappa}B, signifying Rac1 as a key molecule in melanoma progression and metastasis.

  2. Optogenetics: optical control of a photoactivatable Rac in living cells.

    PubMed

    Yin, Taofei; Wu, Yi I

    2015-01-01

    Recent developments in optogenetics have extended optical control of signaling to intracellular proteins, including Rac, a small G protein in the Rho family. A blue light-sensing LOV (light, oxygen, or voltage) domain derived from Avena sativa (oat) phototropin was fused to the N-terminus of a constitutively active mutant of Rac, via an α-helix (Jα) that is conserved among plant phototropins. The fused LOV domain occluded binding of downstream effectors to Rac in the dark. Exposure to blue light caused a conformational change of the LOV domain and unwinding of the Jα helix, relieving steric inhibition. The LOV domain incorporates a flavin as the photon-absorbing cofactor and can be activated by light in a reversible and repeatable fashion. In cultured cells, global illumination with blue light rapidly activated Rac and led to cell spreading and membrane ruffling. Localized and pulsed illumination generated a gradient of Rac activity and induced directional migration. In this chapter, we will describe the techniques in detail and present some examples of applications of using photoactivatable Rac (PA-Rac) in living cells.

  3. Inhibition of Rac1 promotes BMP-2-induced osteoblastic differentiation.

    PubMed

    Onishi, M; Fujita, Y; Yoshikawa, H; Yamashita, T

    2013-01-01

    Small G proteins of the Rho family are pivotal regulators of several signaling networks. The Ras homolog family (Rho) and one of its targets, Rho-associated protein kinase (ROCK), participate in a wide variety of biological processes, including bone formation. A previous study has demonstrated that the ROCK inhibitor Y-27632 enhanced bone formation induced by recombinant human bone morphogenetic protein-2 (BMP-2) in vivo and in vitro. However, the effect of other Rho family members, such as Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division cycle 42 (Cdc42), on bone formation remains unknown. In this study, we investigated whether Rac1 also participates in BMP-2-induced osteogenesis. Expression of a dominant-negative mutant of Rac1 enhanced BMP-2-induced osteoblastic differentiation in C2C12 cells, whereas a constitutively active mutant of Rac1 attenuated that effect. Knockdown of T-lymphoma invasion and metastasis 1 (Tiam1), a Rac-specific guanine nucleotide exchange factor, enhanced BMP-2-induced alkaline phosphatase activity. Further, we demonstrated that BMP-2 stimulated Rac1 activity. These results indicate that the activation of Rac1 attenuates osteoblastic differentiation in C2C12 cells.

  4. Rac1 modulates cardiomyocyte adhesion during mouse embryonic development

    SciTech Connect

    Abu-Issa, Radwan

    2015-01-24

    Highlights: • Conditional knockout of Rac1 using Nkx2.5 Cre line is lethal at E13.5. • The myocardium of the mutant is thin and disorganized. • The phenotype is not due to cardiomyocyte low proliferation or apoptosis. • The phenotype is due to specific defect in cardiomyocyte adhesion. - Abstract: Rac1, a member of the Rho subfamily of small GTPases, is involved in morphogenesis and differentiation of many cell types. Here we define a role of Rac1 in cardiac development by specifically deleting Rac1 in the pre-cardiac mesoderm using the Nkx2.5-Cre transgenic driver line. Rac1-conditional knockout embryos initiate heart development normally until embryonic day 11.5 (E11.5); their cardiac mesoderm is specified, and the heart tube is formed and looped. However, by E12.5-E13.5 the mutant hearts start failing and embryos develop edema and hemorrhage which is probably the cause for the lethality observed soon after. The hearts of Rac1-cKO embryos exhibit disorganized and thin myocardial walls and defects in outflow tract alignment. No significant differences of cardiomyocyte death or proliferation were found between developing control and mutant embryos. To uncover the role of Rac1 in the heart, E11.5 primary heart cells were cultured and analyzed in vitro. Rac1-deficient cardiomyocytes were less spread, round and loosely attached to the substrate and to each other implying that Rac1-mediated signaling is required for appropriate cell–cell and/or cellmatrix adhesion during cardiac development.

  5. The impact of RAC audits on US hospitals.

    PubMed

    Harrison, Jeffrey P; Barksdale, Rachel M

    2013-01-01

    The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) authorized a three-year demonstration program using recovery audit contractors (RACs) to identify and correct improper payments in the Medicare Fee-For-Service program. More recently, Section 6411 of the Affordable Care Act (ACA) expanded the RAC program to include the Medicaid program. This shows the Cent ers for Medicare & Medicaid Services (CMS) believe RAC audits are a cost-effective method to ensure health care providers are paid correctly and thereby protect the Medicare Trust Fund. RAC audits are highly complex and require significant manpower to handle the large volume of requests received during a short period of time. Additionally, the RAC audit appeal process is complicated and requires a high level of technical expertise. The demonstration project found that RAC audits resulted in sizeable amounts of overpayments collected ("take-backs") from many providers. This research study assesses the potential impact of the RAC audit program on US acute care hospitals. Data obtained from CMS show that RAC overpayments collected for FY 2010 were $75.4 million, increased to $797.4 million in FY 2011, and increased to $986.2 million in the first six months of FY 2012. According to the American Hospital Association (AHA) RACTrac audit survey, the vast majority of these collections represent complex denials where hospitals are required to provide medical record documents in support of their billed claims. This study found that the RAC audit program collections are increasing significantly over time. As a result, these collections are having a significant negative impact on the profitability of US hospitals.

  6. The impact of RAC audits on US hospitals.

    PubMed

    Harrison, Jeffrey P; Barksdale, Rachel M

    2013-01-01

    The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) authorized a three-year demonstration program using recovery audit contractors (RACs) to identify and correct improper payments in the Medicare Fee-For-Service program. More recently, Section 6411 of the Affordable Care Act (ACA) expanded the RAC program to include the Medicaid program. This shows the Cent ers for Medicare & Medicaid Services (CMS) believe RAC audits are a cost-effective method to ensure health care providers are paid correctly and thereby protect the Medicare Trust Fund. RAC audits are highly complex and require significant manpower to handle the large volume of requests received during a short period of time. Additionally, the RAC audit appeal process is complicated and requires a high level of technical expertise. The demonstration project found that RAC audits resulted in sizeable amounts of overpayments collected ("take-backs") from many providers. This research study assesses the potential impact of the RAC audit program on US acute care hospitals. Data obtained from CMS show that RAC overpayments collected for FY 2010 were $75.4 million, increased to $797.4 million in FY 2011, and increased to $986.2 million in the first six months of FY 2012. According to the American Hospital Association (AHA) RACTrac audit survey, the vast majority of these collections represent complex denials where hospitals are required to provide medical record documents in support of their billed claims. This study found that the RAC audit program collections are increasing significantly over time. As a result, these collections are having a significant negative impact on the profitability of US hospitals. PMID:24003757

  7. Loss of Either Rac1 or Rac3 GTPase Differentially Affects the Behavior of Mutant Mice and the Development of Functional GABAergic Networks

    PubMed Central

    Pennucci, Roberta; Talpo, Francesca; Astro, Veronica; Montinaro, Valentina; Morè, Lorenzo; Cursi, Marco; Castoldi, Valerio; Chiaretti, Sara; Bianchi, Veronica; Marenna, Silvia; Cambiaghi, Marco; Tonoli, Diletta; Leocani, Letizia; Biella, Gerardo; D'Adamo, Patrizia; de Curtis, Ivan

    2016-01-01

    Rac GTPases regulate the development of cortical/hippocampal GABAergic interneurons by affecting the early development and migration of GABAergic precursors. We have addressed the function of Rac1 and Rac3 proteins during the late maturation of hippocampal interneurons. We observed specific phenotypic differences between conditional Rac1 and full Rac3 knockout mice. Rac1 deletion caused greater generalized hyperactivity and cognitive impairment compared with Rac3 deletion. This phenotype matched with a more evident functional impairment of the inhibitory circuits in Rac1 mutants, showing higher excitability and reduced spontaneous inhibitory currents in the CA hippocampal pyramidal neurons. Morphological analysis confirmed a differential modification of the inhibitory circuits: deletion of either Rac caused a similar reduction of parvalbumin-positive inhibitory terminals in the pyramidal layer. Intriguingly, cannabinoid receptor-1-positive terminals were strongly increased only in the CA1 of Rac1-depleted mice. This increase may underlie the stronger electrophysiological defects in this mutant. Accordingly, incubation with an antagonist for cannabinoid receptors partially rescued the reduction of spontaneous inhibitory currents in the pyramidal cells of Rac1 mutants. Our results show that Rac1 and Rac3 have independent roles in the formation of GABAergic circuits, as highlighted by the differential effects of their deletion on the late maturation of specific populations of interneurons. PMID:26582364

  8. Loss of Either Rac1 or Rac3 GTPase Differentially Affects the Behavior of Mutant Mice and the Development of Functional GABAergic Networks.

    PubMed

    Pennucci, Roberta; Talpo, Francesca; Astro, Veronica; Montinaro, Valentina; Morè, Lorenzo; Cursi, Marco; Castoldi, Valerio; Chiaretti, Sara; Bianchi, Veronica; Marenna, Silvia; Cambiaghi, Marco; Tonoli, Diletta; Leocani, Letizia; Biella, Gerardo; D'Adamo, Patrizia; de Curtis, Ivan

    2016-02-01

    Rac GTPases regulate the development of cortical/hippocampal GABAergic interneurons by affecting the early development and migration of GABAergic precursors. We have addressed the function of Rac1 and Rac3 proteins during the late maturation of hippocampal interneurons. We observed specific phenotypic differences between conditional Rac1 and full Rac3 knockout mice. Rac1 deletion caused greater generalized hyperactivity and cognitive impairment compared with Rac3 deletion. This phenotype matched with a more evident functional impairment of the inhibitory circuits in Rac1 mutants, showing higher excitability and reduced spontaneous inhibitory currents in the CA hippocampal pyramidal neurons. Morphological analysis confirmed a differential modification of the inhibitory circuits: deletion of either Rac caused a similar reduction of parvalbumin-positive inhibitory terminals in the pyramidal layer. Intriguingly, cannabinoid receptor-1-positive terminals were strongly increased only in the CA1 of Rac1-depleted mice. This increase may underlie the stronger electrophysiological defects in this mutant. Accordingly, incubation with an antagonist for cannabinoid receptors partially rescued the reduction of spontaneous inhibitory currents in the pyramidal cells of Rac1 mutants. Our results show that Rac1 and Rac3 have independent roles in the formation of GABAergic circuits, as highlighted by the differential effects of their deletion on the late maturation of specific populations of interneurons.

  9. Life Cycle Assessment of Residential Heating and Cooling Systems in Minnesota A comprehensive analysis on life cycle greenhouse gas (GHG) emissions and cost-effectiveness of ground source heat pump (GSHP) systems compared to the conventional gas furnace and air conditioner system

    NASA Astrophysics Data System (ADS)

    Li, Mo

    Ground Source Heat Pump (GSHP) technologies for residential heating and cooling are often suggested as an effective means to curb energy consumption, reduce greenhouse gas (GHG) emissions and lower homeowners' heating and cooling costs. As such, numerous federal, state and utility-based incentives, most often in the forms of financial incentives, installation rebates, and loan programs, have been made available for these technologies. While GSHP technology for space heating and cooling is well understood, with widespread implementation across the U.S., research specific to the environmental and economic performance of these systems in cold climates, such as Minnesota, is limited. In this study, a comparative environmental life cycle assessment (LCA) is conducted of typical residential HVAC (Heating, Ventilation, and Air Conditioning) systems in Minnesota to investigate greenhouse gas (GHG) emissions for delivering 20 years of residential heating and cooling—maintaining indoor temperatures of 68°F (20°C) and 75°F (24°C) in Minnesota-specific heating and cooling seasons, respectively. Eight residential GSHP design scenarios (i.e. horizontal loop field, vertical loop field, high coefficient of performance, low coefficient of performance, hybrid natural gas heat back-up) and one conventional natural gas furnace and air conditioner system are assessed for GHG and life cycle economic costs. Life cycle GHG emissions were found to range between 1.09 × 105 kg CO2 eq. and 1.86 × 10 5 kg CO2 eq. Six of the eight GSHP technology scenarios had fewer carbon impacts than the conventional system. Only in cases of horizontal low-efficiency GSHP and hybrid, do results suggest increased GHGs. Life cycle costs and present value analyses suggest GSHP technologies can be cost competitive over their 20-year life, but that policy incentives may be required to reduce the high up-front capital costs of GSHPs and relatively long payback periods of more than 20 years. In addition

  10. Effects of a non-rinse conditioner on the enamel of primary teeth.

    PubMed

    Fava, Marcelo; Myaki, Silvio Issáo; Arana-Chavez, Victor Elias; Fava-de-Moraes, Flavio

    2003-01-01

    The aim of this in vitro study was to evaluate by scanning electron microscopy the morphological aspects of the enamel of primary teeth after etching with 36% phosphoric acid or a non-rinse conditioner. Ten naturally exfoliated anterior primary teeth were selected. The samples were subjected to prophylaxis with pumice paste and water using a low-speed hand piece. Etching was done on the buccal surface. Specimens were divided into 2 groups: G1 (n=10): etching with 36% phosphoric acid gel - Conditioner 36 (Dentsply) for 20 s, followed by water rinse for 15 s; G2 (n=10): etching with NRC - Non Rinse Conditioner (Dentsply) for 20 s, followed by air drying for 15 s. The samples were dehydrated, mounted on metal stubs, coated with gold and observed with Jeol JSM-6100 scanning electron microscope. Electron-micrographic analysis showed that both etching agents were effective for etching the enamel of primary teeth causing the formation of microporosities on the enamel surface, although the etching pattern was more effective with the use of 36% phosphoric acid gel. PMID:15057391

  11. 76 FR 16603 - Butte County Resource Advisory Committee (RAC); Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-24

    ... eataylor@fs.fed.us . Other RAC information may be obtained at http://www.fs.usda.gov and http://www.fs.fed.us/srs . Dated: March 18, 2011. Matt Janowiak, Acting Deputy Forest Supervisor. BILLING CODE P...

  12. The small GTPase Rac1 regulates auditory hair cell morphogenesis

    PubMed Central

    Grimsley-Myers, Cynthia M.; Sipe, Conor W.; Géléoc, Gwenaëllle S.G.; Lu, Xiaowei

    2010-01-01

    Morphogenesis of sensory hair cells, in particular their mechanotransduction organelle, the stereociliary bundle, requires highly organized remodeling of the actin cytoskeleton. The roles of Rho family small GTPases during this process remain unknown. Here we show that deletion of Rac1 in the otic epithelium resulted in severe defects in cochlear epithelial morphogenesis. The mutant cochlea was severely shortened with a reduced number of auditory hair cells and cellular organization of the auditory sensory epithelium was abnormal. Rac1 mutant hair cells also displayed defects in planar cell polarity and morphogenesis of the stereociliary bundle, including bundle fragmentation or deformation, and mispositioning or absence of the kinocilium. We further demonstrate that a Rac-PAK signaling pathway mediates kinocilium-stereocilia interactions and is required for cohesion of the stereociliary bundle. Together, these results reveal a critical function of Rac1 in morphogenesis of the auditory sensory epithelium and stereociliary bundle. PMID:20016102

  13. 76 FR 9540 - Humboldt County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ... Rivers National Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Adam...: Notice of meeting. SUMMARY: The Humboldt County Resource Advisory Committee (RAC) will meet in...

  14. 76 FR 14897 - Humboldt County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... Rivers National Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Adam...: Notice of meeting. SUMMARY: The Humboldt County Resource Advisory Committee (RAC) will meet in...

  15. Characterization of EHop-016, novel small molecule inhibitor of Rac GTPase.

    PubMed

    Montalvo-Ortiz, Brenda L; Castillo-Pichardo, Linette; Hernández, Eliud; Humphries-Bickley, Tessa; De la Mota-Peynado, Alina; Cubano, Luis A; Vlaar, Cornelis P; Dharmawardhane, Suranganie

    2012-04-13

    The Rho GTPase Rac regulates actin cytoskeleton reorganization to form cell surface extensions (lamellipodia) required for cell migration/invasion during cancer metastasis. Rac hyperactivation and overexpression are associated with aggressive cancers; thus, interference of the interaction of Rac with its direct upstream activators, guanine nucleotide exchange factors (GEFs), is a viable strategy for inhibiting Rac activity. We synthesized EHop-016, a novel inhibitor of Rac activity, based on the structure of the established Rac/Rac GEF inhibitor NSC23766. Herein, we demonstrate that EHop-016 inhibits Rac activity in the MDA-MB-435 metastatic cancer cells that overexpress Rac and exhibits high endogenous Rac activity. The IC(50) of 1.1 μM for Rac inhibition by EHop-016 is ∼100-fold lower than for NSC23766. EHop-016 is specific for Rac1 and Rac3 at concentrations of ≤5 μM. At higher concentrations, EHop-016 inhibits the close homolog Cdc42. In MDA-MB-435 cells that demonstrate high active levels of the Rac GEF Vav2, EHop-016 inhibits the association of Vav2 with a nucleotide-free Rac1(G15A), which has a high affinity for activated GEFs. EHop-016 also inhibits the Rac activity of MDA-MB-231 metastatic breast cancer cells and reduces Rac-directed lamellipodia formation in both cell lines. EHop-016 decreases Rac downstream effects of PAK1 (p21-activated kinase 1) activity and directed migration of metastatic cancer cells. Moreover, at effective concentrations (<5 μM), EHop-016 does not affect the viability of transformed mammary epithelial cells (MCF-10A) and reduces viability of MDA-MB-435 cells by only 20%. Therefore, EHop-016 holds promise as a targeted therapeutic agent for the treatment of metastatic cancers with high Rac activity.

  16. Rational design and applications of a Rac GTPase-specific small molecule inhibitor.

    PubMed

    Akbar, Huzoor; Cancelas, Jose; Williams, David A; Zheng, Jie; Zheng, Yi

    2006-01-01

    Rac GTPases are involved in the regulation of multiple cell functions and have been implicated in the pathology of certain human diseases. Dominant negative mutants of Rac have been the tool of choice in studying Rac function in cells. Given the difficulty of introducing high concentrations of the Rac mutants into primary cells and nonspecific effects of the mutants on Rho guanine nucleotide exchange factor (GEF) activities, it is desirable to develop small molecule inhibitors that could specifically inhibit Rac activities. Here we describe the rational design, characterization, and applications of a first-generation Rac-specific small molecule inhibitor. On the basis of the structure-function information of Rac interaction with GEFs, in a computer-based virtual screening we have identified NSC23766, a highly soluble and membrane permeable compound, as a specific inhibitor of a subset of GEF binding to Rac and, therefore, Rac activation by these GEFs. In fibroblast cells, NSC23766 inhibited Rac1 GTP-loading without affecting Cdc42 or RhoA activity and suppressed cell proliferation induced by a Rac GEF Tiam1. It has little effect on cell growth induced by a constitutively active Rac1 mutant. In addition, NSC23766 inhibited: (1) the anchorage-independent growth and invasion phenotypes of human prostate cancer PC-3 cells; (2) Rac activation and Rac-dependent aggregation of platelets stimulated by thrombin; and (3) Rac1 and Rac2 activities of hematopoietic stem/progenitor cells and induced their mobilization from mouse bone marrow to peripheral blood. Thus, NSC23766 is a lead small molecule inhibitor of Rac activity and could be useful for studying Rac-mediated cellular functions and for modulating pathological conditions in which Rac-deregulation may play a role.

  17. A compact orifice meter/flow conditioner package

    SciTech Connect

    Karnik, U.

    1995-12-31

    Flow conditioners have been the center of attention within the natural gas industry for several years. Their importance stems from the fact that, in the presence of existing installations such as elbows, accurate orifice metering can be obtained, within a specified meter length, only if the flow non-uniformities are eliminated. The tube bundle has, thus far, proven to be ineffective in terms of repeatability and reliability. Thus, NOVA embarked on the mission to find a flow conditioner which would, within the shortest possible meter length, provide accurate and repeatable metering. Of the several flow conditioners discussed in the literature, the approach adopted by Laws, based on screen theory, is best suited to achieve the desired results. However, the Laws flow conditioner has some functional flaws, for example, the claim of a fully developed flow with no account for the effect of Reynolds number. Hence, NOVA has re-designed and modified the existing Laws flow conditioner has some functional flaws, for example, the claim of a fully developed flow with no account for the effect of Reynolds number. Hence, NOVA has re-designed and modified the existing Laws flow conditioner using screen theory. This program, initiated in 1991, has resulted in a perforated plate flow conditioner sandwiched in a meter run with an overall length of 13D.

  18. Neuronal Rac1 Is Required for Learning-Evoked Neurogenesis

    PubMed Central

    Anderson, Matthew P.; Freewoman, Julia; Cord, Branden; Babu, Harish; Brakebusch, Cord

    2013-01-01

    Hippocampus-dependent learning and memory relies on synaptic plasticity as well as network adaptations provided by the addition of adult-born neurons. We have previously shown that activity-induced intracellular signaling through the Rho family small GTPase Rac1 is necessary in forebrain projection neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus primarily by enhancing the survival of neurons produced just before the learning event. Loss of Rac1 in mature projection neurons did reduce learning-evoked neurogenesis but, contrary to our expectations, these effects were not mediated by altering the survival of young neurons in the hippocampus. Instead, loss of neuronal Rac1 activation selectively impaired a learning-evoked increase in the proliferation and accumulation of neural precursors generated during the learning event itself. This indicates that experience-induced alterations in neurogenesis can be mechanistically resolved into two effects: (1) the well documented but Rac1-independent signaling cascade that enhances the survival of young postmitotic neurons; and (2) a previously unrecognized Rac1-dependent signaling cascade that stimulates the proliferative production and retention of new neurons generated during learning itself. PMID:23884931

  19. Rac GTPases play critical roles in early T-cell development

    PubMed Central

    Dumont, Celine; Corsoni-Tadrzak, Agnieszka; Ruf, Sandra; de Boer, Jasper; Williams, Adam; Turner, Martin; Kioussis, Dimitris

    2009-01-01

    The Rac1 and Rac2 GTPases play important roles in many processes including cytoskeletal reorganization, proliferation, and survival, and are required for B-cell development. Previous studies had shown that deficiency in Rac2 did not affect T-cell development, whereas the function of Rac1 in this process has not been investigated. We now show that simultaneous absence of both GTPases resulted in a very strong developmental block at the pre-TCR checkpoint and in defective positive selection. Unexpectedly, deficiency of Rac1 and Rac2 also resulted in the aberrant survival of thymocytes lacking expression of TCRβ, showing hallmarks of hyperactive Notch signaling. Furthermore, we found a similar novel phenotype in the absence of Vav1, Vav2, and Vav3, which function as guanine nucleotide exchange factors for Rac1 and Rac2. These results show that a pathway containing Vav and Rac proteins may negatively regulate Notch signaling during early thymic development. PMID:19088377

  20. Non-prenylatable, cytosolic Rac1 alters neurite outgrowth while retaining the ability to be activated.

    PubMed

    Reddy, Jairus M; Samuel, Filsy G; McConnell, Jordan A; Reddy, Cristina P; Beck, Brian W; Hynds, DiAnna L

    2015-03-01

    Rac1 is an important regulator of axon extension, cell migration and actin reorganization. Like all Rho guanine triphosphatases (GTPases), Rac1 is targeted to the membrane by the addition of a geranylgeranyl moiety, an action thought to result in Rac1 guanosine triphosphate (GTP) binding. However, the role that Rac1 localization plays in its activation (GTP loading) and subsequent activation of effectors is not completely clear. To address this, we developed a non-prenylatable emerald green fluorescent protein (EmGFP)-Rac1 fusion protein (EmGFP-Rac1(C189A)) and assessed how expressing this construct affected neurite outgrowth, Rac1 localization and activation in neuroblastoma cells. Expression of EmGFP-Rac1(C189A) increased localization to the cytosol and induced cell clustering while increasing neurite initiation. EmGFP-Rac1(C189A) expression also increased Rac1 activation in the cytosol, compared to cells expressing wild-type Rac1 (EmGFP-Rac1). These results suggest that activation of Rac1 may not require plasma membrane localization, potentially leading to differential activation of cytosolic signaling pathways that alter cell morphology. Understanding the consequences of differential localization and activation of Rho GTPases, including Rac1, could lead to new therapeutic targets for treating neurological disorders. PMID:25479592

  1. Rac1 expression in epithelial ovarian cancer: effect on cell EMT and clinical outcome.

    PubMed

    Leng, Ruobing; Liao, Gang; Wang, Haixia; Kuang, Jun; Tang, Liangdan

    2015-02-01

    Ras-related C3 botulinum toxin substrate 1 (rac1) has been implicated in tumor epithelial-mesenchymal transition (EMT); however, limited information is available regarding the role of rac1 in epithelial ovarian cancer (EOC). This study aimed to evaluate the correlation of rac1 expression with EMT and EOC prognosis. Rac1 protein levels of 150 EOC specimens were evaluated by immunohistochemical staining. Survival analysis was performed to determine the correlation between rac1 expression and survival. Cellular and molecular changes were also examined after rac1 in ovarian cancer cells was silenced in vitro and in vivo. The mechanism of rac1 on EMT was investigated by Western blot analysis. Rac1 was highly expressed in EOC. Rac1 overexpression was closely associated with advanced stage based on International Federation of Gynecology and Obstetrics, poor grade, serum Ca-125, and residual tumor size. Survival analyses demonstrated that patients with high rac1 expression levels were more susceptible to early tumor recurrence with very poor prognosis. This study revealed that rac1 downregulation decreased cell EMT and proliferation capability in vitro and in vivo. Rac1 expression possibly altered cell EMT by interacting with p21-activated kinase 1 and p38 mitogen-activated protein kinase signaling pathways. The present study showed that rac1 overexpression is associated with cell EMT and poor EOC prognosis. Rac1 possibly plays an important role in predicting EOC metastasis.

  2. Rac1 expression in epithelial ovarian cancer: effect on cell EMT and clinical outcome.

    PubMed

    Leng, Ruobing; Liao, Gang; Wang, Haixia; Kuang, Jun; Tang, Liangdan

    2015-02-01

    Ras-related C3 botulinum toxin substrate 1 (rac1) has been implicated in tumor epithelial-mesenchymal transition (EMT); however, limited information is available regarding the role of rac1 in epithelial ovarian cancer (EOC). This study aimed to evaluate the correlation of rac1 expression with EMT and EOC prognosis. Rac1 protein levels of 150 EOC specimens were evaluated by immunohistochemical staining. Survival analysis was performed to determine the correlation between rac1 expression and survival. Cellular and molecular changes were also examined after rac1 in ovarian cancer cells was silenced in vitro and in vivo. The mechanism of rac1 on EMT was investigated by Western blot analysis. Rac1 was highly expressed in EOC. Rac1 overexpression was closely associated with advanced stage based on International Federation of Gynecology and Obstetrics, poor grade, serum Ca-125, and residual tumor size. Survival analyses demonstrated that patients with high rac1 expression levels were more susceptible to early tumor recurrence with very poor prognosis. This study revealed that rac1 downregulation decreased cell EMT and proliferation capability in vitro and in vivo. Rac1 expression possibly altered cell EMT by interacting with p21-activated kinase 1 and p38 mitogen-activated protein kinase signaling pathways. The present study showed that rac1 overexpression is associated with cell EMT and poor EOC prognosis. Rac1 possibly plays an important role in predicting EOC metastasis. PMID:25585684

  3. 75 FR 27227 - Energy Conservation Program: Energy Conservation Standards for Residential Central Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... as a public meeting to discuss and receive comment on the preliminary analysis. 75 FR 14368. The NOPM... Central Air Conditioners and Heat Pumps AGENCY: Department of Energy, Office of Energy Efficiency and... conservation standards for residential central air conditioners and heat pumps; the analytical...

  4. 75 FR 31223 - Energy Conservation Program for Consumer Products: Test Procedure for Residential Central Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-02

    ... method for crediting heat pumps that provide a demand defrost capability. 53 FR 8304. The next revision... Central Air Conditioners and Heat Pumps; Proposed Rule #0;#0;Federal Register / Vol. 75, No. 105... Conservation Program for Consumer Products: Test Procedure for Residential Central Air Conditioners and...

  5. Lemongrass-Incorporated Tissue Conditioner Against Candida albicans Culture

    PubMed Central

    Amornvit, Pokpong; Srithavaj, Theerathavaj

    2014-01-01

    Background: Tissue conditioner is applied popularly with dental prosthesis during wound healing process but it becomes a reservoir of oral microbiota, especially Candida species after long-term usage. Several antifungal drugs have been mixed with this material to control fungal level. In this study, lemongrass essential oil was added into COE-COMFORT tissue conditioner before being determined for anti-Candida efficacy. Materials and Methods: Lemongrass (Cymbopogon citratus) essential oil was primarily determined for antifungal activity against C. albicans American type culture collection (ATCC) 10231 and MIC (minimum inhibitory concentration) value by agar disk diffusion and broth microdilution methods, respectively. COE-COMFORT tissue conditioner was prepared as recommended by the manufacturer after a fixed volume of the oil at its MIC or higher concentrations were mixed thoroughly in its liquid part. Antifungal efficacy of the tissue conditioner with/without herb was finally analyzed. Results: Lemongrass essential oil displayed potent antifungal activity against C. albicans ATCC 10231and its MIC value was 0.06% (v/v). Dissimilarly, the tissue conditioner containing the oil at MIC level did not cease the growth of the tested fungus. Both reference and clinical isolates of C. albicans were completely inhibited after exposed to the tissue conditioner containing at least 0.25% (v/v) of the oil (approximately 4-time MIC). The tissue conditioner without herb or with nystatin was employed as negative or positive control, respectively. Conclusion: COE-COMFORT tissue conditioner supplemented with lemongrass essential oil obviously demonstrated another desirable property as in vitro anti-Candida efficacy to minimize the risk of getting Candidal infection. PMID:25177638

  6. Regulating Rac in the Nervous System: Molecular Function and Disease Implication of Rac GEFs and GAPs

    PubMed Central

    Bai, Yanyang; Xiang, Xiaoliang; Liang, Chunmei

    2015-01-01

    Rho family GTPases, including RhoA, Rac1, and Cdc42 as the most studied members, are master regulators of actin cytoskeletal organization. Rho GTPases control various aspects of the nervous system and are associated with a number of neuropsychiatric and neurodegenerative diseases. The activity of Rho GTPases is controlled by two families of regulators, guanine nucleotide exchange factors (GEFs) as the activators and GTPase-activating proteins (GAPs) as the inhibitors. Through coordinated regulation by GEFs and GAPs, Rho GTPases act as converging signaling molecules that convey different upstream signals in the nervous system. So far, more than 70 members of either GEFs or GAPs of Rho GTPases have been identified in mammals, but only a small subset of them have well-known functions. Thus, characterization of important GEFs and GAPs in the nervous system is crucial for the understanding of spatiotemporal dynamics of Rho GTPase activity in different neuronal functions. In this review, we summarize the current understanding of GEFs and GAPs for Rac1, with emphasis on the molecular function and disease implication of these regulators in the nervous system. PMID:25879033

  7. Cocaine activates Rac1 to control structural and behavioral plasticity in caudate putamen.

    PubMed

    Li, Juan; Zhang, Lei; Chen, Zhenzhong; Xie, Minjuan; Huang, Lu; Xue, Jinhua; Liu, Yutong; Liu, Nuyun; Guo, Fukun; Zheng, Yi; Kong, Jiming; Zhang, Lin; Zhang, Lu

    2015-03-01

    Repeated exposure to cocaine was previously found to cause sensitized behavioral responses and structural remodeling on medium spiny neurons of the nucleus accumbens (NAc) and caudate putamen (CPu). Rac1 has emerged as a key integrator of environmental cues that regulates dendritic cytoskeletons. In this study, we investigated the role of Rac1 in cocaine-induced dendritic and behavioral plasticity in the CPu. We found that Rac1 activation was reduced in the NAc but increased in the CPu following repeated cocaine treatment. Inhibition of Rac1 activity by a Rac1-specific inhibitor NSC23766, overexpression of a dominant negative mutant of Rac1 (T17N-Rac1) or local knockout of Rac1 attenuated the cocaine-induced increase in dendrites and spine density in the CPu, whereas overexpression of a constitutively active Rac1 exert the opposite effect. Moreover, NSC23766 reversed the increased number of asymmetric spine synapses in the CPu following chronic cocaine exposure. Downregulation of Rac1 activity likewise attenuates behavioral reward responses to cocaine exposure, with activation of Rac1 producing the opposite effect. Thus, Rac1 signaling is differentially regulated in the NAc and CPu after repeated cocaine treatment, and induction of Rac1 activation in the CPu is important for cocaine exposure-induced dendritic remodeling and behavioral plasticity.

  8. Rac1 signaling modulates BCL-6-mediated repression of gene transcription.

    PubMed

    Barros, Patrícia; Jordan, Peter; Matos, Paulo

    2009-08-01

    Rac1 is a member of the Rho family of small GTPases that not only regulates signaling pathways involved in cell adhesion and migration but also regulates gene transcription. Here we show that the transcriptional repressor BCL-6 is regulated by Rac1 signaling. Transfection of active Rac1 mutants into colorectal DLD-1 cells led to increased expression of a BCL-6-controlled luciferase reporter construct. Conversely, inhibition of endogenous Rac1 activation by the Rac1 inhibitor NSC23766 decreased reporter activity. Moreover, BCL-6 lost its typical localization to nuclear dots upon activation of Rac1 and became predominantly soluble in a non-chromatin-bound cell fraction. Rac1 signaling also regulated the expression of endogenous BCL-6-regulated genes, including the p50 precursor NF-kappaB1/p105 and the cell adhesion molecule CD44. Interestingly, these effects were not stimulated by the alternative splice variant Rac1b. The mechanism of BCL-6 inhibition does not involve formation of a stable Rac1/BCL-6 complex and is independent of Rac-induced reactive oxygen species production or Jun NH(2)-terminal kinase activation. We show that PAK1 mediates inhibition downstream of Rac and can directly phosphorylate BCL-6. Together, these data provide substantial evidence that Rac1 signaling inhibits the transcriptional repressor BCL-6 in colorectal cells and reveal a novel pathway that links Rac1 signaling to the regulation of gene transcription.

  9. 16 CFR Appendix E to Part 305 - Room Air Conditioners

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER...'s/yr Range of Estimated Annual Operating Costs (Dollars/Year) LOW HIGH Without Reverse Cycle and... $112 14,000 to 19,999 Btu $105 $176 20,000 and more Btu $166 $338 Without Reverse Cycle and...

  10. 16 CFR Appendix E to Part 305 - Room Air Conditioners

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND WATER USE LABELING FOR CONSUMER PRODUCTS UNDER THE ENERGY POLICY AND CONSERVATION ACT (âENERGY... Without Reverse Cycle and with Louvered Sides: Less than 6,000 Btu $42 $48 6,000 to 7,999 Btu 50 72 8,000 to 13,999 Btu 66 115 14,000 to 19,999 Btu 117 195 20,000 and more Btu 169 382 Without Reverse...

  11. 16 CFR Appendix E to Part 305 - Room Air Conditioners

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER...'s/yr Range of Estimated Annual Operating Costs (Dollars/Year) LOW HIGH Without Reverse Cycle and... $112 14,000 to 19,999 Btu $105 $176 20,000 and more Btu $166 $338 Without Reverse Cycle and...

  12. 16 CFR Appendix E to Part 305 - Room Air Conditioners

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER...'s/yr Range of Estimated Annual Operating Costs (Dollars/Year) LOW HIGH Without Reverse Cycle and... $112 14,000 to 19,999 Btu $105 $176 20,000 and more Btu $166 $338 Without Reverse Cycle and...

  13. Absorption generator for solar-powered air-conditioner

    NASA Technical Reports Server (NTRS)

    Lowen, D. J.; Murray, J. G.

    1977-01-01

    Device passes solar-heated water through coils. Hot lithium Bromide/Water solution leaves through central stand-pipe, and water vapor leaves through refrigerant outlet at top. Matching generation temperature to collector efficiency helps cut costs.

  14. Rac regulates vascular endothelial growth factor stimulated motility.

    PubMed

    Soga, N; Connolly, J O; Chellaiah, M; Kawamura, J; Hruska, K A

    2001-01-01

    During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood. Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF. These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent

  15. Rac regulates vascular endothelial growth factor stimulated motility.

    PubMed

    Soga, N; Connolly, J O; Chellaiah, M; Kawamura, J; Hruska, K A

    2001-01-01

    During angiogenesis endothelial cells migrate towards a chemotactic stimulus. Understanding the mechanism of endothelial cell migration is critical to the therapeutic manipulation of angiogenesis and ultimately cancer prevention. Vascular endothelial growth factor (VEGF) is a potent chemotactic stimulus of endothelial cells during angiogenesis. The endothelial cell signal transduction pathway of VEGF represents a potential target for cancer therapy, but the mechanisms of post-receptor signal transduction including the roles of rho family GTPases in regulating the cytoskeletal effects of VEGF in endothelial cells are not understood. Here we analyze the mechanisms of cell migration in the mouse brain endothelial cell line (bEND3). Stable transfectants containing a tetracycline repressible expression vector were used to induce expression of Rac mutants. Endothelial cell haptotaxis was stimulated by constitutively active V12Rac on collagen and vitronectin coated supports, and chemotaxis was further stimulated by VEGF. Osteopontin coated supports were the most stimulatory to bEND3 haptotaxis, but VEGF was not effective in further increasing migration on osteopontin coated supports. Haptotaxis on support coated with collagen, vitronectin, and to a lesser degree osteopontin was inhibited by N17 Rac. N17 Rac expression blocked stimulation of endothelial cell chemotaxis by VEGF. As part of the chemotactic stimulation, VEGF caused a loss of actin organization at areas of cell-cell contact and increased stress fiber expression in endothelial cells which were directed towards pores in the transwell membrane. N17 Rac prevented the stimulation of cell-cell contact disruption and the stress fiber stimulation by VEGF. These data demonstrate two pathways of regulating endothelial cell motility, one in which Rac is activated by matrix/integrin stimulation and is a crucial modulator of endothelial cell haptotaxis. The other pathway, in the presence of osteopontin, is Rac independent

  16. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth

    SciTech Connect

    Wang, Jiying; Rao, Qing; Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang

    2009-09-04

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  17. Essential roles of mgcRacGAP in multilineage differentiation and survival of murine hematopoietic cells

    SciTech Connect

    Yamada, Takayuki; Kurosaki, Tomohiro; Hikida, Masaki

    2008-08-08

    MgcRacGAP, a negative regulator for Rho family GTPases, has been shown to play important roles in cytokinesis using several cell lines. However, the physiological role of mgcRacGAP in multilineage hematopoietic development remains unclear. Here, we conditionally ablated mgcRacGAP in vivo to clarify this issue. As the result, we found that normal hematopoietic development including proliferation and survival requires mgcRacGAP. We also found that depletion of mgcRacGAP in hematopoietic cells results in a marked decrease in c-Kit{sup +}Sca-1{sup +}Lin{sup -} cells, suggesting that mgcRacGAP is required for the maintenance of the hematopoietic stem cells. In addition, B cells in which mgcRacGAP had been selectively ablated showed proliferation failure and fell into apoptosis. Taken together, mgcRacGAP is now shown to play a indispensable role in the development of hematopoietic cells in vivo.

  18. Overexpression of Rac1 in leukemia patients and its role in leukemia cell migration and growth.

    PubMed

    Wang, Jiying; Rao, Qing; Wang, Min; Wei, Hui; Xing, Haiyan; Liu, Hang; Wang, Yanzhong; Tang, Kejing; Peng, Leiwen; Tian, Zheng; Wang, Jianxiang

    2009-09-01

    Rac1 belongs to the Rho family that act as critical mediators of signaling pathways controlling cell migration and proliferation and contributes to the interactions of hematopoietic stem cells with their microenvironment. Alteration of Rac1 might result in unbalanced interactions and ultimately lead to leukemogenesis. In this study, we analyze the expression of Rac1 protein in leukemia patients and determine its role in the abnormal behaviours of leukemic cells. Rac1 protein is overexpressed in primary acute myeloid leukemia cells as compared to normal bone marrow mononuclear cells. siRNA-mediated silencing of Rac1 in leukemia cell lines induced inhibition of cell migration, proliferation, and colony formation. Additionally, blocking Rac1 activity by an inhibitor of Rac1-GTPase, NSC23766, suppressed cell migration and growth. We conclude that overexpression of Rac1 contributes to the accelerated migration and high proliferation potential of leukemia cells, which could be implicated in leukemia development and progression.

  19. Embedding Quantum into Classical: Contextualization vs Conditionalization

    PubMed Central

    Dzhafarov, Ehtibar N.; Kujala, Janne V.

    2014-01-01

    We compare two approaches to embedding joint distributions of random variables recorded under different conditions (such as spins of entangled particles for different settings) into the framework of classical, Kolmogorovian probability theory. In the contextualization approach each random variable is “automatically” labeled by all conditions under which it is recorded, and the random variables across a set of mutually exclusive conditions are probabilistically coupled (imposed a joint distribution upon). Analysis of all possible probabilistic couplings for a given set of random variables allows one to characterize various relations between their separate distributions (such as Bell-type inequalities or quantum-mechanical constraints). In the conditionalization approach one considers the conditions under which the random variables are recorded as if they were values of another random variable, so that the observed distributions are interpreted as conditional ones. This approach is uninformative with respect to relations between the distributions observed under different conditions because any set of such distributions is compatible with any distribution assigned to the conditions. PMID:24681665

  20. B and F Signal Conditioner Checkout Unit

    NASA Technical Reports Server (NTRS)

    Magleby, Alyssa; McCool, Alex (Technical Monitor)

    2001-01-01

    ATK Thiokol Propulsion, Test Services uses B&F Signal Conditioning units to provide excitation power and shunt calibration information to the data recording systems. Gage measurements such as force, temperature, pressure, strain, etc. are recorded using this equipment. Approximately 2500 reusable instrumentation B&F Signal Conditioning units were purchased over an interval from 1978 to 1988 at a cost of around $1000 each. Through use and over time, the relay contacts on the signal conditioning mode cards have become corroded, resulting in excessive contact resistance. This causes inaccurate and inconsistent calibration data and could jeopardize the test results. These signal conditioning cards are needed for product testing for an estimated five more years, therefore, it is necessary to develop a solution to isolate the malfunctioning units for repair. The current screening method requires Test Area technicians to check cards manually, however the connections and measurements required for this process are inefficient and time consuming. To resolve this problem, funding was approved to design and build two B&F Signal Conditioner Checkout Units. Each unit will allow technicians to test relay contact resistance on signal conditioning mode cards before they are installed for data collection procedures. This tool will allow Test Area to resolve calibration accuracy problems and extend the life of the data acquisition equipment, as well as save troubleshooting time for the technicians.

  1. Rac limits TGF-β-induced VEGF synthesis in osteoblasts.

    PubMed

    Yamamoto, Naohiro; Otsuka, Takanobu; Kondo, Akira; Matsushima-Nishiwaki, Rie; Kuroyanagi, Gen; Kozawa, Osamu; Tokuda, Haruhiko

    2015-04-15

    We previously showed that transforming growth factor-β (TGF-β) stimulates vascular endothelial growth factor (VEGF) synthesis via p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of Rac, which is a member of the Rho family of small GTPases, in the TGF-β-stimulated VEGF synthesis in MC3T3-E1 cells. TGF-β markedly increased the levels of GTP-bound Rac. NSC23766, a selective inhibitor of Rac-guanine nucleotide exchange factor interaction, significantly increased both the release of VEGF and the mRNA expression levels induced by TGF-β. In addition, the release of VEGF stimulated by TGF-β was amplified in Rac-knock down cells. Meanwhile, SIS3, a specific inhibitor of TGF-β-dependent Smad3 phosphorylation, significantly reduced the TGF-β-stimulated VEGF release. However, the phosphorylation of Smad2 or Smad3 induced by TGF-β was hardly affected by NSC23766. On the other hand, NSC23766 enhanced the TGF-β-induced phosphorylation of p38 MAP kinase without affecting the phosphorylation of p44/p42 MAP kinase or SAPK/JNK. Furthermore, the phosphorylation of p38 MAP kinase induced by TGF-β was markedly upregulated in the Rac-knock down cells. These results strongly suggest that Rac negatively regulates the TGF-β-stimulated VEGF synthesis via the inhibition of p38 MAP kinase in osteoblasts.

  2. Rac is involved in the interkinetic nuclear migration of cortical progenitor cells.

    PubMed

    Minobe, Sayaka; Sakakibara, Akira; Ohdachi, Tomoko; Kanda, Rieko; Kimura, Miyako; Nakatani, Sayaka; Tadokoro, Ryosuke; Ochiai, Wataru; Nishizawa, Yuji; Mizoguchi, Akira; Kawauchi, Takeshi; Miyata, Takaki

    2009-04-01

    The small GTPase Rac regulates neuronal behavior, but whether it also functions in neural progenitor cells has not yet been explored. Here we report that Rac contributes to the regulation of nuclear migration in neocortical progenitor cells. Rac1 is expressed by progenitor cells in a unique spatiotemporal pattern. Cross-sectional immunohistochemical examination revealed intense Rac1 immunoreactivity at the ventricular surface. Similar staining patterns were obtained by immunofluorescence for a Rac-activator, Tiam1, and by reactions to detect the GTP-bound (active) form of Rac. En face inspection of the ventricular surface revealed that apical Rac1 localization was most frequent in M-phase cells, and the endfeet of cells in other cell cycle phases also showed apical Rac1 distribution at lower frequencies. To ask whether progenitor cell behavior prior to and during M phase is Rac-dependent, we monitored individual DiI-labeled progenitor cells live in the presence of a Rac inhibitor, NSC23766. We observed significantly retarded adventricular nuclear migration, as well as cytokinesis failures. Similar inhibitory effects were obtained by forced expression of a dominant-negative Rac1. These results suggest that Rac may play a role in interkinetic nuclear migration in the developing mouse brain.

  3. Spectra of conditionalization and typicality in the multiverse

    NASA Astrophysics Data System (ADS)

    Azhar, Feraz

    2016-02-01

    An approach to testing theories describing a multiverse, that has gained interest of late, involves comparing theory-generated probability distributions over observables with their experimentally measured values. It is likely that such distributions, were we indeed able to calculate them unambiguously, will assign low probabilities to any such experimental measurements. An alternative to thereby rejecting these theories, is to conditionalize the distributions involved by restricting attention to domains of the multiverse in which we might arise. In order to elicit a crisp prediction, however, one needs to make a further assumption about how typical we are of the chosen domains. In this paper, we investigate interactions between the spectra of available assumptions regarding both conditionalization and typicality, and draw out the effects of these interactions in a concrete setting; namely, on predictions of the total number of species that contribute significantly to dark matter. In particular, for each conditionalization scheme studied, we analyze how correlations between densities of different dark matter species affect the prediction, and explicate the effects of assumptions regarding typicality. We find that the effects of correlations can depend on the conditionalization scheme, and that in each case atypicality can significantly change the prediction. In doing so, we demonstrate the existence of overlaps in the predictions of different "frameworks" consisting of conjunctions of theory, conditionalization scheme and typicality assumption. This conclusion highlights the acute challenges involved in using such tests to identify a preferred framework that aims to describe our observational situation in a multiverse.

  4. Rac regulation of transformation, gene expression, and actin organization by multiple, PAK-independent pathways.

    PubMed Central

    Westwick, J K; Lambert, Q T; Clark, G J; Symons, M; Van Aelst, L; Pestell, R G; Der, C J

    1997-01-01

    Rac1 and RhoA are members of the Rho family of Ras-related proteins and function as regulators of actin cytoskeletal organization, gene expression, and cell cycle progression. Constitutive activation of Rac1 and RhoA causes tumorigenic transformation of NIH 3T3 cells, and their functions may be required for full Ras transformation. The effectors by which Rac1 and RhoA mediate these diverse activities, as well as the interrelationship between these events, remain poorly understood. Rac1 is distinct from RhoA in its ability to bind and activate the p65 PAK serine/threonine kinase, to induce lamellipodia and membrane ruffling, and to activate the c-Jun NH2-terminal kinase (JNK). To assess the role of PAK in Rac1 function, we identified effector domain mutants of Rac1 and Rac1-RhoA chimeric proteins that no longer bound PAK. Surprisingly, PAK binding was dispensable for Rac1-induced transformation and lamellipodium formation, as well as activation of JNK, p38, and serum response factor (SRF). However, the ability of Rac1 to bind to and activate PAK correlated with its ability to stimulate transcription from the cyclin D1 promoter. Furthermore, Rac1 activation of JNK or SRF, or induction of lamellipodia, was neither necessary nor sufficient for Rac1 transforming activity. Finally, the signaling pathways that mediate Rac1 activation of SRF or JNK were distinct from those that mediate Rac1 induction of lamellipodia. Taken together, these observations suggest that Rac1 regulates at least four distinct effector-mediated functions and that multiple pathways may contribute to Rac1-induced cellular transformation. PMID:9032259

  5. Allergies to molds caused by fungal spores in air conditioning equipment

    SciTech Connect

    Schata, M.; Jorde, W. ); Elixmann, J.H.; Linskens, H.F. )

    1989-01-01

    People suffering from various symptoms while in air-conditioned rooms often show sensitizations to fungi that can be isolated when the fungi are removed from air conditioners. By using specific challenge tests it was shown that fungal spores in air conditioners can evoke allergic symptoms. Hyposensitization was the specific therapy prescribed for such allergic reactions. After hyposensitization therapy, more than 70% of the patients so treated could live and work again in air-conditioned rooms without developing specific symptoms.

  6. COMPOSITION CHANGES IN REFRIGERANT BLENDS FOR AUTOMOTIVE AIR CONDITIONING

    EPA Science Inventory

    Three refrigerant blends used to replace CFC-12 in automotive air conditioners were evaluated for composition changes due to typical servicing and leakage. When recommended service procedures were followed, changes in blend compositions were relatively small. Small changes in b...

  7. 76 FR 51344 - Butte County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ...The Butte County Resource Advisory Committee (RAC) will hold a meeting on August 29, 2011 in Oroville, CA. The purpose of the meeting is to review Cycle 2 project applications for potential funding recommendations to Lassen, Plumas or Mendocino National Forest Supervisors. The funding is made available under Title II provisions of the Secure Rural Schools and Community Self-Determination Act......

  8. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

    SciTech Connect

    Krauthammer, Michael; Kong, Yong; Ha, Byung Hak; Evans, Perry; Bacchiocchi, Antonella; McCusker, James P.; Cheng, Elaine; Davis, Matthew J.; Goh, Gerald; Choi, Murim; Ariyan, Stephan; Narayan, Deepak; Dutton-Regester, Ken; Capatana, Ana; Holman, Edna C.; Bosenberg, Marcus; Sznol, Mario; Kluger, Harriet M.; Brash, Douglas E.; Stern, David F.; Materin, Miguel A.; Lo, Roger S.; Mane, Shrikant; Ma, Shuangge; Kidd, Kenneth K.; Hayward, Nicholas K.; Lifton, Richard P.; Schlessinger, Joseph; Boggon, Titus J.; Halaban, Ruth

    2012-10-11

    We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1{sup P29S}) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1{sup P29S} showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

  9. 75 FR 12723 - Plumas County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-17

    ... agency #0;statements of organization and functions are examples of documents #0;appearing in this section...; ] DEPARTMENT OF AGRICULTURE Forest Service Plumas County Resource Advisory Committee (RAC) AGENCY: Forest... for Cycle 10 funding and select projects to be recommended to the Plumas National Forest...

  10. 75 FR 21220 - Del Norte Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... agency #0;statements of organization and functions are examples of documents #0;appearing in this section...; ] DEPARTMENT OF AGRICULTURE Forest Service Del Norte Resource Advisory Committee (RAC) AGENCY: Forest Service... Rivers National Forest, 1330 Bayshore Way, Eureka, CA 95503 (707) 441-3673; e-mail...

  11. 77 FR 64099 - Snohomish County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-18

    ... (360) 436-2301, email pforbes@fs.fed.us . Individuals who use telecommunication devices for the deaf.... More information will be posted on the Mt. Baker-Snoqualmie National Forest Web site at http://www.fs.fed.us/r6/mbs/projects/rac.shtml . Comments may be sent via email to pforbes@fs.fed.us or...

  12. 75 FR 36061 - Humboldt Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-24

    ... Rivers National Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Julie Ranieri, Committee Coordinator, Six Rivers National Forest, 1330 Bayshore Way, Eureka, CA 95503... meeting. SUMMARY: The Humboldt Resource Advisory Committee (RAC) will meet in Eureka, California....

  13. 75 FR 27703 - Humboldt Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-18

    ... Rivers National Forest Office, 1330 Bayshore Way, Eureka, CA 95501. FOR FURTHER INFORMATION CONTACT: Julie Ranieri, Committee Coordinator, Six Rivers National Forest, 1330 Bayshore Way, Eureka, CA 95503... meeting. SUMMARY: The Humboldt Resource Advisory Committee (RAC) will meet in Eureka, California....

  14. 21 CFR 872.3750 - Bracket adhesive resin and tooth conditioner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Bracket adhesive resin and tooth conditioner. 872... SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3750 Bracket adhesive resin and tooth conditioner. (a) Identification. A bracket adhesive resin and tooth conditioner is a...

  15. 21 CFR 872.3750 - Bracket adhesive resin and tooth conditioner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Bracket adhesive resin and tooth conditioner. 872... and tooth conditioner. (a) Identification. A bracket adhesive resin and tooth conditioner is a device... to a tooth surface. (b) Classification. Class II....

  16. 21 CFR 872.3750 - Bracket adhesive resin and tooth conditioner.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Bracket adhesive resin and tooth conditioner. 872... and tooth conditioner. (a) Identification. A bracket adhesive resin and tooth conditioner is a device... to a tooth surface. (b) Classification. Class II....

  17. 21 CFR 872.3750 - Bracket adhesive resin and tooth conditioner.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Bracket adhesive resin and tooth conditioner. 872... and tooth conditioner. (a) Identification. A bracket adhesive resin and tooth conditioner is a device... to a tooth surface. (b) Classification. Class II....

  18. Integration of the Rac1- and actin-binding properties of Coronin-1C

    PubMed Central

    Tilley, Frances C; Williamson, Rosalind C; Race, Paul R; Rendall, Thomas C; Bass, Mark D

    2015-01-01

    The coronin family of actin-binding proteins regulate actin branching by inhibiting Arp2/3. We recently reported 2 interactions that were unique to coronin-1C: binding of a Rac1 inhibitor, RCC2, to the unique linker region and Rac1 itself to the propeller domain in a manner that differs from that proposed for other coronins. Through these interactions coronin-1C redistributes Rac1 from the back of the cell to the leading edge for either activation or sequestration by the associated Rac1-inhibitor, RCC2. Here we investigate the relationship between the Rac1- and actin-binding properties of coronin-1C and find that, although actin appears to be involved in the retrafficking of Rac1, signaling by Rac1 lies upstream of the stress fiber-formation, for which the coronins were originally characterized. PMID:25862165

  19. Caspase 3-Mediated Inactivation of Rac GTPases Promotes Drug-Induced Apoptosis in Human Lymphoma Cells

    PubMed Central

    Zhang, Baolin; Zhang, Yaqin; Shacter, Emily

    2003-01-01

    The Rac members of the Rho family GTPases control signaling pathways that regulate diverse cellular activities, including cytoskeletal organization, gene transcription, and cell transformation. Rac is implicated in apoptosis, but little is known about the mechanism by which it responds to apoptotic stimuli. Here we demonstrate that endogenous Rac GTPases are caspase 3 substrates that are cleaved in human lymphoma cells during drug-induced apoptosis. Cleavage of Rac1 occurs at two unconventional caspase 3 sites, VVGD11/G and VMVD47/G, and results in inactivation of the GTPase and effector functions of the protein (binding to the p21-activated protein kinase PAK1). Expression of caspase 3-resistant Rac1 mutants in the cells suppresses drug-induced apoptosis. Thus, proteolytic inactivation of Rac GTPases represents a novel, irreversible mechanism of Rac downregulation that allows maximal cell death following drug treatment. PMID:12897143

  20. Smart sensors enable smart air conditioning control.

    PubMed

    Cheng, Chin-Chi; Lee, Dasheng

    2014-01-01

    In this study, mobile phones, wearable devices, temperature and human motion detectors are integrated as smart sensors for enabling smart air conditioning control. Smart sensors obtain feedback, especially occupants' information, from mobile phones and wearable devices placed on human body. The information can be used to adjust air conditioners in advance according to humans' intentions, in so-called intention causing control. Experimental results show that the indoor temperature can be controlled accurately with errors of less than ±0.1 °C. Rapid cool down can be achieved within 2 min to the optimized indoor capacity after occupants enter a room. It's also noted that within two-hour operation the total compressor output of the smart air conditioner is 48.4% less than that of the one using On-Off control. The smart air conditioner with wearable devices could detect the human temperature and activity during sleep to determine the sleeping state and adjusting the sleeping function flexibly. The sleeping function optimized by the smart air conditioner with wearable devices could reduce the energy consumption up to 46.9% and keep the human health. The presented smart air conditioner could provide a comfortable environment and achieve the goals of energy conservation and environmental protection. PMID:24961213

  1. Smart sensors enable smart air conditioning control.

    PubMed

    Cheng, Chin-Chi; Lee, Dasheng

    2014-06-24

    In this study, mobile phones, wearable devices, temperature and human motion detectors are integrated as smart sensors for enabling smart air conditioning control. Smart sensors obtain feedback, especially occupants' information, from mobile phones and wearable devices placed on human body. The information can be used to adjust air conditioners in advance according to humans' intentions, in so-called intention causing control. Experimental results show that the indoor temperature can be controlled accurately with errors of less than ±0.1 °C. Rapid cool down can be achieved within 2 min to the optimized indoor capacity after occupants enter a room. It's also noted that within two-hour operation the total compressor output of the smart air conditioner is 48.4% less than that of the one using On-Off control. The smart air conditioner with wearable devices could detect the human temperature and activity during sleep to determine the sleeping state and adjusting the sleeping function flexibly. The sleeping function optimized by the smart air conditioner with wearable devices could reduce the energy consumption up to 46.9% and keep the human health. The presented smart air conditioner could provide a comfortable environment and achieve the goals of energy conservation and environmental protection.

  2. Smart Sensors Enable Smart Air Conditioning Control

    PubMed Central

    Cheng, Chin-Chi; Lee, Dasheng

    2014-01-01

    In this study, mobile phones, wearable devices, temperature and human motion detectors are integrated as smart sensors for enabling smart air conditioning control. Smart sensors obtain feedback, especially occupants' information, from mobile phones and wearable devices placed on human body. The information can be used to adjust air conditioners in advance according to humans' intentions, in so-called intention causing control. Experimental results show that the indoor temperature can be controlled accurately with errors of less than ±0.1 °C. Rapid cool down can be achieved within 2 min to the optimized indoor capacity after occupants enter a room. It's also noted that within two-hour operation the total compressor output of the smart air conditioner is 48.4% less than that of the one using On-Off control. The smart air conditioner with wearable devices could detect the human temperature and activity during sleep to determine the sleeping state and adjusting the sleeping function flexibly. The sleeping function optimized by the smart air conditioner with wearable devices could reduce the energy consumption up to 46.9% and keep the human health. The presented smart air conditioner could provide a comfortable environment and achieve the goals of energy conservation and environmental protection. PMID:24961213

  3. Rac1 promotes diethylnitrosamine (DEN)-induced formation of liver tumors.

    PubMed

    Bopp, Anita; Wartlick, Friedrich; Henninger, Christian; Schwarz, Michael; Kaina, Bernd; Fritz, Gerhard

    2015-03-01

    To elucidate the function of the Ras-homologous GTPase Rac1 in hepatocarcinogenesis induced by diethylnitrosamine (DEN), mice lacking hepatic Rac1 expression were treated with DEN and compared to the wild-type (WT). Rac1 knock-out (KO) mice were found to have a lower tumor yield as compared to Rac1 proficient mice. The small-sized tumors formed in the absence of Rac1 lack an activated Ras/Raf/mitogen-activated protein kinase pathway, as indicated by the absence of p-ERK expression. Apparently, Rac1 is required for Ras-driven oncogenic pathways. Moreover, tumors in Rac1 deficient mice were glutamine synthase (GS) negative. They displayed a high number of p-H3-positive and cyclinB1 expressing cells, pointing to a defect in mitotic progression. To elucidate the influence of Rac1 on mechanisms of tumor initiation, acute DEN-induced hepatic stress responses were monitored. Rac1 deficiency caused fairly complex, partially time-dependent, alterations in both basal and/or DEN-induced messenger RNA (mRNA) and protein levels of susceptibility-related genes. Basal protein expression of DNA repair factors Brca1 and DNA repair protein RAD51 homolog (Rad51) and the cell cycle regulatory factor p27 was enhanced in the absence of Rac1. Following DEN treatment, p21 mRNA and protein expression was stimulated independent of the Rac1 status. Lack of Rac1 increased mechanisms of the DNA damage response (DDR), as shown by elevated protein levels of p-ATR, p-p53 and γH2AX 24h after DEN treatment. The data show that Rac1 is essential for DEN-stimulated hepatocarcinogenesis. We hypothesize that it promotes tumor initiation by counteracting the elimination of initiated cells and, moreover, alleviates the outgrowth of transformed cells. Hence, pharmacological targeting of Rac1 could be suitable for chemoprevention.

  4. Seminar 14 - Desiccant Enhanced Air Conditioning: Desiccant Enhanced Evaporative Air Conditioning (Presentation)

    SciTech Connect

    Kozubal, E.

    2013-02-01

    This presentation explains how liquid desiccant based coupled with an indirect evaporative cooler can efficiently produce cool, dry air, and how a liquid desiccant membrane air conditioner can efficiently provide cooling and dehumidification without the carryover problems of previous generations of liquid desiccant systems. It provides an overview to a liquid desiccant DX air conditioner that can efficiently provide cooling and dehumidification to high latent loads without the need for reheat, explains how liquid desiccant cooling and dehumidification systems can outperform vapor compression based air conditioning systems in hot and humid climates, explains how liquid desiccant cooling and dehumidification systems work, and describes a refrigerant free liquid desiccant based cooling system.

  5. Transforming PC Power Supplies into Smart Car Battery Conditioners

    ERIC Educational Resources Information Center

    Rodriguez-Ascariz, J. M.; Boquete-Vazquez, L.

    2011-01-01

    This paper describes a laboratory project consisting of a PC power supply modification into an intelligent car-battery conditioner with both wireless and wired networking capabilities. Adding a microcontroller to an average PC power supply transforms it into a flexible, intelligent device that can be configured and that is suitable to keep car…

  6. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Physiological signal conditioner. 882.1845 Section 882.1845 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... integrator or differentiator used to modify physiological signals for recording and processing....

  7. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Physiological signal conditioner. 882.1845 Section 882.1845 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... integrator or differentiator used to modify physiological signals for recording and processing....

  8. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Physiological signal conditioner. 882.1845 Section 882.1845 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... integrator or differentiator used to modify physiological signals for recording and processing....

  9. 21 CFR 870.2060 - Transducer signal amplifier and conditioner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Transducer signal amplifier and conditioner. 870.2060 Section 870.2060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Monitoring Devices §...

  10. Contraction pre-conditioner in finite-difference electromagnetic modelling

    NASA Astrophysics Data System (ADS)

    Yavich, Nikolay; Zhdanov, Michael S.

    2016-09-01

    This paper introduces a novel approach to constructing an effective pre-conditioner for finite-difference (FD) electromagnetic modelling in geophysical applications. This approach is based on introducing an FD contraction operator, similar to one developed for integral equation formulation of Maxwell's equation. The properties of the FD contraction operator were established using an FD analogue of the energy equality for the anomalous electromagnetic field. A new pre-conditioner uses a discrete Green's function of a 1-D layered background conductivity. We also developed the formulae for an estimation of the condition number of the system of FD equations pre-conditioned with the introduced FD contraction operator. Based on this estimation, we have established that the condition number is bounded by the maximum conductivity contrast between the background conductivity and actual conductivity. When there are both resistive and conductive anomalies relative to the background, the new pre-conditioner is advantageous over using the 1-D discrete Green's function directly. In our numerical experiments with both resistive and conductive anomalies, for a land geoelectrical model with 1:10 contrast, the method accelerates convergence of an iterative method (BiCGStab) by factors of 2-2.5, and in a marine example with 1:50 contrast, by a factor of 4.6, compared to direct use of the discrete 1-D Green's function as a pre-conditioner.

  11. Thermionic reactor power conditioner design for nuclear electric propulsion.

    NASA Technical Reports Server (NTRS)

    Jacobsen, A. S.; Tasca, D. M.

    1971-01-01

    Consideration of the effects of various thermionic reactor parameters and requirements upon spacecraft power conditioning design. A basic spacecraft is defined using nuclear electric propulsion, requiring approximately 120 kWe. The interrelationships of reactor operating characteristics and power conditioning requirements are discussed and evaluated, and the effects on power conditioner design and performance are presented.

  12. Flow conditioner location effects in orifice flowmeters. Technical note

    SciTech Connect

    Scott, J.L.; Sindt, C.F.; Lewis, M.A.

    1993-01-01

    Tests sponsored by Gas Research Institute were conducted with orifice flowmeters of two nominal sizes: 104 mm (4 in) and 52 mm (2 in). For the 104 mm orifice meter the authors compared discharge coefficients measured in two common piping configurations used by laboratories to establish baseline flow conditions. The discharge coefficients are similar for beta ratios of 0.43, 0.55, and 0.67, but not for the 0.73 beta ratio plate. For other tests with the orifice meter, a 90 degree elbow or a reducer was located upstream of the orifice plate and flow conditioner. Two beta ratios (0.54, 0.67) were tested in the 52 mm orifice meter in baseline configuration and with an elbow at 17D and a flow conditioner at 12D. For many of the tests, differential pressures were measured at more than one flange tap location. Placing the flow conditioner too close to the orifice plate in either meter yields discharge coefficients below baseline values. The location of the flow conditioner with respect to the orifice plate appears to influence meter performance more significantly than the type or location of flow disturbance upstream of it.

  13. Inhibition of Rac1 GTPase activity affects porcine oocyte maturation and early embryo development

    PubMed Central

    Song, Si-Jing; Wang, Qiao-Chu; Jia, Ru-Xia; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2016-01-01

    Mammalian oocyte asymmetric division relies on the eccentric positioning of the spindle, resulting in the polar body formation. Small signaling G protein Rac1 is a member of GTPases, which regulates a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. However, effects of Rac1 on the porcine oocyte maturation and early embryo development are not fully understood. In present study we investigated the role of Rac1 in oocyte maturation and embryo cleavage. We first found that Rac1 localized at the cortex of the porcine oocytes, and disrupting the Rac1 activities by treating with NSC 23766 led to the failure of polar body emission. In addition, a majority of treated oocytes exhibited abnormal spindle morphology, indicating that Rac1 may involve into porcine oocyte spindle formation. This might be due to the regulation of Rac1 on MAPK, since p-MAPK expression decreased after NSC 23766 treatments. Moreover, we found that the position of most meiotic spindles in treated oocytes were away from the cortex, indicating the roles of Rac1 on meiotic spindle positioning. Our results also showed that inhibition of Rac1 activity caused the failure of early embryo development. Therefore, our study showed the critical roles of Rac1 GTPase on porcine oocyte maturation and early embryo cleavage. PMID:27694954

  14. RAC1 activation drives pathologic interactions between the epidermis and immune cells

    PubMed Central

    Winge, Mårten C.G.; Ohyama, Bungo; Dey, Clara N.; Boxer, Lisa M.; Li, Wei; Ehsani-Chimeh, Nazanin; Truong, Allison K.; Wu, Diane; Armstrong, April W.; Makino, Teruhiko; Davidson, Matthew; Starcevic, Daniela; Nguyen, Ngon T.; Hashimoto, Takashi; Homey, Bernard; Khavari, Paul A.; Bradley, Maria; Waterman, Elizabeth A.; Marinkovich, M. Peter

    2016-01-01

    Interactions between the epidermis and the immune system govern epidermal tissue homeostasis. These epidermis-immune interactions are altered in the inflammatory disease psoriasis; however, the pathways that underlie this aberrant immune response are not well understood. Here, we determined that Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key mediator of epidermal dysfunction. RAC1 activation was consistently elevated in psoriatic epidermis and primary psoriatic human keratinocytes (PHKCs) exposed to psoriasis-related stimuli, but not in skin from patients with basal or squamous cell carcinoma. Expression of a constitutively active form of RAC1 (RACV12) in mice resulted in the development of lesions similar to those of human psoriasis that required the presence of an intact immune system. RAC1V12-expressing mice and human psoriatic skin showed similar RAC1-dependent signaling as well as transcriptional overlap of differentially expressed epidermal and immune pathways. Coculture of PHKCs with immunocytes resulted in the upregulation of RAC1-dependent proinflammatory cytokines, an effect that was reproduced by overexpressing RAC1 in normal human keratinocytes. In keratinocytes, modulating RAC1 activity altered differentiation, proliferation, and inflammatory pathways, including STAT3, NFκB, and zinc finger protein 750 (ZNF750). Finally, RAC1 inhibition in xenografts composed of human PHKCs and immunocytes abolished psoriasiform hyperplasia and inflammation in vivo. These studies implicate RAC1 as a potential therapeutic target for psoriasis and as a key orchestrator of pathologic epidermis-immune interactions. PMID:27294528

  15. A palmitoylation switch mechanism regulates Rac1 function and membrane organization

    PubMed Central

    Navarro-Lérida, Inmaculada; Sánchez-Perales, Sara; Calvo, María; Rentero, Carles; Zheng, Yi; Enrich, Carlos; Del Pozo, Miguel A

    2012-01-01

    The small GTPase Rac1 plays important roles in many processes, including cytoskeletal reorganization, cell migration, cell-cycle progression and gene expression. The initiation of Rac1 signalling requires at least two mechanisms: GTP loading via the guanosine triphosphate (GTP)/guanosine diphosphate (GDP) cycle, and targeting to cholesterol-rich liquid-ordered plasma membrane microdomains. Little is known about the molecular mechanisms governing this specific compartmentalization. We show that Rac1 can incorporate palmitate at cysteine 178 and that this post-translational modification targets Rac1 for stabilization at actin cytoskeleton-linked ordered membrane regions. Palmitoylation of Rac1 requires its prior prenylation and the intact C-terminal polybasic region and is regulated by the triproline-rich motif. Non-palmitoylated Rac1 shows decreased GTP loading and lower association with detergent-resistant (liquid-ordered) membranes (DRMs). Cells expressing no Rac1 or a palmitoylation-deficient mutant have an increased content of disordered membrane domains, and markers of ordered membranes isolated from Rac1-deficient cells do not correctly partition in DRMs. Importantly, cells lacking Rac1 palmitoylation show spreading and migration defects. These data identify palmitoylation as a mechanism for Rac1 function in actin cytoskeleton remodelling by controlling its membrane partitioning, which in turn regulates membrane organization. PMID:22157745

  16. ROLE OF RAC-1 DEPENDENT NADPH OXIDASE IN THE GROWTH OF PANCREATIC CANCER

    PubMed Central

    Du, Juan; Liu, Jingru; Smith, Brian J.; Tsao, Ming-Sound; Cullen, Joseph J.

    2010-01-01

    K-ras mutations occur in as high as 95% of patients with pancreatic cancer. K-ras activates Rac1-dependent NADPH oxidase, a key source of superoxide. Superoxide plays an important role in pancreatic cancer cell proliferation and scavenging or decreasing the levels of superoxide inhibits pancreatic cancer cell growth both in vitro and in vivo. DNA microarray analysis and RT-PCR has demonstrated that Rac1 is also upregulated in pancreatic cancer. The aim of this study was to determine if inhibiting Rac1 would alter pancreatic tumor cell behavior. Human pancreatic cancer cells with mutant K-ras (MIA PaCa-2), wild-type K-ras (BxPC-3), and the immortal H6c7 cell line (pancreatic ductal epithelium) expressing K-ras oncogene (H6c7eR-KrasT) that is tumorigenic, were infected with a dominant/negative Rac1 construct (AdN17Rac1). In cells with mutant K-ras, AdN17Rac1 decreased rac activity, decreased superoxide levels, and inhibited in vitro growth. However in the BxPC-3 cell line, AdN17Rac1 did not change rac activity, superoxide levels, or in vitro cell growth. Additionally, AdN17Rac1 decreased superoxide levels and inhibited in vitro growth in the KrasT tumorigenic cell line, but had no effect in the immortalized H6c7 cell line. In human pancreatic tumor xenografts, intratumoral injections of AdN17Rac1 inhibited tumor growth. These results suggest that activation of Rac1-dependent superoxide generation leads to pancreatic cancer cell proliferation. In pancreatic cancer inhibition of Rac1 may be a potential therapeutic target. PMID:21037555

  17. Effect of metal conditioner on bonding of porcelain to cobalt-chromium alloy

    PubMed Central

    Kajihara, Yutaro; Takenouchi, Yoshihisa; Tanaka, Takuo; Suzuki, Shiro; Minami, Hiroyuki

    2016-01-01

    PURPOSE The purpose of this study was to evaluate the efficacy of two different metal conditioners for non-precious metal alloys for the bonding of porcelain to a cobalt-chromium (Co-Cr) alloy. MATERIALS AND METHODS Disk-shaped specimens (2.5×10.0 mm) were cast with Co-Cr alloy and used as adherend materials. The bonding surfaces were polished with a 600-grid silicon carbide paper and airborne-particle abraded using 110 µm alumina particles. Bonding specimens were fabricated by applying and firing either of the metal conditioners on the airborne-particle abraded surface, followed by firing porcelain into 5 mm in diameter and 3 mm in height. Specimens without metal conditioner were also fabricated. Shear bond strength for each group (n=8) were measured and compared (α=.05). Sectional view of bonding interface was observed by SEM. EDS analysis was performed to determine the chemical elements of metal conditioners and to determine the failure modes after shear test. RESULTS There were significant differences among three groups, and two metal conditioner-applied groups showed significantly higher values compared to the non-metal conditioner group. The SEM observation of the sectional view at bonding interface revealed loose contact at porcelain-alloy surface for non-metal conditioner group, however, close contact at both alloy-metal conditioner and metal conditioner-porcelain interfaces for both metal conditioner-applied groups. All the specimens showed mixed failures. EDS analysis showed that one metal conditioner was Si-based material, and another was Ti-based material. Si-based metal conditioner showed higher bond strengths compared to the Ti-based metal conditioner, but exhibited more porous failure surface failure. CONCLUSION Based on the results of this study, it can be stated that the application of metal conditioner is recommended for the bonding of porcelain to cobalt-chromium alloys. PMID:26949481

  18. Ubiquitination of Rac1 by inhibitors of apoptosis (IAPs).

    PubMed

    Oberoi-Khanuja, Tripat Kaur; Rajalingam, Krishnaraj

    2014-01-01

    Ubiquitination of proteins has emerged as a vital posttranslational modification at the crux of numerous signalling pathways, regulating them in various ways. Most members of the small GTPase family including Ras and Rho proteins are regulated by GEFs, GAPs, and RhoGDIs that modulate their cycling between the active and inactive states. Ubiquitination has added another layer to the regulation of small GTPases. Recently, we have uncovered that inhibitors of apoptosis (IAPs) function as direct E3 ubiquitin ligases for Rho GTPase Rac1 and target it for proteasomal degradation. Here, we describe in vitro and in vivo ubiquitination assays for detecting the conjugation of ubiquitin to Rac1 by XIAP and cIAP1.

  19. High Energy Efficiency Air Conditioning

    SciTech Connect

    Edward McCullough; Patrick Dhooge; Jonathan Nimitz

    2003-12-31

    This project determined the performance of a new high efficiency refrigerant, Ikon B, in a residential air conditioner designed to use R-22. The refrigerant R-22, used in residential and small commercial air conditioners, is being phased out of production in developed countries beginning this year because of concerns regarding its ozone depletion potential. Although a replacement refrigerant, R-410A, is available, it operates at much higher pressure than R-22 and requires new equipment. R-22 air conditioners will continue to be in use for many years to come. Air conditioning is a large part of expensive summer peak power use in many parts of the U.S. Previous testing and computer simulations of Ikon B indicated that it would have 20 - 25% higher coefficient of performance (COP, the amount of cooling obtained per energy used) than R-22 in an air-cooled air conditioner. In this project, a typical new R-22 residential air conditioner was obtained, installed in a large environmental chamber, instrumented, and run both with its original charge of R-22 and then with Ikon B. In the environmental chamber, controlled temperature and humidity could be maintained to obtain repeatable and comparable energy use results. Tests with Ikon B included runs with and without a power controller, and an extended run for several months with subsequent analyses to check compatibility of Ikon B with the air conditioner materials and lubricant. Baseline energy use of the air conditioner with its original R-22 charge was measured at 90 deg F and 100 deg F. After changeover to Ikon B and a larger expansion orifice, energy use was measured at 90 deg F and 100 deg F. Ikon B proved to have about 19% higher COP at 90 deg F and about 26% higher COP at 100 deg F versus R-22. Ikon B had about 20% lower cooling capacity at 90 deg F and about 17% lower cooling capacity at 100 deg F versus R-22 in this system. All results over multiple runs were within 1% relative standard deviation (RSD). All of these

  20. IAPs as E3 ligases of Rac1: shaping the move.

    PubMed

    Oberoi-Khanuja, Tripat Kaur; Rajalingam, Krishnaraj

    2012-01-01

    Inhibitors of Apoptosis Proteins (IAPs) are well-studied E3 ubiquitin ligases predominantly known for regulation of apoptosis. We uncovered that IAPs can function as a direct E3 ubiquitin ligase of RhoGTPase Rac1. cIAP1 and XIAP directly conjugate polyubiquitin chains to Lysine 147 of activated Rac1 and target it for proteasomal degradation. Consistently, loss of these IAPs by various strategies led to stabilization of Rac1 and mesenchymal mode of migration in tumor cells. IAPs also regulate Rac1 degradation upon RhoGDI1 depletion and CNF1 toxin treatment. Our observations revealed an evolutionarily conserved role of IAPs in regulating Rac1 stability shedding light on to the mechanisms behind ubiquitination-dependent inactivation of Rac1 signaling.

  1. Activated Rac1 requires gp130 for Stat3 activation, cell proliferation and migration

    SciTech Connect

    Arulanandam, Rozanne; Geletu, Mulu; Feracci, Helene; Raptis, Leda

    2010-03-10

    Rac1 (Rac) is a member of the Rho family of small GTPases which controls cell migration by regulating the organization of actin filaments. Previous results suggested that mutationally activated forms of the Rho GTPases can activate the Signal Transducer and Activator of Transcription-3 (Stat3), but the exact mechanism is a matter of controversy. We recently demonstrated that Stat3 activity of cultured cells increases dramatically following E-cadherin engagement. To better understand this pathway, we now compared Stat3 activity levels in mouse HC11 cells before and after expression of the mutationally activated Rac1 (Rac{sup V12}), at different cell densities. The results revealed for the first time a dramatic increase in protein levels and activity of both the endogenous Rac and Rac{sup V12} with cell density, which was due to inhibition of proteasomal degradation. In addition, Rac{sup V12}-expressing cells had higher Stat3, tyrosine-705 phosphorylation and activity levels at all densities, indicating that Rac{sup V12} is able to activate Stat3. Further examination of the mechanism of Stat3 activation showed that Rac{sup V12} expression caused a surge in mRNA of Interleukin-6 (IL6) family cytokines, known potent Stat3 activators. Knockdown of gp130, the common subunit of this family reduced Stat3 activity, indicating that these cytokines may be responsible for the Stat3 activation by Rac{sup V12}. The upregulation of IL6 family cytokines was required for cell migration and proliferation induced by Rac{sup V12}, as shown by gp130 knockdown experiments, thus demonstrating that the gp130/Stat3 axis represents an essential effector of activated Rac for the regulation of key cellular functions.

  2. Bacterial counts associated with sawdust and recycled manure bedding treated with commercial conditioners.

    PubMed

    Hogan, J S; Bogacz, V L; Thompson, L M; Romig, S; Schoenberger, P S; Weiss, W P; Smith, K L

    1999-08-01

    Bacteria counts associated with untreated organic bedding materials were compared with those of bedding treated with either an alkaline commercial bedding conditioner, acidic commercial bedding conditioner, or hydrated lime. Bedding materials were recycled manure and kiln-dried sawdust. The effects of bedding treatments on bacteria counts differed between bedding types. Each of the bedding treatments significantly reduced bacteria in recycled manure prior to use. The alkaline conditioner and hydrated lime effectively inhibited bacteria in recycled manure for 1 d. Bedding counts and teat swabs of cows housed on recycled manure treated with the alkaline conditioner were reduced on d 2. The use of the acid conditioner in recycled manure had little effect on bacteria in bedding. Sawdust differed from recycled manure in that bacteria in untreated sawdust prior to use were minimal, and populations increased rapidly during the first 2 d after use as bedding. The acid conditioner had a bacteriostatic effect in sawdust, evident by the reduction of bacteria on d 2. The alkaline conditioner and hydrated lime did not alter bacteria counts in sawdust compared with untreated sawdust. Antibacterial activity of each conditioner deteriorated between d 2 and d 6 in both beddings. The antibacterial activities of conditioners were related to the pH of bedding materials. The use of commercial bedding conditioners initially reduced bacterial counts; however, the antibacterial effects had diminished between d 2 and 6 after use in bedding. PMID:10480094

  3. Melatonin suppresses hypoxia-induced migration of HUVECs via inhibition of ERK/Rac1 activation.

    PubMed

    Yang, Ling; Zheng, Jianchao; Xu, Rui; Zhang, Yujie; Gu, Luo; Dong, Jing; Zhu, Yichao; Zhou, Ruijue; Zheng, Lu; Zhang, Xiaoying; Du, Jun

    2014-01-01

    Melatonin, a naturally-occurring hormone, possesses antioxidant properties and ameliorates vascular endothelial dysfunction. In this study, we evaluate the impact of melatonin on the migratory capability of human umbilical vein endothelial cells (HUVECs) to hypoxia and further investigate whether ERK/Rac1 signaling is involved in this process. Here, we found that melatonin inhibited hypoxia-stimulated hypoxia-inducible factor-1α (HIF-1α) expression and cell migration in a dose-dependent manner. Mechanistically, melatonin inhibited Rac1 activation and suppressed the co-localized Rac1 and F-actin on the membrane of HUVECs under hypoxic condition. In addition, the blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1-T17N suppressed HIF-1α expression and cell migration in response to hypoxia, as well, but constitutive activation of Rac1 mutant Rac1-V12 restored HIF-1α expression, preventing the inhibition of melatonin on cell migration. Furthermore, the anti-Rac1 effect of melatonin in HUVECs appeared to be associated with its inhibition of ERK phosphorylation, but not that of the PI3k/Akt signaling pathway. Taken together, our work indicates that melatonin exerts an anti-migratory effect on hypoxic HUVECs by blocking ERK/Rac1 activation and subsequent HIF-1α upregulation. PMID:25123138

  4. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

    PubMed Central

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  5. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas.

    PubMed

    Faria, Márcia; Capinha, Liliana; Simões-Pereira, Joana; Bugalho, Maria João; Silva, Ana Luísa

    2016-01-01

    RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. PMID:27127508

  6. Rac1 signaling regulates neutrophil-dependent tissue damage in experimental colitis.

    PubMed

    Yu, Changhui; Zhang, Su; Song, Lei; Wang, Yusheng; Hwaiz, Rundk; Luo, Lingtao; Thorlacius, Henrik

    2014-10-15

    Excessive neutrophil recruitment in the colon is a major feature in acute colitis although the signaling mechanisms behind colonic recruitment of neutrophils remain elusive. Herein, we hypothesized that Rac1 activity might play an important role in neutrophil infiltration in the inflamed colon. Female Balb/c mice were treated with the Rac1 inhibitor NSC23766 (0.5 and 5mg/kg) before and daily after administration of 5% dextran sodium sulfate (DSS). Colonic tissue was collected for quantification of neutrophil recruitment, interleukin-6 (IL-6) and CXC chemokine formation as well as histological damage score five days after challenge with DSS. Rac1 activity was determined by western blot and Mac-1 expression by flow cytometry in neutrophils. Administration of NSC23766 decreased DSS-induced neutrophil recruitment and tissue damage in the colon. Rac1 inhibition decreased colonic formation of IL-6 and CXC chemokines in experimental colitis. Chemokine challenge increased Rac1 activity in neutrophils and NSC23766 markedly reduced this neutrophil activity of Rac1. Inhibition of Rac1 abolished CXC chemokine-induced neutrophil chemotaxis and up-regulation of Mac-1 in vitro. Taken together, Rac1 signaling plays a significant role in controlling accumulation of neutrophils and tissue injury in experimental colitis. Thus, our novel results suggest that targeting Rac1 signaling might be a useful way to protect against neutrophil-mediated tissue injury in acute colitis.

  7. Cell module and fuel conditioner development

    NASA Technical Reports Server (NTRS)

    Hoover, D. Q., Jr.

    1982-01-01

    The phosphoric acid fuel cell module (stack) development which culminated in an 80 cell air-cooled stack with separated gas cooling and treed cooling plates is described. The performance of the 80 cell stack was approx. 100 mV per cell higher than that attained during phase 1. The components and materials performed stably for over 8000 hours in a 5 cell stack. The conceptual design of a fuel conditioning system is described.

  8. Advanced Signal Conditioners for Data-Acquisition Systems

    NASA Technical Reports Server (NTRS)

    Lucena, Angel; Perotti, Jose; Eckhoff, Anthony; Medelius, Pedro

    2004-01-01

    Signal conditioners embodying advanced concepts in analog and digital electronic circuitry and software have been developed for use in data-acquisition systems that are required to be compact and lightweight, to utilize electric energy efficiently, and to operate with high reliability, high accuracy, and high power efficiency, without intervention by human technicians. These signal conditioners were originally intended for use aboard spacecraft. There are also numerous potential terrestrial uses - especially in the fields of aeronautics and medicine, wherein it is necessary to monitor critical functions. Going beyond the usual analog and digital signal-processing functions of prior signal conditioners, the new signal conditioner performs the following additional functions: It continuously diagnoses its own electronic circuitry, so that it can detect failures and repair itself (as described below) within seconds. It continuously calibrates itself on the basis of a highly accurate and stable voltage reference, so that it can continue to generate accurate measurement data, even under extreme environmental conditions. It repairs itself in the sense that it contains a micro-controller that reroutes signals among redundant components as needed to maintain the ability to perform accurate and stable measurements. It detects deterioration of components, predicts future failures, and/or detects imminent failures by means of a real-time analysis in which, among other things, data on its present state are continuously compared with locally stored historical data. It minimizes unnecessary consumption of electric energy. The design architecture divides the signal conditioner into three main sections: an analog signal section, a digital module, and a power-management section. The design of the analog signal section does not follow the traditional approach of ensuring reliability through total redundancy of hardware: Instead, following an approach called spare parts tool box, the

  9. Will RAC change RCM? Hospital leaders are gearing up for the potential of RAC audits to impact the revenue cycle management process.

    PubMed

    Wagner, Steven K

    2010-05-01

    Hospital leaders making headway in anticipating the potential impact of possible RAC audits under the Medicare program are examining their revenue cycle management programs and making those RCM programs more rigorous and specific. Hospitals with experience in the early federal RAC audit demonstration project have accumulated numerous learnings from their participation in the early demo project. One clear learning has been the significant financial impact of going through a RAC audit. CIOs will need to work closely and productively with CFOs, health information management professionals, and others, in order to drill down to the levels at which revenue cycle management programs needto be examined in order to strengthen their effectiveness.

  10. Dimensional stability and weight changes of tissue conditioners.

    PubMed

    Murata, H; Kawamura, M; Hamada, T; Saleh, S; Kresnoadi, U; Toki, K

    2001-10-01

    The dimensional stability of tissue conditioners characterizes the ability of the materials to yield accurate functional impressions of oral mucosa. This study evaluated the linear dimensional changes with time of six tissue conditioners (COE Comfort, FITT, GC Soft-Liner, Hydro-Cast, SR-Ivoseal and Visco-Gel) using a travelling microscope, and relationship between these changes and weight changes. The absorption and solubility of these materials were also determined. The percentage changes in dimension and weight in water storage were measured at 2 (baseline), 8 and 24 h, and 2, 4, 7, 14 and 21 days after specimen preparation. All materials except SR-Ivoseal exhibited shrinkage and weight loss during water storage, whilst SR-Ivoseal exhibited expansion and an increase in weight. The percentage solubility for all materials except SR-Ivoseal was higher than the percentage absorption. A positive linear relationship was found between the percentage changes in linear dimension and those in weight (r=0.797 - 0.986, P < 0.05). Water absorption and solubility of the materials were found to be associated with dimensional changes. The results suggest that the period recommended for forming functional impressions would be 24 h after insertion in the mouth. In addition, it is important to select tissue conditioners suitable for functional impressions because of the wide ranges of dimensional stability among the materials. PMID:11737562

  11. Dimensional stability and weight changes of tissue conditioners.

    PubMed

    Murata, H; Kawamura, M; Hamada, T; Saleh, S; Kresnoadi, U; Toki, K

    2001-10-01

    The dimensional stability of tissue conditioners characterizes the ability of the materials to yield accurate functional impressions of oral mucosa. This study evaluated the linear dimensional changes with time of six tissue conditioners (COE Comfort, FITT, GC Soft-Liner, Hydro-Cast, SR-Ivoseal and Visco-Gel) using a travelling microscope, and relationship between these changes and weight changes. The absorption and solubility of these materials were also determined. The percentage changes in dimension and weight in water storage were measured at 2 (baseline), 8 and 24 h, and 2, 4, 7, 14 and 21 days after specimen preparation. All materials except SR-Ivoseal exhibited shrinkage and weight loss during water storage, whilst SR-Ivoseal exhibited expansion and an increase in weight. The percentage solubility for all materials except SR-Ivoseal was higher than the percentage absorption. A positive linear relationship was found between the percentage changes in linear dimension and those in weight (r=0.797 - 0.986, P < 0.05). Water absorption and solubility of the materials were found to be associated with dimensional changes. The results suggest that the period recommended for forming functional impressions would be 24 h after insertion in the mouth. In addition, it is important to select tissue conditioners suitable for functional impressions because of the wide ranges of dimensional stability among the materials.

  12. Air Conditioning Overflow Sensor

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The Technology Transfer Office at Stennis Space Center helped a local inventor develop a prototype of an attachment for central air conditioners and heat pumps that helps monitor water levels to prevent condensation overflow. The sensor will indicate a need for drain line maintenance and prevent possible damage caused by drain pan water spillover. An engineer in the Stennis Space Center prototype Development Laboratory used SSC sensor technology in the development of the sensor.

  13. Functional characterization and cellular dynamics of the CDC-42 - RAC - CDC-24 module in Neurospora crassa.

    PubMed

    Araujo-Palomares, Cynthia L; Richthammer, Corinna; Seiler, Stephan; Castro-Longoria, Ernestina

    2011-01-01

    Rho-type GTPases are key regulators that control eukaryotic cell polarity, but their role in fungal morphogenesis is only beginning to emerge. In this study, we investigate the role of the CDC-42 - RAC - CDC-24 module in Neurospora crassa. rac and cdc-42 deletion mutants are viable, but generate highly compact colonies with severe morphological defects. Double mutants carrying conditional and loss of function alleles of rac and cdc-42 are lethal, indicating that both GTPases share at least one common essential function. The defects of the GTPase mutants are phenocopied by deletion and conditional alleles of the guanine exchange factor (GEF) cdc-24, and in vitro GDP-GTP exchange assays identify CDC-24 as specific GEF for both CDC-42 and RAC. In vivo confocal microscopy shows that this module is organized as membrane-associated cap that covers the hyphal apex. However, the specific localization patterns of the three proteins are distinct, indicating different functions of RAC and CDC-42 within the hyphal tip. CDC-42 localized as confined apical membrane-associated crescent, while RAC labeled a membrane-associated ring excluding the region labeled by CDC42. The GEF CDC-24 occupied a strategic position, localizing as broad apical membrane-associated crescent and in the apical cytosol excluding the Spitzenkörper. RAC and CDC-42 also display distinct localization patterns during branch initiation and germ tube formation, with CDC-42 accumulating at the plasma membrane before RAC. Together with the distinct cellular defects of rac and cdc-42 mutants, these localizations suggest that CDC-42 is more important for polarity establishment, while the primary function of RAC may be maintaining polarity. In summary, this study identifies CDC-24 as essential regulator for RAC and CDC-42 that have common and distinct functions during polarity establishment and maintenance of cell polarity in N. crassa.

  14. New insights into the dimerization of small GTPase Rac/ROP guanine nucleotide exchange factors in rice

    PubMed Central

    Akamatsu, Akira; Uno, Kazumi; Kato, Midori; Wong, Hann Ling; Shimamoto, Ko; Kawano, Yoji

    2015-01-01

    Molecular links between receptor-kinases and Rac/ROP family small GTPases mediated by activator guanine nucleotide exchange factors (GEFs) govern diverse biological processes. However, it is unclear how the Rac/ROP GTPases orchestrate such a wide variety of activities. Here, we show that rice OsRacGEF1 forms homodimers, and heterodimers with OsRacGEF2, at the plasma membrane (PM) and the endoplasmic reticulum (ER). OsRacGEF2 does not bind directly to the receptor-like kinase (RLK) OsCERK1, but forms a complex with OsCERK1 through OsRacGEF1 at the ER. This complex is transported from ER to the PM and there associates with OsRac1, resulting in the formation of a stable immune complex. Such RLK-GEF heterodimer complexes may explain the diversity of Rac/ROP family GTPase signalings. PMID:26251883

  15. MYADM regulates Rac1 targeting to ordered membranes required for cell spreading and migration.

    PubMed

    Aranda, Juan F; Reglero-Real, Natalia; Kremer, Leonor; Marcos-Ramiro, Beatriz; Ruiz-Sáenz, Ana; Calvo, María; Enrich, Carlos; Correas, Isabel; Millán, Jaime; Alonso, Miguel A

    2011-04-15

    Membrane organization into condensed domains or rafts provides molecular platforms for selective recruitment of proteins. Cell migration is a general process that requires spatiotemporal targeting of Rac1 to membrane rafts. The protein machinery responsible for making rafts competent to recruit Rac1 remains elusive. Some members of the MAL family of proteins are involved in specialized processes dependent on this type of membrane. Because condensed membrane domains are a general feature of the plasma membrane of all mammalian cells, we hypothesized that MAL family members with ubiquitous expression and plasma membrane distribution could be involved in the organization of membranes for cell migration. We show that myeloid-associated differentiation marker (MYADM), a protein with unique features within the MAL family, colocalizes with Rac1 in membrane protrusions at the cell surface and distributes in condensed membranes. MYADM knockdown (KD) cells had altered membrane condensation and showed deficient incorporation of Rac1 to membrane raft fractions and, similar to Rac1 KD cells, exhibited reduced cell spreading and migration. Results of rescue-of-function experiments by expression of MYADM or active Rac1L61 in cells knocked down for Rac1 or MYADM, respectively, are consistent with the idea that MYADM and Rac1 act on parallel pathways that lead to similar functional outcomes. PMID:21325632

  16. Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle.

    PubMed

    Sylow, Lykke; Jensen, Thomas E; Kleinert, Maximilian; Mouatt, Joshua R; Maarbjerg, Stine J; Jeppesen, Jacob; Prats, Clara; Chiu, Tim T; Boguslavsky, Shlomit; Klip, Amira; Schjerling, Peter; Richter, Erik A

    2013-04-01

    In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (~60-100%) and humans (~40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20-58% in extensor digitorum longus (EDL; P < 0.01). In agreement, the contraction-stimulated increment in glucose uptake was decreased by 27% (P = 0.1) and 40% (P < 0.05) in soleus and EDL muscles, respectively, of muscle-specific inducible Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P < 0.01) in soleus and EDL muscles, respectively. These are the first data to show that Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake.

  17. Genetic structure and evolution of RAC-GTPases in Arabidopsis thaliana.

    PubMed Central

    Winge, P; Brembu, T; Kristensen, R; Bones, A M

    2000-01-01

    Rho GTPases regulate a number of important cellular functions in eukaryotes, such as organization of the cytoskeleton, stress-induced signal transduction, cell death, cell growth, and differentiation. We have conducted an extensive screening, characterization, and analysis of genes belonging to the Ras superfamily of GTPases in land plants (embryophyta) and found that the Rho family is composed mainly of proteins with homology to RAC-like proteins in terrestrial plants. Here we present the genomic and cDNA sequences of the RAC gene family from the plant Arabidopsis thaliana. On the basis of amino acid alignments and genomic structure comparison of the corresponding genes, the 11 encoded AtRAC proteins can be divided into two distinct groups of which one group apparently has evolved only in vascular plants. Our phylogenetic analysis suggests that the plant RAC genes underwent a rapid evolution and diversification prior to the emergence of the embryophyta, creating a group that is distinct from rac/cdc42 genes in other eukaryotes. In embryophyta, RAC genes have later undergone an expansion through numerous large gene duplications. Five of these RAC duplications in Arabidopsis thaliana are reported here. We also present an hypothesis suggesting that the characteristic RAC proteins in higher plants have evolved to compensate the loss of RAS proteins. PMID:11102387

  18. 44 CFR 352.23 - Functions of a Regional Assistance Committee (RAC).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Under 44 CFR part 351, the role of a RAC is to assist State and local government officials to develop.... (b) Prior to a determination under subpart A (44 CFR 352.6(d)) that Federal facilities and resources... under subpart A (44 CFR 352.6(d)) that Federal facilities and resources are needed, the RAC will...

  19. 44 CFR 352.23 - Functions of a Regional Assistance Committee (RAC).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Under 44 CFR part 351, the role of a RAC is to assist State and local government officials to develop.... (b) Prior to a determination under subpart A (44 CFR 352.6(d)) that Federal facilities and resources... under subpart A (44 CFR 352.6(d)) that Federal facilities and resources are needed, the RAC will...

  20. IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation.

    PubMed

    Oberoi, Tripat Kaur; Dogan, Taner; Hocking, Jennifer C; Scholz, Rolf-Peter; Mooz, Juliane; Anderson, Carrie L; Karreman, Christiaan; Meyer zu Heringdorf, Dagmar; Schmidt, Gudula; Ruonala, Mika; Namikawa, Kazuhiko; Harms, Gregory S; Carpy, Alejandro; Macek, Boris; Köster, Reinhard W; Rajalingam, Krishnaraj

    2012-01-01

    Inhibitors of apoptosis proteins (IAPs) are a highly conserved class of multifunctional proteins. Rac1 is a well-studied Rho GTPase that controls numerous basic cellular processes. While the regulation of nucleotide binding to Rac1 is well understood, the molecular mechanisms controlling Rac1 degradation are not known. Here, we demonstrate X-linked IAP (XIAP) and cellular IAP1 (c-IAP1) directly bind to Rac1 in a nucleotide-independent manner to promote its polyubiquitination at Lys147 and proteasomal degradation. These IAPs are also required for degradation of Rac1 upon CNF1 toxin treatment or RhoGDI depletion. Consistently, downregulation of XIAP or c-IAP1 by various strategies led to an increase in Rac1 protein levels in primary and tumour cells, leading to an elongated morphology and enhanced cell migration. Further, XIAP counteracts Rac1-dependent cellular polarization in the developing zebrafish hindbrain and promotes the delamination of neurons from the normal tissue architecture. These observations unveil an evolutionarily conserved role of IAPs in controlling Rac1 stability thereby regulating the plasticity of cell migration and morphogenesis.

  1. Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.

    PubMed

    Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin

    2016-10-01

    Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders.

  2. Mitochondrial Dysfunction in Human Leukemic Stem/Progenitor Cells upon Loss of RAC2

    PubMed Central

    Capala, Marta E.; Maat, Henny; Bonardi, Francesco; van den Boom, Vincent; Kuipers, Jeroen; Vellenga, Edo; Giepmans, Ben N. G.; Schuringa, Jan Jacob

    2015-01-01

    Leukemic stem cells (LSCs) reside within bone marrow niches that maintain their relatively quiescent state and convey resistance to conventional treatment. Many of the microenvironmental signals converge on RAC GTPases. Although it has become clear that RAC proteins fulfill important roles in the hematopoietic compartment, little has been revealed about the downstream effectors and molecular mechanisms. We observed that in BCR-ABL-transduced human hematopoietic stem/progenitor cells (HSPCs) depletion of RAC2 but not RAC1 induced a marked and immediate decrease in proliferation, progenitor frequency, cobblestone formation and replating capacity, indicative for reduced self-renewal. Cell cycle analyses showed reduced cell cycle activity in RAC2-depleted BCR-ABL leukemic cobblestones coinciding with an increased apoptosis. Moreover, a decrease in mitochondrial membrane potential was observed upon RAC2 downregulation, paralleled by severe mitochondrial ultrastructural malformations as determined by automated electron microscopy. Proteome analysis revealed that RAC2 specifically interacted with a set of mitochondrial proteins including mitochondrial transport proteins SAM50 and Metaxin 1, and interactions were confirmed in independent co-immunoprecipitation studies. Downregulation of SAM50 also impaired the proliferation and replating capacity of BCR-ABL-expressing cells, again associated with a decreased mitochondrial membrane potential. Taken together, these data suggest an important role for RAC2 in maintaining mitochondrial integrity. PMID:26016997

  3. Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.

    PubMed

    Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin

    2016-10-01

    Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. PMID:27329554

  4. 76 FR 17106 - Secure Rural Schools Resource Advisory Committee (RAC) Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... Forest Service Secure Rural Schools Resource Advisory Committee (RAC) Meeting AGENCY: Forest Service, U.S... the Secure Rural Schools Act and Community Self-Determination Act, Public Law 110-343. SUMMARY: On... Schools Resource Advisory Committee (RAC). The public is invited to attend the meeting and provide...

  5. 77 FR 11127 - Medicaid Program; Announcement of Medicaid Recovery Audit Contractors (RACs) Contingency Fee Update

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... FR 57808), we published a final rule entitled: ``Medicaid Program; Recovery Audit Contractors.'' This... Medicaid RAC programs. In the September 16, 2011 Federal Register (76 FR 57808), we published a final rule... Recovery Audit Contractors (RACs) Contingency Fee Update AGENCY: Centers for Medicare & Medicaid...

  6. A Critical Role for Rac1 in Tumor Progression of Human Colorectal Adenocarcinoma Cells

    PubMed Central

    Espina, Carolina; Céspedes, María Virtudes; García-Cabezas, Miguel Angel; del Pulgar, María Teresa Gómez; Boluda, Alicia; Oroz, Lourdes García; Cejas, Paloma; Nistal, Manuel; Mangues, Ramón; Lacal, Juan Carlos

    2008-01-01

    Colorectal adenocarcinoma is the second cause of cancer mortality in developed countries. Rac1 is a member of the family of Rho GTPases that regulates many intracellular signaling pathways, including those involved in tumorigenesis, invasion, and metastasis. We have investigated the role of Rac1 in colorectal tumor progression by genetic modification of the human colorectal adenocarcinoma cell line SW620 to either overexpress Rac1 or lack Rac1 expression. Tumor behavior was studied by orthotopic injection of stably modified cell lines into the cecal wall of athymic nude mice, a model that replicates the histopathological appearance and clinical behavior of human colorectal adenocarcinoma in humans. While overexpression of Rac1 resulted in an accelerated tumorigenic process, inducing a faster mortality rate, inhibition of Rac1 completely suppressed tumor formation. These results suggest that Rac1 plays a major role in colorectal adenocarcinoma progression. Finally, interference with Rac1 function may provide an important tool to block the malignant phenotype of colorectal adenocarcinoma cells. PMID:18165265

  7. Inhibition of Rac controls NPM-ALK-dependent lymphoma development and dissemination.

    PubMed

    Colomba, A; Giuriato, S; Dejean, E; Thornber, K; Delsol, G; Tronchère, H; Meggetto, F; Payrastre, B; Gaits-Iacovoni, F

    2011-06-01

    Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM-ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM-ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM-ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas.

  8. Aegeline from Aegle marmelos stimulates glucose transport via Akt and Rac1 signaling, and contributes to a cytoskeletal rearrangement through PI3K/Rac1.

    PubMed

    Gautam, Sudeep; Ishrat, Nayab; Singh, Rohit; Narender, Tadigoppula; Srivastava, Arvind K

    2015-09-01

    Aegeline is an alkaloidal-amide, isolated from the leaves of Aegle marmelos and have shown antihyperglycemic as well as antidyslipidemic activities in the validated animal models of type 2 diabetes mellitus. Here we delineate, aegeline enhanced GLUT4 translocation mediated 2-deoxy-glucose uptake in both time and concentration-dependent manner. 2-deoxy-glucose uptake was completely stymied by the transport inhibitors (wortmannin and genistein) in C2C12 myotubes. Pharmacological inhibition of Akt (also known as protein kinase B) and Ras-related C3 botulinum toxin substrate 1 (Rac1) suggest that both Akt and Rac1 operate aegeline-stimulated glucose transport via distinct parallel pathways. Moreover, aegeline activates p21 protein-activated kinase 1 (PAK1) and cofilin (an actin polymerization regulator). Rac1 inhibitor (Rac1 inhib II) and PAK1 inhibitor (IPA-3) completely blocked aegeline-induced phosphorylation of cofilin and p21 protein-activated kinase 1 (PAK1). In summary, these findings suggest that aegeline stimulates the glucose transport through Akt and Rac1 dependent distinct parallel pathways and have cytoskeletal roles via stimulation of the PI3-kinase-Rac1-PAK1-cofilin pathway in the skeletal muscle cells. Therefore, multiple targets of aegeline in the improvement of insulin sensitivity of the skeletal muscle cells may be suggested. PMID:26102565

  9. Aegeline from Aegle marmelos stimulates glucose transport via Akt and Rac1 signaling, and contributes to a cytoskeletal rearrangement through PI3K/Rac1.

    PubMed

    Gautam, Sudeep; Ishrat, Nayab; Singh, Rohit; Narender, Tadigoppula; Srivastava, Arvind K

    2015-09-01

    Aegeline is an alkaloidal-amide, isolated from the leaves of Aegle marmelos and have shown antihyperglycemic as well as antidyslipidemic activities in the validated animal models of type 2 diabetes mellitus. Here we delineate, aegeline enhanced GLUT4 translocation mediated 2-deoxy-glucose uptake in both time and concentration-dependent manner. 2-deoxy-glucose uptake was completely stymied by the transport inhibitors (wortmannin and genistein) in C2C12 myotubes. Pharmacological inhibition of Akt (also known as protein kinase B) and Ras-related C3 botulinum toxin substrate 1 (Rac1) suggest that both Akt and Rac1 operate aegeline-stimulated glucose transport via distinct parallel pathways. Moreover, aegeline activates p21 protein-activated kinase 1 (PAK1) and cofilin (an actin polymerization regulator). Rac1 inhibitor (Rac1 inhib II) and PAK1 inhibitor (IPA-3) completely blocked aegeline-induced phosphorylation of cofilin and p21 protein-activated kinase 1 (PAK1). In summary, these findings suggest that aegeline stimulates the glucose transport through Akt and Rac1 dependent distinct parallel pathways and have cytoskeletal roles via stimulation of the PI3-kinase-Rac1-PAK1-cofilin pathway in the skeletal muscle cells. Therefore, multiple targets of aegeline in the improvement of insulin sensitivity of the skeletal muscle cells may be suggested.

  10. Regulation of Synaptic Rac1 Activity, Long-Term Potentiation Maintenance, and Learning and Memory by BCR and ABR Rac GTPase-Activating Proteins

    PubMed Central

    Oh, Daeyoung; Han, Seungnam; Seo, Jinsoo; Lee, Jae-Ran; Choi, Jeonghoon; Groffen, John; Kim, Karam; Cho, Yi Sul; Choi, Han-Saem; Shin, Hyewon; Woo, Jooyeon; Won, Hyejung; Park, Soon Kwon; Kim, Soo-Young; Jo, Jihoon; Whitcomb, Daniel J.; Cho, Kwangwook; Kim, Hyun; Bae, Yong Chul; Heisterkamp, Nora; Choi, Se-Young; Kim, Eunjoon

    2016-01-01

    Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer’s disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-positive chronic myelogenous leukemia. Despite the fact that BCR mRNAs are abundantly expressed in the brain, the neural functions of BCR protein have remained obscure. We report here that BCR and its close relative active BCR-related (ABR) localize at excitatory synapses and directly interact with PSD-95, an abundant postsynaptic scaffolding protein. Mice deficient for BCR or ABR show enhanced basal Rac1 activity but only a small increase in spine density. Importantly, mice lacking BCR or ABR exhibit a marked decrease in the maintenance, but not induction, of long-term potentiation, and show impaired spatial and object recognition memory. These results suggest that BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions. PMID:20962234

  11. Inhibition of Rac1 activity by controlled release of NSC23766 from chitosan microspheres effectively ameliorates osteoarthritis development in vivo

    PubMed Central

    Zhu, Shouan; Lu, Ping; Liu, Huanhuan; Chen, Pengfei; Wu, Yan; Wang, Yanyan; Sun, Heng; Zhang, Xiaolei; Xia, Qingqing; Heng, Boon Chin; Zhou, Yiting; Ouyang, Hong Wei

    2015-01-01

    Background Osteoarthritis (OA) is a degenerative joint disease characterised by cartilage degradation and chondrocyte hypertrophy. A recent study showed that Rac1 promoted expression of MMP13 and chondrocyte hypertrophy within the growth plate. These findings warrant further investigations on the roles of Rac1 in OA development and therapy in animal models. Objective To investigate the role and mechanistic pathway of Rac1 involvement in pathological changes of OA chondrocytes in vitro and OA development in vivo, as well as to develop a strategy of modulating Rac1 activity for OA treatment. Material and methods OA and normal cartilage from human or mice were used for immunohistochemical study and Rac1 activity assay. Chondrocytes treated with IL1β and the untreated control were subjected to the Rac1 activity assay. Chondrocytes transfected with CA-Rac1, DN-Rac1 or GFP were cultured under conditions for inducing calcification. To evaluate the effect of Rac1 in OA development, an OA model was created by anterior cruciate ligament transection in mice. CA-Rac1, DN-Rac1 and GFP lentivirus, or NSC23766, were injected intra-articularly. Joints were subjected to histological analysis. Results It was found that there is aberrant Rac1 activation in human OA cartilage. Rac1 activity could also be elevated by IL1β. Additionally, activated Rac1 promoted expression of MMP13, ADAMTS-5 and COLX by chondrocytes, partially through the β-catenin pathway. Moreover, activation of Rac1 in knee joints by CA-Rac1 lentivirus accelerated OA progression, while inhibition of Rac1 activity by DN-Rac1 lentivirus or Rac1 inhibitor NSC23766 delayed OA development. Therefore, we developed a strategy of controlled release of NSC23766 from chitosan microspheres to OA joints, which effectively protected cartilage from destruction. Conclusions These findings demonstrated that Rac1 activity is implicated in OA development. Also, controlled release of Rac1 inhibitor is a promising strategy for OA

  12. Hippocampal Activation of Rac1 Regulates the Forgetting of Object Recognition Memory.

    PubMed

    Liu, Yunlong; Du, Shuwen; Lv, Li; Lei, Bo; Shi, Wei; Tang, Yikai; Wang, Lianzhang; Zhong, Yi

    2016-09-12

    Forgetting is a universal feature for most types of memories. The best-defined and extensively characterized behaviors that depict forgetting are natural memory decay and interference-based forgetting [1, 2]. Molecular mechanisms underlying the active forgetting remain to be determined for memories in vertebrates. Recent progress has begun to unravel such mechanisms underlying the active forgetting [3-11] that is induced through the behavior-dependent activation of intracellular signaling pathways. In Drosophila, training-induced activation of the small G protein Rac1 mediates natural memory decay and interference-based forgetting of aversive conditioning memory [3]. In mice, the activation of photoactivable-Rac1 in recently potentiated spines in a motor learning task erases the motor memory [12]. These lines of evidence prompted us to investigate a role for Rac1 in time-based natural memory decay and interference-based forgetting in mice. The inhibition of Rac1 activity in hippocampal neurons through targeted expression of a dominant-negative Rac1 form extended object recognition memory from less than 72 hr to over 72 hr, whereas Rac1 activation accelerated memory decay within 24 hr. Interference-induced forgetting of this memory was correlated with Rac1 activation and was completely blocked by inhibition of Rac1 activity. Electrophysiological recordings of long-term potentiation provided independent evidence that further supported a role for Rac1 activation in forgetting. Thus, Rac1-dependent forgetting is evolutionarily conserved from invertebrates to vertebrates.

  13. Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion

    PubMed Central

    Krtková, Jana; Thomas, Elizabeth B.; Alas, Germain C. M.; Schraner, Elisabeth M.; Behjatnia, Habib R.; Hehl, Adrian B.

    2016-01-01

    ABSTRACT Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia’s sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-RacCA) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-RacCA-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis. PMID:27555307

  14. Hippocampal Activation of Rac1 Regulates the Forgetting of Object Recognition Memory.

    PubMed

    Liu, Yunlong; Du, Shuwen; Lv, Li; Lei, Bo; Shi, Wei; Tang, Yikai; Wang, Lianzhang; Zhong, Yi

    2016-09-12

    Forgetting is a universal feature for most types of memories. The best-defined and extensively characterized behaviors that depict forgetting are natural memory decay and interference-based forgetting [1, 2]. Molecular mechanisms underlying the active forgetting remain to be determined for memories in vertebrates. Recent progress has begun to unravel such mechanisms underlying the active forgetting [3-11] that is induced through the behavior-dependent activation of intracellular signaling pathways. In Drosophila, training-induced activation of the small G protein Rac1 mediates natural memory decay and interference-based forgetting of aversive conditioning memory [3]. In mice, the activation of photoactivable-Rac1 in recently potentiated spines in a motor learning task erases the motor memory [12]. These lines of evidence prompted us to investigate a role for Rac1 in time-based natural memory decay and interference-based forgetting in mice. The inhibition of Rac1 activity in hippocampal neurons through targeted expression of a dominant-negative Rac1 form extended object recognition memory from less than 72 hr to over 72 hr, whereas Rac1 activation accelerated memory decay within 24 hr. Interference-induced forgetting of this memory was correlated with Rac1 activation and was completely blocked by inhibition of Rac1 activity. Electrophysiological recordings of long-term potentiation provided independent evidence that further supported a role for Rac1 activation in forgetting. Thus, Rac1-dependent forgetting is evolutionarily conserved from invertebrates to vertebrates. PMID:27593377

  15. Rac1 modulates acute and subacute genotoxin-induced hepatic stress responses, fibrosis and liver aging

    PubMed Central

    Bopp, A; Wartlick, F; Henninger, C; Kaina, B; Fritz, G

    2013-01-01

    To investigate the importance of the Ras-homologous GTPase Rac1 for the hepatic response to genotoxic insults and liver aging, rac1 was deleted in liver of mice by Mx1-Cre-based recombination. Knockout of rac1 caused complex changes in basal as well as doxorubicin and ionizing radiation-induced mRNA expression of various genotoxic stress response-related genes, including hspa1b, rad51, wrn and xpc. Rac1 deletion protected the liver from acute toxicity following doxorubicin treatment. Moreover, the level of S139 phosphorylated histone H2AX (γH2AX), which is indicative of DNA damage, and mRNA expression of pro-inflammatory (IL-6) and pro-fibrotic (CTGF, TGFβ, αSMA) factors were mitigated in rac1 knockout animals. By contrast, lack of rac1 promoted subacute hepatotoxicity, which was determined 3 weeks after injection of multiple low doses of doxorubicin by assaying the γH2AX level, mitotic index and pro-fibrotic gene expression. Regarding ionizing radiation, rac1 deficiency had no major effects on DNA damage induction or acute pro-inflammatory and pro-fibrotic stress responses. Mice lacking hepatic rac1 for extended period of time (15 months) revealed increased mRNA expression of fibrosis-related factors (CTGF, TGFβ, collagen, MMP1) and fibrotic tissue remodeling. In addition, protein expression of the senescence marker p16 was enhanced in the absence of rac1. Taken together, the data provide evidence that Rac1 is required for doxorubicin-induced DNA damage induction. It is also involved in both the acute and delayed inflammatory and fibrotic stress response in the liver following doxorubicin, but not ionizing radiation, treatment and, furthermore, protects against endogenous liver aging. PMID:23519127

  16. Locally produced natural conditioners for dewatering of faecal sludge.

    PubMed

    Gold, Moritz; Dayer, Pauline; Faye, Marie Christine Amie Sene; Clair, Guillaume; Seck, Alsane; Niang, Seydou; Morgenroth, Eberhard; Strande, Linda

    2016-11-01

    In urban areas of low-income countries, treatment of faecal sludge (FS) is insufficient or non-existent. This results in large amounts of FS being dumped into the environment. Existing treatment technologies for FS, such as settling-thickening tanks and drying beds, are land intensive which is limiting in urban areas. Enhanced settling and dewatering by conditioning was evaluated in order to reduce the treatment footprint (or increase treatment capacity). Conventional wastewater conditioners, such as commercially available lime and polymers, are expensive, and commonly rely on complex supply chains for use in low-income countries. Therefore, the treatment performance of five conditioners which could be produced locally was evaluated: Moringa oleifera seeds and press cake, Jatropha curcas seeds, Jatropha Calotropis leaves and chitosan. M. oleifera seeds and press cake, and chitosan improved settling and dewatering and had a similar performance compared to lime and polymers. Optimal dosages were 400-500 kg M. oleifera/t TS, 300-800 kg lime/t TS and 25-50 kg polymer solution/t TS. In comparison, chitosan required 1.5-3.75 kg/t TS. These dosages are comparable to those recommended for wastewater (sludge). The results indicate that conditioning of FS can reduce total suspended solids (TSS) in the effluent of settling-thickening tanks by 22-81% and reduce dewatering time with drying beds by 59-97%. This means that the area of drying beds could be reduced by 59-97% with end-use as soil conditioner, or 9-26% as solid fuel. Least expensive options and availability will depend on the local context. In Dakar, Senegal, chitosan produced from shrimp waste appears to be most promising. PMID:26984372

  17. Locally produced natural conditioners for dewatering of faecal sludge

    PubMed Central

    Gold, Moritz; Dayer, Pauline; Faye, Marie Christine Amie Sene; Clair, Guillaume; Seck, Alsane; Niang, Seydou; Morgenroth, Eberhard; Strande, Linda

    2016-01-01

    ABSTRACT In urban areas of low-income countries, treatment of faecal sludge (FS) is insufficient or non-existent. This results in large amounts of FS being dumped into the environment. Existing treatment technologies for FS, such as settling-thickening tanks and drying beds, are land intensive which is limiting in urban areas. Enhanced settling and dewatering by conditioning was evaluated in order to reduce the treatment footprint (or increase treatment capacity). Conventional wastewater conditioners, such as commercially available lime and polymers, are expensive, and commonly rely on complex supply chains for use in low-income countries. Therefore, the treatment performance of five conditioners which could be produced locally was evaluated: Moringa oleifera seeds and press cake, Jatropha curcas seeds, Jatropha Calotropis leaves and chitosan. M. oleifera seeds and press cake, and chitosan improved settling and dewatering and had a similar performance compared to lime and polymers. Optimal dosages were 400–500 kg M. oleifera/t TS, 300–800 kg lime/t TS and 25–50 kg polymer solution/t TS. In comparison, chitosan required 1.5–3.75 kg/t TS. These dosages are comparable to those recommended for wastewater (sludge). The results indicate that conditioning of FS can reduce total suspended solids (TSS) in the effluent of settling-thickening tanks by 22–81% and reduce dewatering time with drying beds by 59–97%. This means that the area of drying beds could be reduced by 59–97% with end-use as soil conditioner, or 9–26% as solid fuel. Least expensive options and availability will depend on the local context. In Dakar, Senegal, chitosan produced from shrimp waste appears to be most promising. PMID:26984372

  18. Polysaccharide (guar) as a soil conditioner. [Cyamopsis tetragonoloba

    SciTech Connect

    Wallace, A.

    1986-05-01

    The author tested a polysaccharide (guar) derived from guar bean (Cyamopsis tetragonoloba L. Taub.) was tested in soil flocculation tests and found that use of acid solutions to fully dissolve the guar leads to more effective soil conditioning than otherwise would be possible, and that guar does not lead to strong water-stable aggregates. Larger quantities were needed to improve emergence and growth of plants in a glasshouse than for synthetic soil conditioners. The effects of soil conditioning with guar did not last long.

  19. The GTPase Rac regulates the proliferation and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients.

    PubMed

    Chan, Amanda; Akhtar, Mumtaz; Brenner, Max; Zheng, Yi; Gulko, Percio S; Symons, Marc

    2007-01-01

    Fibroblast-like synoviocytes (FLS) isolated from joints of rheumatoid arthritis (RA) patients display proliferative and invasive properties reminiscent of those of malignant tumor cells. Rac small GTPases play an important role in tumor cell proliferation and invasion. We therefore investigated the potential role of Rac proteins in the proliferative and invasive behavior of RA-FLS. We showed that inhibiting Rac activity with the Rac-specific small molecule inhibitor NSC23766 causes a strong inhibition of RA-FLS proliferation, without affecting cell survival. Rac inhibition also results in a strong reduction in RA-FLS invasion through reconstituted extracellular matrix and a less marked inhibition of two-dimensional migration as measured by monolayer wound healing. We also showed that small interfering RNA-mediated depletion of Rac1 inhibits RA-FLS proliferation and invasion to a similar extent as NSC23766. These results demonstrate for the first time that Rac proteins play an important role in the aggressive behavior of FLS isolated from RA patients. In addition, we observed that inhibiting Rac proteins prevents JNK activation and that the JNK inhibitor SP600125 strongly inhibits RA-FLS invasion, suggesting that Rac-mediated JNK activation contributes to the role of Rac proteins in the invasive behavior of RA-FLS. In conclusion, Rac-controlled signaling pathways may present a new source of drug targets for therapeutic intervention in RA.

  20. Eiger-induced cell death relies on Rac1-dependent endocytosis

    PubMed Central

    Ruan, W; Srinivasan, A; Lin, S; Kara, k-I; Barker, P A

    2016-01-01

    Signaling via tumor necrosis factor receptor (TNFR) superfamily members regulates cellular life and death decisions. A subset of mammalian TNFR proteins, most notably the p75 neurotrophin receptor (p75NTR), induces cell death through a pathway that requires activation of c-Jun N-terminal kinases (JNKs). However the receptor-proximal signaling events that mediate this remain unclear. Drosophila express a single tumor necrosis factor (TNF) ligand termed Eiger (Egr) that activates JNK-dependent cell death. We have exploited this model to identify phylogenetically conserved signaling events that allow Egr to induce JNK activation and cell death in vivo. Here we report that Rac1, a small GTPase, is specifically required in Egr-mediated cell death. rac1 loss of function blocks Egr-induced cell death, whereas Rac1 overexpression enhances Egr-induced killing. We identify Vav as a GEF for Rac1 in this pathway and demonstrate that dLRRK functions as a negative regulator of Rac1 that normally acts to constrain Egr-induced death. Thus dLRRK loss of function increases Egr-induced cell death in the fly. We further show that Rac1-dependent entry of Egr into early endosomes is a crucial prerequisite for JNK activation and for cell death and show that this entry requires the activity of Rab21 and Rab7. These findings reveal novel regulatory mechanisms that allow Rac1 to contribute to Egr-induced JNK activation and cell death. PMID:27054336

  1. Cooperation of distinct Rac-dependent pathways to stabilise E-cadherin adhesion

    PubMed Central

    Erasmus, Jennifer C.; Welsh, Natalie J.; Braga, Vania M.M.

    2015-01-01

    The precise mechanisms via which Rac1 is activated by cadherin junctions are not fully known. In keratinocytes Rac1 activation by cadherin junctions requires EGFR signalling, but how EGFR does so is unclear. To address which activator could mediate E-cadherin signalling to Rac1, we investigated EGFR and two Rac1 GEFs, SOS1 and DOCK180. EGFR RNAi prevented junction-induced Rac1 activation and led to fragmented localization of E-cadherin at cadherin contacts. In contrast, depletion of another EGFR family member, ErbB3, did not interfere with either process. DOCK180 RNAi, but not SOS1, prevented E-cadherin-induced Rac1 activation. However, in a strong divergence from EGFR RNAi phenotype, DOCK180 depletion did not perturb actin recruitment or cadherin localisation at junctions. Rather, reduced DOCK180 levels impaired the resistance to mechanical stress of pre-formed cell aggregates. Thus, within the same cell type, EGFR and DOCK180 regulate Rac1 activation by newly-formed contacts, but control separate cellular events that cooperate to stabilise junctions. PMID:25957131

  2. Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase

    PubMed Central

    Pick, Edgar

    2014-01-01

    The superoxide-generating NADPH oxidase of phagocytes consists of the membrane-associated cytochrome b558 (a heterodimer of Nox2 and p22phox) and 4 cytosolic components: p47phox, p67phox, p40phox, and the small GTPase, Rac, in complex with RhoGDI. Superoxide is produced by the NADPH-driven reduction of molecular oxygen, via a redox gradient located in Nox2. Electron flow in Nox2 is initiated by interaction with cytosolic components, which translocate to the membrane, p67phox playing the central role. The participation of Rac is expressed in the following sequence: (1) Translocation of the RacGDP-RhoGDI complex to the membrane; (2) Dissociation of RacGDP from RhoGDI; (3) GDP to GTP exchange on Rac, mediated by a guanine nucleotide exchange factor; (4) Binding of RacGTP to p67phox; (5) Induction of a conformational change in p67phox, promoting interaction with Nox2. The particular involvement of Rac in NADPH oxidase assembly serves as a paradigm for signaling by Rho GTPases, in general. PMID:24598074

  3. p190RhoGAP has cellular RacGAP activity regulated by a polybasic region.

    PubMed

    Lévay, Magdolna; Bartos, Balázs; Ligeti, Erzsébet

    2013-06-01

    p190RhoGAP is a GTPase-activating protein (GAP) known to regulate actin cytoskeleton dynamics by decreasing RhoGTP levels through activation of the intrinsic GTPase activity of Rho. Although the GAP domain of p190RhoGAP stimulates the intrinsic' GTPase activity of several Rho family members (Rho, Rac, Cdc42) under in vitro conditions, p190RhoGAP is generally regarded as a GAP for RhoA in the cell. The cellular RacGAP activity of the protein has not been proven directly. We have previously shown that the in vitro RacGAP and RhoGAP activity of p190RhoGAP was inversely regulated through a polybasic region of the protein. Here we provide evidence that p190RhoGAP shows remarkable GAP activity toward Rac also in the cell. The cellular RacGAP activity of p190RhoGAP requires an intact polybasic region adjacent to the GAP domain whereas the RhoGAP activity is inhibited by the same domain. Our data indicate that through its alternating RacGAP and RhoGAP activity, p190RhoGAP plays a more complex role in the Rac-Rho antagonism than it was realized earlier.

  4. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

    PubMed

    Terasawa, Masao; Uruno, Takehito; Mori, Sayako; Kukimoto-Niino, Mutsuko; Nishikimi, Akihiko; Sanematsu, Fumiyuki; Tanaka, Yoshihiko; Yokoyama, Shigeyuki; Fukui, Yoshinori

    2012-01-01

    The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs), DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR)-2 (also known as CZH2 or Docker) domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane. PMID:23050005

  5. Rac1 Protein Regulates Glycogen Phosphorylase Activation and Controls Interleukin (IL)-2-dependent T Cell Proliferation*

    PubMed Central

    Arrizabalaga, Onetsine; Lacerda, Hadriano M.; Zubiaga, Ana M.; Zugaza, José L.

    2012-01-01

    Small GTPases of the Rho family have been implicated in important cellular processes such as cell migration and adhesion, protein secretion, and/or gene transcription. In the lymphoid system, these GTPases participate in the signaling cascades that are activated after engagement of antigen receptors. However, little is known about the role that Rho GTPases play in IL-2-mediated responses. Here, we show that IL-2 induces Rac1 activation in Kit 225 T cells. We identified by mass spectrometry the muscle isoform of glycogen phosphorylase (PYGM) as a novel Rac1 effector molecule in IL-2-stimulated cells. The interaction between the active form of Rac1 (Rac1-GTP) and PYGM was established directly through a domain comprising amino acids 191–270 of PYGM that exhibits significant homology with the Rac binding domain of PAK1. The integrity of this region was crucial for PYGM activation. Importantly, IL-2-dependent cellular proliferation was inhibited upon blocking both the activation of Rac1 and the activity of PYGM. These results reveal a new role for Rac1 in cell signaling, showing that this GTPase triggers T cell proliferation upon IL-2 stimulation by associating with PYGM and modulating its enzymatic activity. PMID:22337875

  6. Rac-null leukocytes are associated with increased inflammation-mediated alveolar bone loss.

    PubMed

    Sima, Corneliu; Gastfreund, Shoshi; Sun, Chunxiang; Glogauer, Michael

    2014-02-01

    Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such as decreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis.

  7. Cooperation of distinct Rac-dependent pathways to stabilise E-cadherin adhesion.

    PubMed

    Erasmus, Jennifer C; Welsh, Natalie J; Braga, Vania M M

    2015-09-01

    The precise mechanisms via which Rac1 is activated by cadherin junctions are not fully known. In keratinocytes Rac1 activation by cadherin junctions requires EGFR signalling, but how EGFR does so is unclear. To address which activator could mediate E-cadherin signalling to Rac1, we investigated EGFR and two Rac1 GEFs, SOS1 and DOCK180. EGFR RNAi prevented junction-induced Rac1 activation and led to fragmented localization of E-cadherin at cadherin contacts. In contrast, depletion of another EGFR family member, ErbB3, did not interfere with either process. DOCK180 RNAi, but not SOS1, prevented E-cadherin-induced Rac1 activation. However, in a strong divergence from EGFR RNAi phenotype, DOCK180 depletion did not perturb actin recruitment or cadherin localisation at junctions. Rather, reduced DOCK180 levels impaired the resistance to mechanical stress of pre-formed cell aggregates. Thus, within the same cell type, EGFR and DOCK180 regulate Rac1 activation by newly-formed contacts, but control separate cellular events that cooperate to stabilise junctions. PMID:25957131

  8. The Role of Rac1 in the Growth Cone Dynamics and Force Generation of DRG Neurons

    PubMed Central

    Sayyad, Wasim A.; Fabris, Paolo; Torre, Vincent

    2016-01-01

    We used optical tweezers, video imaging, immunocytochemistry and a variety of inhibitors to analyze the role of Rac1 in the motility and force generation of lamellipodia and filopodia from developing growth cones of isolated Dorsal Root Ganglia neurons. When the activity of Rac1 was inhibited by the drug EHop-016, the period of lamellipodia protrusion/retraction cycles increased and the lamellipodia retrograde flow rate decreased; moreover, the axial force exerted by lamellipodia was reduced dramatically. Inhibition of Arp2/3 by a moderate amount of the drug CK-548 caused a transient retraction of lamellipodia followed by a complete recovery of their usual motility. This recovery was abolished by the concomitant inhibition of Rac1. The filopodia length increased upon inhibition of both Rac1 and Arp2/3, but the speed of filopodia protrusion increased when Rac1 was inhibited and decreased instead when Arp2/3 was inhibited. These results suggest that Rac1 acts as a switch that activates upon inhibition of Arp2/3. Rac1 also controls the filopodia dynamics necessary to explore the environment. PMID:26766136

  9. Eiger-induced cell death relies on Rac1-dependent endocytosis.

    PubMed

    Ruan, W; Srinivasan, A; Lin, S; Kara, k-I; Barker, P A

    2016-01-01

    Signaling via tumor necrosis factor receptor (TNFR) superfamily members regulates cellular life and death decisions. A subset of mammalian TNFR proteins, most notably the p75 neurotrophin receptor (p75NTR), induces cell death through a pathway that requires activation of c-Jun N-terminal kinases (JNKs). However the receptor-proximal signaling events that mediate this remain unclear. Drosophila express a single tumor necrosis factor (TNF) ligand termed Eiger (Egr) that activates JNK-dependent cell death. We have exploited this model to identify phylogenetically conserved signaling events that allow Egr to induce JNK activation and cell death in vivo. Here we report that Rac1, a small GTPase, is specifically required in Egr-mediated cell death. rac1 loss of function blocks Egr-induced cell death, whereas Rac1 overexpression enhances Egr-induced killing. We identify Vav as a GEF for Rac1 in this pathway and demonstrate that dLRRK functions as a negative regulator of Rac1 that normally acts to constrain Egr-induced death. Thus dLRRK loss of function increases Egr-induced cell death in the fly. We further show that Rac1-dependent entry of Egr into early endosomes is a crucial prerequisite for JNK activation and for cell death and show that this entry requires the activity of Rab21 and Rab7. These findings reveal novel regulatory mechanisms that allow Rac1 to contribute to Egr-induced JNK activation and cell death. PMID:27054336

  10. Single Nucleotide Polymorphisms that Increase Expression of the GTPase RAC1 are Associated with Ulcerative Colitis

    PubMed Central

    Muise, Aleixo M; Walters, Thomas; Xu, Wei; Shen-Tu, Grace; Guo, Cong-Hui; Fattouh, Ramzi; Lam, Grace Y; Wolters, Victorien M; Bennitz, Joshua; Van Limbergen, Johan; Renbaum, Paul; Kasirer, Yair; Ngan, Bo-Yee; Turner, Dan; Denson, Lee A; Sherman, Philip M; Duerr, Richard H; Cho, Judy; Lees, Charlie W; Satsangi, Jack; Wilson, David C; Paterson, Andrew D; Griffiths, Anne M; Glogauer, Michael; Silverberg, Mark S; Brumell, John H

    2011-01-01

    Background & Aims RAC1 is a GTPase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases (IBD) are associated with dysregulation of immune defenses. We studied the role of RAC1 in IBD using human genetic and functional studies and animal models of colitis. Methods We used a candidate gene approach to HapMap-Tag single nucleotide polymorphisms (SNPs) in a discovery cohort; findings were confirmed in 2 additional cohorts. RAC1 mRNA expression was examined from peripheral blood cells of patients. Colitis was induced in mice with conditional disruption of Rac1 in phagocytes by administration of dextran sulphate sodium (DSS). Results We observed a genetic association between RAC1 with ulcerative colitis (UC) in a discovery cohort, 2 independent replication cohorts, and in combined analysis for the SNPs rs10951982 (Pcombined UC = 3.3 × 10–8, odds ratio [OR]=1.43 [1.26–1.63]) and rs4720672 (Pcombined UC=4.7 × 10–6, OR=1.36 [1.19–1.58]). Patients with IBD who had the rs10951982 risk allele had increased expression of RAC1, compared to those without this allele. Conditional disruption of Rac1 in macrophage and neutrophils of mice protected them against DSS-induced colitis. Conclusion Studies of human tissue samples and knockout mice demonstrated a role for the GTPase RAC1 in the development of UC; increased expression of RAC1 was associated with susceptibility to colitis. PMID:21684284

  11. Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

    PubMed Central

    2012-01-01

    Background Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines. Methods Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766). Results Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells. Conclusion Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression. PMID:22443139

  12. Rac1 inhibition negatively regulates transcriptional activity of the amyloid precursor protein gene.

    PubMed

    Wang, Pi-Lin; Niidome, Tetsuhiro; Akaike, Akinori; Kihara, Takeshi; Sugimoto, Hachiro

    2009-07-01

    Rac1, a member of the Rho family GTPases, participates in a variety of cellular functions including lamellipodia formation, actin cytoskeleton organization, cell growth, apoptosis, and neuronal development. Recent studies have implicated Rac1 in cytoskeletal abnormalities, production of reactive oxygen species, and generation of the amyloid beta-peptide (Abeta) observed in Alzheimer's disease. In this study, we examined the relationship between Rac1 and amyloid precursor protein (APP), because the abnormal proteolytic processing of APP is a pathologic feature of Alzheimer's disease. In primary hippocampal neurons, the Rac1-specific inhibitor NSC23766 decreased both Rac1 activity and APP protein levels in a concentration-dependent manner. To elucidate how NSC23766 decreases APP protein levels, we examined the effects of NSC23766 on APP processing, degradation, and biosynthesis. NSC23766 did not increase the levels of the proteolytic products of APP, sAPPalpha, Abeta40, and Abeta42. The proteasome inhibitor lactacystin did not reverse the NSC23766-induced decrease in APP protein levels. NSC23766 did, however, decrease the levels of both APP mRNA and APP protein. Decreased levels of APP mRNA and protein were also observed when HEK293 cells were transfected with an expression vector containing a dominant-negative Rac1 mutant or with siRNA targeting Rac1. By overexpressing progressively deleted fragments of the APP promoter in HEK293 cells, we identified a Rac1 response site at positions -233 to -41 bp in the APP promoter. Taken together, our results suggest that Rac1 regulates transcription of the APP gene in primary hippocampal neurons.

  13. Role of Rac1 GTPase in JNK signaling and delayed neuronal cell death following global cerebral ischemia.

    PubMed

    Zhang, Quan-Guang; Wang, Ruimin; Han, Dong; Dong, Yan; Brann, Darrell W

    2009-04-10

    The overall goal of this study was to determine the role of Rac1 in POSH/MLK/JNK signaling and delayed neuronal cell death following cerebral ischemia. Temporal studies revealed that Rac1 GTPase activation was significantly elevated in hippocampus CA1 at 10 min to 72 h after cerebral ischemia reperfusion, with peak levels 30 min to 6 h after reperfusion. Total Rac1 protein levels were not significantly changed following cerebral ischemia. Rac1 has been shown to interact with POSH (plenty of SH3s), a scaffold protein that binds to and regulates MLK3 and JNK activation. Co-immunoprecipitation (Co-IP) studies revealed that POSH-Rac1-MLK3 complex formation displayed a significant and prolonged elevation after reperfusion, with a correlative increase in phosphorylation/activation of MLK3 as compared to sham controls. Intracerebroventricular administration of Rac1 antisense oligonucleotides (AS-ODNs) significantly attenuated Rac1 levels and Rac1 activation at 30 min after reperfusion, with a correlated significant attenuation of POSH-MLK3-Rac1 complex formation and MLK3 activation in hippocampus CA1. Infusion of Rac1 AS-ODNs also significantly attenuated post-ischemic activation of JNK, downstream of MLK3, and strongly protected the hippocampus CA1 from ischemic damage. Missense oligos had no effect on any of the parameters measured. The Rac1 AS-ODNs results were further confirmed by administration of a Rac1 inhibitor (NSC23766), which markedly attenuated activation of Rac1 and JNK, and significantly attenuated apoptotic delayed neuronal cell death following cerebral ischemia. As a whole, these studies demonstrate an important role for Rac1 in activation of the prodeath MLK3-JNK kinase signaling pathway and delayed neuronal cell death following cerebral ischemia.

  14. Provider experiences with RAC appeals point to opportunities for program improvement.

    PubMed

    Jacobs, Robert; Scott, Bonnie; Flood, Elizabeth; Scott, Ellen

    2011-03-01

    Review by an administrative law judge (ALJ) constitutes the third level of appeal for healthcare providers seeking to overturn reverse recovery audit contractor (RAC) findings of overpayment of Medicare claims. An analysis of the results of RAC appeals submitted by 30 New York hospitals during the demonstration project has disclosed two deficiencies in the ALJ review process: inconsistent ALJ decision making and a lack of an appropriate feedback mechanism to correct erroneous overpayment determinations. The Centers for Medicare & Medicaid Services should take advantage of feedback from such studies as an impetus to reevaluate and streamline the RAC appeals process. PMID:21449307

  15. Shampoo and Conditioners: What a Dermatologist Should Know?

    PubMed Central

    D'Souza, Paschal; Rathi, Sanjay K

    2015-01-01

    Dermatologists many a times encounter questions from patients and even colleagues asking about how to keep their hair looking clean, healthy and beautiful. Therefore, familiarity and a basic knowledge of the available hair care products will help them to guide their patients properly. A shampoo not only provides the cleaning of the scalp skin and hair as its primary function, but in addition also serves to condition and beautify hair and acts as an adjunct in the management of various scalp disorders. To achieve this, various ingredients in the correct proportion are mixed to provide a shampoo which is suitable for individuals having different hair types and hair need. Among the ingredients that go into the making of a shampoo are detergents, conditioners, thickeners, sequestering agents, pH adjusters, preservatives and specialty additives. Hair conditioners are designed to improve hair manageability, decrease hair static electricity and add luster. They are used in several ways depending upon the state of hair and requirement of the individual. This article attempts to put forward the basic and practical aspects regarding use of these products. PMID:26120149

  16. Shampoo and Conditioners: What a Dermatologist Should Know?

    PubMed

    D'Souza, Paschal; Rathi, Sanjay K

    2015-01-01

    Dermatologists many a times encounter questions from patients and even colleagues asking about how to keep their hair looking clean, healthy and beautiful. Therefore, familiarity and a basic knowledge of the available hair care products will help them to guide their patients properly. A shampoo not only provides the cleaning of the scalp skin and hair as its primary function, but in addition also serves to condition and beautify hair and acts as an adjunct in the management of various scalp disorders. To achieve this, various ingredients in the correct proportion are mixed to provide a shampoo which is suitable for individuals having different hair types and hair need. Among the ingredients that go into the making of a shampoo are detergents, conditioners, thickeners, sequestering agents, pH adjusters, preservatives and specialty additives. Hair conditioners are designed to improve hair manageability, decrease hair static electricity and add luster. They are used in several ways depending upon the state of hair and requirement of the individual. This article attempts to put forward the basic and practical aspects regarding use of these products.

  17. Tumor-related alternatively spliced Rac1b is not regulated by Rho-GDP dissociation inhibitors and exhibits selective downstream signaling.

    PubMed

    Matos, Paulo; Collard, John G; Jordan, Peter

    2003-12-12

    Rac1 is a member of the Rho family of small GTPases, which control signaling pathways that regulate actin cytoskeletal dynamics and gene transcription. Rac1 is activated by guanine nucleotide exchange factors and inactivated by GTPase-activating proteins. In addition, Rho-GDP dissociation inhibitors (Rho-GDIs) can inhibit Rac1 by sequestering it in the cytoplasm. We have found previously that colorectal tumors express an alternatively spliced variant, Rac1b, containing 19 additional amino acids following the switch II region. Here we characterized the regulation and downstream signaling of Rac1b. Although little Rac1b protein is expressed in cells, the amount of activated Rac1b protein often exceeds that of activated Rac1, suggesting that Rac1b contributes significantly to the downstream signaling of Rac in cells. The regulation of both Rac1 and Rac1b activities is dependent on guanine nucleotide exchange factors and GTPase-activating proteins, but the difference in their activation is mainly determined by the inability of Rac1b to interact with Rho-GDI. As a consequence, most Rac1b remains bound to the plasma membrane and is not sequestered by Rho-GDI in the cytoplasm. Unlike Rac1, activated Rac1b is unable to induce lamellipodia formation and is unable to bind and activate p21-activated protein kinase nor activate the downstream protein kinase JNK. However, both Rac1 and Rac1b are able to activate NFkappaB to the same extent. These data suggest that alternative splicing of Rac1 leads to a highly active Rac variant that differs in regulation and downstream signaling.

  18. Solar-powered air-conditioning

    NASA Technical Reports Server (NTRS)

    Clark, D. C.; Rousseau, J.

    1977-01-01

    Report focuses on recent study on development of solar-powered residential air conditioners and is based on selected literature through 1975. Its purposes are to characterize thermal and mechanical systems that might be useful in development of Rankine-cycle approach to solar cooling and assessment of a Lithium Bromide/Water absorption cycle system.

  19. Air Conditioning. Trade and Industrial Education Trade Preparatory Training Guide.

    ERIC Educational Resources Information Center

    Nebraska State Dept. of Education, Lincoln. Div. of Vocational Education.

    One of a series of curriculum guides prepared for the building occupations cluster of the construction/fabrication occupational group, this guide identifies the essentials of the air conditioning trade as recommended by the successful air conditioner. An instructional program based upon the implementation of the guide is expected to prepare a…

  20. Bond strength of resin-modified glass ionomer restorative materials using a no-rinse conditioner.

    PubMed

    Suihkonen, Rian W; Vandewalle, Kraig S; Dossett, Jon M

    2012-01-01

    A paste-paste resin-modified glass ionomer (RMGI) restorative material has been introduced recently with a new conditioner that requires no rinsing. The purpose of this study was to compare the shear bond strength of an encapsulated RMGI (Fuji II LC) and a new paste-paste RMGI (Fuji Filling LC) to dentin conditioned with 20% polyacrylic acid (Cavity Conditioner), a new no-rinse conditioner (Self Conditioner,), or no conditioner. Mounted human third molars were flattened and the dentin surface was conditioned. The RMGI restorative materials were mixed and incrementally inserted into a mold and photocured. The specimens were loaded until failure in a universal testing machine after 24 hours of storage in distilled water. Fuji II LC had significantly greater bond strength to dentin than Fuji Filling LC. The use of Cavity Conditioner or Self Conditioner resulted in bond strengths that were not significantly different from each other; however, both produced greater bond strengths than those in the non-conditioned groups. PMID:23220322

  1. Regulation of lymphatic-blood vessel separation by endothelial Rac1

    PubMed Central

    D'Amico, Gabriela; Jones, Dylan T.; Nye, Emma; Sapienza, Karen; Ramjuan, Antoine R.; Reynolds, Louise E.; Robinson, Stephen D.; Kostourou, Vassiliki; Martinez, Dolores; Aubyn, Deborah; Grose, Richard; Thomas, Gareth J.; Spencer-Dene, Bradley; Zicha, Daniel; Davies, Derek; Tybulewicz, Victor; Hodivala-Dilke, Kairbaan M.

    2009-01-01

    Sprouting angiogenesis and lymphatic-blood vessel segregation both involve the migration of endothelial cells, but the precise migratory molecules that govern the decision of blood vascular endothelial cells to segregate into lymphatic vasculature are unknown. Here, we deleted endothelial Rac1 in mice (Tie1-Cre+;Rac1fl/fl) and revealed, unexpectedly, that whereas blood vessel morphology appeared normal, lymphatic-blood vessel separation was impaired, with corresponding edema, haemorrhage and embryonic lethality. Importantly, normal levels of Rac1 were essential for directed endothelial cell migratory responses to lymphatic-inductive signals. Our studies identify Rac1 as a crucial part of the migratory machinery required for endothelial cells to separate and form lymphatic vasculature. PMID:19906871

  2. Novel aspects of the roles of Rac1 GTPase in the cardiovascular system.

    PubMed

    Sawada, Naoki; Li, Yuxin; Liao, James K

    2010-04-01

    Rac1 GTPase is an established master regulator of cell motility through cortical actin re-organization and of reactive oxygen species generation through regulation of NADPH oxidase activity. Numerous molecular and cellular studies have implicated Rac1 in various cardiovascular pathologies: vascular smooth muscle proliferation, cardiomyocyte hypertrophy, and endothelial cell shape change. The physiological relevance of these in vitro findings, however, is just beginning to be reassessed with the newly developed, conditional mouse mutagenesis technology. Conditional gene targeting has also revealed unexpected, cell type-specific roles of Rac1. The aim of this review is to summarize the recent advance made in Rac1 research in the cardiovascular system, with special focus on its novel roles in the regulation of endothelial function, angiogenesis, and endothelium-mediated neuroprotection.

  3. Rac1 Is a Critical Mediator of Endothelium-Derived Neurotrophic Activity

    PubMed Central

    Sawada, Naoki; Kim, Hyung-Hwan; Moskowitz, Michael A.; Liao, James K.

    2009-01-01

    The therapeutic potential of neurotrophic factors has been hampered by their inability to achieve adequate tissue penetration. Brain blood vessels, however, could be an alternative target for neuro-salvage therapies by virtue of their close proximity to neurons. Here we show that hemizygous deletion of Rac1 in mouse endothelial cells (ECs) attenuates brain injury and edema after focal cerebral ischemia. Microarray analysis of Rac1+/− ECs revealed enrichment of stress response genes, basement membrane components, and neurotrophic factors that could affect neuronal survival. Consistent with these expression profiles, endothelial Rac1 hemizygosity enhanced antioxidative and endothelial barrier capacities and potentiated paracrine neuroprotective activities through the up-regulation of the neurotrophic factor, artemin. Endothelial Rac1, therefore, could be an important therapeutic target for promoting endothelial barrier integrity and neurotrophic activity. PMID:19278959

  4. WAVE regulatory complex activation by cooperating GTPases Arf and Rac1.

    PubMed

    Koronakis, Vassilis; Hume, Peter J; Humphreys, Daniel; Liu, Tao; Hørning, Ole; Jensen, Ole N; McGhie, Emma J

    2011-08-30

    The WAVE regulatory complex (WRC) is a critical element in the control of actin polymerization at the eukaryotic cell membrane, but how WRC is activated remains uncertain. While Rho GTPase Rac1 can bind and activate WRC in vitro, this interaction is of low affinity, suggesting other factors may be important. By reconstituting WAVE-dependent actin assembly on membrane-coated beads in mammalian cell extracts, we found that Rac1 was not sufficient to engender bead motility, and we uncovered a key requirement for Arf GTPases. In vitro, Rac1 and Arf1 were individually able to bind weakly to recombinant WRC and activate it, but when both GTPases were bound at the membrane, recruitment and concomitant activation of WRC were dramatically enhanced. This cooperativity between the two GTPases was sufficient to induce WAVE-dependent bead motility in cell extracts. Our findings suggest that Arf GTPases may be central components in WAVE signalling, acting directly, alongside Rac1.

  5. Perivascular deletion of murine Rac reverses the ratio of marrow arterioles and sinusoid vessels and alters hematopoiesis in vivo.

    PubMed

    Ciuculescu, Marioara F; Park, Shin-Young; Canty, Kimberly; Mathieu, Ronald; Silberstein, Leslie E; Williams, David A

    2015-05-14

    Hematopoietic stem cells (HSCs) are localized within specialized microenvironments throughout the BM. Nestin-expressing (Nestin(+)) mesenchymal stromal cells (MSCs) are important in the perivascular space. Rac is critical for MSC cell shape in vitro, whereas its function in MSCs in vivo remains poorly characterized. We hypothesized that deletion of Rac in the Nestin(+) cells would perturb the perivascular space, altering HSC localization and hematopoiesis. Nestin-Cre-directed excision of Rac1 in Rac3(-/-) mice reduces Nestin(+) cells in the marrow. We observed a 2.7-fold decrease in homing of labeled wild-type hematopoietic cells into Rac1(Δ/Δ)Rac3(-/-) mice compared with control mice. Rac1(Δ/Δ)Rac3(-/-) mice demonstrated a marked decrease in arterioles and an increase in the number and volume of venous sinusoids in the marrow that was associated with a reduction in the numbers of immunophenotypically and functionally-defined long-term HSCs in the marrow, a decrease in colony-forming cells and a reduction in circulating progenitors. Rac-deleted animals demonstrated a significant increase in trabecular bone. These data demonstrate that Rac GTPases play an important role in the integrity of perivascular space. Increased trabecular bone and sinusoidal space and decreased arteriolar volume in this model were associated with decreased HSC, underscoring the complexity of regulation of hematopoiesis in the perivascular space.

  6. Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells.

    PubMed

    Hofbauer, Sebastian W; Krenn, Peter W; Ganghammer, Sylvia; Asslaber, Daniela; Pichler, Ulrike; Oberascher, Karin; Henschler, Reinhard; Wallner, Michael; Kerschbaum, Hubert; Greil, Richard; Hartmann, Tanja N

    2014-04-01

    Signals from the tumor microenvironment promote the migration, survival, and proliferation of chronic lymphocytic leukemia (CLL) cells. Rho GTPases control various signaling pathways downstream of microenvironmental cues. Here, we analyze the function of Rac1 in the motility and proliferation of CLL cells. We found decreased transcription of the Rac guanine nucleotide exchange factors Tiam1 and Vav1 in unstimulated peripheral blood CLL cells with almost complete loss of Tiam1 but increased transcription of the potential Rac antagonist RhoH. Consistently, stimulation of CLL cells with the chemokine CXCL12 induced RhoA but not Rac1 activation, whereas chemokine-induced CLL cell motility was Rac1-independent. Coculture of CLL cells with activated T cells induced their activation and subsequent proliferation. Here, Tiam1 expression was induced in the malignant cells in line with increased Ki-67 and c-Myc expression. Rac1 or Tiam1 knockdown using siRNA or treatment with the Tiam1/Rac inhibitor NSC-23766 attenuated c-Myc transcription. Furthermore, treatment of CLL cells with NSC-23766 reduced their proliferation. Rac inhibition also antagonized the chemoresistance of activated CLL cells toward fludarabine. Collectively, our data suggest a dynamic regulation of Rac1 function in the CLL microenvironment. Rac inhibition could be of clinical use by selectively interfering with CLL cell proliferation and chemoresistance.

  7. Coronin-1C Protein and Caveolin Protein Provide Constitutive and Inducible Mechanisms of Rac1 Protein Trafficking*

    PubMed Central

    Williamson, Rosalind C.; Cowell, Christopher A. M.; Reville, Thomas; Roper, James A.; Rendall, Thomas C. S.; Bass, Mark D.

    2015-01-01

    Sustained directional fibroblast migration requires both polarized activation of the protrusive signal, Rac1, and redistribution of inactive Rac1 from the rear of the cell so that it can be redistributed or degraded. In this work, we determine how alternative endocytic mechanisms dictate the fate of Rac1 in response to the extracellular matrix environment. We discover that both coronin-1C and caveolin retrieve Rac1 from similar locations at the rear and sides of the cell. We find that coronin-1C-mediated extraction, which is responsible for Rac1 recycling, is a constitutive process that maintains Rac1 protein levels within the cell. In the absence of coronin-1C, the effect of caveolin-mediated endocytosis, which targets Rac1 for proteasomal degradation, becomes apparent. Unlike constitutive coronin-1C-mediated trafficking, caveolin-mediated Rac1 endocytosis is induced by engagement of the fibronectin receptor syndecan-4. Such an inducible endocytic/degradation mechanism would predict that, in the presence of fibronectin, caveolin defines regions of the cell that are resistant to Rac1 activation but, in the absence of fibronectin leaves more of the membrane susceptible to Rac1 activation and protrusion. Indeed, we demonstrate that fibronectin-stimulated activation of Rac1 is accelerated in the absence of caveolin and that, when caveolin is knocked down, polarization of active Rac1 is lost in FRET experiments and culminates in shunting migration in a fibrous fibronectin matrix. Although the concept of polarized Rac1 activity in response to chemoattractants has always been apparent, our understanding of the balance between recycling and degradation explains how polarity can be maintained when the chemotactic gradient has faded. PMID:25925950

  8. GxcDD, a putative RacGEF, is involved in Dictyostelium development

    PubMed Central

    Mondal, Subhanjan; Neelamegan, Dhamodharan; Rivero, Francisco; Noegel, Angelika A

    2007-01-01

    Background Rho subfamily GTPases are implicated in a large number of actin-related processes. They shuttle from an inactive GDP-bound form to an active GTP-bound form. This reaction is catalysed by Guanine nucleotide exchange factor (GEFs). GTPase activating proteins (GAPs) help the GTPase return to the inactive GDP-bound form. The social amoeba Dictyostelium discoideum lacks a Rho or Cdc42 ortholog but has several Rac related GTPases. Compared to our understanding of the downstream effects of Racs our understanding of upstream mechanisms that activate Rac GTPases is relatively poor. Results We report on GxcDD (Guanine exchange factor for Rac GTPases), a Dictyostelium RacGEF. GxcDD is a 180-kDa multidomain protein containing a type 3 CH domain, two IQ motifs, three PH domains, a RhoGEF domain and an ArfGAP domain. Inactivation of the gene results in defective streaming during development under different conditions and a delay in developmental timing. The characterization of single domains revealed that the CH domain of GxcDD functions as a membrane association domain, the RhoGEF domain can physically interact with a subset of Rac GTPases, and the ArfGAP-PH tandem accumulates in cortical regions of the cell and on phagosomes. Our results also suggest that a conformational change may be required for activation of GxcDD, which would be important for its downstream signaling. Conclusion The data indicate that GxcDD is involved in proper streaming and development. We propose that GxcDD is not only a component of the Rac signaling pathway in Dictyostelium, but is also involved in integrating different signals. We provide evidence for a Calponin Homology domain acting as a membrane association domain. GxcDD can bind to several Rac GTPases, but its function as a nucleotide exchange factor needs to be studied further. PMID:17584488

  9. Mas Oncogene Signaling and Transformation Require the Small GTP-Binding Protein Rac

    PubMed Central

    Zohn, Irene E.; Symons, Marc; Chrzanowska-Wodnicka, Magdalena; Westwick, John K.; Der, Channing J.

    1998-01-01

    The Mas oncogene encodes a novel G-protein-coupled receptor that was identified originally as a transforming protein when overexpressed in NIH 3T3 cells. The mechanism and signaling pathways that mediate Mas transformation have not been determined. We observed that the foci of transformed NIH 3T3 cells caused by Mas were similar to those caused by activated Rho and Rac proteins. Therefore, we determined if Mas signaling and transformation are mediated through activation of a specific Rho family protein. First, we observed that, like activated Rac1, Mas cooperated with activated Raf and caused synergistic transformation of NIH 3T3 cells. Second, both Mas- and Rac1-transformed NIH 3T3 cells retained actin stress fibers and showed enhanced membrane ruffling. Third, like Rac, Mas induced lamellipodium formation in porcine aortic endothelial cells. Fourth, Mas and Rac1 strongly activated the JNK and p38, but not ERK, mitogen-activated protein kinases. Fifth, Mas and Rac1 stimulated transcription from common DNA promoter elements: NF-κB, serum response factor (SRF), Jun/ATF-2, and the cyclin D1 promoter. Finally, Mas transformation and some of Mas signaling (SRF and cyclin D1 but not NF-κB activation) were blocked by dominant negative Rac1. Taken together, these observations suggest that Mas transformation is mediated in part by activation of Rac-dependent signaling pathways. Thus, Rho family proteins are common mediators of transformation by a diverse variety of oncogene proteins that include Ras, Dbl family, and G-protein-coupled oncogene proteins. PMID:9488437

  10. Temporal-specific roles of Rac1 during vascular development and retinal angiogenesis.

    PubMed

    Nohata, Nijiro; Uchida, Yutaka; Stratman, Amber N; Adams, Ralf H; Zheng, Yi; Weinstein, Brant M; Mukouyama, Yoh-Suke; Gutkind, J Silvio

    2016-03-15

    Angiogenesis, the formation of new blood vessels by remodeling and growth of pre-existing vessels, is a highly orchestrated process that requires a tight balance between pro-angiogenic and anti-angiogenic factors and the integration of their corresponding signaling networks. The family of Rho GTPases, including RhoA, Rac1, and Cdc42, play a central role in many cell biological processes that involve cytoskeletal changes and cell movement. Specifically for Rac1, we have shown that excision of Rac1 using a Tie2-Cre animal line results in embryonic lethality in midgestation (embryonic day (E) 9.5), with multiple vascular defects. However, Tie2-Cre can be also expressed during vasculogenesis, prior to angiogenesis, and is active in some hematopoietic precursors that can affect vessel formation. To circumvent these limitations, we have now conditionally deleted Rac1 in a temporally controlled and endothelial-restricted fashion using Cdh5(PAC)-iCreERT2 transgenic mice. In this highly controlled experimental in vivo system, we now show that Rac1 is required for embryonic vascular integrity and angiogenesis, and for the formation of superficial and deep vascular networks in the post-natal developing retina, the latter involving a novel specific function for Rac1 in vertical blood vessel sprouting. Aligned with these findings, we show that RAC1 is spatially involved in endothelial cell migration, invasion, and radial sprouting activities in 3D collagen matrix in vitro models. Hence, Rac1 and its downstream molecules may represent potential anti-angiogeneic therapeutic targets for the treatment of many human diseases that involve aberrant neovascularization and blood vessel overgrowth. PMID:26872874

  11. Regulation of Rac1 activation by the low density lipoprotein receptor-related protein.

    PubMed

    Ma, Zhong; Thomas, Keena S; Webb, Donna J; Moravec, Radim; Salicioni, Ana Maria; Mars, Wendy M; Gonias, Steven L

    2002-12-23

    The low density lipoprotein receptor-related protein (LRP-1) binds and mediates the endocytosis of multiple ligands, transports the urokinase-type plasminogen activator receptor (uPAR) and other membrane proteins into endosomes, and binds intracellular adaptor proteins involved in cell signaling. In this paper, we show that in murine embryonic fibroblasts (MEFs) and L929 cells, LRP-1 functions as a major regulator of Rac1 activation, and that this activity depends on uPAR. LRP-1-deficient MEFs demonstrated increased Rac1 activation compared with LRP-1-expressing MEFs, and this property was reversed by expressing the VLDL receptor, a member of the same gene family as LRP-1, with overlapping ligand-binding specificity. Neutralizing the activity of LRP-1 with receptor-associated protein (RAP) increased Rac1 activation and cell migration in MEFs and L929 cells. The same parameters were unaffected by RAP in uPAR-/- MEFs, prepared from uPAR gene knockout embryos, and in uPAR-deficient LM-TK- cells. Untreated uPAR+/+ MEFs demonstrated substantially increased Rac1 activation compared with uPAR-/- MEFs. In addition to Rac1, LRP-1 suppressed activation of extracellular signal-regulated kinase (ERK) in MEFs; however, it was Rac1 (and not ERK) that was responsible for the effects of LRP-1 on MEF migration. Thus, LRP-1 regulates two signaling proteins in the same cell (Rac1 and ERK), both of which may impact on cell migration. In uPAR-negative cells, LRP-1 neutralization does not affect Rac1 activation, and other mechanisms by which LRP-1 may regulate cell migration are not unmasked.

  12. Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo

    PubMed Central

    Joshi, Shweta; Singh, Alok R.; Zulcic, Muamera; Bao, Lei; Messer, Karen; Ideker, Trey; Dutkowski, Janusz; Durden, Donald L.

    2014-01-01

    Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis. PMID:24770346

  13. Regulation of Rac1 and Reactive Oxygen Species Production in Response to Infection of Gastrointestinal Epithelia

    PubMed Central

    Ablack, Amber; Hall, Emily H.; Butcher, Lindsay D.; Bhattacharyya, Asima; Eckmann, Lars; Harris, Paul R.; Das, Soumita; Ernst, Peter B.; Crowe, Sheila E.

    2016-01-01

    Generation of reactive oxygen species (ROS) during infection is an immediate host defense leading to microbial killing. APE1 is a multifunctional protein induced by ROS and after induction, protects against ROS-mediated DNA damage. Rac1 and NAPDH oxidase (Nox1) are important contributors of ROS generation following infection and associated with gastrointestinal epithelial injury. The purpose of this study was to determine if APE1 regulates the function of Rac1 and Nox1 during oxidative stress. Gastric or colonic epithelial cells (wild-type or with suppressed APE1) were infected with Helicobacter pylori or Salmonella enterica and assessed for Rac1 and NADPH oxidase-dependent superoxide production. Rac1 and APE1 interactions were measured by co-immunoprecipitation, confocal microscopy and proximity ligation assay (PLA) in cell lines or in biopsy specimens. Significantly greater levels of ROS were produced by APE1-deficient human gastric and colonic cell lines and primary gastric epithelial cells compared to control cells after infection with either gastric or enteric pathogens. H. pylori activated Rac1 and Nox1 in all cell types, but activation was higher in APE1 suppressed cells. APE1 overexpression decreased H. pylori-induced ROS generation, Rac1 activation, and Nox1 expression. We determined that the effects of APE1 were mediated through its N-terminal lysine residues interacting with Rac1, leading to inhibition of Nox1 expression and ROS generation. APE1 is a negative regulator of oxidative stress in the gastrointestinal epithelium during bacterial infection by modulating Rac1 and Nox1. Our results implicate APE1 in novel molecular interactions that regulate early stress responses elicited by microbial infections. PMID:26761793

  14. Regulatory effect of Rac1 on vascular reactivity after hemorrhagic shock in rats.

    PubMed

    Li, Tao; Yang, Guangming; Xu, Jing; Zhu, Yu; Liu, Liangming

    2011-06-01

    We used isolated superior mesenteric arteries (SMAs) from hemorrhagic-shock rats and hypoxia-treated vascular smooth muscle cells (VSMCs; mimicking the shock state) to observe the effects of platelet-derived growth factor (PDGF; Rac1 stimulator) and NSC23766 (Rac1 antagonist) on vascular reactivity and the relationship with the Rho kinase-myosin light-chain phosphatase (MLCP) and p21-activated kinase (PAK)-myosin light-chain kinase (MLCK) signal pathway. The results indicated that the contractile responses of the SMAs and VSMCs were significantly increased at early shock or after transient hypoxia. NSC23766 (Rac1 antagonist) further increased, whereas PDGF (Rac1 stimulator) decreased the contractile responses of SMAs and VSMCs. In the late period of shock or prolonged hypoxia, the contractile responses of SMAs and VSMCs were significantly decreased; NSC23766 increased (whereas PDGF further decreased) the contractile response of the SMAs and VSMCs. Activation of Rac1 with PDGF significantly increased the activity of PAK and MLCP, and decreased Rho kinase and MLCK activity and 20-kDa myosin light-chain phosphorylation in VSMCs. The PAK inhibitor PAK-18 significantly antagonized the PDGF-induced decrease in MLCK activity, whereas the Rho kinase antagonist Y-27632 further enforced the PDGF-induced increase in MLCP activity. Simple fluid resuscitation did not improve but in combination with NSC23766 significantly improved vascular reactivity and animal survival at 24 hours. This suggested that Rac1 has an inhibitory effect on vasoreactivity after shock. Rac1-mediated regulation of vascular reactivity is mainly through activation of PAK, inhibition of MLCK and inhibition of Rho kinase, unpack the inhibition of Rho kinase to MLCP. Rac1 may be a potential target to treat vascular hyporeactivity in many critical conditions.

  15. Listeria monocytogenes induced Rac1-dependent signal transduction in endothelial cells.

    PubMed

    Schmeck, Bernd; Beermann, Wiebke; van Laak, Vincent; Opitz, Bastian; Hocke, Andreas C; Meixenberger, Karolin; Eitel, Julia; Chakraborty, Trinad; Schmidt, Gudula; Barth, Holger; Suttorp, Norbert; Hippenstiel, Stefan

    2006-11-30

    Infection of endothelial cells by Listeria monocytogenes is an essential step in the pathogenesis of listeriosis. Small GTPases of the Rho family act as molecular switches in signal transduction. We tested the hypothesis that Rho GTPases contribute to the regulation of cytokine expression following L. monocytogenes infection. L. monocytogenes induced release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by endothelial cells and activated RhoA and Rac1. Inhibition of Rac1 by inhibitor Nsc23766 reduced cytokine expression, and slightly yet significantly the uptake of bacteria. Blocking of Rho proteins by Clostridium difficile toxin B-10463 (TcdB) reduced Listeria-dependent cytokine expression, whereas activating Rho proteins by Escherichia coli CNF1 increased it. We analyzed regulation of IL-8 expression in more detail: Listeria-induced IL-8 release was reduced by inhibition of RhoA, Rac1 and Cdc42 (TcdB) or Rac1 while blocking of RhoA/B/C by Clostridium limosum C3 fusion toxin (C3FT) or Rho kinase by Y27632 reduced cytokine expression only slightly. Activation of RhoA, Rac1 and Cdc42 (CNF1), but not of RhoA alone (CNF(Y)), enhanced Listeria-dependent IL-8 release significantly. Furthermore, inhibition of RhoA, Rac1 and Cdc42 (TcdB) and Rac1 (Nsc23766), but not of RhoA (C3FT) reduced Listeria-related recruitment of NF-kappaB/p65 and RNA polymerase II to the il8 promoter, as well as acetylation of histone H4 and Ser10/Lys14-phosphorylation/acetylation of histone H3 at the il8 gene promoter in HUVEC. In conclusion, Rac1 contributed to L. monocytogenes-induced cytokine expression by human endothelial cells.

  16. Rac1 contributes to trastuzumab resistance of breast cancer cells: Rac1 as a potential therapeutic target for the treatment of trastuzumab-resistant breast cancer.

    PubMed

    Dokmanovic, Milos; Hirsch, Dianne S; Shen, Yi; Wu, Wen Jin

    2009-06-01

    Although treatment with trastuzumab improves outcomes for women with ErbB2-positive breast cancer, many patients who achieve an initial response to trastuzumab subsequently acquire resistance within 1 year. Rac1, a Ras-like small GTPase, has been implicated in the control of cell growth and morphology and is believed to be associated with breast cancer progression and metastasis. Here, we show that when parental SKBR3 cells become resistant to trastuzumab, Rac1 activity is increased, leading to altered cell morphology, which is accompanied by significant cytoskeleton disorganization. Furthermore, both trastuzumab-mediated down-regulation of ErbB2 and epidermal growth factor-induced down-regulation of epidermal growth factor receptor are impaired in the trastuzumab-resistant SKBR3 cells, indicating that the endocytic down-regulation of ErbB receptors is compromised in the resistant cells. This results in an aberrant accumulation of ErbB2 on the cell surface and enhanced ErbB2 and extracellular signal-regulated kinase activity in trastuzumab-resistant SKBR3 cells. Additionally, overexpression of constitutively active Rac1G12V in parental SKBR3 cells reduces sensitivity to trastuzumab. After reduction of Rac1 activity by NSC23766, a specific Rac1 inhibitor, trastuzumab-resistant SKBR3 cells display a cellular morphology similar to parental SKBR3 cells. Moreover, we show that NSC23766 restores trastuzumab-mediated endocytic down-regulation of ErbB2 and reduces extracellular signal-regulated kinase activity in resistant SKBR3 cells. Our findings highlight an important role for Rac1 in trastuzumab resistance of human breast cancer cells and identify the impaired trastuzumab-mediated endocytic down-regulation of ErbB2 as a novel mechanism of trastuzumab resistance. The significant effects of NSC23766 on trastuzumab-resistant SKBR3 cells warrant further study of NSC23766 as a potential treatment of trastuzumab-resistant breast cancers.

  17. Fluctuation-based imaging of nuclear Rac1 activation by protein oligomerisation

    NASA Astrophysics Data System (ADS)

    Hinde, Elizabeth; Yokomori, Kyoko; Gaus, Katharina; Hahn, Klaus M.; Gratton, Enrico

    2014-02-01

    Here we describe a fluctuation-based method to quantify how protein oligomerisation modulates signalling activity of a multifunctional protein. By recording fluorescence lifetime imaging microscopy (FLIM) data of a FRET biosensor in a format that enables concomitant phasor and cross Number and Brightness (cN&B) analysis, we measure the nuclear dynamics of a Rac1 FRET biosensor and assess how Rac1 homo-oligomers (N&B) regulate Rac1 activity (hetero-oligomerisation with the biosensor affinity reagent, PBD, by FLIM-FRET) or interaction with an unknown binding partner (cN&B). The high spatiotemporal resolution of this method allowed us to discover that upon DNA damage monomeric and active Rac1 in the nucleus is segregated from dimeric and inactive Rac1 in the cytoplasm. This reorganisation requires Rac1 GTPase activity and is associated with an importin-α2 redistribution. Only with this multiplexed approach can we assess the oligomeric state a molecular complex must form in order to regulate a complex signalling network.

  18. Rac1 deficiency in the forebrain results in neural progenitor reduction and microcephaly

    PubMed Central

    Chen, Lei; Melendez, Jaime; Campbell, Kenneth; Kuan, Chia-Yi; Zheng, Yi

    2009-01-01

    The Rho family of small GTPases has been implicated in many neurological disorders including mental retardation, but whether they are involved in primary microcephaly (microcephalia vera) is unknown. Here, we examine the role of Rac1 in mammalian neural progenitors and forebrain development by a conditional gene-targeting strategy using the Foxg1-Cre line to delete floxed-Rac1 alleles in the telencephalic ventricular zone (VZ) of mouse embryos. We found that Rac1 deletion in the telencephalic VZ progenitors resulted in reduced sizes of both the striatum and cerebral cortex. Analyses further indicated that this abnormality was caused by accelerated cell-cycle exit and increased apoptosis during early corticogenesis (approximately E14.5), leading to a decrease of the neural progenitor pool in mid-to-late telencephalic development (E16.5 to E18.5). Moreover, the formation of patch-matrix compartments in the striatum was impaired by Rac1-deficiency. Together, these results suggest that Rac1 regulates self-renewal, survival, and differentiation of telencephalic neural progenitors, and that dysfunctions of Rac1 may lead to primary microcephaly. PMID:19007770

  19. PLC-gamma1 and Rac1 coregulate EGF-induced cytoskeleton remodeling and cell migration.

    PubMed

    Li, Siwei; Wang, Qian; Wang, Yi; Chen, Xinmei; Wang, Zhixiang

    2009-06-01

    It is well established that epidermal growth factor (EGF) induces the cytoskeleton reorganization and cell migration through two major signaling cascades: phospholipase C-gamma1 (PLC-gamma1) and Rho GTPases. However, little is known about the cross talk between PLC-gamma1 and Rho GTPases. Here we showed that PLC-gamma1 forms a complex with Rac1 in response to EGF. This interaction is direct and mediated by PLC-gamma1 Src homology 3 (SH3) domain and Rac1 (106)PNTP(109) motif. This interaction is critical for EGF-induced Rac1 activation in vivo, and PLC-gamma1 SH3 domain is actually a potent and specific Rac1 guanine nucleotide exchange factor in vitro. We have also demonstrated that the interaction between PLC-gamma1 SH3 domain and Rac1 play a significant role in EGF-induced F-actin formation and cell migration. We conclude that PLC-gamma1 and Rac1 coregulate EGF-induced cell cytoskeleton remodeling and cell migration by a direct functional interaction.

  20. Inhibition of Rac and ROCK signalling influence osteoblast adhesion, differentiation and mineralization on titanium topographies.

    PubMed

    Prowse, Paul D H; Elliott, Christopher G; Hutter, Jeff; Hamilton, Douglas W

    2013-01-01

    Reducing the time required for initial integration of bone-contacting implants with host tissues would be of great clinical significance. Changes in osteoblast adhesion formation and reorganization of the F-actin cytoskeleton in response to altered topography are known to be upstream of osteoblast differentiation, and these processes are regulated by the Rho GTPases. Rac and RhoA (through Rho Kinase (ROCK)). Using pharmacological inhibitors, we tested how inhibition of Rac and ROCK influenced osteoblast adhesion, differentiation and mineralization on PT (Pre-treated) and SLA (sandblasted large grit, acid etched) topographies. Inhibition of ROCK, but not Rac, significantly reduced adhesion number and size on PT, with adhesion size consistent with focal complexes. After 1 day, ROCK, but not Rac inhibition increased osteocalcin mRNA levels on SLA and PT, with levels further increasing at 7 days post seeding. ROCK inhibition also significantly increased bone sialoprotein expression at 7 days, but not BMP-2 levels. Rac inhibition significantly reduced BMP-2 mRNA levels. ROCK inhibition increased nuclear translocation of Runx2 independent of surface roughness. Mineralization of osteoblast cultures was greater on SLA than on PT, but was increased by ROCK inhibition and attenuated by Rac inhibition on both topographies. In conclusion, inhibition of ROCK signalling significantly increases osteoblast differentiation and biomineralization in a topographic dependent manner, and its pharmacological inhibition could represent a new therapeutic to speed bone formation around implanted metals and in regenerative medicine applications.

  1. Inhibition of Rac and ROCK Signalling Influence Osteoblast Adhesion, Differentiation and Mineralization on Titanium Topographies

    PubMed Central

    Prowse, Paul D. H.; Elliott, Christopher G.; Hutter, Jeff; Hamilton, Douglas W.

    2013-01-01

    Reducing the time required for initial integration of bone-contacting implants with host tissues would be of great clinical significance. Changes in osteoblast adhesion formation and reorganization of the F-actin cytoskeleton in response to altered topography are known to be upstream of osteoblast differentiation, and these processes are regulated by the Rho GTPases. Rac and RhoA (through Rho Kinase (ROCK)). Using pharmacological inhibitors, we tested how inhibition of Rac and ROCK influenced osteoblast adhesion, differentiation and mineralization on PT (Pre-treated) and SLA (sandblasted large grit, acid etched) topographies. Inhibition of ROCK, but not Rac, significantly reduced adhesion number and size on PT, with adhesion size consistent with focal complexes. After 1 day, ROCK, but not Rac inhibition increased osteocalcin mRNA levels on SLA and PT, with levels further increasing at 7 days post seeding. ROCK inhibition also significantly increased bone sialoprotein expression at 7 days, but not BMP-2 levels. Rac inhibition significantly reduced BMP-2 mRNA levels. ROCK inhibition increased nuclear translocation of Runx2 independent of surface roughness. Mineralization of osteoblast cultures was greater on SLA than on PT, but was increased by ROCK inhibition and attenuated by Rac inhibition on both topographies. In conclusion, inhibition of ROCK signalling significantly increases osteoblast differentiation and biomineralization in a topographic dependent manner, and its pharmacological inhibition could represent a new therapeutic to speed bone formation around implanted metals and in regenerative medicine applications. PMID:23505566

  2. Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2.

    PubMed

    Ji, Peng; Jayapal, Senthil Raja; Lodish, Harvey F

    2008-03-01

    Mammalian erythroid cells undergo enucleation, an asymmetric cell division involving extrusion of a pycnotic nucleus enveloped by the plasma membrane. The mechanisms that power and regulate the enucleation process have remained obscure. Here, we show that deregulation of Rac GTPase during a late stage of erythropoiesis completely blocks enucleation of cultured mouse fetal erythroblasts without affecting their proliferation or differentiation. Formation of the contractile actin ring (CAR) on the plasma membrane of enucleating erythroblasts was disrupted by inhibition of Rac GTPases. Furthermore, we demonstrate that mDia2, a downstream effector of Rho GTPases and a formin protein required for nucleation of unbranched actin filaments, is also required for enucleation of mouse fetal erythroblasts. We show that Rac1 and Rac2 bind to mDia2 in a GTP-dependent manner and that downregulation of mDia2, but not mDia1, by small interfering RNA (siRNA) during the late stages of erythropoiesis blocked both CAR formation and erythroblast enucleation. Additionally, overexpression of a constitutively active mutant of mDia2 rescued the enucleation defects induced by the inhibition of Rac GTPases. These results reveal important roles for Rac GTPases and their effector mDia2 in enucleation of mammalian erythroblasts.

  3. Rac1 GTPase silencing counteracts microgravity-induced effects on osteoblastic cells.

    PubMed

    Guignandon, Alain; Faure, Céline; Neutelings, Thibaut; Rattner, Aline; Mineur, Pierre; Linossier, Marie-Thérèse; Laroche, Norbert; Lambert, Charles; Deroanne, Christophe; Nusgens, Betty; Demets, René; Colige, Alain; Vico, Laurence

    2014-09-01

    Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblast-like cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [-50% in silenced, scrambled (SiScr) controls vs. -15% for SiRac1], the number of F-actin fibers (-60% in SiScr controls vs. -10% for SiRac1), and the depletion of matrix-bound VEGF (-40% in SiScr controls vs. -8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects. PMID:24903274

  4. Study of Vaccinia and Cowpox viruses' replication in Rac1-N17 dominant-negative cells

    PubMed Central

    Salgado, Ana Paula Carneiro; Soares-Martins, Jamária Adriana Pinheiro; Andrade, Luciana Garcia; Albarnaz, Jonas Dutra; Ferreira, Paulo César Peregrino; Kroon, Erna Geessien; Bonjardim, Cláudio Antônio

    2013-01-01

    Interfering with cellular signal transduction pathways is a common strategy used by many viruses to create a propitious intracellular environment for an efficient replication. Our group has been studying cellular signalling pathways activated by the orthopoxviruses Vaccinia (VACV) and Cowpox (CPXV) and their significance to viral replication. In the present study our aim was to investigate whether the GTPase Rac1 was an upstream signal that led to the activation of MEK/ERK1/2, JNK1/2 or Akt pathways upon VACV or CPXV' infections. Therefore, we generated stable murine fibroblasts exhibiting negative dominance to Rac1-N17 to evaluate viral growth and the phosphorylation status of ERK1/2, JNK1/2 and Akt. Our results demonstrated that VACV replication, but not CPXV, was affected in dominant-negative (DN) Rac1-N17 cell lines in which viral yield was reduced in about 10-fold. Viral late gene expression, but not early, was also reduced. Furthermore, our data showed that Akt phosphorylation was diminished upon VACV infection in DN Rac1-N17 cells, suggesting that Rac1 participates in the phosphoinositide-3 kinase pathway leading to the activation of Akt. In conclusion, our results indicate that while Rac1 indeed plays a role in VACV biology, perhaps another GTPase may be involved in CPXV replication. PMID:23903969

  5. Proapoptotic and antiinvasive activity of Rac1 small molecule inhibitors on malignant glioma cells

    PubMed Central

    Cardama, Georgina A; Gonzalez, Nazareno; Ciarlantini, Matias; Gandolfi Donadío, Lucia; Comin, María Julieta; Alonso, Daniel F; Menna, Pablo Lorenzano; Gomez, Daniel E

    2014-01-01

    Malignant gliomas are characterized by an intrinsic ability to invade diffusely throughout the normal brain tissue. This feature contributes mainly to the failure of existing therapies. Deregulation of small GTPases signaling, in particular Rac1 activity, plays a key role in the invasive phenotype of gliomas. Here we report the effect of ZINC69391, a specific Rac1 inhibitor developed by our group, on human glioma cell lines LN229 and U-87 MG. ZINC69391 is able to interfere with the interaction of Rac1 with Dock180, a relevant Rac1 activator in glioma invasion, and to reduce Rac1-GTP levels. The kinase Pak1, a downstream effector of Dock180–Rac1 signaling, was also downregulated upon ZINC69391 treatment. ZINC69391 reduced cell proliferation, arrested cells in G1 phase, and triggered apoptosis in glioma cells. Importantly, ZINC69391 dramatically affected cell migration and invasion in vitro, interfering with actin cytoskeleton dynamics. We also evaluated the effect of analog 1A-116, a compound derived from ZINC69391 structure. 1A-116 showed an improved antiproliferative and antiinvasive activity on glioma cells. These findings encourage further preclinical testing in clinically relevant animal models. PMID:25378937

  6. Rac1 GTPase silencing counteracts microgravity-induced effects on osteoblastic cells.

    PubMed

    Guignandon, Alain; Faure, Céline; Neutelings, Thibaut; Rattner, Aline; Mineur, Pierre; Linossier, Marie-Thérèse; Laroche, Norbert; Lambert, Charles; Deroanne, Christophe; Nusgens, Betty; Demets, René; Colige, Alain; Vico, Laurence

    2014-09-01

    Bone cells exposed to real microgravity display alterations of their cytoskeleton and focal adhesions, two major mechanosensitive structures. These structures are controlled by small GTPases of the Ras homology (Rho) family. We investigated the effects of RhoA, Rac1, and Cdc42 modulation of osteoblastic cells under microgravity conditions. Human MG-63 osteoblast-like cells silenced for RhoGTPases were cultured in the automated Biobox bioreactor (European Space Agency) aboard the Foton M3 satellite and compared to replicate ground-based controls. The cells were fixed after 69 h of microgravity exposure for postflight analysis of focal contacts, F-actin polymerization, vascular endothelial growth factor (VEGF) expression, and matrix targeting. We found that RhoA silencing did not affect sensitivity to microgravity but that Rac1 and, to a lesser extent, Cdc42 abrogation was particularly efficient in counteracting the spaceflight-related reduction of the number of focal contacts [-50% in silenced, scrambled (SiScr) controls vs. -15% for SiRac1], the number of F-actin fibers (-60% in SiScr controls vs. -10% for SiRac1), and the depletion of matrix-bound VEGF (-40% in SiScr controls vs. -8% for SiRac1). Collectively, these data point out the role of the VEGF/Rho GTPase axis in mechanosensing and validate Rac1-mediated signaling pathways as potential targets for counteracting microgravity effects.

  7. Deletion of Rac1GTPase in the Myeloid Lineage Protects against Inflammation-Mediated Kidney Injury in Mice.

    PubMed

    Nagase, Miki; Kurihara, Hidetake; Aiba, Atsu; Young, Morag J; Sakai, Tatsuo

    2016-01-01

    Macrophage-mediated inflammation has been implicated in various kidney diseases. We previously reported that Rac1, a Rho family small GTP-binding protein, was overactivated in several chronic kidney disease models, and that Rac1 inhibitors ameliorated renal injury, in part via inhibition of inflammation, but the detailed mechanisms have not been clarified. In the present study, we examined whether Rac1 in macrophages effects cytokine production and the inflammatory mechanisms contributing to kidney derangement. Myeloid-selective Rac1 flox control (M-Rac1 FC) and knockout (M-Rac1 KO) mice were generated using the cre-loxP system. Renal function under basal conditions did not differ between M-Rac1 FC and KO mice. Accordingly, lipopolysaccharide (LPS)-evoked kidney injury model was created. LPS elevated blood urea nitrogen and serum creatinine, enhanced expressions of kidney injury biomarkers, Kim-1 and Ngal, and promoted tubular injury in M-Rac1 FC mice. By contrast, deletion of myeloid Rac1 almost completely prevented the LPS-mediated renal impairment. LPS triggered a marked induction of macrophage-derived inflammatory cytokines, IL-6 and TNFα, in M-Rac1 FC mice, which was accompanied by Rac1 activation, stimulation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, and reactive oxygen species overproduction. These changes were inhibited in M-Rac1 KO mice. LPS evoked F4/80-positive macrophages accumulation in the kidney, which was not affected by myeloid Rac1 deficiency. We further tested the role of Rac1 signaling in cytokine production using macrophage cell line, RAW264.7. Exposure to LPS increased IL-6 and TNFα mRNA expression. The LPS-driven cytokine induction was dose-dependently blocked by the Rac1 inhibitor EHT1864, NADPH oxidase inhibitor diphenyleneiodonium, and NF-κB inhibitor BAY11-7082. In conclusion, genetic ablation of Rac1 in the myeloid lineage protected against LPS-induced renal inflammation and injury, by suppressing

  8. Deletion of Rac1GTPase in the Myeloid Lineage Protects against Inflammation-Mediated Kidney Injury in Mice.

    PubMed

    Nagase, Miki; Kurihara, Hidetake; Aiba, Atsu; Young, Morag J; Sakai, Tatsuo

    2016-01-01

    Macrophage-mediated inflammation has been implicated in various kidney diseases. We previously reported that Rac1, a Rho family small GTP-binding protein, was overactivated in several chronic kidney disease models, and that Rac1 inhibitors ameliorated renal injury, in part via inhibition of inflammation, but the detailed mechanisms have not been clarified. In the present study, we examined whether Rac1 in macrophages effects cytokine production and the inflammatory mechanisms contributing to kidney derangement. Myeloid-selective Rac1 flox control (M-Rac1 FC) and knockout (M-Rac1 KO) mice were generated using the cre-loxP system. Renal function under basal conditions did not differ between M-Rac1 FC and KO mice. Accordingly, lipopolysaccharide (LPS)-evoked kidney injury model was created. LPS elevated blood urea nitrogen and serum creatinine, enhanced expressions of kidney injury biomarkers, Kim-1 and Ngal, and promoted tubular injury in M-Rac1 FC mice. By contrast, deletion of myeloid Rac1 almost completely prevented the LPS-mediated renal impairment. LPS triggered a marked induction of macrophage-derived inflammatory cytokines, IL-6 and TNFα, in M-Rac1 FC mice, which was accompanied by Rac1 activation, stimulation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, and reactive oxygen species overproduction. These changes were inhibited in M-Rac1 KO mice. LPS evoked F4/80-positive macrophages accumulation in the kidney, which was not affected by myeloid Rac1 deficiency. We further tested the role of Rac1 signaling in cytokine production using macrophage cell line, RAW264.7. Exposure to LPS increased IL-6 and TNFα mRNA expression. The LPS-driven cytokine induction was dose-dependently blocked by the Rac1 inhibitor EHT1864, NADPH oxidase inhibitor diphenyleneiodonium, and NF-κB inhibitor BAY11-7082. In conclusion, genetic ablation of Rac1 in the myeloid lineage protected against LPS-induced renal inflammation and injury, by suppressing

  9. Deletion of Rac1GTPase in the Myeloid Lineage Protects against Inflammation-Mediated Kidney Injury in Mice

    PubMed Central

    Nagase, Miki; Kurihara, Hidetake; Aiba, Atsu; Young, Morag J.; Sakai, Tatsuo

    2016-01-01

    Macrophage-mediated inflammation has been implicated in various kidney diseases. We previously reported that Rac1, a Rho family small GTP-binding protein, was overactivated in several chronic kidney disease models, and that Rac1 inhibitors ameliorated renal injury, in part via inhibition of inflammation, but the detailed mechanisms have not been clarified. In the present study, we examined whether Rac1 in macrophages effects cytokine production and the inflammatory mechanisms contributing to kidney derangement. Myeloid-selective Rac1 flox control (M-Rac1 FC) and knockout (M-Rac1 KO) mice were generated using the cre-loxP system. Renal function under basal conditions did not differ between M-Rac1 FC and KO mice. Accordingly, lipopolysaccharide (LPS)-evoked kidney injury model was created. LPS elevated blood urea nitrogen and serum creatinine, enhanced expressions of kidney injury biomarkers, Kim-1 and Ngal, and promoted tubular injury in M-Rac1 FC mice. By contrast, deletion of myeloid Rac1 almost completely prevented the LPS-mediated renal impairment. LPS triggered a marked induction of macrophage-derived inflammatory cytokines, IL-6 and TNFα, in M-Rac1 FC mice, which was accompanied by Rac1 activation, stimulation of reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, and reactive oxygen species overproduction. These changes were inhibited in M-Rac1 KO mice. LPS evoked F4/80-positive macrophages accumulation in the kidney, which was not affected by myeloid Rac1 deficiency. We further tested the role of Rac1 signaling in cytokine production using macrophage cell line, RAW264.7. Exposure to LPS increased IL-6 and TNFα mRNA expression. The LPS-driven cytokine induction was dose-dependently blocked by the Rac1 inhibitor EHT1864, NADPH oxidase inhibitor diphenyleneiodonium, and NF-κB inhibitor BAY11-7082. In conclusion, genetic ablation of Rac1 in the myeloid lineage protected against LPS-induced renal inflammation and injury, by suppressing

  10. Air Conditioning with Magnetic Refrigeration : An Efficient, Green Compact Cooling System Using Magnetic Refrigeration

    SciTech Connect

    2010-09-01

    BEETIT Project: Astronautics is developing an air conditioning system that relies on magnetic fields. Typical air conditioners use vapor compression to cool air. Vapor compression uses a liquid refrigerant to circulate within the air conditioner, absorb the heat, and pump the heat out into the external environment. Astronautics’ design uses a novel property of certain materials, called “magnetocaloric materials”, to achieve the same result as liquid refrigerants. These magnetocaloric materials essentially heat up when placed within a magnetic field and cool down when removed, effectively pumping heat out from a cooler to warmer environment. In addition, magnetic refrigeration uses no ozone-depleting gases and is safer to use than conventional air conditioners which are prone to leaks.

  11. A 3D scanning confocal imaging method measures pit volume and captures the role of Rac in osteoclast function.

    PubMed

    Goldberg, Stephanie R; Georgiou, John; Glogauer, Michael; Grynpas, Marc D

    2012-07-01

    Modulation of Rho GTPases Rac1 and Rac2 impacts bone development, remodeling, and disease. In addition, GTPases are considered treatment targets for dysplastic and erosive bone diseases including Neurofibromatosis type 1. While it is important to understand the effects of Rac modulation on osteoclast function, two-dimensional resorption pit area measurements fall short in elucidating the volume aspect of bone resorption activity. Bone marrow from wild-type, Rac1 and Rac2 null mice was isolated from femora. Osteoclastogenesis was induced by adding M-CSF and RANKL in culture plates containing dentin slices and later stained with Picro Sirius Red to image resorption lacunae. Osteoclasts were also plated on glass cover slips and stained with phalloidin and DAPI to measure their surface area and the number of nuclei. Volumetric images were collected on a laser-scanning confocal system. Sirius Red confocal imaging provided an unambiguous, continuous definition of the pit boundary compared to reflected and transmitted light imaging. Rac1- and Rac2-deficient osteoclasts had fewer nuclei in comparison to wild-type counterparts. Rac1-deficient osteoclasts showed reduced resorption pit volume and surface area. Lacunae made by single Rac2 null osteoclasts had reduced volume but surprisingly surface area was unaffected. Surface area measures are deceiving since volume changed independently in resorption pits made by individual Rac2 null osteoclasts. Our innovative confocal imaging technique allows us to derive novel conclusions about Rac1 and Rac2 in osteoclast function. The data and method can be applied to study effects of genes and drugs including Rho GTPase modulators on osteoclast function and to develop pharmacotherapeutics to treat bone lytic disorders.

  12. Effects of flow conditioners and tap location on orifice flowmeter performance

    NASA Astrophysics Data System (ADS)

    Scott, J. L.; Sindt, C. F.; Lewis, M. A.; Brennan, J. A.

    1991-10-01

    Current research is being conducted to provide information which will be used to improve the existing industry standards for proper installation of orifice meters. The research includes experimental investigation of a Zanker, an etoile, and several tube bundle flow conditioners at various positions relative to the orifice plate. Also included are the effects of pressure tap location, both with and without flow conditioning, as reflected in determination of discharge coefficients. Of the flow conditioners tested at approximately 11 pipe diameters upstream of the orifice plate, the Zanker flow conditioner resulted in discharge coefficients most similar to baseline values. There was only a slight difference in orifice meter performance when a flanged or an in-line tube bundle flow conditioner was used at the tested location upstream of the orifice plate. The effect of pressure tap location was found to be significant with the 0.73 beta ratio plate. Recommendations for future research, as a result of these findings, are included.

  13. Effects of conditioners on surface hardness of hair fibers: an investigation using atomic force microscopy.

    PubMed

    Ruetsch, S B; Kamath, Y K; Kintrup, L; Schwark, H-J

    2003-01-01

    Conditioners are known to have a prophylactic effect on hair damage caused by cosmetic chemical treatments or mechanical grooming procedures. They are known to impart softness and smoothness to hair by moisturizing the fiber. Since the amount of conditioners deposited on the fiber is very small in quantity, it is conceivable that mainly the surface is moisturized. This is especially true of polymeric conditioners, which deposit preferentially on the surface of the fiber, rather than penetrate into the cortex. Therefore, this study strictly investigates whether cationic polymeric conditioners impart softness to the surface cuticle cell as a result of their hydrophilicity, with no regard to its applicability to cosmetic effects. Such softening can be detected by indentation of the surface and can be quantified by measuring the depth of the indent in real time. Atomic force microscopy (AFM), equipped with nano-indentation capability, is ideally suited for this purpose. In this work it was used to determine changes in the microhardness (micromechanical properties) of the hair fiber surface as a result of fiber/conditioner/moisture interactions. In a preliminary study, we observed that the scale faces of hair treated with Polyquaternium 10 (PQ-10) conditioner gave deeper indents, while scale edges yielded shallower ones in comparison to cuticle cells of untreated hair. This suggests that the conditioner softens the scale face and hardens the scale edges. However, because of significant amounts of conditioner residues left on the scale face, this conclusion was rather ambiguous. Therefore, the study was repeated in which multiple indentations were made on the surface cuticle cells of a larger number of the same hair fibers before and after multiple applications of the conditioner. This reduces errors due to fiber-to-fiber variation in pre-existing microhardness differences in surface cuticle cells. Also, the larger number of fibers investigated in the current work

  14. Effects of polyacrylamide soil conditioner on the iron status of soybean plants. [Glycine max

    SciTech Connect

    Wallace, A.; Wallace, G.A.; Abouzamzam, A.M.; Char, J.W.

    1986-05-01

    An iron-inefficient cultivar of soybean (Glycine max L. Merr. Bragg cv. PI-54619-5-1 was grown in two different calcareous soils, a Natrargid and a Torrifluvents, to determine if improvement of soil aeration with a synthetic polyacrylamide as a soil conditioner would decrease the tendency of the cultivar to lime-induced chlorosis. The results suggest that when soil is well aerated with good drainage from use of the soil conditioner, the iron status of plants is improved.

  15. Unipolar pulse and bipolar noise testing of wideband signal noise conditioner (MC476-0132-0034)

    NASA Technical Reports Server (NTRS)

    Harris, J. E.

    1977-01-01

    Information is presented on performance characteristics of the shuttle orbiter wideband signal conditioner when subjected to special types of input signals. Design analysis of the signal flow path through the signal conditioning amplifier was performed followed by acutal testing of the amplifier with various signal inputs. Results indicate that the signal conditioner should perform acceptably if the shuttle orbiter flight vibration signal levels are in accord with preflight predictions.

  16. Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice.

    PubMed

    Choudhari, Ramesh; Minero, Valerio Giacomo; Menotti, Matteo; Pulito, Roberta; Brakebusch, Cord; Compagno, Mara; Voena, Claudia; Ambrogio, Chiara; Chiarle, Roberto

    2016-03-10

    Increasing evidence suggests that Rho family GTPases could have a critical role in the biology of T-cell lymphoma. In ALK-rearranged anaplastic large cell lymphoma (ALCL), a specific subtype of T-cell lymphoma, the Rho family GTPases Cdc42 and Rac1 are activated by the ALK oncogenic activity. In vitro studies have shown that Cdc42 and Rac1 control rather similar phenotypes of ALCL biology such as the proliferation, survival, and migration of lymphoma cells. However, their role and possible redundancy in ALK-driven lymphoma development in vivo are still undetermined. We genetically deleted Cdc42 or Rac1 in a mouse model of ALK-rearranged ALCL to show that either Cdc42 or Rac1 deletion impaired lymphoma development, modified lymphoma morphology, actin filament distribution, and migration properties of lymphoma cells. Cdc42 or Rac1 deletion primarily affected survival rather than proliferation of lymphoma cells. Apoptosis of lymphoma cells was equally induced following Cdc42 or Rac1 deletion, was associated with upregulation of the proapoptotic molecule Bid, and was blocked by Bcl2 overexpression. Remarkably, Cdc42/Rac1 double deletion, but not Cdc42 or Rac1 single deletions, completely prevented NPM-ALK lymphoma dissemination in vivo. Thus, Cdc42 and Rac1 have nonredundant roles in controlling ALK-rearranged lymphoma survival and morphology but are redundant for lymphoma dissemination, suggesting that targeting both GTPases could represent a preferable therapeutic option for ALCL treatment.

  17. Molecular insights into DNA binding and anchoring by the Bacillus subtilis sporulation kinetochore-like RacA protein

    PubMed Central

    Schumacher, Maria A.; Lee, Jeehyun; Zeng, Wenjie

    2016-01-01

    During Bacillus subtilis sporulation, segregating sister chromosomes are anchored to cell poles and the chromosome is remodeled into an elongated structure called the axial filament. Data indicate that a developmentally regulated protein called RacA is involved in these functions. To gain insight into how RacA performs these diverse processes we performed a battery of structural and biochemical analyses. These studies show that RacA contains an N-terminal winged-helix-turn-helix module connected by a disordered region to a predicted coiled-coil domain. Structures capture RacA binding the DNA using distinct protein–protein interfaces and employing adjustable DNA docking modes. This unique DNA binding mechanism indicates how RacA can both specifically recognize its GC-rich centromere and also non-specifically bind the DNA. Adjacent RacA molecules within the protein–DNA structure interact leading to DNA compaction, suggesting a mechanism for axial filament formation. We also show that the RacA C-domain coiled coil directly contacts the coiled coil region of the polar protein DivIVA, which anchors RacA and hence the chromosome to the pole. Thus, our combined data reveal unique DNA binding properties by RacA and provide insight into the DNA remodeling and polar anchorage functions of the protein. PMID:27085804

  18. Air conditioning system

    DOEpatents

    Lowenstein, Andrew; Miller, Jeffrey; Gruendeman, Peter; DaSilva, Michael

    2005-02-01

    An air conditioner comprises a plurality of plates arranged in a successively stacked configuration with portions thereof having a spaced apart arrangement, and defining between successive adjacent pairs of plates at the spaced apart portions a first and second series of discrete alternating passages wherein a first air stream is passed through the first series of passages and a second air stream is passed through the second series of passages; and said stacked configuration of plates forming integrally therewith a liquid delivery means for delivering from a source a sufficient quantity of a liquid to the inside surfaces of the first series of fluid passages in a manner which provides a continuous flow of the liquid from a first end to a second end of the plurality of plates while in contact with the first air stream.

  19. Structural and Functional Regulation of Tight Junctions by RhoA and Rac1 Small GTPases

    PubMed Central

    Jou, Tzuu-Shuh; Schneeberger, Eveline E.; James Nelson, W.

    1998-01-01

    Tight junctions (TJ) govern ion and solute diffusion through the paracellular space (gate function), and restrict mixing of membrane proteins and lipids between membrane domains (fence function) of polarized epithelial cells. We examined roles of the RhoA and Rac1 GTPases in regulating TJ structure and function in MDCK cells using the tetracycline repressible transactivator to regulate RhoAV14, RhoAN19, Rac1V12, and Rac1N17 expression. Both constitutively active and dominant negative RhoA or Rac1 perturbed TJ gate function (transepithelial electrical resistance, tracer diffusion) in a dose-dependent and reversible manner. Freeze-fracture EM and immunofluoresence microscopy revealed abnormal TJ strand morphology and protein (occludin, ZO-1) localization in RhoAV14 and Rac1V12 cells. However, TJ strand morphology and protein localization appeared normal in RhoAN19 and Rac1N17 cells. All mutant GTPases disrupted the fence function of the TJ (interdomain diffusion of a fluorescent lipid), but targeting and organization of a membrane protein in the apical membrane were unaffected. Expression levels and protein complexes of occludin and ZO-1 appeared normal in all mutant cells, although ZO-1 was more readily solubilized from RhoAV14-expressing cells with Triton X-100. These results show that RhoA and Rac1 regulate gate and fence functions of the TJ, and play a role in the spatial organization of TJ proteins at the apex of the lateral membrane. PMID:9660866

  20. Novel role of Rac1/WAVE signaling mechanism in regulation of the epithelial Na+ channel.

    PubMed

    Karpushev, Alexey V; Levchenko, Vladislav; Ilatovskaya, Daria V; Pavlov, Tengis S; Staruschenko, Alexander

    2011-05-01

    The epithelial Na(+) channel (ENaC) is an essential channel responsible for Na(+) reabsorption in the aldosterone-sensitive distal nephron. Consequently, ENaC is a major effector impacting systemic blood volume and pressure. We have shown recently that Rac1 increases ENaC activity, whereas Cdc42 fails to change channel activity. Here we tested whether Rac1 signaling plays a physiological role in modulating ENaC in native tissue and polarized epithelial cells. We found that Rac1 inhibitor NSC23766 markedly decreased ENaC activity in freshly isolated collecting ducts. Knockdown of Rac1 in native principal cells decreased ENaC-mediated sodium reabsorption and the number of channels at the apical plasma membrane. Members of the Wiskott-Aldrich syndrome protein (WASP) family play a central role in the control of the actin cytoskeleton. N-WASP functions downstream of Cdc42, whereas WAVEs are effectors of Rac1 activity. N-WASP and all 3 isoforms of WAVE significantly increased ENaC activity when coexpressed in Chinese hamster ovary cells. However, wiskostatin, an inhibitor of N-WASP, had no effect on ENaC activity. Immunoblotting demonstrated the presence of WAVE1 and WAVE2 and absence of N-WASP and WAVE3 in mpkCCD(c14) and M-1 principal cells. Immunohistochemistry analysis also revealed localization of WAVE1 and WAVE2 but not N-WASP in the cortical collecting duct of Sprague-Dawley rat kidneys. Moreover, patch clamp analysis revealed that Rac1 and WAVE1/2 are parts of the same signaling pathway with respect to activation of ENaC. Thus, our findings suggest that Rac1 is essential for ENaC activity and regulates the channel via WAVE proteins.

  1. Design and evaluation of an inlet conditioner to dry particles for real-time particle sizers.

    PubMed

    Peters, Thomas M; Riss, Adam L; Holm, Ricky L; Singh, Manisha; Vanderpool, Robert W

    2008-04-01

    Real-time particle sizers provide rapid information about atmospheric particles, particularly peak exposures, which may be important in the development of adverse health outcomes. However, these instruments are subject to erroneous readings in high-humidity environments when compared with measurements from filter-based, federal reference method (FRM) samplers. Laboratory tests were conducted to evaluate the ability of three inlet conditioners to dry aerosol prior to entering a real-time particle sizer for measuring coarse aerosols (Model 3321 Aerodynamic Particle Sizer, APS) under simulated highly humid conditions. Two 30 day field studies in Birmingham, AL, USA were conducted to compare the response of two APSs operated with and without an inlet conditioner to that measured with FRM samplers. In field studies, the correlation of PM(10-2.5) derived from the APS and that measured with the FRM was substantially stronger with an inlet conditioner applied (r2 ranged from 0.91 to 0.99) than with no conditioner (r2 = 0.61). Laboratory experiments confirmed the ability of the heater and desiccant conditioner to remove particle-borne moisture. In field tests, water was found associated with particles across the sizing range of the APS (0.5 microm to 20 microm) when relative humidity was high in Birmingham. Certain types of inlet conditioners may substantially improve the correlation between particulate mass concentration derived from real-time particle sizers and filter-based samplers in humid conditions. PMID:18385876

  2. Regulation of Kir2.1 channels by the Rho-GTPase, Rac1

    PubMed Central

    Boyer, Stephanie B.; Slesinger, Paul A.; Jones, S.V. Penelope

    2010-01-01

    Mutations in Kir2.1 inwardly rectifying potassium channels are associated with Andersen Syndrome, a disease characterized by potentially fatal cardiac arrhythmias. While several Andersen-associated mutations affect membrane expression, the cytoplasmic signals that regulate Kir2.1 trafficking are poorly understood. Here, we investigated whether the Rho-family of small GTPases regulates trafficking of Kir2.1 channels expressed in HEK-293 cells. Treatment with C. difficile toxin B, an inhibitor of Rho-family GTPases, or co-expression of the dominant-negative mutant of Rac1 (Rac1DN) increased Kir2.1 current density ~2-fold. However, the dominant-negative forms of other Rho-family GTPases, RhoA or Cdc42, did not alter Kir2.1 currents, suggesting a selective effect of Rac1 on Kir2.1 current density. Single-channel properties (γ, τo, τc) and total protein levels of Kir2.1 were unchanged with co-expression of Rac1DN; however, studies using TIRF microscopy and CFP-tagged Kir2.1 revealed increased channel surface expression. Immunohistochemical detection of extracellularly-tagged HA-Kir2.1 channels showed that Rac1DN reduced channel internalization when co-expressed. Finally, the dominant-negative mutant of dynamin, which interferes with endocytosis, occluded the Rac1DN–induced potentiation of Kir2.1 currents. These data suggest that inhibition of Rac1 increases Kir2.1 surface expression by interfering with endocytosis, likely via a dynamin-dependent pathway. Surprisingly, Rac1DN did not alter Kir2.2 current density or internalization, suggesting subunit specific modulation of Kir2.1 channels. Consistent with this, construction of Kir2.1/2.2 chimeras implicated the C-terminal domain of Kir2.1 in mediating the potentiating effect of Rac1DN. This novel pathway for regulating surface expression of cardiac Kir2.1 channels could have implications for normal and diseased cardiac states. PMID:18932198

  3. Distinct predictive performance of Rac1 and Cdc42 in cell migration

    PubMed Central

    Yamao, Masataka; Naoki, Honda; Kunida, Katsuyuki; Aoki, Kazuhiro; Matsuda, Michiyuki; Ishii, Shin

    2015-01-01

    We propose a new computation-based approach for elucidating how signaling molecules are decoded in cell migration. In this approach, we performed FRET time-lapse imaging of Rac1 and Cdc42, members of Rho GTPases which are responsible for cell motility, and quantitatively identified the response functions that describe the conversion from the molecular activities to the morphological changes. Based on the identified response functions, we clarified the profiles of how the morphology spatiotemporally changes in response to local and transient activation of Rac1 and Cdc42, and found that Rac1 and Cdc42 activation triggers laterally propagating membrane protrusion. The response functions were also endowed with property of differentiator, which is beneficial for maintaining sensitivity under adaptation to the mean level of input. Using the response function, we could predict the morphological change from molecular activity, and its predictive performance provides a new quantitative measure of how much the Rho GTPases participate in the cell migration. Interestingly, we discovered distinct predictive performance of Rac1 and Cdc42 depending on the migration modes, indicating that Rac1 and Cdc42 contribute to persistent and random migration, respectively. Thus, our proposed predictive approach enabled us to uncover the hidden information processing rules of Rho GTPases in the cell migration. PMID:26634649

  4. Tum/RacGAP functions as a switch activating the Pav/kinesin-6 motor.

    PubMed

    Tao, Li; Fasulo, Barbara; Warecki, Brandt; Sullivan, William

    2016-01-01

    Centralspindlin is essential for central spindle and cleavage furrow formation. Drosophila centralspindlin consists of a kinesin-6 motor (Pav/kinesin-6) and a GTPase-activating protein (Tum/RacGAP). Centralspindlin localization to the central spindle is mediated by Pav/kinesin-6. While Tum/RacGAP has well-documented scaffolding functions, whether it influences Pav/kinesin-6 function is less well-explored. Here we demonstrate that both Pav/kinesin-6 and the centralspindlin complex (co-expressed Pav/Tum) have strong microtubule bundling activity. Centralspindlin also has robust plus-end-directed motility. In contrast, Pav/kinesin-6 alone cannot move microtubules. However, the addition of Tum/RacGAP or a 65 amino acid Tum/RacGAP fragment to Pav/kinesin-6 restores microtubule motility. Further, ATPase assays reveal that microtubule-stimulated ATPase activity of centralspindlin is seven times higher than that of Pav/kinesin-6. These findings are supported by in vivo studies demonstrating that in Tum/RacGAP-depleted S2 Drosophila cells, Pav/kinesin-6 exhibits severely reduced localization to the central spindle and an abnormal concentration at the centrosomes. PMID:27091402

  5. CD81 regulates cell migration through its association with Rac GTPase

    PubMed Central

    Tejera, Emilio; Rocha-Perugini, Vera; López-Martín, Soraya; Pérez-Hernández, Daniel; Bachir, Alexia I.; Horwitz, Alan Rick; Vázquez, Jesús; Sánchez-Madrid, Francisco; Yáñez-Mo, María

    2013-01-01

    CD81 is a member of the tetraspanin family that has been described to have a key role in cell migration of tumor and immune cells. To unravel the mechanisms of CD81-regulated cell migration, we performed proteomic analyses that revealed an interaction of the tetraspanin C-terminal domain with the small GTPase Rac. Direct interaction was confirmed biochemically. Moreover, microscopy cross-correlation analysis demonstrated the in situ integration of both molecules into the same molecular complex. Pull-down experiments revealed that CD81-Rac interaction was direct and independent of Rac activation status. Knockdown of CD81 resulted in enhanced protrusion rate, altered focal adhesion formation, and decreased cell migration, correlating with increased active Rac. Reexpression of wild-type CD81, but not its truncated form lacking the C-terminal cytoplasmic domain, rescued these effects. The phenotype of CD81 knockdown cells was mimicked by treatment with a soluble peptide with the C-terminal sequence of the tetraspanin. Our data show that the interaction of Rac with the C-terminal cytoplasmic domain of CD81 is a novel regulatory mechanism of the GTPase activity turnover. Furthermore, they provide a novel mechanism for tetraspanin-dependent regulation of cell motility and open new avenues for tetraspanin-targeted reagents by the use of cell-permeable peptides. PMID:23264468

  6. The Rac1 inhibitor NSC23766 suppresses CREB signaling by targeting NMDA receptor function.

    PubMed

    Hou, Hailong; Chávez, Andrés E; Wang, Chih-Chieh; Yang, Hongtian; Gu, Hua; Siddoway, Benjamin A; Hall, Benjamin J; Castillo, Pablo E; Xia, Houhui

    2014-10-15

    NMDA receptor signaling plays a complex role in CREB activation and CREB-mediated gene transcription, depending on the subcellular location of NMDA receptors, as well as how strongly they are activated. However, it is not known whether Rac1, the prototype of Rac GTPase, plays a role in neuronal CREB activation induced by NMDA receptor signaling. Here, we report that NSC23766, a widely used specific Rac1 inhibitor, inhibits basal CREB phosphorylation at S133 (pCREB) and antagonizes changes in pCREB levels induced by NMDA bath application in rat cortical neurons. Unexpectedly, we found that NSC23766 affects the levels of neuronal pCREB in a Rac1-independent manner. Instead, our results indicate that NSC23766 can directly regulate NMDA receptors as indicated by their strong effects on both exogenous and synaptically evoked NMDA receptor-mediated currents in mouse and rat neurons, respectively. Our findings strongly suggest that Rac1 does not affect pCREB signaling in cortical neurons and reveal that NSC23766 could be a novel NMDA receptor antagonist.

  7. Tiam1/Rac1 complex controls Il17a transcription and autoimmunity

    PubMed Central

    Kurdi, Ahmed T.; Bassil, Ribal; Olah, Marta; Wu, Chuan; Xiao, Sheng; Taga, Mariko; Frangieh, Michael; Buttrick, Thomas; Orent, William; Bradshaw, Elizabeth M.; Khoury, Samia J.; Elyaman, Wassim

    2016-01-01

    RORγt is a master transcription factor of Th17 cells and considered as a promising drug target for the treatment of autoimmune diseases. Here, we show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regulate interleukin (IL)17A transcription and autoimmunity. Whereas Tiam1 genetic deficiency weakens IL-17A expression partially and inhibits the development of experimental autoimmune encephalomyelitis (EAE), deletion of Rac1 in T cells exhibits more robust effects on Th17 cells and EAE. We demonstrate Tiam1 and Rac1 form a complex with RORγt in the nuclear compartment of Th17 cells, and together bind and activate the Il17 promoter. The clinical relevance of these findings is emphasized by pharmacological targeting of Rac1 that suppresses both murine and human Th17 cells as well as EAE. Thus, our findings highlight a regulatory pathway of Tiam1/Rac1 in Th17 cells and suggest that it may be a therapeutic target in multiple sclerosis. PMID:27725632

  8. Tum/RacGAP functions as a switch activating the Pav/kinesin-6 motor

    PubMed Central

    Tao, Li; Fasulo, Barbara; Warecki, Brandt; Sullivan, William

    2016-01-01

    Centralspindlin is essential for central spindle and cleavage furrow formation. Drosophila centralspindlin consists of a kinesin-6 motor (Pav/kinesin-6) and a GTPase-activating protein (Tum/RacGAP). Centralspindlin localization to the central spindle is mediated by Pav/kinesin-6. While Tum/RacGAP has well-documented scaffolding functions, whether it influences Pav/kinesin-6 function is less well-explored. Here we demonstrate that both Pav/kinesin-6 and the centralspindlin complex (co-expressed Pav/Tum) have strong microtubule bundling activity. Centralspindlin also has robust plus-end-directed motility. In contrast, Pav/kinesin-6 alone cannot move microtubules. However, the addition of Tum/RacGAP or a 65 amino acid Tum/RacGAP fragment to Pav/kinesin-6 restores microtubule motility. Further, ATPase assays reveal that microtubule-stimulated ATPase activity of centralspindlin is seven times higher than that of Pav/kinesin-6. These findings are supported by in vivo studies demonstrating that in Tum/RacGAP-depleted S2 Drosophila cells, Pav/kinesin-6 exhibits severely reduced localization to the central spindle and an abnormal concentration at the centrosomes. PMID:27091402

  9. The Campylobacter jejuni RacRS system regulates fumarate utilization in a low oxygen environment.

    PubMed

    van der Stel, Anne-Xander; van Mourik, Andries; Heijmen-van Dijk, Linda; Parker, Craig T; Kelly, David J; van de Lest, Chris H A; van Putten, Jos P M; Wösten, Marc M S M

    2015-04-01

    The natural environment of the human pathogen Campylobacter jejuni is the gastrointestinal tract of warm-blooded animals. In the gut, the availability of oxygen is limited; therefore, less efficient electron acceptors such as nitrate or fumarate are used by C. jejuni. The molecular mechanisms that regulate the activity of the highly branched respiratory chain of C. jejuni are still a mystery mainly because C. jejuni lacks homologues of transcription factors known to regulate energy metabolism in other bacteria. Here we demonstrate that dependent on the available electron acceptors the two-component system RacRS controls the production of fumarate from aspartate, as well as its transport and reduction to succinate. Transcription profiling, DNAse protection and functional assays showed that phosphorylated RacR binds to and represses at least five promoter elements located in front of genes involved in the uptake and synthesis of fumarate. The RacRS system is active in the presence of nitrate and trimethyl-amine-N-oxide under oxygen-limited conditions when fumarate is less preferred as an alternative electron acceptor. In the inactive state, RacRS allows utilization of fumarate for respiration. The unique C. jejuni RacRS regulatory system illustrates the disparate evolution of Campylobacter and aids the survival of this pathogen.

  10. Cytotoxic Necrotizing Factor-Y Boosts Yersinia Effector Translocation by Activating Rac Protein*

    PubMed Central

    Wolters, Manuel; Boyle, Erin C.; Lardong, Kerstin; Trülzsch, Konrad; Steffen, Anika; Rottner, Klemens; Ruckdeschel, Klaus; Aepfelbacher, Martin

    2013-01-01

    Pathogenic Yersinia spp. translocate the effectors YopT, YopE, and YopO/YpkA into target cells to inactivate Rho family GTP-binding proteins and block immune responses. Some Yersinia spp. also secrete the Rho protein activator cytotoxic necrotizing factor-Y (CNF-Y), but it has been unclear how the bacteria may benefit from Rho protein activation. We show here that CNF-Y increases Yop translocation in Yersinia enterocolitica-infected cells up to 5-fold. CNF-Y strongly activated RhoA and also delayed in time Rac1 and Cdc42, but when individually expressed, constitutively active mutants of Rac1, but not of RhoA, increased Yop translocation. Consistently, knock-out or knockdown of Rac1 but not of RhoA, -B, or -C inhibited Yersinia effector translocation in CNF-Y-treated and control cells. Activation or knockdown of Cdc42 also affected Yop translocation but much less efficiently than Rac. The increase in Yop translocation induced by CNF-Y was essentially independent of the presence of YopE, YopT, or YopO in the infecting Yersinia strain, indicating that none of the Yops reported to inhibit translocation could reverse the CNF-Y effect. In summary, the CNF-Y activity of Yersinia strongly enhances Yop translocation through activation of Rac. PMID:23803609

  11. In Vitro Prenylation of the Small GTPase Rac13 of Cotton.

    PubMed Central

    Trainin, T.; Shmuel, M.; Delmer, D. P.

    1996-01-01

    Previous work (D.P. Delmer, J. Pear, A. Andrawis, D. Stalker [1995] Mol Gen Genet 248: 43-51) has identified a gene in cotton (Gossypium hirsutum), Rac13, that encodes a small, signal-transducing GTPase and shows high expression in the fiber at the time of transition from primary to secondary wall synthesis. Since Rac13 may be important in signal transduction pathway(s), regulating the onset of fiber secondary wall synthesis, we continue to characterize Rac13 by determining its ability to undergo posttranslational modification. In animals Rac proteins contain the C-terminal consensus sequence CaaL (where "a" can be any aliphatic residue), which is a site for geranylgeranylation (B.T. Kinsella, R.A. Erdman, W.A. Maltese [1994] J Biol Chem 266: 9786-9794). We have identified activities in developing cotton fibers that resemble in specificity the geranylgeranyl- and farnesyltransferases of animals and yeast. In addition, using prenyltransferases from rabbit reticulocytes, we show that Rac13, having a C-terminal sequence of CAFL, can serve as an in vitro substrate for geranylgeranylation but not farnesylation. However, the presence of the uncommon penultimate F residue appears to slow the rate of prenylation considerably compared with other acceptors. PMID:12226460

  12. Matrix compliance regulates Rac1b localization, NADPH oxidase assembly, and epithelial–mesenchymal transition

    PubMed Central

    Lee, KangAe; Chen, Qike K.; Lui, Cecillia; Cichon, Magdalena A.; Radisky, Derek C.; Nelson, Celeste M.

    2012-01-01

    Epithelial–mesenchymal transition (EMT) is a form of epithelial plasticity implicated in fibrosis and tumor metastasis. Here we show that the mechanical rigidity of the microenvironment plays a pivotal role in the promotion of EMT by controlling the subcellular localization and downstream signaling of Rac GTPases. Soft substrata, with compliances comparable to that of normal mammary tissue, are protective against EMT, whereas stiffer substrata, with compliances characteristic of breast tumors, promote EMT. Rac1b, a highly activated splice variant of Rac1 found in tumors, localizes to the plasma membrane in cells cultured on stiff substrata or in collagen-rich regions of human breast tumors. At the membrane, Rac1b forms a complex with NADPH oxidase and promotes the production of reactive oxygen species, expression of Snail, and activation of the EMT program. In contrast, soft microenvironments inhibit the membrane localization of Rac1b and subsequent redox changes. These results reveal a novel mechanotransduction pathway in the regulation of epithelial plasticity via EMT. PMID:22918955

  13. Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation.

    PubMed

    Soon, Lilian L; Yie, Ting-An; Shvarts, Anita; Levine, Arnold J; Su, Fei; Tchou-Wong, Kam-Meng

    2003-03-28

    Wnt-induced-secreted-protein-1 (WISP-1) is a cysteine-rich, secreted factor belonging to the CCN family. These proteins have been implicated in the inhibition of metastasis; however, the mechanisms involved have not been described. We demonstrated that overexpression of WISP-1 in H460 lung cancer cells inhibited lung metastasis and in vitro cell invasion and motility. We investigated the possibility that WISP-1 may regulate activation of Rac, a small GTPase important for cytoskeletal reorganizations during motility. In an indirect assay, WISP-1-expressing cells exhibited marked reduction in Rac activation compared with control cells. Blocking antibodies to alpha(v)beta(5) and alpha(1) integrins restored Rac activation in WISP-1 cells, suggesting that the inhibitory effect of WISP-1 on Rac lies downstream of integrins. Constitutively activated Rac mutant (RacG12V) was transfected into WISP-1 cells to restore Rac activation and these WISP-1/RacG12V transfectants were used for further studies. We performed microarray and real-time PCR analyses to identify genes involved in invasion that may be differentially regulated by WISP-1. Here, we showed decreased expression of metalloproteinase-1 (MMP-1) in WISP-1 cells compared with controls but increased expression in WISP-1/RacG12V cells. In an invasion assay across collagen I, an MMP-1 target matrix, WISP-1 cells were significantly less invasive compared with controls, whereas WISP-1/RacG12V cells showed elevated invasion levels. This work illustrates a negatively regulated pathway by WISP-1 involving integrins and Rac in the down-regulation of invasion.

  14. Electronic Power Conditioner for Ku-band Travelling Wave Tube

    NASA Astrophysics Data System (ADS)

    Kowstubha, Palle; Krishnaveni, K.; Ramesh Reddy, K.

    2016-07-01

    A highly sophisticated regulated power supply is known as electronic power conditioner (EPC) is required to energise travelling wave tubes (TWTs), which are used as RF signal amplifiers in satellite payloads. The assembly consisting of TWT and EPC together is known as travelling wave tube amplifier (TWTA). EPC is used to provide isolated and conditioned voltage rails with tight regulation to various electrodes of TWT and makes its RF performance independent of solar bus variations which are caused due to varying conditions of eclipse and sunlit. The payload mass and their power consumption is mainly due to the existence of TWTAs that represent about 35 % of total mass and about 70-90 % (based on the type of satellite application) of overall dc power consumption. This situation ensures a continuous improvement in the design of TWTAs and their associated EPCs to realize more efficient and light products. Critical technologies involved in EPCs are design and configuration, closed loop regulation, component and material selection, energy limiting of high voltage (HV) outputs and potting of HV card etc. This work addresses some of these critical technologies evolved in realizing and testing the state of art of EPC and it focuses on the design of HV supply with a HV and high power capability, up to 6 kV and 170 WRF, respectively required for a space TWTA. Finally, an experimental prototype of EPC with a dc power of 320 W provides different voltages required by Ku-band TWT in open loop configuration.

  15. The nuclear cofactor RAC3/AIB1/SRC-3 enhances Nrf2 signaling by interacting with transactivation domains

    PubMed Central

    Kim, Jung-Hwan; Yu, Siwang; Chen, J. Don; Kong, A.-N. Tony

    2012-01-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2, NM 006164, 605 AA) is essential for the antioxidant responsive element (ARE)-mediated expression of a group of detoxifying antioxidant genes that detoxify carcinogens and protect against oxidative stress. Several proteins have been identified as Nrf2-interacting molecules. In this study, we found that the overexpression of RAC3/AIB-1/SRC-3, a nuclear co-regulator and oncogene frequently amplified in human breast cancers, induced heme oxygenase-1 (HO-1) through Nrf2 transactivation in HeLa cells. Next, we determined the interaction between RAC3 and Nrf2 proteins using a co-immunoprecipitation assay (co-IP) and fluorescence resonance energy transfer (FRET) analysis. The results showed that RAC3 bound directly to the Nrf2 protein in the nucleus. Subsequently, we identified the interacting domains of Nrf2 and RAC3 using a GST pull-down assay. The results showed that both the N-terminal RAC3-pasB and C-terminal RAC3-R3B3 domains were tightly bound to the Neh4 and Neh5 transactivation domains. Furthermore, chromatin immunoprecipitation (ChIP) showed that RAC3 bound tightly to the ARE enhancer region of the HO-1 promoter via Nrf2 binding. These data suggest that Nrf2 activation is modulated and directly controlled through interactions with the RAC3 protein in HeLa cells. PMID:22370642

  16. Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling

    PubMed Central

    Das, Sulagna; Yin, Taofei; Yang, Qingfen; Zhang, Jingqiao; Wu, Yi I.; Yu, Ji

    2015-01-01

    Polarized Rac1 signaling is a hallmark of many cellular functions, including cell adhesion, motility, and cell division. The two steps of Rac1 activation are its translocation to the plasma membrane and the exchange of nucleotide from GDP to GTP. It is, however, unclear whether these two processes are regulated independent of each other and what their respective roles are in polarization of Rac1 signaling. We designed a single-particle tracking (SPT) method to quantitatively analyze the kinetics of Rac1 membrane translocation in living cells. We found that the rate of Rac1 translocation was significantly elevated in protrusions during cell spreading on collagen. Furthermore, combining FRET sensor imaging with SPT measurements in the same cell, the recruitment of Rac1 was found to be polarized to an extent similar to that of the nucleotide exchange process. Statistical analysis of single-molecule trajectories and optogenetic manipulation of membrane lipids revealed that Rac1 membrane translocation precedes nucleotide exchange, and is governed primarily by interactions with phospholipids, particularly PI(3,4,5)P3, instead of protein factors. Overall, the study highlights the significance of membrane translocation in spatial Rac1 signaling, which is in addition to the traditional view focusing primarily on GEF distribution and exchange reaction. PMID:25561548

  17. Characterization of a RacGTPase up-regulated in the large yellow croaker Pseudosciaena crocea immunity.

    PubMed

    Han, Fang; Wang, Xiaoqing; Yang, Qilian; Cai, Mingyi; Wang, Zhi Yong

    2011-02-01

    The Rac proteins are members of the Rho family of small G proteins and are implicated in the regulation of several pathways, including those leading to cytoskeleton reorganization, gene expression, cell proliferation, cell adhesion and cell migration and survival. In this investigation, a Rac gene (named as LycRac gene) was obtained from the large yellow croaker and it was expressed in Escherichia coli and purified. Subsequently the specific antibody was raised using the purified fusion protein (GST-LycRac). Moreover, the GTP-binding assay showed that the LycRac protein had GTP-binding activity. The LycRac gene was ubiquitously transcribed and expressed in 9 tissues. Quantitative real-time RT-PCR and Western blot analysis revealed the highest expression in gill and the weakest expression in spleen. Time-course analysis revealed that LycRac expression was obviously up-regulated in blood, spleen and liver after immunization with polyinosinic polycytidynic acid (poly I:C), formalin-inactive Gram-negative bacterium Vibrio parahemolyticus and bacterial lipopolysaccharides (LPS). These results suggested that LycRac protein might play an important role in the immune response against microorganisms in large yellow croaker. PMID:21130170

  18. Unraveling a novel Rac1-mediated signaling pathway that regulates cofilin dephosphorylation and secretion in thrombin-stimulated platelets.

    PubMed

    Pandey, Dharmendra; Goyal, Pankaj; Dwivedi, Suman; Siess, Wolfgang

    2009-07-01

    In platelets stimulated by thrombin to secrete and aggregate, cofilin is rapidly dephosphorylated leading to its activation. Cofilin by severing existing actin filaments and stimulating F-actin polymerization on newly created barbed ends dynamizes the actin cytoskeleton. We previously found that cofilin dephosphorylation is Ca(2+)-dependent and occurs upstream of degranulation in stimulated platelets. We report now in thrombin-stimulated platelets that Rac1 and class II PAKs (PAK4/5/6) were rapidly (within 5 seconds) activated, whereas PAK1/2 (class I PAKs) phosphorylation was slower. The Rac1-specific inhibitor NSC23766 blocked phosphorylation of class II PAKs, but not PAK1/2. Moreover, inhibition of the Ca(2+)/calmodulin-dependent phosphatase calcineurin inhibited Rac1 activation and class II PAKs phosphorylation. Prevention of Rac1 activation by calcineurin inhibition or NSC23766 also blocked cofilin dephosphorylation and platelet granule secretion indicating that a calcineurin/Rac1/class II PAKs pathway regulates cofilin dephosphorylation leading to secretion. We further found that PI3-kinases were activated downstream of Rac1, but were not involved in regulating cofilin dephosphorylation and secretion in thrombin-stimulated platelets. Our study unravels a Ca(2+)-dependent pathway of secretion in stimulated platelets as a signaling pathway linking Rac1 activation to actin dynamics: calcineurin-->Rac1-->class II PAKs-->cofilin activation. We further demonstrate that this pathway is separate and independent of the protein kinase C (PKC) pathway mediating secretion.

  19. TNF-alpha/cycloheximide-induced apoptosis in intestinal epithelial cells requires Rac1-regulated reactive oxygen species.

    PubMed

    Jin, Shi; Ray, Ramesh M; Johnson, Leonard R

    2008-04-01

    Previously we have shown that both Rac1 and c-Jun NH(2)-terminal kinase (JNK1/2) are key proapoptotic molecules in tumor necrosis factor (TNF)-alpha/cycloheximide (CHX)-induced apoptosis in intestinal epithelial cells, whereas the role of reactive oxygen species (ROS) in apoptosis is unclear. The present studies tested the hypothesis that Rac1-mediated ROS production is involved in TNF-alpha-induced apoptosis. In this study, we showed that TNF-alpha/CHX-induced ROS production and hydrogen peroxide (H(2)O(2))-induced oxidative stress increased apoptosis. Inhibition of Rac1 by a specific inhibitor NSC23766 prevented TNF-alpha-induced ROS production. The antioxidant, N-acetylcysteine (NAC), or rotenone (Rot), the mitochondrial electron transport chain inhibitor, attenuated mitochondrial ROS production and apoptosis. Rot also prevented JNK1/2 activation during apoptosis. Inhibition of Rac1 by expression of dominant negative Rac1 decreased TNF-alpha-induced mitochondrial ROS production. Moreover, TNF-alpha-induced cytosolic ROS production was inhibited by Rac1 inhibition, diphenyleneiodonium (DPI, an inhibitor of NADPH oxidase), and NAC. In addition, DPI inhibited TNF-alpha-induced apoptosis as judged by morphological changes, DNA fragmentation, and JNK1/2 activation. Mitochondrial membrane potential change is Rac1 or cytosolic ROS dependent. Lastly, all ROS inhibitors inhibited caspase-3 activity. Thus these results indicate that TNF-alpha-induced apoptosis requires Rac1-dependent ROS production in intestinal epithelial cells.

  20. Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling

    PubMed Central

    Konopka, Anna; Zeug, Andre; Skupien, Anna; Kaza, Beata; Mueller, Franziska; Chwedorowicz, Agnieszka; Ponimaskin, Evgeni; Wilczynski, Grzegorz M.; Dzwonek, Joanna

    2016-01-01

    Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM) proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis), we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a “stellate”-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological changes of

  1. Cyclooxygenase-2 knockdown using retinoic acid chalcone (RAC), a promising therapeutic strategy for colon cancer

    PubMed Central

    Jiang, Chao; Wang, Qiong; Xu, Zhe; Li, Wei-Su; Chen, Che; Yao, Xue-Quan; Liu, Fu-Kun

    2015-01-01

    Retinoic acid is an effective agent in the treatment of epithelial and hematological malignancies. The present study demonstrates that retinoic acid chalcone (RAC), an analogue of retinoic acid inhibits cell proliferation and induces apoptosis in HCT-15 and CT26.WT colon cancer cell lines. In HCT-15 cells the percentage of apoptotic cells increased from 32.4 ± 3, 45.0 ± 3 to 72.6 ± 5% respectively at 10, 15 and 20 μg/mL compared to 3.7% in control. Similarly in CT26.WT cells the percentage increased from 28.6 ± 3, 41.2 ± 3 to 65.4 ± 5% on treatment with 10, 15 and 20 μg/mL concentrations of RAC after 72 h compared to 2.9 ± 1% in control. Western blotting, fluorescence-activated cell sorting analysis and reverse transcription-PCR assays were used to investigate these effects. RAC inhibited the overexpression of COX-2, PGE2 and PGE2 receptor (EP1 and EP4) in the colon cancer cell lines. RAC mediated inhibition of cell growth and induction of apoptosis through COX-2 inhibition was also confirmed by treating the HCT-15 and CT26.WT colon cancer cells with COX-2 inhibitor, indomethacin and transfection of cells with COX-2 small interfering RNA. In nude mice with tumor xenografts, treatment with RAC-supplemented diet caused inhibition of COX-2, PGE2, and PGE2 receptors (EP1, EP3, and EP4) in tumors. Thus RAC can be a potential candidate for the treatment of colon cancer through the inhibition of COX-2 expression and subsequent inhibition of PGE2 and PGE2 receptors. PMID:26269760

  2. Prostaglandin E2-mediated migration of human trophoblast requires RAC1 and CDC42.

    PubMed

    Nicola, Catalin; Lala, Peeyush K; Chakraborty, Chandan

    2008-06-01

    The invasion of maternal decidua and uterine spiral arteries by a trophoblast subpopulation called extravillous trophoblast (EVT) is essential for the establishment of a normal placenta and an adequate blood flow toward the fetus. Derangements in these processes underlie pregnancy-related diseases like preeclampsia and intrauterine growth restriction. Many growth factors, growth factor binding proteins, and extracellular matrix components can positively or negatively regulate the proliferation, migration, and/or invasiveness of these EVT cells. RHO GTPases, including RHOA, RAC1, and CDC42, are ubiquitous proteins that control cytoskeletal changes by forming stress fibers and projecting lamellipodia and filopodia during cellular migration. We had previously shown that prostaglandin (PG) E(2) produced in abundance by the decidua promotes the migration of first-trimester human EVTs by increasing the intracellular concentration of calcium and activating calpain. Using our well-characterized immortalized EVT cell line, HTR-8/SVneo, as well as villus explants from first-trimester placentae, this study examined the role of RHO GTPases RAC1 and CDC42 in PGE(2)-mediated migratory responses of these cells. Though a RAC1 inhibitor, NSC23766 as well as RAC1 knockdown by siRNA decreased the migration of HTR-8/SVneo cells in a Transwell migration assay, this inhibition could not be restored by PGE(2) or 17-phenyl trinor PGE(2) (PGE receptor PTGER1 agonist) or PGE(1) Alcohol (PGE receptor PTGER4 agonist). Similar results were noted for EVT cell spreading in villus explants. Furthermore, CDC42 silencing using siRNA inhibited PGE(2)-induced migration of HTR-8/SVneo cells. Finally, the treatment of EVT cells with PGE(2), PTGER1 agonist, or PTGER4 agonist activated RAC1 and CDC42 at 10 min, suggesting that RAC1 and CDC42 play an essential role in PGE(2)-mediated migration of human EVTs.

  3. Breakthrough Video: Desiccant Enhanced Evaporative Air Conditioning

    SciTech Connect

    2012-01-01

    Researchers at the National Renewable Energy Laboratory (NREL) invented a breakthrough technology that improves air conditioning in a novel way—with heat. NREL combined desiccant materials, which remove moisture from the air using heat, and advanced evaporative technologies to develop a cooling unit that uses 90% less electricity and up to 80% less total energy than traditional air conditioning (AC). This solution, called the desiccant enhanced evaporative air conditioner (DEVAP), also controls humidity more effectively to improve the comfort of people in buildings.

  4. Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation.

    PubMed

    Bouchet, Jérôme; Del Río-Iñiguez, Iratxe; Lasserre, Rémi; Agüera-Gonzalez, Sonia; Cuche, Céline; Danckaert, Anne; McCaffrey, Mary W; Di Bartolo, Vincenzo; Alcover, Andrés

    2016-06-01

    The immunological synapse generation and function is the result of a T-cell polarization process that depends on the orchestrated action of the actin and microtubule cytoskeleton and of intracellular vesicle traffic. However, how these events are coordinated is ill defined. Since Rab and Rho families of GTPases control intracellular vesicle traffic and cytoskeleton reorganization, respectively, we investigated their possible interplay. We show here that a significant fraction of Rac1 is associated with Rab11-positive recycling endosomes. Moreover, the Rab11 effector FIP3 controls Rac1 intracellular localization and Rac1 targeting to the immunological synapse. FIP3 regulates, in a Rac1-dependent manner, key morphological events, like T-cell spreading and synapse symmetry. Finally, Rab11-/FIP3-mediated regulation is necessary for T-cell activation leading to cytokine production. Therefore, Rac1 endosomal traffic is key to regulate T-cell activation.

  5. Rac1 Controls Both the Secretory Function of the Mammary Gland and Its Remodeling for Successive Gestations.

    PubMed

    Akhtar, Nasreen; Li, Weiping; Mironov, Aleksander; Streuli, Charles H

    2016-09-12

    An important feature of the mammary gland is its ability to undergo repeated morphological changes during each reproductive cycle with profound tissue expansion in pregnancy and regression in involution. However, the mechanisms that determine the tissue's cyclic regenerative capacity remain elusive. We have now discovered that Cre-Lox ablation of Rac1 in mammary epithelia causes gross enlargement of the epithelial tree and defective alveolar regeneration in a second pregnancy. Architectural defects arise because loss of Rac1 disrupts clearance in involution following the first lactation. We show that Rac1 is crucial for mammary alveolar epithelia to switch from secretion to a phagocytic mode and rapidly remove dying neighbors. Moreover, Rac1 restricts the extrusion of dying cells into the lumen, thus promoting their eradication by live phagocytic neighbors while within the epithelium. Without Rac1, residual milk and cell corpses flood the ductal network, causing gross dilation, chronic inflammation, and defective future regeneration. PMID:27623383

  6. Rac-1 as a new therapeutic target in cerebro- and cardio-vascular diseases.

    PubMed

    Carrizzo, Albino; Forte, Maurizio; Lembo, Maria; Formisano, Luigi; Puca, Annibale A; Vecchione, Carmine

    2014-01-01

    Growing evidence indicates that overproduction of reactive oxygen species (ROS) plays a prominent role in the development of cardio- and cerebro-vascular diseases. Among the mechanisms identified to produce oxidative stress in the vascular wall, those mediated by membrane-bound NAD(P)H oxidases represent a major one. NAD(P)H oxidases are a family of enzymes that generate ROS both in phagocytic and non-phagocytic cell types. Vascular NAD(P)H oxidase contains the membrane-bound subunits Nox1, Nox2 (gp91phox), Nox4 and p22phox, the catalytic site of the oxidase, and the cytosolic components p47phox and p67phox. Rac1 (Ras-related C3 botulinum toxin substrate1) is a small GTPase essential for the assembly and activation of NADPH oxidase. Several molecular and cellular studies have reported the involvement of Rac1 in different cardiovascular pathologies, such as vascular smooth muscle proliferation, cardiomyocyte hypertrophy, endothelial cell shape change, atherosclerosis and endothelial dysfunction in hypertension. In addition, increased activation of NADPH oxidase by Rac1 has been reported in animals and humans after myocardial infarction and heart failure. The Rac1/NADPH pathway has also been found involved in different pathologies of the cerebral district, such as ischemic stroke, cognitive impairment, subaracnoid hemorrhage and neuronal oxidative damage typical of several neurodegenerative disorders. In addition, thrombotic events are an important step in the onset of cardio- and cerebrovascular diseases. Rac1 has been found involved also in platelet activation, inducing actin polymerization and lamellipodia formation, which are necessary steps for platelet aggregation. Taken together, the evidence candidates Rac1 as a new pharmacological target of cardiovascular and cerebrovascular diseases. Although the involvement of Rac1 in the beneficial pleiotropic effects of drugs such as statins is well known, and the onset of numerous side effects has raised concern for the

  7. Rac1 is required for Prkar1a-mediated Nf2 suppression in Schwann cell tumors.

    PubMed

    Manchanda, P K; Jones, G N; Lee, A A; Pringle, D R; Zhang, M; Yu, L; La Perle, K M D; Kirschner, L S

    2013-07-25

    Schwannomas are peripheral nerve sheath tumors that often occur in the setting of an inherited tumor predisposition syndrome, including neurofibromatosis types 1 (NF1) and 2 (NF2), familial schwannomatosis and Carney complex. Loss of the NF2 tumor suppressor (encoding NF2, or Merlin) is associated with upregulation of the Rac1 small GTPase, which is thought to have a key role in mediating tumor formation. In prior studies, we generated a mouse model of schwannomas by performing tissue-specific knockout (KO) of the Carney complex gene Prkar1a, which encodes the type 1A regulatory subunit of protein kinase A. These tumors exhibited down-regulation of Nf2 protein and an increase in activated Rac1. To assess the requirement for Rac1 in schwannoma formation, we generated a double KO (DKO) of Prkar1a and Rac1 in Schwann cells and monitored tumor formation. Loss of Rac1 reduced tumor formation by reducing proliferation and enhancing apoptosis. Surprisingly, the reduction of tumor formation was accompanied by re-expression of the Nf2 protein. Furthermore, activated Rac1 was able to downregulate Nf2 in vitro in a Pak-dependent manner. These in vivo data indicate that activation of Rac1 is responsible for suppression of Nf2 protein production; deficiency of Nf2 in Schwann cells leads to loss of cellular growth control and tumor formation. Further, PKA activation through mutation in Prkar1a is sufficient to initiate Rac1 signaling, with subsequent reduction of Nf2 and schwannomagenesis. Although in vitro evidence has shown that loss of Nf2 activates Rac1, our data indicate that signaling between Nf2 and Rac1 occurs in a bidirectional fashion, and these interactions are modulated by PKA. PMID:23045281

  8. Rac1 is required for Prkar1a-mediated Nf2 suppression in Schwann cell tumors

    PubMed Central

    Manchanda, Parmeet K.; Jones, Georgette N.; Lee, Audrey A.; Pringle, Daphne R.; Zhang, Mei; Yu, Lianbo; La Perle, Krista M. D.; Kirschner, Lawrence S.

    2012-01-01

    Schwannomas are peripheral nerve sheath tumors that often occur in the setting of an inherited tumor predisposition syndrome, including Neurofibromatosis Types 1 (NF1) and 2 (NF2), Familial Schwannomatosis (FS) and Carney Complex (CNC). Loss of the NF2 tumor suppressor (encoding NF2, or Merlin) is associated with upregulation of the Rac1 small GTPase, which is thought to play a key role in mediating tumor formation. In prior studies, we generated a mouse model of schwannomas by performing tissue-specific knockout of the CNC gene Prkar1a, which encodes the type 1A regulatory subunit of Protein Kinase A. These tumors exhibited down-regulation of Nf2 protein and an increase in activated Rac1. To assess the requirement for Rac1 in schwannoma formation, we generated a double knockout of Prkar1a and Rac1 in Schwann cells and monitored tumor formation. Loss of Rac1 reduced tumor formation by reducing proliferation and enhancing apoptosis. Surprisingly, the reduction of tumor formation was accompanied by re-expression of the Nf2 protein. Furthermore, activated Rac1 was able to downregulate Nf2 in vitro in a Pak-dependent manner. These in vivo data indicate that activation of Rac1 is responsible for suppression of Nf2 protein production; deficiency of Nf2 in Schwann cells leads to loss of cellular growth control and tumor formation.. Further, PKA activation through mutation in Prkar1a is sufficient to initiate Rac1 signaling, with subsequent reduction of Nf2 and schwannomagenesis. Although in vitro evidence has shown that loss of Nf2 activates Rac1, our data indicates that signaling between Nf2 and Rac1 occurs in a bidirectional fashion, and these interactions are modulated by PKA. PMID:23045281

  9. Selective Rac1 inhibition protects renal tubular epithelial cells from oxalate-induced NADPH oxidase-mediated oxidative cell injury.

    PubMed

    Thamilselvan, Vijayalakshmi; Menon, Mani; Thamilselvan, Sivagnanam

    2012-08-01

    Oxalate-induced oxidative cell injury is one of the major mechanisms implicated in calcium oxalate nucleation, aggregation and growth of kidney stones. We previously demonstrated that oxalate-induced NADPH oxidase-derived free radicals play a significant role in renal injury. Since NADPH oxidase activation requires several regulatory proteins, the primary goal of this study was to characterize the role of Rac GTPase in oxalate-induced NADPH oxidase-mediated oxidative injury in renal epithelial cells. Our results show that oxalate significantly increased membrane translocation of Rac1 and NADPH oxidase activity of renal epithelial cells in a time-dependent manner. We found that NSC23766, a selective inhibitor of Rac1, blocked oxalate-induced membrane translocation of Rac1 and NADPH oxidase activity. In the absence of Rac1 inhibitor, oxalate exposure significantly increased hydrogen peroxide formation and LDH release in renal epithelial cells. In contrast, Rac1 inhibitor pretreatment, significantly decreased oxalate-induced hydrogen peroxide production and LDH release. Furthermore, PKC α and δ inhibitor, oxalate exposure did not increase Rac1 protein translocation, suggesting that PKC resides upstream from Rac1 in the pathway that regulates NADPH oxidase. In conclusion, our data demonstrate for the first time that Rac1-dependent activation of NADPH oxidase might be a crucial mechanism responsible for oxalate-induced oxidative renal cell injury. These findings suggest that Rac1 signaling plays a key role in oxalate-induced renal injury, and may serve as a potential therapeutic target to prevent calcium oxalate crystal deposition in stone formers and reduce recurrence.

  10. Comparative Evaluation of Physical Properties of Four Tissue Conditioners Relined to Modeling Plastic Material

    PubMed Central

    Monzavi, Abbas; Siadat, Hakimeh; Atai, Mohammad; Alikhasi, Marzieh; Nazari, Vahideh; Sheikhzadeh, Sadigheh

    2013-01-01

    Objective: Little is known about the interaction of tissue conditioners and modeling plastics. This study evaluates the influence of a variety of commercial tissue conditioners on alteration of viscoelastic properties of modeling plastics. Materials and Methods: In this in vitro study, the dynamic viscoelastic properties of four commercially available tissue conditioners (TC), Visco-gel (VG), GC Soft-Liner (SL), FITT (FT), and Coe Comfort (CC), relined to modeling plastics with a thickness of 2mm were evaluated after 1 and 7 days of water immersion with the use of storage modulus, loss modulus, and tan delta parameters. Values for these three parameters for each tissue conditioner were statistically analyzed by Kruskal Wallis and Mann Whitney tests with P value sets at<0.05. Results: Complex modulus and loss tangent values of TC were not significantly different among specimens containing 0, 2, 5 and 10 wt.%-SZ, respectively. In FT and TC containing 2 wt.%-SZ, these values were not significantly different between 1 and 28 days in both water- and saliva immersions. Conclusion: The results suggest that relining with modeling plastics does affect TC’s inherent dynamic viscoelastic properties, while the other tissue conditioners investigated may be found to have changed viscoelastic properties as a consequence of vicinity to the modeling plastics. PMID:24910661

  11. Effect of sealant application and thermal cycling on bond strength of tissue conditioners to acrylic resin.

    PubMed

    Sampaio, Francisca Neta Cruz Soares; Pinto, José Renato Ribeiro; Turssi, Cecília Pedroso; Basting, Roberta Tarkany

    2013-01-01

    The aim of this study was to evaluate the effect of sealer application and thermal cycling on the bond strength between tissue conditioners and acrylic resin, and to observe the type of bond failure. Two hundred eighty-eight specimens (10x16x3 mm) were made of an acrylic resin (Lucitone 500, Dentsply) using a metal muffle. Specimens were divided into four groups according to the tissue conditioner (Coe-Comfort, GC or Dentusoft, Densell) used and whether or not a sealer (Eversoft Soft Liner Sealer, Myerson) was applied. Each of the four groups was subdivided into other six subgroups (n=12) to undergo thermocycling for 45, 90, 135, 180 or 210 cycles with a dwell time of 60 s, or to be left non thermocycled (control). Tensile bond strength was measured in a universal testing machine at a crosshead speed of 5 mm/min. Sealant application had no effect on the tensile bond strength of the relined acrylic resin, regardless of the tissue conditioner used (Coe-Comfort: p=0.306 and Dentusoft: p=0.1501). The number of thermal cycles had a significant effect on the tensile bond strength of the relined acrylic resin (Coe-Comfort: p=0.002 and Dentusoft: p<0.001). Both tissue conditioners presented similar bond strength to acrylic resin. For both tissue conditioners, sealer coatings had no influence on bond strength, while different numbers of thermal cycles affected that mechanical property.

  12. Performance of a photovoltaically powered air-conditioning system

    SciTech Connect

    Kern, Jr, E. C.; Millner, A. R.

    1980-01-01

    A vapor-compression air conditioner coupled directly to a photovoltaic array is discussed. Previous analyses of such a system are reviewed, and a development system designed to test the concept is described. Preliminary experiments indicate that the performance of this initial system falls considerably short of analytic expectations.

  13. All-rac-alpha-tocopherol acetate is a better vitamin E source than all-rac-alpha-tocopherol succinate for broilers.

    PubMed

    Jensen, S K; Engberg, R M; Hedemann, M S

    1999-07-01

    The difference in bioavailabilities of the acetate and succinate esters of all-rac-alpha-tocopherol was investigated in a feeding experiment with broilers. The experiment was initiated with 96 12-d-old male Cobb broilers and lasted for 4 wk. The two sources of vitamin E were fed to eight groups of broilers at four different dietary levels (50, 100, 150 and 200 mg/kg feed, including the naturally occurring alpha-tocopherol). A total collection of droppings for determination of apparent tocopherol absorption were performed at two separate time periods (d 28-34 and d 35-41). There were no differences among the eight experimental groups with respect to animal performance or feed intake. At all dietary levels, the apparent absorption coefficient for all-rac-alpha-tocopherol succinate was significantly lower than that of the acetate ester. The mean (+/- SD) apparent absorption coefficient for all-rac-alpha-tocopherol succinate was 58.0 +/- 5.4 compared with 70. 8 +/- 5.6 for all-rac-alpha-tocopherol acetate. Furthermore, the apparent absorption coefficients for both esters was significantly lower in the first collection period (d 28-34) than in the second collection period (d 35-41). This difference in the apparent absorption coefficient between the succinate and the acetate ester was accompanied by significant differences in alpha-tocopherol concentrations in plasma, breast muscle, liver and adipose tissue of the broilers, which were lower in those fed the succinate ester. Based on a comparison of plasma and tissue responses, the succinate ester was utilized only 69-76% as efficiently as the acetate ester. In vitro studies showed a significantly higher capacity of pancreatic carboxyl ester hydrolase to hydrolyze alpha-tocopherol acetate compared to alpha-tocopherol succinate. This difference in intestinal hydrolysis of the two vitamin E sources may explain the observed differences in biopotency.

  14. 40 CFR 1066.845 - AC17 air conditioning efficiency test procedure.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... voluntary procedure for measuring the net impact of air conditioner operation on CO2 emissions. See 40 CFR... solar heating is disabled for certain test intervals as described in this section. (d) Interior air... tests according to 40 CFR 86.132-00(a) through (g). If the vehicle has been tested within the last...

  15. 44 CFR 352.23 - Functions of a Regional Assistance Committee (RAC).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Functions of a Regional Assistance Committee (RAC). 352.23 Section 352.23 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS COMMERCIAL NUCLEAR POWER PLANTS:...

  16. Osteopontin-Rac1 on Blood-Brain Barrier Stability Following Rodent Neonatal Hypoxia-Ischemia.

    PubMed

    Dixon, Brandon; Malaguit, Jay; Casel, Darlene; Doycheva, Desislava; Tang, Jiping; Zhang, John H; Lekic, Tim

    2016-01-01

    Osteopontin (OPN) is a neuroprotective molecule that is upregulated following rodent neonatal hypoxic-ischemic (nHI) brain injury. Because Rac1 is a regulator of blood-brain barrier (BBB) stability, we hypothesized a role for this in OPN signaling. nHI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8 % oxygen for 2 h) in P10 Sprague-Dawley rat pups. Intranasal (iN) OPN was administered at 1 h post-nHI. Groups consisted of: (1) Sham, (2) Vehicle, (3) OPN, and (4) OPN + Rac1 inhibitor (NSC23766). Evans blue dye extravasation (BBB permeability) was quantified 24 h post-nHI, and brain edema at 48 h. Increased BBB permeability and brain edema following nHI was ameliorated in the OPN treatment group. However, those rat pups receiving OPN co-treatment with the Rac1 inhibitor experienced no improvement compared with vehicle. OPN protects the BBB following nHI, and this was reversed by Rac1 inhibitor (NSC23766). PMID:26463959

  17. Antiviral activity of a Rac GEF inhibitor characterized with a sensitive HIV/SIV fusion assay

    SciTech Connect

    Pontow, Suzanne; Harmon, Brooke; Campbell, Nancy; Ratner, Lee

    2007-11-10

    A virus-dependent fusion assay was utilized to examine the activity of a panel of HIV-1, -2, and SIV isolates of distinct coreceptor phenotypes. This assay allowed identification of entry inhibitors, and characterization of an antagonist of a Rac guanine nucleotide exchange factor, as an inhibitor of HIV-mediated fusion.

  18. Structural details of light activation of the LOV2-based photoswitch PA-Rac1.

    PubMed

    Winkler, Andreas; Barends, Thomas R M; Udvarhelyi, Anikó; Lenherr-Frey, Daniel; Lomb, Lukas; Menzel, Andreas; Schlichting, Ilme

    2015-02-20

    Optical control of cellular processes is an emerging approach for studying biological systems, affording control with high spatial and temporal resolution. Specifically designed artificial photoswitches add an interesting extension to naturally occurring light-regulated functionalities. However, despite a great deal of structural information, the generation of new tools cannot be based fully on rational design yet; in many cases design is limited by our understanding of molecular details of light activation and signal transduction. Our biochemical and biophysical studies on the established optogenetic tool PA-Rac1, the photoactivatable small GTPase Rac1, reveal how unexpected details of the sensor-effector interface, such as metal coordination, significantly affect functionally important structural elements of this photoswitch. Together with solution scattering experiments, our results favor differences in the population of pre-existing conformations as the underlying allosteric activation mechanism of PA-Rac1, rather than the assumed release of the Rac1 domain from the caging photoreceptor domain. These results have implications for the design of new optogenetic tools and highlight the importance of including molecular details of the sensor-effector interface, which is however difficult to assess during the initial design of novel artificial photoswitches.

  19. Responsible Adult Culture (RAC): Cognitive and Behavioral Changes at a Community-Based Correctional Facility

    ERIC Educational Resources Information Center

    Devlin, Renee S.; Gibbs, John C.

    2010-01-01

    This article examined cognitive and behavioral changes among participants in Responsible Adult Culture (RAC), a cognitive-behavioral (especially, cognitive restructuring) treatment program in use at the Franklin County Community-Based Correctional Facility (CBCF). Participants were adult felony offenders (approximately three-fourths male). A…

  20. 44 CFR 352.23 - Functions of a Regional Assistance Committee (RAC).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS COMMERCIAL NUCLEAR POWER PLANTS: EMERGENCY.... (b) Prior to a determination under subpart A (44 CFR 352.6(d)) that Federal facilities and resources... under subpart A (44 CFR 352.6(d)) that Federal facilities and resources are needed, the RAC will...

  1. Comparative effect of lidocaine, bupivacaine and RAC 109 on myocardial conduction and contractility in the rabbit.

    PubMed

    Kariya, Nobutaka; Cosson, Claudine; Mazoit, Jean-Xavier

    2012-09-15

    Local anesthetic toxicity includes a decrease in ventricular conduction velocity and a decrease in myocardial contractile force. We tested the hypothesis that, like conduction, contraction was stereoselectively impaired by bupivacaine. We compared R(+) and S(-) bupivacaine to S(+) and R(-) RAC 109 in order to study the effects of hydrophobicity and ionization. We measured the changes in QRS duration and developed pressure in isolated perfused rabbit hearts. Binding of bupivacaine and RAC 109 to the ryanodine receptor was measured. The effect on cell shortening and relenghtening was measured on isolated rabbit cardiomyocytes. A mixed-effect pharmacodynamic model was used. The decrease in conduction velocity induced by the molecules was markedly stereospecific. All local anesthetics decreased ventricular velocity in a stereospecific manner with a RAC I(+)/II(-) and bupivacaine R(+)/S(-) potency ratio of maximum effect of 1.7 and 2.25 respectively. Contractility decreased in a dose dependent manner but this negative inotropic effect was not stereospecific with a C50 (concentration leading to half maximum effect) of 30 and 23 μM for RAC and bupivacaine respectively. The two drugs exhibited two-site binding to ryanodyne that may partly explain the observed effect. An effect on relaxation was observed only at very high concentrations. In conclusion, bupivacaine, a long acting local anesthetic, decreases ventricular conduction in a stereospecific manner, and decreases contractility non-stereospecifically.

  2. A FAK-Cas-Rac-Lamellipodin Signaling Module Transduces Extracellular Matrix Stiffness into Mechanosensitive Cell Cycling

    PubMed Central

    Bae, Yong Ho; Mui, Keeley L.; Hsu, Bernadette Y.; Liu, Shu-Lin; Cretu, Alexandra; Razinia, Ziba; Xu, Tina; Puré, Ellen; Assoian, Richard K.

    2015-01-01

    Tissue and extracellular matrix (ECM) stiffness is transduced into intracellular stiffness, signaling, and changes in cellular behavior. Integrins and several of their associated focal adhesion proteins have been implicated in sensing ECM stiffness. We investigated how an initial sensing event is translated into intracellular stiffness and a biologically interpretable signal. We found that a pathway consisting of focal adhesion kinase (FAK), the adaptor protein p130Cas (Cas), and the guanosine triphosphatase Rac selectively transduced ECM stiffness into stable intracellular stiffness, increased abundance of the cell cycle protein cyclin D1, and promoted S phase entry. Rac-dependent intracellular stiffening involved its binding partner lamellipodin, a protein that transmits Rac signals to the cytoskeleton during cell migration. Our findings establish that mechanotransduction by a FAK-Cas-Rac-lamellipodin signaling module converts the external information encoded by ECM stiffness into stable intracellular stiffness and mechanosensitive cell cycling. Thus, lamellipodin is not only important in controlling cellular migration, but also for regulating the cell cycle in response to mechanical signals. PMID:24939893

  3. Fibroblastic Transformation of Corneal Keratocytes by Rac Inhibition is Modulated by Extracellular Matrix Structure and Stiffness

    PubMed Central

    Petroll, W. Matthew; Lakshman, Neema

    2015-01-01

    The goal of this study was to investigate how alterations in extracellular matrix (ECM) biophysical properties modulate corneal keratocyte phenotypes in response to specific wound healing cytokines and Rho GTPases. Rabbit corneal keratocytes were plated within standard collagen matrices (2.5 mg/mL) or compressed collagen matrices (~100 mg/mL) and cultured in serum-free media, PDGF BB, IGF, FGF2 or TGFβ1, with or without the Rac1 inhibitor NSC23766 and/or the Rho kinase inhibitor Y-27632. After 1 to 4 days, cells were labeled for F-actin and imaged using confocal microscopy. Keratocytes within standard collagen matrices (which are highly compliant) maintained a dendritic phenotype following culture in serum-free media, PDGF, IGF and FGF, but developed stress fibers in TGFβ1. Keratocytes within compressed collagen (which has high stiffness and low porosity) maintained a dendritic phenotype following culture in serum-free media, PDGF and IGF, but developed stress fibers in both FGF and TGFβ1. The Rac inhibitor had no significant impact on growth factor responses in compliant matrices. Within compressed collagen matrices however, the Rac inhibitor induced fibroblastic transformation in serum-free media, PDGF and IGF. Fibroblast and myofibroblast transformation was blocked by Rho kinase inhibition. Overall, keratocyte growth factor responses appear to be regulated by both the interplay between Rho and Rac signaling, and the structural and mechanical properties of the ECM. PMID:25874856

  4. Fibroblastic Transformation of Corneal Keratocytes by Rac Inhibition is Modulated by Extracellular Matrix Structure and Stiffness.

    PubMed

    Petroll, W Matthew; Lakshman, Neema

    2015-04-14

    The goal of this study was to investigate how alterations in extracellular matrix (ECM) biophysical properties modulate corneal keratocyte phenotypes in response to specific wound healing cytokines and Rho GTPases. Rabbit corneal keratocytes were plated within standard collagen matrices (2.5 mg/mL) or compressed collagen matrices (~100 mg/mL) and cultured in serum-free media, PDGF BB, IGF, FGF2 or TGFβ1, with or without the Rac1 inhibitor NSC23766 and/or the Rho kinase inhibitor Y-27632. After 1 to 4 days, cells were labeled for F-actin and imaged using confocal microscopy. Keratocytes within standard collagen matrices (which are highly compliant) maintained a dendritic phenotype following culture in serum-free media, PDGF, IGF and FGF, but developed stress fibers in TGFβ1. Keratocytes within compressed collagen (which has high stiffness and low porosity) maintained a dendritic phenotype following culture in serum-free media, PDGF and IGF, but developed stress fibers in both FGF and TGFβ1. The Rac inhibitor had no significant impact on growth factor responses in compliant matrices. Within compressed collagen matrices however, the Rac inhibitor induced fibroblastic transformation in serum-free media, PDGF and IGF. Fibroblast and myofibroblast transformation was blocked by Rho kinase inhibition. Overall, keratocyte growth factor responses appear to be regulated by both the interplay between Rho and Rac signaling, and the structural and mechanical properties of the ECM.

  5. A FAK-Cas-Rac-lamellipodin signaling module transduces extracellular matrix stiffness into mechanosensitive cell cycling.

    PubMed

    Bae, Yong Ho; Mui, Keeley L; Hsu, Bernadette Y; Liu, Shu-Lin; Cretu, Alexandra; Razinia, Ziba; Xu, Tina; Puré, Ellen; Assoian, Richard K

    2014-06-17

    Tissue and extracellular matrix (ECM) stiffness is transduced into intracellular stiffness, signaling, and changes in cellular behavior. Integrins and several of their associated focal adhesion proteins have been implicated in sensing ECM stiffness. We investigated how an initial sensing event is translated into intracellular stiffness and a biologically interpretable signal. We found that a pathway consisting of focal adhesion kinase (FAK), the adaptor protein p130Cas (Cas), and the guanosine triphosphatase Rac selectively transduced ECM stiffness into stable intracellular stiffness, increased the abundance of the cell cycle protein cyclin D1, and promoted S-phase entry. Rac-dependent intracellular stiffening involved its binding partner lamellipodin, a protein that transmits Rac signals to the cytoskeleton during cell migration. Our findings establish that mechanotransduction by a FAK-Cas-Rac-lamellipodin signaling module converts the external information encoded by ECM stiffness into stable intracellular stiffness and mechanosensitive cell cycling. Thus, lamellipodin is important not only in controlling cellular migration but also for regulating the cell cycle in response to mechanical signals.

  6. Opsonization modulates Rac-1 activation during cell entry by Leishmania amazonensis.

    PubMed

    Morehead, J; Coppens, I; Andrews, N W

    2002-08-01

    Lesions caused by Leishmania amazonensis normally heal, but relapses occur due to parasite persistence in host tissues. It has been proposed that infection of fibroblasts plays an important role in this process by providing the parasites with a safe haven in which to replicate. However, most previous studies have focused on the entry of Leishmania into macrophages, a process mediated by serum opsonins. To gain insight into a possible role of nonopsonic entry in the intracellular persistence of amastigotes, we examined the invasion of Chinese hamster ovary (CHO) cells. Amastigotes entered CHO cells by a cytochalasin D, genistein, wortmannin, and 2,3-butanedione monoxime-sensitive pathway and replicated within phagolysosomes. However, unlike most phagocytic processes described to date, amastigote internalization in CHO cells involved activation of the GTPases Rho and Cdc42 but not Rac-1. When uptake was mediated by fibronectin or when amastigotes were opsonized with immunoglobulin G and internalized by Fc receptor-expressing CHO cells, Rac-1 activation was restored and found to be required for parasite internalization. Given the essential role of Rac in assembly of the respiratory burst oxidase, invasion through this nonopsonic, Rac-1-independent pathway may play a central role in the intracellular survival of Leishmania in immune hosts.

  7. Opsonization Modulates Rac-1 Activation during Cell Entry by Leishmania amazonensis

    PubMed Central

    Morehead, J.; Coppens, I.; Andrews, N. W.

    2002-01-01

    Lesions caused by Leishmania amazonensis normally heal, but relapses occur due to parasite persistence in host tissues. It has been proposed that infection of fibroblasts plays an important role in this process by providing the parasites with a safe haven in which to replicate. However, most previous studies have focused on the entry of Leishmania into macrophages, a process mediated by serum opsonins. To gain insight into a possible role of nonopsonic entry in the intracellular persistence of amastigotes, we examined the invasion of Chinese hamster ovary (CHO) cells. Amastigotes entered CHO cells by a cytochalasin D, genistein, wortmannin, and 2,3-butanedione monoxime-sensitive pathway and replicated within phagolysosomes. However, unlike most phagocytic processes described to date, amastigote internalization in CHO cells involved activation of the GTPases Rho and Cdc42 but not Rac-1. When uptake was mediated by fibronectin or when amastigotes were opsonized with immunoglobulin G and internalized by Fc receptor-expressing CHO cells, Rac-1 activation was restored and found to be required for parasite internalization. Given the essential role of Rac in assembly of the respiratory burst oxidase, invasion through this nonopsonic, Rac-1-independent pathway may play a central role in the intracellular survival of Leishmania in immune hosts. PMID:12117970

  8. Rac GTPase Activating Protein ARHGAP25 Regulates Leukocyte Transendothelial Migration in Mice.

    PubMed

    Csépányi-Kömi, Roland; Wisniewski, Éva; Bartos, Balázs; Lévai, Petra; Németh, Tamás; Balázs, Bernadett; Kurz, Angela R M; Bierschenk, Susanne; Sperandio, Markus; Ligeti, Erzsébet

    2016-10-01

    ARHGAP25 is a Rac-specific GTPase-activating protein that is expressed primarily in hematopoietic cells. The involvement of ARHGAP25 in regulating the recruitment of leukocytes to inflammatory sites was investigated in genetically modified mice. Using intravital microscopy, we show that Arhgap25 deficiency affects all steps of leukocyte recruitment with a predominant enhancement of transendothelial migration of neutrophilic granulocytes. Increased transmigration of Arhgap25-deficient leukocytes is demonstrated in inflamed cremaster muscle venules, in a peritonitis model, and in an in vitro chemotaxis assay. Using bone marrow chimeric mice lacking ARHGAP25 in the hematopoietic compartment, we show that enhanced migration in the absence of ARHGAP25 is due to defective leukocyte function. In search for potential mechanisms of ARHGAP25-regulated migration of neutrophils, we detected an increase in the amount of active, GTP-bound Rac and Rac-dependent cytoskeletal changes in the absence of ARHGAP25, suggesting a critical role of ARHGAP25 in counterbalancing the Rac-activating effect of nucleotide exchange factors. Taken together, using Arhgap25-deficient mice, we identified ARHGAP25 as a relevant negative regulator of leukocyte transendothelial migration. PMID:27566826

  9. 44 CFR 352.23 - Functions of a Regional Assistance Committee (RAC).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS COMMERCIAL NUCLEAR POWER PLANTS: EMERGENCY...) Under 44 CFR part 351, the role of a RAC is to assist State and local government officials to develop.... (b) Prior to a determination under subpart A (44 CFR 352.6(d)) that Federal facilities and...

  10. 75 FR 5563 - Notice of a Meeting of the Northeast Oregon Forests Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... (RAC) will meet on February 22-23, 2010 in La Grande, Oregon. The purpose of the meeting is to meet as... held in the Blue Mountain Conference Center, 404 12th Street, La Grande, Oregon. FOR FURTHER... Grande Ranger ] District, 3502 Highway 30, La Grande, Oregon 97850; Telephone: (541)...

  11. Plasma Membrane Microdomains Are Essential for Rac1-RbohB/H-Mediated Immunity in Rice.

    PubMed

    Nagano, Minoru; Ishikawa, Toshiki; Fujiwara, Masayuki; Fukao, Yoichiro; Kawano, Yoji; Kawai-Yamada, Maki; Shimamoto, Ko

    2016-08-01

    Numerous plant defense-related proteins are thought to congregate in plasma membrane microdomains, which consist mainly of sphingolipids and sterols. However, the extent to which microdomains contribute to defense responses in plants is unclear. To elucidate the relationship between microdomains and innate immunity in rice (Oryza sativa), we established lines in which the levels of sphingolipids containing 2-hydroxy fatty acids were decreased by knocking down two genes encoding fatty acid 2-hydroxylases (FAH1 and FAH2) and demonstrated that microdomains were less abundant in these lines. By testing these lines in a pathogen infection assay, we revealed that microdomains play an important role in the resistance to rice blast fungus infection. To illuminate the mechanism by which microdomains regulate immunity, we evaluated changes in protein composition, revealing that microdomains are required for the dynamics of the Rac/ROP small GTPase Rac1 and respiratory burst oxidase homologs (Rbohs) in response to chitin elicitor. Furthermore, FAHs are essential for the production of reactive oxygen species (ROS) after chitin treatment. Together with the observation that RbohB, a defense-related NADPH oxidase that interacts with Rac1, is localized in microdomains, our data indicate that microdomains are required for chitin-induced immunity through ROS signaling mediated by the Rac1-RbohB pathway. PMID:27465023

  12. Flow conditioner for fuel injector for combustor and method for low-NO.sub.x combustor

    DOEpatents

    Dutta, Partha; Smith, Kenneth O.; Ritz, Frank J.

    2013-09-10

    An injector for a gas turbine combustor including a catalyst coated surface forming a passage for feed gas flow and a channel for oxidant gas flow establishing an axial gas flow through a flow conditioner disposed at least partially within an inner wall of the injector. The flow conditioner includes a length with an interior passage opening into upstream and downstream ends for passage of the axial gas flow. An interior diameter of the interior passage smoothly reduces and then increases from upstream to downstream ends.

  13. Ocular prosthetics: use of a tissue conditioner material to modify a stock ocular prosthesis.

    PubMed

    Ow, R K; Amrith, S

    1997-08-01

    The custom-made ocular prosthesis contributes to enhanced tissue health of the anophthalmic socket. For this purpose, an acrylic resin ocular prosthesis may be modified, by using an appropriate dental impression material and being adapted closely to the anophthalmic socket. The modeling impression material is subsequently replaced by acrylic resin. This article describes the application of a viscoelastic tissue conditioner material, as an impression medium for prosthetic modification of an ocular prosthesis. The tissue conditioner material exhibits favorable tissue compatibility, adhesion to acrylic resin, and detailed surface registration. These advantages facilitate the clinical procedure and evaluation of modifications made to the ocular prosthesis.

  14. Inhibition of Rac GTPase signaling and downstream prosurvival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia.

    PubMed

    Mizukawa, Benjamin; Wei, Junping; Shrestha, Mahesh; Wunderlich, Mark; Chou, Fu-Sheng; Griesinger, Andrea; Harris, Chad E; Kumar, Ashish R; Zheng, Yi; Williams, David A; Mulloy, James C

    2011-11-10

    The Rac family of small Rho GTPases coordinates diverse cellular functions in hematopoietic cells including adhesion, migration, cytoskeleton rearrangements, gene transcription, proliferation, and survival. The integrity of Rac signaling has also been found to critically regulate cellular functions in the initiation and maintenance of hematopoietic malignancies. Using an in vivo gene targeting approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in a retroviral expression model of MLL-AF9 leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair survival and growth of the transformed MLL-AF9 leukemia. Rac2 is known to positively regulate expression of Bcl-2 family proteins toward a prosurvival balance. We demonstrate that disruption of downstream survival signaling through antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2 deficiency in MLL-AF9 leukemia. Indeed, overexpression of Bcl-xL is able to rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely sensitive to direct inhibition of Bcl-2 family proteins by the BH3-mimetic, ABT-737. Furthermore, concurrent exposure to NSC23766, a small-molecule inhibitor of Rac activation, increases the apoptotic effect of ABT-737, indicating the Rac/Bcl-2 survival pathway may be targeted synergistically.

  15. RAC1 inhibition as a therapeutic target for gefitinib-resistant non-small-cell lung cancer

    PubMed Central

    Kaneto, Naoki; Yokoyama, Satoru; Hayakawa, Yoshihiro; Kato, Shinichiro; Sakurai, Hiroaki; Saiki, Ikuo

    2014-01-01

    Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKI), including gefitinib, provide a significant clinical benefit in non-small-cell lung cancer (NSCLC) patients, the acquisition of drug resistance has been known to limit the efficacy of EGFR-TKI therapy. In this study, we demonstrated the involvement of EGF-EGFR signaling in NSCLC cell migration and the requirement of RAC1 in EGFR-mediated progression of NSCLC. We showed the significant role of RAC1 pathway in the cell migration or lamellipodia formation by using gene silencing of RAC1 or induction of constitutive active RAC1 in EGFR-mutant NSCLC cells. Importantly, the RAC1 inhibition suppressed EGFR-mutant NSCLC cell migration and growth in vitro, and growth in vivo even in the gefitinib-resistant cells. In addition, these suppressions by RAC1 inhibition were mediated through MEK or PI3K independent mechanisms. Collectively, these results open up a new opportunity to control the cancer progression by targeting the RAC1 pathway to overcome the resistance to EGFR-TKI in NSCLC patients. PMID:24750242

  16. Phosphoregulation of MgcRacGAP in mitosis involves Aurora B and Cdk1 protein kinases and the PP2A phosphatase.

    PubMed

    Touré, Aminata; Mzali, Rym; Liot, Caroline; Seguin, Laetitia; Morin, Laurence; Crouin, Catherine; Chen-Yang, Ilin; Tsay, Yeou-Guang; Dorseuil, Olivier; Gacon, Gérard; Bertoglio, Jacques

    2008-04-01

    MgcRacGAP, a Rho GAP essential to cytokinesis, works both as a Rho GTPase regulator and as a scaffolding protein. MgcRacGAP interacts with MKLP1 to form the centralspindlin complex and associates with the RhoGEF Ect2. The GAP activity of MgcRacGAP is regulated by Aurora B phosphorylation. We have isolated B56epsilon, a PP2A regulatory subunit, as a new MgcRacGAP partner. We report here that (i) MgcRacGAP is phosphorylated by Aurora B and Cdk1, (ii) PP2A dephosphorylates Aurora B and Cdk1 phosphorylated sites and (iii) inhibition of PP2A abrogates MgcRacGAP/Ect2 interaction. Therefore, PP2A may regulate cytokinesis by dephosphorylating MgcRacGAP and its interacting partners.

  17. PremAir{trademark} catalyst systems: A new approach to clean air

    SciTech Connect

    Poles, T.; Anderson, D.R.; Durilla, M.; Heck, R.; Hoke, J.; Ober, R.; Rudy, W.

    1996-12-01

    PremAir{trademark} catalyst systems represents a new approach to air pollution control--one that focuses on destroying pollutants already in the air. PremAir is the trademark for a family of developmental catalysts capable of reducing ozone, carbon monoxide and potentially other pollutants in ambient air that comes into contact with catalyst-coated surfaces. The more air that comes into contact with the surface the more pollutants that can be destroyed. For this reason, Engelhard has focused its attention on heat-exchange equipment such as automotive radiators and air-conditioner condensers. It is because of advances in catalysis achieved at Engelhard that PremAir catalysts are active at the low temperatures found in these environments. In Los Angeles, which has the country`s worst smog problem, approximately one trillion cubic feet per day of air pass through car radiators and five trillion cubic feet per day pass through air conditioners. Most of the research, development and testing work performed to date has been on ozone catalysts and their application to car radiators. This paper discusses that work and the potential benefits associated with the PremAir technology. In addition, preliminary work on stationary applications of this new technology is discussed.

  18. The Rac Inhibitor EHop-016 Inhibits Mammary Tumor Growth and Metastasis in a Nude Mouse Model

    PubMed Central

    Castillo-Pichardo, Linette; Humphries-Bickley, Tessa; De La Parra, Columba; Forestier-Roman, Ingrid; Martinez-Ferrer, Magaly; Hernandez, Eliud; Vlaar, Cornelis; Ferrer-Acosta, Yancy; Washington, Anthony V.; Cubano, Luis A.; Rodriguez-Orengo, Jose; Dharmawardhane, Suranganie

    2014-01-01

    Metastatic disease still lacks effective treatments, and remains the primary cause of cancer mortality. Therefore, there is a critical need to develop better strategies to inhibit metastatic cancer. The Rho family GTPase Rac is an ideal target for anti-metastatic cancer therapy, because Rac is a key molecular switch that is activated by a myriad of cell surface receptors to promote cancer cell migration/invasion and survival. Previously, we reported the design and development of EHop-016, a small molecule compound, which inhibits Rac activity of metastatic cancer cells with an IC50 of 1 μM. EHop-016 also inhibits the activity of the Rac downstream effector p21-activated kinase (PAK), lamellipodia extension, and cell migration in metastatic cancer cells. Herein, we tested the efficacy of EHop-016 in a nude mouse model of experimental metastasis, where EHop-016 administration at 25 mg/kg body weight (BW) significantly reduced mammary fat pad tumor growth, metastasis, and angiogenesis. As quantified by UPLC MS/MS, EHop-016 was detectable in the plasma of nude mice at 17 to 23 ng/ml levels at 12 h following intraperitoneal (i.p.) administration of 10 to 25 mg/kg BW EHop-016. The EHop-016 mediated inhibition of angiogenesis In Vivo was confirmed by immunohistochemistry of excised tumors and by In Vitro tube formation assays of endothelial cells. Moreover, EHop-016 affected cell viability by down-regulating Akt and Jun kinase activities and c-Myc and Cyclin D expression, as well as increasing caspase 3/7 activities in metastatic cancer cells. In conclusion, EHop-016 has potential as an anticancer compound to block cancer progression via multiple Rac-directed mechanisms. PMID:25389450

  19. CDK5 knockdown in astrocytes provide neuroprotection as a trophic source via Rac1.

    PubMed

    Posada-Duque, Rafael Andrés; Palacio-Castañeda, Valentina; Cardona-Gómez, Gloria Patricia

    2015-09-01

    Astrocytes perform metabolic and structural support functions in the brain and contribute to the integrity of the blood-brain barrier. Astrocytes influence neuronal survival and prevent gliotoxicity by capturing glutamate (Glu), reactive oxygen species, and nutrients. During these processes, astrocytic morphological changes are supported by actin cytoskeleton remodeling and require the involvement of Rho GTPases, such as Rac1. The protein cyclin-dependent kinase 5 (CDK5) may have a dual effect on astrocytes because it has been shown to be involved in migration, senescence, and the dysfunction of glutamate recapture; however, its role in astrocytes remains unclear. Treating a possible deregulation of CDK5 with RNAi is a strategy that has been proposed as a therapy for neurodegenerative diseases. Models of glutamate gliotoxicity in the C6 astroglioma cell line, primary cultures of astrocytes, and co-cultures with neurons were used to analyze the effects of CDK5 RNAi in astrocytes and the role of Rac1 in neuronal viability. In C6 cells and primary astrocytes, CDK5 RNAi prevented the cell death generated by glutamate-induced gliotoxicity, and this finding was corroborated by pharmacological inhibition with roscovitine. This effect was associated with the appearance of lamellipodia, protrusions, increased cell area, stellation, Rac1 activation, BDNF release, and astrocytic protection in neurons that were exposed to glutamate excitotoxicity. Interestingly, Rac1 inhibition in astrocytes blocked BDNF upregulation and the astrocyte-mediated neuroprotection. Actin cytoskeleton remodeling and stellation may be a functional phenotype for BDNF release that promotes neuroprotection. In summary, our findings suggest that CDK5- knockdown in astrocytes acts as a trophic source for neuronal protection in a Rac1-dependent manner. PMID:26160434

  20. Role of the guanine nucleotide exchange factor Ost in negative regulation of receptor endocytosis by the small GTPase Rac1.

    PubMed

    Ieguchi, Katsuaki; Ueda, Shuji; Kataoka, Tohru; Satoh, Takaya

    2007-08-10

    The Rho family of GTPases has been implicated in the regulation of intracellular vesicle trafficking. Here, we investigated the mechanism underlying the negative regulation of clathrin-mediated endocytosis of cell surface receptors mediated by the Rho family protein Rac1. Contrary to previous reports, only the activated mutant of Rac1, but not other Rho family members including RhoA and Cdc42, suppressed internalization of the transferrin receptor. On the other hand, down-regulation of Rac1 expression by RNA interference resulted in enhanced receptor internalization, suggesting that endogenous Rac1 in fact functions as a negative regulator. We identified a guanine nucleotide exchange factor splice variant designated Ost-III, which contains a unique C-terminal region including an Src homology 3 domain, as a regulator of Rac1 involved in the inhibition of receptor endocytosis. In contrast, other splice variants Ost-I and Ost-II exerted virtually no effect on receptor endocytosis. We also examined subcellular localization of synaptojanin 2, a putative Rac1 effector implicated in negative regulation of receptor endocytosis. Each Ost splice variant induced distinct subcellular localization of synaptojanin 2, depending on Rac1 activation. Furthermore, we isolated gamma-aminobutyric acid type A receptor-associated protein (GABARAP) as a protein that binds to the C-terminal region of Ost-III. When ectopically expressed, GABARAP was co-localized with Ost-III and potently suppressed the Ost-III-dependent Rac1 activation and the inhibition of receptor endocytosis. Lipid modification of GABARAP was necessary for the suppression of Ost-III. These results are discussed in terms of subcellular region-specific regulation of the Rac1-dependent signaling pathway that negatively regulates clathrin-mediated endocytosis.

  1. R-Ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis.

    PubMed

    Guo, Yuna; Kenney, S Ray; Muller, Carolyn Y; Adams, Sarah; Rutledge, Teresa; Romero, Elsa; Murray-Krezan, Cristina; Prekeris, Rytis; Sklar, Larry A; Hudson, Laurie G; Wandinger-Ness, Angela

    2015-10-01

    Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion, and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high-throughput screening and computational shape homology approaches, we identified R-ketorolac as a Cdc42 and Rac1 inhibitor, distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip) and primary patient-derived ovarian cancer cells show that R-ketorolac is a robust inhibitor of growth factor or serum-dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small-molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration, and invasion. In summary, we provide evidence for R-ketorolac as a direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiologic responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA-approved drug, racemic ketorolac, that can be used in humans.

  2. BEETIT: Building Cooling and Air Conditioning

    SciTech Connect

    2010-09-01

    BEETIT Project: The 14 projects that comprise ARPA-E’s BEETIT Project, short for “Building Energy Efficiency Through Innovative Thermodevices,” are developing new approaches and technologies for building cooling equipment and air conditioners. These projects aim to drastically improve building energy efficiency and reduce greenhouse gas emissions such as carbon dioxide (CO2) at a cost comparable to current technologies.

  3. The role of Rac1 in the regulation of NF-kB activity, cell proliferation, and cell migration in non-small cell lung carcinoma

    PubMed Central

    Gastonguay, Adam; Berg, Tracy; Hauser, Andrew D.; Schuld, Nathan; Lorimer, Ellen; Williams, Carol L.

    2012-01-01

    The small GTPase Rac1 regulates many cellular processes, including cytoskeletal reorganization, cell migration, proliferation, and survival. Additionally, Rac1 plays a major role in activating NF-κB-mediated transcription. Both Rac1 and NF-κB regulate many properties of the malignant phenotype, including anchorage-independent proliferation and survival, metastasis, and angiogenesis. Despite these findings, the roles of Rac1and NF-κB in non-small cell lung carcinoma, a leading cause of cancer deaths, have not been thoroughly investigated. Here, we compared the effects of Rac1 siRNA to that of the Rac1 inhibitor NSC23766 on multiple features of the NSCLC malignant phenotype, including NF-κB activity. We show that the siRNA-mediated silencing of Rac1 in lung cancer cells results in decreased cell proliferation and migration. The decrease in proliferation was observed in both anchorage-dependent and anchorage-independent assays. Furthermore, cells with decreased Rac1 expression have a slowed progression through the G1 phase of the cell cycle. These effects induced by Rac1 siRNA correlated with a decrease in NF-κB transcriptional activity. Additionally, inhibition of NF-κB signaling with BAY 11–7082 inhibited proliferation; indicating that the loss of cell proliferation and migration induced by the silencing of Rac1 expression may be attributed in part to loss of NF-κB activity. Interestingly, treatment with the Rac1 inhibitor NSC23766 strongly inhibits cell proliferation, cell cycle progression, and NF-κB activity in lung cancer cells, to an even greater extent than the inhibition induced by Rac1 siRNA. These findings indicate that Rac1 plays an important role in lung cancer cell proliferation and migration, most likely through its ability to promote NF-κB activity, and highlight Rac1 pathways as therapeutic targets for the treatment of lung cancer. PMID:22549160

  4. The role of Rac1 in the regulation of NF-κB activity, cell proliferation, and cell migration in non-small cell lung carcinoma.

    PubMed

    Gastonguay, Adam; Berg, Tracy; Hauser, Andrew D; Schuld, Nathan; Lorimer, Ellen; Williams, Carol L

    2012-06-01

    The small GTPase Rac1 regulates many cellular processes, including cytoskeletal reorganization, cell migration, proliferation, and survival. Additionally, Rac1 plays a major role in activating NF-κB-mediated transcription. Both Rac1 and NF-κB regulate many properties of the malignant phenotype, including anchorage-independent proliferation and survival, metastasis, and angiogenesis. Despite these findings, the roles of Rac1and NF-κB in non-small cell lung carcinoma, a leading cause of cancer deaths, have not been thoroughly investigated. Here, we compared the effects of Rac1 siRNA to that of the Rac1 inhibitor NSC23766 on multiple features of the NSCLC malignant phenotype, including NF-κB activity. We show that the siRNA-mediated silencing of Rac1 in lung cancer cells results in decreased cell proliferation and migration. The decrease in proliferation was observed in both anchorage-dependent and anchorage-independent assays. Furthermore, cells with decreased Rac1 expression have a slowed progression through the G 1 phase of the cell cycle. These effects induced by Rac1 siRNA correlated with a decrease in NF-κB transcriptional activity. Additionally, inhibition of NF-κB signaling with BAY 11-7082 inhibited proliferation; indicating that the loss of cell proliferation and migration induced by the silencing of Rac1 expression may be attributed in part to loss of NF-κB activity. Interestingly, treatment with the Rac1 inhibitor NSC23766 strongly inhibits cell proliferation, cell cycle progression, and NF-κB activity in lung cancer cells, to an even greater extent than the inhibition induced by Rac1 siRNA. These findings indicate that Rac1 plays an important role in lung cancer cell proliferation and migration, most likely through its ability to promote NF-κB activity, and highlight Rac1 pathways as therapeutic targets for the treatment of lung cancer.

  5. A review of polymer-based water conditioners for reduction of handling-related injury

    SciTech Connect

    Harnish, Ryan A.; Colotelo, Alison HA; Brown, Richard S.

    2011-01-01

    Fish are coated with an external layer of protective mucus. This layer serves as the primary barrier against infection or injury, reduces friction, and plays a role in ionic and osmotic regulation. However, the mucus layer is easily disturbed when fish are netted, handled, transported, stressed, or subjected to adverse water conditions. Water additives containing polyvinylpyrrolidone (PVP) or proprietary polymers have been used to prevent the deleterious effects of mucus layer disturbances in the commercial tropical fish industry, aquaculture, and for other fisheries management purposes. This paper reviews research on the effectiveness of water conditioners, and examines the contents and uses of a wide variety of commercially available water conditioners. Water conditioners containing polymers may reduce external damage to fish held in containers during scientific experimentation, including surgical implantation of electronic tags. However, there is a need to empirically test the effectiveness of water conditioners at preventing damage to and promoting healing of the mucus layer. A research agenda is provided to advance the science related to the use of water conditions to improve the condition of fish during handling and tagging.

  6. Heart Rate Conditioning in Newborn Infants: Relationships Among Conditionability, Heart Rate Variability, and Sex

    ERIC Educational Resources Information Center

    Stamps, Leighton E.; Porges, Stephen W.

    1975-01-01

    Trace conditioning was evaluated in newborn infants by measurements of heart rate responses to a conditioned stimulus in anticipation of or in absence of the unconditioned stimulus. Data suggest females have higher levels of heart rate variability than males, which parallels their greater conditionability. (GO)

  7. Investigation of Flow Conditioners for Compact Jet Engine Simulator Rig Noise Reduction

    NASA Technical Reports Server (NTRS)

    Doty, Michael J.; Haskin, Henry H.

    2011-01-01

    The design requirements for two new Compact Jet Engine Simulator (CJES) units for upcoming wind tunnel testing lead to the distinct possibility of rig noise contamination. The acoustic and aerodynamic properties of several flow conditioner devices are investigated over a range of operating conditions relevant to the CJES units to mitigate the risk of rig noise. An impinging jet broadband noise source is placed in the upstream plenum of the test facility permitting measurements of not only flow conditioner self-noise, but also noise attenuation characteristics. Several perforated plate and honeycomb samples of high porosity show minimal self-noise but also minimal attenuation capability. Conversely, low porosity perforated plate and sintered wire mesh conditioners exhibit noticeable attenuation but also unacceptable self-noise. One fine wire mesh sample (DP450661) shows minimal selfnoise and reasonable attenuation, particularly when combined in series with a 15.6 percent open area (POA) perforated plate upstream. This configuration is the preferred flow conditioner system for the CJES, providing up to 20 dB of broadband attenuation capability with minimal self-noise.

  8. 21 CFR 872.3765 - Pit and fissure sealant and conditioner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Pit and fissure sealant and conditioner. 872.3765 Section 872.3765 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3765 Pit and fissure sealant...

  9. 21 CFR 872.3765 - Pit and fissure sealant and conditioner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Pit and fissure sealant and conditioner. 872.3765 Section 872.3765 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3765 Pit and fissure sealant...

  10. 21 CFR 872.3750 - Bracket adhesive resin and tooth conditioner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Bracket adhesive resin and tooth conditioner. 872.3750 Section 872.3750 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3750 Bracket adhesive...

  11. Simulation Models of Leaf Area Index and Yield for Cotton Grown with Different Soil Conditioners

    PubMed Central

    Su, Lijun; Wang, Quanjiu; Wang, Chunxia; Shan, Yuyang

    2015-01-01

    Simulation models of leaf area index (LAI) and yield for cotton can provide a theoretical foundation for predicting future variations in yield. This paper analyses the increase in LAI and the relationships between LAI, dry matter, and yield for cotton under three soil conditioners near Korla, Xinjiang, China. Dynamic changes in cotton LAI were evaluated using modified logistic, Gaussian, modified Gaussian, log normal, and cubic polynomial models. Universal models for simulating the relative leaf area index (RLAI) were established in which the application rate of soil conditioner was used to estimate the maximum LAI (LAIm). In addition, the relationships between LAIm and dry matter mass, yield, and the harvest index were investigated, and a simulation model for yield is proposed. A feasibility analysis of the models indicated that the cubic polynomial and Gaussian models were less accurate than the other three models for simulating increases in RLAI. Despite significant differences in LAIs under the type and amount of soil conditioner applied, LAIm could be described by aboveground dry matter using Michaelis-Menten kinetics. Moreover, the simulation model for cotton yield based on LAIm and the harvest index presented in this work provided important theoretical insights for improving water use efficiency in cotton cultivation and for identifying optimal application rates of soil conditioners. PMID:26536468

  12. Impact of Air-Filter Condition on HVAC Equipment

    SciTech Connect

    Jung, L.

    1987-01-01

    An analysis was performed of changes in energy consumption caused by dirty filters for heating, ventilation, and air-conditioning systems during both heating and cooling cycles. Basic heat-transfer fundamentals and the vapor-compression refrigeration cycle for air conditioners were used. The energy cost savings between a dirty and a clean filter were small and were mainly offset by the filter cost. However, the consequences of deferring filter replacement could be very costly because of early equipment failures.

  13. Keeping cool: use of air conditioning by australians with multiple sclerosis.

    PubMed

    Summers, Michael P; Simmons, Rex D; Verikios, George

    2012-01-01

    Despite the known difficulties many people with MS have with high ambient temperatures, there are no reported studies of air conditioning use and MS. This study systematically examined air conditioner use by Australians with MS. A short survey was sent to all participants in the Australian MS Longitudinal Study cohort with a response rate of 76% (n = 2,385). Questions included hours of air-conditioner use, areas cooled, type and age of equipment, and the personal effects of overheating. Air conditioners were used by 81.9% of respondents, with an additional 9.6% who could not afford an air conditioner. Regional and seasonal variation in air conditioning use was reported, with a national annual mean of 1,557 hours running time. 90.7% reported negative effects from overheating including increased fatigue, an increase in other MS symptoms, reduced household and social activities, and reduced work capacity. Households that include people with MS spend between 4 and 12 times more on keeping cool than average Australian households. PMID:22548176

  14. Modulation of host signaling by a bacterial mimic: structure of the Salmonella effector SptP bound to Rac1.

    PubMed

    Stebbins, C E; Galán, J E

    2000-12-01

    Salmonella spp. utilize a specialized protein secretion system to deliver a battery of effector proteins into host cells. Several of these effectors stimulate Cdc42- and Rac1-dependent cytoskeletal changes that promote bacterial internalization. These potentially cytotoxic alterations are rapidly reversed by the effector SptP, a tyrosine phosphatase and GTPase activating protein (GAP) that targets Cdc42 and Rac1. The 2.3 A resolution crystal structure of an SptP-Rac1 transition state complex reveals an unusual GAP architecture that mimics host functional homologs. The phosphatase domain possesses a conserved active site but distinct surface properties. Binding to Rac1 induces a dramatic stabilization in SptP of a four-helix bundle that makes extensive contacts with the Switch I and Switch II regions of the GTPase.

  15. The Rac1 inhibitor NSC23766 exerts anti-influenza virus properties by affecting the viral polymerase complex activity.

    PubMed

    Dierkes, Rüdiger; Warnking, Kathrin; Liedmann, Swantje; Seyer, Roman; Ludwig, Stephan; Ehrhardt, Christina

    2014-01-01

    The frequent emergence of new influenza viruses in the human population underlines the urgent need for antiviral therapeutics in addition to the preventative vaccination against the seasonal flu. To circumvent the development of resistance, recent antiviral approaches target cellular proteins needed by the virus for efficient replication. We investigated the contribution of the small GTPase Rac1 to the replication of influenza viruses. Inhibition of Rac1 by NSC23766 resulted in impaired replication of a wide variety of influenza viruses, including a human virus strain of the pandemic from 2009 as well as highly pathogenic avian virus strains. Furthermore, we identified a crucial role of Rac1 for the activity of the viral polymerase complex. The antiviral potential of NSC23766 was confirmed in mouse experiments, identifying Rac1 as a new cellular target for therapeutic treatment of influenza virus infections.

  16. A central role for the small GTPase Rac1 in hippocampal plasticity and spatial learning and memory

    PubMed Central

    Haditsch, Ursula; Leone, Dino P.; Farinelli, Mélissa; Chrostek-Grashoff, Anna; Brakebusch, Cord; Mansuy, Isabelle M.; McConnell, Susan K.; Palmer, Theo D.

    2009-01-01

    Rac1 is a member of the Rho family of small GTPases that are important for structural aspects of the mature neuronal synapse including basal spine density and shape, activity-dependent spine enlargement, and AMPA receptor clustering in vitro. Here we demonstrate that selective elimination of Rac1 in excitatory neurons in the forebrain in vivo not only affects spine structure, but also impairs synaptic plasticity in the hippocampus with consequent defects in hippocampus-dependent spatial learning. Furthermore, Rac1 mutants display deficits in working/episodic-like memory in the delayed matching-to-place (DMP) task suggesting that Rac1 is a central regulator of rapid encoding of novel spatial information in vivo. PMID:19394428

  17. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    PubMed Central

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  18. Analysis of Efficiency Standards for Air Conditioners, Heat Pumps, and Other Products

    EIA Publications

    2002-01-01

    A series of analyses showing the impacts of each of the selected provisions of the bills on energy supply, demand, and prices, macroeconomic variables where feasible, import dependence, and emissions.

  19. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... include electrical resistance, steam, hot water, or gas, but may not include reverse cycle refrigeration..., and functional (or hydraulic) characteristics that affect energy consumption, energy efficiency, water consumption, or water efficiency. Coefficient of Performance, or COP means the ratio of the produced...

  20. 75 FR 7987 - Energy Conservation Standards for Residential Clothes Dryers and Room Air Conditioners: Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-23

    ... Analysis The NIA estimates the national energy savings (NES) and the net present value (NPV) of total... the real consumer cost of capital and puts the LCC in present-value terms. The PBP represents the... final rule in the Federal Register (FR) establishing the first set of performance standards...

  1. 77 FR 8178 - Test Procedures for Central Air Conditioners and Heat Pumps: Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-14

    ..., that are designed to use R-22 refrigerant. 74 FR 66450 (Dec. 15, 2009). EPA's rulemaking included an... instructions in the Web site. Registration information, participant instructions, and information about the capabilities available to webinar participants will be published on the following Web site...

  2. 77 FR 28519 - Test Procedure Guidance for Room Air Conditioners, Residential Dishwashers, and Residential...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-15

    .... A link to the docket web page can be found at www.regulations.gov . The www.regulations.gov web page..., DOE launched a new Web site dedicated to DOE guidance: http://www1.eere.energy.gov/guidance/default... publishes guidance in draft form on the guidance Web site. DOE accepts public comment on the draft...

  3. 75 FR 72739 - Compliance Testing Procedures: Correction Factor for Room Air Conditioners

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-26

    ... public record evidence justifying this requested action. See, 75 FR 42579, 42581 (July 22, 2010... Rulemaking (SNOPR) to amend the test procedure. See 75 FR 37594, 37635 (June 29, 2010). DOE states: ``Section... final rule and without prior notice. 75 FR 42579 (July 22, 2010) Here, test procedure revocation is...

  4. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... manufacturer. (iii) The manufacturer may include the ENERGY STAR logo on the bottom right corner of the label... may add the ENERGY STAR logo to labels on qualifying covered products; such manufacturers may add the ENERGY STAR logo to labels only on those covered products that are contemplated by the Memorandum...

  5. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... manufacturer. (iii) The manufacturer may include the ENERGY STAR logo on the bottom right corner of the label... may add the ENERGY STAR logo to labels on qualifying covered products; such manufacturers may add the ENERGY STAR logo to labels only on those covered products that are contemplated by the Memorandum...

  6. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... left and top to bottom). Depth is variable but should follow closely the prototype labels appearing at... manufacturer. (iii) The manufacturer may include the ENERGY STAR logo on the bottom right corner of the label... may add the ENERGY STAR logo to labels on qualifying covered products; such manufacturers may add...

  7. RhoA and Rac1 GTPases Differentially Regulate Agonist-Receptor Mediated Reactive Oxygen Species Generation in Platelets

    PubMed Central

    Akbar, Huzoor; Duan, Xin; Saleem, Saima; Davis, Ashley K.; Zheng, Yi

    2016-01-01

    Agonist induced generation of reactive oxygen species (ROS) by NADPH oxidases (NOX) enhances platelet aggregation and hence the risk of thrombosis. RhoA and Rac1 GTPases are involved in ROS generation by NOX in a variety of cells, but their roles in platelet ROS production remain unclear. In this study we used platelets from RhoA and Rac1 conditional knockout mice as well as human platelets treated with Rhosin and NSC23767, rationally designed small molecule inhibitors of RhoA and Rac GTPases, respectively, to better define the contributions of RhoA and Rac1 signaling to ROS generation and platelet activation. Treatment of platelets with Rhosin inhibited: (a) U46619 induced activation of RhoA; (b) phosphorylation of p47phox, a critical component of NOX; (c) U46619 or thrombin induced ROS generation; (d) phosphorylation of myosin light chain (MLC); (e) platelet shape change; (f) platelet spreading on immobilized fibrinogen; and (g) release of P-selectin, secretion of ATP and aggregation. Conditional deletion of RhoA or Rac1 gene inhibited thrombin induced ROS generation in platelets. Addition of Y27632, a RhoA inhibitor, NSC23766 or Phox-I, an inhibitor of Rac1-p67phox interaction, to human platelets blocked thrombin induced ROS generation. These data suggest that: (a) RhoA/ROCK/p47phox signaling axis promotes ROS production that, at least in part, contributes to platelet activation in conjunction with or independent of the RhoA/ROCK mediated phosphorylation of MLC; and (b) RhoA and Rac1 differentially regulate ROS generation by inhibiting phosphorylation of p47phox and Rac1-p67phox interaction, respectively. PMID:27681226

  8. Agonist Activation of F-Actin-Mediated Eosinophil Shape Change and Mediator Release Is Dependent on Rac2

    PubMed Central

    Lacy, Paige; Willetts, Lian; Kim, John D.; Lo, Andrea N.; Lam, Bon; MacLean, Emily I.; Moqbel, Redwan; Rothenberg, Marc E.; Zimmermann, Nives

    2011-01-01

    Background Tissue recruitment and activation of eosinophils contribute to allergic symptoms by causing airway hyperresponsiveness and inflammation. Shape changes and mediator release in eosinophils may be regulated by mammalian Rho-related guanosine triphosphatases. Of these, Rac2 is essential for F-actin formation as a central process underlying cell motility, exocytosis, and respiratory burst in neutrophils, while the role of Rac2 in eosinophils is unknown. We set out to determine the role of Rac2 in eosinophil mediator release and F-actin-dependent shape change in response to chemotactic stimuli. Methods Rac2-deficient eosinophils from CD2-IL-5 transgenic mice crossed with rac2 gene knockout animals were examined for their ability to release superoxide through respiratory burst or eosinophil peroxidase by degranulation. Eosinophil shape change and actin polymerization were also assessed by flow cytometry and confocal microscopy following stimulation with eotaxin-2 or platelet-activating factor. Results Eosinophils from wild-type mice displayed inducible superoxide release, but at a small fraction (4–5%) of human eosinophils. Rac2-deficient eosinophils showed significantly less superoxide release (p < 0.05, 26% less than wild type). Eosinophils lacking Rac2 had diminished degranulation (p < 0.05, 62% less eosinophil peroxidase) and shape changes in response to eotaxin-2 or platelet-activating factor (with 68 and 49% less F-actin formation, respectively; p < 0.02) compared with wild-type cells. Conclusion These results demonstrate that Rac2 is an important regulator of eosinophil function by contributing to superoxide production, granule protein release, and eosinophil shape change. Our findings suggest that Rho guanosine triphosphatases are key regulators of cellular inflammation in allergy and asthma. PMID:21576984

  9. Role of Rac 1 and cAMP in endothelial barrier stabilization and thrombin-induced barrier breakdown.

    PubMed

    Baumer, Y; Spindler, V; Werthmann, R C; Bünemann, M; Waschke, J

    2009-09-01

    Barrier stabilizing effects of cAMP as well as of the small GTPase Rac 1 are well established. Moreover, it is generally believed that permeability-increasing mediators such as thrombin disrupt endothelial barrier functions primarily via activation of Rho A. In this study, we provide evidence that decrease of both cAMP levels and of Rac 1 activity contribute to thrombin-mediated barrier breakdown. Treatment of human dermal microvascular endothelial cells (HDMEC) with Rac 1-inhibitor NSC-23766 decreased transendothelial electrical resistance (TER) and caused intercellular gap formation. These effects were reversed by addition of forskolin/rolipram (F/R) to increase intracellular cAMP but not by the cAMP analogue 8-pCPT-2'-O-Methyl-cAMP (O-Me-cAMP) which primarily stimulates protein kinase A (PKA)-independent signaling via Epac/Rap 1. However, both F/R and O-Me-cAMP did not increase TER above control levels in the presence of NSC-23766 in contrast to experiments without Rac 1 inhibition. Because Rac 1 was required for maintenance of barrier functions as well as for cAMP-mediated barrier stabilization, we tested the role of Rac 1 and cAMP in thrombin-induced barrier breakdown. Thrombin-induced drop of TER and intercellular gap formation were paralleled by a rapid decrease of cAMP as revealed by fluorescence resonance energy transfer (FRET). The efficacy of F/R or O-Me-cAMP to block barrier-destabilizing effects of thrombin was comparable to Y27632-induced inhibition of Rho kinase but was blunted when Rac 1 was inactivated by NSC-23766. Taken together, these data indicate that decrease of cAMP and Rac 1 activity may be an important step in inflammatory barrier disruption.

  10. Rab5 is required in metastatic cancer cells for Caveolin-1-enhanced Rac1 activation, migration and invasion.

    PubMed

    Díaz, Jorge; Mendoza, Pablo; Ortiz, Rina; Díaz, Natalia; Leyton, Lisette; Stupack, Dwayne; Quest, Andrew F G; Torres, Vicente A

    2014-06-01

    Rab5 is a small GTPase that regulates early endosome trafficking and other cellular processes, including cell adhesion and migration. Specifically, Rab5 promotes Rac1 activation and cancer cell migration, but little is known about the upstream regulators of Rab5. We have previously shown that the scaffolding protein Caveolin-1 (CAV1) promotes Rac1 activation and migration of cancer cells. Here, we hypothesized that CAV1 stimulates Rab5 activation, leading to increased Rac1 activity and cell migration. Expression of CAV1 in B16-F10 mouse melanoma and HT-29(US) human colon adenocarcinoma cells increased the GTP loading of Rab5, whereas shRNA-mediated targeting of endogenous CAV1 in MDA-MB-231 breast cancer cells decreased Rab5-GTP levels. Accordingly, shRNA-mediated downregulation of Rab5 decreased CAV1-mediated Rac1 activation, cell migration and invasion in B16-F10 and HT-29(US) cells. Expression of CAV1 was accompanied by increased recruitment of Tiam1, a Rac1 guanine nucleotide exchange factor (GEF), to Rab5-positive early endosomes. Using the inhibitor NSC23766, Tiam1 was shown to be required for Rac1 activation and cell migration induced by CAV1 and Rab5. Mechanistically, we provide evidence implicating p85α (also known as PIK3R1), a Rab5 GTPase-activating protein (GAP), in CAV1-dependent effects, by showing that CAV1 recruits p85α, precluding p85α-mediated Rab5 inactivation and increasing cell migration. In summary, these studies identify a novel CAV1-Rab5-Rac1 signaling axis, whereby CAV1 prevents Rab5 inactivation, leading to increased Rac1 activity and enhanced tumor cell migration and invasion.

  11. Double-blind, placebo-controlled study to evaluate two miconazole conditioners for the treatment of Malassezia dermatitis in dogs.

    PubMed

    Marsella, R; Nicklin, C E; Nerbonne, J

    2000-01-01

    Eighteen dogs with Malassezia dermatitis participated in a clinical trial to evaluate the efficacy of miconazole conditioners. Dogs were randomly assigned to receive vehicle only, miconazole 1%, or miconazole 2% conditioner. Conditioners were used three times weekly for 2 weeks and then twice weekly for 2 weeks. Investigators evaluated erythema, pruritus, and yeast counts weekly. Owners scored pruritus daily. Yeast number decreased in all treatment groups. Yeast number in the vehicle group was higher than in both the miconazole treatment groups but was not different between the two miconazole groups. Clinical scores decreased but no difference was detected among groups. PMID:19757576

  12. Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b in colorectal cells.

    PubMed

    Gonçalves, Vânia; Henriques, Andreia F A; Henriques, Andreia; Pereira, Joana F S; Pereira, Joana; Neves Costa, Ana; Moyer, Mary Pat; Moita, Luís Ferreira; Gama-Carvalho, Margarida; Matos, Paulo; Jordan, Peter

    2014-04-01

    The premessenger RNA of the majority of human genes can generate various transcripts through alternative splicing, and different tissues or disease states show specific patterns of splicing variants. These patterns depend on the relative concentrations of the splicing factors present in the cell nucleus, either as a consequence of their expression levels or of post-translational modifications, such as protein phosphorylation, which are determined by signal transduction pathways. Here, we analyzed the contribution of protein kinases to the regulation of alternative splicing variant Rac1b that is overexpressed in certain tumor types. In colorectal cells, we found that depletion of AKT2, AKT3, GSK3β, and SRPK1 significantly decreased endogenous Rac1b levels. Although knockdown of AKT2 and AKT3 affected only Rac1b protein levels suggesting a post-splicing effect, the depletion of GSK3β or SRPK1 decreased Rac1b alternative splicing, an effect mediated through changes in splicing factor SRSF1. In particular, the knockdown of SRPK1 or inhibition of its catalytic activity reduced phosphorylation and subsequent translocation of SRSF1 to the nucleus, limiting its availability to promote the inclusion of alternative exon 3b into the Rac1 pre-mRNA. Altogether, the data identify SRSF1 as a prime regulator of Rac1b expression in colorectal cells and provide further mechanistic insight into how the regulation of alternative splicing events by protein kinases can contribute to sustain tumor cell survival.

  13. Caveolin-1 Regulates Rac1 Activation and Rat Pulmonary Microvascular Endothelial Hyperpermeability Induced by TNF-α

    PubMed Central

    Sun, Geng-Yun; You, Qing-Hai; Wang, Nan; Zhang, Dan

    2013-01-01

    A multiplicity of vital cellular and tissue level functions are controlled by caveolin-1 and it is considered to be an important candidate for targeted therapeutics. Rac1-cortactin signaling plays an important role in maintaining the functions of the endothelial barrier in microvascular endothelial cells. The activity of Rac1 has been shown to be regulated by caveolin-1. Therefore, the present study investigated the consequences of down-regulating caveolin-1 and the subsequent changes in activity of Rac1 and the endothelial barrier functions in primary rat pulmonary microvascular endothelial cells (RPMVECs). RPMVECs were transfected with a small hairpin RNA duplex to down-regulate caveolin-1 expression. This procedure significantly increased the activity of Rac1. Moreover, down-regulation of caveolin-1 attenuated TNF-α-induced decrease in TER, increase in the flux of FITC-BSA and the disappearance of cortactin from the cell periphery in RPMVEC. Rac1 inhibitors significantly abolished this barrier-protective effect induced by down-regulation of caveolin-1 in response to TNF-α in RPMVECs. In conclusion, our data suggest a mechanism for the regulation of Rac1 activity by caveolin-1, with consequences for activation of endothelial cells in response to TNF-α. PMID:23383114

  14. Rac-mediated Stimulation of Phospholipase Cγ2 Amplifies B Cell Receptor-induced Calcium Signaling*♦

    PubMed Central

    Walliser, Claudia; Tron, Kyrylo; Clauss, Karen; Gutman, Orit; Kobitski, Andrei Yu.; Retlich, Michael; Schade, Anja; Röcker, Carlheinz; Henis, Yoav I.; Nienhaus, G. Ulrich; Gierschik, Peter

    2015-01-01

    The Rho GTPase Rac is crucially involved in controlling multiple B cell functions, including those regulated by the B cell receptor (BCR) through increased cytosolic Ca2+. The underlying molecular mechanisms and their relevance to the functions of intact B cells have thus far remained unknown. We have previously shown that the activity of phospholipase Cγ2 (PLCγ2), a key constituent of the BCR signalosome, is stimulated by activated Rac through direct protein-protein interaction. Here, we use a Rac-resistant mutant of PLCγ2 to functionally reconstitute cultured PLCγ2-deficient DT40 B cells and to examine the effects of the Rac-PLCγ2 interaction on BCR-mediated changes of intracellular Ca2+ and regulation of Ca2+-regulated and nuclear-factor-of-activated-T-cell-regulated gene transcription at the level of single, intact B cells. The results show that the functional Rac-PLCγ2 interaction causes marked increases in the following: (i) sensitivity of B cells to BCR ligation; (ii) BCR-mediated Ca2+ release from intracellular stores; (iii) Ca2+ entry from the extracellular compartment; and (iv) nuclear translocation of the Ca2+-regulated nuclear factor of activated T cells. Hence, Rac-mediated stimulation of PLCγ2 activity serves to amplify B cell receptor-induced Ca2+ signaling. PMID:25903139

  15. The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc

    SciTech Connect

    Nikolova, Ekaterina; Mitev, Vanio; Zhelev, Nikolai; Deroanne, Christophe F. . E-mail: yves.poumay@fundp.ac.be

    2007-08-03

    Proliferation of dermal fibroblasts is crucial for the maintenance of skin. The small Rho GTPase, Rac1, has been identified as a key transducer of proliferative signals in various cell types, but in normal human dermal fibroblasts its significance to cell growth control has not been studied. In this study, we applied the method of RNA interference to suppress endogenous Rac1 expression and examined the consequences on human skin fibroblasts. Rac1 knock-down resulted in inhibition of DNA synthesis. This effect was not mediated by inhibition of the central transducer of proliferative stimuli, ERK1/2 or by activation of the pro-apoptotic p38. Rather, as a consequence of the suppressed Rac1 expression we observed a significant decrease in phosphorylation of c-myc, revealing for the first time that in human fibroblasts Rac1 exerts control on proliferation through c-myc phosphorylation. Thus Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity.

  16. The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity

    PubMed Central

    Narayanan, Anjana S.; Reyes, Steve B.; Um, Kyongmi; McCarty, Joseph H.; Tolias, Kimberley F.

    2013-01-01

    Cell polarization is essential for many biological processes, including directed cell migration, and loss of polarity contributes to pathological conditions such as cancer. The Par complex (Par3, Par6, and PKCζ) controls cell polarity in part by recruiting the Rac-specific guanine nucleotide exchange factor T-lymphoma invasion and metastasis 1 (Tiam1) to specialized cellular sites, where Tiam1 promotes local Rac1 activation and cytoskeletal remodeling. However, the mechanisms that restrict Par-Tiam1 complex activity to the leading edge to maintain cell polarity during migration remain unclear. We identify the Rac-specific GTPase-activating protein (GAP) breakpoint cluster region protein (Bcr) as a novel regulator of the Par-Tiam1 complex. We show that Bcr interacts with members of the Par complex and inhibits both Rac1 and PKCζ signaling. Loss of Bcr results in faster, more random migration and striking polarity defects in astrocytes. These polarity defects are rescued by reducing PKCζ activity or by expressing full-length Bcr, but not an N-terminal deletion mutant or the homologous Rac-GAP, Abr, both of which fail to associate with the Par complex. These results demonstrate that Bcr is an integral member of the Par-Tiam1 complex that controls polarized cell migration by locally restricting both Rac1 and PKCζ function. PMID:24152735

  17. The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF

    PubMed Central

    Cabeceiras, Peter K.; Mahdavi, Mozhdeh; Gutschner, Tony; Genovese, Giannicola; Wang, Guocan; Fang, Zhuangna; Tepper, James M.; Stemke-Hale, Katherine; Tsai, Kenneth Y.; Davies, Michael A.; Mills, Gordon B.

    2014-01-01

    Following mutations in BRAF and NRAS, the RAC1 c.85C>T single nucleotide variant (SNV) encoding P29S amino acid change represents the next most frequently observed protein-coding hotspot mutation in melanoma. However, the biological and clinical significance of the RAC1 P29S somatic mutation in approximately 4–9% of patients remains unclear. Here, we demonstrate that melanoma cell lines possessing the RAC1 hotspot variant are resistant to RAF inhibitors (vemurafenib and dabrafenib). Enforced expression of RAC1 P29S in sensitive BRAF mutant melanoma cell lines confers resistance manifested by increased viability, decreased apoptosis and enhanced tumor growth in vivo upon treatment with RAF inhibitors. Conversely, RNAi mediated silencing of endogenous RAC1 P29S in a melanoma cell line with a co-occurring BRAF V600 mutation increased sensitivity to vemurafenib and dabrafenib. Our results suggest RAC1 P29S status may offer a predictive biomarker for RAF inhibitor resistance in melanoma patients, where it should be evaluated clinically. PMID:25056119

  18. Up-regulated type I collagen expression by the inhibition of Rac1 signaling pathway in human dermal fibroblasts.

    PubMed

    Igata, Toshikatsu; Jinnin, Masatoshi; Makino, Takamitsu; Moriya, Chikako; Muchemwa, Faith C; Ishihara, Tsuyoshi; Ihn, Hironobu

    2010-02-26

    Tissue remodeling is known to play important roles in wound healing. Although Rac1 is reported to be one of the key signaling molecules in cutaneous wound healing process, the exact mechanisms of Rac1-mediated tissue remodeling is still unknown. This study investigated the role of Rac1 in the regulation of extracellular matrix in cultured human dermal fibroblasts obtained by skin biopsy from three healthy donors. Protein levels of type I collagen in cultured human fibroblasts were increased by the treatment with Rac1 inhibitor NSC23766 in a dose-dependent manner. However, the mRNA levels of alpha2(I) collagen was not altered by the inhibitor. On the other hand, by the addition of inhibitor, half-lives of type I collagen protein were increased and MMP1 levels were reduced. These data suggest that blockade of Rac1 signaling results in accumulation of type I collagen due to decreased collagenase activity. This study also suggests that controlling Rac1 signaling is a new therapeutic approach to chronic/untreatable ulcer.

  19. Activation of Rac1-dependent redox signaling is critically involved in staurosporine-induced neurite outgrowth in PC12 cells.

    PubMed

    Kim, Du Sik; An, Jeong Mi; Lee, Han Gil; Seo, Su Ryeon; Kim, Seon Sook; Kim, Ju Yeon; Kang, Jeong Wan; Bae, Yun Soo; Seo, Jeong Taeg

    2013-02-01

    Staurosporine, a non-specific protein kinase inhibitor, has been shown to induce neurite outgrowth in PC12 cells, but the mechanism by which staurosporine induces neurite outgrowth is still obscure. In the present study, we investigated whether the activation of Rac1 was responsible for the neurite outgrowth triggered by staurosporine. Staurosporine caused rapid neurite outgrowth independent of the ERK signaling pathways. In contrast, neurite outgrowth in response to staurosporine was accompanied by activation of Rac1, and the Rac1 inhibitor NSC23766 attenuated the staurosporine-induced neurite outgrowth in a concentration-dependent manner. In addition, suppression of Rac1 activity by expression of the dominant negative mutant Rac1N17 also blocked the staurosporine-induced morphological differentiation of PC12 cells. Staurosporine caused an activation of NADPH oxidase and increased the production of reactive oxygen species (ROS), which was prevented by NSC23766 and diphenyleneiodonium (DPI), an NADPH oxidase inhibitor. Staurosporine-induced neurite outgrowth was attenuated by pretreatment with DPI and exogenous addition of sublethal concentration of H2O2 accelerated neurite outgrowth triggered by staurosporine. These results indicate that activation of Rac1, which leads to ROS generation, is required for neurite outgrowth induced by staurosporine in PC12 cells.

  20. The Calponin Family Member CHDP-1 Interacts with Rac/CED-10 to Promote Cell Protrusions

    PubMed Central

    Zhang, Jingyan; Liu, Jia-Jia; Wang, Yingchun; Ding, Mei

    2016-01-01

    Eukaryotic cells extend a variety of surface protrusions to direct cell motility. Formation of protrusions is mediated by coordinated actions between the plasma membrane and the underlying actin cytoskeleton. Here, we found that the single calponin homology (CH) domain-containing protein CHDP-1 induces the formation of cell protrusions in C. elegans. CHDP-1 is anchored to the cortex through its amphipathic helix. CHDP-1 associates through its CH domain with the small GTPase Rac1/CED-10, which is a key regulator of the actin cytoskeleton. CHDP-1 preferentially binds to the GTP-bound active form of the CED-10 protein and preserves the membrane localization of GTP-CED-10. Hence, by coupling membrane expansion to Rac1-mediated actin dynamics, CHDP-1 promotes the formation of cellular protrusions in vivo. PMID:27415421