Full Hybrid: Passing

Science.gov Websites

Main stage: See through car with battery, engine, generator, power split device, and electric motor the power split device to the front wheels. Main stage: See through car with battery, engine : See through car with battery, engine, generator, power split device, and electric motor visible while

49 CFR Appendix B to Part 599 - Engine Disablement Procedures for the CARS Program

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Engine Disablement Procedures for the CARS Program B Appendix B to Part 599 Transportation Other Regulations Relating to Transportation (Continued...—Engine Disablement Procedures for the CARS Program ER29JY09.006 ...

49 CFR Appendix B to Part 599 - Engine Disablement Procedures for the CARS Program

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Engine Disablement Procedures for the CARS Program B Appendix B to Part 599 Transportation Other Regulations Relating to Transportation (Continued...—Engine Disablement Procedures for the CARS Program ER29JY09.006 ...

49 CFR Appendix B to Part 599 - Engine Disablement Procedures for the CARS Program

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 7 2011-10-01 2011-10-01 false Engine Disablement Procedures for the CARS Program B Appendix B to Part 599 Transportation Other Regulations Relating to Transportation (Continued...—Engine Disablement Procedures for the CARS Program ER29JY09.006 ...

49 CFR Appendix B to Part 599 - Engine Disablement Procedures for the CARS Program

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 7 2013-10-01 2013-10-01 false Engine Disablement Procedures for the CARS Program B Appendix B to Part 599 Transportation Other Regulations Relating to Transportation (Continued...—Engine Disablement Procedures for the CARS Program ER29JY09.006 ...

49 CFR Appendix B to Part 599 - Engine Disablement Procedures for the CARS Program

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 7 2014-10-01 2014-10-01 false Engine Disablement Procedures for the CARS Program B Appendix B to Part 599 Transportation Other Regulations Relating to Transportation (Continued...—Engine Disablement Procedures for the CARS Program ER29JY09.006 ...

Full Hybrid: Overview

Science.gov Websites

conditions. stage graphic: vertical blue rule Main stage: See through car with battery, engine, generator , power split device, and electric motor visible. The car is stopped at an intersection. Main stage: See through car with battery, engine, generator, power split device, and electric motor visible. The car is

14. AERIAL VIEW OF ENGINE DISPLAY INSIDE PASSENGER CAR SHOP ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. AERIAL VIEW OF ENGINE DISPLAY INSIDE PASSENGER CAR SHOP (NOW A TRANSPORTATION MUSEUM) - Baltimore & Ohio Railroad, Mount Clare Passenger Car Shop, Southwest corner of Pratt & Poppleton Streets, Baltimore, Independent City, MD

Hybrid: Braking

Science.gov Websites

automatically. Go back… stage graphic: vertical blue rule Main stage: See through car with battery, engine, and electric motor visible. The car is stopped at an intersection. Main stage: See through car with battery , engine, and electric motor visible. The car is stopped at an intersection. Battery: The battery stores

Stop/Start: Overview

Science.gov Websites

: vertical blue rule Main stage: See through car with battery, engine, and electric starter/generator visible . The car is stopped at an intersection. Main stage: See through car with battery, engine, and electric starter/generator visible. The car is stopped at an intersection. Battery: The battery is used to store

Full Hybrid: Braking

Science.gov Websites

: vertical blue rule Main stage: See through car with battery, engine, generator, power split device, and electric motor visible. The car is stopped at an intersection. Main stage: See through car with battery , engine, generator, power split device, and electric motor visible. The car is stopped at an intersection

Engineering Chimeric Antigen Receptors

PubMed Central

Kulemzin, S. V.; Kuznetsova, V. V.; Mamonkin, M.; Taranin, A. V.; Gorchakov, A. A.

2017-01-01

Chimeric antigen receptors (CARs) are recombinant protein molecules that redirect cytotoxic lymphocytes toward malignant and other target cells. The high feasibility of manufacturing CAR-modified lymphocytes for the therapy of cancer has spurred the development and optimization of new CAR T cells directed against a broad range of target antigens. In this review, we describe the main structural and functional elements constituting a CAR, discuss the roles of these elements in modulating the anti-tumor activity of CAR T cells, and highlight alternative approaches to CAR engineering. PMID:28461969

Engineering analyses for railroad tank car head puncture resistance

DOT National Transportation Integrated Search

2006-11-06

This paper describes engineering analyses to estimate the : forces, deformations, and puncture resistance of railroad tank : cars. Different approaches to examine puncture of the tank car : head are described. One approach is semi-empirical equations...

Volatile nanoparticle formation and growth within a diluting diesel car exhaust.

PubMed

Uhrner, Ulrich; Zallinger, Michael; von Löwis, Sibylle; Vehkamäki, Hanna; Wehner, Birgit; Stratmann, Frank; Wiedensohler, Alfred

2011-04-01

A major source of particle number emissions is road traffic. However, scientific knowledge concerning secondary particle formation and growth of ultrafine particles within vehicle exhaust plumes is still very limited. Volatile nanoparticle formation and subsequent growth conditions were analyzed here to gain a better understanding of "real-world" dilution conditions. Coupled computational fluid dynamics and aerosol microphysics models together with measured size distributions within the exhaust plume of a diesel car were used. The impact of soot particles on nucleation, acting as a condensational sink, and the possible role of low-volatile organic components in growth were assessed. A prescribed reduction of soot particle emissions by 2 orders of magnitude (to capture the effect of a diesel particle filter) resulted in concentrations of nucleation-mode particles within the exhaust plume that were approximately 1 order of magnitude larger. Simulations for simplified sulfuric acid-water vapor gas-oil containing nucleation-mode particles show that the largest particle growth is located in a recirculation zone in the wake of the car. Growth of particles within the vehicle exhaust plume up to detectable size depends crucially on the relationship between the mass rate of gaseous precursor emissions and rapid dilution. Chassis dynamometer measurements indicate that emissions of possible hydrocarbon precursors are significantly enhanced under high engine load conditions and high engine speed. On the basis of results obtained for a diesel passenger car, the contributions from light diesel vehicles to the observed abundance of measured nucleation-mode particles near busy roads might be attributable to the impact of two different time scales: (1) a short one within the plume, marked by sufficient precursor emissions and rapid dilution; and (2) a second and comparatively long time scale resulting from the mix of different precursor sources and the impact of atmospheric chemistry.

14 CFR 21.27 - Issue of type certificate: surplus aircraft of the Armed Forces.

Code of Federal Regulations, 2012 CFR

2012-01-01

... that apply 1 Small reciprocating-engine powered airplanes Before May 16, 1956After May 15, 1956 CAR Part 3, as effective May 15, 1956.CAR Part 3, or 14 CFR Part 23. Small turbine engine-powered airplanes...-engine powered airplanes Before Aug. 26, 1955After Aug. 25, 1955 CAR Part 4b, as effective Aug. 25, 1955...

14 CFR 21.27 - Issue of type certificate: surplus aircraft of the Armed Forces.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 1 Small reciprocating-engine powered airplanes Before May 16, 1956After May 15, 1956 CAR Part 3, as effective May 15, 1956.CAR Part 3, or FAR Part 23. Small turbine engine-powered airplanes Before Oct. 2... Part 25. Large turbine engine-powered airplanes Before Oct. 2, 1959After Oct. 1, 1959 CAR Part 4b, as...

14 CFR 21.27 - Issue of type certificate: surplus aircraft of the Armed Forces.

Code of Federal Regulations, 2013 CFR

2013-01-01

... that apply 1 Small reciprocating-engine powered airplanes Before May 16, 1956After May 15, 1956 CAR Part 3, as effective May 15, 1956.CAR Part 3, or 14 CFR Part 23. Small turbine engine-powered airplanes...-engine powered airplanes Before Aug. 26, 1955After Aug. 25, 1955 CAR Part 4b, as effective Aug. 25, 1955...

14 CFR 21.27 - Issue of type certificate: surplus aircraft of the Armed Forces.

Code of Federal Regulations, 2014 CFR

2014-01-01

... that apply 1 Small reciprocating-engine powered airplanes Before May 16, 1956After May 15, 1956 CAR Part 3, as effective May 15, 1956.CAR Part 3, or 14 CFR Part 23. Small turbine engine-powered airplanes...-engine powered airplanes Before Aug. 26, 1955After Aug. 25, 1955 CAR Part 4b, as effective Aug. 25, 1955...

Urban traffic pollution reduction for sedan cars using petrol engines by hydro-oxide gas inclusion.

PubMed

Al-Rousan, Ammar A; Alkheder, Sharaf; Musmar, Sa'ed A

2015-12-01

Petrol cars, in particular nonhybrid cars, contribute significantly to the pollution problem as compared with other types of cars. The originality of this article falls in the direction of using hydro-oxy gas to reduce pollution from petrol car engines. Experiments were performed in city areas at low real speeds, with constant engine speeds in the average of 2500 rpm and at variable velocity ratios (first speed was 10-20 km/hr, second speed was 20-35 km/hr, and third speed was 35-50 km/hr). Results indicated that through using hydro-oxy gas, a noticeable reduction in pollution was recorded. Oxygen (O2) percentage has increased by about 2.5%, and nitric oxide (NO) level has been reduced by about 500 ppm. Carbon monoxide (CO) has decreased by about 2.2%, and also CO2 has decreased by 2.1%. It's worth mentioning that for hybrid system in cars at speeds between 10 and 50 km/hr, the emission percentage change is zero. However, hybrid cars are less abundant than petrol cars. The originality of this paper falls in the direction of using hydro-oxy gas to reduce pollution from petrol car engines. Experiments were performed in city areas at low real speeds, with constant engine speeds in the average of 2500 rpm and at variable velocity ratios (first speed was 10-20 km/hr, second speed was 20-35 km/hr, and third speed was 35-50 km/h).

Prototype design and test of a collision protection system for cab car engineers.

DOT National Transportation Integrated Search

2014-12-01

Advancements in the design of rail cars can : potentially prevent the structural collapse of : space occupied by a cab car engineer : during a train collision. With adequate : survival space maintained, the next : crashworthiness objective is to mini...

Prototype design of a collision protection system for cab car engineers - fabrication and test.

DOT National Transportation Integrated Search

2015-06-01

Advancements in the structural crashworthiness of passenger rail cars now make it possible to preserve the compartmentalized : space occupied by a cab car engineer during a train collision. In order to translate this additional protection into improv...

Teleconsultations reduce greenhouse gas emissions.

PubMed

Oliveira, Tiago Cravo; Barlow, James; Gonçalves, Luís; Bayer, Steffen

2013-10-01

Health services contribute significantly to greenhouse gas emissions. New models of delivering care closer to patients have the potential to reduce travelling and associated emissions. We aimed to compare the emissions of patients attending a teleconsultation - an outpatient appointment using video-conferencing equipment - with those of patients attending a face-to-face appointment. We estimated the total distances travelled and the direct and indirect greenhouse gas emissions for 20,824 teleconsultations performed between 2004 and 2011 in Alentejo, a Portuguese region. These were compared to the distances and emissions that would have resulted if teleconsultations were not available and patients had to attend face-to-face outpatient appointments. Estimates were calculated using survey data on mode of transport, and national aggregate data for car engine size and fuel. A sensitivity analysis using the lower and upper quartiles for survey distances was performed. Teleconsultations led to reductions in distances and emissions of 95%. 2,313,819 km of travelling and 455 tonnes of greenhouse gas emissions were avoided (22 kg of carbon dioxide equivalent per patient). The incorporation of modes of transport and car engine size and fuel in the analysis led to emission estimates which were 12% smaller than those assuming all patients used an average car. The availability of remote care services can significantly reduce road travel and associated emissions. At a time when many countries are committed to reducing their carbon footprint, it is desirable to explore how these reductions could be incorporated into technology assessments and economic evaluations.

Conventional engine technology. Volume 2: Status of diesel engine technology

NASA Technical Reports Server (NTRS)

Schneider, H. W.

1981-01-01

The engines of diesel cars marketed in the United States were examined. Prominent design features, performance characteristics, fuel economy and emissions data were compared. Specific problems, in particular those of NO and smoke emissions, the effects of increasing dieselization on diesel fuel price and availability, current R&D work and advanced diesel concepts are discussed. Diesel cars currently have a fuel economy advantage over gasoline engine powered cars. Diesel drawbacks (noise and odor) were reduced to a less objectionable level. An equivalent gasoline engine driveability was obtained with turbocharging. Diesel manufacturers see a growth in the diesel market for the next ten years. Uncertainties regarding future emission regulation may inhibit future diesel production investments. With spark ignition engine technology advancing in the direction of high compression ratios, the fuel economy advantages of the diesel car is expected to diminish. To return its fuel economy lead, the diesel's potential for future improvement must be used.

Technological growth of fuel efficiency in european automobile market 1975–2015

DOE PAGES

Hu, Kejia; Chen, Yuche

2016-08-29

This paper looks at the technological growth of new car fleet fuel efficiency in the European Union between 1975 and 2015. According to the analysis results, from1975 to 2006 the fuel efficiency technology improvements were largely offset by vehicles' increased weight, engine size, and consumer amenities such as acceleration capacity. After 2006, downsizing in weight and engine capacity was observed in new car fleet, while fuel consumption decreased by 32% between 2006 and 2015. We adopt a statistical method and find that from 1975 to 2015, a 1% increase in weight would result in 0.3 to 0.5% increments in fuelmore » consumption per 100 km, and a 1% reduction in 0-100 km/h acceleration time would increase fuel consumption by about 0.3%. Impacts of other attributes on fuel consumption are also assessed. To meet the European Union's 2021 fuel consumption target, downsizing of cars, as well as at least maintaining fuel efficiency technology growth trend observed between 2005 and 2015, are needed. Lastly, government policies on controlling improvement in acceleration performance or promoting alternative fuel vehicles are also important to achieve European Union 2021 target.« less

Technological growth of fuel efficiency in european automobile market 1975–2015

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

Hu, Kejia; Chen, Yuche

This paper looks at the technological growth of new car fleet fuel efficiency in the European Union between 1975 and 2015. According to the analysis results, from1975 to 2006 the fuel efficiency technology improvements were largely offset by vehicles' increased weight, engine size, and consumer amenities such as acceleration capacity. After 2006, downsizing in weight and engine capacity was observed in new car fleet, while fuel consumption decreased by 32% between 2006 and 2015. We adopt a statistical method and find that from 1975 to 2015, a 1% increase in weight would result in 0.3 to 0.5% increments in fuelmore » consumption per 100 km, and a 1% reduction in 0-100 km/h acceleration time would increase fuel consumption by about 0.3%. Impacts of other attributes on fuel consumption are also assessed. To meet the European Union's 2021 fuel consumption target, downsizing of cars, as well as at least maintaining fuel efficiency technology growth trend observed between 2005 and 2015, are needed. Lastly, government policies on controlling improvement in acceleration performance or promoting alternative fuel vehicles are also important to achieve European Union 2021 target.« less

49 CFR 174.85 - Position in train of placarded cars, transport vehicles, freight containers, and bulk packagings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... engine or occupied caboose X X X 2. When train length does not permit, placarded car must be placed near the middle of the train, but not nearer than the second car from an engine or occupied caboose X X X 3... 49 Transportation 2 2013-10-01 2013-10-01 false Position in train of placarded cars, transport...

49 CFR 174.85 - Position in train of placarded cars, transport vehicles, freight containers, and bulk packagings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... engine or occupied caboose X X X 2. When train length does not permit, placarded car must be placed near the middle of the train, but not nearer than the second car from an engine or occupied caboose X X X 3... 49 Transportation 2 2012-10-01 2012-10-01 false Position in train of placarded cars, transport...

49 CFR 174.85 - Position in train of placarded cars, transport vehicles, freight containers, and bulk packagings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... engine or occupied caboose X X X 2. When train length does not permit, placarded car must be placed near the middle of the train, but not nearer than the second car from an engine or occupied caboose X X X 3... 49 Transportation 2 2014-10-01 2014-10-01 false Position in train of placarded cars, transport...

CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond

PubMed Central

Chang, ZeNan L.; Chen, Yvonne Y.

2017-01-01

Chimeric antigen receptors (CARs) are versatile synthetic receptors that provide T cells with engineered specificity. Clinical success in treating B-cell malignancies has demonstrated the therapeutic potential of CAR-T cells against cancer, and efforts are underway to expand the use of engineered T cells to the treatment of diverse medical conditions, including infections and autoimmune diseases. Here, we review current understanding of the molecular properties of CARs, how this knowledge informs the rational design and characterization of novel receptors, successes and shortcomings of CAR-T cells in the clinic, and emerging solutions for the continued improvement of CAR-T cell therapy. PMID:28416139

Full Hybrid: Cruising

Science.gov Websites

for storage. Go back… stage graphic: vertical blue rule Main stage: See through car with battery , engine, generator, power split device, and electric motor visible. The car is moving. There are arrows flowing from the gasoline engine to the generator to the battery. Main stage: See through car with battery

Chemical Characteristics of Particulate Matter from Vehicle emission using High Resolution Time of Flight Aerosol Mass Spectrometer (HR-ToF-AMS)

NASA Astrophysics Data System (ADS)

Park, T.; Lee, T.; Kang, S.; Lee, J.; Kim, J.; Son, J.; Yoo, H. M.; Kim, K.; Park, G.

2015-12-01

Car emissions are major contributors of particulate matter (PM) in the urban environment and effects of air pollution, climate change, and human activities. By increasing of interest in research of car emission for assessment of the PM control, it became require to understand the chemical composition and characteristics of the car exhaust gases and particulate matter. To understand car emission characteristics of PM, we will study PM of car emissions for five driving modes (National Institute Environmental Research (NIER)-5, NIER-9, NIER-12, NIER-14) and three fixed speed driving modes (30km/h, 70km/h, 110km/h) using different fuel types (gasoline, diesel, and LPG) at Transportation Pollution Research Center (TPRC) of NIER in Incheon, South Korea. PM chemical composition of car emission was measured for concentrations of organics, sulfate, nitrate, ammonium, PAHs, oxidation states and size distribution using an Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and engine exhaust particle sizer (EEPS) on real-time. In the study, organics concentration was dominated for all cases of driving modes and the concentration of organics was increased in 110km/h fixed speed mode for gasoline and diesel. The presentation will provide an overview of the chemical composition of PM in the car emissions.

Hybrid: Cruising

Science.gov Websites

battery, engine, and electric motor visible. The car is moving. There are red arrows flowing from the gasoline engine to the front wheels. There are blue arrows flowing from the gasoline engine to the electric car is moving. There are red arrows flowing from the gasoline engine to the front wheels. There are

Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer.

PubMed

Jin, Chuan; Fotaki, Grammatiki; Ramachandran, Mohanraj; Nilsson, Berith; Essand, Magnus; Yu, Di

2016-07-01

Chimeric antigen receptor (CAR) T-cell therapy is a new successful treatment for refractory B-cell leukemia. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. Herein, we describe a novel episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element, for either expression of transgenes or silencing of target genes. The insertional events of this vector into the genome of host cells are below detection level. CD19 CAR T cells engineered with a NILV-S/MAR vector have similar levels of CAR expression as T cells engineered with an integrating LV vector, even after numerous rounds of cell division. NILV-S/MAR-engineered CD19 CAR T cells exhibited similar cytotoxic capacity upon CD19(+) target cell recognition as LV-engineered T cells and are as effective in controlling tumor growth in vivo We propose that NILV-S/MAR vectors are superior to current options as they enable long-term transgene expression without the risk of insertional mutagenesis and genotoxicity. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Hybrid Engine Powered City Car: Fuzzy Controlled Approach

NASA Astrophysics Data System (ADS)

Rahman, Ataur; Mohiuddin, AKM; Hawlader, MNA; Ihsan, Sany

2017-03-01

This study describes a fuzzy controlled hybrid engine powered car. The car is powered by the lithium ion battery capacity of 1000 Wh is charged by the 50 cc hybrid engine and power regenerative mode. The engine is operated with lean mixture at 3000 rpm to charge the battery. The regenerative mode that connects with the engine generates electrical power of 500-600 W for the deceleration of car from 90 km/h to 20 km/h. The regenerated electrical power has been used to power the air-conditioning system and to meet the other electrical power. The battery power only used to propel the car. The regenerative power also found charging the battery for longer operation about 40 minutes and more. The design flexibility of this vehicle starts with whole-vehicle integration based on radical light weighting, drag reduction, and accessory efficiency. The energy efficient hybrid engine cut carbon dioxide (CO2) and nitrogen oxides (N2O) emission about 70-80% as the loads on the crankshaft such as cam-follower and its associated rotating components are replaced by electromagnetic systems, and the flywheel, alternator and starter motor are replaced by a motor generator. The vehicle was tested and found that it was able to travel 70 km/litre with the power of hybrid engine.

Immunotherapy

MedlinePlus

... in the laboratory, see CAR T-Cell Therapy: Engineering Patients' Immune Cells to Treat Their Cancers . Monoclonal ... NCI’s Role in Immunotherapy Research CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers Can ...

The kinematic advantage of electric cars

NASA Astrophysics Data System (ADS)

Meyn, Jan-Peter

2015-11-01

Acceleration of a common car with with a turbocharged diesel engine is compared to the same type with an electric motor in terms of kinematics. Starting from a state of rest, the electric car reaches a distant spot earlier than the diesel car, even though the latter has a better specification for engine power and average acceleration from 0 to 100 km h-1. A three phase model of acceleration as a function of time fits the data of the electric car accurately. The first phase is a quadratic growth of acceleration in time. It is shown that the tenfold higher coefficient for the first phase accounts for most of the kinematic advantage of the electric car.

Associations of health, physical activity and weight status with motorised travel and transport carbon dioxide emissions: a cross-sectional, observational study

PubMed Central

2012-01-01

Background Motorised travel and associated carbon dioxide (CO2) emissions generate substantial health costs; in the case of motorised travel, this may include contributing to rising obesity levels. Obesity has in turn been hypothesised to increase motorised travel and/or CO2 emissions, both because heavier people may use motorised travel more and because heavier people may choose larger and less fuel-efficient cars. These hypothesised associations have not been examined empirically, however, nor has previous research examined associations with other health characteristics. Our aim was therefore to examine how and why weight status, health, and physical activity are associated with transport CO2 emissions. Methods 3463 adults completed questionnaires in the baseline iConnect survey at three study sites in the UK, reporting their health, weight, height and past-week physical activity. Seven-day recall instruments were used to assess travel behaviour and, together with data on car characteristics, were used to estimate CO2 emissions. We used path analysis to examine the extent to which active travel, motorised travel and car engine size explained associations between health characteristics and CO2 emissions. Results CO2 emissions were higher in overweight or obese participants (multivariable standardized probit coefficients 0.16, 95% CI 0.08 to 0.25 for overweight vs. normal weight; 0.16, 95% CI 0.04 to 0.28 for obese vs. normal weight). Lower active travel and, particularly for obesity, larger car engine size explained 19-31% of this effect, but most of the effect was directly explained by greater distance travelled by motor vehicles. Walking for recreation and leisure-time physical activity were associated with higher motorised travel distance and therefore higher CO2 emissions, while active travel was associated with lower CO2 emissions. Poor health and illness were not independently associated with CO2 emissions. Conclusions Establishing the direction of causality between weight status and travel behaviour requires longitudinal data, but the association with engine size suggests that there may be at least some causal effect of obesity on CO2 emissions. More generally, transport CO2 emissions are associated in different ways with different health-related characteristics. These include associations between health goods and environmental harms (recreational physical activity and high emissions), indicating that environment-health ‘co-benefits’ cannot be assumed. Instead, attention should also be paid to identifying and mitigating potential areas of tension, for example by promoting low-carbon recreational physical activity. PMID:22862811

Associations of health, physical activity and weight status with motorised travel and transport carbon dioxide emissions: a cross-sectional, observational study.

PubMed

Goodman, Anna; Brand, Christian; Ogilvie, David

2012-08-03

Motorised travel and associated carbon dioxide (CO₂) emissions generate substantial health costs; in the case of motorised travel, this may include contributing to rising obesity levels. Obesity has in turn been hypothesised to increase motorised travel and/or CO₂ emissions, both because heavier people may use motorised travel more and because heavier people may choose larger and less fuel-efficient cars. These hypothesised associations have not been examined empirically, however, nor has previous research examined associations with other health characteristics. Our aim was therefore to examine how and why weight status, health, and physical activity are associated with transport CO₂ emissions. 3463 adults completed questionnaires in the baseline iConnect survey at three study sites in the UK, reporting their health, weight, height and past-week physical activity. Seven-day recall instruments were used to assess travel behaviour and, together with data on car characteristics, were used to estimate CO2 emissions. We used path analysis to examine the extent to which active travel, motorised travel and car engine size explained associations between health characteristics and CO₂ emissions. CO₂ emissions were higher in overweight or obese participants (multivariable standardized probit coefficients 0.16, 95% CI 0.08 to 0.25 for overweight vs. normal weight; 0.16, 95% CI 0.04 to 0.28 for obese vs. normal weight). Lower active travel and, particularly for obesity, larger car engine size explained 19-31% of this effect, but most of the effect was directly explained by greater distance travelled by motor vehicles. Walking for recreation and leisure-time physical activity were associated with higher motorised travel distance and therefore higher CO₂ emissions, while active travel was associated with lower CO₂ emissions. Poor health and illness were not independently associated with CO₂ emissions. Establishing the direction of causality between weight status and travel behaviour requires longitudinal data, but the association with engine size suggests that there may be at least some causal effect of obesity on CO₂ emissions. More generally, transport CO₂ emissions are associated in different ways with different health-related characteristics. These include associations between health goods and environmental harms (recreational physical activity and high emissions), indicating that environment-health 'co-benefits' cannot be assumed. Instead, attention should also be paid to identifying and mitigating potential areas of tension, for example by promoting low-carbon recreational physical activity.

Fuel Cell Car Design Project for Freshman Engineering Courses

ERIC Educational Resources Information Center

Duke, Steve R.; Davis, Virginia A.

2014-01-01

In the Samuel Ginn College of Engineering at Auburn University, we have integrated a semester long design project based on a toy fuel cell car into our freshman "Introduction to Chemical Engineering Class." The project provides the students a basic foundation in chemical reactions, energy, and dimensional analysis that facilitates…

Research and Engineering Operation, Irradiation Processing Department monthly record report, May 1965

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

Ambrose, T.W.

1965-06-04

Process and development activities reported include: depleted uranium irradiations, thoria irradiation, and hot die sizing. Reactor engineering activities include: brittle fracture of 190-C tanks, increased graphite temperature limits for the F reactor, VSR channel caulking, K reactor downcomer flow, zircaloy hydriding, and ribbed zircaloy process tubes. Reactor physics activities include: thoria irradiations, E-D irradiations, boiling protection with the high speed scanner, and in-core flux monitoring. Radiological engineering activities include: radiation control, classification, radiation occurrences, effluent activity data, and well car shielding. Process standards are listed, along with audits, and fuel failure experience. Operational physics and process physics studies are presented.more » Lastly, testing activities are detailed.« less

Experimental cross-correlation nitrogen Q-branch CARS thermometry in a spark ignition engine

NASA Astrophysics Data System (ADS)

Lockett, R. D.; Ball, D.; Robertson, G. N.

2013-07-01

A purely experimental technique was employed to derive temperatures from nitrogen Q-branch Coherent Anti-Stokes Raman Scattering (CARS) spectra, obtained in a high pressure, high temperature environment (spark ignition Otto engine). This was in order to obviate any errors arising from deficiencies in the spectral scaling laws which are commonly used to represent nitrogen Q-branch CARS spectra at high pressure. The spectra obtained in the engine were compared with spectra obtained in a calibrated high pressure, high temperature cell, using direct cross-correlation in place of the minimisation of sums of squares of residuals. The technique is demonstrated through the measurement of air temperature as a function of crankshaft angle inside the cylinder of a motored single-cylinder Ricardo E6 research engine, followed by the measurement of fuel-air mixture temperatures obtained during the compression stroke in a knocking Ricardo E6 engine. A standard CARS programme (SANDIA's CARSFIT) was employed to calibrate the altered non-resonant background contribution to the CARS spectra that was caused by the alteration to the mole fraction of nitrogen in the unburned fuel-air mixture. The compression temperature profiles were extrapolated in order to predict the auto-ignition temperatures.

5. VAL CAMERA CAR, DETAIL OF HOIST AT SIDE OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VAL CAMERA CAR, DETAIL OF HOIST AT SIDE OF BRIDGE AND ENGINE CAR ON TRACKS, LOOKING NORTHEAST. - Variable Angle Launcher Complex, Camera Car & Track, CA State Highway 39 at Morris Reservior, Azusa, Los Angeles County, CA

KSC-2012-3034a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – Engineers board a NASA Railroad train in preparation for its departure from the NASA Railroad Yard at NASA’s Kennedy Space Center in Florida. The train is headed for the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

CAR-Engineered NK Cells Targeting Wild-Type EGFR and EGFRvIII Enhance Killing of Glioblastoma and Patient-Derived Glioblastoma Stem Cells.

PubMed

Han, Jianfeng; Chu, Jianhong; Keung Chan, Wing; Zhang, Jianying; Wang, Youwei; Cohen, Justus B; Victor, Aaron; Meisen, Walter H; Kim, Sung-hak; Grandi, Paola; Wang, Qi-En; He, Xiaoming; Nakano, Ichiro; Chiocca, E Antonio; Glorioso, Joseph C; Kaur, Balveen; Caligiuri, Michael A; Yu, Jianhua

2015-07-09

Glioblastoma (GB) remains the most aggressive primary brain malignancy. Adoptive transfer of chimeric antigen receptor (CAR)-modified immune cells has emerged as a promising anti-cancer approach, yet the potential utility of CAR-engineered natural killer (NK) cells to treat GB has not been explored. Tumors from approximately 50% of GB patients express wild-type EGFR (wtEGFR) and in fewer cases express both wtEGFR and the mutant form EGFRvIII; however, previously reported CAR T cell studies only focus on targeting EGFRvIII. Here we explore whether both wtEGFR and EGFRvIII can be effectively targeted by CAR-redirected NK cells to treat GB. We transduced human NK cell lines NK-92 and NKL, and primary NK cells with a lentiviral construct harboring a second generation CAR targeting both wtEGFR and EGFRvIII and evaluated the anti-GB efficacy of EGFR-CAR-modified NK cells. EGFR-CAR-engineered NK cells displayed enhanced cytolytic capability and IFN-γ production when co-cultured with GB cells or patient-derived GB stem cells in an EGFR-dependent manner. In two orthotopic GB xenograft mouse models, intracranial administration of NK-92-EGFR-CAR cells resulted in efficient suppression of tumor growth and significantly prolonged the tumor-bearing mice survival. These findings support intracranial administration of NK-92-EGFR-CAR cells represents a promising clinical strategy to treat GB.

Adnectin-Based Design of Chimeric Antigen Receptor for T Cell Engineering.

PubMed

Han, Xiaolu; Cinay, Gunce E; Zhao, Yifan; Guo, Yunfei; Zhang, Xiaoyang; Wang, Pin

2017-11-01

Although chimeric antigen receptor (CAR)-engineered T cell therapy has achieved encouraging clinical trial results for treating hematological cancers, further optimization can likely expand this therapeutic success to more patients and other cancer types. Most CAR constructs used in clinical trials incorporate single chain variable fragment (scFv) as the extracellular antigen recognition domain. The immunogenicity of nonhuman scFv could cause host rejection against CAR T cells and compromise their persistence and efficacy. The limited availability of scFvs and slow discovery of new monoclonal antibodies also limit the development of novel CAR constructs. Adnectin, a class of affinity molecules derived from the tenth type III domain of human fibronectin, can be an alternative to scFv as an antigen-binding moiety in the design of CAR molecules. We constructed adnectin-based CARs targeting epithelial growth factor receptor (EGFR) and found that compared to scFv-based CAR, T cells engineered with adnectin-based CARs exhibited equivalent cell-killing activity against target H292 lung cancer cells in vitro and had comparable antitumor efficacy in xenograft tumor-bearing mice in vivo. In addition, with optimal affinity tuning, adnectin-based CAR showed higher selectivity on target cells with high EGFR expression than on those with low expression. This new design of adnectin CARs can potentially facilitate the development of T cell immunotherapy for cancer and other diseases. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Differential risk of injury in child occupants by passenger car classification.

PubMed

Kallan, Michael J; Durbin, Dennis R; Elliott, Michael R; Menon, Rajiv A; Winston, Flaura K

2003-01-01

In the United States, passenger cars are the most common passenger vehicle, yet they vary widely in size and crashworthiness. Using data collected from a population-based sample of crashes in State Farm-insured vehicles, we quantified the risk of injury to child occupants by passenger car size and classification. Injury risk is predicted by vehicle weight; however, there is an increased risk in both Large vs. Luxury and Sports vs. Small cars, despite similar average vehicle weights in both comparisons. Parents who are purchasing passenger cars should strongly consider the size of the vehicle and its crashworthiness.

Differential Risk of Injury in Child Occupants by Passenger Car Classification

PubMed Central

Kallan, Michael J.; Durbin, Dennis R.; Elliott, Michael R.; Menon, Rajiv A.; Winston, Flaura K.

2003-01-01

In the United States, passenger cars are the most common passenger vehicle, yet they vary widely in size and crashworthiness. Using data collected from a population-based sample of crashes in State Farm-insured vehicles, we quantified the risk of injury to child occupants by passenger car size and classification. Injury risk is predicted by vehicle weight; however, there is an increased risk in both Large vs. Luxury and Sports vs. Small cars, despite similar average vehicle weights in both comparisons. Parents who are purchasing passenger cars should strongly consider the size of the vehicle and its crashworthiness. PMID:12941234

The use of telemetry in testing in high performance racing engines

NASA Astrophysics Data System (ADS)

Hauser, E.

Telemetry measurement data in mobile application and under difficult environmental conditions were recorded. All relevant racing car and engine parameters were measured: pressure, stress, temperature, acceleration, ignition, number of revolutions, control of electronic injection, and flow measurements on the car body. The difficult measuring conditions due to high voltage ignition, mechanical loads and vibrations impose special requirements on a telemetry system built in racing cars. It has to be compact, flexible, light, and mechanically robust and has to fulfil special sheilding conditions. The measured data are transfered to a stationary measurement car via a radio line, involving RF communication problems. The measured data are directly displayed and evaluated in the measurement car.

Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment.

PubMed

Yeku, Oladapo O; Purdon, Terence J; Koneru, Mythili; Spriggs, David; Brentjens, Renier J

2017-09-05

Chimeric antigen receptor (CAR) T cell therapy has shown limited efficacy for the management of solid tumor malignancies. In ovarian cancer, this is in part due to an immunosuppressive cytokine and cellular tumor microenvironment which suppresses adoptively transferred T cells. We engineered an armored CAR T cell capable of constitutive secretion of IL-12, and delineate the mechanisms via which these CAR T cells overcome a hostile tumor microenvironment. In this report, we demonstrate enhanced proliferation, decreased apoptosis and increased cytotoxicity in the presence of immunosuppressive ascites. In vivo, we show enhanced expansion and CAR T cell antitumor efficacy, culminating in improvement in survival in a syngeneic model of ovarian peritoneal carcinomatosis. Armored CAR T cells mediated depletion of tumor associated macrophages and resisted endogenous PD-L1-induced inhibition. These findings highlight the role of the inhibitory microenvironment and how CAR T cells can be further engineered to maintain efficacy.

Putting Up a Big Front: Car Design and Size Affect Road-Crossing Behaviour

PubMed Central

Klatt, Wilhelm K.; Chesham, Alvin; Lobmaier, Janek S.

2016-01-01

Previous research suggests that people tend to see faces in car fronts and that they attribute personality characteristics to car faces. In the present study we investigated whether car design influences pedestrian road-crossing behaviour. An immersive virtual reality environment with a zebra crossing scenario was used to determine a) whether the minimum accepted distance for crossing the street is larger for cars with a dominant appearance than for cars with a friendly appearance and b) whether the speed of dominant-looking cars is overestimated as compared to friendly-looking cars. Participants completed both tasks while either standing on the pavement or on the centre island. We found that people started to cross the road later in front of friendly-looking low-power cars compared to dominant-looking high-power cars, but only if the cars were relatively large in size. For small cars we found no effect of power. The speed of smaller cars was estimated to be higher compared to large cars (size-speed bias). Furthermore, there was an effect of starting position: From the centre island, participants entered the road significantly later (i. e. closer to the approaching car) and left the road later than when starting from the pavement. Similarly, the speed of the cars was estimated significantly lower when standing on the centre island compared to the pavement. To our knowledge, this is the first study to show that car fronts elicit responses on a behavioural level. PMID:27434187

Putting Up a Big Front: Car Design and Size Affect Road-Crossing Behaviour.

PubMed

Klatt, Wilhelm K; Chesham, Alvin; Lobmaier, Janek S

2016-01-01

Previous research suggests that people tend to see faces in car fronts and that they attribute personality characteristics to car faces. In the present study we investigated whether car design influences pedestrian road-crossing behaviour. An immersive virtual reality environment with a zebra crossing scenario was used to determine a) whether the minimum accepted distance for crossing the street is larger for cars with a dominant appearance than for cars with a friendly appearance and b) whether the speed of dominant-looking cars is overestimated as compared to friendly-looking cars. Participants completed both tasks while either standing on the pavement or on the centre island. We found that people started to cross the road later in front of friendly-looking low-power cars compared to dominant-looking high-power cars, but only if the cars were relatively large in size. For small cars we found no effect of power. The speed of smaller cars was estimated to be higher compared to large cars (size-speed bias). Furthermore, there was an effect of starting position: From the centre island, participants entered the road significantly later (i. e. closer to the approaching car) and left the road later than when starting from the pavement. Similarly, the speed of the cars was estimated significantly lower when standing on the centre island compared to the pavement. To our knowledge, this is the first study to show that car fronts elicit responses on a behavioural level.

Vibrational and Rotational CARS Measurements of Nitrogen in Afterglow of Streamer Discharge in Atmospheric Pressure Fuel/Air Mixtures

DTIC Science & Technology

2012-01-01

in a variety of different ignition regimes, including pulsed detonation engines ( PDEs ) and automobile engines, with experiments demonstrating TPI to...Vibrational and rotational CARS measurements of nitrogen in afterglow of streamer discharge in atmospheric pressure fuel/air mixtures This article...DATE 2012 2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Vibrational and rotational CARS measurements of

Fuel economy screening study of advanced automotive gas turbine engines

NASA Technical Reports Server (NTRS)

Klann, J. L.

1980-01-01

Fuel economy potentials were calculated and compared among ten turbomachinery configurations. All gas turbine engines were evaluated with a continuously variable transmission in a 1978 compact car. A reference fuel economy was calculated for the car with its conventional spark ignition piston engine and three speed automatic transmission. Two promising engine/transmission combinations, using gasoline, had 55 to 60 percent gains over the reference fuel economy. Fuel economy sensitivities to engine design parameter changes were also calculated for these two combinations.

Recent Developments in BMW's Diesel Technology

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

Steinparzer, F

2003-08-24

The image of BMW is very strongly associated to high power, sports biased, luxury cars in the premium car segment, however, particularly in the United States and some parts of Asia, the combination of a car in this segment with a diesel engine was up until now almost unthinkable. I feel sure that many people in the USA are not even aware that BMW produces diesel-powered cars. In Europe there is a completely contrary situation which, driven by the relative high fuel price, and the noticeable difference between gasoline and diesel prices, there has been a continuous growth in themore » diesel market since the early eighties. During this time BMW has accumulated more then 20 years experience in developing and producing powerful diesel engines for sports and luxury cars. BMW started the production of its 1st generation diesel engine in 1983 with a 2,4 l, turbocharged IDI engine in the 5 series model range. With a specific power of 35 kW/l, this was the most powerful diesel engine on the market at this time. In 1991 BMW introduced the 2nd generation diesel engine, beginning with a 2,5 l inline six, followed in 1994 by a 1,7 l inline four. All engines of this 2nd BMW diesel engine family were turbocharged and utilized an indirect injection combustion system. With the availability of high-pressure injection systems such as the common rail system, BMW developed its 3rd diesel engine family which consists of four different engines. The first was the 4-cylinder for the 3 series car in the spring of 1998, followed by the 6-cylinder in the fall of 1998 and then in mid 1999 by the worlds first V8 passenger car diesel with direct injection. Beginning in the fall of 2001 with the 4-cylinder, BMW reworked this DI engine family fundamentally. Key elements are an improved core engine design, the use of the common rail system of the 2nd generation and a new engine control unit with even better performance. Step by step, these technological improvements were introduce d to production for all members of this engine family and in all the different vehicle applications. In the next slide you can see the production volume of diesel engines by BMW. From the 1st family we produced {approx} 260,000 units over eight years and from the 2nd family {approx} 630,000 units were produced also during an eight year period. How successful the actual engine family with direct injection is can be seen in the increase of the production volume to 330,000 units for the year 2002 alone. The reason for this is that, in addition to the very low fuel consumption, this new engines provide excellent driving characteristics and a significant improvement in the level of noise and vibration. Page 2 of 5 In 2002, 26% of all BMW cars worldwide, and nearly 40% in Europe, were produced with a diesel engine under the hood. In the X5 we can see the biggest diesel success rate. Of all the X5 vehicles produced, 35% Worldwide and 68% in Europe are powered by a diesel engine.« less

Toward brain-actuated car applications: Self-paced control with a motor imagery-based brain-computer interface.

PubMed

Yu, Yang; Zhou, Zongtan; Yin, Erwei; Jiang, Jun; Tang, Jingsheng; Liu, Yadong; Hu, Dewen

2016-10-01

This study presented a paradigm for controlling a car using an asynchronous electroencephalogram (EEG)-based brain-computer interface (BCI) and presented the experimental results of a simulation performed in an experimental environment outside the laboratory. This paradigm uses two distinct MI tasks, imaginary left- and right-hand movements, to generate a multi-task car control strategy consisting of starting the engine, moving forward, turning left, turning right, moving backward, and stopping the engine. Five healthy subjects participated in the online car control experiment, and all successfully controlled the car by following a previously outlined route. Subject S1 exhibited the most satisfactory BCI-based performance, which was comparable to the manual control-based performance. We hypothesize that the proposed self-paced car control paradigm based on EEG signals could potentially be used in car control applications, and we provide a complementary or alternative way for individuals with locked-in disorders to achieve more mobility in the future, as well as providing a supplementary car-driving strategy to assist healthy people in driving a car. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mode transition coordinated control for a compound power-split hybrid car

NASA Astrophysics Data System (ADS)

Wang, Chen; Zhao, Zhiguo; Zhang, Tong; Li, Mengna

2017-03-01

With a compound power-split transmission directly connected to the engine in hybrid cars, dramatic fluctuations in engine output torque result in noticeable jerks when the car is in mode transition from electric drive mode to hybrid drive mode. This study designed a mode transition coordinated control strategy, and verified that strategy's effectiveness with both simulations and experiments. Firstly, the mode transition process was analyzed, and ride comfort issues during the mode transition process were demonstrated. Secondly, engine ripple torque was modeled using the measured cylinder pumping pressure when the engine was not in operation. The complete dynamic plant model of the power-split hybrid car was deduced, and its effectiveness was validated by a comparison of experimental and simulation results. Thirdly, a coordinated control strategy was designed to determine the desired engine torque, motor torque, and the moment of fuel injection. Active damping control with two degrees of freedom, based on reference output shaft speed estimation, was designed to mitigate driveline speed oscillations. Carrier torque estimation based on transmission kinematics and dynamics was used to suppress torque disturbance during engine cranking. The simulation and experimental results indicate that the proposed strategy effectively suppressed vehicle jerks and improved ride comfort during mode transition.

Analysis of regenerated single-shaft ceramic gas-turbine engines and resulting fuel economy in a compact car

NASA Technical Reports Server (NTRS)

Klann, J. L.; Tew, R. C., Jr.

1977-01-01

Ranges in design and off-design operating conditions of an advanced gas turbine and their effects on fuel economy were analyzed. The assumed engine incorporated a single stage radial flow turbine and compressor with fixed geometry. Fuel economies were calculated over the composite driving cycle with gasoline as the fuel. At a constant turbine-inlet temperature, with a regenerator sized for a full power effectiveness the best fuel economies ranged from 11.1 to 10.2 km/liter (26.2 to 22.5 mpg) for full power turbine tip speeds of 770 to 488m/sec (2530 to 1600ft/sec), respectively.

78 FR 7718 - Review of the General Purpose Costing System

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-04

... for switching cars, regardless of car ownership. These costs are referred to as ``switch engine minute... provide the railroad industry and shippers with a standardized costing model; to cost the Board's Car Load... movement. Next, URCS applies ``efficiency adjustments'' to higher-volume movements (multi-car and trainload...

Decreased ethyl carbamate generation during Chinese rice wine fermentation by disruption of CAR1 in an industrial yeast strain.

PubMed

Wu, Dianhui; Li, Xiaomin; Shen, Chao; Lu, Jian; Chen, Jian; Xie, Guangfa

2014-06-16

Saccharomyces cerevisiae metabolizes arginine to ornithine and urea during wine fermentations. In the fermentation of Chinese rice wine, yeast strains of S. cerevisiae do not fully metabolize urea, which will be secreted into the spirits and spontaneously reacts with ethanol to form ethyl carbamate, a potential carcinogenic agent for humans. To block the pathway of urea production, we genetically engineered two haploid strains to reduce the arginase (encoded by CAR1) activity, which were isolated from a diploid industrial Chinese rice wine strain. Finally the engineered haploids with opposite mating type were mated back to diploid strains, obtaining a heterozygous deletion strain (CAR1/car1) and a homozygous defect strain (car1/car1). These strains were compared to the parental industrial yeast strain in Chinese rice wine fermentations and spirit production. The strain with the homozygous CAR1 deletion showed significant reductions of urea and EC in the final spirits in comparison to the parental strain, with the concentration reductions by 86.9% and 50.5% respectively. In addition, EC accumulation was in a much lower tempo during rice wine storage. Moreover, the growth behavior and fermentation characteristics of the engineered diploid strain were similar to the parental strain. Copyright © 2014 Elsevier B.V. All rights reserved.

Advanced automotive diesel assessment program

NASA Technical Reports Server (NTRS)

Sekar, R.; Tozzi, L.

1983-01-01

Cummins Engine Company completed an analytical study to identify an advanced automotive (light duty) diesel (AAD) power plant for a 3,000-pound passenger car. The study resulted in the definition of a revolutionary diesel engine with several novel features. A 3,000-pound car with this engine is predicted to give 96.3, 72.2, and 78.8 MPG in highway, city, and combined highway-city driving, respectively. This compares with current diesel powered cars yielding 41.7, 35.0, and 37.7 MPG. The time for 0-60 MPH acceleration is 13.9 sec. compared to the baseline of 15.2 sec. Four technology areas were identified as crucial in bringing this concept to fruition. They are: (1) part-load preheating, (2) positive displacement compounding, (3) spark assisted diesel combustion system, and (4) piston development for adiabatic, oilless diesel engine. Marketing and planning studies indicate that an aggressive program with significant commitment could result in a production car in 10 years from the date of commencement.

Car companies look to generate power from waste heat

NASA Astrophysics Data System (ADS)

Schirber, Michael

2008-04-01

You might think that the steam engine is an outdated technology that had its heyday centuries ago, but in fact steam is once again a hot topic with vehicle manufacturers. Indeed, the next generation of hybrid cars and trucks may incorporate some form of steam power. Honda, for example, has just released details of a new prototype hybrid car that recharges its battery using a steam engine that exploits waste heat from the exhaust pipe.

Chemical composition and source of fine and nanoparticles from recent direct injection gasoline passenger cars: Effects of fuel and ambient temperature

NASA Astrophysics Data System (ADS)

Fushimi, Akihiro; Kondo, Yoshinori; Kobayashi, Shinji; Fujitani, Yuji; Saitoh, Katsumi; Takami, Akinori; Tanabe, Kiyoshi

2016-01-01

Particle number, mass, and chemical compositions (i.e., elemental carbon (EC), organic carbon (OC), elements, ions, and organic species) of fine particles emitted from four of the recent direct injection spark ignition (DISI) gasoline passenger cars and a port fuel injection (PFI) gasoline passenger car were measured under Japanese official transient mode (JC08 mode). Total carbon (TC = EC + OC) dominated the particulate mass (90% on average). EC dominated the TC for both hot and cold start conditions. The EC/TC ratios were 0.72 for PFI and 0.88-1.0 (average = 0.92) for DISI vehicles. A size-resolved chemical analysis of a DISI car revealed that the major organic components were the C20-C28 hydrocarbons for both the accumulation-mode particles and nanoparticles. Contribution of engine oil was estimated to be 10-30% for organics and the sum of the measured elements. The remaining major fraction likely originated from gasoline fuel. Therefore, it is suggested that soot (EC) also mainly originated from the gasoline. In experiments using four fuels at three ambient temperatures, the emission factors of particulate mass were consistently higher with regular gasoline than with premium gasoline. This result suggest that the high content of less-volatile compounds in fuel increase particulate emissions. These results suggest that focusing on reducing fuel-derived EC in the production process of new cars would effectively reduce particulate emission from DISI cars.

Confirmation of heavy metal ions in used lubricating oil from a passenger car using chelating self-assembled monolayer.

PubMed

Ko, Young Gun; Kim, Choong Hyun

2006-09-01

In order to prevent engine failure, the oil must be changed before it loses its protective properties. It is necessary to monitor the actual physical and chemical condition of the oil to reliably determine the optimum oil-change interval. Our study focuses on the condition of the lubricating oil in an operated car engine. Shear stress curves and viscosity curves as a function of the shear rate for fresh and used lubricating oil were examined. Metal nitrate was detected in the lubricating oil from the operated car engine through the use of a chelating self-assembled monolayer.

Effects of fresh lubricant oils on particle emissions emitted by a modern gasoline direct injection passenger car.

PubMed

Pirjola, Liisa; Karjalainen, Panu; Heikkilä, Juha; Saari, Sampo; Tzamkiozis, Theodoros; Ntziachristos, Leonidas; Kulmala, Kari; Keskinen, Jorma; Rönkkö, Topi

2015-03-17

Particle emissions from a modern turbocharged gasoline direct injection passenger car equipped with a three-way catalyst and an exhaust gas recirculation system were studied while the vehicle was running on low-sulfur gasoline and, consecutively, with five different lubrication oils. Exhaust particle number concentration, size distribution, and volatility were determined both at laboratory and on-road conditions. The results indicated that the choice of lubricant affected particle emissions both during the cold start and warm driving cycles. However, the contribution of engine oil depended on driving conditions being higher during acceleration and steady state driving than during deceleration. The highest emission factors were found with two oils that had the highest metal content. The results indicate that a 10% decrease in the Zn content of engine oils is linked with an 11-13% decrease to the nonvolatile particle number emissions in steady driving conditions and a 5% decrease over the New European Driving Cycle. The effect of lubricant on volatile particles was even higher, on the order of 20%.

Prototype design of a collision protection system for cab car engineers.

DOT National Transportation Integrated Search

2013-03-01

The objective of this project was to develop and analyze a passive system to protect a cab car engineer from secondary impact injuries that might be experienced due to impact with the cab console. The primary requirement for the system was the abilit...

Picasso, Car Classics, and the Engineers.

ERIC Educational Resources Information Center

Wosk, Julie H.

1982-01-01

Describes a college course which introduces engineering and business students to abstract art. Students study the relationships between abstract styles in painting and abstract styles in twentieth-century architecture and industrial design. The relevance of abstract design principles is shown by referring students to "Car and Driver"…

A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy.

PubMed

Zhang, Erhao; Xu, Hanmei

2017-01-03

Adoptive cell therapy using chimeric antigen receptor (CAR)-engineered T cells has emerged as a very promising approach to combating cancer. Despite its ability to eliminate tumors shown in some clinical trials, CAR-T cell therapy involves some significant safety challenges, such as cytokine release syndrome (CRS) and "on-target, off-tumor" toxicity, which is related to poor control of the dose, location, and timing of T cell activity. In the past few years, some strategies to avoid the side effects of CAR-T cell therapy have been reported, including suicide gene, inhibitory CAR, dual-antigen receptor, and the use of exogenous molecules as switches to control the CAR-T cell functions. Because of the advances of the CAR paradigm and other forms of cancer immunotherapy, the most effective means of defeating the cancer has become the integration therapy with the combinatorial control system of switchable dual-receptor CAR-T cell and immune checkpoint blockade.

Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care.

PubMed

Riccione, Katherine; Suryadevara, Carter M; Snyder, David; Cui, Xiuyu; Sampson, John H; Sanchez-Perez, Luis

2015-02-16

Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo to express chimeric antigen receptors specific for glioma antigens (CAR T cells). The expansion and function of adoptively transferred CAR T cells can be potentiated by the lymphodepletive and tumoricidal effects of standard of care chemotherapy and radiotherapy. We describe a method for generating CAR T cells targeting EGFRvIII, a glioma-specific antigen, and evaluating their efficacy when combined with a murine model of glioblastoma standard of care. T cells are engineered by transduction with a retroviral vector containing the anti-EGFRvIII CAR gene. Tumor-bearing animals are subjected to host conditioning by a course of temozolomide and whole brain irradiation at dose regimens designed to model clinical standard of care. CAR T cells are then delivered intravenously to primed hosts. This method can be used to evaluate the antitumor efficacy of CAR T cells in the context of standard of care.

Classification of energy-conserving engine oil for passenger cars, vans, sport utility vehicles, and light-duty trucks (revised May 97). (SAE standard)

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

NONE

1997-05-01

This SAE Standard was developed cooperatively by SAE, ASTM, and API to define and identify energy conserving engine oils for passenger cars, vans, and light-duty (3856 kg (8500 lb) GVW or less) trucks.

77 FR 6856 - Volkswagen Group of America, Inc., Receipt of Petition for Decision of Inconsequential Noncompliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... Jetta passenger cars equipped with a TDI engine and Goodyear Eagle Vector 205/55 R16 94V XL tires, do... Jetta passenger cars equipped with a TDI engine and Goodyear Eagle Vector 205/55 R16 94V XL tires, and...

Issues and Dimensions of Freight Car Size: A Compendium

DOT National Transportation Integrated Search

1980-10-01

An investigation is made into the effects of the size, weight, and length of freight cars on the safety and efficiency of U.S. rail transportation. A review is made of the historical and present population and usage of the U.S. freight car fleet. Dis...

Aerodynamic effects by cooling flows within engine room of a car model

NASA Astrophysics Data System (ADS)

Sawaguchi, T.; Takakura, Y.

2017-10-01

The purpose of this research is to clarify the change of characteristics of aerodynamic drag and lift of a car by the engine loading system (engine arrangement) and the air inlet system (opening area and position) with and without a radiator in wind-tunnel experiments. A simplified car model with 1/5 scale is generated with reproduction of the engine room covered with the transparent acryl externals for visualization. In the wind-tunnel experiments, the moving-belt ground board is adopted to include ground effects with force measurements by use of load cells. The flows are visualized by the smoke method. As results, with enlargement of the opening area, the drag increased overall although depending largely on the engine loading system and the inlet opening position, the front lift increased and the rear left decreased; the effect of the radiator was to relieve the change of the drag and lift.

Recovery of exhaust waste heat for a hybrid car using steam turbine

NASA Astrophysics Data System (ADS)

Ababatin, Yasser

A number of car engines operate with an efficiency rate of approximately 22% to 25% [1]. The remainder of the energy these engines generate is wasted through heat escape out of the exhaust pipe. There is now an increasing desire to reuse this heat energy, which would improve the overall efficiency of car engines by reducing their consumption of fuel. Another benefit is that such reuse would minimize harmful greenhouse gases that are emitted into the environment. Therefore, the purpose of this project is to examine how the wasted heat energy can be reused and/or recovered by use of a heat recovery system that would store this energy in a hybrid car battery. Green turbines will be analyzed as a possible solution to recycle the lost energy in a way that will also improve the overall automotive energy efficiency.

Strategies for enhancing adoptive T-cell immunotherapy against solid tumors using engineered cytokine signaling and other modalities.

PubMed

Shum, Thomas; Kruse, Robert L; Rooney, Cliona M

2018-05-04

Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms. Areas covered: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells. Expert opinion: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

Application for certification, 1991 model year light-duty vehicles - Sports Car America, Puma Division Inc

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

Not Available

1992-01-01

Every year, each manufacturer of passenger cars, light-duty trucks, motorcycles, or heavy-duty engines submits to EPA an application for certification. The report deals with light-duty vehicles from Sports Car America, PUMA Division Incorporated. In the application, the manufacturer gives a detailed technical description of the vehicles or engines he intends to market during the upcoming model year. These engineering data include explanations and/or drawings which describe engine/vehicle parameters such as basic engine design, fuel systems, ignition systems and exhaust and evaporative emission control systems. It also provides information on emission test procedures, service accumulation procedures, fuels to be used, andmore » proposed maintenance requirements to be followed during testing. Section 16 of the application contains the results of emission testing, a statement of compliance to the regulations, production engine parameters, and a Summary Sheet Input Form on which issuance of a Certificate of Conformity is based.« less

Nitroaromatic carcinogens in diesel soot: a review of laboratory findings.

PubMed Central

Wei, E T; Shu, H P

1983-01-01

The automobile industry plans to increase production of diesel-powered passenger cars because diesel engines provide better fuel economy than conventional gasoline engines. Diesel engines, however, produce more soot, and increased use of diesel cars will result in more discharge of diesel soot into the atmosphere. Recently, a new class of chemicals, called nitroaromatic compounds, have been identified in chemical extracts of diesel soot. Some of these nitroaromatic compounds produce mutations when tested in in vitro bacterial and mammalian cell assays, and cancer when tested in animals. Here, we review the relevance of these new laboratory findings to current deliberations over emission standards for particles from diesel cars. PMID:6192732

The emission of BTEX compounds during movement of passenger car in accordance with the NEDC.

PubMed

Adamović, Dragan; Dorić, Jovan; Vojinović Miloradov, Mirjana; Adamović, Savka; Pap, Sabolč; Radonić, Jelena; Turk Sekulić, Maja

2018-05-20

The results of the research in the field of benzene, toluene, ethylbenzene and xylene isomers (BTEX) concentrations in exhaust gases of spark ignition engines under different operating conditions are presented in this paper. The aim of this paper is to gain a clearer insight into the impact of different engine working parameters on the concentrations of BTEX. The experimental investigation has been performed on the SCHENCK 230 W test stand with the controlled IC engine. The engine operating points have been chosen based on the results of a simulation and they are considered as the typical driving conditions according to the New European Driving Cycle. Concentration levels of BTEX compounds in exhaust gas mixtures have been determined by gas chromatography technique by using the combination of Supelcowax 10-Polyethylene glycol column and the PID detector. Based on the experimental research results, the emission model of BTEX compounds has been defined by the simulation of movement of a Fiat Punto Classic passenger car in accordance with the NEDC cycle. Using the results obtained within the simulation, the official statistics on the number of gasoline-powered cars on the territory of the Republic of Serbia and the European Commission data on the annual distance traveled by car, the amounts of BTEX compounds emitted annually per car have been estimated, as well as the emissions of the entire Serbian car fleet. Copyright © 2018 Elsevier B.V. All rights reserved.

[Steady car engine noise does not affect the cognitive abilities of sleep apnea syndrome patients].

PubMed

Mayoralas, L R; Barbé, F; Muñoz, A; Agustí, A G N

2003-09-01

Traffic accidents are more frequent for sleep apnea syndrome (SAS) patients than in the population at large. The mechanisms that underlie this observation are poorly defined. Our working hypothesis was that in SAS patients the steady noise of a car engine might alter cognitive capacities that may be involved in driving, thus increasing the risk of traffic accidents. To test this hypothesis we designed a prospective randomized controlled trial. Eighteen SAS patients (apnea-hypopnea index [SEM] 62 [6] h1) and 18 healthy controls were studied. All the participants were evaluated in random order both in basal conditions and after exposure to the steady noise of a car engine recorded on a compact disc. Their level of vigilance was evaluated (Steer-Clear) as well as their reaction time (PVT 192). Attention, coordination, and memory were measured using the following tests: Wechsler Memory Scale (digit span), the Wechsler Intelligence Scale (digit symbol), and Lezack's Trail Making tests A and B. The SAS patients were slightly younger than the control group (mean 50 [7] vs 57 [11] years, respectively; P=.05). The patients showed a lower level of vigilance than the controls both in basal and engine noise conditions (P<.05). No differences between groups were found for the other variables studied. Exposure to steady car engine noise had no effect on the tests of either group. In conclusion, the results of our study do not support the hypothesis that steady car engine noise significantly alters the cognitive ability of SAS patients.

75 FR 66390 - Notice of Lodging of Settlement Agreement Under the Comprehensive Environmental Response...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... & Luxury Car Clark Street Site in Michigan; 58. The Delta Engine Plant Site in Michigan; 59. The 1831... GMNA Car--Wilmington Site in Delaware; 2. The GMPT--Danville Landfill Site in Illinois; 3. The Former... Car (Fisher Body)--Lansing Site in Michigan; 21. The Midsize & Luxury Car--Willow Run Site in Michigan...

Rock Magnetic Characterization of fine Particles from car Engines, Break pads and Tobacco: An Environmental Pilot Study

NASA Astrophysics Data System (ADS)

Herrero-Bervera, E.; Lopez, V. A.; Gerstnecker, K.; Swilley, B.

2017-12-01

Today, it is very well known that small magnetic particles are very harmful to the health of humans. For the first time we have conducted an environmental pilot study of fine magnetic particles on the island of Oahu, Hawaii, of particulate matter (pm) 60, pm=10, and pm= 2.5. In order to do a rock magnetic characterization we have preformed low field susceptibility versus temperature (k-T) experiments to determine the Curie points of small particles collected from exhaust pipes, as well as from brake pads of 4 different types of car engines using octane ratings of 85, 87 and 92. The Curie point determinations are very well defined and range from 292 °C through 393 °C to 660 °C. In addition, we have conducted magnetic granulometry experiments on raw tobacco, burnt ashes as well as on car engines and brake pads in question. The results of the experiments show ferro- and ferrimagnetic hysteresis loops with magnetic grain sizes ranging from superparamagnetic-multidomain (SP_MD), multi-domain (MD) and pseudo-single domain (PSD) shown on the modified Day et al. diagram of Dunlop (2002). Thus far, the results we have obtained from this pilot study are in agreement with other studies conducted from cigarette ashes from Bulgaria (Jordanova et al., 2005). Our results could be correlated to the traffic-related PM in Rome, Italy where the SP fraction mainly occurs as coating of MD particles that originated by localized stress in the oxidized outer shell surrounding the unoxidized core of magnetite like grains as published by Sagnotti and Winkler (2012).

Development of turbocharger for improving passenger car acceleration

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

Watanabe, Tsuyoshi; Koike, Takaaki; Furukawa, Hiromu

1996-09-01

Recently, passenger cars require better acceleration from low engine speed including starting-up in order to decrease the amount of particulate matter (PM) of diesel engines or to improve the driver`s feeling. However, turbocharged cars generally have worse response than the non turbo cars because it takes a few seconds to get the turbocharger rotate up to high speed, usually called Turbo-lag. In order to solve this, various technologies have been developed for a turbocharger itself as well as for charging system such as the sequential system. Here in this paper, the authors focus on the development of the following turbochargermore » technology to reduce Turbo-lag and to achieve better transient response.« less

CAR therapy: the CD19 paradigm

PubMed Central

Sadelain, Michel

2015-01-01

Twenty-five years after its inception, the genetic engineering of T cells is now a therapeutic modality pursued at an increasing number of medical centers. This immunotherapeutic strategy is predicated on gene transfer technology to instruct T lymphocytes to recognize and reject tumor cells. Chimeric antigen receptors (CARs) are synthetic receptors that mediate antigen recognition, T cell activation, and — in the case of second-generation CARs — costimulation to augment T cell functionality and persistence. We demonstrated over a decade ago that human T cells engineered with a CD19-specific CAR eradicated B cell malignancies in mice. Several phase I clinical trials eventually yielded dramatic results in patients with leukemia or lymphoma, especially acute lymphoblastic leukemia (ALL). This review recounts the milestones of CD19 CAR therapy and summarizes lessons learned from the CD19 paradigm. PMID:26325036

Weight propagation and equivalent horsepower for alternate-engined cars

NASA Technical Reports Server (NTRS)

Klose, G. J.; Kurtz, D. W.

1978-01-01

In order to evaluate properly the consequences of replacing conventional Otto-cycle engines with alternate power systems, comparisons must be carried out at the vehicle level with functionally equivalent cars. This paper presents the development and application of a procedure for establishing equivalent vehicles. A systematic weight propagation methodology, based on detailed weight breakdowns and influence factors, yields the vehicle weight impacts due to changes in engine weight and power. Performance-matching criteria, utilizing a vehicle simulation program, are then employed to establish Otto-engine-equivalent vehicles, whose characteristics can form the basis for alternative engine evaluations.

AAP Updates Recommendations on Car Seats

MedlinePlus

... Size Email Print Share AAP Updates Recommendations on Car Seats Page Content Article Body Children should ride ... of approved car safety seats. Healthy Children Radio: Car Seat Safety Dennis Durbin, MD, FAAP, lead author ...

Alternative Fuels Data Center: Driving Tips for MPG

Science.gov Websites

Corporation Adds Propane Buses to Its Fleet Nov. 11, 2016 Photo of a man charging a car. Sacramento Powers up with Electric Vehicles Oct. 3, 2016 Photo of a car. Cleveland Car Dealership Working Toward a More Corridor Now Open Feb. 21, 2015 Photo of an electric car. College Students Engineer Efficient Vehicles in

Preclinical Models in Chimeric Antigen Receptor-Engineered T-Cell Therapy.

PubMed

Siegler, Elizabeth Louise; Wang, Pin

2018-05-01

Cancer immunotherapy has enormous potential in inducing long-term remission in cancer patients, and chimeric antigen receptor (CAR)-engineered T cells have been largely successful in treating hematological malignancies in the clinic. CAR-T therapy has not been as effective in treating solid tumors, in part due to the immunosuppressive tumor microenvironment. Additionally, CAR-T therapy can cause dangerous side effects, including off-tumor toxicity, cytokine release syndrome, and neurotoxicity. Animal models of CAR-T therapy often fail to predict such adverse events and frequently overestimate the efficacy of the treatment. Nearly all preclinical CAR-T studies have been performed in mice, including syngeneic, xenograft, transgenic, and humanized mouse models. Recently, a few studies have used primate models to mimic clinical side effects better. To date, no single model perfectly recapitulates the human immune system and tumor microenvironment, and some models have revealed CAR-T limitations that were contradicted or missed entirely in other models. Careful model selection based on the primary goals of the study is a crucial step in evaluating CAR-T treatment. Advancements are being made in preclinical models, with the ultimate objective of providing safer, more effective CAR-T therapy to patients.

Advantages and applications of CAR-expressing natural killer cells

PubMed Central

Glienke, Wolfgang; Esser, Ruth; Priesner, Christoph; Suerth, Julia D.; Schambach, Axel; Wels, Winfried S.; Grez, Manuel; Kloess, Stephan; Arseniev, Lubomir; Koehl, Ulrike

2015-01-01

In contrast to donor T cells, natural killer (NK) cells are known to mediate anti-cancer effects without the risk of inducing graft-versus-host disease (GvHD). In order to improve cytotoxicity against resistant cancer cells, auspicious efforts have been made with chimeric antigen receptor (CAR) expressing T- and NK cells. These CAR-modified cells express antigen receptors against tumor-associated surface antigens, thus redirecting the effector cells and enhancing tumor-specific immunosurveillance. However, many cancer antigens are also expressed on healthy tissues, potentially leading to off tumor/on target toxicity by CAR-engineered cells. In order to control such potentially severe side effects, the insertion of suicide genes into CAR-modified effectors can provide a means for efficient depletion of these cells. While CAR-expressing T cells have entered successfully clinical trials, experience with CAR-engineered NK cells is mainly restricted to pre-clinical investigations and predominantly to NK cell lines. In this review we summarize the data on CAR expressing NK cells focusing on the possible advantage using these short-lived effector cells and discuss the necessity of suicide switches. Furthermore, we address the compliance of such modified NK cells with regulatory requirements as a new field in cellular immunotherapy. PMID:25729364

Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Cancer

PubMed Central

Cartellieri, Marc; Bachmann, Michael; Feldmann, Anja; Bippes, Claudia; Stamova, Slava; Wehner, Rebekka; Temme, Achim; Schmitz, Marc

2010-01-01

CD4+ and CD8+ T lymphocytes are powerful components of adaptive immunity, which essentially contribute to the elimination of tumors. Due to their cytotoxic capacity, T cells emerged as attractive candidates for specific immunotherapy of cancer. A promising approach is the genetic modification of T cells with chimeric antigen receptors (CARs). First generation CARs consist of a binding moiety specifically recognizing a tumor cell surface antigen and a lymphocyte activating signaling chain. The CAR-mediated recognition induces cytokine production and tumor-directed cytotoxicity of T cells. Second and third generation CARs include signal sequences from various costimulatory molecules resulting in enhanced T-cell persistence and sustained antitumor reaction. Clinical trials revealed that the adoptive transfer of T cells engineered with first generation CARs represents a feasible concept for the induction of clinical responses in some tumor patients. However, further improvement is required, which may be achieved by second or third generation CAR-engrafted T cells. PMID:20467460

KSC-2012-2888

NASA Image and Video Library

2012-05-21

CAPE CANAVERAL, Fla. – At the NASA Railroad yard at Kennedy Space Center in Florida, helium tank cars are lifted from their trucks onto flat cars in preparation for a journey to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s tank cars will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-2890

NASA Image and Video Library

2012-05-21

CAPE CANAVERAL, Fla. – At the NASA Railroad yard at Kennedy Space Center in Florida, helium tank cars have been removed from their trucks and loaded onto flat cars in preparation for a journey to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s tank cars will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

The Chem-E-Car as a Vehicle for Service Learning through K-12 Outreach

ERIC Educational Resources Information Center

Chirdon, William

2017-01-01

This article presents the results of combining the American Institute of Chemical Engineers' (AIChE) Chem-E-Car competition activities with engineering outreach to K-12 students in a service-learning course. Survey results are presented to show how the program develops technical skills as well as leadership, teamwork, and communication skills in…

49 CFR 571.114 - Standard No. 114; Theft protection and rollaway prevention.

Code of Federal Regulations, 2013 CFR

2013-10-01

... key to activate the engine or motor. Vehicle type, as used in S5.1.2, refers to passenger car, truck... motion. S3. Application. This standard applies to all passenger cars, and to trucks and multipurpose... (by physical or electronic means), enables the vehicle operator to activate the engine or motor. Open...

49 CFR 571.114 - Standard No. 114; Theft protection and rollaway prevention.

Code of Federal Regulations, 2014 CFR

2014-10-01

... key to activate the engine or motor. Vehicle type, as used in S5.1.2, refers to passenger car, truck... motion. S3. Application. This standard applies to all passenger cars, and to trucks and multipurpose... (by physical or electronic means), enables the vehicle operator to activate the engine or motor. Open...

49 CFR 571.114 - Standard No. 114; Theft protection and rollaway prevention.

Code of Federal Regulations, 2012 CFR

2012-10-01

... key to activate the engine or motor. Vehicle type, as used in S5.1.2, refers to passenger car, truck... motion. S3. Application. This standard applies to all passenger cars, and to trucks and multipurpose... (by physical or electronic means), enables the vehicle operator to activate the engine or motor. Open...

A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer

PubMed Central

Lagisetty, Kiran H.; Tran, Eric; Zheng, Zhili; Gattinoni, Luca; Yu, Zhiya; Burns, William R.; Miermont, Anne M.; Teper, Yaroslav; Rudloff, Udo; Restifo, Nicholas P.; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.

2014-01-01

Abstract Despite advances in the understanding of its molecular pathophysiology, pancreatic cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate stem cell antigen (PSCA), a glycoprotein that is overexpressed in pancreatic cancer starting at early stages of malignant transformation. To optimize the CAR design, we used antigen-recognition domains derived from mouse or human antibodies, and intracellular signaling domains containing one or two T cell costimulatory elements, in addition to CD3zeta. Comparing multiple constructs established that the CAR based on human monoclonal antibody Ha1-4.117 had the greatest reactivity in vitro. To further analyze this CAR, we developed a human pancreatic cancer xenograft model and adoptively transferred CAR-engineered T cells into animals with established tumors. CAR-engineered human lymphocytes induced significant antitumor activity, and unlike what has been described for other CARs, a second-generation CAR (containing CD28 cosignaling domain) induced a more potent antitumor effect than a third-generation CAR (containing CD28 and 41BB cosignaling domains). While our results provide evidence to support PSCA as a target antigen for CAR-based immunotherapy of pancreatic cancer, the expression of PSCA on selected normal tissues could be a source of limiting toxicity. PMID:24694017

deep-orange and carnation define distinct stages in late endosomal biogenesis in Drosophila melanogaster.

PubMed

Sriram, V; Krishnan, K S; Mayor, Satyajit

2003-05-12

Endosomal degradation is severely impaired in primary hemocytes from larvae of eye color mutants of Drosophila. Using high resolution imaging and immunofluorescence microscopy in these cells, products of eye color genes, deep-orange (dor) and carnation (car), are localized to large multivesicular Rab7-positive late endosomes containing Golgi-derived enzymes. These structures mature into small sized Dor-negative, Car-positive structures, which subsequently fuse to form tubular lysosomes. Defective endosomal degradation in mutant alleles of dor results from a failure of Golgi-derived vesicles to fuse with morphologically arrested Rab7-positive large sized endosomes, which are, however, normally acidified and mature with wild-type kinetics. This locates the site of Dor function to fusion of Golgi-derived vesicles with the large Rab7-positive endocytic compartments. In contrast, endosomal degradation is not considerably affected in car1 mutant; fusion of Golgi-derived vesicles and maturation of large sized endosomes is normal. However, removal of Dor from small sized Car-positive endosomes is slowed, and subsequent fusion with tubular lysosomes is abolished. Overexpression of Dor in car1 mutant aggravates this defect, implicating Car in the removal of Dor from endosomes. This suggests that, in addition to an independent role in fusion with tubular lysosomes, the Sec1p homologue, Car, regulates Dor function.

T Cells Engineered With Chimeric Antigen Receptors Targeting NKG2D Ligands Display Lethal Toxicity in Mice

PubMed Central

VanSeggelen, Heather; Hammill, Joanne A; Dvorkin-Gheva, Anna; Tantalo, Daniela GM; Kwiecien, Jacek M; Denisova, Galina F; Rabinovich, Brian; Wan, Yonghong; Bramson, Jonathan L

2015-01-01

Ligands for the NKG2D receptor are overexpressed on tumors, making them interesting immunotherapy targets. To assess the tumoricidal properties of T cells directed to attack NKG2D ligands, we engineered murine T cells with two distinct NKG2D-based chimeric antigen receptors (CARs): (i) a fusion between the NKG2D receptor and the CD3ζ chain and (ii) a conventional second-generation CAR, where the extracellular domain of NKG2D was fused to CD28 and CD3ζ. To enhance the CAR surface expression, we also engineered T cells to coexpress DAP10. In vitro functionality and surface expression levels of all three CARs was greater in BALB/c T cells than C57BL/6 T cells, indicating strain-specific differences. Upon adoptive transfer of NKG2D-CAR-T cells into syngeneic animals, we observed significant clinical toxicity resulting in morbidity and mortality. The severity of these toxicities varied between the CAR configurations and paralleled their in vitro NKG2D surface expression. BALB/c mice were more sensitive to these toxicities than C57BL/6 mice, consistent with the higher in vitro functionality of BALB/c T cells. Treatment with cyclophosphamide prior to adoptive transfer exacerbated the toxicity. We conclude that while NKG2D ligands may be useful targets for immunotherapy, the pursuit of NKG2D-based CAR-T cell therapies should be undertaken with caution. PMID:26122933

Post test review of a single car test of multi-level passenger equipment

DOT National Transportation Integrated Search

2008-04-22

The single car test of multi-level equipment described in : this paper was designed to help evaluate the crashworthiness of : a multi-level car in a controlled collision. The data collected : from this test will be used to refine engineering models. ...

Lead-free bearing alloys for engine applications

NASA Astrophysics Data System (ADS)

Ratke, Lorenz; Ågren, John; Ludwig, Andreas; Tonn, Babette; Gránásy, László; Mathiesen, Ragnvald; Arnberg, Lars; Anger, Gerd; Reifenhäuser, Bernd; Lauer, Michael; Garen, Rune; Gust, Edgar

2005-10-01

Recent developments to reduce the fuel consumption, emission and air pollution, size and weight of engines for automotive, truck, ship propulsion and electrical power generation lead to temperature and load conditions within the engines that cannot be borne by conventional bearings. Presently, only costly multilayer bearings with electroplated or sputtered surface coatings can cope with the load/speed combinations required. Ecological considerations in recent years led to a ban by the European Commission on the use of lead in cars a problem for the standard bronze-lead bearing material. This MAP project is therefore developing an aluminium-based lead-free bearing material with sufficient hardness, wear and friction properties and good corrosion resistance. Only alloys made of components immiscible in the molten state can meet the demanding requirements. Space experimentation plays a crucial role in optimising the cast microstructure for such applications.

Bioengineering Solutions for Manufacturing Challenges in CAR T Cells

PubMed Central

Piscopo, Nicole J.; Mueller, Katherine P.; Das, Amritava; Hematti, Peiman; Murphy, William L.; Palecek, Sean P.; Capitini, Christian M.

2017-01-01

The next generation of therapeutic products to be approved for the clinic is anticipated to be cell therapies, termed “living drugs” for their capacity to dynamically and temporally respond to changes during their production ex vivo and after their administration in vivo. Genetically engineered chimeric antigen receptor (CAR) T cells have rapidly developed into powerful tools to harness the power of immune system manipulation against cancer. Regulatory agencies are beginning to approve CAR T cell therapies due to their striking efficacy in treating some hematological malignancies. However, the engineering and manufacturing of such cells remains a challenge for widespread adoption of this technology. Bioengineering approaches including biomaterials, synthetic biology, metabolic engineering, process control and automation, and in vitro disease modeling could offer promising methods to overcome some of these challenges. Here, we describe the manufacturing process of CAR T cells, highlighting potential roles for bioengineers to partner with biologists and clinicians to advance the manufacture of these complex cellular products under rigorous regulatory and quality control. PMID:28840981

Stock-car racing makes intuitive physicists

NASA Astrophysics Data System (ADS)

Gwynne, Peter

2008-03-01

Formula One races involve cars festooned with gadgets and complex electronic devices, in which millions of dollars are spent refining a vehicle's aerodynamics and reducing its weight. But in events run by America's National Association of Stock Car Auto Racing (NASCAR), cars hurtle round an oval track at speeds of about 300 km h-1 without the help of the complex sensors that are employed in Formula One cars. To avoid crashing, drivers must make their own adjustments to track conditions, engine problems and the traffic around them.

Conflict between internal combustion engine and thermoelectric generator during waste heat recovery in cars

NASA Astrophysics Data System (ADS)

Korzhuev, M. A.

2011-02-01

It is shown that an internal combustion engine and a thermoelectric generator (TEG) arranged on the exhaust pipe of this engine come into the conflict of thermal machines that is related to using the same energy resource. The conflict grows with increasing useful electric power W e of the TEG, which leads to the limitation of both the maximum TEG output power ( W {e/max}) and the possibility of waste heat recovery in cars.

KSC-2012-3055

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train crosses the railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The helium tank cars are positioned in the front and rear of the train. The long, thin tank car in the middle was used for liquid hydrogen, followed by a much larger tank car used for liquid oxygen. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3054

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train crosses the railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The helium tank cars are positioned in the front and rear of the train. The long, thin tank car in the middle was used for liquid hydrogen, followed by a much larger tank car used for liquid oxygen. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

Intelligent Control Electromagnetic Actuated Continuously Variable Transmission System for Passenger Car

NASA Astrophysics Data System (ADS)

Rahman, Ataur; Sharif, Sazzad; Mohiuddin, AKM; Faris Ismail, Ahmed; Izan, Sany Ihsan

2017-03-01

Continuously variable transmission (CVT) system transmits the engine /battery power to the car driving wheel smoothly and efficiently. Cars with CVT produces some noise and slow acceleration to meet the car power demand on initial start-ups and slow speed. The car noise is produced as a result of CVT adjustment the engine speed with the hydraulic pressure. The current CVT problems incurred due to the slow response of hydraulic pressure and CVT fluid viscosity due to the development of heat.The aim of this study is to develop electromagnetic actuated CVT (EMA-CVT) with intelligent switching controlling system (ICS). The experimental results of ¼ scale EMA shows that it make the acceleration time of the car in 3.5-5 sec which is 40% less than the hydraulic CVT in the market. The EMA develops the electromagnetic force in the ranged of 350 -1200 N for the supply current in the range of 10-15 amp. This study introduced fuzzy intelligent system (FIS) to predict the EMA system dynamic behaviour in order to identify the current control for the EMA actuation during operation of the CVT. It is expecting that the up scale EMA-CVT would reduce the 75% of vehicle power transmission loss by accelerating vehicle in 5 sec and save the IC engine power consumption about 20% which will makes the vehicle energy efficient (EEV) and reduction of green house gas reduction.

Materials at 200 mph: Making NASCAR Faster and Safer

NASA Astrophysics Data System (ADS)

Leslie-Pelecky, Diandra

2008-03-01

You cannot win a NASCAR race without understanding science.ootnotetextDiandra Leslie-Pelecky, The Physics of NASCAR (Dutton, New York City, 2008). Materials play important roles in improving performance, as well as ensuring safety. On the performance side, NASCAR limits the materials race car scientists and engineers can use to limit ownership costs. `Exotic metals' are not allowed, so controlling microstructure and nanostructure are important tools. Compacted Graphite Iron, a cast iron in which magnesium additions produce interlocking microscale graphite reinforcements, makes engine blocks stronger and lighter. NASCAR's new car design employs a composite called Tegris^TM that has 70 percent of the strength of carbon fiber composites at about 10 percent of the cost. The most important role of materials in racing is safety. Drivers wear firesuits made of polymers that carbonize (providing thermal protection) and expand (reducing oxygen access) when heated. Catalytic materials originally developed for space-based CO2 lasers filter air for drivers during races. Although materials help cars go fast, they also help cars slow down safely---important because the kinetic energy of a race car going 180 mph is nine times greater than that of a passenger car going 60 mph. Energy-absorbing foams in the cars and on the tracks control energy dissipation during accidents. To say that most NASCAR fans (and there are estimated to be 75 million of them) are passionate about their sport is an understatement. NASCAR fans understand that science and engineering are integral to keeping their drivers safe and helping their teams win. Their passion for racing gives us a great opportunity to share our passion for science with them. NASCAR^ is a registered trademark of the National Association for Stock Car Auto Racing, Inc. Tegris^TM is a trademark of Milliken & Company.

KSC-2012-3053

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train crosses the railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3052

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train crosses the railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3039a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train passes in front of the 525-foot-tall Vehicle Assembly Building at NASA’s Kennedy Space Center in Florida. At the far right is the Orbiter Processing Facility. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-2889

NASA Image and Video Library

2012-05-21

CAPE CANAVERAL, Fla. – At the NASA Railroad yard at Kennedy Space Center in Florida, cranes are enlisted to lift helium tank cars from their trucks onto flat cars in preparation for a journey to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s tank cars will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The yard is located in Kennedy’s Launch Complex 39 near the 525-foot-tall Vehicle Assembly Building, in the background. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3036a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train passes in front of the twin bays of the Orbiter Processing Facility at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3035a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train passes in front of the twin bays of the Orbiter Processing Facility at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3056

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train has crossed the Indian River on the railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3050

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train crosses the railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3051

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train crosses the railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

Heat transfer from an internal combustion (Otto-cycle) engine on the surface of Mars

NASA Technical Reports Server (NTRS)

Gwynne, Owen

1992-01-01

The cooling requirements for an average car sized engine (spark-ignition, V-6, four-stroke, naturally aspirated, about 200 kg, about 100 kW) were looked at for Mars. Several modes of cooling were considered, including forced convection, exhaust, radiation and closed loop systems. The primary goal was to determine the effect of the thinner Martian atmosphere on the cooling system. The results show that there was only a 6-percent difference in the cooling requirements. This difference was due mostly to the thinner atmosphere during forced convection and the heat capacity of the exhaust. A method using a single pass counter-flow heat exchanger is suggested to offset this difference in cooling requirements.

Heat transfer from an internal combustion (Otto-cycle) engine on the surface of Mars

NASA Astrophysics Data System (ADS)

Gwynne, Owen

1992-05-01

The cooling requirements for an average car sized engine (spark-ignition, V-6, four-stroke, naturally aspirated, about 200 kg, about 100 kW) were looked at for Mars. Several modes of cooling were considered, including forced convection, exhaust, radiation and closed loop systems. The primary goal was to determine the effect of the thinner Martian atmosphere on the cooling system. The results show that there was only a 6-percent difference in the cooling requirements. This difference was due mostly to the thinner atmosphere during forced convection and the heat capacity of the exhaust. A method using a single pass counter-flow heat exchanger is suggested to offset this difference in cooling requirements.

Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor

PubMed Central

Richardson, Max W.; Ellebrecht, Christoph T.; Glover, Joshua A.; Secreto, Anthony J.; Kulikovskaya, Irina; Yi, Yanjie; Wang, Jianbin; Dufendach, Keith A.; Holmes, Michael C.; Collman, Ronald G.

2017-01-01

HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy. PMID:29023549

KSC-2012-3033a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – At the NASA Railroad Yard at NASA’s Kennedy Space Center in Florida, preparations are under way for the departure of a train made up of tank cars. The railroad’s track runs past Kennedy’s 525-foot-tall Vehicle Assembly Building in the background. The train is headed for the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3032a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – At the NASA Railroad Yard at NASA’s Kennedy Space Center in Florida, preparations are under way for the departure of a train made up of tank cars. The train will pass by Kennedy’s 525-foot-tall Vehicle Assembly Building in the background. The train is headed for the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

Immunological quality and performance of tumor vessel-targeting CAR-T cells prepared by mRNA-EP for clinical research

PubMed Central

Inoo, Kanako; Inagaki, Ryo; Fujiwara, Kento; Sasawatari, Shigemi; Kamigaki, Takashi; Nakagawa, Shinsaku; Okada, Naoki

2016-01-01

We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR) specific for vascular endothelial growth factor receptor 2 (VEGFR2), demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6–12 hours after mRNA-EP. Triple transfer of murine anti-VEGFR2 CAR-T cells into B16BL6 tumor-bearing mice demonstrated an antitumor effect comparable to that for the single transfer of CAR-T cells engineered with retroviral vector. The mRNA-EP did not cause any damage or defects to human T-cell characteristics, as determined by viability, growth, and phenotypic parameters. Additionally, two kinds of human anti-VEGFR2 CAR-T cells, which expressed different CAR construction, differentiated to effector phase with cytokine secretion and cytotoxic activity in antigen-specific manner. These results indicate that our anti-VEGFR2 CAR-T cells prepared by mRNA-EP have the potential in terms of quality and performance to offer the prospect of safety and efficacy in clinical research as cellular medicine. PMID:27909701

Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma.

PubMed

Chmielewski, Markus; Hombach, Andreas A; Abken, Hinrich

2014-01-01

Adoptive T-cell therapy recently achieved impressive efficacy in early phase trials, in particular in hematologic malignancies, strongly supporting the notion that the immune system can control cancer. A current strategy of favor is based on ex vivo-engineered patient T cells, which are redirected by a chimeric antigen receptor (CAR) and recognize a predefined target by an antibody-derived binding domain. Such CAR T cells can substantially reduce the tumor burden as long as the targeted antigen is present on the cancer cells. However, given the tremendous phenotypic diversity in solid tumor lesions, a reasonable number of cancer cells are not recognized by a given CAR, considerably reducing the therapeutic success. This article reviews a recently described strategy for overcoming this shortcoming of the CAR T-cell therapy by modulating the tumor stroma by a CAR T-cell-secreted transgenic cytokine like interleukin-12 (IL-12). The basic process is that CAR T cells, when activated by their CAR, deposit IL-12 in the targeted tumor lesion, which in turn attracts an innate immune cell response toward those cancer cells that are invisible to CAR T cells. Such TRUCKs, T cells redirected for universal cytokine-mediated killing, exhibited remarkable efficacy against solid tumors with diverse cancer cell phenotypes, suggesting their evaluation in clinical trials. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Full Hybrid: Low Speed

Science.gov Websites

blue rule Main stage: See through car with battery, engine, generator, power split device, and electric motor visible. The car is moving at a low speed. There are arrows flowing from the battery to the electric motor to the power split device to the front wheels. Main stage: See through car with battery

Rev Your Engines!

ERIC Educational Resources Information Center

Blanchard, Margaret; Sharp, Jennifer; Grable, Lisa

2009-01-01

As part of the "Car Lab Project," students constructed rubber band cars, raced them, and worked through a number of automotive activities. The students engaged in this project certainly had fun, but they also used high-tech gear such as motion sensors and graphing calculators to gather data on the distance and time cars traveled and to generate…

Hybrid: Braking

Science.gov Websites

motor slows the vehicle down. Go to next… stage graphic: vertical blue rule Main stage: See through car with battery, engine, and electric motor visible. The car is decelerating. There are arrows flowing from the front wheels to the electric motor to the battery. Main stage: See through car with battery

Study of DC Circuit Breaker of H2-N2 Mixture Gas for High Voltage

NASA Astrophysics Data System (ADS)

Shiba, Yuji; Morishita, Yukinaga; Kaneko, Shuhei; Okabe, Shigemitsu; Mizoguchi, Hitoshi; Yanabu, Satoru

Global warming caused by CO2 etc. is a field where the concern is very high. Especially, automobile emissions are problem for it. Therefore, the hybrid car is widely development and used recently. Hybrid car used electric power and gasoline. So, the car reduces CO2. Hybrid car has engine and motor. To rotate the motor, hybrid car has battery. This battery is large capacity. Therefore, the relay should interrupt high DC current for the switch of the motor and the engine. So, hybrid car used hydrogen gas filling relay We studied interruption test for the research of a basic characteristic of hydrogen gas. DC current has not current zero point. So, it is necessary to make the current zero by high arc voltage and forcible current zero point. The loss coefficient and arc voltage of hydrogen is high. Therefore, we studied interruption test for used high arc voltage. We studied interruption test and dielectric breakdown test of air, pure Hydrogen, and Hydrogen- nitrogen mixture gas. As a result, we realized H2-N2(80%-20%) is the best gas.

Crash fatality and vehicle incompatibility in collisions between cars and light trucks or vans.

PubMed

Ossiander, Eric M; Koepsell, Thomas D; McKnight, Barbara

2014-12-01

In crashes between a car and a light truck or van (LTV), car occupants are more likely to be killed than LTV occupants. The extent this is due to the greater harm imposed by LTVs on cars or the greater protection they offer their own occupants is not known. We conducted a case-control study of collisions between two passenger vehicles in the USA during 1990-2008. Cases were all decedents in fatal crashes (N=157,684); one control was selected from each crash in a national probability sample of crashes (N=379,458). Adjusted for the type of vehicle they were riding in and other confounders, occupants of vehicles colliding with any type of LTVs (categorised as compact sport utility vehicles (SUV), full-size SUVs, minivans, full-size vans, compact pickups and full-size pickups) were at higher risk of death compared with occupants colliding with cars. Adjusted for the type of vehicle they crashed with and other confounders, occupants of LTVs in a collision with any vehicle were at lower risk of death compared with car occupants. Compared with a crash between two cars, the overall RR of death in a crash between any of the other 27 different combinations of vehicle types was 1.0 or greater, except for crashes between two full-size pickups, where the RR of death was 0.9. Although LTVs protect their own occupants better than cars do, LTVs are associated with an excess total risk of death in crashes with cars or other LTVs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

How energy efficient is your car?

NASA Astrophysics Data System (ADS)

Roura, Pere; Oliu, Daniel

2012-07-01

A detailed energy balance indicating how fuel energy is transferred from the engine to the wheels of a commercial car is obtained using non-specialized experiments that can be readily understood using elementary mechanics. These experiments allow us to determine the engine's thermal efficiency, its mechanical losses, and the rolling (friction) and aerodynamic (drag) coefficients. We find that approximately 28% of the fuel energy is transferred to the wheels.

Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma

PubMed Central

Beatty, Gregory L

2014-01-01

Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells is under investigation as an approach to restore productive T cell immunosurveillance in patients with pancreatic ductal adenocarcinoma. Early findings demonstrate safety of this cell-based therapy and the capacity of CAR-expressing T cells to mediate anti-tumor activity as well as induce endogeneous antitumoral immune responses. PMID:25050204

Driving gene-engineered T cell immunotherapy of cancer

PubMed Central

Johnson, Laura A; June, Carl H

2017-01-01

Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for solid tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors (TCRs) were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treatment to solid tumors, however, has just begun, but already certain factors have been made clear: the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, challenges, and future. PMID:28025979

Bandwidth based methodology for designing a hybrid energy storage system for a series hybrid electric vehicle with limited all electric mode

NASA Astrophysics Data System (ADS)

Shahverdi, Masood

The cost and fuel economy of hybrid electrical vehicles (HEVs) are significantly dependent on the power-train energy storage system (ESS). A series HEV with a minimal all-electric mode (AEM) permits minimizing the size and cost of the ESS. This manuscript, pursuing the minimal size tactic, introduces a bandwidth based methodology for designing an efficient ESS. First, for a mid-size reference vehicle, a parametric study is carried out over various minimal-size ESSs, both hybrid (HESS) and non-hybrid (ESS), for finding the highest fuel economy. The results show that a specific type of high power battery with 4.5 kWh capacity can be selected as the winning candidate to study for further minimization. In a second study, following the twin goals of maximizing Fuel Economy (FE) and improving consumer acceptance, a sports car class Series-HEV (SHEV) was considered as a potential application which requires even more ESS minimization. The challenge with this vehicle is to reduce the ESS size compared to 4.5 kWh, because the available space allocation is only one fourth of the allowed battery size in the mid-size study by volume. Therefore, an advanced bandwidth-based controller is developed that allows a hybridized Subaru BRZ model to be realized with a light ESS. The result allows a SHEV to be realized with 1.13 kWh ESS capacity. In a third study, the objective is to find optimum SHEV designs with minimal AEM assumption which cover the design space between the fuel economies in the mid-size car study and the sports car study. Maximizing FE while minimizing ESS cost is more aligned with customer acceptance in the current state of market. The techniques applied to manage the power flow between energy sources of the power-train significantly affect the results of this optimization. A Pareto Frontier, including ESS cost and FE, for a SHEV with limited AEM, is introduced using an advanced bandwidth-based control strategy teamed up with duty ratio control. This controller allows the series hybrid's advantage of tightly managing engine efficiency to be extended to lighter ESS, as compared to the size of the ESS in available products in the market.

Phase 1 studies of central memory-derived CD19 CAR T-cell therapy following autologous HSCT in patients with B-cell NHL.

PubMed

Wang, Xiuli; Popplewell, Leslie L; Wagner, Jamie R; Naranjo, Araceli; Blanchard, M Suzette; Mott, Michelle R; Norris, Adam P; Wong, ChingLam W; Urak, Ryan Z; Chang, Wen-Chung; Khaled, Samer K; Siddiqi, Tanya; Budde, Lihua E; Xu, Jingying; Chang, Brenda; Gidwaney, Nikita; Thomas, Sandra H; Cooper, Laurence J N; Riddell, Stanley R; Brown, Christine E; Jensen, Michael C; Forman, Stephen J

2016-06-16

Myeloablative autologous hematopoietic stem cell transplantation (HSCT) is a mainstay of therapy for relapsed intermediate-grade B-cell non-Hodgkin lymphoma (NHL); however, relapse rates are high. In phase 1 studies designed to improve long-term remission rates, we administered adoptive T-cell immunotherapy after HSCT, using ex vivo-expanded autologous central memory-enriched T cells (TCM) transduced with lentivirus expressing CD19-specific chimeric antigen receptors (CARs). We present results from 2 safety/feasibility studies, NHL1 and NHL2, investigating different T-cell populations and CAR constructs. Engineered TCM-derived CD19 CAR T cells were infused 2 days after HSCT at doses of 25 to 200 × 10(6) in a single infusion. In NHL1, 8 patients safely received T-cell products engineered from enriched CD8(+) TCM subsets, expressing a first-generation CD19 CAR containing only the CD3ζ endodomain (CD19R:ζ). Four of 8 patients (50%; 95% confidence interval [CI]: 16-84%) were progression free at both 1 and 2 years. In NHL2, 8 patients safely received T-cell products engineered from enriched CD4(+) and CD8(+) TCM subsets and expressing a second-generation CD19 CAR containing the CD28 and CD3ζ endodomains (CD19R:28ζ). Six of 8 patients (75%; 95% CI: 35-97%) were progression free at 1 year. The CD4(+)/CD8(+) TCM-derived CD19 CAR T cells (NHL2) exhibited improvement in expansion; however, persistence was ≤28 days, similar to that seen by others using CD28 CARs. Neither cytokine release syndrome nor delayed hematopoietic engraftment was observed in either trial. These data demonstrate the safety and feasibility of CD19 CAR TCM therapy after HSCT. Trials were registered at www.clinicaltrials.gov as #NCT01318317 and #NCT01815749. © 2016 by The American Society of Hematology.

The basics of CAR T design and challenges in immunotherapy of solid tumors - Ovarian cancer as a model.

PubMed

Xu, Xuequn; Qiu, Jin; Sun, Yi

2017-07-03

Chimeric antigen receptor T cells are T cells genetically engineered with CAR constructs which mainly contain scFV and TCR zeta chain. With promising development in blood cancers, CAR T trials are also applied in solid cancers. However, the treatment effect in solid cancers is lower than expected. This review summarizes difference of CAR T applications in solid and blood cancers. Future challenges of CAR T cell treatment in solid cancer are also discussed using ovarian cancer as an example.

Implementation of object-oriented programming in study of electrical race car

NASA Astrophysics Data System (ADS)

Nowak, M.; Baier, M.

2016-08-01

The paper covers issue of conducting advanced research of electrical race car participating in international competition called Sileverline Corporate Challenge. Process of designing race cars in Silesian Greenpower team is aided by a professional engine test stand built particularly in purpose of this research. Phase of testing and simulation is an important part of the implementation of new technologies. Properly developed solutions and test procedures are able to significantly shorten development time and reduce design costs. Testing process must be controlled by a modular and flexible application, easy to modify and ensuring safety. This paper describes the concept of object-oriented programming in LabVIEW and exemplary architecture of object-oriented control application designed to control engine test stand of the electrical race car. Eventually, the task of application will be to steer the electromagnetic brake and the engine load torque to perform according to data from the actual race track. During the designing process of the car, minimizing energy losses and maximizing powertrain efficiency are the main aspects taken into consideration. One of the crucial issues to accomplish these goals is to maintain optimal performance of the motor by applying effective cooling. The paper covers the research verifying the effectiveness of the cooling system.

Combining deep learning and coherent anti-Stokes Raman scattering imaging for automated differential diagnosis of lung cancer.

PubMed

Weng, Sheng; Xu, Xiaoyun; Li, Jiasong; Wong, Stephen T C

2017-10-01

Lung cancer is the most prevalent type of cancer and the leading cause of cancer-related deaths worldwide. Coherent anti-Stokes Raman scattering (CARS) is capable of providing cellular-level images and resolving pathologically related features on human lung tissues. However, conventional means of analyzing CARS images requires extensive image processing, feature engineering, and human intervention. This study demonstrates the feasibility of applying a deep learning algorithm to automatically differentiate normal and cancerous lung tissue images acquired by CARS. We leverage the features learned by pretrained deep neural networks and retrain the model using CARS images as the input. We achieve 89.2% accuracy in classifying normal, small-cell carcinoma, adenocarcinoma, and squamous cell carcinoma lung images. This computational method is a step toward on-the-spot diagnosis of lung cancer and can be further strengthened by the efforts aimed at miniaturizing the CARS technique for fiber-based microendoscopic imaging. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Hydrogen powered sports car series (internal combustion engine and fuel cells)

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

Gotthold, J.P.

The electric hybrid vehicle can solve the problems which today make the pure electric car limited in its acceptance. The primary limitations are excess weight and short range due to a heavy battery pack of limited energy density. Our basic vehicular design makes use of three power technologies in a balanced way. The chassis is the standard Volkswagen Beetle type which carried many millions of the {open_quotes}beetles{close_quotes} across all the Earth`s continents. The body is a fiberfab replica of a 1970s design sports car which provides three compartments from it`s original mid engine design and a classic aerodynamic shape.

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

None

On behalf of the Department of Energy's Office of FreedomCAR and Vehicle Technologies, we are pleased to introduce the Fiscal Year (FY) 2004 Annual Progress Report for the Advanced Combustion Engine R&D Sub-Program. The mission of the FreedomCAR and Vehicle Technologies Program is to develop more energy efficient and environmentally friendly highway transportation technologies that enable Americans to use less petroleum for their vehicles. The Advanced Combustion Engine R&D Sub-Program supports this mission by removing the critical technical barriers to commercialization of advanced internal combustion engines for light-, medium-, and heavy-duty highway vehicles that meet future Federal and state emissionsmore » regulations. The primary objective of the Advanced Combustion Engine R&D Sub-Program is to improve the brake thermal efficiency of internal combustion engines from 30 to 45 percent for light-duty applications by 2010; and 40 to 55 percent for heavy-duty applications by 2012; while meeting cost, durability, and emissions constraints. R&D activities include work on combustion technologies that increase efficiency and minimize in-cylinder formation of emissions, as well as aftertreatment technologies that further reduce exhaust emissions. Work is also being conducted on ways to reduce parasitic and heat transfer losses through the development and application of thermoelectrics and turbochargers that include electricity generating capability, and conversion of mechanically driven engine components to be driven via electric motors. This introduction serves to outline the nature, current progress, and future directions of the Advanced Combustion Engine R&D Sub-Program. The research activities of this Sub-Program are planned in conjunction with the FreedomCAR Partnership and the 21st Century Truck Partnership and are carried out in collaboration with industry, national laboratories, and universities. Because of the importance of clean fuels in achieving low emissions, R&D activities are closely coordinated with the relevant activities of the Fuel Technologies Sub-Program, also within the Office of FreedomCAR and Vehicle Technologies. Research is also being undertaken on hydrogen-fueled internal combustion engines to provide an interim hydrogen-based powertrain technology that promotes the longer-range FreedomCAR Partnership goal of transitioning to a hydrogen-fueled transportation system. Hydrogen engine technologies being developed have the potential to provide diesel-like engine efficiencies with near-zero emissions.« less

Development of CAR T cells designed to improve antitumor efficacy and safety

PubMed Central

Jaspers, Janneke E.; Brentjens, Renier J.

2017-01-01

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models. PMID:28342824

Development of CAR T cells designed to improve antitumor efficacy and safety.

PubMed

Jaspers, Janneke E; Brentjens, Renier J

2017-10-01

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models. Published by Elsevier Inc.

Chimeric antigen receptor for adoptive immunotherapy of cancer: latest research and future prospects.

PubMed

Shi, Huan; Sun, Meili; Liu, Lin; Wang, Zhehai

2014-09-21

Chimeric antigen receptors (CARs) are recombinant receptors that combine the specificity of an antigen-specific antibody with the T-cell's activating functions. Initial clinical trials of genetically engineered CAR T cells have significantly raised the profile of T cell therapy, and great efforts have been made to improve this approach. In this review, we provide a structural overview of the development of CAR technology and highlight areas that require further refinement. We also discuss critical issues related to CAR therapy, including the optimization of CAR T cells, the route of administration, CAR toxicity and the blocking of inhibitory molecules.

Papers on vehicle size : cars and trucks

DOT National Transportation Integrated Search

1988-06-01

The four papers in this volume describe analyses of car size : trends and truck occupant injuries and fatalities. All four were : written between June 1985 and December 1987. The topics : addressed include where heavy truck accidents occur, injury an...

KSC-2012-3038a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train passes in front of the 525-foot-tall Vehicle Assembly Building, left, and the twin bays of the Orbiter Processing Facility, right, at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3046

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A manatee relaxes in the Indian River near the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The manatee was spotted by a cameraman on hand to photograph a NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3044

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A manatee relaxes in the Indian River near the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The manatee was spotted by a cameraman on hand to photograph a NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3037a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A NASA Railroad train passes in front of the 525-foot-tall Vehicle Assembly Building, left, and the twin bays of the Orbiter Processing Facility, right, at NASA’s Kennedy Space Center in Florida. The train is on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3043

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A manatee swims in the Indian River near the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The manatee was spotted by a cameraman on hand to photograph a NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3045

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – Manatees relax in the Indian River near the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The manatees were spotted by a cameraman on hand to photograph a NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3040a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – Bubbles form around a dolphin splashing in the Indian River near the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The dolphin was spotted by a cameraman on hand to photograph a NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3041a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A dolphin plays in the Indian River near the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The dolphin was spotted by a cameraman on hand to photograph a NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3042

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – A dolphin swims in the Indian River near the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida. The dolphin was spotted by a cameraman on hand to photograph a NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

Effective adoptive immunotherapy of triple-negative breast cancer by folate receptor-alpha redirected CAR T cells is influenced by surface antigen expression level.

PubMed

Song, De-Gang; Ye, Qunrui; Poussin, Mathilde; Chacon, Jessica A; Figini, Mariangela; Powell, Daniel J

2016-07-20

The poor prognosis and the limited efficacy of targeted therapy in patients with triple-negative breast cancer (TNBC) have raised the need for alternative therapies. Recent studies have demonstrated that folate receptor-alpha (FRα) may represent an ideal tumor-associated marker for immunotherapy for TNBC. The aim of the present study was to apply a chimeric antigen receptor (CAR) approach for the targeting of FRα expressed on TNBC cells and evaluate the antitumor activity of CAR-engineered T cells in vitro and in vivo. We found that human T cells expressing a FRα-specific CAR were potent and specific killers of TNBC cells that express moderate levels of FRα in vitro and significantly inhibited tumor outgrowth following infusion into immunodeficient mice bearing an MDA-MB-231 tumor xenograft. However, the antitumor activity of the FRα CAR T cells was modest when compared to the same CAR T cells applied in an ovarian tumor xenograft model where FRα expression is more abundant. Notably, FRα CAR T cells induced superior tumor regression in vivo against MDA-MB-231 that was engineered for overexpression of FRα. Taken together, our results show that FRα CAR T cells can mediate antitumor activity against established TNBC tumor, particularly when FRα is expressed at higher levels. These results have significant implications for the pre-selection of patients with high antigen expression levels when utilizing CAR-based adoptive T cell therapies of cancer in future clinical trials.

Lighting innovations in concept cars

NASA Astrophysics Data System (ADS)

Berlitz, Stephan; Huhn, Wolfgang

2005-02-01

Concept cars have their own styling process. Because of the big media interest they give a big opportunity to bring newest technology with styling ideas to different fairgrounds. The LED technology in the concept cars Audi Pikes Peak, Nuvolari and Le Mans will be explained. Further outlook for the Audi LED strategy starting with LED Daytime Running Lamp will be given. The close work between styling and technical engineers results in those concept cars and further technical innovations based on LED technologies.

Potential of Diesel Engine, 1979 Summary Source Document

DOT National Transportation Integrated Search

1980-03-01

This document assesses the fuel economy potential of diesel engines in future passenger cars and light trucks. The primary technologies evaluated include: (1) engine control strategy and implementation, (2) the engine design variables, (3) emissions ...

Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.

PubMed

Thokala, Radhika; Olivares, Simon; Mi, Tiejuan; Maiti, Sourindra; Deniger, Drew; Huls, Helen; Torikai, Hiroki; Singh, Harjeet; Champlin, Richard E; Laskowski, Tamara; McNamara, George; Cooper, Laurence J N

2016-01-01

Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.

How Chimeric Antigen Receptor Design Affects Adoptive T Cell Therapy.

PubMed

Gacerez, Albert T; Arellano, Benjamine; Sentman, Charles L

2016-12-01

Chimeric antigen receptor (CAR) T cells have been developed to treat tumors and have shown great success against B cell malignancies. Exploiting modular designs and swappable domains, CARs can target an array of cell surface antigens and, upon receptor-ligand interactions, direct signaling cascades, thereby driving T cell effector functions. CARs have been designed using receptors, ligands, or scFv binding domains. Different regions of a CAR have each been found to play a role in determining the overall efficacy of CAR T cells. Therefore, this review provides an overview of CAR construction and common designs. Each CAR region is discussed in the context of its importance to a CAR's function. Additionally, the review explores how various engineering strategies have been applied to CAR T cells in order to regulate CAR T cell function and activity. J. Cell. Physiol. 231: 2590-2598, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

How chimeric antigen receptor design affects adoptive T cell therapy

PubMed Central

Gacerez, Albert T.; Arellano, Benjamine; Sentman, Charles L.

2016-01-01

Chimeric antigen receptor (CAR) T cells have been developed to treat tumors and have shown great success against B cell malignancies. Exploiting modular designs and swappable domains, CARs can target an array of cell surface antigens and, upon receptor-ligand interactions, direct signaling cascades, thereby driving T cell effector functions. CARs have been designed using receptors, ligands, or scFv binding domains. Different regions of a CAR have each been found to play a role in determining the overall efficacy of CAR T cells. Therefore, this review provides an overview of CAR construction and common designs. Each CAR region is discussed in the context of its importance to a CAR’s function. Additionally, the review explores how various engineering strategies have been applied to CAR T cells in order to regulate CAR T cell function and activity. PMID:27163336

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors

PubMed Central

Smith, Tyrel T.; Moffett, Howell F.; Stephan, Sirkka B.; Opel, Cary F.; Dumigan, Amy G.; Jiang, Xiuyun; Pillarisetty, Venu G.; Pillai, Smitha P. S.; Wittrup, K. Dane; Stephan, Matthias T.

2017-01-01

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants. PMID:28436934

Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors.

PubMed

Smith, Tyrel T; Moffett, Howell F; Stephan, Sirkka B; Opel, Cary F; Dumigan, Amy G; Jiang, Xiuyun; Pillarisetty, Venu G; Pillai, Smitha P S; Wittrup, K Dane; Stephan, Matthias T

2017-06-01

Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting. Here, we have tested implantable biopolymer devices that deliver CAR T cells directly to the surfaces of solid tumors, thereby exposing them to high concentrations of immune cells for a substantial time period. In immunocompetent orthotopic mouse models of pancreatic cancer and melanoma, we found that CAR T cells can migrate from biopolymer scaffolds and eradicate tumors more effectively than does systemic delivery of the same cells. We have also demonstrated that codelivery of stimulator of IFN genes (STING) agonists stimulates immune responses to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes. Thus, these devices may improve the effectiveness of CAR T cell therapy in solid tumors and help protect against the emergence of escape variants.

A GMP-compliant protocol to expand and transfect cancer patient T cells with mRNA encoding a tumor-specific chimeric antigen receptor.

PubMed

Krug, Christian; Wiesinger, Manuel; Abken, Hinrich; Schuler-Thurner, Beatrice; Schuler, Gerold; Dörrie, Jan; Schaft, Niels

2014-10-01

Chimeric antigen receptors (CARs), which combine an antibody-derived binding domain (single chain fragment variable) with T-cell-activating signaling domains, have become a promising tool in the adoptive cellular therapy of cancer. Retro- and lenti-viral transductions are currently the standard methods to equip T cells with a CAR; permanent CAR expression, however, harbors several risks like uncontrolled auto-reactivity. Modification of T cells by electroporation with CAR-encoding RNA to achieve transient expression likely circumvents these difficulties. We here present a GMP-compliant protocol to activate and expand T cells for clinical application. The protocol is optimized in particular to produce CAR-modified T cells in clinically sufficient numbers under full GMP-compliance from late-stage cancer patients. This protocol allows the generation of 6.7 × 10(8) CAR-expressing T cells from one patient leukapheresis. The CAR-engineered T cells produced pro-inflammatory cytokines after stimulation with antigen-bearing tumor cells and lysed tumor cells in an antigen-specific manner. This functional capacity was maintained after cryopreservation. Taken together, we provide a clinically applicable protocol to transiently engineer sufficient numbers of antigen-specific patient T cells for use in adoptive cell therapy of cancer.

Engineering Hematopoietic Cells for Cancer Immunotherapy: Strategies to Address Safety and Toxicity Concerns.

PubMed

Resetca, Diana; Neschadim, Anton; Medin, Jeffrey A

2016-09-01

Advances in cancer immunotherapies utilizing engineered hematopoietic cells have recently generated significant clinical successes. Of great promise are immunotherapies based on chimeric antigen receptor-engineered T (CAR-T) cells that are targeted toward malignant cells expressing defined tumor-associated antigens. CAR-T cells harness the effector function of the adaptive arm of the immune system and redirect it against cancer cells, overcoming the major challenges of immunotherapy, such as breaking tolerance to self-antigens and beating cancer immune system-evasion mechanisms. In early clinical trials, CAR-T cell-based therapies achieved complete and durable responses in a significant proportion of patients. Despite clinical successes and given the side effect profiles of immunotherapies based on engineered cells, potential concerns with the safety and toxicity of various therapeutic modalities remain. We discuss the concerns associated with the safety and stability of the gene delivery vehicles for cell engineering and with toxicities due to off-target and on-target, off-tumor effector functions of the engineered cells. We then overview the various strategies aimed at improving the safety of and resolving toxicities associated with cell-based immunotherapies. Integrating failsafe switches based on different suicide gene therapy systems into engineered cells engenders promising strategies toward ensuring the safety of cancer immunotherapies in the clinic.

Delayed treatment with hypothermia protects against the no-reflow phenomenon despite failure to reduce infarct size.

PubMed

Hale, Sharon L; Herring, Michael J; Kloner, Robert A

2013-01-04

Many studies have shown that when hypothermia is started after coronary artery reperfusion (CAR), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no-reflow. Our aim was to test the effects of hypothermia on no-reflow when initiated close to reperfusion and 30 minutes after reperfusion, times not associated with a protective effect on myocardial infarct size. Rabbits received 30 minutes coronary artery occlusion/3 hours CAR. In protocol 1, hearts were treated for 1 hour with topical hypothermia (myocardial temperature ≈32°C) initiated at 5 minutes before or 5 minutes after CAR, and the results were compared with a normothermic group. In protocol 2, hypothermia was delayed until 30 minutes after CAR and control hearts remained normothermic. In protocol 1, risk zones were similar and infarct size was not significantly reduced by hypothermia initiated close to CAR. However, the no-reflow defect was significantly reduced by 43% (5 minutes before CAR) and 38% (5 minutes after CAR) in hypothermic compared with normothermic hearts (P=0.004, ANOVA, P=ns between the 2 treated groups). In protocol 2, risk zones and infarct sizes were similar, but delayed hypothermia significantly reduced no-reflow in hypothermic hearts by 30% (55±6% of the necrotic region in hypothermia group versus 79±6% with normothermia, P=0.008). These studies suggest that treatment with hypothermia reduces no-reflow even when initiated too late to reduce infarct size and that the microvasculature is especially receptive to the protective properties of hypothermia and confirm that microvascular damage is in large part a form of true reperfusion injury.

78 FR 13354 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-27

... via the antibody binding fragment of the CAR. Thus, by engineering a T-cell to express a CAR that is... significantly overexpressed in primary and metastasizing tumors relative to normal human tissues. Stimulation of...

Potential of Spark Ignition Engine : Engine Design Concepts

DOT National Transportation Integrated Search

1980-03-01

This report provides a review and assessment of potential improvements in fuel economy for a selected number of spark ignition engine design technologies for passenger cars and light trucks. The engine design technologies examined include: : a) optim...

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

Pearce, T.C.; Waters, M.H.L.

Measurements have been made of the fuel consumption of a petrol and a diesel car when starting from cold. The cars were the 1.1 liter petrol VW Golf and the 1.5 liter diesel version, which have the same passenger accommodation and nearly identical road performance. It was found that the diesel car used less fuel in the warm-up period than the petrol, both when being driven at constant speed on a test track and with the engine idling and the car stationary. (Copyright (c) Crown Copyright 1980.)

Energy and transportation(*)

NASA Astrophysics Data System (ADS)

Hermans, J.

2015-08-01

Transportation takes a considerable and increasing fraction of the energy use worldwide, and more than half the oil consumption. By far the largest part is used by cars powered by internal combustion engines. The advantage of using internal combustion engines is that the energy density of liquid fuels is extremely high. The disadvantage is that gasoline and diesel engines have a poor performance: 20 to 25% only. How does this compare with electric cars? What are the alternative transportation systems and their efficiencies anyway? In this lecture we analyse the efficiency of various transport systems, using elementary physics principles. We will look at cars, buses, trains and TGVs, ships and aircraft. In addition, the efficiency of human powered vehicles will be considered. New and promising developments in the field of Intelligent Transportation Systems, like Cooperative Adaptive Cruise Control, are also discussed.

Biodegradation of long-chain n-paraffins from waste oil of car engine by Acinetobacter sp.

PubMed

Koma, D; Hasumi, F; Yamamoto, E; Ohta, T; Chung, S Y; Kubo, M

2001-01-01

Microorganisms that degrade long-chain n-paraffins from used car engine oil were isolated from soil. For the screening, a fraction of n-paraffin prepared from car engine oil was applied as the sole carbon source. The strain was identified as Acinetobacter sp. The ability of the strain to assimilate long-chain n-paraffins was assessed and characterized. The strain mineralized long-chain n-paraffins (0.1% w/v) in the minimal medium after cultivation for 96 h and also reduced the weight of the waste oil added (1% w/v) by 20% after 72 h without an extracellular biosurfactant. When n-hexadecane was fed as substrate, 1-hexadecanol and 1-hexadecanoic acid were detected as the intermediates by gas chromatography/mass spectrometry. This indicates that the long-chain n-paraffins were metabolized via the terminal oxidation pathway of n-alkane.

Traction studies of piston ring wear using an external radiometric method with proton activation

NASA Astrophysics Data System (ADS)

Scharf, Waldemar; Niewczas, Andrzej

1987-04-01

A method and results are presented of traction studies of piston ring wear in a Polski Fiat 126p passenger car and Star 200 lorry. The rings sliding surface was activated with a beam of 9.6-MeV protons and the measurements were made using a collimated scintillation detector placed outside the engine, i.e. without interfering with the engine's operation. The cars were run under varying traction conditions, their mileages having ranged between 7000 and 12000 km. In stable wear conditions on the road the piston ring wear for the passenger car and the lorry was {0.28%}/{100} km and {0.045%}/{100} km, respectively. The method was found to be particularly suitable for traction studies because it is simple and cheap. It can be employed as early as after the first 100 km of the car mileage.

Immunotherapy of Malignant Disease Using Chimeric Antigen Receptor Engrafted T Cells

PubMed Central

Maher, John

2012-01-01

Chimeric antigen receptor- (CAR-) based immunotherapy has been under development for almost 25 years, over which period it has progressed from a new but cumbersome technology to an emerging therapeutic modality for malignant disease. The approach involves the genetic engineering of fusion receptors (CARs) that couple the HLA-independent binding of cell surface target molecules to the delivery of a tailored activating signal to host immune cells. Engineered CARs are delivered most commonly to peripheral blood T cells using a range of vector systems, most commonly integrating viral vectors. Preclinical refinement of this approach has proceeded over several years to the point that clinical testing is now being undertaken at several centres, using increasingly sophisticated and therapeutically successful genetic payloads. This paper considers several aspects of the pre-clinical and clinical development of CAR-based immunotherapy and how this technology is acquiring an increasing niche in the treatment of both solid and haematological malignancies. PMID:23304553

Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis.

PubMed

Wu, Jiayuan; Tan, Wenkai; Chen, Lin; Huang, Zhe; Mai, Shao

2018-03-02

C-reactive protein/albumin ratio (CAR) was originally used as a novel inflammation-based prognostic score in predicting outcomes in septic patients. Recently, more and more studies have reported the prognostic value of pretreatment CAR in solid tumors. However, the results remain controversial rather than conclusive. We conducted a meta-analysis based on 24 studies with 10203 patients to explore the relationship between CAR and survival outcomes in patients with solid tumors. The correlation between CAR and clinicopathological parameters was also assessed. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was applied to be the effect size estimate. The overall results showed that elevated CAR was associated with shorter overall survival (OS) (including 23 studies and 10067 patients) and poorer disease-free survival (DFS) (including 6 studies and 2904 patients). Significant associations between high CAR level and poor OS were also found in the subgroup analyses of study region, cancer type, primary treatment, clinical stage, cut-off selection, sample size, and cut-off value. Moreover, subgroup analyses demonstrated that study region, primary treatment, clinical stage, sample size, and cut-off value did not alter the prognostic value of CAR for DFS. Furthermore, elevated CAR was correlated with certain phenotypes of tumor aggressiveness, such as poor histological grade, serious clinical stage, advanced tumor depth, positive lymph node metastasis, and positive distant metastasis. Together, our meta-analysis suggests that elevated level of serum CAR predicts worse survival and unfavorable clinical characteristics in cancer patients, and CAR may serve as an effective prognostic factor for solid tumors.

Experimental investigation on the flow around a simplified geometry of automotive engine compartment

NASA Astrophysics Data System (ADS)

D'Hondt, Marion; Gilliéron, Patrick; Devinant, Philippe

2011-05-01

In the current sustainable development context, car manufacturers have to keep doing efforts to reduce the aerodynamic drag of automotive vehicle in order to decrease their CO2 and greenhouse gas emissions. The cooling airflow, through the engine compartment of vehicles, contributes from 5 to 10% to the total aerodynamic drag. By means of simplified car geometry, equipped with an engine compartment, the configurations that favor a low contribution to total drag are identified. PIV (particle image velocimetry) velocity measurements in the wake of the geometry allow explaining these drag reductions. Besides, the cooling flow rate is also assessed and gives indications on the configurations that favor the engine cooling.

Particle emissions from diesel passenger cars equipped with a particle trap in comparison to other technologies.

PubMed

Mohr, Martin; Forss, Anna-Maria; Lehmann, Urs

2006-04-01

Tail pipe particle emissions of passenger cars, with different engine and aftertreatment technologies, were determined with special focus on diesel engines equipped with a particle filter. The particle number measurements were performed, during transient tests, using a condensation particle counter. The measurement procedure complied with the draft Swiss ordinance, which is based on the findings of the UN/ECE particulate measurement program. In addition, particle mass emissions were measured by the legislated and a modified filter method. The results demonstrate the high efficiency of diesel particle filters (DPFs) in curtailing nonvolatile particle emissions over the entire size range. Higher emissions were observed during short periods of DPF regeneration and immediately afterward, when a soot cake has not yet formed on the filter surface. The gasoline vehicles exhibited higher emissions than the DPF equipped diesel vehicles but with a large variation depending on the technology and driving conditions. Although particle measurements were carried out during DPF regeneration, it was impossible to quantify their contribution to the overall emissions, due to the wide variation in intensity and frequency of regeneration. The numbers counting method demonstrated its clear superiority in sensitivity to the mass measurement. The results strongly suggest the application of the particle number counting to quantify future low tailpipe emissions.

The Tol2 transposon system mediates the genetic engineering of T-cells with CD19-specific chimeric antigen receptors for B-cell malignancies.

PubMed

Tsukahara, T; Iwase, N; Kawakami, K; Iwasaki, M; Yamamoto, C; Ohmine, K; Uchibori, R; Teruya, T; Ido, H; Saga, Y; Urabe, M; Mizukami, H; Kume, A; Nakamura, M; Brentjens, R; Ozawa, K

2015-02-01

Engineered T-cell therapy using a CD19-specific chimeric antigen receptor (CD19-CAR) is a promising strategy for the treatment of advanced B-cell malignancies. Gene transfer of CARs to T-cells has widely relied on retroviral vectors, but transposon-based gene transfer has recently emerged as a suitable nonviral method to mediate stable transgene expression. The advantages of transposon vectors compared with viral vectors include their simplicity and cost-effectiveness. We used the Tol2 transposon system to stably transfer CD19-CAR into human T-cells. Normal human peripheral blood lymphocytes were co-nucleofected with the Tol2 transposon donor plasmid carrying CD19-CAR and the transposase expression plasmid and were selectively propagated on NIH3T3 cells expressing human CD19. Expanded CD3(+) T-cells with stable and high-level transgene expression (~95%) produced interferon-γ upon stimulation with CD19 and specifically lysed Raji cells, a CD19(+) human B-cell lymphoma cell line. Adoptive transfer of these T-cells suppressed tumor progression in Raji tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared with control mice. These results demonstrate that the Tol2 transposon system could be used to express CD19-CAR in genetically engineered T-cells for the treatment of refractory B-cell malignancies.

KSC-2012-3047

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – Preparations are under way at the NASA Railroad’s Jay Jay Railroad Bridge north of Launch Complex 39 at NASA’s Kennedy Space Center in Florida for the passage of the NASA Railroad train on its way to the Florida East Coast Railway interchange in Titusville, Fla., where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The permanent configuration of the drawbridge span is open, but the span will be lowered for a train to cross. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3049

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – NASA Railroad locomotive No. 3 delivers tank cars from NASA’s Kennedy Space Center in Florida to the Florida East Coast Railway interchange in Titusville, Fla. The locomotive is one of three NASA Railroad locomotives built for the Toledo, Peoria and Western, or TP&W, between 1968 and 1970. It is a GM Electromotive Division SW-1500 switcher. The locomotive was acquired by NASA from the TP&W in 1984 and painted in the NASA Railroad paint scheme. The power plant was completely overhauled in 2009. The locomotive will pull the train to the interchange in Titusville, where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3031a

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – NASA Railroad locomotive No. 3 is enlisted to deliver tank cars from NASA’s Kennedy Space Center in Florida to the Florida East Coast Railway interchange in Titusville, Fla. The locomotive is one of three NASA Railroad locomotives built for the Toledo, Peoria and Western, or TP&W, between 1968 and 1970. It is a GM Electromotive Division SW-1500 switcher. The locomotive was acquired by NASA from the TP&W in 1984 and painted in the NASA Railroad paint scheme. The power plant was completely overhauled in 2009. The locomotive will pull the train to the interchange in Titusville, where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

KSC-2012-3048

NASA Image and Video Library

2012-05-23

CAPE CANAVERAL, Fla. – NASA Railroad locomotive No. 3 delivers tank cars from NASA’s Kennedy Space Center in Florida to the Florida East Coast Railway interchange in Titusville, Fla. The locomotive is one of three NASA Railroad locomotives built for the Toledo, Peoria and Western, or TP&W, between 1968 and 1970. It is a GM Electromotive Division SW-1500 switcher. The locomotive was acquired by NASA from the TP&W in 1984 and painted in the NASA Railroad paint scheme. The power plant was completely overhauled in 2009. The locomotive will pull the train to the interchange in Titusville, where the train’s helium tank cars, a liquid oxygen tank car, and a liquid hydrogen dewar or tank car will be transferred for delivery to the SpaceX engine test complex outside McGregor, Texas. The railroad cars were needed in support of the Space Shuttle Program but currently are not in use by NASA following the completion of the program in 2011. Originally, the tankers belonged to the U.S. Bureau of Mines. At the peak of the shuttle program, there were approximately 30 cars in the fleet. About half the cars were returned to the bureau as launch activity diminished. Five tank cars are being loaned to SpaceX and repurposed to support their engine tests in Texas. Eight cars previously were shipped to California on loan to support the SpaceX Falcon 9 rocket launches from Space Launch Complex-4 on Vandenberg Air Force Base. SpaceX already has three helium tank cars previously used for the shuttle program at Space Launch Complex-40 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/spacex. Photo credit: NASA/Jim Grossmann

Semi-analytical approach to estimate railroad tank car shell puncture

DOT National Transportation Integrated Search

2011-03-16

This paper describes the development of engineering-based equations to estimate the puncture resistance of railroad tank cars under a generalized shell or side impact scenario. Resistance to puncture is considered in terms of puncture velocity, which...

3. EXTERIOR VIEW TO THE NORTHEAST OF A RAILROAD CAR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. EXTERIOR VIEW TO THE NORTHEAST OF A RAILROAD CAR ON THE TRACKS AND THE PARTS OF AN ENGINE STAND. - Nevada Test Site, Pluto Facility, Area 26, Wahmonie Flats, Cane Spring Road, Mercury, Nye County, NV

From Gas Guzzler to Energy Producer: The Amazing Potential of Fuel Cell Cars

ERIC Educational Resources Information Center

Roman, Harry T.

2008-01-01

As a child, the author and his father built a basement workshop where the father taught himself radio and television repair, and the son learned skills that led him to an engineering career. In this article, the author relates how his father gave him a lesson that showed cars are actually rolling power plants. Here, he explains how cars can be…

Alternative Fuels Data Center: Central Ohio Turns Trash Into Natural Gas

Science.gov Websites

electric car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a Authority of Central Ohio turns trash into compressed natural gas for fleet fuel. For information about this FuelEconomy.gov. Provided by Maryland Public Television Related Videos Photo of a car Electric Vehicles Charge up

Alternative Fuels Data Center: Maryland Conserves Fuel With Hybrid Trucks

Science.gov Websites

reducing fuel consumption, engine noise, and greenhouse gas emissions with hybrid trucks. For information of a car Electric Vehicles Charge up at State Parks in West Virginia Dec. 9, 2017 Photo of a car Smart Car Shopping Nov. 4, 2017 Photo of a truck Natural Gas Vehicles Make a Difference in Tennessee Oct

CARS temperature measurements in the fuel preburner of the Space Shuttle main engine: A feasibility study

NASA Technical Reports Server (NTRS)

Beiting, E. J.; Luthe, J. C.

1983-01-01

This report discusses the feasibility of making temperature profile measurements in the fuel preburner of the main engine of the space shuttle (SSME) using coherent anti-Stokes Raman spectroscopy (CARS). The principal thrust of the work is to identify problems associated with making CARS measurements in high temperature gas phase hydrogen at very high pressures (approx 400 atmospheres). To this end a theoretical study was made of the characteristics of the CAR spectra of H2 as a function of temperature and pressure and the accuracy with which temperatures can be extracted from this spectra. In addition the experimental problems associated with carrying out these measurements on a SSME at NSTL were identified. A conceptual design of a CARS system suitable for this work is included. Many of the results of the calculations made in this report are plotted as a function of temperature. In the course of presenting these results, it was necessary to decide whether the number of density or the pressure should be treated as a fixed parameter.

Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen Receptor to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1α-secreting Glioblastoma.

PubMed

Müller, Nadja; Michen, Susanne; Tietze, Stefanie; Töpfer, Katrin; Schulte, Alexander; Lamszus, Katrin; Schmitz, Marc; Schackert, Gabriele; Pastan, Ira; Temme, Achim

2015-06-01

Natural killer (NK) cells are promising effector cells for adjuvant immunotherapy of cancer. So far, several preclinical studies have shown the feasibility of gene-engineered NK cells, which upon expression of chimeric antigen receptors (CARs) are redirected to otherwise NK cell-resistant tumors. Yet, we reasoned that the efficiency of an immunotherapy using CAR-modified NK cells critically relies on efficient migration to the tumor site and might be improved by the engraftment of a receptor specific for a chemokine released by the tumor. On the basis of the DNAX-activation protein 12 (DAP12), a signaling adapter molecule involved in signal transduction of activating NK cell receptors, we constructed an epidermal growth factor variant III (EGFRvIII)-CAR, designated MR1.1-DAP12 which confers specific cytotoxicity of NK cell towards EGFRvIII glioblastoma cells in vitro and to established subcutaneous U87-MG tumor xenografts. So far, infusion of NK cells with expression of MR1.1-DAP12 caused a moderate but significantly delayed tumor growth and increased median survival time when compared with NK cells transduced with an ITAM-defective CAR. Notably, the further genetic engineering of these EGFRvIII-specific NK cells with the chemokine receptor CXCR4 conferred a specific chemotaxis to CXCL12/SDF-1α secreting U87-MG glioblastoma cells. Moreover, the administration of such NK cells resulted in complete tumor remission in a number of mice and a significantly increased survival when compared with the treatment of xenografts with NK cells expressing only the EGFRvIII-specific CAR or mock control. We conclude that chemokine receptor-engineered NK cells with concomitant expression of a tumor-specific CAR are a promising tool to improve adoptive tumor immunotherapy.

KSC-2011-8009

NASA Image and Video Library

2011-11-26

CAPE CANAVERAL, Fla. -- Smoke and steam billow from the main engine of the United Launch Alliance Atlas V rocket as it launches with NASA's Mars Science Laboratory (MSL) spacecraft. MSL lifted off from Space Launch Complex-41 at Cape Canaveral Air Force Station in Florida at 10:02 a.m. EST Nov. 26. MSL's components include a car-sized rover, Curiosity, which has 10 science instruments designed to search for signs of life, including methane, and help determine if the gas is from a biological or geological source. For more information, visit http://www.nasa.gov/msl. Photo credit: NASA/Tony Gray and Rick Wetherington

Stand for testing the electrical race car engine

NASA Astrophysics Data System (ADS)

Baier, M.; Franiasz, J.; Mierzwa, P.; Wylenzek, D.

2015-11-01

An engine test stand created especially for research of electrical race car is described in the paper. The car is an aim of Silesian Greenpower project whose participants build and test electrical vehicles to take part in international races in Great Britain. The engine test stand is used to test and measure the characteristics of vehicles and their engines. It has been designed particularly to test the electric cars engineered by students of Silesian Greenpower project. The article contains a description how the test stand works and shows its versatility in many areas. The paper presents both construction of the test stand, control system and sample results of conducted research. The engine test stand was designed and modified using PLM Siemens NX 8.5. The construction of the test stand is highly modular, which means it can be used both for testing the vehicle itself or for tests without the vehicle. The test stand has its own wheel, motor, powertrain and braking system with second engine. Such solution enables verifying various concepts without changing the construction of the vehicle. The control system and measurement system are realized by enabling National Instruments product myRIO (RIO - Reconfigurable Input/Output). This controller in combination with powerful LabVIEW environment performs as an advanced tool to control torque and speed simultaneously. It is crucial as far as the test stand is equipped in two motors - the one being tested and the braking one. The feedback loop is realized by an optical encoder cooperating with the rotor mounted on the wheel. The results of tests are shown live on the screen both as a chart and as single values. After performing several tests there is a report generated. The engine test stand is widely used during process of the Silesian Greenpower vehicle design. Its versatility enables powertrain testing, wheels and tires tests, thermal analysis and more.

Comprehensive particle characterization of modern gasoline and diesel passenger cars at low ambient temperatures

NASA Astrophysics Data System (ADS)

Mathis, Urs; Mohr, Martin; Forss, Anna-Maria

Particle measurements were performed in the exhaust of five light-duty vehicles (Euro-3) at +23, -7, and -20 °C ambient temperatures. The characterization included measurements of particle number, active surface area, number size distribution, and mass size distribution. We investigated two port-injection spark-ignition (PISI) vehicles, a direct-injection spark-ignition (DISI) vehicle, a compressed ignition (CI) vehicle with diesel particle filter (DPF), and a CI vehicle without DPF. To minimize sampling effects, particles were directly sampled from the tailpipe with a novel porous tube diluter at controlled sampling parameters. The diluted exhaust was split into two branches to measure either all or only non-volatile particles. Effect of ambient temperature was investigated on particle emission for cold and warmed-up engine. For the gasoline vehicles and the CI vehicle with DPF, the main portion of particle emission was found in the first minutes of the driving cycle at cold engine start. The particle emission of the CI vehicle without DPF was hardly affected by cold engine start. For the PISI vehicles, particle number emissions were superproportionally increased in the diameter size range from 0.1 to 0.3 μm during cold start at low ambient temperature. Based on the particle mass size distribution, the DPF removed smaller particles ( dp<0.5μm) more efficiently than larger particles ( dp>0.5μm). No significant effect of ambient temperature was observed when the engine was warmed up. Peak emission of volatile nanoparticles only took place at specific conditions and was poorly repeatable. Nucleation of particles was predominately observed during or after strong acceleration at high speed and during regeneration of the DPF.

Chemical Pollution from Transportation Vehicles

PubMed Central

Starkman, Ernest S.

1969-01-01

Recent publicity on electrically powered vehicles notwithstanding, the gasoline engine will probably be the principal power plant for passenger cars for at least the next decade. Chemical pollutants discharged by the gasoline engine are now under partial control. Motor cars of 1968 and 1969 model discharge only about 30 percent as much carbon monoxide and unburned hydrocarbons as do older models. In theory, carbon monoxide, unburned hydrocarbons and oxides of nitrogen ultimately can be completely removed from gasoline engine exhaust. In order to accomplish this it would be necessary to modify cars to operate satisfactorily on a lean mixture and perhaps to use a catalyst in the exhaust system. Present designs of gas turbines for aircraft and for future projected application to ground vehicles yield pollutants (except for smoke) at levels below those of gasoline engines for a decade to come. It has also been shown possible to eliminate smoke as well as odor from the gas turbine. Thus with proper effort it is feasible to reduce pollution of the atmosphere due to transportation to an acceptable level, even if electrically or alternatively powered vehicles cannot be developed for a decade. PMID:4183827

On the Use of Thermoelectric (TE) Applications Based on Commercial Modules: The Case of TE Generator and TE Cooler

NASA Astrophysics Data System (ADS)

Zorbas, K.; Hatzikraniotis, E.; Paraskevopoulos, K. M.; Kyratsi, Th.

2010-01-01

In recent years, thermoelectricity sees rapidly increasing usages in applications like portable refrigerators, beverage coolers, electronic component coolers etc. when used as Thermoelectric Cooler (TEC), and Thermoelectric Generators (TEG) which make use of the Seebeck effect in semiconductors for the direct conversion of heat into electrical energy and is of particular interest for systems of highest reliability or for waste heat recovery. In this work, we examine the performance of commercially available TEC and TEG. A prototype TEC-refrigerator has been designed, modeled and constructed for in-car applications. Additionally, a TEG was made, in order to measure the gained power and efficiency. Furthermore, a TEG module was tested on a small size car (Toyota Starlet, 1300 cc), in order to measure the gained power and efficiency for various engine loads. With the use of a modeling approach, we evaluated the thermal contact resistances and their influence on the final device efficiency.

Finite element analyses of railroad tank car head impacts

DOT National Transportation Integrated Search

2008-09-24

This paper describes engineering analyses of a railroad : tank car impacted at its head by a rigid punch. This type of : collision, referred to as a head impact, is examined using : dynamic, nonlinear finite element analysis (FEA). : Commercial softw...

Treatment of solid tumors with chimeric antigen receptor-engineered T cells: current status and future prospects.

PubMed

Di, Shengmeng; Li, Zonghai

2016-04-01

Chimeric antigen receptors (CARs) are artificial recombinant receptors that generally combine the antigen-recognition domain of a monoclonal antibody with T cell activation domains. Recent years have seen great success in clinical trials employing CD19-specific CAR-T cell therapy for B cell leukemia. Nevertheless, solid tumors remain a major challenge for CAR-T cell therapy. This review summarizes the preclinical and clinical studies on the treatment of solid tumors with CAR-T cells. The major hurdles for the success of CAR-T and the novel strategies to address these hurdles have also been described and discussed.

Potential of Diesel Engine, Diesel Engine Design Concepts, Control Strategy and Implementation

DOT National Transportation Integrated Search

1980-03-01

Diesel engine design concepts and control system strategies are surveyed with application to passenger cars and light trucks. The objective of the study is to indicate the fuel economy potential of the technologies investigated. The engine design par...

A PEMS study of the emissions of gaseous pollutants and ultrafine particles from gasoline- and diesel-fueled vehicles

NASA Astrophysics Data System (ADS)

Huang, Cheng; Lou, Diming; Hu, Zhiyuan; Feng, Qian; Chen, Yiran; Chen, Changhong; Tan, Piqiang; Yao, Di

2013-10-01

On-road emission measurements of gasoline- and diesel-fueled vehicles were conducted by a portable emission measurement system (PEMS) in Shanghai, China. Horiba OBS 2200 and TSI EEPS 3090 were employed to detect gaseous and ultrafine particle emissions during the tests. The driving-based emission factors of gaseous pollutants and particle mass and number were obtained on various road types. The average NOx emission factors of the diesel bus, diesel car, and gasoline car were 8.86, 0.68, and 0.17 g km-1, all of which were in excess of their emission limits. The particle number emission factors were 7.06 × 1014, 6.08 × 1014, and 1.57 × 1014 km-1, generally higher than the results for similar vehicle types reported in the previous studies. The size distributions of the particles emitted from the diesel vehicles were mainly concentrated in the accumulation mode, while those emitted from the gasoline car were mainly distributed in the nucleation mode. Both gaseous and particle emission rates exhibit significant correlations with the change in vehicle speed and power demand. The lowest emission rates for each vehicle type were produced during idling. The highest emission rates for each vehicle type were generally found in high-VSP bins. The particle number emission rates of the gasoline car show the strongest growth trend with increasing VSP and speed. The particle number emission for the gasoline car increased by 3 orders of magnitude from idling to the highest VSP and driving speed conditions. High engine power caused by aggressive driving or heavy loads is the main contributor to high emissions for these vehicles in real-world situations.

Your Automobile Dollar. Money Management.

ERIC Educational Resources Information Center

Baran, Nancy H., Ed.

This booklet is designed to help first-time car buyers determine if they can or should buy a car and how to get the most from their car-buying dollar. Leasing and renting options also are discussed. The booklet outlines the process of buying a new car, starting with a review of sizes, types, and features. This is followed by a rundown on showroom…

Versatile CAR T-cells for cancer immunotherapy

PubMed Central

Cao, Jingjing; Neelalpu, Sattva S

2018-01-01

Chimeric antigen receptor (CAR) T-cell therapy has been clinically proven to efficiently combat haematological malignancies. However, continuous efforts are required to increase the specificity of CAR T-cells against tumour versus normal tissues, and are essential to improve their antitumour activity in solid tumours. This review summarises the structure of major CAR designs, and strategies to overcome immunosuppressive tumour microenvironment, and reduce toxicities. Along with reviewing currently available techniques that allow the elimination of CAR T-cells after they fulfil their desired functions, using suicide genes, drug elimination strategies are also introduced. A better understanding of the strengths and pitfalls of CAR T-cell therapy will provide fundamental knowledge for the improvement of engineered T-cell therapy in the near future. PMID:29628798

Modeling of wastewater treatment system of car parks from petroleum products

NASA Astrophysics Data System (ADS)

Savdur, S. N.; Stepanova, Yu V.; Kodolova, I. A.; Fesina, E. L.

2018-05-01

The paper discusses the technological complex of wastewater treatment of car parks from petroleum products. Based on the review of the main modeling methods of discrete-continuous chemical and engineering processes, it substantiates expediency of using the theory of Petri nets (PN) for modeling the process of wastewater treatment of car parks from petroleum products. It is proposed to use a modification of Petri nets which is focused on modeling and analysis of discrete-continuous chemical and engineering processes by prioritizing transitions, timing marks in positions and transitions. A model in the form of modified Petri nets (MPN) is designed. A software package to control the process for wastewater treatment is designed by means of SCADA TRACE MODE.

Chimeric antigen receptors: driving immunology towards synthetic biology

PubMed Central

Sadelain, Michel

2017-01-01

The advent of second generation CARs and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naïve, central memory or stem cell-like memory T cells, is being developed for clinical use in a wide range of cancers. Immunological principles are thus finding a new purpose thanks to advances in genetic engineering, synthetic biology and cell manufacturing sciences. PMID:27372731

Characteristics of particulate matter emissions from toy cars with electric motors.

PubMed

Wang, Xiaofei; Williams, Brent J; Biswas, Pratim

2015-04-01

Aerosol emissions from toy cars with electric motors were characterized. Particle emission rates from the toy cars, as high as 7.47×10(7) particles/s, were measured. This emission rate is lower than other indoor sources such as smoking and cooking. The particles emitted from toy cars are generated from spark discharges inside the electric motors that power the toy cars. Size distribution measurements indicated that most particles were below 100 nm in diameter. Copper was the dominant inorganic species in these particles. By deploying aerosol mass spectrometers, high concentrations of particulate organic matter were also detected and characterized in detail. Several organic compounds were identified using a thermal desorption aerosol gas chromatography. The mass size distribution of particulate organic matter was bimodal. The formation mechanism of particulate organic matter from toy cars was elucidated. A possible new source of indoor air pollution, particles from electric motors in toy cars, was identified. This study characterized aerosol emissions from toy cars in detail. Most of these particles have a diameter less than 100 nm. Copper and some organics are the major components of these particles. Conditions that minimize these emissions were determined.

49 CFR Appendix B to Part 232 - Part 232 Prior to May 31, 2001 as Clarified Effective April 10, 2002

Code of Federal Regulations, 2013 CFR

2013-10-01

... and passenger train car brakes. 232.19End of train device. Appendix A to Part 232 Appendix B to Part... power or train brakes, not less than 85 percent of the cars of such train shall have their brakes used and operated by the engineer of the locomotive drawing such train, and all power-brake cars in every...

49 CFR Appendix B to Part 232 - Part 232 Prior to May 31, 2001 as Clarified Effective April 10, 2002

Code of Federal Regulations, 2014 CFR

2014-10-01

... and passenger train car brakes. 232.19End of train device. Appendix A to Part 232 Appendix B to Part... power or train brakes, not less than 85 percent of the cars of such train shall have their brakes used and operated by the engineer of the locomotive drawing such train, and all power-brake cars in every...

49 CFR Appendix B to Part 232 - Part 232 Prior to May 31, 2001 as Clarified Effective April 10, 2002

Code of Federal Regulations, 2012 CFR

2012-10-01

... and passenger train car brakes. 232.19End of train device. Appendix A to Part 232 Appendix B to Part... power or train brakes, not less than 85 percent of the cars of such train shall have their brakes used and operated by the engineer of the locomotive drawing such train, and all power-brake cars in every...

CAR1 deletion by CRISPR/Cas9 reduces formation of ethyl carbamate from ethanol fermentation by Saccharomyces cerevisiae.

PubMed

Chin, Young-Wook; Kang, Woo-Kyung; Jang, Hae Won; Turner, Timothy L; Kim, Hyo Jin

2016-11-01

Enormous advances in genome editing technology have been achieved in recent decades. Among newly born genome editing technologies, CRISPR/Cas9 is considered revolutionary because it is easy to use and highly precise for editing genes in target organisms. CRISPR/Cas9 technology has also been applied for removing unfavorable target genes. In this study, we used CRISPR/Cas9 technology to reduce ethyl carbamate (EC), a potential carcinogen, which was formed during the ethanol fermentation process by yeast. Because the yeast CAR1 gene encoding arginase is the key gene to form ethyl carbamate, we inactivated the yeast CAR1 gene by the complete deletion of the gene or the introduction of a nonsense mutation in the CAR1 locus using CRISPR/Cas9 technology. The engineered yeast strain showed a 98 % decrease in specific activity of arginase while displaying a comparable ethanol fermentation performance. In addition, the CAR1-inactivated mutants showed reduced formation of EC and urea, as compared to the parental yeast strain. Importantly, CRISPR/Cas9 technology enabled generation of a CAR1-inactivated yeast strains without leaving remnants of heterologous genes from a vector, suggesting that the engineered yeast by CRISPR/Cas9 technology might sidestep GMO regulation.

Degradation of car engine base oil by Rhodococcus sp. NDKK48 and Gordonia sp. NDKY76A.

PubMed

Koma, Daisuke; Sakashita, Yuichi; Kubota, Kenzo; Fujii, Yoshihide; Hasumi, Fumihiko; Chung, Seon-Yong; Kubo, Motoki

2003-07-01

Two microorganisms (NDKK48 and NDKY76A) that degrade long-chain cyclic alkanes (c-alkanes) were isolated from soil samples. Strains NDKK48 and NDKY76A were identified as Rhodococcus sp. and Gordonia sp., respectively. Both strains used not only normal alkane (n-alkane) but also c-alkane as a sole carbon and energy source, and the strains degraded more than 27% of car engine base oil (1% addition).

Potential of Spark Ignition Engine, 1979 Summary Source Document

DOT National Transportation Integrated Search

1980-03-01

This report provides an assessment of the potential for spark ignition engines passenger cars and light trucks. The assessment includes: tradeoffs between fuel economy and emissions; improvements in spark ignition engine efficiency; improvements in e...

Crashworthiness Analysis of the UMTA State-of-the-Art Cars

DOT National Transportation Integrated Search

1975-10-01

An engineering assessment of the crashworthiness of the UMTA State-of-the-Art Car (SOAC) has been conducted as part of a program to provide safer transportation to urban rail vehicles. Crash dynamics and crashworthiness methodology based on post-yiel...

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

PubMed Central

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; Cavusoglu, Ahmet H.; Sabharwal, Nina; DeLay, Michael; Driks, Adam; Sahin, Ozgur

2015-01-01

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth's climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. Here, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air–water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on water while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment. PMID:26079632

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

NASA Astrophysics Data System (ADS)

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; Cavusoglu, Ahmet H.; Sabharwal, Nina; Delay, Michael; Driks, Adam; Sahin, Ozgur

2015-06-01

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth's climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. Here, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air-water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on water while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.

A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases.

PubMed

Chen, Xilin; Han, Jianfeng; Chu, Jianhong; Zhang, Lingling; Zhang, Jianying; Chen, Charlie; Chen, Luxi; Wang, Youwei; Wang, Hongwei; Yi, Long; Elder, J Bradley; Wang, Qi-En; He, Xiaoming; Kaur, Balveen; Chiocca, E Antonio; Yu, Jianhua

2016-05-10

Breast cancer brain metastases (BCBMs) are common in patients with metastatic breast cancer and indicate a poor prognosis. These tumors are especially resistant to currently available treatments due to multiple factors. However, the combination of chimeric antigen receptor (CAR)-modified immune cells and oncolytic herpes simplex virus (oHSV) has not yet been explored in this context. In this study, NK-92 cells and primary NK cells were engineered to express the second generation of EGFR-CAR. The efficacies of anti-BCBMs of EGFR-CAR NK cells, oHSV-1, and their combination were tested in vitro and in a breast cancer intracranial mouse model. In vitro, compared with mock-transduced NK-92 cells or primary NK cells, EGFR-CAR-engineered NK-92 cells and primary NK cells displayed enhanced cytotoxicity and IFN-γ production when co-cultured with breast cancer cell lines MDA-MB-231, MDA-MB-468, and MCF-7. oHSV-1 alone was also capable of lysing and destroying these cells. However, a higher cytolytic effect of EGFR-CAR NK-92 cells was observed when combined with oHSV-1 compared to the monotherapies. In the mice intracranially pre-inoculated with EGFR-expressing MDA-MB-231 cells, intratumoral administration of either EGFR-CAR-transduced NK-92 cells or oHSV-1 mitigated tumor growth. Notably, the combination of EGFR-CAR NK-92 cells with oHSV-1 resulted in more efficient killing of MDA-MB-231 tumor cells and significantly longer survival of tumor-bearing mice when compared to monotherapies. These results demonstrate that regional administration of EGFR-CAR NK-92 cells combined with oHSV-1 therapy is a potentially promising strategy to treat BCBMs.

Reduction of MDSCs with all-trans retinoic acid improves CAR therapy efficacy for sarcomas

PubMed Central

Long, Adrienne H.; Highfill, Steven L.; Cui, Yongzhi; Smith, Jillian P.; Walker, Alec J.; Ramakrishna, Sneha; El-Etriby, Rana; Galli, Susana; Tsokos, Maria G.; Orentas, Rimas J.; Mackall, Crystal L.

2016-01-01

Genetically engineered T cells expressing CD19-specific chimeric antigen receptors (CARs) have shown impressive activity against B cell malignancies, and preliminary results suggest that T cells expressing a first generation disialoganglioside (GD2)-specific CAR can also provide clinical benefit in patients with neuroblastoma. We sought to assess the potential of GD2-CAR therapies to treat pediatric sarcomas. We observed that 18/18 (100%) of osteosarcomas, 2/15 (13%) of rhabdomyosarcomas, and 7/35 (20%) of Ewing sarcomas expressed GD2. T cells engineered to express a third generation GD2-CAR incorporating the 14g2a-scFv with the CD28, OX40, and CD3ζ signaling domains (14g2a.CD28.OX40.ζ) mediated efficient and comparable lysis of both GD2+ sarcoma and neuroblastoma cell lines in vitro. However in xenograft models, GD2-CAR T cells had no antitumor effect against GD2+ sarcoma, despite effectively controlling GD2+ neuroblastoma. We observed that pediatric sarcoma xenografts, but not neuroblastoma xenografts, induced large populations of monocytic and granulocytic murine myeloid-derived suppressor cells (MDSCs) that inhibited human CAR T-cell responses in vitro. Treatment of sarcoma-bearing mice with all-trans retinoic acid (ATRA) largely eradicated monocytic MDSCs and diminished the suppressive capacity of granulocytic MDSCs. Combined therapy using GD2-CAR T cells plus ATRA significantly improved antitumor efficacy against sarcoma xenografts. We conclude that retinoids provide a clinically accessible class of agents capable of diminishing the suppressive effects of MDSCs, and that co-administration of retinoids may enhance the efficacy of CAR therapies targeting solid tumors. PMID:27549124

Recognition of Glioma Stem Cells by Genetically Modified T Cells Targeting EGFRvIII and Development of Adoptive Cell Therapy for Glioma

PubMed Central

Johnson, Laura A.; Davis, Jeremy L.; Zheng, Zhili; Woolard, Kevin D.; Reap, Elizabeth A.; Feldman, Steven A.; Chinnasamy, Nachimuthu; Kuan, Chien-Tsun; Song, Hua; Zhang, Wei; Fine, Howard A.; Rosenberg, Steven A.

2012-01-01

Abstract No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies for glioblastoma, we sought to target antigens expressed in glioma stem cells (GSCs). GSCs have multiple properties that make them significantly more representative of glioma tumors than established glioma cell lines. Epidermal growth factor receptor variant III (EGFRvIII) is the result of a novel tumor-specific gene rearrangement that produces a unique protein expressed in approximately 30% of gliomas, and is an ideal target for immunotherapy. Using PCR primers spanning the EGFRvIII-specific deletion, we found that this tumor-specific gene is expressed in three of three GCS lines. Based on the sequence information of seven EGFRvIII-specific monoclonal antibodies (mAbs), we assembled chimeric antigen receptors (CARs) and evaluated the ability of CAR-engineered T cells to recognize EGFRvIII. Three of these anti-EGFRvIII CAR-engineered T cells produced the effector cytokine, interferon-γ, and lysed antigen-expressing target cells. We concentrated development on a CAR produced from human mAb 139, which specifically recognized GSC lines and glioma cell lines expressing mutant EGFRvIII, but not wild-type EGFR and did not recognize any normal human cell tested. Using the 139-based CAR, T cells from glioblastoma patients could be genetically engineered to recognize EGFRvIII-expressing tumors and could be expanded ex vivo to large numbers, and maintained their antitumor activity. Based on these observations, a γ-retroviral vector expressing this EGFRvIII CAR was produced for clinical application. PMID:22780919

Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma.

PubMed

Morgan, Richard A; Johnson, Laura A; Davis, Jeremy L; Zheng, Zhili; Woolard, Kevin D; Reap, Elizabeth A; Feldman, Steven A; Chinnasamy, Nachimuthu; Kuan, Chien-Tsun; Song, Hua; Zhang, Wei; Fine, Howard A; Rosenberg, Steven A

2012-10-01

No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies for glioblastoma, we sought to target antigens expressed in glioma stem cells (GSCs). GSCs have multiple properties that make them significantly more representative of glioma tumors than established glioma cell lines. Epidermal growth factor receptor variant III (EGFRvIII) is the result of a novel tumor-specific gene rearrangement that produces a unique protein expressed in approximately 30% of gliomas, and is an ideal target for immunotherapy. Using PCR primers spanning the EGFRvIII-specific deletion, we found that this tumor-specific gene is expressed in three of three GCS lines. Based on the sequence information of seven EGFRvIII-specific monoclonal antibodies (mAbs), we assembled chimeric antigen receptors (CARs) and evaluated the ability of CAR-engineered T cells to recognize EGFRvIII. Three of these anti-EGFRvIII CAR-engineered T cells produced the effector cytokine, interferon-γ, and lysed antigen-expressing target cells. We concentrated development on a CAR produced from human mAb 139, which specifically recognized GSC lines and glioma cell lines expressing mutant EGFRvIII, but not wild-type EGFR and did not recognize any normal human cell tested. Using the 139-based CAR, T cells from glioblastoma patients could be genetically engineered to recognize EGFRvIII-expressing tumors and could be expanded ex vivo to large numbers, and maintained their antitumor activity. Based on these observations, a γ-retroviral vector expressing this EGFRvIII CAR was produced for clinical application.

The effectiveness of policy on consumer choices for private road passenger transport emissions reductions in six major economies

NASA Astrophysics Data System (ADS)

Mercure, J.-F.; Lam, A.

2015-06-01

The effectiveness of fiscal policy to influence vehicle purchases for emissions reductions in private passenger road transport depends on its ability to incentivise consumers to make choices oriented towards lower emissions vehicles. However, car purchase choices are known to be strongly socially determined, and this sector is highly diverse due to significant socio-economic differences between consumer groups. Here, we present a comprehensive dataset and analysis of the structure of the 2012 private passenger vehicle fleet-years in six major economies across the World (UK, USA, China, India, Japan and Brazil) in terms of price, engine size and emissions distributions. We argue that choices and aggregate elasticities of substitution can be predicted using this data, enabling us to evaluate the effectiveness of potential fiscal and technological change policies on fleet-year emissions reductions. We provide tools to do so based on the distributive structure of prices and emissions in segments of a diverse market, both for conventional as well as unconventional engine technologies. We find that markets differ significantly between nations, and that correlations between engine sizes, emissions and prices exist strongly in some markets and not strongly in others. We furthermore find that markets for unconventional engine technologies have patchy coverages of varying levels. These findings are interpreted in terms of policy strategy.

Characterization of diesel particles: effects of fuel reformulation, exhaust aftertreatment, and engine operation on particle carbon composition and volatility.

PubMed

Alander, Timo J A; Leskinen, Ari P; Raunemaa, Taisto M; Rantanen, Leena

2004-05-01

Diesel exhaust particles are the major constituent of urban carbonaceous aerosol being linked to a large range of adverse environmental and health effects. In this work, the effects of fuel reformulation, oxidation catalyst, engine type, and engine operation parameters on diesel particle emission characteristics were investigated. Particle emissions from an indirect injection (IDI) and a direct injection (DI) engine car operating under steady-state conditions with a reformulated low-sulfur, low-aromatic fuel and a standard-grade fuel were analyzed. Organic (OC) and elemental (EC) carbon fractions of the particles were quantified by a thermal-optical transmission analysis method and particle size distributions measured with a scanning mobility particle sizer (SMPS). The particle volatility characteristics were studied with a configuration that consisted of a thermal desorption unit and an SMPS. In addition, the volatility of size-selected particles was determined with a tandem differential mobility analyzer technique. The reformulated fuel was found to produce 10-40% less particulate carbon mass compared to the standard fuel. On the basis of the carbon analysis, the organic carbon contributed 27-61% to the carbon mass of the IDI engine particle emissions, depending on the fuel and engine operation parameters. The fuel reformulation reduced the particulate organic carbon emissions by 10-55%. In the particles of the DI engine, the organic carbon contributed 14-26% to the total carbon emissions, the advanced engine technology, and the oxidation catalyst, thus reducing the OC/EC ratio of particles considerably. A relatively good consistency between the particulate organic fraction quantified with the thermal optical method and the volatile fraction measured with the thermal desorption unit and SMPS was found.

Vehicle emissions and consumer information in car advertisements.

PubMed

Wilson, Nick; Maher, Anthony; Thomson, George; Keall, Michael

2008-04-29

The advertising of vehicles has been studied from a safety perspective but not in terms of vehicle air pollutants. We aimed to examine the content and trends of greenhouse gas emissions and air pollution-related information, in light passenger vehicle advertisements. Content analysis of the two most popular current affairs magazines in New Zealand for the five year period 2001-2005 was undertaken (n = 514 advertisements). This was supplemented with vehicle data from official websites. The advertisements studied provided some information on fuel type (52%), and engine size (39%); but hardly any provided information on fuel efficiency (3%), or emissions (4%). Over the five-year period the reported engine size increased significantly, while fuel efficiency did not improve. For the vehicles advertised, for which relevant official website data could be obtained, the average "greenhouse rating" for carbon dioxide (CO2) emissions was 5.1, with a range from 0.5 to 8.5 (on a scale with 10 being the best and 0.5 being the most polluting). The average CO2 emissions were 50% higher than the average for cars made by European manufacturers. The average "air pollution" rating for the advertised vehicles was 5.4 (on the same 1-10 scale). The yearly averages for the "greenhouse" or "air pollution" ratings did not change significantly over the five-year period. One advertised hybrid vehicle had a fuel consumption that was under half the average (4.4 versus 9.9 L/100 km), as well as the best "greenhouse" and "air pollution" ratings. To enhance informed consumer choice and to control greenhouse gas and air pollution emissions, governments should introduce regulations on the content of vehicle advertisements and marketing (as started by the European Union). Similar regulations are already in place for the marketing of many other consumer products.

Hybrid: Starting

Science.gov Websites

: gray bar STARTING When the vehicle is started, the gasoline engine "warms up." If necessary assists the gasoline engine when additional power is needed. It also acts as a generator, converting also starts the gasoline engine instantly when needed. Main stage: See through car with battery, engine

Hybrid: Braking

Science.gov Websites

Button Stopped button highlighted subbanner graphic: gray bar STOPPED When the vehicle is stopped engine when additional power is needed. It also acts as a generator, converting energy from the engine or engine instantly when needed. Main stage: See through car with battery, engine, and electric motor

40 CFR 86.1605 - Information to be submitted.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Regulations for Altitude Performance Adjustments for New and In-Use Motor Vehicles and Engines § 86.1605 Information to be..., car line, model year, engine displacement, engine family, and exhaust emission control systems...

40 CFR 86.1605 - Information to be submitted.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Regulations for Altitude Performance Adjustments for New and In-Use Motor Vehicles and Engines § 86.1605 Information to be..., car line, model year, engine displacement, engine family, and exhaust emission control systems...

40 CFR 86.1605 - Information to be submitted.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Regulations for Altitude Performance Adjustments for New and In-Use Motor Vehicles and Engines § 86.1605 Information to be..., car line, model year, engine displacement, engine family, and exhaust emission control systems...

40 CFR 86.1605 - Information to be submitted.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Regulations for Altitude Performance Adjustments for New and In-Use Motor Vehicles and Engines § 86.1605 Information to be..., car line, model year, engine displacement, engine family, and exhaust emission control systems...

CARS applications to combustion diagnostics

NASA Astrophysics Data System (ADS)

Eckbreth, Alan C.

1986-01-01

Attention is given to broadband or multiplex CARS of combustion processes, using pulsed lasers whose intensity is sufficiently great for instantaneous measurement of medium properties. This permits probability density functions to be assembled from a series of single-pulse measurements, on the basis of which the true parameter average and the magnitude of the turbulent fluctuations can be ascertained. CARS measurements have been conducted along these lines in diesel engines, gas turbine combustors, scramjets, and solid rocket propellants.

East Europe Report, Economic and Industrial Affairs, Number 2425.

DTIC Science & Technology

1983-07-21

the proper tightening of turn buckles, and proper quality repairs and maintenance of car traction systems in car depots and railroad plants . The...Improve the quality of planned engine repairs in depots and repair plants . In 1982 a damaged railroad car has had to be uncoupled in...tons) were applied. The tests were conducted on the press of the G. Dimitrov ZhPZ [Railroad Plant ] in Sofia. Table 1 shows the dependence between

Coherent anti-Stokes Raman scattering microscopy driving the future of loaded mesoporous silica imaging.

PubMed

Fussell, Andrew L; Mah, Pei Ting; Offerhaus, Herman; Niemi, Sanna-Mari; Salonen, Jarno; Santos, Hélder A; Strachan, Clare

2014-11-01

This study reports the use of variants of coherent anti-Stokes Raman scattering (CARS) microscopy as a novel method for improved physicochemical characterization of drug-loaded silica particles. Ordered mesoporous silica is a biomaterial that can be loaded to carry a number of biochemicals, including poorly water-soluble drugs, by allowing the incorporation of drug into nanometer-sized pores. In this work, the loading of two poorly water-soluble model drugs, itraconazole and griseofulvin, in MCM-41 silica microparticles is characterized qualitatively, using the novel approach of CARS microscopy, which has advantages over other analytical approaches used to date and is non-destructive, rapid, label free, confocal and has chemical and physical specificity. The study investigated the effect of two solvent-based loading methods, namely immersion and rotary evaporation, and microparticle size on the three-dimensional (3-D) distribution of the two loaded drugs. Additionally, hyperspectral CARS microscopy was used to confirm the amorphous nature of the loaded drugs. Z-stacked CARS microscopy suggested that the drug, but not the loading method or particle size range, affected 3-D drug distribution. Hyperspectral CARS confirmed that the drug loaded in the MCM-41 silica microparticles was in an amorphous form. The results show that CARS microscopy and hyperspectral CARS microscopy can be used to provide further insights into the structural nature of loaded mesoporous silica microparticles as biomaterials. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fine-tuning the CAR spacer improves T-cell potency

PubMed Central

Watanabe, Norihiro; Bajgain, Pradip; Sukumaran, Sujita; Ansari, Salma; Heslop, Helen E.; Rooney, Cliona M.; Brenner, Malcolm K.; Leen, Ann M.; Vera, Juan F.

2016-01-01

ABSTRACT The adoptive transfer of genetically engineered T cells expressing chimeric antigen receptors (CARs) has emerged as a transformative cancer therapy with curative potential, precipitating a wave of preclinical and clinical studies in academic centers and the private sector. Indeed, significant effort has been devoted to improving clinical benefit by incorporating accessory genes/CAR endodomains designed to enhance cellular migration, promote in vivo expansion/persistence or enhance safety by genetic programming to enable the recognition of a tumor signature. However, our efforts centered on exploring whether CAR T-cell potency could be enhanced by modifying pre-existing CAR components. We now demonstrate how molecular refinements to the CAR spacer can impact multiple biological processes including tonic signaling, cell aging, tumor localization, and antigen recognition, culminating in superior in vivo antitumor activity. PMID:28180032

Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T

PubMed Central

Yoon, Dok Hyun; Osborn, Mark J.; Tolar, Jakub; Kim, Chong Jai

2018-01-01

Chimeric antigen receptor (CAR) T cell therapy represents the first U.S. Food and Drug Administration approved gene therapy and these engineered cells function with unprecedented efficacy in the treatment of refractory CD19 positive hematologic malignancies. CAR translation to solid tumors is also being actively investigated; however, efficacy to date has been variable due to tumor-evolved mechanisms that inhibit local immune cell activity. To bolster the potency of CAR-T cells, modulation of the immunosuppressive tumor microenvironment with immune-checkpoint blockade is a promising strategy. The impact of this approach on hematological malignancies is in its infancy, and in this review we discuss CAR-T cells and their synergy with immune-checkpoint blockade. PMID:29364163

Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities

PubMed Central

Xia, An-Liang; Wang, Xiao-Chen; Lu, Yi-Jun; Lu, Xiao-Jie; Sun, Beicheng

2017-01-01

Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells. However, CAR T-cell therapy for solid tumors currently is faced with numerous challenges such as physical barriers, the immunosuppressive tumor microenvironment and the specificity and safety. The clinical results in solid tumors have been much less encouraging, with multiple cases of toxicity and a lack of therapeutic response. In this review, we will discuss the current stats and challenges of CAR-T cell therapy for solid tumors, and propose possibl e solutions and future perspectives. PMID:29163850

[Novel therapy for malignant lymphoma: adoptive immuno-gene therapy using chimeric antigen receptor(CAR)-expressing T lymphocytes].

PubMed

Ozawa, Keiya

2014-03-01

Adoptive T-cell therapy using chimeric antigen receptor (CAR) technology is a novel approach to cancer immuno-gene therapy. CARs are hybrid proteins consisting of target-antigen-specific single-chain antibody fragment fused to intracellular T-cell activation domains (CD28 or CD137/CD3 zeta receptor). CAR-expressing engineered T lymphocytes can directly recognize and kill tumor cells in an HLA independent manner. In the United States, promising results have been obtained in the clinical trials of adoptive immuno-gene therapy using CD19-CAR-T lymphocytes for the treatment of refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL). In this review article, CD19-CAR-T gene therapy for refractory B-cell non-Hodgkin lymphoma is discussed.

Coal cars - the first three hundred years

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

Martin Robert Karig III

2007-12-15

This is the comprehensive study of the freight cars that conveyed coal across broad swaths of land that had been impassible before the invention of the steam engine. This volume traces the history and evolution of coal cars from their earliest use in England to the construction of major railways for the purpose of coal hauling and the end of the steam era on American railroads. In addition to contextualizing coal cars in the annals of industrial history, the book features extensive design specifications and drawings as well as a complete history of the various safety and mechanical innovations employedmore » on these freight cars. It concludes with a photographic essay illustrating the development of the coal car over its first 300 years of use. 608 photos.« less

Analysing the effects of air flow on a formula prototype vehicle to optimize its performance

NASA Astrophysics Data System (ADS)

Rastogi, Nisha; Shetty, Siddhanth; Ashok, B.

2017-11-01

FSAE (Formula Society of Automotive Engineers) is an_engineering design competition which challenges students to design and build their own Formula Style race-car. The race-car is being judged on basis of various criteria namely, design, cost, business and performance. For the race-car to participate in the dynamic events and traverse through different sorts of challenging tracks in the least time possible, the tyres must generate appropriate amount of lateral and longitudinal force. The car must not topple even at high speeds and needs to manoeuvre quickly. To achieve the above-mentioned criterion, there is a need of implementing aerodynamics in the car. The optimum amount of downforce necessary to execute a smooth and rapid active behaviour of our car with maximum achievable performance is to be measured keeping vehicle dynamics into consideration. In this paper, vehicle dynamics and aerodynamics are related to an extent where all the above criterion can be achieved successfully, thereby bringing about a trade-off without any sort of compromises in either of them. The co-ordination between aerodynamics and vehicle dynamics has been depicted with a detailed methodology, accompanied by Computational Fluid Dynamics (CFD) simulations of the wings and the full body of the car using STAR CCM+. Further the results has been discussed properly in the later sections of this paper. With a systematic approach, thoroughly done with several iterations on MATLAB followed by CFD simulations and analysis, the desired performance was accomplished.

Integrating engineering principles into the medico-legal investigation of a rare fatal rollover car accident involving complex dynamics.

PubMed

Grassi, Vincenzo M; Castagnola, Flaminia; Miscusi, Massimo; De-Giorgio, Fabio

2016-09-01

Rollover car accidents can be the result of forceful steering or hitting an obstacle that acts like a ramp. Mortality from this type of car accident is particularly high, especially when occupants are thrown out of the vehicle. We report a case of a 67-year-old man who died after a rollover accident that occurred when he was driving a car equipped with a glass moonroof. He was found inside his car with his safety belt correctly fastened and the roof shattered. At autopsy, a wide avulsion injury of the head was observed, which was associated with an atlanto-axial dislocation and full-thickness fracture of the cervical body and posterior facet joints of the seventh cervical vertebra. The data collected at the scene of the accident were integrated with the autopsy results to yield a forensic engineering reconstruction. This reconstruction elucidated the dynamics of the event and correctly ascribed the lesions observed at autopsy to the phases of the rollover. Afterward, an analysis of the scientific literature concerning rollover crash tests was conducted to understand why the driver sustained fatal injuries even though his seatbelt was properly fastened.

Electromobility concept for racing cars based on lithium-ion batteries and supercapacitors

NASA Astrophysics Data System (ADS)

Frenzel, B.; Kurzweil, P.; Rönnebeck, H.

For the construction of an all-electric race car, all aspects from engineering design over cost estimation up to the road capability are illuminated. From the most promising batteries for electric vehicle propulsion, the state-of-the art and commercial availability of lithium-ion secondary batteries is critically discussed with respect to cycle-life and unfavorable charge-discharge conditions. A market-overview is given with respect to a small electric car. Different combinations of electric motors and a recuperation system have been investigated. Weight aspects of central drive systems were considered and compared with decentralized wheel-hub drives. As a result, a centralized high-speed drive train based on a permanent-magnet synchronous engine with high-energy magnets seems to be superior due to limited space for assembly.

78 FR 78370 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... via the antibody binding fragment of the CAR. By engineering a T-cell to express a CAR that is...) developed in tissue that has been propagated by serial transplantation (rather than cell culture), (b... marrow transplantation, stem cell therapy, tissue regeneration) Competitive Advantages: Labeling markers...

Driving CAR T-cells forward.

PubMed

Jackson, Hollie J; Rafiq, Sarwish; Brentjens, Renier J

2016-06-01

The engineered expression of chimeric antigen receptors (CARs) on the surface of T cells enables the redirection of T-cell specificity. Early clinical trials using CAR T cells for the treatment of patients with cancer showed modest results, but the impressive outcomes of several trials of CD19-targeted CAR T cells in the treatment of patients with B-cell malignancies have generated an increased enthusiasm for this approach. Important lessons have been derived from clinical trials of CD19-specific CAR T cells, and ongoing clinical trials are testing CAR designs directed at novel targets involved in haematological and solid malignancies. In this Review, we discuss these trials and present strategies that can increase the antitumour efficacy and safety of CAR T-cell therapy. Given the fast-moving nature of this field, we only discuss studies with direct translational application currently or soon-to-be tested in the clinical setting.

Driving CAR T-cells forward

PubMed Central

Jackson, Hollie J.; Rafiq, Sarwish; Brentjens, Renier J.

2017-01-01

The engineered expression of chimeric antigen receptors (CARs) on the surface of T cells enables the redirection of T-cell specificity. Early clinical trials using CAR T cells for the treatment of patients with cancer showed modest results, but the impressive outcomes of several trials of CD19-targeted CAR T cells in the treatment of patients with B-cell malignancies have generated an increased enthusiasm for this approach. Important lessons have been derived from clinical trials of CD19-specific CAR T cells, and ongoing clinical trials are testing CAR designs directed at novel targets involved in haematological and solid malignancies. In this Review, we discuss these trials and present strategies that can increase the antitumour efficacy and safety of CAR T-cell therapy. Given the fast-moving nature of this field, we only discuss studies with direct translational application currently or soon-to-be tested in the clinical setting. PMID:27000958

Research on external flow field of a car based on reverse engineering

NASA Astrophysics Data System (ADS)

Hu, Shushan; Liu, Ronge

2018-05-01

In this paper, the point cloud data of FAW-VOLKSWAGEN car body shape is obtained by three coordinate measuring instrument and laser scanning method. The accurate three dimensional model of the car is obtained using CATIA software reverse modelling technology. The car body is gridded, the calculation field and boundary condition type of the car flow field are determined, and the numerical simulation is carried out in Hyper Mesh software. The pressure cloud diagram, velocity vector diagram, air resistance coefficient and lift coefficient of the car are obtained. The calculation results reflect the aerodynamic characteristics of the car's external flow field. The motion of the separation flow on the surface of the vehicle body is well simulated, and the area where the vortex motion is relatively intense has been determined. The results provide a theoretical basis for improving and optimizing the body shape.

Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.

PubMed

Mirzaei, Hamid R; Rodriguez, Analiz; Shepphird, Jennifer; Brown, Christine E; Badie, Behnam

2017-01-01

Adoptive cellular immunotherapy (ACT) employing engineered T lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

Process for Generating Engine Fuel Consumption Map: Ricardo Cooled EGR Boost 24-bar Standard Car Engine Tier 2 Fuel

EPA Pesticide Factsheets

This document summarizes the process followed to utilize the fuel consumption map of a Ricardo modeled engine and vehicle fuel consumption data to generate a full engine fuel consumption map which can be used by EPA's ALPHA vehicle simulations.

Passenger Car Spark Ignition Data Base : Volume 1. Executive Summary.

DOT National Transportation Integrated Search

1979-12-01

Test data was obtained from spark ignition production and preproduction engines at the engine and vehicle level. The engines were applicable for vehicles 2000 to 3000 pounds in weight. The data obtained provided trade-offs between fuel economy, power...

The Physics of NASCAR

NASA Astrophysics Data System (ADS)

Leslie-Pelecky, Diandra

2008-10-01

A group of racecars piloted by the best drivers in NASCAR are turning a corner. Without warning, one of the cars suddenly hits the outside wall. There were no engine failures, no flat tires, and none of the cars touched so what happened? Understanding and being able to apply physics is a necessary (but far from sufficient) condition for winning races.ootnotetextDiandra Leslie-Pelecky, The Physics of NASCAR (Dutton, New York City, 2008). Every competitive race team has a technical staff involved in everything from applied engineering to basic research and development. Aerodynamicists, chemical engineers, statisticians and physicists have become important participants in the high-stakes world of motorsports. Although some drivers have engineering degrees, even those without them have developed a highly intuitive understanding of physics -- you don't keep your job long without a working knowledge of Newton's Laws of Motion. The inherent science in NASCAR is of interest at many levels, from the fan who wants to understand changes made to the car at pit stops to nanomaterials researchers looking for new ways to make racing simultaneously faster and safer. This presentation will introduce some of the fascinating physics of NASCAR and give teachers some ideas to use in the classroom. I'll touch on a range of topics from: how computational fluid dynamics is used to address the aerodynamic changes that challenge the driver by making his car behave differently around every corner; how advanced materials such as energy-absorbing foams have made racing significantly safer; and how nanoparticles may be able to keep engines from overheating despite running at 9500 rpm for three or four hours. Finally, I'll explore NASCAR, its teams and its sponsors are helping address the challenge of getting people interest math and science.

Increase of diesel car raises health risk in spite of recent development in engine technology.

PubMed

Leem, Jong Han; Jang, Young-Kee

2014-01-01

Diesel exhaust particles (DEP) contain elemental carbon, organic compounds including Polyaromatic hydrocarbons (PAHs), metals, and other trace compounds. Diesel exhaust is complex mixture of thousands of chemicals. Over forty air contaminants are recognized as toxicants, such as carcinogens. Most diesel exhaust particles have aerodynamic diameters falling within a range of 0.1 to 0.25 μm. DEP was classified as a definite human carcinogen (group 1) by the International Agency for Research on Cancer at 2012 based on recently sufficient epidemiological evidence for lung cancer. Significant decreases in DEP and other diesel exhaust constituents will not be evident immediately, and outworn diesel car having longer mileage still threatens health of people in spite of recent remarkable development in diesel engine technology. Policy change in South Korea, such as introduction of diesel taxi, may raise health risk of air pollution in metropolitan area with these limitations of diesel engine. To protect people against DEP in South Korea, progressive strategies are needed, including disallowance of diesel taxi, more strict regulation of diesel engine emission, obligatory diesel particulate filter attachment in outworn diesel car, and close monitoring about health effects of DEP.

Biology and clinical application of CAR T cells for B cell malignancies.

PubMed

Davila, Marco L; Sadelain, Michel

2016-07-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma and B cell acute lymphoblastic leukemia, including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors.

Biology and clinical application of CAR T Cells for B cell malignancies

PubMed Central

Davila, Marco L; Sadelain, Michel

2017-01-01

Chimeric antigen receptor (CAR)-modified T cells have generated broad interest in oncology following a series of dramatic clinical successes in patients with chemorefractory B cell malignancies. CAR therapy now appears to be on the cusp of regulatory approval as a cell-based immunotherapy. We review here the T cell biology and cell engineering research that led to the development of second generation CARs, the selection of CD19 as a CAR target, and the preclinical studies in animal models that laid the foundation for clinical trials targeting CD19+ malignancies. We further summarize the status of CD19 CAR clinical therapy for non-Hodgkin lymphoma (NHL) and B cell acute lymphoblastic leukemia (B-ALL), including their efficacy, toxicities (cytokine release syndrome, neurotoxicity and B cell aplasia) and current management in humans. We conclude with an overview of recent pre-clinical advances in CAR design that argues favorably for the advancement of CAR therapy to tackle other hematological malignancies as well as solid tumors. PMID:27262700

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity.

PubMed

Zhang, Congcong; Oberoi, Pranav; Oelsner, Sarah; Waldmann, Anja; Lindner, Aline; Tonn, Torsten; Wels, Winfried S

2017-01-01

Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated. To enhance their therapeutic utility, NK-92 cells have been modified to express chimeric antigen receptors (CARs) composed of a tumor-specific single chain fragment variable antibody fragment fused via hinge and transmembrane regions to intracellular signaling moieties such as CD3ζ or composite signaling domains containing a costimulatory protein together with CD3ζ. CAR-mediated activation of NK cells then bypasses inhibitory signals and overcomes NK resistance of tumor cells. In contrast to primary NK cells, CAR-engineered NK-92 cell lines suitable for clinical development can be established from molecularly and functionally well-characterized single cell clones following good manufacturing practice-compliant procedures. In preclinical in vitro and in vivo models, potent antitumor activity of NK-92 variants targeted to differentiation antigens expressed by hematologic malignancies, and overexpressed or mutated self-antigens associated with solid tumors has been found, encouraging further development of CAR-engineered NK-92 cells. Importantly, in syngeneic mouse tumor models, induction of endogenous antitumor immunity after treatment with CAR-expressing NK-92 cells has been demonstrated, resulting in cures and long-lasting immunological memory protecting against tumor rechallenge at distant sites. Here, we summarize the current status and future prospects of CAR-engineered NK-92 cells as off-the-shelf cellular therapeutics, with special emphasis on ErbB2 (HER2)-specific NK-92 cells that are approaching clinical application.

Chimeric Antigen Receptor-Engineered NK-92 Cells: An Off-the-Shelf Cellular Therapeutic for Targeted Elimination of Cancer Cells and Induction of Protective Antitumor Immunity

PubMed Central

Zhang, Congcong; Oberoi, Pranav; Oelsner, Sarah; Waldmann, Anja; Lindner, Aline; Tonn, Torsten; Wels, Winfried S.

2017-01-01

Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated. To enhance their therapeutic utility, NK-92 cells have been modified to express chimeric antigen receptors (CARs) composed of a tumor-specific single chain fragment variable antibody fragment fused via hinge and transmembrane regions to intracellular signaling moieties such as CD3ζ or composite signaling domains containing a costimulatory protein together with CD3ζ. CAR-mediated activation of NK cells then bypasses inhibitory signals and overcomes NK resistance of tumor cells. In contrast to primary NK cells, CAR-engineered NK-92 cell lines suitable for clinical development can be established from molecularly and functionally well-characterized single cell clones following good manufacturing practice-compliant procedures. In preclinical in vitro and in vivo models, potent antitumor activity of NK-92 variants targeted to differentiation antigens expressed by hematologic malignancies, and overexpressed or mutated self-antigens associated with solid tumors has been found, encouraging further development of CAR-engineered NK-92 cells. Importantly, in syngeneic mouse tumor models, induction of endogenous antitumor immunity after treatment with CAR-expressing NK-92 cells has been demonstrated, resulting in cures and long-lasting immunological memory protecting against tumor rechallenge at distant sites. Here, we summarize the current status and future prospects of CAR-engineered NK-92 cells as off-the-shelf cellular therapeutics, with special emphasis on ErbB2 (HER2)-specific NK-92 cells that are approaching clinical application. PMID:28572802

Engineering Tests for Energy Storage Cars at the Transportation Test Center : Volume 3. Noise Tests.

DOT National Transportation Integrated Search

1977-05-01

The primary purpose of the tests documented herein was to demonstrate the principles and feasibility of an energy storage type propulsion system, and its adaptability to an existing car design. The test program comprised four phases of tests on two N...

40 CFR 86.1 - Reference materials.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Passenger Cars, Light-Duty Trucks, and Medium-Duty Vehicles and Engines (OBD-II), IBR approved for § 86.1806... Requirements for 2004 and Subsequent Model-Year Passenger Cars, Light-Duty Trucks, and Medium-Duty Vehicles and....1311-94. (2) SAE J1634, Electric Vehicle Energy Consumption and Range Test Procedure, Cancelled October...

Why do we power our cars with gas? NBC Chicago

ScienceCinema

None

2018-02-06

Why can we only power our cars with gas? NBC-Chicago tackles this question with a trip to Argonne National Lab, where work on the Omnivorous Engine (runs on any blend of ethanol, butanol, and gasoline) and electric vehicles continues. A segment from NBC-Chicago's "Good Question" series.

Final Rule for Control of Air Pollution From New Motor Vehicles and New Motor Vehicle Engines: State Commitments to National Low Emission Vehicle Program

EPA Pesticide Factsheets

The Environmental Protection Agency (EPA) is issuing a final rule representing the next step in establishing a voluntary nationwide program to make new cars significantly cleaner burning than today’s current cars.

Engineering Tests for Energy Storage Cars at the Transportation Test Center : Volume 1. Program Description and Test Summary.

DOT National Transportation Integrated Search

1977-05-01

The primary purpose of the tests documented herein was to demonstrate the principles and feasibility of an energy storage type propulsion system, and its adaptability to an existing car design. The test program comprised four phases of tests on two N...

Evaluation of semi-empirical analyses for tank car puncture velocity, part II : correlations with engineering analyses

DOT National Transportation Integrated Search

2001-11-01

This report is the second in a series focusing on methods to determine the puncture velocity of railroad tank car shells. In this context, puncture velocity refers to the impact velocity at which a coupler will completely pierce the shell and punctur...

Evaluation of semi-empirical analyses for railroad tank car puncture velocity, part 2 : correlations with engineering analysis

DOT National Transportation Integrated Search

2001-11-01

This report is the second in a series focusing on methods to determine the puncture velocity of railroad tank car shells. In this : context, puncture velocity refers to the impact velocity at which a coupler will completely pierce the shell and punct...

Civil Engineering in Primary Schools

ERIC Educational Resources Information Center

Brown, Martin; Strong, Alan

2010-01-01

For many children of primary school age, an engineer is the man who comes to service the central heating system or who fixes the family car when it breaks down. Most have never met a "real" professional engineer, and have no idea of what is involved in the exciting world of engineering. Most assume that engineers are men. To try to…

Passenger Car Spark Ignition Data Base : Volume 2. Discussion and Results.

DOT National Transportation Integrated Search

1979-12-01

Test data was obtained from spark ignition production and preproduction engines at the engine and vehicle level. The engines were applicable for vehicles 2000 to 3000 pounds in weight. The data obtained provided trade-offs between fuel economy, power...

Passenger Car Spark Ignition Data Base : Volume 3. Miscellaneous Data. Part 1.

DOT National Transportation Integrated Search

1979-12-01

Test data was obtained from spark ignition production and preproduction engines at the engine and vehicle level. The engines were applicable for vehicles 2000 to 3000 pounds in weight. The data obtained provided trade-offs between fuel economy, power...

Passenger Car Spark Ignition Data Base : Volume 3. Miscellaneous Data. Part 2.

DOT National Transportation Integrated Search

1979-12-01

Test data was obtained from spark ignition production and preproduction engines at the engine and vehicle level. The engines were applicable for vehicles 2000 to 3000 pounds in weight. The data obtained provided trade-offs between fuel economy, power...

[Research on NEDC ultrafine particle emission characters of a port fuel injection gasoline car].

PubMed

Hu, Zhi-Yuan; Li, Jin; Tan, Pi-Qiang; Lou, Di-Ming

2012-12-01

A Santana gasoline car with multi-port fuel injection (PFI) system was used as the research prototype and an engine exhaust particle sizer (EEPS) was employed to investigate the exhaust ultrafine particle number and size distribution characters of the tested vehicle in new European driving cycle (NEDC). The tested results showed that the vehicle's nuclear particle number, accumulation particle number, as well as the total particle number emission increased when the car drove in accelerated passage, and the vehicle's particle number emission was high during the first 40 seconds after test started and when the speed was over 90 km x h(-1) in extra urban driving cycle (EUDC) in NEDC. The ultrafine particle distribution of the whole NEDC showed a single peak logarithmic distribution, with diameters of the peak particle number emission ranging from 10 nm to 30 nm, and the geometric mean diameter was 24 nm. The ultrafine particle distribution of the urban driving cycle named by the economic commission for Europe (ECE) e. g. ECE I, ECE II - IV, the extra urban driving cycle e. g. EUDC, and the idling, constant speed, acceleration, deceleration operation conditions of NEDC all showed a single peak logarithmic distribution, also with particle diameters of the peak particle number emission ranging from 10 nm to 30 nm, and the geometric mean diameters of different driving cycle and different driving mode were from 14 nm to 42 nm. Therefore, the ultrafine particle emissions of the tested PFI gasoline car were mainly consisted of nuclear mode particles with a diameter of less than 50 nm.

Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma.

PubMed

Krishnamurthy, Janani; Rabinovich, Brian A; Mi, Tiejuan; Switzer, Kirsten C; Olivares, Simon; Maiti, Sourindra N; Plummer, Joshua B; Singh, Harjeet; Kumaresan, Pappanaicken R; Huls, Helen M; Wang-Johanning, Feng; Cooper, Laurence J N

2015-07-15

The human endogenous retrovirus (HERV-K) envelope (env) protein is a tumor-associated antigen (TAA) expressed on melanoma but not normal cells. This study was designed to engineer a chimeric antigen receptor (CAR) on T-cell surface, such that they target tumors in advanced stages of melanoma. Expression of HERV-K protein was analyzed in 220 melanoma samples (with various stages of disease) and 139 normal organ donor tissues using immunohistochemical (IHC) analysis. HERV-K env-specific CAR derived from mouse monoclonal antibody was introduced into T cells using the transposon-based Sleeping Beauty (SB) system. HERV-K env-specific CAR(+) T cells were expanded ex vivo on activating and propagating cells (AaPC) and characterized for CAR expression and specificity. This includes evaluating the HERV-K-specific CAR(+) T cells for their ability to kill A375-SM metastasized tumors in a mouse xenograft model. We detected HERV-K env protein on melanoma but not in normal tissues. After electroporation of T cells and selection on HERV-K(+) AaPC, more than 95% of genetically modified T cells expressed the CAR with an effector memory phenotype and lysed HERV-K env(+) tumor targets in an antigen-specific manner. Even though there is apparent shedding of this TAA from tumor cells that can be recognized by HERV-K env-specific CAR(+) T cells, we observed a significant antitumor effect. Adoptive cellular immunotherapy with HERV-K env-specific CAR(+) T cells represents a clinically appealing treatment strategy for advanced-stage melanoma and provides an approach for targeting this TAA on other solid tumors. ©2015 American Association for Cancer Research.

The pharmacology of second-generation chimeric antigen receptors.

PubMed

van der Stegen, Sjoukje J C; Hamieh, Mohamad; Sadelain, Michel

2015-07-01

Second-generation chimeric antigen receptors (CARs) retarget and reprogramme T cells to augment their antitumour efficacy. The combined activating and co-stimulatory domains incorporated in these CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19-targeted CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Both have shown remarkable complete remission rates in patients with refractory B cell malignancies. Recent data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, whereas 4-1BB-based CARs induce a more progressive T cell accumulation that may compensate for less immediate potency. These distinct kinetic features can be exploited to further develop CAR-based T cell therapies for a variety of cancers. A new field of immunopharmacology is emerging.

Chimeric Antigen Receptor (CAR) T Cell Therapy for Malignant Pleural Mesothelioma (MPM)

PubMed Central

Klampatsa, Astero; Haas, Andrew R.; Moon, Edmund K.; Albelda, Steven M.

2017-01-01

Cancer immunotherapy has now become a recognized approach to treating cancers. In addition to checkpoint blockade, adoptive T cell transfer (ACT) using chimeric antigen receptors (CARs) has shown impressive clinical outcomes in leukemias and is now being explored in solid tumors. CARs are engineered receptors, stably or transiently transduced into T cells, that aim to enhance T cell effector function by recognizing and binding to a specific tumor-associated antigen. In this review, we provide a summary of CAR T cell preclinical studies and clinical trials for malignant pleural mesothelioma (MPM), a rare, locally invasive pleural cancer with poor prognosis. We list other attractive potential targets for CAR T cell therapy for MPM, and discuss augmentation strategies of CAR T cell therapy with other forms of immunotherapy in this disease. PMID:28862644

How do CARs work?

PubMed Central

Davila, Marco L.; Brentjens, Renier; Wang, Xiuyan; Rivière, Isabelle; Sadelain, Michel

2012-01-01

Second-generation chimeric antigen receptors (CARs) are powerful tools to redirect antigen-specific T cells independently of HLA-restriction. Recent clinical studies evaluating CD19-targeted T cells in patients with B-cell malignancies demonstrate the potency of CAR-engineered T cells. With results from 28 subjects enrolled by five centers conducting studies in patients with chronic lymphocytic leukemia (CLL) or lymphoma, some insights into the parameters that determine T-cell function and clinical outcome of CAR-based approaches are emerging. These parameters involve CAR design, T-cell production methods, conditioning chemotherapy as well as patient selection. Here, we discuss the potential relevance of these findings and in particular the interplay between the adoptive transfer of T cells and pre-transfer patient conditioning. PMID:23264903

Educational Horsepower: Engine Design and Construction in the Classroom

ERIC Educational Resources Information Center

Christensen, Brad

2007-01-01

Engines, in their many forms and functions, have had a tremendous impact on society and the environment. It is hard for the contemporary student to fathom a world without trains, cars, trucks, powerboats, and airplanes. With the fascination, history, impacts, and importance of engines to modern society, it is only natural that engine technology…

Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation

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

Kamata, Masakazu, E-mail: masa3k@ucla.edu; Kim, Patrick Y.; Ng, Hwee L.

Chimeric antigen receptors (CARs) are artificially engineered receptors that confer a desired specificity to immune effector T cells. As an HIV-1-specific CAR, CD4ζ CAR has been extensively tested in vitro as well as in clinical trials. T cells modified with this CAR mediated highly potent anti-HIV-1 activities in vitro and were well-tolerated in vivo, but exerted limited effects on viral load and reservoir size due to poor survival and/or functionality of the transduced cells in patients. We hypothesize that ectopic expression of CD4ζ on CD8{sup +} T cells renders them susceptible to HIV-1 infection, resulting in poor survival of those cells. To testmore » this possibility, highly purified CD8{sup +} T cells were genetically modified with a CD4ζ-encoding lentiviral vector and infected with HIV-1. CD8{sup +} T cells were vulnerable to HIV-1 infection upon expression of CD4ζ as evidenced by elevated levels of p24{sup Gag} in cells and culture supernatants. Concurrently, the number of CD4ζ-modified CD8{sup +} T cells was reduced relative to control cells upon HIV-1 infection. To protect these cells from HIV-1 infection, we co-expressed two anti-HIV-1 shRNAs previously developed by our group together with CD4ζ. This combination vector was able to suppress HIV-1 infection without impairing HIV-1-dependent effector activities of CD4ζ. In addition, the number of CD4ζ-modified CD8{sup +} T cells maintained similar levels to that of the control even under HIV-1 infection. These results suggest that protecting CD4ζ-modified CD8{sup +} T cells from HIV-1 infection is required for prolonged HIV-1-specific immune surveillance. - Highlights: • Ectopic expression of CD4ζ CAR in CD8{sup +} T cells renders them susceptible to HIV-1 infection. • Co-expression of two anti-HIV-1 shRNAs protects CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection. • Protecting CD4ζ CAR-modified CD8{sup +} T cells from HIV-1 infection suppresses its cytopathic effect.« less

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

DOE PAGES

Chen, Xi; Goodnight, Davis; Gao, Zhenghan; ...

2015-06-16

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth’s climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. In this work, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air–water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on watermore » while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.« less

Scaling up nanoscale water-driven energy conversion into evaporation-driven engines and generators

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

Chen, Xi; Goodnight, Davis; Gao, Zhenghan

Evaporation is a ubiquitous phenomenon in the natural environment and a dominant form of energy transfer in the Earth’s climate. Engineered systems rarely, if ever, use evaporation as a source of energy, despite myriad examples of such adaptations in the biological world. In this work, we report evaporation-driven engines that can power common tasks like locomotion and electricity generation. These engines start and run autonomously when placed at air–water interfaces. They generate rotary and piston-like linear motion using specially designed, biologically based artificial muscles responsive to moisture fluctuations. Using these engines, we demonstrate an electricity generator that rests on watermore » while harvesting its evaporation to power a light source, and a miniature car (weighing 0.1 kg) that moves forward as the water in the car evaporates. Evaporation-driven engines may find applications in powering robotic systems, sensors, devices and machinery that function in the natural environment.« less

Engineering of carboligase activity reaction in Candida glabrata for acetoin production.

PubMed

Li, Shubo; Xu, Nan; Liu, Liming; Chen, Jian

2014-03-01

Utilization of Candida glabrata overproducing pyruvate is a promising strategy for high-level acetoin production. Based on the known regulatory and metabolic information, acetaldehyde and thiamine were fed to identify the key nodes of carboligase activity reaction (CAR) pathway and provide a direction for engineering C. glabrata. Accordingly, alcohol dehydrogenase, acetaldehyde dehydrogenase, pyruvate decarboxylase, and butanediol dehydrogenase were selected to be manipulated for strengthening the CAR pathway. Following the rational metabolic engineering, the engineered strain exhibited increased acetoin biosynthesis (2.24 g/L). In addition, through in silico simulation and redox balance analysis, NADH was identified as the key factor restricting higher acetoin production. Correspondingly, after introduction of NADH oxidase, the final acetoin production was further increased to 7.33 g/L. By combining the rational metabolic engineering and cofactor engineering, the acetoin-producing C. glabrata was improved stepwise, opening a novel pathway for rational development of microorganisms for bioproduction. Copyright © 2013. Published by Elsevier Inc.

The influence of number and values of ratios in stepped gearbox on mileage fuel consumption in NEDC test and real traffic

NASA Astrophysics Data System (ADS)

Bera, P.; Wędrychowicz, D.

2016-09-01

The article presents the influence of number and values of ratios in stepped gearbox on mileage fuel consumption in a city passenger car. The simulations were conducted for a particular vehicle characterized by its mass, body shape, size of tires and equipped with a combustion engine for which the characteristic of fuel consumption in dynamic states was already designated on the basis of engine test bed measurements. Several designs of transmission with different number of gears and their ratios were used in virtual simulations of road traffic, particularly in the NEDC test, to calculate mileage fuel consumption. This allows for a quantitative assessment of transmission parameters in terms of both vehicle economy and dynamic properties. Also, based on obtained results, recommendations for the selection of a particular vehicle for a specific type of exploitation have been formulated.

Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells

PubMed Central

Berger, Carolina; Sommermeyer, Daniel; Hudecek, Michael; Berger, Michael; Balakrishnan, Ashwini; Paszkiewicz, Paulina J.; Kosasih, Paula L.; Rader, Christoph; Riddell, Stanley R.

2014-01-01

Genetic engineering of T cells for adoptive transfer by introducing a tumor-targeting chimeric antigen receptor (CAR) is a new approach to cancer immunotherapy. A challenge for the field is to define cell surface molecules that are both preferentially expressed on tumor cells and can be safely targeted with T cells. The orphan tyrosine kinase receptor ROR1 is a candidate target for T-cell therapy with CAR-modified T cells (CAR-T cells) since it is expressed on the surface of many lymphatic and epithelial malignancies and has a putative role in tumor cell survival. The cell surface isoform of ROR1 is expressed in embryogenesis but absent in adult tissues except for B-cell precursors, and low levels of transcripts in adipocytes, pancreas, and lung. ROR1 is highly conserved between humans and macaques and has a similar pattern of tissue expression. To determine if low-level ROR1-expression on normal cells would result in toxicity or adversely affect CAR-T cell survival and/or function, we adoptively transferred autologous ROR1 CAR-T cells into nonhuman primates. ROR1 CAR-T cells did not cause overt toxicity to normal organs and accumulated in bone marrow and lymph node sites where ROR1-positive B cells were present. The findings support the clinical evaluation of ROR1 CAR-T cells for ROR1+ malignancies and demonstrate the utility of nonhuman primates for evaluating the safety of immunotherapy with engineered T cells specific for tumor-associated molecules that are homologous between humans and nonhuman primates. PMID:25355068

Switching CAR T cells on and off: a novel modular platform for retargeting of T cells to AML blasts

PubMed Central

Cartellieri, M; Feldmann, A; Koristka, S; Arndt, C; Loff, S; Ehninger, A; von Bonin, M; Bejestani, E P; Ehninger, G; Bachmann, M P

2016-01-01

The adoptive transfer of CD19-specific chimeric antigen receptor engineered T cells (CAR T cells) resulted in encouraging clinical trials in indolent B-cell malignancies. However, they also show the limitations of this fascinating technology: CAR T cells can lead to even life-threatening off-tumor, on-target side effects if CAR T cells crossreact with healthy tissues. Here, we describe a novel modular universal CAR platform technology termed UniCAR that reduces the risk of on-target side effects by a rapid and reversible control of CAR T-cell reactivity. The UniCAR system consists of two components: (1) a CAR for an inert manipulation of T cells and (2) specific targeting modules (TMs) for redirecting UniCAR T cells in an individualized time- and target-dependent manner. UniCAR T cells can be armed against different tumor targets simply by replacement of the respective TM for (1) targeting more than one antigen simultaneously or subsequently to enhance efficacy and (2) reducing the risk for development of antigen-loss tumor variants under treatment. Here we provide ‘proof of concept' for retargeting of UniCAR T cells to CD33- and/or CD123-positive acute myeloid leukemia blasts in vitro and in vivo. PMID:27518241

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor.

PubMed

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G; Scholler, John; Levine, Bruce L; Albelda, Steven M; June, Carl H

2010-11-15

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor-reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CAR). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high-level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week after electroporation. Multiple injections of RNA CAR-electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(-/-) mice. Dramatic tumor reduction also occurred when the preexisting intraperitoneal human-derived tumors, which had been growing in vivo for >50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes showing that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA-engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. Copyright © 2010 AACR.

Multiple injections of electroporated autologous T cells expressing a chimeric antigen receptor mediate regression of human disseminated tumor

PubMed Central

Zhao, Yangbing; Moon, Edmund; Carpenito, Carmine; Paulos, Chrystal M.; Liu, Xiaojun; Brennan, Andrea L; Chew, Anne; Carroll, Richard G.; Scholler, John; Levine, Bruce L.; Albelda, Steven M.; June, Carl H.

2010-01-01

Redirecting T lymphocyte antigen specificity by gene transfer can provide large numbers of tumor reactive T lymphocytes for adoptive immunotherapy. However, safety concerns associated with viral vector production have limited clinical application of T cells expressing chimeric antigen receptors (CARs). T lymphocytes can be gene modified by RNA electroporation without integration-associated safety concerns. To establish a safe platform for adoptive immunotherapy, we first optimized the vector backbone for RNA in vitro transcription to achieve high level transgene expression. CAR expression and function of RNA-electroporated T cells could be detected up to a week post electroporation. Multiple injections of RNA CAR electroporated T cells mediated regression of large vascularized flank mesothelioma tumors in NOD/scid/γc(−/−) mice. Dramatic tumor reduction also occurred when the pre-existing intraperitoneal human-derived tumors, that had been growing in vivo for over 50 days, were treated by multiple injections of autologous human T cells electroporated with anti-mesothelin CAR mRNA. This is the first report using matched patient tumor and lymphocytes demonstrating that autologous T cells from cancer patients can be engineered to provide an effective therapy for a disseminated tumor in a robust preclinical model. Multiple injections of RNA engineered T cells are a novel approach for adoptive cell transfer, providing flexible platform for the treatment of cancer that may complement the use of retroviral and lentiviral engineered T cells. This approach may increase the therapeutic index of T cells engineered to express powerful activation domains without the associated safety concerns of integrating viral vectors. PMID:20926399

A comparative study of the elemental composition of the exhaust emissions of cars powered by liquefied petroleum gas and unleaded petrol

NASA Astrophysics Data System (ADS)

Lim, McKenzie C. H.; Ayoko, Godwin A.; Morawska, Lidia; Ristovski, Zoran D.; Jayaratne, E. Rohan; Kokot, Serge

Elements emitted from the exhausts of new Ford Falcon Forte cars powered by unleaded petrol (ULP) and liquefied petroleum gas (LPG) were measured on a chassis dynamometer. The measurements were carried out in February, June and August 2001, and at two steady state driving conditions (60 and 80 km h -1). Thirty seven elements were quantified in the exhaust samples by inductively coupled plasma mass spectrometry (ICPMS). The total emission factors of the elements from the exhausts of ULP cars were higher than those of LPG cars at both engine speeds even though high variability in the exhaust emissions from different cars was noted. The effect of the operating conditions such as mileage of the cars, engine speed, fuel and lubricating oil compositions on the emissions was studied. To investigate the effects of these conditions, multivariate data analysis methods were employed including exploratory principal component analysis (PCA), and the multi-criteria decision making methods (MCDM), preference ranking organization method for enrichment evaluation (PROMETHEE) and geometrical analysis for interactive aid (GAIA), for ranking the cars on the basis of the emission factors of the elements. PCA biplot of the complete data matrix showed a clear discrimination of the February, June and August emission test results. In addition, (i) platinum group elements (PGE) emissions were separated from each other in the three different clusters viz. Pt with February, Pd with June and Rh with August; (ii) the motor oil related elements, Zn and P, were particularly associated with the June and August tests (these vectors were also grouped with V, Al and Cu); and (iii) highest emissions of most major elements were associated with the August test after the cars have recorded their highest mileage. Extensive analysis with the aid of the MCDM ranking methods demonstrated clearly that cars powered by LPG outperform those powered by ULP. In general, cars tested in June perform better than those tested in August, which suggested that mileage was the key criterion of car performance on the basis of elemental emission factors.

The temperature dependence of inelastic light scattering from small particles for use in combustion diagnostic instrumentation

NASA Technical Reports Server (NTRS)

Cloud, Stanley D.

1987-01-01

A computer calculation of the expected angular distribution of coherent anti-Stokes Raman scattering (CARS) from micrometer size polystyrene spheres based on a Mie-type model, and a pilot experiment to test the feasibility of measuring CARS angular distributions from micrometer size polystyrene spheres by simply suspending them in water are discussed. The computer calculations predict a very interesting structure in the angular distributions that depends strongly on the size and relative refractive index of the spheres.

78 FR 41853 - Safety Advisory Guidance: Heating Rail Tank Cars To Prepare Hazardous Material for Unloading or...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-12

... rail tank car due to chemical self-reaction and expansion of the toluene diisocyanate matter wastes. On...: Cheryl West Freeman, Division of Engineering and Research, Pipeline and Hazardous Materials Safety... catastrophically ruptured at a transfer station at the BASF Corporation chemical facility in Freeport, Texas. The...

Estimating GHG Reduction from Combinations of Current Best-Available and Future Powertrain and Vehicle Technologies for a Midsized Car Using EPA’s ALPHA Model (SAE 2016-01-0910)

EPA Science Inventory

EPA identified the best, or most efficient, engines, transmissions and vehicle technologies, and then used ALPHA to predict the GHG emissions would be from a midsized car incorporating the best combination of these technologies.

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2012 CFR

2012-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2011 CFR

2011-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2014 CFR

2014-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

View from northeast of Car Shop showing east wall and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

View from northeast of Car Shop showing east wall and north end; also a portion of (east facade) of Foundry building. Structure between houses the boilers and stationary steam engine - East Broad Top Railroad & Coal Company, State Route 994, West of U.S. Route 522, Rockhill Furnace, Huntingdon County, PA

49 CFR 571.102 - Standard No. 102; Transmission shift position sequence, starter interlock, and transmission...

Code of Federal Regulations, 2013 CFR

2013-10-01

... hour). S2. Application. This standard applies to passenger cars, multi-purpose passenger vehicles... positions on passenger cars. A neutral position shall be located between forward drive and reverse drive... ratio, one forward drive position shall provide a greater degree of engine braking than the highest...

Engineering Tests for Energy Storage Cars at the Transportation Test Center : Volume 2. Performance, Power Consumption and Radio Frequency Interference Tests

DOT National Transportation Integrated Search

1977-05-01

The primary purpose of the tests documented herein was to demonstrate the principles and feasibility of an energy-storage-type propulsion system, and its adaptability to an existing car design. The test program comprised four phases of tests on two N...

Race to improve student understanding of uncertainty: Using LEGO race cars in the physics lab

NASA Astrophysics Data System (ADS)

Parappilly, Maria; Hassam, Christopher; Woodman, Richard J.

2018-01-01

Laboratories using LEGO race cars were developed for students in an introductory physics topic with a high early drop-out rate. In a 2014 pilot study, the labs were offered to improve students' confidence with experiments and laboratory skills, especially uncertainty propagation. This intervention was extended into the intro level physics topic the next year, for comparison and evaluation. Considering the pilot study, we subsequently adapted the delivery of the LEGO labs for a large Engineering Mechanics cohort. A qualitative survey of the students was taken to gain insight into their perception of the incorporation of LEGO race cars into physics labs. For Engineering, the findings show that LEGO physics was instrumental in teaching students the measurement and uncertainty, improving their lab reporting skills, and was a key factor in reducing the early attrition rate. This paper briefly recalls the results of the pilot study, and how variations in the delivery yielded better learning outcomes. A novel method is proposed for how LEGO race cars in a physics lab can help students increase their understanding of uncertainty and motivate them towards physics practicals.

40 CFR 86.085-37 - Production vehicles and engines.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... (d) The following definitions apply to this section: (1) Model type means a unique combination of car..., inertia weight, and transmission class. (3) Vehicle configuration means a unique combination of basic engine, engine code, inertia weight, transmission configuration, and axle ratio within a base level. [48...

40 CFR 86.085-37 - Production vehicles and engines.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... (d) The following definitions apply to this section: (1) Model type means a unique combination of car..., inertia weight, and transmission class. (3) Vehicle configuration means a unique combination of basic engine, engine code, inertia weight, transmission configuration, and axle ratio within a base level. [48...

Treating Cancer with Genetically Engineered T Cells

PubMed Central

Park, Tristen S.; Rosenberg, Steven A.; Morgan, Richard A.

2011-01-01

Administration of ex-vivo cultured, naturally occurring tumor-infiltrating lymphocytes (TILs) have been shown to mediate durable regression of melanoma tumors. However, the generation of TIL is not possible in all patients and there has been limited success in generating TIL in other cancers. Advances in genetic engineering have overcome these limitations by introducing tumor-antigen-targeting receptors into human T lymphocytes. Physicians can now genetically engineer lymphocytes to express highly active T-cell receptors (TCRs) or chimeric antigen receptors (CARs) targeting a variety of tumor antigens expressed in cancer patients. In this review we discuss the development of TCR and CAR gene transfer technology and the expansion of these therapies into different cancers with the recent demonstration of the clinical efficacy of these treatments. PMID:21663987

Vibration measurements of automobile catalyst

NASA Astrophysics Data System (ADS)

Aatola, Seppo

1994-09-01

Vibration of catalyst cell, which is inside the casing of the catalyst, is difficult to measure with usual measuring instrumentation. When catalyst is in use, there is hot exhaust gas flow though the catalyst cell and temperature of the cell is approximately +900 degree(s)C. Therefore non-contact Laser- Doppler-Vibrometer was used to measure vibration velocity of the catalyst cell. The laser beam was directed towards the cell through pipe which was put through and welded to the casing of the catalyst. The outer end of the pipe was screw down with a tempered class to prevent exhaust gas flow from the pipe. The inner end of the pipe was open and few millimeters away from the measuring point. Catalyst was attached to the engine with two ways, rigidly close to the engine and flexible under the engine. The engine was running in test bench under controlled conditions. Vibration measurements were carried out during constant running speeds of the engine. Vibration signals were captured and analyzed with FFT-analyzer. Vibration of catalyst cell was strongest at running speed of 5000 rpm, from 10 to 20 g (1 g equals 9.81 ms-2), when catalyst was attached rigidly close to the engine. At running speed of 3000 rpm, vibration of catalyst cell was from 2 to 3 g in most cases, when catalyst was attached either rigidly or flexible to the engine. It is estimated that in real life, i.e. when catalyst is attached to car with same engine, vibration of catalyst cell at running speed of 5000 rpm is somewhere between 1 and 10 g. At running speed of 3000 rpm, which may be more often used when driving car (car speed approximately 100 kmh-1), vibration of catalyst cell is probably few g's.

Economic and environmental evaluation of compressed-air cars

NASA Astrophysics Data System (ADS)

Creutzig, Felix; Papson, Andrew; Schipper, Lee; Kammen, Daniel M.

2009-10-01

Climate change and energy security require a reduction in travel demand, a modal shift, and technological innovation in the transport sector. Through a series of press releases and demonstrations, a car using energy stored in compressed air produced by a compressor has been suggested as an environmentally friendly vehicle of the future. We analyze the thermodynamic efficiency of a compressed-air car powered by a pneumatic engine and consider the merits of compressed air versus chemical storage of potential energy. Even under highly optimistic assumptions the compressed-air car is significantly less efficient than a battery electric vehicle and produces more greenhouse gas emissions than a conventional gas-powered car with a coal intensive power mix. However, a pneumatic-combustion hybrid is technologically feasible, inexpensive and could eventually compete with hybrid electric vehicles.

Automotive Insulation

NASA Technical Reports Server (NTRS)

1997-01-01

Under a Space Act Agreement between Boeing North America and BSR Products, Space Shuttle Thermal Protection System (TPS) materials are now used to insulate race cars. BSR has created special TPS blanket insulation kits for use on autos that take part in NASCAR events, and other race cars through its nationwide catalog distribution system. Temperatures inside a race car's cockpit can soar to a sweltering 140 to 160 degrees, with the extreme heat coming through the engine firewall, transmission tunnel, and floor. It is common for NASCAR drivers to endure blisters and burns due to the excessive heat. Tests on a car insulated with the TPS material showed a temperature drop of some 50 degrees in the driver's cockpit. BSR-TPS Products, Inc. now manufactures insulation kits for distribution to race car teams around the world.

49 CFR 526.3 - Transfer of vehicle from non-domestic to domestic fleet.

Code of Federal Regulations, 2011 CFR

2011-10-01

... value added), provide the following information: (1) A description of the model type, including engine type and displacement, transmission class, car line designation, and fuel economy; (2) The projected U... actions (e.g., change from imported engine to domestically manufactured engine) which will increase the...

49 CFR 526.3 - Transfer of vehicle from non-domestic to domestic fleet.

Code of Federal Regulations, 2010 CFR

2010-10-01

... value added), provide the following information: (1) A description of the model type, including engine type and displacement, transmission class, car line designation, and fuel economy; (2) The projected U... actions (e.g., change from imported engine to domestically manufactured engine) which will increase the...

Allogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of cancer.

PubMed

Marcus, Assaf; Eshhar, Zelig

2014-07-01

Chimeric antigen (or antibody) receptors (CAR) are fusion proteins typically combining an antibody-derived targeting fragment with signaling domains capable of activating immune cells. Recent clinical trials have shown the tremendous potential of adoptive cell transfer (ACT) of autologous T cells engineered to express a CD19-specific CAR targeting B-cell malignancies. Building on this approach, ACT therapies employing allogeneic CAR-expressing cytotoxic cells are now being explored. The basic principles of CAR-ACT are introduced. The potential benefits as well as problems of using allogeneic CAR-modified cells against tumor antigens are discussed. Various approaches to allogeneic CAR therapy are presented, including donor leukocyte infusion, CAR-redirected γδ T cells and natural killer cells, strategies to avoid graft-versus-host disease, modulation of lymphocyte migration, and exploitation of graft-versus-host reactivity. CAR-modified allogeneic cells have the potential to act as universal effector cells, which can be administered to any patient regardless of MHC type. Such universal effector cells could be used as an 'off-the-shelf' cell-mediated treatment for cancer.

Vehicle mass and injury risk in two-car crashes: A novel methodology.

PubMed

Tolouei, Reza; Maher, Mike; Titheridge, Helena

2013-01-01

This paper introduces a novel methodology based on disaggregate analysis of two-car crash data to estimate the partial effects of mass, through the velocity change, on absolute driver injury risk in each of the vehicles involved in the crash when absolute injury risk is defined as the probability of injury when the vehicle is involved in a two-car crash. The novel aspect of the introduced methodology is in providing a solution to the issue of lack of data on the speed of vehicles prior to the crash, which is required to calculate the velocity change, as well as a solution to the issue of lack of information on non-injury two-car crashes in national accident data. These issues have often led to focussing on relative measures of injury risk that are not independent of risk in the colliding cars. Furthermore, the introduced methodology is used to investigate whether there is any effect of vehicle size above and beyond that of mass ratio, and whether there are any effects associated with the gender and age of the drivers. The methodology was used to analyse two-car crashes to investigate the partial effects of vehicle mass and size on absolute driver injury risk. The results confirmed that in a two-car collision, vehicle mass has a protective effect on its own driver injury risk and an aggressive effect on the driver injury risk of the colliding vehicle. The results also confirmed that there is a protective effect of vehicle size above and beyond that of vehicle mass for frontal and front to side collisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

77 FR 20483 - Michelin North America, Inc., Receipt of Petition for Decision of Inconsequential Noncompliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-04

...: Michelin North America, Inc.\\1\\ (MNA) has determined that certain Michelin brand passenger car replacement...,500 Michelin Primacy MXV4 TL passenger car replacement tires labeled as sizes P205 65 R15 94H, P205 65... MXV4 TL passenger car replacement tires that MNA no longer controlled at the time it determined that...

Things You "Auto" Know When Buying a Car. Teacher's Guide [and] Student Material.

ERIC Educational Resources Information Center

Bookout, Janet

This unit provides high school students with criteria for deciding to buy a new or used car and selecting a reputable dealer. It is divided into three sections. In the first section students analyze uses and identify car sizes, options, and appearances that are important. The second section describes advantages and disadvantages of new and used…

Study of car-sharing diffusion criticality conditions based on human traveling network

NASA Astrophysics Data System (ADS)

Xu, Yan; Ji, Xuehong

Car-sharing program, like Car2go, is an innovative urban transportation mode where the car-sharing company provides a car fleet to offer people with the short-term access of car traveling. As a new traveling service, car-sharing platforms have been struggling hard to trigger initial users and speed up their diffusion process. Unlike new product spreading via geographical proximity people, car-sharing users usually drive sharing cars to different destinations and influence people there, and potential user decision also depends on previous user activity at all their destinations. Car-sharing user connections are mainly affected by their traveling behaviors. The influence of user traveling network on new service/product spreading process has been rarely studied before. Here, we find that the infective rate between users with the same destination is critical to the minimum user base of car-sharing diffusion. Moreover, a city with central user network is more appropriate for car-sharing. It leads to a small critical infective rate for diffusion, and a large stable market size of car-sharing service. Our study can impact car-sharing market strategies ranging from market expansion in one city to optimal market selection among different cities.

Race Car Rally.

ERIC Educational Resources Information Center

Anthony, Joan L.

1994-01-01

Describes an activity where teams of parents and children work together to solve problems involving matchbox-sized race cars. The teams collect, record, and analyze data; measure distances in metric; and explore concepts related to mass, friction, and force. (PR)

Potential of Diesel Engine, Emission Technology

DOT National Transportation Integrated Search

1980-03-01

This report surveys diesel engine emission technologies applicable to passenger cars and light trucks. The general design and operating features are presented and discussed. Current and state-of-the-art concepts are reviewed with the focus on control...

Hybrid cars now, fuel cell cars later.

PubMed

Demirdöven, Nurettin; Deutch, John

2004-08-13

We compare the energy efficiency of hybrid and fuel cell vehicles as well as conventional internal combustion engines. Our analysis indicates that fuel cell vehicles using hydrogen from fossil fuels offer no significant energy efficiency advantage over hybrid vehicles operating in an urban drive cycle. We conclude that priority should be placed on hybrid vehicles by industry and government.

16 CFR 1500.85 - Exemptions from classification as banned hazardous substances.

Code of Federal Regulations, 2012 CFR

2012-01-01

... operation of miniature engines for model airplanes, boats, cars, etc. (6) Novelties consisting of a mixture...: (i) Are designed to be ignited by electrical means. (ii) Contain no more than 62.5 grams (2.2 ounces... cars, and similar models, provided such solid fuel pellets: (i) Weigh not more than 11.5 grams each...

75 FR 52326 - Agency Information Collection Activities; Proposed Collection; Comment Request; EPA's Light-Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... has an ongoing program to evaluate the emission performance of in-use light-duty (passenger car and... number'' of any class or category of vehicles or engines, although properly maintained and used, do not... selects approximately 50 classes of passenger cars and light trucks for in-use testing, at EPA's testing...

Alternative Fuels Data Center: New Jersey Utility Saves With Alternative

Science.gov Websites

electric car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a FuelA> Jersey Utility Saves With Alternative Fuel to someone by E-mail Share Alternative Fuels . For information about this project, contact New Jersey Clean Cities Coalition. Download QuickTime

Alternative Fuels Data Center: Colorado Airport Relies on Natural Gas

Science.gov Websites

electric car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a Fueling StationsA> Colorado Airport Relies on Natural Gas Fueling Stations to someone by E-mail system. For information about this project, contact Denver Metro Clean Cities Coalition. Download

Alternative Fuels Data Center: Phoenix Utility Fleet Drives Smarter with

Science.gov Websites

electric car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a BiodieselA> Phoenix Utility Fleet Drives Smarter with Biodiesel to someone by E-mail Share ... Aug. 26, 2017 Phoenix Utility Fleet Drives Smarter with Biodiesel Watch how a utility company in

16 CFR 1500.85 - Exemptions from classification as banned hazardous substances.

Code of Federal Regulations, 2010 CFR

2010-01-01

... operation of miniature engines for model airplanes, boats, cars, etc. (6) Novelties consisting of a mixture...: (i) Are designed to be ignited by electrical means. (ii) Contain no more than 62.5 grams (2.2 ounces... cars, and similar models, provided such solid fuel pellets: (i) Weigh not more than 11.5 grams each...

Hybrid Cars Now, Fuel Cell Cars Later

NASA Astrophysics Data System (ADS)

Demirdöven, Nurettin; Deutch, John

2004-08-01

We compare the energy efficiency of hybrid and fuel cell vehicles as well as conventional internal combustion engines. Our analysis indicates that fuel cell vehicles using hydrogen from fossil fuels offer no significant energy efficiency advantage over hybrid vehicles operating in an urban drive cycle. We conclude that priority should be placed on hybrid vehicles by industry and government.

Coherence and measurement in quantum thermodynamics

PubMed Central

Kammerlander, P.; Anders, J.

2016-01-01

Thermodynamics is a highly successful macroscopic theory widely used across the natural sciences and for the construction of everyday devices, from car engines to solar cells. With thermodynamics predating quantum theory, research now aims to uncover the thermodynamic laws that govern finite size systems which may in addition host quantum effects. Recent theoretical breakthroughs include the characterisation of the efficiency of quantum thermal engines, the extension of classical non-equilibrium fluctuation theorems to the quantum regime and a new thermodynamic resource theory has led to the discovery of a set of second laws for finite size systems. These results have substantially advanced our understanding of nanoscale thermodynamics, however putting a finger on what is genuinely quantum in quantum thermodynamics has remained a challenge. Here we identify information processing tasks, the so-called projections, that can only be formulated within the framework of quantum mechanics. We show that the physical realisation of such projections can come with a non-trivial thermodynamic work only for quantum states with coherences. This contrasts with information erasure, first investigated by Landauer, for which a thermodynamic work cost applies for classical and quantum erasure alike. Repercussions on quantum work fluctuation relations and thermodynamic single-shot approaches are also discussed. PMID:26916503

Coherence and measurement in quantum thermodynamics.

PubMed

Kammerlander, P; Anders, J

2016-02-26

Thermodynamics is a highly successful macroscopic theory widely used across the natural sciences and for the construction of everyday devices, from car engines to solar cells. With thermodynamics predating quantum theory, research now aims to uncover the thermodynamic laws that govern finite size systems which may in addition host quantum effects. Recent theoretical breakthroughs include the characterisation of the efficiency of quantum thermal engines, the extension of classical non-equilibrium fluctuation theorems to the quantum regime and a new thermodynamic resource theory has led to the discovery of a set of second laws for finite size systems. These results have substantially advanced our understanding of nanoscale thermodynamics, however putting a finger on what is genuinely quantum in quantum thermodynamics has remained a challenge. Here we identify information processing tasks, the so-called projections, that can only be formulated within the framework of quantum mechanics. We show that the physical realisation of such projections can come with a non-trivial thermodynamic work only for quantum states with coherences. This contrasts with information erasure, first investigated by Landauer, for which a thermodynamic work cost applies for classical and quantum erasure alike. Repercussions on quantum work fluctuation relations and thermodynamic single-shot approaches are also discussed.

Coherence and measurement in quantum thermodynamics

NASA Astrophysics Data System (ADS)

Kammerlander, P.; Anders, J.

2016-02-01

Thermodynamics is a highly successful macroscopic theory widely used across the natural sciences and for the construction of everyday devices, from car engines to solar cells. With thermodynamics predating quantum theory, research now aims to uncover the thermodynamic laws that govern finite size systems which may in addition host quantum effects. Recent theoretical breakthroughs include the characterisation of the efficiency of quantum thermal engines, the extension of classical non-equilibrium fluctuation theorems to the quantum regime and a new thermodynamic resource theory has led to the discovery of a set of second laws for finite size systems. These results have substantially advanced our understanding of nanoscale thermodynamics, however putting a finger on what is genuinely quantum in quantum thermodynamics has remained a challenge. Here we identify information processing tasks, the so-called projections, that can only be formulated within the framework of quantum mechanics. We show that the physical realisation of such projections can come with a non-trivial thermodynamic work only for quantum states with coherences. This contrasts with information erasure, first investigated by Landauer, for which a thermodynamic work cost applies for classical and quantum erasure alike. Repercussions on quantum work fluctuation relations and thermodynamic single-shot approaches are also discussed.

Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival.

PubMed

Genßler, Sabrina; Burger, Michael C; Zhang, Congcong; Oelsner, Sarah; Mildenberger, Iris; Wagner, Marlies; Steinbach, Joachim P; Wels, Winfried S

2016-04-01

Epidermal growth factor receptor (EGFR) and its mutant form EGFRvIII are overexpressed in a large proportion of glioblastomas (GBM). Immunotherapy with an EGFRvIII-specific vaccine has shown efficacy against GBM in clinical studies. However, immune escape by antigen-loss variants and lack of control of EGFR wild-type positive clones limit the usefulness of this approach. Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells may represent an alternative immunotherapeutic strategy. For targeting to GBM, we generated variants of the clinically applicable human NK cell line NK-92 that express CARs carrying a composite CD28-CD3ζ domain for signaling, and scFv antibody fragments for cell binding either recognizing EGFR, EGFRvIII, or an epitope common to both antigens. In vitro analysis revealed high and specific cytotoxicity of EGFR-targeted NK-92 against established and primary human GBM cells, which was dependent on EGFR expression and CAR signaling. EGFRvIII-targeted NK-92 only lysed EGFRvIII-positive GBM cells, while dual-specific NK cells expressing a cetuximab-based CAR were active against both types of tumor cells. In immunodeficient mice carrying intracranial GBM xenografts either expressing EGFR, EGFRvIII or both receptors, local treatment with dual-specific NK cells was superior to treatment with the corresponding monospecific CAR NK cells. This resulted in a marked extension of survival without inducing rapid immune escape as observed upon therapy with monospecific effectors. Our results demonstrate that dual targeting of CAR NK cells reduces the risk of immune escape and suggest that EGFR/EGFRvIII-targeted dual-specific CAR NK cells may have potential for adoptive immunotherapy of glioblastoma.

Emissions from diesel and stratified charge powered cars. Final report

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

Springer, K.J.

A total of ten passenger cars, four powered by diesel engines, two by stratified charge gasoline engines, one by a stratified charge operating on gasoline and diesel fuel, two by control equipped conventional engines, and one powered by a gas turbine, have been subjected to a wide variety of emissions evaluations. The vehicles, all late model, low mileage, included a Nissan Datsun, a Mercedes 220D, a Peugeot 504D, an Opel Rekord 2100D, a standard Capri, a stratified charge (PROCO) Capri, a low emission prototype Ford LTD, the Texaco TCCS stratified charge powered Cricket operated on gasoline and on diesel fuel,more » a Honda CVCC stratified charge, and a Chrysler gas turbine car. All were 4-cylinder except the LTD and the gas turbine. Tailpipe emissions were measured by the 1975 light duty Federal Test Procedure for gaseous emissions. Smoke and fuel economy were also determined during this test cycle. Chassis dynamometer versions of the 1974 heavy duty diesel smoke and gaseous emissions tests were employed. Odor and related instrumental-chemical measurements were made under seven steady state and three acceleration conditions. The prototype diesel odor analytical system, developed under CRC contract, was applied to the exhaust from both diesel and gasoline engines. Its use as a predictive method of diesel odor was investigated. Noise measurements were taken by SAE driveby as well as under a variety of exterior-interior conditions. Comparisons of the results for all vehicles are by emission category. The emissions from the group of diesel cars are compared to the conventional gasoline, Ford PROCO, Texas TCCS, and Honda CVCC.« less

49 CFR 571.104 - Standard No. 104; Windshield wiping and washing systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... difference between one-half of the shoulder room dimension and the steering wheel centerline-to-car... frequency or speed shall be at least 45 cycles per minute regardless of engine load and engine speed. S4.1.1.3Regardless of engine speed and engine load, the highest and one lower frequency or speed shall differ by at...

Analysis of car’s frontal collision against pole

NASA Astrophysics Data System (ADS)

Ispas, N.; Nastasoiu, M.

2017-10-01

Reducing the effects of traffic accidents over the occupants is a major objective of collision attempts. Impacts between the car and the pole are very dangerous for the physical integrity of the car’s occupants. To minimalize the effects of such events on the passengers of a vehicle, a whole series of efforts by both designers and experienced engineers led to increasingly the vehicles safety. The main aim of these paper is to quantify the influences over the car passengers of loads involved by car against pole collisions using the same car model at different speeds. Also, this kind on occupant influences were study using a small car model. Other goal of the paper was the study of the cars stiffness in frontal collision against the pole. The paper’s experimental results were obtained by support of DSD, Dr. Steffan Datentechnik GmbH - Linz, Austria. The described tests were performed in full test facility of DSD Linz, in “Easter 2016 PC-Crash Seminar”. Cars accelerations, velocities, rotations angles after pole impact were registered and discussed. The novelty of the paper consists in studies referred for the same car model involved in car against pole collisions at different impact speeds. Paper’s conclusions can be future used for car safety improvement.

A dual chain chimeric antigen receptor (CAR) in the native antibody format for targeting immune cells towards cancer cells without the need of an scFv.

PubMed

Faitschuk, E; Nagy, V; Hombach, A A; Abken, H

2016-10-01

Adoptive cell therapy with chimeric antigen receptor (CAR)-modified T cells showed remarkable therapeutic efficacy in the treatment of leukaemia/lymphoma. However, the application to a variety of cancer entities is often constricted by the non-availability of a single chain antibody (scFv), which is usually the targeting domain in a CAR, while antibodies in the natural format are often available. To overcome the limitation, we designed a CAR that uses an antibody in its natural configuration for binding. Such CAR consists of two chains, the immunoglobulin light and heavy chain with their constant regions, whereby the heavy chain is anchored to the membrane and linked to an intracellular signalling domain for T-cell activation. The two chains form a stable heterodimer, a so-called dual chain CAR (dcCAR), and bind with high affinity and in a specific manner to their cognate antigen. By specific binding, the dcCAR activates engineered T cells for the release of pro-inflammatory cytokines and for target cell lysis. We provide evidence by three examples that the dcCAR format is universally applicable and thereby broadens the CAR cell therapy towards a larger variety of targets for which an scFv antibody is not available.

78 FR 30963 - Michelin North America, Incorporated, Grant of Petition for Decision of Inconsequential...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-23

...: Michelin North America, Inc. (MNA), has determined that certain Michelin brand passenger car replacement...: Affected are approximately 17,500 Michelin Primacy MXV4 TL passenger car replacement tires labeled as sizes...

Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy.

PubMed

Brown, Christine E; Alizadeh, Darya; Starr, Renate; Weng, Lihong; Wagner, Jamie R; Naranjo, Araceli; Ostberg, Julie R; Blanchard, M Suzette; Kilpatrick, Julie; Simpson, Jennifer; Kurien, Anita; Priceman, Saul J; Wang, Xiuli; Harshbarger, Todd L; D'Apuzzo, Massimo; Ressler, Julie A; Jensen, Michael C; Barish, Michael E; Chen, Mike; Portnow, Jana; Forman, Stephen J; Badie, Behnam

2016-12-29

A patient with recurrent multifocal glioblastoma received chimeric antigen receptor (CAR)-engineered T cells targeting the tumor-associated antigen interleukin-13 receptor alpha 2 (IL13Rα2). Multiple infusions of CAR T cells were administered over 220 days through two intracranial delivery routes - infusions into the resected tumor cavity followed by infusions into the ventricular system. Intracranial infusions of IL13Rα2-targeted CAR T cells were not associated with any toxic effects of grade 3 or higher. After CAR T-cell treatment, regression of all intracranial and spinal tumors was observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid. This clinical response continued for 7.5 months after the initiation of CAR T-cell therapy. (Funded by Gateway for Cancer Research and others; ClinicalTrials.gov number, NCT02208362 .).

Formula Student as Part of a Mechanical Engineering Curriculum

ERIC Educational Resources Information Center

Davies, Huw Charles

2013-01-01

Formula Student (FS) is a multi-university student design competition managed by the UK Institution of Mechanical Engineers. Students are required to demonstrate and prove their creativity and engineering skills through the design, manufacture and financing of a small formula style race car. This paper seeks to explore the educational value that…

49 CFR 599.300 - Requirements for qualifying transactions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Requirements for qualifying transactions. (a) In general. To qualify for a credit under the CARS Program, a... owned by or under the control of the dealership until the engine is disabled, disable the engine of the... price of $45,000 or less. (d) Trade-in Vehicle—Disclosure of Scrap Value, Engine Disablement, and Title...

49 CFR 599.300 - Requirements for qualifying transactions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Requirements for qualifying transactions. (a) In general. To qualify for a credit under the CARS Program, a... owned by or under the control of the dealership until the engine is disabled, disable the engine of the... price of $45,000 or less. (d) Trade-in Vehicle—Disclosure of Scrap Value, Engine Disablement, and Title...

49 CFR 599.300 - Requirements for qualifying transactions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Requirements for qualifying transactions. (a) In general. To qualify for a credit under the CARS Program, a... owned by or under the control of the dealership until the engine is disabled, disable the engine of the... price of $45,000 or less. (d) Trade-in Vehicle—Disclosure of Scrap Value, Engine Disablement, and Title...

49 CFR 599.300 - Requirements for qualifying transactions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Requirements for qualifying transactions. (a) In general. To qualify for a credit under the CARS Program, a... owned by or under the control of the dealership until the engine is disabled, disable the engine of the... price of $45,000 or less. (d) Trade-in Vehicle—Disclosure of Scrap Value, Engine Disablement, and Title...

4. Engine Stores Building, Southern Pacific Railroad Carlin Shops, oblique ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. Engine Stores Building, Southern Pacific Railroad Carlin Shops, oblique view of the southwest end and southeast side (135mm lens). Condemned freight cars spotted on the adjacent track prevented clear photography of southeast side. - Southern Pacific Railroad, Carlin Shops, Engine Stores Building, Foot of Sixth Street, Carlin, Elko County, NV

3. Engine Stores Building, Southern Pacific Railroad Carlin Shops, oblique ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. Engine Stores Building, Southern Pacific Railroad Carlin Shops, oblique view of the northeast end and southeast side (90mm lens). Condemned freight cars spotted on the adjacent track prevented clear photography of southeast side. - Southern Pacific Railroad, Carlin Shops, Engine Stores Building, Foot of Sixth Street, Carlin, Elko County, NV

78 FR 56226 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Motor...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-12

... importers of passenger cars, motorcycles, light trucks, heavy duty truck engines, non-road vehicles or... Submitted to OMB for Review and Approval; Comment Request; Motor Vehicle and Engine Compliance Program Fees... Protection Agency has submitted an information collection request (ICR), Motor Vehicle and Engine Compliance...

Study and Test to Confirm Automobile Drivetrain Components to Improve Fuel Economy : Volume 1. History of the Automobile Transmission in the United States

DOT National Transportation Integrated Search

1979-05-01

Since the earliest days of the motor car, engineers have tinkered together various means of connecting the engine to the ground. While the wheel rapidly became the norm for the ground/vehicle interface, many different engine/wheel coupling techniques...

Hybrid: Passing

Science.gov Websites

accelerating or when additional power is needed, the gasoline engine and electric motor are both used to propel . The car is passing another vehicle. There are red arrows flowing from the gasoline engine to the front wheels. There are blue arrows flowing from the battery to the electric engine to the front wheels. Main

Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma.

PubMed

Oelsner, Sarah; Friede, Miriam E; Zhang, Congcong; Wagner, Juliane; Badura, Susanne; Bader, Peter; Ullrich, Evelyn; Ottmann, Oliver G; Klingemann, Hans; Tonn, Torsten; Wels, Winfried S

2017-02-01

Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications. To enhance their therapeutic utility for the treatment of B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to express chimeric antigen receptors (CARs) that target CD19 and contain human CD3ζ (CAR 63.z), composite CD28-CD3ζ or CD137-CD3ζ signaling domains (CARs 63.28.z and 63.137.z). Exposure of CD19-positive targets to CAR NK-92 cells resulted in formation of conjugates between NK and cancer cells, NK-cell degranulation and selective cytotoxicity toward established B-cell leukemia and lymphoma cells. Likewise, the CAR NK cells displayed targeted cell killing of primary pre-B-ALL blasts that were resistant to parental NK-92. Although all three CAR NK-92 cell variants were functionally active, NK-92/63.137.z cells were less effective than NK-92/63.z and NK-92/63.28.z in cell killing and cytokine production, pointing to differential effects of the costimulatory CD28 and CD137 domains. In a Raji B-cell lymphoma model in NOD-SCID IL2R γ null mice, treatment with NK-92/63.z cells, but not parental NK-92 cells, inhibited disease progression, indicating that selective cytotoxicity was retained in vivo. Our data demonstrate that it is feasible to generate CAR-engineered NK-92 cells with potent and selective antitumor activity. These cells may become clinically useful as a continuously expandable off-the-shelf cell therapeutic agent. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Recent evidence concerning higher NO x emissions from passenger cars and light duty vehicles

NASA Astrophysics Data System (ADS)

Carslaw, David C.; Beevers, Sean D.; Tate, James E.; Westmoreland, Emily J.; Williams, Martin L.

2011-12-01

Ambient trends in nitrogen oxides (NO x) and nitrogen dioxide (NO 2) for many air pollution monitoring sites in European cities have stabilised in recent years. The lack of a decrease in the concentration of NO x and in particular NO 2 is of concern given European air quality standards are set in law. The lack of decrease in the concentration of NO x and NO 2 is also in clear disagreement with emission inventory estimates and projections. This work undertakes a comprehensive analysis of recent vehicle emissions remote sensing data from seven urban locations across the UK. The large sample size of 84,269 vehicles was carefully cross-referenced to a detailed and comprehensive database of vehicle information. We find that there are significant discrepancies between current UK/European estimates of NO x emissions and those derived from the remote sensing data for several important classes of vehicle. In the case of light duty diesel vehicles it is found that NO x emissions have changed little over 20 years or so over a period when the proportion of directly emitted NO 2 has increased substantially. For diesel cars it is found that absolute emissions of NO x are higher across all legislative classes than suggested by UK and other European emission inventories. Moreover, the analysis shows that more recent technology diesel cars (Euro 3-5) have clear increasing NO x emissions as a function of Vehicle Specific Power, which is absent for older technology vehicles. Under higher engine loads, these newer model diesel cars have a NO x/CO 2 ratio twice that of older model cars, which may be related to the increased use of turbo-charging. Current emissions of NO x from early technology catalyst-equipped petrol cars (Euro 1/2) were also found to be higher than emission inventory estimates - and comparable with NO x emissions from diesel cars. For heavy duty vehicles, it is found that NO x emissions were relatively stable until the introduction of Euro IV technology when emissions decreased by about 30%. The more limited data available for urban buses shows that there has been little change in NO x emissions from Euro I to Euro IV. There is general much better consistency across the different estimates of heavy duty vehicle NO x emissions than for light duty vehicles.

Co-stimulatory signaling determines tumor antigen sensitivity and persistence of CAR T cells targeting PSCA+ metastatic prostate cancer

PubMed Central

Priceman, Saul J.; Gerdts, Ethan A.; Tilakawardane, Dileshni; Kennewick, Kelly T.; Murad, John P.; Park, Anthony K.; Jeang, Brook; Yamaguchi, Yukiko; Urak, Ryan; Weng, Lihong; Chang, Wen-Chung; Wright, Sarah; Pal, Sumanta; Reiter, Robert E.; Brown, Christine E.; Forman, Stephen J.

2018-01-01

ABSTRACT Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with “on-target off-tumor” activity. Here, we show that the intracellular co-stimulatory signaling domain can determine a CAR's sensitivity for tumor antigen expression. A 4-1BB intracellular co-stimulatory signaling domain in PSCA-CARs confers improved selectivity for higher tumor antigen density, reduced T cell exhaustion phenotype, and equivalent tumor killing ability compared to PSCA-CARs containing the CD28 co-stimulatory signaling domain. PSCA-CARs exhibit robust in vivo anti-tumor activity in patient-derived bone-metastatic prostate cancer xenograft models, and 4-1BB-containing CARs show superior T cell persistence and control of disease compared with CD28-containing CARs. Our study demonstrates the importance of co-stimulation in defining an optimal CAR T cell, and also highlights the significance of clinically relevant models in developing solid cancer CAR T cell therapies. PMID:29308300

Masked Chimeric Antigen Receptor for Tumor-Specific Activation.

PubMed

Han, Xiaolu; Bryson, Paul D; Zhao, Yifan; Cinay, Gunce E; Li, Si; Guo, Yunfei; Siriwon, Natnaree; Wang, Pin

2017-01-04

Adoptive cellular therapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells is a powerful form of cancer immunotherapy. CAR-T cells can be redirected to specifically recognize tumor-associated antigens (TAAs) and induce high levels of antitumor activity. However, they may also display "on-target off-tumor" toxicities, resulting from low-level expression of TAAs in healthy tissues. These adverse effects have raised considerable safety concerns and limited the clinical application of this otherwise promising therapeutic modality. To minimize such side effects, we have designed an epidermal growth factor receptor (EGFR)-specific masked CAR (mCAR), which consists of a masking peptide that blocks the antigen-binding site and a protease-sensitive linker. Proteases commonly active in the tumor microenvironment can cleave the linker and disengage the masking peptide, thereby enabling CAR-T cells to recognize target antigens only at the tumor site. In vitro mCAR showed dramatically reduced antigen binding and antigen-specific activation in the absence of proteases, but normal levels of binding and activity upon treatment with certain proteases. Masked CAR-T cells also showed antitumor efficacy in vivo comparable to that of unmasked CAR. Our study demonstrates the feasibility of improving the safety profile of conventional CARs and may also inspire future design of CAR molecules targeting broadly expressed TAAs. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

40 CFR 86.129-80 - Road load power, test weight, and inertia weight class determination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... power, test weight, and inertia weight class determination. (a) Flywheels, electrical or other means of... equipment exceeding 0.1 ft2 which are anticipated to be sold on more than 33 pct of the car line. Frontal... expected that more than 33 percent of a car line within an engine-system combination will be equipped with...

40 CFR 86.129-80 - Road load power, test weight, and inertia weight class determination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... power, test weight, and inertia weight class determination. (a) Flywheels, electrical or other means of... equipment exceeding 0.1 ft2 which are anticipated to be sold on more than 33 pct of the car line. Frontal... expected that more than 33 percent of a car line within an engine-system combination will be equipped with...

78 FR 2236 - Federal Motor Vehicle Safety Standards; New Pneumatic Tires for Motor Vehicles With a GVWR of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-10

... Society of Automotive Engineers (SAE) Recommended Practice J918b--Passenger Car Tire Performance Requirements and Test Procedures (January 1967). 2, 3 As part of the strength test, a plunger is driven into a...--Passenger Car Tire Performance Requirements and Test Procedures (January 1967) Section 3.1. \\5\\ FMVSS No...

40 CFR 86.1842-01 - Addition of a vehicle after certification; and changes to a vehicle covered by certification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air... certification. (a) Addition of a car line after certification. (1) If a manufacturer proposes to add to its product line a new car line of the same test group as vehicles previously certified but which was not...

40 CFR 86.1842-01 - Addition of a vehicle after certification; and changes to a vehicle covered by certification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air... certification. (a) Addition of a car line after certification. (1) If a manufacturer proposes to add to its product line a new car line of the same test group as vehicles previously certified but which was not...

40 CFR 86.1842-01 - Addition of a vehicle after certification; and changes to a vehicle covered by certification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES General Compliance Provisions for Control of Air Pollution... certification. (a) Addition of a car line after certification. (1) If a manufacturer proposes to add to its product line a new car line of the same test group as vehicles previously certified but which was not...

40 CFR 86.1842-01 - Addition of a vehicle after certification; and changes to a vehicle covered by certification.

Code of Federal Regulations, 2010 CFR

2010-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air... certification. (a) Addition of a car line after certification. (1) If a manufacturer proposes to add to its product line a new car line of the same test group as vehicles previously certified but which was not...

40 CFR 86.1842-01 - Addition of a vehicle after certification; and changes to a vehicle covered by certification.

Code of Federal Regulations, 2011 CFR

2011-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) General Compliance Provisions for Control of Air... certification. (a) Addition of a car line after certification. (1) If a manufacturer proposes to add to its product line a new car line of the same test group as vehicles previously certified but which was not...

Idling Reduction for Emergency and Other Service Vehicles

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

None

2015-05-07

This is a fact sheet about reducing idling for emergency and service vehicles. Emergency vehicles, such as police cars, ambulances, and fire trucks, along with other service vehicles such as armored cars, are often exempt from laws that limit engine idling. However, these vehicles can save fuel and reduce emissions with technologies that allow them to perform vital services without idling.

Alternative Fuels Data Center: Yellow Cab Converts Taxis to Propane in

Science.gov Websites

electric car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a Columbus, OhioA> Yellow Cab Converts Taxis to Propane in Columbus, Ohio to someone by E-mail how Yellow Cab is overhauling their fleet in Columbus, Ohio, with propane power. For information about

Alternative Fuels Data Center: MedCorp Fuels Emergency Vehicles With

Science.gov Websites

. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a police Propane in OhioA> MedCorp Fuels Emergency Vehicles With Propane in Ohio to someone by E-mail Television Related Videos Photo of a car Hydrogen Powers Fuel Cell Vehicles in California Nov. 18, 2017 Photo

Alternative Fuels Data Center: Los Angeles Public Works Fleet Converts to

Science.gov Websites

electric car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a Natural GasA> Los Angeles Public Works Fleet Converts to Natural Gas to someone by E-mail Share . For information about this project, contact Los Angeles Clean Cities Coalition. Download QuickTime

40 CFR 86.129-80 - Road load power, test weight, and inertia weight class determination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... power, test weight, and inertia weight class determination. (a) Flywheels, electrical or other means of... equipment exceeding 0.1 ft2 which are anticipated to be sold on more than 33 pct of the car line. Frontal... expected that more than 33 percent of a car line within an engine-system combination will be equipped with...

40 CFR 86.129-80 - Road load power, test weight, and inertia weight class determination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... power, test weight, and inertia weight class determination. (a) Flywheels, electrical or other means of... equipment exceeding 0.1 ft2 which are anticipated to be sold on more than 33 pct of the car line. Frontal... expected that more than 33 percent of a car line within an engine-system combination will be equipped with...

Real-time augmented reality overlay for an energy-efficient car study

NASA Astrophysics Data System (ADS)

Wozniak, Peter; Javahiraly, Nicolas; Curticapean, Dan

2017-06-01

Our university carries out various research projects. Among others, the project Schluckspecht is an interdisciplinary work on different ultra-efficient car concepts for international contests. Besides the engineering work, one part of the project deals with real-time data visualization. In order to increase the efficiency of the vehicle, an online monitoring of the runtime parameters is necessary. The driving parameters of the vehicle are transmitted to a processing station via a wireless network connection. We plan to use an augmented reality (AR) application to visualize different data on top of the view of the real car. By utilizing a mobile Android or iOS device a user can interactively view various real-time and statistical data. The car and its components are meant to be augmented by various additional information, whereby that information should appear at the correct position of the components. An engine e.g. could show the current rpm and consumption values. A battery on the other hand could show the current charge level. The goal of this paper is to evaluate different possible approaches, their suitability and to expand our application to other projects at our university.

Effect of rear end spoiler angle of a sedan car

NASA Astrophysics Data System (ADS)

Mashud, Mohammad; Das, Rubel Chandra

2017-06-01

Automotive vehicle's performance, safety, maneuverability can be influenced by multi-disciplinary factors such as car engine, tires, aerodynamics, and ergonomics of design. With the recent years, inflation in the fuel prices & the demand to have reduced greenhouse emissions has played a significant role in redefining the car aerodynamics. The shape of the vehicle uses about 3% of fuel to overcome the resistance in urban driving, while it takes 11% of fuel for the highway driving. This considerable high value of fuel usage in highway driving attracts several design engineers to enhance the aerodynamics of the vehicle using minimal design changes. Besides, automotive vehicles have become so much faster experiencing uplift force which creates unexpected accidents. This brings the idea of using external devices, which could be attached to the present vehicle without changing the body. This paper is based on the design, developments and numeral calculation of the effects of external device, which will be spoiler that mounted at the rear side of the sedan car to make the present vehicles more aerodynamically attractive. The influence of rear spoiler on the generated lift, drag, and pressure distributions are investigated and reported using commercially available Autodesk Simulation CFD software tool.

Full Hybrid: Stopped

Science.gov Websites

than batteries used to start conventional vehicles. Main stage: See through car with battery, engine electric motor or stored in the battery. It is also used to start the gasoline engine instantly when needed used to start conventional vehicles

Chimeric antigen receptor (CAR)-directed adoptive immunotherapy: a new era in targeted cancer therapy.

PubMed

Chen, Yamei; Liu, Delong

2014-01-01

As a result of the recent advances in molecular immunology, virology, genetics, and cell processing, chimeric antigen receptor (CAR)-directed cancer therapy has finally arrived for clinical application. CAR-directed adoptive immunotherapy represents a novel form of gene therapy, cellular therapy, and immunotherapy, a combination of three in one. Early phase clinical trial was reported in patients with refractory chronic lymphoid leukemia with 17p deletion. Accompanying the cytokine storm and tumor lysis syndrome was the shocking disappearance of the leukemia cells refractory to chemotherapy and monoclonal antibodies. CAR therapy was reproduced in both children and adults with refractory acute lymphoid leukemia. The CAR technology is being explored for solid tumor therapy, such as glioma. Close to 30 clinical trials are underway in the related fields (www.clinicaltrials.gov). Further improvement in gene targeting, cell expansion, delivery constructs (such as using Sleeping Beauty or Piggyback transposons) will undoubtedly enhance clinical utility. It is foreseeable that CAR-engineered T cell therapy will bring targeted cancer therapy into a new era.

Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice.

PubMed

Li, He; Huang, Yao; Jiang, Du-Qing; Cui, Lian-Zhen; He, Zhou; Wang, Chao; Zhang, Zhi-Wei; Zhu, Hai-Li; Ding, Yong-Mei; Li, Lin-Fang; Li, Qiang; Jin, Hua-Jun; Qian, Qi-Jun

2018-02-07

Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. EGFR-CAR T therapy is a promising strategy to improve the efficacy and potency of the adoptive immunotherapy in NSCLC. Moreover, EGFR-CAR T therapy could become a clinical application for NSCLC patients in the future.

Rapid-scan Fourier-transform coherent anti-Stokes Raman scattering spectroscopy with heterodyne detection.

PubMed

Hiramatsu, Kotaro; Luo, Yizhi; Ideguchi, Takuro; Goda, Keisuke

2017-11-01

High-speed Raman spectroscopy has become increasingly important for analyzing chemical dynamics in real time. To address the need, rapid-scan Fourier-transform coherent anti-Stokes Raman scattering (FT-CARS) spectroscopy has been developed to realize broadband CARS measurements at a scan rate of more than 20,000 scans/s. However, the detection sensitivity of FT-CARS spectroscopy is inherently low due to the limited number of photons detected during each scan. In this Letter, we show our experimental demonstration of enhanced sensitivity in rapid-scan FT-CARS spectroscopy by heterodyne detection. Specifically, we implemented heterodyne detection by superposing the CARS electric field with an external local oscillator (LO) for their interference. The CARS signal was amplified by simply increasing the power of the LO without the need for increasing the incident power onto the sample. Consequently, we achieved enhancement in signal intensity and the signal-to-noise ratio by factors of 39 and 5, respectively, compared to FT-CARS spectroscopy with homodyne detection. The sensitivity-improved rapid-scan FT-CARS spectroscopy is expected to enable the sensitive real-time observation of chemical dynamics in a broad range of settings, such as combustion engines and live biological cells.

Large and Small Cars in Real-World Crashes -Patterns of Use, Collision Types and Injury Outcomes

PubMed Central

Thomas, Pete; Frampton, Richard

1999-01-01

Previous work examining the effect of vehicle mass has demonstrated the link with occupant injury severity. The principal factor has been related to Newtonian mechanics. This paper analyses data from the UK Co-operative Crash Injury Study and identifies other factors associated with car size. The mass of the car is found to have a predominant effect on injury outcome in frontal collisions only where the effect is seen most in injuries to the head, face and chest. Most fatal casualties in small cars die when in collision with another car in front or side collisions while the key group for large cars is frontal collisions with road-side objects. There are several characteristics of small car occupants that differ from those in large cars including gender, age and vehicle occupancy. New information in the analysis concerns the priorities in casualty reduction between small and large car occupants and the paper argues that vehicle design should take account of this variation to produce vehicles optimised for the complete range of crashes and car occupants.

Correction of engineering servicing regularity of transporttechnological machines in operational process

NASA Astrophysics Data System (ADS)

Makarova, A. N.; Makarov, E. I.; Zakharov, N. S.

2018-03-01

In the article, the issue of correcting engineering servicing regularity on the basis of actual dependability data of cars in operation is considered. The purpose of the conducted research is to increase dependability of transport-technological machines by correcting engineering servicing regularity. The subject of the research is the mechanism of engineering servicing regularity influence on reliability measure. On the basis of the analysis of researches carried out before, a method of nonparametric estimation of car failure measure according to actual time-to-failure data was chosen. A possibility of describing the failure measure dependence on engineering servicing regularity by various mathematical models is considered. It is proven that the exponential model is the most appropriate for that purpose. The obtained results can be used as a separate method of engineering servicing regularity correction with certain operational conditions taken into account, as well as for the technical-economical and economical-stochastic methods improvement. Thus, on the basis of the conducted researches, a method of engineering servicing regularity correction of transport-technological machines in the operational process was developed. The use of that method will allow decreasing the number of failures.

Challenges and prospects of chimeric antigen receptor T cell therapy in solid tumors.

PubMed

Jindal, Vishal; Arora, Ena; Gupta, Sorab

2018-05-05

Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors. In this article, we will discuss the challenges faced in improving the outcome of CAR T cell therapy in solid tumors and various strategies adopted to curb them.

Study of Automobile Market Dynamics : Volume 1. Description.

DOT National Transportation Integrated Search

1977-08-01

To determine the effects of alternative energy conservation policies on total sales of new cars and upon the distribution by size-class and origin (foreign vs. domestic), in-depth interviews were administered to seven hundred recent new-car buyers. E...

Vehicle emissions and consumer information in car advertisements

PubMed Central

Wilson, Nick; Maher, Anthony; Thomson, George; Keall, Michael

2008-01-01

Background The advertising of vehicles has been studied from a safety perspective but not in terms of vehicle air pollutants. We aimed to examine the content and trends of greenhouse gas emissions and air pollution-related information, in light passenger vehicle advertisements. Methods Content analysis of the two most popular current affairs magazines in New Zealand for the five year period 2001–2005 was undertaken (n = 514 advertisements). This was supplemented with vehicle data from official websites. Results The advertisements studied provided some information on fuel type (52%), and engine size (39%); but hardly any provided information on fuel efficiency (3%), or emissions (4%). Over the five-year period the reported engine size increased significantly, while fuel efficiency did not improve. For the vehicles advertised, for which relevant official website data could be obtained, the average "greenhouse rating" for carbon dioxide (CO2) emissions was 5.1, with a range from 0.5 to 8.5 (on a scale with 10 being the best and 0.5 being the most polluting). The average CO2 emissions were 50% higher than the average for cars made by European manufacturers. The average "air pollution" rating for the advertised vehicles was 5.4 (on the same 1–10 scale). The yearly averages for the "greenhouse" or "air pollution" ratings did not change significantly over the five-year period. One advertised hybrid vehicle had a fuel consumption that was under half the average (4.4 versus 9.9 L/100 km), as well as the best "greenhouse" and "air pollution" ratings. Conclusion To enhance informed consumer choice and to control greenhouse gas and air pollution emissions, governments should introduce regulations on the content of vehicle advertisements and marketing (as started by the European Union). Similar regulations are already in place for the marketing of many other consumer products. PMID:18445291

Combining deep learning and coherent anti-Stokes Raman scattering imaging for automated differential diagnosis of lung cancer

NASA Astrophysics Data System (ADS)

Weng, Sheng; Xu, Xiaoyun; Li, Jiasong; Wong, Stephen T. C.

2017-10-01

Lung cancer is the most prevalent type of cancer and the leading cause of cancer-related deaths worldwide. Coherent anti-Stokes Raman scattering (CARS) is capable of providing cellular-level images and resolving pathologically related features on human lung tissues. However, conventional means of analyzing CARS images requires extensive image processing, feature engineering, and human intervention. This study demonstrates the feasibility of applying a deep learning algorithm to automatically differentiate normal and cancerous lung tissue images acquired by CARS. We leverage the features learned by pretrained deep neural networks and retrain the model using CARS images as the input. We achieve 89.2% accuracy in classifying normal, small-cell carcinoma, adenocarcinoma, and squamous cell carcinoma lung images. This computational method is a step toward on-the-spot diagnosis of lung cancer and can be further strengthened by the efforts aimed at miniaturizing the CARS technique for fiber-based microendoscopic imaging.

CARS Temperature and Species Measurements For Air Vehicle Propulsion Systems

NASA Technical Reports Server (NTRS)

Danehy, Paul M.; Gord, James R.; Grisch, Frederic; Klimenko, Dmitry; Clauss, Walter

2005-01-01

The coherent anti-Stokes Raman spectroscopy (CARS) method has recently been used in the United States and Europe to probe several different types of propulsion systems for air vehicles. At NASA Langley Research Center in the United States, CARS has been used to simultaneously measure temperature and the mole fractions of N2, O2 and H2 in a supersonic combustor, representative of a scramjet engine. At Wright- Patterson Air Force Base in the United States, CARS has been used to simultaneously measure temperature and mole fractions of N2, O2 and CO2, in the exhaust stream of a liquid-fueled, gas-turbine combustor. At ONERA in France and the DLR in Germany researchers have used CARS to measure temperature and species concentrations in cryogenic LOX-H2 rocket combustion chambers. The primary aim of these measurements has been to provide detailed flowfield information for computational fluid dynamics (CFD) code validation.

An Inexpensive Source of High Voltage

NASA Astrophysics Data System (ADS)

Saraiva, Carlos

2012-04-01

As a physics teacher I like recycling old apparatus and using them for demonstrations in my classes.1-4 In physics laboratories in schools, sources of high voltage include induction coils or electronic systems that can be bought from companies that sell lab equipment. But these sources can be very expensive. In this article, I will explain how you can use a car ignition coil as a high voltage source. Such a coil can be obtained from an old car found in a car salvage yard and used to power cathode ray tubes and discharge tubes to observe the spectra. It can also be used as a source of ignition to simulate explosive combustion that occurs in car engines, rockets, etc. You can also buy these coils in shops that sell car accessories and they are cheaper than induction coils. In Fig. 1 you can see a coil that I used.

A Day at the Races: NREL Hosts Colorado Middle School Students With STEM Skills

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

Lung, Linda

Technology and imagination came together at the National Renewable Energy Laboratory on May 20 when 53 teams from 18 Colorado middle schools turned a parking lot into a raceway. The students used the technological know-how picked up in science, technology, engineering, and math (STEM) classes to design and build model electric cars. Powered either by a solar panel or a lithium-ion battery, each car competed in time trials and double elimination races. The final races, between eight cars competing in each category, were over in less than 10 seconds.

78 FR 60900 - Kiewit Power Constructors Co. et al. (Avalotis Corp., Bowen Engineering Corporation, Commonwealth...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... the Occupational Safety and Health Act of 1970 (29 U.S.C. 655) and 29 CFR 1905.11 (``Variances and... or gates to the hoistway and cars; (c)(13)--Emergency stop switch located in the car; (c)(14)(i... approved by OSHA under Section 18 of the Occupational Safety and Health (OSH) Act (29 U.S.C. 667) and 29...

Populating the Semantic Web

DTIC Science & Technology

2004-07-01

Cars domain. We wrapped two used cars sites — Anaheim Lincoln Mer- cury and Mercedes Benz of Laguna Niguel — and collected on the order of 250 records...Make Mileage Engine < 1.31± 0.46 > < 2.38± 0.92 > < 3.83± 0.38 > [ mercedes , benz ] [47K] [5 . 0l v8] [ford] [21 , 3DIGIT] [4 . 3l v8] [mercury] [20

40 CFR Appendix Xiii to Part 86 - State Requirements Incorporated by Reference in Part 86 of the Code of Federal Regulations

Code of Federal Regulations, 2012 CFR

2012-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Pt. 86, App. XIII Appendix XIII to Part 86—State...-Line Test Procedures for 1983 Through 1997 Model-Year Passenger Cars, Light-Duty Trucks and Medium-Duty...: California Assembly-Line Test Procedures for 1998 and Subsequent Model-Year Passenger Cars, Light-Duty Trucks...

40 CFR Appendix Xiii to Part 86 - State Requirements Incorporated by Reference in Part 86 of the Code of Federal Regulations

Code of Federal Regulations, 2013 CFR

2013-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Pt. 86, App. XIII Appendix XIII to Part 86—State...-Line Test Procedures for 1983 Through 1997 Model-Year Passenger Cars, Light-Duty Trucks and Medium-Duty...: California Assembly-Line Test Procedures for 1998 and Subsequent Model-Year Passenger Cars, Light-Duty Trucks...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2012 CFR

2012-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2014 CFR

2014-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2013 CFR

2013-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

40 CFR Appendix Xiii to Part 86 - State Requirements Incorporated by Reference in Part 86 of the Code of Federal Regulations

Code of Federal Regulations, 2011 CFR

2011-07-01

... AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Pt. 86, App. XIII Appendix XIII to Part 86—State...-Line Test Procedures for 1983 Through 1997 Model-Year Passenger Cars, Light-Duty Trucks and Medium-Duty...: California Assembly-Line Test Procedures for 1998 and Subsequent Model-Year Passenger Cars, Light-Duty Trucks...

Alternative Fuels Data Center: Natural Gas Vehicles Make a Difference in

Science.gov Websites

District built a clean fuel alliance for natural gas vehicles in Tennessee. For information about this car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug. 2, 2014 Photo of a TennesseeA> Natural Gas Vehicles Make a Difference in Tennessee to someone by E-mail Share

Alternative Fuels Data Center: Yellowstone Park Recycles Vehicle Batteries

Science.gov Websites

school bus Michigan Transports Students in Hybrid Electric School Buses Jan. 4, 2014 Photo of a natural of a school bus. California School District Creates First-of-Its-Kind Zero-Emissions Bus Dec. 20 , 2014 Photo of an electric car. College Students Engineer Efficient Vehicles in EcoCAR 2 Competition Aug

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2011 CFR

2011-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

49 CFR 174.112 - Loading Division 1.3 materials and Division 1.2 (explosive) materials (Also see § 174.101).

Code of Federal Regulations, 2010 CFR

2010-10-01

... materials and Division 1.2 (explosive) materials may not be loaded, transported or stored in a rail car equipped with any type of lighted heater or open-flame device, or in a rail car equipped with any apparatus or mechanism utilizing an internal combustion engine in its operation. (b) Except as provided in...

Development and Evaluation of an Optimal Human Single-Chain Variable Fragment-Derived BCMA-Targeted CAR T Cell Vector.

PubMed

Smith, Eric L; Staehr, Mette; Masakayan, Reed; Tatake, Ishan J; Purdon, Terence J; Wang, Xiuyan; Wang, Pei; Liu, Hong; Xu, Yiyang; Garrett-Thomson, Sarah C; Almo, Steven C; Riviere, Isabelle; Liu, Cheng; Brentjens, Renier J

2018-06-06

B cell maturation antigen (BCMA) has recently been identified as an important multiple myeloma (MM)-specific target for chimeric antigen receptor (CAR) T cell therapy. In CAR T cell therapy targeting CD19 for lymphoma, host immune anti-murine CAR responses limited the efficacy of repeat dosing and possibly long-term persistence. This clinically relevant concern can be addressed by generating a CAR incorporating a human single-chain variable fragment (scFv). We screened a human B cell-derived scFv phage display library and identified a panel of BCMA-specific clones from which human CARs were engineered. Despite a narrow range of affinity for BCMA, dramatic differences in CAR T cell expansion were observed between unique scFvs in a repeat antigen stimulation assay. These results were confirmed by screening in a MM xenograft model, where only the top preforming CARs from the repeat antigen stimulation assay eradicated disease and prolonged survival. The results of this screening identified a highly effective CAR T cell therapy with properties, including rapid in vivo expansion (>10,000-fold, day 6), eradication of large tumor burden, and durable protection to tumor re-challenge. We generated a bicistronic construct including a second-generation CAR and a truncated-epithelial growth factor receptor marker. CAR T cell vectors stemming from this work are under clinical investigation. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy

PubMed Central

Maus, Marcela V.; June, Carl H.

2016-01-01

Chimeric antigen receptors (CARs) are engineered fusion proteins constructed from antigen recognition, signaling, and costimulatory domains that can be expressed in cytotoxic T cells with the purpose of reprograming the T cells to specifically target tumor cells. CAR T-cell therapy uses gene transfer technology to reprogram a patient's own T cells to stably express CARs, thereby combining the specificity of an antibody with the potent cytotoxic and memory functions of a T cell. In early phase clinical trials, CAR T cells targeting CD19 have resulted in sustained complete responses within a population of otherwise refractory patients with B-cell malignancies and, more specifically, have shown complete response rates of ≈90% in patients with relapsed or refractory acute lymphoblastic leukemia. Given this clinical efficacy, preclinical development of CAR T-cell therapy for a number of cancer indications has been actively investigated, and the future of the CAR T-cell field is extensive and dynamic. Several approaches to increase the feasibility and safety of CAR T cells are currently being explored, including investigation into mechanisms regulating the persistence of CAR T cells. Additionally, numerous early-phase clinical trials are now investigating CAR T-cell therapy beyond targeting CD19, especially in solid tumors. Trials investigating combinations of CAR T cells with immune checkpoint blockade therapies are now beginning and results are eagerly awaited. This review evaluates several of the ongoing and future directions of CAR T-cell therapy. PMID:27084741

Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

PubMed

Boardman, D A; Philippeos, C; Fruhwirth, G O; Ibrahim, M A A; Hannen, R F; Cooper, D; Marelli-Berg, F M; Watt, F M; Lechler, R I; Maher, J; Smyth, L A; Lombardi, G

2017-04-01

Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Hybrid and electric low-noise cars cause an increase in traffic accidents involving vulnerable road users in urban areas.

PubMed

Brand, Stephan; Petri, Maximilian; Haas, Philipp; Krettek, Christian; Haasper, Carl

2013-01-01

Due to resource scarcity, the number of low-noise and electric cars is expected to increase rapidly. The frequent use of these cars will lead to a significant reduction of traffic related noise and pollution. On the other hand, due to the adaption and conditioning of vulnerable road users the number of traffic accidents involving pedestrians and bicyclists is postulated to increase as well. Children, older people with reduced eyesight and the blind are especially reliant on a combination of acoustic and visual warning signals with approaching or accelerating vehicles. This is even more evident in urban areas where the engine sound is the dominating sound up to 30 kph (kilometres per hour). Above this, tyre-road interaction is the main cause of traffic noise. With the missing typical engine sound a new sound design is necessary to prevent traffic accidents in urban areas. Drivers should not be able to switch the sound generator off.

CooLN2Car: An Experimental Car Which Uses Liquid Nitrogen as Its Fuel

NASA Astrophysics Data System (ADS)

Parker, M. E.; Plummer, M. C.; Ordonez, C. A.

1997-10-01

A ``cryogenic" heat engine which operates using the atmosphere as a heat source and a cryogenic medium as a heat sink has been incorporated as the power system for an automobile. A 1973 Volkswagen Beetle has been converted and uses liquid nitrogen as its ``fuel." A Dewar was mounted in the car and provides nitrogen under pressure to two heat exchangers connected in parallel which use atmospheric heat to heat the nitrogen. The heat exchangers deliver compressed nitrogen gas to a vane-type pneumatic motor mounted in place of the original gasoline engine. Pressure in the tank is maintained internally at 1.2 MPa and is reduced to 0.7 MPa before the motor by a pressure regulator. A throttle, composed of a butterfly valve, is mounted between the regulator and the motor and is connected to the driver's accelerator peddle. The vehicle has good acceleration, a maximum range of 15 miles, and a maximum speed of 25 mph. A demonstration with the vehicle is planned.

Prospects for adoptive immunotherapy of pancreatic cancer using chimeric antigen receptor-engineered T-cells.

PubMed

Alrifai, Doraid; Sarker, Debashis; Maher, John

2016-01-01

Adoptive immunotherapy using chimeric antigen receptor (CAR) engineered T-cells is emerging as a powerful new approach to cancer immunotherapy. CARs are fusion molecules that couple the antibody-like binding of a native cell surface target to the delivery of a bespoke T-cell activating signal. Recent studies undertaken by several centers have demonstrated highly compelling efficacy in patients with acute and chronic B-cell malignancies. However, comparable therapeutic activity has not been achieved in solid tumors. Modern management of pancreatic ductal adenocarcinoma (PDAC) remains ineffective, reflected in the virtual equivalence of annual incidence and mortality statistics for this tumor type. Increasing evidence indicates that these tumors are recognized by the immune system, but deploy powerful evasion strategies that limit natural immune surveillance and render efforts at immunotherapy challenging. Here, we review preclinical and clinical studies that have been initiated or completed in an effort to develop CAR-based immunotherapy for PDAC. We also consider the hurdles to the effective clinical development of this exciting new therapeutic modality.

The Otto-engine-equivalent vehicle concept

NASA Technical Reports Server (NTRS)

Dowdy, M. W.; Couch, M. D.

1978-01-01

A vehicle comparison methodology based on the Otto-Engine Equivalent (OEE) vehicle concept is described. As an illustration of this methodology, the concept is used to make projections of the fuel economy potential of passenger cars using various alternative power systems. Sensitivities of OEE vehicle results to assumptions made in the calculational procedure are discussed. Factors considered include engine torque boundary, rear axle ratio, performance criteria, engine transient response, and transmission shift logic.

Chimeric Antigen Receptor- and TCR-Modified T Cells Enter Main Street and Wall Street.

PubMed

Barrett, David M; Grupp, Stephan A; June, Carl H

2015-08-01

The field of adoptive cell transfer (ACT) is currently comprised of chimeric Ag receptor (CAR)- and TCR-engineered T cells and has emerged from principles of basic immunology to paradigm-shifting clinical immunotherapy. ACT of T cells engineered to express artificial receptors that target cells of choice is an exciting new approach for cancer, and it holds equal promise for chronic infection and autoimmunity. Using principles of synthetic biology, advances in immunology, and genetic engineering have made it possible to generate human T cells that display desired specificities and enhanced functionalities. Clinical trials in patients with advanced B cell leukemias and lymphomas treated with CD19-specific CAR T cells have induced durable remissions in adults and children. The prospects for the widespread availability of engineered T cells have changed dramatically given the recent entry of the pharmaceutical industry to this arena. In this overview, we discuss some of the challenges and opportunities that face the field of ACT. Copyright © 2015 by The American Association of Immunologists, Inc.

Near-field engineering of Fano resonances in a plasmonic assembly for maximizing CARS enhancements.

PubMed

He, Jinna; Fan, Chunzhen; Ding, Pei; Zhu, Shuangmei; Liang, Erjun

2016-02-10

Surface enhanced coherent anti-Stokes Raman scattering (SECARS) is a sensitive tool and promising for single molecular detection and chemical selective imaging. However, the enhancement factors (EF) were only 10~100 for colloidal silver and gold nanoparticles usually used as SECARS substrates. In this paper, we present a design of SECARS substrate consisting of three asymmetric gold disks and strategies for maximizing the EF by engineering near-field properties of the plasmonic Fano nanoassembly. It is found that the E-field "hot spots" corresponding to three different frequencies involved in SECARS process can be brought to the same spatial locations by tuning incident orientations, giving rise to highly confined SECARS "hot spots" with the EF reaching single-molecule sensitivity. Besides, an even higher EF of SECARS is achieved by introducing double Fano resonances in this plasmonic nanoassembly via further enlarging the sizes of the constituent disks. These findings put an important step forward to the plasmonic substrate design for SECARS as well as for other nonlinear optical processes.

Selective Inhibition of Tumor Growth by Clonal NK Cells Expressing an ErbB2/HER2-Specific Chimeric Antigen Receptor

PubMed Central

Schönfeld, Kurt; Sahm, Christiane; Zhang, Congcong; Naundorf, Sonja; Brendel, Christian; Odendahl, Marcus; Nowakowska, Paulina; Bönig, Halvard; Köhl, Ulrike; Kloess, Stephan; Köhler, Sylvia; Holtgreve-Grez, Heidi; Jauch, Anna; Schmidt, Manfred; Schubert, Ralf; Kühlcke, Klaus; Seifried, Erhard; Klingemann, Hans G; Rieger, Michael A; Tonn, Torsten; Grez, Manuel; Wels, Winfried S

2015-01-01

Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expanding and clinically usable established human NK-92 cells to the tumor-associated ErbB2 (HER2) antigen. Following GMP-compliant procedures, we generated a stable clonal cell line expressing a humanized CAR based on ErbB2-specific antibody FRP5 harboring CD28 and CD3ζ signaling domains (CAR 5.28.z). These NK-92/5.28.z cells efficiently lysed ErbB2-expressing tumor cells in vitro and exhibited serial target cell killing. Specific recognition of tumor cells and antitumor activity were retained in vivo, resulting in selective enrichment of NK-92/5.28.z cells in orthotopic breast carcinoma xenografts, and reduction of pulmonary metastasis in a renal cell carcinoma model, respectively. γ-irradiation as a potential safety measure for clinical application prevented NK cell replication, while antitumor activity was preserved. Our data demonstrate that it is feasible to engineer CAR-expressing NK cells as a clonal, molecularly and functionally well-defined and continuously expandable cell therapeutic agent, and suggest NK-92/5.28.z cells as a promising candidate for use in adoptive cancer immunotherapy. PMID:25373520

Lean Gasoline System Development for Fuel Efficient Small Cars

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

Smith, Stuart R.

2013-11-25

The General Motors and DOE cooperative agreement program DE-EE0003379 is completed. The program has integrated and demonstrated a lean-stratified gasoline engine, a lean aftertreatment system, a 12V Stop/Start system and an Active Thermal Management system along with the necessary controls that significantly improves fuel efficiency for small cars. The fuel economy objective of an increase of 25% over a 2010 Chevrolet Malibu and the emission objective of EPA T2B2 compliance have been accomplished. A brief review of the program, summarized from the narrative is: The program accelerates development and synergistic integration of four cost competitive technologies to improve fuel economymore » of a light-duty vehicle by at least 25% while meeting Tier 2 Bin 2 emissions standards. These technologies can be broadly implemented across the U.S. light-duty vehicle product line between 2015 and 2025 and are compatible with future and renewable biofuels. The technologies in this program are: lean combustion, innovative passive selective catalyst reduction lean aftertreatment, 12V stop/start and active thermal management. The technologies will be calibrated in a 2010 Chevrolet Malibu mid-size sedan for final fuel economy demonstration.« less

KSC-2011-7889

NASA Image and Video Library

2011-11-23

CAPE CANAVERAL, Fla. – Families visiting the Kennedy Space Center Visitor Complex in Florida participate in a LEGO "Build the Future" event. The festivities coincide with the launch of NASA's Mars Science Laboratory (MSL), carrying a compact car-sized rover, Curiosity, to the red planet. Part of the Space Act Agreement between NASA and LEGO A/S, the activities are designed to inspire students of every age to consider an education and careers in the science, technology, engineering and mathematics, or STEM, disciplines. Launch of MSL aboard a United Launch Alliance Atlas V rocket is scheduled for Nov. 26 from Space Launch Complex-41 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/audience/foreducators/nasa-lego-partnership.html. Photo credit: NASA/Kim Shiflett

Five-cylinder engine as an economical, smooth-running power plant

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

Hauk, F.; Dommes, W.

For the first time in the history of automobile engineering, AUDI NSU has introduced a 5-cylinder in-line gasoline engine for production cars designed to run at speeds up to about 7,000 rpm. This unusual new design makes it possible to set new standards of performance and smoothness, while still retaining the advantages of front wheel drive.

Service Cart For Engines

NASA Technical Reports Server (NTRS)

Ng, Gim Shek

1995-01-01

Cart supports rear-mounted air-cooled engine from Volkswagen or Porsche automobile. One person removes, repairs, tests, and reinstalls engine of car, van, or home-built airplane. Consists of framework of wood, steel, and aluminum components supported by four wheels. Engine lifted from vehicle by hydraulic jack and gently lowered onto waiting cart. Jack removed from under engine. Rear of vehicle raised just enough that engine can be rolled out from under it. Cart easily supports 200-lb engine. Also used to hold transmission. With removable sheet-metal top, cart used as portable seat.

76 FR 19518 - Safety Advisory 2011-01

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... Jersey, when a conventional two-person switching crew was shoving rolling equipment into an industrial facility. The locomotive engineer was in the locomotive control compartment and the conductor was..., engineer, and a conductor-in-training was switching cars on a switching lead track and using various other...

49 CFR 571.124 - Standard No. 124; Accelerator control systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... and injuries resulting from engine overspeed caused by malfunctions in the accelerator control system. S3. Application. This standard applies to passenger cars, multi-purpose passenger vehicles, trucks... components, except the fuel metering device, that regulate engine speed in direct response to movement of the...

Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

PubMed

Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

2018-01-01

Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

Folate receptor 1 (FOLR1) targeted chimeric antigen receptor (CAR) T cells for the treatment of gastric cancer

PubMed Central

Pyo, Suhkneung; Kang, Chung Hyo; Lee, Chong Ock; Lee, Heung Kyoung; Choi, Sang Un; Park, Chi Hoon

2018-01-01

Gastric cancer is a malignancy that has a high mortality rate. Although progress has been made in the treatment of gastric cancer, many patients experience cancer recurrence and metastasis. Folate receptor 1 (FOLR1) is overexpressed on the cell surface in over one-third of gastric cancer patients, but rarely is expressed in normal tissue. This makes FOLR1 a potential target for chimeric antigen receptor (CAR) T cell immunotherapy, although the function of FOLR1 has not been elucidated. CAR are engineered fusion receptor composed of an antigen recognition region and signaling domains. T cells expressing CAR have specific activation and cytotoxic effects against cancer cells containing the target antigen. In this study, we generated a CAR that targets FOLR1 composed of a single-chain variable fragment (scFv) of FOLR1 antibody and signaling domains consisting of CD28 and CD3ζ. Both FOLR1-CAR KHYG-1, a natural killer cell line, and FOLR1-CAR T cells recognized FOLR1-positive gastric cancer cells in a MHC-independent manner and induced secretion of various cytokines and caused cell death. Conclusively, this is the first study to demonstrate that CAR KHYG-1/T cells targeting FOLR1 are effective against FOLR1-positive gastric cancer cells. PMID:29874279

Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T-lymphocytes

PubMed Central

Caruana, Ignazio; Savoldo, Barbara; Hoyos, Valentina; Weber, Gerrit; Liu, Hao; Kim, Eugene S.; Ittmann, Michael M.; Marchetti, Dario; Dotti, Gianpietro

2015-01-01

Adoptive transfer of chimeric antigen receptor (CAR)-redirected T lymphocytes (CAR-T cells) has had less striking effects in solid tumors1–3 than in lymphoid malignancies4, 5. Although active tumor-mediated immunosuppression may play a role in limiting efficacy6, functional changes in T lymphocytes following their ex vivo manipulation may also account for cultured CAR-T cells’ reduced ability to penetrate stroma-rich solid tumors. We therefore studied the capacity of human in vitro-cultured CAR-T cells to degrade components of the extracellular matrix (ECM). In contrast to freshly isolated T lymphocytes, we found that in vitro-cultured T lymphocytes lack expression of the enzyme heparanase (HPSE) that degrades heparan sulphate proteoglycans, which are main components of ECM. We found that HPSE mRNA is down regulated in in vitro-expanded T cells, which may be a consequence of p53 binding to the HPSE gene promoter. We therefore engineered CAR-T cells to express HPSE and showed improved capacity to degrade ECM, which promoted tumor T-cell infiltration and antitumor activity. Employing this strategy may enhance the activity of CAR-T cells in individuals with stroma-rich solid tumors. PMID:25849134

A statistical analysis of seat belt effectiveness in 1973-1975 model cars involved in towaway crashes. Volume 1

DOT National Transportation Integrated Search

1976-09-01

Standardized injury rates and seat belt effectiveness measures are derived from a probability sample of towaway accidents involving 1973-1975 model cars. The data were collected in five different geographic regions. Weighted sample size available for...

Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice.

PubMed

Chinnasamy, Dhanalakshmi; Yu, Zhiya; Theoret, Marc R; Zhao, Yangbing; Shrimali, Rajeev K; Morgan, Richard A; Feldman, Steven A; Restifo, Nicholas P; Rosenberg, Steven A

2010-11-01

Immunotherapies based on adoptive cell transfer are highly effective in the treatment of metastatic melanoma, but the use of this approach in other cancer histologies has been hampered by the identification of appropriate target molecules. Immunologic approaches targeting tumor vasculature provide a means for the therapy of multiple solid tumor types. We developed a method to target tumor vasculature, using genetically redirected syngeneic or autologous T cells. Mouse and human T cells were engineered to express a chimeric antigen receptor (CAR) targeted against VEGFR-2, which is overexpressed in tumor vasculature and is responsible for VEGF-mediated tumor progression and metastasis. Mouse and human T cells expressing the relevant VEGFR-2 CARs mediated specific immune responses against VEGFR-2 protein as well as VEGFR-2-expressing cells in vitro. A single dose of VEGFR-2 CAR-engineered mouse T cells plus exogenous IL-2 significantly inhibited the growth of 5 different types of established, vascularized syngeneic tumors in 2 different strains of mice and prolonged the survival of mice. T cells transduced with VEGFR-2 CAR showed durable and increased tumor infiltration, correlating with their antitumor effect. This approach provides a potential method for the gene therapy of a variety of human cancers.

Toward reconciling instantaneous roadside measurements of light duty vehicle exhaust emissions with type approval driving cycles.

PubMed

Rhys-Tyler, Glyn A; Bell, Margaret C

2012-10-02

A method is proposed to relate essentially instantaneous roadside measurements of vehicle exhaust emissions, with emission results generated over a type approval driving cycle. An urban remote sensing data set collected in 2008 is used to define the dynamic relationship between vehicle specific power and exhaust emissions, across a range of vehicle ages, engine capacities, and fuel types. The New European Driving Cycle is synthesized from the remote sensing data using vehicle specific power to characterize engine load, and the results compared with official published emissions data from vehicle type approval tests over the same driving cycle. Mean carbon monoxide emissions from gasoline-powered cars ≤ 3 years old measured using remote sensing are found to be 1.3 times higher than published original type approval test values; this factor increases to 2.2 for cars 4-8 years old, and 6.4 for cars 9-12 years old. The corresponding factors for diesel cars are 1.1, 1.4, and 1.2, respectively. Results for nitric oxide, hydrocarbons, and particulate matter are also reported. The findings have potential implications for the design of traffic management interventions aimed at reducing emissions, fleet inspection and maintenance programs, and the specification of vehicle emission models.

A chimeric switch-receptor targeting PD1 augments the efficacy of second generation CAR T-Cells in advanced solid tumors

PubMed Central

Liu, Xiaojun; Ranganathan, Raghuveer; Jiang, Shuguang; Fang, Chongyun; Sun, Jing; Kim, Soyeon; Newick, Kheng; Lo, Albert; June, Carl H.; Zhao, Yangbing; Moon, Edmund K.

2015-01-01

Chimeric antigen receptor (CAR)-modified adoptive T-cell therapy (ATC) has been successfully applied to the treatment of hematologic malignancies, but faces many challenges in solid tumors. One major obstacle is the immune-suppressive effects induced in both naturally-occurring and genetically-modified tumor infiltrating lymphocytes (TILs) by inhibitory receptors (IRs), namely PD1. We hypothesized that interfering with PD1 signaling would augment CAR T cell activity against solid tumors. To address this possibility, we introduced a genetically-engineered switch receptor construct, comprising the truncated extracellular domain of PD1 and the transmembrane and cytoplasmic signaling domains of CD28, into CAR T-cells. We tested the effect of this supplement, “PD1CD28”, on human CAR T-cells targeting aggressive models of human solid tumors expressing relevant tumor antigens. Treatment of mice bearing large, established solid tumors with PD1CD28 CAR T-cells led to significant regression in tumor volume due to enhanced CAR TIL infiltrate, decreased susceptibility to tumor-induced hypofunction, and attenuation of IR expression compared to treatments with CAR T-cells alone or PD1 antibodies. Taken together, our findings suggest that the application of PD1CD28 to boost CAR T-cell activity is efficacious against solid tumors via a variety of mechanisms, prompting clinical investigation of this potentially promising treatment modality. PMID:26979791

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor

PubMed Central

Wu, Chia-Yung; Roybal, Kole T.; Puchner, Elias M.; Onuffer, James; Lim, Wendell A.

2016-01-01

There is growing promise in using engineered cells as therapeutic agents. For example, synthetic Chimeric Antigen Receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, excessive activity and poor control over such engineered T cells can cause severe toxicities. We present the design of “ON-switch” CARs that enable small molecule-control over T cell therapeutic functions, while still retaining antigen specificity. In these split receptors, antigen binding and intracellular signaling components only assemble in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate both cell autonomous recognition and user control. PMID:26405231

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor.

PubMed

Wu, Chia-Yung; Roybal, Kole T; Puchner, Elias M; Onuffer, James; Lim, Wendell A

2015-10-16

There is growing interest in using engineered cells as therapeutic agents. For example, synthetic chimeric antigen receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, these engineered T cells can exhibit excessive activity that is difficult to control and can cause severe toxicity. We designed "ON-switch" CARs that enable small-molecule control over T cell therapeutic functions while still retaining antigen specificity. In these split receptors, antigen-binding and intracellular signaling components assemble only in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate cell-autonomous recognition and user control. Copyright © 2015, American Association for the Advancement of Science.

Torque coordinating robust control of shifting process for dry dual clutch transmission equipped in a hybrid car

NASA Astrophysics Data System (ADS)

Zhao, Z.-G.; Chen, H.-J.; Yang, Y.-Y.; He, L.

2015-09-01

For a hybrid car equipped with dual clutch transmission (DCT), the coordination control problems of clutches and power sources are investigated while taking full advantage of the integrated starter generator motor's fast response speed and high accuracy (speed and torque). First, a dynamic model of the shifting process is established, the vehicle acceleration is quantified according to the intentions of the driver, and the torque transmitted by clutches is calculated based on the designed disengaging principle during the torque phase. Next, a robust H∞ controller is designed to ensure speed synchronisation despite the existence of model uncertainties, measurement noise, and engine torque lag. The engine torque lag and measurement noise are used as external disturbances to initially modify the output torque of the power source. Additionally, during the torque switch phase, the torque of the power sources is smoothly transitioned to the driver's demanded torque. Finally, the torque of the power sources is further distributed based on the optimisation of system efficiency, and the throttle opening of the engine is constrained to avoid sharp torque variations. The simulation results verify that the proposed control strategies effectively address the problem of coordinating control of clutches and power sources, establishing a foundation for the application of DCT in hybrid cars.

Prospects for chimeric antigen receptor (CAR) γδ T cells: A potential game changer for adoptive T cell cancer immunotherapy.

PubMed

Mirzaei, Hamid Reza; Mirzaei, Hamed; Lee, Sang Yun; Hadjati, Jamshid; Till, Brian G

2016-10-01

Excitement is growing for therapies that harness the power of patients' immune systems to combat their diseases. One approach to immunotherapy involves engineering patients' own T cells to express a chimeric antigen receptor (CAR) to treat advanced cancers, particularly those refractory to conventional therapeutic agents. Although these engineered immune cells have made remarkable strides in the treatment of patients with certain hematologic malignancies, success with solid tumors has been limited, probably due to immunosuppressive mechanisms in the tumor niche. In nearly all studies to date, T cells bearing αβ receptors have been used to generate CAR T cells. In this review, we highlight biological characteristics of γδ T cells that are distinct from those of αβ T cells, including homing to epithelial and mucosal tissues and unique functions such as direct antigen recognition, lack of alloreactivity, and ability to present antigens. We offer our perspective that these features make γδ T cells promising for use in cellular therapy against several types of solid tumors, including melanoma and gastrointestinal cancers. Engineered γδ T cells should be considered as a new platform for adoptive T cell cancer therapy for mucosal tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Study of intake manifold for Universiti Malaysia Perlis automotive racing team formula student race car

NASA Astrophysics Data System (ADS)

Norizan, A.; Rahman, M. T. A.; Amin, N. A. M.; Basha, M. H.; Ismail, M. H. N.; Hamid, A. F. A.

2017-10-01

This paper describes the design differences between the intake manifold and restrictor used in racing cars that participate in the Formula Student (FSAE) competition. To fulfil the criteria of rules and regulation of the race, each race car must have a restriction device that has a maximum diameter of 20 mm installed between the throttle body and intake manifold. To overcome these problems, a restrictor has been designed and analysed using the steady state analysis, to reduce the loss of pressure in the restrictor. Design of the restrictor has a fixed parameter of the maximum diameter of 20mm. There are some differences that have been taken to make the comparison between the design of the restrictor, the diameter of the inlet and outlet, the curvature of the surface, convergence and divergence angle and length of the restrictor. Intake manifold was designed based on the design of the chassis, which shall not exceed the envelope defined by the FSAE competition. A good intake manifold design will affect the performance of the engine. Each design have made an analysis designed to ensure that each cylinder engine gets its air evenly. To verify the design, steady state analysis was made for a total mass flow rate and the velocity of air leaving a runner in each engine. Data such as the engine MAP reading was recorded by using Haltech ECU Management Software as reference purposes.

Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy.

PubMed

Tang, Xiang-Jun; Sun, Xu-Yong; Huang, Kuan-Ming; Zhang, Li; Yang, Zhuo-Shun; Zou, Dan-Dan; Wang, Bin; Warnock, Garth L; Dai, Long-Jun; Luo, Jie

2015-12-29

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.

Application for certification 1988 model year light-duty vehicles - US Technical Research Company (Peugeot)

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

Not Available

Every year, each manufacturer of passenger cars, light-duty trucks, motorcycles, or heavy-duty engines submits to EPA an application for certification. In the application, the manufacturer gives a detailed technical description of the vehicles or engines he intends to market during the upcoming model year. These engineering data include explanations and/or drawings that describe engine/vehicle parameters such as basic engine design, fuel systems, ignition systems, and exhaust and evaporative emission control systems.

Measurement of locomotive head end power engine fuel and emissions : draft final report.

DOT National Transportation Integrated Search

2015-09-01

In the U.S., there were more than 5,000 commuter rail diesel locomotives in use in 2011. Many of these have head end : power (HEP) engines that provide power for hotel services in the passenger cars. The North Carolina Department of : Transportation ...

10 Tips to Protect Yourself from Unhealthy Air

MedlinePlus

... parts of the country. Use hand-powered or electric lawn care equipment rather than gasoline-powered. Old two-stroke engines like lawnmowers and leaf or snow blowers often have no pollution control devices. They can pollute the air even more than cars, though engines sold since 2011 are cleaner. Don' ...

76 FR 10024 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-23

... Engine Testing Program (Renewal) AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY... electronic docket, go to http://www.regulations.gov . Title: EPA's In-Use Vehicle and Engine Testing Programs...-use light-duty (passenger car and light truck) motor vehicles. This program operates in conjunction...

Engineering at the Elementary Level

ERIC Educational Resources Information Center

McGrew, Cheryl

2012-01-01

Can engineering technology be taught at the elementary level? Designing and building trebuchets, catapults, solar cars, and mousetrap vehicles in a west central Florida elementary class was considered very unusual in recent years. After a review of current research on failing schools and poor curriculum, the author wondered what her school could…

Progress in industrial holography in France

NASA Astrophysics Data System (ADS)

Smigielski, Paul

1992-01-01

Industrial applications of holography in France are briefly reviewed. Particular attention is given to nondestructive testing of helicopter blades at Aerospatiale Central Laboratory, the use of holography at Renault for car-engine vibration study, vibration characterization of turbo-jet engine components at SNECMA, and vibration analysis of plates in an industrial hemodynamic tunnel.

Stop/Start: Driving

Science.gov Websites

/generator visible. The car is moving. There are purple arrows flowing from the gasoline engine to the electric starter/generator. There are red arrows flowing from the gasoline engine to the front wheels . There are blue arrows flowing from the electric starter/generator to the battery. Main stage: See

Relationship Between Vehicle Size and Fatality Risk in Model Year 1985-93 Passenger Cars and Light Trucks

DOT National Transportation Integrated Search

1997-01-01

Fatality rates per million exposure years are computed by make, model and model year, : based on the crash experience of model year 1985-93 passenger cars and light trucks (pickups) vans : and sport utility vehicles) in the United States during calen...

Scaling Study of Wave Rotor Turbo-normalization of a Small Internal Combustion Engine

DTIC Science & Technology

2012-09-01

14 Figure 6: Acceleration response of turbocharger versus Comprex...for increased engine performance. Turbo-normalization can be accomplished through the addition of a turbocharger , supercharger, or a pressure wave... turbocharger over the same test regime (12). The Comprex® was first used on a passenger car in 1978 on an Opel 2.1 liter diesel engine (13). In 1987

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

Dowdy, M.W.; Couch, M.D.

A vehicle comparison methodology based on the Otto-Engine Equivalent (OEE) vehicle concept is described. As an illustration of this methodology, the concept is used to make projections of the fuel economy potential of passenger cars using various alternative power systems. Sensitivities of OEE vehicle results to assumptions made in the calculational procedure are discussed. Factors considered include engine torque boundary, rear axle ratio, performance criteria, engine transient response, and transmission shift logic.

Fall Protection Procedures for Sealing Bulk Waste Shipments by Rail Cars at Formerly Utilized Sites Remedial Action Program (FUSRAP) Sites - 13509

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

Boyle, J.D.; Fort, E. Joseph; Lorenz, William

2013-07-01

Rail-cars loaded with radioactive materials must be closed and fastened to comply with United States Department of Transportation (DOT) requirements before they shipped. Securing waste shipments in a manner that meets these regulations typically results in the use of a sealable rail-car liner. Workers accessing the tops of the 2.74 m high rail-cars to seal and inspect liners for compliance prior to shipment may be exposed to a fall hazard. Relatively recent revisions to the Fall Protection requirements in the Safety and Health Requirements Manual (EM385-1-1, U.S. Army Corps of Engineers) have necessitated modifications to the fall protection systems previouslymore » employed for rail-car loading at Formerly Utilized Sites Remedial Action Program (FUSRAP) sites. In response these projects have developed site-specific procedures to protect workers and maintain compliance with the improved fall protection regulations. (authors)« less

Nitrogen dioxide in exhaust emissions from motor vehicles

NASA Astrophysics Data System (ADS)

Lenner, Magnus

NO 2/NO x (v/v) fractions and NO 2 exhaust emission rates were determined for diesel- and gasoline-powered passenger cars and a diesel truck, at several conditions of constant engine load and speed. Vehicles with various kinds of emission control equipment were investigated. Also, integrations of NO 2/NO x percentages during Federal Test Procedure driving cycles were made for six types of passenger car. High (> 30 %) NO 2 fractions were measured for gasoline cars with air injection, and for diesel vehicles. A gasoline car with a 3-way catalyst had low NO x totals with small (< 1 %) NO 2 fractions. A passenger diesel with particle trap yielded surprisingly small (0-2%) NO 2 fractions at moderate speeds. The results have implications for NO 2 concentration in the atmosphere of northern cities during wintertime inversions, in view of the increasing use of air injection systems for passenger cars to meet legal restrictions on vehicle emissions of hydrocarbons and CO.

Self-Driving Cars and Engineering Ethics: The Need for a System Level Analysis.

PubMed

Borenstein, Jason; Herkert, Joseph R; Miller, Keith W

2017-11-13

The literature on self-driving cars and ethics continues to grow. Yet much of it focuses on ethical complexities emerging from an individual vehicle. That is an important but insufficient step towards determining how the technology will impact human lives and society more generally. What must complement ongoing discussions is a broader, system level of analysis that engages with the interactions and effects that these cars will have on one another and on the socio-technical systems in which they are embedded. To bring the conversation of self-driving cars to the system level, we make use of two traffic scenarios which highlight some of the complexities that designers, policymakers, and others should consider related to the technology. We then describe three approaches that could be used to address such complexities and their associated shortcomings. We conclude by bringing attention to the "Moral Responsibility for Computing Artifacts: The Rules", a framework that can provide insight into how to approach ethical issues related to self-driving cars.

A Cloud-Based Car Parking Middleware for IoT-Based Smart Cities: Design and Implementation

PubMed Central

Ji, Zhanlin; Ganchev, Ivan; O'Droma, Máirtín; Zhao, Li; Zhang, Xueji

2014-01-01

This paper presents the generic concept of using cloud-based intelligent car parking services in smart cities as an important application of the Internet of Things (IoT) paradigm. This type of services will become an integral part of a generic IoT operational platform for smart cities due to its pure business-oriented features. A high-level view of the proposed middleware is outlined and the corresponding operational platform is illustrated. To demonstrate the provision of car parking services, based on the proposed middleware, a cloud-based intelligent car parking system for use within a university campus is described along with details of its design, implementation, and operation. A number of software solutions, including Kafka/Storm/Hbase clusters, OSGi web applications with distributed NoSQL, a rule engine, and mobile applications, are proposed to provide ‘best’ car parking service experience to mobile users, following the Always Best Connected and best Served (ABC&S) paradigm. PMID:25429416

A cloud-based car parking middleware for IoT-based smart cities: design and implementation.

PubMed

Ji, Zhanlin; Ganchev, Ivan; O'Droma, Máirtín; Zhao, Li; Zhang, Xueji

2014-11-25

This paper presents the generic concept of using cloud-based intelligent car parking services in smart cities as an important application of the Internet of Things (IoT) paradigm. This type of services will become an integral part of a generic IoT operational platform for smart cities due to its pure business-oriented features. A high-level view of the proposed middleware is outlined and the corresponding operational platform is illustrated. To demonstrate the provision of car parking services, based on the proposed middleware, a cloud-based intelligent car parking system for use within a university campus is described along with details of its design, implementation, and operation. A number of software solutions, including Kafka/Storm/Hbase clusters, OSGi web applications with distributed NoSQL, a rule engine, and mobile applications, are proposed to provide 'best' car parking service experience to mobile users, following the Always Best Connected and best Served (ABC&S) paradigm.

Improving Therapy of Chronic Lymphocytic Leukemia (CLL) with Chimeric Antigen Receptor (CAR) T Cells

PubMed Central

Fraietta, Joseph A.; Schwab, Robert D.; Maus, Marcela V.

2016-01-01

Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically-engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and re-directing the immune system against cancer. This review will briefly summarize T cell therapies in development for CLL disease. We discuss the role of T cell function and phenotype, T cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. PMID:27040708

Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy.

PubMed

Dai, Hanren; Wang, Yao; Lu, Xuechun; Han, Weidong

2016-07-01

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. © The Author 2016. Published by Oxford University Press.

ErbB-targeted CAR T-cell immunotherapy of cancer.

PubMed

Whilding, Lynsey M; Maher, John

2015-01-01

Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy

PubMed Central

Dai, Hanren; Wang, Yao; Lu, Xuechun

2016-01-01

The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

Aerodynamic characteristics of the Fiat UNO car

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

Costelli, A.F.

1984-01-01

The purpose of this article is to describe the work conducted in the aerodynamic field throughout the 4-year development and engineering time span required by the project of the UNO car. A description is given of all the parametric studies carried out. Through these studies two types of cars at present in production were defined and the characteristics of a possible future sports version laid down. A movable device, to be fitted in the back window, was also set up and patented. When actuated it reduces soiling of back window. A description is also provided of the measurements made inmore » the car flow field and some considerations are outlined about the method applied. This method is still in development phase but it already permits some considerations and in-depth investigations to be made on the vehicle wake.« less

Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical Hematopoietic Progenitor-Cell Transplant

DTIC Science & Technology

2009-05-01

adoptive therapy using CD19-specific chimeric antigen receptor re-directed T cells for recurrent/refrctory follicular lymphoma...Beauty (SB) transposon/transposase system to express a CD19-specific chimeric antigen receptor (CAR). T cells that have undergone transposition...accomplished using genetic engineering to express a chimeric antigen receptor (CAR) to redirect the specificity of T cells for CD19 on malignant B cells

Blasting Rocks and Blasting Cars: Applied Engineering (LBNL Summer Lecture Series)

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

Hopkins, Deborah

2004-06-30

Summer Lecture Series 2004: Deb Hopkins works with industries like automobile, mining and paper to improve their evaluation and measuring techniques. For several years, she has coordinated a program at Berkeley Lab funded under the Partnership for a New Generation of Vehicles, a collaboration between the federal government and the U.S. Council for Automotive Research. Nondestructive evaluation techniques to test a car's structural integrity are being developed for auto assembly lines.

Blasting Rocks and Blasting Cars: Applied Engineering (LBNL Summer Lecture Series)

ScienceCinema

Hopkins, Deborah [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Engineering Division

2017-12-09

Summer Lecture Series 2004: Deb Hopkins works with industries like automobile, mining and paper to improve their evaluation and measuring techniques. For several years, she has coordinated a program at Berkeley Lab funded under the Partnership for a New Generation of Vehicles, a collaboration between the federal government and the U.S. Council for Automotive Research. Nondestructive evaluation techniques to test a car's structural integrity are being developed for auto assembly lines.

A curious autopsy case of accidental carbon monoxide poisoning in a motor vehicle.

PubMed

Kumazawa, T; Watanabe-Suzuki, K; Seno, H; Ishii, A; Suzuki, O

2000-10-01

A 26-year-old man was found dead in his car. All doors and windows were locked inside. The ignition key was in the "on" position; but the engine was not running and the fuel tank was empty. His post-mortem lividity was cherry-pink, and marked congestion was observed in the lungs and brain macroscopically. Massive intracardiac blood containing a small amount of cruor was found in the heart. In histological examination of the heart, partial disarrangement or necrosis was found in the myocardium. The liver cells showed derangement and degenerative changes, with focal lymphocyte infiltration in the portal regions, although they were not severe. The chemical tests showed that the blood concentration of carboxyhemoglobin was 46.6%. Stimulants were also detected from his blood and urine; the concentrations of methamphetamine and amphetamine were 3.25 and 0.84 microg/ml, respectively, for his cardiac blood. Therefore, it seemed reasonable to judge that the cause of his death was carbon monoxide poisoning; the cardiomyopathy and the presence of stimulants in blood might facilitate his death. Upon careful investigation of his car, it was disclosed that exhaust gas, leaked from small holes of the exhaust pipe due to rust-through, invaded the interior through four holes on the floor of the car during parking with the engine being on for the purpose of air-conditioning of the interior. It is very common to commit suicide by introducing exhaust gas into an interior of a closed motor car, but the present accidental case of carbon monoxide poisoning in a car seems rare and worthwhile reporting.

Development and Implementation of Degree Programs in Electric Drive Vehicle Technology

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

Ng, Simon

2013-09-30

The Electric-drive Vehicle Engineering (EVE) MS degree and graduate certificate programs have been continuing to make good progress, thanks to the funding and the guidance from DOE grant management group, the support from our University and College administrations, and to valuable inputs and feedback from our Industrial Advisory Board as well as our project partners Macomb Community College and NextEnergy. Table 1 below lists originally proposed Statement of Project Objectives (SOPO), which have all been completed successfully. Our program and course enrollments continue to be good and increasing, as shown in later sections. Our graduating students continue to get goodmore » job offers from local EV-related companies. Following the top recommendation from our Industrial Advisory Board, we were fortunate enough to be accepted into the prestigious EcoCAR2 (http://www.ecocar2.org/) North America university design competition, and have been having some modest success with the competition. But most importantly, EcoCAR2 offers the most holistic educational environment for integrating real-world engineering and design with our EVE graduate curriculum. Such integrations include true real-world hands-on course projects based on EcoCAR2 related tasks for the students, and faculty curricular and course improvements based on lessons and best practices learned from EcoCAR2. We are in the third and last year of EcoCAR2, and we have already formed a core group of students in pursuit of EcoCAR”3”, for which the proposal is due in early December.« less

A novel nanobody-based target module for retargeting of T lymphocytes to EGFR-expressing cancer cells via the modular UniCAR platform

PubMed Central

Albert, Susann; Arndt, Claudia; Feldmann, Anja; Bachmann, Dominik; Koristka, Stefanie; Ludwig, Florian; Ziller-Walter, Pauline; Kegler, Alexandra; Gärtner, Sebastian; Schmitz, Marc; Ehninger, Armin; Cartellieri, Marc; Ehninger, Gerhard; Pietzsch, Hans-Jürgen; Steinbach, Jörg; Bachmann, Michael

2017-01-01

ABSTRACT Recent treatments of leukemias with chimeric antigen receptor (CAR) expressing T cells underline their impressive therapeutic potential. However, once adoptively transferred into patients, there is little scope left to shut them down after elimination of tumor cells or in case adverse side effects occur. This becomes of special relevance if they are directed against commonly expressed tumor associated antigens (TAAs) such as receptors of the ErbB family. To overcome this limitation, we recently established a modular CAR platform technology termed UniCAR. UniCARs are not directed against TAAs but instead against a unique peptide epitope on engineered recombinant targeting modules (TMs), which guide them to the target. In the absence of a TM UniCAR T cells are inactive. Thus an interruption of any UniCAR activity requires an elimination of unbound TM and the TM complexed with UniCAR T cells. Elimination of the latter one requires a disassembly of the UniCAR-TM complexes. Here, we describe a first nanobody (nb)-based TM directed against EGFR. The novel TM efficiently retargets UniCAR T cells to EGFR positive tumors and mediates highly efficient target-specific and target-dependent tumor cell lysis both in vitro and in vivo. After radiolabeling of the novel TM with 64Cu and 68Ga, we analyzed its biodistribution and clearance as well as the stability of the UniCAR-TM complexes. As expected unbound TM is rapidly eliminated while the elimination of the TM complexed with UniCAR T cells is delayed. Nonetheless, we show that UniCAR-TM complexes dissociate in vitro and in vivo in a concentration-dependent manner in line with the concept of a repeated stop and go retargeting of tumor cells via the UniCAR technology. PMID:28507794

Simulation of diesel engine emissions on the example of Fiat Panda in the NEDC test

NASA Astrophysics Data System (ADS)

Botwinska, Katarzyna; Mruk, Remigiusz; Słoma, Jacek; Tucki, Karol; Zaleski, Mateusz

2017-10-01

Road transport may be deemed a strategic branch of modern economy. Unfortunately, a rapid increase in the number of on-road motor vehicles entails some negative consequences as well, for instance, excessive concentration of exhausts produced by engines which results in deterioration of air quality. EURO emission standards which define acceptable limits for exhaust emissions of power units is an example of an activity performed in attempt to improve air quality. The EURO standard defines permissible amount of exhausts produced by a vehicle. Presently new units are examined through NEDC test. For the purpose of this thesis, a virtual test stand in a form of a computer simulation of a chassis dynamometer was used to simulate emission of a diesel engine (compression-ignition engine) in the NEDC test. Actual parameters of the 1.3 MultiJet engine of the Fiat Panda passenger car of 2014 were applied in the model. The simulation was carried out in the Matlab Simulink environment. The simulation model of the Fiat Panda passenger car enables the designation of the emission waveform for all test stages which corresponds to the values received during an approval test in real-life conditions.

U.S. Department of Energy FreedomCAR & Vehicle Technologies Program Oil Bypass Filter Technology Evaluation Fifth Quarterly Report October - December 2003

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

Larry Zirker; James Francfort

2004-02-01

This Oil Bypass Filter Technology Evaluation quarterly report (October-December 2003) details the ongoing fleet evaluation of an oil bypass filter technology by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy's FreedomCAR & Vehicle Technologies Program. Eight four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass filter systems from the puraDYN Corporation. The bypass filters are reported to have engine oil filtering capability of <1 micron and a built-in additive package to facilitate extended oil-drain intervals. To date, the eight buses have accumulated 324,091 test miles. Thismore » represents an avoidance of 27 oil changes, which equate to 952 quarts (238 gallons) of new oil not conserved and therefore, 952 quarts of waste oil not generated. To validate the extended oil-drain intervals, an oil-analysis regime is used to evaluate the fitness of the oil for continued service by monitoring the presence of necessary additives, undesirable contaminants, and engine-wear metals. The test fleet has been expanded to include six Chevrolet Tahoe sport utility vehicles with gasoline engines.« less

High Performances of Artificial Nacre-Like Graphene Oxide-Carrageenan Bio-Nanocomposite Films.

PubMed

Zhu, Wenkun; Chen, Tao; Li, Yi; Lei, Jia; Chen, Xin; Yao, Weitang; Duan, Tao

2017-05-16

This study was inspired by the unique multi-scale and multi-level 'brick-and-mortar' (B&M) structure of nacre layers. We prepared the B&M, environmentally-friendly graphene oxide-carrageenan (GO-Car) nanocomposite films using the following steps. A natural polyhydroxy polymer, carrageenan, was absorbed on the surface of monolayer GO nanosheets through hydrogen-bond interactions. Following this, a GO-Car hybridized film was produced through a natural drying process. We conducted structural characterization in addition to analyzing mechanical properties and cytotoxicity of the films. Scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses showed that the nanocomposite films had a similar morphology and structure to nacre. Furthermore, the results from Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Thermogravimetric (TG/DTG) were used to explain the GO-Car interaction. Analysis from static mechanical testers showed that GO-Car had enhanced Young's modulus, maximum tensile strength and breaking elongation compared to pure GO. The GO-Car nanocomposite films, containing 5% wt. of Car, was able to reach a tensile strength of 117 MPa. The biocompatibility was demonstrated using a RAW264.7 cell test, with no significant alteration found in cellular morphology and cytotoxicity. The preparation process for GO-Car films is simple and requires little time, with GO-Car films also having favorable biocompatibility and mechanical properties. These advantages make GO-Car nanocomposite films promising materials in replacing traditional petroleum-based plastics and tissue engineering-oriented support materials.

Highly efficient gene transfer using a retroviral vector into murine T cells for preclinical chimeric antigen receptor-expressing T cell therapy

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

Kusabuka, Hotaka; Fujiwara, Kento; Tokunaga, Yusuke

Adoptive immunotherapy using chimeric antigen receptor-expressing T (CAR-T) cells has attracted attention as an efficacious strategy for cancer treatment. To prove the efficacy and safety of CAR-T cell therapy, the elucidation of immunological mechanisms underlying it in mice is required. Although a retroviral vector (Rv) is mainly used for the introduction of CAR to murine T cells, gene transduction efficiency is generally less than 50%. The low transduction efficiency causes poor precision in the functional analysis of CAR-T cells. We attempted to improve the Rv gene transduction protocol to more efficiently generate functional CAR-T cells by optimizing the period ofmore » pre-cultivation and antibody stimulation. In the improved protocol, gene transduction efficiency to murine T cells was more than 90%. In addition, almost all of the prepared murine T cells expressed CAR after puromycin selection. These CAR-T cells had antigen-specific cytotoxic activity and secreted multiple cytokines by antigen stimulation. We believe that our optimized gene transduction protocol for murine T cells contributes to the advancement of T cell biology and development of immunotherapy using genetically engineered T cells. - Highlights: • We established highly efficient gene transduction protocols for murine T cells. • CD8{sup +} CAR-T cells had antigen-specific cytotoxic activity. • CD4{sup +} CAR-T cells secreted multiple cytokines by antigen stimulation. • This finding can contribute to the development of T-cell biology and immunotherapy.« less

Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies

PubMed Central

Rodgers, David T.; Mazagova, Magdalena; Hampton, Eric N.; Cao, Yu; Ramadoss, Nitya S.; Hardy, Ian R.; Schulman, Andrew; Du, Juanjuan; Wang, Feng; Singer, Oded; Ma, Jennifer; Nunez, Vanessa; Shen, Jiayin; Woods, Ashley K.; Wright, Timothy M.; Schultz, Peter G.; Kim, Chan Hyuk; Young, Travis S.

2016-01-01

Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T). The switch redirects the activity of the bio-orthogonal sCAR-T cells through the selective formation of immunological synapses, in which the sCAR-T cell, switch, and target cell interact in a structurally defined and temporally controlled manner. Optimized switches specific for CD19 controlled the activity, tissue-homing, cytokine release, and phenotype of sCAR-T cells in a dose-titratable manner in a Nalm-6 xenograft rodent model of B-cell leukemia. The sCAR–T-cell dosing regimen could be tuned to provide efficacy comparable to the corresponding conventional CART-19, but with lower cytokine levels, thereby offering a method of mitigating cytokine release syndrome in clinical translation. Furthermore, we demonstrate that this methodology is readily adaptable to targeting CD20 on cancer cells using the same sCAR-T cell, suggesting that this approach may be broadly applicable to heterogeneous and resistant tumor populations, as well as other liquid and solid tumor antigens. PMID:26759369

Increasing fuel efficiency of passenger cars with the “climate-control” system as a method of improving the ecological safety of the urban infrastructure

NASA Astrophysics Data System (ADS)

Burakova, L. N.; Burakova, A. D.; Burakova, O. D.; Dovbysh, V. O.

2018-01-01

Motor vehicle should provide safety and a high ecological standard of living for the population. One of the methods to improve the ecological friendliness of motor vehicles in particular passenger cars (cars), which are considered in this article, is the growth of their fuel economy. It is established that fuel consumption and the amount of specific emissions of harmful substances with exhaust gases of cars when using the “climate control” system depend on the effective ambient temperature, the color of the opaque car body elements, the power of the car engine and the interior volume. However, the simplest controlled factor is the color of the opaque car body elements, which is characterized by the coefficient of light reflection. In the course of experimental studies, we established the dependences of a change in fuel consumption and a share of reducing emissions of harmful substances with exhaust gases of passenger cars with the “climate control” system on the coefficient of light reflection. A method has been developed to reduce fuel consumption and the amount of specific emissions of harmful substances with the exhaust gases of passenger cars when using the “climate control” system, which involves painting the vehicle roof white and allows reducing fuel consumption by 5.5-10.3% and the amount of specific emissions of harmful substances by 0.37-1.13% (CO) and 0.47-1.08% (CH).

CAR T-cells targeting FLT3 have potent activity against FLT3-ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib.

PubMed

Jetani, Hardikkumar; Garcia-Cadenas, Irene; Nerreter, Thomas; Thomas, Simone; Rydzek, Julian; Meijide, Javier Briones; Bonig, Halvard; Herr, Wolfgang; Sierra, Jordi; Einsele, Hermann; Hudecek, Michael

2018-05-01

FMS-like tyrosine kinase 3 (FLT3) is a transmembrane protein expressed on normal hematopoietic stem and progenitor cells (HSC) and retained on malignant blasts in acute myeloid leukemia (AML). We engineered CD8 + and CD4 + T-cells expressing a FLT3-specific chimeric antigen receptor (CAR) and demonstrate they confer potent reactivity against AML cell lines and primary AML blasts that express either wild-type FLT3 or FLT3 with internal tandem duplication (FLT3-ITD). We also show that treatment with the FLT3-inhibitor crenolanib leads to increased surface expression of FLT3 specifically on FLT3-ITD + AML cells and consecutively, enhanced recognition by FLT3-CAR T-cells in vitro and in vivo. As anticipated, we found that FLT3-CAR T-cells recognize normal HSCs in vitro and in vivo, and disrupt normal hematopoiesis in colony-formation assays, suggesting that adoptive therapy with FLT3-CAR T-cells will require subsequent CAR T-cell depletion and allogeneic HSC transplantation to reconstitute the hematopoietic system. Collectively, our data establish FLT3 as a novel CAR target in AML with particular relevance in high-risk FLT3-ITD + AML. Further, our data provide the first proof-of-concept that CAR T-cell immunotherapy and small molecule inhibition can be used synergistically, as exemplified by our data showing superior antileukemia efficacy of FLT3-CAR T-cells in combination with crenolanib.

High Performances of Artificial Nacre-Like Graphene Oxide-Carrageenan Bio-Nanocomposite Films

PubMed Central

Zhu, Wenkun; Chen, Tao; Li, Yi; Lei, Jia; Chen, Xin; Yao, Weitang; Duan, Tao

2017-01-01

This study was inspired by the unique multi-scale and multi-level ‘brick-and-mortar’ (B&M) structure of nacre layers. We prepared the B&M, environmentally-friendly graphene oxide-carrageenan (GO-Car) nanocomposite films using the following steps. A natural polyhydroxy polymer, carrageenan, was absorbed on the surface of monolayer GO nanosheets through hydrogen-bond interactions. Following this, a GO-Car hybridized film was produced through a natural drying process. We conducted structural characterization in addition to analyzing mechanical properties and cytotoxicity of the films. Scanning electron microscope (SEM) and X-ray diffraction (XRD) analyses showed that the nanocomposite films had a similar morphology and structure to nacre. Furthermore, the results from Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Thermogravimetric (TG/DTG) were used to explain the GO-Car interaction. Analysis from static mechanical testers showed that GO-Car had enhanced Young’s modulus, maximum tensile strength and breaking elongation compared to pure GO. The GO-Car nanocomposite films, containing 5% wt. of Car, was able to reach a tensile strength of 117 MPa. The biocompatibility was demonstrated using a RAW264.7 cell test, with no significant alteration found in cellular morphology and cytotoxicity. The preparation process for GO-Car films is simple and requires little time, with GO-Car films also having favorable biocompatibility and mechanical properties. These advantages make GO-Car nanocomposite films promising materials in replacing traditional petroleum-based plastics and tissue engineering-oriented support materials. PMID:28772897

Study of method for reducing fuel consumption and amount of specific emissions of harmful substances with exhaust gases of passenger cars when using “climate control” system

NASA Astrophysics Data System (ADS)

Burakova, L. N.; Anisimov, I. A.; Burakova, A. D.; Burakova, O. D.

2018-05-01

The article deals with the issue of improving fuel efficiency and the ecological nature of passenger cars, servicing the administrative and management personnel of the oil and gas complex. It is established that fuel consumption and the amount of specific emissions of harmful substances with exhaust gases of cars when using the “climate control” system depend on the effective ambient temperature, the color of the opaque car body elements, the power of the car engine and the interior volume. However, the simplest controlled factor is the color of the opaque car body elements, which is characterized by the coefficient of light reflection. In the course of experimental studies, the authors established the dependences of a change in fuel consumption and a share of reducing emissions of harmful substances with exhaust gases of passenger cars with the “climate control” system on the coefficient of light reflection. A method has been developed to reduce fuel consumption and the amount of specific emissions of harmful substances with the exhaust gases of passenger cars using the “climate control” system, which involves painting the vehicle roof white and allows reducing fuel consumption by 5.5-10.3%, and the amount of specific emissions of harmful substances by 0.8-2.3%.

Novel anti-CD3 chimeric antigen receptor targeting of aggressive T cell malignancies

PubMed Central

Firor, Amelia E.; Pinz, Kevin G.; Jares, Alexander; Liu, Hua; Salman, Huda; Golightly, Marc; Lan, Fengshuo; Jiang, Xun; Ma, Yupo

2016-01-01

Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design. We engineered a robust 3rd generation anti-CD3 CAR construct (CD3CAR) into an NK cell line (NK-92). We found that CD3CAR NK-92 cells specifically and potently lysed diverse CD3+ human PTCL primary samples as well as T-cell leukemia cells lines ex vivo. Furthermore, CD3CAR NK-92 cells effectively controlled and suppressed Jurkat tumor cell growth in vivo and significantly prolonged survival. In this study, we present the CAR directed targeting of a novel target - CD3 using CAR modified NK-92 cells with an emphasis on efficacy, specificity, and potential for new therapeutic approaches that could improve the current standard of care for PTCLs. PMID:27494836

JPL's electric and hybrid vehicles project: Project activities and preliminary test results. [power conditioning and battery charge efficiency

NASA Technical Reports Server (NTRS)

Barber, T. A.

1980-01-01

Efforts to achieve a 100 mile urban range, to reduce petroleum usage 40% to 70%, and to commercialize battery technology are discussed with emphasis on an all plastic body, four passenger car that is flywheel assisted and battery powered, and on an all metal body, four passenger car with front wheel drive and front motor. For the near term case, a parallel hybrid in which the electric motor and the internal combustion engine may directly power the drive wheels, is preferred to a series design. A five passenger car in which the electric motor and the gasoline engine both feed into the same transmission is discussed. Upgraded demonstration vehicles were tested using advanced lead acid, nickel zinc, nickel iron, and zinc chloride batteries to determine maximum acceleration, constant speed, and battery behavior. The near term batteries demonstrated significant improvement relative to current lead acid batteries. The increase in range was due to improved energy density, and ampere hour capacity, with relatively 1 small weight and volume differences.

Influence of driving cycles on unit emissions from passenger cars

NASA Astrophysics Data System (ADS)

Joumard, R.; André, M.; Vidon, R.; Tassel, P.; Pruvost, C.

Small samples of petrol engine or diesel cars, equipped with or without catalysts, were tested over 36 driving cycles divided into four categories - standard cycles and three sets of cycles more representative of real-world driving conditions. The tests addressed standard gaseous pollutants and fuel consumption and also less frequently measured pollutant such as CH 4. In the first part of this paper we examine cold emissions in order to assess the duration of the cold start impact and the representativity of the cold ECE15 cycle. Then unit emissions are compared over the four driving cycle families. As compared to representative cycles, the standardised cycles underestimate hot emissions by almost 50% for petrol engine cars and 30% for diesel vehicles. Conversely, the results obtained for the three representative cycle families are in relatively close agreement with each other - within approximately 10%. However, the cinematic properties of the three families differ. Finally, we demonstrate that weighting all emission data equally, not taking into account the weight of each cycle in overall traffic, introduces significant biases, particularly when plotting emission vs. average speed curves.

40 CFR Appendix II to Subpart S of... - As-Received Testing Vehicle Rejection Criteria

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES... vehicle has been used for severe duty (trailer towing for passenger cars, snow plowing, racing) 4. The vehicle has a history of extensive collision damage or major engine repair (piston, crank, cylinder head...

40 CFR Appendix II to Subpart S of... - As-Received Testing Vehicle Rejection Criteria

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES... vehicle has been used for severe duty (trailer towing for passenger cars, snow plowing, racing) 4. The vehicle has a history of extensive collision damage or major engine repair (piston, crank, cylinder head...

40 CFR Appendix II to Subpart S of... - As-Received Testing Vehicle Rejection Criteria

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES... vehicle has been used for severe duty (trailer towing for passenger cars, snow plowing, racing) 4. The vehicle has a history of extensive collision damage or major engine repair (piston, crank, cylinder head...

40 CFR Appendix II to Subpart S of... - As-Received Testing Vehicle Rejection Criteria

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES... vehicle has been used for severe duty (trailer towing for passenger cars, snow plowing, racing) 4. The vehicle has a history of extensive collision damage or major engine repair (piston, crank, cylinder head...

Advances in engineering of high contrast CARS imaging endoscopes

PubMed Central

Deladurantaye, Pascal; Paquet, Alex; Paré, Claude; Zheng, Huimin; Doucet, Michel; Gay, David; Poirier, Michel; Cormier, Jean-François; Mermut, Ozzy; Wilson, Brian C.; Seibel, Eric J.

2014-01-01

The translation of CARS imaging towards real time, high resolution, chemically selective endoscopic tissue imaging applications is limited by a lack of sensitivity in CARS scanning probes sufficiently small for incorporation into endoscopes. We have developed here a custom double clad fiber (DCF)-based CARS probe which is designed to suppress the contaminant Four-Wave-Mixing (FWM) background generated within the fiber and integrated it into a fiber based scanning probe head of a few millimeters in diameter. The DCF includes a large mode area (LMA) core as a first means of reducing FWM generation by ~3 dB compared to commercially available, step-index single mode fibers. A micro-fabricated miniature optical filter (MOF) was grown on the distal end of the DCF to block the remaining FWM background from reaching the sample. The resulting probe was used to demonstrate high contrast images of polystyrene beads in the forward-CARS configuration with > 10 dB suppression of the FWM background. In epi-CARS geometry, images exhibited lower contrast due to the leakage of MOF-reflected FWM from the fiber core. Improvements concepts for the fiber probe are proposed for high contrast epi-CARS imaging to enable endoscopic implementation in clinical tissue assessment contexts, particularly in the early detection of endoluminal cancers and in tumor margin assessment. PMID:25401538

Dual-Pump Coherent Anti-Stokes Raman Scattering Temperature and CO2 Concentration Measurements

NASA Technical Reports Server (NTRS)

Lucht, Robert P.; Velur-Natarajan, Viswanathan; Carter, Campbell D.; Grinstead, Keith D., Jr.; Gord, James R.; Danehy, Paul M.; Fiechtner, G. J.; Farrow, Roger L.

2003-01-01

Measurements of temperature and CO2 concentration using dual-pump coherent anti-Stokes Raman scattering, (CARS) are described. The measurements were performed in laboratory flames,in a room-temperature gas cell, and on an engine test stand at the U.S. Air Force Research Laboratory, Wright-Patterson Air Force Base. A modeless dye laser, a single-mode Nd:YAG laser, and an unintensified back-illuminated charge-coupled device digital camera were used for these measurements. The CARS measurements were performed on a single-laser-shot basis. The standard deviations of the temperatures and CO2 mole fractions determined from single-shot dual-pump CARS spectra in steady laminar propane/air flames were approximately 2 and 10% of the mean values of approximately 2000 K and 0.10, respectively. The precision and accuracy of single-shot temperature measurements obtained from the nitrogen part of the dual-pump CARS system were investigated in detail in near-adiabatic hydrogen/air/CO2 flames. The precision of the CARS temperature measurements was found to be comparable to the best results reported in the literature for conventional two-laser, single-pump CARS. The application of dual-pump CARS for single-shot measurements in a swirl-stabilized combustor fueled with JP-8 was also demonstrated.

CFD analysis on effect of front windshield angle on aerodynamic drag

NASA Astrophysics Data System (ADS)

Abdellah, Essaghouri; Wang, Bo

2017-09-01

The external aerodynamics plays an important role in the design process of any automotive. The whole performance of the vehicle can be improved with the help of external aerodynamics. The aerodynamic analysis nowadays is implemented in the recent research in the automotive industry to achieve better cars in terms of design and efficiency. The major objective of the present work is to find out the effect of changing the angle between the engine hood and the front windshield on reducing the car air resistance. A full scale three dimensional (BMW 3 series) sedan car model was carried out using the ALIAS AUTOSTUDIO 2016 a NURBS modeling tool with high quality surfaces, only the external shape of the car was modeled while the interior was not modeled. The ANSYS 17.0 WORKBENCH software package was used to analyse the airflow around the external shape of the car - the solutions of Reynolds Average Navier Stokes (RANS) equations has been carried out using realizable k-epsilon turbulence model (which is perfectly suitable for the automated calculation process) for the given car domain. In this work, the boundary layer, mesh quality, and turbulent value simulation has been compared and discussed in the result section. Finally the optimal model was selected and the redesigned car was analysed to verify the results.

Local laser-strengthening: Customizing the forming behavior of car body steel sheets

NASA Astrophysics Data System (ADS)

Wagner, M.; Jahn, A.; Beyer, E.; Balzani, D.

2018-05-01

Future trends in designing lightweight components especially for automotive applications increasingly require complex and delicate structures with highest possible level of capacity [1]. The manufacturing of metallic car body components is primarily realized by deep or stretch drawing. The forming process of especially cold rolled and large-sized components is typically characterized by inhomogeneous stress and strain distributions. As a result, the avoidance of undesirable deep drawing effects like earing and local necking is among the greatest challenges in forming complex car body structures [2]. Hence, a novel local laser-treatment approach with the objective of customizing the forming behavior of car body steel sheets is currently explored.

Nanostructured lipid carriers as a potential vehicle for Carvedilol delivery: Application of factorial design approach.

PubMed

Patil, Ganesh B; Patil, Nandkishor D; Deshmukh, Prashant K; Patil, Pravin O; Bari, Sanjay B

2016-01-01

Present invention relates to design of nanostructured lipid carriers (NLC) to augment oral bioavailability of Carvedilol (CAR). In this attempt, formulations of CAR-NLCs were prepared with glyceryl-monostearate (GMS) as a lipid, poloxamer 188 as a surfactant and tween 80 as a co-surfactant using high pressure homogenizer by 2(3) factorial design approach. Formed CAR-NLCs were assessed for various performance parameters. Accelerated stability studies demonstrated negligible change in particle size and entrapment efficiency, after storage at specified time up to 3 months. The promising findings in this investigation suggest the practicability of these systems for enhancement of bioavailability of drugs like CAR.

KSC-2011-7888

NASA Image and Video Library

2011-11-23

CAPE CANAVERAL, Fla. – Parents and children of all ages participate in a LEGO "Build the Future" event at the Kennedy Space Center Visitor Complex in Florida. The festivities coincide with the launch of NASA's Mars Science Laboratory (MSL), carrying a compact car-sized rover, Curiosity, to the red planet. Part of the Space Act Agreement between NASA and LEGO A/S, the activities are designed to inspire students of every age to consider an education and careers in the science, technology, engineering and mathematics, or STEM, disciplines. Launch of MSL aboard a United Launch Alliance Atlas V rocket is scheduled for Nov. 26 from Space Launch Complex-41 on Cape Canaveral Air Force Station in Florida. For more information, visit http://www.nasa.gov/audience/foreducators/nasa-lego-partnership.html. Photo credit: NASA/Kim Shiflett

Role of YAP activation in nuclear receptor CAR-mediated proliferation of mouse hepatocytes.

PubMed

Abe, Taiki; Amaike, Yuto; Shizu, Ryota; Takahashi, Miki; Kano, Makoto; Hosaka, Takuomi; Sasaki, Takamitsu; Kodama, Susumu; Matsuzawa, Atsushi; Yoshinari, Kouichi

2018-06-08

Constitutive androstane receptor (CAR) is a xenobiotic-responsive nuclear receptor that is highly expressed in the liver. CAR activation induces hepatocyte proliferation and hepatocarcinogenesis in rodents, but the mechanisms remain unclear. In this study, we investigated the association of CAR-dependent cell proliferation with Yes-associated protein (YAP), which is a transcriptional cofactor controlling organ size and cell growth through the interaction with various transcriptional factors including TEAD. In mouse livers, TCPOBOP (a mouse CAR activator) treatment increased the nuclear YAP accumulation and mRNA levels of YAP target genes as well as cell-cycle related genes along with liver hypertrophy and verteporfin (an inhibitor of YAP/TEAD interaction) cotreatment tended to attenuate them. Furthermore, in cell-based reporter gene assays, CAR activation enhanced the YAP/TEAD-dependent transcription. To investigate the role of YAP/TEAD activation in the CAR-dependent hepatocyte proliferation, we sought to establish an in vitro system completely reproducing CAR-dependent cell proliferation. Since CAR was only slightly expressed in cultured mouse primary hepatocytes compared to mouse livers and no proliferation was observed after treatment with TCPOBOP, we overexpressed CAR using mouse CAR expressing adenovirus (Ad-mCAR-V5) in mouse primary hepatocytes. Ad-mCAR-V5 infection and TCPOBOP treatment induced hepatocyte proliferation. Similar results were obtained with immortalized normal mouse hepatocytes as well. In the established in vitro system, CAR-dependent proliferation was strongly inhibited by Yap knockdown and completely abolished by verteporfin treatment. Our present results obtained in in vivo and in vitro experiments suggest that YAP/TEAD activation plays key roles in CAR-dependent proliferation of murine hepatocytes.

National Program for Inspection of Non-Federal Dams. Collins Company Upper Dam (CT 00674), Connecticut River Basin, Canton, Connecticut. Phase I Inspection Report.

DTIC Science & Technology

1979-07-01

Engineering Division p 0 CAR WE H FRZIAN, NENBER Design Branch Engineering Division J SEPE FIN~EGAN, JR.,CIV ater Control Branch * Engineering Division...Operator g. Purpose of Dam h. Design and Construction History i. Normal Operational Procedures 1.3 PERTINENT DATA ........................... 4 a...Tunnel i. Spillways j. Regulating Outlets SECTION 2: ENGINEERING DATA 2.1 DESIGN .............................. 9 a. Available Data b. Design Features c

Antigen-Specific T-Cell Activation Independently of the MHC: Chimeric Antigen Receptor-Redirected T Cells

PubMed Central

Chmielewski, Markus; Hombach, Andreas A.; Abken, Hinrich

2013-01-01

Adoptive T-cell therapy has recently shown promise in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T-cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient’s T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR) which consists in the extracellular part of an antibody-derived domain for binding with a “tumor-associated antigen” and in the intracellular part of a T-cell receptor (TCR)-derived signaling moiety for T-cell activation. The specificity of CAR-mediated T-cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T-cell targeting by an engineered CAR in comparison to TCR modified T cells and the impact of the CAR activation threshold on redirected T-cell activation. Finally we review most significant progress recently made in early stage clinical trials to treat cancer. PMID:24273543

Antigen-Specific T-Cell Activation Independently of the MHC: Chimeric Antigen Receptor-Redirected T Cells.

PubMed

Chmielewski, Markus; Hombach, Andreas A; Abken, Hinrich

2013-01-01

Adoptive T-cell therapy has recently shown promise in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T-cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR) which consists in the extracellular part of an antibody-derived domain for binding with a "tumor-associated antigen" and in the intracellular part of a T-cell receptor (TCR)-derived signaling moiety for T-cell activation. The specificity of CAR-mediated T-cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T-cell targeting by an engineered CAR in comparison to TCR modified T cells and the impact of the CAR activation threshold on redirected T-cell activation. Finally we review most significant progress recently made in early stage clinical trials to treat cancer.

Obesity and vehicle type as risk factors for injury caused by motor vehicle collision.

PubMed

Donnelly, John P; Griffin, Russell Lee; Sathiakumar, Nalini; McGwin, Gerald

2014-04-01

This study sought to describe variations in the risk of motor vehicle collision (MVC) injury and death by occupant body mass index (BMI) class and vehicle type. We hypothesized that the relationship between BMI and the risk of MVC injury or mortality would be modified by vehicle type. This is a retrospective cohort study of occupants involved in MVCs using data from the Crash Injury Research and Engineering Network and the National Automotive Sampling System Crashworthiness Data System. Occupants were grouped based on vehicle body style (passenger car, sport utility vehicle, or light truck) and vehicle size (compact or normal, corresponding to below- or above-average curb weight). The relationship between occupant BMI class (underweight, normal weight, overweight, or obese) and risk of injury or mortality was examined for each vehicle type. Odds ratios (ORs) adjusted for various occupant and collision characteristics were estimated. Of an estimated 44 million occupants of MVCs sampled from 2000 to 2009, 37.1% sustained an injury. We limited our analysis to injuries achieving an Abbreviated Injury Scale (AIS) score of 2 or more severe, totaling 17 million injuries. Occupants differed substantially in terms of demographic and collision characteristics. After adjustment for confounding factors, we found that obesity was a risk factor for mortality caused by MVC (OR, 1.6; 95% confidence interval [CI], 1.2-2.0). When stratified by vehicle type, we found that obesity was a risk factor for mortality in larger vehicles, including any-sized light trucks (OR, 2.1; 95% CI, 1.3-3.5), normal-sized passenger cars (OR, 1.6; 95% CI, 1.1-2.3), and normal-sized sports utility vehicles or vans (OR, 2.0; 95% CI, 1.0-3.8). Being overweight was a risk factor in any-sized light trucks (OR, 1.5; 95% CI, 1.1-2.1). We identified a significant interaction between occupant BMI class and vehicle type in terms of MVC-related mortality risk. Both factors should be taken into account when considering occupant safety, and additional study is needed to determine underlying causes of the observed relationships. Epidemiologic study, level III.

Direct emission of nitrous acid (HONO) from gasoline cars in China determined by vehicle chassis dynamometer experiments

NASA Astrophysics Data System (ADS)

Liu, Yuhan; Lu, Keding; Ma, Yufang; Yang, Xinping; Zhang, Wenbin; Wu, Yusheng; Peng, Jianfei; Shuai, Shijin; Hu, Min; Zhang, Yuanhang

2017-11-01

HONO plays a key role in atmospheric chemistry, and while its importance is well-known, the sources of HONO are still not completely understood. As a component of ambient HONO sources, direct emission from vehicles is an area that should be extensively studied. In this study, we determined the HONO emission index for typical gasoline vehicles in the car population of China through a chassis dynamometer with different types of engines (PFI/GDI), starting conditions (cold/warm) and running styles (Beijing cycle). Emission ratios of HONO to nitrogen oxide (NOX) for the Chinese gasoline cars are determined to be in the range of (0.03-0.42) % and an averaged value is about 0.18%, which are comparable to those reported in the few studies available in Europe, the United States and Japan for gasoline cars while smaller for those of the diesel cars. The atmospheric impact of the direct HONO emission from gasoline cars was analyzed for a typical urban site in Beijing, significant contributions of the direct emission toward the HONO budget were found during morning rush hours or twilight conditions to be 8-12%.

Aerodynamics of Race Cars

NASA Astrophysics Data System (ADS)

Katz, Joseph

2006-01-01

Race car performance depends on elements such as the engine, tires, suspension, road, aerodynamics, and of course the driver. In recent years, however, vehicle aerodynamics gained increased attention, mainly due to the utilization of the negative lift (downforce) principle, yielding several important performance improvements. This review briefly explains the significance of the aerodynamic downforce and how it improves race car performance. After this short introduction various methods to generate downforce such as inverted wings, diffusers, and vortex generators are discussed. Due to the complex geometry of these vehicles, the aerodynamic interaction between the various body components is significant, resulting in vortex flows and lifting surface shapes unlike traditional airplane wings. Typical design tools such as wind tunnel testing, computational fluid dynamics, and track testing, and their relevance to race car development, are discussed as well. In spite of the tremendous progress of these design tools (due to better instrumentation, communication, and computational power), the fluid dynamic phenomenon is still highly nonlinear, and predicting the effect of a particular modification is not always trouble free. Several examples covering a wide range of vehicle shapes (e.g., from stock cars to open-wheel race cars) are presented to demonstrate this nonlinear nature of the flow field.

Chimeric Antigen Receptor T Cell Therapy in Hematology.

PubMed

Ataca, Pınar; Arslan, Önder

2015-12-01

It is well demonstrated that the immune system can control and eliminate cancer cells. Immune-mediated elimination of tumor cells has been discovered and is the basis of both cancer vaccines and cellular therapies including hematopoietic stem cell transplantation. Adoptive T cell transfer has been improved to be more specific and potent and to cause less off-target toxicity. Currently, there are two forms of engineered T cells being tested in clinical trials: T cell receptor (TCR) and chimeric antigen receptor (CAR) modified T cells. On 1 July 2014, the United States Food and Drug Administration granted 'breakthrough therapy' designation to anti-CD19 CAR T cell therapy. Many studies were conducted to evaluate the benefits of this exciting and potent new treatment modality. This review summarizes the history of adoptive immunotherapy, adoptive immunotherapy using CARs, the CAR manufacturing process, preclinical and clinical studies, and the effectiveness and drawbacks of this strategy.

Energy efficiency of engines and appliances for transport on land, water, and in air.

PubMed

Furfari, Samuele

2016-01-01

The transport sector is fundamental for the economy but also for personal life. With a growing population and the globalization process, it is not surprising that the demand of transport is set to grow in the near future and certainly until 2050. This paper focuses on the huge potential of progress in the sector of technology for transport. As the principal sector for transport will remain on roads, the paper emphasizes the progress in the automotive sector. Since car manufacturers are investing massively into research and technology development to offer ever more efficient cars--not only energy efficient but also efficient in terms of safety and comfort--the car of tomorrow will be very different from the present one. The increasing role of electronics in cars will synergistically cooperate with that of so-called smart cities. The potential development of methane in the transport sector, mainly used for heavy transportation is discussed.

Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist

PubMed Central

Levine, Bruce L.

2016-01-01

The field of cancer immunotherapy has rapidly progressed in the past decade as several therapeutic modalities have entered into the clinic. One such immunotherapy that has shown promise in the treatment of cancer is the use of chimeric antigen receptor (CAR)-modified T lymphocytes. CARs are engineered receptors constructed from antigen recognition regions of antibodies fused to T-cell signaling and costimulatory domains that can be used to reprogram a patient’s T cells to specifically target tumor cells. CAR T-cell therapy has demonstrated sustained complete responses for some patients with advanced leukemia, and a number of CAR therapies are being evaluated in clinical studies. CAR T-cell therapy-associated toxicities, including cytokine release syndrome, macrophage activation syndrome, and tumor lysis syndrome, have been observed and effectively managed in the clinic. In patients with significant clinical responses, sustained B-cell aplasia has also been observed and is a marker of CAR T-cell persistence that might provide long-term disease control. Education on CAR T-cell therapy efficacy and safety management is critical for clinicians and patients who are considering this novel type of treatment. In the present report, the current landscape of CAR T-cell therapy, the effective management of patients undergoing treatment, and which patients are the most suitable candidates for current trials are discussed. Implications for Practice: The present report describes the current status of chimeric antigen receptor (CAR) T lymphocytes as an immunotherapy for patients with relapsed or refractory B-cell malignancies. CAR T cells targeting CD19, a protein expressed on many B-cell malignancies, typically induce high complete response rates in patients with B-cell leukemia or lymphoma who have very limited therapeutic options. Recent clinical trial results of CD19 CAR T-cell therapies and the management of CAR T-cell-associated adverse events are discussed. The present report will therefore inform physicians regarding the efficacy and safety of CAR T cells as a therapy for B-cell malignancies. PMID:27009942

Study of Consumer Automotive Preference with Regard to Fuel Economy Measures

DOT National Transportation Integrated Search

1978-09-01

An analysis is made of the effects of size and weight reduction of 1977 General Motors standard size cars. A buyer profile describing demographic characteristics, age, sex, education, marital status, size of family and income by make is prepared for ...

Hybrid propulsion system with a gyro component for economic and dynamic operation. [of motor vehicle

NASA Technical Reports Server (NTRS)

Giera, B.; Helling, J.; Schreck, J.

1977-01-01

The design of a hybrid drive with gyro components is described and its drive components for a medium class private car are discussed. The gyro component affects the short-period output of the drive by accelerating and slowing down and -- because of the mechanical transfer of kinetic energy between the gyro and the vehicle -- it affects also the energy balance in the case of intermittent operation. Energy can be taken in as desired either in the form of fuel or as fuel and current. A high energy recovery efficiency as well as the favorable operating range of the interval combustion engine makes it possible to reduce the fuel consumption per unit distance travelled to almost half that for a private car with a traditional engine.

Influences of Vehicle Size and Mass and Selected Driver Factors on Odds of Driver Fatality

PubMed Central

Padmanaban, Jeya

2003-01-01

Research was undertaken to determine vehicle size parameters influencing driver fatality odds, independent of mass, in two-vehicle collisions. Forty vehicle parameters were evaluated for 1,500 vehicle groupings. Logistic regression analyses show driver factors (belt use, age, drinking) collectively contribute more to fatality odds than vehicle factors, and that mass is the most important vehicular parameter influencing fatality odds for all crash configurations. In car crashes, other vehicle parameters with statistical significance had a second order effect compared to mass. In light truck-to-car crashes, “vehicle type-striking vehicle is light truck” was the most important parameter after mass, followed by vehicle height and bumper height, with second order effect. To understand the importance of “vehicle type” variable, further investigation of vehicle “stiffness” and other passenger car/light truck differentiating parameters is warranted. PMID:12941244

Coherent anti-Stokes Raman scattering microscopy of single nanodiamonds

NASA Astrophysics Data System (ADS)

Pope, Iestyn; Payne, Lukas; Zoriniants, George; Thomas, Evan; Williams, Oliver; Watson, Peter; Langbein, Wolfgang; Borri, Paola

2014-11-01

Nanoparticles have attracted enormous attention for biomedical applications as optical labels, drug-delivery vehicles and contrast agents in vivo. In the quest for superior photostability and biocompatibility, nanodiamonds are considered one of the best choices due to their unique structural, chemical, mechanical and optical properties. So far, mainly fluorescent nanodiamonds have been utilized for cell imaging. However, their use is limited by the efficiency and costs in reliably producing fluorescent defect centres with stable optical properties. Here, we show that single non-fluorescing nanodiamonds exhibit strong coherent anti-Stokes Raman scattering (CARS) at the sp3 vibrational resonance of diamond. Using correlative light and electron microscopy, the relationship between CARS signal strength and nanodiamond size is quantified. The calibrated CARS signal in turn enables the analysis of the number and size of nanodiamonds internalized in living cells in situ, which opens the exciting prospect of following complex cellular trafficking pathways quantitatively.

Coherent anti-Stokes Raman scattering microscopy of single nanodiamonds

PubMed Central

Pope, Iestyn; Payne, Lukas; Zoriniants, George; Thomas, Evan; Williams, Oliver; Watson, Peter; Langbein, Wolfgang; Borri, Paola

2016-01-01

Nanoparticles have attracted enormous attention for biomedical applications as optical labels, drug delivery vehicles, and contrast agents in vivo. In the quest for superior photostability and bio-compatibility, nanodiamonds (NDs) are considered one of the best choices due to their unique structural, chemical, mechanical, and optical properties. So far, mainly fluorescent NDs have been utilized for cell imaging. However, their use is limited by the efficiency and costs in reliably producing fluorescent defect centers with stable optical properties. Here, we show that single non-fluorescing NDs exhibit strong coherent anti-Stokes Raman scattering (CARS) at the sp3 vibrational resonance of diamond. Using correlative light and electron microscopy, the relationship between CARS signal strength and ND size is quantified. The calibrated CARS signal in turn enables the analysis of the number and size of NDs internalized in living cells in situ, which opens the exciting prospect of following complex cellular trafficking pathways quantitatively. PMID:25305746

Coherent anti-Stokes Raman scattering microscopy of single nanodiamonds.

PubMed

Pope, Iestyn; Payne, Lukas; Zoriniants, George; Thomas, Evan; Williams, Oliver; Watson, Peter; Langbein, Wolfgang; Borri, Paola

2014-11-01

Nanoparticles have attracted enormous attention for biomedical applications as optical labels, drug-delivery vehicles and contrast agents in vivo. In the quest for superior photostability and biocompatibility, nanodiamonds are considered one of the best choices due to their unique structural, chemical, mechanical and optical properties. So far, mainly fluorescent nanodiamonds have been utilized for cell imaging. However, their use is limited by the efficiency and costs in reliably producing fluorescent defect centres with stable optical properties. Here, we show that single non-fluorescing nanodiamonds exhibit strong coherent anti-Stokes Raman scattering (CARS) at the sp(3) vibrational resonance of diamond. Using correlative light and electron microscopy, the relationship between CARS signal strength and nanodiamond size is quantified. The calibrated CARS signal in turn enables the analysis of the number and size of nanodiamonds internalized in living cells in situ, which opens the exciting prospect of following complex cellular trafficking pathways quantitatively.

Electric Vehicle Modeling and Simulation.

DTIC Science & Technology

1983-08-01

RD-RI39 709 ELECTRIC VEHICLE MODELING RHD SIMULRTION(U) AIR FORCE lit INST OF TECH NRIGHT-PRTTERSON RFD OH SCHOOL OF ENGINEERING A R DEMISPELARE RUG...for Public Release Distribution Unlimited Fl School of Engineering Air Force Institute of Technology Wright-Patterson Air Force Base, Ohio Table of... Engineering , 49: 49-51 (27 August 1979). 36. Renner -Smith, S. "Battery-Saving Flywheel Gives Electric Car Freeway Zip," Popular Science, 215(10): 82-84

Combustion Engineering, Inc. [LMFBR

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

Not Available

1980-01-01

Four (4) 3 '' O.D. x 0.470'' nominal wall thickness (NWT) hot rotary pierced/roll reduced modified AOD/ESR tube hollows were cold pilger reduced through one pass to 2'' O.D. x 0.250'' NWT tubing. Two (2) additional hollows of same size and process history were cold pilger reduced through one pass to 2 1/8'' O.D. x 0.200'' NWT. Six (6) 3 3/4'' O.D. x 0.600'' NWT hot extruded tube hollows were cold pilger reduced through two passes to 2'' O.D. x 0.250'' NWT tubing. Four of the extrusions represented duplex AOD/ESR melting practice and two extrusions represented AOD melting practice. Twelvemore » (12) pieces of 2 1/8'' O.D. x 0.200'' NWT x approx. 9' long tubing were final heat treated, straightened, and ultrasonically tested. Twelve (12) more pieces of 2 1/8'' O.D. tubing have been solution austenitized (1177/sup 0/C) and are to be reaustenitized (1066/sup 0/C), tempered (760/sup 0/C), straightened, and ultrasonically inspected. All 2'' O.D. x 0.250'' NWT tubing is in the solution austenitized condition. Creep and stress rupture testing has continued on aged material from CarTech heat 91887 and on unaged material from CarTech heat 30182A.« less

SOAC - State-of-the-Art Car Engineering Tests at Department of Transportation High Speed Ground Test Center : Volume 7. Post-Repair Tests.

DOT National Transportation Integrated Search

1976-11-01

This document presents the test results from the State-of-the-Art Post-Repair Engineering Test Program conducted at the DOT High-Speed Ground Test Center, Pueblo, Colorado, from March 18th to 29th, 1974. The SOAC has been developed under UMTA's Urban...

The Requirement for Vocational Skills in the Engineering Industry in the Areas of Modena and Vienna. Synthesis Report.

ERIC Educational Resources Information Center

Gatti, Mario; Mereu, Maria Grazia; Tagliaferro, Claudio; Markowitsch, Jorg; Neuberger, Robert

Requirements for vocational skills in the engineering industry in Modena, Italy, and Vienna, Austria, were studied. In Modena, employees of a representative sample of 90 small, medium, and large firms in the mechanical processing, agricultural machinery, and sports car manufacturing sectors were interviewed. In Vienna, data were collected through…

Methanol decomposition bottoming cycle for IC engines

NASA Technical Reports Server (NTRS)

Purohit, G.; Houseman, J.

1979-01-01

This paper presents the concept of methanol decomposition using engine exhaust heat, and examines its potential for use in the operation of passenger cars, diesel trucks, and diesel-electric locomotives. Energy economy improvements of 10-20% are calculated over the representative driving cycles without a net loss in power. Some reductions in exhaust emissions are also projected.

Effectiveness of Using a Video Game to Teach a Course in Mechanical Engineering

ERIC Educational Resources Information Center

Coller, B. D.; Scott, M. J.

2009-01-01

One of the core courses in the undergraduate mechanical engineering curriculum has been completely redesigned. In the new numerical methods course, all assignments and learning experiences are built around a video/computer game. Students are given the task of writing computer programs to race a simulated car around a track. In doing so, students…

Carbamylated albumin is one of the target antigens of anti-carbamylated protein antibodies.

PubMed

Nakabo, Shuichiro; Hashimoto, Motomu; Ito, Shinji; Furu, Moritoshi; Ito, Hiromu; Fujii, Takao; Yoshifuji, Hajime; Imura, Yoshitaka; Nakashima, Ran; Murakami, Kosaku; Kuramoto, Nobuo; Tanaka, Masao; Satoh, Junko; Ishigami, Akihito; Morita, Satoshi; Mimori, Tsuneyo; Ohmura, Koichiro

2017-07-01

Anti-carbamylated protein (anti-CarP) antibodies are detected in RA patients. Fetal calf serum is used as an antigen source in anti-CarP ELISA, and the precise target antigens have not been found. We aimed to identify the target antigens of anti-CarP antibodies. Western blotting of anti-CarP antibodies was conducted. Anti-carbamylated human albumin (CarALB) antibody was detected by in-house ELISA for 493 RA patients and 144 healthy controls (HCs). An inhibition ELISA of anti-CarP antibodies by CarALB and citrullinated albumin (citALB) was performed using eight RA patients' sera. Serum CarALB was detected by liquid chromatography-tandem mass spectroscopy (LC/MS/MS), and the serum MPO concentration was measured by ELISA. We focused on carbamylated albumin because it corresponded to the size of the thickest band detected by western blotting of anti-CarP antibodies. Anti-CarALB antibody was detected in 31.4% of RA patients, and the correlation of the titres between anti-CarALB and anti-CarP was much closer than that between anti-citALB and anti-CCP antibodies (ρ = 0.59 and ρ = 0.16, respectively). The inhibition ELISA showed that anti-CarP antibodies were inhibited by CarALB, but not by citALB. CarALB was detected in sera from RA patients by LC/MS/MS. The serum MPO concentration was correlated with disease activity and was higher in RA patients with anti-CarALB antibody than in those without. We found that carbamylated albumin is a novel target antigen of anti-CarP antibodies, and it is the first reported target antigen that has not been reported as the target of ACPA. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity

PubMed Central

Li, Wenpeng; Guo, Linjie; Rathi, Purva; Marinova, Ekaterina; Gao, Xiuhua; Wu, Meng-Feng; Liu, Hao; Dotti, Gianpietro; Gottschalk, Stephen; Metelitsa, Leonid S.; Heczey, Andras

2017-01-01

T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies. However, similar therapeutic efficacy of CAR T cells in solid tumors is yet to be achieved. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3ζ (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz). All GPC3-CARs rendered T cells highly cytotoxic to GPC3-positive hepatocellular carcinoma, hepatoblastoma, and malignant rhabdoid tumor cell lines in vitro. GBBz induced the preferential production of Th1 cytokines (interferon γ/granulocyte macrophage colony-stimulating factor) while G28z preferentially induced Th2 cytokines (interleukin-4/interleukin-10). Inclusion of 4-1BB in G28BBz could only partially ameliorate the Th2-polarizing effect of CD28. 4-1BB induced superior expansion of CAR T cells in vitro and in vivo. T cells expressing GPC3-CARs incorporating CD28, 4-1BB, or both induced sustained tumor regressions in two xenogeneic tumor models. Thus, GBBz CAR endows T cells with superior proliferative potential, potent antitumor activity, and a Th1-biased cytokine profile, justifying further clinical development of GBBz CAR for immunotherapy of GPC3-positive solid tumors. PMID:27530312

Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy

PubMed Central

Smith, Jenessa B; Lanitis, Evripidis; Dangaj, Denarda; Buza, Elizabeth; Poussin, Mathilde; Stashwick, Caitlin; Scholler, Nathalie; Powell, Daniel J

2016-01-01

B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets. In vivo, B7-H4 CAR T cells displayed antitumor reactivity against B7-H4(+) human ovarian tumor xenografts. Unexpectedly, B7-H4 CAR T cell treatment reproducibly showed delayed, lethal toxicity 6–8 weeks after therapy. Comprehensive assessment of murine B7-H4 protein distribution uncovered expression in ductal and mucosal epithelial cells in normal tissues. Postmortem analysis revealed the presence of widespread histologic lesions that correlated with B7-H4(+) expression, and were inconsistent with graft versus host disease. Lastly, expression patterns of B7-H4 protein in normal human tissue were comparable to distribution in mice, advancing our understanding of B7-H4. We conclude that B7-H4 CAR therapy mediates control of cancer outgrowth. However, long-term engraftment of B7-H4 CAR T cells mediates lethal, off-tumor toxicity that is likely due to wide expression of B7-H4 in healthy mouse organs. This model system provides a unique opportunity for preclinical evaluation of safety approaches that limit CAR-mediated toxicity after tumor destruction in vivo. PMID:27439899

Rigorous optimization and validation of potent RNA CAR T cell therapy for the treatment of common epithelial cancers expressing folate receptor

PubMed Central

Schutsky, Keith; Song, De-Gang; Lynn, Rachel; Smith, Jenessa B.; Poussin, Mathilde; Figini, Mariangela; Zhao, Yangbing; Powell, Daniel J.

2015-01-01

Using lentiviral technology, we recently demonstrated that incorporation of CD27 costimulation into CARs greatly improves antitumor activity and T cell persistence. Still, virus-mediated gene transfer is expensive, laborious and enables long-term persistence, creating therapies which cannot be easily discontinued if toxic. To address these concerns, we utilized a non-integrating RNA platform to engineer human T cells to express FRα-specific, CD27 CARs and tested their capacity to eliminate human FRα+ cancer. Novel CARs comprised of human components were constructed, C4-27z and C4opt-27z, a codon-optimized variant created for efficient expression. Following RNA electroporation, C4-27z and C4opt-27z CAR expression is initially ubiquitous but progressively declines across T cell populations. In addition, C4-27z and C4opt-27z RNA CAR T cells secrete high levels of Th-1 cytokines and display strong cytolytic function against human FRα+ cancers in a time- and antigen-dependent manner. Further, C4-27z and C4opt-27z CAR T cells exhibit significant proliferation in vivo, facilitate the complete regression of fully disseminated human ovarian cancer xenografts in mice and reduce the progression of solid ovarian cancer. These results advocate for rapid progression of C4opt-27z RNA CAR to the clinic and establish a new paradigm for preclinical optimization and validation of RNA CAR candidates destined for clinical translation. PMID:26359629

Improved Killing of Ovarian Cancer Stem Cells by Combining a Novel Chimeric Antigen Receptor-Based Immunotherapy and Chemotherapy.

PubMed

Klapdor, Rüdiger; Wang, Shuo; Hacker, Ulrich; Büning, Hildegard; Morgan, Michael; Dörk, Thilo; Hillemanns, Peter; Schambach, Axel

2017-10-01

Ovarian cancer represents the most lethal gynecological cancer. Although cytoreductive chemotherapy and surgery lead to complete macroscopic tumor removal, most of the patients in advanced stages suffer from recurrent disease and subsequently die. This may be explained by the activity of cancer stem cells (CSC), which are a subpopulation of cells with an elevated chemoresistance and an increased capacity for self-renewal and metastatic spread. Specifically targeting these cells by adoptive immunotherapy represents a promising strategy to reduce the risk for recurrent disease. This study selected the widely accepted CSC marker CD133 as a target for a chimeric antigen receptor (CAR)-based immunotherapeutic approach to treat ovarian cancer. A lentiviral vector was generated encoding a third-generation anti-CD133-CAR, and clinically used NK92 cells were transduced. These engineered natural killer (NK) cells showed specific killing against CD133-positive ovarian cancer cell lines and primary ovarian cancer cells cultured from sequential ascites harvests. Additionally, specific activation of these engineered NK cells was demonstrated via interferon-gamma secretion assays. To improve clinical efficacy of ovarian cancer treatment, the effect of the chemotherapeutic agent cisplatin was evaluated together with CAR-transduced NK cell treatment. It was demonstrated that NK cells remain cytotoxic and active under cisplatin treatment and, importantly, that sequential treatment with cisplatin followed by CAR-NK cells led to the strongest killing effect. The specific eradication of ovarian CSCs by anti-CD133-CAR expressing NK92 cells represents a promising strategy and, when confirmed in vivo, shall be the basis of future clinical studies with the aim to prevent recurrent disease.

Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma.

PubMed

Brown, Christine E; Badie, Behnam; Barish, Michael E; Weng, Lihong; Ostberg, Julie R; Chang, Wen-Chung; Naranjo, Araceli; Starr, Renate; Wagner, Jamie; Wright, Christine; Zhai, Yubo; Bading, James R; Ressler, Julie A; Portnow, Jana; D'Apuzzo, Massimo; Forman, Stephen J; Jensen, Michael C

2015-09-15

A first-in-human pilot safety and feasibility trial evaluating chimeric antigen receptor (CAR)-engineered, autologous primary human CD8(+) cytotoxic T lymphocytes (CTL) targeting IL13Rα2 for the treatment of recurrent glioblastoma (GBM). Three patients with recurrent GBM were treated with IL13(E13Y)-zetakine CD8(+) CTL targeting IL13Rα2. Patients received up to 12 local infusions at a maximum dose of 10(8) CAR-engineered T cells via a catheter/reservoir system. We demonstrate the feasibility of manufacturing sufficient numbers of autologous CTL clones expressing an IL13(E13Y)-zetakine CAR for redirected HLA-independent IL13Rα2-specific effector function for a cohort of patients diagnosed with GBM. Intracranial delivery of the IL13-zetakine(+) CTL clones into the resection cavity of 3 patients with recurrent disease was well-tolerated, with manageable temporary brain inflammation. Following infusion of IL13-zetakine(+) CTLs, evidence for transient anti-glioma responses was observed in 2 of the patients. Analysis of tumor tissue from 1 patient before and after T-cell therapy suggested reduced overall IL13Rα2 expression within the tumor following treatment. MRI analysis of another patient indicated an increase in tumor necrotic volume at the site of IL13-zetakine(+) T-cell administration. These findings provide promising first-in-human clinical experience for intracranial administration of IL13Rα2-specific CAR T cells for the treatment of GBM, establishing a foundation on which future refinements of adoptive CAR T-cell therapies can be applied. ©2015 American Association for Cancer Research.

Simplified process for the production of anti-CD19-CAR engineered T cells

PubMed Central

Tumaini, Barbara; Lee, Daniel W.; Lin, Tasha; Castiello, Luciano; Stroncek, David F.; Mackall, Crystal; Wayne, Alan; Sabatino, Marianna

2014-01-01

Background Adoptive Immunotherapy using chimeric antigen receptor (CAR) engineered T cells specific for CD19 has shown promising results for the treatment of B cell lymphomas and leukemia. This therapy involves the transduction of autologous T cells with a viral vector and the subsequent cell expansion. Here, we describe a new, simplified method to produce anti-CD19-CAR T cells. Methods T cells were isolated from peripheral blood mononuclear cell (PBMC) with anti-CD3/anti-CD28 paramagnetic beads. After 2 days, the T cells were added to culture bags pre-treated with RetroNectin and loaded with the retroviral anti-CD19 CAR vector. The cells, beads and vector were incubated for 24 hours and then a second transduction was performed. No spinoculation was used. Cells were then expanded for an additional 9 days. Results The method was validated using 2 PBMC products from a patient with B-CLL and one PBMC product from a healthy subject. The 2 PBMC products from the B-CLL patient contained 11.4% and 12.9% T cells. The manufacture process led to final products highly enriched in T cells with a mean CD3+ cell content of 98%, a mean expansion of 10.6 fold and a mean transduction efficiency of 68%. Similar results were obtained from the PBMCs of the first 4 ALL patients treated at our institution. Discussion We developed a simplified semi-closed system for the initial selection, activation, transduction and expansion of T cells using anti-CD3/anti-CD28 beads and bags, to produce autologous anti-CD19 CAR transduced T cells to support an ongoing clinical trial. PMID:23992830

An Alternative Approach to ``Measuring Horsepower and Torque Curves of a Car''

NASA Astrophysics Data System (ADS)

Graney, Chris M.

2005-09-01

The article in the September 2003 issue of TPT by John Ross Buschert of Goshen College entitled "Measuring Horsepower and Torque Curves of a Car" was excellent. I attained similar results using existing automobile test data. Automobile performance tests done by magazines such as Road & Track are a treasure trove of good-quality physics data. Performance tests often contain all the data needed to replicate Professor Buschert's analysis of the power and torque output of automobile engines.

Oil Bypass Filter Technology Evaluation - Third Quarterly Report, April--June 2003

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

Laurence R. Zirker; James E. Francfort

2003-08-01

This Third Quarterly report details the ongoing fleet evaluation of an oil bypass filter technology by the Idaho National Engineering and Environmental Laboratory (INEEL) for the U.S. Department of Energy’s FreedomCAR & Vehicle Technologies Program. Eight full-size, four-cycle diesel-engine buses used to transport INEEL employees on various routes have been equipped with oil bypass filter systems from the PuraDYN Corporation. The reported engine lubricating oil-filtering capability (down to 0.1 microns) and additive package of the bypass filter system is intended to extend oil-drain intervals. To validate the extended oil-drain intervals, an oil-analysis regime monitors the presence of necessary additives inmore » the oil, detects undesirable contaminants and engine wear metals, and evaluates the fitness of the oil for continued service. The eight buses have accumulated 185,000 miles to date without any oil changes. The preliminary economic analysis suggests that the per bus payback point for the oil bypass filter technology should be between 108,000 miles when 74 gallons of oil use is avoided and 168,000 miles when 118 gallons of oil use is avoided. As discussed in the report, the variation in the payback point is dependant on the assumed cost of oil. In anticipation of also evaluating oil bypass systems on six Chevrolet Tahoe sport utility vehicles, the oil is being sampled on the six Tahoes to develop an oil characterization history for each engine.« less

NREL Model Car Competitions | NREL

Science.gov Websites

skills in both math and science. The goals of the competition include: Generating enthusiasm for science , technology, engineering, and math (STEM) Improving students' understanding of scientific concepts and

40 CFR 204.51 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... compressor or compressor means any wheel, skid, truck, or railroad car mounted, but not self-propelled... reciprocating rotary or turbine engine rigidly connected in permanent alignment and mounted on a common frame...

40 CFR 204.51 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... compressor or compressor means any wheel, skid, truck, or railroad car mounted, but not self-propelled... reciprocating rotary or turbine engine rigidly connected in permanent alignment and mounted on a common frame...

40 CFR 204.51 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... compressor or compressor means any wheel, skid, truck, or railroad car mounted, but not self-propelled... reciprocating rotary or turbine engine rigidly connected in permanent alignment and mounted on a common frame...