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Sample records for air conditioners racs

  1. Accelerating Improvements in the Energy Efficiency of Room Air Conditioners (RACs) in India: Potential, Cost-Benefit, and Policies (Interim Assessment)

    SciTech Connect

    Abhyankar, Nikit; Shah, Nihar; Park, Won Young; Phadke, Amol

    2016-06-01

    Falling AC prices, increasing incomes, increasing urbanization, and high cooling requirements due to hot climate are all driving increasing uptake of Room Air Conditioners (RACs) in the Indian market. Air conditioning already comprises 40-60% of summer peak load in large metropolitan Indian cities such as Delhi and is likely to contribute 150 GW to the peak demand in 2030. Standards and labeling policies have contributed to improving the efficiency of RACs in India by about 2.5% in the last 10 years (2.5% per year) while inflation adjusted RAC prices have continued to decline. In this paper, we assess the technical feasibility, cost-benefit, and required policy enhancements by further accelerating the efficiency improvement of RACs in India. We find that there are examples of significantly more accelerated improvements such as those in Japan and Korea where AC efficiency improved by more than 7% per year resulting in almost a doubling of energy efficiency in 7 to 10 years while inflation adjusted AC prices continued to decline. We find that the most efficient RAC sold on the Indian market is almost twice as efficient as the typical AC sold on the market and hence see no technology constraints in a similar acceleration of improvement of efficiency. If starting 2018, AC efficiency improves at a rate of 6% instead of 3%, 40-60 GW of peak load (equivalent to connected load of 5-6 billion LED bulbs), and over 75 TWh/yr (equivalent to 60 million consumers consuming 100 kWh/month) will be saved by 2030; total peak load reduction would be as high as 50 GW. The net present value (NPV) of the consumer benefit between 2018-2030 will range from Rs 18,000 Cr in the most conservative case (in which prices don’t continue to decline and increase based estimates of today’s cost of efficiency improvement) to 140,000 Cr in a more realistic case (in which prices are not affected by accelerated efficiency improvement as shown by historical experience). This benefit is achievable by

  2. 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.

  3. 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.

  4. 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.

  5. 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%.

  6. On noise indices for domestic air conditioners

    NASA Astrophysics Data System (ADS)

    Tang, S. K.; Wong, M. Y.

    2004-07-01

    A survey was carried out in the present study to determine the noise indices which are capable of describing the nuisance caused by exposure to air-conditioner noise inside residential apartments. This survey consisted of a questionnaire, which asked the respondents to rate their feelings of annoyance and loudness on the air-conditioner noise and to give their preference of a change in the noise levels. Physical noise measurements were also carried out. A total of 57 noise spectra and 399 respondents were involved in the survey. Results show that the Zwicker's loudness level and the percentile level of 90% exceedence are the two major indices for air-conditioner noise assessment. Tonality appears not to be a good indicator for such a purpose.

  7. ENERGY STAR Certified Room Air Conditioners

    EPA Pesticide Factsheets

    Certified models meet all ENERGY STAR requirements as listed in the Version 4.0 ENERGY STAR Program Requirements for Room Air Conditioners that are effective as of October 26, 2015. A detailed listing of key efficiency criteria are available at http://www.energystar.gov/index.cfm?c=roomac.pr_crit_room_ac

  8. 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 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE... Appendix E to Part 305—Room Air Conditioners Range Information Manufacturer's rated cooling capacity in...

  9. 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.

  10. 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.

  11. 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

  12. Thermal Comfort Study of a Compact Thermoelectric Air Conditioner

    NASA Astrophysics Data System (ADS)

    Maneewan, S.; Tipsaenprom, W.; Lertsatitthanakorn, C.

    2010-09-01

    This paper evaluates the cooling performance and thermal comfort of a compact thermoelectric (TE) air conditioner. The compact TE air conditioner is composed of three TE modules. The cold and hot sides of the TE modules were fixed to rectangular fin heat sinks and fans. Thermal acceptability assessment was performed to find out whether the cooled air met the American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) Standard-55’s 80% acceptability criteria. A suitable condition occurred at 1 A current flow with a corresponding cooling capacity of 29.2 W, giving an average cooled air temperature of 28°C and 0.9 m/s cooled air velocity. The coefficient of performance was calculated and found to be ˜0.34. Economic analysis indicates that the payback period is 0.75 years when one compact TE air conditioner unit is used instead of a 1-ton conventional air conditioner.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., and functional (or hydraulic) characteristics that affect energy consumption, energy efficiency, water..., steam, or electricity. Packaged terminal heat pump means a packaged terminal air conditioner...

  4. 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.

  5. 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.

  6. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... pumps, and furnaces. 305.12 Section 305.12 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS... air conditioners, heat pumps, and furnaces. (a) Layout. All energy labels for central air conditioners, heat pumps, and furnaces (including boilers) shall use one size, similar colors, and typefaces...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Refrigeration Equipment... 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. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Refrigeration Equipment... 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...

  9. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Refrigeration Equipment... 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...

  10. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Refrigeration Equipment... 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...

  11. 48 CFR 52.223-12 - Refrigeration Equipment and Air Conditioners.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Refrigeration Equipment... 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...

  12. 10 CFR 429.16 - Central air conditioners and heat pumps.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CONSUMER PRODUCTS AND COMMERCIAL AND INDUSTRIAL EQUIPMENT Certification § 429.16 Central air conditioners... mean divided by 1.05, where: ER02MY11.030 and (B) Any represented value of the energy efficiency or other measure of energy consumption of the central air conditioner or heat pump for which...

  13. 10 CFR 429.16 - Central air conditioners and heat pumps.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CONSUMER PRODUCTS AND COMMERCIAL AND INDUSTRIAL EQUIPMENT Certification § 429.16 Central air conditioners... mean divided by 1.05, where: ER02MY11.030 and (B) Any represented value of the energy efficiency or other measure of energy consumption of the central air conditioner or heat pump for which...

  14. 10 CFR 429.16 - Central air conditioners and heat pumps.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CONSUMER PRODUCTS AND COMMERCIAL AND INDUSTRIAL EQUIPMENT Certification § 429.16 Central air conditioners... mean divided by 1.05, where: ER02MY11.030 and (B) Any represented value of the energy efficiency or other measure of energy consumption of the central air conditioner or heat pump for which...

  15. 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... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Cooling Performance and Cost for Central...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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...

  17. 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...

  18. 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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...

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

    PubMed

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

    2012-12-04

    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.

  1. 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.

  2. Motor current signature analysis: A potential diagnostic for air conditioners

    SciTech Connect

    Miller, W.A.; Haynes, H.D.; Griffin, F.P.; Levins, W.P.; Karnitz, M.A.

    1988-03-01

    Recent advancements in modern electronics have made it possible to collect the various ''transient noise'' signals which are present on electric power lines of motor-driven equipment while using a simple non-intrusive clamp-on inductive pickup. Electronic filters are used to analyze the noise signal with an on-the-spot, real-time analysis. An exploratory study, conducted at ORNL, examined the potential for using the motor current signature on heat pumps and air conditioners as a diagnostic tool. Preliminary results show that there is some correlation between the motor current signature and the performance of a heat pump. However, the tests and associated analysis were limited, and additional research is needed to determine the full potential of motor current signature analysis (MCSA).

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Transition to Low-GWP Alternatives in Passenger Vehicle Air Conditioners

    EPA Pesticide Factsheets

    This fact sheet provides current information on low global warming potential (GWP) alternatives in newly manufactured passenger vehicle air conditioners (ACs), in lieu of high-GWP hydrofluorocarbons (HFCs).

  8. 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.

  9. 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.

  10. Centrifugal compressors for automotive air conditioners -- Component design

    SciTech Connect

    Yun, H.; Smith, J.L. Jr.

    1996-12-31

    The application of a novel, electric motor-driven, variable-speed centrifugal compressor for automotive air conditioners has been investigated. For the feasibility analysis, a configuration design has been performed. It includes refrigerant selection, thermodynamic cycle analysis, compressor aerodynamic design, and mechanical layout of the integrated motor-compressor structure. Both the motor constraints (provided by the Laboratory for Electromagnetic and Electronic Systems at M.I.T.) and the compressor constraints were considered for the configuration design. The result is an inter-cooled two-stage compression system using R123 as the refrigerant. The inter-cooling is achieved by feeding back a small fraction of the condenser liquid into the return channel between the first and the second stage through the electric motor. At the design condition, the pressure ratio is 3.2 for the first stage and 1.9 for the second stage. The design rotational speed is 75,000 rpm, and the maximum cooling capacity is 5,275 Watts. High efficiency is expected by varying the compressor speed to match the required cooling load at each instant.

  11. [Fungus microbiota in air conditioners in intensive care units in Teresina, Piauí].

    PubMed

    Mobin, Mitra; do Amparo Salmito, Maria

    2006-01-01

    With the aim of identifying the fungus microbiota in air conditioners in intensive care units (ICUs) within public and private hospitals in Teresina, Piauí, solid material was collected from ten different ICUs. Thirty-three species of Moniliaceae and Dematiaceae were isolated, which was the first report of these in Piauí. High frequencies of Aspergillus niger Van Tieghem (60%), Aspergillus fumigatus Fres (50%), Trichoderma koningii Oudem (50%) and Aspergillus flavus Link: Fr. (40%) were recorded. The air conditioner cleanliness validity had expired in all the ICUs, and the quantity of colony-forming units exceeded the levels permitted by Law 176/00 from the Ministry of Health. It is important to provide individual protection equipment for professionals, adopt hospital infection control measures, raise the awareness of the presence of fungus infection, improve air circulation around the environment, periodically clean the air conditioners, and make health professionals alert to the importance of these fungi in the hospital environment.

  12. 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

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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

    ... efficiency of commercial air conditioners and heat pumps. 431.96 Section 431.96 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT Commercial... energy efficiency of commercial air conditioners and heat pumps. (a) Scope. This section contains...

  19. 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.

  20. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... pumps, and furnaces. 305.12 Section 305.12 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS... pumps, and furnaces. (a) Layout. All energy labels for central air conditioners, heat pumps, and furnaces (including boilers) shall use one size, similar colors, and typefaces with consistent...

  1. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... pumps, and furnaces. 305.12 Section 305.12 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS... pumps, and furnaces. (a) Layout. All energy labels for central air conditioners, heat pumps, and furnaces (including boilers) shall use one size, similar colors, and typefaces with consistent...

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... pumps, and furnaces. 305.12 Section 305.12 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS... pumps, and furnaces. (a) Layout. All energy labels for central air conditioners, heat pumps, and furnaces (including boilers) shall use one size, similar colors, and typefaces with consistent...

  3. 16 CFR 305.12 - Labeling for central air conditioners, heat pumps, and furnaces.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... pumps, and furnaces. 305.12 Section 305.12 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS... pumps, and furnaces. (a) Layout. All energy labels for central air conditioners, heat pumps, and furnaces (including boilers) shall use one size, similar colors, and typefaces with consistent...

  4. 75 FR 72739 - Compliance Testing Procedures: Correction Factor for Room Air Conditioners

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-26

    ... of Energy November 15, 2010 Petition for Rulemaking Petition of the Association of the Home Appliance... terms of energy efficiency and environmental protection. New appliances often represent the most... air conditioner has technically incorrect ratings, does not qualify for Energy Star, or fails to...

  5. 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.

  6. 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.

  7. Experimental Validation of the Optimum Design of an Automotive Air-to-Air Thermoelectric Air Conditioner (TEAC)

    NASA Astrophysics Data System (ADS)

    Attar, Alaa; Lee, HoSung; Weera, Sean

    2015-06-01

    The optimization of thermoelectric air conditioners (TEAC) has been a challenging topic due to the multitude of variables that must be considered. The present work discusses an experimental validation of the optimum design for an automotive air-to-air TEAC. The TEAC optimum design was obtained by using a new optimal design method with dimensional analysis that has been recently developed. The design constraints were obtained through a previous analytical study on the same topic. To simplify the problem, a unit cell representing the entire TEAC system was analytically simulated and experimentally tested. Moreover, commercial TEC modules and heat sinks were selected and tested based on the analytical optimum design results.

  8. ENERGY STAR Certified Non-AHRI Central Air Conditioner Equipment and Air Source Heat Pump

    EPA Pesticide Factsheets

    Certified models meet all ENERGY STAR requirements as listed in the Version 5.0 ENERGY STAR Program Requirements for Air Source Heat Pump and Central Air Conditioner Equipment that are effective as of September 15, 2015. A detailed listing of key efficiency criteria are available at http://www.energystar.gov/index.cfm?c=airsrc_heat.pr_crit_as_heat_pumps Listed products have been submitted to EPA by ENERGY STAR partners that do not participate in the AHRI certification program. EPA will continue to update this list with products that are certified by EPA-recognized certification bodies other than AHRI. The majority of ENERGY STAR products, certified by AHRI, can be found on the CEE/AHRI Verified Directory at http://www.ceedirectory.org/

  9. 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.

  10. 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

  11. Automatic Unit Number Binding with Refrigeration Circuit Identification for Air-Conditioner Control Network

    NASA Astrophysics Data System (ADS)

    Ninagawa, Chuzo; Mizoguchi, Masanobu; Tsuji, Kohkichi

    This paper proposes an automatic unit number binding method so that a number of logical subsystems are defined in the whole control network for distributed air-conditioners. Each air-conditioner unit starts the proposed algorithm at random timing to allocate its own unit number without any server. Then each outside unit one by one broadcasts the check signal and flows refrigerant gas to the refrigerant circuit between units to make each inside unit discover its piping connection. As a result, a number of logical subsystems are defined in the whole control network. A Petri net model was constructed for verification of our proposed system. For the case of two outside units and three inside units, the reachability to the required states and the deadlock free property were verified. The generalized module-by-module Petri net construction procedure shows applicability to general cases of arbitrary number of units.

  12. 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.

  13. Deaths Due to Accidental Air Conditioner Compressor Explosion: A Case Series.

    PubMed

    Behera, Chittaranjan; Bodwal, Jatin; Sikary, Asit K; Chauhan, Mohit Singh; Bijarnia, Manjul

    2017-01-01

    In an air-conditioning system, the compressor is a large electric pump that pressurizes the refrigerant gas as part of the process of turning it back into a liquid. The explosion of an air conditioner (AC) compressor is an uncommon event, and immediate death resulted from the blast effect is not reported in forensic literature. We report three such cases in which young AC mechanics were killed on the spot due to compressor blast, while repairing the domestic split AC unit. The autopsy findings, the circumstances leading to the explosion of the compressor, are discussed in this study.

  14. 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:…

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Experimental study on heat transfer performance of aluminium foam parallel-flow condenser in air conditioner

    NASA Astrophysics Data System (ADS)

    Zhang, X.; Wan, Z. M.; Chang, H. W.; Wang, Y. D.

    2017-01-01

    Open cell aluminium foam was used in parallel-flow condenser in air conditioner, and two condensers with different pore density were fabricated. The experimental study was conducted on the heat transfer performance and temperature distribution. The experimental results show that both of the heat transfer load and air pressure drop increase with the increase of pore density, air velocity is 2.5m/s, the heat transfer capacities of the condenser with 10PPI and 8PPI are 4.786kw and 3.344kW respectively. Along the flow direction of refrigerant, the outlet temperatures of refrigerant drop with the rise of air velocity when the inlet temperature is constant. The outlet temperature of the refrigerant decreases with the increase of pore density.

  2. Modeling of a second-generation solar-driven Rankine air conditioner

    NASA Astrophysics Data System (ADS)

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

    1984-07-01

    Ten configurations of a second-generation, 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. The generated data are also presented. Experimental work was done 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.

  3. 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.

  4. 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

    ... 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 Air... appendix F) until the compliance date of any amended energy conservation standards for room...

  5. 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

    ... 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 Air... appendix F) until the compliance date of any amended energy conservation standards for room...

  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, 2012 CFR

    2012-01-01

    ... 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 Air... appendix F) until the compliance date of any amended energy conservation standards for room...

  7. 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.

  8. Human location and recognition for intelligent air conditioners

    NASA Astrophysics Data System (ADS)

    Sun, Bing; Li, Ke; Weng, Fei; Liu, Yuncai

    2010-08-01

    Through analyzing the low resolution video captured by a single camera fixed on the air condition, this paper proposes an approach that can automatically estimate the person's location and recognize the person's identification in real time. Human location can be obtained by smart geometry calculation with the knowledge of the camera intrinsic parameters and living experience. Human recognition has been found to be very difficult in reality, especially when the person is walking at a distance in the complexity indoor conditions. For optimal performance, we use the shape feature gait energy image (GEI) as the basis, since it isn't sensitive the noise. Then we extract more efficient features using the histograms of oriented gradients (HOG) and do the dimensionality reduction by the coupled subspaces analysis and discriminant analysis with tensor representation (CSA+DATER), Finally the classical Bayesian Theory is used for fusion of the result of HOG and the result of CSA+DATER. The proposed approach is tested on our lab database to evaluate the performance of the human location and recognition. To verify the robust of our human recognition approach especially, CMU MoBo gait database is used. Experimental results show that the proposed approach has a high accuracy rate in both human identification recognition and location estimation.

  9. 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

  10. Isolation and characterization of Acanthamoeba spp. from air-conditioners in Kuala Lumpur, Malaysia.

    PubMed

    Chan, Li-Li; Mak, Joon-Wah; Low, Yoon-Tong; Koh, Thuan-Tzen; Ithoi, Init; Mohamed, Shar Mariam

    2011-01-01

    During a study on the quality of the indoor environment, Acanthamoeba spp. were detected in 20 out of 87 dust samples collected from air-conditioners installed in a four-story campus building located in Kuala Lumpur, Malaysia. Twenty-one cloned Acanthamoeba isolates designated as IMU1 to IMU21 were established from the positive primary cultures. Five species were identified from the 16 isolates according to the morphological criteria of Pussard and Pons; i.e. A. castellanii, A. culbertsoni, A. griffini, A. hatchetti and A. polyphaga. Species identities for the remaining five isolates (IMU4, IMU5, IMU15, IMU20 and IMU21), however, could not be determined morphologically. At genotypic characterization, these isolates were placed into T3 (IMU14); T5 (IMU16 and IMU17) and T4 (all the remaining isolates). To predict the potential pathogenicity of these Acanthamoeba isolates, thermo- and osmotolerance tests were employed; many isolates were predicted as potential human pathogens based on the outcome of these tests. This is the first time potentially pathogenic Acanthamoeba have been isolated from air-conditioners in Malaysia.

  11. 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.

  12. Experimental Determination of Demand Response Control Models and Cost of Control for Ensembles of Window-Mount Air Conditioners

    SciTech Connect

    Geller, Drew Adam; Backhaus, Scott N.

    2016-09-29

    Control of consumer electrical devices for providing electrical grid services is expanding in both the scope and the diversity of loads that are engaged in control, but there are few experimentally-based models of these devices suitable for control designs and for assessing the cost of control. A laboratory-scale test system is developed to experimentally evaluate the use of a simple window-mount air conditioner for electrical grid regulation services. The experimental test bed is a single, isolated air conditioner embedded in a test system that both emulates the thermodynamics of an air conditioned room and also isolates the air conditioner from the real-world external environmental and human variables that perturb the careful measurements required to capture a model that fully characterizes both the control response functions and the cost of control. The control response functions and cost of control are measured using harmonic perturbation of the temperature set point and a test protocol that further isolates the air conditioner from low frequency environmental variability.

  13. 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.

  14. 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

    ... paragraphs (d) and (e) of this section will be used. Energy Efficiency Standards ... efficiency of commercial air conditioners and heat pumps. 431.96 Section 431.96 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY PROGRAM FOR CERTAIN COMMERCIAL AND INDUSTRIAL EQUIPMENT...

  15. 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

    ... 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...

  16. 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...

  17. 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

  18. Procuring High-Efficiency Air Conditioners: Harnessing Competition to Achieve Advances in Technology

    SciTech Connect

    Hollomon, J Bradford; Gordon, Kelly L.

    2002-03-01

    The Departments of Energy and Defense have joined forces to devise an innovative approach to acquiring more efficient unitary air conditioners that minimize life-cycle cost through improved technology. The resulting procurement solicitation challenges manufacturers to offer products with reduced life-cycle cost, taking into account both the initial prices of their units and the costs of their ongoing electric consumption. Competing products are evaluated according to a formula that reflects both full- and part-load efficiencies under a simulated set of time-varying climate conditions. The authors will report on the progress of the procurement, including the choice of target product based on market prospects and technology readiness, development of the technical specifications and electric consumption simulator, approaches to administrative and procedural challenges, responses from manufacturers, and plans for product promotion in the future.

  19. 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.

  20. 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.

  1. Development of Small Gas-fired Ammonia Absorption Air Conditioner for Residential Use

    NASA Astrophysics Data System (ADS)

    Sawada, Takashi; Yamamoto, Yoshiaki; Kobayashi, Hirotake; Shimaoka, Takaharu; Kawahara, Michinori; Uedono, Norio

    Due to the global environmental problems, the usage of natural refrigerants, such as water, ammonia, and hydrocarbons, are examined widely. Especially, absorption heat pump system using ammonia and water is penetrated widely for residential use in the U.S. and Europe, because it is easy to make the air-cooled system and to perform with high COP for heating. Authors have been developing an ammonia/water heat pump system for residential use. This system is driven by natural gas and supplies chilled water for cooling and hot water for heating. The results of performance tests indicated 6.8kW for cooling capacity and 10.3kW for heating capacity. And, some indexes which were related the charge of ammonium and the weight of the out-door unit, were compared with the same item of other equipments, such as, gas-fired LiBr absorption air-conditioners and gas engine driven heat pumps for residential use. The objective of this paper is to introduce the specifications and performance test results of the latest model, and to evaluate the performance of this heat pump system.

  2. 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.

  3. 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.

  4. 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.

  5. Alternative Refrigerant Evaluation for High-Ambient-Temperature Environments: R-22 and R-410A Alternatives for Rooftop Air Conditioners

    SciTech Connect

    Abdelaziz, Omar; Shrestha, Som S.; Shen, Bo; Linkous, Randall Lee; Goetzler, William; Guernsey, Matt; Bargach, Youssef

    2016-09-01

    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 relative to hydrochlorofluorocarbon (HCFC) and hydrofluorocarbon (HFC) refrigerants in packaged or Rooftop Unit (RTU) air conditioners under high-ambient-temperature conditions. This final report describes the parties involved, the alternative refrigerants selection process, the test procedures, and the final results.

  6. 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)

  7. Cooling the Planet: Opportunities for Deployment of Superefficient Room Air Conditioners

    SciTech Connect

    Shah, Nihar; Waide, Paul; Phadke, Amol

    2013-04-01

    This report presents the results of an analysis, commissioned by the U.S. Department of Energy, of Air Conditioner (AC) efficiency in support of the Super-efficient Equipment and Appliance Deployment (SEAD) initiative.1 The International Energy Studies group at Lawrence Berkeley National Laboratory in collaboration with Navigant Consulting Inc. performed the analysis. SEAD aims to transform the global market by increasing the penetration of highly efficient equipment and appliances. SEAD partners work together in voluntary activities to: (1) “raise the efficiency ceiling” by pulling superefficient appliances and equipment into the market through cooperation on measures like incentives, procurement, awards, and research and development (R&D) investments; (2) “raise the efficiency floor” by working together to bolster national or regional policies like minimum efficiency standards; and (3) “strengthen the efficiency foundations” of programs by coordinating technical work to support these activities.2 The objective of this analysis is to provide the background technical information necessary to improve the efficiency of ACs and to provide a foundation for the activities of SEAD participating countries. We find that even the best currently available technology offers large efficiency improvement opportunities (35% to 50% reduction in energy consumption from the market average) in most SEAD countries. The cost effective efficiency improvements range from 20% to 30% reduction in energy consumption based on a consumer perspective.

  8. 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.

  9. 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

  10. 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,…

  11. 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

  12. Flow, stock, and impact assessment of refrigerants in the Japanese household air conditioner sector.

    PubMed

    Xue, Mianqiang; Kojima, Naoya; Machimura, Takashi; Tokai, Akihiro

    2017-05-15

    Refrigerants provide society with great benefits while have the potential to cause adverse effects on the environment and human health. The present study estimated time-dependent flows and stocks and assessed the effects of refrigerants (R-22, R-410a, and R-32) in household air conditioners in Japan. It was found that stock of R-22 and R-410a peaked at 49,147t in 2000 and 55,994t in 2017, respectively. The largest flow of R-22 and R-410a to waste phase occurred at 3417t/yr. in 2005 and 4011t/yr. in 2023, respectively. The total global warming potential (GWP) due to refrigerant emissions increased from 3.6kt CO2 eq. in 1952 to 6999kt CO2 eq. in 2019, and then decreased to 5314kt CO2 eq. in 2030. The ozone depletion potential (ODP) peaked at 141t CFC-11 eq. in 2002. When substituting R-410a for R-22, the ODP decreased 50% while the GDP increased 8%. When substituting R-32 for R-410a, there was no effect on the ODP while the GDP decreased 6%. The human health damage due to the global warming effect of refrigerant emission was much higher than that due to the ozone depleting effect. The refrigerant emission in use and waste management phases dominated the human health damage. The dynamic estimation not only allows us to evaluate the performance of past policies but also supports the future sustainable management associated with the health effects of refrigerants.

  13. 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

    2012-02-07

    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

  14. 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

  15. Experimental analysis of a window air conditioner with a R-22 and R32/R125/R134a mixture

    SciTech Connect

    Mei, V.C.; Chen, F.C.; Chen, D.T.; HuangFu, E.P.

    1995-07-01

    Much experimental and theoretical analysis of potential R-22 replacements has been accomplished. However, published information about the experimental analysis of any off-the-shelf air conditioner with a potential R-22 replacement at realistic, operating conditions is still rare. This type of work could be useful because it provides baseline data for comparing the performance of R-22 and its potential replacement at drop-in conditions. In this study, an off-the-shelf window air conditioner was tested at Air Conditioning and Refrigeration Institute (ARI)-rated indoor conditions and at different ambient temperatures, including the ARI-rated outdoor condition, with R-22 and with its potential replacement, a ternary mixture of R-32(30%)/R-125(10%)/R-134a(60%) (the ternary mixture). A test rig was built that provided for baseline operation and for the option of operating the system with a flooded evaporator by means of liquid over-feeding (LOF). The test results indicated the cooling capacity of the ternary mixture was 7.7% less than that of R-22 at 95{degrees}F ambient for baseline operation. The cooling capacity for both refrigerants improved when a flooded evaporator, or LOF, was used. For LOF operation, the cooling capacity of the ternary mixture was only 1.1% less than that of R-22. The ternary mixture had slightly higher compressor discharge pressure, a lower compressor discharge temperature, slightly lower compressor power consumption, and a higher compressor high/low pressure ratio.

  16. 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.

  17. Study on the complexity pricing game and coordination of the duopoly air conditioner market with disturbance demand

    NASA Astrophysics Data System (ADS)

    Ma, Junhai; Xie, Lei

    2016-03-01

    The paper focuses on the dynamic pricing game of the duopoly air conditioner market with disturbance in demand and analyzes the influence of disturbance on the dynamic game system. Considering the demand for products, such as air conditioner, varies with different seasons, we assume three cases based on the condition of disturbance, including growth market (Case 1), declining market (Case 2) and completely random market (Case 3). By analyzing these three cases and making comparison among them, the paper shows that the growth market is more sensitive to the changing parameters such as the adjustment variable and the competitive factor than the declining market. It is more difficult to keep the system stable in a growth market. Although the demand is completely random, the dynamic system can reach a stable state, on condition that the adjustment variable is small enough. The results also indicate that the bullwhip effect between the order quantity and the actual demand is weakened gradually along with the price adjustment.

  18. 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

  19. 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.

  20. Methodology for Automated Detection of Degradation and Faults in Packaged Air Conditioners and Heat Pumps Using Only Two Sensors

    SciTech Connect

    2016-02-10

    The software was created in the process of developing a system known as the Smart Monitoring and Diagnostic System (SMDS) for packaged air conditioners and heat pumps used on commercial buildings (known as RTUs). The SMDS provides automated remote monitoring and detection of performance degradation and faults in these RTUs and could increase the awareness by building owners and maintenance providers of the condition of the equipment, the cost of operating it in degraded condition, and the quality of maintenance and repair service when it is performed. The SMDS provides these capabilities and would enable conditioned-based maintenance rather than the reactive and schedule-based preventive maintenance commonly used today, when maintenance of RTUs is done at all. Improved maintenance would help ensure persistent peak operating efficiencies, reducing energy consumption by an estimated 10% to 30%.

  1. 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.

  2. 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.

  3. 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.

  4. Experimental Analysis of 3D Flow in Scroll Casing of Multi-Blade Fan for Air-Conditioner

    NASA Astrophysics Data System (ADS)

    Kitadume, Michio; Kawahashi, Masaaki; Hirahara, Hiroyuki; Uchida, Tadashi; Yanagawa, Hideki

    The multi-blade fan, which has been widely used as a blower for air-conditioning systems of vehicles, is one of the well-established fluid machinery. However, many factors must be considered in its practical design because the flow generated in the fan is quite complicated with three-dimensionality and unsteadiness. The fundamental fan performance is primarily determined by the impeller of the fan, and is also affected by the scroll casing. However, the theoretical estimation of the effect of the casing on the performance has not been well established. In order to estimate the casing effect on fan performance, detailed three-dimensional (3D) flow analysis in the casing is necessary. Stereoscopic PIV (SPIV) is one of the useful techniques for experimental analysis of 3D flow fields. There are some difficulties in practical application of SPIV for flow analysis in fluid machinery with complicated geometry, but the results obtained provide useful information for understanding the 3D flow field. In this report, experimental investigation of the flow in the scroll casing has been carried out using PIV and SPIV under the premise of downsizing automobile air conditioner fans.

  5. 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.

  6. 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.

  7. New and Green Multi-component Scaling and Corrosion Inhibitor for the Cooling Water of Central Air Conditioners

    NASA Astrophysics Data System (ADS)

    Li, Maodong; Dai, Chenlin; Yang, Bo; Qiao, Yue; Zhu, Zhiping

    2016-12-01

    A green multi-component inhibitor was developed in this study to obtain suitable scale and corrosion inhibitor for the cooling water treatment of central air conditioners. The inhibitor formulation consisted of hydrolyzed polymaleic anhydride/Tween-80/sodium N-lauroyl sarcosinate/tolyltriazole (named 4-HTSA). Weight loss test and electrochemical method were used to investigate the corrosion inhibition performance of 4-HTSA on A3 carbon steel and T2 red copper in synthetic cooling water, and the scale inhibition performance of 4-HTSA was studied by the calcium carbonate precipitation method. The influence of parameters, such as pH, temperature, scaling and corrosive ion, on 4-HTSA was researched. Scanning electron microscopy (SEM) and x-ray diffraction were used for examination of the scale, and corrosion coupons were analyzed by SEM/energy-dispersive x-ray spectroscopy. Results showed that 4-HTSA had excellent scale and corrosion inhibition performance and wide tolerance to pH, temperature and the concentration of scaling and corrosive ion. Polarization curves indicated that 4-HTSA was anodic inhibitor.

  8. New and Green Multi-component Scaling and Corrosion Inhibitor for the Cooling Water of Central Air Conditioners

    NASA Astrophysics Data System (ADS)

    Li, Maodong; Dai, Chenlin; Yang, Bo; Qiao, Yue; Zhu, Zhiping

    2017-02-01

    A green multi-component inhibitor was developed in this study to obtain suitable scale and corrosion inhibitor for the cooling water treatment of central air conditioners. The inhibitor formulation consisted of hydrolyzed polymaleic anhydride/Tween-80/sodium N-lauroyl sarcosinate/tolyltriazole (named 4-HTSA). Weight loss test and electrochemical method were used to investigate the corrosion inhibition performance of 4-HTSA on A3 carbon steel and T2 red copper in synthetic cooling water, and the scale inhibition performance of 4-HTSA was studied by the calcium carbonate precipitation method. The influence of parameters, such as pH, temperature, scaling and corrosive ion, on 4-HTSA was researched. Scanning electron microscopy (SEM) and x-ray diffraction were used for examination of the scale, and corrosion coupons were analyzed by SEM/energy-dispersive x-ray spectroscopy. Results showed that 4-HTSA had excellent scale and corrosion inhibition performance and wide tolerance to pH, temperature and the concentration of scaling and corrosive ion. Polarization curves indicated that 4-HTSA was anodic inhibitor.

  9. Cost-Benefit of Improving the Efficiency of Room Air Conditioners (Inverter and Fixed Speed) in India

    SciTech Connect

    Shah, Nihar; Abhyankar, Nikit; Park, Won Young; Phadke, Amol; Diddi, Saurabh; Ahuja, Deepanshu; Mukherjee, P. K.; Walia, Archana

    2016-06-30

    Improving efficiency of air conditioners (ACs) typically involves improving the efficiency of various components such as compressors, heat exchangers, expansion valves, refrigerant and fans. We estimate the incremental cost of improving the efficiency of room ACs based on the cost of improving the efficiency of its key components. Further, we estimate the retail price increase required to cover the cost of efficiency improvement, compare it with electricity bill savings, and calculate the payback period for consumers to recover the additional price of a more efficient AC. We assess several efficiency levels, two of which are summarized below in the report. The finding that significant efficiency improvement is cost effective from a consumer perspective is robust over a wide range of assumptions. If we assume a 50% higher incremental price compared to our baseline estimate, the payback period for the efficiency level of 3.5 ISEER is 1.1 years. Given the findings of this study, establishing more stringent minimum efficiency performance criteria (one star level) should be evaluated rigorously considering significant benefits to consumers, energy security and environment.

  10. 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.

  11. Resources and Fact Sheets on Servicing Motor Vehicle Air Conditioners (Summary Page)

    EPA Pesticide Factsheets

    Page provides links to resources that can assist motor vehicle air-conditioning system technicians in understanding system servicing requirements and best practices, and learn about alternative refrigerants.

  12. 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...

  13. Solar-Powered, Liquid-Desiccant Air Conditioner for Low-Electricity Humidity Control

    DTIC Science & Technology

    2012-11-01

    42 6.1.1 ASHRAE Comfort Zone...Laboratory AHU air-handling unit AILR AIL Research ASHRAE American Society of Heating, Refrigerating, and Air- Conditioning Engineers Btu...psychrometric comfort zone • Chiller power • Reheat run-time • ə% of hours outside ASHRAE summer comfort zone • Reduce chiller/reheat run-time

  14. 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...

  15. Solar Powered Liquid Desiccant Air Conditioner for Low-Electricity Humidity Control

    DTIC Science & Technology

    2012-07-01

    thermal comfort conditions. Liquid-desiccants are solutions that are hygroscopic but are easily able to be pumped and applied within heating, ventilating, and air conditioning (HVAC) equipment as necessary.

  16. 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.

  17. 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...

  18. 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.

  19. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... total heating output of a central air-conditioning heat pump during its normal annual usage period for... heat pump (or its produced heating effect, depending on the mode of operation) to its net work input, when both the cooling (or heating) effect and the net work input are expressed in identical units...

  20. 10 CFR 431.92 - Definitions concerning commercial air conditioners and heat pumps.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... heat pumps. 431.92 Section 431.92 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY EFFICIENCY... that affect energy consumption, energy efficiency, water consumption, or water efficiency. Coefficient... humidity control of the supplied air, and reheating function. Energy Efficiency Ratio, or EER means...

  1. High-efficiency gas heat pump air-conditioner equipped with absorption refrigerator

    NASA Astrophysics Data System (ADS)

    Kawakami, Ryuichiro; Imai, Kazuya; Nakajima, Hidekazu; Okamoto, Hiroaki; Hihara, Eiji

    To improve rated efficiency and partial load efficiency of gas engine heat pump (GHP), we are developing a new type air-cooled absorption refrigerator which is driven by the engine waste hot water. To shape the compact absorption refrigerator body that was able to be built into the space of a GHP outdoor-unit, an air-cooled sub-cooled adiabatic absorber and flowing liquid film plate type generator were newly developed. Maximum cooling capacity was increased about 20%, rated load COP was increased 40%, and partial load COP was increased 46% or less, as a result of the combination examination of a prototype 8.0kW absorption refrigerator and a 56kW GHP at a laboratory.

  2. 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

  3. High-efficiency gas heat pump air-conditioner equipped with absorption refrigerator

    NASA Astrophysics Data System (ADS)

    Imai, Yosuke; Ohashi, Toshinori; Okamoto, Hiroaki; Hihara, Eiji; Kawakami, Ryuichiro

    On conventional gas heat pump(GHP), waste heat from gas engine that uses as driving source is emitted into outside. So from the standpoint of efficient use of waste heat, it is assumed that waste heat from gas engine is used as driving source of absorption chiller, and high temperature condensate refrigerant in GHP is subcooled to middle temperature by cold source from absorption cycle, and as a result, GHP makes more efficiency. However, in equipping GHP with absorption cycle, downsizing and high-efficiency of absorption cycle is required. In this study, air-cooled subcooled adiabatic absorber is focused and physical phenomenon in it is analyzed, and finally one perception of the optimized designing is shown.

  4. 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

  5. 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.

  6. 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.

  7. 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)).

  8. 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.

  9. Cost benefit analysis and energy savings of using compression and absorption chillers for air conditioners in hot and humid climates

    NASA Astrophysics Data System (ADS)

    Shekarchian, M.; Moghavvemi, M.; Motasemi, F.; Mahlia, T. M. I.

    2012-06-01

    The electricity consumption growth has increased steadily in the recent decade which is a great concern for the environment. Increasing the number of high-rise air-conditioned buildings and the rapid use of electrical appliances in residential and commercial sectors are two important factors for high electricity consumption. This paper investigates the annual energy required for cooling per unit area and the total energy cost per unit area for each type of air conditioning systems in hot and humid climates. The effects of changing the coefficient of performance (COP) of absorption chillers on cost saving was also investigated in this study. The results showed that using absorption chillers for cooling will increase the amount of energy consumption per unit area; however the energy cost per unit area will decrease. In addition this research indicates that for each 0.1 increment in COP of absorption chillers, there is about 500 USD/m2 saved cost.

  10. Physiological Signal Conditioner

    NASA Technical Reports Server (NTRS)

    Friedericks, C.

    1999-01-01

    Sensors 2000! is developing a Physiological Signal Conditioner (PSC) for monitoring of astronauts in the ISS Human Research Facility. The PSC is battery powered and worn by the crew. The Engineering Development Unit (PSC EDU) and the form-and-fit PSC Tooling Model will be displayed along with associated graphics and text explanations. Results of a recent advanced PSC-2 feasibility study will be presented. The presentation will stimulate discussion of the functional capabilities of a wireless, crew worn Physiological Signal Conditioner. Application of advanced technology to meet the conflicting demands of size, power, and functional capability will be of interest.

  11. Portable Body Temperature Conditioner

    DTIC Science & Technology

    2013-10-18

    TITLE: Portable Body Temperature Conditioner PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0792 Portable Body Temperature ...also have decreased thermoregulation due to blood loss. Normal core body temperature is defined as 37oC and core body temperature below 35oC and above

  12. 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.

  13. 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.

  14. 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.

  15. Attenuator And Conditioner

    DOEpatents

    Anderson, Gene R.; Armendariz, Marcelino G.; Carson, Richard F.; Bryan, Robert P.; Duckett, III, Edwin B.; Kemme, Shanalyn Adair; McCormick, Frederick B.; Peterson, David W.

    2006-04-04

    An apparatus and method of attenuating and/or conditioning optical energy for an optical transmitter, receiver or transceiver module is disclosed. An apparatus for attenuating the optical output of an optoelectronic connector including: a mounting surface; an array of optoelectronic devices having at least a first end; an array of optical elements having at least a first end; the first end of the array of optical elements optically aligned with the first end of the array of optoelectronic devices; an optical path extending from the first end of the array of optoelectronic devices and ending at a second end of the array of optical elements; and an attenuator in the optical path for attenuating the optical energy emitted from the array of optoelectronic devices. Alternatively, a conditioner may be adapted in the optical path for conditioning the optical energy emitted from the array of optoelectronic devices.

  16. 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....

  17. 46 CFR 56.15-5 - Fluid-conditioner fittings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... allowable working pressure does not exceed one-fourth of the burst pressure or produce a primary stress... of the burst pressure or produce a primary stress greater than one-fifth of the ultimate tensile... brazed boiler steam air heaters are not considered fluid conditioner fittings and must meet...

  18. 46 CFR 56.15-5 - Fluid-conditioner fittings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... allowable working pressure does not exceed one-fourth of the burst pressure or produce a primary stress... of the burst pressure or produce a primary stress greater than one-fifth of the ultimate tensile... brazed boiler steam air heaters are not considered fluid conditioner fittings and must meet...

  19. 46 CFR 56.15-5 - Fluid-conditioner fittings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... allowable working pressure does not exceed one-fourth of the burst pressure or produce a primary stress... of the burst pressure or produce a primary stress greater than one-fifth of the ultimate tensile... brazed boiler steam air heaters are not considered fluid conditioner fittings and must meet...

  20. 46 CFR 56.15-5 - Fluid-conditioner fittings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... allowable working pressure does not exceed one-fourth of the burst pressure or produce a primary stress... of the burst pressure or produce a primary stress greater than one-fifth of the ultimate tensile... brazed boiler steam air heaters are not considered fluid conditioner fittings and must meet...

  1. 46 CFR 56.15-5 - Fluid-conditioner fittings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... allowable working pressure does not exceed one-fourth of the burst pressure or produce a primary stress... of the burst pressure or produce a primary stress greater than one-fifth of the ultimate tensile... brazed boiler steam air heaters are not considered fluid conditioner fittings and must meet...

  2. 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

    ... entering and leaving the indoor coil. If needed, use an air sampling device to divert air to a sensor(s... device may also divert air to a remotely located sensor(s) that measures dry bulb temperature. The air sampling device and the remotely located temperature sensor(s) may be used to determine the entering...

  3. 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.

  4. 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

    ... testing with the following installed: (1) the most restrictive filter(s); (2) supplementary heating coils... ducted unit without having an indoor air filter installed is permissible as long as the minimum external... on region IV.) For heat pumps that use a time-adaptive defrost control system (see Definition...

  5. 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

    ... for testing. Conduct testing with the following installed: (1) the most restrictive filter(s); (2... restriction. c. Testing a ducted unit without having an indoor air filter installed is permissible as long as... of section 4.2 for information on region IV.) For heat pumps that use a time-adaptive defrost...

  6. 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, 2011 CFR

    2011-01-01

    ... testing with the following installed: (1) the most restrictive filter(s); (2) supplementary heating coils... ducted unit without having an indoor air filter installed is permissible as long as the minimum external... on region IV.) For heat pumps that use a time-adaptive defrost control system (see Definition...

  7. 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

    ... testing with the following installed: (1) the most restrictive filter(s); (2) supplementary heating coils... ducted unit without having an indoor air filter installed is permissible as long as the minimum external... on region IV.) For heat pumps that use a time-adaptive defrost control system (see Definition...

  8. RVACS/RACS (reactor vessel auxiliary cooling system/reactor air cooling system) shutdown heat removal in a modular sized LMR (liquid metal reactor)

    SciTech Connect

    Dunn, F.E.; Wigeland, R.A.; Lo, R.K.

    1988-01-01

    Shutdown heat removal by a RVACS for an unprotected loss of flow case in a modular sized LMR has been analyzed with the SASSYS-1 LMR systems analysis code. For this case it was assumed that all power was lost to the primary and intermediate sodium pumps, and feedwater flow to the steam generators was lost. The control rods failed to scram, but reactivity feedback shut down the power to decay heat levels. The only heat removal was by sodium natural circulation from the core to the vessel wall and by cooling of the vessel wall by radiation and air natural circulation in the Reactor Air Cooling System. The case was run until the system temperatures peaked when the decay heat power level dropped below the heat removal rate.

  9. Rac[e] to the pole

    PubMed Central

    Collins, Caitlin; Tzima, Ellie

    2014-01-01

    Mechanical forces influence many biological processes via activation of signaling molecules, including the family of Rho GTPases. Within the endothelium, the mechanical force of fluid shear stress regulates the spatiotemporal activation of Rho GTPases, including Rac1. Shear stress-induced Rac1 activation is required for numerous essential biological processes, including changes in permeability, alignment of the actin cytoskeleton, redox signaling, and changes in gene expression. Thus, identifying mechanisms of Rac1 activation and the spatial cues that direct proper localization of the GTPase is essential in order to gain a comprehensive understanding the role of Rac1 in shear stress responses. This commentary will highlight our current understanding of how Rac1 activity is regulated in response to shear stress, as well as the downstream consequences of Rac1 activation. PMID:25202973

  10. 75 FR 27227 - Energy Conservation Program: Energy Conservation Standards for Residential Central Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-14

    ... 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 framework... preliminary technical support document for central air conditioners and heat pumps. The comment period...

  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. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. Cdc42, Rac1, and Rac2 Display Distinct Patterns of Activation during PhagocytosisV⃞

    PubMed Central

    Hoppe, Adam D.; Swanson, Joel A.

    2004-01-01

    The small G proteins Cdc42, Rac1, and Rac2 regulate the rearrangements of actin and membrane necessary for Fcγ receptor-mediated phagocytosis by macrophages. Activated, GTP-bound Cdc42, Rac1, and Rac2 bind to the p21-binding domain (PBD) of PAK1, and this interaction provided a basis for microscopic methods to localize activation of these G proteins inside cells. Fluorescence resonance energy transfer-based stoichiometry of fluorescent chimeras of actin, PBD, Cdc42, Rac1, and Rac2 was used to quantify G protein activation relative to actin movements during phagocytosis of IgG-opsonized erythrocytes. The activation dynamics of endogenous G proteins, localized using yellow fluorescent protein-labeled PBD, was restricted to phagocytic cups, with a prominent spike of activation over an actin-poor region at the base of the cup. Refinements of fluorescence resonance energy transfer stoichiometry allowed calculation of the fractions of activated GTPases in forming phagosomes. Cdc42 activation was restricted to the leading margin of the cell, whereas Rac1 was active throughout the phagocytic cup. During phagosome closure, activation of Rac1 and Rac2 increased uniformly and transiently in the actin-poor region of phagosomal membrane. These distinct roles for Cdc42, Rac1, and Rac2 in the component activities of phagocytosis indicate mechanisms by which their differential regulation coordinates rearrangements of actin and membranes. PMID:15169870

  19. The RAC program: are you ready?

    PubMed

    Machisko, Francine; Snecinski, Jane

    2008-01-01

    Providers should take these steps to prepare for an RAC review: Educate physicians and all direct care staff on the basic infrastructure for the provision of care as well as the RAC initiative itself. Create compliance assessment tools and programs and conduct internal assessment. Develop and implement a corrective action plan based on findings from internal reviews.

  20. 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.

  1. 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.

  2. Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling.

    PubMed

    Walmsley, Marita J; Ooi, Steen K T; Reynolds, Lucinda F; Smith, Susan Harless; Ruf, Sandra; Mathiot, Anne; Vanes, Lesley; Williams, David A; Cancro, Michael P; Tybulewicz, Victor L J

    2003-10-17

    The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.

  3. Redox regulation of Rac1 by thiol oxidation

    PubMed Central

    Hobbs, G. Aaron; Mitchell, Lauren E.; Arrington, Megan E.; Gunawardena, Harsha P.; DeCristo, Molly J.; Loeser, Richard F.; Chen, Xian; Cox, Adrienne D.; Campbell, Sharon L.

    2016-01-01

    The Rac1 GTPase is an essential and ubiquitous protein that signals through numerous pathways to control critical cellular processes, including cell growth, morphology, and motility. Rac1 deletion is embryonic lethal, and its dysregulation or mutation can promote cancer, arthritis, cardiovascular disease, and neurological disorders. Rac1 activity is highly regulated by modulatory proteins and posttranslational modifications. Whereas much attention has been devoted to guanine nucleotide exchange factors that act on Rac1 to promote GTP loading and Rac1 activation, cellular oxidants may also regulate Rac1 activation by promoting guanine nucleotide exchange. Herein, we show that Rac1 contains a redox-sensitive cysteine (Cys18) that can be selectively oxidized at physiological pH because of its lowered pKa. Consistent with these observations, we show that Rac1 is glutathiolated in primary chondrocytes. Oxidation of Cys18 by glutathione greatly perturbs Rac1 guanine nucleotide binding and promotes nucleotide exchange. As aspartate substitutions have been previously used to mimic cysteine oxidation, we characterized the biochemical properties of Rac1C18D. We also evaluated Rac1C18S as a redox-insensitive variant and found that it retains structural and biochemical properties similar to those of Rac1WT but is resistant to thiol oxidation. In addition, Rac1C18D, but not Rac1C18S, shows greatly enhanced nucleotide exchange, similar to that observed for Rac1 oxidation by glutathione. We employed Rac1C18D in cell-based studies to assess whether this fast-cycling variant, which mimics Rac1 oxidation by glutathione, affects Rac1 activity and function. Expression of Rac1C18D in Swiss 3T3 cells showed greatly enhanced GTP-bound Rac1 relative to Rac1WT and the redox-insensitive Rac1C18S variant. Moreover, expression of Rac1C18D in HEK-293T cells greatly promoted lamellipodia formation. Our results suggest that Rac1 oxidation at Cys18 is a novel posttranslational modification that

  4. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... signal conditioner. (a) Identification. A physiological signal conditioner is a device such as an integrator or differentiator used to modify physiological signals for recording and processing. (b... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Physiological signal conditioner. 882.1845...

  5. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... signal conditioner. (a) Identification. A physiological signal conditioner is a device such as an integrator or differentiator used to modify physiological signals for recording and processing. (b... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Physiological signal conditioner. 882.1845...

  6. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... signal conditioner. (a) Identification. A physiological signal conditioner is a device such as an integrator or differentiator used to modify physiological signals for recording and processing. (b... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Physiological signal conditioner. 882.1845...

  7. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... signal conditioner. (a) Identification. A physiological signal conditioner is a device such as an integrator or differentiator used to modify physiological signals for recording and processing. (b... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Physiological signal conditioner. 882.1845...

  8. 21 CFR 882.1845 - Physiological signal conditioner.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... signal conditioner. (a) Identification. A physiological signal conditioner is a device such as an integrator or differentiator used to modify physiological signals for recording and processing. (b... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Physiological signal conditioner. 882.1845...

  9. 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

  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. 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.

  12. 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

  13. 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.

  14. 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...

  15. 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... 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 870.2050 - 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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... Transducer signal amplifier and conditioner. (a) Identification. A transducer signal amplifier...

  3. 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...

  4. Antimicrobial and antifungal effects of tissue conditioners containing a photocatalyst.

    PubMed

    Uchimaru, Masayuki; Sakai, Takako; Moroi, Ryoji; Shiota, Susumu; Shibata, Yukie; Deguchi, Mikito; Sakai, Hidetaka; Yamashita, Yoshihisa; Terada, Yoshihiro

    2011-01-01

    This study examined the antimicrobial/antifungal ability of a tissue conditioner containing a photocatalyst for Escherichia coli, Streptococcus mutans, Staphylococcus aureus and Candida albicans. The photocatalyst was mixed with tissue conditioners powders at concentrations of 0, 10, 15, and 20 wt%. Tissue conditioners powders containing a photocatalyst were mixed with liquid to make test specimens. Test specimens inoculated by each microorganism were irradiated by ultraviolet light for 0-, 2- and 4 hours. The antimicrobial/antifungal effects were evaluated by the CFU technique. The CFU values of each microorganism for tissue conditioners containing a photocatalyst showed significant decrease following UV-irradiation. The improvement in antimicrobial/antifungal effects was concomitant with the increase of the mixing ratio and the irradiation time. Therefore, the results indicated that tissue conditioners containing a photocatalyst might have photocatalytic ability.

  5. Rac1 is deactivated at integrin activation sites through an IQGAP1–filamin-A–RacGAP1 pathway

    PubMed Central

    Jacquemet, Guillaume; Morgan, Mark R.; Byron, Adam; Humphries, Jonathan D.; Choi, Colin K.; Chen, Christopher S.; Caswell, Patrick T.; Humphries, Martin J.

    2013-01-01

    Summary Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are required for directional migration. Although the pathways that control integrin-mediated Rac1 activation are reasonably well defined, the mechanisms that are responsible for switching off activity are poorly understood. Here, proteomic analysis of activated integrin-associated complexes suggests filamin-A and IQ-motif-containing GTPase-activating protein 1 (IQGAP1) as candidates that link β1 integrin to Rac1. siRNA-mediated knockdown of either filamin-A or IQGAP1 induced high, dysregulated Rac1 activity during cell spreading on fibronectin. Using immunoprecipitation and immunocytochemistry, filamin-A and IQGAP1 were shown to be part of a complex that is recruited to active β1 integrin. Mass spectrometric analysis of individual filamin-A, IQGAP1 and Rac1 pull-downs and biochemical analysis, identified RacGAP1 as a novel IQGAP1 binding partner. Further immunoprecipitation and immunocytochemistry analyses demonstrated that RacGAP1 is recruited to IQGAP1 and active β1 integrin, and that suppression of RacGAP1 expression triggered elevated Rac1 activity during spreading on fibronectin. Consistent with these findings, reduced expression of filamin-A, IQGAP1 or RacGAP1 triggered unconstrained membrane protrusion and disrupted directional cell migration on fibrillar extracellular matrices. These findings suggest a model whereby integrin engagement, followed by filamin-A, IQGAP1 and RacGAP1 recruitment, deactivates Rac1 to constrain its activity spatially and thereby coordinate directional cell migration. PMID:23843620

  6. 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.

  7. Characterization of Novel Molecular Mechanisms Favoring Rac1 Membrane Translocation.

    PubMed

    Castro-Castro, Antonio; Muriel, Olivia; Del Pozo, Miguel A; Bustelo, Xosé R

    2016-01-01

    The Rac1 GTPase plays key roles in cytoskeletal organization, cell motility and a variety of physiological and disease-linked responses. Wild type Rac1 signaling entails dissociation of the GTPase from cytosolic Rac1-Rho GDP dissociation inhibitor (GDI) complexes, translocation to membranes, activation by exchange factors, effector binding, and activation of downstream signaling cascades. Out of those steps, membrane translocation is the less understood. Using transfections of a expression cDNA library in cells expressing a Rac1 bioreporter, we previously identified a cytoskeletal feedback loop nucleated by the F-actin binding protein coronin 1A (Coro1A) that promotes Rac1 translocation to the plasma membrane by facilitating the Pak-dependent dissociation of Rac1-Rho GDI complexes. This screening identified other potential regulators of this process, including WDR26, basigin, and TMEM8A. Here, we show that WDR26 promotes Rac1 translocation following a Coro1A-like and Coro1A-dependent mechanism. By contrast, basigin and TMEM8A stabilize Rac1 at the plasma membrane by inhibiting the internalization of caveolin-rich membrane subdomains. This latter pathway is F-actin-dependent but Coro1A-, Pak- and Rho GDI-independent.

  8. Rac1 modulates cardiomyocyte adhesion during mouse embryonic development.

    PubMed

    Abu-Issa, Radwan

    2015-01-24

    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.

  9. Characterization of Novel Molecular Mechanisms Favoring Rac1 Membrane Translocation

    PubMed Central

    Castro-Castro, Antonio; Muriel, Olivia; del Pozo, Miguel A.

    2016-01-01

    The Rac1 GTPase plays key roles in cytoskeletal organization, cell motility and a variety of physiological and disease-linked responses. Wild type Rac1 signaling entails dissociation of the GTPase from cytosolic Rac1-Rho GDP dissociation inhibitor (GDI) complexes, translocation to membranes, activation by exchange factors, effector binding, and activation of downstream signaling cascades. Out of those steps, membrane translocation is the less understood. Using transfections of a expression cDNA library in cells expressing a Rac1 bioreporter, we previously identified a cytoskeletal feedback loop nucleated by the F-actin binding protein coronin 1A (Coro1A) that promotes Rac1 translocation to the plasma membrane by facilitating the Pak-dependent dissociation of Rac1-Rho GDI complexes. This screening identified other potential regulators of this process, including WDR26, basigin, and TMEM8A. Here, we show that WDR26 promotes Rac1 translocation following a Coro1A-like and Coro1A-dependent mechanism. By contrast, basigin and TMEM8A stabilize Rac1 at the plasma membrane by inhibiting the internalization of caveolin-rich membrane subdomains. This latter pathway is F-actin-dependent but Coro1A-, Pak- and Rho GDI-independent. PMID:27835684

  10. 42 CFR 455.508 - Eligibility requirements for Medicaid RACs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Eligibility requirements for Medicaid RACs. 455.508 Section 455.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Contractors Program § 455.508 Eligibility requirements for Medicaid RACs. An entity that wishes to perform...

  11. 42 CFR 455.508 - Eligibility requirements for Medicaid RACs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Eligibility requirements for Medicaid RACs. 455.508 Section 455.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Contractors Program § 455.508 Eligibility requirements for Medicaid RACs. An entity that wishes to perform...

  12. 42 CFR 455.508 - Eligibility requirements for Medicaid RACs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Eligibility requirements for Medicaid RACs. 455.508 Section 455.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Contractors Program § 455.508 Eligibility requirements for Medicaid RACs. An entity that wishes to perform...

  13. 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.

  14. 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

  15. An outbreak of Serratia marcescens infection in a special-care baby unit of a community hospital in United Arab Emirates: the importance of the air conditioner duct as a nosocomial reservoir.

    PubMed

    Uduman, S A; Farrukh, A S; Nath, K N R; Zuhair, M Y H; Ifrah, A; Khawla, A D; Sunita, P

    2002-11-01

    We report an outbreak of Serratia marcescens infection in a special-care baby unit (SCBU) of a university-affiliated community hospital in the United Arab Emirates. The outbreak involved 36 infants and lasted for 20 weeks. Seven of the colonized infants developed invasive illnesses in the form of bacteraemia (four cases), bacteraemic meningitis (two) and clinical sepsis (one). Three other term infants had purulent conjunctivitis. There were five deaths with an overall mortality of 14%. S. marcescens was cultured from airflow samples from the air conditioning (AC) which was the reservoir of infection in this outbreak. Elimination of the nosocomial source and outbreak containment were eventually achieved by specialized robotic cleaning of the entire AC duct system of the SCBU. Strict adherence to the infection control policies was reinforced to prevent transmission of cross-infection.

  16. Project Themis: PIV Measurement of Elbow Flow through a Flow Conditioner

    DTIC Science & Technology

    2011-12-01

    Charts 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Project Themis: PIV Measurement of Elbow Flow through a Flow...Project Themis: PIV Measurement of Elbow Flow through a Flow Conditioner Benjamin Miller AFRL/RZSE (Jackson and Tull) Air Force Research...Max power = 20mJ @ 1kHz • Phantom V210 • 2,000 frames per second 45 CFM hose 90 ̊ long curve elbow VORTAB L/D = 30 • VORTAB placed one

  17. 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.

  18. 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.

  19. Power Conditioner with Variable Switching Control for Thermoelectric Generator Systems

    NASA Astrophysics Data System (ADS)

    Nagayoshi, Hiroshi; Maiwa, Hiroshi; Kajikawa, Takenobu

    2013-07-01

    A thermoelectric (TE) power conditioner maintaining high efficiency over a wide input power range has been developed. Variable switching frequency operation is shown to give an improvement in efficient operating range. The input range showing more than 90% conversion efficiency is expanded to more than 25% by introducing a low-power controller circuit and variable switching frequency control. The TE power conditioner showed excellent response against a change in thermoelectric generator (TEG) output and load, making it suitable for automotive applications.

  20. 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.

  1. Rac1 Regulates Endometrial Secretory Function to Control Placental Development.

    PubMed

    Davila, Juanmahel; Laws, Mary J; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

    2015-08-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  2. Rac1 Regulates Endometrial Secretory Function to Control Placental Development

    PubMed Central

    Davila, Juanmahel; Laws, Mary J.; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N.; Bagchi, Milan K.; Bagchi, Indrani C.

    2015-01-01

    During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal

  3. 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.

  4. Phosphorylation of Rac1 T108 by Extracellular Signal-Regulated Kinase in Response to Epidermal Growth Factor: a Novel Mechanism To Regulate Rac1 Function

    PubMed Central

    Tong, Junfeng; Li, Laiji; Ballermann, Barbara

    2013-01-01

    Accumulating evidence has implicated Rho GTPases, including Rac1, in many aspects of cancer development. Recent findings suggest that phosphorylation might further contribute to the tight regulation of Rho GTPases. Interestingly, sequence analysis of Rac1 shows that Rac1 T108 within the 106PNTP109 motif is likely an extracellular signal-regulated kinase (ERK) phosphorylation site and that Rac1 also has an ERK docking site, 183KKRKRKCLLL192 (D site), at the C terminus. Indeed, we show here that both transfected and endogenous Rac1 interacts with ERK and that this interaction is mediated by its D site. Green fluorescent protein (GFP)-Rac1 is threonine (T) phosphorylated in response to epidermal growth factor (EGF), and EGF-induced Rac1 threonine phosphorylation is dependent on the activation of ERK. Moreover, mutant Rac1 with the mutation of T108 to alanine (A) is not threonine phosphorylated in response to EGF. In vitro ERK kinase assay further shows that pure active ERK phosphorylates purified Rac1 but not mutant Rac1 T108A. We also show that Rac1 T108 phosphorylation decreases Rac1 activity, partially due to inhibiting its interaction with phospholipase C-γ1 (PLC-γ1). T108 phosphorylation targets Rac1 to the nucleus, which isolates Rac1 from other guanine nucleotide exchange factors (GEFs) and hinders Rac1's role in cell migration. We conclude that Rac1 T108 is phosphorylated by ERK in response to EGF, which plays an important role in regulating Rac1. PMID:24043306

  5. 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

  6. 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

  7. Purification, crystallization and preliminary X-ray crystallographic analysis of a rice Rac/Rop GTPase, OsRac1

    PubMed Central

    Kosami, Ken-ichi; Ohki, Izuru; Hayashi, Kokoro; Tabata, Ryo; Usugi, Sayaka; Kawasaki, Tsutomu; Fujiwara, Toshimichi; Nakagawa, Atsushi; Shimamoto, Ko; Kojima, Chojiro

    2014-01-01

    Small GTPases regulate a large variety of key cellular processes. Plant small Rac/Rop GTPases have recently received broad attention as it is becoming clear that these enzymes regulate various plant cellular processes. OsRac1, a rice Rac/Rop protein, is a key regulator of reactive oxygen species (ROS) production and induces immune responses. Although four structures of plant small GTPases have been reported, all of these were of the inactive form. Here, OsRac1 was purified and co-crystallized with the GTP analogue 5′-guanylyl imidodiphos­phate (GMPPNP). The crystal belonged to space group P212121 and a complete data set was collected to 1.9 Å resolution. PMID:24419631

  8. 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.

  9. 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 ...

  10. 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.

  11. 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.

  12. 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....

  13. 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... and tooth conditioner. (a) Identification. A bracket adhesive resin and tooth conditioner is a device... to a tooth surface. (b) Classification. Class II....

  14. 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... and tooth conditioner. (a) Identification. A bracket adhesive resin and tooth conditioner is a device... to a tooth surface. (b) Classification. Class II....

  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, 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....

  17. 10 CFR 429.15 - Room air conditioners.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... DEPARTMENT OF ENERGY ENERGY CONSERVATION CERTIFICATION, COMPLIANCE, AND ENFORCEMENT FOR CONSUMER PRODUCTS AND... certification report shall include the following public product-specific information: The energy efficiency... consumption or other measure of energy consumption of a basic model for which consumers would favor...

  18. 10 CFR 429.15 - Room air conditioners.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... DEPARTMENT OF ENERGY ENERGY CONSERVATION CERTIFICATION, COMPLIANCE, AND ENFORCEMENT FOR CONSUMER PRODUCTS AND... certification report shall include the following public product-specific information: The energy efficiency... consumption or other measure of energy consumption of a basic model for which consumers would favor...

  19. 10 CFR 429.15 - Room air conditioners.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... DEPARTMENT OF ENERGY ENERGY CONSERVATION CERTIFICATION, COMPLIANCE, AND ENFORCEMENT FOR CONSUMER PRODUCTS AND... certification report shall include the following public product-specific information: The energy efficiency... consumption or other measure of energy consumption of a basic model for which consumers would favor...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. Rac GTPase signaling through the PP5 protein phosphatase

    PubMed Central

    Gentile, Saverio; Darden, Thomas; Erxleben, Christian; Romeo, Charles; Russo, Angela; Martin, Negin; Rossie, Sandra; Armstrong, David L.

    2006-01-01

    We have investigated the Rac-dependent mechanism of KCNH2 channel stimulation by thyroid hormone in a rat pituitary cell line, GH4C1, with the patch-clamp technique. Here we present physiological evidence for the protein serine/threonine phosphatase, PP5, as an effector of Rac GTPase signaling. We also propose and test a specific molecular mechanism for PP5 stimulation by Rac-GTP. Inhibition of PP5 with the microbial toxin, okadaic acid, blocked channel stimulation by thyroid hormone and by Rac, but signaling was restored by expression of a toxin-insensitive mutant of PP5, Y451A, which we engineered. PP5 is unique among protein phosphatases in that it contains an N-terminal regulatory domain with three tetratricopeptide repeats (TPR) that inhibit its activity. Expression of the TPR domain coupled to GFP blocked channel stimulation by the thyroid hormone. We also show that the published structures of the PP5 TPR domain and the TPR domain of p67, the Rac-binding subunit of NADPH oxidase, superimpose over 92 α carbons. Mutation of the PP5 TPR domain at two predicted contact points with Rac-GTP prevents the TPR domain from functioning as a dominant negative and blocks the ability of Y451A to rescue signaling in the presence of okadaic acid. PP5 stimulation by Rac provides a unique molecular mechanism for the antagonism of Rho-dependent signaling through protein kinases in many cellular processes, including metastasis, immune cell chemotaxis, and neuronal development. PMID:16549782

  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. 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

  8. 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.

  9. Adhesive bonding of super-elastic titanium-nickel alloy castings with a phosphate metal conditioner and an acrylic adhesive.

    PubMed

    Matsumura, H; Tanoue, N; Yanagida, H; Atsuta, M; Koike, M; Yoneyama, T

    2003-06-01

    The purpose of the current study was to evaluate the bonding characteristics of super-elastic titanium-nickel (Ti-Ni) alloy castings. Disk specimens were cast from a Ti-Ni alloy (Ti-50.85Ni mol%) using an arc centrifugal casting machine. High-purity titanium and nickel specimens were also prepared as experimental references. The specimens were air-abraded with alumina, and bonded with an adhesive resin (Super-Bond C & B). A metal conditioner containing a phosphate monomer (Cesead II Opaque Primer) was also used for priming the specimens. Post-thermocycling average bond strengths (MPa) of the primed groups were 41.5 for Ti-Ni, 30.4 for Ti and 19.5 for Ni, whereas those of the unprimed groups were 21.6 for Ti, 19.3 for Ti-Ni and 9.3 for Ni. Application of the phosphate conditioner elevated the bond strengths of all alloy/metals (P < 0.05). X-ray fluorescence analysis revealed that nickel was attached to the debonded resin surface of the resin-to-nickel bonded specimen, indicating that corrosion of high-purity nickel occurred at the resin-nickel interface. Durable bonding to super-elastic Ti-Ni alloy castings can be achieved with a combination of a phosphate metal conditioner and a tri-n-butylborane-initiated adhesive resin.

  10. 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.

  11. 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

  12. 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.

  13. Role of Rac GTPases in Chemokine-Stimulated Breast Carcinoma Metastasis

    DTIC Science & Technology

    2009-01-01

    during breast cancer progression. We have shown that Rac1b is induced under stress-related conditions, including hypoxia, ionizing radiation and serum...and ionizing radiation . We found that both hypoxia and application of CoCl2, which mimics hypoxic conditions, significantly induced Rac1b expression...in MCF10ADCIS cells (Figure 1A, B). Ionizing radiation (IR) also strongly induced Rac1b expression (Figure 2). 6 Figure 1: Rac1b is induced

  14. Rac1 is Required for Matrix Metalloproteinase-13 Production by Chondrocytes in Response to Fibronectin Fragments

    PubMed Central

    Long, David L.; Willey, Jeffrey S.; Loeser, Richard F.

    2013-01-01

    Summary Objective Matrix fragments, including fibronectin fragments (Fnf), accumulate during the development of osteoarthritis (OA) stimulating chondrocyte matrix metalloproteinase (MMP) production. The objective of this study was to determine the role of the small GTPase Rac1 in chondrocyte signaling stimulated by Fnf that results in MMP-13 production. Methods Normal human cartilage was from tissue donors and OA cartilage from knee arthroplasty specimens. Rac1 activity was modulated with a chemical inhibitor, siRNA knock-down, constitutively active (CA)-Rac or dominant negative (DN)-Rac adenovirus. Cells were treated with Fnf or without known Rac activators, epidermal growth factor (EGF) or transforming growth factorα (TGFα). Rac1 activity was measured with a colorometric activity ELISA, pulldown assay, and immunostaining with a monoclonal antibody against active Rac. Results Chemical inhibition of Rac1, as well as knockdown by siRNA and expression of DN-Rac blocked Fnf stimulated MMP-13 production while expression of CA-Rac increased MMP-13. Inhibition of Rho-associated kinase had no effect. EGF and TGFα, but not Fnf, increased Rac1 activity and promoted the increase in MMP-13 above that stimulated by Fnf alone. Active Rac was detected by immunostaining in OA cartilage. Conclusion Rac1 is required for Fnf induced signaling that results in increased MMP-13 production. EGF receptor ligands, which activate Rac, can promote this effect. The presence of active Rac in OA cartilage and the ability of Rac to stimulate MMP-13 production suggests that it could play a role in the cartilage matrix destruction seen in OA. PMID:23460186

  15. 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

  16. 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…

  17. 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

    ... Recovery Audit Contractors (RACs) Contingency Fee Update AGENCY: Centers for Medicare & Medicaid Services... Recovery Audit Contractors (RAC) by State Medicaid programs as authorized by section 1902(a)(42)(B) of the... that ties the Medicaid RAC contingency fee to the Medicare Recovery Audit Program with an...

  18. 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.

  19. 42 CFR 455.510 - Payments to RACs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455... and recovery of Medicaid provider overpayments. (1) The contingency fees paid to Medicaid RACs must...

  20. 42 CFR 455.516 - Exceptions from Medicaid RAC programs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Exceptions from Medicaid RAC programs. 455.516 Section 455.516 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery...

  1. 42 CFR 455.512 - Medicaid RAC provider appeals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Medicaid RAC provider appeals. 455.512 Section 455.512 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit...

  2. 42 CFR 455.512 - Medicaid RAC provider appeals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Medicaid RAC provider appeals. 455.512 Section 455.512 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit...

  3. 42 CFR 455.516 - Exceptions from Medicaid RAC programs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Exceptions from Medicaid RAC programs. 455.516 Section 455.516 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery...

  4. 42 CFR 455.512 - Medicaid RAC provider appeals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Medicaid RAC provider appeals. 455.512 Section 455.512 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit...

  5. 42 CFR 455.516 - Exceptions from Medicaid RAC programs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Exceptions from Medicaid RAC programs. 455.516 Section 455.516 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery...

  6. 42 CFR 455.510 - Payments to RACs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455... and recovery of Medicaid provider overpayments. (1) The contingency fees paid to Medicaid RACs must...

  7. 42 CFR 455.516 - Exceptions from Medicaid RAC programs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Exceptions from Medicaid RAC programs. 455.516 Section 455.516 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery...

  8. 42 CFR 455.512 - Medicaid RAC provider appeals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Medicaid RAC provider appeals. 455.512 Section 455.512 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit...

  9. 42 CFR 455.510 - Payments to RACs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455... and recovery of Medicaid provider overpayments. (1) The contingency fees paid to Medicaid RACs must...

  10. 42 CFR 455.510 - Payments to RACs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455... and recovery of Medicaid provider overpayments. (1) The contingency fees paid to Medicaid RACs must...

  11. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

    PubMed Central

    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

    2012-01-01

    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 (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S 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. PMID:22842228

  12. 77 FR 54608 - Southeast Oregon Resource Advisory Council (RAC); Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-05

    ... ecosystems of burned areas within the Southeast Oregon RAC jurisdictional boundary; updates on travel management planning in the Lakeview Resource Area, the Chiloquin Ranger District, and the Malheur National...; and a partial-day field tour to the Miller Homestead wildfire area near Frenchglen, Oregon....

  13. 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.

  14. 76 FR 39434 - Notice of Utah's Resource Advisory Council (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-06

    ... August 4, the RAC will meet at the Park-N-Ride, Exit 405 (South Weber Drive), from Highway 89 (South Ogden). The South Weber Park & Ride is the first right crossing Highway 89 on the north side of South... opportunities of ``time control'' grazing. A presentation on data collected from DLL from Open Range...

  15. 78 FR 37220 - Proposed Information Collection Request; Comment Request; EPA-ICR No. 1774.05-Mobile Air...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... AGENCY Proposed Information Collection Request; Comment Request; EPA-ICR No. 1774.05--Mobile Air Conditioner Retrofitting Program AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The... Conditioner Retrofitting Program'' (EPA ICR No. 1774.05, OMB Control No. 2060-0450) to the Office...

  16. Dynamic Control of Excitatory Synapse Development by a Rac1 GEF/GAP Regulatory Complex

    PubMed Central

    Um, Kyongmi; Niu, Sanyong; Duman, Joseph G.; Cheng, Jinxuan; Tu, Yen-Kuei; Schwechter, Brandon; Liu, Feng; Hiles, Laura; Narayanan, Anjana; Ash, Ryan T.; Mulherkar, Shalaka; Alpadi, Kannan; Smirnakis, Stelios M.; Tolias, Kimberley F.

    2014-01-01

    SUMMARY The small GTPase Rac1 orchestrates actin-dependent remodeling essential for numerous cellular processes including synapse development. While precise spatiotemporal regulation of Rac1 is necessary for its function, little is known about the mechanisms that enable Rac1 activators (GEFs) and inhibitors (GAPs) to act in concert to regulate Rac1 signaling. Here we identify a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control excitatory synapse development. Disruption of Bcr function within this complex increases Rac1 activity and dendritic spine remodeling, resulting in excessive synaptic growth that is rescued by Tiam1 inhibition. Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis. Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bcr prevents Rac1-mediated receptor internalization, promoting spine growth over retraction. The finding that a Rac-specific GEF/GAP complex is required to maintain optimal levels of Rac1 signaling provides an important insight into the regulation of small GTPases. PMID:24960694

  17. Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.

    PubMed

    Jiang, Lizhu; Mao, Rongrong; Zhou, Qixin; Yang, Yuexiong; Cao, Jun; Ding, Yuqiang; Yang, Yuan; Zhang, Xia; Li, Lingjiang; Xu, Lin

    2016-03-01

    Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus.

  18. 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

  19. Constitutive phosphorylation of a Rac GAP MgcRacGAP is implicated in v-Src-induced transformation of NIH3T3 cells.

    PubMed

    Doki, Noriko; Kawashima, Toshiyuki; Nomura, Yasushi; Tsuchiya, Akiho; Oneyama, Chitose; Akagi, Tsuyoshi; Nojima, Yoshihisa; Kitamura, Toshio

    2009-09-01

    MgcRacGAP plays critical roles in cell division through regulating Rho family small GTPases. As we previously reported, phosphorylation of MgcRacGAP on serine 387 (S387) is induced by Aurora B kinase at the midbody during cytokinesis, which is a critical step of cytokinesis. Phosphorylation of S387-MgcRacGAP converts it from RacGAP to RhoGAP, leading to completion of cytokinesis. Here we show that MgcRacGAP is prominently phosphorylated on S387 even in the interphase of v-Src-transformed NIH3T3 cells in the cytoplasm, but not in the interphase of parental NIH3T3 or H-RasV12-transformed NIH3T3 cells. Interestingly, levels of phosphorylation on S387 (pS387) correlated with soft agar colony-forming abilities of v-Src-transformed NIH3T3 cells. Expression of a phosphorylation-mimic mutant MgcRacGAP-S387D enhanced colony formation of v-Src-transformed NIH3T3 cells. Surprisingly, a Rac1 inhibitor but not kinase inhibitors including Aurora B kinase inhibitor specifically inhibited phosphorylation of S387-MgcRacGAP in v-Src-transformed NIH3T3 cells, suggesting the v-Src-induced pathological positive feedback mechanisms towards Rac1 activation using pS387-MgcRacGAP. These results indicated the difference in the mechanisms between v-Src- and H-RasV12-induced transformation, and should shed some light on pathological roles of disordered phosphorylation of MgcRacGAP at S387 in v-Src-induced cell transformation.

  20. 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

  1. An air quality sensing system for cool air storage

    NASA Astrophysics Data System (ADS)

    Ngoy, T. J.; Joubert, T.-H.

    2016-02-01

    Cooling and ventilation systems play an important role in human occupied spaces. However, cooling using reversible air conditioners systems pollutes the environment and consumes a significant amount of energy. With global warming that experiences our environment, the large consumption of electrical energy and the operating instructions for reversible air conditioners, there is a need to find alternatives to those cooling systems. Hence this research project aims to investigate an air storage system, a microsystem reversible ventilation system using natural atmospheric air (renewable energy) for cooling at low consumption of energy. For the variation of the temperature range of comfort due to thermal heat produces by occupants, equipment and environment, an optimal transient automatic regulation of air flow as to be design in order to maintain the temperature of comfort in occupied spaces during peak hours.

  2. Performance Evaluation Method of Chemical Mechanical Polishing Pad Conditioner Using Digital Image Correlation Processing

    NASA Astrophysics Data System (ADS)

    Uneda, Michio; Omote, Tatsunori; Ishikawa, Ken-ichi; Ichikawa, Koichiro; Doi, Toshiro; Kurokawa, Syuhei; Ohnishi, Osamu

    2012-05-01

    In chemical mechanical polishing (CMP), conditioning is generally used for the regeneration of the pad surface texture. Currently, the performance evaluation of conditioners depends on the user's experience so that it is important to develop a novel quantitative evaluation method for conditioner performance. In this paper, we propose a novel evaluation method for conditioner performance using digital image correlation (DIC) processing. The proposed method can measure the in-plane micro-deformation distribution of the pad surface texture by conditioning. It is found that a pad surface deforms over 40 µm with conditioning and that the in-plane deformation value increases with a decrease in the mesh size of conditioner grains.

  3. 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.

  4. RAC1P29S is a spontaneously activating cancer-associated GTPase

    PubMed Central

    Davis, Matthew J.; Ha, Byung Hak; Holman, Edna C.; Halaban, Ruth; Schlessinger, Joseph; Boggon, Titus J.

    2013-01-01

    RAC1 is a small, Ras-related GTPase that was recently reported to harbor a recurrent UV-induced signature mutation in melanoma, resulting in substitution of P29 to serine (RAC1P29S), ranking this the third most frequently occurring gain-of-function mutation in melanoma. Although the Ras family GTPases are mutated in about 30% of all cancers, mutations in the Rho family GTPases have rarely been observed. In this study, we demonstrate that unlike oncogenic Ras proteins, which are primarily activated by mutations that eliminate GTPase activity, the activated melanoma RAC1P29S protein maintains intrinsic GTP hydrolysis and is spontaneously activated by substantially increased inherent GDP/GTP nucleotide exchange. Determination and comparison of crystal structures for activated RAC1 GTPases suggest that RAC1F28L—a known spontaneously activated RAC1 mutant—and RAC1P29S are self-activated in distinct fashions. Moreover, the mechanism of RAC1P29S and RAC1F28L activation differs from the common oncogenic mutations found in Ras-like GTPases that abrogate GTP hydrolysis. The melanoma RAC1P29S gain-of-function point mutation therefore represents a previously undescribed class of cancer-related GTPase activity. PMID:23284172

  5. 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

  6. 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

  7. Rac-GTPases Regulate Microtubule Stability and Axon Growth of Cortical GABAergic Interneurons.

    PubMed

    Tivodar, Simona; Kalemaki, Katerina; Kounoupa, Zouzana; Vidaki, Marina; Theodorakis, Kostas; Denaxa, Myrto; Kessaris, Nicoletta; de Curtis, Ivan; Pachnis, Vassilis; Karagogeos, Domna

    2015-09-01

    Cortical interneurons are characterized by extraordinary functional and morphological diversity. Although tremendous progress has been made in uncovering molecular and cellular mechanisms implicated in interneuron generation and function, several questions still remain open. Rho-GTPases have been implicated as intracellular mediators of numerous developmental processes such as cytoskeleton organization, vesicle trafficking, transcription, cell cycle progression, and apoptosis. Specifically in cortical interneurons, we have recently shown a cell-autonomous and stage-specific requirement for Rac1 activity within proliferating interneuron precursors. Conditional ablation of Rac1 in the medial ganglionic eminence leads to a 50% reduction of GABAergic interneurons in the postnatal cortex. Here we examine the additional role of Rac3 by analyzing Rac1/Rac3 double-mutant mice. We show that in the absence of both Rac proteins, the embryonic migration of medial ganglionic eminence-derived interneurons is further impaired. Postnatally, double-mutant mice display a dramatic loss of cortical interneurons. In addition, Rac1/Rac3-deficient interneurons show gross cytoskeletal defects in vitro, with the length of their leading processes significantly reduced and a clear multipolar morphology. We propose that in the absence of Rac1/Rac3, cortical interneurons fail to migrate tangentially towards the pallium due to defects in actin and microtubule cytoskeletal dynamics.

  8. Positive Displacement Compressor Technology for Air Congitioners

    NASA Astrophysics Data System (ADS)

    Nagatomo, Shigemi

    Trends of compressor technologies for air conditioners are presented in this paper. HFC refrigerants such is R410A and R407C are promising candidates as an alternative for R22. Performance of rotary and scroll compressors in the operation with R410A and R407C are described. In addition, compressor technologies such as efficiency improvement, reliability and simulation methods are described in both cases of rotary and scroll compressors. Advanced compressor technologies developed for air conditioners are desired in the field of the global environment protection and the energy saving.

  9. Rac[e] to the pole: setting up polarity in endothelial cells.

    PubMed

    Collins, Caitlin; Tzima, Ellie

    2014-01-01

    Mechanical forces influence many biological processes via activation of signaling molecules, including the family of Rho GTPases. Within the endothelium, the mechanical force of fluid shear stress regulates the spatiotemporal activation of Rho GTPases, including Rac1. Shear stress-induced Rac1 activation is required for numerous essential biological processes, including changes in permeability, alignment of the actin cytoskeleton, redox signaling, and changes in gene expression. Thus, identifying mechanisms of Rac1 activation and the spatial cues that direct proper localization of the GTPase is essential in order to gain a comprehensive understanding the role of Rac1 in shear stress responses. This commentary will highlight our current understanding of how Rac1 activity is regulated in response to shear stress, as well as the downstream consequences of Rac1 activation.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Bioconversion of eucalyptus bark waste into soil conditioner.

    PubMed

    Yadav, K R; Sharma, R K; Kothari, R M

    2002-01-01

    An optimized protocol for the bioconversion of eucalyptus bark was devised. It comprised: (i) mechanical reduction in bark size to 0.5-3.0 cm, (ii) moistening to 60-65%, (iii) fortification with ligninase-rich fungus Volvariella sp. (S-1) and 2% urea and (iv) maintenance of this composting mix under aerobic and ambient condition for 14-15 weeks. The resulting bark soil conditioner (BSC) was an easily crumbling, reddish brown biomass, with physico-chemical and microbial properties which would enrich soil fertility/productivity.

  17. 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.

  18. 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.

  19. NADPH Oxidase Contributes to Photoreceptor Degeneration in Constitutively Active RAC1 Mice

    PubMed Central

    Song, Hongman; Vijayasarathy, Camasamudram; Zeng, Yong; Marangoni, Dario; Bush, Ronald A.; Wu, Zhijian; Sieving, Paul A.

    2016-01-01

    Purpose The active form of small GTPase RAC1 is required for activation of NADPH oxidase (NOX), which in turn generates reactive oxygen species (ROS) in nonphagocytic cells. We explored whether NOX-induced oxidative stress contributes to rod degeneration in retinas expressing constitutively active (CA) RAC1. Methods Transgenic (Tg)–CA-RAC1 mice were given apocynin (10 mg/kg, intraperitoneal), a NOX inhibitor, or vehicle daily for up to 13 weeks. Superoxide production and oxidative damage were assessed by dihydroethidium staining and by protein carbonyls and malondialdehyde levels, respectively. Outer nuclear layer (ONL) cells were counted and electroretinogram (ERG) amplitudes measured in Tg-CA-RAC1 mice. Outer nuclear layer cells were counted in wild-type (WT) mice after transfer of CA-Rac1 gene by subretinal injection of AAV8-pOpsin-CA Rac1-GFP. Results Transgenic-CA-RAC1 retinas had significantly fewer photoreceptor cells and more apoptotic ONL cells than WT controls from postnatal week (Pw) 3 to Pw13. Superoxide accumulation and protein and lipid oxidation were increased in Tg-CA-RAC1 retinas and were reduced in mice treated with apocynin. Apocynin reduced the loss of photoreceptors and increased the rod ERG a- and b-wave amplitudes when compared with vehicle-injected transgenic controls. Photoreceptor loss was also observed in regions of adult WT retina transduced with AAV8-pOpsin-CA Rac1-GFP but not in neighboring regions that were not transduced or in AAV8-pOpsin-GFP–transduced retinas. Conclusions Constitutively active RAC1 promotes photoreceptor cell death by oxidative damage that occurs, at least partially, through NOX-induced ROS. Reactive oxygen species are likely involved in multiple forms of retinal degenerations, and our results support investigating RAC1 inhibition as a therapeutic approach that targets this disease pathway. PMID:27233035

  20. 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

  1. 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.

  2. Spatio-Temporal Regulation of Rac1 Mobility by Actin Islands.

    PubMed

    Lakhani, Vinal V; Hinde, Elizabeth; Gratton, Enrico; Elston, Timothy C

    2015-01-01

    Rho GTPases play important roles in many aspects of cell migration, including polarity establishment and organizing actin cytoskeleton. In particular, the Rho GTPase Rac1 has been associated with the generation of protrusions at leading edge of migrating cells. Previously we showed the mobility of Rac1 molecules is not uniform throughout a migrating cell (Hinde E et. al. PNAS 2013). Specifically, the closer a Rac1 molecule is to the leading edge, the slower the molecule diffuses. Because actin-bound Rac1 diffuses slower than unbound Rac1, we hypothesized that regions of high actin concentration, called "actin islands", act as diffusive traps and are responsible for the non-uniform diffusion observed in vivo. Here, in silico model simulations demonstrate that equally spaced actin islands can regulate the time scale for Rac1 diffusion in a manner consistent with data from live-cell imaging experiments. Additionally, we find this mechanism is robust; different patterns of Rac1 mobility can be achieved by changing the actin islands' positions or their affinity for Rac1.

  3. Spatio-Temporal Regulation of Rac1 Mobility by Actin Islands

    PubMed Central

    Lakhani, Vinal V.; Hinde, Elizabeth; Gratton, Enrico; Elston, Timothy C.

    2015-01-01

    Rho GTPases play important roles in many aspects of cell migration, including polarity establishment and organizing actin cytoskeleton. In particular, the Rho GTPase Rac1 has been associated with the generation of protrusions at leading edge of migrating cells. Previously we showed the mobility of Rac1 molecules is not uniform throughout a migrating cell (Hinde E et. al. PNAS 2013). Specifically, the closer a Rac1 molecule is to the leading edge, the slower the molecule diffuses. Because actin-bound Rac1 diffuses slower than unbound Rac1, we hypothesized that regions of high actin concentration, called “actin islands”, act as diffusive traps and are responsible for the non-uniform diffusion observed in vivo. Here, in silico model simulations demonstrate that equally spaced actin islands can regulate the time scale for Rac1 diffusion in a manner consistent with data from live-cell imaging experiments. Additionally, we find this mechanism is robust; different patterns of Rac1 mobility can be achieved by changing the actin islands’ positions or their affinity for Rac1. PMID:26606145

  4. 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.

  5. 75 FR 52551 - Notice of Utah's Resource Advisory Council (RAC) Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ..., mandate, and purpose of rapid ecoregional assessments; a discussion on the governor's balanced resources... Bureau of Land Management Notice of Utah's Resource Advisory Council (RAC) Meeting AGENCY: Bureau of Land Management, Interior. ACTION: Notice of Utah's Resource Advisory Council (RAC) Meeting. SUMMARY:...

  6. 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

  7. Zinc-Catalyzed Highly Isoselective Ring Opening Polymerization of rac-Lactide

    PubMed Central

    2015-01-01

    A family of chiral zinc amido-oxazolinate complexes are shown to be highly active and isoselective initiators for the ring-opening polymerization (ROP) of rac-lactide, yielding isotactic stereoblock polylactides (PLA) with Pm up to 0.91. This represents the highest isoselectivity observed with zinc-based catalysts for ROP of rac-lactide. PMID:25068079

  8. The levels of RAC3 expression are up regulated by TNF in the inflammatory response.

    PubMed

    Alvarado, Cecilia Viviana; Rubio, María Fernanda; Fernández Larrosa, Pablo Nicolas; Panelo, Laura Carolina; Azurmendi, Pablo Javier; Ruiz Grecco, Marina; Martínez-Nöel, Giselle Astrid; Costas, Mónica Alejandra

    2014-01-01

    RAC3 is a coactivator of glucocorticoid receptor and nuclear factor-κB (NF-κB) that is usually over-expressed in tumors and which also has important functions in the immune system. We investigated the role of the inflammatory response in the control of RAC3 expression levels in vivo and in vitro. We found that inflammation regulates RAC3 levels. In mice, sub-lethal doses of lipopolysaccharide induce the increase of RAC3 in spleen and the administration of the synthetic anti-inflammatory glucocorticoid dexamethasone has a similar effect. However, the simultaneous treatment with both stimuli is mutually antagonistic. In vitro stimulation of the HEK293 cell line with tumor necrosis factor (TNF), one of the cytokines induced by lipopolysaccharide, also increases the levels of RAC3 mRNA and protein, which correlates with an enhanced transcription dependent on the RAC3 gene promoter. We found that binding of the transcription factor NF-κB to the RAC3 gene promoter could be responsible for these effects. Our results suggest that increase of RAC3 during the inflammatory response could be a molecular mechanism involved in the control of sensitivity to both pro- and anti-inflammatory stimuli in order to maintain the normal healthy course of the immune response.

  9. 76 FR 8334 - White Pine-Nye County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service White Pine-Nye County Resource Advisory Committee (RAC) AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The White Pine-Nye County Resource Advisory Committee (RAC) will...

  10. 76 FR 85 - Nye/White Pine County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-03

    ... Forest Service Nye/White Pine County Resource Advisory Committee (RAC) AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The Nye/White Pine County Resource Advisory Committee (RAC) will hold...: The meeting will be held in Nye County at the Bureau of Land Management, 1553 S. Erie Main...

  11. 76 FR 13600 - White Pine-Nye County Resource Advisory Committee (RAC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Forest Service White Pine-Nye County Resource Advisory Committee (RAC) AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The White Pine-Nye County Resource Advisory Committee (RAC) will...

  12. Synthesis and characterization of amine-bridged bis(phenolate)lanthanide alkoxides and their application in the controlled polymerization of rac-lactide and rac-β-butyrolactone.

    PubMed

    Nie, Kun; Fang, Lei; Yao, Yingming; Zhang, Yong; Shen, Qi; Wang, Yaorong

    2012-10-15

    A series of neutral lanthanide alkoxides supported by an amine-bridged bis(phenolate) ligand were synthesized, and their catalytic behaviors for the polymerization of rac-lactide (LA) and rac-β-butyrolactone (BBL) were explored. The reactions of (C(5)H(5))(3)Ln(THF) with amine-bridged bis(phenol) LH(2) [L = Me(2)NCH(2)CH(2)N{CH(2)-(2-OC(6)H(2)Bu(t)(2)-3,5)}(2)] in a 1:1 molar ratio in THF for 1 h and then with 1 equiv each of 2,2,2-trifluoroethanol, benzyl alcohol, and 2-propanol gave the neutral lanthanide alkoxides LLn(OCH(2)CF(3))(THF) [Ln = Y (1), Yb (2), Er (3), Sm (4)], LY(OCH(2)Ph)(THF) (5), and LY(OPr(i))(THF) (6), respectively. These lanthanide alkoxides are sensitive to moisture, and the yttrium complex [(LY)(2)(μ-OPr(i))(μ-OH)] (7) was also isolated as a byproduct during the synthesis of complex 6. Complexes 1-6 were well characterized by elemental analyses and IR and NMR spectroscopy in the cases of complexes 1 and 4-6. The definitive molecular structures of all of these complexes were determined by single-crystal X-ray analysis. It was found that complexes 1-6 can initiate efficiently the ring-opening polymerization of rac-LA and rac-BBL in a controlled manner. For rac-LA, polymerization gave polymers with very narrow molecular weight distributions (PDI ≤ 1.12) and very high heterotacticity (P(r) up to 0.99). The observed activity-increasing order is in agreement with the order of the ionic radii, whereas the order for stereoselectivity is in the reverse order. For rac-BBL polymerization, the resultant polymers have narrow molecular distributions (PDI ≤ 1.26) and high syndiotacticity (P(r) up to 0.83). It is worth noting that the activity-decreasing order Yb > Er > Y > Sm is observed for rac-BBL polymerization, which is opposite to the order of ionic radii and to the order of activity for rac-LA polymerization. The ionic radii of lanthanide metals have no obvious effect on the stereoselectivity for rac-BBL polymerization, which is quite

  13. The Drosophila small GTPase Rac2 is required for normal feeding and mating behaviour.

    PubMed

    Goergen, Philip; Kasagiannis, Anna; Schiöth, Helgi B; Williams, Michael J

    2014-03-01

    All multicellular organisms require the ability to regulate bodily processes in order to maintain a stable condition, which necessitates fluctuations in internal metabolics, as well as modifications of outward behaviour. Understanding the genetics behind this modulation is important as a general model for the metabolic modification of behaviour. This study demonstrates that the activity of the small GTPase Rac2 is required in Drosophila for the proper regulation of lipid storage and feeding behaviour, as well as aggression and mating behaviours. Rac2 mutant males and females are susceptible to starvation and contain considerably less lipids than controls. Furthermore, Rac2 mutants also have disrupted feeding behaviour, eating fewer but larger meals than controls. Intriguingly, Rac2 mutant males rarely initiate aggressive behaviour and display significantly increased levels of courtship behaviour towards other males and mated females. From these results we conclude that Rac2 has a central role in regulating the Drosophila homeostatic system.

  14. [Toxicity effects of Rac- and S-metolachlor on two algaes].

    PubMed

    Cai, Wei-Dan; Liu, Hui-Jun; Fang, Zhi-Guo

    2012-02-01

    The enantioselective toxicity of the chiral herbicides Rac- and S-metolachlor to Scenedesmus obliquus and Chlorella vulgaris was determined, and the effect of humic acid was studied by using acute toxicity testing method. The results indicated that the toxicity of Rac- and S-metolachlor increased with increasing concentration and exposure time. The EC(50, 96 h) ratio of Rac-metolachlor to S-metolachlor was 2.25 for C. vulgaris and 1.81 for S. obliquus, indicating that S-metolachlor had higher effect on two algaes, and S. obliquus was more sensitive to Rac- and S-metolachlor. Linear correlation between toxicity on S. obliquus and C. vulgaris was observed. The toxicity of Rac- and S-metolachlor changed with humic acid, with more significant change was observed in S-metolachlor (P<0.05).

  15. 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

  16. 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.

  17. A function for Rac1 in the terminal differentiation and pigmentation of hair.

    PubMed

    Behrendt, Kristina; Klatte, Jennifer; Pofahl, Ruth; Bloch, Wilhelm; Smyth, Neil; Tscharntke, Michael; Krieg, Thomas; Paus, Ralf; Niessen, Carien; Niemann, Catherin; Brakebusch, Cord; Haase, Ingo

    2012-02-15

    The small GTPase Rac1 is ubiquitously expressed in proliferating and differentiating layers of the epidermis and hair follicles. Previously, Rac1 was shown to regulate stem cell behaviour in these compartments. We have asked whether Rac1 has, in addition, a specific, stem-cell-independent function in the regulation of terminal hair follicle differentiation. To address this, we have expressed a constitutively active mutant of Rac1, L61Rac1, only in the basal epidermal layer and outer root sheath of mice possessing an epidermis-specific deletion of endogenous Rac1, which experience severe hair loss. The resulting 'rescue' mice exhibited a hair coat throughout their lives. Therefore, expression of Rac1 activity in the keratin-14-positive compartment of the skin is sufficient for the formation of hair follicles and hair in normal quantities. The quality of hair formed in rescue mice was, however, not normal. Rescue mice showed a grey, dull hair coat, whereas that of wild-type and L61Rac1-transgenic mice was black and shiny. Hair analysis in rescue mice revealed altered structures of the hair shaft and the cuticle and disturbed organization of medulla cells and pigment distribution. Disorganization of medulla cells correlates with the absence of cortical, keratin-filled spikes that normally protrude from the cortex into the medulla. The desmosomal cadherin Dsc2, which normally decorates these protrusions, was found to be reduced or absent in the hair of rescue mice. Our study demonstrates regulatory functions for Rac1 in the formation of hair structure and pigmentation and thereby identifies, for the first time, a role for Rac1 in terminal differentiation.

  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. RotundRacGAP Functions with Ras during Spermatogenesis and Retinal Differentiation in Drosophila melanogaster

    PubMed Central

    Bergeret, Evelyne; Pignot-Paintrand, Isabelle; Guichard, Annabel; Raymond, Karine; Fauvarque, Marie-Odile; Cazemajor, Michel; Griffin-Shea, Ruth

    2001-01-01

    Our analysis of rotund (rn) null mutations in Drosophila melanogaster revealed that deletion of the rn locus affects both spermatid and retinal differentiation. In the male reproductive system, the absence of RnRacGAP induced small testes, empty seminal vesicles, short testicular cysts, reduced amounts of interspermatid membrane, the absence of individualization complexes, and incomplete mitochondrial condensation. Flagellar growth continued within the short rn null cysts to produce large bulbous terminations of intertwined mature flagella. Organization of the retina was also severely perturbed as evidenced by grossly misshapen ommatidia containing reduced numbers of photoreceptor and pigment cells. These morphological phenotypes were rescued by genomic rnRacGAP transgenes, demonstrating that RnRacGAP function is critical to spermatid and retinal differentiation. The testicular phenotypes were suppressed by heterozygous hypomorphic mutations in the Dras1 and drk genes, indicating cross talk between RacGAP-regulated signaling and that of the Ras pathway. The observed genetic interactions are consistent with a model in which Rac signaling is activated by Ras and negatively regulated by RnRacGAP during spermatid differentiation. RnRacGAP and Ras cross talk also operated during retinal differentiation; however, while the heterozygous hypomorphic drk mutation continued to act as a suppressor of the rn null mutation, the heterozygous hypomorphic Dras1 mutation induced novel retinal phenotypes. PMID:11509670

  20. 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

  1. 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

  2. [RAC3 overexpression is a transforming and proliferative signal that contributes to tumoral development].

    PubMed

    Alvarado, Cecilia V; Micenmacher, Sabrina; Ruiz Grecco, Marina; Rubio, Maria F; Fernandez Larrosa, Nicolas; Costas, Monica A

    2011-01-01

    RAC3 has been firstly characterized as a nuclear receptor coactivator that is found in limited amounts in normal cells, but is over-expressed in tumors and is also an NF-kB coactivator. Although the mechanisms involved in its over-expression are not clear, it is well known that it enhances resistance to apoptosis. In this work, we investigated if there are any additional mechanisms by which RAC3 may contribute to tumor development and if TNF-a, an inflammatory cytokine that is found at high levels in cancer could increase RAC3 levels. We found that enhancement of RAC3 levels by transfection of HEK293 cells with a RAC3 expression vector induces a significant increase of cell proliferation not only in the presence, but also in the absence of serum growth factors. Moreover, the cells were transformed showing an anchorage independent growth, similar to that observed in tumoral cells. The treatment of HEK293 cells with TNF-a induced an increase in the protein levels of RAC3 and this was blocked by an NF-kB specific inhibitor, suggesting that this transcription factor is involved in the cytokine effect. We conclude that RAC3, in addition to is anti-apoptotic action, is a transforming factor that promotes the proliferation and growth independent of anchorage, and that its levels could be elevated by the action of inflammatory cytokines that are involved in the anti-tumoral response.

  3. 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.

  4. Rac signaling in breast cancer: a tale of GEFs and GAPs.

    PubMed

    Wertheimer, Eva; Gutierrez-Uzquiza, Alvaro; Rosemblit, Cinthia; Lopez-Haber, Cynthia; Sosa, Maria Soledad; Kazanietz, Marcelo G

    2012-02-01

    Rac GTPases, small G-proteins widely implicated in tumorigenesis and metastasis, transduce signals from tyrosine-kinase, G-protein-coupled receptors (GPCRs), and integrins, and control a number of essential cellular functions including motility, adhesion, and proliferation. Deregulation of Rac signaling in cancer is generally a consequence of enhanced upstream inputs from tyrosine-kinase receptors, PI3K or Guanine nucleotide Exchange Factors (GEFs), or reduced Rac inactivation by GTPase Activating Proteins (GAPs). In breast cancer cells Rac1 is a downstream effector of ErbB receptors and mediates migratory responses by ErbB1/EGFR ligands such as EGF or TGFα and ErbB3 ligands such as heregulins. Recent advances in the field led to the identification of the Rac-GEF P-Rex1 as an essential mediator of Rac1 responses in breast cancer cells. P-Rex1 is activated by the PI3K product PIP3 and Gβγ subunits, and integrates signals from ErbB receptors and GPCRs. Most notably, P-Rex1 is highly overexpressed in human luminal breast tumors, particularly those expressing ErbB2 and estrogen receptor (ER). The P-Rex1/Rac signaling pathway may represent an attractive target for breast cancer therapy.

  5. Two Rac paralogs regulate polarized growth in the human fungal pathogen Cryptococcus neoformans

    PubMed Central

    Ballou, Elizabeth Ripley; Selvig, Kyla; Narloch, Jessica L.; Nichols, Connie B.; Alspaugh, J. Andrew

    2013-01-01

    A genome wide analysis of the human fungal pathogen Cryptococcus neoformans var. grubii has revealed a number of duplications of highly conserved genes involved in morphogenesis. Previously, we reported that duplicate Cdc42 paralogs provide C. neoformans with niche-specific responses to environmental stresses: Cdc42 is required for thermotolerance, while Cdc420 supports the formation of titan cells. The related Rho-GTPase Rac1 has been shown in C. neoformans var. neoformans to play a major role in filamentation and to share Cdc42/Cdc420 binding partners. Here we report the characterization of a second Rac paralog in C. neoformans, Rac2, and describe its overlapping function with the previously described CnRac, Rac1. Further, we demonstrate that the Rac paralogs play a primary role in polarized growth via the organization of reactive oxygen species and play only a minor role in the organization of actin. Finally, we provide preliminary evidence that pharmacological inhibitors of Rac activity and actin stability have synergistic activity. PMID:23748012

  6. 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.

  7. 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.

  8. 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

  9. RacGAP1-driven focal adhesion formation promotes melanoma transendothelial migration through mediating adherens junction disassembly.

    PubMed

    Zhang, Pu; Bai, Huiyuan; Fu, Changliang; Chen, Feng; Zeng, Panying; Wu, Chengxiang; Ye, Qichao; Dong, Cheng; Song, Yang; Song, Erqun

    2015-03-27

    Melanoma cell migration across vascular endothelial cells is an essential step of tumor metastasis. Here, we provide evidence that RacGAP1, a cytokinesis-related Rho GTPase-activating protein, contributed to this process. Depletion of RacGAP1 with RacGAP1-targeting siRNA or overexpression of RacGAP1 mutant (T249A) attenuated melanoma cell transendothelial migration and concomitant changes of adherens junctions. In addition, RacGAP1 promoted the activations of RhoA, FAK, paxillin and triggered focal adhesion formation and cytoskeletal rearrangement. By overexpressing FAK-related non-kinase (FRNK) in endothelium, we showed that RacGAP1 mediated endothelial barrier function loss and melanoma transmigration in a focal adhesion-dependent manner. These results suggest that endothelial RacGAP1 may play critical roles in pathogenic processes of cancer by regulating endothelial permeability.

  10. Photolysis of rac-leucine with circularly polarized synchrotron radiation.

    PubMed

    Meierhenrich, Uwe J; Filippi, Jean-Jacques; Meinert, Cornelia; Hoffmann, Søren V; Bredehöft, Jan Hendrik; Nahon, Laurent

    2010-06-01

    Amino acids that pass the RNA machinery in living organisms occur in L-configuration. The question on the evolutionary origin of this biomolecular asymmetry remains unanswered to this day. Amino acids were detected in artificially produced interstellar ices, and L-enantiomer-enriched amino acids were identified in CM-type meteorites. This hints at a possible interstellar/circumstellar origin of the amino acids themselves as well as their stereochemical asymmetry. Based upon the current knowledge about the occurrence of circularly-polarized electromagnetic radiation in interstellar environments, we subjected rac-leucine to far-UV circularly-polarized synchrotron radiation. Asymmetric photolysis was followed by an analysis in an enantioselective GC/MS system. Here, we report on an advanced photolysis rate of more than 99% for leucine. The results indicate that high photolysis rates can occur under the chosen conditions, favoring enantioselective photolysis. In 2014, the obtained results will be reexamined by cometary mission Rosetta.

  11. 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.

  12. 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.

  13. RCP-driven α5β1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1-IQGAP1 complex.

    PubMed

    Jacquemet, Guillaume; Green, David M; Bridgewater, Rebecca E; von Kriegsheim, Alexander; Humphries, Martin J; Norman, Jim C; Caswell, Patrick T

    2013-09-16

    Inhibition of αvβ3 or expression of mutant p53 promotes invasion into fibronectin (FN)-containing extracellular matrix (ECM) by enhancing Rab-coupling protein (RCP)-dependent recycling of α5β1 integrin. RCP and α5β1 cooperatively recruit receptor tyrosine kinases, including EGFR1, to regulate their trafficking and downstream signaling via protein kinase B (PKB)/Akt, which, in turn, promotes invasive migration. In this paper, we identify a novel PKB/Akt substrate, RacGAP1, which is phosphorylated as a consequence of RCP-dependent α5β1 trafficking. Phosphorylation of RacGAP1 promotes its recruitment to IQGAP1 at the tips of invasive pseudopods, and RacGAP1 then locally suppresses the activity of the cytoskeletal regulator Rac and promotes the activity of RhoA in this subcellular region. This Rac to RhoA switch promotes the extension of pseudopodial processes and invasive migration into FN-containing matrices, in a RhoA-dependent manner. Thus, the localized endocytic trafficking of α5β1 within the tips of invasive pseudopods elicits signals that promote the reorganization of the actin cytoskeleton, protrusion, and invasion into FN-rich ECM.

  14. ARF1 and ARF6 regulate recycling of GRASP/Tamalin and the Rac1-GEF Dock180 during HGF-induced Rac1 activation.

    PubMed

    Koubek, Emily J; Santy, Lorraine C

    2016-08-12

    Hepatocyte growth factor (HGF) is a potent signaling factor that acts on epithelial cells, causing them to dissociate and scatter. This migration is coordinated by a number of small GTPases, such as ARF6 and Rac1. Active ARF6 is required for HGF-stimulated migration and intracellular levels of ARF6-GTP and Rac1-GTP increase following HGF treatment. During migration, cross talk between ARF6 and Rac1 occurs through formation of a multi-protein complex containing the ARF-GEF cytohesin-2, the scaffolding protein GRASP/Tamalin, and the Rac1-GEF Dock180. Previously, the role of ARF6 in this process was unclear. We have now found that ARF6 and ARF1 regulate trafficking of GRASP and Dock180 to the plasma membrane following HGF treatment. Trafficking of GRASP and Dock180 is impaired by blocking ARF6-mediated recycling pathways and is required for HGF-stimulated Rac1 activation. Finally, HGF treatment stimulates association of GRASP and Dock180. Inhibition of ARF6 trafficking pathways traps GRASP and Dock180 as a complex in the cell.

  15. 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

  16. 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

  17. 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.

  18. RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells.

    PubMed

    Faria, Márcia; Matos, Paulo; Pereira, Teresa; Cabrera, Rafael; Cardoso, Bruno A; Bugalho, Maria João; Silva, Ana Luísa

    2017-01-01

    Overexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-kB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b-WT, confirming NF-kB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-kB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-kB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-kB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas.

  19. Epidermal growth factor stimulates Rac activation through Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migration.

    PubMed

    Dise, Rebecca S; Frey, Mark R; Whitehead, Robert H; Polk, D Brent

    2008-01-01

    Regulated intestinal epithelial cell migration plays a key role in wound healing and maintenance of a healthy gastrointestinal tract. Epidermal growth factor (EGF) stimulates cell migration and wound closure in intestinal epithelial cells through incompletely understood mechanisms. In this study we investigated the role of the small GTPase Rac in EGF-induced cell migration using an in vitro wound-healing assay. In mouse colonic epithelial (MCE) cell lines, EGF-stimulated wound closure was accompanied by a doubling of the number of cells containing lamellipodial extensions at the wound margin, increased Rac membrane translocation in cells at the wound margin, and rapid Rac activation. Either Rac1 small interfering (si)RNA or a Rac1 inhibitor completely blocked EGF-stimulated wound closure. Whereas EGF failed to activate Rac in colon cells from EGF receptor (EGFR) knockout mice, stable expression of wild-type EGFR restored EGF-stimulated Rac activation and migration. Pharmacological inhibition of either phosphatidylinositol 3-kinase (PI3K) or Src family kinases reduced EGF-stimulated Rac activation. Cotreatment of cells with both inhibitors completely blocked EGF-stimulated Rac activation and localization to the leading edge of cells and lamellipodial extension. Our results present a novel mechanism by which the PI3K and Src signaling cascades cooperate to activate Rac and promote intestinal epithelial cell migration downstream of EGFR.

  20. RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells

    PubMed Central

    Faria, Márcia; Matos, Paulo; Pereira, Teresa; Cabrera, Rafael; Cardoso, Bruno A.; Bugalho, Maria João

    2017-01-01

    Overexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-kB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b-WT, confirming NF-kB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-kB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-kB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-kB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas. PMID:28234980

  1. Regulation of Rac1 and Reactive Oxygen Species Production in Response to Infection of Gastrointestinal Epithelia.

    PubMed

    den Hartog, Gerco; Chattopadhyay, Ranajoy; 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.

  2. Distinct Effects of Rac1 on Differentiation of Primary Avian Myoblasts

    PubMed Central

    Gallo, Rita; Serafini, Marco; Castellani, Loriana; Falcone, Germana; Alemà, Stefano

    1999-01-01

    Rho family GTPases have been implicated in the regulation of the actin cytoskeleton in response to extracellular cues and in the transduction of signals from the membrane to the nucleus. Their role in development and cell differentiation, however, is little understood. Here we show that the transient expression of constitutively active Rac1 and Cdc42 in unestablished avian myoblasts is sufficient to cause inhibition of myogenin expression and block of the transition to the myocyte compartment, whereas activated RhoA affects myogenic differentiation only marginally. Activation of c-Jun N-terminal kinase (JNK) appears not to be essential for block of differentiation because, although Rac1 and Cdc42 GTPases modestly activate JNK in quail myoblasts, a Rac1 mutant defective for JNK activation can still inhibit myogenic differentiation. Stable expression of active Rac1, attained by infection with a recombinant retrovirus, is permissive for terminal differentiation, but the resulting myotubes accumulate severely reduced levels of muscle-specific proteins. This inhibition is the consequence of posttranscriptional events and suggests the presence of a novel level of regulation of myogenesis. We also show that myotubes expressing constitutively active Rac1 fail to assemble ordered sarcomeres. Conversely, a dominant-negative Rac1 variant accelerates sarcomere maturation and inhibits v-Src–induced selective disassembly of I-Z-I complexes. Collectively, our findings provide a role for Rac1 during skeletal muscle differentiation and strongly suggest that Rac1 is required downstream of v-Src in the signaling pathways responsible for the dismantling of tissue-specific supramolecular structures. PMID:10512856

  3. A Minimal Rac Activation Domain in the Unconventional Guanine Nucleotide Exchange Factor Dock180†

    PubMed Central

    Wu, Xin; Ramachandran, Sekar; Cerione, Richard A.; Erickson, Jon W.

    2011-01-01

    Guanine nucleotide exchange factors (GEFs) activate Rho GTPases by catalyzing the exchange of bound GDP for GTP, thereby resulting in downstream effector recognition. Two metazoan families of GEFs have been described: Dbl-GEF family members that share conserved Dbl homology (DH) and Pleckstrin homology (PH) domains and the more recently described Dock180 family members that share little sequence homology with the Dbl family and are characterized by conserved Dock homology regions 1 and 2 (DHR-1 and -2). While extensive characterization of the Dbl family has been performed, less is known about how Dock180 family members act as GEFs, with only a single x-ray structure having recently been reported for the Dock9-Cdc42 complex. In order to learn more about the mechanisms used by the founding member of the family, Dock180, to act as a Rac-specific GEF, we set out to identify and characterize its limit functional GEF domain. A C-terminal portion of the DHR-2 domain, composed of approximately 300 residues (designated as Dock180DHR-2c), is shown to be necessary and sufficient for robust Rac-specific GEF activity both in vitro and in vivo. We further show that Dock180DHR-2c binds to Rac in a manner distinct from Rac-GEFs of the Dbl family. Specifically, Ala27 and Trp56 of Rac appear to provide a bipartite binding site for the specific recognition of Dock180DHR-2c, whereas, for Dbl family Rac-GEFs, Trp56 of Rac is the sole primary determinant of GEF specificity. Based on our findings, we are able to define the core of Dock180 responsible for its Rac-GEF activity as well as highlight key recognition sites that distinguish different Dock180 family members and determine their corresponding GTPase specificities. PMID:21033699

  4. Inhibition of Rac GTPases in the Therapy of Chronic Myelogenous Leukemia

    DTIC Science & Technology

    2008-04-01

    subcellular localization of the GTPase Rac3. In ‘‘Proceedings of the Small GTPase Meeting Snowmass’’ (T. S. R. Institute, ed.). La Jolla, CA. Burridge...cell localization . Methods Enzymol 2008;439:365-93. 3. Thomas EK*, Cancelas JA*, Chae H-D, Cox AD, Keller PJ, Perrotti D, Neviani, Druker BJ...302(5644): p. 445-9. 33. Cancelas, J.A., et al., Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization . Nat

  5. Remedial Strategies in Structural Proteomics: Expression, Purification and Crystallization of the Vav1/Rac1 Complex

    PubMed Central

    Brooun, Alexei; Foster, Scott A.; Chrencik, Jill E.; Chien, Ellen Y.T.; Kolatkar, Anand R.; Streiff, Markus; Ramage, Paul; Widmer, Hans; Weckbecker, Gisbert; Kuhn, Peter

    2007-01-01

    The signal transduction pathway involving the Vav1 guanine nucleotide exchange factor (GEF) and the Rac1 GTPase plays several key roles in the immune response mediated by the T cell receptor. Vav1 is also a unique member of the GEF family in that it contains a cysteine-rich domain (CRD) that is critical for Rac1 binding and maximal guanine nucleotide exchange activity, and thus may provide a unique protein-protein interface compared to other GEF/GTPase pairs. Here we have applied a number of remedial structural proteomics strategies, such as construct and expression optimization, surface mutagenesis, limited proteolysis, and protein formulation to successfully express, purify, and crystallize the Vav1-DH-PH-CRD/Rac1 complex in an active conformation. We have also systematically characterized various Vav1 domains in a GEF assay, and Rac1 in vitro binding experiments. In the context of Vav1-DH-PH-CRD, the zinc finger motif of the CRD is required for the expression of stable Vav1, as well as for activity in both a GEF assay and in vitro formation of a Vav1/Rac1 complex suitable for biophysical and structural characterization. Our data also indicate that the isolated CRD maintains a low level of specific binding to Rac1, appears to be folded based on 1D-NMR analysis and coordinates two zinc ions based on ICP-MS analysis. The protein reagents generated here are essential tools for the determination of a three dimensional Vav1/Rac1 complex crystal structure and possibly for the identification of inhibitors of the Vav1/Rac1 protein-protein interaction with potential to inhibit lymphocyte activation. PMID:17275330

  6. 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

  7. Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis.

    PubMed

    Deshmukh, Jayesh; Pofahl, Ruth; Haase, Ingo

    2017-03-09

    Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways.

  8. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases.

    PubMed

    Shutes, Adam; Onesto, Cercina; Picard, Virginie; Leblond, Bertrand; Schweighoffer, Fabien; Der, Channing J

    2007-12-07

    There is now considerable experimental evidence that aberrant activation of Rho family small GTPases promotes the uncontrolled proliferation, invasion, and metastatic properties of human cancer cells. Therefore, there is considerable interest in the development of small molecule inhibitors of Rho GTPase function. However, to date, most efforts have focused on inhibitors that indirectly block Rho GTPase function, by targeting either enzymes involved in post-translational processing or downstream protein kinase effectors. We recently determined that the EHT 1864 small molecule can inhibit Rac function in vivo. In this study, we evaluated the biological and biochemical specificities and biochemical mechanism of action of EHT 1864. We determined that EHT 1864 specifically inhibited Rac1-dependent platelet-derived growth factor-induced lamellipodia formation. Furthermore, our biochemical analyses with recombinant Rac proteins found that EHT 1864 possesses high affinity binding to Rac1, as well as the related Rac1b, Rac2, and Rac3 isoforms, and this association promoted the loss of bound nucleotide, inhibiting both guanine nucleotide association and Tiam1 Rac guanine nucleotide exchange factor-stimulated exchange factor activity in vitro. EHT 1864 therefore places Rac in an inert and inactive state, preventing its engagement with downstream effectors. Finally, we evaluated the ability of EHT 1864 to block Rac-dependent growth transformation, and we determined that EHT 1864 potently blocked transformation caused by constitutively activated Rac1, as well as Rac-dependent transformation caused by Tiam1 or Ras. Taken together, our results suggest that EHT 1864 selectively inhibits Rac downstream signaling and transformation by a novel mechanism involving guanine nucleotide displacement.

  9. Adenylyl cyclase localization to the uropod of aggregating Dictyostelium cells requires RacC

    PubMed Central

    Wang, C.; Jung, D.; Cao, Z.; Chung, C. Y.

    2015-01-01

    The localization of adenylyl cyclase A (ACA) to uropod of cells is required for the stream formation during Dictyostelium development. RacC is a Dictyostelium orthologue of Cdc42. We identified a streaming defect of racC− cells as they are clearly less polarized and form smaller and fragmented streams. ACA-YFP is mainly associated with intracellular vesicular structures, but not with the plasma membrane in racC− cells. racC− cells have a slightly higher number of vesicles than Ax3 cells, suggesting that the defect of ACA trafficking is not simply due to the lack of vesicle formation. While the ACA-YFP vesicles traveled with an average velocity of 9.1 µm/min in Ax3 cells, a slow and diffusional movement without direction with an average velocity of 4 µm/min was maintained in racC− cells. Images acquired by using total internal reflection fluorescence (TIRF) microscopy and fluorescence recovery after photobleaching (FRAP) analysis revealed that a significantly decreased number of ACA-YFP vesicles appeared near the cell membrane, indicating a defect in ACA-YFP vesicle trafficking. These results suggest an important role of RacC in the rapid and directional movements of ACA vesicles on microtubules to the plasma membrane, especially to the back of polarized cell. PMID:26315268

  10. Adenylyl cyclase localization to the uropod of aggregating Dictyostelium cells requires RacC.

    PubMed

    Wang, C; Jung, D; Cao, Z; Chung, C Y

    2015-09-25

    The localization of adenylyl cyclase A (ACA) to uropod of cells is required for the stream formation during Dictyostelium development. RacC is a Dictyostelium orthologue of Cdc42. We identified a streaming defect of racC(-) cells as they are clearly less polarized and form smaller and fragmented streams. ACA-YFP is mainly associated with intracellular vesicular structures, but not with the plasma membrane in racC(-) cells. racC(-) cells have a slightly higher number of vesicles than Ax3 cells, suggesting that the defect of ACA trafficking is not simply due to the lack of vesicle formation. While the ACA-YFP vesicles traveled with an average velocity of 9.1 μm/min in Ax3 cells, a slow and diffusional movement without direction with an average velocity of 4 μm/min was maintained in racC(-) cells. Images acquired by using total internal reflection fluorescence (TIRF) microscopy and fluorescence recovery after photobleaching (FRAP) analysis revealed that a significantly decreased number of ACA-YFP vesicles appeared near the cell membrane, indicating a defect in ACA-YFP vesicle trafficking. These results suggest an important role of RacC in the rapid and directional movements of ACA vesicles on microtubules to the plasma membrane, especially to the back of polarized cell.

  11. Fluctuation-based imaging of nuclear Rac1 activation by protein oligomerisation

    PubMed Central

    Hinde, Elizabeth; Yokomori, Kyoko; Gaus, Katharina; Hahn, Klaus M.; Gratton, Enrico

    2014-01-01

    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. PMID:24573109

  12. 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.

  13. Rac1 functions as a reversible tension modulator to stabilize VE-cadherin trans-interaction

    PubMed Central

    Daneshjou, Nazila; Sieracki, Nathan; van Nieuw Amerongen, Geerten P.; Conway, Daniel E.; Schwartz, Martin A.

    2015-01-01

    The role of the RhoGTPase Rac1 in stabilizing mature endothelial adherens junctions (AJs) is not well understood. In this paper, using a photoactivatable probe to control Rac1 activity at AJs, we addressed the relationship between Rac1 and the dynamics of vascular endothelial cadherin (VE-cadherin). We demonstrated that Rac1 activation reduced the rate of VE-cadherin dissociation, leading to increased density of VE-cadherin at AJs. This response was coupled to a reduction in actomyosin-dependent tension across VE-cadherin adhesion sites. We observed that inhibiting myosin II directly or through photo-release of the caged Rho kinase inhibitor also reduced the rate of VE-cadherin dissociation. Thus, Rac1 functions by stabilizing VE-cadherin trans-dimers in mature AJs by counteracting the actomyosin tension. The results suggest a new model of VE-cadherin adhesive interaction mediated by Rac1-induced reduction of mechanical tension at AJs, resulting in the stabilization of VE-cadherin adhesions. PMID:25559184

  14. 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

  15. Characterization of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases.

    PubMed

    Onesto, Cercina; Shutes, Adam; Picard, Virginie; Schweighoffer, Fabien; Der, Channing J

    2008-01-01

    There is now considerable experimental evidence that aberrant activation of Rho family small GTPases promotes uncontrolled proliferation, invasion, and metastatic properties of human cancer cells. Therefore, there is considerable interest in the development of small molecule inhibitors of Rho GTPase function. However, to date, most efforts have focused on inhibitors that block Rho GTPase function indirectly, either by targeting enzymes involved in post-translational processing or downstream protein kinase effectors. We have reported the identification and characterization of the EHT 1864 small molecule as an inhibitor of Rac family small GTPases, placing Rac1 in an inert and inactive state and then impairing Rac1-mediated functions in vivo. Our work suggests that EHT 1864 selectively inhibits Rac1 downstream signaling and cellular transformation by a novel mechanism involving guanine nucleotide displacement. This chapter provides the details for some of the biochemical and biological methods used to characterize the mode of action of EHT 1864 on Rac1 and its impact on Rac1-dependent cellular functions.

  16. Coronin1 Proteins Dictate Rac1 Intracellular Dynamics and Cytoskeletal Output

    PubMed Central

    Ojeda, Virginia; Castro-Castro, Antonio

    2014-01-01

    Rac1 regulates lamellipodium formation, myosin II-dependent contractility, and focal adhesions during cell migration. While the spatiotemporal assembly of those processes is well characterized, the signaling mechanisms involved remain obscure. We report here that the cytoskeleton-related Coronin1A and -1B proteins control a myosin II inactivation-dependent step that dictates the intracellular dynamics and cytoskeletal output of active Rac1. This step is signaling-branch specific, since it affects the functional competence of active Rac1 only when forming complexes with downstream ArhGEF7 and Pak proteins in actomyosin-rich structures. The pathway is used by default unless Rac1 is actively rerouted away from the structures by upstream activators and signals from other Rho GTPases. These results indicate that Coronin1 proteins are at the center of a regulatory hub that coordinates Rac1 activation, effector exchange, and the F-actin organization state during cell signaling. Targeting this route could be useful to hamper migration of cancer cells harboring oncogenic RAC1 mutations. PMID:24980436

  17. Regulation of cell-matrix adhesion dynamics and Rac-1 by integrin linked kinase.

    PubMed

    Boulter, Etienne; Grall, Dominique; Cagnol, Sébastien; Van Obberghen-Schilling, Ellen

    2006-07-01

    Extracellular matrix (ECM) receptors of the integrin family initiate changes in cell shape and motility by recruiting signaling components that coordinate these events. Integrin-linked kinase (ILK) is one such partner of beta1 integrins that participates in dynamic rearrangement of cell-matrix adhesions and cell spreading by mechanisms that are not well understood. To further elucidate the role of ILK in these events, we engineered a chimeric molecule comprising ILK fused to a membrane-targeted green fluorescent protein (ILK-GFP-F). ILK-GFP-F is highly enriched in cell-matrix adhesions, and its expression in fibroblasts leads to an accumulation of focal adhesions (2-5 microm) and elongated adhesions (>5 microm). ILK-GFP-F enhances cell spreading on fibronectin and induces a constitutive increase in the levels of GTP-bound Rac-1. Conversely, ILK knock-down by siRNA transfection decreases active Rac-1. Endogenous ILK was found to associate with PKL (paxillin kinase linker) and the Rac/Cdc42 guanine nucleotide exchange factor betaPIX. Further, expression of a dominant negative betaPIX mutant reversed the increase in active Rac-1 levels of ILK-GFP-F-expressing cells, thus placing betaPIX in the pathway leading from ILK to Rac-1 activation. However, expression of constitutively active Rac only partially restores the spreading defects of ILK-depleted cells, suggesting that an additional ILK-dependent signal is required for cell spreading.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. p21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase.

    PubMed

    Barrows, Douglas; Schoenfeld, Sarah M; Hodakoski, Cindy; Silkov, Antonina; Honig, Barry; Couvillon, Anthony; Shymanets, Aliaksei; Nürnberg, Bernd; Asara, John M; Parsons, Ramon

    2015-11-27

    Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 2 (PREX2) is a guanine nucleotide exchange factor (GEF) for the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase, facilitating the exchange of GDP for GTP on Rac1. GTP-bound Rac1 then activates its downstream effectors, including p21-activated kinases (PAKs). PREX2 and Rac1 are frequently mutated in cancer and have key roles within the insulin-signaling pathway. Rac1 can be inactivated by multiple mechanisms; however, negative regulation by insulin is not well understood. Here, we show that in response to being activated after insulin stimulation, Rac1 initiates its own inactivation by decreasing PREX2 GEF activity. Following PREX2-mediated activation of Rac1 by the second messengers PIP3 or Gβγ, we found that PREX2 was phosphorylated through a PAK-dependent mechanism. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. Cell fractionation experiments also revealed that phosphorylation prevented PREX2 from localizing to the cellular membrane. Furthermore, the onset of insulin-induced phosphorylation of PREX2 was delayed compared with AKT. Altogether, we propose that second messengers activate the Rac1 signal, which sets in motion a cascade whereby PAKs phosphorylate and negatively regulate PREX2 to decrease Rac1 activation. This type of regulation would allow for transient activation of the PREX2-Rac1 signal and may be relevant in multiple physiological processes, including diseases such as diabetes and cancer when insulin signaling is chronically activated.

  3. p21-activated Kinases (PAKs) Mediate the Phosphorylation of PREX2 Protein to Initiate Feedback Inhibition of Rac1 GTPase*

    PubMed Central

    Barrows, Douglas; Schoenfeld, Sarah M.; Hodakoski, Cindy; Silkov, Antonina; Honig, Barry; Couvillon, Anthony; Shymanets, Aliaksei; Nürnberg, Bernd; Asara, John M.; Parsons, Ramon

    2015-01-01

    Phosphatidylinositol 3,4,5-trisphosphate (PIP3)-dependent Rac exchanger 2 (PREX2) is a guanine nucleotide exchange factor (GEF) for the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase, facilitating the exchange of GDP for GTP on Rac1. GTP-bound Rac1 then activates its downstream effectors, including p21-activated kinases (PAKs). PREX2 and Rac1 are frequently mutated in cancer and have key roles within the insulin-signaling pathway. Rac1 can be inactivated by multiple mechanisms; however, negative regulation by insulin is not well understood. Here, we show that in response to being activated after insulin stimulation, Rac1 initiates its own inactivation by decreasing PREX2 GEF activity. Following PREX2-mediated activation of Rac1 by the second messengers PIP3 or Gβγ, we found that PREX2 was phosphorylated through a PAK-dependent mechanism. PAK-mediated phosphorylation of PREX2 reduced GEF activity toward Rac1 by inhibiting PREX2 binding to PIP3 and Gβγ. Cell fractionation experiments also revealed that phosphorylation prevented PREX2 from localizing to the cellular membrane. Furthermore, the onset of insulin-induced phosphorylation of PREX2 was delayed compared with AKT. Altogether, we propose that second messengers activate the Rac1 signal, which sets in motion a cascade whereby PAKs phosphorylate and negatively regulate PREX2 to decrease Rac1 activation. This type of regulation would allow for transient activation of the PREX2-Rac1 signal and may be relevant in multiple physiological processes, including diseases such as diabetes and cancer when insulin signaling is chronically activated. PMID:26438819

  4. Tiam1 Regulates the Wnt/Dvl/Rac1 Signaling Pathway and the Differentiation of Midbrain Dopaminergic Neurons

    PubMed Central

    Čajánek, Lukáš; Ganji, Ranjani Sri; Henriques-Oliveira, Catarina; Theofilopoulos, Spyridon; Koník, Peter

    2013-01-01

    Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are poorly understood. Here, we present the molecular and functional characterization of a signaling pathway downstream of Wnt5a, the Wnt/Dvl/Rac1 pathway. First, we characterize the interaction between Rac1 and Dvl and identify the N-terminal part of Dvl3 as necessary for Rac1 binding. Next, we show that Tiam1, a Rac1 guanosine exchange factor (GEF), is expressed in the ventral midbrain, interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Dvl- or Wnt5a-induced activation of Rac1. Moreover, we show that Wnt5a promotes whereas casein kinase 1 (CK1), a negative regulator of the Wnt/Dvl/Rac1 pathway, abolishes the interactions between Dvl and Tiam1. Finally, using ventral midbrain neurosphere cultures, we demonstrate that the generation of DA neurons in culture is impaired after Tiam1 knockdown, indicating that Tiam1 is required for midbrain DA differentiation. In summary, our data identify Tiam1 as a novel regulator of DA neuron development and as a Dvl-associated and Rac1-specific GEF acting in the Wnt/Dvl/Rac1 pathway. PMID:23109420

  5. Frictional Characterization of Chemical-Mechanical Polishing Pad Surface and Diamond Conditioner Wear

    NASA Astrophysics Data System (ADS)

    Yamada, Yohei; Kawakubo, Masanori; Hirai, Osamu; Konishi, Nobuhiro; Kurokawa, Syuhei; Doi, Toshiro

    2008-08-01

    We evaluated a contact metrology instrument used in chemical-mechanical polishing (CMP) systems for high-volume manufacture and examined in situ coefficient of friction (COF) monitoring to identify the tribology of CMP, and subsequently to determine the useful lifespan of consumables. The results showed that the direct measurement of the wear of the pad allowed for an accurate determination of both pad thickness and the ideal time to replace the pad and conditioner disk based on pad wear rate. We also presented a clear correlation between the working grid area of the conditioner disk and the tribological behavior of the pad break-in procedure, leading to the result showing that the variation in tungsten film removal rate decreased as the working grid density of the conditioner disk increased. This study has proven the effectiveness of measuring friction force for better CMP control.

  6. 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.

  7. 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.

  8. Rac2 is involved in bleomycin-induced lung inflammation leading to pulmonary fibrosis

    PubMed Central

    2014-01-01

    Background Pulmonary fibrotic diseases induce significant morbidity and mortality, for which there are limited therapeutic options available. Rac2, a ras-related guanosine triphosphatase expressed mainly in hematopoietic cells, is a crucial molecule regulating a diversity of mast cell, macrophage, and neutrophil functions. All these cell types have been implicated in the development of pulmonary fibrosis in a variety of animal models. For the studies described here we hypothesized that Rac2 deficiency protects mice from bleomycin-induced pulmonary fibrosis. Methods To determine the role of Rac2 in pulmonary fibrosis we used a bleomycin-induced mouse model. Anesthetized C57BL/6 wild type and rac2 -/- mice were instilled intratracheally with bleomycin sulphate (1.25 U/Kg) or saline as control. Bronchoalveolar lavage (BAL) samples were collected at days 3 and 7 of treatment and analyzed for matrix metalloproteinases (MMPs). On day 21 after bleomycin treatment, we measured airway resistance and elastance in tracheotomized animals. Lung sections were stained for histological analysis, while homogenates were analyzed for hydroxyproline and total collagen content. Results BLM-treated rac2 -/- mice had reduced MMP-9 levels in the BAL on day 3 and reduced neutrophilia and TNF and CCL3/MIP-1α levels in the BAL on day 7 compared to BLM-treated WT mice. We also showed that rac2 -/- mice had significantly lower mortality (30%) than WT mice (70%) at day 21 of bleomycin treatment. Lung function was diminished in bleomycin-treated WT mice, while it was unaffected in bleomycin-treated rac2 -/- mice. Histological analysis of inflammation and fibrosis as well as collagen and hydroxyproline content in the lungs did not show significant differences between BLM-treated rac2 -/- and WT and mice that survived to day 21. Conclusion Rac2 plays an important role in bleomycin-induced lung injury. It is an important signaling molecule leading to BLM-induced mortality and it also mediates the

  9. Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Rac1.

    PubMed

    Wittmann, Torsten; Bokoch, Gary M; Waterman-Storer, Clare M

    2004-02-13

    In the leading edge of migrating cells, a subset of microtubules exhibits net growth in a Rac1- and p21-activated kinase-dependent manner. Here, we explore the possibility of whether phosphorylation and inactivation of the microtubule-destabilizing protein Op18/stathmin could be a mechanism regulating microtubule dynamics downstream of Rac1 and p21-activated kinases. We find that, in vitro, Pak1 phosphorylates Op18/stathmin specifically at serine 16 and inactivates its catastrophe promoting activity in biochemical and time lapse microscopy microtubule assembly assays. Furthermore, phosphorylation of either serine 16 or 63 is sufficient to inhibit Op18/stathmin in vitro. In cells, the microtubule-destabilizing effect of an excess of Op18/stathmin can be partially overcome by expression of constitutively active Rac1(Q61L), which is dependent on Pak activity, suggesting that the microtubule cytoskeleton can be regulated through inactivation of Op18/stathmin downstream of Rac1 and Pak in vivo. However, in vivo, Pak1 activity alone is not sufficient to phosphorylate Op18, indicating that additional pathways downstream of Rac1 are required for Op18 regulation.

  10. 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

  11. 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

  12. Defective Rac-mediated proliferation and survival after targeted mutation of the β1 integrin cytodomain

    PubMed Central

    Hirsch, Emilio; Barberis, Laura; Brancaccio, Mara; Azzolino, Ornella; Xu, Dazhong; Kyriakis, John M.; Silengo, Lorenzo; Giancotti, Filippo G.; Tarone, Guido; Fässler, Reinhard; Altruda, Fiorella

    2002-01-01

    Cell matrix adhesion is required for cell proliferation and survival. Here we report that mutation by gene targeting of the cytoplasmic tail of β1 integrin leads to defective proliferation and survival both in vivo and in vitro. Primary murine embryonic fibroblasts (MEFs) derived from mutant homozygotes display defective cell cycle coupled to impaired activation of the FAK-PI3K-Akt and Rac-JNK signaling pathways. Expression in homozygous MEFs of a constitutively active form of Rac is able to rescue proliferation, survival, and JNK activation. Moreover, although showing normal Erk phosphorylation, mutant cells fail to display Erk nuclear translocation upon fibronectin adhesion. However, expression of the constitutively activated form of Rac restores Erk nuclear localization, suggesting that adhesion-dependent Rac activation is necessary to integrate signals directed to promote MAPK activity. Altogether, our data provide the evidence for an epistatic interaction between the β1 integrin cytoplasmic domain and Rac, and indicate that this anchorage-dependent signaling pathway is crucial for cell growth control. PMID:11980921

  13. TIPE1 induces apoptosis by negatively regulating Rac1 activation in hepatocellular carcinoma cells.

    PubMed

    Zhang, Z; Liang, X; Gao, L; Ma, H; Liu, X; Pan, Y; Yan, W; Shan, H; Wang, Z; Chen, Y H; Ma, C

    2015-05-14

    TIPE1 (tumor necrosis factor-α-induced protein 8-like 1 or TNFAIP8L1) is a newly identified member of the TIPE (TNFAIP8) family, which play roles in regulating cell death. However, the biologic functions of TIPE1 in physiologic and pathologic conditions are largely unknown. Here, we report the roles of TIPE1 in hepatocellular carcinoma (HCC). Evaluated by immunohistochemical staining, HCC tissues showed significantly downregulated TIPE1 expression compared with adjacent non-tumor tissues, which positively correlated with tumor pathologic grades and patient survival. Using a homograft tumor model in Balb/c mice, we discovered that TIPE1 significantly diminished the growth and tumor weight of murine liver cancer homografts. Consistently, TIPE1 inhibited both cell growth and colony formation ability of cultured HCC cell lines, which was further identified to be due to TIPE1-inducing apoptosis in a caspase-independent, necrostatin-1 (Nec-1)-insensitive manner. Furthermore, mechanistic investigations revealed that TIPE1 interacted with Rac1, and inhibited the activation of Rac1 and its downstream p65 and c-Jun N-terminal kinase pathway. Moreover, overexpression of constitutively active Rac1 partially rescued the apoptosis induced by TIPE1, and Rac1 knockdown significantly restored the deregulated cell growth induced by TIPE1 small interfering RNA. Our findings revealed that TIPE1 induced apoptosis in HCC cells by negatively regulating Rac1 pathway, and loss of TIPE1 might be a new prognostic indicator for HCC patients.

  14. RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border

    PubMed Central

    Marcos-Ramiro, Beatriz; García-Weber, Diego; Barroso, Susana; Feito, Jorge; Ortega, María C.; Cernuda-Morollón, Eva; Reglero-Real, Natalia; Fernández-Martín, Laura; Durán, Maria C.; Alonso, Miguel A.; Correas, Isabel; Cox, Susan; Ridley, Anne J.

    2016-01-01

    Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new proteins essential to the human endothelial inflammatory response, we have found that the endosomal GTPase RhoB is up-regulated in response to inflammatory cytokines and expressed in the endothelium of some chronically inflamed tissues. We show that although RhoB and the related RhoA and RhoC play additive and redundant roles in various aspects of endothelial barrier function, RhoB specifically inhibits barrier restoration after acute cell contraction by preventing plasma membrane extension. During barrier restoration, RhoB trafficking is induced between vesicles containing RhoB nanoclusters and plasma membrane protrusions. The Rho GTPase Rac1 controls membrane spreading and stabilizes endothelial barriers. We show that RhoB colocalizes with Rac1 in endosomes and inhibits Rac1 activity and trafficking to the cell border during barrier recovery. Inhibition of endosomal trafficking impairs barrier reformation, whereas induction of Rac1 translocation to the plasma membrane accelerates it. Therefore, RhoB-specific regulation of Rac1 trafficking controls endothelial barrier integrity during inflammation. PMID:27138256

  15. 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

  16. Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes.

    PubMed

    Ram, Rashmi; Wescott, Andrew P; Varandas, Katherine; Dirksen, Robert T; Blaxall, Burns C

    2014-01-01

    Mena, a member of the Ena/VASP family of actin regulatory proteins, modulates microfilaments and interacts with cytoskeletal proteins associated with heart failure. Mena is localized at the intercalated disc (ICD) of adult cardiac myocytes, colocalizing with numerous cytoskeletal proteins. Mena's role in the maintainence of mechanical myocardial stability at the cardiomyocyte ICD remains unknown. We hypothesized that Mena may modulate signals from the sarcolemma to the actin cytoskeleton at the ICD to regulate the expression and localization of connexin 43 (Cx43). The small GTPase Rac1 plays a pivotal role in the regulation of actin cytoskeletal reorganization and mediating morphological and transcriptional changes in cardiomyocytes. We found that Mena is associated with active Rac1 in cardiomyocytes and that RNAi knockdown of Mena increased Rac1 activity significantly. Furthermore, Mena knockdown increased Cx43 expression and altered Cx43 localization and trafficking at the ICD, concomitant with faster intercellular communication, as assessed by dye transfer between cardiomyocyte pairs. In mice overexpressing constitutively active Rac1, left ventricular Mena expression was increased significantly, concomitant with lateral redistribution of Cx43. These results suggest that Mena is a critical regulator of the ICD and is required for normal localization of Cx43 in part via regulation of Rac1.

  17. RAC1 GTPase plays an important role in γ-irradiation induced G2/M checkpoint activation

    PubMed Central

    2012-01-01

    Introduction In response to gamma-irradiation (IR)-induced double-strand DNA breaks, cells undergo cell-cycle arrest, allowing time for DNA repair before reentering the cell cycle. G2/M checkpoint activation involves activation of ataxia telangiectasia mutated (ATM)/ATM- and rad3-related (ATR) kinases and inhibition of Cdc25 phosphatases, resulting in inhibition of Cdc2 kinase and subsequent G2/M cell-cycle arrest. Previous studies from our laboratory showed that the G2/M checkpoint activation after IR exposure of MCF-7 breast cancer cells is dependent on the activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signaling. In the present studies, we investigated the role of Ras-related C3 botulinum toxin substrate 1 (Rac1) guanosine triphosphatase (GTPase) in IR-induced G2/M checkpoint response and ERK1/2 activation, as well as in cell survival after IR. Methods With Rac1-specific inhibitor, dominant negative mutant Rac1 (N17Rac1) and specific small interfering RNA, the effect of Rac1 on IR-induced G2/M checkpoint response and ERK1/2 activation was examined in human breast cancer cells. In addition, the effect of Rac1 on cell survival after irradiation was assessed by using Rac1-specific inhibitor. Results IR exposure of MCF-7 breast cancer cells was associated with a marked activation of Rac1 GTPase. Furthermore, inhibition of Rac1 by using specific inhibitor, dominant-negative Rac1 mutant, or specific siRNA resulted in attenuation of IR-induced G2/M arrest and concomitant diminution of IR-induced activation of ATM, ATR, Chk1, and Chk2 kinases, as well as phosphorylation of Cdc2-Tyr15. Moreover, Rac1 inhibition or decreased Rac1 expression also abrogated IR-induced phosphorylation of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) and ERK1/2. Ultimately, inhibition of Rac1 markedly increased cellular sensitivity to IR exposure, which involves induction of apoptosis. Conclusion Studies in this report suggest that Rac1 GTPase plays an

  18. Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells.

    PubMed

    Naud, Nathalie; Touré, Aminata; Liu, Jianfeng; Pineau, Charles; Morin, Laurence; Dorseuil, Olivier; Escalier, Denise; Chardin, Pierre; Gacon, Gérard

    2003-05-15

    The male-germ-cell Rac GTPase-activating protein gene (MgcRacGAP) was initially described as a human RhoGAP gene highly expressed in male germ cells at spermatocyte stage, but exhibits significant levels of expression in most cell types. In somatic cells, MgcRacGAP protein was found to both concentrate in the midzone/midbody and be required for cytokinesis. As a RhoGAP, MgcRacGAP has been proposed to down-regulate RhoA, which is localized to the cleavage furrow and midbody during cytokinesis. Due to embryonic lethality in MgcRacGAP -null mutant mice and to the lack of an in vitro model of spermatogenesis, nothing is known regarding the role and mode of action of MgcRacGAP in male germ cells. We have analysed the expression, subcellular localization and molecular interactions of MgcRacGAP in male germ cells. Whereas MgcRacGAP was found only in spermatocytes and early spermatids, the widespread RhoGTPases RhoA, Rac1 and Cdc42 (which are, to various extents, in vitro substrates for MgcRacGAP activity) were, surprisingly, not detected at these stages. In contrast, Rnd2, a Rho family GTPase-deficient G-protein was found to be co-expressed with MgcRacGAP in spermatocytes and spermatids. MgcRacGAP was detected in the midzone of meiotic cells, but also, unexpectedly, in the Golgi-derived pro-acrosomal vesicle, co-localizing with Rnd2. In addition, a stable Rnd2-MgcRacGAP molecular complex could be evidenced by glutathione S-transferase pull-down and co-immunoprecipitation experiments. We conclude that Rnd2 is a probable physiological partner of MgcRacGAP in male germ cells and we propose that MgcRacGAP, and, quite possibly, other RhoGAPs, may participate in signalling pathways involving Rnd family proteins.

  19. The insert region of the Rac GTPases is dispensable for activation of superoxide-producing NADPH oxidases.

    PubMed

    Miyano, Kei; Koga, Hirofumi; Minakami, Reiko; Sumimoto, Hideki

    2009-08-13

    Rac1 and Rac2, which belong to the Rho subfamily of Ras-related GTPases, play an essential role in activation of gp91phox/Nox2 (cytochrome b-245, beta polypeptide; also known as Cybb), the catalytic core of the superoxide-producing NADPH oxidase in phagocytes. Rac1 also contributes to activation of the non-phagocytic oxidases Nox1 (NADPH oxidase 1) and Nox3 (NADPH oxidase 3), each related closely to gp91phox/Nox2. It has remained controversial whether the insert region of Rac (amino acids 123-135), unique to the Rho subfamily proteins, is involved in gp91phox/Nox2 activation. In the present study we show that removal of the insert region from Rac1 neither affects activation of gp91phox/Nox2, which is reconstituted under cell-free and whole-cell conditions, nor blocks its localization to phagosomes during ingestion of IgG-coated beads by macrophage-like RAW264.7 cells. The insert region of Rac2 is also dispensable for gp91phox/Nox2 activation at the cellular level. Although Rac2, as well as Rac1, is capable of enhancing superoxide production by Nox1 and Nox3, the enhancements by the two GTPases are both independent of the insert region. We also demonstrate that Rac3, a third member of the Rac family in mammals, has an ability to activate the three oxidases and that the activation does not require the insert region. Thus the insert region of the Rac GTPases does not participate in regulation of the Nox family NADPH oxidases.

  20. Induction of Non-Apoptotic Cell Death by Activated Ras Requires Inverse Regulation of Rac1 and Arf6

    PubMed Central

    Bhanot, Haymanti; Young, Ashley M.; Overmeyer, Jean H.; Maltese, William A.

    2010-01-01

    Methuosis is a unique form of non-apoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. Methuosis can be induced in glioblastoma cells by expression of constitutively active Ras. This study identifies the small GTPases, Rac1 and Arf6, and the Arf6 GTPase-activating-protein, GIT1, as key downstream components of the signaling pathway underlying Ras-induced methuosis. The extent to which graded expression of active H-Ras(G12V) triggers cytoplasmic vacuolization correlates with the amount of endogenous Rac1 in the active GTP state. Blocking Rac1 activation with the specific Rac inhibitor, EHT 1864, or co-expression of dominant-negative Rac1(T17N), prevents the accumulation of vacuoles induced by H-Ras(G12V). Coincident with Rac1 activation, H-Ras(G12V) causes a decrease in the amount of active Arf6, a GTPase that functions in recycling of clathrin-independent endosomes. The effect of H-Ras(G12V) on Arf6 is blocked by EHT 1864, indicating that the decrease in Arf6-GTP is directly linked to activation of Rac1. Constitutively active Rac1(G12V) interacts with GIT1 in immunoprecipitation assays. Ablation of GIT1 by shRNA prevents the decrease in active Arf6, inhibits vacuolization, and prevents loss of cell viability in cells expressing Rac1(G12V). Together the results suggest that perturbations of endosome morphology associated with Ras-induced methuosis are due to downstream activation of Rac1, combined with reciprocal inactivation of Arf6. The latter appears to be mediated through Rac1 stimulation of GIT1. Further insights into this pathway could suggest opportunities for induction of methuosis in cancers that are resistant to apoptotic cell death. PMID:20713492

  1. miR-101 inhibits cell proliferation by targeting Rac1 in papillary thyroid carcinoma

    PubMed Central

    LIN, XIAOJIE; GUAN, HONGYU; LI, HAI; LIU, LIEHUA; LIU, JUAN; WEI, GUOHONG; HUANG, ZHIMIN; LIAO, ZHIHONG; LI, YANBING

    2014-01-01

    Accumulating evidence suggests that some microRNAs (miRNAs) are involved in papillary thyroid carcinoma (PTC) progression. However, it remains necessary to elucidate the underlying molecular mechanisms involved. In the present study, we investigated the role of microRNA-101 (miR-101) in PTC via targeting of Ras-related C3 botulinum toxin substrate 1 (Rac1). The results showed that miR-101 was significantly downregulated in PTC tissues compared with adjacent normal tissues. Restoration of miR-101 expression significantly inhibited cell proliferation in the K1 PTC cell line. Moreover, algorithm-based and experimental strategies verified Rac1 as a direct target of miR-101 in the K1 cell line. Taken together, these findings suggest that miR-101 inhibited PTC growth via the downregulation of Rac1 expression, providing a better understanding of miRNA-modulated signaling networks for future cancer therapeutics. PMID:24649082

  2. p95-APP1 links membrane transport to Rac-mediated reorganization of actin.

    PubMed

    Di Cesare, A; Paris, S; Albertinazzi, C; Dariozzi, S; Andersen, J; Mann, M; Longhi, R; de Curtis, I

    2000-08-01

    Motility requires protrusive activity at the cellular edge, where Rho family members regulate actin dynamics. Here we show that p95-APP1 (ArfGAP-putative, Pix-interacting, paxillin-interacting protein 1), a member of the GIT1/PKL family, is part of a complex that interacts with Rac. Wild-type and truncated p95-APP1 induce actin-rich protrusions mediated by Rac and ADP-ribosylation factor 6 (Arf6). Distinct p95-APP1-derived polypeptides have different distributions, indicating that p95-APP1 cycles between the cell surface and endosomes. Our results show that p95-APP1 functionally interacts with Rac and localizes to endosomal compartments, thus identifying p95-APP1 as a molecular link between actin organization, adhesion, and membrane transport during cell motility.

  3. Coronin7 regulates WASP and SCAR through CRIB mediated interaction with Rac proteins

    PubMed Central

    Swaminathan, Karthic; Stumpf, Maria; Müller, Rolf; Horn, Anna-Carolin; Schmidbauer, Julia; Eichinger, Ludwig; Müller-Taubenberger, Annette; Faix, Jan; Noegel, Angelika A.

    2015-01-01

    Coronin7 (CRN7) stabilizes F-actin and is a regulator of processes associated with the actin cytoskeleton. Its loss leads to defects in phagocytosis, motility and development. It harbors a CRIB (Cdc42- and Rac-interactive binding) domain in each of its WD repeat domains which bind to Rac GTPases preferably in their GDP-loaded forms. Expression of wild type CRN7 in CRN7 deficient cells rescued these defects, whereas proteins with mutations in the CRIB motifs which were associated with altered Rac binding were effective to varying degrees. The presence of one functional CRIB was sufficient to reestablish phagocytosis, cell motility and development. Furthermore, by molecular modeling and mutational analysis we identified the contact regions between CRN7 and the GTPases. We also identified WASP, SCAR and PAKa as downstream effectors in phagocytosis, development and cell surface adhesion, respectively, since ectopic expression rescued these functions. PMID:26411260

  4. GEFs and Rac GTPases control directional specificity of neurite extension along the anterior–posterior axis

    PubMed Central

    Zheng, Chaogu; Diaz-Cuadros, Margarete; Chalfie, Martin

    2016-01-01

    Although previous studies have identified many extracellular guidance molecules and intracellular signaling proteins that regulate axonal outgrowth and extension, most were conducted in the context of unidirectional neurite growth, in which the guidance cues either attract or repel growth cones. Very few studies addressed how intracellular signaling molecules differentially specify bidirectional outgrowth. Here, using the bipolar PLM neurons in Caenorhabditis elegans, we show that the guanine nucleotide exchange factors (GEFs) UNC-73/Trio and TIAM-1 promote anterior and posterior neurite extension, respectively. The Rac subfamily GTPases act downstream of the GEFs; CED-10/Rac1 is activated by TIAM-1, whereas CED-10 and MIG-2/RhoG act redundantly downstream of UNC-73. Moreover, these two pathways antagonize each other and thus regulate the directional bias of neuritogenesis. Our study suggests that directional specificity of neurite extension is conferred through the intracellular activation of distinct GEFs and Rac GTPases. PMID:27274054

  5. The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner

    PubMed Central

    Vikis, Haris G.; Li, Weiquan; He, Zhigang; Guan, Kun-Liang

    2000-01-01

    Semaphorin molecules serve as axon guidance signals that regulate the navigation of neuronal growth cones. Semaphorins have also been implicated in other biological processes, including the immune response. Plexins, acting either alone or in complex with neuropilins, have recently been identified as functional semaphorin receptors. However, the mechanisms of signal transduction by plexins remain largely unknown. We have demonstrated a direct interaction between plexin-B1 and activated Rac. Rac specifically interacts with the cytosolic domain of plexin-B1, but not with that of plexin-A3 or -C1. Neither RhoA nor Cdc42 interacts with plexin-B1, indicating that the Rac/plexin-B1 interaction is highly specific. The binding of GTP and the integrity of the Rac effector domain are required for the interaction with plexin-B1. Furthermore, we have identified that a Cdc42/Rac interactive binding (CRIB) motif in the cytosolic domain of plexin-B1 is essential for its interaction with active Rac. We have also observed that the semaphorin CD100, a ligand for plexin-B1, stimulates the interaction between plexin-B1 and active Rac. Our results support a model by which activated Rac plays a role in mediating semaphorin signals, resulting in reorganization of actin cytoskeletal structure. PMID:11035813

  6. Vav1 and Rac Control Chemokine-promoted T Lymphocyte Adhesion Mediated by the Integrin α4β1D⃞

    PubMed Central

    García-Bernal, David; Wright, Natalia; Sotillo-Mallo, Elena; Nombela-Arrieta, César; Stein, Jens V.; Bustelo, Xosé R.; Teixidó, Joaquin

    2005-01-01

    The chemokine CXCL12 promotes T lymphocyte adhesion mediated by the integrin α4β1. CXCL12 activates the GTPase Rac, as well as Vav1, a guanine-nucleotide exchange factor for Rac, concomitant with up-regulation of α4β1-dependent adhesion. Inhibition of CXCL12-promoted Rac and Vav1 activation by transfection of dominant negative Rac or Vav1 forms, or by transfection of their siRNA, remarkably impaired the increase in T lymphocyte attachment to α4β1 ligands in response to this chemokine. Importantly, inhibition of Vav1 expression by RNA interference resulted in a blockade of Rac activation in response to CXCL12. Adhesions in flow chambers and soluble binding assays using these transfectants indicated that initial ligand binding and adhesion strengthening mediated by α4β1 were dependent on Vav1 and Rac activation by CXCL12. Finally, CXCL12-promoted T-cell transendothelial migration involving α4β1-mediated adhesion was notably inhibited by expression of dominant negative Vav1 and Rac. These results indicate that activation of Vav1-Rac signaling pathway by CXCL12 represents an important inside-out event controlling efficient up-regulation of α4β1-dependent T lymphocyte adhesion. PMID:15872091

  7. P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration.

    PubMed

    Hernández-Negrete, Ivette; Carretero-Ortega, Jorge; Rosenfeldt, Hans; Hernández-García, Ricardo; Calderón-Salinas, J Victor; Reyes-Cruz, Guadalupe; Gutkind, J Silvio; Vázquez-Prado, José

    2007-08-10

    Polarized cell migration results from the transduction of extra-cellular cues promoting the activation of Rho GTPases with the intervention of multidomain proteins, including guanine exchange factors. P-Rex1 and P-Rex2 are Rac GEFs connecting Gbetagamma and phosphatidylinositol 3-kinase signaling to Rac activation. Their complex architecture suggests their regulation by protein-protein interactions. Novel mechanisms of activation of Rho GTPases are associated with mammalian target of rapamycin (mTOR), a serine/threonine kinase known as a central regulator of cell growth and proliferation. Recently, two independent multiprotein complexes containing mTOR have been described. mTORC1 links to the classical rapamycin-sensitive pathways relevant for protein synthesis; mTORC2 links to the activation of Rho GTPases and cytoskeletal events via undefined mechanisms. Here we demonstrate that P-Rex1 and P-Rex2 establish, through their tandem DEP domains, interactions with mTOR, suggesting their potential as effectors in the signaling of mTOR to Rac activation and cell migration. This possibility was consistent with the effect of dominant-negative constructs and short hairpin RNA-mediated knockdown of P-Rex1, which decreased mTOR-dependent leucine-induced activation of Rac and cell migration. Rapamycin, a widely used inhibitor of mTOR signaling, did not inhibit Rac activity and cell migration induced by leucine, indicating that P-Rex1, which we found associated to both mTOR complexes, is only active when in the mTORC2 complex. mTORC2 has been described as the catalytic complex that phosphorylates AKT/PKB at Ser-473 and elicits activation of Rho GTPases and cytoskeletal reorganization. Thus, P-Rex1 links mTOR signaling to Rac activation and cell migration.

  8. 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

  9. 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

  10. Simulation Models of Leaf Area Index and Yield for Cotton Grown with Different Soil Conditioners.

    PubMed

    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.

  11. 2-in-1 shampoo technology: state-of-the-art shampoo and conditioner in one.

    PubMed

    Rushton, H; Gummer, C L; Flasch, H

    1994-01-01

    Consumers have expressed a need for cleaning and conditioning in one step. Conventional shampoo technology using anionic surfactants and cationic conditioners results in charge interaction and complexing of the ingredients. Neither shampoo nor conditioners achieves the desired result. The successful solution was to incorporate charge neutral dimethicone conditioning ingredients, suspended as microfine droplets within complex crystal lattices, into anionic surfactant shampoo technology. The same solution has also been applied to amphoteric surfactant systems. This provides complete cleaning, and hair conditioning fully equal to separate conditioners without the problems of sebum interactions and conditioner build-up. This was achieved by keeping the dimethicone in suspension throughout the shampoo process. During rinsing, excess water breaks the crystalline lattice and allows deposition of the dimethicone droplets onto the hair. Full cleaning and conditioning are, therefore, achieved in one application. Dimethicone build-up is not encountered as subsequent washes first remove soil and previously deposited dimethicone. Neither do neutral dimethicones show any reactions with sebum. The development of effective 2-in-1 technology has had a major impact on shampoo technology and consumer habits and practices. This has significantly changed the way consumers care for their hair.

  12. 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.

  13. 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.

  14. 21 CFR 872.3765 - Pit and fissure sealant and conditioner.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 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... depressions (faults in the enamel) in the biting surfaces of teeth to prevent cavities. (b)...

  15. 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... depressions (faults in the enamel) in the biting surfaces of teeth to prevent cavities. (b)...

  16. 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... depressions (faults in the enamel) in the biting surfaces of teeth to prevent cavities. (b)...

  17. 21 CFR 872.3765 - Pit and fissure sealant and conditioner.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 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... depressions (faults in the enamel) in the biting surfaces of teeth to prevent cavities. (b)...

  18. 21 CFR 872.3765 - Pit and fissure sealant and conditioner.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 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... depressions (faults in the enamel) in the biting surfaces of teeth to prevent cavities. (b)...

  19. 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)

  20. 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

  1. A critical role of the small GTPase Rac1 in Akt2-mediated GLUT4 translocation in mouse skeletal muscle.

    PubMed

    Takenaka, Nobuyuki; Izawa, Rumi; Wu, Junyuan; Kitagawa, Kaho; Nihata, Yuma; Hosooka, Tetsuya; Noguchi, Tetsuya; Ogawa, Wataru; Aiba, Atsu; Satoh, Takaya

    2014-03-01

    Insulin promotes glucose uptake in skeletal muscle by inducing the translocation of the glucose transporter GLUT4 to the plasma membrane. The serine/threonine kinase Akt2 has been implicated as a key regulator of this insulin action. However, the mechanisms whereby Akt2 regulates multiple steps of GLUT4 translocation remain incompletely understood. Recently, the small GTPase Rac1 has been identified as a skeletal muscle-specific regulator of insulin-stimulated glucose uptake. Here, we show that Rac1 is a critical downstream component of the Akt2 pathway in mouse skeletal muscle as well as cultured myocytes. GLUT4 translocation induced by constitutively activated Akt2 was totally dependent on the expression of Rac1 in L6 myocytes. Moreover, we observed the activation of Rac1 when constitutively activated Akt2 was ectopically expressed. Constitutively activated Akt2-triggered Rac1 activation was diminished by knockdown of FLJ00068, a guanine nucleotide exchange factor for Rac1. Knockdown of Akt2, on the other hand, markedly reduced Rac1 activation by a constitutively activated mutant of phosphoinositide 3-kinase. In mouse skeletal muscle, constitutively activated mutants of Akt2 and phosphoinositide 3-kinase, when ectopically expressed, induced GLUT4 translocation. Muscle-specific rac1 knockout markedly diminished Akt2- or phosphoinositide 3-kinase-induced GLUT4 translocation, highlighting a crucial role of Rac1 downstream of Akt2. Taken together, these results strongly suggest a novel regulatory link between Akt2 and Rac1 in insulin-dependent signal transduction leading to glucose uptake in skeletal muscle.

  2. Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer.

    PubMed

    Rosenblatt, Adena E; Garcia, Maria Ines; Lyons, Leah; Xie, Yingqiu; Maiorino, Carol; Désiré, Laurent; Slingerland, Joyce; Burnstein, Kerry L

    2011-04-01

    Rac1, a Rho GTPase, modulates diverse cellular processes and is hyperactive in some cancers. Estrogen receptor-alpha (ERα) in concert with intracellular signaling pathways regulates genes associated with cell proliferation, tumor development, and breast cancer cell survival. Therefore, we examined the possibility of Rac1 and ERα crosstalk in breast cancer cells. We found that Rac1 enhanced ERα transcriptional activity in breast cancer cells. Vav3, a Rho guanine nucleotide exchange factor that activates Rac1, was an upstream mediator, and P21/Cdc42/Rac1 activating kinase-1 (Pak-1) was a downstream effector of Rac1 enhancement of ERα activity. These results suggest that Rac1 may prove to be a therapeutic target. To test this hypothesis, we used a small molecule Rac inhibitor, EHT 1864, and found that EHT 1864 inhibited ERα transcriptional activity. Furthermore, EHT 1864 inhibited estrogen-induced cell proliferation in breast cancer cells and decreased tamoxifen-resistant breast cancer cell growth. EHT 1864 decreased activity of the promoter of the ERα gene resulting in down-regulation of ERα mRNA and protein levels. Therefore, ERα down-regulation by EHT 1864 is the likely mechanism of EHT 1864-mediated inhibition of ERα activity and estrogen-stimulated breast cancer cell proliferation. Since ERα plays a critical role in the pathogenesis of breast cancer and the Rac inhibitor EHT 1864 down-regulates ERα expression and breast cancer cell proliferation, further investigation of the therapeutic potential of Rac1 targeting in the treatment of breast cancer is warranted.

  3. The Crystal Structure of the Plant Small GTPase OsRac1 Reveals Its Mode of Binding to NADPH Oxidase*

    PubMed Central

    Kosami, Ken-ichi; Ohki, Izuru; Nagano, Minoru; Furuita, Kyoko; Sugiki, Toshihiko; Kawano, Yoji; Kawasaki, Tsutomu; Fujiwara, Toshimichi; Nakagawa, Atsushi; Shimamoto, Ko; Kojima, Chojiro

    2014-01-01

    Rac/Rop proteins are Rho-type small GTPases that act as molecular switches in plants. Recent studies have identified these proteins as key components in many major plant signaling pathways, such as innate immunity, pollen tube growth, and root hair formation. In rice, the Rac/Rop protein OsRac1 plays an important role in regulating the production of reactive oxygen species (ROS) by the NADPH oxidase OsRbohB during innate immunity. However, the molecular mechanism by which OsRac1 regulates OsRbohB remains unknown. Here, we report the crystal structure of OsRac1 complexed with the non-hydrolyzable GTP analog guanosine 5′-(β,γ-imido)triphosphate at 1.9 Å resolution; this represents the first active-form structure of a plant small GTPase. To elucidate the ROS production in rice cells, structural information was used to design OsRac1 mutants that displayed reduced binding to OsRbohB. Only mutations in the OsRac1 Switch I region showed attenuated interactions with OsRbohB in vitro. In particular, Tyr39 and Asp45 substitutions suppressed ROS production in rice cells, indicating that these residues are critical for interaction with and activation of OsRbohB. Structural comparison of active-form OsRac1 with AtRop9 in its GDP-bound inactive form showed a large conformational difference in the vicinity of these residues. Our results provide new insights into the molecular mechanism of the immune response through OsRac1 and the various cellular responses associated with plant Rac/Rop proteins. PMID:25128531

  4. A Rac1 GTPase is a critical factor in the immune response of shrimp (Litopenaeus vannamei) to Vibrio alginolyticus infection.

    PubMed

    Cha, Gui-Hong; Wang, Wei-Na; Peng, Ting; Huang, Ming-Zhu; Liu, Yuan

    2015-08-01

    The small GTPase Rac1 acts as a molecular switch for signal transduction that regulates various cellular functions. However, its functions in crustaceans remain unclear. In this study, a cDNA encoding a RAS GTPase (LvRac1) in the Pacific white shrimp (L. vannamei) was identified and characterized. A recombinant variant of this GTPase, rLvRac1, was expressed in the model organism P. pastoris and its expression was confirmed by mass spectrometry. Biochemical assays indicated that the recombinant protein retained GTPase activity and was expressed in all of the organism's tested tissues. Injection of the bacterium V. alginolyticus into L. vannamei induced hepatopancreatic upregulation of LvRac1 expression. Moreover, knocking down LvRac1 in vivo significantly reduced the expression of the L. vannamei p53 and Cu/Zn superoxide dismutase genes (Lvp53 and LvCu/Zn SOD, respectively) while increasing that of the galectin gene (Lvgal). Hemolymph samples from control and LvRac1-silenced L. vannamei individuals were analyzed by flow cytometry, revealing that the latter exhibited significantly reduced respiratory burst activity and total hemocyte counts. Cumulative mortality in shrimp lacking LvRac1 was significantly greater than in control groups following V. alginolyticus challenge. The silencing of LvRac1 by double-stranded RNA injection thus increased the V. alginolyticus challenge sensitivity of L. vannamei and weakened its bacterial clearance ability in vivo. Suppressing LvRac1 also promoted the upregulation of Lvp53, LvCu/ZnSOD, and Lvgal following V. alginolyticus injection. Taken together, these results suggest that LvRac1 is important in the innate immune response of shrimp to V. alginolyticus infection.

  5. 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.

  6. Keeping Cool: Use of Air Conditioning by Australians with Multiple Sclerosis

    PubMed Central

    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

  7. 76 FR 17106 - Secure Rural Schools Resource Advisory Committee (RAC) Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ..., Olustee, Florida 32072. FOR FURTHER INFORMATION CONTACT: Denise Rains, Public Services Staff Officer, 850... Forest Service Secure Rural Schools Resource Advisory Committee (RAC) Meeting AGENCY: Forest Service, U.S.D.A. ACTION: Announcement of Meeting; Federal Advisory Committee meeting to be held authorized...

  8. 44 CFR 352.23 - Functions of a Regional Assistance Committee (RAC).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 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:...

  9. 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:...

  10. 42 CFR 455.506 - Activities to be conducted by Medicaid RACs and States.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... States. 455.506 Section 455.506 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.506 Activities to be conducted by Medicaid RACs and States....

  11. 42 CFR 455.514 - Federal share of State expense of the Medicaid RAC program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... program. 455.514 Section 455.514 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.514 Federal share of State expense of the Medicaid RAC program....

  12. 42 CFR 455.514 - Federal share of State expense of the Medicaid RAC program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... program. 455.514 Section 455.514 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.514 Federal share of State expense of the Medicaid RAC program....

  13. 42 CFR 455.514 - Federal share of State expense of the Medicaid RAC program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... program. 455.514 Section 455.514 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.514 Federal share of State expense of the Medicaid RAC program....

  14. 42 CFR 455.506 - Activities to be conducted by Medicaid RACs and States.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... States. 455.506 Section 455.506 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.506 Activities to be conducted by Medicaid RACs and States....

  15. 42 CFR 455.514 - Federal share of State expense of the Medicaid RAC program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... program. 455.514 Section 455.514 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.514 Federal share of State expense of the Medicaid RAC program....

  16. 42 CFR 455.506 - Activities to be conducted by Medicaid RACs and States.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... States. 455.506 Section 455.506 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.506 Activities to be conducted by Medicaid RACs and States....

  17. 42 CFR 455.506 - Activities to be conducted by Medicaid RACs and States.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... States. 455.506 Section 455.506 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PROGRAM INTEGRITY: MEDICAID Medicaid Recovery Audit Contractors Program § 455.506 Activities to be conducted by Medicaid RACs and States....

  18. Role of Rac GTPases in Chemokine-Stimulated Breast Carcinoma Metastasis

    DTIC Science & Technology

    2008-07-01

    clinically relevant, including hypoxia, ionizing radiation and chemotherapeutic drugs. We also examined whether rhMMP9 or MDA-MB-231 conditioned medium...Interestingly, Rac1b is poorly expressed in MCF10A , a normal human breast epithelial cell line, and is undetectable in all the highly invasive breast

  19. Junctional actin assembly is mediated by Formin-like 2 downstream of Rac1

    PubMed Central

    Grikscheit, Katharina; Frank, Tanja; Wang, Ying

    2015-01-01

    Epithelial integrity is vitally important, and its deregulation causes early stage cancer. De novo formation of an adherens junction (AJ) between single epithelial cells requires coordinated, spatial actin dynamics, but the mechanisms steering nascent actin polymerization for cell–cell adhesion initiation are not well understood. Here we investigated real-time actin assembly during daughter cell–cell adhesion formation in human breast epithelial cells in 3D environments. We identify formin-like 2 (FMNL2) as being specifically required for actin assembly and turnover at newly formed cell–cell contacts as well as for human epithelial lumen formation. FMNL2 associates with components of the AJ complex involving Rac1 activity and the FMNL2 C terminus. Optogenetic control of Rac1 in living cells rapidly drove FMNL2 to epithelial cell–cell contact zones. Furthermore, Rac1-induced actin assembly and subsequent AJ formation critically depends on FMNL2. These data uncover FMNL2 as a driver for human epithelial AJ formation downstream of Rac1. PMID:25963818

  20. 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.

  1. Benefit of Mineralocorticoid Receptor Antagonism in AKI: Role of Vascular Smooth Muscle Rac1.

    PubMed

    Barrera-Chimal, Jonatan; André-Grégoire, Gwennan; Nguyen Dinh Cat, Aurelie; Lechner, Sebastian M; Cau, Jérôme; Prince, Sonia; Kolkhof, Peter; Loirand, Gervaise; Sauzeau, Vincent; Hauet, Thierry; Jaisser, Frédéric

    2017-01-13

    AKI is a frequent complication in hospitalized patients. Unfortunately, there is no effective pharmacologic approach for treating or preventing AKI. In rodents, mineralocorticoid receptor (MR) antagonism prevents AKI induced by ischemia-reperfusion (IR). We investigated the specific role of vascular MR in mediating AKI induced by IR. We also assessed the protective effect of MR antagonism in IR-induced AKI in the Large White pig, a model of human AKI. In mice, MR deficiency in smooth muscle cells (SMCs) protected against kidney IR injury. MR blockade by the novel nonsteroidal MR antagonist, finerenone, or genetic deletion of MR in SMCs associated with weaker oxidative stress production. Moreover, ischemic kidneys had higher levels of Rac1-GTP, required for NADPH oxidase activation, than sham control kidneys, and genetic deletion of Rac1 in SMCs protected against AKI. Furthermore, genetic deletion of MR in SMCs blunted the production of Rac1-GTP after IR. Pharmacologic inhibition of MR also prevented AKI induced by IR in the Large White pig. Altogether, we show that MR antagonism, or deletion of the MR gene in SMCs, limited the renal injury induced by IR through effects on Rac1-mediated MR signaling. The benefits of MR antagonism in the pig provide a rational basis for future clinical trials assessing the benefits of this approach in patients with IR-mediated AKI.

  2. MAP1B Regulates Axonal Development by Modulating Rho-GTPase Rac1 Activity

    PubMed Central

    Montenegro-Venegas, Carolina; Tortosa, Elena; Rosso, Silvana; Peretti, Diego; Bollati, Flavia; Bisbal, Mariano; Jausoro, Ignacio; Avila, Jesus; Cáceres, Alfredo

    2010-01-01

    Cultured neurons obtained from MAP1B-deficient mice have a delay in axon outgrowth and a reduced rate of axonal elongation compared with neurons from wild-type mice. Here we show that MAP1B deficiency results in a significant decrease in Rac1 and cdc42 activity and a significant increase in Rho activity. We found that MAP1B interacted with Tiam1, a guanosine nucleotide exchange factor for Rac1. The decrease in Rac1/cdc42 activity was paralleled by decreases in the phosphorylation of the downstream effectors of these proteins, such as LIMK-1 and cofilin. The expression of a constitutively active form of Rac1, cdc42, or Tiam1 rescued the axon growth defect of MAP1B-deficient neurons. Taken together, these observations define a new and crucial function of MAP1B that we show to be required for efficient cross-talk between microtubules and the actin cytoskeleton during neuronal polarization. PMID:20719958

  3. 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

  4. Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways

    PubMed Central

    Wang, Hong; Wei, Si-Si; Chen, Jie; Chen, Yi-He; Xu, Wei-Ping; Jie, Qi-Qiang; Zhou, Qing; Li, Yi-Gang; Wei, Yi-Dong; Wang, Yue-Peng

    2016-01-01

    Rac1b is a constitutively activated, alternatively spliced form of the small GTPase Rac1. Previous studies showed that Rac1b promotes cell proliferation and inhibits apoptosis. In the present study, we used microarray analysis to detect genes differentially expressed in HEK293T cells and SW480 human colon cancer cells stably overexpressing Rac1b. We found that the pro-proliferation genes JNK2, c-JUN and cyclin-D1 as well as anti-apoptotic AKT2 and MCL1 were all upregulated in both lines. Rac1b promoted cell proliferation and inhibited apoptosis by activating the JNK2/c-JUN/cyclin-D1 and AKT2/MCL1 pathways, respectively. Very low Rac1b levels were detected in the colonic epithelium of wild-type Sprague-Dawley rats. Knockout of the rat Rac1 gene exon-3b or knockdown of endogenous Rac1b in HT29 human colon cancer cells downregulated only the AKT2/MCL1 pathway. Our study revealed that very low levels of endogenous Rac1b inhibit apoptosis, while Rac1b upregulation both promotes cell proliferation and inhibits apoptosis. It is likely the AKT2/MCL1 pathway is more sensitive to Rac1b regulation. PMID:26918455

  5. Rac1 regulates skin tumors by regulation of keratin 17 through recruitment and interaction with CD11b+Gr1+ cells

    PubMed Central

    Zhou, Ying; Zhu, Shaojun; Liu, Juanjuan; Wang, Dong; Deng, Anmei; Wang, Zhipeng

    2014-01-01

    Rac1 is a member of the Rho family of small GTPases that control cells proliferation, differentiation, migration, and inflammation. Rac1 is crucial in tumorigenesis and development. Keratin17 and CD11b+Gr1+ cells are considered to regulate skin inflmmation. Here we discuss the regulation of Rac1 on skin tumor formation and its relationship. In samples from human skin squamous cell carcinoma (SCC), Rac1 activity was higher in cancer tissues than in normal skin and activity correlated with keratin 17 overexpression. In a DMBA/TPA-induced mouse skin tumor model, inhibition of Rac1 activity and depletion of CD11b+Gr1+ cells resulted in significant tumor formation. TPA induced recruitment of CD11b+Gr1+ cells into dermis; however, Rac1 inhibitor abolished this recruitment. In vitro, Rac1 induced interferon (IFN) and interlukin (IL6) production in keratinocytes, repression of keratin 17 inhibited IFN and IL6 production induced by Rac1. Moreover, both inhibition of Rac1 activity and repression of keratin 17 restricted proliferation and induction of differentiation in keratinocytes. Coculture of CD11b+Gr1+ cells with keratinocytes activated Wnt pathway in keratinocytes, resulting in enhanced Rac1 activity, overexpression of keratin 17, and hyperproliferation of keratinocytes. Our results suggested that hyperactive Rac1 recruited and interacted with CD11b+Gr1+ cells, inducing keratin 17-regulated inflammation and promoting skin tumor formation. PMID:24962779

  6. The positive allosteric modulator of the GABA(B) receptor, rac-BHFF, suppresses alcohol self-administration.

    PubMed

    Maccioni, Paola; Thomas, Andrew W; Carai, Mauro A M; Gessa, Gian Luigi; Malherbe, Pari; Colombo, Giancarlo

    2010-06-01

    The present study was designed to extend to the newly synthesized rac-BHFF [(R,S)-5,7-di-tert-butyl-3-hydroxy-3-trifluoromethyl-3H-benzofuran-2-one] the investigation on the capacity of positive allosteric modulators of the GABA(B) receptor to reduce alcohol self-administration in rats. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were initially trained to respond on a lever [on a fixed ratio 4 (FR4) schedule of reinforcement] to orally self-administer alcohol (15%, v/v) or sucrose (0.7%, w/v) in daily 30-min sessions. Once responding reached stable levels, the effect of rac-BHFF (0, 50, 100, and 200mg/kg; i.g.) on responding for alcohol and sucrose was determined. Pretreatment with rac-BHFF produced a dose-dependent suppression in responding for alcohol; reduction in the total number of responses for alcohol, in comparison to vehicle-treated rats, averaged approximately 30%, 65%, and 90% in 50, 100, and 200mg/kg rac-BHFF-treated rats, respectively. Pretreatment with 200mg/kg rac-BHFF markedly increased the latency to the first response on the alcohol lever. The effect of pretreatment with rac-BHFF on alcohol self-administration was highly specific, since (a) responding for sucrose was reduced (to approximately 50%, in comparison to vehicle-treated rats) only by pretreatment with 200mg/kg rac-BHFF, and (b) latency to the first response on the sucrose lever was completely unaltered by any rac-BHFF dose. Treatment with rac-BHFF did not alter spontaneous locomotor activity in an independent group of sP rats. The present data constitute a further piece of evidence on the capacity of positive allosteric modulators of the GABA(B) receptor to reduce alcohol's reinforcing properties in rats.

  7. Cryptococcus neoformans phospholipase B1 activates host cell Rac1 for traversal across the blood-brain barrier.

    PubMed

    Maruvada, Ravi; Zhu, Longkun; Pearce, Donna; Zheng, Yi; Perfect, John; Kwon-Chung, Kyung J; Kim, Kwang Sik

    2012-10-01

    Cryptococcus neoformans penetration into the central nervous system (CNS) requires traversal of the blood-brain barrier that is composed of a single layer of human brain microvascular endothelial cells (HBMEC), but the underlying mechanisms of C. neoformans traversal remain incompletely understood. C. neoformans transcytosis of HBMEC monolayer involves rearrangements of the host cell actin cytoskeleton and small GTP-binding Rho family proteins such as Rac1 are shown to regulate host cell actin cytoskeleton. We, therefore, examined whether C. neoformans traversal of the blood-brain barrier involves host Rac1. While the levels of activated Rac1 (GTP-Rac1) in HBMEC increased significantly upon incubation with C. neoformans strains, pharmacological inhibition and down-modulation of Rac1 significantly decreased C. neoformans transcytosis of HBMEC monolayer. Also, Rac1 inhibition was efficient in preventing C. neoformans penetration into the brain. In addition, C. neoformans phospholipase B1 (Plb1) was shown to contribute to activating host cell Rac1, andSTAT3 was observed to associate with GTP-Rac1 in HBMEC that were incubated with C. neoformans strain but not with its Δplb1 mutant. These findings demonstrate for the first time that C. neoformans Plb1 aids fungal traversal across the blood-brain barrier by activating host cell Rac1 and its association with STAT3, and suggest that pharmacological intervention of host-microbial interaction contributing to traversal of the blood-brain barrier may prevent C. neoformans penetration into the brain.

  8. Rac1 GTPase-deficient mouse lens exhibits defects in shape, suture formation, fiber cell migration and survival.

    PubMed

    Maddala, Rupalatha; Chauhan, Bharesh K; Walker, Christopher; Zheng, Yi; Robinson, Michael L; Lang, Richard A; Rao, Ponugoti V

    2011-12-01

    Morphogenesis and shape of the ocular lens depend on epithelial cell elongation and differentiation into fiber cells, followed by the symmetric and compact organization of fiber cells within an enclosed extracellular matrix-enriched elastic capsule. The cellular mechanisms orchestrating these different events however, remain obscure. We investigated the role of the Rac1 GTPase in these processes by targeted deletion of expression using the conditional gene knockout (cKO) approach. Rac1 cKO mice were derived from two different Cre (Le-Cre and MLR-10) transgenic mice in which lens-specific Cre expression starts at embryonic day 8.75 and 10.5, respectively, in both the lens epithelium and fiber cells. The Le-Cre/Rac1 cKO mice exhibited an early-onset (E12.5) and severe lens phenotype compared to the MLR-10/Rac1 cKO (E15.5) mice. While the Le-Cre/Rac1 cKO lenses displayed delayed primary fiber cell elongation, lenses from both Rac1 cKO strains were characterized by abnormal shape, impaired secondary fiber cell migration, sutural defects and thinning of the posterior capsule which often led to rupture. Lens fiber cell N-cadherin/β-catenin/Rap1/Nectin-based cell-cell junction formation and WAVE-2/Abi-2/Nap1-regulated actin polymerization were impaired in the Rac1 deficient mice. Additionally, the Rac1 cKO lenses were characterized by a shortened epithelial sheet, reduced levels of extracellular matrix (ECM) proteins and increased apoptosis. Taken together, these data uncover the essential role of Rac1 GTPase activity in establishment and maintenance of lens shape, suture formation and capsule integrity, and in fiber cell migration, adhesion and survival, via regulation of actin cytoskeletal dynamics, cell adhesive interactions and ECM turnover.

  9. VE-cadherin trans-interactions modulate Rac activation and enhancement of lung endothelial barrier by iloprost.

    PubMed

    Birukova, Anna A; Tian, Yufeng; Dubrovskyi, Oleksii; Zebda, Noureddine; Sarich, Nicolene; Tian, Xinyong; Wang, Yingxiao; Birukov, Konstantin G

    2012-10-01

    Small GTPase Rac is important regulator of endothelial cell (EC) barrier enhancement by prostacyclin characterized by increased peripheral actin cytoskeleton and increased interactions between VE-cadherin and other adherens junction (AJ) proteins. This study utilized complementary approaches including siRNA knockdown, culturing in Ca(2+) -free medium, and VE-cadherin blocking antibody to alter VE-cadherin extracellular interactions to investigate the role of VE-cadherin outside-in signaling in modulation of Rac activation and EC barrier regulation by prostacyclin analog iloprost. Spatial analysis of Rac activation in pulmonary EC by FRET revealed additional spike in iloprost-induced Rac activity at the sites of newly formed cell-cell junctions. In contrast, disruption of VE-cadherin extracellular trans-interactions suppressed iloprost-activated Rac signaling and attenuated EC barrier enhancement and cytoskeletal remodeling. These inhibitory effects were associated with decreased membrane accumulation and activation of Rac-specific guanine nucleotide exchange factors (GEFs) Tiam1 and Vav2. Conversely, plating of pulmonary EC on surfaces coated with extracellular VE-cadherin domain further promoted iloprost-induced Rac signaling. In the model of thrombin-induced EC barrier recovery, blocking of VE-cadherin trans-interactions attenuated activation of Rac pathway during recovery phase and delayed suppression of Rho signaling and restoration of EC barrier properties. These results suggest that VE-cadherin outside-in signaling controls locally Rac activity stimulated by barrier protective agonists. This control is essential for maximal EC barrier enhancement and accelerated barrier recovery.

  10. Type II cyclic guanosine monophosphate-dependent protein kinase inhibits Rac1 activation in gastric cancer cells

    PubMed Central

    WANG, YING; CHEN, YONGCHANG; WU, MIN; LAN, TING; WU, YAN; LI, YUEYING; QIAN, HAI

    2015-01-01

    Enhanced motility of cancer cells is a critical step in promoting tumor metastasis, which remains the major cause of gastric cancer-associated mortality. The small GTPase Rac1 is a key signaling component in the regulation of cell migration. Previous studies have demonstrated that Rac1 activity may be regulated by protein kinase G (PKG); however, the underlying mechanism is not yet clear. The current study aimed to investigate the effect of type II cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG II) on Rac1 activity. The human gastric cancer cell line AGS was infected with adenoviral constructs encoding PKG II to increase the expression of this enzyme, and treated with a cGMP analog (8-pCPT-cGMP) to induce its activation. A Transwell assay was employed to measure cell migration, and the activity of Rac1 was assessed using a pull-down assay. Immunoprecipitation was used to isolate the Rac1 protein. Phosphorylation of phosphatidylinositol 4,5 bisphosphate 3 kinase (PI3K) and its downstream effecter protein kinase B (Akt) are associated with lysophosphatidic acid (LPA)-induced motility/migration of cancer cells. Extracellular signal regulated kinase (ERK) is the major signaling molecule of the Mitogen activated protein kinase (MAPK) mediated signaling pathway. ERK and its upstream activator MAPK kinase (MEK) are also involved in LPA-induced motility/migration of cancer cells. Phosphorylation of PI3K/Akt, MEK/ERK and enriched Rac1 were detected by western blotting. The results revealed that blocking the activation of Rac1 by ectopically expressing an inactive Rac1 mutant (T17N) impeded LPA-induced cell migration. Increased PKG II activity inhibited LPA-induced migration and LPA-induced activation of Rac1; however, it had no effect on the phosphorylation of Rac1. PKG II also inhibited the activation of PI3K/Akt and MEK/ERK mediated signaling, which is important for LPA-induced Rac1 activation. These results suggest that PKG II affects LPA

  11. Method and apparatus for analog signal conditioner for high speed, digital x-ray spectrometer

    DOEpatents

    Warburton, W.K.; Hubbard, B.

    1999-02-09

    A signal processing system which accepts input from an x-ray detector-preamplifier and produces a signal of reduced dynamic range for subsequent analog-to-digital conversion is disclosed. The system conditions the input signal to reduce the number of bits required in the analog-to-digital converter by removing that part of the input signal which varies only slowly in time and retaining the amplitude of the pulses which carry information about the x-rays absorbed by the detector. The parameters controlling the signal conditioner`s operation can be readily supplied in digital form, allowing it to be integrated into a feedback loop as part of a larger digital x-ray spectroscopy system. 13 figs.

  12. Dynamic modeling of brushless dc motor-power conditioner unit for electromechanical actuator application

    NASA Technical Reports Server (NTRS)

    Demerdash, N. A.; Nehl, T. W.

    1979-01-01

    A comprehensive digital model for the analysis of the dynamic-instantaneous performance of a power conditioner fed samarium-cobalt permanent magnet brushless DC motor is presented. The particular power conditioner-machine system at hand, for which this model was developed, is a component of an actual prototype electromechanical actuator built for NASA-JSC as a possible alternative to hydraulic actuators as part of feasibility studies for the shuttle orbiter applications. Excellent correlation between digital simulated and experimentally obtained performance data was achieved for this specific prototype. This is reported on in this paper. Details of one component of the model, its applications and the corresponding results are given in this paper.

  13. 77 FR 8178 - Test Procedures for Central Air Conditioners and Heat Pumps: Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-14

    ... 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 https://www1.... A link to the docket web page can be found at www.regulations.gov . The www.regulations.gov web...

  14. 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...

  15. 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.

  16. Value Engineering Study of Standard Family of Military Horizontal and Vertical Air Conditioners.

    DTIC Science & Technology

    1988-01-29

    Landino/ Cloetingh - STREE SUPIERIOR~ ELIITRtIc COMP~ANY Sn1STOC CONNECtICUT 060 0 fl(NONt E 203, $02 3B I MARTIN KAPLAN Vice President for Reseerch...MOST INEXPENSIVE INJ BOTH DAVID CLOETINGH TESTNG AND VERIFICATION: ENGINEERING COSTS, AND IN MASS QUA TITY FFI. WITHl 14OM TVEY WOZULD 1 SUBCONTRACT AND

  17. Investigation of Source of Irritant Gas Produced by PATRIOT Missile System Air Conditioners

    DTIC Science & Technology

    1986-03-31

    Octafluoro- 1 C3F8 188 Heptane, Hexadecafluoro- 2 CF 1 6 388 Propene, Hexafluoro- 1 C3F6 150 Pentane, Dodecafluoro- 2 C5F12 288 Butane, Decafluoro- 1...FORMULA M.WT. Cyclobutane, Octafluoro- 3 C4 F8 200 Ethene, Tetrafluoro- 2 C2F4 - 100 Ethane, Hexafluoro- 2 C2F6 138 Propane, Ocflouoro- 1 C3F8 188

  18. 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

    .... Summary of the Analyses Performed by DOE A. Engineering Analysis B. Markups To Determine Product Prices C... areas: (1) Engineering, (2) markups to determine product price, (3) energy-use characterization, (4.... Markups To Determine Product Prices DOE derives consumer prices for products based on manufacturer...

  19. 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

    ... characterization, (3) markups to determine product price, (4) life-cycle cost and payback period, and (5) national... scheme including material and labor costs, and manufacturer's markups. In this way, DOE developed ``manufacturer selling prices'' for the baseline and more efficient motor designs. Later, in its Markups...

  20. 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...

  1. Evaluation of a clay-based acidic bedding conditioner for dairy cattle bedding.

    PubMed

    Proietto, R L; Hinckley, L S; Fox, L K; Andrew, S M

    2013-02-01

    This study investigated the effects of a clay-based acidic bedding conditioner on sawdust bedding pH, dry matter (DM), environmental pathogen counts, and environmental bacterial counts on teat ends of lactating dairy cows. Sixteen lactating Holstein cows were paired based on parity, days in milk, milk yield, and milk somatic cell count, and were negative for the presence of an intramammary pathogen. Within each pair, cows were randomly assigned to 1 of 2 treatments with 3-wk periods in a crossover design. Treatment groups consisted of 9 freestalls per group bedded with either untreated sawdust or sawdust with a clay-based acidic bedding conditioner, added at 3- to 4-d intervals over each 21-d period. Bedding and teat ends were aseptically sampled on d 0, 1, 2, 7, 14, and 21 for determination of environmental bacterial counts. At the same time points, bedding was sampled for DM and pH determination. The bacteria identified in the bedding material were total gram-negative bacteria, Streptococcus spp., and coliform bacteria. The bacteria identified on the teat ends were Streptococcus spp., coliform bacteria, and Klebsiella spp. Teat end score, milk somatic cell count, and intramammary pathogen presence were measured weekly. Bedding and teat cleanliness, environmental high and low temperatures, and dew point data were collected daily. The bedding conditioner reduced the pH, but not the DM, of the sawdust bedding compared with untreated sawdust. Overall environmental bacterial counts in bedding were lower for treated sawdust. Total bacterial counts in bedding and on teat ends increased with time over both periods. Compared with untreated sawdust, the treated bedding had lower counts of total gram-negative bacteria and streptococci, but not coliform counts. Teat end bacterial counts were lower for cows bedded on treated sawdust for streptococci, coliforms, and Klebsiella spp. compared with cows bedded on untreated sawdust. The clay-based acidic bedding conditioner

  2. Exposure data for cosmetic products: facial cleanser, hair conditioner, and eye shadow.

    PubMed

    Loretz, L J; Api, A M; Babcock, L; Barraj, L M; Burdick, J; Cater, K C; Jarrett, G; Mann, S; Pan, Y H L; Re, T A; Renskers, K J; Scrafford, C G

    2008-05-01

    Reliable exposure information for cosmetic and other personal care products and ingredients is needed in order to conduct safety assessments. Essential information includes both the amount of product applied, and the frequency of use. To obtain current data, a study to assess consumer use practices was undertaken. Three widely used types of cosmetic products - facial cleanser, hair conditioner, and eye shadow - were included in the study. Three hundred and sixty women, ages 18-69 years, who regularly use the products of interest, were recruited nationwide within the US. Subjects were provided with a new container of the brand of product they normally use and kept diaries and recorded detailed daily usage information over a two week period. Products were weighed at the start and completion of the study in order to determine the total amount of product used. Statistical analyses of the data were conducted to derive summary distributions of use patterns. The mean and median usage per application, respectively, for the three product types were: facial cleanser, 2.57 g and 2.11 g; hair conditioner, 13.13 g and 10.21 g; and eye shadow, 0.03 g and 0.009 g. The mean and median usage per day for the three product types was: facial cleanser, 4.06 g and 3.25 g; hair conditioner, 13.77 g and 10.62 g; and eye shadow, 0.04 g and 0.010 g. The mean number of applications per day for facial cleanser, hair conditioner, and eye shadow was 1.6, 1.1, and 1.2, respectively. This study provides an estimate of current exposure information for commonly used products which will be useful for risk assessment purposes.

  3. Rac1 overexpression is correlated with epithelial mesenchymal transition and predicts poor prognosis in non-small cell lung cancer

    PubMed Central

    Zhou, Yujuan; Liao, Qianjin; Han, Yaqian; Chen, Jie; Liu, Zhigang; Ling, Hang; Zhang, Jing; Yang, Wenjuan; Oyang, Linda; Xia, Longzheng; Wang, Li; Wang, Heran; Xue, Lei; Wang, Hui; Hu, Bingqiang

    2016-01-01

    Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial mesenchymal transition (EMT) are key therapeutic targets in cancer. We investigated the clinical significance of Rac1 and markers of EMT expression in non-small cell lung cancer (NSCLC), and their possible correlation with EMT phenotype. Methods: Immunohistochemistry was used to assess the expression of Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad) in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to tumors. The correlation of Rac1 and EMT markers with clinicopathological characteristics and the relationship between the protein levels and progression-free survival (PFS) and overall survival (OS) were analyzed. Results: Compared with non-tumor tissues, the NSCLC tissues showed marked elevation in the levels of Rac1, Snail1, Twist1, N-cad, and Vim levels, whereas the E-cad levels were significantly decreased (P < 0.05). The aberrant expression of Rac1 and EMT markers was significantly associated with TNM stage and metastasis (P < 0.05). Increased expression of Rac1 may be associated with poor OS and PFS compared with low expression (P<0.001 and P=0.004). Significant correlations were observed between the EMT markers expressed and OS or PFS(P<0.01). In addition, multivariate analysis indicated that the expression of Rac1, Snail1, Twist1, N-cad, Vim, and E-cad was an independent prognostic factor in NSCLC. Interestingly, Rac1 expression was positively correlated with Snail1, Twist1, N-cad, and Vim levels (r=0.563, r=0.440, r=0.247 r=0.536, P<0.01, respectively) and negatively correlated with E-cad levels (r=-0.464, P<0.001) in NSCLC tissues. Rac1, Twist, Snail1, Vim and N-cad were highly expressed in lung cancer patients resistant to radiotherapy, while E-cad was poorly expressed. Conclusion: Rac1 may promote NSCLC progression and metastasis via EMT, which may be considered as a potential therapeutic target. PMID:27877226

  4. Regulation of Rac1 GTPase activity by quinine through G-protein and bitter taste receptor T2R4.

    PubMed

    Sidhu, Crystal; Jaggupilli, Appalaraju; Chelikani, Prashen; Bhullar, Rajinder P

    2017-02-01

    Rac1 belongs to the Rho family of small GTPases and regulates actin cytoskeleton reorganization. T2R4 is a bitter taste receptor belonging to the G protein-coupled receptor family of proteins. In addition to mediating bitter taste perception from the tongue, T2R4s are found in extra-oral tissues, e.g., nasal epithelium, airways, brain, testis suggesting a much broader physiological function for these receptors. Anti-malarial drug and a bitter tasting compound, quinine, is a known agonist for T2R4, whereas BCML (Nα,Nα-Bis(carboxymethyl)-L-lysine) acts as an inverse agonist. Using western blot and Ca(++) mobilization assays, the effects of quinine on Rac1 activity in HEK293T cells stably expressing T2R4/Gα16/44, T2R4, or Gα16/44 and transiently transfected with HA-Rac1 were investigated. Quinine treatment caused a significant reduction in the amount of active Rac1, whereas in the presence of BCML, quinine failed to cause any significant change in active Rac1. No significant change in Rac1 activity was observed in BAPTA-AM plus quinine-treated Gα16/44 cells, suggesting possibility of a pathway in addition to the canonical Ca(++)-dependent pathway. A noticeable role for Gα16/44 independent of T2R4 is observed in quinine-mediated Rac1 inactivation. Further, a significant difference in quinine-induced Ca(++) response in T2R4/Gα16/44 or T2R4 cells was observed validating the partial role of calcium and importance of Gα16/44. This study is the first to show an inhibitory downstream action of a T2R4 agonist on Rac1 function. Further investigation will help in better understanding the downstream signal transduction network of T2R4 and its extra-oral physiological roles.

  5. Estrogen and the Dietary Phytoestrogen Tesveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Research

    DTIC Science & Technology

    2008-06-01

    AD_________________ Award Number: W81XWH-07-1-0330 TITLE: Estrogen and the Dietary Phytoestrogen ...COVERED 7 May 2007 – 6 May 2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Estrogen and the Dietary Phytoestrogen Tesveratrol as Regulators of the... estrogen (E2), or resveratrol (Res). PAK-PBD-GST beads were used to pull-down active GTP- bound Rac from the cell lysates. Active and total Rac levels

  6. Geometry sensing through POR1 regulates Rac1 activity controlling early osteoblast differentiation in response to nanofiber diameter.

    PubMed

    Higgins, A M; Banik, B L; Brown, J L

    2015-02-01

    Bone grafting procedures in the United States rely heavily upon autografts and allografts, which are donor-dependent, cause donor site pain, and can transmit disease. Synthetic bone grafts can reduce these risks; however, synthetics lack the bone differentiating (osteoinductive) abilities of auto- and allografts. Achieving innate osteoinductive properties of synthetics through surface modifications is currently under investigation. This study focuses on nanofibers, with emphasis on how fiber diameter and the potential curvature sensor POR1 affect the activation of the signaling molecules Rac1 and Arf1, and leading to expression of alkaline phosphatase (ALP), an osteoinductive marker. Diameters of 0.1, 0.3, and 1.0 μm were compared against a flat control. The highest level of Rac1 activation was achieved on the smallest fibers (0.1 μm), a trend that was lost in POR1 knockdowns. This supports the hypothesis that on small nanofibers, POR1 favorably binds to highly curved cell membranes, which allows Rac1 to subsequently dissociate and activate. When the curvature is insufficient to bind POR1, POR1 binds to inactive Rac1 and competitively inhibits its activation. Arf1 activation followed an opposite trend, with the largest nanofibers exhibiting the highest activity. This trend reinforces the known interaction between Rac1 and Arf1 through the GIT-PIX complex, an Arf1 GAP and Rac1 GEF, respectively. Large, (1.0 μm), nanofibers demonstrated the highest ALP activity, indicating that ALP expression is inversely dependent on Rac1 activation. Knockdown of POR1 resulted in increased ALP activity across the substrates but without regard to the curvature sensing trend seen previously. Thus, POR1 senses curvature and increases Rac1 activity, which negatively regulates bone differentiation.

  7. ARF1 controls Rac1 signaling to regulate migration of MDA-MB-231 invasive breast cancer cells.

    PubMed

    Lewis-Saravalli, Sebastian; Campbell, Shirley; Claing, Audrey

    2013-09-01

    ADP-ribosylation factors (ARFs) are monomeric G proteins that regulate many cellular processes such as reorganization of the actin cytoskeleton. We have previously shown that ARF1 is overexpressed in highly invasive breast cancer cells and contribute to their enhanced migration. In this study, we propose to define the molecular mechanism by which ARF1 regulates this complex cellular response by investigating the role of this ARF GTPase on the activation process of Rac1, a Rho GTPase, associated with lamellipodia formation during cell migration. Here, we first show that inhibition of ARF1 or Rac1 expression markedly impacts the ability of MDA-MB-231 cells to migrate upon EGF stimulation. However, the effect of ARF1 depletion can be reversed by overexpression of the Rac1 active mutant, Rac1 Q(61)L. Depletion of ARF1 also impairs the ability of EGF stimulation to promote GTP-loading of Rac1. To further investigate the possible cross-talk between ARF1 and Rac1, we next examined whether they could form a complex. We observed that the two GTPases could directly interact independently of the nature of the nucleotide bound to them. EGF treatment however resulted in the association of Rac1 with its effector IRSp53, which was completely abrogated in ARF1 depleted cells. We present evidences that this ARF isoform is responsible for the plasma membrane targeting of both Rac1 and IRSp53, a step essential for lamellipodia formation. In conclusion, this study provides a new mechanism by which ARF1 regulates cell migration and identifies this GTPase as a promising pharmacological target to reduce metastasis formation in breast cancer patients.

  8. 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

  9. BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells.

    PubMed

    Ishiai, M; Kurosaki, M; Pappu, R; Okawa, K; Ronko, I; Fu, C; Shibata, M; Iwamatsu, A; Chan, A C; Kurosaki, T

    1999-01-01

    Signaling through the B cell receptor (BCR) is essential for B cell function and development. Despite the key role of Syk in BCR signaling, little is known about the mechanism by which Syk transmits downstream effectors. BLNK (B cell LiNKer protein), a substrate for Syk, is now shown to be essential in activating phospholipase C (PLC)gamma 2 and JNK. The BCR-induced PLC gamma 2 activation, but not the JNK activation, was restored by introduction of PLC gamma 2 membrane-associated form into BLNK-deficient B cells. As JNK activation requires both Rac1 and PLC gamma 2, our results suggest that BLNK regulates the Rac1-JNK pathway, in addition to modulating PLC gamma 2 localization.

  10. Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase

    NASA Technical Reports Server (NTRS)

    Shimizu, M.; Wang, W.; Walch, E. T.; Dunne, P. W.; Epstein, H. F.

    2000-01-01

    Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kinase encoded by the myotonic dystrophy (DM) locus on human chromosome 19q13.3. It is a close relative of other kinases that interact with members of the Rho family of small GTPases. We show here that the actin cytoskeleton-linked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activates its transphosphorylation activity in a GTP-sensitive manner. DMPK can also bind Raf-1 kinase, the Ras-activated molecule of the MAP kinase pathway. Purified Raf-1 kinase phosphorylates and activates DMPK. The interaction of DMPK with these distinct signals suggests that it may play a role as a nexus for cross-talk between their respective pathways and may partially explain the remarkable pleiotropy of DM.

  11. Distinctive and selective route of PI3K/PKCα-PKCδ/RhoA-Rac1 signaling in osteoclastic cell migration.

    PubMed

    Kim, Jin-Man; Kim, Mi Yeong; Lee, Kyunghee; Jeong, Daewon

    2016-12-05

    Cell migration during specialized stages of osteoclast precursors, mononuclear preosteoclasts, and multinucleated mature osteoclasts remain uncertain. M-CSF- and osteopontin-induced osteoclastic cell migration was inhibited by function-blocking monoclonal antibodies specific to the integrin αv and β3 subunits, suggesting that integrin αvβ3 mediates migratory signaling induced by M-CSF and osteopontin. M-CSF and osteopontin stimulation was shown to regulate two branched signaling processes, PI3K/PKCα/RhoA axis and PI3K/PKCδ/Rac1 axis. Interestingly, inactivation of RhoA or Rac1 blocked preosteoclast and mature osteoclast migration but not osteoclast precursor migration in a transwell-based cell migration assay. Moreover, the inhibitory effect on preosteoclast and mature osteoclast migration induced by Rac1 inactivation was more effective than that by RhoA inactivation. Collectively, our findings suggest that osteoclast precursor migration depends on PI3K/PKCα-PKCδ signaling mediated via integrin αvβ3 bypassing RhoA and Rac1, whereas preosteoclast and mature osteoclast migration relies on PI3K/PKCα-PKCδ/RhoA-Rac1 axis signaling mediated via integrin αvβ3 with increased dependency on PKCδ/Rac1 signaling route as differentiation progresses.

  12. Prelamin A Accumulation Attenuates Rac1 Activity and Increases the Intrinsic Migrational Persistence of Aged Vascular Smooth Muscle Cells

    PubMed Central

    Porter, Lauren J.; Holt, Mark R.; Soong, Daniel; Shanahan, Catherine M.; Warren, Derek T.

    2016-01-01

    Vascular smooth muscle cell (VSMC) motility is essential during both physiological and pathological vessel remodeling. Although ageing has emerged as a major risk factor in the development of cardiovascular disease, our understanding of the impact of ageing on VSMC motility remains limited. Prelamin A accumulation is known to drive VSMC ageing and we show that presenescent VSMCs, that have accumulated prelamin A, display increased focal adhesion dynamics, augmented migrational velocity/persistence and attenuated Rac1 activity. Importantly, prelamin A accumulation in proliferative VSMCs, induced by depletion of the prelamin A processing enzyme FACE1, recapitulated the focal adhesion, migrational persistence and Rac1 phenotypes observed in presenescent VSMCs. Moreover, lamin A/C-depleted VSMCs also display reduced Rac1 activity, suggesting that prelamin A influences Rac1 activity by interfering with lamin A/C function at the nuclear envelope. Taken together, these data demonstrate that lamin A/C maintains Rac1 activity in VSMCs and prelamin A disrupts lamin A/C function to reduce Rac1 activity and induce migrational persistence during VSMC ageing. PMID:27854297

  13. 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

  14. [RAC3 nuclear receptor co-activator has a protective role in the apoptosis induced by different stimuli].

    PubMed

    Coló, Georgina P; Rubio, María F; Alvarado, Cecilia V; Costas, Mónica A

    2007-01-01

    RAC3 belongs to the family of p160 nuclear receptors coactivators and it is over-expressed in several tumors. We have previously shown that RAC3 is a NF-kappaB coactivator. In this paper, we investigated the role of RAC3 in cell-sensitivity to apoptosis, using H2O2 in the human embryonic kidney cell line (HEK293), and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) in a human chronic myeloid leukemia cell line (K562) naturally resistant to TRAIL. We observed that the tumoral K562 cells have high levels of RAC3 if compared with the non-tumoral HEK293 cells. The normal or transfected coactivator over-expression inhibits apoptosis through a diminished caspase activity and AIF nuclear translocation, increased NF-kappaB, AKT and p38, and decreased ERK activities. In contrast, inhibition of RAC3 by siRNA induced sensitivity of K562 to TRAIL-induced apoptosis. Such results suggest that over-expression of RAC3 contributes to tumor development through molecular mechanisms that do not depend strictly on acetylation and/or steroid hormones, which control cell death. This could be a possible target for future tumor therapies.

  15. Identification of cancer-associated missense mutations in hace1 that impair cell growth control and Rac1 ubiquitylation

    PubMed Central

    Andrio, Emilie; Lotte, Romain; Hamaoui, Daniel; Cherfils, Jacqueline; Doye, Anne; Daugaard, Mads; Sorensen, Poul H.; Bost, Frédéric; Ruimy, Raymond; Mettouchi, Amel; Lemichez, Emmanuel

    2017-01-01

    The E3 ubiquitin ligase HACE1 is a potent tumor suppressor that controls cell proliferation and ubiquitylates the small GTPase Rac1 to target it to proteasomal degradation. Whether and how the activity of HACE1 is regulated by the N-terminal ankyrin (ANK) and the middle (MID) domains is ill defined. Here, we identified in the version 64 of the Catalogue of Somatic Mutations in Cancer (COSMIC) 13 missense mutations of hace1 located outside the HECT domain, and found that all lead to defective control of cell proliferation. In addition, several mutations located in the ankyrin domain displayed a dramatic reduction in Rac1 ubiquitylation associated with a decrease of colony formation in soft agar. 3D structure modelling of the 7 ankyrin-repeats coupled to functional analysis identified a surface epitope centered on one of the mutated residue, Gly-175, which is critical for controlling Rac1 binding and ubiquitylation. We also identified a role for the MID domain in conferring the specificity of association of HACE1 to the active form of Rac1. Our study of the functional interplay between HACE1 and Rac1 in cancer thus sheds a new light on the molecular mechanism of Rac1 ubiquitylation by HACE1 and the impact of its cancer-associated mutations in cell proliferation. PMID:28317937

  16. 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.

  17. Inhibition of Rac GTPases in the Therapy of Chronic Myelogenous Leukemia

    DTIC Science & Technology

    2009-04-01

    reported data and different outcome definitions, we could not perform a meta - analysis and thus, a final judgment about the influence of corticosteroids...myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) characterized by the expression of the p210-BCR/ABL fusion gene [1]. This gene...components downstream of BCR/ABL. During the first year of this award, we reported our progress on the analysis of the role of Rac GTPases in

  18. Nuclear PKCι-ECT2-Rac1 and Ribosome Biogenesis: A Novel Axis in Lung Tumorigenesis.

    PubMed

    Baker, Martin J; Cooke, Mariana; Kazanietz, Marcelo G

    2017-02-13

    The RhoGEF Ect2 controls cell division and exerts oncogenic functions in multiple cancers. In this issue of Cancer Cell, Justilien et al. report that Ect2 is required for lung tumorigenesis and identified a role for this GEF in ribosomal RNA (rRNA) synthesis that is mediated by Rac1 and PKCι-dependent phosphorylation.

  19. CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling.

    PubMed

    Chen, Qian; Zhu, Yong-Chuan; Yu, Jing; Miao, Sheng; Zheng, Jing; Xu, Li; Zhou, Yang; Li, Dan; Zhang, Chi; Tao, Jiong; Xiong, Zhi-Qi

    2010-09-22

    Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.

  20. Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

    PubMed Central

    Jiang, Wei; Sheng, Chunjie; Gu, Xiuling; Liu, Dong; Yao, Chen; Gao, Shijuan; Chen, Shuai; Huang, Yinghui; Huang, Wenlin; Fang, Min

    2016-01-01

    Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets. PMID:27869202

  1. Establishing epithelial glandular polarity: interlinked roles for ARF6, Rac1, and the matrix microenvironment.

    PubMed

    Monteleon, Christine L; Sedgwick, Alanna; Hartsell, Alyssa; Dai, Michael; Whittington, Catherine; Voytik-Harbin, Sherry; D'Souza-Schorey, Crislyn

    2012-12-01

    Epithelial cysts comprise the structural units of the glandular epithelium. Although glandular inversion in epithelial tumors is thought to be a potential mechanism for the establishment of metastatic disease, little is known about the morphogenic cues and signaling pathways that govern glandular polarity and organization. Using organotypic cultures of Madin-Darby canine kidney cells in reconstituted basement membrane, we show that cellular depletion of the small GTP-binding protein ARF6 promotes the formation of inverted cysts, wherein the apical cell membrane faces the cyst exterior, and the basal domain faces the central lumen, while individual cell polarity is maintained. These cysts are also defective in interactions with laminin at the cyst-matrix interface. This inversion of glandular orientation is accompanied by Rac1 inactivation during early cystogenesis, and temporal activation of Rac1 is sufficient to recover the normal cyst phenotype. In an unnatural collagen I microenvironment, ARF6-depleted, inverted epithelial cysts exhibit some loss of cell polarity, a marked increase in Rho activation and Rac1 inactivation, and striking rearrangement of the surrounding collagen I matrix. These studies demonstrate the importance of ARF6 as a critical determinant of glandular orientation and the matrix environment in dictating structural organization of epithelial cysts.

  2. Thiol-modifying phenylarsine oxide inhibits guanine nucleotide binding of Rho but not of Rac GTPases.

    PubMed

    Gerhard, Ralf; John, Harald; Aktories, Klaus; Just, Ingo

    2003-06-01

    Phenylarsine oxide (PAO) is a phosphotyrosine phosphatase inhibitor that cross-links vicinal thiol groups, thereby inactivating phosphatases possessing XCysXXCysX motifs. The RhoA-GTPase, but not the Rac1-GTPase, also possesses vicinal cysteines within the guanine nucleotide-binding region (aa 13-20) and the phosphohydrolase activity site. Treatment of Caco-2 cells with PAO showed a dose-dependent reorganization of the actin cytoskeleton, indicating involvement of Rho GTPases. As tested by pull-down experiments, RhoA, but not Rac1, from cell lysates was inactivated by PAO in a concentration-dependent manner. Modification of RhoA by PAO resulted in altered mobility on SDS-polyacrylamide gel electrophoresis, and PAO-modified RhoA was no longer substrate for C3-catalyzed ADP-ribosylation. Furthermore, RhoA treated with PAO, but not Rac1 treated with PAO, lost its property to bind to guanine nucleotides. Matrix-assisted laser desorption ionization-mass analysis of PAO-modified RhoA showed a mass shift according to an adduction of a single PAO molecule per molecule RhoA. Further analysis of Glu-C-generated RhoA peptides confirmed binding of PAO to a peptide harboring the guanine nucleotide binding region. Thus, PAO does not exclusively inhibit phosphotyrosine phosphatases but also inactivates RhoA by alteration of nucleotide binding.

  3. Pharmacokinetics of rac-leucovorin vs [S]-leucovorin in patients with advanced gastrointestinal cancer.

    PubMed Central

    Mader, R M; Steger, G G; Rizovski, B; Sieder, A E; Locker, G; Gnant, M F; Jakesz, R; Rainer, H

    1994-01-01

    1. The pharmacokinetics of [R]-leucovorin ([R]-LV), [S]-leucovorin ([S]-LV) and the circulating metabolite [S]-5-methyltetrahydrofolate ([S]-5-MTHF) were studied after administration of racemic LV and [S]-LV in 21 subjects. 2. After intravenous infusion of 600 mg m-2 rac-LV (group 1, n = 7) or 300 mg m-2 [S]-LV (group 3, n = 7), the decay of [S]-LV in plasma was biexponential with a distribution half-life of 0.8 to 1 h and an elimination half-life of 11 to 23 h. When rac-LV was administered as a 2 h i.v. infusion (400 mg m-2) following a loading dose of 200 mg m-2 (group 2, n = 7), the plasma concentrations of [R]-LV and [S]-5-MTHF decayed monoexponentially with mean (+/- s.d.) half-lives of 10 +/- 3 h and 7 +/- 2 h, respectively. 3. The AUC of [S]-5-MTHF was significantly higher after infusion of 300 mg m-2 [S]-LV than after infusion of 600 mg m-2 rac-LV (83 +/- 22 micrograms ml-1 h vs 53 +/- 22 micrograms ml-1 h; P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8198932

  4. Pharmacokinetics of rac-leucovorin vs [S]-leucovorin in patients with advanced gastrointestinal cancer.

    PubMed

    Mader, R M; Steger, G G; Rizovski, B; Sieder, A E; Locker, G; Gnant, M F; Jakesz, R; Rainer, H

    1994-03-01

    1. The pharmacokinetics of [R]-leucovorin ([R]-LV), [S]-leucovorin ([S]-LV) and the circulating metabolite [S]-5-methyltetrahydrofolate ([S]-5-MTHF) were studied after administration of racemic LV and [S]-LV in 21 subjects. 2. After intravenous infusion of 600 mg m-2 rac-LV (group 1, n = 7) or 300 mg m-2 [S]-LV (group 3, n = 7), the decay of [S]-LV in plasma was biexponential with a distribution half-life of 0.8 to 1 h and an elimination half-life of 11 to 23 h. When rac-LV was administered as a 2 h i.v. infusion (400 mg m-2) following a loading dose of 200 mg m-2 (group 2, n = 7), the plasma concentrations of [R]-LV and [S]-5-MTHF decayed monoexponentially with mean (+/- s.d.) half-lives of 10 +/- 3 h and 7 +/- 2 h, respectively. 3. The AUC of [S]-5-MTHF was significantly higher after infusion of 300 mg m-2 [S]-LV than after infusion of 600 mg m-2 rac-LV (83 +/- 22 micrograms ml-1 h vs 53 +/- 22 micrograms ml-1 h; P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  5. PTEN controls immunoreceptor (immunoreceptor tyrosine-based activation motif) signaling and the activation of Rac.

    PubMed

    Kim, Jong Suk; Peng, Xiaodong; De, Pradip K; Geahlen, Robert L; Durden, Donald L

    2002-01-15

    Fcgamma receptor-mediated phagocytosis is a model for the study of immunoreceptor (immunoreceptor tyrosine-based activation motif [ITAM]) signaling and involves the activation of protein tyrosine kinases, protein tyrosine phosphatases, and downstream effectors including phosphatidylinositol-3 (PI-3) kinase. Relatively little is known of the role of lipid phosphatases in the control of ITAM signaling and inflammation. A heterologous COS7 cell system was used to examine the roles played by PI-3 kinase and the dual-specificity phosphatase, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), in the signal transduction pathway leading to Fcgamma receptor IIA-mediated phagocytosis and the activation of Rac. The expression of wildtype PTEN completely abrogated the phagocytosis of immunoglobulin-G-sensitized sheep red blood cells, as compared with the catalytically inactive mutant of PTEN, which had no effect. This is the first direct evidence that PTEN, an inositol 3' phosphatase, regulates Fcgamma receptor-mediated phagocytosis, an ITAM-based signaling event. The data suggest that PTEN exerts control over phagocytosis potentially by controlling the downstream conversion of guanosine diphosphate-Rac to guanosine triphosphate-Rac following ITAM stimulation.

  6. Rac1 Activation in Podocytes Induces Rapid Foot Process Effacement and Proteinuria

    PubMed Central

    Yu, Haiyang; Suleiman, Hani; Kim, Alfred H. J.; Miner, Jeffrey H.; Dani, Adish; Akilesh, Shreeram

    2013-01-01

    The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton. PMID:24061480

  7. Modulation of Rac1 Activity by ADMA/DDAH Regulates Pulmonary Endothelial Barrier Function

    PubMed Central

    Torondel, Belen; Zhao, Lan; Renné, Thomas; Leiper, James M.

    2009-01-01

    Endogenously produced nitric oxide synthase inhibitor, asymmetric methylarginine (ADMA) is associated with vascular dysfunction and endothelial leakage. We studied the role of ADMA, and the enzymes metabolizing it, dimethylarginine dimethylaminohydrolases (DDAH) in the regulation of endothelial barrier function in pulmonary macrovascular and microvascular cells in vitro and in lungs of genetically modified heterozygous DDAHI knockout mice in vivo. We show that ADMA increases pulmonary endothelial permeability in vitro and in in vivo and that this effect is mediated by nitric oxide (NO) acting via protein kinase G (PKG) and independent of reactive oxygen species formation. ADMA-induced remodeling of actin cytoskeleton and intercellular adherens junctions results from a decrease in PKG-mediated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and a subsequent down-regulation of Rac1 activity. The effects of ADMA on endothelial permeability, Rac1 activation and VASP phosphorylation are prevented by overexpression of active DDAHI and DDAHII, whereas inactive DDAH mutants have no effect. These findings demonstrate for the first time that ADMA metabolism critically determines pulmonary endothelial barrier function by modulating Rac1-mediated remodeling of the actin cytoskeleton and intercellular junctions. PMID:18923147

  8. Involvement of a Rac1-Dependent Macropinocytosis Pathway in Plasmid DNA Delivery by Electrotransfection.

    PubMed

    Mao, Mao; Wang, Liangli; Chang, Chun-Chi; Rothenberg, Katheryn E; Huang, Jianyong; Wang, Yingxiao; Hoffman, Brenton D; Liton, Paloma B; Yuan, Fan

    2017-03-01

    Electrotransfection is a widely used method for delivering genes into cells with electric pulses. Although different hypotheses have been proposed, the mechanism of electrotransfection remains controversial. Previous studies have indicated that uptake and intracellular trafficking of plasmid DNA (pDNA) are mediated by endocytic pathways, but it is still unclear which pathways are directly involved in the delivery. To this end, the present study investigated the dependence of electrotransfection on macropinocytosis. Data from the study demonstrated that electric pulses induced cell membrane ruffling and actin cytoskeleton remodeling. Using fluorescently labeled pDNA and a macropinocytosis marker (i.e., dextran), the study showed that electrotransfected pDNA co-localized with dextran in intracellular vesicles. Furthermore, electrotransfection efficiency could be decreased significantly by reducing temperature or treatment of cells with a pharmacological inhibitor of Rac1 and could be altered by changing Rac1 activity. Taken together, the findings suggested that electrotransfection of pDNA involved Rac1-dependent macropinocytosis.

  9. Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons.

    PubMed

    Lundström, Annika; Gallio, Marco; Englund, Camilla; Steneberg, Pär; Hemphälä, Johanna; Aspenström, Pontus; Keleman, Krystyna; Falileeva, Ludmilla; Dickson, Barry J; Samakovlis, Christos

    2004-09-01

    Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.

  10. Enantioselective Ring-Opening Polymerization of rac-Lactide Dictated by Densely Substituted Amino Acids.

    PubMed

    Sanchez-Sanchez, Ana; Rivilla, Ivan; Agirre, Maddalen; Basterretxea, Andere; Etxeberria, Agustin; Veloso, Antonio; Sardon, Haritz; Mecerreyes, David; Cossío, Fernando P

    2017-04-05

    Organocatalysis is becoming an important tool in polymer science because of its versatility and specificity. To date a limited number of organic catalysts have demonstrated the ability to promote stereocontrolled polymerizations. In this work we report one of the first examples of chirality transfer from a catalyst to a polymer in the organocatalyzed ring-opening polymerization (ROP) of rac-lactide (rac-LA). We have polymerized rac-LA using the diastereomeric densely substituted amino acids (2S,3R,4S,5S)-1-methyl-4-nitro-3,5-diphenylpyrrolidine-2-carboxylic acid (endo-6) and (2S,3S,4R,5S)-1-methyl-4-nitro-3,5-diphenylpyrrolidine-2-carboxylic acid (exo-6), combined with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a cocatalyst. Both diastereoisomers not only showed the ability to synthesize enriched isotactic polylactide with a Pm higher than 0.90 at room temperature but also were able to preferentially promote the polymerization of one of the isomers (l or d) with respect to the other. Thus, exo-6 preferentially polymerized l-lactide, whereas endo-6 preferred d-lactide as the substrate. Density functional theory calculations were conducted to investigate the origins of this unique stereocontrol in the polymerization, providing mechanistic insight and explaining why the chirality of the catalyst is able to define the stereochemistry of the monomer insertion.

  11. Comparative toxicity of rac- and S-tebuconazole to Daphnia magna.

    PubMed

    Qi, Su Z; Chen, Xiao F; Liu, Yong; Jiang, Jia Z; Wang, Cheng J

    2015-01-01

    Tebuconazole is a chiral triazole fungicide used as raceme in a variety of agricultural applications. Earlier studies showed that tebuconazole is toxic to many non-target aquatic organisms but relative data for tebuconazole enantiomers are lacking. Thus, goal of this study was to evaluate and compare the toxicity of rac- and S-tebuconazole with Daphnia magna at both acute and chronic levels according to Organization for Economic Cooperation and Development (OECD) guidelines 202 and 211 respectively, to provide some guidelines for optimizing chiral pesticides application and management. The exposure concentrations were 0.1, 0.5, 1, 2, 4, 8, 10 mg L(-1) for both rac- and S-tebuconazole and their 48-h EC(50) values to D. magna were 3.53 (3.32-3.78) and 2.74 (2.33-3.10) mg L(-1) respectively, indicating that these both are medium toxic to D. magna with no significant toxicity difference at acute level. In chronic test, <24-h old D. magna were exposed to 0.01, 0.05, 0.10, 0.20, and 0.40 mg L(-1) of rac- and S-tebuconazole with one blank and one solvent control for 21 days according to OECD guideline 211. Four developmental (molting rate, days to the 1st and 3rd brood, and body length) and five reproductive (size of the 1st and 3rd brood, number of broods, and number of neonates) parameters for each D. magna were determined. Results showed that both rac- and S-tebuconazole significantly reduced the reproduction and impacted the development of D. magna at concentrations of 0.05 mg L(-1) or higher. Furthermore, S-tebuconazole was more toxic than raceme, and the difference between effects on the same parameters induced by rac- and S-tebuconazole was statistically significant. These results demonstrated that the chronic toxicity of S-tebuconazole might be underestimated in general use, and further studies should focus more on the biological behaviors of enantiomers and not just the raceme of tebuconazole and other chiral pesticides in the environment.

  12. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases

    PubMed Central

    Oprea, Tudor I.; Sklar, Larry A.; Agola, Jacob O.; Guo, Yuna; Silberberg, Melina; Roxby, Joshua; Vestling, Anna; Romero, Elsa; Surviladze, Zurab; Murray-Krezan, Cristina; Waller, Anna; Ursu, Oleg; Hudson, Laurie G.; Wandinger-Ness, Angela

    2015-01-01

    Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses—using the rotationally constrained carboxylate in R-naproxen—led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and

  13. Rac1 GTPase-deficient HeLa cells present reduced DNA repair, proliferation, and survival under UV or gamma irradiation.

    PubMed

    Espinha, Gisele; Osaki, Juliana H; Magalhaes, Yuli T; Forti, Fabio Luis

    2015-06-01

    Rac1 GTPase controls essential cellular functions related to the cytoskeleton, such as motility and adhesion. Rac1 is overexpressed in many tumor cells, including breast cancers, where it is also involved in the proliferation and checkpoint control necessary for the cell's recovery after exposure to ionizing radiation. However, its role in DNA damage and repair remains obscure in other tumor cells and under different genotoxic conditions. Here, we compare HeLa cells with mutants exogenously expressing a dominant-negative Rac1 (HeLa-Rac1-N17) by their responses to DNA damage induced by gamma or UV radiation. In HeLa cells, these treatments led to increased levels of active Rac1 (Rac1-GTP) and of stress fibers, with a diminished ability to migrate compared to untreated cells. However, the reduction of Rac1-GTP in Rac1-N17-deficient clones resulted in much higher levels of polymerized stress fibers accompanied by a strong impairment of cell migration, even after both radiation treatments. With regard to proliferation and genomic stability, dominant-negative Rac1 cells were more sensitive to gamma and UV radiation, exhibiting reduced proliferation and survival consistent with increased DNA damage and delayed or reduced DNA repair observed in this Rac1-deficient clone. The DNA damage response, as indicated by pH2AX and pChk1 levels, was increased in HeLa cells but was not effectively triggered in the Rac1-N17 clone after radiation treatment, which is likely the main cause of DNA damage accumulation. These data suggest that Rac1 GTPase plays an important role in signaling and contributes to the sensitivity of cervical cancer cells under UV or gamma radiation treatments.

  14. Effects of soil conditioners on emergence and growth of tomato-cotton, and lettuce seedlings. [Lycopersicon esculentum; Gossypium hirsutum; Lactuea sativa

    SciTech Connect

    Wallace, A.; Wallace, G.A.

    1986-05-01

    The purpose of this paper is to demonstrate the extent to which seedling emergence and plant growth can be improved with use of new soil conditioners. The early findings regarding polymeric soil conditioners are still valid today, with the exception that much lower application rates are needed today, and different application methodology is available.

  15. Rac3 induces a molecular pathway triggering breast cancer cell aggressiveness: differences in MDA-MB-231 and MCF-7 breast cancer cell lines

    PubMed Central

    2013-01-01

    Background Rho GTPases are involved in cellular functions relevant to cancer. The roles of RhoA and Rac1 have already been established. However, the role of Rac3 in cancer aggressiveness is less well understood. Methods This work was conducted to analyze the implication of Rac3 in the aggressiveness of two breast cancer cell lines, MDA-MB-231 and MCF-7: both express Rac3, but MDA-MB-231 expresses more activated RhoA. The effect of Rac3 in cancer cells was also compared with its effect on the non-tumorigenic mammary epithelial cells MCF-10A. We analyzed the consequences of Rac3 depletion by anti-Rac3 siRNA. Results Firstly, we analyzed the effects of Rac3 depletion on the breast cancer cells’ aggressiveness. In the invasive MDA-MB-231 cells, Rac3 inhibition caused a marked reduction of both invasion (40%) and cell adhesion to collagen (84%), accompanied by an increase in TNF-induced apoptosis (72%). This indicates that Rac3 is involved in the cancer cells’ aggressiveness. Secondly, we investigated the effects of Rac3 inhibition on the expression and activation of related signaling molecules, including NF-κB and ERK. Cytokine secretion profiles were also analyzed. In the non-invasive MCF-7 line; Rac3 did not influence any of the parameters of aggressiveness. Conclusions This discrepancy between the effects of Rac3 knockdown in the two cell lines could be explained as follows: in the MDA-MB-231 line, the Rac3-dependent aggressiveness of the cancer cells is due to the Rac3/ERK-2/NF-κB signaling pathway, which is responsible for MMP-9, interleukin-6, -8 and GRO secretion, as well as the resistance to TNF-induced apoptosis, whereas in the MCF-7 line, this pathway is not functional because of the low expression of NF-κB subunits in these cells. Rac3 may be a potent target for inhibiting aggressive breast cancer. PMID:23388133

  16. Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis.

    PubMed

    Deshmukh, Jayesh; Pofahl, Ruth; Pfister, Herbert; Haase, Ingo

    2016-09-06

    Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin.To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas.

  17. Actin depolymerization mediated loss of SNTA1 phosphorylation and Rac1 activity has implications on ROS production, cell migration and apoptosis.

    PubMed

    Bhat, Sehar Saleem; Parray, Arif Ali; Mushtaq, Umar; Fazili, Khalid Majid; Khanday, Firdous Ahmad

    2016-06-01

    Alpha-1-syntrophin (SNTA1) and Rac1 are part of a signaling pathway via the dystrophin glycoprotein complex (DGC). Both SNTA1 and Rac1 proteins are over-expressed in various carcinomas. It is through the DGC signaling pathway that SNTA1 has been shown to act as a link between the extra cellular matrix, the internal cell signaling apparatus and the actin cytoskeleton. SNTA1 is involved in the modulation of the actin cytoskeleton and actin reorganization. Rac1 also controls actin cytoskeletal organization in the cell. In this study, we present the interplay between f-actin, SNTA1 and Rac1. We analyzed the effect of actin depolymerization on SNTA1 tyrosine phosphorylation and Rac1 activity using actin depolymerizing drugs, cytochalasin D and latrunculin A. Our results indicate a marked decrease in the tyrosine phosphorylation of SNTA1 upon actin depolymerization. Results suggest that actin depolymerization mediated loss of SNTA1 phosphorylation leads to loss of interaction between SNTA1 and Rac1, with a concomitant loss of Rac1 activation. The loss of SNTA1tyrosine phosphorylation and Rac1 activity by actin depolymerization results in increased apoptosis, decreased cell migration and decreased reactive oxygen species (ROS) levels in breast carcinoma cells. Collectively, our results present a possible role of f-actin in the SNTA1-Rac1 signaling pathway and implications of actin depolymerization on cell migration, ROS production and apoptosis.

  18. Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis

    PubMed Central

    Deshmukh, Jayesh; Pofahl, Ruth; Pfister, Herbert; Haase, Ingo

    2016-01-01

    Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin. To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas. PMID:27506937

  19. Preclinical Development of Novel Rac1-GEF Signaling Inhibitors using a Rational Design Approach in Highly Aggressive Breast Cancer Cell Lines

    PubMed Central

    Cardama, Georgina A; Comin, Maria J; Hornos, Leandro; Gonzalez, Nazareno; Defelipe, Lucas; Turjanski, Adrian G; Alonso, Daniel F; Gomez, Daniel E; Menna, Pablo Lorenzano

    2014-01-01

    Rho GTPases play a key role in the regulation of multiple essential cellular processes, including actin dynamics, gene transcription and cell cycle progression. Aberrant activation of Rac1, a member of Rho family of small GTPases, is associated with tumorigenesis, cancer progression, invasion and metastasis. Particularly, Rac1 is overexpressed and hyperactivated in highly aggressive breast cancer. Thus, Rac1 appears to be a promising and relevant target for the development of novel anticancer drugs. We identified the novel Rac1 inhibitor ZINC69391 through a docking-based virtual library screening targeting Rac1 activation by GEFs. This compound was able to block Rac1 interaction with its GEF Tiam1, prevented EGF-induced Rac1 activation and inhibited cell proliferation, cell migration and cell cycle progression in highly aggressive breast cancer cell lines. Moreover, ZINC69391 showed an in vivo antimetastatic effect in a syngeneic animal model. We further developed the novel analog 1A-116 by rational design and showed to be specific and more potent than the parental compound in vitro and interfered Rac1-P-Rex1 interaction. We also showed an enhanced in vivo potency of 1A-116 analog. These results show that we have developed novel Rac1 inhibitors that may be used as a novel anticancer therapy. PMID:24066799

  20. The Botrytis cinerea PAK kinase BcCla4 mediates morphogenesis, growth and cell cycle regulating processes downstream of BcRac.

    PubMed

    Minz-Dub, Anna; Sharon, Amir

    2017-02-06

    Rac proteins are involved in a variety of cellular processes. Effector proteins that interact with active Rac convey the GTPase-generated signal to downstream developmental cascades and processes. Here we report on the analysis of the main effector and signal cascade downstream of BcRac, the Rac homolog of the grey mold fungus Botrytis cinerea. Several lines of evidence highlighted the p21-activated kinase Cla4 as an important effector of Rac in fungi. Analysis of Δbccla4 strains revealed that the BcCla4 protein was sufficient to mediate all of the examined BcRac-driven processes, including hyphal growth and morphogenesis, conidia production and pathogenicity. In addition, the Δbccla4 strains had altered nuclei content, a phenomenon that was previously observed in Δbcrac isolates, thus connecting the BcRac/BcCla4 module with cell cycle control. Further analyses revealed that BcRac/BcCla4 control mitotic entry through changes in phosphorylation status of the cyclin dependent kinase BcCdk1. The complete cascade includes the kinase BcWee1, which is downstream of BcCla4 and upstream of BcCdk1. These results provide a mechanistic insight on the connection of cell cycle, morphogenesis and pathogenicity in fungi, and position BcCla4 as the most essential effector and central regulator of all of these processes downstream of BcRac.

  1. Relationship between Fear Conditionability and Aversive Memories: Evidence from a Novel Conditioned-Intrusion Paradigm

    PubMed Central

    Wegerer, Melanie; Blechert, Jens; Kerschbaum, Hubert; Wilhelm, Frank H.

    2013-01-01

    Intrusive memories – a hallmark symptom of posttraumatic stress disorder (PTSD) – are often triggered by stimuli possessing similarity with cues that predicted or accompanied the traumatic event. According to learning theories, intrusive memories can be seen as a conditioned response to trauma reminders. However, direct laboratory evidence for the link between fear conditionability and intrusive memories is missing. Furthermore, fear conditioning studies have predominantly relied on standardized aversive stimuli (e.g. electric stimulation) that bear little resemblance to typical traumatic events. To investigate the general relationship between fear conditionability and aversive memories, we tested 66 mentally healthy females in a novel conditioned-intrusion paradigm designed to model real-life traumatic experiences. The paradigm included a differential fear conditioning procedure with neutral sounds as conditioned stimuli and short violent film clips as unconditioned stimuli. Subsequent aversive memories were assessed through a memory triggering task (within 30 minutes, in the laboratory) and ambulatory assessment (involuntary aversive memories in the 2 days following the experiment). Skin conductance responses and subjective ratings demonstrated successful differential conditioning indicating that naturalistic aversive film stimuli can be used in a fear conditioning experiment. Furthermore, aversive memories were elicited in response to the conditioned stimuli during the memory triggering task and also occurred in the 2 days following the experiment. Importantly, participants who displayed higher conditionability showed more aversive memories during the memory triggering task and during ambulatory assessment. This suggests that fear conditioning constitutes an important source of persistent aversive memories. Implications for PTSD and its treatment are discussed. PMID:24244407

  2. Diamond Conditioner Microwear Effect on Pad Surface Height Distribution in Tungsten Chemical Mechanical Polishing

    NASA Astrophysics Data System (ADS)

    Yamada, Yohei; Kawakubo, Masanori; Kadomura, Kazunori

    2011-05-01

    In this study, the surface topographies of chemical mechanical polishing (CMP) pad samples for varying levels of diamond microwear of a conditioner have been measured using a confocal microscope and an X-ray computer tomography (CT) scanner. The experimental results showed that the increase in the pad debris on the pad surface reduced the pad height ratio of the asperity called the “top surface area (TSA) ratio”. In addition, the overall removal rate in tungsten CMP was more dependent on the TSA ratio after polishing than on that after conditioning because the pad surface condition became worse with deformed asperities and micropores due to the insufficient conditioning.

  3. An experimental investigation of compressor stall using an on-line distortion indicator and signal conditioner

    NASA Technical Reports Server (NTRS)

    Costakis, W. G.; Wenzel, L. M.

    1975-01-01

    The relation of the steady-state and dynamic distortions and the stall margin of a J85-13 turbojet engine was investigated. A distortion indicator capable of computing two distortion indices was used. A special purpose signal conditioner was also used as an interface between transducer signals and distortion indicator. A good correlation of steady-state distortion and stall margin was established. The prediction of stall by using the indices as instantaneous distortion indicators was not successful. A sensitivity factor that related the loss of stall margin to the turbulence level was found.

  4. Investigation into the common mode rejection ratio of the physiological signal conditioner circuit

    NASA Technical Reports Server (NTRS)

    Obrien, Edward M.

    1992-01-01

    The common mode rejection ratio (CMRR) of the single operational amplifier (op amp) differential amplifier and of the three operational amplifier differential amplifier was investigated. The three op amp differential amplifier circuit is used in the signal conditioner circuit which amplifies signals such as the electromyograph or electrocardiogram. The investigation confirmed via SPICE modeling what has been observed by others in the recent literature that the CMRR for the circuit can be maximized without precision resistor values or precisely matched op amps. This can be done if one resistor in the final stage can be adjusted either by a potentiometer or by laser trimming in the case of hybrid circuit fabrication.

  5. Loss of the E3 ubiquitin ligase HACE1 results in enhanced Rac1 signaling contributing to breast cancer progression

    PubMed Central

    Goka, E T; Lippman, M E

    2015-01-01

    The transition from ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC) is a crucial step in breast cancer progression. The specific alterations that govern this transition have not been elucidated. HER2/neu is frequently overexpressed in DCIS but is less common in IBC, thereby suggesting additional requirements for transformation. To identify genes capable of cooperating with HER2/neu to fully transform mammary epithelial cells, we used an insertional mutagenesis screen on cells isolated from wild-type neu expressing mice and identified the E3 ligase HACE1 as HER2 cooperative tumor suppressor gene. Loss of HACE1 expression is commonly seen in clinical breast cancer data sets. HACE1 downregulation in normal human mammary epithelial cells (HMECs) results in the accumulation of the activated GTP-bound Rac1 partially transforming these cells. Overexpression of HER2 activates Rac1, which further accumulates upon HACE1 loss resulting in Rac1 hyperactivation. Although the knockdown of HACE1 or overexpression of HER2 alone in HMECs is not sufficient for tumorigenesis, HER2 overexpression combined with HACE1 downregulation fully transforms HMECs resulting in robust tumor formation. The pharmaceutical interference of Rac function abrogates the effects of HACE1 loss both in vitro and in vivo, resulting in marked reduction in tumor burden. Our work supports a critical role for HACE1 in breast cancer progression and identifies patients that may benefit from Rac-targeted therapies. PMID:25659579

  6. Polo kinase interacts with RacGAP50C and is required to localize the cytokinesis initiation complex.

    PubMed

    Ebrahimi, Saman; Fraval, Hamilton; Murray, Michael; Saint, Robert; Gregory, Stephen L

    2010-09-10

    The assembly and constriction of an actomyosin contractile ring in cytokinesis is dependent on the activation of Rho at the equatorial cortex by a complex, here termed the cytokinesis initiation complex, between a microtubule-associated kinesin-like protein (KLP), a member of the RacGAP family, and the RhoGEF Pebble. Recently, the activity of the mammalian Polo kinase ortholog Plk1 has been implicated in the formation of this complex. We show here that Polo kinase interacts directly with the cytokinesis initiation complex by binding RacGAP50C. We find that a new domain of Polo kinase, termed the intermediate domain, interacts directly with RacGAP50C and that Polo kinase is essential for localization of the KLP-RacGAP centralspindlin complex to the cell equator and spindle midzone. In the absence of Polo kinase, RacGAP50C and Pav-KLP fail to localize normally, instead decorating microtubules along their length. Our results indicate that Polo kinase directly binds the conserved cytokinesis initiation complex and is required to trigger centralspindlin localization as a first step in cytokinesis.

  7. F-box protein complex FBXL19 regulates TGFβ1-induced E-cadherin down-regulation by mediating Rac3 ubiquitination and degradation

    PubMed Central

    2014-01-01

    Background Rac3 is a small GTPase multifunctional protein that regulates cell adhesion, migration, and differentiation. It has been considered as an oncogene in breast cancer; however, its role in esophageal cancer and the regulation of its stability have not been studied. F-box proteins are major subunits within the Skp1-Cullin-1-F-box (SCF) E3 ubiquitin ligases that recognize particular substrates for ubiquitination and proteasomal degradation. Recently, we have shown that SCFFBXL19 targets Rac1 and RhoA, thus regulating Rac1 and RhoA ubiquitination and degradation. Here, we demonstrate the role of FBXL19 in the regulation of Rac3 site-specific ubiquitination and stability. Expression of TGFβ1 is associated with poor prognosis of esophageal cancer. TGFβ1 reduces tumor suppressor, E-cadherin, expression in various epithelial-derived cancers. Here we investigate the role of FBXL19-mediated Rac3 degradation in TGFβ1-induced E-cadherin down-regulation in esophageal cancer cells. Methods FBXL19-regulated endogenous and over-expressed Rac3 stability were determined by immunoblotting and co-immunoprecipitation. Esophageal cancer cells (OE19 and OE33) were used to investigate TGFβ1-induced E-cadherin down-regulation by Immunoblotting and Immunostaining. Results Overexpression of FBXL19 decreased endogenous and over-expressed Rac3 expression by interacting and polyubiquitinating Rac3, while down-regulation of FBXL19 suppressed Rac3 degradation. Lysine166 within Rac3 was identified as an ubiquitination acceptor site. The FBXL19 variant with truncation at the N-terminus resulted in an increase in Rac3 degradation; however, the FBXL19 variant with truncation at the C-terminus lost its ability to interact with Rac3 and ubiquitinate Rac3 protein. Further, we found that Rac3 plays a critical role in TGFβ1-induced E-cadherin down-regulation in esophageal cancer cells. Over-expression of FBXL19 attenuated TGFβ1-induced E-cadherin down-regulation and esophageal cancer cells

  8. Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4.

    PubMed

    Lee, Jae-Wook; Ryu, Yun-Kyoung; Ji, Young-Hoon; Kang, Joo Hyun; Moon, Eun-Yi

    2015-01-01

    Signaling by small guanosine triphosphatases (GTPase), Rap1/Rac1, is one of the major pathways controlling cancer cell migration and tumor metastasis. Thymosin beta-4 (Tβ4), an actin-sequestering protein, has been shown to increase migration of cancer cells. Episodes of hypoxia and re-oxygenation (H/R) are an important phenomenon in tumor microenvironment (TME). We investigated whether Tβ4 could play as an intermediary to crosstalk between Rac1- and Rap1- GTPase activation under hypoxia/reoxygenation (H/R) conditions. Inhibition of Tβ4 expression using transcription activator-like effector nucleases (TALEN) significantly decreased lung metastasis of B16F10 cells. Rac1 and Rap1 activity, as well as cancer cell migration, increased following induction of Tβ4 expression in normoxia- or H/R-experienced cells, but were barely detectable in Tβ4-depleted cells. Rap1-regulated Rac1 activity was decreased by a dominant negative Rap1 (Rap1N17), and increased by 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (CPT), a Rap1 activator. In contrast, a Rac1-specific inhibitor, NSC23766, and dominant negative Rac1 (Rac1N17) enhanced Tβ4 expression and aberrant Rap1 activity. While NSC23766 and Rac1N17 incompletely inhibited tumor metastasis in vivo, and H/R-experienced cancer cell migration in vitro, more efficient attenuation of cancer cell migration was accomplished by simultaneous inactivation of Rap1 and Rac1 with Rap1N17 and Rac1N17, respectively. These data suggest that a combination therapy targeting both Rap1 and Rac1 activity may be an effective method of inhibiting tumor metastasis.

  9. Rac1 protein signaling is required for DNA damage response stimulated by topoisomerase II poisons.

    PubMed

    Huelsenbeck, Stefanie C; Schorr, Anne; Roos, Wynand P; Huelsenbeck, Johannes; Henninger, Christian; Kaina, Bernd; Fritz, Gerhard

    2012-11-09

    To investigate the potency of the topoisomerase II (topo II) poisons doxorubicin and etoposide to stimulate the DNA damage response (DDR), S139 phosphorylation of histone H2AX (γH2AX) was analyzed using rat cardiomyoblast cells (H9c2). Etoposide caused a dose-dependent increase in the γH2AX level as shown by Western blotting. By contrast, the doxorubicin response was bell-shaped with high doses failing to increase H2AX phosphorylation. Identical results were obtained by immunohistochemical analysis of γH2AX focus formation, comet assay-based DNA strand break analysis, and measuring the formation of the topo II-DNA cleavable complex. At low dose, doxorubicin activated ataxia telangiectasia mutated (ATM) but not ATM and Rad3-related (ATR). Both the lipid-lowering drug lovastatin and the Rac1-specific inhibitor NSC23766 attenuated doxorubicin- and etoposide-stimulated H2AX phosphorylation, induction of DNA strand breaks, and topo II-DNA complex formation. Lovastatin and NSC23766 acted in an additive manner. They did not attenuate doxorubicin-induced increase in p-ATM and p-Chk2 levels. DDR stimulated by topo II poisons was partially blocked by inhibition of type I p21-associated kinases. DDR evoked by the topoisomerase I poison topotecan remained unaffected by lovastatin. The data show that the mechanisms involved in DDR stimulated by topo II poisons are agent-specific with anthracyclines lacking DDR-stimulating activity at high doses. Pharmacological inhibition of Rac1 signaling counteracts doxorubicin- and etoposide-stimulated DDR by disabling the formation of the topo II-DNA cleavable complex. Based on the data we suggest that Rac1-regulated mechanisms are required for DNA damage induction and subsequent activation of the DDR following treatment with topo II but not topo I poisons.

  10. Dynamic Assessment of Fibroblast Mechanical Activity during Rac-induced Cell Spreading in 3-D Culture

    PubMed Central

    Petroll, W. Matthew; Ma, Lisha; Kim, Areum; Ly, Linda; Vishwanath, Mridula

    2009-01-01

    The goal of this study was to determine the morphological and sub-cellular mechanical effects of Rac activation on fibroblasts within 3-D collagen matrices. Corneal fibroblasts were plated at low density inside 100 μm thick fibrillar collagen matrices and cultured for 1 to 2 days in serum-free media. Time-lapse imaging was then performed using Nomarski DIC. After an acclimation period, perfusion was switched to media containing PDGF. In some experiments, Y-27632 or blebbistatin were used to inhibit Rho-kinase (ROCK) or myosin II, respectively. PDGF activated Rac and induced cell spreading, which resulted in an increase in cell length, cell area, and the number of pseudopodial processes. Tractional forces were generated by extending pseudopodia, as indicated by centripetal displacement and realignment of collagen fibrils. Interestingly, the pattern of pseudopodial extension and local collagen fibril realignment was highly dependent upon the initial orientation of fibrils at the leading edge. Following ROCK or myosin II inhibition, significant ECM relaxation was observed, but small displacements of collagen fibrils continued to be detected at the tips of pseudopodia. Taken together, the data suggests that during Rac-induced cell spreading within 3-D matrices, there is a shift in the distribution of forces from the center to the periphery of corneal fibroblasts. ROCK mediates the generation of large myosin II-based tractional forces during cell spreading within 3-D collagen matrices, however residual forces can be generated at the tips of extending pseudopodia that are both ROCK and myosin II-independent. PMID:18452153

  11. The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases

    PubMed Central

    1995-01-01

    Interaction of cells with extracellular matrix via integrin adhesion receptors plays an important role in a wide range of cellular: functions, for example cell growth, movement, and differentiation. Upon interaction with substrate, integrins cluster and associate with a variety of cytoplasmic proteins to form focal complexes and with the actin cytoskeleton. Although the intracellular signals induced by integrins are at present undefined, it is thought that they are mediated by proteins recruited to the focal complexes. It has been suggested, for example, that after recruitment to focal adhesions p125FAK can activate the ERK1/2 MAP kinase cascade. We have previously reported that members of the rho family of small GTPases can trigger the assembly of focal complexes when activated in cells. Using microinjection techniques, we have now examined the role of the extracellular matrix and of the two GTP-binding proteins, rac and rho, in the assembly of integrin complexes in both mouse and human fibroblasts. We find that the interaction of integrins with extracellular matrix alone is not sufficient to induce integrin clustering and focal complex formation. Similarly, activation of rho or rac by extracellular growth factors does not lead to focal complex formation in the absence of matrix. Focal complexes are only assembled in the presence of both matrix and functionally active members of the rho family. In agreement with this, the interaction of integrins with matrix in the absence of rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In fact, ERK1/2 can be activated fully by growth factors in the absence of matrix and it seems unlikely, therefore, that the adhesion dependence of fibroblast growth is mediated through the ras/MAP kinase pathway. We conclude that extracellular matrix is not sufficient to trigger focal complex assembly and subsequent integrin-dependent signal transduction in the absence of functionally active members of the rho

  12. Disease-causing mutations of RhoGDIα induce Rac1 hyperactivation in podocytes

    PubMed Central

    Auguste, David; Maier, Mirela; Baldwin, Cindy; Aoudjit, Lamine; Robins, Richard; Gupta, Indra R.; Takano, Tomoko

    2016-01-01

    ABSTRACT Nephrotic syndrome (NS) describes a group of kidney disorders in which there is injury to podocyte cells, specialized cells within the kidney's glomerular filtration barrier, allowing proteins to leak into the urine. Three mutations in ARHGDIA, which encodes Rho GDP dissociation inhibitor α (GDIα), have been reported in patients with heritable NS and encode the following amino acid changes: ΔD185, R120X, and G173V. To investigate the impact of these mutations on podocyte function, endogenous GDIα was knocked-down in cultured podocytes by shRNA and then the cells were re-transfected with wild-type or mutant GDIα constructs. Among the 3 prototypical Rho-GTPases, Rac1 was markedly hyperactivated in podocytes with any of the 3 mutant forms of GDIα while the activation of RhoA and Cdc42 was modest and variable. All three mutant GDIα proteins resulted in slow podocyte motility, suggesting that podocytes are sensitive to the relative balance of Rho-GTPase activity. In ΔD185 podocytes, both random and directional movements were impaired and kymograph analysis of the leading edge showed increased protrusion and retraction of leading edge (phase switching). The mutant podocytes also showed impaired actin polymerization, smaller cell size, and increased cellular projections. In the developing kidney, GDIα expression increased as podocytes matured. Conversely, active Rac1 was detected only in immature, but not in mature, podocytes. The results indicate that GDIα has a critical role in suppressing Rac1 activity in mature podocytes, to prevent podocyte injury and nephrotic syndrome. PMID:26726844

  13. The 2Πg shape resonance of acetylene anion: an investigation with the RAC method

    NASA Astrophysics Data System (ADS)

    Čurík, Roman; Paidarová, Ivana; Horáček, Jiří

    2016-07-01

    Recently developed method of regularized analytic continuation (RAC) is applied to determination of the 2Πg resonance of acetylene anion. The method is based on continuation of the electron affinities calculated for the anion in presence of an external perturbation field. Its independence on the correlation treatment of the many-electron system allows application of accurate coupled-clusters methods for electronic structure calculations utilized in determination of the resonance position and width. Contribution to the Topical Issue "Advances in Positron and Electron Scattering", edited by Paulo Limao-Vieira, Gustavo Garcia, E. Krishnakumar, James Sullivan, Hajime Tanuma and Zoran Petrovic.

  14. Yttrium phosphasalen initiators for rac-lactide polymerization: excellent rates and high iso-selectivities.

    PubMed

    Bakewell, Clare; Cao, Thi-Phuong-Anh; Long, Nicholas; Le Goff, Xavier F; Auffrant, Audrey; Williams, Charlotte K

    2012-12-26

    Highly active yttrium phosphasalen initiators for the stereocontrolled ring-opening polymerization of rac-lactide are reported. The initiators are coordinated by a new class of ancillary ligand: an iminophosphorane derivative of the popular "salen" ligand, termed "phosphasalen". Changing the phosphasalen structure enables access to high iso-selectivities (P(i) = 0.84) or hetero-selectivities (P(s) = 0.87). The initiators also show very high rates, excellent polymerization control, and tolerance to low loadings; furthermore, no chiral auxiliaries/ligands are needed for the stereocontrol. The combination of such high rates with high iso-selectivities is very unusual.

  15. Design of Interline Unified Power Quality Conditioner for Power Quality Disturbances using Simulink

    NASA Astrophysics Data System (ADS)

    Kumaraswamy, G.; Reddy, Y. Rajasekhar; Harikrishna, Ch.

    2012-10-01

    Proliferation of electronic equipment in commercial and industrial processes has resulted in increasingly sensitive electrical loads to be fed from power distribution system which introduce contamination to voltage and current waveforms at the point of common coupling of industrial loads. The unified power quality conditioner (UPQC) is connected between two different feeders (lines), hence this method of connection of the UPQC is called as Interline UPQC (IUPQC).This paper proposes a new connection for a UPQC to improve the power quality of two feeders in a distribution system. Interline Unified Power Quality Conditioner (IUPQC), specifically aims at the integration of series VSC and Shunt VSC to provide high quality power supply by means of voltage sag/swell compensation, harmonic elimination and power factor correction in a power distribution network, so that improved power quality can be made available at the point of common coupling. The structure, control and capability of the IUPQC are discussed in this paper. The efficiency of the proposed configuration has been verified through simulation using MATLAB/ SIMULINK.

  16. Cross GTPase-activating protein (CrossGAP)/Vilse links the Roundabout receptor to Rac to regulate midline repulsion.

    PubMed

    Hu, Hailan; Li, Ming; Labrador, Juan-Pablo; McEwen, Jason; Lai, Eric C; Goodman, Corey S; Bashaw, Greg J

    2005-03-22

    The regulators of the Rho-family GTPases, GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs), play important roles in axon guidance. By means of a functional genomic study of the Rho-family GEFs and GAPs in Drosophila, we have identified a Rho-family GAP, CrossGAP (CrGAP), which is involved in Roundabout (Robo) receptor-mediated repulsive axon guidance. CrGAP physically associates with the Robo receptor. Too much or too little CrGAP activity leads to defects in Robo-mediated repulsion at the midline choice point. The CrGAP gain-of-function phenotype mimics the loss-of-function phenotypes of both Robo and Rac. Dosage-sensitive genetic interactions among CrGAP, Robo, and Rac support a model in which CrGAP transduces signals downstream of Robo receptor to regulate Rac-dependent cytoskeletal changes.

  17. Chemo-enzymatic synthesis of rac 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine and its analogues.

    PubMed

    Vijeeta, Tadla; Balakrishna, Marrapu; Lakshmi Karuna, Mallampalli Sri; Surya Koppeswara Rao, Bhamidipati Venkata; Narayana Prasad, Rachapudi Badari

    2014-01-01

    The synthesis of rac 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholines (6a-c), blood platelet activating ether lipid analogues has been achieved in a four-step sequence from epichlorohydrin (1). Etherification of epichlorohydrin with different alcohols namely tetradecyl (2a), hexadecyl (2b) and octadecyl (2c) alcohols gave glycidyl ethers (3a-c) with 78-80% yields. The second step involved opening of the epoxide by acetic anhydride to give acetylated products (4a-c, 76-78% yield), which were subsequently hydrolyzed selectively, a key step of the method employing a 1,3 specific lipase to obtain rac 1-O-alkyl-2- acetylglycerol (5a-c) with 45-50% yields. The hydrolyzed products (5a-c) were phosphorylated to obtain rac 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholines (6a-c) in 80-85% yields.

  18. The role of chemokine activation of Rac GTPases in hematopoietic stem cell marrow homing, retention, and peripheral mobilization.

    PubMed

    Cancelas, Jose A; Jansen, Michael; Williams, David A

    2006-08-01

    Signaling downstream from the chemokine receptor CXCR4, the tyrosine kinase receptor c-kit and beta1-integrins has been shown to be crucial in the regulation of migration, homing, and engraftment of hematopoietic stem cells and progenitors. Each of these receptors signal through Rac-type Rho guanosine triphosphatases (GTPases). Rac GTPases play a major role in the organization of the actin cytoskeleton and also in the control of gene expression and the activation of proliferation and survival pathways. Here we review the specific roles of the members of the Rac subfamily of the Rho GTPase family in regulating the intracellular signaling of hematopoietic cells responsible for regulation of homing, marrow retention, and peripheral mobilization.

  19. Dock10, a Cdc42 and Rac1 GEF, induces loss of elongation, filopodia, and ruffles in cervical cancer epithelial HeLa cells

    PubMed Central

    Ruiz-Lafuente, Natalia; Alcaraz-García, María-José; García-Serna, Azahara-María; Sebastián-Ruiz, Silvia; Moya-Quiles, María-Rosa; García-Alonso, Ana-María; Parrado, Antonio

    2015-01-01

    Dock10 is one of the three members of the Dock-D family of Dock proteins, a class of guanine nucleotide exchange factors (GEFs) for Rho GTPases. Its homologs Dock9 and Dock11 are Cdc42 GEFs. Dock10 is required for maintenance of rounded morphology and amoeboid-type movement. Full-length isoforms of Dock10 have been recently cloned. Here, we address GTPase specificity and GEF activity of Dock10. In order of decreasing intensity, Dock10 interacted with nucleotide-free Rac1, Cdc42, and Rac3, and more weakly with Rac2, RhoF, and RhoG. Inducible expression of Dock10 in HeLa epithelial cells promoted GEF activity on Cdc42 and Rac1, and a morphologic change in two-dimensional culture consisting in loss of cell elongation, increase of filopodia, and ruffles. Area in contact with the substrate of cells that spread with non-elongated morphology was larger in cells expressing Dock10. Inducible expression of constitutively active mutants of Cdc42 and Rac1 in HeLa cells also induced loss of elongation. However, Cdc42 induced filopodia and contraction, and Rac1 induced membrane ruffles and flattening. When co-expressed with Dock10, Cdc42 potentiated filopodia, and Rac1 potentiated ruffles. These results suggest that Dock10 functions as a dual GEF for Cdc42 and Rac1, affecting cell morphology, spreading and actin cytoskeleton protrusions of adherent HeLa cells. PMID:25862245

  20. Dissociation of GDP dissociation inhibitor and membrane translocation are required for efficient activation of Rac by the Dbl homology-pleckstrin homology region of Tiam.

    PubMed

    Robbe, Karine; Otto-Bruc, Annie; Chardin, Pierre; Antonny, Bruno

    2003-02-14

    Small G proteins of the Rho/Rac/Cdc42 family are associated with lipid membranes through their prenylated C termini. Alternatively, these proteins form soluble complexes with GDI proteins. To assess how this membrane partitioning influences the activation of Rac by guanine nucleotide exchange factors, GDP-to-GTP exchange reactions were performed in the presence of liposomes using different forms of Rac-GDP. We show that both non-prenylated Rac-GDP and the soluble complex between prenylated Rac-GDP and GDI are poorly activated by the Dbl homology-pleckstrin homology (DH-PH) domain of the exchange factor Tiam1, whereas prenylated Rac-GDP bound to liposomes is activated about 10 times more rapidly. Sedimentation experiments with liposomes reveal that the DH-PH region of Tiam1 forms, with nucleotide-free prenylated Rac, a membrane-bound complex from which GDI is excluded. Taken together, these experiments demonstrate that the dissociation of Rac-GDP from GDI and its translocation to membrane lipids favor DH-PH-catalyzed nucleotide exchange because the steric hindrance caused by GDI is relieved and because the membrane environment favors functional interaction between the DH-PH domain and the small G protein.