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Sample records for driving cycles induce

  1. Driving and engine cycles

    CERN Document Server

    Giakoumis, Evangelos G

    2017-01-01

    This book presents in detail the most important driving and engine cycles used for the certification and testing of new vehicles and engines around the world. It covers chassis and engine-dynamometer cycles for passenger cars, light-duty vans, heavy-duty engines, non-road engines and motorcycles, offering detailed historical information and critical review. The book also provides detailed examples from SI and diesel engines and vehicles operating during various cycles, with a focus on how the engine behaves during transients and how this is reflected in emitted pollutants, CO2 and after-treatment systems operation. It describes the measurement methods for the testing of new vehicles and essential information on the procedure for creating a driving cycle. Lastly, it presents detailed technical specifications on the most important chassis-dynamometer cycles around the world, together with a direct comparison of those cycles.

  2. Naturalistic drive cycle synthesis for pickup trucks.

    Science.gov (United States)

    Liu, Zifan; Ivanco, Andrej; Filipi, Zoran

    2015-09-01

    Future pick-up trucks are meeting much stricter fuel economy and exhaust emission standards. Design tradeoffs will have to be carefully evaluated to satisfy consumer expectations within the regulatory and cost constraints. Boundary conditions will obviously be critical for decision making: thus, the understanding of how customers are driving in naturalistic settings is indispensable. Federal driving schedules, while critical for certification, do not capture the richness of naturalistic cycles, particularly the aggressive maneuvers that often shape consumer perception of performance. While there are databases with large number of drive cycles, applying all of them directly in the design process is impractical. Therefore, representative drive cycles that capture the essence of the naturalistic driving should be synthesized from naturalistic driving data. Naturalistic drive cycles are firstly categorized by investigating their micro-trip components, defined as driving activities between successive stops. Micro-trips are expected to characterize underlying local traffic conditions, and separate different driving patterns. Next, the transitions from one vehicle state to another vehicle state in each cycle category are captured with Transition Probability Matrix (TPM). Candidate drive cycles can subsequently be synthesized using Markov Chain based on TPMs for each category. Finally, representative synthetic drive cycles are selected through assessment of significant cycle metrics to identify the ones with smallest errors. This paper provides a framework for synthesis of representative drive cycles from naturalistic driving data, which can subsequently be used for efficient optimization of design or control of pick-up truck powertrains. Manufacturers will benefit from representative drive cycles in several aspects, including quick assessments of vehicle performance and energy consumption in simulations, component sizing and design, optimization of control strategies, and

  3. CHOOSING DRIVING CYCLE OF HYBRID VEHICLE

    Directory of Open Access Journals (Sweden)

    A. Vorona

    2011-01-01

    Full Text Available The analysis of existing driving cycles was performed. After comparing some of the cycles, one specific driving cycle was selected for the hybrid vehicle as the most reliable in representing the real moving of the vehicle in operating conditions and which may be reproduced at experimental tests at the modeling roller stand.

  4. VEHICLE DRIVING CYCLE OPTIMISATION ON THE HIGHWAY

    Directory of Open Access Journals (Sweden)

    Zinoviy STOTSKO

    2016-06-01

    Full Text Available This paper is devoted to the problem of reducing vehicle energy consumption. The authors consider the optimisation of highway driving cycle a way to use the kinetic energy of a car more effectively at various road conditions. The model of a vehicle driving control at the highway which consists of elementary cycles, such as accelerating, free rolling and deceleration under forces of external resistance, was designed. Braking, as an energy dissipation regime, was not included. The influence of the various longitudinal profiles of the road was taken into consideration and included in the model. Ways to use the results of monitoring road and traffic conditions are presented. The method of non-linear programming is used to design the optimal vehicle control function and phase trajectory. The results are presented by improved typical driving cycles that present energy saving as a subject of choice at a specified schedule.

  5. Evolutionary algorithm for vehicle driving cycle generation.

    Science.gov (United States)

    Perhinschi, Mario G; Marlowe, Christopher; Tamayo, Sergio; Tu, Jun; Wayne, W Scott

    2011-09-01

    Modeling transit bus emissions and fuel economy requires a large amount of experimental data over wide ranges of operational conditions. Chassis dynamometer tests are typically performed using representative driving cycles defined based on vehicle instantaneous speed as sequences of "microtrips", which are intervals between consecutive vehicle stops. Overall significant parameters of the driving cycle, such as average speed, stops per mile, kinetic intensity, and others, are used as independent variables in the modeling process. Performing tests at all the necessary combinations of parameters is expensive and time consuming. In this paper, a methodology is proposed for building driving cycles at prescribed independent variable values using experimental data through the concatenation of "microtrips" isolated from a limited number of standard chassis dynamometer test cycles. The selection of the adequate "microtrips" is achieved through a customized evolutionary algorithm. The genetic representation uses microtrip definitions as genes. Specific mutation, crossover, and karyotype alteration operators have been defined. The Roulette-Wheel selection technique with elitist strategy drives the optimization process, which consists of minimizing the errors to desired overall cycle parameters. This utility is part of the Integrated Bus Information System developed at West Virginia University.

  6. 40 CFR 600.109-78 - EPA driving cycles.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false EPA driving cycles. 600.109-78 Section... Model Year Automobiles-Test Procedures § 600.109-78 EPA driving cycles. (a) The driving cycle to be... driving cycle to be utilized for generation of the highway fuel economy data is specified in this...

  7. 40 CFR 600.109-08 - EPA driving cycles.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false EPA driving cycles. 600.109-08 Section... Model Year Automobiles-Test Procedures § 600.109-08 EPA driving cycles. (a) The FTP driving cycle is prescribed in § 86.115 of this chapter. (b) The highway fuel economy driving cycle is specified in this...

  8. Batu Pahat Driving Cycle for Light Duty Gasoline Engine

    Science.gov (United States)

    Zainul Abidin, Zainul Ameerul Ikhsan B.; Faisal Hushim, Mohd; Ahmad, Osman Bin

    2017-08-01

    Driving cycle is a series of data points that represents the vehicle speed versus time. Transient driving cycles involve many changes such as frequent speed changes during typical on-road driving condition [2]. Model driving cycles involve protracted periods at constant speeds. The Batu Pahat Driving Cycle (BPDC) developed to represent the driving pattern of people in a district of Batu Pahat. Based on this driving cycle, it will be a reference to other researchers to study about the gases emission release and fuel consumption by the vehicle on the dynamometer or automotive simulation based on this driving cycle. Existing driving cycles used such as the New European Driving Cycle (NEDC), the Federal Test Procedure (FTP-72/75, and Japan 10-15 Mode Cycle is not appropriate for Batu Pahat district because of different road conditions, driving habits and environmental of developed driving cycle countries are not same [2][14]. Batu Pahat drive cycle was developed for low-capacity gasoline engine under 150 cc and operating on urban roads, rural roads and road around Universiti Tun Hussein Onn. The importance of these driving cycle as the reference for other research to measure and do automotive simulation regarding fuel consumption and gas emission release from the motorcycle for these three type of driving cycle area. Another use for driving cycles is in vehicle simulations [3]. More specifically, they are used in propulsion system simulations to predict the performance of internal combustion engines, transmissions, electric drive systems, batteries, fuel cell systems, and similar components [18]. Data collection methods used in this study is the use of Global Positioning System (GPS). The results obtained are not similar to each other due to differences in congestion on data taken. From the driving cycle graph obtained, such as the average velocity, maximum velocity, the duration and Positive Acceleration Kinetic Energy (PKE) can be determined. In addition, the best

  9. The ARTEMIS European driving cycles for measuring car pollutant emissions

    OpenAIRE

    ANDRE, M

    2004-01-01

    In the past 10 years, various work has been undertaken to collect data on the actual driving of European cars and to derive representative real-world driving cycles. A compilation and synthesis of this work is provided in this paper. In the frame of the European research project: ARTEMIS, this work has been considered to derive a set of reference driving cycles. The main objectives were as follows:- to derive a common set of reference real-world driving cycles to be used in the frame of the A...

  10. Development of Urban Driving Cycle with GPS Data Post Processing

    Directory of Open Access Journals (Sweden)

    Peter Lipar

    2016-08-01

    Full Text Available This paper presents GIS-based methodology for urban area driving cycle construction. The approach reaches beyond the frames of usual driving cycle development methods and takes into account another perspective of data collection. Rather than planning data collection, the approach is based on available in-vehicle measurement data post processing using Geographic Information Systems to manipulate the excessive database and extract only the representative and geographically limited individual trip data. With such data post processing the data was carefully adjusted to include only the data that describe representative driving in Ljubljana urban area. The selected method for the driving cycle development is based on searching for the best microtrips combination while minimizing the difference between two vectors; one based on generated cycle and the other on the database. Accounting for a large random sample of actual trip data, our approach enables more representative area-specific driving cycle development than the previously used techniques.

  11. The ARTEMIS European driving cycles for measuring car pollutant emissions.

    Science.gov (United States)

    André, Michel

    2004-12-01

    In the past 10 years, various work has been undertaken to collect data on the actual driving of European cars and to derive representative real-world driving cycles. A compilation and synthesis of this work is provided in this paper. In the frame of the European research project: ARTEMIS, this work has been considered to derive a set of reference driving cycles. The main objectives were as follows: to derive a common set of reference real-world driving cycles to be used in the frame of the ARTEMIS project but also in the frame of on-going national campaigns of pollutant emission measurements, to ensure the compatibility and integration of all the resulting emission data in the European systems of emission inventory; to ensure and validate the representativity of the database and driving cycles by comparing and taking into account all the available data regarding driving conditions; to include in three real-world driving cycles (urban, rural road and motorway) the diversity of the observed driving conditions, within sub-cycles allowing a disaggregation of the emissions according to more specific driving conditions (congested and free-flow urban). Such driving cycles present a real advantage as they are derived from a large database, using a methodology that was widely discussed and approved. In the main, these ARTEMIS driving cycles were designed using the available data, and the method of analysis was based to some extent on previous work. Specific steps were implemented. The study includes characterisation of driving conditions and vehicle uses. Starting conditions and gearbox use are also taken into account.

  12. Simulation of Automated Vehicles' Drive Cycles

    Science.gov (United States)

    2018-02-28

    This research has two objectives: 1) To develop algorithms for plausible and legally-justifiable freeway car-following and arterial-street gap acceptance driving behavior for AVs 2) To implement these algorithms on a representative road network, in o...

  13. Performance Analysis of Hybrid Electric Vehicle over Different Driving Cycles

    Science.gov (United States)

    Panday, Aishwarya; Bansal, Hari Om

    2017-02-01

    Article aims to find the nature and response of a hybrid vehicle on various standard driving cycles. Road profile parameters play an important role in determining the fuel efficiency. Typical parameters of road profile can be reduced to a useful smaller set using principal component analysis and independent component analysis. Resultant data set obtained after size reduction may result in more appropriate and important parameter cluster. With reduced parameter set fuel economies over various driving cycles, are ranked using TOPSIS and VIKOR multi-criteria decision making methods. The ranking trend is then compared with the fuel economies achieved after driving the vehicle over respective roads. Control strategy responsible for power split is optimized using genetic algorithm. 1RC battery model and modified SOC estimation method are considered for the simulation and improved results compared with the default are obtained.

  14. The Development of Vocational Vehicle Drive Cycles and Segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Duran, Adam W. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Phillips, Caleb T. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Konan, Arnaud M. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Kelly, Kenneth J. [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2017-09-28

    Under a collaborative interagency agreement between the U.S. Environmental Protection Agency and the U.S Department of Energy (DOE), the National Renewable Energy Laboratory (NREL) performed a series of in-depth analyses to characterize the on-road driving behavior including distributions of vehicle speed, idle time, accelerations and decelerations, and other driving metrics of medium- and heavy-duty vocational vehicles operating within the United States. As part of this effort, NREL researchers segmented U.S. medium- and heavy-duty vocational vehicle driving characteristics into three distinct operating groups or clusters using real world drive cycle data collected at 1 Hz and stored in NREL's Fleet DNA database. The Fleet DNA database contains millions of miles of historical real-world drive cycle data captured from medium- and heavy vehicles operating across the United States. The data encompass data from existing DOE activities as well as contributions from valued industry stakeholder participants. For this project, data captured from 913 unique vehicles comprising 16,250 days of operation were drawn from the Fleet DNA database and examined. The Fleet DNA data used as a source for this analysis has been collected from a total of 30 unique fleets/data providers operating across 22 unique geographic locations spread across the United States. This includes locations with topology ranging from the foothills of Denver, Colorado, to the flats of Miami, Florida. The range of fleets, geographic locations, and total number of vehicles analyzed ensures results that include the influence of these factors. While no analysis will be perfect without unlimited resources and data, it is the researchers understanding that the Fleet DNA database is the largest and most thorough publicly accessible vocational vehicle usage database currently in operation. This report includes an introduction to the Fleet DNA database and the data contained within, a presentation of the

  15. Development of a driving cycle to evaluate the energy economy of electric vehicles in urban areas

    International Nuclear Information System (INIS)

    Brady, John; O’Mahony, Margaret

    2016-01-01

    Highlights: • Development of a driving cycle to evaluate energy economy of electric vehicles. • Improves on existing driving cycles by using real world data from electric vehicles. • Driving data from different road types and traffic conditions included. - Abstract: Understanding real-world driving conditions in the form of driving cycles is instrumental in the design of efficient powertrains and energy storage systems for electric vehicles. In addition, driving cycles serve as a standardised measurement procedure for the certification of a vehicle’s fuel economy and driving range. They also facilitate the evaluation of the economic and lifecycle costs of emerging vehicular technologies. However, discrepancies between existing driving cycles and real-world driving conditions exist due to a number of factors such as insufficient data, inadequate driving cycle development methodologies and methods to assess the representativeness of developed driving cycles. The novel aspect of the work presented here is the use of real-world data from electric vehicles, over a six month period, to derive a driving cycle appropriate for their assessment. A stochastic and statistical methodology is used to develop and assess the representativeness of the driving cycle against a separate set of real world electric vehicle driving data and the developed cycle performs well in that comparison. Although direct comparisons with internal combustion engine driving cycles are not that informative or relevant due to the marked differences between how they and electric vehicles operate, some discussion around how the developed electric vehicle cycle relates to them is also included.

  16. 40 CFR Appendix E to Subpart S of... - Transient Test Driving Cycle

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 2 2010-07-01 2010-07-01 false Transient Test Driving Cycle E Appendix... Driving Cycle (I) Driver's trace. All excursions in the transient driving cycle shall be evaluated by the... shall cause a test to be void. In addition, provisions shall be available to utilize cycle validation...

  17. Comparison of real driving cycles and consumed braking power in suburban Slovakian driving

    Directory of Open Access Journals (Sweden)

    Gechev Tsvetomir

    2017-01-01

    Full Text Available The paper compares the features of suburban real driving cycles performed with CORRSYS DATRON measurement equipment on routes in the region of Žilina, Slovakia. It observes differences in the maximum and average vehicle velocities and the amount of braking in relation to the elevation profile of each individual cycle. Consumed braking power was also calculated in the different cycles in order to review the potential electricity regeneration capabilities of hybrid electric vehicles, operating on the same routes. The change in braking energy depending on vehicle mass and presence of grade on the routes in the measured cycles was also assessed. The calculations and plotting were done by using Matlab software.

  18. Evaluation of the Renault Express Electrique over six different driving cycles

    NARCIS (Netherlands)

    2000-01-01

    A Renault Express Electrique with a conventional drive line has been evaluated by IAE over a range of six different drive cycles. Each cycle was driven once, with a fully charged battery. From the measurement results the energy consumption and the cycle length were examined. This document contains a

  19. Influence of driving cycles on exhaust emissions and fuel consumption of gasoline passenger car in Bangkok.

    Science.gov (United States)

    Nutramon, Tamsanya; Supachart, Chungpaibulpatana

    2009-01-01

    The influence of different driving cycles on their exhaust emissions and fuel consumption rate of gasoline passenger car was investigated in Bangkok based on the actual measurements obtained from a test vehicle driving on a standard chassis dynamometer. A newly established Bangkok driving cycle (BDC) and the European driving cycle (EDC) which is presently adopted as the legislative cycle for testing automobiles registered in Thailand were used. The newly developed BDC is constructed using the driving characteristic data obtained from the real on-road driving tests along selected traffic routes. A method for selecting appropriate road routes for real driving tests is also introduced. Variations of keyed driving parameters of BDC with different driving cycles were discussed. The results showed that the HC and CO emission factors of BDC are almost two and four times greater than those of EDC, respectively. Although the difference in the NOx emission factor is small, the value from BDC is still greater than that of EDC by 10%. Under BDC, the test vehicle consumes fuel about 25% more than it does under EDC. All these differences are mainly attributed to the greater proportion of idle periods and higher fluctuations of vehicle speed in the BDC cycle. This result indicated that the exhausted emissions and fuel consumption of vehicles obtained from tests under the legislative modal-type driving cycle (EDC) are significantly different from those actually produced under real traffic conditions especially during peak periods.

  20. Synthesis of realistic driving cycles with high accuracy and computational speed, including slope information

    NARCIS (Netherlands)

    Silvas, E.; Hereijgers, K.; Peng, Huei; Hofman, T.; Steinbuch, M.

    2016-01-01

    This paper describes a new method to synthesize driving cycles, where not only the velocity is considered, yet also the road slope information of the real-world measured driving cycle. Driven by strict emission regulations and tight fuel targets, hybrid or electric vehicle manufacturers aim to

  1. A Dynamic Control Strategy for Hybrid Electric Vehicles Based on Parameter Optimization for Multiple Driving Cycles and Driving Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Zhenzhen Lei

    2017-01-01

    Full Text Available The driving pattern has an important influence on the parameter optimization of the energy management strategy (EMS for hybrid electric vehicles (HEVs. A new algorithm using simulated annealing particle swarm optimization (SA-PSO is proposed for parameter optimization of both the power system and control strategy of HEVs based on multiple driving cycles in order to realize the minimum fuel consumption without impairing the dynamic performance. Furthermore, taking the unknown of the actual driving cycle into consideration, an optimization method of the dynamic EMS based on driving pattern recognition is proposed in this paper. The simulation verifications for the optimized EMS based on multiple driving cycles and driving pattern recognition are carried out using Matlab/Simulink platform. The results show that compared with the original EMS, the former strategy reduces the fuel consumption by 4.36% and the latter one reduces the fuel consumption by 11.68%. A road test on the prototype vehicle is conducted and the effectiveness of the proposed EMS is validated by the test data.

  2. Study on the effect of driving cycles on energy efficiency of electric vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Ji Fenzhu; Xu Licong [School of Transportation Science and Engineering of Beihang Univ., BJ (China); Wu Zhixin [Tianjin Qing Yuan Electric Vehicle Corp. Ltd., TJ (China)

    2009-07-01

    The energy usage efficiency of electric vehicles (EVS) and evaluation index of electromotor efficiency were studied. The idea of ''interval usage percentage of energy efficiency'' and ''exertion degree of energy efficiency'' of electromotor was brought forward. The effect of driving cycles on the distribution of running status of electromotor and its efficiency was investigated. The electromotor efficiency and the variety trend of average driving force at different driving cycles were discussed. Based on several typical domestic and foreign driving cycles, the exertion degree of energy efficiency and the whole efficiency of power train on some types of EVS were analyzed and calculated. The result indicates that there is a difference of 9.64% in exertion degree of energy efficiency of electromotor at different driving cycles. The efficiency distribution of electromotor and control system is different, and the average driving force is different, too. That cause the great variety in driving range. The idiographic reference data are provided to the establishment of driving cycles' criterion of EVS in our country. (orig.)

  3. Influence of driving cycles on Euro 3 scooter emissions and fuel consumption

    International Nuclear Information System (INIS)

    Prati, Maria V.; Zamboni, Giorgio; Costagliola, Maria A.; Meccariello, Giovanni; Carraro, Chiara; Capobianco, Massimo

    2011-01-01

    Highlights: → Fuel consumption and emissions of Euro 3 scooters defined on different driving cycles. → Comparison of standard, real world driving cycles and measured urban speed patterns. → Statistical analysis of kinematic parameters to group driving cycle in clusters. → Clusters can explain pollutant and fuel consumption behaviour in hot conditions. → Cold start mixture enrichment strategy has a major influence on extra-emissions. - Abstract: Regulated pollutant emissions and fuel consumption were characterized at the exhaust of two Euro 3 4-stroke medium-size motorcycles during the execution of both standard and real world driving cycles. A principal component analysis was carried out to group in a cluster the driving cycles with similar kinematic parameters. Hot start results, analysed according to this cluster grouping, show that the main differences are explained by overall mean speed and high positive acceleration of driving cycles. Lower mean speeds produce higher CO 2 emission factors, while the influence on CO and HC is more complex. NO X are not significantly affected by the driving pattern. Inside the same cluster, the whole duration of the acceleration phases could discriminate emission behaviour. In-depth analysis of cold start results was conducted in order to assess the influence of the driving cycle and vehicle characteristics on cold start duration. Cold start extra emissions are more influenced by the duration of the enrichment phase than by the catalyst light-off. The larger number of accelerations occurring during real world driving cycles produces higher variability of air fuel ratio and hence higher cold start extra emissions.

  4. Comparison of Plug-In Hybrid Electric Vehicle Battery Life Across Geographies and Drive-Cycles

    International Nuclear Information System (INIS)

    Smith, K.; Warleywine, M.; Wood, E.; Neubauer, J.; Pesaran, A.

    2012-01-01

    In a laboratory environment, it is cost prohibitive to run automotive battery aging experiments across a wide range of possible ambient environment, drive cycle and charging scenarios. Since worst-case scenarios drive the conservative sizing of electric-drive vehicle batteries, it is useful to understand how and why those scenarios arise and what design or control actions might be taken to mitigate them. In an effort to explore this problem, this paper applies a semi-empirical life model of the graphite/nickel-cobalt-aluminum lithium-ion chemistry to investigate impacts of geographic environments under storage and simplified cycling conditions. The model is then applied to analyze complex cycling conditions, using battery charge/discharge profiles generated from simulations of PHEV10 and PHEV40 vehicles across 782 single-day driving cycles taken from Texas travel survey data.

  5. Real-world and specific to vehicle driving cycles for measuring car pollutant emissions

    OpenAIRE

    ANDRE, M; JOUMARD, R

    2004-01-01

    In the frame of the European research project ARTEMIS, a set of representative real-world driving cycles has been developed, to ensure a coherency between the pollutant emissions measurements conducted in the frame of the ARTEMIS project and of on-going national campaigns and to enable the integration of all the resulting emission data in the European systems of emission inventory. The 3 real-world ARTEMIS driving cycles (urban, rural road and motorway) represent the observed European drivi...

  6. Stochastic Real-World Drive Cycle Generation Based on a Two Stage Markov Chain Approach

    NARCIS (Netherlands)

    Balau, A.E.; Kooijman, D.; Vazquez Rodarte, I.; Ligterink, N.

    2015-01-01

    This paper presents a methodology and tool that stochastically generates drive cycles based on measured data, with the purpose of testing and benchmarking light duty vehicles in a simulation environment or on a test-bench. The WLTP database, containing real world driving measurements, was used as

  7. Modeling Heavy/Medium-Duty Fuel Consumption Based on Drive Cycle Properties

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lijuan; Duran, Adam; Gonder, Jeffrey; Kelly, Kenneth

    2015-10-13

    This paper presents multiple methods for predicting heavy/medium-duty vehicle fuel consumption based on driving cycle information. A polynomial model, a black box artificial neural net model, a polynomial neural network model, and a multivariate adaptive regression splines (MARS) model were developed and verified using data collected from chassis testing performed on a parcel delivery diesel truck operating over the Heavy Heavy-Duty Diesel Truck (HHDDT), City Suburban Heavy Vehicle Cycle (CSHVC), New York Composite Cycle (NYCC), and hydraulic hybrid vehicle (HHV) drive cycles. Each model was trained using one of four drive cycles as a training cycle and the other three as testing cycles. By comparing the training and testing results, a representative training cycle was chosen and used to further tune each method. HHDDT as the training cycle gave the best predictive results, because HHDDT contains a variety of drive characteristics, such as high speed, acceleration, idling, and deceleration. Among the four model approaches, MARS gave the best predictive performance, with an average absolute percent error of -1.84% over the four chassis dynamometer drive cycles. To further evaluate the accuracy of the predictive models, the approaches were first applied to real-world data. MARS outperformed the other three approaches, providing an average absolute percent error of -2.2% of four real-world road segments. The MARS model performance was then compared to HHDDT, CSHVC, NYCC, and HHV drive cycles with the performance from Future Automotive System Technology Simulator (FASTSim). The results indicated that the MARS method achieved a comparative predictive performance with FASTSim.

  8. Heavy-Duty Vehicle Port Drayage Drive Cycle Characterization and Development

    Energy Technology Data Exchange (ETDEWEB)

    Prohaska, Robert; Konan, Arnaud; Kelly, Kenneth; Lammert, Michael

    2016-10-06

    In an effort to better understand the operational requirements of port drayage vehicles and their potential for adoption of advanced technologies, National Renewable Energy Laboratory (NREL) researchers collected over 36,000 miles of in-use duty cycle data from 30 Class 8 drayage trucks operating at the Port of Long Beach and Port of Los Angeles in Southern California. These data include 1-Hz global positioning system location and SAE J1939 high-speed controller area network information. Researchers processed the data through NREL's Drive-Cycle Rapid Investigation, Visualization, and Evaluation tool to examine vehicle kinematic and dynamic patterns across the spectrum of operations. Using the k-medoids clustering method, a repeatable and quantitative process for multi-mode drive cycle segmentation, the analysis led to the creation of multiple drive cycles representing four distinct modes of operation that can be used independently or in combination. These drive cycles are statistically representative of real-world operation of port drayage vehicles. When combined with modeling and simulation tools, these representative test cycles allow advanced vehicle or systems developers to efficiently and accurately evaluate vehicle technology performance requirements to reduce cost and development time while ultimately leading to the commercialization of advanced technologies that meet the performance requirements of the port drayage vocation. The drive cycles, which are suitable for chassis dynamometer testing, were compared to several existing test cycles. This paper presents the clustering methodology, accompanying results of the port drayage duty cycle analysis and custom drive cycle creation.

  9. Heavy-Duty Vehicle Port Drayage Drive Cycle Characterization and Development: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Prohaska, Robert; Konan, Arnaud; Kelly, Kenneth; Lammert, Michael

    2016-08-01

    In an effort to better understand the operational requirements of port drayage vehicles and their potential for adoption of advanced technologies, National Renewable Energy Laboratory (NREL) researchers collected over 36,000 miles of in-use duty cycle data from 30 Class 8 drayage trucks operating at the Port of Long Beach and Port of Los Angeles in Southern California. These data include 1-Hz global positioning system location and SAE J1939 high-speed controller area network information. Researchers processed the data through NREL's Drive-Cycle Rapid Investigation, Visualization, and Evaluation tool to examine vehicle kinematic and dynamic patterns across the spectrum of operations. Using the k-medoids clustering method, a repeatable and quantitative process for multi-mode drive cycle segmentation, the analysis led to the creation of multiple drive cycles representing four distinct modes of operation that can be used independently or in combination. These drive cycles are statistically representative of real-world operation of port drayage vehicles. When combined with modeling and simulation tools, these representative test cycles allow advanced vehicle or systems developers to efficiently and accurately evaluate vehicle technology performance requirements to reduce cost and development time while ultimately leading to the commercialization of advanced technologies that meet the performance requirements of the port drayage vocation. The drive cycles, which are suitable for chassis dynamometer testing, were compared to several existing test cycles. This paper presents the clustering methodology, accompanying results of the port drayage duty cycle analysis and custom drive cycle creation.

  10. Energy Management Strategy Based on the Driving Cycle Model for Plugin Hybrid Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Xiaoling Fu

    2014-01-01

    Full Text Available The energy management strategy (EMS for a plugin hybrid electric vehicle (PHEV is proposed based on the driving cycle model and dynamic programming (DP algorithm. A driving cycle model is constructed by collecting and processing the driving data of a certain school bus. The state of charge (SOC profile can be obtained by the DP algorithm for the whole driving cycle. In order to optimize the energy management strategy in the hybrid power system, the optimal motor torque control sequence can be calculated using the DP algorithm for the segments between the traffic intersections. Compared with the traditional charge depleting-charge sustaining (CDCS strategy, the test results on the ADVISOR platform show a significant improvement in fuel consumption using the EMS proposed in this paper.

  11. Driving cycle characterization and generation, for design and control of fuel cell buses

    NARCIS (Netherlands)

    Tazelaar, E.; Bruinsma, J.; Veenhuizen, P.A.; Bosch, van den P.P.J.

    2009-01-01

    Optimization routines for battery, supercap and fuel cell stack in a fuel cell based propulsion system face two problems: the tendency to cycle beating and the necessity to maintain identical amounts of stored energy in battery and supercap at the start and end of the driving cycle used in the

  12. Dynamic behavior of Rankine cycle system for waste heat recovery of heavy duty diesel engines under driving cycle

    International Nuclear Information System (INIS)

    Xie, Hui; Yang, Can

    2013-01-01

    Highlights: • Waste heat recovery behavior of the RCS during driving cycle was investigated. • Four operating modes were defined to describe the operating process of the RCS under driving cycle. • The operating mode switching is the crucial reason for on-road inefficiency. • The dry and isentropic fluids are superior to the wet ones on the adaptability to unsteady ExGE. • The effects of the vapor parameters on RCT-E and power mode percentage are opposite. - Abstract: The RCS (Rankine cycle system) used to recover the WHE (waste heat energy) from engines has been regarded as one of the most potential ways of achieving higher efficiency. However, it is of great challenge to keep the RCS still in good performance under driving cycle. This paper tries to reveal and explain its on-road inefficiency. The operating process of the RCS under driving cycle was analyzed in advance. Afterwards, four basic operating modes were defined, including startup mode, turbine turning mode, power mode and protection mode. Then, a RCS model was established and operating performances of the RCS under an actual driving cycle were discussed based on this model. The results indicate that the on-road RCS-E (Rankine cycle system efficiency) is as low as 3.63%, which is less than half of the design RCS-E (7.77%) at the rated operating point. Despite the inevitable vapor state fluctuation, it is the operating mode switching during the driving cycle that leads to the on-road inefficiency. Further investigations indicate that the expander safety temperature and its safety margin affected by the working fluids, designed superheat degree and evaporating pressure are the main factors determining the operating mode switching. Finally, the effects of the working fluids, designed superheat degree and evaporating pressure on the operating mode switching and RC (Rankine cycle) efficiencies were profoundly investigated. The study shows that the dry and isentropic fluids are superior to the wet

  13. Real-world European driving cycles, for measuring pollutant emissions from high- and low-powered cars

    OpenAIRE

    ANDRE, Michel; JOUMARD, Robert; VIDON, Robert; TASSEL, Patrick; PERRET, Pascal

    2006-01-01

    Pollutant emissions from cars are usually measured on a test bench using driving cycles. However, the use of one unique set of driving cycles to test all cars can be seen as a weak point of emission estimation, as vehicles could conceivably be tested differently depending on their performance levels and usage characteristics. A specific study was then conducted to characterize driving conditions and vehicle usage as a function of vehicle categories, as well as to derive driving cycles special...

  14. The Microbial Engines That Drive Earth’s Biogeochemical Cycles

    Science.gov (United States)

    Falkowski, Paul G.; Fenchel, Tom; Delong, Edward F.

    2008-05-01

    Virtually all nonequilibrium electron transfers on Earth are driven by a set of nanobiological machines composed largely of multimeric protein complexes associated with a small number of prosthetic groups. These machines evolved exclusively in microbes early in our planet’s history yet, despite their antiquity, are highly conserved. Hence, although there is enormous genetic diversity in nature, there remains a relatively stable set of core genes coding for the major redox reactions essential for life and biogeochemical cycles. These genes created and coevolved with biogeochemical cycles and were passed from microbe to microbe primarily by horizontal gene transfer. A major challenge in the coming decades is to understand how these machines evolved, how they work, and the processes that control their activity on both molecular and planetary scales.

  15. A driving cycle for vehicle emissions estimation in the metropolitan area of Mexico City.

    Science.gov (United States)

    Schifter, I; Díaz, L; Rodríguez, R; López-Salinas, E

    2005-02-01

    A driving cycle derived from driving behavior and real traffic conditions in Mexico City (MC) is proposed. Data acquisition was carried out over diverse MC routes, representing travel under congested and uncongested conditions, using the chase-car approach. Thirteen different on-road patterns, including the four main access roads to MC, trips in both directions and different timetables, a total of 108 trips spanning 1044 km were evaluated in this study. The MC cycle lasts 1360 seconds with a distance of 8.8 km and average speed of 23.4 km h(-1). Both maximum speed (73.6 km h(-1)) and maximum acceleration (2.22 km h(-1)s(-1)) are lower than those of the new vehicles certification employed in Mexico ,FTP-75 cycle., that is, the MC cycle exhibits less cruising time and more transient events than the FTP cycle. A total of 30 light duty gasoline vehicles were classified into different technological groups and tested in an FTP-75 and MC driving cycles in order to compare their emission factors A potential concern is that in Mexico manufacturers design vehicles to meet the emission standards in the FTP, but emission levels increase significantly in a more representative cycle of present driving patterns in the Metropolitan Area of Mexico City (MAMC). The use of a more representative cycle during certification testing, would provide an incentive for vehicle manufacturers to design emissions control systems to remain effective during operation modes that are not currently represented in the official test procedures used in the certification process. Based on the results of the study, the use of MC cycle, which better represents current day driving patterns during testing of vehicle fleets in emissions laboratories, would improve the accuracy of emissions factors used in the MAMC emissions inventories.

  16. Combined cycles for pipeline compressor drives using heat

    International Nuclear Information System (INIS)

    Malewski, W.F.; Holldorff, G.M.

    1979-01-01

    Combined cycles for pipeline-booster stations using waste heat from gas turbines exhaust can improve the overall efficiency of such stations remarkably. Several working fluids are suitable. Due to existing criteria for selecting a working medium under mentioned conditions, water, ammonia, propane and butane can be considered as practical working fluids. The investigations have shown that: (1) ammonia is advantageous at low exhaust gas and ambient temperatures, (2) water is most effective at high exhaust gas and ambient temperatures, and (3), additionally, hydrocarbons are suitable in a medium range for exhaust gas and condensing temperatures. Not only thermodynamic but also operational features have to be considered. There is not one optimum working fluid but a best one suitable according to the prevailing site conditions

  17. A DCT-Based Driving Cycle Generation Method and Its Application for Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Cheng Lin

    2015-01-01

    Full Text Available Nowadays, many widely used driving cycle (DC representing and generating methods are designed for traditional vehicles with internal combustion engines (ICE. The real-world driving is viewed as a sequence of acceleration, cruise, deceleration, and idle modes. The emission and fuel consumption in each period should be taken into account carefully. However, for electric vehicles (EVs, most of them are powered by low or zero-emission renewable energy sources. The working status and energy management algorithms of them are very different from traditional vehicles. To facilitate the EV design, we proposed a novel DC representing and construction method to generate DCs for EVs. The whole driving route is divided into several length-fixed segments and each of these segments is converted into a frequency sequence. After doing that, we can adjust the frequency and amplitude of the generated driving cycle directly. The experiment results showed that the proposed method was effective and convenient.

  18. Cell cycle arrest induced by radiation

    International Nuclear Information System (INIS)

    Okaichi, Yasuo; Matsumoto, Hideki; Ohnishi, Takeo

    1994-01-01

    It is known that various chemical reactions, such as cell cycle arrest, DNA repair and cell killing, can occur within the cells when exposed to ionizing radiation and ultraviolet radiation. Thus protein dynamics involved in such chemical reactions has received considerable attention. In this article, cell cycle regulation is first discussed in terms of the G2/M-phase and the G1/S-phase. Then, radiation-induced cell cycle arrest is reviewed. Cell cycle regulation mechanism involved in the G2 arrest, which is well known to occur when exposed to radiation, has recently been investigated using yeasts. In addition, recent study has yielded a noticeable finding that the G1 arrest can occur with intracellular accumulation of p53 product following ionization radiation. p53 is also shown to play an extremely important role in both DNA repair and cell killing due to DNA damage. Studies on the role of genes in protein groups induced by radiation will hold promise for the elucidation of cell cycle mechanism. (N.K.) 57 refs

  19. Texas-specific drive cycles and idle emissions rates for using with EPA's MOVES model : final report.

    Science.gov (United States)

    2014-05-01

    The U.S. Environmental Protection Agencys (EPA) newest emissions model, MOtor Vehicle : Emission Simulator (MOVES), uses a disaggregate approach that enables the users of the model to create : and use local drive schedules (drive cycles) in order ...

  20. Study of emissions and fuel economy for parallel hybrid versus conventional vehicles on real world and standard driving cycles

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Samari

    2017-12-01

    Full Text Available Parallel hybrid electric vehicles (PHEVs increasing rapidly in the automobile markets. However, the benefits out of using this kind of vehicles are still concerned a lot of costumers. This work investigated the expected benefits (such as decreasing emissions and increasing fuel economy from using the parallel HEV in comparison to the conventional vehicle model of the real-world and standard driving cycles. The software Autonomie used in this study to simulate the parallel HEV and conventional models on these driving cycles.The results show that the fuel economy (FE can be improved significantly up to 68% on real-world driving cycle, which is represented mostly city activities. However, the FE improvement was limited (10% on the highway driving cycle, and this is expected since the using of brake system was infrequent. Moreover, the emissions from parallel HEV decreased about 40% on the real-world driving cycle, and decreased 11% on the highway driving cycle. Finally, the engine efficiency, improved about 12% on the real-world driving cycle, and about 7% on highway driving cycle. Keywords: Emissions, Hybrid electric vehicles, Fuel economy, Real-world driving cycle

  1. Developing Singapore Driving Cycle for passenger cars to estimate fuel consumption and vehicular emissions

    Science.gov (United States)

    Ho, Sze-Hwee; Wong, Yiik-Diew; Chang, Victor Wei-Chung

    2014-11-01

    Singapore has pledged to attain 7-11% Business-As-Usual carbon emissions reduction by 2020. Road transport sector is a significant source of carbon emissions, estimated to be the third largest sector in Singapore. A current gap in environmental evaluation for road transport activities in Singapore is the lack of a representative driving cycle for passenger cars (64% of the total population of 974,170 vehicles). This Singapore Driving Cycle (SDC) is hence developed for Singapore roads and traffic conditions. A chase-car (instrumented vehicle) was used to collect on-road data along 12 designed routes, and circulation driving on highly utilized arterial roads (including those in Central Business District (CBD) and both inner and outer ring roads fringing the CBD area). The SDC was thus hence constructed, with consideration of road type proportions, time periods and desired distance, duration and peak-lull proportion. In essence, the SDC is a 2400-s speed-time profile to represent the driving pattern for passenger car in Singapore. Microscopic estimation model (CMEM) shows that, as compared to SDC, the New European Driving Cycle (NEDC) underestimates most of the vehicular emissions (fuel, CO2, HC and NOx by 5%, 5%, 22% and 47%, respectively) and overestimates CO by 8%. The SDC is thus more suitable than the NEDC that is currently in use in Singapore; the SDC can be used to generate more accurate fuel consumption and emissions ratings for various uses (for example, inventory of vehicular emissions and fuel economy labelling).

  2. Analysis of a Temperature-Controlled Exhaust Thermoelectric Generator During a Driving Cycle

    Science.gov (United States)

    Brito, F. P.; Alves, A.; Pires, J. M.; Martins, L. B.; Martins, J.; Oliveira, J.; Teixeira, J.; Goncalves, L. M.; Hall, M. J.

    2016-03-01

    Thermoelectric generators can be used in automotive exhaust energy recovery. As car engines operate under wide variable loads, it is a challenge to design a system for operating efficiently under these variable conditions. This means being able to avoid excessive thermal dilution under low engine loads and being able to operate under high load, high temperature events without the need to deflect the exhaust gases with bypass systems. The authors have previously proposed a thermoelectric generator (TEG) concept with temperature control based on the operating principle of the variable conductance heat pipe/thermosiphon. This strategy allows the TEG modules’ hot face to work under constant, optimized temperature. The variable engine load will only affect the number of modules exposed to the heat source, not the heat transfer temperature. This prevents module overheating under high engine loads and avoids thermal dilution under low engine loads. The present work assesses the merit of the aforementioned approach by analysing the generator output during driving cycles simulated with an energy model of a light vehicle. For the baseline evaporator and condenser configuration, the driving cycle averaged electrical power outputs were approximately 320 W and 550 W for the type-approval Worldwide harmonized light vehicles test procedure Class 3 driving cycle and for a real-world highway driving cycle, respectively.

  3. Performance Analysis of Permanent Magnet Motors for Electric Vehicles (EV Traction Considering Driving Cycles

    Directory of Open Access Journals (Sweden)

    Thanh Anh Huynh

    2018-05-01

    Full Text Available This paper evaluates the electromagnetic and thermal performance of several traction motors for electric vehicles (EVs. Two different driving cycles are employed for the evaluation of the motors, one for urban and the other for highway driving. The electromagnetic performance to be assessed includes maximum motor torque output for vehicle acceleration and the flux weakening capability for wide operating range under current and voltage limits. Thermal analysis is performed to evaluate the health status of the magnets and windings for the prescribed driving cycles. Two types of traction motors are investigated: two interior permanent magnet motors and one permanent magnet-assisted synchronous reluctance motor. The analysis results demonstrate the benefits and disadvantages of these motors for EV traction and provide suggestions for traction motor design. Finally, experiments are conducted to validate the analysis.

  4. Sizing for fuel cell/supercapacitor hybrid vehicles based on stochastic driving cycles

    International Nuclear Information System (INIS)

    Feroldi, Diego; Carignano, Mauro

    2016-01-01

    Highlights: • A sizing procedure based on the fulfilment of real driving conditions is proposed. • A methodology to generate long-term stochastic driving cycles is proposed. • A parametric optimization of the real-time EMS is conducted. • A trade-off design is adopted from a Pareto front. • A comparison with optimal consumption via Dynamic Programming is performed. - Abstract: In this article, a methodology for the sizing and analysis of fuel cell/supercapacitor hybrid vehicles is presented. The proposed sizing methodology is based on the fulfilment of power requirements, including sustained speed tests and stochastic driving cycles. The procedure to generate driving cycles is also presented in this paper. The sizing algorithm explicitly accounts for the Equivalent Consumption Minimization Strategy (ECMS). The performance is compared with optimal consumption, which is found using an off-line strategy via Dynamic Programming. The sizing methodology provides guidance for sizing the fuel cell and the supercapacitor number. The results also include analysis on oversizing the fuel cell and varying the parameters of the energy management strategy. The simulation results highlight the importance of integrating sizing and energy management into fuel cell hybrid vehicles.

  5. Using Map Service API for Driving Cycle Detection for Wearable GPS Data: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Lei [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Gonder, Jeffrey D [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2017-12-06

    Following advancements in smartphone and portable global positioning system (GPS) data collection, wearable GPS data have realized extensive use in transportation surveys and studies. The task of detecting driving cycles (driving or car-mode trajectory segments) from wearable GPS data has been the subject of much research. Specifically, distinguishing driving cycles from other motorized trips (such as taking a bus) is the main research problem in this paper. Many mode detection methods only focus on raw GPS speed data while some studies apply additional information, such as geographic information system (GIS) data, to obtain better detection performance. Procuring and maintaining dedicated road GIS data are costly and not trivial, whereas the technical maturity and broad use of map service application program interface (API) queries offers opportunities for mode detection tasks. The proposed driving cycle detection method takes advantage of map service APIs to obtain high-quality car-mode API route information and uses a trajectory segmentation algorithm to find the best-matched API route. The car-mode API route data combined with the actual route information, including the actual mode information, are used to train a logistic regression machine learning model, which estimates car modes and non-car modes with probability rates. The experimental results show promise for the proposed method's ability to detect vehicle mode accurately.

  6. Temperature oscillations drive cycles in the activity of MMP-2,9 secreted by a human trabecular meshwork cell line.

    Science.gov (United States)

    Li, Stanley Ka-Lok; Banerjee, Juni; Jang, Christopher; Sehgal, Amita; Stone, Richard A; Civan, Mortimer M

    2015-02-05

    Aqueous humor inflow falls 50% during sleeping hours without proportional fall in IOP, partly reflecting reduced outflow facility. The mechanisms underlying outflow facility cycling are unknown. One outflow facility regulator is matrix metalloproteinase (MMP) release from trabecular meshwork (TM) cells. Because anterior segment temperature must oscillate due to core temperature cycling and eyelid closure during sleep, we tested whether physiologically relevant temperature oscillations drive cycles in the activity of secreted MMP. Temperature of transformed normal human TM cells (hTM5 line) was fixed or alternated 12 hours/12 hours between 33°C and 37°C. Activity of secreted MMP-2 and MMP-9 was measured by zymography, and gene expression by RT-PCR and quantitative PCR. Raising temperature to 37°C increased, and lowering to 33°C reduced, activity of secreted MMP. Switching between 37°C and 33°C altered MMP-9 by 40% ± 3% and MMP-2 by 22% ± 2%. Peripheral circadian clocks did not mediate temperature-driven cycling of MMP secretion because MMP-release oscillations did not persist at constant temperature after 3 to 6 days of alternating temperatures, and temperature cycles did not entrain clock-gene expression in these cells. Furthermore, inhibiting heat shock transcription factor 1, which links temperature and peripheral clock-gene oscillations, inhibited MMP-9 but not MMP-2 temperature-driven MMP cycling. Inhibition of heat-sensitive TRPV1 channels altered total MMP secretion but not temperature-induced modulations. Inhibiting cold-sensitive TRPM-8 channels had no effect. Physiologically relevant temperature oscillations drive fluctuations of secreted MMP-2 and MMP-9 activity in hTM5 cells independent of peripheral clock genes and temperature-sensitive TRP channels. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  7. Analysis and modelling of the pollutant emissions from European cars regarding the driving characteristics and test cycles

    Science.gov (United States)

    André, Michel; Rapone, Mario

    Within the European research project ARTEMIS, significant works have been conducted to analyse the hot emissions of pollutant from the passenger cars regarding the driving cycles and to propose modelling approaches taking into account large but heterogeneous datasets recorded in Europe. The review and analysis of a large range of test cycles enabled first the building-up of a set of contrasted cycles specifically designed for characterizing the influence of the driving conditions. These cycles were used for the measurement of the pollutants emission rates from nine passenger cars on a chassis dynamometer. Emissions measured on 30 vehicles tested on cycles adapted to their motorization (i.e., cycles for high- or low-powered cars, inducing thus a significant difference in the dynamic) were also considered for analysing the influence of the cycles and of the kinematic parameters on the hot emission rates of the regulated pollutants (CO, HC, NO x, CO 2, PM). An analyses of variance demonstrated the preponderance of the driving type (urban, rural road, motorway), of the vehicle category (fuel, emission standard) and emitting status (high/normal emitter) and thus the pertinence of analysing and modelling separately the corresponding emissions. It also demonstrated that Urban driving led systematically to high diesel emission rates and to high CO 2, HC and NO x emissions from petrol cars. Congested driving implied high CO 2 (diesel and petrol) and high diesel NO x emission. On motorway, the very high speeds generated high CO 2, while unsteady speeds induced diesel NO x and petrol CO over-emissions. A search for pertinent kinematic parameters showed that urban diesel emissions were mostly sensitive to stops and speed parameters, while petrol emissions were rather sensitive to acceleration parameters. On the motorway, diesel NO x and CO 2 emissions rates increased with the speed variability and occurrence of high speeds, while CO 2 and CO over-emission from petrol cars were

  8. Development and review of Euro 5 passenger car emission factors based on experimental results over various driving cycles

    OpenAIRE

    Fontaras, Georgios; Franco, Vicente; Dilara, Panagiota; Martini, Giorgio; Manfredi, Urbano

    2014-01-01

    The mass emissions of CO2 and regulated pollutants (NOX, HC, CO, PM) of thirteen Euro 5 compliant passenger cars (seven gasoline, six Diesel) were measured on a chassis dynamometer. The vehicles were driven repeatedly over the European type-approval driving cycle (NEDC) and the more dynamic WMTC and CADC driving cycles. Distance-specific emission factors were derived for each pollutant and sub-cycle which were subsequently compared to the corresponding emission factors provided by the referen...

  9. Analysis of Wave Fields induced by Offshore Pile Driving

    Science.gov (United States)

    Ruhnau, M.; Heitmann, K.; Lippert, T.; Lippert, S.; von Estorff, O.

    2015-12-01

    Impact pile driving is the common technique to install foundations for offshore wind turbines. With each hammer strike the steel pile - often exceeding 6 m in diameter and 80 m in length - radiates energy into the surrounding water and soil, until reaching its targeted penetration depth. Several European authorities introduced limitations regarding hydroacoustic emissions during the construction process to protect marine wildlife. Satisfying these regulations made the development and application of sound mitigation systems (e.g. bubble curtains or insulation screens) inevitable, which are commonly installed within the water column surrounding the pile or even the complete construction site. Last years' advances have led to a point, where the seismic energy tunneling the sound mitigation systems through the soil and radiating back towards the water column gains importance, as it confines the maximum achievable sound mitigation. From an engineering point of view, the challenge of deciding on an effective noise mitigation layout arises, which especially requires a good understanding of the soil-dependent wave field. From a geophysical point of view, the pile acts like a very unique line source, generating a characteristic wave field dominated by inclined wave fronts, diving as well as head waves. Monitoring the seismic arrivals while the pile penetration steadily increases enables to perform quasi-vertical seismic profiling. This work is based on datasets that have been collected within the frame of three comprehensive offshore measurement campaigns during pile driving and demonstrates the potential of seismic arrivals induced by pile driving for further soil characterization.

  10. Greenhouse gas emission impacts of electric vehicles under varying driving cycles in various counties and US cities

    International Nuclear Information System (INIS)

    Wang, M.Q.; Marr, W.W.

    1994-01-01

    Electric vehicles (EVs) can reduce greenhouse gas emissions, relative to emissions from gasoline-fueled vehicles. However, those studies have not considered all aspects that determine greenhouse gas emissions from both gasoline vehicles (GVs) and EVs. Aspects often overlooked include variations in vehicle trip characteristics, inclusion of all greenhouse gases, and vehicle total fuel cycle. In this paper, we estimate greenhouse gas emission reductions for EVs, including these important aspects. We select four US cities (Boston, Chicago, Los Angeles, and Washington, D.C.) and six countries (Australia, France, Japan, Norway, the United Kingdom, and the United States) and analyze greenhouse emission impacts of EVs in each city or country. We also select six driving cycles developed around the world (i.e., the US federal urban driving cycle, the Economic Community of Europe cycle 15, the Japanese 10-mode cycle, the Los Angeles 92 cycle, the New York City cycle, and the Sydney cycle). Note that we have not analyzed EVs in high-speed driving (e.g., highway driving), where the results would be less favorable to EVs; here, EVs are regarded as urban vehicles only. We choose one specific driving cycle for a given city or country and estimate the energy consumption of four-passenger compact electric and gasoline cars in the given city or country. Finally, we estimate total fuel cycle greenhouse gas emissions of both GVs and EVs by accounting for emissions from primary energy recovery, transportation, and processing; energy product transportation; and powerplant and vehicle operations

  11. The Impact of Drive Cycles and Auxiliary Power on Passenger Car Fuel Economy

    Directory of Open Access Journals (Sweden)

    Thomas Grube

    2018-04-01

    Full Text Available In view of the advancement of zero emission transportation and current discussions on the reliability of nominal passenger car fuel economy, this article considers the procedure for assessing the potential for reducing the fuel consumption of passenger cars by using electric power to operate them. The analysis compares internal combustion engines, hybrid and fully electric concepts utilizing batteries and fuel cells. The starting point for the newly developed, simulation-based fuel consumption analysis is a longitudinal vehicle model. Mechanical power requirements on the drive side incorporate a large variety of standardized drive cycles to simulate typical patterns of car usage. The power requirements of electric heating and air conditioning are also included in the simulation, as these are especially relevant to electric powertrains. Moreover, on-board grid-load profiles are considered in the assessment. Fuel consumption is optimized by applying concept-specific operating strategies. The results show that the combination of low average driving speed and elevated onboard power requirements have severe impacts on the fuel efficiency of all powertrain configurations analyzed. In particular, the operational range of battery-electric vehicles is strongly affected by this due to the limited storage capacity of today’s batteries. The analysis confirms the significance of considering different load patterns of vehicle usage related to driving profiles and onboard electrical and thermal loads.

  12. Caffeine antagonism of alcohol-induced driving impairment.

    Science.gov (United States)

    Liguori, A; Robinson, J H

    2001-07-01

    The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

  13. Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

    Science.gov (United States)

    Paijmans, Joris; Bosman, Mark; Ten Wolde, Pieter Rein; Lubensky, David K

    2016-04-12

    Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push-pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene.

  14. Development of real-world driving cycles and estimation of emission factors for in-use light-duty gasoline vehicles in urban areas.

    Science.gov (United States)

    Hwa, Mei-Yin; Yu, Tai-Yi

    2014-07-01

    This investigation adopts vehicle tracking manner to establish real-world driving patterns and estimates emission factors with dynamometers with 23 traffic-driving variables for 384 in-use light-duty passenger vehicles during non-rush hour. Adequate numbers of driving variables were decided with factor analysis and cluster analysis. The dynamometer tests were performed on FTP75 cycle and five local driving cycles derived from real-world speed profiles. Results presented that local driving cycles and FTP75 cycle were completely different in driving characteristic parameters of typical driving cycles and emission factors. The highest values of emission factor ratios of local driving cycle and FTP75 cycle for CO, NMHC, NO x , CH4, and CO2 were 1.38, 1.65, 1.58, 1.39, and 1.14, respectively.

  15. Method for modeling driving cycles, fuel use, and emissions for over snow vehicles.

    Science.gov (United States)

    Hu, Jiangchuan; Frey, H Christopher; Sandhu, Gurdas S; Graver, Brandon M; Bishop, Gary A; Schuchmann, Brent G; Ray, John D

    2014-07-15

    As input to a winter use plan, activity, fuel use, and tailpipe exhaust emissions of over snow vehicles (OSV), including five snow coaches and one snowmobile, were measured on a designated route in Yellowstone National Park (YNP). Engine load was quantified in terms of vehicle specific power (VSP), which is a function of speed, acceleration, and road grade. Compared to highway vehicles, VSP for OSVs is more sensitive to rolling resistance and less sensitive to aerodynamic drag. Fuel use rates increased linearly (R2>0.96) with VSP. For gasoline-fueled OSVs, fuel-based emission rates of carbon monoxide (CO) and nitrogen oxides (NOx) typically increased with increasing fuel use rate, with some cases of very high CO emissions. For the diesel OSVs, which had selective catalytic reduction and diesel particulate filters, fuel-based NOx and particulate matter (PM) emission rates were not sensitive to fuel flow rate, and the emission controls were effective. Inter vehicle variability in cycle average fuel use and emissions rates for CO and NOx was substantial. However, there was relatively little inter-cycle variation in cycle average fuel use and emission rates when comparing driving cycles. Recommendations are made regarding how real-world OSV activity, fuel use, and emissions data can be improved.

  16. Influence of driving patterns on life cycle cost and emissions of hybrid and plug-in electric vehicle powertrains

    International Nuclear Information System (INIS)

    Karabasoglu, Orkun; Michalek, Jeremy

    2013-01-01

    We compare the potential of hybrid, extended-range plug-in hybrid, and battery electric vehicles to reduce lifetime cost and life cycle greenhouse gas emissions under various scenarios and simulated driving conditions. We find that driving conditions affect economic and environmental benefits of electrified vehicles substantially: Under the urban NYC driving cycle, hybrid and plug-in vehicles can cut life cycle emissions by 60% and reduce costs up to 20% relative to conventional vehicles (CVs). In contrast, under highway test conditions (HWFET) electrified vehicles offer marginal emissions reductions at higher costs. NYC conditions with frequent stops triple life cycle emissions and increase costs of conventional vehicles by 30%, while aggressive driving (US06) reduces the all-electric range of plug-in vehicles by up to 45% compared to milder test cycles (like HWFET). Vehicle window stickers, fuel economy standards, and life cycle studies using average lab-test vehicle efficiency estimates are therefore incomplete: (1) driver heterogeneity matters, and efforts to encourage adoption of hybrid and plug-in vehicles will have greater impact if targeted to urban drivers vs. highway drivers; and (2) electrified vehicles perform better on some drive cycles than others, so non-representative tests can bias consumer perception and regulation of alternative technologies. We discuss policy implications. - Highlights: • Electrified vehicle life cycle emissions and cost depend on driving conditions. • GHGs can triple in NYC conditions vs. highway (HWFET), cost +30%. • Under NYC conditions hybrid and plug-in vehicles cut GHGs up to 60%, cost 20%. • Under HWFET conditions they offer few GHG reductions at higher costs. • Federal tests for window labels and CAFE standards favor some technologies over others

  17. Metagenomic potential for and diversity of N-cycle driving microorganisms in the Bothnian Sea sediment.

    Science.gov (United States)

    Rasigraf, Olivia; Schmitt, Julia; Jetten, Mike S M; Lüke, Claudia

    2017-08-01

    The biological nitrogen cycle is driven by a plethora of reactions transforming nitrogen compounds between various redox states. Here, we investigated the metagenomic potential for nitrogen cycle of the in situ microbial community in an oligotrophic, brackish environment of the Bothnian Sea sediment. Total DNA from three sediment depths was isolated and sequenced. The characterization of the total community was performed based on 16S rRNA gene inventory using SILVA database as reference. The diversity of diagnostic functional genes coding for nitrate reductases (napA;narG), nitrite:nitrate oxidoreductase (nxrA), nitrite reductases (nirK;nirS;nrfA), nitric oxide reductase (nor), nitrous oxide reductase (nosZ), hydrazine synthase (hzsA), ammonia monooxygenase (amoA), hydroxylamine oxidoreductase (hao), and nitrogenase (nifH) was analyzed by blastx against curated reference databases. In addition, Polymerase chain reaction (PCR)-based amplification was performed on the hzsA gene of anammox bacteria. Our results reveal high genomic potential for full denitrification to N 2 , but minor importance of anaerobic ammonium oxidation and dissimilatory nitrite reduction to ammonium. Genomic potential for aerobic ammonia oxidation was dominated by Thaumarchaeota. A higher diversity of anammox bacteria was detected in metagenomes than with PCR-based technique. The results reveal the importance of various N-cycle driving processes and highlight the advantage of metagenomics in detection of novel microbial key players. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  18. Hydraulic Hybrid and Conventional Parcel Delivery Vehicles' Measured Laboratory Fuel Economy on Targeted Drive Cycles

    Energy Technology Data Exchange (ETDEWEB)

    Lammert, M. P.; Burton, J.; Sindler, P.; Duran, A.

    2014-10-01

    This research project compares laboratory-measured fuel economy of a medium-duty diesel powered hydraulic hybrid vehicle drivetrain to both a conventional diesel drivetrain and a conventional gasoline drivetrain in a typical commercial parcel delivery application. Vehicles in this study included a model year 2012 Freightliner P100H hybrid compared to a 2012 conventional gasoline P100 and a 2012 conventional diesel parcel delivery van of similar specifications. Drive cycle analysis of 484 days of hybrid parcel delivery van commercial operation from multiple vehicles was used to select three standard laboratory drive cycles as well as to create a custom representative cycle. These four cycles encompass and bracket the range of real world in-use data observed in Baltimore United Parcel Service operations. The NY Composite cycle, the City Suburban Heavy Vehicle Cycle cycle, and the California Air Resources Board Heavy Heavy-Duty Diesel Truck (HHDDT) cycle as well as a custom Baltimore parcel delivery cycle were tested at the National Renewable Energy Laboratory's Renewable Fuels and Lubricants Laboratory. Fuel consumption was measured and analyzed for all three vehicles. Vehicle laboratory results are compared on the basis of fuel economy. The hydraulic hybrid parcel delivery van demonstrated 19%-52% better fuel economy than the conventional diesel parcel delivery van and 30%-56% better fuel economy than the conventional gasoline parcel delivery van on cycles other than the highway-oriented HHDDT cycle.

  19. Driving cycles for measuring passenger car emissions on roads with traffic calming measures

    International Nuclear Information System (INIS)

    Boulter, P.G.; Latham, S.; Ainge, M.

    1999-01-01

    Although local authorities in the UK need to be aware of any air quality impacts resulting from their traffic calming operations, there is little information relating to the effects of different traffic calming measures. The effects on air quality on this scale are complex, and so TRL is providing guidance by developing performance indices for different measures based on their effects on vehicle emissions. The emissions indices for passenger cars are based on tests conducted on a chassis dynamometer, and this paper describes the development of the methodology for constructing the driving cycles to be used. The technique involves the measurement of the speed profiles of a large number of vehicles using a roadside LIDAR system, and the determination of typical gear selections using three-instrumented cars

  20. Thermal modelling of Li-ion polymer battery for electric vehicle drive cycles

    Science.gov (United States)

    Chacko, Salvio; Chung, Yongmann M.

    2012-09-01

    Time-dependent, thermal behaviour of a lithium-ion (Li-ion) polymer cell has been modelled for electric vehicle (EV) drive cycles with a view to developing an effective battery thermal management system. The fully coupled, three-dimensional transient electro-thermal model has been implemented based on a finite volume method. To support the numerical study, a high energy density Li-ion polymer pouch cell was tested in a climatic chamber for electric load cycles consisting of various charge and discharge rates, and a good agreement was found between the model predictions and the experimental data. The cell-level thermal behaviour under stressful conditions such as high power draw and high ambient temperature was predicted with the model. A significant temperature increase was observed in the stressful condition, corresponding to a repeated acceleration and deceleration, indicating that an effective battery thermal management system would be required to maintain the optimal cell performance and also to achieve a full battery lifesapn.

  1. Ammonia-lithium nitrate absorption chiller with an integrated low-pressure compression booster cycle for low driving temperatures

    International Nuclear Information System (INIS)

    Ventas, R.; Lecuona, A.; Zacarias, A.; Venegas, M.

    2010-01-01

    Single-effect absorption refrigeration hybridized with mechanical vapor compression in a vapor circuit is known as the absorption cycle with an integrated booster compressor. In this study, the compressor is located between the evaporator and the absorber. This paper presents a numerical model of this cycle with ammonia-lithium nitrate solution as the working pair. It is based on UA-ΔT lm models for separate regions of plate-type heat exchangers. The results are offered as a function of external circuit flow parameters. Different pressure ratios of the compressor were tested for a wide range of hot water driving temperatures (55-95 deg. C), showing that low values are more beneficial. This cycle allows for working at lower driving temperatures than the single-effect cycle, with low electricity consumption. At the same driving temperature, the capacity is augmented with an increased compressor pressure ratio, thus allowing for demand matching of the cooling. This cycle, operating with hot water at 67 deg. C with a pressure ratio of 2.0, has the capacity of a single-effect absorption cycle at 94 deg. C. The electrical COP was found to be higher than that in an ammonia vapor compression cycle for comprehensive working conditions.

  2. Leveraging Big Data Analysis Techniques for U.S. Vocational Vehicle Drive Cycle Characterization, Segmentation, and Development

    Energy Technology Data Exchange (ETDEWEB)

    Duran, Adam W [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Phillips, Caleb T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Perr-Sauer, Jordan [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kelly, Kenneth J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Konan, Arnaud M [National Renewable Energy Laboratory (NREL), Golden, CO (United States)

    2018-04-03

    Under a collaborative interagency agreement between the U.S. Environmental Protection Agency and the U.S. Department of Energy (DOE), the National Renewable Energy Laboratory (NREL) performed a series of in-depth analyses to characterize on-road driving behavior including distributions of vehicle speed, idle time, accelerations and decelerations, and other driving metrics of medium- and heavy-duty vocational vehicles operating within the United States. As part of this effort, NREL researchers segmented U.S. medium- and heavy-duty vocational vehicle driving characteristics into three distinct operating groups or clusters using real-world drive cycle data collected at 1 Hz and stored in NREL's Fleet DNA database. The Fleet DNA database contains millions of miles of historical drive cycle data captured from medium- and heavy-duty vehicles operating across the United States. The data encompass existing DOE activities as well as contributions from valued industry stakeholder participants. For this project, data captured from 913 unique vehicles comprising 16,250 days of operation were drawn from the Fleet DNA database and examined. The Fleet DNA data used as a source for this analysis has been collected from a total of 30 unique fleets/data providers operating across 22 unique geographic locations spread across the United States. This includes locations with topographies ranging from the foothills of Denver, Colorado, to the flats of Miami, Florida. This paper includes the results of the statistical analysis performed by NREL and a discussion and detailed summary of the development of the vocational drive cycle weights and representative transient drive cycles for testing and simulation. Additional discussion of known limitations and potential future work is also included.

  3. Development and review of Euro 5 passenger car emission factors based on experimental results over various driving cycles.

    Science.gov (United States)

    Fontaras, Georgios; Franco, Vicente; Dilara, Panagiota; Martini, Giorgio; Manfredi, Urbano

    2014-01-15

    The emissions of CO2 and regulated pollutants (NOx, HC, CO, PM) of thirteen Euro 5 compliant passenger cars (seven gasoline, six Diesel) were measured on a chassis dynamometer. The vehicles were driven repeatedly over the European type-approval driving cycle (NEDC) and the more dynamic WMTC and CADC driving cycles. Distance-specific emission factors were derived for each pollutant and sub-cycle, and these were subsequently compared to the corresponding emission factors provided by the reference European models used for vehicle emission inventory compilation (COPERT and HBEFA) and put in context with the applicable European emission limits. The measured emissions stayed below the legal emission limits when the type-approval cycle (NEDC) was used. Over the more dynamic cycles (considered more representative of real-world driving) the emissions were consistently higher but in most cases remained below the type-approval limit. The high NOx emissions of Diesel vehicles under real-world driving conditions remain the main cause for environmental concern regarding the emission profile of Euro 5 passenger cars. Measured emissions of NOx exceeded the type-approval limits (up to 5 times in extreme cases) and presented significantly increased average values (0.35 g/km for urban driving and 0.56 g/km for motorway driving). The comparison with the reference models showed good correlation in all cases, a positive finding considering the importance of these tools in emission monitoring and policy-making processes. © 2013. Published by Elsevier B.V. All rights reserved.

  4. Estimates the Emission of Passenger Cars Based on the First Developed Driving Cycle in Nakhon Ratchasima Municipality, Thailand

    Directory of Open Access Journals (Sweden)

    Muangnak Noppatsorn

    2017-01-01

    Full Text Available This study aims to estimate emissions of passenger cars traveled on the highways in Nakhon Ratchasima Municipality (NRM based on recently developed driving cycles. A mobile phone application (SafeMate was used to record speed-time of passenger car on the highways both weekday and weekend. The results showed that the driving cycles of the passenger cars on highway 224 and 304 were quite different. More traffic congestion on highway 224 impacted the average speeds, ranging from 10 to 34 km/h with longer idling time. The average speeds on highway 304 ranged from 49 to 69 km/h with more cruise time. The combined driving cycles on both highways showed the average speeds of 20-40 km/h depending upon the time of days. The traffic density on weekday was higher than the weekend. Peak-hour weekday showed lower traffic flow than off-peak hour which was the opposite of the weekend. Based on the derived driving cycles, the passenger car traveled on the highways in NRM emitted CO, NOx and HC approximately 90.7-129.8, 25.5-34.5 and 6.9-11.7 tons/year, respectively. The passenger cars were estimated to emit about 13,927.7-20,419.3 tons/year of carbon dioxide on the highways. The highway 2 accounted more of the emissions due to the traffic volume and coverage distance in NRM.

  5. Evaluating the Impact of Road Grade on Simulated Commercial Vehicle Fuel Economy Using Real-World Drive Cycles

    Energy Technology Data Exchange (ETDEWEB)

    Lopp, Sean; Wood, Eric; Duran, Adam

    2015-10-13

    Commercial vehicle fuel economy is known to vary significantly with both positive and negative road grade. Medium- and heavy-duty vehicles operating at highway speeds require incrementally larger amounts of energy to pull heavy payloads up inclines as road grade increases. Non-hybrid vehicles are then unable to recapture energy on descent and lose energy through friction braking. While the on-road effects of road grade are well understood, the majority of standard commercial vehicle drive cycles feature no climb or descent requirements. Additionally, existing literature offers a limited number of sources that attempt to estimate the on-road energy implications of road grade in the medium- and heavy-duty space. This study uses real-world commercial vehicle drive cycles from the National Renewable Energy Laboratory's Fleet DNA database to simulate the effects of road grade on fuel economy across a range of vocations, operating conditions, and locations. Drive-cycles are matched with vocation-specific vehicle models and simulated with and without grade. Fuel use due to grade is presented, and variation in fuel consumption due to drive cycle and vehicle characteristics is explored through graphical and statistical comparison. The results of this study suggest that road grade accounts for 1%-9% of fuel use in commercial vehicles on average and up to 40% on select routes.

  6. Development of a hybrid energy storage sizing algorithm associated with the evaluation of power management in different driving cycles

    International Nuclear Information System (INIS)

    Masoud, Masih Tehrani; Mohammad Reza, Ha'iri Yazdi; Esfahanian, Vahid; Sagha, Hossein

    2012-01-01

    In this paper, a hybrid energy storage sizing algorithm for electric vehicles is developed to achieve a semi optimum cost effective design. Using the developed algorithm, a driving cycle is divided into its micro-trips and the power and energy demands in each micro trip are determined. The battery size is estimated because the battery fulfills the power demands. Moreover, the ultra capacitor (UC) energy (or the number of UC modules) is assessed because the UC delivers the maximum energy demands of the different micro trips of a driving cycle. Finally, a design factor, which shows the power of the hybrid energy storage control strategy, is utilized to evaluate the newly designed control strategies. Using the developed algorithm, energy saving loss, driver satisfaction criteria, and battery life criteria are calculated using a feed forward dynamic modeling software program and are utilized for comparison among different energy storage candidates. This procedure is applied to the hybrid energy storage sizing of a series hybrid electric city bus in Manhattan and to the Tehran driving cycle. Results show that a higher aggressive driving cycle (Manhattan) requires more expensive energy storage system and more sophisticated energy management strategy

  7. Imagery-inducing distraction leads to cognitive tunnelling and deteriorated driving performance.

    NARCIS (Netherlands)

    Briggs, G.F. Hole, G.J. & Land, M.F.

    2016-01-01

    The effects of imagery-induced distraction on hazard perception and eye movements were investigated in 2 simulated driving experiments. Experiment 1: sixty participants viewed and responded to 2 driving films containing hazards. Group 1 completed the task without distraction; group 2 completed a

  8. Energy conversion efficiency of hybrid electric heavy-duty vehicles operating according to diverse drive cycles

    Energy Technology Data Exchange (ETDEWEB)

    Banjac, Titina [AVL-AST d.o.o., Trg Leona Stuklja 5, SI-2000 Maribor (Slovenia); Trenc, Ferdinand; Katrasnik, Tomaz [Faculty of Mechanical Engineering, Univ. of Ljubljana, Askerceva 6, SI-1000 Ljubljana (Slovenia)

    2009-12-15

    Energy consumption and exhaust emissions of hybrid electric vehicles (HEVs) strongly depend on the HEV topology, power ratios of their components and applied control strategy. Combined analytical and simulation approach was applied to analyze energy conversion efficiency of different HEV topologies. Analytical approach is based on the energy balance equations and considers all energy paths in the HEVs from the energy sources to the wheels and to other energy sinks. Simulation approach is based on a fast forward-facing simulation model for simulating parallel and series HEVs as well as for conventional internal combustion engine vehicles, and considers all components relevant for modeling energy conversion phenomena. Combined approach enables evaluation of energy losses on different energy paths and provides their impact on the fuel economy. It therefore enables identification of most suitable HEV topology and of most suitable power ratios of the components for targeted vehicle application, since it reveals and quantifies the mechanisms that could lead to improved energy conversion efficiency of particular HEV. The paper exposes characteristics of the test cycles that lead to improved energy conversion efficiency of HEVs. Mechanisms leading to improved fuel economy of parallel HEVs through drive-away and vehicle propulsion at low powertrain loads by electric motor are also analyzed. It was also shown that control strategies managing energy flow through electric storage devices significantly influence energy conversion efficiency of series HEVs. (author)

  9. Mortality and community changes drive sudden oak death impacts on litterfall and soil nitrogen cycling.

    Science.gov (United States)

    Cobb, Richard C; Eviner, Valerie T; Rizzo, David M

    2013-10-01

    Few studies have quantified pathogen impacts to ecosystem processes, despite the fact that pathogens cause or contribute to regional-scale tree mortality. We measured litterfall mass, litterfall chemistry, and soil nitrogen (N) cycling associated with multiple hosts along a gradient of mortality caused by Phytophthora ramorum, the cause of sudden oak death. In redwood forests, the epidemiological and ecological characteristics of the major overstory species determine disease patterns and the magnitude and nature of ecosystem change. Bay laurel (Umbellularia californica) has high litterfall N (0.992%), greater soil extractable NO3 -N, and transmits infection without suffering mortality. Tanoak (Notholithocarpus densiflorus) has moderate litterfall N (0.723%) and transmits infection while suffering extensive mortality that leads to higher extractable soil NO3 -N. Redwood (Sequoia sempervirens) has relatively low litterfall N (0.519%), does not suffer mortality or transmit the pathogen, but dominates forest biomass. The strongest impact of pathogen-caused mortality was the potential shift in species composition, which will alter litterfall chemistry, patterns and dynamics of litterfall mass, and increase soil NO3 -N availability. Patterns of P. ramorum spread and consequent mortality are closely associated with bay laurel abundances, suggesting this species will drive both disease emergence and subsequent ecosystem function. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  10. Coupled chaotic attractors and driving-induced bistability: A brief ...

    Indian Academy of Sciences (India)

    2015-02-04

    Feb 4, 2015 ... In the 'drive–response' scenario, a system is unidirectionally coupled to another sys- tem. Here, the ... where R1 and R2 are the dynamical variables of the drive and response systems, respec- tively. F and G ..... [3] K Kaneko, Theory and applications of coupled map lattices (John Wiley and Sons, NY, 1993).

  11. Magnetic field aberration induced by cycle stress

    International Nuclear Information System (INIS)

    Yang En; Li Luming; Chen Xing

    2007-01-01

    Magneto-mechanical effect has been causing people's growing interest because of its relevance to several technology problems. One of them is the variation of surface magnetic field induced by stress concentration under the geomagnetic field. It can be used as an innovative, simple and convenient potential NDE method, called as magnetic memory method. However, whether and how this can be used as a quantitative measurement method, is still a virginal research field where nobody sets foot in. In this paper, circle tensile stress within the elastic region was applied to ferromagnetic sample under geomagnetic field. Experiment results on the relation between surface magnetic field and elastic stress were presented, and a simple model was derived. Simulation of the model was reconciled with the experimental results. This can be of great importance for it provides a brighter future for the promising Magnetic Memory NDE method-the potential possibility of quantitative measurement

  12. Dynamic simulation of a fuel cell hybrid vehicle during the federal test procedure-75 driving cycle

    International Nuclear Information System (INIS)

    Kang, Sanggyu; Min, Kyoungdoug

    2016-01-01

    Highlights: • Development of a FCHV dynamic model. • Integration of a PEMFC system dynamic model with the electric vehicle model. • Investigation of the dynamic behavior of the FCEV and PEMFC system during FTP-75. • Capturing the dynamic correlation among components in PEMFC system during FTP-75. - Abstract: The dynamic behavior of a proton exchange membrane fuel cell (PEMFC) system is a crucial factor to ensure the safe and effective operation of fuel cell hybrid vehicles (FCHVs). Specifically, water and thermal management are critical to stabilize the performance of the PEMFC during severe load changes. In the present study, the FCHV dynamic model is developed. The dynamic model of the PEMFC system developed by Matlab–Simulink® is integrated into the electric vehicle model embedded in the Amesim®. The dynamic model of the PEMFC system is composed of a PEMFC stack, an air feeding system, and a thermal management system (TMS). The component models of PEMFC, a shell-and-tube gas-to-gas membrane humidifier, and a heat exchanger are validated via a comparison with the experimental data. The FCHV model is simulated during a federal test procedure (FTP)-75 driving cycle. One system configuration and control strategy is adopted to attain optimal water and thermal management in the PEMFC system. The vehicle speed obtained from the FCHV model aptly tracks the target velocity profile of the FTP-75 cycle within an error of ±0.5%. The dynamic behavior and correlation of each component in the PEMFC system is investigated. The mass and heat transfer in the PEMFC, a humidifier, and a heat exchanger are resolved to determine the species concentration and the temperature more accurately with discretization in the flow’s perpendicular direction. Discretization in the flow parallel direction of humidifier and heat exchanger model makes it possible to capture the distribution of the characteristics. The present model can be used to attain the optimization of the system

  13. Medium Truck Duty Cycle Data from Real-World Driving Environments: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lascurain, Mary Beth [ORNL; Franzese, Oscar [ORNL; Capps, Gary J [ORNL; Siekmann, Adam [ORNL; Thomas, Neil [ORNL; LaClair, Tim J [ORNL; Barker, Alan M [ORNL; Knee, Helmut E [ORNL

    2012-11-01

    Since the early part of the 20th century, the US trucking industry has provided a safe and economical means of moving commodities across the country. At present, nearly 80% of US domestic freight movement involves the use of trucks. The US Department of Energy (DOE) is spearheading a number of research efforts to improve heavy vehicle fuel efficiencies. This includes research in engine technologies (including hybrid and fuel cell technologies), lightweight materials, advanced fuels, and parasitic loss reductions. In addition, DOE is developing advanced tools and models to support heavy vehicle research and is leading the 21st Century Truck Partnership and the SuperTruck development effort. Both of these efforts have the common goal of decreasing the fuel consumption of heavy vehicles. In the case of SuperTruck, a goal of improving the overall freight efficiency of a combination tractor-trailer has been established. This Medium Truck Duty Cycle (MTDC) project is a critical element in DOE s vision for improved heavy vehicle energy efficiency; it is unique in that there is no other existing national database of characteristic duty cycles for medium trucks based on collecting data from Class 6 and 7 vehicles. It involves the collection of real-world data on medium trucks for various situational characteristics (e.g., rural/urban, freeway/arterial, congested/free-flowing, good/bad weather) and looks at the unique nature of medium trucks drive cycles (stop-and-go delivery, power takeoff, idle time, short-radius trips). This research provides a rich source of data that can contribute to the development of new tools for FE and modeling, provide DOE a sound basis upon which to make technology investment decisions, and provide a national archive of real-world-based medium-truck operational data to support energy efficiency research. The MTDC project involved a two-part field operational test (FOT). For the Part-1 FOT, three vehicles each from two vocations (urban transit and

  14. Complexation-induced supramolecular assembly drives metal-ion extraction.

    Science.gov (United States)

    Ellis, Ross J; Meridiano, Yannick; Muller, Julie; Berthon, Laurence; Guilbaud, Philippe; Zorz, Nicole; Antonio, Mark R; Demars, Thomas; Zemb, Thomas

    2014-09-26

    Combining experiment with theory reveals the role of self-assembly and complexation in metal-ion transfer through the water-oil interface. The coordinating metal salt Eu(NO3)3 was extracted from water into oil by a lipophilic neutral amphiphile. Molecular dynamics simulations were coupled to experimental spectroscopic and X-ray scattering techniques to investigate how local coordination interactions between the metal ion and ligands in the organic phase combine with long-range interactions to produce spontaneous changes in the solvent microstructure. Extraction of the Eu(3+)-3(NO3(-)) ion pairs involves incorporation of the "hard" metal complex into the core of "soft" aggregates. This seeds the formation of reverse micelles that draw the water and "free" amphiphile into nanoscale hydrophilic domains. The reverse micelles interact through attractive van der Waals interactions and coalesce into rod-shaped polynuclear Eu(III) -containing aggregates with metal centers bridged by nitrate. These preorganized hydrophilic domains, containing high densities of O-donor ligands and anions, provide improved Eu(III) solvation environments that help drive interfacial transfer, as is reflected by the increasing Eu(III) partitioning ratios (oil/aqueous) despite the organic phase approaching saturation. For the first time, this multiscale approach links metal-ion coordination with nanoscale structure to reveal the free-energy balance that drives the phase transfer of neutral metal salts. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. The impact of music on affect during anger inducing drives

    NARCIS (Netherlands)

    Zwaag, M. van der; Fairclough, S.; Spiridon, E.; Westerink, J.H.D.

    2012-01-01

    Driver anger could be potentially harmful for road safety and long-term health. Because of its mood inducing properties, music is assumed to be a potential medium that could prevent anger induction duringdriving. In the current study the influence of music on anger, mood, skin conductance, and

  16. Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations

    Science.gov (United States)

    Samoilov, Michael; Plyasunov, Sergey; Arkin, Adam P.

    2005-02-01

    Stochastic effects in biomolecular systems have now been recognized as a major physiologically and evolutionarily important factor in the development and function of many living organisms. Nevertheless, they are often thought of as providing only moderate refinements to the behaviors otherwise predicted by the classical deterministic system description. In this work we show by using both analytical and numerical investigation that at least in one ubiquitous class of (bio)chemical-reaction mechanisms, enzymatic futile cycles, the external noise may induce a bistable oscillatory (dynamic switching) behavior that is both quantitatively and qualitatively different from what is predicted or possible deterministically. We further demonstrate that the noise required to produce these distinct properties can itself be caused by a set of auxiliary chemical reactions, making it feasible for biological systems of sufficient complexity to generate such behavior internally. This new stochastic dynamics then serves to confer additional functional modalities on the enzymatic futile cycle mechanism that include stochastic amplification and signaling, the characteristics of which could be controlled by both the type and parameters of the driving noise. Hence, such noise-induced phenomena may, among other roles, potentially offer a novel type of control mechanism in pathways that contain these cycles and the like units. In particular, observations of endogenous or externally driven noise-induced dynamics in regulatory networks may thus provide additional insight into their topology, structure, and kinetics. network motif | signal transduction | chemical reaction | synthetic biology | systems biology

  17. Drive-induced delocalization in the Aubry-André model

    Science.gov (United States)

    Ray, S.; Ghosh, A.; Sinha, S.

    2018-01-01

    Motivated by the recent experiment by Bordia et al. [Nat. Phys. 13, 460 (2017), 10.1038/nphys4020], we study the single particle delocalization phenomena of the Aubry-André (AA) model subjected to periodic drives. In two distinct cases we construct an equivalent classical description to illustrate that the drive-induced delocalization phenomena stems from an instability and the onset of chaos in the underlying dynamics. In the first case we analyze the delocalization and the thermalization in a time modulated AA potential with respect to driving frequency and demonstrate that there exists a threshold value of the amplitude of the drive. In the next example, we show that the periodic modulation of the phase of the hopping amplitude induced by a gauge field leads to an unusual effect on delocalization with a nonmonotonic dependence on the driving frequency. Within a window of such a driving frequency a delocalized Floquet band with a mobility edge appears, exhibiting multifractality in the spectrum as well as in the Floquet eigenfunctions. Finally, we explore the effect of interaction and discuss how the results of the present analysis can be tested experimentally.

  18. Internet Enabled Remote Driving of a Combat Hybrid Electric Power System for Duty Cycle Measurement

    National Research Council Canada - National Science Library

    Goodell, Jarrett; Compere, Marc; Smith, Wilford; Holtz, Dale; Brudnak, Mark; Pozolo, Mike; Paul, Victor; Mohammad, Syed; Mortsfield, Todd; Shvartsman, Andrey

    2007-01-01

    This paper describes a human-in-the-loop motion-based simulator interfaced to hybrid-electric power system hardware, both of which were used to measure the duty cycle of a combat vehicle in a virtual...

  19. Modelling and Improvement of Thermal Cycling in Power Electronics for Motor Drive Applications

    DEFF Research Database (Denmark)

    Vernica, Ionut; Ma, Ke; Blaabjerg, Frede

    2016-01-01

    It is well known that the dynamical change of the thermal stress in the power devices is one of the major factors that have influences on the overall efficiency and reliability of power electronics. The main objective of this paper consists of identifying the main parameters that affect the thermal...... are identified during the acceleration and deceleration periods of the motor. The main causes for these adverse thermal cycles have been presented and, consequently, the influence of the deceleration slope, modulation technique and reactive current on the thermal cycles has been analyzed. Finally, the improved...

  20. Large herbivores as a driving force of woodland-grassland cycles

    NARCIS (Netherlands)

    Cornelissen, Perry

    2017-01-01

    This thesis examines the mutual interactions between the population dynamics of large herbivores and wood-pasture cycles in eutrophic wetlands. Therefore, habitat use and population dynamics of large herbivores, the effects of large herbivores on vegetation development, and the mutual

  1. Uncovering driving forces on greenhouse gas emissions in China’ aluminum industry from the perspective of life cycle analysis

    International Nuclear Information System (INIS)

    Liu, Zhe; Geng, Yong; Adams, Michelle; Dong, Liang; Sun, Lina; Zhao, Jingjing; Dong, Huijuan; Wu, Jiao; Tian, Xu

    2016-01-01

    Highlights: • Energy-related GHG emission trajectories, features and driving forces of CAI are analyzed from the perspective of LCA. • CAI experienced a rapid growth of energy-related GHG emissions from 2004 to 2013. • Energy-scale effect is the main driving force for energy-related GHG emissions increase in CAI. • Construction and transportation-related activities account for more than 40% of the total embodied emissions. • Policy implications such as developing secondary aluminum industry, improving energy mix etc, are raised. - Abstract: With the rapid growth of aluminum production, reducing greenhouse gas (GHG) emissions in China’s aluminum industry (CAI) is posing a significant challenge. In this study, the energy-related GHG emission trajectories, features and driving forces of CAI are analyzed from the perspective of life cycle analysis (LCA) from 2004 to 2013. Results indicate that CAI experienced a rapid growth of energy-related GHG emissions with an average annual growth of 28.5 million tons CO_2e from 2004 to 2013. Energy-scale effect is the main driving force for energy-related GHG emissions increase in CAI, while emission-factor effect of secondary aluminum production plays a marginal effect. Construction and transportation-related activities account for the bulk of the embodied emissions, accounting for more than 40% of the total embodied emissions from CAI. Policy implications for GHG mitigation within the CAI, such as developing secondary aluminum industry, improving energy mix and optimizing resource efficiency of production, are raised.

  2. Accidents can happen to any of us, whether we are on foot, cycling or driving

    CERN Multimedia

    2012-01-01

    Excessive speeding, STOP signs not respected, a cyclist on the wrong side of the road, a pedestrian not paying attention, someone on a mobile phone while driving - are you familiar with any of these situations? The HSE Unit would like to express its opinion in light of the road accident statistics involving personnel at CERN.   In 2011, the HSE Unit's Accident/Incident Prevention and Follow-up Service recorded 28 motoring accidents involving personnel either on the CERN site or on journeys to and from work - double the 2010 statistics! These include accidents that could have been avoided by reducing speed or not using a mobile phone while driving. At CERN, the majority of accidents linked to journeys continues to affect cyclists, with the number of cases now close to 30 each year. In order to ensure the safety of personnel, the HSE Unit would like to remind cyclists that wearing a protective helmet is highly recommended and that it is essential to ensure that you can be seen (bicycle lig...

  3. Modelling Supported Driving as an Optimal Control Cycle : Framework and Model Characteristics

    NARCIS (Netherlands)

    Wang, M.; Treiber, M.; Daamen, W.; Hoogendoorn, S.P.; Van Arem, B.

    2013-01-01

    Driver assistance systems support drivers in operating vehicles in a safe, comfortable and efficient way, and thus may induce changes in traffic flow characteristics. This paper puts forward a receding horizon control framework to model driver assistance and cooperative systems. The accelerations of

  4. Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction.

    Science.gov (United States)

    Walsted, Emil S; Faisal, Azmy; Jolley, Caroline J; Swanton, Laura L; Pavitt, Matthew J; Luo, Yuan-Ming; Backer, Vibeke; Polkey, Michael I; Hull, James H

    2018-02-01

    Exercise-induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly understood. The objective of this study was to evaluate exercise-related changes in laryngeal aperture on ventilation, pulmonary mechanics, and respiratory neural drive. We prospectively evaluated 12 subjects (6 with EILO and 6 healthy age- and gender-matched controls). Subjects underwent baseline spirometry and a symptom-limited incremental exercise test with simultaneous and synchronized recording of endoscopic video and gastric, esophageal, and transdiaphragmatic pressures, diaphragm electromyography, and respiratory airflow. The EILO and control groups had similar peak work rates and minute ventilation (V̇e) (work rate: 227 ± 35 vs. 237 ± 35 W; V̇e: 103 ± 20 vs. 98 ± 23 l/min; P > 0.05). At submaximal work rates (140-240 W), subjects with EILO demonstrated increased work of breathing ( P respiratory neural drive ( P respiratory mechanics and diaphragm electromyography with endoscopic video, we demonstrate, for the first time, increased work of breathing and respiratory neural drive in association with the development of EILO. Future detailed investigations are now needed to understand the role of upper airway closure in causing exertional dyspnea and exercise limitation. NEW & NOTEWORTHY Exercise-induced laryngeal obstruction is a prevalent cause of exertional dyspnea in young individuals; yet, how laryngeal closure affects breathing is unknown. In this study we synchronized endoscopic video with respiratory physiological measurements, thus providing the first detailed commensurate assessment of respiratory mechanics and neural drive in relation to laryngeal closure. Laryngeal closure was associated with increased work of breathing and respiratory neural drive preceded by an

  5. ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, J.; Sindelar, C; Mulko, N; Collins, K; Kong, S; Hawley, R; Kull, F

    2009-01-01

    Segregation of nonexchange chromosomes during Drosophila melanogaster meiosis requires the proper function of NOD, a nonmotile kinesin-10. We have determined the X-ray crystal structure of the NOD catalytic domain in the ADP- and AMPPNP-bound states. These structures reveal an alternate conformation of the microtubule binding region as well as a nucleotide-sensitive relay of hydrogen bonds at the active site. Additionally, a cryo-electron microscopy reconstruction of the nucleotide-free microtubule-NOD complex shows an atypical binding orientation. Thermodynamic studies show that NOD binds tightly to microtubules in the nucleotide-free state, yet other nucleotide states, including AMPPNP, are weakened. Our pre-steady-state kinetic analysis demonstrates that NOD interaction with microtubules occurs slowly with weak activation of ADP product release. Upon rapid substrate binding, NOD detaches from the microtubule prior to the rate-limiting step of ATP hydrolysis, which is also atypical for a kinesin. We propose a model for NOD's microtubule plus-end tracking that drives chromosome movement.

  6. Anaerobic Respiration Using a Complete Oxidative TCA Cycle Drives Multicellular Swarming in Proteus mirabilis

    Science.gov (United States)

    Alteri, Christopher J.; Himpsl, Stephanie D.; Engstrom, Michael D.; Mobley, Harry L. T.

    2012-01-01

    ABSTRACT Proteus mirabilis rapidly migrates across surfaces using a periodic developmental process of differentiation alternating between short swimmer cells and elongated hyperflagellated swarmer cells. To undergo this vigorous flagellum-mediated motility, bacteria must generate a substantial proton gradient across their cytoplasmic membranes by using available energy pathways. We sought to identify the link between energy pathways and swarming differentiation by examining the behavior of defined central metabolism mutants. Mutations in the tricarboxylic acid (TCA) cycle (fumC and sdhB mutants) caused altered patterns of swarming periodicity, suggesting an aerobic pathway. Surprisingly, the wild-type strain swarmed on agar containing sodium azide, which poisons aerobic respiration; the fumC TCA cycle mutant, however, was unable to swarm on azide. To identify other contributing energy pathways, we screened transposon mutants for loss of swarming on sodium azide and found insertions in the following genes that involved fumarate metabolism or respiration: hybB, encoding hydrogenase; fumC, encoding fumarase; argH, encoding argininosuccinate lyase (generates fumarate); and a quinone hydroxylase gene. These findings validated the screen and suggested involvement of anaerobic electron transport chain components. Abnormal swarming periodicity of fumC and sdhB mutants was associated with the excretion of reduced acidic fermentation end products. Bacteria lacking SdhB were rescued to wild-type pH and periodicity by providing fumarate, independent of carbon source but dependent on oxygen, while fumC mutants were rescued by glycerol, independent of fumarate only under anaerobic conditions. These findings link multicellular swarming patterns with fumarate metabolism and membrane electron transport using a previously unappreciated configuration of both aerobic and anaerobic respiratory chain components. PMID:23111869

  7. Can Mn–S redox cycling drive sedimentary dolomite formation? A hypothesis

    Energy Technology Data Exchange (ETDEWEB)

    Petrash, Daniel A.; Lalonde, Stefan V.; González-Arismendi, Gabriela; Gordon, Robert A.; Méndez, José A.; Gingras, Murray K.; Konhauser, Kurt O. (CLS); (UCV-Venezuela); (CNRS-UMR); (Alberta)

    2016-06-10

    The formation of dolomite in modern peritidal environments is linked to the degradation of buried microbial mats, with complexation of Ca and Mg by extracellular polymeric substances (EPSs) and alkalinity generation through organic carbon respiration facilitating the nucleation of dolomite precursors. In the past two decades, microbial sulfate reduction, methanogenesis, and methanotrophy have all been considered as potential drivers of the nucleation process, but it remains unclear why dolomite formation could not also occur in suboxic sediments where abundant alkalinity is produced by processes linked to Mn(IV) and/or Fe(III) reduction coupled with the diffusion and reoxidation of reduced sulfur species. Here we report the interstitial occurrence of spheroidal aggregates of nanometer-scale Ca-rich dolomite rhombohedra within suboxic sediments associated with remnant microbial mats that developed in the peritidal zone of the Archipelago Los Roques, Venezuela. Multiple analytical tools, including EPMA, ICP-MS, synchrotron-based XRF and XRD, and spatially resolved XANES microanalyses, show that the dolomite-cemented interval exhibits depleted bulk iron concentrations, but is interstitially enriched in Mn and elemental sulfur (S⁰). Manganese occurs in several oxidation states, indicating that the dolomite-cemented interval was the locus of complex biological redox transformations characterized by coupled Mn and S cycling. The tight correspondence between sedimentary Mn and MgCO₃ concentrations further hints at a direct role for Mn during dolomitization. While additional studies are required to confirm its relevance in natural settings, we propose a model by which coupled Mn–S redox cycling may promote alkalinity generation and thus dolomite formation in manner similar to, or even more efficiently, than bacterial sulfate reduction alone.

  8. On Current Drive and Wave Induced Bootstrap Current in Toroidal Plasmas

    International Nuclear Information System (INIS)

    Hellsten, T.; Johnson, T.

    2008-01-01

    A comprehensive treatment of wave-particle interactions in toroidal plasmas including collisional relaxation, applicable to heating or anomalous wave induced transport, has been obtained by using Monte Carlo operators satisfying quasi-neutrality. This approach enables a self-consistent treatment of wave-particle interactions applicable to the banana regime in the neoclassical theory. It allows an extension into a regime with large temperature and density gradients, losses and transport of particles by wave-particle interactions making the method applicable to transport barriers. It is found that at large gradients the relationship between radial electric field, parallel velocity, temperature and density gradient in the neoclassical theory is modified such that coefficient in front of the logarithmic ion temperature gradient, which in the standard neoclassical theory is small and counteracts the electric field caused by the density gradient, now changes sign and contributes to the built up of the radial electric field. The possibility to drive current by absorbing the waves on trapped particles has been studied and how the wave-particle interactions affect the bootstrap current. Two new current drive mechanisms are studied: current drive by wave induced bootstrap current and selective detrapping into passing orbits by directed waves.

  9. Vehicle driving cycle performance of the spark-less di-ji hydrogen engine

    Energy Technology Data Exchange (ETDEWEB)

    Boretti, Alberto A. [School of Science and Engineering, University of Ballarat, PO Box663, Ballarat, VIC 3353 (Australia)

    2010-05-15

    The paper describes coupled CFD combustion simulations and CAE engine performance computations to describe the operation over the full range of load and speed of an always lean burn, Direct Injection Jet Ignition (DI-JI) hydrogen engine. Jet ignition pre-chambers and direct injection are enablers of high efficiencies and load control by quantity of fuel injected. Towards the end of the compression stroke, a small quantity of hydrogen is injected within the spark-less pre-chamber of the DI-JI engine, where it mixes with the air entering from the main chamber and auto-ignites because of the high temperature of the hot glow plug. Then, jets of partially combusted hot gases enter the main chamber igniting there in the bulk, over multiple ignition points, lean stratified mixtures of air and fuel. Engine maps of brake specific fuel consumption vs. speed and brake mean effective pressure are computed first. CAE vehicle simulations are finally performed evaluating the fuel consumption over emission cycles of a vehicle equipped with this engine. (author)

  10. Environmental assessment of plug-in hybrid electric vehicles using naturalistic drive cycles and vehicle travel patterns: A Michigan case study

    International Nuclear Information System (INIS)

    Marshall, Brandon M.; Kelly, Jarod C.; Lee, Tae-Kyung; Keoleian, Gregory A.; Filipi, Zoran

    2013-01-01

    Plug-in hybrid electric vehicles (PHEVs) use grid electricity as well as on-board gasoline for motive force. These multiple energy sources make prediction of PHEV energy consumption challenging and also complicate evaluation of their environmental impacts. This paper introduces a novel PHEV energy consumption modeling approach and compares it to a second approach from the literature, each using actual trip patterns from the 2009 National Household Travel Survey (NHTS). The first approach applies distance-dependent fuel efficiency and on-road electricity consumption rates based on naturalistic or real world, driving information to determine gasoline and electricity consumption. The second uses consumption rates derived in accordance with government certification testing. Both approaches are applied in the context of a location-specific case study that focuses on the state of Michigan. The two PHEV models show agreement in electricity demand due to vehicle charging, gasoline consumption, and life cycle environmental impacts for this case study. The naturalistic drive cycle approach is explored as a means of extending location-specific driving data to supplement existing PHEV impact assessments methods. - Highlights: • Travel patterns from survey data are combined with naturalistic drive cycles. • More realistic PHEV energy modeling using these synthesized real-world drive cycles. • Methodology is demonstrated for PHEVs in Michigan but applicable for other regions. • Energy and emissions findings have major implications for PHEV standards and policy

  11. The Enright phenomenon. Stereoscopic distortion of perceived driving speed induced by monocular pupil dilation.

    Science.gov (United States)

    Carkeet, Andrew; Wood, Joanne M; McNeill, Kylie M; McNeill, Hamish J; James, Joanna A; Holder, Leigh S

    The Enright phenomenon describes the distortion in speed perception experienced by an observer looking sideways from a moving vehicle when viewing with interocular differences in retinal image brightness, usually induced by neutral density filters. We investigated whether the Enright phenomenon could be induced with monocular pupil dilation using tropicamide. We tested 17 visually normal young adults on a closed road driving circuit. Participants were asked to travel at Goal Speeds of 40km/h and 60km/h while looking sideways from the vehicle with: (i) both eyes with undilated pupils; (ii) both eyes with dilated pupils; (iii) with the leading eye only dilated; and (iv) the trailing eye only dilated. For each condition we recorded actual driving speed. With the pupil of the leading eye dilated participants drove significantly faster (by an average of 3.8km/h) than with both eyes dilated (p=0.02); with the trailing eye dilated participants drove significantly slower (by an average of 3.2km/h) than with both eyes dilated (p<0.001). The speed, with the leading eye dilated, was faster by an average of 7km/h than with the trailing eye dilated (p<0.001). There was no significant difference between driving speeds when viewing with both eyes either dilated or undilated (p=0.322). Our results are the first to show a measurable change in driving behaviour following monocular pupil dilation and support predictions based on the Enright phenomenon. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  12. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  13. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    Solhaug, A.; Vines, L.L.; Ivanova, L.; Spilsberg, B.; Holme, J.A.; Pestka, J.; Collins, A.; Eriksen, G.S.

    2012-01-01

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15–30 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 μM for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  14. High potential for temperate viruses to drive carbon cycling in chemoautotrophy-dominated shallow-water hydrothermal vents.

    Science.gov (United States)

    Rastelli, Eugenio; Corinaldesi, Cinzia; Dell'Anno, Antonio; Tangherlini, Michael; Martorelli, Eleonora; Ingrassia, Michela; Chiocci, Francesco L; Lo Martire, Marco; Danovaro, Roberto

    2017-11-01

    Viruses are the most abundant life forms in the world's oceans and they are key drivers of biogeochemical cycles, but their impact on the microbial assemblages inhabiting hydrothermal vent ecosystems is still largely unknown. Here, we analysed the viral life strategies and virus-host interactions in the sediments of a newly discovered shallow-water hydrothermal field of the Mediterranean Sea. Our study reveals that temperate viruses, once experimentally induced to replicate, can cause large mortality of vent microbes, significantly reducing the chemoautotrophic carbon production, while enhancing the metabolism of microbial heterotrophs and the re-cycling of the organic matter. These results provide new insights on the factors controlling primary and secondary production processes in hydrothermal vents, suggesting that the inducible provirus-host interactions occurring in these systems can profoundly influence the functioning of the microbial food web and the efficiency in the energy transfer to the higher trophic levels. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  15. Freeway Driving Cycle Construction Based on Real-Time Traffic Information and Global Optimal Energy Management for Plug-In Hybrid Electric Vehicles

    Directory of Open Access Journals (Sweden)

    Hongwen He

    2017-11-01

    Full Text Available This paper presents a freeway driving cycle (FDC construction method based on traffic information. A float car collected different type of roads in California and we built a velocity fragment database. We selected a real freeway driving cycle (RFDC and established the corresponding time traffic information tensor model by using the data in California Department of Transportation performance measure system (PeMS. The correlation of road velocity in the time dimension and spatial dimension are analyzed. According to the average velocity of road sections at different times, the kinematic fragments are stochastically selected in the velocity fragment database to construct a real-time FDC of each section. The comparison between construction freeway driving cycle (CFDC and real freeway driving cycle (RFDC show that the CFDC well reflects the RFDC characteristic parameters. Compared to its application in plug-in electric hybrid vehicle (PHEV optimal energy management based on a dynamic programming (DP algorithm, CFDC and RFDC fuel consumption are similar within approximately 5.09% error, and non-rush hour fuel economy is better than rush hour 3.51 (L/100 km at non-rush hour, 4.29 (L/km at rush hour. Moreover, the fuel consumption ratio can be up to 13.17% in the same CFDC at non-rush hour.

  16. Reliability assessment of shut-off rod drive mechanism for TAPP - 3 and 4 and critical facility through life cycle testing

    International Nuclear Information System (INIS)

    Singh, Manjit; Badodkar, D.N.; Singh, N.K.; Dalal, N.S.; Mishra, M.K.; Veda Vyas, G.; Kothari, C.B.; Rao, V.V.S.S.; Saraf, R.K.

    2006-01-01

    Shut-off rod drive mechanism forms a safety critical system of a nuclear reactor. It is the space constraints for the given reactor layout, which makes design of shut-off rod drive mechanism (SRDM) a custom built design. Design of SRDM adopts fail-safe, replaceability and the simplicity criterion ensuring very high reliability of its operation. Shut-off rod drive mechanism for TAPP-3 and 4 and 'Critical Facility' have been recently designed and developed at Division of Remote Handling and Robotics (DRHR), BARC. These are designed with a number of advanced features and these are significantly different than those used in Dhruva and 220 MWe PHWRs. Design of SRDM is qualified through proto typing and life cycle testing on a full-scale test set-up. This paper gives details of qualification and life cycle test data for prototype SRDM for TAPP-3 and 4 and 'Critical Facility' and reliability assessment. (author)

  17. Development of emission factors for motorcycles and shared auto-rickshaws using real-world driving cycle for a typical Indian city.

    Science.gov (United States)

    Adak, Prasenjit; Sahu, Ravi; Elumalai, Suresh Pandian

    2016-02-15

    Vehicular emission is one of the most important contributors of urban air pollution. To quantify the impact of traffic on urban air quality, it is necessary to quantify vehicular emission. In many cities of India, such as Dhanbad, shared auto-rickshaw is the pre-dominant mode of transportation. Indian Driving Cycle (IDC) and Modified Indian Driving Cycle (MIDC) are used for emission testing of motorcycles, shared auto-rickshaws and passenger cars in India for regulatory purposes. IDC used for motorcycles and shared auto-rickshaws does not recognize the difference in two vehicle classes in terms of driving pattern. In real world, shared auto-rickshaws, behave differently than motorcycles. To quantify the impact of shared auto-rickshaws on urban air quality accurately, emission factors (EFs) are required to derive from real-world driving cycles (DCs). In heterogeneous traffic, vehicles of one class affect the behavior of vehicles of other classes. To estimate the emissions from different vehicle classes accurately, EFs for motorcycles and passenger cars are also required to be revised. In this study, real-world DCs were developed for motorcycles, shared auto-rickshaws and passenger cars in Dhanbad. Developed DCs were used to calculate EFs for respective classes. Shared auto-rickshaws were found to have the highest deviation from EFs derived using IDC. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Gaseous nitrous acid (HONO) and nitrogen oxides (NOx) emission from gasoline and diesel vehicles under real-world driving test cycles.

    Science.gov (United States)

    Trinh, Ha T; Imanishi, Katsuma; Morikawa, Tazuko; Hagino, Hiroyuki; Takenaka, Norimichi

    2017-04-01

    Reactive nitrogen species emission from the exhausts of gasoline and diesel vehicles, including nitrogen oxides (NO x ) and nitrous acid (HONO), contributes as a significant source of photochemical oxidant precursors in the ambient air. Multiple laboratory and on-road exhaust measurements have been performed to estimate the NO x emission factors from various vehicles and their contribution to atmospheric pollution. Meanwhile, HONO emission from vehicle exhaust has been under-measured despite the fact that HONO can contribute up to 60% of the total hydroxyl budget during daytime and its formation pathway is not fully understood. A profound traffic-induced HONO to NO x ratio of 0.8%, established by Kurtenbach et al. since 2001, has been widely applied in various simulation studies and possibly linked to under-estimation of HONO mixing ratios and OH radical budget in the morning. The HONO/NO x ratios from direct traffic emission have become debatable when it lacks measurements for direct HONO emission from vehicles upon the fast-changing emission reduction technology. Several recent studies have reported updated values for this ratio. This study has reported the measurement of HONO and NO x emission as well as the estimation of exhaust-induced HONO/NO x ratios from gasoline and diesel vehicles using different chassis dynamometer tests under various real-world driving cycles. For the tested gasoline vehicle, which was equipped with three-way catalyst after-treatment device, HONO/NO x ratios ranged from 0 to 0.95 % with very low average HONO concentrations. For the tested diesel vehicle equipped with diesel particulate active reduction device, HONO/NO x ratios varied from 0.16 to 1.00 %. The HONO/NO x ratios in diesel exhaust were inversely proportional to the average speeds of the tested vehicles. Photolysis of HONO is a dominant source of morning OH radicals. Conventional traffic-induced HONO/NO x ratio of 0.8% has possibly linked to underestimation of the total HONO

  19. Could driving safety be compromised by noise exposure at work and noise-induced hearing loss?

    Science.gov (United States)

    Picard, Michel; Girard, Serge André; Courteau, Marilène; Leroux, Tony; Larocque, Richard; Turcotte, Fernand; Lavoie, Michel; Simard, Marc

    2008-10-01

    A study was conducted to verify if there is an association between occupational noise exposure, noise-induced hearing loss and driving safety expanding on previous findings by Picard, et al. (2008) that the two factors did increase accident risk in the workplace. This study was made possible when driving records of all Quebec drivers were made available by the Societe de l'assurance automobile du Quebec (SAAQ is the state monopoly responsible for the provision of motor vehicle insurance and the compensation of victims of traffic accidents). These records were linked with personal records maintained by the Quebec National Institute of Public Health as part of its mission to prevent noise induced hearing loss in the workplace. Individualized information on occupational noise exposure and hearing sensitivity was available for 46,030 male workers employed in noisy industries who also held a valid driver's permit. The observation period is of five years duration, starting with the most recent audiometric examination. The associations between occupational noise exposure levels, hearing status, and personal driving record were examined by log-binomial regression on data adjusted for age and duration of exposure. Daily noise exposures and bilateral average hearing threshold levels at 3, 4, and 6 kHz were used as independent variables while the dependent variables were 1) the number of motor vehicle accidents experienced by participants during the study period and 2) participants' records of registered traffic violations of the highway safety code. The findings are reported as prevalence ratios (PRs) with their 95% confidence intervals (CIs). Attributable numbers of events were computed with the relevant PRs, lesser-noise, exposed workers and those with normal hearing levels making the group of reference. Adjusting for age confirmed that experienced workers had fewer traffic accidents. The data show that occupational noise exposure and hearing loss have the same effect on

  20. Symmetry Induced Heteroclinic Cycles in Coupled Sensor Devices

    Science.gov (United States)

    2012-01-01

    of an array of magnetic sensors. In particular, we consider arrays made up of fluxgate magnetometers inductively coupled through electronic circuits. c...cycle can significantly enhance the sensitivity of an array of magnetic sensors. In particular, we consider arrays made up of fluxgate magnetometers ...IUTAM 5 ( 2012 ) 144 – 150 4. A Cycle in A Coupled-Core Fluxgate Magnetometer 4.1. Modeling In its most basic form, a fluxgate magnetometer

  1. Definición de un ciclo de movimiento básico para camiones diesel. // Definition of a basic driving cycle for diesel trucks.

    Directory of Open Access Journals (Sweden)

    V. Millo Carmenate

    2004-05-01

    Full Text Available Se define un ciclo básico de movimiento, cuya modelación matemática posibilite la determinación de indicadoresdinámicos básicos y de consumo de combustible para poder comparar vehículos con iguales fines pero con diferenteprocedencia, marca o parámetros constructivos, bajo similares condiciones a los fines de la selección.Palabras claves: Dinámica de vehículos, selección, ciclos de viaje._____________________________________________________________________________Abstract.A basic driving cycle is defined, whose mathematical modeling enable the determination of basic dynamic indicators andfuel consumption in order to compare vehicles with the same purpose but with different origin, brands or constructiveparameters, under similar operating conditions for the selection.Key words: Vehicle dynamics, selection, driving cycle.

  2. Two-way shape memory effect induced by repetitive compressive loading cycles

    International Nuclear Information System (INIS)

    Kim, Hyun-Chul; Yoo, Young-Ik; Lee, Jung-Ju

    2009-01-01

    The NiTi alloy can be trained by repetitive loading or heating cycles. As a result of the training, a two-way shape memory effect (TWSME) can be induced. Considerable research has been reported regarding the TWSME trained by tensile loading. However, the TWSME trained by compressive loading has not been investigated nearly as much. In this paper, the TWSME is induced by compressive loading cycles and the two-way shape memory strain is evaluated by using two types of specimen: a solid cylinder type and a tube type. The TWSME trained by compressive loading is different from that trained by tensile loading owing to the severe tension/compression asymmetry as described in previous research. After repetitive compressive loading cycles, strain variation upon cooling is observed, and this result proves that the TWSME is induced by compressive loading cycles. By performing compressive loading cycles, plastic deformation in NiTi alloy occurs more than for tensile loading cycles, which brings about the appearance of TWSME. It can be said that the TWSME is induced by compressive loading cycles more easily. The two-way shape memory strain increases linearly as the maximum strain of compressive loading cycles increases, regardless of the shape and the size of the NiTi alloy; this two-way shape memory strain then shows a tendency towards saturation after some repeated cycles

  3. Processes driving sea ice variability in the Bering Sea in an eddying ocean/sea ice model: Mean seasonal cycle

    Science.gov (United States)

    Li, Linghan; McClean, Julie L.; Miller, Arthur J.; Eisenman, Ian; Hendershott, Myrl C.; Papadopoulos, Caroline A.

    2014-12-01

    The seasonal cycle of sea ice variability in the Bering Sea, together with the thermodynamic and dynamic processes that control it, are examined in a fine resolution (1/10°) global coupled ocean/sea-ice model configured in the Community Earth System Model (CESM) framework. The ocean/sea-ice model consists of the Los Alamos National Laboratory Parallel Ocean Program (POP) and the Los Alamos Sea Ice Model (CICE). The model was forced with time-varying reanalysis atmospheric forcing for the time period 1970-1989. This study focuses on the time period 1980-1989. The simulated seasonal-mean fields of sea ice concentration strongly resemble satellite-derived observations, as quantified by root-mean-square errors and pattern correlation coefficients. The sea ice energy budget reveals that the seasonal thermodynamic ice volume changes are dominated by the surface energy flux between the atmosphere and the ice in the northern region and by heat flux from the ocean to the ice along the southern ice edge, especially on the western side. The sea ice force balance analysis shows that sea ice motion is largely associated with wind stress. The force due to divergence of the internal ice stress tensor is large near the land boundaries in the north, and it is small in the central and southern ice-covered region. During winter, which dominates the annual mean, it is found that the simulated sea ice was mainly formed in the northern Bering Sea, with the maximum ice growth rate occurring along the coast due to cold air from northerly winds and ice motion away from the coast. South of St Lawrence Island, winds drive the model sea ice southwestward from the north to the southwestern part of the ice-covered region. Along the ice edge in the western Bering Sea, model sea ice is melted by warm ocean water, which is carried by the simulated Bering Slope Current flowing to the northwest, resulting in the S-shaped asymmetric ice edge. In spring and fall, similar thermodynamic and dynamic

  4. Study of flow induce vibration inside 3.5 inch hard disk drives

    Directory of Open Access Journals (Sweden)

    Wichitpon Seepangmon

    2014-06-01

    Full Text Available This study focused on flow induced vibration of head stack assembly (HSA in a 3.5 inch hard disk drive with 5 disks and 10 read/write heads. We studied the effects of air flow on gimbal flex and resonance on arm. The comparison of vibrations on slider between the normal model and the experiment has been done for verifying the model. The peaks of frequency in experiment match the normal model at 1,040 1,320 and 1,400 Hz respectively. After that, the RNG K-ε turbulence model was used to determine the turbulent air flow of 7,200 rpm hard disk drive. The comparison between the normal model and the model with spoiler was investigated by using, computational fluid dynamics software (ANSYS and FLUENT. The results shown velocity magnitudes at the arm were decreased by 0.725 - 57.689 % and pressure dropped by 74.028 - 87.222 %. The velocity magnitudes at the gimbal flex were decreased by 5.522 - 14.291 % and pressure dropped by 48.440 - 82.947 %. The peak of vibrations on arm and gimbal flex was occurred at the frequency 1200 Hz. The model with spoiler could reduce vibration at arm by 2.56 - 95.601 % and reduce vibration at gimbal flex by 4.065 - 95.503 %. In the conclusion, the model with a spoiler could decrease the vibration at all surface of the arm and gimbal flex due to the velocity and pressure reduction[1][4].

  5. TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling

    International Nuclear Information System (INIS)

    Ding, Li; Huang, Yong; Du, Qian; Dong, Feng; Zhao, Xiaomin; Zhang, Wenlong; Xu, Xingang; Tong, Dewen

    2014-01-01

    Highlights: • TGEV N protein reduces cell viability by inducing cell cycle arrest and apoptosis. • TGEV N protein induces cell cycle arrest and apoptosis by regulating p53 signaling. • TGEV N protein plays important roles in TGEV-induced cell cycle arrest and apoptosis. - Abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressed cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence

  6. Novel BCH Code Design for Mitigation of Phase Noise Induced Cycle Slips in DQPSK Systems

    DEFF Research Database (Denmark)

    Leong, M. Y.; Larsen, Knud J.; Jacobsen, G.

    2014-01-01

    We show that by proper code design, phase noise induced cycle slips causing an error floor can be mitigated for 28 Gbau d DQPSK systems. Performance of BCH codes are investigated in terms of required overhead......We show that by proper code design, phase noise induced cycle slips causing an error floor can be mitigated for 28 Gbau d DQPSK systems. Performance of BCH codes are investigated in terms of required overhead...

  7. 0-6629 : Texas specific drive cycles and idle emissions rates for using with EPA's MOVES model, [project summary].

    Science.gov (United States)

    2013-08-01

    The U.S. Environmental Protection Agencys : newest emissions model, Motor Vehicle Emission : Simulator (MOVES), enables users to use local : drive schedules(representative vehicle speed : profiles) in order to perform an accurate analysis : of emi...

  8. Cell cycle related /sup 125/IUDR-induced-division delay

    International Nuclear Information System (INIS)

    Scheniderman, M.H.; Hofer, K.G.

    1987-01-01

    A series of experiments were run to determine if /sup 125/I-decays, in /sup 125/IUdR labeled DNA, specifically accumulated at 1, 3, 5, 7 and 9 hours after plating labeled mitotic cells caused a change in the rate or time of cell entry into mitosis. To accomplish this, a pool of labeled mitotic cells was selected in mitosis and plated in replicate flasks. /sup 125/I decays were accumulated in groups of cells by cooling (4 0 C) for 2 hours starting at the designated times. After rewarding, colcemid was added to arrest cells in mitosis. The rate of cell progression into mitosis for each cell cycle time of accumulation was determined by scoring the mitotic index of cells sampled as a function of time after addition of the colcemid. The results are summarized: (1) Decays from /sup 125/I in /sup 125/I(UdR) labeled DNA reduced the rate of cell progression into mitosis and delayed the time of initiation of mitosis. (2) The reduced rate of progression and the delayed time of initiation of mitosis were independent of the cell cycle time that /sup 125/I-decays were accumulated. (3) The reduced rate of progression after cell cycle accumulation of /sup 125/I decay was statistically indistinguishable from the corresponding controls. (4) The delayed initiation of mitosis after specific cell cycle accumulation of /sup 125/I- decays was greater than the corresponding control. The relationship of these data to DNA and non-DNA division delay target(s) is emphasized

  9. RTV Silicone Rubber Degradation Induced by Temperature Cycling

    Directory of Open Access Journals (Sweden)

    Xishan Wen

    2017-07-01

    Full Text Available Room temperature vulcanized (RTV silicone rubber is extensively used in power system due to its hydrophobicity and hydrophobicity transfer ability. Temperature has been proven to markedly affect the performance of silicone rubbers. This research investigated the degradation of RTV silicone rubber under temperature cycling treatment. Hydrophobicity and its transfer ability, hardness, functional groups, microscopic appearance, and thermal stability were analyzed using the static contact angle method, a Shore A durometer, Fourier transform infrared spectroscopy (FTIR, scanning electron microscopy (SEM, and thermogravimetry (TG, respectively. Some significant conclusions were drawn. After the temperature was cycled between −25 °C and 70 °C, the hydrophobicity changed modestly, but its transfer ability changed remarkably, which may result from the competition between the formation of more channels for the transfer of low molecular weight (LMW silicone fluid and the reduction of LMW silicone fluid in the bulk. A hardness analysis and FTIR analysis demonstrated that further cross-linking reactions occurred during the treatment. SEM images showed the changes in roughness of the RTV silicone rubber surfaces. TG analysis also demonstrated the degradation of RTV silicone rubber by presenting evidence that the content of organic materials decreased during the temperature cycling treatment.

  10. Pressure cycling induced modification of a cemented carbide

    International Nuclear Information System (INIS)

    Beste, U.; Engqvist, H.; Jacobson, S.

    2001-01-01

    The wear of cemented carbide rock drill buttons is due to a complex mixture of mechanisms. One important of such mechanism is the surface fatigue that occurs due to the percussive conditions of rock drilling. To isolate the effects of this mechanism, a mechanical pressure cycling test has been performed on a cemented carbide with 11 % Co and 2 μm WC grain size. The test was ended after 60000 pressure cycles. No signs of fatigue crack nucleation were found. The changes in hardness, fracture toughness, erosion resistance, magnetical coercivity and thermal shock resistance were measured. The microstructure of the sample was investigated with x-ray diffraction, plus scanning and transmission electron microscopy. The fracture toughness decreased 14 % due to the pressure cycling while the hardness did not change. In addition, the thermal shock resistance and the erosion resistance decreased. The magnetical coercivity increased 90 % indicating significant phase transformations or high defect density in the Co binder phase. The TEM revealed no deformation of the WC phase, but important alterations of the Co phase. The Co phase was transformed from fcc into a new unidentified phase, characterized by atomic inter planar distance present in fcc and hcp plus an unfamiliar distance of 2.35 Aa. This phase is suggested to be due to a more complex stacking sequence of the close-packed planes than in hcp or fcc. (author)

  11. Neonatal handling induces anovulatory estrous cycles in rats

    Directory of Open Access Journals (Sweden)

    Gomes C.M.

    1999-01-01

    Full Text Available Since previous work has shown that stimulation early in life decreases sexual receptiveness as measured by the female lordosis quotient, we suggested that neonatal handling could affect the function of the hypothalamus-pituitary-gonadal axis. The effects of neonatal handling on the estrous cycle and ovulation were analyzed in adult rats. Two groups of animals were studied: intact (no manipulation, N = 10 and handled (N = 11. Pups were either handled daily for 1 min during the first 10 days of life or left undisturbed. At the age of 90 days, a vaginal smear was collected daily at 9:00 a.m. and analyzed for 29 days; at 9:00 a.m. on the day of estrus, animals were anesthetized with thiopental (40 mg/kg, ip, the ovaries were removed and the oviduct was dissected and squashed between 2 glass slides. The number of oocytes of both oviductal ampullae was counted under the microscope. The average numbers for each phase of the cycle (diestrus I, diestrus II, proestrus and estrus during the period analyzed were compared between the two groups. There were no significant differences between intact and handled females during any of the phases. However, the number of handled females that showed anovulatory cycles (8 out of 11 was significantly higher than in the intact group (none out of 10. Neonatal stimulation may affect not only the hypothalamus-pituitary-adrenal axis, as previously demonstrated, but also the hypothalamus-pituitary-gonadal axis in female rats.

  12. UV-induced changes in cell cycle and gene expression within rabbit lens epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Sidjanin, D. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences; Grdina, D. [Argonne National Lab., IL (United States); Woloschak, G.E. [Northern Illinois Univ., De Kalb, IL (United States). Dept. of Biological Sciences

    1994-11-01

    Damage to lens epithelial cells is a probable initiation process in cataract formation induced by ultraviolet radiation. These experiments investigated the ability of 254 nm radiation on cell cycle progression and gene expression in rabbit lens epithelial cell line N/N1003A. No changes in expression of c-fos, c-jun, alpha- tubulin, or vimentin was observed following UV exposure. Using flow cytometry, an accumulation of cells in G1/S phase of the cell cycle 1 hr following exposure. The observed changes in gene expression, especially the decreased histone transcripts reported here may play a role in UV induced inhibition of cell cycle progression.

  13. Brief rewarming blunts hypothermia-induced alterations in sensation, motor drive and cognition

    Directory of Open Access Journals (Sweden)

    Marius Brazaitis

    2016-12-01

    hypothermia-induced alterations in neural drive transmission (4.3±0.5 versus 3.4±0.8 mV H-reflex and 4.9±0.2 versus 4.4±0.4 mV V-wave, P<0.05, which increased central fatigue during a 2-min maximum load (P<0.05. Furthermore, only in brief warm water rewarming cerebral alterations were restored to the control level and it was indicated by shortened reaction times (P<0.05.Conclusions: Brief rewarming in warm water rather than the same duration rewarming in thermoneutral environment blunted the hypothermia-induced alterations for thermoregulation, sensation, motor drive and cognition, despite the fact that rectal and deep muscle temperature remained lowered.

  14. Effect of Drive Cycle and Gasoline Particulate Filter on the Size and Morphology of Soot Particles Emitted from a Gasoline-Direct-Injection Vehicle.

    Science.gov (United States)

    Saffaripour, Meghdad; Chan, Tak W; Liu, Fengshan; Thomson, Kevin A; Smallwood, Gregory J; Kubsh, Joseph; Brezny, Rasto

    2015-10-06

    The size and morphology of particulate matter emitted from a light-duty gasoline-direct-injection (GDI) vehicle, over the FTP-75 and US06 transient drive cycles, have been characterized by transmission-electron-microscope (TEM) image analysis. To investigate the impact of gasoline particulate filters on particulate-matter emission, the results for the stock-GDI vehicle, that is, the vehicle in its original configuration, have been compared to the results for the same vehicle equipped with a catalyzed gasoline particulate filter (GPF). The stock-GDI vehicle emits graphitized fractal-like aggregates over all driving conditions. The mean projected area-equivalent diameter of these aggregates is in the 78.4-88.4 nm range and the mean diameter of primary particles varies between 24.6 and 26.6 nm. Post-GPF particles emitted over the US06 cycle appear to have an amorphous structure, and a large number of nucleation-mode particles, depicted as low-contrast ultrafine droplets, are observed in TEM images. This indicates the emission of a substantial amount of semivolatile material during the US06 cycle, most likely generated by the incomplete combustion of accumulated soot in the GPF during regeneration. The size of primary particles and soot aggregates does not vary significantly by implementing the GPF over the FTP-75 cycle; however, particles emitted by the GPF-equipped vehicle over the US06 cycle are about 20% larger than those emitted by the stock-GDI vehicle. This may be attributed to condensation of large amounts of organic material on soot aggregates. High-contrast spots, most likely solid nonvolatile cores, are observed within many of the nucleation-mode particles emitted over the US06 cycle by the GPF-equipped vehicle. These cores are either generated inside the engine or depict incipient soot particles which are partially carbonized in the exhaust line. The effect of drive cycle and the GPF on the fractal parameters of particles, such as fractal dimension and

  15. Muscle damage induced by stretch-shortening cycle exercise.

    Science.gov (United States)

    Kyröläinen, H; Takala, T E; Komi, P V

    1998-03-01

    Strenuous stretch-shortening cycle exercise was used as a model to study the leakage of proteins from skeletal muscle. The analysis included serum levels of creatine kinase (S-CK), myoglobin (S-Mb), and carbonic anhydrase (S-CA III). Blood samples from power- (N=11) and endurance-trained (N=10) athletes were collected before, 0, and 2 h after the exercise, which consisted of a total of 400 jumps. The levels of all determined myocellular proteins increased immediately after the exercise (P exercise, and the ratio of S-CA III and S-Mb decreased (P recruitment order of motor units, and/or differences in training background.

  16. Impact of Different Driving Cycles and Operating Conditions on CO2 Emissions and Energy Management Strategies of a Euro-6 Hybrid Electric Vehicle

    Directory of Open Access Journals (Sweden)

    Claudio Cubito

    2017-10-01

    Full Text Available Although Hybrid Electric Vehicles (HEVs represent one of the key technologies to reduce CO2 emissions, their effective potential in real world driving conditions strongly depends on the performance of their Energy Management System (EMS and on its capability to maximize the efficiency of the powertrain in real life as well as during Type Approval (TA tests. Attempting to close the gap between TA and real world CO2 emissions, the European Commission has decided to introduce from September 2017 the Worldwide Harmonized Light duty Test Procedure (WLTP, replacing the previous procedure based on the New European Driving Cycle (NEDC. The aim of this work is the analysis of the impact of different driving cycles and operating conditions on CO2 emissions and on energy management strategies of a Euro-6 HEV through the limited number of information available from the chassis dyno tests. The vehicle was tested considering different initial battery State of Charge (SOC, ranging from 40% to 65%, and engine coolant temperatures, from −7 °C to 70 °C. The change of test conditions from NEDC to WLTP was shown to lead to a significant reduction of the electric drive and to about a 30% increase of CO2 emissions. However, since the specific energy demand of WLTP is about 50% higher than that of NEDC, these results demonstrate that the EMS strategies of the tested vehicle can achieve, in test conditions closer to real life, even higher efficiency levels than those that are currently evaluated on the NEDC, and prove the effectiveness of HEV technology to reduce CO2 emissions.

  17. Investigation of the purging effect on a dead-end anode PEM fuel cell-powered vehicle during segments of a European driving cycle

    International Nuclear Information System (INIS)

    Gomez, Alberto; Sasmito, Agus P.; Shamim, Tariq

    2015-01-01

    Highlights: • Experimental study of a dead-end anode PEM fuel cell stack during a driving cycle. • Low purging duration is preferred at high current. • High purging frequency can sustain a better performance over time. • Lower cathode stoichiometry is preferred to minimize the parasitic loads. - Abstract: The dynamic performance of the PEM fuel cell is one of the key factors for successful operation of a fuel cell-powered vehicle. Maintaining fast time response while keeping stable and high stack performance is of importance, especially during acceleration and deceleration. In this paper, we evaluate the transient response of a PEM fuel cell stack with a dead-end anode during segments of a legislated European driving cycle together with the effect of purging factors. The PEM fuel cell stack comprises of 24 cells with a 300 cm"2 active catalyst area and operates at a low hydrogen and air pressure. Humidified air is supplied to the cathode side and the dry hydrogen is fed to the anode. The liquid coolant is circulated to the stack and the radiator to maintain the thermal envelope throughout the stack. The stack performance deterioration over time is prevented by utilizing the purging, which removes the accumulated water and impurities. The effect of purging period, purging duration, coolant flow rate and cathode stoichiometry are examined with regard to the fuel cell’s transient performance during the driving cycle. The results show that a low purging duration may avoid the undesired deceleration at a high current, and a high purging period may sustain a better performance over time. Moreover, the coolant flow rate is found to be an important parameter, which affects the stack temperature–time response of the cooling control and the stack performance, especially at high operating currents.

  18. Cycle training induces muscle hypertrophy and strength gain: strategies and mechanisms.

    Science.gov (United States)

    Ozaki, Hayao; Loenneke, J P; Thiebaud, R S; Abe, T

    2015-03-01

    Cycle training is widely performed as a major part of any exercise program seeking to improve aerobic capacity and cardiovascular health. However, the effect of cycle training on muscle size and strength gain still requires further insight, even though it is known that professional cyclists display larger muscle size compared to controls. Therefore, the purpose of this review is to discuss the effects of cycle training on muscle size and strength of the lower extremity and the possible mechanisms for increasing muscle size with cycle training. It is plausible that cycle training requires a longer period to significantly increase muscle size compared to typical resistance training due to a much slower hypertrophy rate. Cycle training induces muscle hypertrophy similarly between young and older age groups, while strength gain seems to favor older adults, which suggests that the probability for improving in muscle quality appears to be higher in older adults compared to young adults. For young adults, higher-intensity intermittent cycling may be required to achieve strength gains. It also appears that muscle hypertrophy induced by cycle training results from the positive changes in muscle protein net balance.

  19. Emissions of toxic pollutants from compressed natural gas and low sulfur diesel-fueled heavy-duty transit buses tested over multiple driving cycles.

    Science.gov (United States)

    Kado, Norman Y; Okamoto, Robert A; Kuzmicky, Paul A; Kobayashi, Reiko; Ayala, Alberto; Gebel, Michael E; Rieger, Paul L; Maddox, Christine; Zafonte, Leo

    2005-10-01

    The number of heavy-duty vehicles using alternative fuels such as compressed natural gas (CNG) and new low-sulfur diesel fuel formulations and equipped with after-treatment devices are projected to increase. However, few peer-reviewed studies have characterized the emissions of particulate matter (PM) and other toxic compounds from these vehicles. In this study, chemical and biological analyses were used to characterize the identifiable toxic air pollutants emitted from both CNG and low-sulfur-diesel-fueled heavy-duty transit buses tested on a chassis dynamometer over three transient driving cycles and a steady-state cruise condition. The CNG bus had no after-treatment, and the diesel bus was tested first equipped with an oxidation catalyst (OC) and then with a catalyzed diesel particulate filter (DPF). Emissions were analyzed for PM, volatile organic compounds (VOCs; determined on-site), polycyclic aromatic hydrocarbons (PAHs), and mutagenic activity. The 2000 model year CNG-fueled vehicle had the highest emissions of 1,3-butadiene, benzene, and carbonyls (e.g., formaldehyde) of the three vehicle configurations tested in this study. The 1998 model year diesel bus equipped with an OC and fueled with low-sulfur diesel had the highest emission rates of PM and PAHs. The highest specific mutagenic activities (revertants/microg PM, or potency) and the highest mutagen emission rates (revertants/mi) were from the CNG bus in strain TA98 tested over the New York Bus (NYB) driving cycle. The 1998 model year diesel bus with DPF had the lowest VOCs, PAH, and mutagenic activity emission. In general, the NYB driving cycle had the highest emission rates (g/mi), and the Urban Dynamometer Driving Schedule (UDDS) had the lowest emission rates for all toxics tested over the three transient test cycles investigated. Also, transient emissions were, in general, higher than steady-state emissions. The emissions of toxic compounds from an in-use CNG transit bus (without an oxidation

  20. Deformation-induced martensitic transformation in a 201 austenitic steel: The synergy of stacking fault energy and chemical driving force

    Energy Technology Data Exchange (ETDEWEB)

    Moallemi, M., E-mail: m.moallemi@ma.iut.ac.ir [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Kermanpur, A. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Najafizadeh, A. [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Fould Institute of Technology, Fouladshahr, Isfahan, 8491663763 (Iran, Islamic Republic of); Rezaee, A.; Baghbadorani, H. Samaei; Nezhadfar, P. Dastranjy [Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

    2016-01-20

    The present study deals with the correlation of stacking fault energy's synergy and driving force in the formation of deformation-induced martensitic transformation in a 201 austenitic stainless steel. The fraction of deformation-induced martensite was characterized by means of X-ray diffraction and magnetic induction techniques. The kinetics of the martensite formation versus applied strain was evaluated through the sigmoidal model. It was shown that the volume fraction of ά-martensite is closely related to the driving force/SFE ratio of the alloy. The results also showed that the martensite content is similar in both XRD and magnetic methods and the applied sigmoidal model was consistent with the obtained experimental data.

  1. Merkel Cell Polyomavirus Small T Antigen Drives Cell Motility via Rho-GTPase-Induced Filopodium Formation.

    Science.gov (United States)

    Stakaitytė, Gabrielė; Nwogu, Nnenna; Dobson, Samuel J; Knight, Laura M; Wasson, Christopher W; Salguero, Francisco J; Blackbourn, David J; Blair, G Eric; Mankouri, Jamel; Macdonald, Andrew; Whitehouse, Adrian

    2018-01-15

    Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β 1 integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC. IMPORTANCE Merkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus. It causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer. However, the molecular mechanisms implicating MCPyV-encoded proteins in cancer development are yet to be fully elucidated. This study builds

  2. Nature of macroeconomic equilibrium and driving force of economic cycles in the light of difference between money and exergy forms in cost estimations

    Energy Technology Data Exchange (ETDEWEB)

    Bandura, A.V. [National Politechnical Univ., Kiev (Ukraine); Brodianskii, V.M. [Moscow Power Engineering Inst. Technical Univ. (Russian Federation)

    1996-11-01

    The main problem of exergy application directly in economic analysis is to find valid correlation between money-based cost and exergy based one (including exergy expenses of labour) and to define exergy cost as an economic category among the existing traditional economic ones. The present report is aimed to search the way for this macroeconomic problems` solution. It is demonstrated that exergy-based cost can be recalculated in a monetary form using a coefficient, defined as a ratio between money supply and the total exergy of all natural resources involved in production process, i.e. as a ratio between monetary and exergy bases. The difference between `natural` and current prices (P) can be used directly both for general quantitative characteristics of an economic cycles driving force and for control of market relationship imperfection. It is shown that for the period of time with the positive P, that is, current price is lower than a `natural` one, the recoveries in business cycles are observed. For the period of time with the negative P, that is, current price is higher than a natural one, economic recessions are observed. The moment of time when P = 0 corresponds to the turning point of a business cycle. In such a way the possibility to predict the turning points of business cycles is demonstrated. 14 refs, 2 figs, 2 tabs

  3. Mean Annual Temperature Drives Microbial Nitrogen Cycling and Fine Root Nutrient Foraging Across a Tropical Montane Wet Forest Elevation Gradient

    Science.gov (United States)

    Pierre, S.; Litton, C. L. M.; Giardina, C. P.; Sparks, J. P.; Groffman, P. M.; Hewson, I.; Fahey, T. J.

    2017-12-01

    Mean annual temperature (MAT) is positively correlated with rates of primary production and carbon (C) turnover in forests globally, but the underlying biotic drivers of these relationships remain poorly resolved. We hypothesized that (1) MAT increases nitrifier abundance and thereby nitrate (NO-) bioavailability in soils and (2) increased NO- bioavailability reduces fine root nitrogen (N) demand. We used an ecologically well-constrained natural elevation gradient (13˚C -18˚C) in a tropical wet motane forest on the Island of Hawaii to study to role of MAT in situ. Our previous work showed that MAT drives increased soil NO- bioavailability in situ (r²=0.79, P=0.003), and indicated that the abundance of ammonia oxidizing archaea is strongly and positively correlated with MAT in situ (r²=0.34, Preduce fine root foraging effort. Further, higher MAT and greater N fertility in soils may reduce the C limitation of AM fungal colonization. We conclude that MAT drives N-rich conditions, which allow for lower N foraging effort, but greater C investment in P acquisition through AM fine root colonization.

  4. Friction induced hunting limit cycles : a comparison between the LuGre and switch friction model

    NARCIS (Netherlands)

    Hensen, R.H.A.; Molengraft, van de M.J.G.; Steinbuch, M.

    2003-01-01

    In this paper, friction induced limit cycles are predicted for a simple motion system consisting of a motor-driven inertia subjected to friction and a PID-controlled regulator task. The two friction models used, i.e., (i) the dynamic LuGre friction model and (ii) the static switch friction model,

  5. On the use of time resolved laser-induced spectrofluorometry in the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Moulin, C.; Decambox, P.; Mauchien, P.; Davin, T.; Pradel, B.

    1991-01-01

    Time Resolved Laser-Induced Spectrofluorometry (TRLIS) has been used for actinides trace analysis and complexation analysis in the nuclear fuel cycle. Results obtained in the different fields such as in geology, in the Purex process, in the environment, in the medical and in waste storage assessment are presented. 4 figs., 6 refs

  6. The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity.

    Science.gov (United States)

    Rauckhorst, Adam J; Gray, Lawrence R; Sheldon, Ryan D; Fu, Xiaorong; Pewa, Alvin D; Feddersen, Charlotte R; Dupuy, Adam J; Gibson-Corley, Katherine N; Cox, James E; Burgess, Shawn C; Taylor, Eric B

    2017-11-01

    Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. The goal of this investigation was to test whether hepatocyte MPC disruption provides sustained protection from hyperglycemia during long-term HFD and the differential effects of hepatocyte MPC disruption on TCA cycle metabolism in NCD versus HFD conditions. We utilized long-term high fat feeding, serial measurements of postabsorptive blood glucose and metabolomic profiling and 13 C-lactate/ 13 C-pyruvate tracing to investigate the contribution of the MPC to hyperglycemia and altered hepatic TCA cycle metabolism during HFD-induced obesity. Hepatocyte MPC disruption resulted in long-term attenuation of hyperglycemia induced by HFD. HFD increased hepatic mitochondrial pyruvate utilization and TCA cycle capacity in an MPC-dependent manner. Furthermore, MPC disruption decreased progression of fibrosis and levels of transcript markers of inflammation. By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  7. Determination of the Optimum Heat Transfer Coefficient and Temperature Rise Analysis for a Lithium-Ion Battery under the Conditions of Harbin City Bus Driving Cycles

    Directory of Open Access Journals (Sweden)

    Xiaogang Wu

    2017-10-01

    Full Text Available This study investigated the heat problems that occur during the operation of power batteries, especially thermal runaway, which usually take place in high temperature environments. The study was conducted on a ternary polymer lithium-ion battery. In addition, a lumped parameter thermal model was established to analyze the thermal behavior of the electric bus battery system under the operation conditions of the driving cycles of the Harbin city electric buses. Moreover, the quantitative relationship between the optimum heat transfer coefficient of the battery and the ambient temperature was investigated. The relationship between the temperature rise (Tr, the number of cycles (c, and the heat transfer coefficient (h under three Harbin bus cycles have been investigated at 30 °C, because it can provide a basis for the design of the battery thermal management system. The results indicated that the heat transfer coefficient that meets the requirements of the battery thermal management system is the cubic power function of the ambient temperature. Therefore, if the ambient temperature is 30 °C, the heat transfer coefficient should be at least 12 W/m2K in the regular bus lines, 22 W/m2K in the bus rapid transit lines, and 32 W/m2K in the suburban lines.

  8. Cracking and induced steel stresses of reinforced and prestressed piles during driving

    NARCIS (Netherlands)

    Zorn, N.F.

    1984-01-01

    The problem of steel stresses during driving of reinforced and prestressed piles in case of concrete failure is analysed in this report using a momentum trap model that includes amplitude and shape of the reflected compressive wave. Special reference is made to the different performance of

  9. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    International Nuclear Information System (INIS)

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun; Zheng, Lemin; Zhou, Boda; Zhang, Wei; Lv, He; Yuan, Yun

    2014-01-01

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21

  10. Dux4 induces cell cycle arrest at G1 phase through upregulation of p21 expression

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Hongliang; Wang, Zhaoxia; Jin, Suqin; Hao, Hongjun [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Zheng, Lemin [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing 100191 (China); Zhou, Boda [The Department of Cardiology, Peking University Third Hospital, Beijing 100191 (China); Zhang, Wei; Lv, He [Department of Neurology, Peking University First Hospital, Beijing 100034 (China); Yuan, Yun, E-mail: yuanyun2002@sohu.com [Department of Neurology, Peking University First Hospital, Beijing 100034 (China)

    2014-03-28

    Highlights: • Dux4 induced TE671 cell proliferation defect and G1 phase arrest. • Dux4 upregulated p21 expression without activating p53. • Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. • Sp1 binding site was required for Dux4-induced p21 promoter activation. - Abstract: It has been implicated that Dux4 plays crucial roles in development of facioscapulohumeral dystrophy. But the underlying myopathic mechanisms and related down-stream events of this retrogene were far from clear. Here, we reported that overexpression of Dux4 in a cell model TE671 reduced cell proliferation rate, and increased G1 phase accumulation. We also determined the impact of Dux4 on p53/p21 signal pathway, which controls the checkpoint in cell cycle progression. Overexpression of Dux4 increased p21 mRNA and protein level, while expression of p53, phospho-p53 remained unchanged. Silencing p21 rescued Dux4 mediated proliferation defect and cell cycle arrest. Furthermore, we demonstrated that enhanced Dux4 expression increased p21 promoter activity and elevated expression of Sp1 transcription factor. Mutation of Sp1 binding site decreased dux4 induced p21 promoter activation. Chromatin immunoprecipitation (ChIP) assays confirmed the Dux4-induced binding of Sp1 to p21 promoter in vivo. These results suggest that Dux4 might induce proliferation inhibition and G1 phase arrest through upregulation of p21.

  11. Role of ACNU-induced cell cycle perturbations in enhancing effect on radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Naoto (Niigata Univ. (Japan). Brain Research Inst.)

    1992-05-01

    The cell cycle perturbations induced by ACNU and their role in enhancing effect on radiotherapy were studied using C[sub 6] rat glioma cells. The cell cycle perturbations were analyzed with flow cytometry from 3 to 72 hours after ACNU treatment. The major effect of ACNU on cell cycle progression was G[sub 2]M accumulation. Alteration of the DNA histograms after exposure to ACNU (10, 25 [mu]g/ml) showed common features; the G[sub 2]M accumulation increased to a maximum at 24 hr, remained by 30 hr, then decreased gradually. From these analyses, the temporal course of accumulation to G[sub 2]M phase of cell cycle in the presence of ACNU (10, 25 [mu]g/ml) was demonstrated. To examine whether the G[sub 2]M accumulation induced by ACNU is responsible for the potentiation of irradiation, the following study was performed. Cells were irradiated (6 Gy) at various time intervals after ACNU treatment (25 [mu]g/ml, 1 hr), and posttreatment survival was assessed by colony forming assay. All survival values obtained from the combination treatment schedules were normalized for the ACNU cell kill and then compared with the survival value obtained after irradiation alone. It appeared that combined treatment had a similar synergistic effect in all combination schedules. From these studies, it was concluded that the G[sub 2]M accumulation induced by ACNU would not be the partial synchronization as the mechanism responsible for the potentiation of irradiation. (author).

  12. Capsaicin induces cell cycle arrest and apoptosis in human KB cancer cells.

    Science.gov (United States)

    Lin, Chia-Han; Lu, Wei-Cheng; Wang, Che-Wei; Chan, Ya-Chi; Chen, Mu-Kuan

    2013-02-25

    Capsaicin, a pungent phytochemical in a variety of red peppers of the genus Capsicum, has shown an anti-proliferative effect on various human cancer cell lines. In contrast, capsaicin has also been considered to promote the growth of cancer cells. Thus, the effects of capsaicin on various cell types need to be explored. The anti-proliferative effects of capsaicin on human KB cancer cells are still unknown. Therefore, we examined the viability, cell cycle progression, and factors associated with apoptosis in KB cells treated with capsaicin. The cell proliferation/viability and cytotoxicity of KB cells exposed to capsaicin were determined by a sulforhodamine B colorimetric assay and trypan blue exclusion. Apoptosis was detected by Hoechst staining and confirmed by western blot analysis of poly-(ADP-ribose) polymerase cleavage. Cell cycle distribution and changes of the mitochondrial membrane potential were analyzed by flow cytometry. Furthermore, the expression of caspase 3, 8 and 9 was evaluated by immunoblotting. We found that treatment of KB cells with capsaicin significantly reduced cell proliferation/viability and induced cell death in a dose-dependent manner compared with that in the untreated control. Cell cycle analysis indicated that exposure of KB cells to capsaicin resulted in cell cycle arrest at G2/M phase. Capsaicin-induced growth inhibition of KB cells appeared to be associated with induction of apoptosis. Moreover, capsaicin induced disruption of the mitochondrial membrane potential as well as activation of caspase 9, 3 and poly-(ADP-ribose) polymerase in KB cells. Our data demonstrate that capsaicin modulates cell cycle progression and induces apoptosis in human KB cancer cells through mitochondrial membrane permeabilization and caspase activation. These observations suggest an anti-cancer activity of capsaicin.

  13. G2 phase arrest of cell cycle induced by ionizing radiation

    International Nuclear Information System (INIS)

    Liu Guangwei; Gong Shouliang

    2002-01-01

    The exposure of mammalian cells to X rays results in the prolongation of the cell cycle, including the delay or the arrest in G 1 , S and G 2 phase. The major function of G 1 arrest may be to eliminate the cells containing DNA damage and only occurs in the cells with wild type p53 function whereas G 2 arrest following ionizing radiation has been shown to be important in protecting the cells from death and occurs in all cells regardless of p53 status. So the study on G 2 phase arrest of the cell cycle induced by ionizing radiation has currently become a focus at radiobiological fields

  14. Analysis of the repeatability of the exhaust pollutants emission research results for cold and hot starts under controlled driving cycle conditions.

    Science.gov (United States)

    Jaworski, Artur; Kuszewski, Hubert; Ustrzycki, Adam; Balawender, Krzysztof; Lejda, Kazimierz; Woś, Paweł

    2018-04-20

    Measurement of car engines exhaust pollutants emissions is very important because of their harmful effects on the environment. This article presents the assessment of repeatability of the passenger car engine exhaust pollutants emission research results obtained in the conditions of a chassis dynamometer. The research was conducted in a climate chamber, enabling the temperature conditions to be determined from - 20 to + 30 °C. The emission of CO, CH 4 , CO 2 , NO X , THC, and NMHC was subjected to the analysis. The aim of the research is to draw attention to the accuracy of the pollutant emission research results in driving cycles, and the comparison of pollutant emission results and their repeatability obtained in successive NEDC cycles under cold and hot start conditions. The results of the analysis show that, in the case of a small number of measurements, the results repeatability analysis is necessary for a proper interpretation of the pollutant emission results on the basis of the mean value. According to the authors' judgment, it is beneficial to determine the coefficient of variation for a more complete assessment of exhaust emission result repeatability obtained from a small number of measurements. This parameter is rarely presented by the authors of papers on exhaust components emission research.

  15. Pollutant emissions from vehicles with regenerating after-treatment systems in regulatory and real-world driving cycles.

    Science.gov (United States)

    Alvarez, Robert; Weilenmann, Martin; Novak, Philippe

    2008-07-15

    Regenerating exhaust after-treatment systems are increasingly employed in passenger cars in order to comply with regulatory emission standards. These systems include pollutant storage units that occasionally have to be regenerated. The regeneration strategy applied, the resultant emission levels and their share of the emission level during normal operation mode are key issues in determining realistic overall emission factors for these cars. In order to investigate these topics, test series with four cars featuring different types of such after-treatment systems were carried out. The emission performance in legislative and real-world cycles was monitored as well as at constant speeds. The extra emissions determined during regeneration stages are presented together with the methodology applied to calculate their impact on overall emissions. It can be concluded that exhaust after-treatment systems with storage units cause substantial overall extra emissions during regeneration mode and can appreciably affect the emission factors of cars equipped with such systems, depending on the frequency of regenerations. Considering that the fleet appearance of vehicles equipped with such after-treatment systems will increase due to the evolution of statutory pollutant emission levels, extra emissions originating from regenerations of pollutant storage units consequently need to be taken into account for fleet emission inventories. Accurately quantifying these extra emissions is achieved by either conducting sufficient repetitions of emission measurements with an individual car or by considerably increasing the size of the sample of cars with comparable after-treatment systems.

  16. Effect of supporting structure stiffness on the drive train assembly of an induced draft cooling tower under seismic effects

    International Nuclear Information System (INIS)

    Raghavan, N.; Ramasubramanian, S.; Khan, K.

    2005-01-01

    In a nuclear power project an induced draft cooling tower, as a safety-related structure and part of the main cooling system, has to perform satisfactorily under designated seismic effects. While the structural elements can be designed by conventional methods to ensure adequate safety, the seismic qualification of the mechanical components poses a challenge. The paper describes a methodology adopted for the seismic qualification of a typical Drive Train Assembly for the axial flow fan of an induced draft cooling tower, to ensure the structural integrity and functional operability of the assembly during Operating Base Earthquake and Safe Shutdown Earthquake conditions. This is achieved by performing a detailed finite element analysis of the rotating equipment assembly consisting of the electric motor, gear box and fan along with the drive shaft between the motor and the gear box. The various components are modeled using beam elements, plate elements and spring elements to idealize the flexible connections and supports. The floor response spectra derived from a dynamic analysis of the overall structure under stipulated seismic acceleration spectra are the main excitation inputs into the system. The results validate the adequacy of gaps for movement and the strengths of the couplings and bolts to withstand the applied loads. The assumed modeling and analysis methodology are seen to be acceptable procedures for seismic qualification of important components of the cooling tower. (authors)

  17. Role of Kupffer Cells in Thioacetamide-Induced Cell Cycle Dysfunction

    Directory of Open Access Journals (Sweden)

    Mirandeli Bautista

    2011-09-01

    Full Text Available It is well known that gadolinium chloride (GD attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. In the present study the effect of GD in reference to cell cycle and postnecrotic liver regeneration induced by thioacetamide (TA in rats was studied. Two months male rats, intraveously pretreated with a single dose of GD (0.1 mmol/Kg, were intraperitoneally injected with TA (6.6 mmol/Kg. Samples of blood and liver were obtained from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the levels of cyclin D and cyclin E as well as protein p27 and Proliferating Cell Nuclear Antigen (PCNA were determined in liver extracts because of their roles in the control of cell cycle check-points. The results showed that GD significantly reduced the extent of necrosis. Noticeable changes were detected in the levels of cyclin D1, cyclin E, p27 and PCNA when compared to those induced by thioacetamide. Thus GD pre-treatment reduced TA-induced liver injury and accelerated the postnecrotic liver regeneration. These results demonstrate that Kupffer cells are involved in TA-induced liver and also in the postnecrotic proliferative liver states.

  18. Dihydromyricetin induces cell cycle arrest and apoptosis in melanoma SK-MEL-28 cells.

    Science.gov (United States)

    Zeng, Guofang; Liu, Jie; Chen, Hege; Liu, Bin; Zhang, Qingyu; Li, Mingyi; Zhu, Runzhi

    2014-06-01

    Dihydromyricetin (DHM) exhibits multiple pharmacological activities; however, the role of DHM in anti-melanoma activities and the underlying molecular mechanisms are unclear. The aim of the present study was to evaluate the effects of DHM on cell proliferation, cell cycle distribution and apoptosis in the human melanoma SK-MEL-28 cell line, and to explore the related mechanisms. The effect of DHM on cell proliferation was investigated by MTT assay, and cell cycle distribution was determined by flow cytometry. TUNEL assay was used to evaluate DHM-mediated apoptosis, and western blotting was applied to examine expression levels of p53, p21, Cdc25A, Cdc2, P-Cdc2, Bax, IKK-α, NF-κB p65, p38 and P-p38 proteins. The results revealed that DHM suppressed cell proliferation of SK-MEL-28 cells in a concentration- and time-dependent manner, and caused cell cycle arrest at the G1/S phase. DHM increased the production of p53 and p21 proteins and downregulated the production of Cdc25A, Cdc2 and P-Cdc2 proteins, which induced cell cycle arrest. Additionally, DHM significantly induced the apoptosis of SK-MEL-28 cells, and enhanced the expression levels of Bax proteins and decreased the protein levels of IKK-α, NF-κB (p65) and P-p38. The results suggest that DHM may be a novel and effective candidate agent to inhibit the growth of melanoma.

  19. Time-resolved laser-induced fluorescence in the nuclear fuel cycle

    International Nuclear Information System (INIS)

    Moulin, C.; Decambox, P.; Mauchien, P.; Petit, A.

    1995-01-01

    Time-Resolved Laser-Induced Fluorescence (TRLIF) is a very sensitive and selective method that has been used for actinides and lanthanides analysis in the nuclear fuel cycle. This technique has been used in different fields such as in geology, in the Purex process, in the environment, in the medical and in waste storage assessment. Spectroscopic data, limits of detection and results obtained in previously quoted fields are presented. (author)

  20. Thermomechanical cycling and two-way memory effect induced in Cu-Zn-Al

    International Nuclear Information System (INIS)

    Pons, J.

    1999-01-01

    The two-way shape memory effect (TWME) has been induced by thermomechanical cycling in Cu-Zn-Al alloys using a dedicated hydraulic mechanical testing soft machine with complete computer control of force, elongation and temperature. The results concerning single crystals (composition Cu-16.9 wt.% Zn-7.7 wt.% Al, nominal M s of 273 K) and polycrystals (Cu-15.8 wt.% Zn-8.3 wt.% Al, nominal M s of 230 K, mean grain size of 1 mm) are reported for two training protocols (sequence of one thermomechanical cycle of education followed by one stress free thermal cycle to check the TWME or twenty consecutive thermomechanical cycles followed by one or two checking thermal cycles). The capacity of the trained specimen for producing work under an antagonist compressive stress is also studied and the behaviour of the deformation of the specimen under such a condition at different temperatures is analysed in terms of a competition between the contributions of the different variants: trained variants with an intrinsic deformation in the direction of the tensile stress of the training process, trained variants with an intrinsic deformation which is not well orientated with respect to this direction (in the polycrystal) and new variants with an intrinsic deformation in the direction of the compressive stress which can replace the educated variants. (orig.)

  1. Molecular signature of cell cycle exit induced in human T lymphoblasts by IL-2 withdrawal

    Directory of Open Access Journals (Sweden)

    Pfeifer Aleksandra

    2009-06-01

    Full Text Available Abstract Background The molecular mechanisms of cell cycle exit are poorly understood. Studies on lymphocytes at cell cycle exit after growth factor deprivation have predominantly focused on the initiation of apoptosis. We aimed to study gene expression profile of primary and immortalised IL-2-dependent human T cells forced to exit the cell cycle by growth factor withdrawal, before apoptosis could be evidenced. Results By the Affymetrix microarrays HG-U133 2.0 Plus, 53 genes were distinguished as differentially expressed before and soon after IL-2 deprivation. Among those, PIM1, BCL2, IL-8, HBEGF, DUSP6, OSM, CISH, SOCS2, SOCS3, LIF and IL13 were down-regulated and RPS24, SQSTM1, TMEM1, LRRC8D, ECOP, YY1AP1, C1orf63, ASAH1, SLC25A46 and MIA3 were up-regulated. Genes linked to transcription, cell cycle, cell growth, proliferation and differentiation, cell adhesion, and immune functions were found to be overrepresented within the set of the differentially expressed genes. Conclusion Cell cycle exit of the growth factor-deprived T lymphocytes is characterised by a signature of differentially expressed genes. A coordinate repression of a set of genes known to be induced during T cell activation is observed. However, growth arrest following exit from the cell cycle is actively controlled by several up-regulated genes that enforce the non-dividing state. The identification of genes involved in cell cycle exit and quiescence provides new hints for further studies on the molecular mechanisms regulating the non-dividing state of a cell, the mechanisms closely related to cancer development and to many biological processes.

  2. Increased respiratory neural drive and work of breathing in exercise-induced laryngeal obstruction

    DEFF Research Database (Denmark)

    Walsted, Emil Schwarz; Faisal, Azmy; Jolley, Caroline J

    2017-01-01

    Rationale: Exercise induced laryngeal obstruction (EILO), a phenomenon in which the larynx closes inappropriately during physical activity, is a prevalent cause of exertional dyspnea in young individuals. The physiological ventilatory impact of EILO and its relationship to dyspnea are poorly...

  3. Middle infrared radiation induces G2/M cell cycle arrest in A549 lung cancer cells.

    Science.gov (United States)

    Chang, Hsin-Yi; Shih, Meng-Her; Huang, Hsuan-Cheng; Tsai, Shang-Ru; Juan, Hsueh-Fen; Lee, Si-Chen

    2013-01-01

    There were studies investigating the effects of broadband infrared radiation (IR) on cancer cell, while the influences of middle-infrared radiation (MIR) are still unknown. In this study, a MIR emitter with emission wavelength band in the 3-5 µm region was developed to irradiate A549 lung adenocarcinoma cells. It was found that MIR exposure inhibited cell proliferation and induced morphological changes by altering the cellular distribution of cytoskeletal components. Using quantitative PCR, we found that MIR promoted the expression levels of ATM (ataxia telangiectasia mutated), ATR (ataxia-telangiectasia and Rad3-related and Rad3-related), TP53 (tumor protein p53), p21 (CDKN1A, cyclin-dependent kinase inhibitor 1A) and GADD45 (growth arrest and DNA-damage inducible), but decreased the expression levels of cyclin B coding genes, CCNB1 and CCNB2, as well as CDK1 (Cyclin-dependent kinase 1). The reduction of protein expression levels of CDC25C, cyclin B1 and the phosphorylation of CDK1 at Thr-161 altogether suggest G(2)/M arrest occurred in A549 cells by MIR. DNA repair foci formation of DNA double-strand breaks (DSB) marker γ-H2AX and sensor 53BP1 was induced by MIR treatment, it implies the MIR induced G(2)/M cell cycle arrest resulted from DSB. This study illustrates a potential role for the use of MIR in lung cancer therapy by initiating DSB and blocking cell cycle progression.

  4. Topography induced spatial variations in diurnal cycles of assimilation and latent heat of Mediterranean forest

    Science.gov (United States)

    van der Tol, C.; Dolman, A. J.; Waterloo, M. J.; Raspor, K.

    2007-02-01

    The aim of this study is to explain topography induced spatial variations in the diurnal cycles of assimilation and latent heat of Mediterranean forest. Spatial variations of the fluxes are caused by variations in weather conditions and in vegetation characteristics. Weather conditions reflect short-term effects of climate, whereas vegetation characteristics, through adaptation and acclimation, long-term effects of climate. In this study measurements of plant physiology and weather conditions are used to explain observed differences in the fluxes. A model is used to study which part of the differences in the fluxes is caused by weather conditions and which part by vegetation characteristics. Data were collected at four experimental sub-Mediterranean deciduous forest plots in a heterogeneous terrain with contrasting aspect, soil water availability, humidity and temperature. We used a sun-shade model to scale fluxes from leaf to canopy, and calculated the canopy energy balance. Parameter values were derived from measurements of light interception, leaf chamber photosynthesis, leaf nitrogen content and 13C isotope discrimination in leaf material. Leaf nitrogen content is a measure of photosynthetic capacity, and 13C isotope discrimination of water use efficiency. For validation, sap-flux based measurements of transpiration were used. The model predicted diurnal cycles of transpiration and stomatal conductance, both their magnitudes and differences in afternoon stomatal closure between slopes of different aspect within the confidence interval of the validation data. Weather conditions mainly responsible for the shape of the diurnal cycles, and vegetation parameters for the magnitude of the fluxes. Although the data do not allow for a quantification of the two effects, the differences in vegetation parameters and weather among the plots and the sensitivity of the fluxes to them suggest that the diurnal cycles were more strongly affected by spatial variations in

  5. Topography induced spatial variations in diurnal cycles of assimilation and latent heat of Mediterranean forest

    Directory of Open Access Journals (Sweden)

    C. van der Tol

    2007-01-01

    Full Text Available The aim of this study is to explain topography induced spatial variations in the diurnal cycles of assimilation and latent heat of Mediterranean forest. Spatial variations of the fluxes are caused by variations in weather conditions and in vegetation characteristics. Weather conditions reflect short-term effects of climate, whereas vegetation characteristics, through adaptation and acclimation, long-term effects of climate. In this study measurements of plant physiology and weather conditions are used to explain observed differences in the fluxes. A model is used to study which part of the differences in the fluxes is caused by weather conditions and which part by vegetation characteristics. Data were collected at four experimental sub-Mediterranean deciduous forest plots in a heterogeneous terrain with contrasting aspect, soil water availability, humidity and temperature. We used a sun-shade model to scale fluxes from leaf to canopy, and calculated the canopy energy balance. Parameter values were derived from measurements of light interception, leaf chamber photosynthesis, leaf nitrogen content and 13C isotope discrimination in leaf material. Leaf nitrogen content is a measure of photosynthetic capacity, and 13C isotope discrimination of water use efficiency. For validation, sap-flux based measurements of transpiration were used. The model predicted diurnal cycles of transpiration and stomatal conductance, both their magnitudes and differences in afternoon stomatal closure between slopes of different aspect within the confidence interval of the validation data. Weather conditions mainly responsible for the shape of the diurnal cycles, and vegetation parameters for the magnitude of the fluxes. Although the data do not allow for a quantification of the two effects, the differences in vegetation parameters and weather among the plots and the sensitivity of the fluxes to them suggest that the diurnal cycles were more strongly affected by spatial

  6. Gain with and without population inversion via vacuum-induced coherence in a V-type atom without external coherent driving

    International Nuclear Information System (INIS)

    Xu Weihua; Wu Jinhui; Gao Jinyue

    2006-01-01

    In a three-level V-type atomic system without any external coherent driving, owing to the coherence that results from the vacuum of the radiation field, both the probe gain with and without population inversion can be achieved with very weak incoherent pumping. The gain is achieved in the absence of any external coherent driving field, so it is different from the gain without inversion in ordinary laser-driven schemes where a coherent driving field is necessary to create the coherence. The gain is also different from the conventional lasing gain because the population inversion is achieved via vacuum-induced coherence, which is dependent on the atomic coherence

  7. Aag-initiated base excision repair drives alkylation-induced retinal degeneration in mice.

    Science.gov (United States)

    Meira, Lisiane B; Moroski-Erkul, Catherine A; Green, Stephanie L; Calvo, Jennifer A; Bronson, Roderick T; Shah, Dharini; Samson, Leona D

    2009-01-20

    Vision loss affects >3 million Americans and many more people worldwide. Although predisposing genes have been identified their link to known environmental factors is unclear. In wild-type animals DNA alkylating agents induce photoreceptor apoptosis and severe retinal degeneration. Alkylation-induced retinal degeneration is totally suppressed in the absence of the DNA repair protein alkyladenine DNA glycosylase (Aag) in both differentiating and postmitotic retinas. Moreover, transgenic expression of Aag activity restores the alkylation sensitivity of photoreceptors in Aag null animals. Aag heterozygotes display an intermediate level of retinal degeneration, demonstrating haploinsufficiency and underscoring that Aag expression confers a dominant retinal degeneration phenotype.

  8. Springs-neaps cycles in daily total seabed light: Daylength-induced changes

    Science.gov (United States)

    Roberts, E. M.; Bowers, D. G.; Davies, A. J.

    2014-04-01

    In shallow, tidal seas, daily total seabed light is determined largely by the interaction of the solar elevation cycle, the tidal cycle in water depth, and any temporal variability in turbidity. Since tidal range, times of low water, and often turbidity vary in regular ways over the springs-neaps cycle, daily total seabed light exhibits cycles of the same periodicity. Corresponding cycles are likely to be induced in the daily total primary production of benthic algae and plants, particularly those light-limited specimens occupying the lower reaches of a sub-tidal population. Consequently, this effect is an important control on the growth patterns, depth distribution and survival of, for example, macroalgal forests and seagrass meadows. Seasonal changes in daylength exert an important additional control on these cycles, as they alter the fraction of the tidal and turbidity cycles occurring within daylight hours. Bowers et al. (1997) modelled this phenomenon numerically and predicted that for a site with low water at about midday and midnight at neaps tides, 6 am and 6 pm at springs, daily total seabed light peaks at neaps in winter, but the ‘sense' of the cycle ‘switches' so that it peaks at springs in summer - the longer daylength permits the morning and evening low water springs to contribute substantially to the daily total. Observations for such a site in North Wales (UK), presented in this paper, show that no such ‘switch' occurs, and neaps tides host the largest daily totals throughout the year. The predicted ‘switch' is not observed because turbidity increases generally at spring tides, and specifically at low water springs, both of which were not accounted for in the model. Observations at a second site in Brittany (France), diametrically opposite in terms of the times of low water at neaps and at springs, indicate a peak at springs throughout the year. Analytical tools are developed to calculate the percentage of daily total sea surface irradiance

  9. Cell cycle progression, but not genotoxic activity, mainly contributes to citrinin-induced renal carcinogenesis

    International Nuclear Information System (INIS)

    Kuroda, Ken; Ishii, Yuji; Takasu, Shinji; Kijima, Aki; Matsushita, Kohei; Watanabe, Maiko; Takahashi, Haruo; Sugita-Konishi, Yoshiko; Sakai, Hiroki; Yanai, Tokuma; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

    2013-01-01

    Citrinin (CTN) is a food-contaminating mycotoxin that efficiently induces renal tumors in rats. However, the modes of carcinogenic action are still unknown, preventing assessment of the risks of CTN in humans. In the present study, the proliferative effects of CTN and its causal factors were investigated in the kidneys of gpt delta rats. In addition, three in vivo genotoxicity assays (reporter gene mutation using gpt delta rats and comet and micronucleus assays using F344 rats) were performed to clarify whether CTN was genotoxic in vivo. CTN was administrated at 20 and 40 mg/kg/day, the higher dose being the maximal tolerated dose and a nearly carcinogenic dose. In the kidney cortex of gpt delta rats, significant increases in the labeling indices of proliferating cell nuclear antigen (PCNA)-positive cells were observed at all doses of CTN. Increases in the mRNA expression levels of Ccna2, Ccnb1, Ccne1, and its transcription factor E2f1 were also detected, suggesting induction of cell cycle progression at all tested doses of CTN. However, histopathological changes were found only in rats treated with the higher dose of CTN, which was consistent with increases in the mRNA expression levels of mitogenic factors associated with tissue damage/regeneration, such as Hgf and Lcn2, at the same dose. Thus, the proliferative effects of CTN may result not only from compensatory reactions, but also from direct mitogenic action. Western blot analysis showed that ERK phosphorylation was increased at all doses, implying that cell cycle progression may be mediated by activation of the ERK pathway. On the other hand, in vivo genotoxicity analyses were negative, implying that CTN did not have the potential for inducing DNA damage, gene mutations, or chromosomal aberrations. The overall data clearly demonstrated the molecular events underlying CTN-induced cell cycle progression, which could be helpful to understand CTN-induced renal carcinogenesis

  10. Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.

    Science.gov (United States)

    Kazak, Lawrence; Chouchani, Edward T; Lu, Gina Z; Jedrychowski, Mark P; Bare, Curtis J; Mina, Amir I; Kumari, Manju; Zhang, Song; Vuckovic, Ivan; Laznik-Bogoslavski, Dina; Dzeja, Petras; Banks, Alexander S; Rosen, Evan D; Spiegelman, Bruce M

    2017-10-03

    Diet-induced thermogenesis is an important homeostatic mechanism that limits weight gain in response to caloric excess and contributes to the relative stability of body weight in most individuals. We previously demonstrated that creatine enhances energy expenditure through stimulation of mitochondrial ATP turnover, but the physiological role and importance of creatine energetics in adipose tissue have not been explored. Here, we have inactivated the first and rate-limiting enzyme of creatine biosynthesis, glycine amidinotransferase (GATM), selectively in fat (Adipo-Gatm KO). Adipo-Gatm KO mice are prone to diet-induced obesity due to the suppression of elevated energy expenditure that occurs in response to high-calorie feeding. This is paralleled by a blunted capacity for β3-adrenergic activation of metabolic rate, which is rescued by dietary creatine supplementation. These results provide strong in vivo genetic support for a role of GATM and creatine metabolism in energy expenditure, diet-induced thermogenesis, and defense against diet-induced obesity. Published by Elsevier Inc.

  11. Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng-Yuan Wang

    2010-02-01

    Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

  12. Counter flow induced draft cooling tower option for supercritical carbon dioxide Brayton cycle

    Energy Technology Data Exchange (ETDEWEB)

    Pidaparti, Sandeep R., E-mail: sandeep.pidaparti@gmail.com [Georgia Institute of Technology, George W. Woodruff School of Mechanical Engineering, Atlanta, GA 30332 (United States); Moisseytsev, Anton; Sienicki, James J. [Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); Ranjan, Devesh, E-mail: devesh.ranjan@me.gatech.edu [Georgia Institute of Technology, George W. Woodruff School of Mechanical Engineering, Atlanta, GA 30332 (United States)

    2015-12-15

    Highlights: • A code was developed to investigate the various aspects of using cooling tower for S-CO{sub 2} Brayton cycles. • Cooling tower option to reject heat is quantitatively compared to the direct water cooling and dry air cooling options. • Optimum water conditions resulting in minimal plant capital cost per unit power consumption are calculated. - Abstract: A simplified qualitative analysis was performed to investigate the possibility of using counter flow induced draft cooling tower option to reject heat from the supercritical carbon dioxide Brayton cycle for advanced fast reactor (AFR)-100 and advanced burner reactor (ABR)-1000 plants. A code was developed to estimate the tower dimensions, power and water consumption, and to perform economic analysis. The code developed was verified against a vendor provided quotation and is used to understand the effect of ambient air and water conditions on the design of cooling tower. The calculations indicated that there exists optimum water conditions for given ambient air conditions which will result in minimum power consumption, thereby increasing the cycle efficiency. A cost-based optimization technique is used to estimate the optimum water conditions which will improve the overall plant economics. A comparison of different cooling options for the S-CO{sub 2} cycle indicated that the cooling tower option is a much more practical and economical option compared to the dry air cooling or direct water cooling options.

  13. Driving p53 Response to Bax Activation Greatly Enhances Sensitivity to Taxol by Inducing Massive Apoptosis

    Directory of Open Access Journals (Sweden)

    Paola De Feudis

    2000-05-01

    Full Text Available The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3 were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

  14. Snowmelt induced hydrologic perturbations drive dynamic microbiological and geochemical behaviors across a shallow riparian aquifer

    Directory of Open Access Journals (Sweden)

    Robert eDanczak

    2016-05-01

    Full Text Available Shallow riparian aquifers represent hotspots of biogeochemical activity in the arid western US. While these environments provide extensive ecosystem services, little is known of how natural environmental perturbations influence subsurface microbial communities and associated biogeochemical processes. Over a six-month period we tracked the annual snowmelt-driven incursion of groundwater into the vadose zone of an aquifer adjacent to the Colorado River, leading to increased dissolved oxygen (DO concentrations in the normally suboxic saturated zone. Strong biogeochemical heterogeneity was measured across the site, with abiotic reactions between DO and sulfide minerals driving rapid DO consumption and mobilization of redox active species in reduced aquifer regions. Conversely, extensive DO increases were detected in less reduced sediments. 16S rRNA gene surveys tracked microbial community composition within the aquifer, revealing strong correlations between increases in putative oxygen-utilizing chemolithoautotrophs and heterotrophs and rising DO concentrations. The gradual return to suboxic aquifer conditions favored increasing abundances of 16S rRNA sequences matching members of the Microgenomates (OP11 and Parcubacteria (OD1 that have been strongly implicated in fermentative processes. Microbial community stability measurements indicated that deeper aquifer locations were relatively less affected by geochemical perturbations, while communities in shallower locations exhibited the greatest change. Reactive transport modeling of the geochemical and microbiological results supported field observations, suggesting that a predictive framework can be applied to develop a greater understanding of such environments.

  15. Snowmelt induced hydrologic perturbations drive dynamic microbiological and geochemical behaviors across a shallow riparian aquifer

    Science.gov (United States)

    Danczak, Robert; Yabusaki, Steven; Williams, Kenneth; Fang, Yilin; Hobson, Chad; Wilkins, Michael

    2016-05-01

    Shallow riparian aquifers represent hotspots of biogeochemical activity in the arid western US. While these environments provide extensive ecosystem services, little is known of how natural environmental perturbations influence subsurface microbial communities and associated biogeochemical processes. Over a six-month period we tracked the annual snowmelt-driven incursion of groundwater into the vadose zone of an aquifer adjacent to the Colorado River, leading to increased dissolved oxygen (DO) concentrations in the normally suboxic saturated zone. Strong biogeochemical heterogeneity was measured across the site, with abiotic reactions between DO and sulfide minerals driving rapid DO consumption and mobilization of redox active species in reduced aquifer regions. Conversely, extensive DO increases were detected in less reduced sediments. 16S rRNA gene surveys tracked microbial community composition within the aquifer, revealing strong correlations between increases in putative oxygen-utilizing chemolithoautotrophs and heterotrophs and rising DO concentrations. The gradual return to suboxic aquifer conditions favored increasing abundances of 16S rRNA sequences matching members of the Microgenomates (OP11) and Parcubacteria (OD1) that have been strongly implicated in fermentative processes. Microbial community stability measurements indicated that deeper aquifer locations were relatively less affected by geochemical perturbations, while communities in shallower locations exhibited the greatest change. Reactive transport modeling of the geochemical and microbiological results supported field observations, suggesting that a predictive framework can be applied to develop a greater understanding of such environments.

  16. α-Mangostin Induces Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma Cell

    Directory of Open Access Journals (Sweden)

    Hyun-Ho Kwak

    2016-01-01

    Full Text Available Mangosteen has long been used as a traditional medicine and is known to have antibacterial, antioxidant, and anticancer effects. Although the effects of α-mangostin, a natural compound extracted from the pericarp of mangosteen, have been investigated in many studies, there is limited data on the effects of the compound in human oral squamous cell carcinoma (OSCC. In this study, α-mangostin was assessed as a potential anticancer agent against human OSCC cells. α-Mangostin inhibited cell proliferation and induced cell death in OSCC cells in a dose- and time-dependent manner with little to no effect on normal human PDLF cells. α-Mangostin treatment clearly showed apoptotic evidences such as nuclear fragmentation and accumulation of annexin V and PI-positive cells on OSCC cells. α-Mangostin treatment also caused the collapse of mitochondrial membrane potential and the translocation of cytochrome c from the mitochondria into the cytosol. The expressions of the mitochondria-related proteins were activated by α-mangostin. Treatment with α-mangostin also induced G1 phase arrest and downregulated cell cycle-related proteins (CDK/cyclin. Hence, α-mangostin specifically induces cell death and inhibits proliferation in OSCC cells via the intrinsic apoptosis pathway and cell cycle arrest at the G1 phase, suggesting that α-mangostin may be an effective agent for the treatment of OSCC.

  17. Interplay between cell cycle and autophagy induced by boswellic acid analog

    Science.gov (United States)

    Pathania, Anup S.; Guru, Santosh K.; Kumar, Suresh; Kumar, Ashok; Ahmad, Masroor; Bhushan, Shashi; Sharma, Parduman R.; Mahajan, Priya; Shah, Bhahwal A.; Sharma, Simmi; Nargotra, Amit; Vishwakarma, Ram; Korkaya, Hasan; Malik, Fayaz

    2016-01-01

    In this study, we investigated the role of autophagy induced by boswellic acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins. It was further observed that BA145 induced autophagy by targeting mTOR kinase (IC50 1 μM), leading to reduced expression of p-mTOR, p-p70S6K (T389), p-4EBP (T37/46) and p-S6 (S240/244). Notably, inhibition of mTOR signalling by BA145 was followed by attendant activation of AKT and its membrane translocation. Inhibition of Akt through pharmacological inhibitors or siRNAs enhanced BA145 mediated autophagy, G2/M arrest and reduced expression of G2/M regulators. Further studies revealed that BA145 arbitrated inhibition of mTOR led to the activation of Akt through IGFR/PI3k/Akt feedback loop. Intervention in IGFR/PI3k/Akt loop further depreciated Akt phosphorylation and its membrane translocation that culminates in augmented autophagy with concomitant G2/M arrest and cell death. PMID:27680387

  18. High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.

    Directory of Open Access Journals (Sweden)

    Hee Jin Shim

    Full Text Available Ionizing radiation (IR treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis.

  19. Urea cycle pathway targeted therapeutic action of naringin against ammonium chloride induced hyperammonemic rats.

    Science.gov (United States)

    Ramakrishnan, Arumugam; Vijayakumar, Natesan

    2017-10-01

    Ammonia is a well-known neurotoxin that causes liver disease and urea cycle disorder. Excessive ammonia content in the blood leads to hyperammonemic condition and affects both excitatory and inhibitory neurotransmission including brain edema and coma. Naringin, a plant bioflavonoid present in various citrus fruits and mainly extracted from the grape fruit. This study was designed to assess the protective effect of naringin on ammonium chloride (NH 4 Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitoneal injections (i.p) of NH 4 Cl (100mg/kg body weight (b.w.)) thrice a week for 8 consecutive weeks. Hyperammonemic rats were treated with naringin (80mg/kg b.w.) via oral gavage. Naringin administration significantly augmented the level of blood ammonia and plasma urea. Naringin also upregulate the expression of urea cycle enzymes such as carbamoyl phosphate synthase I (CPS I) and ornithine transcarbamylase (OTC), arininosuccinate synthase (ASS), argininosuccinate lyase (ASL) and arginase I (ARG) and metabotropic glutamate receptors (mGluRs) such as mGluRs I and mGluRs V and down regulate the expression of inflammatory markers like tumor necrosis factor (TNF-α), nuclear factor kappa B (NF-kB), Interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS). In addition, to this, the protective effect of naringin was also revealed through the immunohistochemical changes in tissues. Thus our present study result suggest that naringin modulates the expression of proteins involved in urea cycle pathway and suppresses the expression of inflammatory markers and acts as a potential agent to treat condition in rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. DNA Damage and Cell Cycle Arrest Induced by Protoporphyrin IX in Sarcoma 180 Cells

    Directory of Open Access Journals (Sweden)

    Qing Li

    2013-09-01

    Full Text Available Background: Porphyrin derivatives have been widely used in photodynamic therapy as effective sensitizers. Protoporphyrin IX (PpIX, a well-known hematoporphyrin derivative component, shows great potential to enhance light induced tumor cell damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms underlying those direct effects are incompletely understood. This study thus investigated the putative mechanisms underlying the anti-tumor effects of PpIX on sarcoma 180 (S180 cells. Methods: S180 cells were treated with different concentrations of PpIX. Following the treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl-2, 5-diphenyltetrazoliumbromide (MTT assay; Disruption of mitochondrial membrane potential was measured by flow cytometry; The trans-location of apoptosis inducer factor (AIF from mitochondria to nucleus was visualized by confocal laser scanning microscopy; DNA damage was detected by single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA content with flow cytometry; Cell cycle associated proteins were detected by western blotting. Results: PpIX (≥ 1 µg/ml significantly inhibited proliferation and reduced viability of S180 cells in a dose-dependent manner. PpIX rapidly and significantly triggered mitochondrial membrane depolarization, AIF (apoptosis inducer factor translocation from mitochondria to nucleus and DNA damage, effects partially relieved by the specific inhibitor of MPTP (mitochondrial permeability transition pore. Furthermore, S phase arrest and upregulation of the related proteins of P53 and P21 were observed following 12 and 24 h PpIX exposure. Conclusion: PpIX could inhibit tumor cell proliferation by induction of DNA damage and cell cycle arrest in the S phase.

  1. NDE of Possible Service-Induced PWSCC in Control Rod Drive Mechanism Housings Removed from Service

    International Nuclear Information System (INIS)

    Cumblidge, Stephen E.; Doctor, Steven R.; Schuster, George J.; Harris, Robert V.; Crawford, Susan L.

    2006-01-01

    Studies being conducted at the Pacific Northwest National Laboratory (PNNL) in Richland, Washington are being performed to assess the effectiveness of nondestructive examination (NDE) techniques on removed-from-service control rod drive mechanism (CRDM) nozzles and the associated J-groove attachment welds. This work is being performed to provide information to the United States Nuclear Regulatory Commission (US NRC) on the effectiveness of NDE techniques such as ultrasonic testing (UT), eddy current testing (ET), and visual testing (VT) as related to the in-service inspection of CRDM nozzles and J-groove weldments, and to enhance the knowledge base of primary water stress corrosion cracking (PWSCC) through destructive characterization of the CRDM assemblies. The basic NDE measurements follow standard industry techniques for conducting in-service inspections of CRDM nozzles and the crown of the J-groove welds and buttering. In addition, laboratory-based NDE methods were employed to conduct inspections of the CRDM assemblies, with particular emphasis on the J-groove weld and buttering. This paper describes the NDE measurements that were employed on the two CRDMs to detect and characterize the indications and the analysis of these indications. The two CRDM assemblies were removed from service from the North Anna 2 vessel head, including the CRDM nozzle, the J-groove weld, buttering, and a portion of the ferritic head material. One nozzle contains suspected PWSCC, based on in-service inspection data; the second contains evidence suggesting through-wall leakage, although this was unconfirmed. A destructive test plan is being developed to directly characterize the indications found using nondestructive testing. The results of this destructive testing will be included when the destructive testing is completed.

  2. Perturbing an electromagnetically induced transparency in a Λ system using a low-frequency driving field. II. Four-level system

    International Nuclear Information System (INIS)

    Wilson, E. A.; Manson, N. B.; Wei, C.

    2005-01-01

    The effect a perturbing field has on an electromagnetically induced transparency within a three-level Λ system is presented. The perturbing field is applied resonant between one of the lower levels of the Λ system and a fourth level. The electromagnetically induced transparency feature is split and this is measured experimentally for both single and bichromatic driving fields. In the single-driving-field case a density matrix treatment is shown to be in reasonable agreement with experiment and in both single and bichromatic cases the structure in the spectrum can be explained using a dressed-state analysis

  3. The adverse effects of high fat induced obesity on female reproductive cycle and hormones

    Science.gov (United States)

    Donthireddy, Laxminarasimha Reddy

    The prevalence of obesity, an established risk and progression factor for abnormal reproductive cycle and tissue damage in female mice. It leads to earlier puberty, menarche in young females and infertility. There are extensive range of consequences of obesity which includes type-2 diabetes, cardiovascular disease and insulin resistance. Obesity is the interaction between dietary intake, genes, life style and environment. The interplay of hormones estrogen, insulin, and leptin is well known on energy homeostasis and reproduction. The aim of this study is to determine the effect of high fat induced obesity on reproductive cycles and its hormonal abnormalities on mice model. Two week, 3 month and 8 month long normal (WT) and very high fat diet (VHFD) diet course is followed. When mice are fed with very high fat diet, there is a drastic increase in weight within the first week later. There was a significant (p<0.001) increase in leptin levels in 6 month VHFD treated animals. 2 week, 3 month and 6 month time interval pap smear test results showed number of cells, length of estrous cycle and phases of the estrous cycle changes with VHFD mice(n=30) compared to normal diet mice(n=10). These results also indicate that the changes in the reproductive cycles in VHFD treated female mice could be due to the changes in hormones. Histo-pathological analyses of kidney, ovary, liver, pancreas, heart and lungs showed remarkable changes in some tissue on exposure to very high fat. Highly deposited fat packets observed surrounding the hepatocytes and nerve cells.

  4. Radiation-induced apoptosis and cell cycle checkpoints in human colorectal tumour cell lines

    International Nuclear Information System (INIS)

    Playle, L.C.

    2001-03-01

    The p53 tumour suppressor gene is mutated in 75% of colorectal carcinomas and is critical for DNA damage-induced G1 cell cycle arrest. Data presented in this thesis demonstrate that after treatment with Ionizing Radiation (IR), colorectal tumour cell lines with mutant p53 are unable to arrest at G1 and undergo cell cycle arrest at G2. The staurosporine derivative, UCN-01, was shown to abrogate the IR-induced G2 checkpoint in colorectal tumour cell lines. Furthermore, in some cell lines, abrogation of the G2 checkpoint was associated with radiosensitisation. Data presented in this study demonstrate that 2 out of 5 cell lines with mutant p53 were sensitised to IR by UCN-01. In order to determine whether radiosensitisation correlated with lack of functional p53, transfected derivatives of an adenoma-derived cell line were studied, in which endogenous wild type p53 was disrupted by expression of a dominant negative p53 mutant protein (and with a vector control). In both these cell lines UCN-01 abrogated the G2 arrest however this was not associated with radiosensitisation, indicating that radiosensitisation is a cell type-specific phenomenon. Although 2 colorectal carcinoma cell lines, with mutant p53, were sensitised to IR by UCN-01, the mechanisms of p53-independent IR-induced apoptosis in the colon are essentially unknown. The mitogen-activated protein kinase (MAPK) pathways (that is the JNK, p38 and ERK pathways) have been implicated in apoptosis in a range of cell systems and in IR-induced apoptosis in some cell types. Data presented in this study show that, although the MAPKs can be activated by the known activator anisomycin, there is no evidence of a role for MAPKs in IR-induced apoptosis in colorectal tumour cell lines, regardless of p53 status. In summary, some colorectal tumour cell lines with mutant p53 can be sensitised to IR-induced cell death by G2 checkpoint abrogation and this may be an important treatment strategy, however mechanisms of IR-induced p53

  5. Vorinostat-induced autophagy switches from a death-promoting to a cytoprotective signal to drive acquired resistance.

    Science.gov (United States)

    Dupéré-Richer, D; Kinal, M; Ménasché, V; Nielsen, T H; Del Rincon, S; Pettersson, F; Miller, W H

    2013-02-07

    Histone deacetylase inhibitors (HDACi) have shown promising activity against hematological malignancies in clinical trials and have led to the approval of vorinostat for the treatment of cutaneous T-cell lymphoma. However, de novo or acquired resistance to HDACi therapy is inevitable, and their molecular mechanisms are still unclear. To gain insight into HDACi resistance, we developed vorinostat-resistant clones from the hematological cell lines U937 and SUDHL6. Although cross-resistant to some but not all HDACi, the resistant cell lines exhibit dramatically increased sensitivity toward chloroquine, an inhibitor of autophagy. Consistent with this, resistant cells growing in vorinostat show increased autophagy. Inhibition of autophagy in vorinostat-resistant U937 cells by knockdown of Beclin-1 or Lamp-2 (lysosome-associated membrane protein 2) restores sensitivity to vorinostat. Interestingly, autophagy is also activated in parental U937 cells by de novo treatment with vorinostat. However, in contrast to the resistant cells, inhibition of autophagy decreases sensitivity to vorinostat. These results indicate that autophagy can switch from a proapoptotic signal to a prosurvival function driving acquired resistance. Moreover, inducers of autophagy (such as mammalian target of rapamycin inhibitors) synergize with vorinostat to induce cell death in parental cells, whereas the resistant cells remain insensitive. These data highlight the complexity of the design of combination strategies using modulators of autophagy and HDACi for the treatment of hematological malignancies.

  6. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death.

    Science.gov (United States)

    Armstrong, Jane L; Hill, David S; McKee, Christopher S; Hernandez-Tiedra, Sonia; Lorente, Mar; Lopez-Valero, Israel; Eleni Anagnostou, Maria; Babatunde, Fiyinfoluwa; Corazzari, Marco; Redfern, Christopher P F; Velasco, Guillermo; Lovat, Penny E

    2015-06-01

    Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.

  7. Electron Drift Speed And Current-Induced Drive Torques On A Domain Wall

    Science.gov (United States)

    Berger, Luc

    2009-03-01

    It has become fashionable to describe [1] current-induced torques on a DW in terms of an electron drift speed u = - P*j*muB/e*M where muB is the Bohr magneton and M the saturation magnetization. While appropriate for adiabatic torques, this quantity u is misleading and not the best choice in the case of non-adiabatic torques. For example, it leads [2] to beta not equal to alpha, where beta represents the intensity of the non-adiabatic torque, and alpha is the damping parameter. By writing equations of motion for conduction- electron spins in a moving frame where the electron gas is at rest, we find [3] a direct relation between damping and non- adiabatic torques. The correct electron drift speed turns out to be the speed of the frame, and is v = P*j/(n*q) where n and q are the carrier density and charge. It is related to the ordinary Hall constant R0 by v P*R0*j. After substituting v for u in the expression of the non-adiabatic torque, we find that beta = alpha holds now. Because v is larger than u in Permalloy, it can explain better the large current-induced DW speeds found [4] experimentally. In materials where R0> 0 and the carriers are dominantly hole-like, v and u have opposite signs, leading to different predictions for the sense of DW motion. We discuss examples of such materials. 1. G. Tatara and H. Kohno, Phys. Rev. Lett. 92, 086601 (2004). 2. H. Kohno et al., J. Phys. Soc. Japan, 75, 113706 (2006). 3. L. Berger, Phys. Rev. B 75, 174401 (2007). 4. M. Hayashi et al., Phys. Rev. Lett. 98, 037204 (2007).

  8. UV-induced changes in cell cycle and gene expression within rabbit lens epithelial cells

    International Nuclear Information System (INIS)

    Sidjanin, D.; Grdina, D.; Woloschak, G.E.

    1996-01-01

    Damage to lens epithelial cells is a probable initiation process in cataract formation mediated by UV radiation. In these experiments, we investigated the effects of exposure to 254 nm radiation on cell cycle progression in the rabbit lens epithelial cell line N/N1003A. The RNA was harvested at various times following exposure to UV (254 nm) radiation and analyzed by dot-blot and northern blot hybridizations. These results revealed that during the first 6 h following exposure of the cells to UV, there was, associated with decreasing dose, a decrease in accumulation of transcripts specific for histones H3 and H4 and an increase in the mRNA encoding protein kinase C and β- and γ-actin. Using flow cytometry, we detected an accumulation of cells in G1/S phase of the cell cycle 1 h following exposure to 254 nm radiation. The observed changes in gene expression, especially the decreased accumulation of histone transcripts reported here, may play a role in UV-induced inhibition of cell cycle progression. (Author)

  9. Conditional inactivation of PDCD2 induces p53 activation and cell cycle arrest

    Directory of Open Access Journals (Sweden)

    Celine J. Granier

    2014-08-01

    Full Text Available PDCD2 (programmed cell death domain 2 is a highly conserved, zinc finger MYND domain-containing protein essential for normal development in the fly, zebrafish and mouse. The molecular functions and cellular activities of PDCD2 remain unclear. In order to better understand the functions of PDCD2 in mammalian development, we have examined PDCD2 activity in mouse blastocyst embryos, as well as in mouse embryonic stem cells (ESCs and embryonic fibroblasts (MEFs. We have studied mice bearing a targeted PDCD2 locus functioning as a null allele through a splicing gene trap, or as a conditional knockout, by deletion of exon2 containing the MYND domain. Tamoxifen-induced knockout of PDCD2 in MEFs, as well as in ESCs, leads to defects in progression from the G1 to the S phase of cell cycle, associated with increased levels of p53 protein and p53 target genes. G1 prolongation in ESCs was not associated with induction of differentiation. Loss of entry into S phase of the cell cycle and marked induction of nuclear p53 were also observed in PDCD2 knockout blastocysts. These results demonstrate a unique role for PDCD2 in regulating the cell cycle and p53 activation during early embryonic development of the mouse.

  10. Curcumin Induces Autophagy, Apoptosis, and Cell Cycle Arrest in Human Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yaping Zhu

    2017-01-01

    Full Text Available Objective. Curcumin is an active extract from turmeric. The aim of this study was to identify the underlying mechanism of curcumin on PCa cells and the role of autophagy in this process. Methods. The inhibitory effect of curcumin on the growth of PANC1 and BxPC3 cell lines was detected by CCK-8 assay. Cell cycle distribution and apoptosis were tested by flow cytometry. Autophagosomes were tested by cell immunofluorescence assay. The protein expression was detected by Western blot. The correlation between LC3II/Bax and cell viability was analyzed. Results. Curcumin inhibited the cell proliferation in a dose- and time-dependent manner. Curcumin could induce cell cycle arrest at G2/M phase and apoptosis of PCa cells. The autophagosomes were detected in the dosing groups. Protein expression of Bax and LC3II was upregulated, while Bcl2 was downregulated in the high dosing groups of curcumin. There was a significant negative correlation between LC3II/Bax and cell viability. Conclusions. Autophagy could be triggered by curcumin in the treatment of PCa. Apoptosis and cell cycle arrest also participated in this process. These findings imply that curcumin is a multitargeted agent for PCa cells. In addition, autophagic cell death may predominate in the high concentration groups of curcumin.

  11. Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

    Science.gov (United States)

    Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

  12. Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis.

    Science.gov (United States)

    Zhang, Huan-Tian; Yang, Jie; Liang, Gui-Hong; Gao, Xue-Juan; Sang, Yuan; Gui, Tao; Liang, Zu-Jian; Tam, Man-Seng; Zha, Zhen-Gang

    2017-12-01

    Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of β-catenin were not altered upon the treatment of Andro, suggesting that β-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells.

    Science.gov (United States)

    Vieira Torquato, Heron F; Ribeiro-Filho, Antonio C; Buri, Marcus V; Araújo Júnior, Roberto T; Pimenta, Renata; de Oliveira, José Salvador R; Filho, Valdir C; Macho, Antonio; Paredes-Gamero, Edgar J; de Oliveira Martins, Domingos T

    2017-04-01

    Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. In the present study, we evaluate the antitumor effects of canthin-6-one in human myeloid leukemia lineages. Kasumi-1 lineage was used as a model for acute myeloid leukemia. Cells were treated with canthin-6-one and cell death, cell cycle and differentiation were evaluated in both total cells (Lin + ) and leukemia stem cell population (CD34 + CD38 - Lin -/low ). Among the human lineages tested, Kasumi-1 was the most sensitive to canthin-6-one. Canthin-6-one induced cell death with apoptotic (caspase activation, decrease of mitochondrial potential) and necrotic (lysosomal permeabilization, double labeling of annexin V/propidium iodide) characteristics. Moreover, canthin-6-one induced cell cycle arrest at G 0 /G 1 (7μM) and G 2 (45μM) evidenced by DNA content, BrdU incorporation and cyclin B1/histone 3 quantification. Canthin-6-one also promoted differentiation of Kasumi-1, evidenced by an increase in the expression of myeloid markers (CD11b and CD15) and the transcription factor PU.1. Furthermore, a reduction of the leukemic stem cell population and clonogenic capability of stem cells were observed. These results show that canthin-6-one can affect Kasumi-1 cells by promoting cell death, cell cycle arrest and cell differentiation depending on concentration used. Canthin-6-one presents an interesting cytotoxic activity against leukemic cells and represents a promising scaffold for the development of molecules for anti-leukemic applications, especially by its anti-leukemic stem cell activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Serum Proteases Potentiate BMP-Induced Cell Cycle Re-entry of Dedifferentiating Muscle Cells during Newt Limb Regeneration

    NARCIS (Netherlands)

    Wagner, Ines; Wang, Heng; Weissert, Philipp M.; Straube, Werner L.; Shevchenko, Anna; Gentzel, Marc; Brito, Goncalo; Tazaki, Akira; Oliveira, Catarina; Sugiura, Takuji; Shevchenko, Andrej; Simon, Andras; Drechsel, David N.; Tanaka, Elly M.

    2017-01-01

    Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell

  15. Epigenetic regulation leading to induced pluripotency drives cancer development in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Ohnishi, Kotaro [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Department of Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194 (Japan); Semi, Katsunori [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507 (Japan); Yamada, Yasuhiro, E-mail: y-yamada@cira.kyoto-u.ac.jp [Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507 (Japan); Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507 (Japan)

    2014-12-05

    Highlights: • Epigenetic regulation of failed reprogramming-associated cancer cells is discussed. • Similarity between pediatric cancer and reprogramming-associated cancer is discussed. • Concept for epigenetic cancer is discussed. - Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by the transient expression of reprogramming factors. During the reprogramming process, somatic cells acquire the ability to undergo unlimited proliferation, which is also an important characteristic of cancer cells, while their underlying DNA sequence remains unchanged. Based on the characteristics shared between pluripotent stem cells and cancer cells, the potential involvement of the factors leading to reprogramming toward pluripotency in cancer development has been discussed. Recent in vivo reprogramming studies provided some clues to understanding the role of reprogramming-related epigenetic regulation in cancer development. It was shown that premature termination of the in vivo reprogramming result in the development of tumors that resemble pediatric cancers. Given that epigenetic modifications play a central role during reprogramming, failed reprogramming-associated cancer development may have provided a proof of concept for epigenetics-driven cancer development in vivo.

  16. Epigenetic regulation leading to induced pluripotency drives cancer development in vivo

    International Nuclear Information System (INIS)

    Ohnishi, Kotaro; Semi, Katsunori; Yamada, Yasuhiro

    2014-01-01

    Highlights: • Epigenetic regulation of failed reprogramming-associated cancer cells is discussed. • Similarity between pediatric cancer and reprogramming-associated cancer is discussed. • Concept for epigenetic cancer is discussed. - Abstract: Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by the transient expression of reprogramming factors. During the reprogramming process, somatic cells acquire the ability to undergo unlimited proliferation, which is also an important characteristic of cancer cells, while their underlying DNA sequence remains unchanged. Based on the characteristics shared between pluripotent stem cells and cancer cells, the potential involvement of the factors leading to reprogramming toward pluripotency in cancer development has been discussed. Recent in vivo reprogramming studies provided some clues to understanding the role of reprogramming-related epigenetic regulation in cancer development. It was shown that premature termination of the in vivo reprogramming result in the development of tumors that resemble pediatric cancers. Given that epigenetic modifications play a central role during reprogramming, failed reprogramming-associated cancer development may have provided a proof of concept for epigenetics-driven cancer development in vivo

  17. Cell cycle delays induced by heavy ion irradiation of synchronous mammalian cells

    International Nuclear Information System (INIS)

    Scholz, M.; Kraft-Weyrather, W.; Ritter, S.; Kraft, G.

    1994-01-01

    Cell cycle delays in V79 Chinese hamster cells induced by heavy ion exposure have been investigated using flow cytometry. Synchronous cell populations in G 1 -, S- and late-S/G 2 M-phase were used. Cells were irradiated with particles from Z = 10 (neon) up to Z = 96 (uranium) in the energy range from 2.4 to 17.4 MeV/u and the LET range from 415 to 16225 keV/μm at the UNILAC at GSI, Darmstadt. For comparison, experiments with 250 kV X-rays were performed. For light particles like neon, cell cycle perturbations comparable to those after X-ray irradiation were found, and with increasing LET an increasing delay per particle traversal was observed. For the highest LET-values, extended delays in G 1 -, S- and G 2 M-phase were detected immediately after irradiation. A large fraction of the cells remained in S-phase or G 2 M-phase up to 48 h or longer after irradiation. No significant cell age dependence of cycle delays was detected for the very high LET values. In addition to cell cycle delays, two effects related to the DNA-content as determined by flow cytometry were found after irradiation with very high LET particles, which were attributed to cell fusion and to drastic morphological changes of the cells. Estimations based on the dose deposited by a single particle hit in the cell nucleus and the actual number of hits show, that the basic trend of the experimental results can be explained by the stochastic properties of particle radiation. (orig.)

  18. Early postnatal treatment with clomipramine induces female sexual behavior and estrous cycle impairment.

    Science.gov (United States)

    Molina-Jiménez, Tania; Limón-Morales, Ofelia; Bonilla-Jaime, Herlinda

    2018-03-01

    Administration of clomipramine (CMI), a tricyclic antidepressant, in early stages of development in rats, is considered an animal model for the study of depression. This pharmacological manipulation has induced behavioral and physiological alterations, i.e., less pleasure-seeking behaviors, despair, hyperactivity, cognitive dysfunction, alterations in neurotransmitter systems and in HPA axis. These abnormalities in adult male rats are similar to the symptoms observed in major depressive disorders. One of the main pleasure-seeking behaviors affected in male rats treated with CMI is sexual behavior. However, to date, no effects of early postnatal CMI treatment have been reported on female reproductive cyclicity and sexual behavior. Therefore, we explored CMI administration in early life (8-21 PN) on the estrous cycle and sexual behavior of adult female rats. Compared to the rats in the early postnatal saline treatment (CTRL group), the CMI rats had fewer estrous cycles, fewer days in the estrous stage, and longer cycles during a 20-day period of vaginal cytology analysis. On the behavioral test, the CMI rats displayed fewer proceptive behaviors (hopping, darting) and had lower lordosis quotients. Also, they usually failed to display lordosis and only rarely manifested marginal or normal lordosis. In contrast, the CTRL rats tended to display normal lordosis. These results suggest that early postnatal CMI treatment caused long-term disruptions of the estrous cycle and female sexual behavior, perhaps by alteration in the hypothalamic-pituitary-gonadal (HPG) axes and in neuronal circuits involved in the regulation of the performance and motivational of sexual behavior as the noradrenergic and serotonergic systems. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Toxicity of drinking water disinfection byproducts: cell cycle alterations induced by the monohaloacetonitriles.

    Science.gov (United States)

    Komaki, Yukako; Mariñas, Benito J; Plewa, Michael J

    2014-10-07

    Haloacetonitriles (HANs) are a chemical class of drinking water disinfection byproducts (DBPs) that form from reactions between disinfectants and nitrogen-containing precursors, the latter more prevalent in water sources impacted by algae bloom and municipal wastewater effluent discharge. HANs, previously demonstrated to be genotoxic, were investigated for their effects on the mammalian cell cycle. Treating Chinese hamster ovary (CHO) cells with monoHANs followed by the release from the chemical treatment resulted in the accumulation of abnormally high DNA content in cells over time (hyperploid). The potency for the cell cycle alteration followed the order: iodoacetonitrile (IAN) > bromoacetonitrile (BAN) ≫ chloroacetonitrile (CAN). Exposure to 6 μM IAN, 12 μM BAN and 900 μM CAN after 26 h post-treatment incubation resulted in DNA repair; however, subsequent cell cycle alteration effects were observed. Cell proliferation of HAN-treated cells was suppressed for as long as 43 to 52 h. Enlarged cell size was observed after 52 h post-treatment incubation without the induction of cytotoxicity. The HAN-mediated cell cycle alteration was mitosis- and proliferation-dependent, which suggests that HAN treatment induced mitosis override, and that HAN-treated cells proceeded into S phase and directly into the next cell cycle. Cells with multiples genomes would result in aneuploidy (state of abnormal chromosome number and DNA content) at the next mitosis since extra centrosomes could compromise the assembly of bipolar spindles. There is accumulating evidence of a transient tetraploid state proceeding to aneuploidy in cancer progression. Biological self-defense systems to ensure genomic stability and to eliminate tetraploid cells exist in eukaryotic cells. A key tumor suppressor gene, p53, is oftentimes mutated in various types of human cancer. It is possible that HAN disruption of the normal cell cycle and the generation of aberrant cells with an abnormal number of

  20. Galiellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cells.

    Science.gov (United States)

    García, Víctor; Lara-Chica, Maribel; Cantarero, Irene; Sterner, Olov; Calzado, Marco A; Muñoz, Eduardo

    2016-01-26

    Galiellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer.

  1. Chemogenetic activation of the lateral hypothalamus reverses early life stress-induced deficits in motivational drive.

    Science.gov (United States)

    Campbell, Erin J; Mitchell, Caitlin S; Adams, Cameron D; Yeoh, Jiann Wei; Hodgson, Deborah M; Graham, Brett A; Dayas, Christopher V

    2017-10-01

    Altered motivated behaviour is a cardinal feature of several neuropsychiatric conditions including mood disorders. One well-characterized antecedent to the development of mood disorders is exposure to early life stress (ELS). A key brain substrate controlling motivated behaviour is the lateral hypothalamus (LH). Here, we examined the effect of ELS on LH activation and the motivation to self-administer sucrose. We tested whether chemogenetic activation of LH circuits could modify sucrose responding in ELS rats and examined the impact on LH cell populations. Male rat pups were maternally separated for 0 or 3 h on postnatal days 2-14. During adolescence, rats received bilateral injections of hM3D(Gq), the excitatory designer receptor exclusively activated by designer drugs, into LH. In adulthood, rats were trained to self-administer sucrose and tested under a progressive ratio schedule to determine their motivation for reward following injection with either vehicle or 5 mg/kg clozapine-N-oxide. Brains were processed for Fos-protein immunohistochemistry. ELS significantly suppressed lever responding for sucrose, indicating a long-lasting impact of ELS on motivation circuits. hM3D(Gq) activation of LH increased responding, normalizing deficits in ELS rats, and increased Fos-positive orexin and MCH cell numbers within LH. Our findings indicate that despite being susceptible to environmental stressors, LH circuits retain the capacity to overcome ELS-induced deficits in motivated behaviour. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.

    Science.gov (United States)

    Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A

    2014-12-01

    Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and

  3. Nek1 silencing slows down DNA repair and blocks DNA damage-induced cell cycle arrest.

    Science.gov (United States)

    Pelegrini, Alessandra Luíza; Moura, Dinara Jaqueline; Brenner, Bethânia Luise; Ledur, Pitia Flores; Maques, Gabriela Porto; Henriques, João Antônio Pegas; Saffi, Jenifer; Lenz, Guido

    2010-09-01

    Never in mitosis A (NIMA)-related kinases (Nek) are evolutionarily conserved proteins structurally related to the Aspergillus nidulans mitotic regulator NIMA. Nek1 is one of the 11 isoforms of the Neks identified in mammals. Different lines of evidence suggest the participation of Nek1 in response to DNA damage, which is also supported by the interaction of this kinase with proteins involved in DNA repair pathways and cell cycle regulation. In this report, we show that cells with Nek1 knockdown (KD) through stable RNA interference present a delay in DNA repair when treated with methyl-methanesulfonate (MMS), hydrogen peroxide (H(2)O(2)) and cisplatin (CPT). In particular, interstrand cross links induced by CPT take much longer to be resolved in Nek1 KD cells when compared to wild-type (WT) cells. In KD cells, phosphorylation of Chk1 in response to CPT was strongly reduced. While WT cells accumulate in G(2)/M after DNA damage with MMS and H(2)O(2), Nek1 KD cells do not arrest, suggesting that G(2)/M arrest induced by the DNA damage requires Nek1. Surprisingly, CPT-treated Nek1 KD cells arrest with a 4N DNA content similar to WT cells. This deregulation in cell cycle control in Nek1 KD cells leads to an increased sensitivity to genotoxic agents when compared to WT cells. These results suggest that Nek1 is involved in the beginning of the cellular response to genotoxic stress and plays an important role in preventing cell death induced by DNA damage.

  4. Inducible nucleotide excision repair (NER) of UV-induced cyclobutane pyrimidine dimers in the cell cycle of the budding yeast Saccharomyces cerevisiae: evidence that inducible NER is confined to the G1 phase of the mitotic cell cycle

    International Nuclear Information System (INIS)

    Scott, A.D.; Waters, R.

    1997-01-01

    We previously reported on an inducible component of nucleotide excision repair in Saccharomyces cerevisiae that is controlled by the RAD16 gene. Here we describe a study of this event at the MAT alpha and HML alpha mating-type loci and on the transcribed (TS) and nontranscribed (NTS) strands of the RAD16 gene. Events were examined at various stages of the mitotic cycle in cells synchronised by centrifugal elutriation. Repair of cyclobutane pyrimidine dimers (CPDs) following a single UV dose does not vary significantly in different stages of the mitotic cell cycle. CPDs are removed more rapidly from the transcriptionally active MAT alpha locus than from the silent HML alpha locus, and the TS of RAD16 is repaired faster than the NTS in all stages of the cycle following a single UV irradiation. Enhanced excision of CPDs at MAT alpha and HML alpha can be induced only in the G1 and early S stages of the cell cycle. Here prior irradiation of cells with 25 J/m 2 enhances the removal of CPDs following a second UV dose of 70 J/m 2 . The level of enhancement of repair does not differ significantly between MAT alpha and HML alpha in G1. Enhanced removal of CPDs is absent when cells receive the inducing dose in late S or G2/M. Repair of CPDs in both strands of RAD16 is similarly enhanced only if cells receive the initial irradiation in G1 and early S. The level of enhanced removal of CPDs is not significantly different in the TS and NTS of RAD16 either in asynchronous cells or in cells preirradiated in G1 and early S. It has been shown by others that UV-induced expression of RAD16 remains at high levels if cells are held in G1 by treatment with alpha factor. Therefore the increase in RAD16 transcript levels in G1 may be responsible for the ability to enhance NER solely in this stage of the cell cycle

  5. Drive Stands

    Data.gov (United States)

    Federal Laboratory Consortium — The Electrical Systems Laboratory (ESL)houses numerous electrically driven drive stands. A drive stand consists of an electric motor driving a gearbox and a mounting...

  6. Periodic driving control of Raman-induced spin-orbit coupling in Bose-Einstein condensates: The heating mechanisms

    Science.gov (United States)

    Gomez Llorente, J. M.; Plata, J.

    2016-06-01

    We focus on a technique recently implemented for controlling the magnitude of synthetic spin-orbit coupling (SOC) in ultracold atoms in the Raman-coupling scenario. This technique uses a periodic modulation of the Raman-coupling amplitude to tune the SOC. Specifically, it has been shown that the effect of a high-frequency sinusoidal modulation of the Raman-laser intensity can be incorporated into the undriven Hamiltonian via effective parameters, whose adiabatic variation can therefore be used to tune the SOC. Here, we characterize the heating mechanisms that can be relevant to this method. We identify the main mechanism responsible for the heating observed in the experiments as basically rooted in driving-induced transfer of population to excited states. Characteristics of that process determined by the harmonic trapping, the decay of the excited states, and the technique used for preparing the system are discussed. Additional heating, rooted in departures from adiabaticity in the variation of the effective parameters, is also described. Our analytical study provides some clues that may be useful in the design of strategies for curbing the effects of heating on the efficiency of the control methods.

  7. Directed motion of spheres induced by unbiased driving forces in viscous fluids beyond the Stokes' law regime

    Science.gov (United States)

    Casado-Pascual, Jesús

    2018-03-01

    The emergence of directed motion is investigated in a system consisting of a sphere immersed in a viscous fluid and subjected to time-periodic forces of zero average. The directed motion arises from the combined action of a nonlinear drag force and the applied driving forces, in the absence of any periodic substrate potential. Necessary conditions for the existence of such directed motion are obtained and an analytical expression for the average terminal velocity is derived within the adiabatic approximation. Special attention is paid to the case of two mutually perpendicular forces with sinusoidal time dependence, one with twice the period of the other. It is shown that, although neither of these two forces induces directed motion when acting separately, when added together, the resultant force generates directed motion along the direction of the force with the shortest period. The dependence of the average terminal velocity on the system parameters is analyzed numerically and compared with that obtained using the adiabatic approximation. Among other results, it is found that, for appropriate parameter values, the direction of the average terminal velocity can be reversed by varying the forcing strength. Furthermore, certain aspects of the observed phenomenology are explained by means of symmetry arguments.

  8. Nucleoporins redistribute inside the nucleus after cell cycle arrest induced by histone deacetylases inhibition.

    Science.gov (United States)

    Pérez-Garrastachu, Miguel; Arluzea, Jon; Andrade, Ricardo; Díez-Torre, Alejandro; Urtizberea, Marta; Silió, Margarita; Aréchaga, Juan

    2017-09-03

    Nucleoporins are the main components of the nuclear-pore complex (NPC) and were initially considered as mere structural elements embedded in the nuclear envelope, being responsible for nucleocytoplasmic transport. Nevertheless, several recent scientific reports have revealed that some nucleoporins participate in nuclear processes such as transcription, replication, DNA repair and chromosome segregation. Thus, the interaction of NPCs with chromatin could modulate the distribution of chromosome territories relying on the epigenetic state of DNA. In particular, the nuclear basket proteins Tpr and Nup153, and the FG-nucleoporin Nup98 seem to play key roles in all these novel functions. In this work, histone deacetylase inhibitors (HDACi) were used to induce a hyperacetylated state of chromatin and the behavior of the mentioned nucleoporins was studied. Our results show that, after HDACi treatment, Tpr, Nup153 and Nup98 are translocated from the nuclear pore toward the interior of the cell nucleus, accumulating as intranuclear nucleoporin clusters. These transitory structures are highly dynamic, and are mainly present in the population of cells arrested at the G0/G1 phase of the cell cycle. Our results indicate that the redistribution of these nucleoporins from the nuclear envelope to the nuclear interior may be implicated in the early events of cell cycle initialization, particularly during the G1 phase transition.

  9. Resveratrol induces cell cycle arrest and apoptosis in human eosinophils from asthmatic individuals.

    Science.gov (United States)

    Hu, Xin; Wang, Jing; Xia, Yu; Simayi, Mihereguli; Ikramullah, Syed; He, Yuanbing; Cui, Shihong; Li, Shuang; Wushouer, Qimanguli

    2016-12-01

    Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit‑8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double‑staining. The protein expression levels of p53, p21, cyclin‑dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B‑cell lymphoma (Bcl)‑2 and Bcl‑2‑associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration‑ and time‑dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G1/S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl‑2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.

  10. Competition in size-structured populations: mechanisms inducing cohort formation and population cycles.

    Science.gov (United States)

    de Roos, André M; Persson, Lennart

    2003-02-01

    In this paper we investigate the consequences of size-dependent competition among the individuals of a consumer population by analyzing the dynamic properties of a physiologically structured population model. Only 2 size-classes of individuals are distinguished: juveniles and adults. Juveniles and adults both feed on one and the same resource and hence interact by means of exploitative competition. Juvenile individuals allocate all assimilated energy into development and mature on reaching a fixed developmental threshold. The combination of this fixed threshold and the resource-dependent developmental rate, implies that the juvenile delay between birth and the onset of reproduction may vary in time. Adult individuals allocate all assimilated energy to reproduction. Mortality of both juveniles and adults is assumed to be inversely proportional to the amount of energy assimilated. In this setting we study how the dynamics of the population are influenced by the relative foraging capabilities of juveniles and adults. In line with results that we previously obtained in size-structured consumer-resource models with pulsed reproduction, population cycles primarily occur when either juveniles or adults have a distinct competitive advantage. When adults have a larger per capita feeding rate and are hence competitively superior to juveniles, population oscillations occur that are primarily induced by the fact that the duration of the juvenile period changes with changing food conditions. These cycles do not occur when the juvenile delay is a fixed parameter. When juveniles are competitively superior, two different types of population fluctuations can occur: (1) rapid, low-amplitude fluctuations having a period of half the juvenile delay and (2) slow, large-amplitude fluctuations characterized by a period, which is roughly equal to the juvenile delay. The analysis of simplified versions of the structured model indicates that these two types of oscillations also occur if

  11. Deoxyelephantopin from Elephantopus scaber L. induces cell-cycle arrest and apoptosis in the human nasopharyngeal cancer CNE cells

    International Nuclear Information System (INIS)

    Su, Miaoxian; Chung, Hau Yin; Li, Yaolan

    2011-01-01

    Highlights: → Deoxyelephantopin (ESD) inhibited cell proliferation in the human nasopharyngeal cancer CNE cells. → ESD induced cell cycle arrest in S and G2/M phases via modulation of cell cycle regulatory proteins. → ESD triggered apoptosis by dysfunction of mitochondria and induction of both intrinsic and extrinsic apoptotic signaling pathways. → ESD also triggered Akt, ERK, and JNK signaling pathways. -- Abstract: Deoxyelephantopin (ESD), a naturally occurring sesquiterpene lactone present in the Chinese medicinal herb, Elephantopus scaber L. exerted anticancer effects on various cultured cancer cells. However, the cellular mechanisms by which it controls the development of the cancer cells are unavailable, particularly the human nasopharyngeal cancer CNE cells. In this study, we found that ESD inhibited the CNE cell proliferation. Cell cycle arrest in S and G2/M phases was also found. Western blotting analysis showed that modulation of cell cycle regulatory proteins was responsible for the ESD-induced cell cycle arrest. Besides, ESD also triggered apoptosis in CNE cells. Dysfunction in mitochondria was found to be associated with the ESD-induced apoptosis as evidenced by the loss of mitochondrial membrane potential (ΔΨm), the translocation of cytochrome c, and the regulation of Bcl-2 family proteins. Despite the Western blotting analysis showed that both intrinsic and extrinsic apoptotic pathways (cleavage of caspases-3, -7, -8, -9, and -10) were triggered in the ESD-induced apoptosis, additional analysis also showed that the induction of apoptosis could be achieved by the caspase-independent manner. Besides, Akt, ERK and JNK pathways were found to involve in ESD-induced cell death. Overall, our findings provided the first evidence that ESD induced cell cycle arrest, and apoptosis in CNE cells. ESD could be a potential chemotherapeutic agent in the treatment of nasopharyngeal cancer (NPC).

  12. Deoxyelephantopin from Elephantopus scaber L. induces cell-cycle arrest and apoptosis in the human nasopharyngeal cancer CNE cells

    Energy Technology Data Exchange (ETDEWEB)

    Su, Miaoxian [Biology Programme (Formally Biology Dept.), School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR (China); Chung, Hau Yin, E-mail: anthonychung@cuhk.edu.hk [Biology Programme (Formally Biology Dept.), School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR (China); Food and Nutritional Sciences Programme, School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR (China); Li, Yaolan [Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou (China); Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drug Research, Guangzhou (China)

    2011-07-29

    Highlights: {yields} Deoxyelephantopin (ESD) inhibited cell proliferation in the human nasopharyngeal cancer CNE cells. {yields} ESD induced cell cycle arrest in S and G2/M phases via modulation of cell cycle regulatory proteins. {yields} ESD triggered apoptosis by dysfunction of mitochondria and induction of both intrinsic and extrinsic apoptotic signaling pathways. {yields} ESD also triggered Akt, ERK, and JNK signaling pathways. -- Abstract: Deoxyelephantopin (ESD), a naturally occurring sesquiterpene lactone present in the Chinese medicinal herb, Elephantopus scaber L. exerted anticancer effects on various cultured cancer cells. However, the cellular mechanisms by which it controls the development of the cancer cells are unavailable, particularly the human nasopharyngeal cancer CNE cells. In this study, we found that ESD inhibited the CNE cell proliferation. Cell cycle arrest in S and G2/M phases was also found. Western blotting analysis showed that modulation of cell cycle regulatory proteins was responsible for the ESD-induced cell cycle arrest. Besides, ESD also triggered apoptosis in CNE cells. Dysfunction in mitochondria was found to be associated with the ESD-induced apoptosis as evidenced by the loss of mitochondrial membrane potential ({Delta}{Psi}m), the translocation of cytochrome c, and the regulation of Bcl-2 family proteins. Despite the Western blotting analysis showed that both intrinsic and extrinsic apoptotic pathways (cleavage of caspases-3, -7, -8, -9, and -10) were triggered in the ESD-induced apoptosis, additional analysis also showed that the induction of apoptosis could be achieved by the caspase-independent manner. Besides, Akt, ERK and JNK pathways were found to involve in ESD-induced cell death. Overall, our findings provided the first evidence that ESD induced cell cycle arrest, and apoptosis in CNE cells. ESD could be a potential chemotherapeutic agent in the treatment of nasopharyngeal cancer (NPC).

  13. Dementia & Driving

    Science.gov (United States)

    ... have to give up driving. Many people associate driving with self-reliance and freedom; the loss of driving privileges ... familiar roads and avoid long distances. Avoid heavy traffic and heavily traveled roads. Avoid driving at night and in bad weather. Reduce the ...

  14. Francisella tularensis elicits IL-10 via a PGE₂-inducible factor, to drive macrophage MARCH1 expression and class II down-regulation.

    Directory of Open Access Journals (Sweden)

    Danielle Hunt

    Full Text Available Francisella tularensis is a bacterial pathogen that uses host-derived PGE₂ to subvert the host's adaptive immune responses in multiple ways. Francisella-induced PGE₂ acts directly on CD4 T cells to blunt production of IFN-γ. Francisella-induced PGE₂ can also elicit production of a >10 kDa soluble host factor termed FTMØSN (F. tularensismacrophage supernatant, which acts on IFN-γ pre-activated MØ to down-regulate MHC class II expression via a ubiquitin-dependent mechanism, blocking antigen presentation to CD4 T cells. Here, we report that FTMØSN-induced down-regulation of MØ class II is the result of the induction of MARCH1, and that MØ expressing MARCH1 "resistant" class II molecules are resistant to FTMØSN-induced class II down-regulation. Since PGE₂ can induce IL-10 production and IL-10 is the only reported cytokine able to induce MARCH1 expression in monocytes and dendritic cells, these findings suggested that IL-10 is the active factor in FTMØSN. However, use of IL-10 knockout MØ established that IL-10 is not the active factor in FTMØSN, but rather that Francisella-elicited PGE₂ drives production of a >10 kDa host factor distinct from IL-10. This factor then drives MØ IL-10 production to induce MARCH1 expression and the resultant class II down-regulation. Since many human pathogens such as Salmonella typhi, Mycobacterium tuberculosis and Legionella pneumophila also induce production of host PGE₂, these results suggest that a yet-to-be-identified PGE₂-inducible host factor capable of inducing IL-10 is central to the immune evasion mechanisms of multiple important human pathogens.

  15. Biostimulation induces syntrophic interactions that impact C, S and N cycling in a sediment microbial community

    Energy Technology Data Exchange (ETDEWEB)

    Handley, KM [University of California, Berkeley; Verberkmoes, Nathan C [ORNL; Steefel, Carl I [Lawrence Berkeley National Laboratory (LBNL); Sharon, I [University of California, Berkeley; Williams, Ken [Lawrence Berkeley National Laboratory (LBNL); Miller, CS [University of California, Berkeley; Frischkorn, Kyle C [University of California, Berkeley; Chourey, Karuna [ORNL; Thomas, Brian [University of California, Berkeley; Shah, Manesh B [ORNL; Long, Phil [Pacific Northwest National Laboratory (PNNL); Hettich, Robert {Bob} L [ORNL; Banfield, Jillian F. [University of California, Berkeley

    2013-01-01

    Stimulation of subsurface microorganisms to induce reductive immobilization of metals is a promising approach for bioremediation, yet the overall microbial community response is typically poorly understood. Here we used community proteogenomics to test the hypothesis that excess input of acetate activates syntrophic interactions among autotrophs and heterotrophs. A flow-through sediment column was incubated in a groundwater well of an acetate-amended aquifer. Genomic sequences from the community recovered during microbial sulfate reduction were used to econstruct, de novo, near-complete genomes for Desulfobacter (Deltaproteobacteria) and relatives of Sulfurovum and Sulfurimonas (Epsilonproteobacteria), and Bacteroidetes. Partial genomes were obtained for Clostridiales (Firmicutes) and Desulfuromonadales-like Deltaproteobacteria. The majority of proteins identified by mass spectrometry corresponded to Desulfobacter-like species, and demonstrate the role of this organism in sulfate reduction (Dsr and APS), nitrogen-fixation (Nif) and acetate oxidation to CO2 during amendment. Results suggest less abundant Desulfuromonadales and Bacteroidetes also actively contributed to CO2 production via the TCA cycle. Proteomic data indicate that sulfide was partially re-oxidized by Epsilonproteobacteria through nitrate-dependent sulfide oxidation (using Nap, Nir, Nos, SQR and Sox), with CO2 fixed using the reverse TCA cycle. Modeling shows that this reaction was thermodynamically possible, and kinetically favorable relative to acetate-dependent denitrification. We conclude that high-levels of carbon amendment aimed to stimulate anaerobic heterotrophy led to carbon fixation in co-dependent chemoautotrophs. These results have implications for understanding complex ecosystem behavior, and show that high levels of organic carbon supplementation can expand the range of microbial functionalities accessible for ecosystem manipulation.

  16. Crack propagation under thermal cycling loading inducing a thermal gradient in the specimen thickness

    International Nuclear Information System (INIS)

    Le, H.N.

    2009-05-01

    This study aims to figure out the crack growth phenomenon by thermal fatigue induced by thermal gradient through thickness of specimen. Firstly, an experimental facility has been developed: a rectangular parallelepiped specimen is subjected to thermal cycling between 350 C and 100 C; the specimen is freed to expand and contract. Two semi-circular notches (0,1 mm depth and 4 mm length) have been machined on the surface of the specimen. A series of interrupted tests has been carried out to characterize and quantify the crack growth in depth and surface of the pre-existing crack. Next, a three-dimensional crack growth simulation has been implemented in ABAQUS. Automation using Python was used to simulate the propagation of a crack under thermal cycling, with re-meshing at crack front after each calculation step. No assumption has been taken on the crack front during the crack propagation. A comparison with test results showed very good agreement on the evolution of crack front shape and on the kinetics of propagation on the edge and the heart of pre-existing crack. An analytical approach was also developed based on the calculation of stress intensity factors (SIC). A two-dimensional approach was first introduced enabling us to better understand the influence of various thermal and geometric parameters. Finally, a three dimensional approach, with an elliptical assumption crack shape during the propagation, leading to a prediction of crack growth on the surface and in depth which is very similar to that obtained numerically, but with computational time much lower. (author)

  17. Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs

    Directory of Open Access Journals (Sweden)

    Mei-Yin Chang

    2015-11-01

    Full Text Available Plantaginaceae, a popular traditional Chinese medicine, has long been used for treating various diseases from common cold to cancer. Linalool is one of the biologically active compounds that can be isolated from Plantaginaceae. Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible tumor cells. However, the signaling pathway for apoptosis remains undefined. In this study, the cytotoxic effect of linalool on human cancer cell lines was investigated. Water-soluble tetrazolium salts (WST-1 based colorimetric cellular cytotoxicity assay, was used to test the cytotoxic ability of linalool against U937 and HeLa cells, and flow cytometry (FCM and genechip analysis were used to investigate the possible mechanism of apoptosis. These results demonstrated that linalool exhibited a good cytotoxic effect on U937 and HeLa cells, with the IC50 value of 2.59 and 11.02 μM, respectively, compared with 5-FU with values of 4.86 and 12.31 μM, respectively. After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby these cells were arrested at the G0/G1 phase. Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. Therefore, this study verified that linalool can arrest the cell cycle of U937 cells at the G0/G1 phase and can arrest the cell cycle of HeLa cells at the G2/M phase. Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs p53, p21, p27, p16, and p18, as well as the non-expression of cyclin-dependent kinases (CDKs activity.

  18. Effect of magnetic nanoparticles on apoptosis and cell cycle induced by wogonin in Raji cells

    Directory of Open Access Journals (Sweden)

    Wang XM

    2012-02-01

    Full Text Available Lei Wang1,2,*, Haijun Zhang1,2,*, Baoan Chen1,2, Guohua Xia1,2, Shuai Wang1,2, Jian Cheng1,2, Zeye Shao1,2, Chong Gao1,2, Wen Bao1,2, Liang Tian1,2, Yanyan Ren1,2, Peipei Xu1,2, Xiaohui Cai1,2, Ran Liu1,2, Xuemei Wang3 1Department of Hematology and Oncology, Zhongda Hospital, Medical School, 2Faculty of Oncology, Medical School, 3State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory, Southeast University, Nanjing, China*These authors contributed equally to this workAbstract: Traditional Chinese medicine is gradually becoming a new source of anticancer drugs. One such example is wogonin, which is cytotoxic to various cancer cell lines in vitro. However, due to its low water solubility, wogonin is restricted to clinical administration. Recently, the application of drug-coated magnetic nanoparticles (MNPs to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. In this study, wogonin was conjugated with the drug delivery system of MNPs by mechanical absorption polymerization to fabricate wogonin-loaded MNPs. It was demonstrated that MNPs could strengthen wogonin-induced cell inhibition, apoptosis, and cell cycle arrest in Raji cells by methylthiazol tetrazolium assay, flow cytometer assay, and nuclear 4',6-diamidino-2-phenylindole staining. Furthermore, the molecular mechanisms of these phenomena were explored by western blot, in which the protein levels of caspase 8 and caspase 3 were increased significantly while those of survivin and cyclin E were decreased significantly in wogonin-MNPs group. These findings suggest that the combination of wogonin and MNPs provides a promising strategy for lymphoma therapy.Keywords: wogonin, magnetic nanoparticles, Raji cell, apoptosis, cell cycle, caspase 8, caspase 3, survivin, cyclin E

  19. Serum Proteases Potentiate BMP-Induced Cell Cycle Re-entry of Dedifferentiating Muscle Cells during Newt Limb Regeneration.

    Science.gov (United States)

    Wagner, Ines; Wang, Heng; Weissert, Philipp M; Straube, Werner L; Shevchenko, Anna; Gentzel, Marc; Brito, Goncalo; Tazaki, Akira; Oliveira, Catarina; Sugiura, Takuji; Shevchenko, Andrej; Simon, András; Drechsel, David N; Tanaka, Elly M

    2017-03-27

    Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell cycle entry by dedifferentiating newt muscle cells. Protease-activated BMP4/7 heterodimers that are present in serum strongly induced myotube cell cycle re-entry with protease cleavage yielding a 30-fold potency increase of BMP4/7 compared with canonical BMP4/7. Inhibition of BMP signaling via muscle-specific dominant-negative receptor expression reduced cell cycle entry in vitro and in vivo. In vivo inhibition of serine protease activity depressed cell cycle re-entry, which in turn was rescued by cleaved-mimic BMP. This work identifies a mechanism of BMP activation that generates blastema cells from differentiated muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Non-homologous end joining dependency of {gamma}-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Heidenreich, Erich [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)]. E-mail: erich.heidenreich@meduniwien.ac.at; Eisler, Herfried [Institute of Cancer Research, Division of Molecular Genetics, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)

    2004-11-22

    There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by {gamma}-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the {gamma}-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development.

  1. Non-homologous end joining dependency of γ-irradiation-induced adaptive frameshift mutation formation in cell cycle-arrested yeast cells

    International Nuclear Information System (INIS)

    Heidenreich, Erich; Eisler, Herfried

    2004-01-01

    There is a strong selective pressure favoring adaptive mutations which relieve proliferation-limiting adverse living conditions. Due to their importance for evolution and pathogenesis, we are interested in the mechanisms responsible for the formation of such adaptive, gain-of-fitness mutations in stationary-phase cells. During previous studies on the occurrence of spontaneous reversions of an auxotrophy-causing frameshift allele in the yeast Saccharomyces cerevisiae, we noticed that about 50% of the adaptive reversions depended on a functional non-homologous end joining (NHEJ) pathway of DNA double-strand break (DSB) repair. Here, we show that the occasional NHEJ component Pol4, which is the yeast ortholog of mammalian DNA polymerase lambda, is not required for adaptive mutagenesis. An artificially imposed excess of DSBs by γ-irradiation resulted in a dramatic increase in the incidence of adaptive, cell cycle arrest-releasing frameshift reversions. By the use of DNA ligase IV-deficient strains we detected that the majority of the γ-induced adaptive mutations were also dependent on a functional NHEJ pathway. This suggests that the same mutagenic NHEJ mechanism acts on spontaneously arising as well as on ionizing radiation-induced DSBs. Inaccuracy of the NHEJ repair pathway may extensively contribute to the incidence of frameshift mutations in resting (non-dividing) eukaryotic cells, and thus act as a driving force in tumor development

  2. Distracted driving

    Science.gov (United States)

    ... including maps) The Dangers of Talking on the Phone While Driving You are four times more likely to get ... of reach. If you are caught using a phone while driving, you may risk a ticket or fine. Most ...

  3. Distracted Driving

    Science.gov (United States)

    ... and increased awareness of distracted driving using radio advertisements, news stories, and similar media. After the projects ... available at www.trafficsafetymarketing.gov . Distracted Driving Enforcement – TV Ads (Paid). For re-tagging, go to: www. ...

  4. Modifications of cell cycle according to conditions of photodynamic therapy induced by hypericin

    International Nuclear Information System (INIS)

    Mikes, J.; Kleban, J.; Szilardiova, B.; Sackova, V; Fedorocko, P.; Horvath, V.; Brezani, P.

    2004-01-01

    Photodynamic therapy (PDT) is becoming a rapidly developing method in cancer therapy, recently. PDT is based on administration of nontoxic/weakly toxic photosensitive compound and its activation with light of appropriate wave length. Although PDT is of use in clinical practise, new promising photosensitive compounds with advantageous attributes are discovered continuously. Hypericin, one of these compounds, is known to induce cell cycle arrest in G 2 /M phase at low doses. This arrest is caused by microtubules destruction linked to Bcl-2 phosphorylation as a consequence of CDK-1/cyclin B1 complex activation, but data about combinations of different hypericin concentrations and light doses are missing. PDT effect is effected by multiple factors. In our experiment, we have been shown, by cytokinetical and flow-cytometric analysis, the way how the cells response to photo-cytotoxic effect of hypericin. By combination of two factors, light doses and concentrations of hypericin, we eliminated inappropriate combinations and chose for another analysis narrow ranges of both factors. We discovered a breakpoint between a controlled cell death - apoptosis and cell signalling disaster followed by necrosis. (authors)

  5. Heat-induced accumulation and futile cycling of trehalose in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Hottiger, T.; Schmutz, P.; Wiemken, A.

    1987-01-01

    Heat shock resulted in rapid accumulation of large amounts of trehalose in Saccharomyces cerevisiae. In cultures growing exponentially on glucose, the trehalose content of the cells increased from 0.01 to 1 g/g of protein within 1 h after the incubation temperature was shifted from 27 to 40 0 C. When the temperature was readjusted to 27 0 C, the accumulated trehalose was rapidly degraded. In parallel, the activity of the trehalose-phosphate synthase, the key enzyme of trehalose biosynthesis, increased about six fold during the heat shock and declined to normal level after readjustment of the temperature. Surprisingly, the activity of neutral trehalase, the key enzyme of trehalose degradation, also increased about threefold during the heat shock and remained almost constant during recovery of the cells at 27 0 C. In pulse-labeling experiments with [ 14 C] glucose, trehalose was found to be turned over rapidly in heat-shocked cells, indicating that both anabolic and catabolic enzymes of trehalose metabolism were active in vivo. Possible functions of the heat-induced accumulation of trehalose and its rapid turnover in an apparently futile cycle during heat shock are discussed

  6. Forecasting Low-Cycle Fatigue Performance of Twinning-Induced Plasticity Steels: Difficulty and Attempt

    Science.gov (United States)

    Shao, C. W.; Zhang, P.; Zhang, Z. J.; Liu, R.; Zhang, Z. F.

    2017-12-01

    We find the existing empirical relations based on monotonic tensile properties and/or hardness cannot satisfactorily predict the low-cycle fatigue (LCF) performance of materials, especially for twinning-induced plasticity (TWIP) steels. Given this, we first identified the different deformation mechanisms under monotonic and cyclic deformation after a comprehensive study of stress-strain behaviors and microstructure evolutions for Fe-Mn-C alloys during tension and LCF, respectively. It is found that the good tensile properties of TWIP steel mainly originate from the large activation of multiple twinning systems, which may be attributed to the grain rotation during tensile deformation; while its LCF performance depends more on the dislocation slip mode, in addition to its strength and plasticity. Based on this, we further investigate the essential relations between microscopic damage mechanism (dislocation-dislocation interaction) and cyclic stress response, and propose a hysteresis loop model based on dislocation annihilation theory, trying to quickly assess the LCF resistance of Fe-Mn-C steels as well as other engineering materials. It is suggested that the hysteresis loop and its evolution can provide significant information on cyclic deformation behavior, e.g., (point) defect multiplication and vacancy aggregation, which may help estimate the LCF properties.

  7. Deformation mechanisms induced under high cycle fatigue tests in a metastable austenitic stainless steel

    Energy Technology Data Exchange (ETDEWEB)

    Roa, J.J., E-mail: joan.josep.roa@upc.edu [CIEFMA-Departament de Ciència dels Materials i Enginyeria Metallúrgica, ETSEIB, Universitat Politècnica de Catalunya, Avda. Diagonal 647, 08028 Barcelona (Spain); CRnE, Campus Diagonal Sud, Edificio C’, Universitat Politècnica de Catalunya, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Fargas, G. [CIEFMA-Departament de Ciència dels Materials i Enginyeria Metallúrgica, ETSEIB, Universitat Politècnica de Catalunya, Avda. Diagonal 647, 08028 Barcelona (Spain); Jiménez-Piqué, E. [CIEFMA-Departament de Ciència dels Materials i Enginyeria Metallúrgica, ETSEIB, Universitat Politècnica de Catalunya, Avda. Diagonal 647, 08028 Barcelona (Spain); CRnE, Campus Diagonal Sud, Edificio C’, Universitat Politècnica de Catalunya, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Mateo, A. [CIEFMA-Departament de Ciència dels Materials i Enginyeria Metallúrgica, ETSEIB, Universitat Politècnica de Catalunya, Avda. Diagonal 647, 08028 Barcelona (Spain)

    2014-03-01

    Advanced techniques were used to study the deformation mechanisms induced by fatigue tests in a metastable austenitic stainless steel AISI 301LN. Observations by Atomic Force Microscopy were carried out to study the evolution of a pre-existing martensite platelet at increasing number of cycles. The sub-superficial deformation mechanisms of the austenitic grains were studied considering the cross-section microstructure obtained by Focused Ion Beam and analysed by Scanning Electron Microscopy and Transmission Electron Microscopy. The results revealed no deformation surrounding the pre-existing martensitic platelet during fatigue tests, only the growth on height was observed. Martensite formation was associated with shear bands on austenite, mainly in the {111} plane, and with the activation of the other intersecting austenite {111}〈110〉 slip system. Furthermore, transmission electron microscopy results showed that the nucleation of ε-martensite follows a two stages phase transformation (γ{sub fcc}→ε{sub hcp}→α'{sub bcc})

  8. Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication.

    Directory of Open Access Journals (Sweden)

    Giuseppe Balistreri

    2016-02-01

    Full Text Available Kaposi's sarcoma herpesvirus (KSHV causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.

  9. Cell cycle-dependent regulation of kainate-induced inward currents in microglia

    International Nuclear Information System (INIS)

    Yamada, Jun; Sawada, Makoto; Nakanishi, Hiroshi

    2006-01-01

    Microglia are reported to have α-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8 ± 3.0 and 8.4 ± 0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7 ± 0.8 and 6.2 ± 1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism

  10. Full-Length Fibronectin Drives Fibroblast Accumulation at the Surface of Collagen Microtissues during Cell-Induced Tissue Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Jasper Foolen

    Full Text Available Generating and maintaining gradients of cell density and extracellular matrix (ECM components is a prerequisite for the development of functionality of healthy tissue. Therefore, gaining insights into the drivers of spatial organization of cells and the role of ECM during tissue morphogenesis is vital. In a 3D model system of tissue morphogenesis, a fibronectin-FRET sensor recently revealed the existence of two separate fibronectin populations with different conformations in microtissues, i.e. 'compact and adsorbed to collagen' versus 'extended and fibrillar' fibronectin that does not colocalize with the collagen scaffold. Here we asked how the presence of fibronectin might drive this cell-induced tissue morphogenesis, more specifically the formation of gradients in cell density and ECM composition. Microtissues were engineered in a high-throughput model system containing rectangular microarrays of 12 posts, which constrained fibroblast-populated collagen gels, remodeled by the contractile cells into trampoline-shaped microtissues. Fibronectin's contribution during the tissue maturation process was assessed using fibronectin-knockout mouse embryonic fibroblasts (Fn-/- MEFs and floxed equivalents (Fnf/f MEFs, in fibronectin-depleted growth medium with and without exogenously added plasma fibronectin (full-length, or various fragments. In the absence of full-length fibronectin, Fn-/- MEFs remained homogenously distributed throughout the cell-contracted collagen gels. In contrast, in the presence of full-length fibronectin, both cell types produced shell-like tissues with a predominantly cell-free compacted collagen core and a peripheral surface layer rich in cells. Single cell assays then revealed that Fn-/- MEFs applied lower total strain energy on nanopillar arrays coated with either fibronectin or vitronectin when compared to Fnf/f MEFs, but that the presence of exogenously added plasma fibronectin rescued their contractility. While collagen

  11. Analysis of X-ray induced cell-cycle perturbations in mouse osteosarcoma cells: a two-signal cell-cycle model

    International Nuclear Information System (INIS)

    Meeteren, A. van; Wijk, R. van; Stap, J.; Deys, B.F.

    1984-01-01

    The effects of X-irradiation on mouse osteosarcoma cells have been studied by time-lapse cinematography and the resulting pedigrees have been analysed statistically. It is shown that the irradiation treatment causes three types of cell kinetic lesions: cell death (disintegration), cell sterilization (failure to divide) and proliferation delay. The first two lesions are the most important with regard to survival of the irradiated cell in a clonal assay. Of these two lesions, sterilization appears to be highly correlated for sister cells, while this is not true for cell disintegration. This indicates that cell survival in a clonal assay may be a function of the ratio of the incidences of these two types of lesions. The X-ray-induced proliferation delay was studied in terms of intermitotic time distributions, mother-daughter correlation and sibling correlation in relation to the current cell-cycle phase at the time of treatment. This analysis shows that the effects of irradiation on these cell-cycle characteristics is highly cell-cycle-dependent. A qualitative model to account for the observations is presented. (author)

  12. Analysis of X-ray induced cell-cycle perturbations in mouse osteosarcoma cells: a two-signal cell-cycle model

    Energy Technology Data Exchange (ETDEWEB)

    Meeteren, A van; Wijk, R van [Rijksuniversiteit Utrecht (Netherlands); Stap, J; Deys, B F [Amsterdam Univ. (Netherlands)

    1984-03-01

    The effects of X-irradiation on mouse osteosarcoma cells have been studied by time-lapse cinematography and the resulting pedigrees have been analysed statistically. It is shown that the irradiation treatment causes three types of cell kinetic lesions: cell death (disintegration), cell sterilization (failure to divide) and proliferation delay. The first two lesions are the most important with regard to survival of the irradiated cell in a clonal assay. Of these two lesions, sterilization appears to be highly correlated for sister cells, while this is not true for cell disintegration. This indicates that cell survival in a clonal assay may be a function of the ratio of the incidences of these two types of lesions. The X-ray-induced proliferation delay was studied in terms of intermitotic time distributions, mother-daughter correlation and sibling correlation in relation to the current cell-cycle phase at the time of treatment. This analysis shows that the effects of irradiation on these cell-cycle characteristics is highly cell-cycle-dependent. A qualitative model to account for the observations is presented.

  13. Extrinsic pseudocapacitve Li-ion storage of SnS anode via lithiation-induced structural optimization on cycling

    Science.gov (United States)

    Lian, Qingwang; Zhou, Gang; Liu, Jiatu; Wu, Chen; Wei, Weifeng; Chen, Libao; Li, Chengchao

    2017-10-01

    Here, we report a new enhanced extrinsic pseudocapacitve Li-ion storage mechanism via lithiation-induced structural optimization strategy. The flower-like C@SnS and bulk SnS exhibit initial capacity decay and subsequent increase of capacity on cycling. After a long-term lithiation/delithiation process, flower-like C@SnS and bulk SnS exhibit improved rate performance and reversible capacity in comparison with those of initial state. Moreover, a high capacity of 530 mAh g-1 is still remained even after 1550 cycles at a high current density of 5.0 A g-1 for flower-like C@SnS after pre-lithiation of 350 cycles. According to the comprehensive analysis of structural evolution and electrochemical performance, it demonstrates that SnS electrodes experience crystal size reduction and further amorphization on cycling, which enhances the reversibility of conversion reaction for SnS, leading to increasing capacity. On the other hand, surface-dominated extrinsic pseudocapacitive contribution results in enhanced rate performance because electrodes expose a large fraction of Li+ sites on surface or near-surface region with structural optimization on cycling. This study reveals that extrinsic pseudocapacitance of SnS can be stimulated via lithiation-induced structural optimization, which gives rise to high-rate and long-lived performances.

  14. Tributyltin induces G2/M cell cycle arrest via NAD(+)-dependent isocitrate dehydrogenase in human embryonic carcinoma cells.

    Science.gov (United States)

    Asanagi, Miki; Yamada, Shigeru; Hirata, Naoya; Itagaki, Hiroshi; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

    2016-04-01

    Organotin compounds, such as tributyltin (TBT), are well-known endocrine-disrupting chemicals (EDCs). We have recently reported that TBT induces growth arrest in the human embryonic carcinoma cell line NT2/D1 at nanomolar levels by inhibiting NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the irreversible conversion of isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we examined whether TBT at nanomolar levels affects cell cycle progression in NT2/D1 cells. Propidium iodide staining revealed that TBT reduced the ratio of cells in the G1 phase and increased the ratio of cells in the G2/M phase. TBT also reduced cell division cycle 25C (cdc25C) and cyclin B1, which are key regulators of G2/M progression. Furthermore, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. The G2/M arrest induced by TBT was abolished by NAD-IDHα knockdown. Treatment with a cell-permeable α-ketoglutarate analogue recovered the effect of TBT, suggesting the involvement of NAD-IDH. Taken together, our data suggest that TBT at nanomolar levels induced G2/M cell cycle arrest via NAD-IDH in NT2/D1 cells. Thus, cell cycle analysis in embryonic cells could be used to assess cytotoxicity associated with nanomolar level exposure of EDCs.

  15. Characterization and modeling of SET/RESET cycling induced read-disturb failure time degradation in a resistive switching memory

    Science.gov (United States)

    Su, Po-Cheng; Hsu, Chun-Chi; Du, Sin-I.; Wang, Tahui

    2017-12-01

    Read operation induced disturbance in SET-state in a tungsten oxide resistive switching memory is investigated. We observe that the reduction of oxygen vacancy density during read-disturb follows power-law dependence on cumulative read-disturb time. Our study shows that the SET-state read-disturb immunity progressively degrades by orders of magnitude as SET/RESET cycle number increases. To explore the cause of the read-disturb degradation, we perform a constant voltage stress to emulate high-field stress effects in SET/RESET cycling. We find that the read-disturb failure time degradation is attributed to high-field stress-generated oxide traps. Since the stress-generated traps may substitute for some of oxygen vacancies in forming conductive percolation paths in a switching dielectric, a stressed cell has a reduced oxygen vacancy density in SET-state, which in turn results in a shorter read-disturb failure time. We develop an analytical read-disturb degradation model including both cycling induced oxide trap creation and read-disturb induced oxygen vacancy reduction. Our model can well reproduce the measured read-disturb failure time degradation in a cycled cell without using fitting parameters.

  16. Electric drives

    CERN Document Server

    Boldea, Ion

    2005-01-01

    ENERGY CONVERSION IN ELECTRIC DRIVESElectric Drives: A DefinitionApplication Range of Electric DrivesEnergy Savings Pay Off RapidlyGlobal Energy Savings Through PEC DrivesMotor/Mechanical Load MatchMotion/Time Profile MatchLoad Dynamics and StabilityMultiquadrant OperationPerformance IndexesProblemsELECTRIC MOTORS FOR DRIVESElectric Drives: A Typical ConfigurationElectric Motors for DrivesDC Brush MotorsConventional AC MotorsPower Electronic Converter Dependent MotorsEnergy Conversion in Electric Motors/GeneratorsPOWER ELECTRONIC CONVERTERS (PECs) FOR DRIVESPower Electronic Switches (PESs)The

  17. Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

    Science.gov (United States)

    Maalouf, Katia; Baydoun, Elias; Rizk, Sandra

    2011-01-01

    Background: Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer. Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes. Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry. Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 μg/μL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF-β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines. Conclusion: In conclusion, kefir is

  18. 3D additive manufactured 316L components microstructural features and changes induced by working life cycles

    Science.gov (United States)

    Pace, M. L.; Guarnaccio, A.; Dolce, P.; Mollica, D.; Parisi, G. P.; Lettino, A.; Medici, L.; Summa, V.; Ciancio, R.; Santagata, A.

    2017-10-01

    The ability of processing through laser beams different kinds of metallic powders for direct production of 3D components with complex geometries has been gaining an impressive and growing attention for specific industrial applications. The process which can be distinguished as Selective Laser Sintering or Selective Laser Melting is even considered, more generally, as Additive Manufacturing where layer by layer material is built by the interaction between a laser beam and a powder bed. The rapid heating of the powder due to the laser beam energy transfer process followed by a rapid cooling rate induces within the manufactured material a cellular structure with fine sub-grains, which are in the range of few hundreds of micrometers. These metastable structures, which are smaller than the grain size in conventionally manufactured 316L stainless steel components, can undertake towards a recrystallization process due to either heat or mechanical treatments. For instance, when sub-grain boundaries of the cells are enriched with Mo and higher concentration of dislocation, dynamical processes occur generating local residual stresses. In these circumstances the segregation of Mo in cell boundaries is out of thermodynamic equilibrium conditions so that microstructures and phases are metastable. In the range of 1100-1400 °C heat treatments a complete dissolution of Mo in the Fe matrix with a gradual disappearance of sub-microns cell is observed feeding the growth of larger austenitic sub-grains formation. It follows a higher degree of Mo dissolution in the material matrix and a decrease of dislocation's concentration (Saeidi et al., 2015) [1]. In the work here presented we point out which are the microstructural features of stainless steel 316L components realized by Additive Manufacturing. Furthermore, the occurrence of a microstructural evolution is presented after experiencing to fatigue of 80000 cycles some door joints obtained by this technique. A decrease of dislocation

  19. Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

    Directory of Open Access Journals (Sweden)

    Katia Maalouf

    2011-02-01

    Full Text Available Katia Maalouf1, Elias Baydoun2, Sandra Rizk11Department of Natural Sciences, Lebanese American University, Beirut, Lebanon; 2Department of Biology, American University of Beirut, Beirut, LebanonBackground: Adult lymphoblastic leukemia (ALL is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer.Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1-negative malignant T-lymphocytes.Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α, transforming growth factor- beta1 (TGF-β1, matrix metalloproteinase-2 (MMP-2, and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR. Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA and flow cytometry.Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 µg/µL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF- β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was

  20. Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

    International Nuclear Information System (INIS)

    Maalouf, Katia; Baydoun, Elias; Rizk, Sandra

    2011-01-01

    Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer. The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes. Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry. The maximum cytotoxicity recorded after 48-hours treatment with 80 μg/μL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF-β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG 1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines. In conclusion, kefir is effective in inhibiting proliferation and inducing

  1. Direct Yaw-Moment Control of All-Wheel-Independent-Drive Electric Vehicles with Network-Induced Delays through Parameter-Dependent Fuzzy SMC Approach

    Directory of Open Access Journals (Sweden)

    Wanke Cao

    2017-01-01

    Full Text Available This paper investigates the robust direct yaw-moment control (DYC through parameter-dependent fuzzy sliding mode control (SMC approach for all-wheel-independent-drive electric vehicles (AWID-EVs subject to network-induced delays. AWID-EVs have obvious advantages in terms of DYC over the traditional centralized-drive vehicles. However it is one of the most principal issues for AWID-EVs to ensure the robustness of DYC. Furthermore, the network-induced delays would also reduce control performance of DYC and even deteriorate the EV system. To ensure robustness of DYC and deal with network-induced delays, a parameter-dependent fuzzy sliding mode control (FSMC method based on the real-time information of vehicle states and delays is proposed in this paper. The results of cosimulations with Simulink® and CarSim® demonstrate the effectiveness of the proposed controller. Moreover, the results of comparison with a conventional FSMC controller illustrate the strength of explicitly dealing with network-induced delays.

  2. Combination of ascorbate/epigallocatechin-3-gallate/gemcitabine synergistically induces cell cycle deregulation and apoptosis in mesothelioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Martinotti, Simona [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy); Ranzato, Elia, E-mail: ranzato@unipmn.it [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy); Parodi, Monica [IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova (Italy); DI.ME.S., Università degli Studi di Genova, Via L. Alberti 2, 16132 Genova (Italy); Vitale, Massimo [IRCCS A.O.U. S. Martino-IST, Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova (Italy); Burlando, Bruno [Dipartimento di Scienze e Innovazione Tecnologica, Università del Piemonte Orientale “Amedeo Avogadro”, viale T. Michel 11, 15121 Alessandria (Italy)

    2014-01-01

    Malignant mesothelioma (MMe) is a poor-prognosis tumor in need of innovative therapies. In a previous in vivo study, we showed synergistic anti-MMe properties of the ascorbate/epigallocatechin-3-gallate/gemcitabine combination. We have now focused on the mechanism of action, showing the induction of apoptosis and cell cycle arrest through measurements of caspase 3, intracellular Ca{sup 2+}, annexin V, and DNA content. StellArray™ PCR technology and Western immunoblotting revealed DAPK2-dependent apoptosis, upregulation of cell cycle promoters, downregulation of cell cycle checkpoints and repression of NFκB expression. The complex of data indicates that the mixture is synergistic in inducing cell cycle deregulation and non-inflammatory apoptosis, suggesting its possible use in MMe treatment. - Highlights: • Ascorbate/epigallocathechin-gallate/gemcitabine has been tested on mesothelioma cells • A synergistic mechanism has been shown for cell cycle arrest and apoptosis • PCR-array analysis has revealed the de-regulation of apoptosis and cell cycle genes • Maximum upregulation has been found for the Death-Associated Protein Kinase-2 gene • Data suggest that the mixture could be used as a clinical treatment.

  3. Arctic sea-ice melting: Effects on hydroclimatic variability and on UV-induced carbon cycling

    Science.gov (United States)

    Sulzberger, Barbara

    2016-04-01

    change on biogeochemical cycling: interactions and feedbacks, Photochemical & Photobiological Sciences, 14(1), 127-148. Francis, J. A., S. J. Vavrus (2012), Evidence linking Arctic amplification to extreme weather in mid-latitudes, Geophysical Research Letters, 39, doi: 10.1029/2012GL051000. Haaland, S., D. Hongve, H. Laudon, G. Riise, R. D. Vogt (2010), Quantifying the drivers of the increasing colored organic matter in boreal surface waters, Environmental Science & Technology, 44(8), 2975-2980. IPCC Climate Change 2013 - The Physical Science Bases (2013). Schubert, S., H. Wang, M. Suarez (2011), Warm season subseasonal variability and climate extremes in the Northern Hemisphere: The role of stationary Rossby waves, Journal of Climate, 24(18), 4773-4792. Screen, J. A. (2013), Influence of Arctic sea ice on European summer precipitation, Environmental Research Letters, 8(4), doi: 10.1088/1748-9326/8/4/044015. Sulzberger, B., E. Durisch-Kaiser (2009), Chemical characterization of dissolved organic matter (DOM): A prerequisite for understanding UV-induced changes of DOM absorption properties and bioavailability, Aquatic Sciences, 71(2), 104-126.

  4. Dietary Deficiency of Essential Amino Acids Rapidly Induces Cessation of the Rat Estrous Cycle

    Science.gov (United States)

    Bannai, Makoto; Ichimaru, Toru; Nakano, Sayako; Murata, Takuya; Higuchi, Takashi; Takahashi, Michio

    2011-01-01

    Reproductive functions are regulated by the sophisticated coordination between the neuronal and endocrine systems and are sustained by a proper nutritional environment. Female reproductive function is vulnerable to effects from dietary restrictions, suggesting a transient adaptation that prioritizes individual survival over reproduction until a possible future opportunity for satiation. This adaptation could also partially explain the existence of amenorrhea in women with anorexia nervosa. Because amino acid nutritional conditions other than caloric restriction uniquely alters amino acid metabolism and affect the hormonal levels of organisms, we hypothesized that the supply of essential amino acids in the diet plays a pivotal role in the maintenance of the female reproductive system. To test this hypothesis, we examined ovulatory cyclicity in female rats under diets that were deficient in threonine, lysine, tryptophan, methionine or valine. Ovulatory cyclicity was monitored by daily cytological evaluations of vaginal smears. After continuous feeding of the deficient diet, a persistent diestrus or anovulatory state was induced most quickly by the valine-deficient diet and most slowly by the lysine-deficient diet. A decline in the systemic insulin-like growth factor 1 level was associated with a dietary amino acid deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet with balanced amino acids maintained normal estrous cyclicity. These disturbances of the estrous cycle by amino acid deficiency were quickly reversed by the consumption of a normal diet. The continuous anovulatory state in this study is not attributable to a decrease in caloric intake but to an imbalance in the dietary amino acid composition. With a shortage of well-balanced amino acid sources, reproduction becomes risky for both the mother and the fetus. It could be viewed as an adaptation to the diet, diverting resources away from reproduction and reallocating them to

  5. Freeze-thaw cycles induce content exchange between cell-sized lipid vesicles

    Science.gov (United States)

    Litschel, Thomas; Ganzinger, Kristina A.; Movinkel, Torgeir; Heymann, Michael; Robinson, Tom; Mutschler, Hannes; Schwille, Petra

    2018-05-01

    Early protocells are commonly assumed to consist of an amphiphilic membrane enclosing an RNA-based self-replicating genetic system and a primitive metabolism without protein enzymes. Thus, protocell evolution must have relied on simple physicochemical self-organization processes within and across such vesicular structures. We investigate freeze-thaw (FT) cycling as a potential environmental driver for the necessary content exchange between vesicles. To this end, we developed a conceptually simple yet statistically powerful high-throughput procedure based on nucleic acid-containing giant unilamellar vesicles (GUVs) as model protocells. GUVs are formed by emulsion transfer in glass bottom microtiter plates and hence can be manipulated and monitored by fluorescence microscopy without additional pipetting and sample handling steps. This new protocol greatly minimizes artefacts, such as unintended GUV rupture or fusion by shear forces. Using DNA-encapsulating phospholipid GUVs fabricated by this method, we quantified the extent of content mixing between GUVs under different FT conditions. We found evidence of nucleic acid exchange in all detected vesicles if fast freezing of GUVs at ‑80 °C is followed by slow thawing at room temperature. In contrast, slow freezing and fast thawing both adversely affected content mixing. Surprisingly, and in contrast to previous reports for FT-induced content mixing, we found that the content is not exchanged through vesicle fusion and fission, but that vesicles largely maintain their membrane identity and even large molecules are exchanged via diffusion across the membranes. Our approach supports efficient screening of prebiotically plausible molecules and environmental conditions, to yield universal mechanistic insights into how cellular life may have emerged.

  6. Cytokinin delays dark-induced senescence in rice by maintaining the chlorophyll cycle and photosynthetic complexes.

    Science.gov (United States)

    Talla, Sai Krishna; Panigrahy, Madhusmita; Kappara, Saivishnupriya; Nirosha, P; Neelamraju, Sarla; Ramanan, Rajeshwari

    2016-03-01

    The phytohormone cytokinin (CK) is known to delay senescence in plants. We studied the effect of a CK analog, 6-benzyl adenine (BA), on rice leaves to understand the possible mechanism by which CK delays senescence in a drought- and heat-tolerant rice cultivar Nagina22 (N22) using dark-induced senescence (DIS) as a surrogate for natural senescence of leaves. Leaves of N22-H-dgl162, a stay-green mutant of N22, and BA-treated N22 showed retention of chlorophyll (Chl) pigments, maintenance of the Chl a/b ratio, and delay in reduction of both photochemical efficiency and rate of oxygen evolution during DIS. HPLC analysis showed accumulation of 7-hydroxymethyl chlorophyll (HmChl) during DIS, and the kinetics of its accumulation correlated with progression of senescence. Transcriptome analysis revealed that several plastid-localized genes, specifically those associated with photosystem II (PSII), showed higher transcript levels in BA-treated N22 and the stay-green mutant leaves compared with naturally senescing N22 leaves. Real-time PCR analyses showed that genes coding for enzymes associated with Chl a/b interconversion and proteins associated with light-harvesting complexes maintained higher transcript levels up to 72h of DIS following BA treatment. The pigment-protein complexes analyzed by green gel remained intact in both N22-H-dgl162 and BA-treated N22 leaves even after 96h of DIS. Thus, CK delays senescence by accumulation of HmChl and up-regulating genes in the Chl cycle, thereby maintaining the Chl a/b ratio. Also, CK treatment retains higher transcript levels of PSII-related genes, resulting in the stability of photosynthetic pigment complexes and functional stay-greenness in rice. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  7. Features of single and double ionization processes induced by few cycle laser pulses

    International Nuclear Information System (INIS)

    Starace, A.F.

    2005-01-01

    Full text: The advent of laser pulses with attosecond pulse lengths ushers in the regime of few cycle laser pulse interactions with atoms and ions, including the interesting cases of single and half cycle laser pulses. In this talk I will present results of recent studies of single electron ionization/detachment and double electron ionization/detachment produced by a few cycle laser pulse. For the former case, we shall demonstrate that the ionized/detached electron momentum distribution reflects the interference of electron probability wave packets produced by each half cycle of a single cycle pulse. Also, that the ionized/detached electron momentum distribution uniquely characterizes the phase of the single cycle laser pulse within the laser pulse envelope. Regarding double ionization/detachment, our numerical experiments have shown that single cycle and double half cycle pulses produce different electron angular distributions. Some double ionization features that are present only in the single cycle case can only have been produced by electron impact ionization during rescattering of an initially ionized electron and thus represent a sensitive measure of the rescattering process. Refs. 2 (author)

  8. Cycling Hypoxia Induces a Specific Amplified Inflammatory Phenotype in Endothelial Cells and Enhances Tumor-Promoting Inflammation In Vivo

    Directory of Open Access Journals (Sweden)

    Céline Tellier

    2015-01-01

    Full Text Available Abnormal architecture of the tumor blood network, as well as heterogeneous erythrocyte flow, leads to temporal fluctuations in tissue oxygen tension exposing tumor and stromal cells to cycling hypoxia. Inflammation is another feature of tumor microenvironment and is considered as a new enabling characteristic of tumor progression. As cycling hypoxia is known to participate in tumor aggressiveness, the purpose of this study was to evaluate its role in tumor-promoting inflammation. Firstly, we assessed the impact of cycling hypoxia in vitro on endothelial inflammatory response induced by tumor necrosis factor α. Results showed that endothelial cells exposed to cycling hypoxia displayed an amplified proinflammatory phenotype, characterized by an increased expression of inflammatory cytokines, namely, interleukin (IL-6 and IL-8; by an increased expression of adhesion molecules, in particular intercellular adhesion molecule–1 (ICAM-1; and consequently by an increase in THP-1 monocyte adhesion. This exacerbation of endothelial inflammatory phenotype occurs through nuclear factor–κB overactivation. Secondly, the role of cycling hypoxia was studied on overall tumor inflammation in vivo in tumor-bearing mice. Results showed that cycling hypoxia led to an enhanced inflammation in tumors as prostaglandin-endoperoxide synthase 2 (PTGS2, IL-6, CXCL1 (C-X-C motif ligand 1, and macrophage inflammatory protein 2 (murine IL-8 functional homologs mRNA expression was increased and as a higher leukocyte infiltration was evidenced. Furthermore, cycling hypoxia–specific inflammatory phenotype, characterized by a simultaneous (baculoviral inhibitor of apoptosis repeat-containing 5low/PTGS2high/ICAM-1high/IL-6high/IL-8high expression, is associated with a poor prognosis in human colon cancer. This new phenotype could thus be used in clinic to more precisely define prognosis for colon cancer patients. In conclusion, our findings evidenced for the first time the

  9. Investigating Human-Induced Changes of Elemental Cycles in the Great Lakes

    Science.gov (United States)

    Baskaran, Mark; Bratton, John

    2013-07-01

    Food webs and associated elemental cycles in the Laurentian Great Lakes have been considerably altered over the past 30 years due to factors such as phosphorus abatement, introduction of zebra and quagga mussels, and climate change. These perturbations provide a unique opportunity to document how this natural system has responded and possibly to predict future changes in biogeochemical cycling.

  10. Calotropin from Asclepias curasavica induces cell cycle arrest and apoptosis in cisplatin-resistant lung cancer cells.

    Science.gov (United States)

    Mo, En-Pan; Zhang, Rong-Rong; Xu, Jun; Zhang, Huan; Wang, Xiao-Xiong; Tan, Qiu-Tong; Liu, Fang-Lan; Jiang, Ren-Wang; Cai, Shao-Hui

    2016-09-16

    Calotropin (M11), an active compound isolated from Asclepias curasavica L., was found to exert strong inhibitory and pro-apoptotic activity specifically against cisplatin-induced resistant non-small cell lung cancer (NSCLC) cells (A549/CDDP). Molecular mechanism study revealed that M11 induced cell cycle arrest at the G2/M phase through down-regulating cyclins, CDK1, CDK2 and up-regulating p53 and p21. Furthermore, M11 accelerated apoptosis through the mitochondrial apoptotic pathway which was accompanied by increase Bax/Bcl-2 ratio, decrease in mitochondrial membrane potential, increase in reactive oxygen species production, activations of caspases 3 and 9 as well as cleavage of poly ADP-ribose polymerase (PARP). The activation and phosphorylation of JNK was also found to be involved in M11-induced apoptosis, and SP610025 (specific JNK inhibitor) partially prevented apoptosis induced by M11. In contrast, all of the effects that M11 induce cell cycle arrest and apoptosis in A549/CDDP cells were not significant in A549 cells. Drugs with higher sensitivity against resistant tumor cells than the parent cells are rather rare. Results of this study supported the potential application of M11 on the non-small lung cancer (NSCLC) with cisplatin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The nonstructural protein NP1 of human bocavirus 1 induces cell cycle arrest and apoptosis in Hela cells

    International Nuclear Information System (INIS)

    Sun, Bin; Cai, Yingyue; Li, Yongshu; Li, Jingjing; Liu, Kaiyu; Li, Yi; Yang, Yongbo

    2013-01-01

    Human bocavirus type 1 (HBoV1) is a newly identified pathogen associated with human respiratory tract illnesses. Previous studies demonstrated that proteins of HBoV1 failed to cause cell death, which is considered as a possible common feature of bocaviruses. However, our work showed that the NP1 of HBoV1 induced apoptotic cell death in Hela cells in the absence of viral genome replication and expression of other viral proteins. Mitochondria apoptotic pathway was involved in the NP1-induced apoptosis that was confirmed by apoptotic characteristics including morphological changes, DNA fragmentation and caspase activation. We also demonstrated that the cell cycle of NP1-transfected Hela cells was transiently arrested at G2/M phase followed by rapid appearance of apoptosis and that the N terminal domain of NP1 was critical to its nuclear localization and function in apoptosis induction in Hela cells. These findings might provide alternative information for further study of mechanism of HBoV1 pathogenesis. - Highlights: ► NP1 protein of HBoV1 induced apoptosis in Hela cells was first reported. ► NP1 induced-apoptosis followed the cell cycle arrest at G2/M phase. ► The NP1 induced-apoptosis was mediated by mitochondrion apoptotic pathway. ► N terminal of NP1 was critical for apoptosis induction and nuclear localization

  12. The nonstructural protein NP1 of human bocavirus 1 induces cell cycle arrest and apoptosis in Hela cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Bin; Cai, Yingyue; Li, Yongshu [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China); Li, Jingjing [College of Life Science, Hubei Normal University, Huangshi 435002, Hubei (China); Liu, Kaiyu [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China); Li, Yi, E-mail: johnli2668@hotmail.com [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China); Bioengineering Department, Wuhan Bioengineering Institute, Wuhan 430415, Hubei (China); Yang, Yongbo, E-mail: yongboyang@mail.ccnu.edu.cn [College of Life Science, Central China Normal University, Wuhan 430079, Hubei (China)

    2013-05-25

    Human bocavirus type 1 (HBoV1) is a newly identified pathogen associated with human respiratory tract illnesses. Previous studies demonstrated that proteins of HBoV1 failed to cause cell death, which is considered as a possible common feature of bocaviruses. However, our work showed that the NP1 of HBoV1 induced apoptotic cell death in Hela cells in the absence of viral genome replication and expression of other viral proteins. Mitochondria apoptotic pathway was involved in the NP1-induced apoptosis that was confirmed by apoptotic characteristics including morphological changes, DNA fragmentation and caspase activation. We also demonstrated that the cell cycle of NP1-transfected Hela cells was transiently arrested at G2/M phase followed by rapid appearance of apoptosis and that the N terminal domain of NP1 was critical to its nuclear localization and function in apoptosis induction in Hela cells. These findings might provide alternative information for further study of mechanism of HBoV1 pathogenesis. - Highlights: ► NP1 protein of HBoV1 induced apoptosis in Hela cells was first reported. ► NP1 induced-apoptosis followed the cell cycle arrest at G2/M phase. ► The NP1 induced-apoptosis was mediated by mitochondrion apoptotic pathway. ► N terminal of NP1 was critical for apoptosis induction and nuclear localization.

  13. H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

    Directory of Open Access Journals (Sweden)

    Anne-France Petit-Bertron

    Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

  14. A synthetic NO reduction cycle on a bis(pyrazolato)-bridged dinuclear ruthenium complex including photo-induced transformation.

    Science.gov (United States)

    Arikawa, Yasuhiro; Hiura, Junko; Tsuchii, Chika; Kodama, Mika; Matsumoto, Naoki; Umakoshi, Keisuke

    2018-05-17

    A synthetic NO reduction cycle (2NO + 2H+ + 2e- → N2O + H2O) on a dinuclear platform {(TpRu)2(μ-pz)2} (Tp = HB(pyrazol-1-yl)3) was achieved, where an unusual N-N coupling complex was included. Moreover, an interesting photo-induced conversion of the N-N coupling complex to an oxido-bridged complex was revealed.

  15. Pile Driving

    Science.gov (United States)

    1987-01-01

    Machine-oriented structural engineering firm TERA, Inc. is engaged in a project to evaluate the reliability of offshore pile driving prediction methods to eventually predict the best pile driving technique for each new offshore oil platform. Phase I Pile driving records of 48 offshore platforms including such information as blow counts, soil composition and pertinent construction details were digitized. In Phase II, pile driving records were statistically compared with current methods of prediction. Result was development of modular software, the CRIPS80 Software Design Analyzer System, that companies can use to evaluate other prediction procedures or other data bases.

  16. Radiotherapy induces cell cycle arrest and cell apoptosis in nasopharyngeal carcinoma via the ATM and Smad pathways.

    Science.gov (United States)

    Li, Ming-Yi; Liu, Jin-Quan; Chen, Dong-Ping; Li, Zhou-Yu; Qi, Bin; He, Lu; Yu, Yi; Yin, Wen-Jin; Wang, Meng-Yao; Lin, Ling

    2017-09-02

    Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. In this study, we performed in vitro assays with human nasopharyngeal carcinoma CNE-2 cells and in vivo assays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy. The results suggested that radiation induced activation of ATM pathway by inducing expression of p-ATM, p-CHK1, p-CHK2, p15 and inhibiting expression of p-Smad3. In addition, Caspase3 expression was increased while CDC25A was decreased, leading to cell cycle arrest and cell apoptosis. On the other hand, activation of Smad3 can inhibited the ATM pathway and attenuated the efficacy of radiation. In summary, we suggest that both ATM and Smad pathways contribute to the cell cycle arrest and cell apoptosis during nasopharyngeal carcinoma cells treated with radiation.

  17. Evaluación de la eficiencia energética de vehículos pesados en el ciclo // Evaluation of the heavy duty trucks energy efficiency in the modified drive cycle.

    Directory of Open Access Journals (Sweden)

    Ramón Pérez-Gálvez

    2010-01-01

    Full Text Available ResumenEn este trabajo, se presenta la reformulación de un ciclo teórico que consta de los elementosbásicos de un ciclo de viaje real con condiciones prefijadas de movimiento y operación. En lamodificación se tomaron en cuenta los siguientes elementos: frecuencia de rotación mínima enmovimiento estable; eficiencia de la transmisión variable con la velocidad, la carga y la marchaconectada; un nuevo criterio de frecuencia de rotación del motor para el cambio de marchas; elfrenado con el motor embragado y; nuevas expresiones de cuantificación del consumo decombustible. Obteniéndose nuevos modelos matemáticos para la determinación de los indicadoresdel consumo de combustible de vehículos pesados de transmisión mecánica. Se presenta además,un indicador “Coeficiente de Efectividad del Trabajo del Automóvil” (CETA que describe laeficiencia energética durante el periodo de impulso, expresada a través del grado deaprovechamiento de la energía del automóvil para llevar hasta determinada velocidad la masa de lacarga útil.Palabras claves: ciclo de viaje, consumo de combustible, evaluación vehicular, modelos matemáticos._________________________________________________________________AbstractIn this paper, the new formulation of a theoretical drive cycle is presented. It is integrated by stagesof a real drive cycle with the prefix settings of movement and operation. In the cycle modificationthe following approaches are taken account: minimal rotation frequency in stable movement; thetransmission efficiency is variable with the speed, the weight, and the gear ratio; a new rotationfrequency for gear shifting; a motor braking stage and; a group of new equations for the fuelconsumption. New mathematical models were obtained for the fuel consumption indicators of theheavy duty trucks with manual transmission. Furthermore, the indicator Automobile WorkEffectiveness Coefficient is presented. It describes the energy efficiency in the

  18. Compensation of head-on beam-beam induced resonance driving terms and tune spread in the Relativistic Heavy Ion Collider

    Directory of Open Access Journals (Sweden)

    W. Fischer

    2017-09-01

    Full Text Available A head-on beam-beam compensation scheme was implemented for operation in the Relativistic Heavy Ion Collider (RHIC at Brookhaven National Laboratory [Phys. Rev. Lett. 115, 264801 (2015PRLTAO0031-900710.1103/PhysRevLett.115.264801]. The compensation consists of electron lenses for the reduction of the beam-beam induced tune spread, and a lattice for the minimization of beam-beam generated resonance driving terms. We describe the implementations of the lattice and electron lenses, and report on measurements of lattice properties and the effect of the electron lenses on the hadron beam.

  19. The p75NTR tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

    International Nuclear Information System (INIS)

    Khwaja, Fatima; Tabassum, Arshia; Allen, Jeff; Djakiew, Daniel

    2006-01-01

    The p75 neurotrophin receptor (p75 NTR ) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75 NTR retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted (ΔDD) dominant-negative antagonist of p75 NTR showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75 NTR -dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75 NTR expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75 NTR rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75 NTR was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75 NTR -dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75 NTR expressing prostate cancer cells

  20. The p75{sup NTR} tumor suppressor induces cell cycle arrest facilitating caspase mediated apoptosis in prostate tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Khwaja, Fatima [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057-1436 (United States); Tabassum, Arshia [Toronto Western Hospital, Toronto, ON, M5T258 (Canada); Allen, Jeff [National Center for Complementary and Alternative Medicine, N.I.H., Bethesda, MD 20892 (United States); Djakiew, Daniel [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC 20057-1436 (United States) and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057-1436 (United States)

    2006-03-24

    The p75 neurotrophin receptor (p75{sup NTR}) is a death receptor which belongs to the tumor necrosis factor receptor super-family of membrane proteins. This study shows that p75{sup NTR} retarded cell cycle progression by induced accumulation of cells in G0/G1 and a reduction in the S phase of the cell cycle. The rescue of tumor cells from cell cycle progression by a death domain deleted ({delta}DD) dominant-negative antagonist of p75{sup NTR} showed that the death domain transduced anti-proliferative activity in a ligand-independent manner. Conversely, addition of NGF ligand rescued retardation of cell cycle progression with commensurate changes in components of the cyclin/cdk holoenzyme complex. In the absence of ligand, p75{sup NTR}-dependent cell cycle arrest facilitated an increase in apoptotic nuclear fragmentation of the prostate cancer cells. Apoptosis of p75{sup NTR} expressing cells occurred via the intrinsic mitochondrial pathway leading to a sequential caspase-9 and -7 cascade. Since the death domain deleted dominant-negative antagonist of p75{sup NTR} rescued intrinsic caspase associated apoptosis in PC-3 cells, this shows p75{sup NTR} was integral to ligand independent induction of apoptosis. Moreover, the ability of ligand to ameliorate the p75{sup NTR}-dependent intrinsic apoptotic cascade indicates that NGF functioned as a survival factor for p75{sup NTR} expressing prostate cancer cells.

  1. S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

    Science.gov (United States)

    Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

    2018-05-04

    Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

  2. Characterization and Suppression of the Electromagnetic Interference Induced Phase Shift in the JLab FEL Photo - Injector Advanced Drive Laser System

    Energy Technology Data Exchange (ETDEWEB)

    F. G. Wilson, D. Sexton, S. Zhang

    2011-09-01

    The drive laser for the photo-cathode gun used in the JLab Free Electron Laser (FEL) facility had been experiencing various phase shifts on the order of tens of degrees (>20{sup o} at 1497 MHz or >40ps) when changing the Advanced Drive Laser (ADL) [2][3][4] micro-pulse frequencies. These phase shifts introduced multiple complications when trying to setup the accelerator for operation, ultimately inhibiting the robustness and overall performance of the FEL. Through rigorous phase measurements and systematic characterizations, we determined that the phase shifts could be attributed to electromagnetic interference (EMI) coupling into the ADL phase control loop, and subsequently resolved the issue of phase shift to within tenths of a degree (<0.5{sup o} at 1497 MHz or <1ps). The diagnostic method developed and the knowledge gained through the entire process will prove to be invaluable for future designs of similar systems.

  3. Terahertz radiation-induced sub-cycle field electron emission across a split-gap dipole antenna

    International Nuclear Information System (INIS)

    Zhang, Jingdi; Averitt, Richard D.; Zhao, Xiaoguang; Fan, Kebin; Wang, Xiaoning; Zhang, Xin; Zhang, Gu-Feng; Geng, Kun

    2015-01-01

    We use intense terahertz pulses to excite the resonant mode (0.6 THz) of a micro-fabricated dipole antenna with a vacuum gap. The dipole antenna structure enhances the peak amplitude of the in-gap THz electric field by a factor of ∼170. Above an in-gap E-field threshold amplitude of ∼10 MV/cm −1 , THz-induced field electron emission is observed as indicated by the field-induced electric current across the dipole antenna gap. Field emission occurs within a fraction of the driving THz period. Our analysis of the current (I) and incident electric field (E) is in agreement with a Millikan-Lauritsen analysis where log (I) exhibits a linear dependence on 1/E. Numerical estimates indicate that the electrons are accelerated to a value of approximately one tenth of the speed of light

  4. PRM1 and KAR5 function in cell-cell fusion and karyogamy to drive distinct bisexual and unisexual cycles in the Cryptococcus pathogenic species complex.

    Directory of Open Access Journals (Sweden)

    Ci Fu

    2017-11-01

    Full Text Available Sexual reproduction is critical for successful evolution of eukaryotic organisms in adaptation to changing environments. In the opportunistic human fungal pathogens, the Cryptococcus pathogenic species complex, C. neoformans primarily undergoes bisexual reproduction, while C. deneoformans undergoes both unisexual and bisexual reproduction. During both unisexual and bisexual cycles, a common set of genetic circuits regulates a yeast-to-hyphal morphological transition, that produces either monokaryotic or dikaryotic hyphae. As such, both the unisexual and bisexual cycles can generate genotypic and phenotypic diversity de novo. Despite the similarities between these two cycles, genetic and morphological differences exist, such as the absence of an opposite mating-type partner and monokaryotic instead of dikaryotic hyphae during C. deneoformans unisexual cycle. To better understand the similarities and differences between these modes of sexual reproduction, we focused on two cellular processes involved in sexual reproduction: cell-cell fusion and karyogamy. We identified orthologs of the plasma membrane fusion protein Prm1 and the nuclear membrane fusion protein Kar5 in both Cryptococcus species, and demonstrated their conserved roles in cell fusion and karyogamy during C. deneoformans α-α unisexual reproduction and C. deneoformans and C. neoformans a-α bisexual reproduction. Notably, karyogamy occurs inside the basidum during bisexual reproduction in C. neoformans, but often occurs earlier following cell fusion during bisexual reproduction in C. deneoformans. Characterization of these two genes also showed that cell fusion is dispensable for solo unisexual reproduction in C. deneoformans. The blastospores produced along hyphae during C. deneoformans unisexual reproduction are diploid, suggesting that diploidization occurs early during hyphal development, possibly through either an endoreplication pathway or cell fusion-independent karyogamy

  5. Mutations induced by X-rays and UV radiation during the nuclear cycle in the yeast Schizosarccharomyces pombe

    International Nuclear Information System (INIS)

    Barale, R.; Rusciano, D.; Loprieno, N.

    1982-01-01

    The availability of a cell-division-cycle (cdc) mutant in the fission yeast S. pombe, wee 1-50, has made possible the production of a large population of G 1 nuclear-stage synchronized cells. During their development, yeast cells from the G 1 into the G 2 nuclear stages were treated with X-rays and UV radiation at various doses. The DNA pre-replicative and replicative phases were the most sensitive to both cell lethality and mutant induction with either X-rays or UV radiation. The trends of induced biological effects that were observed suggest that the induction of mutations is dependent on the number of unrepaired DNA lesions that reach the replicating fork or of those that occur at that time. The X-ray-induced mutations were earlier saturated, possibly because of the higher number of lethal lesions so induced. (orig.)

  6. Study on phase noise induced by 1/f noise of the modulator drive circuit in high-sensitivity fiber optic gyroscope

    Science.gov (United States)

    Teng, Fei; Jin, Jing; Li, Yong; Zhang, Chunxi

    2018-05-01

    The contribution of modulator drive circuit noise as a 1/f noise source to the output noise of the high-sensitivity interferometric fiber optic gyroscope (IFOG) was studied here. A noise model of closed-loop IFOG was built. By applying the simulated 1/f noise sequence into the model, a gyroscope output data series was acquired, and the corresponding power spectrum density (PSD) and the Allan variance curve were calculated to analyze the noise characteristic. The PSD curve was in the spectral shape of 1/f, which verifies that the modulator drive circuit induced a low frequency 1/f phase noise into the gyroscope. The random walk coefficient (RWC), a standard metric to characterize the noise performance of the IFOG, was calculated according to the Allan variance curve. Using an operational amplifier with an input 1/f noise of 520 nV/√Hz at 1 Hz, the RWC induced by this 1/f noise was 2 × 10-4°/√h, which accounts for 63% of the total RWC. To verify the correctness of the noise model we proposed, a high-sensitivity gyroscope prototype was built and tested. The simulated Allan variance curve gave a good rendition of the prototype actual measured curve. The error percentage between the simulated RWC and the measured value was less than 13%. According to the model, a noise reduction method is proposed and the effectiveness is verified by the experiment.

  7. Effect of Locomotor Respiratory Coupling Induced by Cortical Oxygenated Hemoglobin Levels During Cycle Ergometer Exercise of Light Intensity.

    Science.gov (United States)

    Oyanagi, Keiichi; Tsubaki, Atsuhiro; Yasufuku, Yuichi; Takai, Haruna; Kera, Takeshi; Tamaki, Akira; Iwata, Kentaro; Onishi, Hideaki

    This study aimed to clarify the effects of locomotor-respiratory coupling (LRC) induced by light load cycle ergometer exercise on oxygenated hemoglobin (O2Hb) in the dorsolateral prefrontal cortex (DLPFC), supplementary motor area (SMA), and sensorimotor cortex (SMC). The participants were 15 young healthy adults (9 men and 6 women, mean age: 23.1 ± 1.8 (SEM) years). We conducted a task in both LRC-inducing and LRC-non-inducing conditions for all participants. O2Hb was measured using near-infrared spectroscopy. The LRC frequency ratio during induction was 2:1; pedaling rate, 50 rpm; and intensity of load, 30 % peak volume of oxygen uptake. The test protocol included a 3-min rest prior to exercise, steady loading motion for 10 min, and 10-min rest post exercise (a total of 23 min). In the measurement of O2Hb, we focused on the DLPFC, SMA, and SMC. The LRC frequency was significantly higher in the LRC-inducing condition (p < 0.05). O2Hb during exercise was significantly lower in the DLPFC and SMA, under the LRC-inducing condition (p < 0.05). The study revealed that even light load could induce LRC and that O2Hb in the DLPFC and SMA decreases during exercise via LRC induction.

  8. Solar Cycle Variability and Grand Minima Induced by Joy's Law Scatter

    Science.gov (United States)

    Karak, Bidya Binay; Miesch, Mark S.

    2017-08-01

    The strength of the solar cycle varies from one cycle to another in an irregular manner and the extreme example of this irregularity is the Maunder minimum when Sun produced only a few spots for several years. We explore the cause of these variabilities using a 3D Babcock--Leighton dynamo. In this model, based on the toroidal flux at the base of the convection zone, bipolar magnetic regions (BMRs) are produced with flux, tilt angle, and time of emergence all obtain from their observed distributions. The dynamo growth is limited by a tilt quenching.The randomnesses in the BMR emergences make the poloidal field unequal and eventually cause an unequal solar cycle. When observed fluctuations of BMR tilts around Joy's law, i.e., a standard deviation of 15 degrees, are considered, our model produces a variation in the solar cycle comparable to the observed solar cycle variability. Tilt scatter also causes occasional Maunder-like grand minima, although the observed scatter does not reproduce correct statistics of grand minima. However, when we double the tilt scatter, we find grand minima consistent with observations. Importantly, our dynamo model can operate even during grand minima with only a few BMRs, without requiring any additional alpha effect.

  9. Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

    International Nuclear Information System (INIS)

    Sun, Ting; Zhang, Zizhu; Li, Bin; Chen, Guilin; Xie, Xueshun; Wei, Yongxin; Wu, Jie; Zhou, Youxin; Du, Ziwei

    2013-01-01

    Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma

  10. Cell cycle age dependence for radiation-induced G2 arrest: evidence for time-dependent repair

    International Nuclear Information System (INIS)

    Rowley, R.

    1985-01-01

    Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G 2 . The sensitivity of Chinese hamster ovary cells to G 2 arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G 2 . This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G 2 arrest and/or by changes in capability for postirradiation recovery from G 2 arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G 2 arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G 2 arrest, while inhibiting repair of G 2 arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G 2 arrest was expressed. The duration of G 2 arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G 2 arrest induction is present throughout the cell cycle and that the level of G 2 arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G 2 arrest

  11. Impaired Driving

    Science.gov (United States)

    ... Get the Facts What Works: Strategies to Increase Car Seat and Booster Seat ... narcotics. 3 That’s one percent of the 111 million self-reported episodes of alcohol-impaired driving among U.S. ...

  12. Indirect immobilized Jagged1 suppresses cell cycle progression and induces odonto/osteogenic differentiation in human dental pulp cells.

    Science.gov (United States)

    Manokawinchoke, Jeeranan; Nattasit, Praphawi; Thongngam, Tanutchaporn; Pavasant, Prasit; Tompkins, Kevin A; Egusa, Hiroshi; Osathanon, Thanaphum

    2017-08-31

    Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction. Downregulated genes predominantly participated in the cell cycle, DNA replication, and DNA repair. Indirect immobilized Jagged1 significantly reduced cell proliferation, colony forming unit ability, and the number of cells in S phase. Jagged1 treated hDPs exhibited significantly higher ALP enzymatic activity, osteogenic marker gene expression, and mineralization compared with control. Pretreatment with a γ-secretase inhibitor attenuated the Jagged1-induced ALP activity and mineral deposition. NOTCH2 shRNA reduced the Jagged1-induced osteogenic marker gene expression, ALP enzymatic activity, and mineral deposition. In conclusion, indirect immobilized Jagged1 suppresses cell cycle progression and induces the odonto/osteogenic differentiation of hDPs via the canonical Notch signaling pathway.

  13. Dermal white adipose tissue undergoes major morphological changes during the spontaneous and induced murine hair follicle cycling: a reappraisal.

    Science.gov (United States)

    Foster, April R; Nicu, Carina; Schneider, Marlon R; Hinde, Eleanor; Paus, Ralf

    2018-07-01

    In murine skin, dermal white adipose tissue (DWAT) undergoes major changes in thickness in synchrony with the hair cycle (HC); however, the underlying mechanisms remain unclear. We sought to elucidate whether increased DWAT thickness during anagen is mediated by adipocyte hypertrophy or adipogenesis, and whether lipolysis or apoptosis can explain the decreased DWAT thickness during catagen. In addition, we compared HC-associated DWAT changes between spontaneous and depilation-induced hair follicle (HF) cycling to distinguish between spontaneous and HF trauma-induced events. We show that HC-dependent DWAT remodelling is not an artefact caused by fluctuations in HF down-growth, and that dermal adipocyte (DA) proliferation and hypertrophy are HC-dependent, while classical DA apoptosis is absent. However, none of these changes plausibly accounts for HC-dependent oscillations in DWAT thickness. Contrary to previous studies, in vivo BODIPY uptake suggests that increased DWAT thickness during anagen occurs via hypertrophy rather than hyperplasia. From immunohistomorphometry, DWAT thickness likely undergoes thinning during catagen by lipolysis. Hence, we postulate that progressive, lipogenesis-driven DA hypertrophy followed by dynamic switches between lipogenesis and lipolysis underlie DWAT fluctuations in the spontaneous HC, and dismiss apoptosis as a mechanism of DWAT reduction. Moreover, the depilation-induced HC displays increased DWAT thickness, area, and DA number, but decreased DA volume/area compared to the spontaneous HC. Thus, DWAT shows additional, novel HF wounding-related responses during the induced HC. This systematic reappraisal provides important pointers for subsequent functional and mechanistic studies, and introduces the depilation-induced murine HC as a model for dissecting HF-DWAT interactions under conditions of wounding/stress.

  14. Numerical model for predicting thermodynamic cycle and thermal efficiency of a beta-type Stirling engine with rhombic-drive mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Chin-Hsiang; Yu, Ying-Ju [Department of Aeronautics and Astronautics, National Cheng Kung University, No. 1, Ta-Shieh Road, Tainan 70101, Taiwan (China)

    2010-11-15

    This study is aimed at development of a numerical model for a beta-type Stirling engine with rhombic-drive mechanism. By taking into account the non-isothermal effects, the effectiveness of the regenerative channel, and the thermal resistance of the heating head, the energy equations for the control volumes in the expansion chamber, the compression chamber, and the regenerative channel can be derived and solved. Meanwhile, a fully developed flow velocity profile in the regenerative channel, in terms of the reciprocating velocity of the displacer and the instantaneous pressure difference between the expansion and the compression chambers, is derived for calculation of the mass flow rate through the regenerative channel. In this manner, the internal irreversibility caused by pressure difference in the two chambers and the viscous shear effects due to the motion of the reciprocating displacer on the fluid flow in the regenerative channel gap are included. Periodic variation of pressures, volumes, temperatures, masses, and heat transfers in the expansion and the compression chambers are predicted. A parametric study of the dependence of the power output and thermal efficiency on the geometrical and physical parameters, involving regenerative gap, distance between two gears, offset distance from the crank to the center of gear, and the heat source temperature, has been performed. (author)

  15. Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

    Directory of Open Access Journals (Sweden)

    Morris Robert

    2010-03-01

    Full Text Available Abstract Background Sulforaphane (SFN, an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC. The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC. Results SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose-polymerase (PARP. Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex. Conclusions SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.

  16. Thermally Induced Ultra High Cycle Fatigue of Copper Alloys of the High Gradient Accelerating Structures

    CERN Document Server

    Heikkinen, Samuli; Wuensch, Walter

    2010-01-01

    In order to keep the overall length of the compact linear collider (CLIC), currently being studied at the European Organization for Nuclear Research (CERN), within reasonable limits, i.e. less than 50 km, an accelerating gradient above 100 MV/m is required. This imposes considerable demands on the materials of the accelerating structures. The internal surfaces of these core components of a linear accelerator are exposed to pulsed radio frequency (RF) currents resulting in cyclic thermal stresses expected to cause surface damage by fatigue. The designed lifetime of CLIC is 20 years, which results in a number of thermal stress cycles of the order of 2.33•1010. Since no fatigue data existed in the literature for CLIC parameter space, a set of three complementary experiments were initiated: ultra high cycle mechanical fatigue by ultrasound, low cycle fatigue by pulsed laser irradiation and low cycle thermal fatigue by high power microwaves, each test representing a subset of the original problem. High conductiv...

  17. Estrous cycle and food availability affect feeding induced by amygdala 5-HT receptor blockade.

    Science.gov (United States)

    Parker, Graham C; Bishop, Christopher; Coscina, Donald V

    2002-04-01

    We have recently reported that bilateral infusions of the 5-HT receptor antagonist metergoline (MET) into the posterior basolateral amygdala (pBLA) elicit feeding in female rats tested at mid-light cycle. The present study was performed to determine whether (1) testing at two different phases of the estrous cycle, and/or (2) the palatability of the food might modify this effect. Subjects were 18 adult females with bilateral pBLA cannulae. Following familiarization with Froot Loops cereal, a within-subjects design tested all animals for 1- and 2-h food intake under 2 Drug (0.3 nmol MET vs. Vehicle), 2 Estrous Cycle (diestrus vs. estrus) and 2 Food (lab chow vs. Froot Loops) conditions. Rats weighed more at diestrus than at proestrus (Pestrus (Pestrus. A three-way interaction (Pestrus than in diestrus to lab chow but not Froot Loops. These data suggest pBLA MET differentially affects feeding over the estrous cycle depending on the palatability of food available.

  18. Modification of creep and low cycle fatigue behaviour induced by welding

    Directory of Open Access Journals (Sweden)

    A. Carofalo

    2014-10-01

    Full Text Available In this work, the mechanical properties of Waspaloy superalloy have been evaluated in case of welded repaired material and compared to base material. Test program considered flat specimens on base and TIG welded material subjected to static, low-cycle fatigue and creep test at different temperatures. Results of uniaxial tensile tests showed that the presence of welded material in the gage length specimen does not have a relevant influence on yield strength and UTS. However, elongation at failure of TIG material was reduced with respect to the base material. Moreover, low-cycle fatigue properties have been determined carrying out tests at different temperature (room temperature RT and 538°C in both base and TIG welded material. Welded material showed an increase of the data scatter and lower fatigue strength, which was anyway not excessive in comparison with base material. During test, all the hysteresis cycles were recorded in order to evaluate the trend of elastic modulus and hysteresis area against the number of cycles. A clear correlation between hysteresis and fatigue life was found. Finally, creep test carried out on a limited number of specimens allowed establishing some changes about the creep rate and time to failure of base and welded material. TIG welded specimen showed a lower time to reach a fixed strain or failure when a low stress level is applied. In all cases, creep behaviour of welded material is characterized by the absence of the tertiary creep.

  19. Cell cycle perturbations induced by Cisplatin in normal and tumor transformed cells

    Czech Academy of Sciences Publication Activity Database

    Mareš, Vladislav; Mazzini, G.; Lisá, Věra; Ferrari, C.; Malík, Radek; Šedo, A.

    2001-01-01

    Roč. 5, - (2001), s. 23-29 ISSN 1212-3137 Grant - others:GA UK(XC) 58/1999/C; LF UK(XC) 206019-2-"Oncology" Institutional research plan: CEZ:AV0Z5011922 Keywords : cell cycle * cisplatin * DNA content Subject RIV: FD - Oncology ; Hematology

  20. Influence of cycle number, temperature and manufacturing process on deformation-induced martensite in meta-stable austenitic stainless steels

    International Nuclear Information System (INIS)

    Kalkhof, D.; Niffenegger, M.; Grosse, M.; Bart, G.

    2002-01-01

    During cyclic loading of austenitic stainless steel, microstructural changes occur, which affect both the mechanical and the physical properties. Typical features are the rearrangement of dislocations and, in some cases, a deformation-induced martensitic phase transformation. In our investigation martensite formation was used as an indication for material degradation due to fatigue. Knowledge about mechanisms and influencing parameters of the martensitic transformation process is essential for the application in a lifetime monitoring system. The investigations showed that for a given meta-stable austenitic stainless steel the deformation-induced martensite depends on the applied strain amplitude, the cycle number (accumulated plastic strain) and the temperature. It was demonstrated that the volume fraction of martensite continuously increases with the cycle number. Therefore, martensite content could be used for indication of the fatigue usage. According to the Coffin-Manson relation the dependence of the martensite content on the cycle number could be described with a power law. The exponent was determined to be equal to 0.5 for the applied loading and temperature conditions. The influence of temperature on deformation-induced martensite was considered by means of a thermodynamic relation. Furthermore, the initial material state (initial defect density) played an important role for the martensite formation rate. Material properties and microstructures were characterised by metallography, neutron diffraction, and advanced magnetic non-destructive techniques. In order to investigate the correlation between the martensite content in the austenitic matrix and magnetic properties, the magnetic susceptibility was determined. Furthermore, a high sensitive Giant Magneto Resistant sensor was used to visualize the martensite distribution at the surface of the fatigue specimens. All applied techniques, neutron diffraction and advanced magnetic methods allowed the detection

  1. Analysis of the economic and ecological performances in the transient regimes of the European driving cycle for a midsize SUV equipped with a DHEP, using the simulation platforms

    Science.gov (United States)

    Bancă, Gheorghe; Ivan, Florian; Iozsa, Daniel; Nisulescu, Valentin

    2017-10-01

    Currently, the tendency of the car manufacturers is to continue the expansion of the global production of SUVs (Sport Utility Vehicle), while observing the requirements imposed by the new pollution standards by developing new technologies like DHEP (Diesel Hybrid Electric Powertrain). Experience has shown that the transient regimes are the most difficult to control from an economic and ecological perspective. As a result, this paper will highlight the behaviour of such engines that are provided in a middle class SUV (Sport Utility Vehicle), which operates in such states. We selected the transient regimes characteristic to the NMVEG (New Motor Vehicle Emissions Group) cycle. The investigations using the modelling platform AMESim allowed for rigorous interpretations for the 16 acceleration and 18 deceleration states. The results obtained from the simulation will be validated by experiments.

  2. Life Cycle Building Carbon Emissions Assessment and Driving Factors Decomposition Analysis Based on LMDI—A Case Study of Wuhan City in China

    Directory of Open Access Journals (Sweden)

    Yuanyuan Gong

    2015-12-01

    Full Text Available Carbon emissions calculation at the sub-provincial level has issues in limited data and non-unified measurements. This paper calculated the life cycle energy consumption and carbon emissions of the building industry in Wuhan, China. The findings showed that the proportion of carbon emissions in the construction operation phase was the largest, followed by the carbon emissions of the indirect energy consumption and the construction material preparation phase. With the purpose of analyzing the contributors of the construction carbon emissions, this paper conducted decomposition analysis using Logarithmic Mean Divisia Index (LMDI. The results indicated that the increasing buidling area was the major driver of energy consumption and carbon emissions increase, followed by the behavior factor. Population growth and urbanization, to some extent, increased the carbon emissions as well. On the contrary, energy efficiency was the main inhibitory factor for reducing the carbon emissions. Policy implications in terms of low-carbon construction development were highlighted.

  3. Very low dose and dose-rate X-ray induced adaptive response in human lymphocytes at various cell cycle stages against bleomycin induced chromatid aberrations

    International Nuclear Information System (INIS)

    Hossein Mozdarani; Moghadam, R.N.

    2007-01-01

    Complete text of publication follows. Objective: To study the adaptive response induced by very low doses of X-rays at very low dose rate in human lymphocytes at different cell cycle stages followed by a challenge dose of bleomycin sulphate at G2 phase. Materials and Methods: Human peripheral blood lymphocytes before (G0) and after PHA stimulation (G1 and G2) were exposed to 1 and 5 cGy X-rays generated by a fluoroscopy unit with a dose rate of 5.56 mGy/min and challenged with 5 μg/ml bleomycin sulphate (BLM) 48 hours after culture initiation. Mitotic cells were arrested at metaphase by addition of colcemid in cultures 1.5 h before harvesting. Harvesting and slide preparation was performed using standard method. 100 well spread metaphases were analyzed for the presence of chromatid type aberrations for each sample. Results: Results obtained indicate that there is a linear relationship between the dose of BLM and chromatid aberrations below 5 μg/ml (R=0.93, p<0.0001). The results also show that pretreatment of lymphocytes with low dose X-rays at G0, G1 and G2 phases of the cell cycle significantly reduced the sensitivity of lymphocytes to the clastogenic effects of BLM in G2. Much lower frequencies of chromatid aberrations were observed in X-ray irradiated lymphocytes following BLM treatment (p<0.05). The magnitudes of adaptation induced at different phases of the cell cycle were not significantly different. Furthermore, there was no a significant difference in the magnitude of adaptive response induced by either 1 or 5 cGy X-rays. Conclusion: These observations might indicate that resistance of pre-exposure of lymphocytes to very low doses of X-rays protects them from clastogenic effects of BLM. This effect might be due to initial DNA damage induced in these cells leading to provocation of an active DNA repair mechanism independent of cell cycle stage.

  4. Finite Element Modeling of Thermal Cycling Induced Microcracking in Carbon/Epoxy Triaxial Braided Composites

    Science.gov (United States)

    Zhang, Chao; Binienda, Wieslaw K.; Morscher, Gregory; Martin, Richard E.

    2012-01-01

    The microcrack distribution and mass change in PR520/T700s and 3502/T700s carbon/epoxy braided composites exposed to thermal cycling was evaluated experimentally. Acoustic emission was utilized to record the crack initiation and propagation under cyclic thermal loading between -55 C and 120 C. Transverse microcrack morphology was investigated using X-ray Computed Tomography. Different performance of two kinds of composites was discovered and analyzed. Based on the observations of microcrack formation, a meso-mechanical finite element model was developed to obtain the resultant mechanical properties. The simulation results exhibited a decrease in strength and stiffness with increasing crack density. Strength and stiffness reduction versus crack densities in different orientations were compared. The changes of global mechanical behavior in both axial and transverse loading conditions were studied. Keywords: Thermal cycles; Microcrack; Finite Element Model; Braided Composite

  5. Life Cycle Inventory Modelling of Land Use Induced by Crop Consumption

    DEFF Research Database (Denmark)

    Kløverpris, Jesper; Wenzel, Henrik; Nielsen, Per Henning

    2008-01-01

    The actual land use consequences of crop consumption are not very well reflected in existing life cycle inventories. The state of the art is that such inventories typically include data from crop production in the country in which the crop is produced, and consequently the inventories do...... establishment of a link between crop demand and technological development. Through this approach, life cycle inventories for crops reflecting the actual land use consequences of consumption can be established. Further work (based on the methodological framework in this study) will address the practical....... Based on the current market trend for crops and an analysis of basic mechanisms in crop production, concepts for modelling how crop consumption affects the global agricultural area and the intensity of crop production are suggested. It is demonstrated how the assumptions concerning drivers...

  6. Metabolic reprogramming of the urea cycle pathway in experimental pulmonary arterial hypertension rats induced by monocrotaline.

    Science.gov (United States)

    Zheng, Hai-Kuo; Zhao, Jun-Han; Yan, Yi; Lian, Tian-Yu; Ye, Jue; Wang, Xiao-Jian; Wang, Zhe; Jing, Zhi-Cheng; He, Yang-Yang; Yang, Ping

    2018-05-11

    Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. A single subcutaneous injection of monocrotaline (MCT) (60 mg kg - 1 ) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile.

  7. Solar Cycle Variability Induced by Tilt Angle Scatter in a Babcock-Leighton Solar Dynamo Model

    Science.gov (United States)

    Karak, Bidya Binay; Miesch, Mark

    2017-09-01

    We present results from a three-dimensional Babcock-Leighton (BL) dynamo model that is sustained by the emergence and dispersal of bipolar magnetic regions (BMRs). On average, each BMR has a systematic tilt given by Joy’s law. Randomness and nonlinearity in the BMR emergence of our model produce variable magnetic cycles. However, when we allow for a random scatter in the tilt angle to mimic the observed departures from Joy’s law, we find more variability in the magnetic cycles. We find that the observed standard deviation in Joy’s law of {σ }δ =15^\\circ produces a variability comparable to the observed solar cycle variability of ˜32%, as quantified by the sunspot number maxima between 1755 and 2008. We also find that tilt angle scatter can promote grand minima and grand maxima. The time spent in grand minima for {σ }δ =15^\\circ is somewhat less than that inferred for the Sun from cosmogenic isotopes (about 9% compared to 17%). However, when we double the tilt scatter to {σ }δ =30^\\circ , the simulation statistics are comparable to the Sun (˜18% of the time in grand minima and ˜10% in grand maxima). Though the BL mechanism is the only source of poloidal field, we find that our simulations always maintain magnetic cycles even at large fluctuations in the tilt angle. We also demonstrate that tilt quenching is a viable and efficient mechanism for dynamo saturation; a suppression of the tilt by only 1°-2° is sufficient to limit the dynamo growth. Thus, any potential observational signatures of tilt quenching in the Sun may be subtle.

  8. Glucose capped silver nanoparticles induce cell cycle arrest in HeLa cells.

    Science.gov (United States)

    Panzarini, Elisa; Mariano, Stefania; Vergallo, Cristian; Carata, Elisabetta; Fimia, Gian Maria; Mura, Francesco; Rossi, Marco; Vergaro, Viviana; Ciccarella, Giuseppe; Corazzari, Marco; Dini, Luciana

    2017-06-01

    This study aims to determine the interaction (uptake and biological effects on cell viability and cell cycle progression) of glucose capped silver nanoparticles (AgNPs-G) on human epithelioid cervix carcinoma (HeLa) cells, in relation to amount, 2×10 3 or 2×10 4 NPs/cell, and exposure time, up to 48h. The spherical and well dispersed AgNPs (30±5nm) were obtained by using glucose as reducing agent in a green synthesis method that ensures to stabilize AgNPs avoiding cytotoxic soluble silver ions Ag + release. HeLa cells take up abundantly and rapidly AgNPs-G resulting toxic to cells in amount and incubation time dependent manner. HeLa cells were arrested at S and G2/M phases of the cell cycle and subG1 population increased when incubated with 2×10 4 AgNPs-G/cell. Mitotic index decreased accordingly. The dissolution experiments demonstrated that the observed effects were due only to AgNPs-G since glucose capping prevents Ag + release. The AgNPs-G influence on HeLa cells viability and cell cycle progression suggest that AgNPs-G, alone or in combination with chemotherapeutics, may be exploited for the development of novel antiproliferative treatment in cancer therapy. However, the possible influence of the cell cycle on cellular uptake of AgNPs-G and the mechanism of AgNPs entry in cells need further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Training effects induced by cycling of magnetic field in ferromagnetic rich phase-separated nanocomposite manganites

    Energy Technology Data Exchange (ETDEWEB)

    Das, Kalipada, E-mail: kalipada.das@saha.ac.in; Das, I.

    2015-12-01

    We have carried out an experimental investigation of magneto-transport and magnetic properties of charge-ordered Pr{sub 0.67}Ca{sub 0.33}MnO{sub 3} (PCMO) and ferromagnetic La{sub 0.67}Sr{sub 0.33}MnO{sub 3} (LSMO) nanoparticles along with a nanocomposite consisting of those two types of nanoparticles. From the magneto-transport measurements, clear irreversibility is observed in the field dependence of resistance due to magnetic field cycling in the case of PCMO nanoparticles. The value of resistance increases during such a field cycling. However such an irreversibility is absent in the case of LSMO nanoparticles as well as nanocomposites. On the other hand, the magnetic measurements indicate the gradual growth of antiferromagnetic phases in all samples leading to a decrease in magnetization. These inconsistencies between magneto-transport and magnetic behaviors are attributed to the magnetic training effects. - Highlights: • The resistance value in Pr{sub 0.67}Ca{sub 0.33}MnO{sub 3} nanoparticles is found to increase owing to the magnetic field cycling. • No anomaly in resistance was found in Pr{sub 0.67}Ca{sub 0.33}MnO{sub 3}–La{sub 0.67}Sr{sub 0.33}MnO{sub 3} nanocomposite. • Magnetic measurements indicate the training effect in nanostructure compounds.

  10. Inactivity-induced respiratory plasticity: Protecting the drive to breathe in disorders that reduce respiratory neural activity☆

    Science.gov (United States)

    Strey, K.A.; Baertsch, N.A.; Baker-Herman, T.L.

    2013-01-01

    Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

  11. Driving things

    DEFF Research Database (Denmark)

    Nevile, Maurice Richard

    2015-01-01

    I explore how participants organise involvement with objects brought into the car, relative to the demands of driving and social activity. Objects in cars commonly include phones or other technologies, food, body care products, texts, clothing, bags and carry items, toys, and even animals...... 2004, Haddington et al. 2012). I focus here especially on how the practical and interactional work of locating, seeing, placing, handling, hearing, and relinquishing, is ordered and accomplished relative to the emerging and contingent demands of both driving and social participation......, such that involvement with objects is constituted as secondary to driving in a multiactivity setting (e.g. Haddington et al. 2014). We see how events with, for, of, and even by objects can occur as predictable, planned and even designed for (e.g. changing glasses, applying body lotion), or might be unexpected...

  12. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition.

    Science.gov (United States)

    Quoc Trung, Ly; Espinoza, J Luis; Takami, Akiyoshi; Nakao, Shinji

    2013-01-01

    Natural killer (NK) cell malignancies, particularly aggressive NK cell leukaemias and lymphomas, have poor prognoses. Although recent regimens with L-asparaginase substantially improved outcomes, novel therapeutic approaches are still needed to enhance clinical response. Resveratrol, a naturally occurring polyphenol, has been extensively studied for its anti-inflammatory, cardioprotective and anti-cancer activities. In this study, we investigated the potential anti-tumour activities of resveratrol against the NK cell lines KHYG-1, NKL, NK-92 and NK-YS. Resveratrol induced robust G0/G1 cell cycle arrest, significantly suppressed cell proliferation and induced apoptosis in a dose- and time-dependent manner for all four cell lines. In addition, resveratrol suppressed constitutively active STAT3 in all the cell lines and inhibited JAK2 phosphorylation but had no effect on other upstream mediators of STAT3 activation, such as PTEN, TYK2, and JAK1. Resveratrol also induced downregulation of the anti-apoptotic proteins MCL1 and survivin, two downstream effectors of the STAT3 pathway. Finally, resveratrol induced synergistic effect on the apoptotic and antiproliferative activities of L-asparaginase against KHYG-1, NKL and NK-92 cells. These results suggest that resveratrol may have therapeutic potential against NK cell malignancies. Furthermore, our finding that resveratrol is a bonafide JAK2 inhibitor extends its potential benefits to other diseases with dysregulated JAK2 signaling.

  13. Resveratrol induces cell cycle arrest and apoptosis in malignant NK cells via JAK2/STAT3 pathway inhibition.

    Directory of Open Access Journals (Sweden)

    Ly Quoc Trung

    Full Text Available Natural killer (NK cell malignancies, particularly aggressive NK cell leukaemias and lymphomas, have poor prognoses. Although recent regimens with L-asparaginase substantially improved outcomes, novel therapeutic approaches are still needed to enhance clinical response. Resveratrol, a naturally occurring polyphenol, has been extensively studied for its anti-inflammatory, cardioprotective and anti-cancer activities. In this study, we investigated the potential anti-tumour activities of resveratrol against the NK cell lines KHYG-1, NKL, NK-92 and NK-YS. Resveratrol induced robust G0/G1 cell cycle arrest, significantly suppressed cell proliferation and induced apoptosis in a dose- and time-dependent manner for all four cell lines. In addition, resveratrol suppressed constitutively active STAT3 in all the cell lines and inhibited JAK2 phosphorylation but had no effect on other upstream mediators of STAT3 activation, such as PTEN, TYK2, and JAK1. Resveratrol also induced downregulation of the anti-apoptotic proteins MCL1 and survivin, two downstream effectors of the STAT3 pathway. Finally, resveratrol induced synergistic effect on the apoptotic and antiproliferative activities of L-asparaginase against KHYG-1, NKL and NK-92 cells. These results suggest that resveratrol may have therapeutic potential against NK cell malignancies. Furthermore, our finding that resveratrol is a bonafide JAK2 inhibitor extends its potential benefits to other diseases with dysregulated JAK2 signaling.

  14. The cytotoxic effect of oxybuprocaine on human corneal epithelial cells by inducing cell cycle arrest and mitochondria-dependent apoptosis.

    Science.gov (United States)

    Fan, W-Y; Wang, D-P; Wen, Q; Fan, T-J

    2017-08-01

    Oxybuprocaine (OBPC) is a widely used topical anesthetic in eye clinic, and prolonged and repeated usage of OBPC might be cytotoxic to the cornea, especially to the outmost corneal epithelium. In this study, we characterized the cytotoxic effect of OBPC on human corneal epithelial (HCEP) cells and investigated its possible cellular and molecular mechanisms using an in vitro model of non-transfected HCEP cells. Our results showed that OBPC at concentrations ranging from 0.025% to 0.4% had a dose- and time-dependent cytotoxicity to HCEP cells. Moreover, OBPC arrested the cells at S phase and induced apoptosis of these cells by inducing plasma membrane permeability, phosphatidylserine externalization, DNA fragmentation, and apoptotic body formation. Furthermore, OBPC could trigger the activation of caspase-2, -3, and -9, downregulate the expression of Bcl-xL, upregulate the expression of Bax along with the cytoplasmic amount of mitochondria-released apoptosis-inducing factor, and disrupt mitochondrial transmembrane potential. Our results suggest that OBPC has a dose- and time-dependent cytotoxicity to HCEP cells by inducing cell cycle arrest and cell apoptosis via a death receptor-mediated mitochondria-dependent proapoptotic pathway, and this novel finding provides new insights into the acute cytotoxicity and its toxic mechanisms of OBPC on HCEP cells.

  15. Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yiting; Wu, Dan; Xia, Fengjie; Xian, Hongyu; Zhu, Xinyue [Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, Southwest University, Chongqing, 400716 (China); Huang, Zhenping, E-mail: huangzhenping19633@163.com [Medical School of Nanjing University, Department of Ophthalmology, Jinling Hospital, Nanjing, 210002 (China)

    2016-04-29

    Histone deacetylase 9 (HDAC9) is a member of class II HDACs, which regulates a wide variety of normal and abnormal physiological functions. Recently, HDAC9 has been found to be overexpressed in some types of human cancers. However, the role of HDAC9 in retinoblastoma remains unclear. In this study, we found that HDAC9 was commonly expressed in retinoblastoma tissues and HDAC9 was overexpressed in prognostically poor retinoblastoma patients. Through knocking down HDAC9 in Y79 and WERI-Rb-1 cells, the expression level of HDAC9 was found to be positively related to cell proliferation in vitro. Further investigation indicated that knockdown HDAC9 could significantly induce cell cycle arrest at G1 phase in retinoblastoma cells. Western blot assay showed downregulation of HDAC9 could significantly decrease cyclin E2 and CDK2 expression. Lastly, xenograft study in nude mice showed that downregulation of HDAC9 inhibited tumor growth and development in vivo. Therefore, our results suggest that HDAC9 could serve as a novel potential therapeutic target in the treatment of retinoblastoma. - Highlights: • High expression of HDAC9 correlates with poor patient prognosis. • Downregulation of HDAC9 inhibits cell proliferation in retinoblastoma cells. • Downregulation of HDAC9 induces cell cycle arrest at G1 phase in retinoblastoma cells. • Downregulation of HDAC9 suppresses tumor growth in nude mice.

  16. Bypass of cell cycle arrest induced by transient DNMT1 post-transcriptional silencing triggers aneuploidy in human cells

    Directory of Open Access Journals (Sweden)

    Barra Viviana

    2012-02-01

    Full Text Available Abstract Background Aneuploidy has been acknowledged as a major source of genomic instability in cancer, and it is often considered the result of chromosome segregation errors including those caused by defects in genes controlling the mitotic spindle assembly, centrosome duplication and cell-cycle checkpoints. Aneuploidy and chromosomal instability has been also correlated with epigenetic alteration, however the molecular basis of this correlation is poorly understood. Results To address the functional connection existing between epigenetic changes and aneuploidy, we used RNA-interference to silence the DNMT1 gene, encoding for a highly conserved member of the DNA methyl-transferases. DNMT1 depletion slowed down proliferation of near-diploid human tumor cells (HCT116 and triggered G1 arrest in primary human fibroblasts (IMR90, by inducing p53 stabilization and, in turn, p21waf1 transactivation. Remarkably, p53 increase was not caused by DNA damage and was not observed after p14-ARF post-transcriptional silencing. Interestingly, DNMT1 silenced cells with p53 or p14-ARF depleted did not arrest in G1 but, instead, underwent DNA hypomethylation and became aneuploid. Conclusion Our results suggest that DNMT1 depletion triggers a p14ARF/p53 dependent cell cycle arrest to counteract the aneuploidy induced by changes in DNA methylation.

  17. Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation.

    Science.gov (United States)

    He, Kangmin; Sakai, Tsuyoshi; Tsukasaki, Yoshikazu; Watanabe, Tomonobu M; Ikebe, Mitsuo

    2017-10-20

    Filopodia protrude from the leading edge of cells and play important roles in cell motility. Here we report the mechanism of myosin X (encoded by Myo10)-induced multi-cycle filopodia extension. We found that actin, Arp2/3, vinculin and integrin-β first accumulated at the cell's leading edge. Myosin X was then gathered at these sites, gradually clustered by lateral movement, and subsequently initiated filopodia formation. During filopodia extension, we found the translocation of Arp2/3 and integrin-β along filopodia. Arp2/3 and integrin-β then became localized at the tip of filopodia, from where myosin X initiated the second extension of filopodia with a change in extension direction, thus producing long filopodia. Elimination of integrin-β, Arp2/3 and vinculin by siRNA significantly attenuated the myosin-X-induced long filopodia formation. We propose the following mechanism. Myosin X accumulates at nascent focal adhesions at the cell's leading edge, where myosin X promotes actin convergence to create the base of filopodia. Then myosin X moves to the filopodia tip and attracts integrin-β and Arp2/3 for further actin nucleation. The tip-located myosin X then initiates the second cycle of filopodia elongation to produce the long filopodia.

  18. PLCζ Induced Ca2+ Oscillations in Mouse Eggs Involve a Positive Feedback Cycle of Ca2+ Induced InsP3 Formation From Cytoplasmic PIP2

    Science.gov (United States)

    Sanders, Jessica R.; Ashley, Bethany; Moon, Anna; Woolley, Thomas E.; Swann, Karl

    2018-01-01

    Egg activation at fertilization in mammalian eggs is caused by a series of transient increases in the cytosolic free Ca2+ concentration, referred to as Ca2+ oscillations. It is widely accepted that these Ca2+ oscillations are initiated by a sperm derived phospholipase C isoform, PLCζ that hydrolyses its substrate PIP2 to produce the Ca2+ releasing messenger InsP3. However, it is not clear whether PLCζ induced InsP3 formation is periodic or monotonic, and whether the PIP2 source for generating InsP3 from PLCζ is in the plasma membrane or the cytoplasm. In this study we have uncaged InsP3 at different points of the Ca2+ oscillation cycle to show that PLCζ causes Ca2+ oscillations by a mechanism which requires Ca2+ induced InsP3 formation. In contrast, incubation in Sr2+ media, which also induces Ca2+ oscillations in mouse eggs, sensitizes InsP3-induced Ca2+ release. We also show that the cytosolic level Ca2+ is a key factor in setting the frequency of Ca2+ oscillations since low concentrations of the Ca2+ pump inhibitor, thapsigargin, accelerates the frequency of PLCζ induced Ca2+ oscillations in eggs, even in Ca2+ free media. Given that Ca2+ induced InsP3 formation causes a rapid wave during each Ca2+ rise, we use a mathematical model to show that InsP3 generation, and hence PLCζ's substate PIP2, has to be finely distributed throughout the egg cytoplasm. Evidence for PIP2 distribution in vesicles throughout the egg cytoplasm is provided with a rhodamine-peptide probe, PBP10. The apparent level of PIP2 in such vesicles could be reduced by incubating eggs in the drug propranolol which also reversibly inhibited PLCζ induced, but not Sr2+ induced, Ca2+ oscillations. These data suggest that the cytosolic Ca2+ level, rather than Ca2+ store content, is a key variable in setting the pace of PLCζ induced Ca2+ oscillations in eggs, and they imply that InsP3 oscillates in synchrony with Ca2+ oscillations. Furthermore, they support the hypothesis that PLCζ and sperm

  19. SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1

    Science.gov (United States)

    Leal, Paulo C.; Bhasin, Manoj K.; Zenatti, Priscila Pini; Nunes, Ricardo J.; Yunes, Rosendo A.; Nowill, Alexandre E.; Libermann, Towia A.; Zerbini, Luiz Fernando; Yunes, José Andrés

    2015-01-01

    Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In the effort to find new anti-leukemic agents, we evaluated the small drug SB225002 (N-(2-hydroxy-4-nitrophenyl)-N’-(2-bromophenyl)urea). Although initially described as a selective antagonist of CXCR2, later studies have identified other cellular targets for SB225002, with potential medicinal use in cancer. We found that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated apoptosis triggered a transcriptional program typical of tubulin binding agents. Network analysis revealed the activation of genes linked to the JUN and p53 pathways and inhibition of genes linked to the TNF pathway. Early cellular effects activated by SB225002 included the up-regulation of GLIPR1, a p53-target gene shown to have pro-apoptotic activities in prostate and bladder cancer. Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N-Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS. Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function with concurrent activation of the p53 pathway, in particular, its downstream target GLIPR1, seems to underlie the anti-leukemic effect of SB225002. PMID:26302043

  20. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, R. Jason [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Qi, Feng [Sanford Burnham Prebys Medical Discovery Institute, Applied Bioinformatics Facility, 6400 Sanger Rd, Orlando, FL 32827 (United States); Phatak, Sharangdhar; Smith, Layton H. [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States); Malany, Siobhan, E-mail: smalany@sbpdiscovery.org [Sanford Burnham Prebys Medical Discovery Institute, Conrad Prebys Center for Chemical Genomics, 6400 Sanger Rd, Orlando, FL 32827 (United States)

    2016-08-15

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data.

  1. Fungal-induced cell cycle impairment, chromosome instability and apoptosis via differential activation of NF-κB.

    Directory of Open Access Journals (Sweden)

    Mariem Ben-Abdallah

    Full Text Available Microbial pathogens have developed efficient strategies to compromise host immune responses. Cryptococcus neoformans is a facultative intracellular pathogen, recognised as the most common cause of systemic fungal infections leading to severe meningoencephalitis, mainly in immunocompromised patients. This yeast is characterized by a polysaccharide capsule, which inhibits its phagocytosis. Whereas phagocytosis escape and macrophage intracellular survival have been intensively studied, extracellular survival of this yeast and restraint of host innate immune response are still poorly understood. In this study, we have investigated whether C. neoformans affected macrophage cell viability and whether NF-κB (nuclear factor-κB, a key regulator of cell growth, apoptosis and inflammation, was involved. Using wild-type (WT as well as mutant strains of C. neoformans for the pathogen side, and WT and mutant cell lines with altered NF-κB activity or signalling as well as primary macrophages for the host side, we show that C. neoformans manipulated NF-κB-mediated signalling in a unique way to regulate macrophage cell fate and viability. On the one hand, serotype A strains reduced macrophage proliferation in a capsule-independent fashion. This growth decrease, which required a critical dosage of NF-κB activity, was caused by cell cycle disruption and aneuploidy, relying on fungal-induced modification of expression of several cell cycle checkpoint regulators in S and G2/M phases. On the other hand, C. neoformans infection induced macrophage apoptosis in a capsule-dependent manner with a differential requirement of the classical and alternative NF-κB signalling pathways, the latter one being essential. Together, these findings shed new light on fungal strategies to subvert host response through uncoupling of NF-κB activity in pathogen-controlled apoptosis and impairment of cell cycle progression. They also provide the first demonstration of induction of

  2. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility

    International Nuclear Information System (INIS)

    Kirby, R. Jason; Qi, Feng; Phatak, Sharangdhar; Smith, Layton H.; Malany, Siobhan

    2016-01-01

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. - Highlights: • Impedance-based monitoring of human iPSC-derived cardiomyocyte contractility • Limit cycle analysis of impedance data identifies aberrant oscillation patterns. • Nonlinear autocorrelation function quantifies beat irregularity. • Identification of hERG and non-hERG inhibitors with known risk of arrhythmia • Automated software processes limit cycle and autocorrelation analyses of 96w data

  3. Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response.

    Science.gov (United States)

    Blasco-Baque, Vincent; Garidou, Lucile; Pomié, Céline; Escoula, Quentin; Loubieres, Pascale; Le Gall-David, Sandrine; Lemaitre, Mathieu; Nicolas, Simon; Klopp, Pascale; Waget, Aurélie; Azalbert, Vincent; Colom, André; Bonnaure-Mallet, Martine; Kemoun, Philippe; Serino, Matteo; Burcelin, Rémy

    2017-05-01

    To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis ( Pg ), Fusobacterium nucleatum and Prevotella intermedia . The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  4. Reactive Oxygen Species-Induced TXNIP Drives Fructose-Mediated Hepatic Inflammation and Lipid Accumulation Through NLRP3 Inflammasome Activation

    Science.gov (United States)

    Zhang, Xian; Zhang, Jian-Hua; Chen, Xu-Yang; Hu, Qing-Hua; Wang, Ming-Xing; Jin, Rui; Zhang, Qing-Yu; Wang, Wei; Wang, Rong; Kang, Lin-Lin; Li, Jin-Sheng; Li, Meng

    2015-01-01

    Abstract Aims: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. Results: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. Innovation and Conclusions: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant

  5. ALKBH7 drives a tissue and sex-specific necrotic cell death response following alkylation-induced damage

    Science.gov (United States)

    Jordan, Jennifer J; Chhim, Sophea; Margulies, Carrie M; Allocca, Mariacarmela; Bronson, Roderick T; Klungland, Arne; Samson, Leona D; Fu, Dragony

    2017-01-01

    Regulated necrosis has emerged as a major cell death mechanism in response to different forms of physiological and pharmacological stress. The AlkB homolog 7 (ALKBH7) protein is required for regulated cellular necrosis in response to chemotherapeutic alkylating agents but its role within a whole organism is unknown. Here, we show that ALKBH7 modulates alkylation-induced cellular death through a tissue and sex-specific mechanism. At the whole-animal level, we find that ALKBH7 deficiency confers increased resistance to MMS-induced toxicity in male but not female mice. Moreover, ALKBH7-deficient mice exhibit protection against alkylation-mediated cytotoxicity in retinal photoreceptor and cerebellar granule cells, two cell types that undergo necrotic death through the initiation of the base excision repair pathway and hyperactivation of the PARP1/ARTD1 enzyme. Notably, the protection against alkylation-induced cerebellar degeneration is specific to ALKBH7-deficient male but not female mice. Our results uncover an in vivo role for ALKBH7 in mediating a sexually dimorphic tissue response to alkylation damage that could influence individual responses to chemotherapies based upon alkylating agents. PMID:28726787

  6. Calculation of the driving force for the radiation induced precipitation of Ni3Si in nickel-silicon alloys

    International Nuclear Information System (INIS)

    Miodownik, A.P.; Watkin, J.S.

    1979-01-01

    The appearance of precipitates which have been identified as Ni 3 Si in irradiated stainless steels and nickel rich alloys such as Inconel is of considerable interest in relation to the swelling behaviour of such materials. Work on binary nickel-silicon alloys has shown that Ni 3 Si can be induced to precipitate in alloys whose silicon content is well below the accepted solubility limit, and it has also been shown that such precipitates redissolve when heat-treatment is continued at the same temperature in the absence of irradiation. Such effects imply an irradiation induced shift of chemical potential, and cannot be explained by merely involving accelerated diffusion. This paper represents an attempt to calculate the shift in chemical potential required to precipitate Ni 3 Si in alloys containing 1-10% Si (at%) over a range of temperatures (300-1000K), and then proceeds to relate this calculated chemical potential with available information concerning the dose rates required to induce such precipitates at various temperatures. Presentation of the results is modelled on the well established methods for handling the Time-Temperature-Transformation behaviour of ordinary alloy systems, with dose rate being substituted for the time axis. Analogous calculations are presented for nickel-germanium alloys, in order to check whether the numerical values deduced from the nickel silicon system have more general applicability, and also to see whether there are any significant differences in a system where the size factor of the solute is of the opposite sign. (orig.) [de

  7. Prolonged mechanical ventilation induces cell cycle arrest in newborn rat lung.

    Directory of Open Access Journals (Sweden)

    Andreas A Kroon

    Full Text Available RATIONALE: The molecular mechanism(s by which mechanical ventilation disrupts alveolar development, a hallmark of bronchopulmonary dysplasia, is unknown. OBJECTIVE: To determine the effect of 24 h of mechanical ventilation on lung cell cycle regulators, cell proliferation and alveolar formation in newborn rats. METHODS: Seven-day old rats were ventilated with room air for 8, 12 and 24 h using relatively moderate tidal volumes (8.5 mL.kg⁻¹. MEASUREMENT AND MAIN RESULTS: Ventilation for 24 h (h decreased the number of elastin-positive secondary crests and increased the mean linear intercept, indicating arrest of alveolar development. Proliferation (assessed by BrdU incorporation was halved after 12 h of ventilation and completely arrested after 24 h. Cyclin D1 and E1 mRNA and protein levels were decreased after 8-24 h of ventilation, while that of p27(Kip1 was significantly increased. Mechanical ventilation for 24 h also increased levels of p57(Kip2, decreased that of p16(INK4a, while the levels of p21(Waf/Cip1 and p15(INK4b were unchanged. Increased p27(Kip1 expression coincided with reduced phosphorylation of p27(Kip1 at Thr¹⁵⁷, Thr¹⁸⁷ and Thr¹⁹⁸ (p<0.05, thereby promoting its nuclear localization. Similar -but more rapid- changes in cell cycle regulators were noted when 7-day rats were ventilated with high tidal volume (40 mL.kg⁻¹ and when fetal lung epithelial cells were subjected to a continuous (17% elongation cyclic stretch. CONCLUSION: This is the first demonstration that prolonged (24 h of mechanical ventilation causes cell cycle arrest in newborn rat lungs; the arrest occurs in G₁ and is caused by increased expression and nuclear localization of Cdk inhibitor proteins (p27(Kip1, p57(Kip2 from the Kip family.

  8. Cell cycle arrest and cell survival induce reverse trends of cardiolipin remodeling.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chao

    Full Text Available Cell survival from the arrested state can be a cause of the cancer recurrence. Transition from the arrest state to the growth state is highly regulated by mitochondrial activity, which is related to the lipid compositions of the mitochondrial membrane. Cardiolipin is a critical phospholipid for the mitochondrial integrity and functions. We examined the changes of cardiolipin species by LC-MS in the transition between cell cycle arrest and cell reviving in HT1080 fibrosarcoma cells. We have identified 41 cardiolipin species by MS/MS and semi-quantitated them to analyze the detailed changes of cardiolipin species. The mass spectra of cardiolipin with the same carbon number form an envelope, and the C64, C66, C68, C70 C72 and C74 envelopes in HT1080 cells show a normal distribution in the full scan mass spectrum. The cardiolipin quantity in a cell decreases while entering the cell cycle arrest, but maintains at a similar level through cell survival. While cells awakening from the arrested state and preparing itself for replication, the groups with short acyl chains, such as C64, C66 and C68 show a decrease of cardiolipin percentage, but the groups with long acyl chains, such as C70 and C72 display an increase of cardiolipin percentage. Interestingly, the trends of the cardiolipin species changes during the arresting state are completely opposite to cell growing state. Our results indicate that the cardiolipin species shift from the short chain to long chain cardiolipin during the transition from cell cycle arrest to cell progression.

  9. Phospho-Rb mediating cell cycle reentry induces early apoptosis following oxygen-glucose deprivation in rat cortical neurons.

    Science.gov (United States)

    Yu, Ying; Ren, Qing-Guo; Zhang, Zhao-Hui; Zhou, Ke; Yu, Zhi-Yuan; Luo, Xiang; Wang, Wei

    2012-03-01

    The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons following oxygen-glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and pharmacological interventions for neuroprotection may be useful directed at this keypoint.

  10. Application of Nuclear Volume Measurements to Comprehend the Cell Cycle in Root-Knot Nematode-Induced Giant Cells

    Directory of Open Access Journals (Sweden)

    José Dijair Antonino de Souza Junior

    2017-06-01

    Full Text Available Root-knot nematodes induce galls that contain giant-feeding cells harboring multiple enlarged nuclei within the roots of host plants. It is recognized that the cell cycle plays an essential role in the set-up of a peculiar nuclear organization that seemingly steers nematode feeding site induction and development. Functional studies of a large set of cell cycle genes in transgenic lines of the model host Arabidopsis thaliana have contributed to better understand the role of the cell cycle components and their implication in the establishment of functional galls. Mitotic activity mainly occurs during the initial stages of gall development and is followed by an intense endoreduplication phase imperative to produce giant-feeding cells, essential to form vigorous galls. Transgenic lines overexpressing particular cell cycle genes can provoke severe nuclei phenotype changes mainly at later stages of feeding site development. This can result in chaotic nuclear phenotypes affecting their volume. These aberrant nuclear organizations are hampering gall development and nematode maturation. Herein we report on two nuclear volume assessment methods which provide information on the complex changes occurring in nuclei during giant cell development. Although we observed that the data obtained with AMIRA tend to be more detailed than Volumest (Image J, both approaches proved to be highly versatile, allowing to access 3D morphological changes in nuclei of complex tissues and organs. The protocol presented here is based on standard confocal optical sectioning and 3-D image analysis and can be applied to study any volume and shape of cellular organelles in various complex biological specimens. Our results suggest that an increase in giant cell nuclear volume is not solely linked to increasing ploidy levels, but might result from the accumulation of mitotic defects.

  11. Cardiovascular and ventilatory responses to electrically induced cycling with complete epidural anaesthesia in humans

    DEFF Research Database (Denmark)

    Kjaer, M; Perko, G; Secher, N H

    1994-01-01

    Cardiovascular and ventilatory responses to electrically induced dynamic exercise were investigated in eight healthy young males with afferent neural influence from the legs blocked by epidural anaesthesia (25 ml 2% lidocaine) at L3-L4. This caused cutaneous sensory anaesthesia below T8-T9 and co...

  12. Globally important nitrous oxide emissions from croplands induced by freeze-thaw cycles

    NARCIS (Netherlands)

    Wagner-Riddle, Claudia; Congreves, Katelyn A.; Abalos Rodriguez, Diego; Berg, Aaron A.; Brown, Shannon E.; Ambadan, Jaison Thomas; Gao, Xiaopeng; Tenuta, Mario

    2017-01-01

    Seasonal freezing induces large thaw emissions of nitrous oxide, a trace gas that contributes to stratospheric ozone destruction and atmospheric warming. Cropland soils are by far the largest anthropogenic source of nitrous oxide. However, the global contribution of seasonal freezing to nitrous

  13. Knockdown of human deubiquitinase PSMD14 induces cell cycle arrest and senescence

    Energy Technology Data Exchange (ETDEWEB)

    Byrne, Ann; McLaren, Rajashree P.; Mason, Paul; Chai, Lilly; Dufault, Michael R.; Huang, Yinyin; Liang, Beirong; Gans, Joseph D.; Zhang, Mindy; Carter, Kara; Gladysheva, Tatiana B.; Teicher, Beverly A.; Biemann, Hans-Peter N.; Booker, Michael; Goldberg, Mark A.; Klinger, Katherine W.; Lillie, James [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Madden, Stephen L., E-mail: steve.madden@genzyme.com [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States); Jiang, Yide, E-mail: yide.jiang@genzyme.com [Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701 (United States)

    2010-01-15

    The PSMD14 (POH1, also known as Rpn11/MPR1/S13/CepP1) protein within the 19S complex (19S cap; PA700) is responsible for substrate deubiquitination during proteasomal degradation. The role of PSMD14 in cell proliferation and senescence was explored using siRNA knockdown in carcinoma cell lines. Our results reveal that down-regulation of PSMD14 by siRNA transfection had a considerable impact on cell viability causing cell arrest in the G0-G1 phase, ultimately leading to senescence. The molecular events associated with decreased cell proliferation, cell cycle arrest and senescence include down-regulation of cyclin B1-CDK1-CDC25C, down-regulation of cyclin D1 and up-regulation of p21{sup /Cip} and p27{sup /Kip1}. Most notably, phosphorylation of the retinoblastoma protein was markedly reduced in PSMD14 knockdown cells. A comparative study with PSMB5, a subunit of the 20S proteasome, revealed that PSMB5 and PSMD14 have different effects on cell cycle, senescence and associated molecular events. These data support the view that the 19S and 20S subunits of the proteasome have distinct biological functions and imply that targeting 19S and 20S would have distinct molecular consequences on tumor cells.

  14. Activation of PPARγ mediates icaritin-induced cell cycle arrest and apoptosis in glioblastoma multiforme.

    Science.gov (United States)

    Liu, Yongji; Shi, Ling; Liu, Yuan; Li, Peng; Jiang, Guoping; Gao, Xiaoning; Zhang, Yongbin; Jiang, Chuanwu; Zhu, Weiping; Han, Hongxing; Ju, Fang

    2018-04-01

    Glioblastoma multiforme (GBM) is the most prevalent primary malignancy of the brain. This study was designed to investigate whether icaritin exerts anti-neoplastic activity against GBM in vitro. Cell Counting Kit-8 (CCK-8) assay was utilized to examine the viability of GBM cells. The apoptotic cell population was measured by flow cytometry analysis. Cell cycle distribution was detected by flow cytometry as well. Western blot analysis was performed to examine the level of biomarker proteins in GBM cells. Levels of PPARγ mRNA and protein were detected by qPCR and western blot analysis, respectively. To examine the role of PPARγ in the anti-neoplastic activity of icaritin, PPARγ antagonist GW9662 or PPARγ siRNA was used. The activity of PPARγ was determined by DNA binding and luciferase assays. Our findings revealed that icaritin markedly suppresses cell growth in a dose-dependent and time-dependent fashion. The cell population at the G0/G1 phase of the cell cycle was significantly increased following icaritin treatment. Meanwhile, icaritin promoted apoptotic cell death in T98G and U87MG cells. Further investigation showed upregulation of PPARγ played a key role in the anti-neoplastic activities of icaritin. Moreover, our result demonstrated activation of AMPK signaling by icaritin mediated the modulatory effect of icaritin on PPARγ. Our results suggest the PPARγ may mediate anti-neoplastic activities against GBM. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  15. Supercritical carbon dioxide extract of Physalis peruviana induced cell cycle arrest and apoptosis in human lung cancer H661 cells.

    Science.gov (United States)

    Wu, Shu-Jing; Chang, Shun-Pang; Lin, Doung-Liang; Wang, Shyh-Shyan; Hou, Fwu-Feuu; Ng, Lean-Teik

    2009-06-01

    Physalis peruviana L. (PP) is a popular folk medicine used for treating cancer, leukemia, hepatitis, rheumatism and other diseases. In this study, our objectives were to examine the total flavonoid and phenol content of different PP extracts (aqueous: HWEPP; ethanolic: EEPP; supercritical carbon dioxide: SCEPP-0, SCEPP-4 and SCEPP-5) and their antiproliferative effects in human lung cancer H661 cells. Among all the extracts tested, results showed that SCEPP-5 possessed the highest total flavonoid (226.19 +/- 4.15 mg/g) and phenol (100.82 +/- 6.25 mg/g) contents. SCEPP-5 also demonstrated the most potent inhibitory effect on H661 cell proliferation. Using DNA ladder and flow cytometry analysis, SCEPP-5 effectively induced H661 cell apoptosis as demonstrated by the accumulation of Sub-G1 peak and fragmentation of DNA. SCEPP-5 not only induced cell cycle arrest at S phase, it also up-regulated the expression of pro-apoptotic protein (Bax) and down-regulated the inhibitor of apoptosis protein (IAP). Furthermore, the apoptotic induction in H661 cells was found to associate with an elevated p53 protein expression, cytochrome c release, caspase-3 activation and PARP cleavage. Taken together, these results conclude that SCEPP-5 induced cell cycle arrest at S phase, and its apoptotic induction could be mediated through the p53-dependent pathway and modification of Bax and XIAP proteins expression. The results have also provided important pharmacological backgrounds for the potential use of PP supercritical fluid extract as products for cancer prevention.

  16. Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?

    Directory of Open Access Journals (Sweden)

    Nadine Schuler

    Full Text Available Accumulation of DNA damage leading to stem cell exhaustion has been proposed to be a principal mechanism of aging. Using 53BP1-foci as a marker for DNA double-strand breaks (DSBs, hair follicle stem cells (HFSCs in mouse epidermis were analyzed for age-related DNA damage response (DDR. We observed increasing amounts of 53BP1-foci during the natural aging process independent of telomere shortening and after protracted low-dose radiation, suggesting substantial accumulation of DSBs in HFSCs. Electron microscopy combined with immunogold-labeling showed multiple small 53BP1 clusters diffusely distributed throughout the highly compacted heterochromatin of aged HFSCs, but single large 53BP1 clusters in irradiated HFSCs. These remaining 53BP1 clusters did not colocalize with core components of non-homologous end-joining, but with heterochromatic histone modifications. Based on these results we hypothesize that these lesions were not persistently unrepaired DSBs, but may reflect chromatin rearrangements caused by the repair or misrepair of DSBs. Flow cytometry showed increased activation of repair proteins and damage-induced chromatin modifications, triggering apoptosis and cellular senescence in irradiated, but not in aged HFSCs. These results suggest that accumulation of DNA damage-induced chromatin alterations, whose structural dimensions reflect the complexity of the initial genotoxic insult, may lead to different DDR events, ultimately determining the biological outcome of HFSCs. Collectively, our findings support the hypothesis that aging might be largely the remit of structural changes to chromatin potentially leading to epigenetically induced transcriptional deregulation.

  17. Platelet activating factor-induced ceramide micro-domains drive endothelial NOS activation and contribute to barrier dysfunction.

    Directory of Open Access Journals (Sweden)

    Sanda Predescu

    Full Text Available The spatial and functional relationship between platelet activating factor-receptor (PAF-R and nitric oxide synthase (eNOS in the lateral plane of the endothelial plasma membrane is poorly characterized. In this study, we used intact mouse pulmonary endothelial cells (ECs as well as endothelial plasma membrane patches and subcellular fractions to define a new microdomain of plasmalemma proper where the two proteins colocalize and to demonstrate how PAF-mediated nitric oxide (NO production fine-tunes ECs function as gatekeepers of vascular permeability. Using fluorescence microscopy and immunogold labeling electron microscopy (EM on membrane patches we demonstrate that PAF-R is organized as clusters and colocalizes with a subcellular pool of eNOS, outside recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase activation generates a ceramide-based microdomain on the external leaflet of plasma membrane, inside of which a signalosome containing eNOS shapes PAF-stimulated NO production. Real-time measurements of NO after PAF-R ligation indicated a rapid (5 to 15 min increase in NO production followed by a > 45 min period of reduction to basal levels. Moreover, at the level of this new microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr and Tyr residues of eNOS that correlates with NO production. Altogether, our findings establish the existence of a functional partnership PAF-R/eNOS on EC plasma membrane, at the level of PAF-induced ceramide plasma membrane microdomains, outside recognized vesicular profiles.

  18. microRNA Alterations Driving Acute and Late Stages of Radiation-Induced Fibrosis in a Murine Skin Model

    Energy Technology Data Exchange (ETDEWEB)

    Simone, Brittany A. [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Ly, David; Savage, Jason E. [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Hewitt, Stephen M. [Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Dan, Tu D. [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Ylaya, Kris [Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Shankavaram, Uma [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Lim, Meng; Jin, Lianjin [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Camphausen, Kevin [Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Mitchell, James B. [Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Simone, Nicole L., E-mail: nicole.simone@jeffersonhospital.org [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States)

    2014-09-01

    Purpose: Although ionizing radiation is critical in treating cancer, radiation-induced fibrosis (RIF) can have a devastating impact on patients' quality of life. The molecular changes leading to radiation-induced fibrosis must be elucidated so that novel treatments can be designed. Methods and Materials: To determine whether microRNAs (miRs) could be responsible for RIF, the fibrotic process was induced in the right hind legs of 9-week old CH3 mice by a single-fraction dose of irradiation to 35 Gy, and the left leg served as an unirradiated control. Fibrosis was quantified by measurements of leg length compared with control leg length. By 120 days after irradiation, the irradiated legs were 20% (P=.013) shorter on average than were the control legs. Results: Tissue analysis was done on muscle, skin, and subcutaneous tissue from irradiated and control legs. Fibrosis was noted on both gross and histologic examination by use of a pentachrome stain. Microarrays were performed at various times after irradiation, including 7 days, 14 days, 50 days, 90 days, and 120 days after irradiation. miR-15a, miR-21, miR-30a, and miR-34a were the miRs with the most significant alteration by array with miR-34a, proving most significant on confirmation by reverse transcriptase polymerase chain reaction, c-Met, a known effector of fibrosis and downstream molecule of miR-34a, was evaluated by use of 2 cell lines: HCT116 and 1522. The cell lines were exposed to various stressors to induce miR changes, specifically ionizing radiation. Additionally, in vitro transfections with pre-miRs and anti-miRs confirmed the relationship of miR-34a and c-Met. Conclusions: Our data demonstrate an inverse relationship with miR-34a and c-Met; the upregulation of miR-34a in RIF causes inhibition of c-Met production. miRs may play a role in RIF; in particular, miR-34a should be investigated as a potential target to prevent or treat this devastating side effect of irradiation.

  19. Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

    Science.gov (United States)

    Hultman, Rainbo; Mague, Stephen D; Li, Qiang; Katz, Brittany M; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D; Dzirasa, Kafui

    2016-07-20

    Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Senp1 drives hypoxia-induced polycythemia via GATA1 and Bcl-xL in subjects with Monge's disease.

    Science.gov (United States)

    Azad, Priti; Zhao, Huiwen W; Cabrales, Pedro J; Ronen, Roy; Zhou, Dan; Poulsen, Orit; Appenzeller, Otto; Hsiao, Yu Hsin; Bafna, Vineet; Haddad, Gabriel G

    2016-11-14

    In this study, because excessive polycythemia is a predominant trait in some high-altitude dwellers (chronic mountain sickness [CMS] or Monge's disease) but not others living at the same altitude in the Andes, we took advantage of this human experiment of nature and used a combination of induced pluripotent stem cell technology, genomics, and molecular biology in this unique population to understand the molecular basis for hypoxia-induced excessive polycythemia. As compared with sea-level controls and non-CMS subjects who responded to hypoxia by increasing their RBCs modestly or not at all, respectively, CMS cells increased theirs remarkably (up to 60-fold). Although there was a switch from fetal to adult HgbA0 in all populations and a concomitant shift in oxygen binding, we found that CMS cells matured faster and had a higher efficiency and proliferative potential than non-CMS cells. We also established that SENP1 plays a critical role in the differential erythropoietic response of CMS and non-CMS subjects: we can convert the CMS phenotype into that of non-CMS and vice versa by altering SENP1 levels. We also demonstrated that GATA1 is an essential downstream target of SENP1 and that the differential expression and response of GATA1 and Bcl-xL are a key mechanism underlying CMS pathology. © 2016 Azad et al.

  1. The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity

    OpenAIRE

    Rauckhorst, Adam J.; Gray, Lawrence R.; Sheldon, Ryan D.; Fu, Xiaorong; Pewa, Alvin D.; Feddersen, Charlotte R.; Dupuy, Adam J.; Gibson-Corley, Katherine N.; Cox, James E.; Burgess, Shawn C.; Taylor, Eric B.

    2017-01-01

    Objective: Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. T...

  2. NBPF1, a tumor suppressor candidate in neuroblastoma, exerts growth inhibitory effects by inducing a G1 cell cycle arrest

    International Nuclear Information System (INIS)

    Andries, Vanessa; Vandepoele, Karl; Staes, Katrien; Berx, Geert; Bogaert, Pieter; Van Isterdael, Gert; Ginneberge, Daisy; Parthoens, Eef; Vandenbussche, Jonathan; Gevaert, Kris; Roy, Frans van

    2015-01-01

    NBPF1 (Neuroblastoma Breakpoint Family, member 1) was originally identified in a neuroblastoma patient on the basis of its disruption by a chromosomal translocation t(1;17)(p36.2;q11.2). Considering this genetic defect and the frequent genomic alterations of the NBPF1 locus in several cancer types, we hypothesized that NBPF1 is a tumor suppressor. Decreased expression of NBPF1 in neuroblastoma cell lines with loss of 1p36 heterozygosity and the marked decrease of anchorage-independent clonal growth of DLD1 colorectal carcinoma cells with induced NBPF1 expression further suggest that NBPF1 functions as tumor suppressor. However, little is known about the mechanisms involved. Expression of NBPF was analyzed in human skin and human cervix by immunohistochemistry. The effects of NBPF1 on the cell cycle were evaluated by flow cytometry. We investigated by real-time quantitative RT-PCR the expression profile of a panel of genes important in cell cycle regulation. Protein levels of CDKN1A-encoded p21 CIP1/WAF1 were determined by western blotting and the importance of p53 was shown by immunofluorescence and by a loss-of-function approach. LC-MS/MS analysis was used to investigate the proteome of DLD1 colon cancer cells with induced NBPF1 expression. Possible biological interactions between the differentially regulated proteins were investigated with the Ingenuity Pathway Analysis tool. We show that NBPF is expressed in the non-proliferative suprabasal layers of squamous stratified epithelia of human skin and cervix. Forced expression of NBPF1 in HEK293T cells resulted in a G1 cell cycle arrest that was accompanied by upregulation of the cyclin-dependent kinase inhibitor p21 CIP1/WAF1 in a p53-dependent manner. Additionally, forced expression of NBPF1 in two p53-mutant neuroblastoma cell lines also resulted in a G1 cell cycle arrest and CDKN1A upregulation. However, CDKN1A upregulation by NBPF1 was not observed in the DLD1 cells, which demonstrates that NBPF1 exerts cell

  3. Network-induced oscillatory behavior in material flow networks and irregular business cycles

    Science.gov (United States)

    Helbing, Dirk; Lämmer, Stefen; Witt, Ulrich; Brenner, Thomas

    2004-11-01

    Network theory is rapidly changing our understanding of complex systems, but the relevance of topological features for the dynamic behavior of metabolic networks, food webs, production systems, information networks, or cascade failures of power grids remains to be explored. Based on a simple model of supply networks, we offer an interpretation of instabilities and oscillations observed in biological, ecological, economic, and engineering systems. We find that most supply networks display damped oscillations, even when their units—and linear chains of these units—behave in a nonoscillatory way. Moreover, networks of damped oscillators tend to produce growing oscillations. This surprising behavior offers, for example, a different interpretation of business cycles and of oscillating or pulsating processes. The network structure of material flows itself turns out to be a source of instability, and cyclical variations are an inherent feature of decentralized adjustments.

  4. Boletus edulis biologically active biopolymers induce cell cycle arrest in human colon adenocarcinoma cells.

    Science.gov (United States)

    Lemieszek, Marta Kinga; Cardoso, Claudia; Ferreira Milheiro Nunes, Fernando Hermínio; Ramos Novo Amorim de Barros, Ana Isabel; Marques, Guilhermina; Pożarowski, Piotr; Rzeski, Wojciech

    2013-04-25

    The use of biologically active compounds isolated from edible mushrooms against cancer raises global interest. Anticancer properties are mainly attributed to biopolymers including mainly polysaccharides, polysaccharopeptides, polysaccharide proteins, glycoproteins and proteins. In spite of the fact that Boletus edulis is one of the widely occurring and most consumed edible mushrooms, antitumor biopolymers isolated from it have not been exactly defined and studied so far. The present study is an attempt to extend this knowledge on molecular mechanisms of their anticancer action. The mushroom biopolymers (polysaccharides and glycoproteins) were extracted with hot water and purified by anion-exchange chromatography. The antiproliferative activity in human colon adenocarcinoma cells (LS180) was screened by means of MTT and BrdU assays. At the same time fractions' cytotoxicity was examined on the human colon epithelial cells (CCD 841 CoTr) by means of the LDH assay. Flow cytometry and Western blotting were applied to cell cycle analysis and protein expression involved in anticancer activity of the selected biopolymer fraction. In vitro studies have shown that fractions isolated from Boletus edulis were not toxic against normal colon epithelial cells and in the same concentration range elicited a very prominent antiproliferative effect in colon cancer cells. The best results were obtained in the case of the fraction designated as BE3. The tested compound inhibited cancer cell proliferation which was accompanied by cell cycle arrest in the G0/G1-phase. Growth inhibition was associated with modulation of the p16/cyclin D1/CDK4-6/pRb pathway, an aberration of which is a critical step in the development of many human cancers including colon cancer. Our results indicate that a biopolymer BE3 from Boletus edulis possesses anticancer potential and may provide a new therapeutic/preventive option in colon cancer chemoprevention.

  5. Feedback of mechanical effectiveness induces adaptations in motor modules during cycling

    Science.gov (United States)

    De Marchis, Cristiano; Schmid, Maurizio; Bibbo, Daniele; Castronovo, Anna Margherita; D'Alessio, Tommaso; Conforto, Silvia

    2013-01-01

    Recent studies have reported evidence that the motor system may rely on a modular organization, even if this behavior has yet to be confirmed during motor adaptation. The aim of the present study is to investigate the modular motor control mechanisms underlying the execution of pedaling by untrained subjects in different biomechanical conditions. We use the muscle synergies framework to characterize the muscle coordination of 11 subjects pedaling under two different conditions. The first one consists of a pedaling exercise with a strategy freely chosen by the subjects (Preferred Pedaling Technique, PPT), while the second condition constrains the gesture by means of a real time visual feedback of mechanical effectiveness (Effective Pedaling Technique, EPT). Pedal forces, recorded using a pair of instrumented pedals, were used to calculate the Index of Effectiveness (IE). EMG signals were recorded from eight muscles of the dominant leg and Non-negative Matrix Factorization (NMF) was applied for the extraction of muscle synergies. All the synergy vectors, extracted cycle by cycle for each subject, were pooled across subjects and conditions and underwent a 2-dimensional Sammon's non-linear mapping. Seven representative clusters were identified on the Sammon's projection, and the corresponding eight-dimensional synergy vectors were used to reconstruct the repertoire of muscle activation for all subjects and all pedaling conditions (VAF > 0.8 for each individual muscle pattern). Only 5 out of the 7 identified modules were used by the subjects during the PPT pedaling condition, while 2 additional modules were found specific for the pedaling condition EPT. The temporal recruitment of three identified modules was highly correlated with IE. The structure of the identified modules was found similar to that extracted in other studies of human walking, partly confirming the existence of shared and task specific muscle synergies, and providing further evidence on the modularity

  6. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

    Directory of Open Access Journals (Sweden)

    Natalia Bailon-Moscoso

    Full Text Available Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL, a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

  7. Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

    Science.gov (United States)

    Bailon-Moscoso, Natalia; González-Arévalo, Gabriela; Velásquez-Rojas, Gabriela; Malagon, Omar; Vidari, Giovanni; Zentella-Dehesa, Alejandro; Ratovitski, Edward A; Ostrosky-Wegman, Patricia

    2015-01-01

    Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

  8. Securinine from Phyllanthus glaucus Induces Cell Cycle Arrest and Apoptosis in Human Cervical Cancer HeLa Cells.

    Directory of Open Access Journals (Sweden)

    Justyna Stefanowicz-Hajduk

    Full Text Available The Securinega-type alkaloids occur in plants belonging to Euphorbiaceae family. One of the most widely distributed alkaloid of this group is securinine, which was identified next to allosecurinine in Phyllanthus glaucus (leafflower. Recently, some Securinega-type alkaloids have paid attention to its antiproliferative potency towards different cancer cells. However, the cytotoxic properties of allosecurinine have not yet been evaluated.The cytotoxicity of the extract, alkaloid fraction obtained from P. glaucus, isolated securinine and allosecurinine against HeLa cells was evaluated by real-time xCELLigence system and 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Apoptosis was detected by annexin V and 7-amino-actinomycin (7-AAD staining and confirmed with fluorescent Hoechst 33342 dye. The assessment of mitochondrial membrane potential (MMP, reactive oxygen species (ROS generation, the level of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2, caspase-3/7 activity and cell cycle analysis were measured by flow cytometry. The enzymatic activity of caspase-9 was assessed by a luminometric assay. The expression of apoptosis associated genes was analyzed by real-time PCR.The experimental data revealed that securinine and the alkaloid fraction were significantly potent on HeLa cells growth inhibition with IC50 values of 7.02 ± 0.52 μg/ml (32.3 μM and 25.46 ± 1.79 μg/ml, respectively. The activity of allosecurinine and Phyllanthus extract were much lower. Furthermore, our study showed that the most active securinine induced apoptosis in a dose-dependent manner in the tested cells, increased the percentage of ROS positive cells and depolarized cells as well as stimulated the activity of ERK1/2, caspase-9 and -3/7. Securinine also induced cell cycle arrest in S phase. Real-time PCR analysis showed high expression of TNFRSF genes in the cells stimulated with securinine.Securinine induces apoptosis and activates

  9. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Li-Wen [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hsieh, Bau-Shan; Cheng, Hsiao-Ling [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hu, Yu-Chen [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Chang, Wen-Tsan [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Division of Hepatobiliarypancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan (China); Chang, Kee-Lung, E-mail: Chang.KeeLung@msa.hinet.net [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M

  10. Community Drive

    DEFF Research Database (Denmark)

    Magnussen, Rikke

    2018-01-01

    Schools and educational institutions are challenged by not adequately educating students for independent knowledge collaboration and solving of complex societal challenges (Bundsgaard & Hansen, 2016; Slot et al., 2017). As an alternative strategy to formal learning has Community-driven research...... opportunity to break boundaries between research institutions and surrounding communities through the involvement of new types of actors, knowledge forms and institutions (OECD, 2011). This paper presents the project Community Drive a three year cross disciplinary community-driven game– and data-based project....... In the paper we present how the project Community Drive initiated in May 2018 is based on results from pilot projects conducted from 2014 – 2017. Overall these studies showed that it is a strong motivational factor for students to be given the task to change their living conditions through redesign...

  11. Boron neutron capture therapy induces cell cycle arrest and DNA fragmentation in murine melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Faiao-Flores, F. [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)] [Faculty of Medicine, University of Sao Paulo, 455 Doutor Arnaldo Avenue, Sao Paulo (Brazil); Coelho, P.R.P. [Institute for Nuclear and Energy Research, 2242 Lineu Prestes Avenue, Sao Paulo (Brazil); Arruda-Neto, J. [Physics Institute, University of Sao Paulo, 187 Matao Street, Sao Paulo (Brazil)] [FESP, Sao Paulo Engineering School, 5520 Nove de Julho Avenue, Sao Paulo (Brazil); Maria, Durvanei A., E-mail: durvaneiaugusto@yahoo.br [Biochemical and Biophysical Laboratory, Butantan Institute, 1500 Vital Brasil Avenue, Sao Paulo (Brazil)

    2011-12-15

    The melanoma is a highly lethal skin tumor, with a high incidence. Boron Neutron Capture Therapy (BNCT) is a radiotherapy which combines Boron with thermal neutrons, constituting a binary system. B16F10 melanoma and L929 fibroblasts were treated with Boronophenylalanine and irradiated with thermal neutron flux. The electric potential of mitochondrial membrane, cyclin D1 and caspase-3 markers were analyzed. BNCT induced a cell death increase and cyclin D1 amount decreased only in B16F10 melanoma. Besides, there was not caspase-3 phosphorylation.

  12. Agricultural induced impacts on soil carbon cycling and sequestration in a seasonally saturated wetland

    Science.gov (United States)

    Maynard, J. J.; O'Geen, A. T.; Dahlgren, R. A.

    2011-06-01

    The fate of organic carbon (C) lost by erosion is not well understood in agricultural settings. Recent models suggest that wetlands and other small water bodies may serve as important long-term sinks of eroded C, receiving ~30 % of all eroded material in the US. To better understand the role of seasonally-saturated wetlands in sequestering eroded C, we examined the spatial and temporal dynamics of C and sediment accumulation in a 13-yr-old constructed wetland used to treat agricultural runoff. The fate of C sequestered within deposited sediment was modeled using point-sampling, remote sensing, and geostatistics. Using a spatially-explicit sampling design, annual net rates of sedimentation and above ground biomass were measured during two contrasting years (vegetated, 2004 vs. non-vegetated, 2005), followed by collection of sediment cores to the antecedent soil layer, representing 13 yr of sediment and C accumulation. We documented high annual variation in the relative contribution of endogenous and exogenous C sources, as well as absolute rates of sediment and C deposition. This annual variation, however, was muted in the long-term (13-yr) sediment record, which showed consistent vertical patterns of uniform C distribution (~14 g kg-1) and δ13C signatures in high depositional environments. This was in contrast to low depositional environments which had high levels of surface C enrichment (20-35 g kg-1) underlain by C depleted (5-10 g kg-1) sediments and an increasing δ13C signature with depth indicating increasing decomposition. These results highlight the importance of sedimentation in physically protecting soil organic carbon and its role in controlling the long-term C concentration of seasonally-saturated wetland soils. While significant enrichment of surface sediments with endogenous C occurred in newly deposited sediment (i.e., 125 kg m2 in 2004), fluctuating cycles of flooding and drying maintained the long-term C concentration at the same level as

  13. Life cycle energy and greenhouse gas emission effects of biodiesel in the United States with induced land use change impacts

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Rui; Qin, Zhangcai; Han, Jeongwoo; Wang, Michael; Taheripour, Farzad; Tyner, Wallace; O' Connor, Don; Duffield, James

    2018-03-01

    This study conducted the updated simulations to depict a life cycle analysis (LCA) of the biodiesel production from soybeans and other feedstocks in the U.S. It addressed in details the interaction between LCA and induced land use change (ILUC) for biodiesel. Relative to the conventional petroleum diesel, soy biodiesel could achieve 76% reduction in GHG emissions without considering ILUC, or 66-72% reduction in overall GHG emissions when various ILUC cases were considered. Soy biodiesel’s fossil fuel consumption rate was also 80% lower than its petroleum counterpart. Furthermore, this study examined the cause and the implication of each key parameter affecting biodiesel LCA results using a sensitivity analysis, which identified the hot spots for fossil fuel consumption and GHG emissions of biodiesel so that future efforts can be made accordingly. Finally, biodiesel produced from other feedstocks (canola oil and tallow) were also investigated to contrast with soy biodiesel and petroleum diesel

  14. Solena amplexicaulis induces cell cycle arrest, apoptosis and inhibits angiogenesis in hepatocarcinoma cells and HUVECs.

    Science.gov (United States)

    Ren, Jie; Xu, Yuan Yuan; Jiang, He Fei; Yang, Meng; Huang, Qian Hui; Yang, Jie; Hu, Kun; Wei, Kun

    2014-01-01

    Solena amplexicaulis (Lam.) Gandhi (SA) has been used as a traditional medicine for the treatment of dysentery, multiple abscess, gastralgia, urethritis, and eczema in the minority area of China. This study was aimed to examine the cell proliferation inhibitory activity of the SA extract (SACE) and its mechanism of action in human hepatoma cell line (HepG2) and evaluate its anti-angiogenesis activity in human umbilical vein endothelial cell line (HUVEC). SACE could inhibit the growth of HepG2 cells in a dose- and time-dependent manner. FCM analysis showed that SACE could induce G2/M phase arrest, cell apoptosis, the mitochondrial membrane potential loss (ΔΨm) and increase the production of intracellular ROS of HepG2 cells. After treatment with SACE, topical morphological changes of apoptotic body formation, obvious increase of apoptosis-related protein expressions, such as Bax, cytochrome c, caspase-3, PARP-1, and decrease of Bcl-2, procaspase-9 protein expressions were observed at the same time. Moreover, SACE caused the significant inhibition of endothelial cell migration and tube formation in HUVEC cells. The results suggested that SACE could act as an angiogenesis inhibitor and induce cell apoptosis via a caspase-dependent mitochondrial pathway. Therefore, SACE could be a potent candidate for the prevention and treatment of liver cancer.

  15. Life cycle stage and water depth affect flooding-induced adventitious root formation in the terrestrial species Solanum dulcamara.

    Science.gov (United States)

    Zhang, Qian; Visser, Eric J W; de Kroon, Hans; Huber, Heidrun

    2015-08-01

    Flooding can occur at any stage of the life cycle of a plant, but often adaptive responses of plants are only studied at a single developmental stage. It may be anticipated that juvenile plants may respond differently from mature plants, as the amount of stored resources may differ and morphological changes can be constrained. Moreover, different water depths may require different strategies to cope with the flooding stress, the expression of which may also depend on developmental stage. This study investigated whether flooding-induced adventitious root formation and plant growth were affected by flooding depth in Solanum dulcamara plants at different developmental stages. Juvenile plants without pre-formed adventitious root primordia and mature plants with primordia were subjected to shallow flooding or deep flooding for 5 weeks. Plant growth and the timing of adventitious root formation were monitored during the flooding treatments. Adventitious root formation in response to shallow flooding was significantly constrained in juvenile S. dulcamara plants compared with mature plants, and was delayed by deep flooding compared with shallow flooding. Complete submergence suppressed adventitious root formation until up to 2 weeks after shoots restored contact with the atmosphere. Independent of developmental stage, a strong positive correlation was found between adventitious root formation and total biomass accumulation during shallow flooding. The potential to deploy an escape strategy (i.e. adventitious root formation) may change throughout a plant's life cycle, and is largely dependent on flooding depth. Adaptive responses at a given stage of the life cycle thus do not necessarily predict how the plant responds to flooding in another growth stage. As variation in adventitious root formation also correlates with finally attained biomass, this variation may form the basis for variation in resistance to shallow flooding among plants. © The Author 2015. Published by

  16. Arctigenin, a natural lignan compound, induces G0/G1 cell cycle arrest and apoptosis in human glioma cells.

    Science.gov (United States)

    Maimaitili, Aisha; Shu, Zunhua; Cheng, Xiaojiang; Kaheerman, Kadeer; Sikandeer, Alifu; Li, Weimin

    2017-02-01

    The aim of the current study was to investigate the anticancer potential of arctigenin, a natural lignan compound, in malignant gliomas. The U87MG and T98G human glioma cell lines were treated with various concentrations of arctigenin for 48 h and the effects of arctigenin on the aggressive phenotypes of glioma cells were assessed. The results demonstrated that arctigenin dose-dependently inhibited the growth of U87MG and T98G cells, as determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays. Arctigenin exposure also induced a 60-75% reduction in colony formation compared with vehicle-treated control cells. However, arctigenin was not observed to affect the invasiveness of glioma cells. Arctigenin significantly increased the proportion of cells in the G 0 /G 1 phase and reduced the number of cells in the S phase, as compared with the control group (Parctigenin increased the expression levels of p21, retinoblastoma and p53 proteins, and significantly decreased the expression levels of cyclin D1 and cyclin-dependent kinase 4 proteins. Additionally, arctigenin was able to induce apoptosis in glioma cells, coupled with increased expression levels of cleaved caspase-3 and the pro-apoptotic BCL2-associated X protein. Furthermore, arctigenin-induced apoptosis was significantly suppressed by the pretreatment of cells with Z-DEVD-FMK, a caspase-3 inhibitor. In conclusion, the results suggest that arctigenin is able to inhibit cell proliferation and may induce apoptosis and cell cycle arrest at the G 0 /G 1 phase in glioma cells. These results warrant further investigation of the anticancer effects of arctigenin in animal models of gliomas.

  17. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    International Nuclear Information System (INIS)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing; Guo Chun; Zhu Faliang; Yang Qiaozi; Gao Guimin; Gong Yaoqin; Shao Changshun

    2009-01-01

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis

  18. Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Guo Chun; Zhu Faliang [Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Yang Qiaozi [Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States); Gao Guimin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Gong Yaoqin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China)], E-mail: yxg8@sdu.edu.cn; Shao Changshun [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)], E-mail: shao@biology.rutgers.edu

    2009-03-09

    Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis.

  19. A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jing-Ru Weng

    2017-03-01

    Full Text Available Abstract: Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4′-dimethoxy-3′,5,7-trihydroxyflavone (compound 1, along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC50 values ranging from 3.3 μM (MCF-7 to 8.6 μM (SCC4. Flow cytometric analysis indicated that compound 1 induced G2/M cell cycle arrest in MCF-7 cells. Mechanistic evidence suggests that the G2/M arrest could be attributable to compound 1’s modulatory effects on the phosphorylation and expression of numerous key signaling effectors, including cell division cycle 2 (CDC2, CDC25C, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 2 (HDAC2 and HDAC4, leading to increased histone H3 acetylation and p21 upregulation. Together, these findings suggest the translational potential of compound 1 as a breast cancer treatment.

  20. Nucleolar TRF2 attenuated nucleolus stress-induced HCC cell-cycle arrest by altering rRNA synthesis.

    Science.gov (United States)

    Yuan, Fuwen; Xu, Chenzhong; Li, Guodong; Tong, Tanjun

    2018-05-03

    The nucleolus is an important organelle that is responsible for the biogenesis of ribosome RNA (rRNA) and ribosomal subunits assembly. It is also deemed to be the center of metabolic control, considering the critical role of ribosomes in protein translation. Perturbations of rRNA synthesis are closely related to cell proliferation and tumor progression. Telomeric repeat-binding factor 2 (TRF2) is a member of shelterin complex that is responsible for telomere DNA protection. Interestingly, it was recently reported to localize in the nucleolus of human cells in a cell-cycle-dependent manner, while the underlying mechanism and its role on the nucleolus remained unclear. In this study, we found that nucleolar and coiled-body phosphoprotein 1 (NOLC1), a nucleolar protein that is responsible for the nucleolus construction and rRNA synthesis, interacted with TRF2 and mediated the shuttle of TRF2 between the nucleolus and nucleus. Abating the expression of NOLC1 decreased the nucleolar-resident TRF2. Besides, the nucleolar TRF2 could bind rDNA and promoted rRNA transcription. Furthermore, in hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, TRF2 overexpression participated in the nucleolus stress-induced rRNA inhibition and cell-cycle arrest.

  1. Radiation could induce p53-independent and cell cycle - unrelated apoptosis in 5-fluorouracil radiosensitized head and neck carcinoma cells

    International Nuclear Information System (INIS)

    Didelot, C.; Mirjolet, J.F.; Barberi-Heyob, M.; Ramacci, C.; Merlin, J.L.

    2002-01-01

    The effect of chemoresistance induction in radio sensitivity and cellular behavior after irradiation remains misunderstood. This study was designed to understand the relationship between radiation-induced cell cycle arrest, apoptosis, and radiosensitivity in KB cell line and KB3 subline selected after 5-fluorouracil (5FU) exposure. Exposure of KB cells to 5FU led to an increase in radiosensitivity. G 2 /M cell cycle arrest was observed in the two cell lines after irradiation. The radioresistant KB cell line reached the maximum arrest two hours before KB3. The cellular exit from this arrest was found to be related to the wild type p53 protein expression induction. After irradiation, only KB3 cell line underwent apoptosis. This apoptosis induction seemed to be independent of G 2 /M arrest exit, which was carried out later. The difference in radiosensitivity between KB and KB3 subline may result therefore from both a difference in apoptosis induction and a difference in G 2 /M arrest maximum duration. Moreover, 5FU exposure has led to an increase in constitutive p53 protein expression, which may be associated with an increase in basal apoptosis cell fraction. Given the existing correlation between radiosensitivity and the percentage of basal apoptosis. the constitutive p53 protein expression may be related to intrinsic radiosensitivity in our cellular model. (author)

  2. Restoration of Radiation-Induced Damage Related to the Cell Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Petrovic, D.; Ferle-Vidovic, Ana [Institute Ruder Boskovic, Zagreb, Yugoslavia (Croatia)

    1968-08-15

    A restorative effect of DNA and its precursors in asynchronously growing L-cells after X-irradiation had previously been found. The fact that the precursors were active only if all four of them were added in the form of an equimolar solution, as well as some other d ata, indicated that such treatment might support certain repair processes in the damaged metabolism of nucleic acids. To obtain more information on this problem, synchronized populations of L-cells were irradiated at different stages of the cell cycle with 500 R of X-rays and then treated with either highly polymerized DNA or with nucleotides or nucleosides. The survival of the treated and untreated cells was then calculated and compared. It was found that the cells were over ten times more sensitive in the DNA-synthetic (S) period than in the presynthetic (G{sub 1}) period. The restorative effect of all three materials was related to the S period. The highly polymerized DNA and the deoxytibonucleosides were much more effective than the deoxyribonucleotides. The results indicate that the influence of small molecules and the role they play in the damaged metabolism of nucleic acids could be of considerable importance in the mechanism of the restorative effect produced by nucleic-acid treatment. (author)

  3. Power harvesting by electromagnetic coupling from wind-induced limit cycle oscillations

    Science.gov (United States)

    Boccalero, G.; Olivieri, S.; Mazzino, A.; Boragno, C.

    2017-09-01

    Recent developments of low-power microprocessors open to new applications such as wireless sensor networks (WSN) with the consequent problem of autonomous powering. For this purpose, a possible strategy is represented by energy harvesting from wind or other flows exploiting fluid-structure interactions. In this work, we present an updated picture of a flutter-based device characterized by fully passive dynamics and a simple constructive layout, where limit cycle oscillations are undergone by an elastically bounded wing. In this case, the conversion from mechanical to electrical energy is performed by means of an electromagnetic coupling between a pair of coils and magnets. A centimetric-size prototype is shown to harvest energy from low wind velocities (between 2 and 4 m s-1), reaching a power peak of 14 mW, representing a valuable amount for applications related to WSN. A mathematical description of the nonlinear dynamics is then provided by a quasi-steady phenomenological model, revealing satisfactory agreement with the experimental framework within a certain parametric range and representing a useful tool for future optimizations.

  4. Sulforaphane induces cell cycle arrest and apoptosis in acute lymphoblastic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Koramit Suppipat

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common hematological cancer in children. Although risk-adaptive therapy, CNS-directed chemotherapy, and supportive care have improved the survival of ALL patients, disease relapse is still the leading cause of cancer-related death in children. Therefore, new drugs are needed as frontline treatments in high-risk disease and as salvage agents in relapsed ALL. In this study, we report that purified sulforaphane, a natural isothiocyanate found in cruciferous vegetables, has anti-leukemic properties in a broad range of ALL cell lines and primary lymphoblasts from pediatric T-ALL and pre-B ALL patients. The treatment of ALL leukemic cells with sulforaphane resulted in dose-dependent apoptosis and G2/M cell cycle arrest, which was associated with the activation of caspases (3, 8, and 9, inactivation of PARP, p53-independent upregulation of p21(CIP1/WAF1, and inhibition of the Cdc2/Cyclin B1 complex. Interestingly, sulforaphane also inhibited the AKT and mTOR survival pathways in most of the tested cell lines by lowering the levels of both total and phosphorylated proteins. Finally, the administration of sulforaphane to the ALL xenograft models resulted in a reduction of tumor burden, particularly following oral administration, suggesting a potential role as an adjunctive agent to improve the therapeutic response in high-risk ALL patients with activated AKT signaling.

  5. In Situ Measurement of Seeking Speed and Seeking Induced Head-Disk Interface Instability in Hard Disk Drives

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2015-01-01

    Full Text Available This paper investigated the instability of head-disk interface caused by the voice coil motor (VCM end crashing the crash stop during the seeking of magnetic head. To make the whole process of that clear, an in situ measurement method based on maximum likelihood estimation and extended Kalman filter for seeking speed at component level was developed first and was then calibrated by a high speed camera. Given a crash between VCM end and crash stop that may be a consequence of the continuous increasing seeking speed, the seeking speed was carefully controlled by using our developed method to find a critical value that may induce vigorous head-disk interface instability. Acoustic emission sensor and laser Doppler vibrometer were used to capture the transient dynamic behaviors of magnetic head when the crash is happening. Damage analysis and mode identification were carried out to reveal the relationship between the damage patterns on disk surface and head dynamics. The results of this study are helpful to optimize the track seeking profile during the HDD operation, as well as the design of components such as head and head arm.

  6. Mechano-Signal Transduction in Mesenchymal Stem Cells Induces Prosaposin Secretion to Drive the Proliferation of Breast Cancer Cells.

    Science.gov (United States)

    Ishihara, Seiichiro; Inman, David R; Li, Wan-Ju; Ponik, Suzanne M; Keely, Patricia J

    2017-11-15

    In response to chemical stimuli from cancer cells, mesenchymal stem cells (MSC) can differentiate into cancer-associated fibroblasts (CAF) and promote tumor progression. How mechanical stimuli such as stiffness of the extracellular matrix (ECM) contribute to MSC phenotype in cancer remains poorly understood. Here, we show that ECM stiffness leads to mechano-signal transduction in MSC, which promotes mammary tumor growth in part through secretion of the signaling protein prosaposin. On a stiff matrix, MSC cultured with conditioned media from mammary cancer cells expressed increased levels of α-smooth muscle actin, a marker of CAF, compared with MSC cultured on a soft matrix. By contrast, MSC cultured on a stiff matrix secreted prosaposin that promoted proliferation and survival of mammary carcinoma cells but inhibited metastasis. Our findings suggest that in addition to chemical stimuli, increased stiffness of the ECM in the tumor microenvironment induces differentiation of MSC to CAF, triggering enhanced proliferation and survival of mammary cancer cells. Cancer Res; 77(22); 6179-89. ©2017 AACR . ©2017 American Association for Cancer Research.

  7. Changes in N cycling induced by Ulva detritus enrichment of sediments

    DEFF Research Database (Denmark)

    Garcia-Robledo, Emilio; Revsbech, Niels Peter; Risgaard-Petersen, Nils

    2013-01-01

    Macroalgal accumulation and decomposition in shallow water environments typically result in an increase in the organic matter content of the sediment, affecting both benthic metabolism and nutrient dynamics. The present study investigates how a pulse addition of Ulva detritus to estuarine sediment...... of oxygen and nitrate. Nitrification increased significantly in response to enhanced NH4 + supply from decomposition of the Ulva detritus. Aerobic ammonia oxidation exceeded rates of nitrite oxidation, leading to accumulation of NO2 − in the oxic zone of the sediment. Nitrite and NO3 − produced via...... nitrification diffused up to the sediment surface, inducing a net efflux to the water column, and downwards, supporting a high rate of denitrification coupled to nitrification. The present study shows that organic enrichment with Ulva detritus enhances sediment oxygen uptake, nitrification and denitrification...

  8. Differential biologic effects of CPD and 6-4PP UV-induced DNA damage on the induction of apoptosis and cell-cycle arrest

    International Nuclear Information System (INIS)

    Lo, Hsin-Lung; Nakajima, Satoshi; Ma, Lisa; Walter, Barbara; Yasui, Akira; Ethell, Douglas W; Owen, Laurie B

    2005-01-01

    UV-induced damage can induce apoptosis or trigger DNA repair mechanisms. Minor DNA damage is thought to halt the cell cycle to allow effective repair, while more severe damage can induce an apoptotic program. Of the two major types of UV-induced DNA lesions, it has been reported that repair of CPD, but not 6-4PP, abrogates mutation. To address whether the two major forms of UV-induced DNA damage, can induce differential biological effects, NER-deficient cells containing either CPD photolyase or 6-4 PP photolyase were exposed to UV and examined for alterations in cell cycle and apoptosis. In addition, pTpT, a molecular mimic of CPD was tested in vitro and in vivo for the ability to induce cell death and cell cycle alterations. NER-deficient XPA cells were stably transfected with CPD-photolyase or 6-4PP photolyase to specifically repair only CPD or only 6-4PP. After 300 J/m 2 UVB exposure photoreactivation light (PR, UVA 60 kJ/m 2 ) was provided for photolyase activation and DNA repair. Apoptosis was monitored 24 hours later by flow cytometric analysis of DNA content, using sub-G1 staining to indicate apoptotic cells. To confirm the effects observed with CPD lesions, the molecular mimic of CPD, pTpT, was also tested in vitro and in vivo for its effect on cell cycle and apoptosis. The specific repair of 6-4PP lesions after UVB exposure resulted in a dramatic reduction in apoptosis. These findings suggested that 6-4PP lesions may be the primary inducer of UVB-induced apoptosis. Repair of CPD lesions (despite their relative abundance in the UV-damaged cell) had little effect on the induction of apoptosis. Supporting these findings, the molecular mimic of CPD, (dinucleotide pTpT) could mimic the effects of UVB on cell cycle arrest, but were ineffective to induce apoptosis. The primary response of the cell to UV-induced 6-4PP lesions is to trigger an apoptotic program whereas the response of the cell to CPD lesions appears to principally involve cell cycle arrest. These

  9. Repeated supra-maximal sprint cycling with and without sodium bicarbonate supplementation induces endothelial microparticle release.

    Science.gov (United States)

    Kirk, Richard J; Peart, Daniel J; Madden, Leigh A; Vince, Rebecca V

    2014-01-01

    Under normal homeostatic conditions, the endothelium releases microparticles (MPs), which are known to increase under stressful conditions and in disease states. CD105 (endoglin) and CD106 (vascular cell adhesion molecule-1) are expressed on the surface of endothelial cells and increased expression in response to stress may be observed. A randomised-controlled double-blinded study aimed to examine the use of endothelial MPs as a marker for the state of one's endothelium, as well as whether maintaining acid-base homeostasis affects the release of these MPs. This study tested seven healthy male volunteers, who completed a strenuous cycling protocol, with venous blood analysed for CD105+ and CD106+ MPs by flow cytometry at regular intervals. Prior to each trial participants consumed either 0.3 g·kg(-1) body mass of sodium bicarbonate (NaHCO3), or 0.045 g·kg(-1) body mass of sodium chloride (NaCl). A significant rise in endothelial CD105+ MPs and CD106+ MPs (p<0.05) was observed at 90 min post-exercise. A significant trend was shown for these MPs to return to resting levels 180 min post-exercise in both groups. No significance was found between experimental groups, suggesting that maintaining acid-base variables closer to basal levels has little effect upon the endothelial stress response for this particular exercise mode. In conclusion, strenuous exercise is accompanied by MP release and the endothelium is able to rapidly recover in healthy individuals, whilst maintaining acid-base homeostasis does not attenuate the MP release from the endothelium after exercise.

  10. Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

    Science.gov (United States)

    Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

    2018-01-01

    Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

  11. Casticin impairs cell growth and induces cell apoptosis via cell cycle arrest in human oral cancer SCC-4 cells.

    Science.gov (United States)

    Chou, Guan-Ling; Peng, Shu-Fen; Liao, Ching-Lung; Ho, Heng-Chien; Lu, Kung-Wen; Lien, Jin-Cherng; Fan, Ming-Jen; La, Kuang-Chi; Chung, Jing-Gung

    2018-02-01

    Casticin, a polymethoxyflavone, present in natural plants, has been shown to have biological activities including anti-cancer activities. Herein, we investigated the anti-oral cancer activity of casticin on SCC-4 cells in vitro. Viable cells, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS) production, and Ca 2+ production, levels of ΔΨ m and caspase activity were measured by flow cytometric assay. Cell apoptosis associated protein expressions were examined by Western blotting and confocal laser microscopy. Results indicated that casticin induced cell morphological changes, DNA condensation and damage, decreased the total viable cells, induced G 2 /M phase arrest in SCC-4 cells. Casticin promoted ROS and Ca 2+ productions, decreases the levels of ΔΨ m , promoted caspase-3, -8, and -9 activities in SCC-4 cells. Western blotting assay demonstrated that casticin affect protein level associated with G2/M phase arrest and apoptosis. Confocal laser microscopy also confirmed that casticin increased the translocation of AIF and cytochrome c in SCC-4 cells. In conclusion, casticin decreased cell number through G 2 /M phase arrest and the induction of cell apoptosis through caspase- and mitochondria-dependent pathways in SCC-4 cells. © 2017 Wiley Periodicals, Inc.

  12. Mechanism for ginkgolic acid (15 : 1)-induced MDCK cell necrosis: Mitochondria and lysosomes damages and cell cycle arrest.

    Science.gov (United States)

    Yao, Qing-Qing; Liu, Zhen-Hua; Xu, Ming-Cheng; Hu, Hai-Hong; Zhou, Hui; Jiang, Hui-Di; Yu, Lu-Shan; Zeng, Su

    2017-05-01

    Ginkgolic acids (GAs), primarily found in the leaves, nuts, and testa of ginkgo biloba, have been identified with suspected allergenic, genotoxic and cytotoxic properties. However, little information is available about GAs toxicity in kidneys and the underlying mechanism has not been thoroughly elucidated so far. Instead of GAs extract, the renal cytotoxicity of GA (15 : 1), which was isolated from the testa of Ginkgo biloba, was assessed in vitro by using MDCK cells. The action of GA (15 : 1) on cell viability was evaluated by the MTT and neutral red uptake assays. Compared with the control, the cytotoxicity of GA (15 : 1) on MDCK cells displayed a time- and dose-dependent manner, suggesting the cells mitochondria and lysosomes were damaged. It was confirmed that GA (15 : 1) resulted in the loss of cells mitochondrial trans-membrane potential (ΔΨm). In propidium iodide (PI) staining analysis, GA (15 : 1) induced cell cycle arrest at the G0/G1 and G2/M phases, influencing on the DNA synthesis and cell mitosis. Characteristics of necrotic cell death were observed in MDCK cells at the experimental conditions, as a result of DNA agarose gel electrophoresis and morphological observation of MDCK cells. In conclusion, these findings might provide useful information for a better understanding of the GA (15 : 1) induced renal toxicity. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  13. A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

    Science.gov (United States)

    Sellers, W R; Rodgers, J W; Kaelin, W G

    1995-01-01

    An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F. Images Fig. 4 Fig. 5 PMID:8524800

  14. Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1986-01-01

    A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different...... sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow...

  15. Electric drives

    Energy Technology Data Exchange (ETDEWEB)

    1986-10-01

    Several electric vehicles have been tested in long-term tests, i.e. an electric passenger car (maximum speed 115 km/h) and several busses for use in pedestrians' zones, spas, airports, natural reserves, and urban transportation (DUO busses). The ICE high-speed train is discussed in some detail, i.e. its aeroacoustic and aerodynamic design, running gear, computer-controlled drives and brakes, diagnostic systems, and electrical equipment. The Berlin Maglev system is mentioned as well as current inverters in rail vehicles. (HWJ).

  16. An APC:WNT counter-current-like mechanism regulates cell division along the colonic crypt axis: a mechanism that explains how APC mutations induce proliferative abnormalities that drive colon cancer development.

    Directory of Open Access Journals (Sweden)

    Bruce M Boman

    2013-11-01

    Full Text Available APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside. WNT signaling, in contrast, is high at the bottom (where SCs reside and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g. survivin are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric. APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly-proliferating cells during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes.

  17. An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development

    Science.gov (United States)

    Boman, Bruce M.; Fields, Jeremy Z.

    2013-01-01

    APC normally down-regulates WNT signaling in human colon, and APC mutations cause proliferative abnormalities in premalignant crypts leading to colon cancer, but the mechanisms are unclear at the level of spatial and functional organization of the crypt. Accordingly, we postulated a counter-current-like mechanism based on gradients of factors (APC;WNT) that regulate colonocyte proliferation along the crypt axis. During crypt renewal, stem cells (SCs) at the crypt bottom generate non-SC daughter cells that proliferate and differentiate while migrating upwards. The APC concentration is low at the crypt bottom and high at the top (where differentiated cells reside). WNT signaling, in contrast, is high at the bottom (where SCs reside) and low at the top. Given that WNT and APC gradients are counter to one another, we hypothesized that a counter-current-like mechanism exists. Since both APC and WNT signaling components (e.g., survivin) are required for mitosis, this mechanism establishes a zone in the lower crypt where conditions are optimal for maximal cell division and mitosis orientation (symmetric versus asymmetric). APC haploinsufficiency diminishes the APC gradient, shifts the proliferative zone upwards, and increases symmetric division, which causes SC overpopulation. In homozygote mutant crypts, these changes are exacerbated. Thus, APC-mutation-induced changes in the counter-current-like mechanism cause expansion of proliferative populations (SCs, rapidly proliferating cells) during tumorigenesis. We propose this mechanism also drives crypt fission, functions in the crypt cycle, and underlies adenoma development. Novel chemoprevention approaches designed to normalize the two gradients and readjust the proliferative zone downwards, might thwart progression of these premalignant changes. PMID:24224156

  18. CXXC5 suppresses hepatocellular carcinoma by promoting TGF-β-induced cell cycle arrest and apoptosis.

    Science.gov (United States)

    Yan, Xiaohua; Wu, Jingyi; Jiang, Quanlong; Cheng, Hao; Han, Jing-Dong J; Chen, Ye-Guang

    2018-02-01

    Evading TGF-β-mediated growth inhibition is often associated with tumorigenesis in liver, including hepatocellular carcinoma (HCC). To better understand the functions and the underlying molecular mechanisms of TGF-β in HCC initiation and progression, we carried out transcriptome sequencing (RNA-Seq) to identify the target genes of TGF-β. CXXC5, a member of the CXXC-type zinc finger domain-containing protein family, was identified as a novel TGF-β target gene in Hep3B HCC cells. Knockdown of CXXC5 attenuated the expression of a substantial portion of TGF-β target genes and ameliorated TGF-β-induced growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required for TGF-β-mediated inhibition of HCC progression. Analysis of the TCGA database indicated that CXXC5 expression is reduced in the majority of HCC tissue samples in comparison to that in normal tissues. Furthermore, CXXC5 associates with the histone deacetylase HDAC1 and competes its interaction with Smad2/3, thereby abolishing the inhibitory effect of HDAC1 on TGF-β signaling. These observations together suggest that CXXC5 may act as a tumor suppressor by promoting TGF-β signaling via a positive feedback loop, and reveal a strategy for HCC to bypass TGF-β-mediated cytostasis by disrupting the positive feedback regulation. Our findings shed new light on TGF-β signaling regulation and demonstrate the function of CXXC5 in HCC development.

  19. Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3 human prostate cancer cells.

    Science.gov (United States)

    Xiao, Dong; Johnson, Candace S; Trump, Donald L; Singh, Shivendra V

    2004-05-01

    Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, offers significant protection against cancer in animals induced by a variety of carcinogens. The present study demonstrates that PEITC suppresses proliferation of PC-3 cells in a dose-dependent manner by causing G(2)-M-phase cell cycle arrest and apoptosis. Interestingly, phenyl isothiocyanate (PITC), which is a structural analogue of PEITC but lacks the -CH(2) spacers that link the aromatic ring to the -N=C=S group, neither inhibited PC-3 cell viability nor caused cell cycle arrest or apoptosis. These results indicated that even a subtle change in isothiocyanate (ITC) structure could have a significant impact on its biological activity. The PEITC-induced cell cycle arrest was associated with a >80% reduction in the protein levels of cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C (Cdc25C; 24 h after treatment with 10 micro M PEITC), which led to an accumulation of Tyr(15) phosphorylated (inactive) Cdk1. On the other hand, PITC treatment neither reduced protein levels of Cdk1 or Cdc25C nor affected Cdk1 phosphorylation. The PEITC-induced decline in Cdk1 and Cdc25C protein levels and cell cycle arrest were significantly blocked on pretreatment of PC-3 cells with proteasome inhibitor lactacystin. A 24 h exposure of PC-3 cells to 10 micro M PEITC, but not PITC, resulted in about 56% and 44% decrease in the levels of antiapoptotic proteins Bcl-2 and Bcl-X(L), respectively. However, ectopic expression of Bcl-2 failed to alter sensitivity of PC-3 cells to growth inhibition or apoptosis induction by PEITC. Treatment of cells with PEITC, but not PITC, also resulted in cleavage of procaspase-3, procaspase-9, and procaspase-8. Moreover, the PEITC-induced apoptosis was significantly attenuated in the presence of general caspase inhibitor and specific inhibitors of caspase-8 and caspase-9. In conclusion, our data indicate that PEITC-induced cell cycle arrest in PC-3 cells is likely due

  20. Copper-induced immunotoxicity involves cell cycle arrest and cell death in the spleen and thymus

    International Nuclear Information System (INIS)

    Mitra, Soham; Keswani, Tarun; Dey, Manali; Bhattacharya, Shaswati; Sarkar, Samrat; Goswami, Suranjana; Ghosh, Nabanita; Dutta, Anuradha; Bhattacharyya, Arindam

    2012-01-01

    Copper is an essential trace element for human physiological processes. To evaluate the potential adverse health impact/immunotoxicological effects of this metal in situ due to over exposure, Swiss albino mice were treated (via intraperitoneal injections) with copper (II) chloride (copper chloride) at doses of 0, 5, or 7.5 mg copper chloride/kg body weight (b.w.) twice a week for 4 wk; these values were derived from LD 50 studies using copper chloride doses that ranged from 0 to 40 mg/kg BW (2×/wk, for 4 wk). Copper treated mice evidenced immunotoxicity as indicated by dose-related decreases and increases, respectively, in thymic and splenic weights. Histomorphological changes evidenced in these organs were thymic atrophy, white pulp shrinkage in the spleen, and apoptosis of splenocytes and thymocytes; these observations were confirmed by microscopic analyses. Cell count analyses indicated that the proliferative functions of the splenocytes and thymocytes were also altered because of the copper exposures. Among both cell types from the copper treated hosts, flow cytometric analyses revealed a dose related increase in the percentages of cells in the Sub-G 0 /G 1 state, indicative of apoptosis which was further confirmed by Annexin V binding assay. In addition, the copper treatments altered the expression of selected cell death related genes such as EndoG and Bax in a dose related manner. Immunohistochemical analyses revealed that there was also increased ubiquitin expression in both the cell types. In conclusion, these studies show that sublethal exposure to copper (as copper chloride) induces toxicity in the thymus and spleen, and increased Sub G 0 /G 1 population among splenocytes and thymocytes that is mediated, in part, by the EndoG–Bax–ubiquitin pathway. This latter damage to these cells that reside in critical immune system organs are likely to be important contributing factors underlying the immunosuppression that has been documented by other

  1. Safe driving for teens

    Science.gov (United States)

    Driving and teenagers; Teens and safe driving; Automobile safety - teenage drivers ... months before taking friends as passengers. Teenage-related driving deaths occur more often in certain conditions. OTHER SAFETY TIPS FOR TEENS Reckless driving is still a ...

  2. Energetic particle drive for toroidicity-induced Alfven eigenmodes and kinetic toroidicity-induced Alfven eigenmodes in a low-shear Tokamak. Revised

    International Nuclear Information System (INIS)

    Breizman, B.N.; Sharapov, S.E.

    1994-10-01

    The structure of toroidicity-induced Alfven eigenmodes (TAE) and kinetic TAE (KTAE) with large mode numbers is analyzed and the linear power transfer from energetic particles to these modes is calculated in the low shear limit when each mode is localized near a single gap within an interval whose total width Δ out is much smaller than the radius r m of the mode location. Near its peak where most of the mode energy is concentrated, the mode has an inner scalelength Δ in , which is much smaller than Δ out . The scale Δ in is determined by toroidicity and kinetic effects, which eliminate the singularity of the potential at the resonant surface. This work examines the case when the drift orbit width of energetic particles Δ b is much larger than the inner scalelength Δ in , but arbitrary compared to the total width of the mode. It is shown that the particle-to-wave linear power transfer is comparable for the TAE and KTAE modes in this case. The ratio of the energetic particle contributions to the growth rates of the TAE and KTAE modes is then roughly equal to the inverse ratio of the mode energies. It is found that, in the low shear limit the growth rate of the KTAE modes can be larger than that for the TAE modes

  3. Expression of hypoxia-inducible factor-1α and cell cycle proteins in invasive breast cancer are estrogen receptor related

    International Nuclear Information System (INIS)

    Bos, Reinhard; Diest, Paul J van; Groep, Petra van der; Shvarts, Avi; Greijer, Astrid E; Wall, Elsken van der

    2004-01-01

    The transcription factor hypoxia-inducible factor-1 (HIF-1) is a key regulator of the cellular response to hypoxia. Previous studies showed that concentrations of its subunit HIF-1α, as a surrogate for HIF-1 activity, are increased during breast carcinogenesis and can independently predict prognosis in breast cancer. During carcinogenesis, the cell cycle is progressively deregulated, and proliferation rate is a strong prognostic factor in breast cancer. In this study we undertook a detailed evaluation of the relationships between HIF-1α and cell cycle-associated proteins. In a representative estrogen receptor (ER) group of 150 breast cancers, the expression of HIF-1α, vascular endothelial growth factor, the ER, HER-2/neu, Ki-67, cyclin A, cyclin D 1 , p21, p53, and Bcl-2 was investigated by immunohistochemistry. High concentrations (5% or more) of HIF-1α were associated with increased proliferation as shown by positive correlations with Ki-67 (P < 0.001) and the late S–G2-phase protein cyclin A (P < 0.001), but not with the G1-phase protein cyclin D 1 . High HIF-1α concentrations were also strongly associated with p53 positivity (P < 0.001) and loss of Bcl-2 expression (P = 0.013). No association was found between p21 and HIF-1α (P = 0.105) in the whole group of patients. However, the subgroup of ER-positive cancers was characterized by a strong positive association between HIF-1α and p21 (P = 0.023), and HIF-1α lacked any relation with proliferation. HIF-1α overexpression is associated with increased proliferation, which might explain the adverse prognostic impact of increased concentrations of HIF-1α in invasive breast cancer. In ER-positive tumors, HIF-1α is associated with p21 but not against proliferation. This shows the importance of further functional analysis to unravel the role of HIF-1 in late cell cycle progression, and the link between HIF-1, p21, and ER

  4. Dynamic Contractility and Efficiency Impairments in Stretch-Shortening Cycle Are Stretch-Load-Dependent After Training-Induced Muscle Damage

    NARCIS (Netherlands)

    Vaczi, Mark; Racz, Levente; Hortobagyi, Tibor; Tihanyi, Jozsef

    Vaczi, M, Racz, L, Hortobagyi, T, and Tihanyi, J. Dynamic contractility and efficiency impairments in stretch-shortening cycle are stretch-load-dependent after training-induced muscle damage. J Strength Cond Res 27(8): 2171-2179, 2013To determine the acute task and stretch-load dependency of

  5. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury: Effect of duty cycle

    NARCIS (Netherlands)

    MSc Karin J.A. Legemate; MD Christof A. J. Smit; MSc Anja de Koning; PhD Sonja de Groot; MD, PhD Janneke M. Stolwijk-Swuste; PhD Thomas W.H. Janssen

    2013-01-01

    Abstract—Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation

  6. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury : Effect of duty cycle

    NARCIS (Netherlands)

    Smit, Christof A. J.; Legemate, Karin J. A.; de Koning, Anja; de Groot, Sonja; Stolwijk-Swuste, Janneke M.; Janssen, Thomas W. J.

    2013-01-01

    Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation on

  7. Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.

    Science.gov (United States)

    Rapoport, Bernardo; Schwartzberg, Lee; Chasen, Martin; Powers, Dan; Arora, Sujata; Navari, Rudolph; Schnadig, Ian

    2016-04-01

    Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Oxygen-Glucose Deprivation Induces G2/M Cell Cycle Arrest in Brain Pericytes Associated with ERK Inactivation.

    Science.gov (United States)

    Wei, Wenjie; Yu, Zhiyuan; Xie, Minjie; Wang, Wei; Luo, Xiang

    2017-01-01

    Growing evidence has revealed that brain pericytes are multifunctional and contribute to the pathogenesis of a number of neurological disorders. However, the role of pericytes in cerebral ischemia, and especially the pathophysiological alterations in pericytes, remains unclear. In the present study, our aim was to determine whether the proliferation of pericytes is affected by cerebral ischemia and, if so, to identify the underlying mechanism(s). Cultured brain pericytes subjected to oxygen-glucose deprivation (OGD) were used as our model of cerebral ischemia; the protein expression levels of cyclin D1, cyclin E, cdk4, and cyclin B1 were determined by Western blot analysis, and cell cycle analysis was assessed by flow cytometry. The OGD treatment reduced the brain pericyte proliferation by causing G2/M phase arrest and downregulating the protein levels of cyclin D1, cyclin E, cdk4, and cyclin B1. Further studies demonstrated a simultaneous decrease in the activity of extracellular regulated protein kinases (ERK), suggesting a critical role of the ERK signaling cascade in the inhibition of OGD-induced pericyte proliferation. We suggest that OGD inhibition of the proliferation of brain pericytes is associated with the inactivation of the ERK signaling pathway, which arrests them in the G2/M phase.

  9. Involvement of apoptotic cell death and cell cycle perturbation in retinoic acid-induced cleft palate in mice

    International Nuclear Information System (INIS)

    Okano, Junko; Suzuki, Shigehiko; Shiota, Kohei

    2007-01-01

    Retinoic acid (RA), a metabolite of vitamin A, plays a key role in a variety of biological processes and is essential for normal embryonic development. On the other hand, exogenous RA could cause cleft palate in offspring when it is given to pregnant animals at either the early or late phases of palatogenesis, but the pathogenetic mechanism of cleft palate caused by excess RA remains not fully elucidated. The aim of the present study was to investigate the effects of excess of RA on early palatogenesis in mouse fetuses and analyze the teratogenic mechanism, especially at the stage prior to palatal shelf elevation. We gave all-trans RA (100 mg/kg) orally to E11.5 ICR pregnant mice and observed the changes occurring in the palatal shelves of their fetuses. It was found that apoptotic cell death increased not only in the epithelium of the palatal shelves but also in the tongue primordium, which might affect tongue withdrawal movement during palatogenesis and impair the horizontal elevation of palatal shelves. In addition, RA was found to prevent the G 1 /S progression of palatal mesenchymal cells through upregulation of p21 Cip1 , leading to Rb hypophospholylation. Thus, RA appears to cause G 1 arrest in palatal mesenchymal cells in a similar manner as in various cancer and embryonic cells. It is likely that apoptotic cell death and cell cycle disruption are involved in cleft palate formation induced by RA

  10. Life cycle energy and greenhouse gas emission effects of biodiesel in the United States with induced land use change impacts.

    Science.gov (United States)

    Chen, Rui; Qin, Zhangcai; Han, Jeongwoo; Wang, Michael; Taheripour, Farzad; Tyner, Wallace; O'Connor, Don; Duffield, James

    2018-03-01

    This study conducted the updated simulations to depict a life cycle analysis (LCA) of the biodiesel production from soybeans and other feedstocks in the U.S. It addressed in details the interaction between LCA and induced land use change (ILUC) for biodiesel. Relative to the conventional petroleum diesel, soy biodiesel could achieve 76% reduction in GHG emissions without considering ILUC, or 66-72% reduction in overall GHG emissions when various ILUC cases were considered. Soy biodiesel's fossil fuel consumption rate was also 80% lower than its petroleum counterpart. Furthermore, this study examined the cause and the implication of each key parameter affecting biodiesel LCA results using a sensitivity analysis, which identified the hot spots for fossil fuel consumption and GHG emissions of biodiesel so that future efforts can be made accordingly. Finally, biodiesel produced from other feedstocks (canola oil and tallow) were also investigated to contrast with soy biodiesel and petroleum diesel. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Umbilical Cord Tissue-Derived Mesenchymal Stem Cells Induce T Lymphocyte Apoptosis and Cell Cycle Arrest by Expression of Indoleamine 2, 3-Dioxygenase

    Directory of Open Access Journals (Sweden)

    Xiuying Li

    2016-01-01

    Full Text Available It has been reported that human mesenchymal stem cells are able to inhibit T lymphocyte activation; however, the discrepancy among different sources of MSCs is not well documented. In this study, we have compared the MSCs from bone marrow (BM, adipose tissue (AT, placenta (PL, and umbilical cord (UC to determine which one displayed the most efficient immunosuppressive effects on phytohemagglutinin-induced T cell proliferation. Among them we found that hUC-MSC has the strongest effects on inhibiting T cell proliferation and is chosen to do the further study. We observed that T lymphocyte spontaneously released abundant IFN-γ. And IFN-γ secreted by T lymphocyte could induce the expression of indoleamine 2, 3-dioxygenase (IDO in hUC-MSCs. IDO was previously reported to induce T lymphocyte apoptosis and cell cycle arrest in S phase. When cocultured with hUC-MSCs, T lymphocyte expression of caspase 3 was significantly increased, while Bcl2 and CDK4 mRNA expression decreased dramatically. Addition of 1-methyl tryptophan (1-MT, an IDO inhibitor, restored T lymphocyte proliferation, reduced apoptosis, and induced resumption of the cell cycle. In addition, the changes in caspase 3, CDK4, and Bcl2 expression were reversed by 1-MT. These findings demonstrate that hUC-MSCs induce T lymphocyte apoptosis and cell cycle arrest by expressing abundant IDO and provide an explanation for some of the immunomodulatory effects of MSCs.

  12. Radiation-induced genetic instability: no association with changes in radiosensitivity or cell cycle checkpoints in C3H 10T1/2 mouse fibroblasts

    International Nuclear Information System (INIS)

    Crompton, N.E.A.; Emery, G.C.; Shi Yuquan; Sigg, M.; Blattmann, H.

    1998-01-01

    We investigated various phenotypic characteristics of radiation-induced morphologically transformed C3H 10T1/2 mouse fibroblasts. The cells were treated with 8 Gy x-rays, and type II/III foci were isolated. Cell lines were developed from these foci, and subsequently clones were established from these focal lines. The clones were examined for DNA content, radiosensitivity and inducible cell cycle arrests. Besides the morphological changes associated with the transformed state, the major difference between the isolated focal lines or derived clones and the parental C3H 10T1/2 line was one of ploidy. The transformed cells often displayed aneuploid and multiple polyploid populations. No change in the radiosensitivity of the transformed cells was observed. Furthermore, the two major radiation- and staurosporine-induced G1 and G2 cell cycle arrests observed in the parental cell line were also observed in the morphological transformants, suggesting that checkpoint function was normal. (orig.)

  13. A sea urchin lectin, SUL-1, from the Toxopneustid sea urchin induces DC maturation from human monocyte and drives Th1 polarization in vitro

    International Nuclear Information System (INIS)

    Takei, Masao; Nakagawa, Hideyuki

    2006-01-01

    The sea urchin Toxopneustes pileolus belonging to the family Toxopneustidae, they have well-developed globiferous pedicellariae with pharmacologically active substances. We have purified a novel sea urchin lectin-1 (SUL-1) from the large globiferous pedicellariae of T. pileolus. Dendritic cells (DC) are professional APC and play a pivotal role in controlling immune responses. This study investigated whether SUL-1 can drive DC maturation from human immature monocyte-derived DC in vitro. Human monocytes were cultured with GM-CSF and IL-4 for 6 days followed by another 1 day in the presence of SUL-1 or LPS. DC harvested on day 7 were examined using functional assays. The expression levels of CD1a, CD80, CD83, CD86 and HLA-DR as expressed by mean fluorescence intensity (MFI) on DC differentiated from immature DC after culture with 1.0 μg/ml of SUL-1 for 1 day were enhanced and decreased endocytic activity. SUL-1-treated DC also displayed enhanced T cell stimulatory capacity in an MLR, as measured by T cell proliferation. Cell surface expression of CD80, CD83 and CD86 on SUL-1-treated DC was inhibited by anti-DC-SIGN mAb, while anti-DC-SIGN mAb had no influence on allogeneic T cell proliferation by SUL-1-treated DC. DC differentiated with SUL-1 induced the differentiation of naive T cell towards a helper T cell type 1 (Th1) response at DC/T (1:5) cells ratio depending on IL-12 secretion. In CTL assay, the production of IFN-γ and 51 Cr release on SUL-1-treated DC were more augmented than of immature DC or LPS-treated DC. SUL-1-treated DC expressed CCR7 and had a high migration to MIP-3β. Intracellular Ca 2+ mobilization in SUL-1-treated DC was also induced by MIP-3β. These results suggest that SUL-1 bindings to DC-SIGN on surface of immature DC may lead to differentiate DC from immature DC. Moreover, it suggests that SUL-1 may be used on DC-based vaccines for cancer immunotherapy

  14. A simple method to prevent hard X-ray-induced preheating effects inside the cone tip in indirect-drive fast ignition implosions

    International Nuclear Information System (INIS)

    Liu, Dongxiao; Shan, Lianqiang; Zhou, Weimin; Wu, Yuchi; Zhu, Bin; Zhang, Feng; Bi, Bi; Zhang, Bo; Zhang, Zhimeng; Shui, Min; He, Yingling; Gu, Yuqiu; Zhang, Baohan; Peng, Xiaoshi; Xu, Tao; Wang, Feng; Yang, Zhiwen; Chen, Tao; Chen, Li; Chen, Ming

    2016-01-01

    During fast-ignition implosions, preheating of inside the cone tip caused by hard X-rays can strongly affect the generation and transport of hot electrons in the cone. Although indirect-drive implosions have a higher implosion symmetry, they cause stronger preheating effects than direct-drive implosions. To control the preheating of the cone tip, we propose the use of indirect-drive fast-ignition targets with thicker tips. Experiments carried out at the ShenGuang-III prototype laser facility confirmed that thicker tips are effective for controlling preheating. Moreover, these results were consistent with those of 1D radiation hydrodynamic simulations.

  15. A simple method to prevent hard X-ray-induced preheating effects inside the cone tip in indirect-drive fast ignition implosions

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dongxiao; Shan, Lianqiang; Zhou, Weimin; Wu, Yuchi; Zhu, Bin; Zhang, Feng; Bi, Bi; Zhang, Bo; Zhang, Zhimeng; Shui, Min; He, Yingling; Gu, Yuqiu, E-mail: yqgu@caep.cn; Zhang, Baohan [Science and Technology on Plasma Physics Laboratory, China Academy of Engineering Physics, Mianyang 621900 (China); Research Center of Laser Fusion, China Academy of Engineering Physics, Mianyang 621900 (China); Peng, Xiaoshi; Xu, Tao; Wang, Feng; Yang, Zhiwen; Chen, Tao; Chen, Li; Chen, Ming [Research Center of Laser Fusion, China Academy of Engineering Physics, Mianyang 621900 (China); and others

    2016-06-15

    During fast-ignition implosions, preheating of inside the cone tip caused by hard X-rays can strongly affect the generation and transport of hot electrons in the cone. Although indirect-drive implosions have a higher implosion symmetry, they cause stronger preheating effects than direct-drive implosions. To control the preheating of the cone tip, we propose the use of indirect-drive fast-ignition targets with thicker tips. Experiments carried out at the ShenGuang-III prototype laser facility confirmed that thicker tips are effective for controlling preheating. Moreover, these results were consistent with those of 1D radiation hydrodynamic simulations.

  16. Mechanisms underlying enhancements in muscle force and power output during maximal cycle ergometer exercise induced by chronic β2-adrenergic stimulation in men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Onslev, Johan

    2015-01-01

    The study was a randomized placebo-controlled trial investigating mechanisms by which chronic β2-adrenergic stimulation enhances muscle force and power output during maximal cycle ergometer exercise in young men. Eighteen trained men were assigned to an experimental group (oral terbutaline 5 mg∙30...... of muscle proteins involved in growth, ion handling, lactate production and clearance increased (P≤0.05) with the intervention in TER compared to PLA, with no change in oxidative enzymes. Our observations suggest that muscle hypertrophy is the primary mechanism underlying enhancements in muscle force...... and peak power during maximal cycling induced by chronic β2-adrenergic stimulation in humans....

  17. Nucleolin down-regulation is involved in ADP-induced cell cycle arrest in S phase and cell apoptosis in vascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Wenmeng Wang

    Full Text Available High concentration of extracellular ADP has been reported to induce cell apoptosis, but the molecular mechanisms remain not fully elucidated. In this study, we found by serendipity that ADP treatment of human umbilical vein endothelial cells (HUVEC and human aortic endothelial cells (HAEC down-regulated the protein level of nucleolin in a dose- and time-dependent manner. ADP treatment did not decrease the transcript level of nucloelin, suggesting that ADP might induce nucleolin protein degradation. HUVEC and HAEC expressed ADP receptor P2Y13 receptor, but did not express P2Y1 or P2Y12 receptors. However, P2Y1, 12, 13 receptor antagonists MRS2179, PSB0739, MRS2211 did not inhibit ADP-induced down-regulation of nucleolin. Moreover, MRS2211 itself down-regulated nucleolin protein level. In addition, 2-MeSADP, an agonist for P2Y1, 12 and 13 receptors, did not down-regulate nucleolin protein. These results suggested that ADP-induced nucleolin down-regulation was not due to the activation of P2Y1, 12, or 13 receptors. We also found that ADP treatment induced cell cycle arrest in S phase, cell apoptosis and cell proliferation inhibition via nucleolin down-regulation. The over-expression of nucleolin by gene transfer partly reversed ADP-induced cell cycle arrest, cell apoptosis and cell proliferation inhibition. Furthermore, ADP sensitized HUVEC to cisplatin-induced cell death by the down-regulation of Bcl-2 expression. Taken together, we found, for the first time to our knowledge, a novel mechanism by which ADP regulates cell proliferation by induction of cell cycle arrest and cell apoptosis via targeting nucelolin.

  18. The role of reactive oxygen species (ROS) production on diallyl disulfide (DADS) induced apoptosis and cell cycle arrest in human A549 lung carcinoma cells

    International Nuclear Information System (INIS)

    Wu Xinjiang; Kassie, Fekadu; Mersch-Sundermann, Volker

    2005-01-01

    Diallyl disulfide (DADS), an oil soluble constituent of garlic (Allium sativum), has been reported to cause antimutagentic and anticarcinogenic effects in vitro and in vivo by modulating phases I and II enzyme activities. In recent years, several studies suggested that the chemopreventive effects of DADS can also be attributed to induction of cell cycle arrest and apoptosis in cancer cells. In the present study, we reported that DADS-induced cell cycle arrest at G2/M and apoptosis in human A549 lung cancer cells in a time- and dose-dependent manner. Additionally, a significant increase of intracellular reactive oxygen species (ROS) was induced in A549 cells less than 0.5 h after DADS treatment, indicating that ROS may be an early event in DADS-modulated apoptosis. Treatment of A549 cells with N-acetyl cysteine (NAC) completely abrogated DADS-induced cell cycle arrest and apoptosis. The result indicated that oxidative stress modulates cell proliferation and cell death induced by DADS

  19. The role of reactive oxygen species (ROS) production on diallyl disulfide (DADS) induced apoptosis and cell cycle arrest in human A549 lung carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu Xinjiang [Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen (Germany); Kassie, Fekadu [Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen (Germany); Mersch-Sundermann, Volker [Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen (Germany)]. E-mail: Volker.mersch-sundermann@uniklinikum-giessen.de

    2005-11-11

    Diallyl disulfide (DADS), an oil soluble constituent of garlic (Allium sativum), has been reported to cause antimutagentic and anticarcinogenic effects in vitro and in vivo by modulating phases I and II enzyme activities. In recent years, several studies suggested that the chemopreventive effects of DADS can also be attributed to induction of cell cycle arrest and apoptosis in cancer cells. In the present study, we reported that DADS-induced cell cycle arrest at G2/M and apoptosis in human A549 lung cancer cells in a time- and dose-dependent manner. Additionally, a significant increase of intracellular reactive oxygen species (ROS) was induced in A549 cells less than 0.5 h after DADS treatment, indicating that ROS may be an early event in DADS-modulated apoptosis. Treatment of A549 cells with N-acetyl cysteine (NAC) completely abrogated DADS-induced cell cycle arrest and apoptosis. The result indicated that oxidative stress modulates cell proliferation and cell death induced by DADS.

  20. Arctigenin induces cell cycle arrest by blocking the phosphorylation of Rb via the modulation of cell cycle regulatory proteins in human gastric cancer cells.

    Science.gov (United States)

    Jeong, Jin Boo; Hong, Se Chul; Jeong, Hyung Jin; Koo, Jin Suk

    2011-10-01

    Gastric cancer is a leading cause of cancer-related deaths, worldwide being second only to lung cancer as a cause of death. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms of arctigenin for anti-tumor effect on gastric cancer have not been examined. This study examined the biological effects of arctigenin on the human gastric cancer cell line SNU-1 and AGS. Cell proliferation was determined by MTT assay. In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by arctigenin in a time and dose dependent manner, as compared with SNU-1 and AGS cells cultured in the absence of arctigenin. Inhibition of cell proliferation by arctigenin was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bcl-2 to Bax by arctigenin. Also, arctigenin blocked cell cycle arrest from G(1) to S phase by regulating the expression of cell cycle regulatory proteins such as Rb, cyclin D1, cyclin E, CDK4, CDK2, p21Waf1/Cip1 and p15 INK4b. The antiproliferative effect of arctigenin on SNU-1 and AGS gastric cancer cells revealed in this study suggests that arctigenin has intriguing potential as a chemopreventive or chemotherapeutic agent. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  1. A novel curcumin derivative which inhibits P-glycoprotein, arrests cell cycle and induces apoptosis in multidrug resistance cells.

    Science.gov (United States)

    Lopes-Rodrigues, Vanessa; Oliveira, Ana; Correia-da-Silva, Marta; Pinto, Madalena; Lima, Raquel T; Sousa, Emília; Vasconcelos, M Helena

    2017-01-15

    Cancer multidrug resistance (MDR) is a major limitation to the success of cancer treatment and is highly associated with the overexpression of drug efflux pumps such as P-glycoprotein (P-gp). In order to achieve more effective chemotherapeutic treatments, it is important to develop P-gp inhibitors to block/decrease its activity. Curcumin (1) is a secondary metabolite isolated from the turmeric of Curcuma longa L.. Diverse biological activities have been identified for this compound, particularly, MDR modulation in various cancer cell models. However, curcumin (1) has low chemical stability, which severely limits its application. In order to improve stability and P-gp inhibitory effect, two potential more stable curcumin derivatives were synthesized as building blocks, followed by several curcumin derivatives. These compounds were then analyzed in terms of antitumor and anti-P-gp activity, in two MDR and sensitive tumor lines (from chronic myeloid leukemia and non-small cell lung cancer). We identified from a series of curcumin derivatives a novel curcumin derivative (1,7-bis(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)hepta-1,6-diene-3,5-dione, 10) with more potent antitumor and anti-P-gp activity than curcumin (1). This compound (10) was shown to promote cell cycle arrest (at the G2/M phase) and induce apoptosis in the MDR chronic myeloid leukemia cell line. Therefore it is a really interesting P-gp inhibitor due to its ability to inhibit both P-gp function and expression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Facile construction of fused benzimidazole-isoquinolinones that induce cell-cycle arrest and apoptosis in colorectal cancer cells.

    Science.gov (United States)

    He, Liu-Jun; Yang, Dong-Lin; Li, Shi-Qiang; Zhang, Ya-Jun; Tang, Yan; Lei, Jie; Frett, Brendan; Lin, Hui-Kuan; Li, Hong-Yu; Chen, Zhong-Zhu; Xu, Zhi-Gang

    2018-06-12

    Colorectal cancer (CRC) is one of the most frequent, malignant gastrointestinal tumors, and strategies and effectiveness of current therapy are limited. A series of benzimidazole-isoquinolinone derivatives (BIDs) was synthesized and screened to identify novel scaffolds for CRC. Of the compounds evaluated, 7g exhibited the most promising anti-cancer properties. Employing two CRC cell lines, SW620 and HT29, 7g was found to suppress growth and proliferation of the cell lines at a concentration of ∼20 µM. Treatment followed an increase in G 2 /M cell cycle arrest, which was attributed to cyclin B1 and cyclin-dependent kinase 1 (CDK1) signaling deficiencies with simultaneous enhancement in p21 and p53 activity. In addition, mitochondrial-mediated apoptosis was induced in CRC cells. Interestingly, 7g decreased phosphorylated AKT, mTOR and 4E-BP1 levels, while promoting the expression/stability of PTEN. Since PTEN controls input into the PI3K/AKT/mTOR pathway, antiproliferative effects can be attributed to PTEN-mediated tumor suppression. Collectively, these results suggest that BIDs exert antitumor activity in CRC by impairing PI3K/AKT/mTOR signaling. Against a small kinase panel, 7g exhibited low affinity at 5 µM suggesting anticancer properties likely stem through a non-kinase mechanism. Because of the novelty of BIDs, the structure can serve as a lead scaffold to design new CRC therapies. Copyright © 2018. Published by Elsevier Ltd.

  3. Diet-induced obesity reduces core body temperature across the estrous cycle and pregnancy in the rat.

    Science.gov (United States)

    Crew, Rachael C; Waddell, Brendan J; Maloney, Shane K; Mark, Peter J

    2018-04-16

    Obesity during pregnancy causes adverse maternal and fetal health outcomes and programs offspring for adult-onset diseases, including cardiovascular disease. Obesity also disrupts core body temperature (T c ) regulation in nonpregnant rodents; however, it is unknown whether obesity alters normal maternal T c adaptations to pregnancy. Since T c is influenced by the circadian system, and both obesity and pregnancy alter circadian biology, it was hypothesized that obesity disrupts the normal rhythmic patterns of T c before and during gestation. Obesity was induced by cafeteria (CAF) feeding in female Wistar rats for 8 weeks prior to and during gestation, whereas control (CON) animals had free access to chow. Intraperitoneal temperature loggers measured daily T c profiles throughout the study, while maternal body composition and leptin levels were assessed near term. Daily temperature profiles were examined for rhythmic features (mesor, amplitude and acrophase) by cosine regression analysis. CAF animals exhibited increased fat mass (93%) and associated hyperleptinemia (3.2-fold increase) compared to CON animals. CAF consumption reduced the average T c (by up to 0.29°C) across the estrous cycle and most of pregnancy; however, T c for CAF and CON animals converged toward the end of gestation. Obesity reduced the amplitude of T c rhythms at estrus and proestrus and on day 8 of pregnancy, but increased the amplitude at day 20 of pregnancy. Photoperiod analysis revealed that obesity reduced T c exclusively in the light period during pre-pregnancy but only during the dark period in late gestation. In conclusion, obesity alters rhythmic T c profiles and reduces the magnitude of the T c decline late in rat gestation, which may have implications for maternal health and fetal development.

  4. Radiation-induced micronucleus frequencies in female peripheral blood lymphocytes collected during the first and second half of the menstrual cycle

    International Nuclear Information System (INIS)

    Krol, M.; Lankoff, A.; Buraczewska, I.; Derezinska, E.; Wojcik, A.

    2007-01-01

    Biological dosimetry relies on the assessment of dose in peripheral blood lymphocytes (PBL) of a victim. Variability in the individual radiosensitivity of PBL has an impact on the precision of dose estimate and radiation-induced micronuclei show a strong individual variability. A factor which can influence the radiosensitivity of PBL is the hormonal status of female donors, which shows a regular pattern during the menstrual cycle. The aim of the present investigation was to verify whether the position within the menstrual cycle has an impact on the level of micronuclei in PBL. Blood was collected from 19 donors during the first and second half of the menstrual cycle and exposed to 2 Gy. Although statistically significant differences between the MN frequencies in PBL collected during the different time points were observed in the case of some donors, no reproducible trend that could find application in biological dosimetry could be detected. (authors)

  5. Protection of myocytes against free radical-induced damage by accelerated turnover of the glutathione redox cycle

    NARCIS (Netherlands)

    Le, C. T.; Hollaar, L.; van der Valk, E. J.; Franken, N. A.; van Ravels, F. J.; Wondergem, J.; van der Laarse, A.

    1995-01-01

    The primary defence mechanism of myocytes against peroxides and peroxide-derived peroxyl and alkoxyl radicals is the glutathione redox cycle. The purpose of the present study was to increase the turnover rate of this cycle by stimulating the glutathione peroxidase catalysed reaction (2GSH-->GSSG),

  6. Test chip for detecting thin film cracking induced by fast temperature cycling and electromigration in multilevel interconnect systems

    NARCIS (Netherlands)

    Nguyen, Van Hieu; Nguyen, H.; Salm, Cora; Vroemen, J.; Voets, J.; Krabbenborg, B.H.; Bisschop, J.; Mouthaan, A.J.; Kuper, F.G.

    2002-01-01

    Temperature cycling in power ICs is a reliability hazard, even more so when electromigration is playing a role as well. The frequency of the temperature cycling is in the audio domain, which makes it impossible to test in environmental chambers. In the paper, the design and application of a novel

  7. Test chip for Detecting Thin Film Cracking Induced by Fast Temperature Cycling and Electromigration in Multilevel Interconnect Systems

    NARCIS (Netherlands)

    Nguyen, Van Hieu; Salm, Cora; Vroemen, J.; Voets, J.; Krabbenborg, B.H.; Krabbenborg, B.; Bisschop, J.; Mouthaan, A.J.; Kuper, F.G.

    2002-01-01

    Temperature cycling in power ICs is a reliability hazard, even more so when electromigration is playing a role as well. The frequency of the temperature cycling is in the audio domain, which makes it impossible to test in environmental chambers. In the paper, the design and application of a novel

  8. When Product Life Cycle Meets Customer Activity Cycle

    DEFF Research Database (Denmark)

    Tan, Adrian Ronald

    2007-01-01

    Manufacturing companies have traditionally focused their efforts on designing, developing and producing products to offer on the market. Today global competition and demands for greater company responsibility of products throughout their entire life cycle are driving manufacturing companies to sh...

  9. Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2017-01-01

    ABSTRACT We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G2 phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression. PMID:27715464

  10. Prolonged electrical stimulation-induced gluteal and hamstring muscle activation and sitting pressure in spinal cord injury: Effect of duty cycle

    OpenAIRE

    Christof A. J. Smit, MD; Karin J. A. Legemate, MSc; Anja de Koning, MSc; Sonja de Groot, PhD; Janneke M. Stolwijk-Swuste, MD, PhD; Thomas W. J. Janssen, PhD

    2013-01-01

    Pressure ulcers (PUs) are highly prevalent in people with spinal cord injury (SCI). Electrical stimulation (ES) activates muscles and might reduce risk factors. Our objectives were to study and compare the effects of two duty cycles during 3 h of ES-induced gluteal and hamstring activation on interface pressure distribution in sitting individuals with SCI and study the usability of a newly developed electrode garment (ES shorts). Ten individuals with SCI participated in this study, in which t...

  11. Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal fibrosis by releasing from G2/M cell cycle arrest.

    Science.gov (United States)

    Chen, Wenxia; Yan, Yongbin; Song, Chundong; Ding, Ying; Du, Tao

    2017-12-14

    Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI); however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated. Tubular cell proliferation and apoptosis were identified by Ki67 or terminal-deoxynucleotidyl transferase-mediated nick end labeling immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin staining were used for assessing renal fibrosis. The mRNA or protein expression in the kidney was measured by quantitative reverse transcription-PCR or Western blot, respectively. The total collagen concentration was also determined. In vitro , NRK-52E cells that treated with MVs under hypoxia injury and with HGF or U0126 administration were used, and cell cycle analysis was performed. The effects of hWJMSC-MVs on enhancing the proliferation and mitigating the apoptosis of renal cells, abrogating IRI-induced fibrosis, improving renal function, decreasing collagen deposition, and altering the expression levels of epithelial-mesenchymal transition and cell cycle-related proteins in IRI rats were found. In vitro experiment showed that hWJMSC-MVs could induce G2/M cell cycle arrest and decrease the expression of collagen deposition-related proteins in NRK-52E cells after 24 or 48 h. However, U0126 treatment reversed these effects. In conclusion, MVs derived from hWJMSCs ameliorate IR-induced renal fibrosis by inducing G2/M cell cycle arrest via Erk1/2 signaling. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  12. Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8.

    Science.gov (United States)

    Gysler, Stefan M; Mulla, Melissa J; Guerra, Marta; Brosens, Jan J; Salmon, Jane E; Chamley, Lawrence W; Abrahams, Vikki M

    2016-07-01

    What is the role of microRNAs (miRs) in antiphospholipid antibody (aPL)-induced trophoblast inflammation? aPL-induced up-regulation of trophoblast miR-146a-3p is mediated by Toll-like receptor 4 (TLR4), and miR-146a-3p in turn drives the cells to secrete interleukin (IL)-8 by activating the RNA sensor, TLR8. Obstetric antiphospholipid syndrome (APS) is an autoimmune disorder characterized by circulating aPL and an increased risk of pregnancy complications. We previously showed that aPL recognizing beta2 glycoprotein I (β2GPI) elicit human first trimester trophoblast secretion of IL-8 by activating TLR4. Since some miRs control TLR responses, their regulation in trophoblast cells by aPL and functional role in the aPL-mediated inflammatory response was investigated. miRs can be released from cells via exosomes, and therefore, miR exosome expression was also examined. A panel of miRs was selected based on their involvement with TLR signaling: miR-9; miR-146a-5p and its isomiR, miR-146a-3p; miR-155, miR-210; and Let-7c. Since certain miRs can activate the RNA sensor, TLR8, this was also investigated. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR8 was studied. HTR8 cells transfected to express a TLR8 dominant negative (DN) were also used. Plasma was evaluated from pregnant women who have aPL, either with or without systemic lupus erythematous (SLE) (n = 39); SLE patients without aPL (n = 30); and healthy pregnant controls (n = 20). Trophoblast HTR8 wildtype and TLR8-DN cells were incubated with or without aPL (mouse anti-human β2GPI mAb) for 48-72 h. HTR8 cells were also treated with or without aPL in the presence and the absence of a TLR4 antagonist (lipopolysaccharide from Rhodobacter sphaeroides; LPS-RS), specific miR inhibitors or specific miR mimics. miR expression levels in trophoblast cells, trophoblast-derived exosomes and exosomes isolated from patient plasma were measured by qPCR. Trophoblast IL-8 secretion was

  13. The production of reactive oxygen species and the mitochondrial membrane potential are modulated during onion oil-induced cell cycle arrest and apoptosis in A549 cells.

    Science.gov (United States)

    Wu, Xin-jiang; Stahl, Thorsten; Hu, Ying; Kassie, Fekadu; Mersch-Sundermann, Volker

    2006-03-01

    Protective effects of Allium vegetables against cancers have been shown extensively in experimental animals and epidemiologic studies. We investigated cell proliferation and the induction of apoptosis by onion oil extracted from Allium cepa, a widely consumed Allium vegetable, in human lung cancer A549 cells. GC/MS analysis suggested that propyl sulfides but not allyl sulfides are major sulfur-containing constituents of onion oil. Onion oil at 12.5 mg/L significantly induced apoptosis (13% increase of apoptotic cells) as indicated by sub-G1 DNA content. It also caused cell cycle arrest at the G2/M phase; 25 mg/L onion oil increased the percentage of G2/M cells almost 6-fold compared with the dimethyl sulfoxide control. The action of onion oil may occur via a reactive oxygen species-dependent pathway because cell cycle arrest and apoptosis were blocked by the antioxidants N-acetylcysteine and exogenous glutathione. Marked collapse of the mitochondrial membrane potential suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by onion oil. Expression of phospho-cdc2 and phospho-cyclin B1 were downregulated by onion oil, perhaps accounting for the G2/M arrest. Overall, these results suggest that onion oil may exert chemopreventive action by inducing cell cycle arrest and apoptosis in tumor cells.

  14. Dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro

    International Nuclear Information System (INIS)

    Liu Shuchun; Lu Zhe; Li Yanbo; Kang Shunai; Gong Shouliang; Zhao Wenju

    2008-01-01

    Objective: To observe the dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro in order to reveal the possible mechanism of biological effect and adaptive response induced by low dose radiation. Methods: The experiment was divided into D2 (challenging dose), D1 (inductive dose) + D2 and sham-irradiation groups. EL-4 lymphoma cells were irradiated with D1 (75 mGy, 6.25-200.00 mGy·mm -1 ) and D2(1.5 Gy, 287 mGy·min -1 ), the time interval between D1 and D2 was 6 h. The percentage of apoptosis and each cell cycle phase were measured with flow cytometry. Results: When the dose rates of D1 were 6.25-50.00 mGy·min -1 , the percentages of apoptosis in the D1 + D2 group were significantly lower than those in the D2 group (P 0 /G 1 phase cells decreased significantly (P -1 , D2 is 1.5 Gy (287 mGy·min -1 ), and the time interval between D1 and D2 is 6 h, the adaptive response of apoptosis and cell cycle progression in EL-4 lymphoma cells in vitro could be induced. (authors)

  15. Cell kinetics of hypoxic cells in a murine tumour in vivo: flow cytometric determination of the radiation-induced blockage of cell cycle progression

    International Nuclear Information System (INIS)

    Rutgers, D.H.; Niessen, D.P.P.; Linden, P.M. van der

    1987-01-01

    Cells from the small cell population of viable cells in the large necrotic centre of murine M8013 tumours were investigated with respect to their cell kinetics. Flow cytometry (FCM) of this part of subcutaneously transplanted tumours revealed the presence of tumour cells with G1,S and G2 + M phase DNA-contents. These severely hypoxic cells could have stopped cell cycle progression due to the nutritional deprivation, irrespective of their position within the cell cycle. Labelling methods, used to disclose the cell kinetics of this cell population, are hampered by the absence of a transport system in these large necrotic areas. Therefore FCM was used to monitor radiation induced changes in the cell cycle distribution. From this investigation it was concluded that hypoxic cells in the necrotic centre of the M8013 tumour progress through the cell cycle. As well as a cell population with a cell cycle time (Tsub(c)) of approximately 84 hr, a subpopulation with a Tsub(c) of approximately 21 hr occurred. (author)

  16. MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Yukari Takahashi

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. CONCLUSIONS/SIGNIFICANCE: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors.

  17. Andrographis paniculata extracts and major constituent diterpenoids inhibit growth of intrahepatic cholangiocarcinoma cells by inducing cell cycle arrest and apoptosis.

    Science.gov (United States)

    Suriyo, Tawit; Pholphana, Nanthanit; Rangkadilok, Nuchanart; Thiantanawat, Apinya; Watcharasit, Piyajit; Satayavivad, Jutamaad

    2014-05-01

    Andrographis paniculata is an important herbal medicine widely used in several Asian countries for the treatment of various diseases due to its broad range of pharmacological activities. The present study reports that A. paniculata extracts potently inhibit the growth of liver (HepG2 and SK-Hep1) and bile duct (HuCCA-1 and RMCCA-1) cancer cells. A. paniculata extracts with different contents of major diterpenoids, including andrographolide, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and 14-deoxyandrographolide, exhibited a different potency of growth inhibition. The ethanolic extract of A. paniculata at the first true leaf stage, which contained a high amount of 14-deoxyandrographolide but a low amount of andrographolide, showed a cytotoxic effect to cancer cells about 4 times higher than the water extract of A. paniculata at the mature leaf stage, which contained a high amount of andrographolide but a low amount of 14-deoxyandrographolide. Andrographolide, not 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, or 14-deoxyandrographolide, possessed potent cytotoxic activity against the growth of liver and bile duct cancer cells. The cytotoxic effect of the water extract of A. paniculata at the mature leaf stage could be explained by the present amount of andrographolide, while the cytotoxic effect of the ethanolic extract of A. paniculata at the first true leaf stage could not. HuCCA-1 cells showed more sensitivity to A. paniculata extracts and andrographolide than RMCCA-1 cells. Furthermore, the ethanolic extract of A. paniculata at the first true leaf stage increased cell cycle arrest at the G0/G1 and G2/M phases, and induced apoptosis in both HuCCA-1 and RMCCA-1 cells. The expressions of cyclin-D1, Bcl-2, and the inactive proenzyme form of caspase-3 were reduced by the ethanolic extract of A. paniculata in the first true leaf stage treatment, while a proapoptotic protein Bax was increased. The cleavage of poly (ADP

  18. Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

    International Nuclear Information System (INIS)

    Arachchige Don, Aruni S.; Dallapiazza, Robert F.; Bennin, David A.; Brake, Tiffany; Cowan, Colleen E.; Horne, Mary C.

    2006-01-01

    Cyclin G2 is an atypical cyclin that associates with active protein phosphatase 2A. Cyclin G2 gene expression correlates with cell cycle inhibition; it is significantly upregulated in response to DNA damage and diverse growth inhibitory stimuli, but repressed by mitogenic signals. Ectopic expression of cyclin G2 promotes cell cycle arrest, cyclin dependent kinase 2 inhibition and the formation of aberrant nuclei [Bennin, D. A., Don, A. S., Brake, T., McKenzie, J. L., Rosenbaum, H., Ortiz, L., DePaoli-Roach, A. A., and Horne, M. C. (2002). Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B' subunits in active complexes and induces nuclear aberrations and a G 1 /S-phase cell cycle arrest. J Biol Chem 277, 27449-67]. Here we report that endogenous cyclin G2 copurifies with centrosomes and microtubules (MT) and that ectopic G2 expression alters microtubule stability. We find exogenous and endogenous cyclin G2 present at microtubule organizing centers (MTOCs) where it colocalizes with centrosomal markers in a variety of cell lines. We previously reported that cyclin G2 forms complexes with active protein phosphatase 2A (PP2A) and colocalizes with PP2A in a detergent-resistant compartment. We now show that cyclin G2 and PP2A colocalize at MTOCs in transfected cells and that the endogenous proteins copurify with isolated centrosomes. Displacement of the endogenous centrosomal scaffolding protein AKAP450 that anchors PP2A at the centrosome resulted in the depletion of centrosomal cyclin G2. We find that ectopic expression of cyclin G2 induces microtubule bundling and resistance to depolymerization, inhibition of polymer regrowth from MTOCs and a p53-dependent cell cycle arrest. Furthermore, we determined that a 100 amino acid carboxy-terminal region of cyclin G2 is sufficient to both direct GFP localization to centrosomes and induce cell cycle inhibition. Colocalization of endogenous cyclin G2 with only one of two GFP-centrin-tagged centrioles, the

  19. Extended driving impairs nocturnal driving performances.

    Directory of Open Access Journals (Sweden)

    Patricia Sagaspe

    Full Text Available Though fatigue and sleepiness at the wheel are well-known risk factors for traffic accidents, many drivers combine extended driving and sleep deprivation. Fatigue-related accidents occur mainly at night but there is no experimental data available to determine if the duration of prior driving affects driving performance at night. Participants drove in 3 nocturnal driving sessions (3-5 am, 1-5 am and 9 pm-5 am on open highway. Fourteen young healthy men (mean age [+/-SD] = 23.4 [+/-1.7] years participated Inappropriate line crossings (ILC in the last hour of driving of each session, sleep variables, self-perceived fatigue and sleepiness were measured. Compared to the short (3-5 am driving session, the incidence rate ratio of inappropriate line crossings increased by 2.6 (95% CI, 1.1 to 6.0; P<.05 for the intermediate (1-5 am driving session and by 4.0 (CI, 1.7 to 9.4; P<.001 for the long (9 pm-5 am driving session. Compared to the reference session (9-10 pm, the incidence rate ratio of inappropriate line crossings were 6.0 (95% CI, 2.3 to 15.5; P<.001, 15.4 (CI, 4.6 to 51.5; P<.001 and 24.3 (CI, 7.4 to 79.5; P<.001, respectively, for the three different durations of driving. Self-rated fatigue and sleepiness scores were both positively correlated to driving impairment in the intermediate and long duration sessions (P<.05 and increased significantly during the nocturnal driving sessions compared to the reference session (P<.01. At night, extended driving impairs driving performances and therefore should be limited.

  20. Hypothalamic miR-219 regulates individual metabolic differences in response to diet-induced weight cycling

    Directory of Open Access Journals (Sweden)

    Mariana Schroeder

    2018-03-01

    Full Text Available Consumption of a low calorie diet is the most common approach to lose weight. While generally effective at first, it is frequently followed by a relapse where the pre-diet weight is regained, and often exceeded. This pattern of repeated weight loss/regain is referred to as weight cycling and the resulting metabolic response varies greatly between individuals. Objective: We attempted to address the issue of individual differences in the response to weight cycling in male mice. Methods: We first exposed adult wild type mice to repeated cycles of high/low fat food. Next, using a lentiviral approach, we knocked-down or over-expressed miR-219 in the ventromedial hypothalamus (VMH of an additional mouse cohort and performed a full metabolic assessment. Results: Exposure of wild type males to weight cycling resulted in the division of the cohort into subsets of resistant versus metabolic-syndrome-prone (MS animals, which differed in their metabolic profile and hypothalamic miR-219 levels. Lentiviral knock-down of miR-219 in the VMH led to exacerbation of metabolic syndrome. In contrast, over-expression of miR-219 resulted in moderation of the metabolic syndrome phenotype. Conclusions: Our results suggest a role for miR-219 in the mediation of the metabolic phenotype resulting from repeated weight cycling. Keywords: Weight cycling, Metabolic syndrome, miRNAs, Ventromedial hypothalamus, High fat diet, Diabetes

  1. Controlling successive ionic layer absorption and reaction cycles to optimize silver nanoparticle-induced localized surface plasmon resonance effects on the paper strip

    Science.gov (United States)

    Lee, Jae-Chul; Kim, Wansun; Park, Hun-Kuk; Choi, Samjin

    2017-03-01

    This study investigates why a silver nanoparticle (SNP)-induced surface-enhanced Raman scattering (SERS) paper chip fabricated at low successive ionic layer absorption and reaction (SILAR) cycles leads to a high SERS enhancement factor (7 × 108) with an inferior nanostructure and without generating a hot spot effect. The multi-layered structure of SNPs on cellulose fibers, verified by magnified scanning electron microscopy (SEM) and analyzed by a computational simulation method, was hypothesized as the reason. The pattern of simulated local electric field distribution with respect to the number of SILAR cycles showed good agreement with the experimental Raman intensity, regardless of the wavelength of the excitation laser sources. The simulated enhancement factor at the 785-nm excitation laser source (2.8 × 109) was 2.5 times greater than the experimental enhancement factor (1.1 × 109). A 532-nm excitation laser source exhibited the highest maximum local electric field intensity (1.9 × 1011), particularly at the interparticle gap called a hot spot. The short wavelength led to a strong electric field intensity caused by strong electromagnetic coupling arising from the SNP-induced local surface plasmon resonance (LSPR) effects through high excitation energy. These findings suggest that our paper-based SILAR-fabricated SNP-induced LSPR model is valid for understanding SNP-induced LSPR effects.

  2. The production of monokaryotic hyphae by Cryptococcus neoformans can be induced by high temperature arrest of the cell cycle and is independent of same-sex mating.

    Science.gov (United States)

    Fu, Jianmin; Morris, Ian R; Wickes, Brian L

    2013-01-01

    Cryptococcus neoformans is a heterothallic fungal pathogen of humans and animals. Although the fungus grows primarily as a yeast, hyphae are produced during the sexual phase and during a process called monokaryotic fruiting, which is also believed to involve sexual reproduction, but between cells of the same mating type. Here we report a novel monokaryotic fruiting mechanism that is dependent on the cell cycle and occurs in haploid cells in the absence of sexual reproduction. Cells grown at 37°C were found to rapidly produce hyphae (∼4 hrs) and at high frequency (∼40% of the population) after inoculation onto hyphae-inducing agar. Microscopic examination of the 37°C seed culture revealed a mixture of normal-sized and enlarged cells. Micromanipulation of single cells demonstrated that only enlarged cells were able to produce hyphae and genetic analysis confirmed that hyphae did not arise from α-α mating or endoduplication. Cell cycle analysis revealed that cells grown at 37°C had an increased population of cells in G2 arrest, with the proportion correlated with the frequency of monokaryotic fruiting. Cell sorting experiments demonstrated that enlarged cells were only found in the G2-arrested population and only this population contained cells able to produce hyphae. Treatment of cells at low temperature with the G2 cell cycle arrest agent, nocodazole, induced hyphal growth, confirming the role of the cell cycle in this process. Taken together, these results reveal a mating-independent mechanism for monokaryotic fruiting, which is dependent on the cell cycle for induction of hyphal competency.

  3. Melanogenesis stimulation in B16-F10 melanoma cells induces cell cycle alterations, increased ROS levels and a differential expression of proteins as revealed by proteomic analysis

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Elizabeth S.; Kawahara, Rebeca [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Kadowaki, Marina K. [Universidade Estadual do Oeste do Parana, Cascavel, PR (Brazil); Amstalden, Hudson G.; Noleto, Guilhermina R.; Cadena, Silvia Maria S.C.; Winnischofer, Sheila M.B. [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil); Martinez, Glaucia R., E-mail: grmartinez@ufpr.br [Departamento de Bioquimica e Biologia Molecular, Setor de Ciencias Biologicas, Universidade Federal do Parana, P.O. Box 19046, CEP 81531-990, Curitiba, PR (Brazil)

    2012-09-10

    Considering that stimulation of melanogenesis may lead to alterations of cellular responses, besides melanin production, our main goal was to study the cellular effects of melanogenesis stimulation of B16-F10 melanoma cells. Our results show increased levels of the reactive oxygen species after 15 h of melanogenesis stimulation. Following 48 h of melanogenesis stimulation, proliferation was inhibited (by induction of cell cycle arrest in the G1 phase) and the expression levels of p21 mRNA were increased. In addition, melanogenesis stimulation did not induce cellular senescence. Proteomic analysis demonstrated the involvement of proteins from other pathways besides those related to the cell cycle, including protein disulfide isomerase A3, heat-shock protein 70, and fructose biphosphate aldolase A (all up-regulated), and lactate dehydrogenase (down-regulated). In RT-qPCR experiments, the levels of pyruvate kinase M2 mRNA dropped, whereas the levels of ATP synthase (beta-F1) mRNA increased. These data indicate that melanogenesis stimulation of B16-F10 cells leads to alterations in metabolism and cell cycle progression that may contribute to an induction of cell quiescence, which may provide a mechanism of resistance against cellular injury promoted by melanin synthesis. -- Highlights: Black-Right-Pointing-Pointer Melanogenesis stimulation by L-tyrosine+NH{sub 4}Cl in B16-F10 melanoma cells increases ROS levels. Black-Right-Pointing-Pointer Melanogenesis inhibits cell proliferation, and induced cell cycle arrest in the G1 phase. Black-Right-Pointing-Pointer Proteomic analysis showed alterations in proteins of the cell cycle and glucose metabolism. Black-Right-Pointing-Pointer RT-qPCR analysis confirmed alterations of metabolic targets after melanogenesis stimulation.

  4. Wogonin induced G1 cell cycle arrest by regulating Wnt/β-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells

    International Nuclear Information System (INIS)

    He, Licheng; Lu, Na; Dai, Qinsheng; Zhao, Yue; Zhao, Li; Wang, Hu; Li, Zhiyu; You, Qidong; Guo, Qinglong

    2013-01-01

    Highlights: • Wogonin inhibited HCT116 cells growth and arrested at G1 phase of the cell cycle. • Wogonin down-regulated the canonical Wnt/β-catenin signaling pathway. • Wogonin interfered in the combination of β-catenin and TCF/Lef. • Wogonin limited the kinase activity of CDK8. - Abstract: Wogonin, a naturally occurring mono-flavonoid, has been reported to have tumor therapeutic potential and good selectivity both in vitro and in vivo. Herein, we investigated the anti-proliferation effects and associated mechanisms of wogonin in human colorectal cancer in vitro. The flow-cytometric analysis showed that wogonin induced a G1 phase cell cycle arrest in HCT116 cells in a concentration- and time-dependent manner. Meanwhile, the cell cycle-related proteins, such as cyclin A, E, D1, and CDK2, 4 were down-regulated in wogonin-induced G1 cell cycle arrest. Furthermore, we showed that the anti-proliferation and G1 arrest effect of wogonin on HCT116 cells was associated with deregulation of Wnt/β-catenin signaling pathway. Wogonin-treated cells showed decreased intracellular levels of Wnt proteins, and activated degradation complex to phosphorylated and targeted β-catenin for proteasomal degradation. Wogonin inhibited β-catenin-mediated transcription by interfering in the transcriptional activity of TCF/Lef, and repressing the kinase activity of CDK8 which has been considered as an oncogene involving in the development of colorectal cancers. Moreover, CDK8 siRNA-transfected HCT116 cells showed similar results to wogonin treated cells. Thus, our data suggested that wogonin induced anti-proliferation and G1 arrest via Wnt/β-catenin signaling pathway and it can be developed as a therapeutic agent against human colorectal cancer

  5. Impact Of Real-World Driving Characteristics On Vehicular Emissions

    OpenAIRE

    Nesamani, K S; Subramanian, K. P.

    2005-01-01

    With increase in traffic volume and change in travel related characteristics, vehicular emissions and energy consumption have increased significantly since two decades in India. Current models are not capable of estimating vehicular emissions accurately due to inadequate representation of real-world driving. The focus of this paper is to understand the level of Indian Driving cycle (IDC) in representing the real-world driving and to assess the impact of real-world driving on vehicular emissio...

  6. SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes.

    NARCIS (Netherlands)

    Diepen, van Janna A.; Hooiveld, Guido; Stienstra, Rinke; Deen, Peter M.

    2017-01-01

    Obesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal induced by

  7. WLTP Random Cycle Generator

    NARCIS (Netherlands)

    Kooijman, D.G.; Balau, A.E.; Wilkins, S.; Ligterink, N.; Cuelenaere, R.

    2015-01-01

    European light duty vehicle emission legislation is gradually shifting the focus from test procedures with merely static test cycles, towards procedures including Real Driving Emissions (RDE), as they are a mean to achieve the European (NOx) emission reduction target. Hence a RDE trip must represent

  8. WLTP random cycle generator

    NARCIS (Netherlands)

    Kooijman, D.G.; Balau, A.E.; Wilkins, S.; Ligterink, N.; Cuelenaere, R.

    2015-01-01

    European light duty vehicle emission legislation is gradually shifting the focus from test procedures with merely static test cycles, towards procedures including Real Driving Emissions (RDE), as they are a mean to achieve the European (NOx) emission reduction target. Hence a RDE trip must represent

  9. Lebein, a snake venom disintegrin, suppresses human colon cancer cells proliferation and tumor-induced angiogenesis through cell cycle arrest, apoptosis induction and inhibition of VEGF expression.

    Science.gov (United States)

    Zakraoui, Ons; Marcinkiewicz, Cezary; Aloui, Zohra; Othman, Houcemeddine; Grépin, Renaud; Haoues, Meriam; Essafi, Makram; Srairi-Abid, Najet; Gasmi, Ammar; Karoui, Habib; Pagès, Gilles; Essafi-Benkhadir, Khadija

    2017-01-01

    Lebein, is an heterodimeric disintegrin isolated from Macrovipera lebetina snake venom that was previously characterized as an inhibitor of ADP-induced platelet aggregation. In this study, we investigated the effect of Lebein on the p53-dependent growth of human colon adenocarcinoma cell lines. We found that Lebein significantly inhibited LS174 (p53wt), HCT116 (p53wt), and HT29 (p53mut) colon cancer cell viability by inducing cell cycle arrest through the modulation of expression levels of the tumor suppression factor p53, cell cycle regulating proteins cyclin D1, CDK2, CDK4, retinoblastoma (Rb), CDK1, and cyclin-dependent kinase inhibitors p21 and p27. Interestingly, Lebein-induced apoptosis of colon cancer cells was dependent on their p53 status. Thus, in LS174 cells, cell death was associated with PARP cleavage and the activation of caspases 3 and 8 while in HCT116 cells, Lebein induced caspase-independent apoptosis through increased expression of apoptosis inducing factor (AIF). In LS174 cells, Lebein triggers the activation of the MAPK ERK1/2 pathway through induction of reactive oxygen species (ROS). It also decreased cell adhesion and migration to fibronectin through down regulation of α5β1 integrin. Moreover, Lebein significantly reduced the expression of two angiogenesis stimulators, Vascular Endothelial Growth Factor (VEGF) and Neuropilin 1 (NRP1). It inhibited the VEGF-induced neovascularization process in the quail embryonic CAM system and blocked the development of human colon adenocarcinoma in nude mice. Overall, our work indicates that Lebein may be useful to design a new therapy against colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells

    International Nuclear Information System (INIS)

    Zhang, Xiuhua; Chen, Minxiao; Zou, Peng; Kanchana, Karvannan; Weng, Qiaoyou; Chen, Wenbo; Zhong, Peng; Ji, Jiansong; Zhou, Huiping; He, Langchong; Liang, Guang

    2015-01-01

    Prostate cancer is the most commonly diagnosed malignancy among men. The Discovery of new agents for the treatment of prostate cancer is urgently needed. Compound WZ35, a novel analog of the natural product curcumin, exhibited good anti-prostate cancer activity, with an IC 50 of 2.2 μM in PC-3 cells. However, the underlying mechanism of WZ35 against prostate cancer cells is still unclear. Human prostate cancer PC-3 cells and DU145 cells were treated with WZ35 for further proliferation, apoptosis, cell cycle, and mechanism analyses. NAC and CHOP siRNA were used to validate the role of ROS and ER stress, respectively, in the anti-cancer actions of WZ35. Our results show that WZ35 exhibited much higher cell growth inhibition than curcumin by inducing ER stress-dependent cell apoptosis in human prostate cells. The reduction of CHOP expression by siRNA partially abrogated WZ35-induced cell apoptosis. WZ35 also dose-dependently induced cell cycle arrest in the G2/M phase. Furthermore, we found that WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells. Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis, ER stress activation, and cell cycle arrest, indicating an upstream role of ROS generation in mediating the anti-cancer effect of WZ35. Taken together, this work presents the novel anticancer candidate WZ35 for the treatment of prostate cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human prostate cancer treatment. The online version of this article (doi:10.1186/s12885-015-1851-3) contains supplementary material, which is available to authorized users

  11. Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

    Science.gov (United States)

    2012-01-01

    Background Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Methods Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. Results We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. Conclusions We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin. PMID:22280307

  12. Citric acid induces cell-cycle arrest and apoptosis of human immortalized keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling pathways.

    Science.gov (United States)

    Ying, Tsung-Ho; Chen, Chia-Wei; Hsiao, Yu-Ping; Hung, Sung-Jen; Chung, Jing-Gung; Yang, Jen-Hung

    2013-10-01

    Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and skincare products. However, there is concern regarding its safety for the skin. In this study, we investigated the cytotoxic effects of citric acid on the human keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5-12.5 mM for different time periods. Cell-cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, flow cytometry, western blot and confocal microscopy. Citric acid not only inhibited proliferation of HaCaT cells in a dose-dependent manner, but also induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced apoptosis via caspase-dependent and caspase-independent pathways. Citric acid also activated death receptors and increased the levels of caspase-8, activated BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The study results suggest that citric acid is cytotoxic to HaCaT cells via induction of apoptosis and cell-cycle arrest in vitro.

  13. Silkworm Pupa Protein Hydrolysate Induces Mitochondria-Dependent Apoptosis and S Phase Cell Cycle Arrest in Human Gastric Cancer SGC-7901 Cells

    Directory of Open Access Journals (Sweden)

    Xiaotong Li

    2018-03-01

    Full Text Available Silkworm pupae (Bombyx mori are a high-protein nutrition source consumed in China since more than 2 thousand years ago. Recent studies revealed that silkworm pupae have therapeutic benefits to treat many diseases. However, the ability of the compounds of silkworm pupae to inhibit tumourigenesis remains to be elucidated. Here, we separated the protein of silkworm pupae and performed alcalase hydrolysis. Silkworm pupa protein hydrolysate (SPPH can specifically inhibit the proliferation and provoke abnormal morphologic features of human gastric cancer cells SGC-7901 in a dose- and time-dependent manner. Moreover, flow cytometry indicated that SPPH can induce apoptosis and arrest the cell-cycle in S phase. Furthermore, SPPH was shown to provoke accumulation of reactive oxygen species (ROS and depolarization of mitochondrial membrane potential. Western blotting analysis indicated that SPPH inhibited Bcl-2 expression and promoted Bax expression, and subsequently induced apoptosis-inducing factor and cytochrome C release, which led to the activation of initiator caspase-9 and executioner caspase-3, cleavage of poly (ADP-ribose polymerase (PARP, eventually caused cell apoptosis. Moreover, SPPH-induced S-phase arrest was mediated by up-regulating the expression of E2F1 and down-regulating those of cyclin E, CDK2 and cyclin A2. Transcriptome sequencing and gene set enrichment analysis (GSEA also revealed that SPPH treatment could affect gene expression and pathway regulation related to tumourigenesis, apoptosis and cell cycle. In summary, our results suggest that SPPH could specifically suppress cell growth of SGC-7901 through an intrinsic apoptotic pathway, ROS accumulation and cell cycle arrest, and silkworm pupae have a potential to become a source of anticancer agents in the future.

  14. Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

    International Nuclear Information System (INIS)

    Lee, Seung Joon; Langhans, Sigrid A

    2012-01-01

    Curcumin (diferuloylmethane), the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC), is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C) which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to curcumin

  15. Anaphase-promoting complex/cyclosome protein Cdc27 is a target for curcumin-induced cell cycle arrest and apoptosis

    Directory of Open Access Journals (Sweden)

    Lee Seung Joon

    2012-01-01

    Full Text Available Abstract Background Curcumin (diferuloylmethane, the yellow pigment in the Asian spice turmeric, is a hydrophobic polyphenol from the rhizome of Curcuma longa. Because of its chemopreventive and chemotherapeutic potential with no discernable side effects, it has become one of the major natural agents being developed for cancer therapy. Accumulating evidence suggests that curcumin induces cell death through activation of apoptotic pathways and inhibition of cell growth and proliferation. The mitotic checkpoint, or spindle assembly checkpoint (SAC, is the major cell cycle control mechanism to delay the onset of anaphase during mitosis. One of the key regulators of the SAC is the anaphase promoting complex/cyclosome (APC/C which ubiquitinates cyclin B and securin and targets them for proteolysis. Because APC/C not only ensures cell cycle arrest upon spindle disruption but also promotes cell death in response to prolonged mitotic arrest, it has become an attractive drug target in cancer therapy. Methods Cell cycle profiles were determined in control and curcumin-treated medulloblastoma and various other cancer cell lines. Pull-down assays were used to confirm curcumin binding. APC/C activity was determined using an in vitro APC activity assay. Results We identified Cdc27/APC3, a component of the APC/C, as a novel molecular target of curcumin and showed that curcumin binds to and crosslinks Cdc27 to affect APC/C function. We further provide evidence that curcumin preferably induces apoptosis in cells expressing phosphorylated Cdc27 usually found in highly proliferating cells. Conclusions We report that curcumin directly targets the SAC to induce apoptosis preferably in cells with high levels of phosphorylated Cdc27. Our studies provide a possible molecular mechanism why curcumin induces apoptosis preferentially in cancer cells and suggest that phosphorylation of Cdc27 could be used as a biomarker to predict the therapeutic response of cancer cells to

  16. HARMONIC DRIVE SELECTION

    Directory of Open Access Journals (Sweden)

    Piotr FOLĘGA

    2014-03-01

    Full Text Available The variety of types and sizes currently in production harmonic drive is a problem in their rational choice. Properly selected harmonic drive must meet certain requirements during operation, and achieve the anticipated service life. The paper discusses the problems associated with the selection of the harmonic drive. It also presents the algorithm correct choice of harmonic drive. The main objective of this study was to develop a computer program that allows the correct choice of harmonic drive by developed algorithm.

  17. Recognition memory for low- and high-frequency-filtered emotional faces: Low spatial frequencies drive emotional memory enhancement, whereas high spatial frequencies drive the emotion-induced recognition bias.

    Science.gov (United States)

    Rohr, Michaela; Tröger, Johannes; Michely, Nils; Uhde, Alarith; Wentura, Dirk

    2017-07-01

    This article deals with two well-documented phenomena regarding emotional stimuli: emotional memory enhancement-that is, better long-term memory for emotional than for neutral stimuli-and the emotion-induced recognition bias-that is, a more liberal response criterion for emotional than for neutral stimuli. Studies on visual emotion perception and attention suggest that emotion-related processes can be modulated by means of spatial-frequency filtering of the presented emotional stimuli. Specifically, low spatial frequencies are assumed to play a primary role for the influence of emotion on attention and judgment. Given this theoretical background, we investigated whether spatial-frequency filtering also impacts (1) the memory advantage for emotional faces and (2) the emotion-induced recognition bias, in a series of old/new recognition experiments. Participants completed incidental-learning tasks with high- (HSF) and low- (LSF) spatial-frequency-filtered emotional and neutral faces. The results of the surprise recognition tests showed a clear memory advantage for emotional stimuli. Most importantly, the emotional memory enhancement was significantly larger for face images containing only low-frequency information (LSF faces) than for HSF faces across all experiments, suggesting that LSF information plays a critical role in this effect, whereas the emotion-induced recognition bias was found only for HSF stimuli. We discuss our findings in terms of both the traditional account of different processing pathways for HSF and LSF information and a stimulus features account. The double dissociation in the results favors the latter account-that is, an explanation in terms of differences in the characteristics of HSF and LSF stimuli.

  18. The effect of bicarbonate on menadione-induced redox cycling and cytotoxicity: potential involvement of the carbonate radical.

    Science.gov (United States)

    Aljuhani, Naif; Michail, Karim; Karapetyan, Zubeida; Siraki, Arno G

    2013-10-01

    We have investigated the effect of NaHCO3 on menadione redox cycling and cytotoxicity. A cell-free system utilized menadione and ascorbic acid to catalyze a redox cycle, and we utilized murine hepatoma (Hepa 1c1c7) cells for in vitro experiments. Experiments were performed using low (2 mmol/L) and physiological (25 mmol/L) levels of NaHCO3 in buffer equilibrated to physiological pH. Using oximetry, ascorbic acid oxidation, and ascorbyl radical detection, we found that menadione redox cycling was enhanced by NaHCO3. Furthermore, Hepa 1c1c7 cells treated with menadione demonstrated cytotoxicity that was significantly increased with physiological concentrations of NaHCO3 in the media, compared with low levels of NaHCO3. Interestingly, the inhibition of superoxide dismutase (SOD) with 2 different metal chelators was associated with a protective effect against menadione cytotoxicity. Using isolated protein, we found a significant increase in protein carbonyls with menadione-ascorbate-SOD with physiological NaHCO3 levels; low NaHCO3 or SOD-free reactions produced lower levels of protein carbonyls. In conclusion, these findings suggest that the hydrogen peroxide generated by menadione redox cycling together with NaHCO3-CO2 are potential substrates for SOD peroxidase activity that can lead to carbonate-radical-enhanced cytotoxicity. These findings demonstrate the importance of NaHCO3 in menadione redox cycling and cytotoxicity.

  19. Greenhouse Gas Induced Changes in the Seasonal Cycle of the Amazon Basin in Coupled Climate-Vegetation Regional Model

    Directory of Open Access Journals (Sweden)

    Flavio Justino

    2016-01-01

    Full Text Available Previous work suggests that changes in seasonality could lead to a 70% reduction in the extent of the Amazon rainforest. The primary cause of the dieback of the rainforest is a lengthening of the dry season due to a weakening of the large-scale tropical circulation. Here we examine these changes in the seasonal cycle. Under present day conditions the Amazon climate is characterized by a zonal separation of the dominance of the annual and semi-annual seasonal cycles. This behavior is strongly modified under greenhouse warming conditions, with the annual cycle becoming dominant throughout the Amazon basin, increasing differences between the dry and wet seasons. In particular, there are substantial changes in the annual cycle of temperature due to the increase in the temperature of the warmest month, but the lengthening of the dry season is believed to be particularly important for vegetation-climate feedbacks. Harmonic analysis performed to regional climate model simulations yields results that differ from the global climate model that it is forced from, with the regional model being more sensitive to changes in the seasonal cycle.

  20. Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver[S

    Science.gov (United States)

    Satapati, Santhosh; Sunny, Nishanth E.; Kucejova, Blanka; Fu, Xiaorong; He, Tian Teng; Méndez-Lucas, Andrés; Shelton, John M.; Perales, Jose C.; Browning, Jeffrey D.; Burgess, Shawn C.

    2012-01-01

    The manner in which insulin resistance impinges on hepatic mitochondrial function is complex. Although liver insulin resistance is associated with respiratory dysfunction, the effect on fat oxidation remains controversial, and biosynthetic pathways that traverse mitochondria are actually increased. The tricarboxylic acid (TCA) cycle is the site of terminal fat oxidation, chief source of electrons for respiration, and a metabolic progenitor of gluconeogenesis. Therefore, we tested whether insulin resistance promotes hepatic TCA cycle flux in mice progressing to insulin resistance and fatty liver on a high-fat diet (HFD) for 32 weeks using standard biomolecular and in vivo 2H/13C tracer methods. Relative mitochondrial content increased, but respiratory efficiency declined by 32 weeks of HFD. Fasting ketogenesis became unresponsive to feeding or insulin clamp, indicating blunted but constitutively active mitochondrial β-oxidation. Impaired insulin signaling was marked by elevated in vivo gluconeogenesis and anaplerotic and oxidative TCA cycle flux. The induction of TCA cycle function corresponded to the development of mitochondrial respiratory dysfunction, hepatic oxidative stress, and inflammation. Thus, the hepatic TCA cycle appears to enable mitochondrial dysfunction during insulin resistance by increasing electron deposition into an inefficient respiratory chain prone to reactive oxygen species production and by providing mitochondria-derived substrate for elevated gluconeogenesis. PMID:22493093

  1. Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver.

    Science.gov (United States)

    Satapati, Santhosh; Sunny, Nishanth E; Kucejova, Blanka; Fu, Xiaorong; He, Tian Teng; Méndez-Lucas, Andrés; Shelton, John M; Perales, Jose C; Browning, Jeffrey D; Burgess, Shawn C

    2012-06-01

    The manner in which insulin resistance impinges on hepatic mitochondrial function is complex. Although liver insulin resistance is associated with respiratory dysfunction, the effect on fat oxidation remains controversial, and biosynthetic pathways that traverse mitochondria are actually increased. The tricarboxylic acid (TCA) cycle is the site of terminal fat oxidation, chief source of electrons for respiration, and a metabolic progenitor of gluconeogenesis. Therefore, we tested whether insulin resistance promotes hepatic TCA cycle flux in mice progressing to insulin resistance and fatty liver on a high-fat diet (HFD) for 32 weeks using standard biomolecular and in vivo (2)H/(13)C tracer methods. Relative mitochondrial content increased, but respiratory efficiency declined by 32 weeks of HFD. Fasting ketogenesis became unresponsive to feeding or insulin clamp, indicating blunted but constitutively active mitochondrial β-oxidation. Impaired insulin signaling was marked by elevated in vivo gluconeogenesis and anaplerotic and oxidative TCA cycle flux. The induction of TCA cycle function corresponded to the development of mitochondrial respiratory dysfunction, hepatic oxidative stress, and inflammation. Thus, the hepatic TCA cycle appears to enable mitochondrial dysfunction during insulin resistance by increasing electron deposition into an inefficient respiratory chain prone to reactive oxygen species production and by providing mitochondria-derived substrate for elevated gluconeogenesis.

  2. Influence of the menstrual cycle on compression-induced pain during mammography: correlation with the thickness and volume of the mammary gland.

    Science.gov (United States)

    Kitaoka, Hitomi; Kawashima, Hiroko

    2018-03-01

    In mammography, breast compression is necessary and an important factor influencing image quality. The purpose of this study was to determine the influence of the menstrual cycle on compression-induced pain during mammography and to evaluate the association between the thickness and volume of the mammary gland and pain. We examined basal body temperature and categorized the menstrual cycle into five phases. We executed breast compression in the craniocaudal view using a customized compression plate, to which we introduced an opening. We measured the thickness of the mammary gland under compression using echography. Immediately after releasing the compression, we evaluated pain using the visual analogue scale. We performed magnetic resonance imaging (MRI) on the same day and measured the volume of the mammary gland. The thickness of the mammary gland, pain, and the volume of the mammary gland were minimal in the late follicular phase and maximal in the late luteal and early follicular phases. It was shown that the changes in the thickness and volume of the mammary gland during the menstrual cycle accounted for the changes in compression-induced pain. On MRI examination of each breast quadrant, the same changes were observed in areas A and C. In area A, it was shown that both the anatomical characteristics and the increase in volume of the mammary gland were associated with pain. We concluded that the late follicular phase constitutes the optimal timing for mammography.

  3. The neem limonoids azadirachtin and nimbolide induce cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells.

    Science.gov (United States)

    Priyadarsini, R Vidya; Murugan, R Senthil; Sripriya, P; Karunagaran, D; Nagini, S

    2010-06-01

    Limonoids from the neem tree (Azadirachta indica) have attracted considerable research attention in recent years owing to their potent antioxidant and anti-proliferative effects. The present study was designed to investigate the cellular and molecular mechanisms by which azadirachtin and nimbolide exert cytotoxic effects in the human cervical cancer (HeLa) cell line. Both azadirachtin and nimbolide significantly suppressed the viability of HeLa cells in a dose-dependent manner by inducing cell cycle arrest at G0/G1 phase accompanied by p53-dependent p21 accumulation and down-regulation of the cell cycle regulatory proteins cyclin B, cyclin D1 and PCNA. Characteristic changes in nuclear morphology, presence of a subdiploid peak and annexin-V staining pointed to apoptosis as the mode of cell death. Increased generation of reactive oxygen species with decline in the mitochondrial transmembrane potential and release of cytochrome c confirmed that the neem limonoids transduced the apoptotic signal via the mitochondrial pathway. Altered expression of the Bcl-2 family of proteins, inhibition of NF-kappaB activation and over-expression of caspases and survivin provide compelling evidence that azadirachtin and nimbolide induce a shift of balance toward a pro-apoptotic phenotype. Antioxidants such as azadirachtin and nimbolide that can simultaneously arrest the cell cycle and target multiple molecules involved in mitochondrial apoptosis offer immense potential as anti-cancer therapeutic drugs.

  4. Phytol isolated from watermelon (Citrullus lanatus) sprouts induces cell death in human T-lymphoid cell line Jurkat cells via S-phase cell cycle arrest.

    Science.gov (United States)

    Itoh, Tomohiro; Ono, Akito; Kawaguchi, Kaori; Teraoka, Sayaka; Harada, Mayo; Sumi, Keitaro; Ando, Masashi; Tsukamasa, Yasuyuki; Ninomiya, Masayuki; Koketsu, Mamoru; Hashizume, Toshiharu

    2018-05-01

    The phytol isolated from watermelon (Citrullus lanatus) sprouts inhibited the growth of a human T-cell leukemia line Jurkat cell and suppressed tumor progression in a xenograft model of human lung adenocarcinoma epithelial cell line A549 in nude mice. To elucidate the mechanisms underlying the phytol-induced cell death in the present study, we examined the changes in cell morphology, DNA fragmentation, and intracellular reactive oxygen species (ROS) levels and performed flow cytometric analysis to evaluate cell cycle stage. There were no significant changes in apoptosis, autophagy, and necrosis marker in cells treated with the phytol. But, we found, for the first time, that phytol remarkably induced S-phase cell cycle arrest accompanied with intracellular ROS production. Western blot analyses showed that phytolinduced S-phase cell cycle arrest was mediated through the decreased expression of cyclins A and D and the downregulations of MAPK and PI3K/Akt. The tumor volume levels in mice treated with phytol were lower than those of non-treatment groups, and it showed very similar suppression compared with those of mice treated with cyclophosphamide. Based on the data of in vitro and in vivo studies and previous studies, we suggest phytol as a potential therapeutic compound for cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. A methoxyflavanone derivative from the Asian medicinal herb (Perilla frutescens) induces p53-mediated G2/M cell cycle arrest and apoptosis in A549 human lung adenocarcinoma.

    Science.gov (United States)

    Abd El-Hafeez, Amer Ali; Fujimura, Takashi; Kamei, Rikiya; Hirakawa, Noriko; Baba, Kenji; Ono, Kazuhisa; Kawamoto, Seiji

    2017-07-14

    Perilla frutescens is an Asian dietary herb consumed as an essential seasoning in Japanese cuisine as well as used for a Chinese medicine. Here, we report that a newly found methoxyflavanone derivative from P. frutescens (Perilla-derived methoxyflavanone, PDMF; 8-hydroxy-5,7-dimethoxyflavanone) shows carcinostatic activity on human lung adenocarcinoma, A549. We found that treatment with PDMF significantly inhibited cell proliferation and decreased viability through induction of G 2 /M cell cycle arrest and apoptosis. The PDMF stimulation induces phosphorylation of tumor suppressor p53 on Ser15, and increases its protein amount in conjunction with up-regulation of downstream cyclin-dependent kinase inhibitor p21 Cip1/Waf1 and proapoptotic caspases, caspase-9 and caspase-3. We also found that small interfering RNA knockdown of p53 completely abolished the PDMF-induced G 2 /M cell cycle arrest, and substantially abrogated its proapoptotic potency. These results suggest that PDMF represents a useful tumor-preventive phytochemical that triggers p53-driven G 2 /M cell cycle arrest and apoptosis.

  6. The terminal basal mitosis of chicken retinal Lim1 horizontal cells is not sensitive to cisplatin-induced cell cycle arrest.

    Science.gov (United States)

    Shirazi Fard, Shahrzad; Thyselius, Malin; All-Ericsson, Charlotta; Hallböök, Finn

    2014-01-01

    For proper development, cells need to coordinate proliferation and cell cycle-exit. This is mediated by a cascade of proteins making sure that each phase of the cell cycle is controlled before the initiation of the next. Retinal progenitor cells divide during the process of interkinetic nuclear migration, where they undergo S-phase on the basal side, followed by mitoses on the apical side of the neuroepithelium. The final cell cycle of chicken retinal horizontal cells (HCs) is an exception to this general cell cycle behavior. Lim1 expressing (+) horizontal progenitor cells (HPCs) have a heterogenic final cell cycle, with some cells undergoing a terminal mitosis on the basal side of the retina. The results in this study show that this terminal basal mitosis of Lim1+ HPCs is not dependent on Chk1/2 for its regulation compared to retinal cells undergoing interkinetic nuclear migration. Neither activating nor blocking Chk1 had an effect on the basal mitosis of Lim1+ HPCs. Furthermore, the Lim1+ HPCs were not sensitive to cisplatin-induced DNA damage and were able to continue into mitosis in the presence of γ-H2AX without activation of caspase-3. However, Nutlin3a-induced expression of p21 did reduce the mitoses, suggesting the presence of a functional p53/p21 response in HPCs. In contrast, the apical mitoses were blocked upon activation of either Chk1/2 or p21, indicating the importance of these proteins during the process of interkinetic nuclear migration. Inhibiting Cdk1 blocked M-phase transition both for apical and basal mitoses. This confirmed that the cyclin B1-Cdk1 complex was active and functional during the basal mitosis of Lim1+ HPCs. The regulation of the final cell cycle of Lim1+ HPCs is of particular interest since it has been shown that the HCs are able to sustain persistent DNA damage, remain in the cell cycle for an extended period of time and, consequently, survive for months.

  7. Tributyltin induces a G2/M cell cycle arrest in human amniotic cells via PP2A inhibition-mediated inactivation of the ERK1/2 cascades.

    Science.gov (United States)

    Zhang, Yali; Guo, Zonglou; Xu, Lihong

    2014-03-01

    The molecular mechanisms underlying the cell cycle alterations induced by tributyltin (TBT), a highly toxic environmental contaminant, remain elusive. In this study, cell cycle progression and some key regulators in G2/M phase were investigated in human amniotic cells treated with TBT. Furthermore, protein phosphatase (PP) 2A and the ERK cascades were examined. The results showed that TBT caused a G2/M cell cycle arrest that was accompanied by a decrease in the total cdc25C protein level and an increase in the p-cdc2 level in the nucleus. TBT caused a decrease in PP2A activity and inhibited the ERK cascade by inactivating Raf-1, resulting in the dephosphorylation of MEK1/2, ERK1/2, and c-Myc. Taken together, TBT leads to a G2/M cell cycle arrest in FL cells, an increase in p-cdc2 and a decrease in the levels of total cdc25C protein, which may be caused by the PP2A inhibition-mediated inactivation of the ERK1/2 cascades. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Observation of a new turbulence-driven limit-cycle state in H-modes with lower hybrid current drive and lithium-wall conditioning in the EAST superconducting tokamak

    DEFF Research Database (Denmark)

    Wang, H.Q.; Xu, G.S.; Guo, H.Y.

    2012-01-01

    The first high confinement H-mode plasma has been obtained in the Experimental Advanced Superconducting Tokamak (EAST) with about 1 MW lower hybrid current drive after wall conditioning by lithium evaporation and real-time injection of Li powder. Following the L–H transition, a small-amplitude, low...

  9. 5-AED Enhances Survival of Irradiated Mice in a G-CSF-Dependent Manner, Stimulates Innate Immune Cell Function, Reduces Radiation-Induced DNA Damage and Induces Genes that Modulate Cell Cycle Progression and Apoptosis

    Science.gov (United States)

    2012-07-22

    modulate cell cycle progression and apoptosis. INTRODUCTION Because of the increasing threat posed by nuclear weapons [1], there is a pressing need for both...Detection System ( Bio -Rad Laboratories, Hercules CA) on 96-well microtiter plates with optical caps. Reactions were performed in a total volume of 50 µL... antigen -induced arthritis by dehydroepiandrosterone (DHEA). Inflamm Res 2004;53:189–98. 56. Auci D, Nicoletti F, Mangano K et al. Anti-inflammatory and

  10. Greenhouse Gas Induced Changes in the Seasonal Cycle of the Amazon Basin in Coupled Climate-Vegetation Regional Model

    OpenAIRE

    Flavio Justino; Frode Stordal; Edward K. Vizy; Kerry H. Cook; Marcos P. S. Pereira

    2016-01-01

    Previous work suggests that changes in seasonality could lead to a 70% reduction in the extent of the Amazon rainforest. The primary cause of the dieback of the rainforest is a lengthening of the dry season due to a weakening of the large-scale tropical circulation. Here we examine these changes in the seasonal cycle. Under present day conditions the Amazon climate is characterized by a zonal separation of the dominance of the annual and semi-annual seasonal cycles. This behavior is strongly ...

  11. Oscillating in synchrony with a metronome: serial dependence, limit cycle dynamics, and modeling.

    Science.gov (United States)

    Torre, Kjerstin; Balasubramaniam, Ramesh; Delignières, Didier

    2010-07-01

    We analyzed serial dependencies in periods and asynchronies collected during oscillations performed in synchrony with a metronome. Results showed that asynchronies contain 1/f fluctuations, and the series of periods contain antipersistent dependence. The analysis of the phase portrait revealed a specific asymmetry induced by synchronization. We propose a hybrid limit cycle model including a cycle-dependent stiffness parameter provided with fractal properties, and a parametric driving function based on velocity. This model accounts for most experimentally evidenced statistical features, including serial dependence and limit cycle dynamics. We discuss the results and modeling choices within the framework of event-based and emergent timing.

  12. Castration and testosterone induced changes in the pinealocytes of roseringed parakeet, Psittacula krameri, during different phases of the annual testicular cycle.

    Science.gov (United States)

    Maitra, S K; Dey, M

    1994-08-01

    The pinealocytes in male roseringed parakeets (Psittacula krameri) were studied following bilateral castration and/or therapeutic administration of testosterone during the preparatory (June-July), progressive (Nov.-Dec.), pre-breeding (Jan.-Feb.) and breeding (March-April) phases of the annual testicular cycle. The responses of the pineal to either treatment were found to be almost identical throughout the investigation. In each reproductive phase, the pineal appeared to be hypertrophied following castration and the effect was reversed by therapeutic administration of testosterone, while hormonal treatment to the intact parakeets induced regressive changes in the pinealocytes. Collectively, the results of the current study support the hypothesis that the testis through its hormone testosterone exerts inhibitory influences on the activity of pineal, and may thus be considered as being involved in the determination of an inverse relationship between the pineal and the testis during the annual cycle of free-living parakeets.

  13. Mitochondrial ribosomal protein L41 mediates serum starvation-induced cell-cycle arrest through an increase of p21WAF1/CIP1

    International Nuclear Information System (INIS)

    Kim, Mi Jin; Yoo, Young A.; Kim, Hyung Jung; Kang, Seongman; Kim, Yong Geon; Kim, Jun Suk; Yoo, Young Do

    2005-01-01

    Ribosomal proteins not only act as components of the translation apparatus but also regulate cell proliferation and apoptosis. A previous study reported that MRPL41 plays an important role in p53-dependent apoptosis. It also showed that MRPL41 arrests the cell cycle by stabilizing p27 Kip1 in the absence of p53. This study found that MRPL41 mediates the p21 WAF1/CIP1 -mediated G1 arrest in response to serum starvation. The cells were released from serum starvation-induced G1 arrest via the siRNA-mediated blocking of MRPL41 expression. Overall, these results suggest that MRPL41 arrests the cell cycle by increasing the p21 WAF1/CIP1 and p27 Kip1 levels under the growth inhibitory conditions

  14. Cucurbitacin B inhibits proliferation, induces G2/M cycle arrest and autophagy without affecting apoptosis but enhances MTT reduction in PC12 cells

    Directory of Open Access Journals (Sweden)

    Chuanhong Wu

    2016-03-01

    Full Text Available In the present study, the effect of cucurbitacin B (a natural product with anti-cancer effect was studied on PC12 cells. It significantly reduced the cell number, changed cell morphology and inhibited colony formation while MTT results showed increased cell viability. Cucurbitacin B treatment increased activity of succinode hydrogenase. No alteration in the integrity of mem-brane, the release of lactic dehydrogenase, the mitochondrial membrane potential, and the expression of apoptotic proteins suggested that cucurbitacin B did not induce apoptosis. The cell cycle was remarkably arrested at G2/M phase. Furthermore, cucurbitacin B induced autophagy as evidence by accumulation of autophagic vacuoles and the increase of LC3II. In addition, cucurbitacin B up-regulated the expression of p-beclin-1, p-ULK1, p-Wee1, p21 and down-regulated p-mTOR, p-p70S6K, CDC25C, CDK1, Cyclin B1. In conclusion, cucurbitacin B inhibited PC12 proliferation but caused MTT pitfall. Cucurbitacin B induced G2/M cell cycle arrest, autophagy, but not the apoptosis in PC12 cells.

  15. 5-(2-Carboxyethenyl) isatin derivative induces G2/M cell cycle arrest and apoptosis in human leukemia K562 cells

    International Nuclear Information System (INIS)

    Zhou, Yao; Zhao, Hong-Ye; Han, Kai-Lin; Yang, Yao; Song, Bin-Bin; Guo, Qian-Nan; Fan, Zhen-Chuan; Zhang, Yong-Min; Teng, Yu-Ou; Yu, Peng

    2014-01-01

    Highlights: • 5-(2-Carboxyethenyl) isatin derivative (HKL 2H) inhibited K562’s proliferation. • HKL 2H caused the morphology change of G 2 /M phase arrest and typical apoptosis. • HKL 2H induced G2/M cell cycle phase arrest in K562 cells. • HKL 2H induced apoptosis in K562 cells through the mitochondrial pathway. - Abstract: Our previous study successfully identified that the novel isatin derivative (E)-methyl 3-(1-(4-methoxybenzyl)-2,3-dioxoindolin-5-yl) acrylate (HKL 2H) acts as an anticancer agent at an inhibitory concentration (IC 50 ) level of 3 nM. In this study, the molecular mechanism how HKL 2H induces cytotoxic activity in the human chronic myelogenous leukemia K562 cells was investigated. Flow cytometric analysis showed that the cells were arrested in the G 2 /M phase and accumulated subsequently in the sub-G 1 phase in the presence of HKL 2H. HKL 2H treatment down-regulated the expressions of CDK1 and cyclin B but up-regulated the level of phosphorylated CDK1. Annexin-V staining and the classic DNA ladder studies showed that HKL 2H induced the apoptosis of K562 cells. Our study further showed that HKL 2H treatment caused the dissipation of mitochondrial membrane potential, activated caspase-3 and lowered the Bcl-2/Bax ratio in K562 cells, suggesting that the HKL 2H-causing programmed cell death of K562 cells was caused via the mitochondrial apoptotic pathway. Taken together, our data demonstrated that HKL 2H, a 5-(2-carboxyethenyl) isatin derivative, notably induces G 2 /M cell cycle arrest and mitochondrial-mediated apoptosis in K562 cells, indicating that this compound could be a promising anticancer candidate for further investigation

  16. 5-(2-Carboxyethenyl) isatin derivative induces G{sub 2}/M cell cycle arrest and apoptosis in human leukemia K562 cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yao; Zhao, Hong-Ye; Han, Kai-Lin; Yang, Yao; Song, Bin-Bin; Guo, Qian-Nan [Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Fan, Zhen-Chuan [Key Laboratory of Food Nutrition and Safety (Tianjin University of Science and Technology), Ministry of Education, Tianjin 300457 (China); Obesita and Algaegen LLC, College Station, TX 77845 (United States); Zhang, Yong-Min [Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 Place Jussieu, 75005 Paris (France); Teng, Yu-Ou, E-mail: tyo201485@tust.edu.cn [Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Yu, Peng, E-mail: yupeng@tust.edu.cn [Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)

    2014-08-08

    Highlights: • 5-(2-Carboxyethenyl) isatin derivative (HKL 2H) inhibited K562’s proliferation. • HKL 2H caused the morphology change of G{sub 2}/M phase arrest and typical apoptosis. • HKL 2H induced G2/M cell cycle phase arrest in K562 cells. • HKL 2H induced apoptosis in K562 cells through the mitochondrial pathway. - Abstract: Our previous study successfully identified that the novel isatin derivative (E)-methyl 3-(1-(4-methoxybenzyl)-2,3-dioxoindolin-5-yl) acrylate (HKL 2H) acts as an anticancer agent at an inhibitory concentration (IC{sub 50}) level of 3 nM. In this study, the molecular mechanism how HKL 2H induces cytotoxic activity in the human chronic myelogenous leukemia K562 cells was investigated. Flow cytometric analysis showed that the cells were arrested in the G{sub 2}/M phase and accumulated subsequently in the sub-G{sub 1} phase in the presence of HKL 2H. HKL 2H treatment down-regulated the expressions of CDK1 and cyclin B but up-regulated the level of phosphorylated CDK1. Annexin-V staining and the classic DNA ladder studies showed that HKL 2H induced the apoptosis of K562 cells. Our study further showed that HKL 2H treatment caused the dissipation of mitochondrial membrane potential, activated caspase-3 and lowered the Bcl-2/Bax ratio in K562 cells, suggesting that the HKL 2H-causing programmed cell death of K562 cells was caused via the mitochondrial apoptotic pathway. Taken together, our data demonstrated that HKL 2H, a 5-(2-carboxyethenyl) isatin derivative, notably induces G{sub 2}/M cell cycle arrest and mitochondrial-mediated apoptosis in K562 cells, indicating that this compound could be a promising anticancer candidate for further investigation.

  17. Dynamic Chemical and Structural Changes of Heterogeneous Catalysts Observed in Real Time: From Catalysis-Induced Fluxionality to Catalytic Cycles

    Science.gov (United States)

    2014-11-26

    obtained from the fit of the “Clean Pd NCs” (Figure 5 and Table 1) under the approximation the surface atoms have a bond length and EXAFS Debye -Waller...evidence for a model in which Ar drives restructuring of under-coordinated Pd atoms, leading to an increased Pd-Pd bond length of surface Pd atoms... length expansion was calculated by taking the difference between the average NN bond length of each atom before and after being exposed to Ar. The

  18. Variation in sensitivity to #betta#-ray-induced chromosomal aberrations during the mitotic cycle of the sea urchin egg

    International Nuclear Information System (INIS)

    Ejima, Y.; Nakamura, I.; Shiroya, T.

    1982-01-01

    Sea urchin eggs were irradiated with 137 Cs #betta# rays at various stages of the mitotic cycle, and chromosomal aberrations at the first postirradiation mitosis and embryonic abnormalities at later developmental stages were examined. The radiosensitivity of the eggs to both endpoints varied in parallel with the mitotic stage at the time of irradiation, suggesting a possible relationship between chromosomal damage and embryonic abnormalities

  19. DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by Ruta graveolens in human colon cancer cells.

    Science.gov (United States)

    Arora, Shagun; Tandon, Simran

    2015-01-01

    In the present study, we investigated the anti-cancer effect of various potencies of Ruta graveolens (Ruta) on COLO-205 cell line, as evidenced by cytotoxicity, migration, clonogenecity, morphological and biochemical changes and modification in the levels of genes associated with apoptosis and cell cycle. On treatment of COLO-205 cells maximal effects were seen with mother tincture (MT) and 30C potencies, wherein decrease in cell viability along with reduced clonogenecity and migration capabilities were noted. In addition morphological and biochemical alterations such as nuclear changes (fragmented nuclei with condensed chromatin) and DNA ladder-like pattern (increased amount of fragmented DNA) in COLO-205 cells indicating apoptotic related cell death were seen. The expression of apoptosis and cell-cycle related regulatory genes assessed by reverse transcriptase-PCR revealed an up-regulation of caspase 9, caspase-3, Bax, p21 and p27 expression and down-regulation of Bcl-2 expression in treated cells. The mode of cell death was suggestive of intrinsic apoptotic pathway along with cell cycle arrest at the G2/M of the cell cycle. Our findings indicate that phytochemicals present in Ruta showed potential for natural therapeutic product development for colon carcinoma. Copyright © 2014 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  20. Elucidating the transcription cycle of the UV-inducible hyperthermophilic archaeal virus SSV1 by DNA microarrays

    International Nuclear Information System (INIS)

    Froels, Sabrina; Gordon, Paul M.K.; Panlilio, Mayi Arcellana; Schleper, Christa; Sensen, Christoph W.

    2007-01-01

    The spindle-shaped Sulfolobus virus SSV1 was the first of a series of unusual and uniquely shaped viruses isolated from hyperthermophilic Archaea. Using whole-genome microarrays we show here that the circular 15.5 kb DNA genome of SSV1 exhibits a chronological regulation of its transcription upon UV irradiation, reminiscent to the life cycles of bacteriophages and eukaryotic viruses. The transcriptional cycle starts with a small UV-specific transcript and continues with early transcripts on both its flanks. The late transcripts appear after the onset of viral replication and are extended to their full lengths towards the end of the approximately 8.5 h cycle. While we detected only small differences in genome-wide analysis of the host Sulfolobus solfataricus comparing infected versus uninfected strains, we found a marked difference with respect to the strength and speed of the general UV response of the host. Models for the regulation of the virus cycle, and putative functions of genes in SSV1 are presented

  1. Climate-induced interannual variability of marine primary and export production in three global coupled climate carbon cycle models

    Directory of Open Access Journals (Sweden)

    B. Schneider

    2008-04-01

    Full Text Available Fully coupled climate carbon cycle models are sophisticated tools that are used to predict future climate change and its impact on the land and ocean carbon cycles. These models should be able to adequately represent natural variability, requiring model validation by observations. The present study focuses on the ocean carbon cycle component, in particular the spatial and temporal variability in net primary productivity (PP and export production (EP of particulate organic carbon (POC. Results from three coupled climate carbon cycle models (IPSL, MPIM, NCAR are compared with observation-based estimates derived from satellite measurements of ocean colour and results from inverse modelling (data assimilation. Satellite observations of ocean colour have shown that temporal variability of PP on the global scale is largely dominated by the permanently stratified, low-latitude ocean (Behrenfeld et al., 2006 with stronger stratification (higher sea surface temperature; SST being associated with negative PP anomalies. Results from all three coupled models confirm the role of the low-latitude, permanently stratified ocean for anomalies in globally integrated PP, but only one model (IPSL also reproduces the inverse relationship between stratification (SST and PP. An adequate representation of iron and macronutrient co-limitation of phytoplankton growth in the tropical ocean has shown to be the crucial mechanism determining the capability of the models to reproduce observed interactions between climate and PP.

  2. Driving range estimation for electric vehicles based on driving condition identification and forecast

    Science.gov (United States)

    Pan, Chaofeng; Dai, Wei; Chen, Liao; Chen, Long; Wang, Limei

    2017-10-01

    With the impact of serious environmental pollution in our cities combined with the ongoing depletion of oil resources, electric vehicles are becoming highly favored as means of transport. Not only for the advantage of low noise, but for their high energy efficiency and zero pollution. The Power battery is used as the energy source of electric vehicles. However, it does currently still have a few shortcomings, noticeably the low energy density, with high costs and short cycle life results in limited mileage compared with conventional passenger vehicles. There is great difference in vehicle energy consumption rate under different environment and driving conditions. Estimation error of current driving range is relatively large due to without considering the effects of environmental temperature and driving conditions. The development of a driving range estimation method will have a great impact on the electric vehicles. A new driving range estimation model based on the combination of driving cycle identification and prediction is proposed and investigated. This model can effectively eliminate mileage errors and has good convergence with added robustness. Initially the identification of the driving cycle is based on Kernel Principal Component feature parameters and fuzzy C referring to clustering algorithm. Secondly, a fuzzy rule between the characteristic parameters and energy consumption is established under MATLAB/Simulink environment. Furthermore the Markov algorithm and BP(Back Propagation) neural network method is utilized to predict the future driving conditions to improve the accuracy of the remaining range estimation. Finally, driving range estimation method is carried out under the ECE 15 condition by using the rotary drum test bench, and the experimental results are compared with the estimation results. Results now show that the proposed driving range estimation method can not only estimate the remaining mileage, but also eliminate the fluctuation of the

  3. Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells.

    Science.gov (United States)

    Zhang, Zhiyu; Wang, Chong-Zhi; Du, Guang-Jian; Qi, Lian-Wen; Calway, Tyler; He, Tong-Chuan; Du, Wei; Yuan, Chun-Su

    2013-07-01

    Soybean isoflavones have been used as a potential preventive agent in anticancer research for many years. Genistein is one of the most active flavonoids in soybeans. Accumulating evidence suggests that genistein alters a variety of biological processes in estrogen-related malignancies, such as breast and prostate cancers. However, the molecular mechanism of genistein in the prevention of human colon cancer remains unclear. Here we attempted to elucidate the anticarcinogenic mechanism of genistein in human colon cancer cells. First we evaluated the growth inhibitory effect of genistein and two other isoflavones, daidzein and biochanin A, on HCT-116 and SW-480 human colon cancer cells. In addition, flow cyto-metry was performed to observe the morphological changes in HCT-116/SW-480 cells undergoing apoptosis or cell cycle arrest, which had been visualized using Annexin V-FITC and/or propidium iodide staining. Real-time PCR and western blot analyses were also employed to study the changes in expression of several important genes associated with cell cycle regulation. Our data showed that genistein, daidzein and biochanin A exhibited growth inhibitory effects on HCT-116/SW-480 colon cancer cells and promoted apoptosis. Genistein showed a significantly greater effect than the other two compounds, in a time- and dose-dependent manner. In addition, genistein caused cell cycle arrest in the G2/M phase, which was accompanied by activation of ATM/p53, p21waf1/cip1 and GADD45α as well as downregulation of cdc2 and cdc25A demonstrated by q-PCR and immunoblotting assay. Interestingly, genistein induced G2/M cell cycle arrest in a p53-dependent manner. These findings exemplify that isoflavones, especially genistein, could promote colon cancer cell growth inhibition and facilitate apoptosis and cell cycle arrest in the G2/M phase. The ATM/p53-p21 cross-regulatory network may play a crucial role in mediating the anticarcinogenic activities of genistein in colon cancer.

  4. Molecular mechanisms of celery seed extract induced apoptosis via s phase cell cycle arrest in the BGC-823 human stomach cancer cell line.

    Science.gov (United States)

    Gao, Lin-Lin; Feng, Lei; Yao, Shu-Tong; Jiao, Peng; Qin, Shu-Cun; Zhang, Wei; Zhang, Ya-Bin; Li, Fu-Rong

    2011-01-01

    Mechanisms of apoptosis in tumor cells is an important field of tumor therapy and cancer molecular biology. Loss of cell cycle control, leading to uncontrolled proliferation, is common in cancer. Therefore, the identification of potent and selective cyclin dependent kinase inhibitors is a priority for anti-cancer drug discovery. There are at least two major apoptotic pathways, initiated by caspase-8 and caspase-9, respectively, which can activate caspase cascades. Apoptosis triggered by activation of the mitochondrial-dependent caspase pathway represents the main programmed cell death mechanism. This is activated by various intracellular stresses that induce permeabilization of the mitochondrial membrane. Anti-tumor effects of celery seed extract (CSE) and related mechanisms regarding apoptosis were here investigated in human gastric cancer BGC-823 cells. CSE was produced by supercritical fluid extraction. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl-tetrazolium bromide (MTT) assay and apoptosis by flow cytometry using Annexin/PI staining and DAPI staining and a laser scanning confocal microscope (LSCM). Cell cycling was evaluated using PI staining with flow cytometry and expression of cell cycle and apoptosis-related proteins cyclin A, CDK2, bcl-2 and bax was assessed by immunohistochemical staining. CSE had an anti-proliferation effect on human gastric cancer BGC-823 cells in a dose- and time-dependent manner. After treatment, the apoptotic rate significantly increased, with morphological changes typical of apoptosis observed with LSCM by DAPI staining. Cell cycle and apoptosis related proteins, such as cyclin A, CDK2 and bcl-2 were all down-regulated, whereas bax was up-regulated. The molecular determinants of inhibition of cell proliferation as well as apoptosis of CSE may be associated with cycle arrest in the S phase.

  5. Anti-fatigue effect of percutaneous stimulation of the hepatic region by mid-frequency pulse current in different diadynamic cycles in soldiers with exercise-induced fatigue

    Directory of Open Access Journals (Sweden)

    Peng-yi DAI

    2012-01-01

    Full Text Available Objective  To investigate the anti-fatigue effect of percutaneous stimulation of the hepatic region with the mid-frequency pulse current in different diadynamic cycles in exercise-induced fatigued soldiers. Methods  One hundred twenty healthy PLA recruits who did not have physical exercise were randomly divided into four groups with thirty ones in each: control, stimulation group A, stimulation group B, and stimulation group C. All the subjects of four groups were ordered intensive training (exercise from Monday to Saturday, with rest on Sunday for five weeks to establish the exercise-induced fatigue model. Each day after the exercise, the recruits of stimulation groups A, B, and C were treated immediately with mid-frequency (1204Hz, current intensity ≤80mA stimulation to the hepatic region with diadynamic cycles of 0.5, 1, and 2 seconds, respectively. No pulse current stimulation was given in the control group. Venous blood was collected before breakfast on Sundays to measure the fasting plasma glucose (FPG and blood lactate (LAC contents, and liver function was determined by determination of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and lactate dehydrogenase (LDH. The 3000-m running performance of the recruits in each group was recorded on the same day. Results  There was no significant difference between the four groups in terms of the FPG level at the end of the first week (P>0.05. At the end of the third and fifth weeks, the FPG level was significantly higher in the three stimulation groups than in the control group (PPP>0.05. At the end of the first, third, and fifth weeks, the ALT, AST, LDH, and LAC levels were significantly lower in every stimulation group than in the control group (PPPPP>0.05. At the end of the first week, there was no significant difference in 3000-m running performance (P>0.05 between the 4 groups. At the end of the third and fifth weeks, the 3000-m running performance was significantly

  6. Cycling-induced degradation of LiCoO2 thin-film cathodes at elevated temperature

    International Nuclear Information System (INIS)

    Van Sluytman, J.S.; West, W.C.; Whitacre, J.F.; Alamgir, F.M.; Greenbaum, S.G.

    2006-01-01

    The cycle life of LiCoO 2 -based all solid-state thin-film cells has been studied at room temperature, and at elevated temperatures of 50, 100, and 150 deg. C. X-ray diffraction, as well as Raman analysis, has been used to complement the electrochemical data in examining structural and chemical changes. XRD and Raman spectroscopy data indicate that elevated temperature soaks of the thin-film batteries in the quiescent state causes no discernable changes in the LiCoO 2 cathode layer. However, when the thin-film batteries are cycled at elevated temperatures, decreases in average grain size of the LiCoO 2 film occur with dramatic concomitant charge and discharge capacity loss

  7. Cycling-induced degradation of LiCoO{sub 2} thin-film cathodes at elevated temperature

    Energy Technology Data Exchange (ETDEWEB)

    Van Sluytman, J.S.; Alamgir, F.M.; Greenbaum, S.G. [Department of Physics and Astronomy, Hunter College of the City University of New York, 695 Park Avenue, New York, NY 10021 (United States); West, W.C.; Whitacre, J.F. [Electrochemical Technologies Group, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States)

    2006-04-01

    The cycle life of LiCoO{sub 2}-based all solid-state thin-film cells has been studied at room temperature, and at elevated temperatures of 50, 100, and 150{sup o}C. X-ray diffraction, as well as Raman analysis, has been used to complement the electrochemical data in examining structural and chemical changes. XRD and Raman spectroscopy data indicate that elevated temperature soaks of the thin-film batteries in the quiescent state causes no discernible changes in the LiCoO{sub 2} cathode layer. However, when the thin-film batteries are cycled at elevated temperatures, decreases in average grain size of the LiCoO{sub 2} film occur with dramatic concomitant charge and discharge capacity loss. (author)

  8. Life cycle inventory modelling of land use induced by crop consumption - Part 1: Conceptual analysis and methodological proposal

    DEFF Research Database (Denmark)

    Kløverpris, Jesper; Wenzel, Henrik; Nielsen, Per H.

    2008-01-01

    Background, Aims and Scope. The actual land use consequences of crop consumption are not very well reflected in existing life cycle inventories. The state of the art is that such inventories typically include data from crop production in the country in which the crop is produced, and consequently...... to reflect long-term changes, and possibly establishment of a link between crop demand and technological development. Through this approach, life cycle inventories for crops reflecting the actual land use consequences of consumption can be established.Recommendations and Perspectives. Further work (based...... use consequences of crop consumption.Results. Based on the current market trend for crops and an analysis of basic mechanisms in crop production, concepts for modelling how crop consumption affects the global agricultural area and the intensity of crop production are suggested. It is demonstrated how...

  9. A Destructive Validation of NDE Responses of Service-Induced PWSCC Found in North Anna 2 Control Rod Drive Nozzle 31

    International Nuclear Information System (INIS)

    Cumblidge, Stephen E.; Doctor, Steven R.; Schuster, George J.; Harris, Robert V.; Crawford, Susan L.; Seffens, Rob J.; Toloczko, Mychailo B.; Bruemmer, Stephen M.; Moyer, C.

    2009-01-01

    Studies conducted at the Pacific Northwest National Laboratory (PNNL) in Richland, Washington focused on assessing the effectiveness of nondestructive examination (NDE) techniques for inspecting control rod drive mechanism (CRDM) nozzles and J-groove weldments. The primary objective of this work is to provide information to the United States Nuclear Regulatory Commission (NRC) on the effectiveness of NDE methods as related to the in-service inspection of CRDM nozzles and J-groove weldments, and to enhance the knowledge base of primary water stress corrosion cracking (PWSCC) through destructive characterization of the CRDM assemblies.

  10. 6-Nitro-2-(3-hydroxypropyl-1H-benz[de]isoquinoline-1,3-dione, a potent antitumor agent, induces cell cycle arrest and apoptosis

    Directory of Open Access Journals (Sweden)

    Singh Shashank K

    2010-12-01

    Full Text Available Abstract Background Anticancer activities of several substituted naphthalimides (1H-benz[de]isoquinoline-1,3-diones are well documented. Some of them have undergone Phase I-II clinical trials. Presently a series of ten N-(hydroxyalkyl naphthalimides (compounds 1a-j were evaluated as antitumor agents. Methods Compounds 1a-j were initially screened in MOLT-4, HL-60 and U-937 human tumor cell lines and results were compared with established clinical drugs. Cytotoxicities of compounds 1d and 1i were further evaluated in a battery of human tumor cell lines and in normal human peripheral blood mononuclear cells. Cell cycle analysis of compound 1i treated MOLT-4 cells was studied by flow cytometry. Its apoptosis inducing effect was carried out in MOLT-4 and HL-60 cells by flow cytometry using annexin V-FITC/PI double staining method. The activities of caspase-3 and caspase-6 in MOLT-4 cells following incubation with compound 1i were measured at different time intervals. Morphology of the MOLT-4 cells after treatment with 1i was examined under light microscope and transmission electron microscope. 3H-Thymidine and 3H-uridine incorporation in S-180 cells in vitro following treatment with 8 μM concentration of compounds 1d and 1i were studied. Results 6-Nitro-2-(3-hydroxypropyl-1H-benz[de]isoquinoline-1,3-dione (compound 1i, has exhibited maximum activity as it induced significant cytotoxicity in 8 out of 13 cell lines employed. Interestingly it did not show any cytotoxicity against human PBMC (IC50 value 273 μM. Cell cycle analysis of compound 1i treated MOLT-4 cells demonstrated rise in sub-G1 fraction and concomitant accumulation of cells in S and G2/M phases, indicating up-regulation of apoptosis along with mitotic arrest and/or delay in exit of daughter cells from mitotic cycle respectively. Its apoptosis inducing effect was confirmed in flow cytometric study in MOLT-4 and the action was mediated by activation of both caspase 3 and 6. Light and

  11. Platinum(IV) complex LA-12 induces cell cycle phase specific apoptosis in colon carcinoma cell line HCT-116

    Czech Academy of Sciences Publication Activity Database

    Vondálová Blanářová, Olga; Jelínková, Iva; Jendželovský, R.; Souček, Karel; Hofmanová, Jiřina; Sova, P.; Kozubík, Alois

    2009-01-01

    Roč. 276, č. 1 (2009), s. 256-257 ISSN 1742-464X. [34th FEBS Congress. 04.07.2009-09.07.2009, Prague] R&D Projects: GA AV ČR(CZ) 1QS500040507; GA ČR(CZ) GA301/07/1557 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : platinum drugs * cell cycle apoptosis Subject RIV: BO - Biophysics

  12. Cell cycle sensitivity of HL-60 cells to the differentiation-inducing effects of 1-alpha,25-dihydroxyvitamin D3

    International Nuclear Information System (INIS)

    Studzinski, G.P.; Bhandal, A.K.; Brelvi, Z.S.

    1985-01-01

    A recently described system for monocyte-like differentiation of HL-60 cells was utilized to determine if the initiation of this pathway can be linked to a set of replicative cellular events. The standard induction system consisted of a 4-h exposure to 100 nM 1-alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] followed by determination of nonspecific esterase and phagocytic activity 24 h later. The cell cycle status was ascertained by the incorporation of [ 3 H]thymidine and autoradiography. Studies in which cell cycle block in the G1/S phase boundary region was produced by a partial inhibition of DNA synthesis with thymidine, or sodium butyrate, showed that the exposure of such semisynchronous cultures to 1,25(OH)2D3 resulted in an increased proportion of differentiated cells. Conversely, blocking the cell cycle with vinblastine (G2/M block) or theobromine (mid-G1 block) inhibited the initiation of differentiation by 1,25(OH)2D3. Experiments in which the differentiated cells were examined for the cell cycle position at the time of the exposure to 1,25(OH)2D3 by [ 3 H]thymidine labeling and autoradiography confirmed that the late G1 and early S phase cells are those which predominate in the differentiated fraction of 1,25(OH)2D3-treated HL-60 cultures. These results link pre- and early replicative cellular events to the induction of monocytic differentiation by 1,25(OH)2D3

  13. Electric Vehicle - Economical driving

    DEFF Research Database (Denmark)

    Jensen, VCE, Steen V.; Schøn, Henriette

    1999-01-01

    Instruct the reader in getting most satisfaction out of an EV, especially concerning driving and loading.......Instruct the reader in getting most satisfaction out of an EV, especially concerning driving and loading....

  14. Dementia and driving

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000028.htm Dementia and driving To use the sharing features on ... please enable JavaScript. If your loved one has dementia , deciding when they can no longer drive may ...

  15. Vitamin E δ-tocotrienol induces p27(Kip1-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism.

    Directory of Open Access Journals (Sweden)

    Pamela J Hodul

    Full Text Available Vitamin E δ-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that δ-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that δ-tocotrienol-induced growth inhibition occurred concomitantly with G(1 cell-cycle arrest and increased p27(Kip1 nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1 expression is a well-established adverse prognostic factor in PDCA. Furthermore, δ-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1 expression. To determine whether p27(Kip1 induction is required for δ-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1, in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1 silencing suppressed cell-cycle arrest induced by δ-tocotrienol. Furthermore, δ-tocotrienol induced p27(Kip1 mRNA expression but not its protein degradation. p27(Kip1 gene promoter activity was induced by δ-tocotrienol through the promoter's E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1 expression by δ-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1 induction, by which δ-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1 as a biomarker for δ-tocotrienol efficacy in pancreatic cancer prevention and therapy.

  16. Achillea millefolium L. hydroethanolic extract inhibits growth of human tumor cell lines by interfering with cell cycle and inducing apoptosis.

    Science.gov (United States)

    Pereira, Joana M; Peixoto, Vanessa; Teixeira, Alexandra; Sousa, Diana; Barros, Lillian; Ferreira, Isabel C F R; Vasconcelos, M Helena

    2018-06-05

    The cell growth inhibitory activity of the hydroethanolic extract of Achillea millefolium was studied in human tumor cell lines (NCI-H460 and HCT-15) and its mechanism of action was investigated. The GI 50 concentration was determined with the sulforhodamine B assay and cell cycle and apoptosis were analyzed by flow cytometry following incubation with PI or Annexin V FITC/PI, respectively. The expression levels of proteins involved in cell cycle and apoptosis were analyzed by Western blot. The extracts were characterized regarding their phenolic composition by LC-DAD-ESI/MS. 3,5-O-Dicaffeoylquinic acid, followed by 5-O-caffeoylquinic acid, were the main phenolic acids, while, luteolin-O-acetylhexoside and apigenin-O-acetylhexoside were the main flavonoids. This extract decreased the growth of the tested cell lines, being more potent in HCT-15 and then in NCI-H460 cells. Two different concentrations of the extract (75 and 100 μg/mL) caused alterations in cell cycle profile and increased apoptosis levels in HCT-15 and NCI-H460 cells. Moreover, the extract caused an increase in p53 and p21 expression in NCI-H460 cells (which have wt p53), and reduced XIAP levels in HCT-15 cells (with mutant p53). This work enhances the importance of A. millefolium as source of bioactive phenolic compounds, particularly of XIAP inhibitors. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. The numerical high cycle fatigue damage model of fillet weld joint under weld-induced residual stresses

    Science.gov (United States)

    Nguyen Van Do, Vuong

    2018-04-01

    In this study, a development of nonlinear continuum damage mechanics (CDM) model for multiaxial high cycle fatigue is proposed in which the cyclic plasticity constitutive model has been incorporated in the finite element (FE) framework. T-joint FE simulation of fillet welding is implemented to characterize sequentially coupled three-dimensional (3-D) of thermo-mechanical FE formulation and simulate the welding residual stresses. The high cycle fatigue damage model is then taken account into the fillet weld joints under the various cyclic fatigue load types to calculate the fatigue life considering the residual stresses. The fatigue crack initiation and the propagation in the present model estimated for the total fatigue is compared with the experimental results. The FE results illustrated that the proposed high cycle fatigue damage model in this study could become a powerful tool to effectively predict the fatigue life of the welds. Parametric studies in this work are also demonstrated that the welding residual stresses cannot be ignored in the computation of the fatigue life of welded structures.

  18. On the formation of limit cycle of the friction-induced stick-slip vibration in oilwell drillstring

    Directory of Open Access Journals (Sweden)

    Xiaohua Zhu

    2015-03-01

    Full Text Available In this paper, the stick-slip vibration in oilwell drillstring is studied. The drilling system is modelled as a lumped-parameter torsional pendulum and the interaction between the drill bit and the rock is treated as Coulomb friction. Equation of motion of the drill bit is established and the dynamic responses of the drill bit are obtained. A drilling system with the drillstring length 3000 m is analysed, in which the system parameters are selected by reference to the actual drilling situation. After the slip vibrations in the initial stage, final state of the drill bit is a stable stick-slip vibration of which the limit cycle is a closed loop. In order to find the stability of the limit cycle corresponds to the periodically stick-slip vibration, different initial conditions for the drill bit are studied. Results show that the drill bit will lead to a periodic motion and the phase trajectories ultimately converge to the same limit cycle corresponds to stable stick-slip vibration.

  19. Fisetin and hesperetin induced apoptosis and cell cycle arrest in chronic myeloid leukemia cells accompanied by modulation of cellular signaling.

    Science.gov (United States)

    Adan, Aysun; Baran, Yusuf

    2016-05-01

    Fisetin and hesperetin, naturally occurring flavonoids, have been reported as novel antioxidants with chemopreventive/chemotherapeutic potential against various types of cancer. However, their mechanism of action in CML is still unknown. This particular study aims to evaluate the therapeutic potentials of fisetin and hesperetin and their effects on cell proliferation, apoptosis, and cell cycle progression in human K562 CML cells. The results indicated that fisetin and hesperetin inhibited cell proliferation and triggered programmed cell death in these cells. The latter was confırmed by mitochondrial membrane depolarization and an increase in caspase-3 activation. In addition to that, we have detected S and G2/M cell cycle arrests and G0/G1 arrest upon fisetin and hesperetin treatment, respectively. To identify the altered genes and genetic networks in response to fisetin and hesperetin, whole-genome microarray analysis was performed. The microarray gene profiling analysis revealed some important signaling pathways including JAK/STAT pathway, KIT receptor signaling, and growth hormone receptor signaling that were altered upon fisetin and hesperetin treatment. Moreover, microarray data suggested potential candidate genes for targeted CML therapy. Fisetin and hesperetin significantly modulated the expression of genes involved in cell proliferation and division, apoptosis, cell cycle regulation, and other significant cellular processes such as replication, transcription, and translation. In conclusion, our results suggest that fisetin and hesperetin as potential natural agents for CML therapy.

  20. Gear bearing drive

    Science.gov (United States)

    Mavroidis, Constantinos (Inventor); Vranish, John M. (Inventor); Weinberg, Brian (Inventor)

    2011-01-01

    A gear bearing drive provides a compact mechanism that operates as an actuator providing torque and as a joint providing support. The drive includes a gear arrangement integrating an external rotor DC motor within a sun gear. Locking surfaces maintain the components of the drive in alignment and provide support for axial loads and moments. The gear bearing drive has a variety of applications, including as a joint in robotic arms and prosthetic limbs.

  1. Driving for shorter outages

    International Nuclear Information System (INIS)

    Tritch, S.

    1996-01-01

    Nuclear plant outages are necessary to complete activities that cannot be completed during the operating cycle, such as steam generator inspection and testing, refueling, installing modifications, and performing maintenance tests. The time devoted to performing outages is normally the largest contributor to plant unavailability. Similarly, outage costs are a sizable portion of the total plant budget. The scope and quality of work done during outages directly affects operating reliability and the number of unplanned outages. Improved management and planning of outages enhances the margin of safety during the outage and results in increased plant reliability. The detailed planning and in-depth preparation that has become a necessity for driving shorter outage durations has also produced safer outages and improved post-outage reliability. Short outages require both plant and vendor management to focus on all aspects of the outage. Short outage durations, such as 26 days at South Texas or 29 days at North Anna, require power plant inter-department and intra-department teamwork and communication and vendor participation. In this paper shorter and safer outage at the 3-loop plants in the United States are explained. (J.P.N.)

  2. Methodology for kinematic cycle characterization of vehicles with fixed routes in urban areas

    OpenAIRE

    Jiménez Alonso, Felipe; Román de Andrés, Alfonso; López Martínez, José María

    2013-01-01

    This paper analyses the driving cycles of a fleet of vehicles with predetermined urban itineraries. Most driving cycles developed for such type of vehicles do not properly address variability among itineraries. Here we develop a polygonal driving cycle that assesses each group of related routes, based on microscopic parameters. It measures the kinematic cycles of the routes traveled by the vehicle fleet, segments cycles into micro-cycles, and characterizes their properties, groups them int...

  3. Antihistamines and driving safety.

    Science.gov (United States)

    O'Hanlon, J F

    1988-10-27

    The results of two placebo-controlled driving performance studies confirm laboratory data showing that the nonsedating antihistamine terfenadine does not influence the driving performance of users. The amplitude of vehicle weaving calculated for drivers who received this agent did not differ from control values. Neither terfenadine nor loratadine, another nonsedating antihistamine, potentiated the adverse effects of alcohol on driving performance.

  4. Driving After a Stroke

    Science.gov (United States)

    ... 23,2015 Can I drive after a stroke? Driving is often a major concern after someone has a stroke. It’s not unusual for stroke survivors to want to drive. Being able to get around after a stroke is important. Safety behind the wheel is even more important after ...

  5. Sequential Dependencies in Driving

    Science.gov (United States)

    Doshi, Anup; Tran, Cuong; Wilder, Matthew H.; Mozer, Michael C.; Trivedi, Mohan M.

    2012-01-01

    The effect of recent experience on current behavior has been studied extensively in simple laboratory tasks. We explore the nature of sequential effects in the more naturalistic setting of automobile driving. Driving is a safety-critical task in which delayed response times may have severe consequences. Using a realistic driving simulator, we find…

  6. Simple Driving Techniques

    DEFF Research Database (Denmark)

    Rosendahl, Mads

    2002-01-01

    -like language. Our aim is to extract a simple notion of driving and show that even in this tamed form it has much of the power of more general notions of driving. Our driving technique may be used to simplify functional programs which use function composition and will often be able to remove intermediate data...

  7. 17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical Hsp90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells

    International Nuclear Information System (INIS)

    Karkoulis, Panagiotis K; Stravopodis, Dimitrios J; Margaritis, Lukas H; Voutsinas, Gerassimos E

    2010-01-01

    17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinone ansamycin antibiotic, specifically targets heat shock protein 90 (Hsp90) and interferes with its function as a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in cellular signaling. In this study, we have investigated the effect of 17-AAG on the regulation of Hsp90-dependent signaling pathways directly implicated in cell cycle progression, survival and motility of human urinary bladder cancer cell lines. We have used MTT-based assays, FACS analysis, Western blotting, semi-quantitative RT-PCR, immunocytochemistry and scratch-wound assay in RT4, RT112 and T24 human urinary bladder cancer cell lines. We have demonstrated that, upon 17-AAG treatment, bladder cancer cells are arrested in the G1 phase of the cell cycle and eventually undergo apoptotic cell death in a dose-dependent manner. Furthermore, 17-AAG administration was shown to induce a pronounced downregulation of multiple Hsp90 protein clients and other downstream effectors, such as IGF-IR, Akt, IKK-α, IKK-β, FOXO1, ERK1/2 and c-Met, resulting in sequestration-mediated inactivation of NF-κB, reduced cell proliferation and decline of cell motility. In total, we have clearly evinced a dose-dependent and cell type-specific effect of 17-AAG on cell cycle progression, survival and motility of human bladder cancer cells, due to downregulation of multiple Hsp90 clients and subsequent disruption of signaling integrity

  8. [Effects of drying and wetting cycles induced by tides on net ecosystem exchange of CO2 over a salt marsh in the Yellow River Delta, China.

    Science.gov (United States)

    He, Wen Jun; Han, Guang Xuan; Xu, Yan Ning; Zhang, Xi Tao; Wang, An Dong; Che, Chun Guang; Sun, Bao Yu; Zhang, Xiao Shuai

    2018-01-01

    As a unique hydrological characteristic, the tidal action can strongly affect carbon balance in a salt marsh despite their short duration. Using the eddy covariance technique, we measured the net ecosystem CO 2 exchange (NEE) and its environmental factors and tidal change over a salt marsh in the Yellow River Delta. It aimed to investigate the effect of tidal process and drying and wetting cycles induced by tides on NEE. The results showed that the tidal process promoted the daytime CO 2 uptake, but it didn't clearly affect the nighttime CO 2 release. Tidal inundation was a major factor influencing daytime NEE. The diurnal change of NEE showed a distinct U-shaped curve on both drought and wet stages, but not with substantial variation in its amplitude during the drought stage. The drying and wetting cycles enhanced the absorption of daytime CO 2 . Under drought stage, the mean of the maximum photosynthetic rate (A max ), apparent quantum yield (α) and ecosystem respiration (R eco ) were higher than those in wet stage. In addition, the drying and wetting cycles suppressed the nighttime CO 2 release from the salt marsh but increased its temperature sensitivity.

  9. Ovarian matrix metalloproteinases are differentially regulated during the estrous cycle but not during short photoperiod induced regression in Siberian hamsters (Phodopus sungorus

    Directory of Open Access Journals (Sweden)

    Vrooman Lisa A

    2010-06-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are implicated as mediators for ovarian remodeling events, and are involved with ovarian recrudescence during seasonal breeding cycles in Siberian hamsters. However, involvement of these proteases as the photoinhibited ovary undergoes atrophy and regression had not been assessed. We hypothesized that 1 MMPs and their tissue inhibitors, the TIMPs would be present and differentially regulated during the normal estrous cycle in Siberian hamsters, and that 2 MMP/TIMP mRNA and protein levels would increase as inhibitory photoperiod induced ovarian degeneration. Methods MMP-2, -9, -14 and TIMP-1 and -2 mRNA and protein were examined in the stages of estrous (proestrus [P], estrus [E], diestrus I [DI], and diestrus II [DII] in Siberian hamsters, as well as after exposure to 3, 6, 9, and 12 weeks of inhibitory short photoperiod (SD. Results MMP-9 exhibited a 1.6-1.8 fold decrease in mRNA expression in DII (p Conclusions Although MMPs appear to be involved in the normal ovarian estrus cycle at the protein level in hamsters, those examined in the present study are unlikely to be key players in the slow atrophy of tissue as seen in Siberian hamster ovarian regression.

  10. A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C. [College of Life Science, Hebei University, Baoding (China); Yang, R.L. [Key Laboratory of Microbial Diversity Research and Application of Hebei Province, Baoding, China, Key Laboratory of Microbial Diversity Research and Application of Hebei Province, Baoding (China)

    2013-07-30

    MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27{sup KIP1} protein and p21{sup CIP1} mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21{sup CIP1}, p16{sup INK4a} and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.

  11. Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation.

    Science.gov (United States)

    Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

    2016-04-01

    To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Splenocytes and IM-9 cells were uniformly irradiated with various doses of a (137)Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

    International Nuclear Information System (INIS)

    Cho, Seong-Jun; Kang, Hana; Kim, Min Young; Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun; Pyo, Suhkneung; Yang, Kwang Hee

    2016-01-01

    Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a "1"3"7Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

  13. A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells

    International Nuclear Information System (INIS)

    Chen, C.; Yang, R.L.

    2013-01-01

    MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27 KIP1 protein and p21 CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21 CIP1 , p16 INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer

  14. Site-Specific Phosphorylation of Ikaros Induced by Low-Dose Ionizing Radiation Regulates Cell Cycle Progression of B Lymphoblast Through CK2 and AKT Activation

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Seong-Jun; Kang, Hana [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Kim, Min Young [Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan (Korea, Republic of); Lee, Jung Eun; Kim, Sung Jin; Nam, Seon Young; Kim, Ji Young; Kim, Hee Sun [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of); Pyo, Suhkneung [College of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do (Korea, Republic of); Yang, Kwang Hee, E-mail: kwangheey@khnp.co.kr [KHNP Radiation Health Institute, Korea Hydro & Nuclear Power Co, Seoul (Korea, Republic of)

    2016-04-01

    Purpose: To determine how low-dose ionizing radiation (LDIR) regulates B lympho-proliferation and its molecular mechanism related with Ikaros, transcription factor. Methods and Materials: Splenocytes and IM-9 cells were uniformly irradiated with various doses of a {sup 137}Cs γ-source, and cell proliferation was analyzed. To determine the LDIR-specific phosphorylation of Ikaros, immunoprecipitation and Western blot analysis were performed. To investigate the physiologic function of LDIR-mediatied Ikaros phosphorylation, Ikaros mutants at phosphorylation sites were generated, and cell cycle analysis was performed. Results: First, we found that LDIR enhances B lymphoblast proliferation in an Ikaros-dependent manner. Moreover, we found that LDIR elevates the phosphorylation level of Ikaros protein. Interestingly, we showed that CK2 and AKT are involved in LDIR-induced Ikaros phosphorylation and capable of regulating DNA binding activity of Ikaros via specific phosphorylation. Finally, we identified LDIR-specific Ikaros phosphorylation sites at S391/S393 and showed that the Ikaros phosphorylations at these sites control Ikaros's ability to regulate G1/S cell cycle progression. Conclusion: Low-dose ionizing radiation specifically phosphorylates Ikaros protein at Ser 391/393 residues to regulate cell cycle progression in B lymphoblast.

  15. F-box protein FBXO31 is a dedicated checkpoint protein to facilitate cell cycle arrest through activation of regulators in radiation induced DNA damage

    International Nuclear Information System (INIS)

    Santra, Manas Kumar

    2017-01-01

    In response to radiation-induced DNA damage, eukaryotic cells initiate a complex signalling pathway, termed the DNA damage response (DDR), which coordinates cell cycle arrest with DNA repair. Previous study showed that induction of G1 arrest in response to radiation induced DNA damage is minimally a two-step process: a fast p53-independent initiation of G1 arrest mediated by cyclin D1 proteolysis and a slower maintenance of arrest resulting from increased p53 stability. We elucidated the molecular mechanism of slow and fast response of radiation induced DDR. We showed that FBXO31, a member of F-box family proteins, plays important role in DDR induced by ionizing radiation. We show that FBXO31 is responsible for promoting MDM2 degradation following radiation. FBXO31 interacts with and directs the degradation of MDM2 in ATM dependent phosphorylation of MDM2. FBXO31-mediated loss of MDM2 leads to elevated levels of p53, resulting in growth arrest. In cells depleted of FBXO31, MDM2 is not degraded and p53 levels do not increase following genotoxic stress. Thus, FBXO31 is essential for the classic robust increase in p53 levels following DNA damage

  16. Alpinia pricei Rhizome Extracts Induce Cell Cycle Arrest in Human Squamous Carcinoma KB Cells and Suppress Tumor Growth in Nude Mice

    Directory of Open Access Journals (Sweden)

    You-Cheng Hseu

    2011-01-01

    Full Text Available Alpinia pricei has been shown to induce apoptosis in human squamous carcinoma (KB cells. In this study, we report the effectiveness of the ethanol (70% extracts of A. pricei rhizome (AP extracts in terms of tumor regression as determined using both in vitro cell culture and in vivo athymic nude mice models of KB cells. We found that the AP extract (25–200 μg/mL treatment decreased the proliferation of KB cells by arresting progression through the G2/M phase of the cell cycle. This cell cycle blockade was associated with reductions in cyclin A and B1, Cdc2, and Cdc25C, and increased p21/WAF1, Wee1, p53 and phospho-p53 (p-p53 in a dose- and time-dependent manner. Moreover, we found that AP extract treatment decreased metalloproteinase-9 (MMP-9 and urokinase plasminogen activator (u-PA expression, while expression of their endogenous inhibitors, tissue inhibitor of MMP-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1, were increased in KB cells. Furthermore, AP extract treatment effectively delayed tumor incidence in nude mice inoculated with KB cells and reduced the tumor burden. AP extract treatment also induced apoptotic DNA fragmentation, as detected by in situ TUNEL staining. Thus, A. pricei may possess antitumor activity in human squamous carcinoma (KB cells.

  17. CyclinG1 Amplification Enhances Aurora Kinase Inhibitor-Induced Polyploid Resistance and Inhibition of Bcl-2 Pathway Reverses the Resistance

    Directory of Open Access Journals (Sweden)

    Wenfeng Zhang

    2017-08-01

    Full Text Available Background/Aims: CyclinG1 (CycG1 is frequently overexpressed in solid tumors and overexpression of CycG1 promotes cell survival upon paclitaxel exposure by inducing polyploidy. Whether and how CycG1 regulates polyploidization caused by small molecular targeted inhibitors remains unclear. Methods: Immunohistochemistry and immunoblotting were utilized to examine protein expression. Cell proliferation was measured by ATPlite assay, and cell cycle distribution and apoptosis were measured by flow cytometry and/or DNA fragmentation assays. Results: Overexpression of CycG1 in breast cancer cells caused apoptosis-resistant polyploidy upon treatment with Aurora kinase inhibitor, ZM447439 (ZM. Addition of ABT-263, a small-molecule BH3 mimetic, to ZM, produced a synergistic loss of cell viability with greater sustained tumor growth inhibition in breast cancer cell lines. Decrease of Mcl-1 and increase of NOXA caused by ZM treatment, were responsible for the synergy. Furthermore, CycG1 was highly expressed in Triple-Negative-Breast-Cancer patients treated with paclitaxel and was paralleled by decreased cell survival. Conclusion: CycG1 is a crucial factor in ZM-induced polyploidy resistance, and ABT-263/ZM combination hold therapeutic utility in the CycG1-amplified subset of breast cancer and CycG1, thus, is a promising target in breast cancer.

  18. DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line.

    Science.gov (United States)

    Bakshi, Hamid; Sam, Smitha; Rozati, Roya; Sultan, Phalisteen; Islam, Tajamul; Rathore, Babita; Lone, Zahoor; Sharma, Manik; Triphati, Jagrati; Saxena, Ramesh Chand

    2010-01-01

    Apoptosis, a widely important mechanism that contributes to cell growth reduction, is reported to be induced by Crocus sativus in different cancer types. The present study was designed to elucidate apoptosis induction by crocin, a main component of Crocus sativus in a human pancreatic cancer cell line (BxPC-3). Cell viability was measured by MTT assay, Hoechest33258 staining was used to detect the chromatin condensation characteristic of apoptosis, and DNA fragmentation was assessed by gel electrophoresis and cell cycle analysis by flow cytometry. Crocin induced apoptosis and G1-phase cell cycle arrest of BxPC-3 cells, while decreasing cell viability in a dose dependent and time dependent manner. Cells treated with 10μg/L crocin exhibited apoptotic morphology (brightly blue-fluorescent condensed nuclei on Hoechst 33258 staining) and reduction of volume. DNA analysis revealed typical ladders as early as 12 hours after treatment indicative of apoptosis. Our preclinical study demonstrated a pancreatic cancer cell line to be highly sensitive to crocin-mediated growth inhibition and apoptotic cell death. Although the molecular mechanisms of crocin action are not yet clearly understood, it appears to have potential as a therapeutic agent.

  19. Alkali-soluble polysaccharide, isolated from Lentinus edodes, induces apoptosis and G2/M cell cycle arrest in H22 cells through microtubule depolymerization.

    Science.gov (United States)

    You, Ru-Xu; Liu, Jin-Yu; Li, Shi-Jun; Wang, Liu; Wang, Kai-Ping; Zhang, Yu

    2014-12-01

    The aim of the study was to evaluate the pro-apoptotic effects of polysaccharides derived from Lentinus edodes and further elucidated the mechanisms of this action. Our results demonstrated that marked morphological changes of apoptosis were observed after treatment of L. edodes polysaccharides [Lentinan (LTN)]. Moreover, LTN-induced cell apoptosis was characterized by a rapid stimulation of reactive oxygen species production, the loss of mitochondrial membrane potential and an increase in intracellular concentration of Ca(2+) . In addition, the results of the haematoxylin and eosin and TUNEL assay further confirmed that LTN-induced apoptosis in vivo. Furthermore, flow cytometry analysis showed that LTN could arrest the cell cycle at G2/M phase, and immunofluorescence showed LTN caused disruption of microtubule. These results suggest that disruption of cellular microtubule network, arrest of the cell cycle at G2/M phase and induction of apoptosis may be one of the possible mechanisms of anti-tumour effect of LTN. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Do emotions drive psychosis?

    Directory of Open Access Journals (Sweden)

    João G. Ribeiro

    2012-12-01

    Full Text Available Introduction: How important is the emotional life of persons who manifest psychotic symptoms? Aims: The aim of this paper is to review evidence on a causal role for emotions in psychotic processes. Methods: Selective review of literature on affective symptoms in psychoses, on emotions in the production of psychotic symptoms and on dopaminergic models of psychosis. Results: Affective symptoms are relevant across psychoses. Persons with schizophrenia have high levels of emotional reactivity and the intensification of negative affects not only is associated with but also precedes the intensification of psychotic symptoms, which is evidence that negative emotions drive the course of psychotic symptoms. Negative self‑representations are central in psychotic processes and can be the link between negative emotions and psychosis. Evidence favours the notion that persecutory delusions are consistent with negative affects and self‑representations, while grandiose delusions are consistent with a defensive amplification of positive affects and self‑representations. Shame has been proposed as the core emotional experience of psychosis, one in which the self becomes vulnerable to the external world, which is consistent with persecutory experiences. Assaults on the self, under the form of hostility in the family environment and society, are strong predictors of relapse and development of schizophrenia. Assaults on the self which induce social defeat are also strong stimulants of mesolimbic dopaminergic pathways, whose hyperactivity is associated with acute psychotic episodes and the experience of “aberrant salience”, put forward as a dopaminergic model of psychosis. Conclusions: The “defeat of the self” emerges as a central link that binds the experience of negative emotions to the expression of psychotic symptoms and its psychological and neurobiological correlates. The hypothesis gains support that the emotions related to that defeat control

  1. Anti-inflammatory drugs suppress proliferation and induce apoptosis through altering expressions of cell cycle regulators and pro-apoptotic factors in cultured human osteoblasts

    International Nuclear Information System (INIS)

    Chang, J.-K.; Li, C.-J.; Liao, H.-J.; Wang, C.-K.; Wang, G.-J.; Ho, M.-L.

    2009-01-01

    It has been reported that anti-inflammatory drugs (AIDs) inhibited bone repair in animal studies, and suppressed proliferation and induced cell death in rat osteoblast cultures. In this study, we further investigated the molecular mechanisms of AID effects on proliferation and cell death in human osteoblasts (hOBs). We examined the effects of dexamethasone (10 -7 and 10 -6 M), non-selective non-steroidal anti-inflammatory drugs (NSAIDs): indomethacin, ketorolac, piroxicam and diclofenac (10 -5 and 10 -4 M), and COX-2 inhibitor: celecoxib (10 -6 and 10 -5 M) on proliferation, cytotoxicity, cell death, and mRNA and pro