Human Exploration and Settlement of the Moon Using LUNOX-Augmented NTR Propulsion

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Culver, Donald W.; Bulman, Melvin J.

1995-01-01

An innovative trimodal nuclear thermal rocket (NTR) concept is described which combines conventional liquid hydrogen (LH2)-cooled NTR, Brayton cycle power generation and supersonic combustion ramjet (scramjet) technologies. Known as the liquid oxygen (LOX) augmented NTR (LANTR), this concept utilizes the large divergent section of the NTR nozzle as an 'afterburner' into which LOX is injected and supersonically combusted with nuclear preheated hydrogen emerging from the LANTR's choked sonic throat--'scramjet propulsion in reverse.' By varying the oxygen-to-hydrogen mixture ratio (MR), the LANTR can operate over a wide range of thrust and specific impulse (Isp) values while the reactor core power level remains relatively constant. As the MR varies from zero to seven, the thrust-to-weight ratio for a 15 thousand pound force (klbf) NTR increases by approximately 440%--from 3 to 13--while the Isp decreases by only approximately 45%--from 940 to 515 seconds. This thrust augmentation feature of the LANTR means that 'big engine' performance can be obtained using smaller more affordable, easier to test NTR engines. 'Reoxidizing' the bipropellant LANTR system in low lunar orbit (LLO) with high density 'lunar-derived' LOX (LUNOX) enables a reusable, reduced size and mass lunar transfer vehicle (LTV) which can be deployed and resupplied using two 66 t-class Shuttle-derived launch vehicles. The reusable LANTR can also transport 200 to 300% more payload on each piloted round trip mission than an expendable 'all LH2' NTR system. As initial outposts grow to eventual lunar settlements and LUNOX production capacity increases, the LANTR concept can also enable a rapid 'commuter' shuttle capable of 36 to 24 hour 'one way' trips to the Moon and back with reasonable size vehicles and initial mass in low Earth orbit (IMLEO) requirements.

Human exploration and settlement of the Moon using LUNOX-augmented NTR propulsion

NASA Astrophysics Data System (ADS)

Borowski, Stanley K.; Culver, Donald W.; Bulman, Melvin J.

1995-10-01

An innovative trimodal nuclear thermal rocket (NTR) concept is described which combines conventional liquid hydrogen (LH2)-cooled NTR, Brayton cycle power generation and supersonic combustion ramjet (scramjet) technologies. Known as the liquid oxygen (LOX) augmented NTR (LANTR), this concept utilizes the large divergent section of the NTR nozzle as an 'afterburner' into which LOX is injected and supersonically combusted with nuclear preheated hydrogen emerging from the LANTR's choked sonic throat--'scramjet propulsion in reverse.' By varying the oxygen-to-hydrogen mixture ratio (MR), the LANTR can operate over a wide range of thrust and specific impulse (Isp) values while the reactor core power level remains relatively constant. As the MR varies from zero to seven, the thrust-to-weight ratio for a 15 thousand pound force (klbf) NTR increases by approximately 440%--from 3 to 13--while the Isp decreases by only approximately 45%--from 940 to 515 seconds. This thrust augmentation feature of the LANTR means that 'big engine' performance can be obtained using smaller more affordable, easier to test NTR engines. 'Reoxidizing' the bipropellant LANTR system in low lunar orbit (LLO) with high density 'lunar-derived' LOX (LUNOX) enables a reusable, reduced size and mass lunar transfer vehicle (LTV) which can be deployed and resupplied using two 66 t-class Shuttle-derived launch vehicles. The reusable LANTR can also transport 200 to 300% more payload on each piloted round trip mission than an expendable 'all LH2' NTR system. As initial outposts grow to eventual lunar settlements and LUNOX production capacity increases, the LANTR concept can also enable a rapid 'commuter' shuttle capable of 36 to 24 hour 'one way' trips to the Moon and back with reasonable size vehicles and initial mass in low Earth orbit (IMLEO) requirements.

Human exploration and settlement of the moon using lunox-augmented NTR propulsion

NASA Astrophysics Data System (ADS)

Borowski, Stanley K.; Culver, Donald W.; Bulman, Melvin J.

1995-01-01

An innovative trimodal nuclear thermal rocket (NTR) concept is described which combines conventional liquid hydrogen (LH2)-cooled NTR, Brayton cycle power generation and supersonic combustion ramjet (scramjet) technologies. Known as the liquid oxygen (LOS)-augmented NTR (LANTR), this concept utilizes the large divergent section of the NTR nozzle as an ``afterburner'' into which LOX is injected and supersonically combusted with nuclear preheated hydrogen emerging from the LANTR's choked sonic throat—``scramjet propulsion in reverse.'' By varying the oxygen-to-hydrogen mixture ratio (MR), the LANTR can operate over a wide range of thrust and specific impulse (Isp) values while the reactor core power level remains relatively constant. As the MR varies from zero to seven, the thrust-to-weight ratio for a 15 thousand pound force (klbf) NTR increases by ˜440%—from 3 to 13—while the Isp decreases by only ˜45%—from 940 to 515 seconds. This thrust augmentation feature of the LANTR means that ``big engine'' performance can be obtained using smaller, more affordable, easier to test NTR engines. ``Reoxidizing'' the bipropellant LANTR system in low lunar orbit (LLO) with high density ``lunar-derived'' LOX (LUNOX) enables a reusable, reduced size and mass lunar transfer vehicle (LTV) which can be deployed and resupplied using two 66 t-class Shuttle-derived launch vehicles. The reusable LANTR can also transport 200 to 300% more payload on each piloted round trip mission than an expendable ``all LH2'' NTR system. As initial outposts grow to eventual lunar settlements and LUNOX production capacity increases, the LANTR concept can also enable a rapid ``commuter'' shuttle capable of 36 to 24 hour ``one way'' trip to the Moon and back with reasonable size vehicles and initial mass in low Earth orbit (IMLEO) requirements.

Report of the Nuclear Propulsion Mission Analysis, Figures of Merit Subpanel: Quantifiable figures of merit for nuclear thermal propulsion

NASA Technical Reports Server (NTRS)

Haynes, Davy A.

1991-01-01

The results of an inquiry by the Nuclear Propulsion Mission Analysis, Figures of Merit subpanel are given. The subpanel was tasked to consider the question of what are the appropriate and quantifiable parameters to be used in the definition of an overall figure of merit (FoM) for Mars transportation system (MTS) nuclear thermal rocket engines (NTR). Such a characterization is needed to resolve the NTR engine design trades by a logical and orderly means, and to provide a meaningful method for comparison of the various NTR engine concepts. The subpanel was specifically tasked to identify the quantifiable engine parameters which would be the most significant engine factors affecting an overall FoM for a MTS and was not tasked with determining 'acceptable' or 'recommended' values for the identified parameters. In addition, the subpanel was asked not to define an overall FoM for a MTS. Thus, the selection of a specific approach, applicable weighting factors, to any interrelationships, for establishing an overall numerical FoM were considered beyond the scope of the subpanel inquiry.

Fast Track Lunar NTR Systems Assessment for NASA's First Lunar Outpost and Its Evolvability to Mars

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Alexander, Stephen W.

1995-01-01

Integrated systems and missions studies are presented for an evolutionary lunar-to-Mars space transportation system (STS) based on nuclear thermal rocket (NTR) technology. A 'standardized' set of engine and stage components are identified and used in a 'building block' fashion to configure a variety of piloted and cargo, lunar and Mars vehicles. The reference NTR characteristics include a thrust of 50 thousand pounds force (klbf), specific impulse (I(sub sp)) of 900 seconds, and an engine thrust-to-weight ratio of 4. 3. For the National Aeronautics and Space Administrations (NASA) First Lunar Outpost (FLO) mission, and expendable NTR stage powered by two such engines can deliver approximately 96 metric tonnes (t) to trans-lunar injection (TLI) conditions for an initial mass in low Earth orbit (IMLEO) of approximately 198 t compared to 250 t for a cryogenic chemical system. The stage liquid hydrogen (LH2) tank has a diameter, length, and capacity of 10 m, 14.5 m and 66 t, respectively. By extending the stage length and LH2 capacity to approximately 20 m and 96 t, a single launch Mars cargo vehicle could deliver to an elliptical Mars parking orbit a 63 t Mars excursion vehicle (MEV) with a 45 t surface payload. Three 50 klbf engines and the two standardized LH2 tanks developed for the lunar and Mars cargo vehicles are used to configure the vehicles supporting piloted Mars missions as early as 2010. The 'modular' NTR vehicle approach forms the basis for an efficient STS able to handle the needs of a wide spectrum of lunar and Mars missions.

Nuclear thermal rocket workshop reference system Rover/NERVA

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.

1991-01-01

The Rover/NERVA engine system is to be used as a reference, against which each of the other concepts presented in the workshop will be compared. The following topics are reviewed: the operational characteristics of the nuclear thermal rocket (NTR); the accomplishments of the Rover/NERVA programs; and performance characteristics of the NERVA-type systems for both Mars and lunar mission applications. Also, the issues of ground testing, NTR safety, NASA's nuclear propulsion project plans, and NTR development cost estimates are briefly discussed.

Assessment of Methane Emissions – Impact of Using Natural Gas Engines in Unconventional Resource Development

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

Nix, Andrew; Johnson, Derek; Heltzel, Robert

Researchers at the Center for Alternative Fuels, Engines, and Emissions (CAFEE) completed a multi-year program under DE-FE0013689 entitled, “Assessing Fugitive Methane Emissions Impact Using Natural Gas Engines in Unconventional Resource Development.” When drilling activity was high and industry sought to lower operating costs and reduce emissions they began investing in dual fuel and dedicated natural gas engines to power unconventional well equipment. From a review of literature we determined that the prime-movers (or major fuel consumers) of unconventional well development were the service trucks (trucking), horizontal drilling rig (drilling) engines, and hydraulic stimulation pump (fracturing) engines. Based on early findingsmore » from on-road studies we assessed that conversion of prime movers to operate on natural gas could contribute to methane emissions associated with unconventional wells. As such, we collected significant in-use activity data from service trucks and in-use activity, fuel consumption, and gaseous emissions data from drilling and fracturing engines. Our findings confirmed that conversion of the prime movers to operate as dual fuel or dedicated natural gas – created an additional source of methane emissions. While some gaseous emissions were decreased from implementation of these technologies – methane and CO 2 equivalent emissions tended to increase, especially for non-road engines. The increases were highest for dual fuel engines due to methane slip from the exhaust and engine crankcase. Dedicated natural gas engines tended to have lower exhaust methane emissions but higher CO 2 emissions due to lower efficiency. Therefore, investing in currently available natural gas technologies for prime movers will increase the greenhouse gas footprint of the unconventional well development industry.« less

Nuclear Thermal Rocket/Vehicle Design Options for Future NASA Missions to the Moon and Mars

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Corban, Robert R.; Mcguire, Melissa L.; Beke, Erik G.

1995-01-01

The nuclear thermal rocket (NTR) provides a unique propulsion capability to planners/designers of future human exploration missions to the Moon and Mars. In addition to its high specific impulse (approximately 850-1000 s) and engine thrust-to-weight ratio (approximately 3-10), the NTR can also be configured as a 'dual mode' system capable of generating electrical power for spacecraft environmental systems, communications, and enhanced stage operations (e.g., refrigeration for long-term liquid hydrogen storage). At present the Nuclear Propulsion Office (NPO) is examining a variety of mission applications for the NTR ranging from an expendable, single-burn, trans-lunar injection (TLI) stage for NASA's First Lunar Outpost (FLO) mission to all propulsive, multiburn, NTR-powered spacecraft supporting a 'split cargo-piloted sprint' Mars mission architecture. Each application results in a particular set of requirements in areas such as the number of engines and their respective thrust levels, restart capability, fuel operating temperature and lifetime, cryofluid storage, and stage size. Two solid core NTR concepts are examined -- one based on NERVA (Nuclear Engine for Rocket Vehicle Application) derivative reactor (NDR) technology, and a second concept which utilizes a ternary carbide 'twisted ribbon' fuel form developed by the Commonwealth of Independent States (CIS). The NDR and CIS concepts have an established technology database involving significant nuclear testing at or near representative operating conditions. Integrated systems and mission studies indicate that clusters of two to four 15 to 25 klbf NDR or CIS engines are sufficient for most of the lunar and Mars mission scenarios currently under consideration. This paper provides descriptions and performance characteristics for the NDR and CIS concepts, summarizes NASA's First Lunar Outpost and Mars mission scenarios, and describes characteristics for representative cargo and piloted vehicles compatible with a reference 240 t-class heavy lift launch vehicle (HLLV) and smaller 120 t HLLV option. Attractive performance characteristics and high-leverage technologies associated with both the engine and stage are identified, and supporting parametric sensitivity data is provided. The potential for commonality of engine and stage components to satisfy a broad range of lunar and Mars missions is also discussed.

Fast track lunar NTR systems assessment for the First Lunar Outpost and its evolvability to Mars

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Alexander, Stephen W.

1992-01-01

The objectives of the 'fast track' lunar Nuclear Thermal Rocket (NTR) analysis are to quantify necessary engine/stage characteristics to perform NASA's 'First Lunar Outpost' scenario and to assess the potential for evolution to Mars mission applications. By developing NTR/stage technologies for use in NASA's 'First Lunar Outpost' scenario, NASA will make a major down payment on the key components needed for the follow-on Mars Space Transportation System. A faster, cheaper approach to overall lunar/Mars exploration is expected.

A Potential NASA Research Reactor to Support NTR Development

NASA Technical Reports Server (NTRS)

Eades, Michael; Gerrish, Harold; Hardin, Leroy

2013-01-01

In support of efforts for research into the design and development of a man rated Nuclear Thermal Rocket (NTR) engine, the National Aeronautics and Space Administration (NASA), Marshall Space Flight Center (MSFC), is evaluating the potential for building a Nuclear Regulatory Commission (NRC) licensed research reactor. The proposed reactor would be licensed by NASA and operated jointly by NASA and university partners. The purpose of this reactor would be to perform further research into the technologies and systems needed for a successful NTR project and promote nuclear training and education.

Nuclear Thermal Propulsion (NTP): A Proven Growth Technology for Human NEO/Mars Exploration Missions

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

2012-01-01

The nuclear thermal rocket (NTR) represents the next "evolutionary step" in high performance rocket propulsion. Unlike conventional chemical rockets that produce their energy through combustion, the NTR derives its energy from fission of Uranium-235 atoms contained within fuel elements that comprise the engine s reactor core. Using an "expander" cycle for turbopump drive power, hydrogen propellant is raised to a high pressure and pumped through coolant channels in the fuel elements where it is superheated then expanded out a supersonic nozzle to generate high thrust. By using hydrogen for both the reactor coolant and propellant, the NTR can achieve specific impulse (Isp) values of 900 seconds (s) or more - twice that of today s best chemical rockets. From 1955 - 1972, twenty rocket reactors were designed, built and ground tested in the Rover and NERVA (Nuclear Engine for Rocket Vehicle Applications) programs. These programs demonstrated: (1) high temperature carbide-based nuclear fuels; (2) a wide range of thrust levels; (3) sustained engine operation; (4) accumulated lifetime at full power; and (5) restart capability - all the requirements needed for a human Mars mission. Ceramic metal "cermet" fuel was pursued as well, as a backup option. The NTR also has significant "evolution and growth" capability. Configured as a "bimodal" system, it can generate its own electrical power to support spacecraft operational needs. Adding an oxygen "afterburner" nozzle introduces a variable thrust and Isp capability and allows bipropellant operation. In NASA s recent Mars Design Reference Architecture (DRA) 5.0 study, the NTR was selected as the preferred propulsion option because of its proven technology, higher performance, lower launch mass, versatile vehicle design, simple assembly, and growth potential. In contrast to other advanced propulsion options, no large technology scale-ups are required for NTP either. In fact, the smallest engine tested during the Rover program - the 25,000 lbf (25 klbf) "Pewee" engine is sufficient when used in a clustered engine arrangement. The "Copernicus" crewed spacecraft design developed in DRA 5.0 has significant capability and a human exploration strategy is outlined here that uses Copernicus and its key components for precursor near Earth object (NEO) and Mars orbital missions prior to a Mars landing mission. The paper also discusses NASA s current activities and future plans for NTP development that include system-level Technology Demonstrations - specifically ground testing a small, scalable NTR by 2020, with a flight test shortly thereafter.

In vivo bacterial imaging without engineering; A novel probe-based strategy facilitated by endogenous nitroreductase enzymes.

PubMed

Stanton, Michael; Cronin, Michelle; Lehouritis, Panos; Tangney, Mark

2015-01-01

The feasibility of utilising bacteria as vectors for gene therapy is becoming increasingly recognised. This is primarily due to a number of intrinsic properties of bacteria such as their tumour targeting capabilities, their ability to carry large genetic or protein loads and the availability of well-established genetic engineering tools for a range of common lab strains. However, a number of issues relating to the use of bacteria as vectors for gene therapy need to be addressed in order for the field to progress. Amongst these is the need for the development of non-invasive detection/imaging systems for bacteria within a living host. In vivo optical imaging has advanced preclinical research greatly, and typically involves engineering of bacteria with genetic expression constructs for luminescence (e.g. the lux operon) or fluorescent proteins (GFP etc.). This requirement for genetic modification can be restrictive, where engineering is not experimentally appropriate or technologically feasible (e.g. due to lack of suitable engineering tools). We describe a novel strategy exploiting endogenous bacterial enzymatic activity to specifically activate an exogenously administered fluorescent imaging probe. The red shifted, quenched fluorophore CytoCy5S is reduced to a fluorescent form by bacterial-specific nitroreductase (NTR) enzymes. NTR enzymes are present in a wide range of bacterial genera and absent in mammalian systems, permitting highly specific detection of Gram-negative and Gram-positive bacteria in vivo. In this study, dose-responsive bacterial-specific signals were observed in vitro from all genera examined - E. coli, Salmonella, Listeria, Bifidobacterium and Clostridium difficile. Examination of an NTR-knockout strain validated the enzyme specificity of the probe. In vivo whole-body imaging permitted specific, dose-responsive monitoring of bacteria over time in various infection models, and no toxicity to bacteria or host was observed. This study demonstrates the concept of exploiting innate NTR activity as a reporting strategy for wild-type bacteria using optical imaging, while the concept may also be extended to NTR-specific probes for use with other imaging modalities.

The Benefits of Nuclear Thermal Propulsion (NTP) in an Evolvable Mars Campaign

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Mccurdy, David R.

2014-01-01

NTR: High thrust high specific impulse (2 x LOXLH2chemical) engine uses high power density fission reactor with enriched uranium fuel as thermal power source. Reactor heat is removed using H2propellant which is then exhausted to produce thrust. Conventional chemical engine LH2tanks, turbopumps, regenerative nozzles and radiation-cooled shirt extensions used --NTR is next evolutionary step in high performance liquid rocket engines During the Rover program, a common fuel element tie tube design was developed and used in the design of the 50 klbf Kiwi-B4E (1964), 75 klbf Phoebus-1B (1967), 250 klbf Phoebus-2A (June 1968), then back down to the 25 klbf Pewee engine (Nov-Dec 1968) NASA and DOE are using this same approach: design, build, ground then flight test a small engine using a common fuel element that is scalable to a larger 25 klbf thrust engine needed for human missions

Study of unconventional aircraft engines designed for low energy consumption

NASA Technical Reports Server (NTRS)

Gray, D. E.

1976-01-01

Declining U.S. oil reserves and escalating energy costs underline the need for reducing fuel consumption in aircraft engines. The most promising unconventional aircraft engines based on their potential for fuel savings and improved economics are identified. The engines installed in both a long-range and medium-range aircraft were evaluated. Projected technology advances are identified and evaluated for their state-of-readiness for application to a commercial transport. Programs are recommended for developing the necessary technology.

Robust Exploration and Commercial Missions to the Moon Using NTR LANTR Propulsion and Lunar-Derived Propellants

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Ryan, Stephen W.; Burke, Laura M.; McCurdy, David R.; Fittje, James E.; Joyner, Claude R.

2017-01-01

The nuclear thermal rocket (NTR) has frequently been identified as a key space asset required for the human exploration of Mars. This proven technology can also provide the affordable access through cislunar space necessary for commercial development and sustained human presence on the Moon. In his post-Apollo Integrated Space Program Plan (1970-1990), Wernher von Braun, proposed a reusable nuclear thermal propulsion stage (NTPS) to deliver cargo and crew to the Moon to establish a lunar base before undertaking human missions to Mars. The NTR option was selected by von Braun because it was a demonstrated technology capable of generating both high thrust and high specific impulse (Isp 900 s) twice that of todays best chemical rockets. In NASAs Mars Design Reference Architecture (DRA) 5.0 study, the crewed Mars transfer vehicle used three 25 klbf Pewee engines the smallest and highest performing engine tested in the Rover program along with graphite composite fuel. Smaller, lunar transfer vehicles consisting of a NTPS using three approximately 16.5 klbf Small Nuclear Rocket Engines (SNREs), an in-line propellant tank, plus the payload can enable a variety of reusable lunar missions. These include cargo delivery and crewed lunar landing missions. Even weeklong tourism missions carrying passengers into lunar orbit for a day of sightseeing and picture taking are possible. The NTR can play an important role in the next phase of lunar exploration and development by providing an affordable in-space lunar transportation system (LTS) that can allow initial outposts to evolve into settlements supported by a variety of commercial activities such as in-situ propellant production used to supply strategically located propellant depots and transportation nodes. The utilization of iron-rich volcanic glass or lunar polar ice (LPI) deposits (each estimated at billions of metric tons) for propellant production can significantly reduce the launch mass requirements from Earth and can enable reusable, surface-based lunar landing vehicles (LLVs) using liquid oxygen/hydrogen (LOX/LH2) chemical rocket engines. Afterwards, LOX/LH2 propellant depots can be established in lunar equatorial and polar orbits to supply the LTS. At this point a modified version of the conventional NTR called the LOX-augmented NTR, or LANTR would be introduced into the LTS allowing bipropellant operation and leveraging the mission benefits of refueling with lunar-derived propellants for Earth return. The bipropellant LANTR engine utilizes the large divergent section of its nozzle as an afterburner into which oxygen is injected and supersonically combusted with nuclear preheated hydrogen emerging from the engines choked sonic throat essentially scramjet propulsion in reverse. By varying the oxygen-to-hydrogen mixture ratio, LANTR engines can operate over a range of thrust and Isp values while the reactor core power level remains relatively constant. Eventually, a LANTR-based LTS can enable a rapid commuter shuttle with one-way trip times to and from the Moon ranging from 36 to 24 hours. Even if only 1 of the extracted propellant from identified volcanic glass and polar ice deposits were available for use in lunar orbit, such a supply could support daily commuter flights to the Moon for many thousands of years! An evolutionary mission architecture is outlined and a variety of lunar missions and transfer vehicle designs are examined, along with the increasing demands on propellant production as mission complexity increases. A comparison of vehicle features and engine operating characteristics, for both NTR and LANTR engines, is also provided along with a brief discussion on the propellant production issues associated with using volcanic glass and LPI as source material.

Overcoming Present-Day Powerplant Limitations Via Unconventional Engine Configurations

NASA Technical Reports Server (NTRS)

Meitner, Peter L.

2006-01-01

The Army Research Laboratory s Vehicle Technology Directorate is sponsoring the prototype development of three unconventional engine concepts - two intermittent combustion (IC) engines and one turbine engine (via SBIR (Small Business Innovative Research) contracts). The IC concepts are the Nutating Engine and the Bonner Engine, and the turbine concept is the POWER Engine. Each of the three engines offers unique and greatly improved capabilities (which cannot be achieved by present-day powerplants), while offering significant reductions in size and weight. This paper presents brief descriptions of the physical characteristics of the three engines, and discusses their performance potentials, as well as their development status.

Affordable Development and Demonstration of a Small NTR Engine and Stage: How Small is Big Enough?

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Sefcik, Robert J.; Fittje, James E.; McCurdy, David R.; Qualls, Arthur L.; Schnitzler, Bruce G.; Werner, James E.; Weitzberg (Abraham); Joyner, Claude R.

2015-01-01

The Nuclear Thermal Rocket (NTR) derives its energy from fission of uranium-235 atoms contained within fuel elements that comprise the engine's reactor core. It generates high thrust and has a specific impulse potential of approximately 900 seconds - a 100% increase over today's best chemical rockets. The Nuclear Thermal Propulsion (NTP) project, funded by NASA's AES program, includes five key task activities: (1) Recapture, demonstration, and validation of heritage graphite composite (GC) fuel (selected as the "Lead Fuel" option); (2) Engine Conceptual Design; (3) Operating Requirements Definition; (4) Identification of Affordable Options for Ground Testing; and (5) Formulation of an Affordable Development Strategy. During FY'14, a preliminary DDT&E plan and schedule for NTP development was outlined by GRC, DOE and industry that involved significant system-level demonstration projects that included GTD tests at the NNSS, followed by a FTD mission. To reduce cost for the GTD tests and FTD mission, small NTR engines, in either the 7.5 or 16.5 klbf thrust class, were considered. Both engine options used GC fuel and a "common" fuel element (FE) design. The small approximately 7.5 klbf "criticality-limited" engine produces approximately 157 megawatts of thermal power (MWt) and its core is configured with parallel rows of hexagonal-shaped FEs and tie tubes (TTs) with a FE to TT ratio of approximately 1:1. The larger approximately 16.5 klbf Small Nuclear Rocket Engine (SNRE), developed by LANL at the end of the Rover program, produces approximately 367 MWt and has a FE to TT ratio of approximately 2:1. Although both engines use a common 35 inch (approximately 89 cm) long FE, the SNRE's larger diameter core contains approximately 300 more FEs needed to produce an additional 210 MWt of power. To reduce the cost of the FTD mission, a simple "1-burn" lunar flyby mission was considered to reduce the LH2 propellant loading, the stage size and complexity. Use of existing and flight proven liquid rocket and stage hardware (e.g., from the RL10B-2 engine and Delta Cryogenic Second Stage) was also maximized to further aid affordability. This paper examines the pros and cons of using these two small engine options, including their potential to support future human exploration missions to the Moon, near Earth asteroids, and Mars, and recommends a preferred size. It also provides a preliminary assessment of the key activities, development options, and schedule required to affordably build, ground test and fly a small NTR engine and stage within a 10-year timeframe.

"2001: A Space Odyssey" Revisited--The Feasibility of 24 Hour Commuter Flights to the Moon Using NTR Propulsion with LUNOX Afterburners

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Dudzinski, Leonard A.

1998-01-01

The prospects for "24 hour" commuter flights to the Moon, similar to that portrayed in 2001: A Space Odyssey but on a more Spartan scale, are examined using two near term, "high leverage" technologies--liquid oxygen (LOX)-augmented nuclear thermal rocket (NTR) propulsion and "lunar-derived" oxygen (LUNOX) production. Ironrich volcanic glass, or "orange soil," discovered during the Apollo 17 mission to Taurus-Littrow, has produced a 4% oxygen yield in recent NASA experiments using hydrogen reduction. LUNOX development and utilization would eliminate the need to transport oxygen supplies from Earth and is expected to dramatically reduce the size, cost and complexity of space transportation systems. The LOX-augmented NTR concept (LANTR) exploits the high performance capability of the conventional liquid hydrogen (LH2)-cooled NTR and the mission leverage provided by LUNOX in a unique way, LANTR utilizes the large divergent section of its nozzle as an "afterburner" into which oxygen is injected and supersonically combusted with nuclear preheated hydrogen emerging front the engine's choked sonic throat--essentially "scramjet propulsion in reverse." By varying the oxygen-to-hydrogen mixture ratio, the LANTR engine can operate over a wide range of thrust and specific impulse (Isp) values while the reactor core power level remains relatively constant. The thrust augmentation feature of LANTR means that "big engine" performance can be obtained using smaller, more affordable, easier to test NTR engines. The use of high-density LOX in place of low-density LH2 also reduces hydrogen mass and tank volume resulting in smaller space vehicles. An implementation strategy and evolutionary lunar mission architecture is outlined which requires only Shuttle C or "in-line" Shuttle-derived launch vehicles, and utilizes conventional NTR-powered lunar transfer vehicles (LTVs), operating in an "expendable mode" initially, to maximize delivered surface payload on each mission. The increased payload is dedicated to installing "modular" LUNOX production units with the intent of supplying LUNOX to lunar landing vehicles (LLVS) and then LTVs at the earliest possible opportunity. Once LUNOX becomes available in low lunar orbit (LLO), monopropellant NTRs would be outfitted with an oxygen propellant module, feed system and afterburner nozzle for "bipropellant" operation. Transition to a "reusable" mission architecture now occurs with smaller, LANTR-powered LTVs delivering approximately 400% more payload on each piloted round trip mission than earlier expendable "all LH2" NTR systems. As initial lunar outposts grow to eventual lunar settlements and LUNOX production capacity increases, the LANTR concept can enable a rapid "commuter" shuttle capable of 24 hour "one way" trips to and from the Moon, A vast deposit of"iron-rich" volcanic glass beads identified at just one candidate site--located at the southeastern edge of Mare Serenitatis--could supply, sufficient LUNOX to support daily commuter flights to the Moon for the next 9000 years!

2001: A Space Odyssey Revisited: The Feasibility of 24 Hour Commuter Flights to the Moon Using NTR Propulsion with LUNOX Afterburners. Revised

NASA Technical Reports Server (NTRS)

Borowski, Stanley; Dudzinski, Leonard A.

2003-01-01

The prospects for 24 hour commuter flights to the Moon, similar to that portrayed in 2001: A Space Odyssey but on a more Spartan scale, are examined using two near term, high leverage technologies: liquid oxygen (LOX)-augmented nuclear thermal rocket (NTR) propulsion and lunar-derived oxygen (LUNOX) production. Iron-rich volcanic glass, or orange soil, discovered during the Apollo 17 mission to Taurus-Littrow, has produced a 4 percent oxygen yield in recent NASA experiments using hydrogen reduction. LUNOX development and utilization would eliminate the need to transport oxygen supplies from Earth and is expected to dramatically reduce the size, cost and complexity of space transportation systems. The LOX-augmented NTR concept (LANTR) exploits the high performance capability of the conventional liquid hydrogen (LH2)-cooled NTR and the mission leverage provided by LUNOX in a unique way. LANTR utilizes the large divergent section of its nozzle as an afterburner into which oxygen is injected and supersonically combusted with nuclear preheated hydrogen emerging from the engine's choked sonic throat, essentially scramjet propulsion in reverse. By varying the oxygen-to-hydrogen mixture ratio, the LANTR engine can operate over a wide range of thrust and specific impulse (Isp) values while the reactor core power level remains relatively constant. The thrust augmentation feature of LANTR means that big engine performance can be obtained using smaller, more affordable, easier to test NTR engines. The use of high-density LOX in place of low density LH2 also reduces hydrogen mass and tank volume resulting in smaller space vehicles. An implementation strategy and evolutionary lunar mission architecture is outlined which requires only Shuttle C or in-line Shuttle-derived launch vehicles, and utilizes conventional NTR-powered lunar transfer vehicles (LTVs), operating in an expendable mode initially, to maximize delivered surface payload on each mission. The increased payload is dedicated to installing modular LUNOX production units with the intent of supplying LUNOX to lunar landing vehicles (LLVs) and then LTVs at the earliest possible opportunity. Once LUNOX becomes available in low lunar orbit (LLO), monopropellant NTRs would be outfitted with an oxygen propellant module, feed system and afterburner nozzle for bipropellant operation. Transition to a reusable mission architecture now occurs with smaller, LANTR-powered LTVs delivering 400% more payload on each piloted round trip mission than earlier expendable all LH2 NTR systems. As initial lunar outposts grow to eventual lunar settlements and LUNOX production capacity increases, the LANTR concept can enable a rapid commuter shuttle capable of 24 hour one way trips to and from the Moon. A vast deposit of iron-rich volcanic glass beads identified at just one candidate site located at the southeastern edge of Mare Serenitatis could supply sufficient LUNOX to support daily commuter flights to the Moon for the next 9000 years!

"2001: A Space Odyssey" Revisited: The Feasibility of 24 Hour Commuter Flights to the Moon Using NTR Propulsion with LUNOX Afterburners. Revised

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Dudzinski, Leonard A.

2001-01-01

The prospects for "24 hour" commuter flights to the Moon. similar to that portrayed in 2001: A Space Odyssey but on a more Spartan scale. are examined using two near term. "high leverage" technologies-liquid oxygen (LOX)-augmented nuclear thermal rocket (NTR) propulsion and "lunar-derived" oxygen (LUNOX) production. Iron-rich volcanic glass. or "orange soil," discovered during the Apollo 17 mission to Taurus-Littrow. has produced a 4% oxygen yield in recent NASA experiments using hydrogen reduction. LUNOX development and utilization would eliminate the need to transport oxygen supplies from Earth and is expected to dramatically reduce the size, cost and complexity of space transportation systems. The LOX-augmented NTR concept (LANTR) exploits the high performance capability of the conventional liquid hydrogen (LH2)-cooled NTR and the mission leverage provided by LUNOX in a unique way. LANTR utilizes the large divergent section of its nozzle as an "afterburner" into which oxygen is injected and supersonically combusted with nuclear preheated hydrogen emerging from the engine's choked sonic throat-essentially "scramjet propulsion in reverse." By varying the oxygen-to-hydrogen mixture ratio, the LANTR engine can operate over a wide range of thrust and specific impulse (Isp) values while the reactor core power level remains relatively constant. The thrust augmentation feature of LANTR means that "big engine" performance can be obtained using smaller. more affordable. easier to test NTR engines. The use of high-density LOX in place of low-density LH2 also reduces hydrogen mass and tank volume resulting in smaller space vehicles. An implementation strategy and evolutionary lunar mission architecture is outlined which requires only Shuttle C or "in-line" Shuttle-derived launch vehicles, and utilizes conventional NTR-powered lunar transfer vehicles (LTVs), operating in an "expendable mode" initially, to maximize delivered surface payload on each mission. The increased payload is dedicated to installing "modular" LUNOX production units with the intent of supplying LUNOX to lunar landing vehicles (LLVs) and then LTVs at the earliest possible opportunity. Once LUNOX becomes available in low lunar orbit (LLO), monopropellant NTRs would be outfitted with an oxygen propellant module, feed system and afterburner nozzle for "bipropellant" operation. Transition to a "reusable" mission architecture now occurs with smaller, LANTR-powered LTVs delivering approximately 400% more payload on each piloted round trip mission than earlier expendable "all LH2" NTR systems. As initial lunar outposts grow to eventual lunar settlements and LUNOX production capacity increases, the LANTR concept can enable a rapid "commuter" shuttle capable of 24 hour "one way" trips to and from the Moon. A vast deposit of "iron-rich" volcanic glass beads identified at just one candidate site - located at the southeastern edge of Mare Serenitatis - could supply sufficient LUNOX to support daily commuter flights to the Moon for the next 9000 years'.

NTREES Testing and Operations Status

NASA Technical Reports Server (NTRS)

Emrich, Bill

2007-01-01

Nuclear Thermal Rockets or NTR's have been suggested as a propulsion system option for vehicles traveling to the moon or Mars. These engines are capable of providing high thrust at specific impulses at least twice that of today's best chemical engines. The performance constraints on these engines are mainly the result of temperature limitations on the fuel coupled with a limited ability to withstand chemical attack by the hot hydrogen propellant. To operate at maximum efficiency, fuel forms are desired which can withstand the extremely hot, hostile environment characteristic of NTR operation for at least several hours. The simulation of such an environment would require an experimental device which could simultaneously approximate the power, flow, and temperature conditions which a nuclear fuel element (or partial element) would encounter during NTR operation. Such a simulation would allow detailed studies of the fuel behavior and hydrogen flow characteristics under reactor like conditions to be performed. Currently, the construction of such a simulator has been completed at the Marshall Space Flight Center, and will be used in the future to evaluate a wide variety of fuel element designs and the materials of which they are fabricated. This present work addresses the operational status of the Nuclear Thermal Rocket Element Environmental Simulator or NTREES and some of the design considerations which were considered prior to and during its construction.

Nuclear Thermal Rocket (Ntr) Propulsion: A Proven Game-Changing Technology for Future Human Exploration Missions

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

2012-01-01

The NTR represents the next evolutionary step in high performance rocket propulsion. It generates high thrust and has a specific impulse (Isp) of approx.900 seconds (s) or more V twice that of today s best chemical rockets. The technology is also proven. During the previous Rover and NERVA (Nuclear Engine for Rocket Vehicle Applications) nuclear rocket programs, 20 rocket reactors were designed, built and ground tested. These tests demonstrated: (1) a wide range of thrust; (2) high temperature carbide-based nuclear fuel; (3) sustained engine operation; (4) accumulated lifetime; and (5) restart capability V all the requirements needed for a human mission to Mars. Ceramic metal cermet fuel was also pursued, as a backup option. The NTR also has significant growth and evolution potential. Configured as a bimodal system, it can generate electrical power for the spacecraft. Adding an oxygen afterburner nozzle introduces a variable thrust and Isp capability and allows bipropellant operation. In NASA s recent Mars Design Reference Architecture (DRA) 5.0 study, the NTR was selected as the preferred propulsion option because of its proven technology, higher performance, lower launch mass, simple assembly and mission operations. In contrast to other advanced propulsion options, NTP requires no large technology scale-ups. In fact, the smallest engine tested during the Rover program V the 25,000 lbf (25 klbf) Pewee engine is sufficient for human Mars missions when used in a clustered engine arrangement. The Copernicus crewed spacecraft design developed in DRA 5.0 has significant capability and a human exploration strategy is outlined here that uses Copernicus and its key components for precursor near Earth asteroid (NEA) and Mars orbital missions prior to a Mars landing mission. Initially, the basic Copernicus vehicle can enable reusable 1-year round trip human missions to candidate NEAs like 1991 JW and Apophis in the late 2020 s to check out vehicle systems. Afterwards, the Copernicus spacecraft and its 2 key components, now configured as an Earth Return Vehicle / propellant tanker, would be used for a short round trip (approx.18 - 20 months)/short orbital stay (60 days) Mars / Phobos survey mission in 2033 using a split mission approach. The paper also discusses NASA s current Foundational Technology Development activities and its pre-decisional plans for future system-level Technology Demonstrations that include ground testing a small (approx.7.5 klbf) scalable NTR before the decade is out with a flight test shortly thereafter.

Future Propulsion Opportunities for Commuter Airplanes

NASA Technical Reports Server (NTRS)

Strack, W. C.

1982-01-01

Commuter airplane propulsion opportunities are summarized. Consideration is given to advanced technology conventional turboprop engines, advanced propellers, and several unconventional alternatives: regenerative turboprops, rotaries, and diesels. Advanced versions of conventional turboprops (including propellers) offer 15-20 percent savings in fuel and 10-15 percent in DOC compared to the new crop of 1500-2000 SHP engines currently in development. Unconventional engines could boost the fuel savings to 30-40 percent. The conclusion is that several important opportunities exist and, therefore, powerplant technology need not plateau.

Affordable Development and Demonstration of a Small NTR Engine and Stage: A Preliminary NASA, DOE, and Industry Assessment

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Sefcik, Robert J.; Fittje, James E.; McCurdy, David R.; Qualls, Arthur L.; Schnitzler, Bruce G.; Werner, James E.; Weitzberg, Abraham; Joyner, Claude R.

2015-01-01

The Nuclear Thermal Rocket (NTR) represents the next evolutionary step in cryogenic liquid rocket engines. Deriving its energy from fission of uranium-235 atoms contained within fuel elements that comprise the engine's reactor core, the NTR can generate high thrust at a specific impulse of approx. 900 seconds or more - twice that of today's best chemical rockets. In FY'11, as part of the AISP project, NASA proposed a Nuclear Thermal Propulsion (NTP) effort that envisioned two key activities - "Foundational Technology Development" followed by system-level "Technology Demonstrations". Five near-term NTP activities identified for Foundational Technology Development became the basis for the NCPS project started in FY'12 and funded by NASA's AES program. During Phase 1 (FY'12-14), the NCPS project was focused on (1) Recapturing fuel processing techniques and fabricating partial length "heritage" fuel elements for the two candidate fuel forms identified by NASA and the DOE - NERVA graphite "composite" and the uranium dioxide (UO2) in tungsten "cermet". The Phase 1 effort also included: (2) Engine Conceptual Design; (3) Mission Analysis and Requirements Definition; (4) Identification of Affordable Options for Ground Testing; and (5) Formulation of an Affordable and Sustainable NTP Development Strategy. During FY'14, a preliminary plan for DDT&E was outlined by GRC, the DOE and industry for NASA HQ that involved significant system-level demonstration projects that included GTD tests at the NNSS, followed by a FTD mission. To reduce development costs, the GTD and FTD tests use a small, low thrust (approx. 7.5 or 16.5 klbf) engine. Both engines use graphite composite fuel and a "common" fuel element design that is scalable to higher thrust (approx. 25 klbf) engines by increasing the number of elements in a larger diameter core that can produce greater thermal power output. To keep the FTD mission cost down, a simple "1-burn" lunar flyby mission was considered along with maximizing the use of existing and flight proven liquid rocket and stage hardware (e.g., from the RL10-B2 engine and Delta Cryogenic Second Stage) to further ensure affordability. This paper provides a preliminary NASA, DOE and industry assessment of what is required - the key DDT&E activities, development options, and the associated schedule - to affordably build, ground test and fly a small NTR engine and stage within a 10-year timeframe.

Vehicle and Mission Design Options for the Human Exploration of Mars/Phobos Using "Bimodal" NTR and LANTR Propulsion

NASA Astrophysics Data System (ADS)

Borowski, Stanley K.; Dudzinski, Leonard A.; McGuire, Melissa L.

2002-12-01

The nuclear thermal rocket (NTR) is one of the leading propulsion options for future human missions to Mars because of its high specific impulse (1sp is approximately 850-1000 s) capability and its attractive engine thrust-to-weight ratio (approximately 3-10). To stay within the available mass and payload volume limits of a "Magnum" heavy lift vehicle, a high performance propulsion system is required for trans-Mars injection (TMI). An expendable TMI stage, powered by three 15 thousand pounds force (klbf) NTR engines is currently under consideration by NASA for its Design Reference Mission (DRM). However, because of the miniscule burnup of enriched uranium-235 during the Earth departure phase (approximately 10 grams out of 33 kilograms in each NTR core), disposal of the TMI stage and its engines after a single use is a costly and inefficient use of this high performance stage. By reconfiguring the engines for both propulsive thrust and modest power generation (referred to as "bimodal" operation), a robust, multiple burn, "power-rich" stage with propulsive Mars capture and reuse capability is possible. A family of modular bimodal NTR (BNTR) vehicles are described which utilize a common "core" stage powered by three 15 klbf BNTRs that produce 50 kWe of total electrical power for crew life support, an active refrigeration / reliquification system for long term, zero-boiloff liquid hydrogen (LH2) storage, and high data rate communications. An innovative, spine-like "saddle truss" design connects the core stage and payload element and is open underneath to allow supplemental "in-line" propellant tanks and contingency crew consumables to be easily jettisoned to improve vehicle performance. A "modified" DRM using BNTR transfer vehicles requires fewer transportation system elements, reduces IMLEO and mission risk, and simplifies space operations. By taking the next logical step--use of the BNTR for propulsive capture of all payload elements into Mars orbit--the power available in Mars orbit grows to 150 kWe compared to 30 kWe for the DRM. Propulsive capture also eliminates the complex, higher risk aerobraking and capture maneuver which is replaced by a simpler reentry using a standardized, lower mass "aerodescent" shell. The attractiveness of the "all BNTR" option is further increased by the substitution of the lightweight, inflatable "TransHab" module in place of the heavier, hard-shell hab module. Use of TransHab introduces the potential for propulsive recovery and reuse of the BNTR / Earth return vehicle (ERV). It also allows the crew to travel to and from Mars on the same BNTR transfer vehicle thereby cutting the duration of the ERV mission in half--from approximately 4.7 to 2.5 years. Finally, for difficult Mars options, such as Phobos rendezvous and sample return missions, volume (not mass) constraints limit the performance of the "all LH2" BNTR stage. The use of "LOX-augmented" NTR (LANTR) engines, operating at a modest oxygen-to-hydrogen mixture ratio (MR) of 0.5, helps to increase "bulk" propellant density and total thrust during the TMI burn. On all subsequent burns, the bimodal LANTR engines operate on LH2 only (MR=0) to maximize vehicle performance while staying within the mass limits of two Magnum launches.

Vehicle and Mission Design Options for the Human Exploration of Mars/Phobos Using "Bimodal" NTR and LANTR Propulsion. Revised Dec. 1998

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Dudzinski, Leonard A.; McGuire, Melissa L.

2002-01-01

The nuclear thermal rocket (NTR) is one of the leading propulsion options for future human missions to Mars because of its high specific impulse (1sp is approximately 850-1000 s) capability and its attractive engine thrust-to-weight ratio (approximately 3-10). To stay within the available mass and payload volume limits of a "Magnum" heavy lift vehicle, a high performance propulsion system is required for trans-Mars injection (TMI). An expendable TMI stage, powered by three 15 thousand pounds force (klbf) NTR engines is currently under consideration by NASA for its Design Reference Mission (DRM). However, because of the miniscule burnup of enriched uranium-235 during the Earth departure phase (approximately 10 grams out of 33 kilograms in each NTR core), disposal of the TMI stage and its engines after a single use is a costly and inefficient use of this high performance stage. By reconfiguring the engines for both propulsive thrust and modest power generation (referred to as "bimodal" operation), a robust, multiple burn, "power-rich" stage with propulsive Mars capture and reuse capability is possible. A family of modular bimodal NTR (BNTR) vehicles are described which utilize a common "core" stage powered by three 15 klbf BNTRs that produce 50 kWe of total electrical power for crew life support, an active refrigeration / reliquification system for long term, zero-boiloff liquid hydrogen (LH2) storage, and high data rate communications. An innovative, spine-like "saddle truss" design connects the core stage and payload element and is open underneath to allow supplemental "in-line" propellant tanks and contingency crew consumables to be easily jettisoned to improve vehicle performance. A "modified" DRM using BNTR transfer vehicles requires fewer transportation system elements, reduces IMLEO and mission risk, and simplifies space operations. By taking the next logical step--use of the BNTR for propulsive capture of all payload elements into Mars orbit--the power available in Mars orbit grows to 150 kWe compared to 30 kWe for the DRM. Propulsive capture also eliminates the complex, higher risk aerobraking and capture maneuver which is replaced by a simpler reentry using a standardized, lower mass "aerodescent" shell. The attractiveness of the "all BNTR" option is further increased by the substitution of the lightweight, inflatable "TransHab" module in place of the heavier, hard-shell hab module. Use of TransHab introduces the potential for propulsive recovery and reuse of the BNTR / Earth return vehicle (ERV). It also allows the crew to travel to and from Mars on the same BNTR transfer vehicle thereby cutting the duration of the ERV mission in half--from approximately 4.7 to 2.5 years. Finally, for difficult Mars options, such as Phobos rendezvous and sample return missions, volume (not mass) constraints limit the performance of the "all LH2" BNTR stage. The use of "LOX-augmented" NTR (LANTR) engines, operating at a modest oxygen-to-hydrogen mixture ratio (MR) of 0.5, helps to increase "bulk" propellant density and total thrust during the TMI burn. On all subsequent burns, the bimodal LANTR engines operate on LH2 only (MR=0) to maximize vehicle performance while staying within the mass limits of two Magnum launches.

Vehicle and Mission Design Options for the Human Exploration of Mars/Phobos Using "Bimodal" NTR and LANTR Propulsion

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Dudzinski, Leonard A.; McGuire, Melissa L.

1998-01-01

The nuclear thermal rocket (NTR) is one of the leading propulsion options for future human missions to Mars because of its high specific impulse (Isp-850-1000 s) capability and its attractive engine thrust-to-weight ratio (approximately equal 3-10). To stay within the available mass and payload volume limits of a "Magnum" heavy lift vehicle, a high performance propulsion system is required for trans-Mars injection (TMI). An expendable TMI stage, powered by three 15 thousand pounds force (klbf) NTR engines is currently under consideration by NASA for its Design Reference Mission (DRM). However, because of the miniscule burnup of enriched uranium-235 during the Earth departure phase (approximately 10 grams out of 33 kilograms in each NTR core), disposal of the TMI stage and its engines after a single use is a costly and inefficient use of this high performance stage. By reconfiguring the engines for both propulsive thrust and modest power generation (referred to as "bimodal" operation), a robust, multiple burn, "power-rich" stage with propulsive Mars capture and reuse capability is possible, A family of modular "bimodal" NTR (BNTR) vehicles are described which utilize a common "core" stage powered by three 15 klbf BNTRs that produce 50 kWe of total electrical power for crew life support, an active refrigeration / reliquification system for long term, "zero-boiloff" liquid hydrogen (LH2) storage, and high data rate communications. An innovative, spine-like "saddle truss" design connects the core stage and payload element and is open underneath to allow supplemental "in-line" propellant tanks and contingency crew consumables to be easily jettisoned to improve vehicle performance. A "modified" DRM using BNTR transfer vehicles requires fewer transportation system elements, reduces IMLEO and mission risk, and simplifies space operations. By taking the next logical step--use of the BNTR for propulsive capture of all payload elements into Mars orbit--the power available in Mars orbit grows to 150 kWe compared to 30 kWe for the DRM. Propulsive capture also eliminates the complex, higher risk aerobraking and capture maneuver which is replaced by a simpler reentry using a standardized, lower mass "aerodescent" shell. The attractiveness of the "all BNTR" option is further increased by the substitution of the lightweight, inflatable "TransHab" module in place of the heavier, hard-shell hab module. Use of TransHab introduces the potential for propulsive recovery and reuse of the BNTR/ERV. It also allows the crew to travel to and from Mar on the same BNTR transfer vehicle thereby cutting the duration of the ERV mission in half--from approximately 4.7 to 2.5 years. Finally, for difficult Mars options, such as Phobos rendezvous and sample return missions, volume (not mass) constraints limit the performance of the "all LH2" BNTR stage. The use of "LOX-augmented" NTR (LANTR) engines, operating at a modest oxygen-to-hydrogen mixutre ratio (MR) of 0.5, helps to increase "bulk" propellant density and total thrust during the TMI burn. On all subsequent burns, the bimodal LANTR engines operate on LH2 only (MR=0) to maximize vehicle performance while staying within the lift capability of two Magnum launches.

Modular Growth NTR Space Transportation System for Future NASA Human Lunar, NEA and Mars Exploration Missions

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

2012-01-01

The nuclear thermal rocket (NTR) is a proven, high thrust propulsion technology that has twice the specific impulse (I(sub sp) approx.900 s) of today's best chemical rockets. During the Rover and NERVA (Nuclear Engine for Rocket Vehicle Applications) programs, twenty rocket reactors were designed, built and ground tested. These tests demonstrated: (1) a wide range of thrust; (2) high temperature carbide-based nuclear fuel; (3) sustained engine operation; (4) accumulated lifetime; and (5) restart capability - everything required for affordable human missions beyond LEO. In NASA's recent Mars Design Reference Architecture (DRA) 5.0 study, the NTR was selected as the preferred propulsion option because of its proven technology, higher performance, lower IMLEO, versatile vehicle design, and growth potential. Furthermore, the NTR requires no large technology scale-ups since the smallest engine tested during the Rover program - the 25 klb(sub f) "Pewee" engine is sufficient for human Mars missions when used in a clustered engine configuration. The "Copernicus" crewed Mars transfer vehicle developed for DRA 5.0 was an expendable design sized for fast-conjunction, long surface stay Mars missions. It therefore has significant propellant capacity allowing a reusable "1-year" round trip human mission to a large, high energy near Earth asteroid (NEA) like Apophis in 2028. Using a "split mission" approach, Copernicus and its two key elements - a common propulsion stage and integrated "saddle truss" and LH2 drop tank assembly - configured as an Earth Return Vehicle / propellant tanker, can also support a short round trip (approx.18 month) / short orbital stay (60 days) Mars reconnaissance mission in the early 2030's before a landing is attempted. The same short stay orbital mission can be performed with an "all-up" vehicle by adding an "in-line" LH2 tank to Copernicus to supply the extra propellant needed for this higher energy, opposition-class mission. To transition to a reusable Mars architecture, Copernicus' saddle truss / drop tank assembly is replaced by an in-line tank and "star truss" assembly with paired modular drop tanks to further increase the vehicle's propellant capacity. Shorter "1-way" transit time fast-conjunction Mars missions are another possibility using this vehicle configuration but, as with reusability, increased launch mass is required. "Scaled down" versions of Copernicus (sized to a SLS lift capability of approx.70 t - 100 t) can be developed initially allowing reusable lunar cargo delivery and crewed landing missions, easy NEA missions (e.g., 2000 SG344 also in 2028) or an expendable mission to Apophis. Mission scenario descriptions, key vehicle features and operational characteristics are provided along with a brief discussion of NASA's current activities and its "pre-decisional" plans for future NTR development.

Affordable Development and Demonstration of a Small Nuclear Thermal Rocket (NTR) Engine and Stage: How Small Is Big Enough?

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Sefcik, Robert J.; Fittje, James E.; McCurdy, David R.; Qualls, Arthur L.; Schnitzler, Bruce G.; Werner, James E.; Weitzberg, Abraham; Joyner, Claude R.

2016-01-01

The Nuclear Thermal Rocket (NTR) derives its energy from fission of uranium-235 atoms contained within fuel elements that comprise the engine's reactor core. It generates high thrust and has a specific impulse potential of approximately 900 specific impulse - a 100 percent increase over today's best chemical rockets. The Nuclear Thermal Propulsion (NTP) project, funded by NASA's Advanced Exploration Systems (AES) program, includes five key task activities: (1) Recapture, demonstration, and validation of heritage graphite composite (GC) fuel (selected as the Lead Fuel option); (2) Engine Conceptual Design; (3) Operating Requirements Definition; (4) Identification of Affordable Options for Ground Testing; and (5) Formulation of an Affordable Development Strategy. During fiscal year (FY) 2014, a preliminary Design Development Test and Evaluation (DDT&E) plan and schedule for NTP development was outlined by the NASA Glenn Research Center (GRC), Department of Energy (DOE) and industry that involved significant system-level demonstration projects that included Ground Technology Demonstration (GTD) tests at the Nevada National Security Site (NNSS), followed by a Flight Technology Demonstration (FTD) mission. To reduce cost for the GTD tests and FTD mission, small NTR engines, in either the 7.5 or 16.5 kilopound-force thrust class, were considered. Both engine options used GC fuel and a common fuel element (FE) design. The small approximately 7.5 kilopound-force criticality-limited engine produces approximately157 thermal megawatts and its core is configured with parallel rows of hexagonal-shaped FEs and tie tubes (TTs) with a FE to TT ratio of approximately 1:1. The larger approximately 16.5 kilopound-force Small Nuclear Rocket Engine (SNRE), developed by Los Alamos National Laboratory (LANL) at the end of the Rover program, produces approximately 367 thermal megawatts and has a FE to TT ratio of approximately 2:1. Although both engines use a common 35-inch (approximately 89-centimeters) -long FE, the SNRE's larger diameter core contains approximately 300 more FEs needed to produce an additional 210 thermal megawatts of power. To reduce the cost of the FTD mission, a simple one-burn lunar flyby mission was considered to reduce the liquid hydrogen (LH2) propellant loading, the stage size and complexity. Use of existing and flight proven liquid rocket and stage hardware (e.g., from the RL10B-2 engine and Delta Cryogenic Second Stage) was also maximized to further aid affordability. This paper examines the pros and cons of using these two small engine options, including their potential to support future human exploration missions to the Moon, near Earth asteroids (NEA), and Mars, and recommends a preferred size. It also provides a preliminary assessment of the key activities, development options, and schedule required to affordably build, ground test and fly a small NTR engine and stage within a 10-year timeframe.

High Leverage Space Transportation System Technologies for Human Exploration Missions to the Moon and Beyond

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Dudzinski, Leonard A.

1996-01-01

The feasibility of returning humans to the Moon by 2004, the 35th anniversary of the Apollo 11 landing, is examined assuming the use of existing launch vehicles (the Space Shuttle and Titan 4B), a near term, advanced technology space transportation system, and extraterrestrial propellant--specifically 'lunar-derived' liquid oxygen or LUNOX. The lunar transportation system (LTS) elements consist of an expendable, nuclear thermal rocket (NTR)-powered translunar injection (TLI) stage and a combination lunar lander/Earth return vehicle (LERV) using cryogenic liquid oxygen and hydrogen (LOX/LH2) chemical propulsion. The 'wet' LERV, carrying a crew of 2, is configured to fit within the Shuttle orbiter cargo bay and requires only modest assembly in low Earth orbit. After Earth orbit rendezvous and docking of the LERV with the Titan 4B-launched NTR TLI stage, the initial mass in low Earth orbit (IMLEO) is approx. 40 t. To maximize mission performance at minimum mass, the LERV carries no return LOX but uses approx. 7 t of LUNOX to 'reoxidize' itself for a 'direct return' flight to Earth followed by an 'Apollo-style' capsule recovery. Without LUNOX, mission capability is constrained and the total LTS mass approaches the combined Shuttle-Titan 4B IMLEO limit of approx. 45 t even with enhanced NTR and chemical engine performance. Key technologies are discussed, lunar mission scenarios described, and LTS vehicle designs and characteristics are presented. Mission versatility provided by using a small 'all LH2' NTR engine or a 'LOX-augmented' derivative, either individually or in clusters, for outer planet robotic orbiter, small Mars cargo, lunar 'commuter', and human Mars exploration class missions is also briefly discussed.

Neutral and Ion Measurements in the Ionosphere and Thermosphere: Neutral Wind, Ion-drift, Temperatures and Composition

DTIC Science & Technology

2009-09-30

NTR 5025703. HONORS/AWARDS/PRIZES Hollis H. Jones, NASA Goddard AETD Award for Innovative Technology Development, July 2009, Applied Engineering and Technology Directorate, NASA GSFC, Greenbelt, Maryland. 5

Robust Exploration and Commercial Missions to the Moon Using Nuclear Thermal Rocket Propulsion and Lunar Liquid Oxygen Derived from FeO-Rich Pyroclasitc Deposits

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Ryan, Stephen W.; Burke, Laura M.; McCurdy, David R.; Fittje, James E.; Joyner, Claude R.

2018-01-01

The nuclear thermal rocket (NTR) has frequently been identified as a key space asset required for the human exploration of Mars. This proven technology can also provide the affordable access through cislunar space necessary for commercial development and sustained human presence on the Moon. It is a demonstrated technology capable of generating both high thrust and high specific impulse (I(sub sp) approx. 900 s) twice that of today's best chemical rockets. Nuclear lunar transfer vehicles-consisting of a propulsion stage using three approx. 16.5-klb(sub f) small nuclear rocket engines (SNREs), an in-line propellant tank, plus the payload-are reusable, enabling a variety of lunar missions. These include cargo delivery and crewed lunar landing missions. Even weeklong ''tourism'' missions carrying passengers into lunar orbit for a day of sightseeing and picture taking are possible. The NTR can play an important role in the next phase of lunar exploration and development by providing a robust in-space lunar transportation system (LTS) that can allow initial outposts to evolve into settlements supported by a variety of commercial activities such as in-situ propellant production used to supply strategically located propellant depots and transportation nodes. The use of lunar liquid oxygen (LLO2) derived from iron oxide (FeO)-rich volcanic glass beads, found in numerous pyroclastic deposits on the Moon, can significantly reduce the launch mass requirements from Earth by enabling reusable, surface-based lunar landing vehicles (LLVs)that use liquid oxygen and hydrogen (LO2/LH2) chemical rocket engines. Afterwards, a LO2/LH2 propellant depot can be established in lunar equatorial orbit to supply the LTS. At this point a modified version of the conventional NTR-called the LO2-augmented NTR, or LANTR-is introduced into the LTS allowing bipropellant operation and leveraging the mission benefits of refueling with lunar-derived propellants for Earth return. The bipropellant LANTR engine utilizes the large divergent section of its nozzle as an ''afterburner'' into which oxygen is injected and supersonically combusted with nuclear preheated hydrogen emerging from the engine's choked sonic throat-essentially ''scramjet propulsion in reverse.'' By varying the oxygen-to-hydrogen mixture ratio, LANTR engines can operate over a range of thrust and I(sub sp) values while the reactor core power level remains relatively constant. A LANTR-based LTS offers unique mission capabilities including short-transit-time crewed cargo transports. Even a ''commuter'' shuttle service may be possible allowing ''one-way'' trip times to and from the Moon on the order of 36 hours or less. If only 1% of the extracted LLO2 propellant from identified resource sites were available for use in lunar orbit, such a supply could support daily commuter flights to the Moon for many thousands of years! This report outlines an evolutionary architecture and examines a variety of mission types and transfer vehicle designs, along with the increasing demands on LLO2 production as mission complexity and velocity change delta V requirements increase. A comparison of vehicle features and engine operating characteristics, for both NTR and LANTR engines, is also provided along with a discussion of the propellant production and mining requirements associated with using FeO-rich volcanic glass as source material.

Robust Exploration and Commercial Missions to the Moon Using LANTR Propulsion and Lunar Liquid Oxygen Derived from FeO-Rich Pyroclastic Deposits

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Ryan, Stephen W.; Burke, Laura M.; McCurdy, David R.; Fittje, James E.; Joyner, Claude R.

2017-01-01

The nuclear thermal rocket (NTR) has frequently been identified as a key space asset required for the human exploration of Mars. This proven technology can also provide the affordable access through cislunar space necessary for commercial development and sustained human presence on the Moon. It is a demonstrated technology capable of generating both high thrust and high specific impulse (Isp approx.900 s) twice that of todays best chemical rockets. Nuclear lunar transfer vehicles consisting of a propulsion stage using three approx.16.5 klbf Small Nuclear Rocket Engines (SNREs), an in-line propellant tank, plus the payload can enable a variety of reusable lunar missions. These include cargo delivery and crewed lunar landing missions. Even weeklong tourism missions carrying passengers into lunar orbit for a day of sightseeing and picture taking are possible. The NTR can play an important role in the next phase of lunar exploration and development by providing a robust in-space lunar transportation system (LTS) that can allow initial outposts to evolve into settlements supported by a variety of commercial activities such as in-situ propellant production used to supply strategically located propellant depots and transportation nodes. The use of lunar liquid oxygen (LLO2) derived from iron oxide (FeO)-rich volcanic glass beads, found in numerous pyroclastic deposits on the Moon, can significantly reduce the launch mass requirements from Earth by enabling reusable, surface-based lunar landing vehicles (LLVs) using liquid oxygen/hydrogen (LO2/H2) chemical rocket engines. Afterwards, a LO2/H2 propellant depot can be established in lunar equatorial orbit to supply the LTS. At this point a modified version of the conventional NTR called the LOX-augmented NTR, or LANTR is introduced into the LTS allowing bipropellant operation and leveraging the mission benefits of refueling with lunar-derived propellants for Earth return. The bipropellant LANTR engine utilizes the large divergent section of its nozzle as an afterburner into which oxygen is injected and supersonically combusted with nuclear preheated hydrogen emerging from the engines choked sonic throat - essentially scramjet propulsion in reverse. By varying the oxygen-to-hydrogen mixture ratio, LANTR engines can operate over a range of thrust and Isp values while the reactor core power level remains relatively constant. A LANTR-based LTS offers unique mission capabilities including short transit time crewed cargo transports. Even a commuter shuttle service may be possible allowing one-way trip times to and from the Moon on the order of 36 hours or less. If only 1 of the extracted LLO2 propellant from identified resource sites were available for use in lunar orbit, such a supply could support daily commuter flights to the Moon for many thousands of years! The proposed paper outlines an evolutionary architecture and examines a variety of mission types and transfer vehicle designs, along with the increasing demands on LLO2 production as mission complexity and (Delta)V requirements increase. A comparison of vehicle features and engine operating characteristics, for both NTR and LANTR engines, is also provided along with a discussion of the propellant production and mining requirements associated with using FeO-rich volcanic glass as source material.

Development of engine activity cycles for the prime movers of unconventional natural gas well development.

PubMed

Johnson, Derek; Heltzel, Robert; Nix, Andrew; Barrow, Rebekah

2017-03-01

With the advent of unconventional natural gas resources, new research focuses on the efficiency and emissions of the prime movers powering these fleets. These prime movers also play important roles in emissions inventories for this sector. Industry seeks to reduce operating costs by decreasing the required fuel demands of these high horsepower engines but conducting in-field or full-scale research on new technologies is cost prohibitive. As such, this research completed extensive in-use data collection efforts for the engines powering over-the-road trucks, drilling engines, and hydraulic stimulation pump engines. These engine activity data were processed in order to make representative test cycles using a Markov Chain, Monte Carlo (MCMC) simulation method. Such cycles can be applied under controlled environments on scaled engines for future research. In addition to MCMC, genetic algorithms were used to improve the overall performance values for the test cycles and smoothing was applied to ensure regression criteria were met during implementation on a test engine and dynamometer. The variations in cycle and in-use statistics are presented along with comparisons to conventional test cycles used for emissions compliance. Development of representative, engine dynamometer test cycles, from in-use activity data, is crucial in understanding fuel efficiency and emissions for engine operating modes that are different from cycles mandated by the Code of Federal Regulations. Representative cycles were created for the prime movers of unconventional well development-over-the-road (OTR) trucks and drilling and hydraulic fracturing engines. The representative cycles are implemented on scaled engines to reduce fuel consumption during research and development of new technologies in controlled laboratory environments.

Turbopump options for nuclear thermal rockets

NASA Astrophysics Data System (ADS)

Bissell, W. R.; Gunn, S. V.

1992-07-01

Several turbopump options for delivering liquid nitrogen to nuclear thermal rocket (NTR) engines were evaluated and compared. Axial and centrifugal flow pumps were optimized, with and without boost pumps, utilizing current design criteria within the latest turbopump technology limits. Two possible NTR design points were used, a modest pump pressure rise of 1,743 psia and a relatively higher pump pressure rise of 4,480 psia. Both engines utilized the expander cycle to maximize engine performance for the long duration mission. Pump suction performance was evaluated. Turbopumps with conventional cavitating inducers were compared with zero NPSH (saturated liquid in the tanks) pumps over a range of tank saturation pressures, with and without boost pumps. Results indicate that zero NSPH pumps at high tank vapor pressures, 60 psia, are very similar to those with the finite NPSHs. At low vapor pressures efficiencies fall and turbine pressure ratios increase leading to decreased engine chamber pressures and or increased pump pressure discharges and attendant high-pressure component weights. It may be concluded that zero tank NSPH capabilities can be obtained with little penalty to the engine systems but boost pumps are needed if tank vapor pressure drops below 30 psia. Axial pumps have slight advantages in weight and chamber pressure capability while centrifugal pumps have a greater operating range.

Revised Point of Departure Design Options for Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Fittje, James E.; Schnitzler, Bruce G.; Borowoski, Stanley

2015-01-01

Four Revised Point of Departure NTR Engines were Designed and Analyzed using MCNP and NESS. All Four Engines Have Thermodynamically Closed Cycles at Nominal Chamber Pressures. 111 kilonewton (25 kip-force) Cermet Design Required Dedicated Heater Elements to Close the Cycle. Cermet Based Designs had Slightly Higher TW Ratios, but Required Substantially More U-235. NERVA Derived Criticality Limited Engine Could Operate at Lower Power and Thrust Levels Compared to the Criticality Limited Cermet Design.

The transcriptional activator NtrC controls the expression and activity of glutamine synthetase in Herbaspirillum seropedicae.

PubMed

Persuhn, D C; Souza, E M; Steffens, M B; Pedrosa, F O; Yates, M G; Rigo, L U

2000-11-15

The role of the Ntr system in Herbaspirillum seropedicae was determined via ntrB and ntrC mutants. Three phenotypes were identified in these mutants: Nif(-), deficiency in growth using nitrate, and low glutamine synthetase (GS) activity. All phenotypes were restored by the plasmid pKRT1 containing the intact glnA, ntrB and ntrC genes of H. seropedicae. The promoter region of glnA was subcloned into a beta-galactosidase fusion vector and the results suggested that NtrC positively regulates the glnA promoter in response to low nitrogen. The H. seropedicae ntrC and ntrB mutant strains showed a deficiency of adenylylation/deadenylylation of GS, indicating that NtrC and NtrB are involved in both transcription and activity control of GS in this organism.

The ntrB and ntrC Genes Are Involved in the Regulation of Poly-3-Hydroxybutyrate Biosynthesis by Ammonia in Azospirillum brasilense Sp7

PubMed Central

Sun, Jun; Peng, Xuan; Van Impe, Jan; Vanderleyden, Jos

2000-01-01

Azospirillum brasilense Sp7 and its ntrA (rpoN), ntrBC, and ntrC mutants have been evaluated for their capabilities of poly-3-hydroxybutyrate (PHB) accumulation in media with high and low ammonia concentrations. It was observed that the ntrBC and ntrC mutants can produce PHB in both low- and high-C/N-ratio media, while no significant PHB production was observed for the wild type or the ntrA mutant in low-C/N-ratio media. Further investigation by fermentation analysis indicated that the ntrBC and ntrC mutants were able to grow and accumulate PHB simultaneously in the presence of a high concentration of ammonia in the medium, while little PHB was produced in the wild type and ntrA (rpoN) mutant during active growth phase. These results provide the first genetic evidence that the ntrB and ntrC genes are involved in the regulation of PHB synthesis by ammonia in A. brasilense Sp7. PMID:10618211

The NtrY-NtrX two-component system is involved in controlling nitrate assimilation in Herbaspirillum seropedicae strain SmR1.

PubMed

Bonato, Paloma; Alves, Lysangela R; Osaki, Juliana H; Rigo, Liu U; Pedrosa, Fabio O; Souza, Emanuel M; Zhang, Nan; Schumacher, Jörg; Buck, Martin; Wassem, Roseli; Chubatsu, Leda S

2016-11-01

Herbaspirillum seropedicae is a diazotrophic β-Proteobacterium found endophytically associated with gramineae (Poaceae or graminaceous plants) such as rice, sorghum and sugar cane. In this work we show that nitrate-dependent growth in this organism is regulated by the master nitrogen regulatory two-component system NtrB-NtrC, and by NtrY-NtrX, which functions to specifically regulate nitrate metabolism. NtrY is a histidine kinase sensor protein predicted to be associated with the membrane and NtrX is the response regulator partner. The ntrYntrX genes are widely distributed in Proteobacteria. In α-Proteobacteria they are frequently located downstream from ntrBC, whereas in β-Proteobacteria these genes are located downstream from genes encoding an RNA methyltransferase and a proline-rich protein with unknown function. The NtrX protein of α-Proteobacteria has an AAA+ domain, absent in those from β-Proteobacteria. An ntrY mutant of H. seropedicae showed the wild-type nitrogen fixation phenotype, but the nitrate-dependent growth was abolished. Gene fusion assays indicated that NtrY is involved in the expression of genes coding for the assimilatory nitrate reductase as well as the nitrate-responsive two-component system NarX-NarL (narK and narX promoters, respectively). The purified NtrX protein was capable of binding the narK and narX promoters, and the binding site at the narX promoter for the NtrX protein was determined by DNA footprinting. In silico analyses revealed similar sequences in other promoter regions of H. seropedicae that are related to nitrate assimilation, supporting the role of the NtrY-NtrX system in regulating nitrate metabolism in H. seropedicae. © 2016 Federation of European Biochemical Societies.

Effects of p75NTR deficiency on cholinergic innervation of the amygdala and anxiety-like behavior.

PubMed

Busch, Ruben; Baldus, Marian; Vogt, Miriam A; Berger, Stefan M; Bartsch, Dusan; Gass, Peter; von Bohlen Und Halbach, Oliver

2017-05-01

The p75 neurotrophin receptor (p75NTR) is a low-affinity receptor that is capable of binding neurotrophins. Two different p75NTR knockout mouse lines are available either with a deletion in Exon III (p75NTR E x III -/- ) or in Exon IV (p75NTR E x IV -/- ). In p75NTR E x III knockout mice, only the full-length p75NTR is deleted, whereas in p75NTR E x IV knockout mice, the full-length as well as the truncated isoform of the receptor is deleted. Deletion of p75NTR has been shown to affect, among others, the septohippocampal cholinergic innervation pattern and neuronal plasticity within the hippocampus. We hypothesize that deletion of p75NTR also alters the morphology and physiology of a further key structure of the limbic system, the amygdala. Our results indicate that deletion of p75NTR also increases cholinergic innervation in the basolateral amygdala in adult as well as aged p75NTR E x III -/- and p75NTR E x IV -/- mice. The p75NTR E x IV -/- mice did not display altered long-term potentiation (LTP) in the basolateral amygdala as compared to age-matched control littermates. However, p75NTR E x III -/- mice display stronger LTP in the basolateral amygdala compared to age-matched controls. Bath-application of K252a (a trk antagonist) did not inhibit the induction of LTP in the basolateral amygdala, but reduced the level of LTP in p75NTR E x III -/- mice to levels seen in respective controls. Moreover, p75NTR E x III -/- mice display altered behavior in the dark/light box. Thus, deletion of p75NTR in mice leads to physiological and morphological changes in the amygdala and altered behavior that is linked to the limbic system. © 2017 International Society for Neurochemistry.

Low Pressure Nuclear Thermal Rocket (LPNTR) concept

NASA Technical Reports Server (NTRS)

Ramsthaler, J. H.

1991-01-01

A background and a description of the low pressure nuclear thermal system are presented. Performance, mission analysis, development, critical issues, and some conclusions are discussed. The following subject areas are covered: LPNTR's inherent advantages in critical NTR requirement; reactor trade studies; reference LPNTR; internal configuration and flow of preliminary LPNTR; particle bed fuel assembly; preliminary LPNTR neutronic study results; multiple LPNTR engine concept; tank and engine configuration for mission analysis; LPNTR reliability potential; LPNTR development program; and LPNTR program costs.

Analytical study of nozzle performance for nuclear thermal rockets

NASA Technical Reports Server (NTRS)

Davidian, Kenneth O.; Kacynski, Kenneth J.

1991-01-01

Nuclear propulsion has been identified as one of the key technologies needed for human exploration of the Moon and Mars. The Nuclear Thermal Rocket (NTR) uses a nuclear reactor to heat hydrogen to a high temperature followed by expansion through a conventional convergent-divergent nozzle. A parametric study of NTR nozzles was performed using the Rocket Engine Design Expert System (REDES) at the NASA Lewis Research Center. The REDES used the JANNAF standard rigorous methodology to determine nozzle performance over a range of chamber temperatures, chamber pressures, thrust levels, and different nozzle configurations. A design condition was set by fixing the propulsion system exit radius at five meters and throat radius was varied to achieve a target thrust level. An adiabatic wall was assumed for the nozzle, and its length was assumed to be 80 percent of a 15 degree cone. The results conclude that although the performance of the NTR, based on infinite reaction rates, looks promising at low chamber pressures, finite rate chemical reactions will cause the actual performance to be considerably lower. Parameters which have a major influence on the delivered specific impulse value include the chamber temperature and the chamber pressures in the high thrust domain. Other parameters, such as 2-D and boundary layer effects, kinetic rates, and number of nozzles, affect the deliverable performance of an NTR nozzle to a lesser degree. For a single nozzle, maximum performance of 930 seconds and 1030 seconds occur at chamber temperatures of 2700 and 3100 K, respectively.

NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR.

PubMed

Mukai, J; Hachiya, T; Shoji-Hoshino, S; Kimura, M T; Nadano, D; Suvanto, P; Hanaoka, T; Li, Y; Irie, S; Greene, L A; Sato, T A

2000-06-09

The low affinity neurotrophin receptor p75NTR can mediate cell survival as well as cell death of neural cells by NGF and other neurotrophins. To elucidate p75NTR-mediated signal transduction, we screened p75NTR-associated proteins by a yeast two-hybrid system. We identified one positive clone and named NADE (p75NTR-associated cell death executor). Mouse NADE has marked homology to the human HGR74 protein. NADE specifically binds to the cell-death domain of p75NTR. Co-expression of NADE and p75NTR induced caspase-2 and caspase-3 activities and the fragmentation of nuclear DNA in 293T cells. However, in the absence of p75NTR, NADE failed to induce apoptosis, suggesting that NADE expression is necessary but insufficient for p75NTR-mediated apoptosis. Furthermore, p75NTR/NADE-induced cell death was dependent on NGF but not BDNF, NT-3, or NT-4/5, and the recruitment of NADE to p75NTR (intracellular domain) was dose-dependent. We obtained similar results from PC12 cells, nnr5 cells, and oligodendrocytes. Taken together, NADE is the first signaling adaptor molecule identified in the involvement of p75NTR-mediated apoptosis induced by NGF, and it may play an important role in the pathogenesis of neurogenetic diseases.

Affordable Development and Demonstrationof a Small NTR Engine and Stage: A Preliminary NASA, DOE and Industry Assessment

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Sefcik, Robert J.; Qualls, A. L.; Schnitzler, B.G.; Joyner, C. R.

2014-01-01

Formulation of Affordable and Sustainable NTP Development Strategy is Underway Involving NASA, DOE and Industry. In FY11, Nuclear Thermal Propulsion (NTP) was identified as a key propulsion option under the Advanced In-Space Propulsion (AISP) component of NASA's Exploration Technology Development and Demonstration (ETDD) program.

Physical Limitations of Nuclear Propulsion for Earth to Orbit

NASA Technical Reports Server (NTRS)

Blevins, John A.; Patton, Bruce; Rhys, Noah O.; Schafer, Charles F. (Technical Monitor)

2001-01-01

An assessment of current nuclear propulsion technology for application in Earth to Orbit (ETO) missions has been performed. It can be shown that current nuclear thermal rocket motors are not sufficient to provide single stage performance as has been stated by previous studies. Further, when taking a systems level approach, it can be shown that NTRs do not compete well with chemical engines where thrust to weight ratios of greater than I are necessary, except possibly for the hybrid chemical/nuclear LANTR (LOX Augmented Nuclear Thermal Rocket) engine. Also, the ETO mission requires high power reactors and consequently large shielding weights compared to NTR space missions where shadow shielding can be used. In the assessment, a quick look at the conceptual ASPEN vehicle proposed in 1962 in provided. Optimistic NTR designs are considered in the assessment as well as discussion on other conceptual nuclear propulsion systems that have been proposed for ETO. Also, a quick look at the turbulent, convective heat transfer relationships that restrict the exchange of nuclear energy to thermal energy in the working fluid and consequently drive the reactor mass is included.

Design analysis and risk assessment for a single stage to orbit nuclear thermal rocket

NASA Astrophysics Data System (ADS)

Labib, Satira I.

Recent advances in high power density fuel materials have renewed interest in nuclear thermal rockets (NTRs) as a viable propulsion technology for future space exploration. This thesis describes the design of three NTR reactor engines designed for the single stage to orbit launch of payloads from 1-15 metric tons. Thermal hydraulic and rocket engine analyses indicate that the proposed rocket engines are able to reach specific impulses in excess of 700 seconds. Neutronics analyses performed using MCNP5 demonstrate that the hot excess reactivity, shutdown margin, and submersion criticality requirements are satisfied for each NTR reactor. The reactors each consist of a 40 cm diameter core packed with hexagonal tungsten cermet fuel elements. The core is surrounded by radial and axial beryllium reflectors and eight boron carbide control drums. At the same power level, the 40 cm reactor results in the lowest radiation dose rate of the three reactors. Radiation dose rates decrease to background levels ~3.5 km from the launch site. After a one-year decay time, all of the activated materials produced by an NTR launch would be classified as Class A low-level waste. The activation of air produces significant amounts of argon-41 and nitrogen-16 within 100 m of the launch. The derived air concentration, DAC, from the activation products decays to less than unity within two days, with only argon-41 remaining. After 10 minutes of full power operation the 120 cm core corresponding to a 15 MT payload contains 2.5 x 1013, 1.4 x 1012, 1.5 x 1012, and 7.8 x 10 7 Bq of 131I, 137Cs, 90Sr, and 239Pu respectively. The decay heat after shutdown increases with increasing reactor power with a maximum decay heat of 108 kW immediately after shutdown for the 15 MT payload.

p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells.

PubMed

Forsyth, Peter A; Krishna, Niveditha; Lawn, Samuel; Valadez, J Gerardo; Qu, Xiaotao; Fenstermacher, David A; Fournier, Michelle; Potthast, Lisa; Chinnaiyan, Prakash; Gibney, Geoffrey T; Zeinieh, Michele; Barker, Philip A; Carter, Bruce D; Cooper, Michael K; Kenchappa, Rajappa S

2014-03-21

Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target.

p75 Neurotrophin Receptor Cleavage by α- and γ-Secretases Is Required for Neurotrophin-mediated Proliferation of Brain Tumor-initiating Cells*

PubMed Central

Forsyth, Peter A.; Krishna, Niveditha; Lawn, Samuel; Valadez, J. Gerardo; Qu, Xiaotao; Fenstermacher, David A.; Fournier, Michelle; Potthast, Lisa; Chinnaiyan, Prakash; Gibney, Geoffrey T.; Zeinieh, Michele; Barker, Philip A.; Carter, Bruce D.; Cooper, Michael K.; Kenchappa, Rajappa S.

2014-01-01

Malignant gliomas are highly invasive, proliferative, and resistant to treatment. Previously, we have shown that p75 neurotrophin receptor (p75NTR) is a novel mediator of invasion of human glioma cells. However, the role of p75NTR in glioma proliferation is unknown. Here we used brain tumor-initiating cells (BTICs) and show that BTICs express neurotrophin receptors (p75NTR, TrkA, TrkB, and TrkC) and their ligands (NGF, brain-derived neurotrophic factor, and neurotrophin 3) and secrete NGF. Down-regulation of p75NTR significantly decreased proliferation of BTICs. Conversely, exogenouous NGF stimulated BTIC proliferation through α- and γ-secretase-mediated p75NTR cleavage and release of its intracellular domain (ICD). In contrast, overexpression of the p75NTR ICD induced proliferation. Interestingly, inhibition of Trk signaling blocked NGF-stimulated BTIC proliferation and p75NTR cleavage, indicating a role of Trk in p75NTR signaling. Further, blocking p75NTR cleavage attenuated Akt activation in BTICs, suggesting role of Akt in p75NTR-mediated proliferation. We also found that p75NTR, α-secretases, and the four subunits of the γ-secretase enzyme were elevated in glioblastoma multiformes patients. Importantly, the ICD of p75NTR was commonly found in malignant glioma patient specimens, suggesting that the receptor is activated and cleaved in patient tumors. These results suggest that p75NTR proteolysis is required for BTIC proliferation and is a novel potential clinical target. PMID:24519935

Assessment of the Noise Reduction Potential of Advanced Subsonic Transport Concepts for NASA's Environmentally Responsible Aviation Project

NASA Technical Reports Server (NTRS)

Thomas, Russell H.; Burley, Casey L.; Nickol, Craig L.

2016-01-01

Aircraft system noise is predicted for a portfolio of NASA advanced concepts with 2025 entry-into-service technology assumptions. The subsonic transport concepts include tube-and-wing configurations with engines mounted under the wing, over the wing nacelle integration, and a double deck fuselage with engines at a mid-fuselage location. Also included are hybrid wing body aircraft with engines upstream of the fuselage trailing edge. Both advanced direct drive engines and geared turbofan engines are modeled. Recent acoustic experimental information was utilized in the prediction for several key technologies. The 301-passenger class hybrid wing body with geared ultra high bypass engines is assessed at 40.3 EPNLdB cumulative below the Stage 4 certification level. Other hybrid wing body and unconventional tube-and-wing configurations reach levels of 33 EPNLdB or more below the certification level. Many factors contribute to the system level result; however, the hybrid wing body in the 301-passenger class, as compared to a tubeand- wing with conventional engine under wing installation, has 11.9 EPNLdB of noise reduction due to replacing reflection with acoustic shielding of engine noise sources. Therefore, the propulsion airframe aeroacoustic interaction effects clearly differentiate the unconventional configurations that approach levels close to or exceed the 42 EPNLdB goal.

An antagonistic monoclonal antibody (B-N6) specific for the human neurotensin receptor-1.

PubMed

Ovigne, J M; Vermot-Desroches, C; Lecron, J C; Portier, M; Lupker, J; Pecceu, F; Wijdenes, J

1998-06-01

The neuropeptide neurotensin (NT) interacts with two types of human receptors (hNTR) termed hNTR-1 and hNTR-2. This study describes a monoclonal antibody (MAb) specific for hNTR-1, B-N6. This MAb binds specifically to hNTR-1, but not to hNTR-2 transfected CHO cells. B-N6 and NT display a reciprocal competition and react in a similar way to trypsin, suggesting that the B-N6 epitope is at or close to the NT binding site on the third extracellular loop. Unlike B-N6, NT induces hNTR-1 internalization. Although neither NT-FITC nor B-N6 binding was detected by flow cytometry on different human cells, specific mRNA expression for hNTR-1 was detected in these cells. In CHO cells expressing hNTR-1 and a luciferase gene coupled to the krox24 reporter, B-N6 and the antagonist SR 48692 inhibited NT-induced intracellular activation of krox24 in a dose-dependent manner. From these results it is concluded that B-N6 is an antagonistic anti-hNTR-1 MAb.

Co-induction of p75NTR and p75NTR-associated death executor in neurons after zinc exposure in cortical culture or transient ischemia in the rat.

PubMed

Park, J A; Lee, J Y; Sato, T A; Koh, J Y

2000-12-15

Recently, a 22 kDa protein termed p75(NTR)-associated death executor (NADE) was discovered to be a necessary factor for p75(NTR)-mediated apoptosis in certain cells. However, the possible role for p75(NTR)/NADE in pathological neuronal death has yet been undetermined. In the present study, we have examined this possibility in vivo and in vitro. Exposure of cortical cultures to zinc induced both p75(NTR) and NADE in neurons, whereas exposure to NMDA, ionomycin, iron, or H(2)O(2) induced neither. In addition, zinc exposure increased neuronal NGF expression and its release into the medium. A function-blocking antibody of p75(NTR) (REX) inhibited association between p75(NTR) and NADE as well as neuronal death induced by zinc. Conversely, NGF augmented zinc-induced neuronal death. Caspase inhibitors reduced zinc-induced neuronal death, indicating that caspases were involved. Because reduction of NADE expression with cycloheximide or NADE antisense oligonucleotides attenuated zinc-induced neuronal death, NADE appears to contribute to p75(NTR)-induced cortical neuronal death as shown in other cells. Because zinc neurotoxicity may be a key mechanism of neuronal death after transient forebrain ischemia, we next examined this model. After ischemia, p75(NTR) and NADE were induced in degenerating rat hippocampal CA1 neurons. There was a close correlation between zinc accumulation and p75(NTR)/NADE induction. Suggesting the role of zinc here, injection of a metal chelator, CaEDTA, into the lateral ventricle completely blocked the induction of p75(NTR) and NADE. Our results suggest that co-induction of p75(NTR) and NADE plays a role in zinc-triggered neuronal death in vitro and in vivo.

The glnAntrBC operon of Herbaspirillum seropedicae is transcribed by two oppositely regulated promoters upstream of glnA.

PubMed

Schwab, Stefan; Souza, Emanuel M; Yates, Marshall G; Persuhn, Darlene C; Steffens, M Berenice R; Chubatsu, Leda S; Pedrosa, Fábio O; Rigo, Liu U

2007-01-01

Herbaspirillum seropedicae is an endophytic bacterium that fixes nitrogen under microaerophilic conditions. The putative promoter sequences glnAp1 (sigma70-dependent) and glnAp2 (sigma54), and two NtrC-binding sites were identified upstream from the glnA, ntrB and ntrC genes of this microorganism. To study their transcriptional regulation, we used lacZ fusions to the H. seropedicae glnA gene, and the glnA-ntrB and ntrB-ntrC intergenic regions. Expression of glnA was up-regulated under low ammonium, but no transcription activity was detected from the intergenic regions under any condition tested, suggesting that glnA, ntrB and ntrC are co-transcribed from the promoters upstream of glnA. Ammonium regulation was lost in the ntrC mutant strain. A point mutation was introduced in the conserved -25/-24 dinucleotide (GG-->TT) of the putative sigma54-dependent promoter (glnAp2). Contrary to the wild-type promoter, glnA expression with the mutant glnAp2 promoter was repressed in the wild-type strain under low ammonium levels, but this repression was abolished in an ntrC background. Together our results indicate that the H. seropedicae glnAntrBC operon is regulated from two functional promoters upstream from glnA, which are oppositely regulated by the NtrC protein.

Estimated Emissions from the Prime-Movers of Unconventional Natural Gas Well Development Using Recently Collected In-Use Data in the United States.

PubMed

Johnson, Derek; Heltzel, Robert; Nix, Andrew; Darzi, Mahdi; Oliver, Dakota

2018-05-01

Natural gas from shale plays dominates new production and growth. However, unconventional well development is an energy intensive process. The prime movers, which include over-the-road service trucks, horizontal drilling rigs, and hydraulic fracturing pumps, are predominately powered by diesel engines that impact air quality. Instead of relying on certification data or outdated emission factors, this model uses new in-use emissions and activity data combined with historical literature to develop a national emissions inventory. For the diesel only case, hydraulic fracturing engines produced the most NO x emissions, while drilling engines produced the most CO emissions, and truck engines produced the most THC emissions. By implementing dual-fuel and dedicated natural gas engines, total fuel energy consumed, CO 2 , CO, THC, and CH 4 emissions would increase, while NO x emissions, diesel fuel consumption, and fuel costs would decrease. Dedicated natural gas engines offered significant reductions in NO x emissions. Additional scenarios examined extreme cases of full fleet conversions. While deep market penetrations could reduce fuel costs, both technologies could significantly increase CH 4 emissions. While this model is based on a small sample size of engine configurations, data were collected during real in-use activity and is representative of real world activity.

The p75 neurotrophin receptor localization in blood-CSF barrier: expression in choroid plexus epithelium.

PubMed

Spuch, Carlos; Carro, Eva

2011-05-11

The presence of neurotrophins and their receptors Trk family has been reported in the choroid plexus. High levels of Nerve Growth Factor (NGF), Neurotrophin-4 (NT-4) and TrkB receptor were detected, while nothing was know about p75 neurotrophin receptor (p75NTR) in the choroid plexus epithelial cells. In neurons, p75NTR receptor has a dual function: promoting survival together with TrkA in response to NGF, and inducing apoptotic signaling through p75NTR. We postulated that p75NTR may also affect the survival pathways in the choroid plexus and also undergoes regulated proteolysis with metalloproteases. Here, we demonstrated the presence of p75NTR receptor in the choroid plexus epithelial cells. The p75NTR receptor would be involved in cell death mechanisms and in the damaged induced by amyloid beta (Aβ) in the choroid plexus and finally, we propose an essential role of p75NTR in the Aβ transcytosis through out choroid plexus barrier. The presence analysis reveals the new localization of p75NTR in the choroid plexus and, the distribution mainly in the cytoplasm and cerebrospinal fluid (CSF) side of the epithelial cells. We propose that p75NTR receptor plays a role in the survival pathways and Aβ-induced cell death. These data suggest that p75NTR dysfunction play an important role in the pathogenesis of brain diseases. The importance and novelty of this expression expands a new role of p75NTR.

TRAF6 and p62 inhibit amyloid β-induced neuronal death through p75 neurotrophin receptor

PubMed Central

Geetha, Thangiah; Zheng, Chen; McGregor, Wade C.; White, B. Douglas; Diaz-Meco, Maria T.; Moscat, Jorge; Babu, Jeganathan Ramesh

2014-01-01

Amyloid β (Aβ) aggregates are the primary component of senile plaques in Alzheimer disease (AD) patient’s brain. Aβ is known to bind p75 neurotrophin receptor (p75NTR) and mediates Aβ-induced neuronal death. Recently, we showed that NGF leads to p75NTR polyubiquitination, which promotes neuronal cell survival. Here, we demonstrate that Aβ stimulation impaired the p75NTR polyubiquitination. TRAF6 and p62 are required for polyubiquitination of p75NTR on NGF stimulation. Interestingly, we found that overexpression of TRAF6/p62 restored p75NTR polyubiquitination upon Aβ/NGF treatment. Aβ significantly reduced NF-κB activity by attenuating the interaction of p75NTR with IKKβ. p75NTR increased NF-κB activity by recruiting TRAF6/p62, which thereby mediated cell survival. These findings indicate that TRAF6/p62 abrogated the Aβ-mediated inhibition of p75NTR polyubiquitination and restored neuronal cell survival. PMID:23017601

Expression, purification, and DNA-binding activity of the solubilized NtrC protein of Herbaspirillum seropedicae.

PubMed

Twerdochlib, Adriana L; Chubatsu, Leda S; Souza, Emanuel M; Pedrosa, Fábio O; Steffens, M Berenice R; Yates, M Geoffrey; Rigo, Liu U

2003-07-01

NtrC is a bacterial enhancer-binding protein (EBP) that activates transcription by the sigma54 RNA polymerase holoenzyme. NtrC has a three domain structure typical of EBP family. In Herbaspirillum seropedicae, an endophytic diazotroph, NtrC regulates several operons involved in nitrogen assimilation, including glnAntrBC. In order to over-express and purify the NtrC protein, DNA fragments containing the complete structural gene for the whole protein, and for the N-terminal+Central and Central+C-terminal domains were cloned into expression vectors. The NtrC and NtrC(N-terminal+Central) proteins were over-expressed as His-tag fusion proteins upon IPTG addition, solubilized using N-lauryl-sarcosyl and purified by metal affinity chromatography. The over-expressed His-tag-NtrC(Central+C-terminal) fusion protein was partially soluble and was also purified by affinity chromatography. DNA band-shift assays showed that the NtrC protein and the Central+C-terminal domains bound specifically to the H. seropedicae glnA promoter region. The C-terminal domain is presumably necessary for DNA-protein interaction and DNA-binding does not require a phosphorylated protein.

Nuclear thermal propulsion transportation systems for lunar/Mars exploration

NASA Technical Reports Server (NTRS)

Clark, John S.; Borowski, Stanley K.; Mcilwain, Melvin C.; Pellaccio, Dennis G.

1992-01-01

Nuclear thermal propulsion technology development is underway at NASA and DoE for Space Exploration Initiative (SEI) missions to Mars, with initial near-earth flights to validate flight readiness. Several reactor concepts are being considered for these missions, and important selection criteria will be evaluated before final selection of a system. These criteria include: safety and reliability, technical risk, cost, and performance, in that order. Of the concepts evaluated to date, the Nuclear Engine for Rocket Vehicle Applications (NERVA) derivative (NDR) is the only concept that has demonstrated full power, life, and performance in actual reactor tests. Other concepts will require significant design work and must demonstrate proof-of-concept. Technical risk, and hence, development cost should therefore be lowest for the concept, and the NDR concept is currently being considered for the initial SEI missions. As lighter weight, higher performance systems are developed and validated, including appropriate safety and astronaut-rating requirements, they will be considered to support future SEI application. A space transportation system using a modular nuclear thermal rocket (NTR) system for lunar and Mars missions is expected to result in significant life cycle cost savings. Finally, several key issues remain for NTR's, including public acceptance and operational issues. Nonetheless, NTR's are believed to be the 'next generation' of space propulsion systems - the key to space exploration.

Engineering DNA Backbone Interactions Results in TALE Scaffolds with Enhanced 5-Methylcytosine Selectivity.

PubMed

Rathi, Preeti; Witte, Anna; Summerer, Daniel

2017-11-08

Transcription activator-like effectors (TALEs) are DNA major-groove binding proteins widely used for genome targeting. TALEs contain an N-terminal region (NTR) and a central repeat domain (CRD). Repeats of the CRD selectively recognize each one DNA nucleobase, offering programmability. Moreover, repeats with selectivity for 5-methylcytosine (5mC) and its oxidized derivatives can be designed for analytical applications. However, both TALE domains also nonspecifically interact with DNA phosphates via basic amino acids. To enhance the 5mC selectivity of TALEs, we aimed to decrease the nonselective binding energy of TALEs. We substituted basic amino acids with alanine in the NTR and identified TALE mutants with increased selectivity. We then analysed conserved, DNA phosphate-binding KQ diresidues in CRD repeats and identified further improved mutants. Combination of mutations in the NTR and CRD was highly synergetic and resulted in TALE scaffolds with up to 4.3-fold increased selectivity in genomic 5mC analysis via affinity enrichment. Moreover, transcriptional activation in HEK293T cells by a TALE-VP64 construct based on this scaffold design exhibited a 3.5-fold increased 5mC selectivity. This provides perspectives for improved 5mC analysis and for the 5mC-conditional control of TALE-based editing constructs in vivo.

Robust Exploration and Commercial Missions to the Moon Using LANTR Propulsion and In-Situ Propellants Derived from Lunar Polar Ice (LPI) Deposits

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Ryan, Stephen W.; Burke, Laura M.; McCurdy, David R.; Fittje, James E.; Joyner, Claude R.

2017-01-01

The nuclear thermal rocket (NTR) has frequently been identified as a key space asset required for the human exploration of Mars. This proven technology can also provide the affordable access through cislunar space necessary for commercial development and sustained human presence on the Moon. It is a demonstrated technology capable of generating both high thrust and high specific impulse (Isp 900 s) twice that of todays best chemical rockets. Nuclear lunar transfer vehicles consisting of a propulsion stage using three approx.16.5 klbf "Small Nuclear Rocket Engines (SNREs)", an in-line propellant tank, plus the payload can enable a variety of reusable lunar missions. These include cargo delivery and crewed lunar landing missions. Even weeklong "tourism" missions carrying passengers into lunar orbit for a day of sightseeing and picture taking are possible. The NTR can play an important role in the next phase of lunar exploration and development by providing a robust in-space lunar transportation system (LTS) that can allow initial outposts to evolve into settlements supported by a variety of commercial activities such as in-situ propellant production used to supply strategically located propellant depots and transportation nodes. The processing of LPI deposits (estimated to be approx. 2 billion metric tons) for propellant production - specifically liquid oxygen (LO2) and hydrogen (LH2) can significantly reduce the launch mass requirements from Earth and can enable reusable, surface-based lunar landing vehicles (LLVs) using LO2/LH2 chemical rocket engines. Afterwards, LO2/LH2 propellant depots can be established in lunar polar and equatorial orbits to supply the LTS. At this point a modified version of the conventional NTR called the LO2-augmented NTR, or LANTR would be introduced into the LTS allowing bipropellant operation and leveraging the mission benefits of refueling with lunar-derived propellants (LDPs) for Earth return. The bipropellant LANTR engine utilizes the large divergent section of its nozzle as an afterburner into which oxygen is injected and supersonically combusted with nuclear preheated hydrogen emerging from the engines choked sonic throat essentially scramjet propulsion in reverse. By varying the oxygen-to-hydrogen mixture ratio, LANTR engines can operate over a range of thrust and Isp values while the reactor core power level remains relatively constant. A LANTR-based LTS offers unique mission capabilities including short transit time crewed cargo transports. Even a commuter shuttle service may be possible allowing one-way trip times to and from the Moon on the order of 36 hours or less. If only 1 of the postulated water ice trapped in deep shadowed craters at the lunar poles were available for use in lunar orbit, such a supply could support daily commuter flights to the Moon for many thousands of years! The proposed paper outlines an evolutionary mission architecture and examines a variety of mission types and transfer vehicle designs, along with the increasing demands on LDP production as mission complexity and delta V requirements increase. A comparison of vehicle features and engine operating characteristics are also provided together with a discussion of the propellant production and mining requirements, and issues, associated with using LPI as the source material.

Effects of diesel/ethanol dual fuel on emission characteristics in a heavy-duty diesel engine

NASA Astrophysics Data System (ADS)

Liu, Junheng; Sun, Ping; Zhang, Buyun

2017-09-01

In order to reduce emissions and diesel consumption, the gas emissions characteris-tics of diesel/aqueous ethanol dual fuel combustion (DFC) were carried out on a heavy-duty turbocharged and intercooled automotive diesel engine. The aqueous ethanol is prepared by a blend of anhydrous ethanol and water in certain volume proportion. In DFC mode, aqueous ethanol is injected into intake port to form homogeneous charge, and then ignited by the diesel fuel. Results show that DFC can reduce NOx emissions but increase HC and CO emissions, and this trend becomes more prominent with the increase of water blending ratio. Increased emissions of HC and CO could be efficiently cleaned by diesel oxidation catalytic converter (DOC), even better than those of diesel fuel. It is also found that DFC mode reduces smoke remarkably, while increases some unconventional emissions such as formaldehyde and acetal-dehyde. However, unconventional emissions could be reduced approximately to the level of baseline engine with a DOC.

Nitrogen and Carbon Status Are Integrated at the Transcriptional Level by the Nitrogen Regulator NtrC In Vivo

PubMed Central

Schumacher, Jörg; Behrends, Volker; Pan, Zhensheng; Brown, Dan R.; Heydenreich, Franziska; Lewis, Matthew R.; Bennett, Mark H.; Razzaghi, Banafsheh; Komorowski, Michal; Barahona, Mauricio; Stumpf, Michael P. H.; Wigneshweraraj, Sivaramesh; Bundy, Jacob G.; Buck, Martin

2013-01-01

ABSTRACT Nitrogen regulation in Escherichia coli is a model system for gene regulation in bacteria. Growth on glutamine as a sole nitrogen source is assumed to be nitrogen limiting, inferred from slow growth and strong NtrB/NtrC-dependent gene activation. However, we show that under these conditions, the intracellular glutamine concentration is not limiting but 5.6-fold higher than in ammonium-replete conditions; in addition, α-ketoglutarate concentrations are elevated. We address this glutamine paradox from a systems perspective. We show that the dominant role of NtrC is to regulate glnA transcription and its own expression, indicating that the glutamine paradox is not due to NtrC-independent gene regulation. The absolute intracellular NtrC and GS concentrations reveal molecular control parameters, where NtrC-specific activities were highest in nitrogen-starved cells, while under glutamine growth, NtrC showed intermediate specific activity. We propose an in vivo model in which α-ketoglutarate can derepress nitrogen regulation despite nitrogen sufficiency. PMID:24255125

Carprofen Induction of p75NTR Dependent Apoptosis via the p38 MAPK Pathway in Prostate Cancer Cells

PubMed Central

Khwaja, Fatima S.; Quann, Emily J.; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel

2008-01-01

The p75NTR functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we demonstrated that treatment with R-flurbiprofen or ibuprofen induced p75NTR expression in several prostate cancer cell lines leading to p75NTR mediated decreased survival. Utilizing the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico data base of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75NTR levels and inhibition of cell survival. Prostate (PC-3, DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75NTR associated loss of survival than breast (MCF7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant negative form of p75NTR prior to carprofen treatment partially rescued cell survival demonstrating a cause and effect relationship between carprofen induction of p75NTR levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF7 and 3T3 cells. Furthermore, siRNA knockdown of the p38 MAPK protein prevented induction of p75NTR by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 minute. Expression of a dominant negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75NTR protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75NTR dependent apoptosis via the p38 MAPK pathway in prostate cancer cells. PMID:18974393

The Extracellular Domain of p75NTR Is Necessary to Inhibit Neurotrophin-3 Signaling through TrkA*

PubMed Central

Mischel, Paul S.; Smith, Shane G.; Vining, Ella R.; Valletta, Janice S.; Mobley, William C.; Reichardt, Louis F.

2009-01-01

The TrkA receptor is activated primarily by nerve growth factor (NGF), but it can also be activated by high concentrations of neurotrophin 3 (NT-3). The pan-neurotrophin receptor p75NTR strongly inhibits activation of TrkA by NT-3 but not by NGF. To examine the role of p75NTR in regulating the specificity of TrkA signaling, we expressed both receptors in Xenopus oocytes. Application of NGF or NT-3 to oocytes expressing TrkA alone resulted in efflux of 45Ca2+ by a phospholipase C-γ-dependent pathway. Coexpression of p75NTR with TrkA inhibited 45Ca2+ efflux in response to NT-3 but not NGF. The inhibitory effect on NT-3 activation of TrkA increased with increasing expression of p75NTR. Coexpression of a truncated p75NTR receptor lacking all but the first 9 amino acids of the cytoplasmic domain inhibited NT-3 stimulation of 45Ca2+ efflux, whereas coexpression of an epidermal growth factor receptor/p75NTR chimera (extracellular domain of epidermal growth factor receptor with transmembrane and cytoplasmic domains of p75NTR) did not inhibit NT-3 signaling through TrkA. These studies demonstrated that the extracellular domain of p75NTR was necessary to inhibit NT-3 signaling through TrkA. Remarkably, p75NTR binding to NT-3 was not required to prevent signaling through TrkA, since occupying p75NTR with brain-derived neurotrophic factor or anti-p75 antibody (REX) did not rescue the ability of NT-3 to activate 45Ca2+ efflux. These data suggested a physical association between TrkA and p75NTR. Documenting this physical interaction, we showed that p75NTR and TrkA could be coimmunoprecipitated from Xenopus oocytes. Our results suggest that the interaction of these two receptors on the cell surface mediated the inhibition of NT-3-activated signaling through TrkA. PMID:11150291

Water Use for Unconventional Energy Development: How Much, What Kind, and to What Reaction?

NASA Astrophysics Data System (ADS)

Grubert, E.

2017-12-01

Water resources—access to water, protection of water, and allocation of water in particular—are a major priority for Americans, but water use for the energy sector has not previously been well characterized. Water use and management associated with unconventional energy development is of special interest, in part because it is often new to the locations and contexts where it occurs. This presentation focuses on three major questions about water use for unconventional energy development, drawing on both engineering and anthropological research. First, using results from a recent study of water use for energy in the entire United States, how much water does the US use for unconventional energy resources, and how does that compare with water use for more mature fuel cycles? Second, based on that same study, what kind of water is used for these unconventional energy resource fuel cycles? Specifically, where does the water come from, and what is its quality? Finally, drawing on recent case studies in the US and elsewhere, what has the reaction been to these water uses, and why does that matter? Case studies focused on oil and natural gas resources illustrate societal reactions to issues of both water management, particularly related to induced seismicity associated with produced water injection, and water allocation, particularly related to hydraulic fracturing. Overall, recent work finds that public concern about water used for unconventional energy resources is often better explained by observed or anticipated local impacts and the uncertainty surrounding these impacts than by specifics about quantities, allocation, and management techniques. This work provides both quantitative and qualitative characterization of water management and allocation for unconventional energy development.

p75 Neurotrophin Receptor in the Skin: Beyond Its Neurotrophic Function.

PubMed

Pincelli, Carlo

2017-01-01

p75 neurotrophin receptor (p75 NTR ), also known as CD271, is the low-affinity receptor that, together with the tyrosine kinase receptor tropomyosin-receptor kinase (Trk), mediate neurotrophin (NT) functions. Beside their classic role in skin innervation, NT and their receptors constitute a complex cutaneous network associated with a number of autocrine and paracrine activities. In this context, the role of p75 NTR is becoming more and more important. This review will focus on the intriguing functions of p75 NTR in healthy and diseased skin. First, p75 NTR counterbalances the proliferative and survival activities of its cognate receptor Trk by inducing keratinocyte apoptosis. In addition, p75 NTR identifies an early transit-amplifying (TA) keratinocyte population and plays a critical role in keratinocyte stem cell transition to its progeny as well as in epidermal differentiation. p75 NTR is absent in psoriatic TA cells, thus rendering these cells resistant to apoptosis. On the other hand, p75 NTR infection restores NT-induced apoptosis in psoriatic keratinocytes. Taken together, these results provide evidence for a critical role of p75 NTR in epidermal homeostasis, while its lack may account for the TA defect in psoriasis. While the issue of p75 NTR as a marker of melanoma initiating cells is still to be solved, there is strong evidence that downregulation of this receptor is a precondition to melanoma invasion and metastasis in vitro and in vivo . All in all, this review points to p75 NTR as a major actor in both physiologic and pathologic conditions at the skin level.

Generation and characterization of a human oral squamous carcinoma cell line SCC-9 with CRISPR/Cas9-mediated deletion of the p75 neurotrophin receptor.

PubMed

Huang, Ping; Tong, Dongdong; Sun, Jing; Li, Qing; Zhang, Fenghe

2017-10-01

To investigate the importance of the p75 neurotrophin receptor (p75 NTR ) in human tongue squamous carcinoma cells, we exploited the CRISPR/Cas9 technology to establish a p75 NTR -knockout SCC-9 cell line and to explore the effect on biological functions. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonuclease (Cas9) system was used to generate genomic deletion mutants of p75 NTR in the tongue squamous carcinoma cell lines SCC-9. Single-guide RNA (sgRNA) sequences were designed to target the p75 NTR genomic sequence and were cloned into plasmid pGK1.1. The linearized vector was electroporated into SCC-9 cells and p75 NTR deletion was confirmed using Cruiser™ enzyme digestion and PCR amplification. SCC-9 clones with successful deletion of p75 NTR were identified and verified by sequencing and selected for functional testing in cell proliferation, invasion, migration, and colony-forming assays. Compared with control cells, p75 NTR -knockout SCC-9 cells showed significantly diminished abilities to proliferate, invade, migrate, and form colonies, indicating a reduction in pro-tumorigenic behavior. These data demonstrate, first, that the CRISPR/Cas9 system is a simplified method for generating p75 NTR knockouts with relatively high efficiency, and second, that deletion of p75 NTR suppresses several tumor-promoting properties of SCC-9 cells, suggesting that p75 NTR is a potential target for the development of novel therapies for tongue cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Trichomonas vaginalis Metronidazole Resistance Is Associated with Single Nucleotide Polymorphisms in the Nitroreductase Genes ntr4Tv and ntr6Tv

PubMed Central

Paulish-Miller, Teresa E.; Augostini, Peter; Schuyler, Jessica A.; Smith, William L.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.; Secor, William E.

2014-01-01

Metronidazole resistance in the sexually transmitted parasite Trichomonas vaginalis is a problematic public health issue. We have identified single nucleotide polymorphisms (SNPs) in two nitroreductase genes (ntr4Tv and ntr6Tv) associated with resistance. These SNPs were associated with one of two distinct T. vaginalis populations identified by multilocus sequence typing, yet one SNP (ntr6Tv A238T), which results in a premature stop codon, was associated with resistance independent of population structure and may be of diagnostic value. PMID:24550324

Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and Activation

PubMed Central

Barker, Phillip A.; Chao, Moses V.

2015-01-01

The p75 neurotrophin receptor (p75NTR) is a multifunctional receptor that participates in many critical processes in the nervous system, ranging from apoptosis to synaptic plasticity and morphological events. It is a member of the tumor necrosis factor receptor (TNFR) superfamily, whose members undergo trimeric oligomerization. Interestingly, p75NTR interacts with dimeric ligands (i.e., proneurotrophins or mature neurotrophins), but several of the intracellular adaptors that mediate p75NTR signaling are trimeric (i.e., TNFR-associated factor 6 or TRAF6). Consequently, the active receptor signaling unit remains uncertain. To identify the functional receptor complex, we evaluated its oligomerization in vitro and in mice brain tissues using a combination of biochemical techniques. We found that the most abundant homotypic arrangement for p75NTR is a trimer and that monomers and trimers coexist at the cell surface. Interestingly, trimers are not required for ligand-independent or ligand-dependent p75NTR activation in a growth cone retraction functional assay. However, monomers are capable of inducing acute morphological effects in neurons. We propose that p75NTR activation is regulated by its oligomerization status and its levels of expression. These results indicate that the oligomeric state of p75NTR confers differential responses and offers an explanation for the diverse and contradictory actions of this receptor in the nervous system. SIGNIFICANCE STATEMENT The p75 neurotrophin receptor (p75NTR) regulates a wide range of cellular functions, including apoptosis, neuronal processes remodeling, and synaptic plasticity. The goal of our work was to inquire whether oligomers of the receptor are required for function. Here we report that p75NTR predominantly assembles as a trimer, similar to other tumor necrosis factor receptors. Interestingly, monomers and trimers coexist at the cell surface, but trimers are not required for p75NTR activation in a functional assay. However, monomers are capable of inducing acute morphological effects in neurons. Identification of the oligomerization state of p75NTR begins to provide insights to the mechanisms of signal initiation of this noncatalytic receptor, as well as to develop therapeutic interventions to diminish its activity. PMID:26311773

Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and Activation.

PubMed

Anastasia, Agustin; Barker, Phillip A; Chao, Moses V; Hempstead, Barbara L

2015-08-26

The p75 neurotrophin receptor (p75(NTR)) is a multifunctional receptor that participates in many critical processes in the nervous system, ranging from apoptosis to synaptic plasticity and morphological events. It is a member of the tumor necrosis factor receptor (TNFR) superfamily, whose members undergo trimeric oligomerization. Interestingly, p75(NTR) interacts with dimeric ligands (i.e., proneurotrophins or mature neurotrophins), but several of the intracellular adaptors that mediate p75(NTR) signaling are trimeric (i.e., TNFR-associated factor 6 or TRAF6). Consequently, the active receptor signaling unit remains uncertain. To identify the functional receptor complex, we evaluated its oligomerization in vitro and in mice brain tissues using a combination of biochemical techniques. We found that the most abundant homotypic arrangement for p75(NTR) is a trimer and that monomers and trimers coexist at the cell surface. Interestingly, trimers are not required for ligand-independent or ligand-dependent p75(NTR) activation in a growth cone retraction functional assay. However, monomers are capable of inducing acute morphological effects in neurons. We propose that p75(NTR) activation is regulated by its oligomerization status and its levels of expression. These results indicate that the oligomeric state of p75(NTR) confers differential responses and offers an explanation for the diverse and contradictory actions of this receptor in the nervous system. The p75 neurotrophin receptor (p75(NTR)) regulates a wide range of cellular functions, including apoptosis, neuronal processes remodeling, and synaptic plasticity. The goal of our work was to inquire whether oligomers of the receptor are required for function. Here we report that p75(NTR) predominantly assembles as a trimer, similar to other tumor necrosis factor receptors. Interestingly, monomers and trimers coexist at the cell surface, but trimers are not required for p75(NTR) activation in a functional assay. However, monomers are capable of inducing acute morphological effects in neurons. Identification of the oligomerization state of p75(NTR) begins to provide insights to the mechanisms of signal initiation of this noncatalytic receptor, as well as to develop therapeutic interventions to diminish its activity. Copyright © 2015 the authors 0270-6474/15/3511911-10$15.00/0.

Carprofen induction of p75NTR-dependent apoptosis via the p38 mitogen-activated protein kinase pathway in prostate cancer cells.

PubMed

Khwaja, Fatima S; Quann, Emily J; Pattabiraman, Nagarajan; Wynne, Shehla; Djakiew, Daniel

2008-11-01

The p75 neurotrophin receptor (p75(NTR)) functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75(NTR) expression in several prostate cancer cell lines leading to p75(NTR)-mediated decreased survival. Using the 2-phenyl propionic acid moiety of these profens as a pharmacophore, we screened an in silico database of 30 million compounds and identified carprofen as having an order of magnitude greater activity for induction of p75(NTR) levels and inhibition of cell survival. Prostate (PC-3 and DU-145) and bladder (T24) cancer cells were more sensitive to carprofen induction of p75(NTR)-associated loss of survival than breast (MCF-7) and fibroblast (3T3) cells. Transfection of prostate cell lines with a dominant-negative form of p75(NTR) before carprofen treatment partially rescued cell survival, showing a cause-and-effect relationship between carprofen induction of p75(NTR) levels and inhibition of survival. Carprofen induced apoptotic nuclear fragmentation in prostate but not in MCF-7 and 3T3 cells. Furthermore, small interfering RNA knockdown of the p38 mitogen-activated protein kinase (MAPK) protein prevented induction of p75(NTR) by carprofen in both prostate cell lines. Carprofen treatment induced phosphorylation of p38 MAPK as early as within 1 min. Expression of a dominant-negative form of MK2, the kinase downstream of p38 MAPK frequently associated with signaling cascades leading to apoptosis, prevented carprofen induction of the p75(NTR) protein. Collectively, we identify carprofen as a highly potent profen capable of inducing p75(NTR)-dependent apoptosis via the p38 MAPK pathway in prostate cancer cells.

'Beautiful' unconventional synthesis and processing technologies of superconductors and some other materials.

PubMed

Badica, Petre; Crisan, Adrian; Aldica, Gheorghe; Endo, Kazuhiro; Borodianska, Hanna; Togano, Kazumasa; Awaji, Satoshi; Watanabe, Kazuo; Sakka, Yoshio; Vasylkiv, Oleg

2011-02-01

Superconducting materials have contributed significantly to the development of modern materials science and engineering. Specific technological solutions for their synthesis and processing helped in understanding the principles and approaches to the design, fabrication and application of many other materials. In this review, we explore the bidirectional relationship between the general and particular synthesis concepts. The analysis is mostly based on our studies where some unconventional technologies were applied to different superconductors and some other materials. These technologies include spray-frozen freeze-drying, fast pyrolysis, field-assisted sintering (or spark plasma sintering), nanoblasting, processing in high magnetic fields, methods of control of supersaturation and migration during film growth, and mechanical treatments of composite wires. The analysis provides future research directions and some key elements to define the concept of 'beautiful' technology in materials science. It also reconfirms the key position and importance of superconductors in the development of new materials and unconventional synthesis approaches.

Ultrasensitive near-infrared fluorescence-enhanced probe for in vivo nitroreductase imaging.

PubMed

Li, Yuhao; Sun, Yun; Li, Jiachang; Su, Qianqian; Yuan, Wei; Dai, Yu; Han, Chunmiao; Wang, Qiuhong; Feng, Wei; Li, Fuyou

2015-05-20

Nitroreductase (NTR) can be overexpressed in hypoxic tumors, thus the selective and efficient detection of NTR is of great importance. To date, although a few optical methods have been reported for the detection of NTR in solution, an effective optical probe for NTR monitoring in vivo is still lacking. Therefore, it is necessary to develop a near-infrared (NIR) fluorescent detection probe for NTR. In this study, five NIR cyanine dyes with fluorescence reporting structure decorated with different nitro aromatic groups, Cy7-1-5, have been designed and explored for possible rapid detection of NTR. Our experimental results presented that only a para-nitro benzoate group modified cyanine probe (Cy7-1) could serve as a rapid NIR fluorescence-enhanced probe for monitoring and bioimaging of NTR. The structure-function relationship has been revealed by theoretical study. The linker connecting the detecting and fluorescence reporting groups and the nitro group position is a key factor for the formation of hydrogen bonds and spatial structure match, inducing the NTR catalytic ability enhancement. The in vitro response and mechanism of the enzyme-catalyzed reduction of Cy7-1 have been investigated through kinetic optical studies and other methods. The results have indicated that an electro-withdrawing group induced electron-transfer process becomes blocked when Cy7-1 is catalytically reduced to Cy7-NH2 by NTR, which is manifested in enhanced fluorescence intensity during the detection process. Confocal fluorescence imaging of hypoxic A549 cells has confirmed the NTR detection ability of Cy7-1 at the cellular level. Importantly, Cy7-1 can detect tumor hypoxia in a murine hypoxic tumor model, showing a rapid and significant enhancement of its NIR fluorescence characteristics suitable for fluorescence bioimaging. This method may potentially be used for tumor hypoxia diagnosis.

Imaging Neurotensin Receptor in Prostate Cancer With 64Cu-Labeled Neurotensin Analogs.

PubMed

Deng, Huaifu; Wang, Hui; Zhang, He; Wang, Mengzhe; Giglio, Ben; Ma, Xiaofen; Jiang, Guihua; Yuan, Hong; Wu, Zhanhong; Li, Zibo

2017-01-01

Neurotensin receptor 1 (NTR-1) is expressed and activated in prostate cancer cells. In this study, we explore the NTR expression in normal mouse tissues and study the positron emission tomography (PET) imaging of NTR in prostate cancer models. Three 64 Cu chelators (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid [DOTA], 1,4,7-triazacyclononane-N,N',N″-triacetic acid [NOTA], or AmBaSar) were conjugated to an NT analog. Neurotensin receptor binding affinity was evaluated using cell binding assay. The imaging profile of radiolabeled probes was compared in well-established NTR + HT-29 tumor model. Stability of the probes was tested. The selected agents were further evaluated in human prostate cancer PC3 xenografts. All 3 NT conjugates retained the majority of NTR binding affinity. In HT-29 tumor, all agents demonstrated prominent tumor uptake. Although comparable stability was observed, 64 Cu-NOTA-NT and 64 Cu-AmBaSar-NT demonstrated improved tumor to background contrast compared with 64 Cu-DOTA-NT. Positron emission tomography/computed tomography imaging of the NTR expression in PC-3 xenografts showed high tumor uptake of the probes, correlating with the in vitro Western blot results. Blocking experiments further confirmed receptor specificity. Our results demonstrated that 64 Cu-labeled neurotensin analogs are promising imaging agents for NTR-positive tumors. These agents may help us identify NTR-positive lesions and predict which patients and individual tumors are likely to respond to novel interventions targeting NTR-1.

Enhanced Cell-Specific Ablation in Zebrafish Using a Triple Mutant of Escherichia Coli Nitroreductase

PubMed Central

Mathias, Jonathan R.; Zhang, Zhanying; Saxena, Meera T.

2014-01-01

Abstract Transgenic expression of bacterial nitroreductase (NTR) facilitates chemically-inducible targeted cell ablation. In zebrafish, the NTR system enables studies of cell function and cellular regeneration. Metronidazole (MTZ) has become the most commonly used prodrug substrate for eliciting cell loss in NTR-expressing transgenic zebrafish due to the cell-specific nature of its cytotoxic derivatives. Unfortunately, MTZ treatments required for effective cell ablation border toxic effects, and, thus, likely incur undesirable nonspecific effects. Here, we tested whether a triple mutant variant of NTR, previously shown to display improved activity in bacterial assays, can solve this issue by promoting cell ablation in zebrafish using reduced prodrug treatment regimens. We generated several complementary transgenic zebrafish lines expressing either wild-type or mutant NTR (mutNTR) in specific neural cell types, and assayed prodrug-induced cell ablation kinetics using confocal time series imaging and plate reader-based quantification of fluorescent reporters expressed in targeted cell types. The results show that cell ablation can be achieved in mutNTR expressing transgenic lines with markedly shortened prodrug exposure times and/or at lower prodrug concentrations. The mutNTR variant characterized here can circumvent problematic nonspecific/toxic effects arising from low prodrug conversion efficiency, thus increasing the effectiveness and versatility of this selective cell ablation methodology. PMID:24428354

Enhanced cell-specific ablation in zebrafish using a triple mutant of Escherichia coli nitroreductase.

PubMed

Mathias, Jonathan R; Zhang, Zhanying; Saxena, Meera T; Mumm, Jeff S

2014-04-01

Transgenic expression of bacterial nitroreductase (NTR) facilitates chemically-inducible targeted cell ablation. In zebrafish, the NTR system enables studies of cell function and cellular regeneration. Metronidazole (MTZ) has become the most commonly used prodrug substrate for eliciting cell loss in NTR-expressing transgenic zebrafish due to the cell-specific nature of its cytotoxic derivatives. Unfortunately, MTZ treatments required for effective cell ablation border toxic effects, and, thus, likely incur undesirable nonspecific effects. Here, we tested whether a triple mutant variant of NTR, previously shown to display improved activity in bacterial assays, can solve this issue by promoting cell ablation in zebrafish using reduced prodrug treatment regimens. We generated several complementary transgenic zebrafish lines expressing either wild-type or mutant NTR (mutNTR) in specific neural cell types, and assayed prodrug-induced cell ablation kinetics using confocal time series imaging and plate reader-based quantification of fluorescent reporters expressed in targeted cell types. The results show that cell ablation can be achieved in mutNTR expressing transgenic lines with markedly shortened prodrug exposure times and/or at lower prodrug concentrations. The mutNTR variant characterized here can circumvent problematic nonspecific/toxic effects arising from low prodrug conversion efficiency, thus increasing the effectiveness and versatility of this selective cell ablation methodology.

Roles of p75NTR, long-term depression and cholinergic transmission in anxiety and acute stress coping

PubMed Central

Martinowich, Keri; Schloesser, Robert J.; Lu, Yuan; Jimenez, Dennisse V.; Paredes, Daniel; Greene, Joshua S.; Greig, Nigel H.; Manji, Husseini K.; Lu, Bai

2011-01-01

Background Stress is causally associated with anxiety. While the underlying cellular mechanisms are not well understood, the basal forebrain cholinergic neurons (BFCNs) have been implicated in stress response. p75NTR is a pan-neurotrophin receptor expressed almost exclusively in BFCNs in adult brain. The present study investigates whether and how p75NTR, via regulation of the cholinergic system and hippocampal synaptic plasticity, influences stress-related behaviors. Methods We used a combination of slice electrophysiology, behavioral analyses, pharmacology, in vivo microdialysis and neuronal activity mapping to assess the role of p75NTR in mood and stress-related behaviors and its underlying cellular and molecular mechanisms. Results We show that acute stress enables hippocampal long-term depression (LTD) in adult wild-type mice, but not in mice lacking p75NTR. The p75NTR mutant mice also exhibit two distinct behavioral impairments: baseline anxiety-like behavior and a deficit in coping with and recovering from stressful situations. Blockade of stress-enabled LTD with a GluA2-derived peptide impaired stress recovery without affecting baseline anxiety. Pharmacological manipulations of cholinergic transmission mimicked the p75NTR perturbation in both baseline anxiety and responses to acute stress. Finally, we show evidence of misregulated cholinergic signaling in animals with p75NTR deletion. Conclusions Our results suggest that loss of p75NTR leads to changes in hippocampal cholinergic signaling, which may be involved in regulation of stress-enabled hippocampal LTD and in modulating behaviors related to stress and anxiety. PMID:21978521

BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis.

PubMed

Pediaditakis, Iosif; Kourgiantaki, Alexandra; Prousis, Kyriakos C; Potamitis, Constantinos; Xanthopoulos, Kleanthis P; Zervou, Maria; Calogeropoulou, Theodora; Charalampopoulos, Ioannis; Gravanis, Achille

2016-01-01

Neurotrophin receptors mediate a plethora of signals affecting neuronal survival. The p75 pan-neurotrophin receptor controls neuronal cell fate after its selective activation by immature and mature isoforms of all neurotrophins. It also exerts pleiotropic effects interacting with a variety of ligands in different neuronal or non-neuronal cells. In the present study, we explored the biophysical and functional interactions of a blood-brain-barrier (BBB) permeable, C17-spiroepoxy steroid derivative, BNN27, with p75 NTR receptor. BNN27 was recently shown to bind to NGF high-affinity receptor, TrkA. We now tested the p75 NTR -mediated effects of BNN27 in mouse Cerebellar Granule Neurons (CGNs), expressing p75 NTR , but not TrkA receptors. Our findings show that BNN27 physically interacts with p75 NTR receptors in specific amino-residues of its extracellular domain, inducing the recruitment of p75 NTR receptor to its effector protein RIP2 and the simultaneous release of RhoGDI in primary neuronal cells. Activation of the p75 NTR receptor by BNN27 reverses serum deprivation-induced apoptosis of CGNs resulting in the decrease of the phosphorylation of pro-apoptotic JNK kinase and of the cleavage of Caspase-3, effects completely abolished in CGNs, isolated from p75 NTR null mice. In conclusion, BNN27 represents a lead molecule for the development of novel p75 NTR ligands, controlling specific p75 NTR -mediated signaling of neuronal cell fate, with potential applications in therapeutics of neurodegenerative diseases and brain trauma.

BNN27, a 17-Spiroepoxy Steroid Derivative, Interacts With and Activates p75 Neurotrophin Receptor, Rescuing Cerebellar Granule Neurons from Apoptosis

PubMed Central

Pediaditakis, Iosif; Kourgiantaki, Alexandra; Prousis, Kyriakos C.; Potamitis, Constantinos; Xanthopoulos, Kleanthis P.; Zervou, Maria; Calogeropoulou, Theodora; Charalampopoulos, Ioannis; Gravanis, Achille

2016-01-01

Neurotrophin receptors mediate a plethora of signals affecting neuronal survival. The p75 pan-neurotrophin receptor controls neuronal cell fate after its selective activation by immature and mature isoforms of all neurotrophins. It also exerts pleiotropic effects interacting with a variety of ligands in different neuronal or non-neuronal cells. In the present study, we explored the biophysical and functional interactions of a blood-brain-barrier (BBB) permeable, C17-spiroepoxy steroid derivative, BNN27, with p75NTR receptor. BNN27 was recently shown to bind to NGF high-affinity receptor, TrkA. We now tested the p75NTR-mediated effects of BNN27 in mouse Cerebellar Granule Neurons (CGNs), expressing p75NTR, but not TrkA receptors. Our findings show that BNN27 physically interacts with p75NTR receptors in specific amino-residues of its extracellular domain, inducing the recruitment of p75NTR receptor to its effector protein RIP2 and the simultaneous release of RhoGDI in primary neuronal cells. Activation of the p75NTR receptor by BNN27 reverses serum deprivation-induced apoptosis of CGNs resulting in the decrease of the phosphorylation of pro-apoptotic JNK kinase and of the cleavage of Caspase-3, effects completely abolished in CGNs, isolated from p75NTR null mice. In conclusion, BNN27 represents a lead molecule for the development of novel p75NTR ligands, controlling specific p75NTR-mediated signaling of neuronal cell fate, with potential applications in therapeutics of neurodegenerative diseases and brain trauma. PMID:28082899

A small molecule p75NTR ligand normalizes signalling and reduces Huntington’s disease phenotypes in R6/2 and BACHD mice

PubMed Central

Belichenko, Nadia P.; Ford, Ellen C.; Semaan, Sarah; Monbureau, Marie; Aiyaswamy, Sruti; Holman, Cameron M.; Condon, Christina; Shamloo, Mehrdad; Massa, Stephen M.; Longo, Frank M.

2016-01-01

Abstract Decreases in the ratio of neurotrophic versus neurodegenerative signalling play a critical role in Huntington’s disease (HD) pathogenesis and recent evidence suggests that the p75 neurotrophin receptor (NTR) contributes significantly to disease progression. p75NTR signalling intermediates substantially overlap with those promoting neuronal survival and synapse integrity and with those affected by the mutant huntingtin (muHtt) protein. MuHtt increases p75NTR-associated deleterious signalling and decreases survival signalling suggesting that p75NTR could be a valuable therapeutic target. This hypothesis was investigated by examining the effects of an orally bioavailable, small molecule p75NTR ligand, LM11A-31, on HD-related neuropathology in HD mouse models (R6/2, BACHD). LM11A-31 restored striatal AKT and other pro-survival signalling while inhibiting c-Jun kinase (JNK) and other degenerative signalling. Normalizing p75NTR signalling with LM11A-31 was accompanied by reduced Htt aggregates and striatal cholinergic interneuron degeneration as well as extended survival in R6/2 mice. The p75NTR ligand also decreased inflammation, increased striatal and hippocampal dendritic spine density, and improved motor performance and cognition in R6/2 and BACHD mice. These results support small molecule modulation of p75NTR as an effective HD therapeutic strategy. LM11A-31 has successfully completed Phase I safety and pharmacokinetic clinical trials and is therefore a viable candidate for clinical studies in HD. PMID:28171570

A new aggregation-induced emission fluorescent probe for rapid detection of nitroreductase and its application in living cells

NASA Astrophysics Data System (ADS)

Xu, Gaoping; Tang, Yonghe; Ma, Yanyan; Xu, An; Lin, Weiying

2018-01-01

The biological activity of nitroreductase (NTR) is closely related to biological hypoxia status in organisms. The development of effective methods for monitoring the activity of NTR is of great significance for medical diagnosis and tumor research. Toward this goal, we have developed a new aggregation-induced emission (AIE) fluorescence NTR probe TPE-HY used the tetraphenylethene as the fluorophore, and used the nitro group as the NTR recognition site. The probe TPE-HY has many excellent properties, including rapid response, AIE characteristics, high sensitivity and selectivity, and low cytotoxicity. Importantly, the probe TPE-HY is successfully applied to monitor endogenous NTR in living HeLa cells.

p75 neurotrophin receptor and pro-BDNF promote cell survival and migration in clear cell renal cell carcinoma

PubMed Central

Sánchez-Prieto, Ricardo; Saada, Sofiane; Naves, Thomas; Guillaudeau, Angélique; Perraud, Aurélie; Sindou, Philippe; Lacroix, Aurélie; Descazeaud, Aurélien; Lalloué, Fabrice; Jauberteau, Marie-Odile

2016-01-01

p75NTR, a member of TNF receptor family, is the low affinity receptor common to several mature neurotrophins and the high affinity receptor for pro-neurotrophins. Brain-Derived Neurotrophic Factor (BDNF), a member of neurotrophin family has been described to play an important role in development and progression of several cancers, through its binding to a high affinity tyrosine kinase receptor B (TrkB) and/or p75NTR. However, the functions of these two receptors in renal cell carcinoma (RCC) have never been investigated. An overexpression of p75NTR, pro-BDNF, and to a lesser extent for TrkB and sortilin, was detected by immunohistochemistry in a cohort of 83 clear cell RCC tumors. p75NTR, mainly expressed in tumor tissues, was significantly associated with higher Fuhrman grade in multivariate analysis. In two derived-RCC lines, 786-O and ACHN cells, we demonstrated that pro-BDNF induced cell survival and migration, through p75NTR as provided by p75NTR RNA silencing or blocking anti-p75NTR antibody. This mechanism is independent of TrkB activation as demonstrated by k252a, a tyrosine kinase inhibitor for Trk neurotrophin receptors. Taken together, these data highlight for the first time an important role for p75NTR in renal cancer and indicate a putative novel target therapy in RCC. PMID:27120782

JPRS Report, Science & Technology USSR: Science & Technology Policy.

DTIC Science & Technology

1988-04-06

YESTESTVOZNANIYA I TEKHNIKI, No 3, Mar 87] 15 Work of Nadezhnost mashin Interbranch Complex [K. Frolov et al; NTR: PROBLEMYIRESHEN1YA, No 21, 3-16 Nov 86...Equipment By Rotor Complex [L. Koshkin; PLANOVOYE KHOZYAYSTVO, No 3, Mar 87] 29 Training, Use of Engineers Severely Criticized [V.G. Aynshteyn; ZNANIYE... complex systems, were painful lessons. In other words, the social role and, let us stress, the social responsibility of science today have increased

Early Downregulation of p75NTR by Genetic and Pharmacological Approaches Delays the Onset of Motor Deficits and Striatal Dysfunction in Huntington's Disease Mice.

PubMed

Suelves, Nuria; Miguez, Andrés; López-Benito, Saray; Barriga, Gerardo García-Díaz; Giralt, Albert; Alvarez-Periel, Elena; Arévalo, Juan Carlos; Alberch, Jordi; Ginés, Silvia; Brito, Verónica

2018-05-27

Deficits in striatal brain-derived neurotrophic factor (BDNF) delivery and/or BDNF/tropomyosin receptor kinase B (TrkB) signaling may contribute to neurotrophic support reduction and selective early degeneration of striatal medium spiny neurons in Huntington's disease (HD). Furthermore, we and others have demonstrated that TrkB/p75 NTR imbalance in vitro increases the vulnerability of striatal neurons to excitotoxic insults and induces corticostriatal synaptic alterations. We have now expanded these studies by analyzing the consequences of BDNF/TrkB/p75 NTR imbalance in the onset of motor behavior and striatal neuropathology in HD mice. Our findings demonstrate for the first time that the onset of motor coordination abnormalities, in a full-length knock-in HD mouse model (KI), correlates with the reduction of BDNF and TrkB levels, along with an increase in p75 NTR expression. Genetic normalization of p75 NTR expression in KI mutant mice delayed the onset of motor deficits and striatal neuropathology, as shown by restored levels of striatal-enriched proteins and dendritic spine density and reduced huntingtin aggregation. We found that the BDNF/TrkB/p75 NTR imbalance led to abnormal BDNF signaling, manifested as a diminished activation of TrkB-phospholipase C-gamma pathway but upregulation of c-Jun kinase pathway. Moreover, we confirmed the contribution of the proper balance of BDNF/TrkB/p75 NTR on HD pathology by a pharmacological approach using fingolimod. We observed that chronic infusion of fingolimod normalizes p75 NTR levels, which is likely to improve motor coordination and striatal neuropathology in HD transgenic mice. We conclude that downregulation of p75 NTR expression can delay disease progression suggesting that therapeutic approaches aimed to restore the balance between BDNF, TrkB, and p75 NTR could be promising to prevent motor deficits in HD.

[Expression and significance of p75NTR in dorsal root ganglia in different injury models].

PubMed

Li, Fang; Cai, Yan; Zhang, Jian-Yi

2008-12-01

To determine the expression and significance of p75NTR in the neuron and glia of dorsal root ganglia (DRG) in different injury models. The models of sciatic nerve injury, spinal cord injury, and combined injury (sciatic nerve injury one week prior to spinal cord injury) were established. The rats were randomly divided into a normal group,a sciatic nerve injury group,a spinal cord injury group, and a combined injury group. The sensory neurons in the DRG were labeled by fast blue (FB) injected in the dorsal column of spinal cord 0.5mm rostral to the transection site. The expression of p75NTR in the neurons and glia of the DRG was examined with immunofluorescence histochemistry after different kinds of injury and its expression in the FB positive neurons was further observed with immunofluorescence histochemistry combined with FB retrograde labeling. The expression of p75NTR was increased in the glia, but was downregulated in sensory neurons in the sciatic nerve injury group compared with the normal group. p75NTR immunoreactive products were downregulated in the glia in the spinal cord injury group compared with the sciatic nerve injury group or the combined injury group. In the combined lesion animals, the expression of p75NTR was similar to that of the sciatic nerve injury group. Its expression in the sensory neurons of DRG was downregulated,but was upregulated in the glia. The majority of sensory neurons labeled by FB in the combined injury group were p75NTR-negative, but surrounded by p75NTR-positive glia. p75NTR immunoreactive products in the glia and neurons of DRG have significant discrepancy after injury. The glial p75NTR in the DRG may play a role in the enhanced regeneration of acsending tract in the injured spinal cord after combined injury.

Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport Machinery

PubMed Central

Gluska, Shani; Zahavi, Eitan Erez; Chein, Michael; Gradus, Tal; Bauer, Anja; Finke, Stefan; Perlson, Eran

2014-01-01

Rabies virus (RABV) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS). The strategy RABV uses to hijack the cellular transport machinery is still not clear. It is thought that RABV interacts with membrane receptors in order to internalize and exploit the endosomal trafficking pathway, yet this has never been demonstrated directly. The p75 Nerve Growth Factor (NGF) receptor (p75NTR) binds RABV Glycoprotein (RABV-G) with high affinity. However, as p75NTR is not essential for RABV infection, the specific role of this interaction remains in question. Here we used live cell imaging to track RABV entry at nerve terminals and studied its retrograde transport along the axon with and without the p75NTR receptor. First, we found that NGF, an endogenous p75NTR ligand, and RABV, are localized in corresponding domains along nerve tips. RABV and NGF were internalized at similar time frames, suggesting comparable entry machineries. Next, we demonstrated that RABV could internalize together with p75NTR. Characterizing RABV retrograde movement along the axon, we showed the virus is transported in acidic compartments, mostly with p75NTR. Interestingly, RABV is transported faster than NGF, suggesting that RABV not only hijacks the transport machinery but can also manipulate it. Co-transport of RABV and NGF identified two modes of transport, slow and fast, that may represent a differential control of the trafficking machinery by RABV. Finally, we determined that p75NTR-dependent transport of RABV is faster and more directed than p75NTR-independent RABV transport. This fast route to the neuronal cell body is characterized by both an increase in instantaneous velocities and fewer, shorter stops en route. Hence, RABV may employ p75NTR-dependent transport as a fast mechanism to facilitate movement to the CNS. PMID:25165859

Co-induction of p75(NTR) and the associated death executor NADE in degenerating hippocampal neurons after kainate-induced seizures in the rat.

PubMed

Yi, Jung-Sun; Lee, Soon-Keum; Sato, Taka-Aki; Koh, Jae-Young

2003-08-21

Zinc induces in cultured cortical neurons both p75(NTR) and p75(NTR)-associated death executor (NADE), which together contribute to caspase-dependent neuronal apoptosis. Since zinc neurotoxicity may contribute to neuronal death following seizures, we examined whether p75(NTR) and NADE are co-induced also in rat hippocampal neurons degenerating after seizures. Staining of brain sections with a zinc-specific fluorescent dye (N-(6-methoxy-8-quinolyl)-p-carboxybenzoylsulphonamide) and acid fuchsin revealed zinc accumulation in degenerating neuronal cell bodies in CA1 and CA3 of hippocampus 24 h after kainate injection. Both anti-p75(NTR) and anti-NADE immunoreactivities appeared in zinc-accumulating/degenerating neurons in both areas. Intraventricular injection of CaEDTA, without altering the severity or time course of kainate-induced seizures, markedly attenuated the induction of p75(NTR)/NADE in hippocampus, which correlated with the decrease of caspase-3 activation and zinc accumulation/cell death. The present study has demonstrated that p75(NTR) and NADE are co-induced in neurons degenerating after kainate-induced seizures in rats, likely in a zinc-dependent manner.

The transcriptional regulator NtrC controls glucose-6-phosphate dehydrogenase expression and polyhydroxybutyrate synthesis through NADPH availability in Herbaspirillum seropedicae.

PubMed

Sacomboio, Euclides Nenga Manuel; Kim, Edson Yu Sin; Correa, Henrique Leonardo Ruchaud; Bonato, Paloma; Pedrosa, Fabio de Oliveira; de Souza, Emanuel Maltempi; Chubatsu, Leda Satie; Müller-Santos, Marcelo

2017-10-19

The NTR system is the major regulator of nitrogen metabolism in Bacteria. Despite its broad and well-known role in the assimilation, biosynthesis and recycling of nitrogenous molecules, little is known about its role in carbon metabolism. In this work, we present a new facet of the NTR system in the control of NADPH concentration and the biosynthesis of molecules dependent on reduced coenzyme in Herbaspirillum seropedicae SmR1. We demonstrated that a ntrC mutant strain accumulated high levels of polyhydroxybutyrate (PHB), reaching levels up to 2-fold higher than the parental strain. In the absence of NtrC, the activity of glucose-6-phosphate dehydrogenase (encoded by zwf) increased by 2.8-fold, consequently leading to a 2.1-fold increase in the NADPH/NADP + ratio. A GFP fusion showed that expression of zwf is likewise controlled by NtrC. The increase in NADPH availability stimulated the production of polyhydroxybutyrate regardless the C/N ratio in the medium. The mutant ntrC was more resistant to H 2 O 2 exposure and controlled the propagation of ROS when facing the oxidative condition, a phenotype associated with the increase in PHB content.

Identification of linker regions and domain borders of the transcription activator protein NtrC from Escherichia coli by limited proteolysis, in-gel digestion, and mass spectrometry.

PubMed

Bantscheff, M; Weiss, V; Glocker, M O

1999-08-24

We have developed a mass spectrometry based method for the identification of linker regions and domain borders in multidomain proteins. This approach combines limited proteolysis and in-gel proteolytic digestions and was applied to the determination of linkers in the transcription factor NtrC from Escherichia coli. Limited proteolysis of NtrC with thermolysin and papain revealed that initial digestion yielded two major bands in SDS-PAGE that were identified by mass spectrometry as the R-domain and the still covalently linked OC-domains. Subsequent steps in limited proteolysis afforded further cleavage of the OC-fragment into the O- and the C-domain at accessible amino acid residues. Mass spectrometric identification of the tryptic/thermolytic peptides obtained after in-gel total proteolysis of the SDS-PAGE-separated domains determined the domain borders and showed that the protease accessible linker between R- and O-domain comprised amino acids Val-131 and Gln-132 within the "Q-linker" in agreement with papain and subtilisin digestion. The region between amino acid residues Thr-389 and Gln-396 marked the hitherto unknown linker sequence that connects the O- with the C-domain. High abundances of proline-, alanine-, serine-, and glutamic acid residues were found in this linker structure (PASE-linker) of related NtrC response regulator proteins. While R- and C-domains remained stable under the applied limited proteolysis conditions, the O-domain was further truncated yielding a core fragment that comprised the sequence from Ile-140 to Arg-320. ATPase activity was lost after separation of the R-domain from the OC-fragment. However, binding of OC- and C- fragments to specific DNA was observed by characteristic band-shifts in migration retardation assays, indicating intact tertiary structures of the C-domain. The outlined strategy proved to be highly efficient and afforded lead information of tertiary structural features necessary for protein design and engineering and for structure-function studies.

Ground Testing a Nuclear Thermal Rocket: Design of a sub-scale demonstration experiment

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

David Bedsun; Debra Lee; Margaret Townsend

In 2008, the NASA Mars Architecture Team found that the Nuclear Thermal Rocket (NTR) was the preferred propulsion system out of all the combinations of chemical propulsion, solar electric, nuclear electric, aerobrake, and NTR studied. Recently, the National Research Council committee reviewing the NASA Technology Roadmaps recommended the NTR as one of the top 16 technologies that should be pursued by NASA. One of the main issues with developing a NTR for future missions is the ability to economically test the full system on the ground. In the late 1990s, the Sub-surface Active Filtering of Exhaust (SAFE) concept was firstmore » proposed by Howe as a method to test NTRs at full power and full duration. The concept relied on firing the NTR into one of the test holes at the Nevada Test Site which had been constructed to test nuclear weapons. In 2011, the cost of testing a NTR and the cost of performing a proof of concept experiment were evaluated.« less

Poly(3-hydroxybutyrate) hyperproduction by a global nitrogen regulator NtrB mutant strain of Paracoccus denitrificans PD1222

PubMed Central

Olaya-Abril, Alfonso; Luque-Almagro, Víctor M; Manso, Isabel; Gates, Andrew J; Moreno-Vivián, Conrado; Richardson, David J

2017-01-01

Abstract Paracoccus denitrificans PD1222 accumulates short-length polyhydroxyalkanoates, poly(3-hydroxybutyrate), under nitrogen-deficient conditions. Polyhydroxybutyrate metabolism requires the 3-ketoacyl-CoA thiolase PhaA, the acetoacetyl-CoA dehydrogenase/reductase PhaB and the synthase PhaC for polymerization. Additionally, P. denitrificans PD1222 grows aerobically with nitrate as sole nitrogen source. Nitrate assimilation is controlled negatively by ammonium through the two-component NtrBC system. NtrB is a sensor kinase that autophosphorylates a histidine residue under low-nitrogen concentrations and, in turn, transfers a phosphoryl group to an aspartate residue of the response regulator NtrC protein, which acts as a transcriptional activator of the P. denitrificans PD1222 nasABGHC genes. The P. denitrificans PD1222 NtrB mutant was unable to use nitrate efficiently as nitrogen source when compared to the wild-type strain, and it also overproduced poly(3-hydroxybutyrate). Acetyl-CoA concentration in the P. denitrificans PD1222 NtrB mutant strain was higher than in the wild-type strain. The expression of the phaC gene was also increased in the NtrB mutant when compared to the wild-type strain. These results suggest that accumulation of poly(3-hydroxybutyrate) in the NtrB mutant strain of PD1222 responds to the high levels of acetyl-CoA that accumulate in the cytoplasm as consequence of its inability to efficiently use nitrate as nitrogen source. PMID:29228177

Neurotrophin responsiveness of sympathetic neurons is regulated by rapid mobilization of the p75 receptor to the cell surface through TrkA activation of Arf6.

PubMed

Edward Hickman, F; Stanley, Emily M; Carter, Bruce D

2018-05-22

The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is up regulated resulting in formation of TrkA-p75 complexes, which are high affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 GEFs. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth while the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface availability, may provide insight into how and why neurodegenerative processes manifest and reveal new therapeutic targets. Results from this study indicate a novel mechanism by which p75NTR can be rapidly shuttled to the cell surface from existing intracellular pools and explores a unique pathway by which NGF regulates the sympathetic innervation of target tissues, which has profound consequences for the function of these organs. Copyright © 2018 the authors.

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

PubMed Central

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-01-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ-rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ-rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ-rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ-ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma. PMID:27840931

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.

PubMed

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-12-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

Unconventional fermionic pairing states in a monochromatically tilted optical lattice

DOE PAGES

Nocera, Alberto; Polkovnikov, Anatoli; Feiguin, Adrian E.

2017-02-01

We study the one-dimensional attractive fermionic Hubbard model under the influence of periodic driving with the time-dependent density matrix renormalization group method. We show that the system can be driven into an unconventional pairing state characterized by a condensate made of Cooper pairs with a finite center-of-mass momentum similar to a Fulde-Ferrell state. We obtain results both in the laboratory and the rotating reference frames demonstrating that the momentum of the condensate can be finely tuned by changing the ratio between the amplitude and the frequency of the driving. In particular, by quenching this ratio to the value corresponding tomore » suppression of the tunneling and the Coulomb interaction strength to zero, we are able to “freeze” the condensate. We finally study the effects of different initial conditions and compare our numerical results to those obtained from a time-independent Floquet theory in the large frequency regime. Lastly, our work offers the possibility of engineering and controlling unconventional pairing states in fermionic condensates.« less

Nitric oxide is required for the auxin-induced activation of NADPH-dependent thioredoxin reductase and protein denitrosylation during root growth responses in arabidopsis.

PubMed

Correa-Aragunde, Natalia; Cejudo, Francisco J; Lamattina, Lorenzo

2015-09-01

Auxin is the main phytohormone controlling root development in plants. This study uses pharmacological and genetic approaches to examine the role of auxin and nitric oxide (NO) in the activation of NADPH-dependent thioredoxin reductase (NTR), and the effect that this activity has on root growth responses in Arabidopsis thaliana. Arabidopsis seedlings were treated with auxin with or without the NTR inhibitors auranofin (ANF) and 1-chloro-2, 4-dinitrobenzene (DNCB). NTR activity, lateral root (LR) formation and S-nitrosothiol content were measured in roots. Protein S-nitrosylation was analysed by the biotin switch method in wild-type arabidopsis and in the double mutant ntra ntrb. The auxin-mediated induction of NTR activity is inhibited by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), suggesting that NO is downstream of auxin in this regulatory pathway. The NTR inhibitors ANF and DNCB prevent auxin-mediated activation of NTR and LR formation. Moreover, ANF and DNCB also inhibit auxin-induced DR5 : : GUS and BA3 : : GUS gene expression, suggesting that the auxin signalling pathway is compromised without full NTR activity. Treatment of roots with ANF and DNCB increases total nitrosothiols (SNO) content and protein S-nitrosylation, suggesting a role of the NTR-thioredoxin (Trx)-redox system in protein denitrosylation. In agreement with these results, the level of S-nitrosylated proteins is increased in the arabidopsis double mutant ntra ntrb as compared with the wild-type. The results support for the idea that NTR is involved in protein denitrosylation during auxin-mediated root development. The fact that a high NO concentration induces NTR activity suggests that a feedback mechanism to control massive and unregulated protein S-nitrosylation could be operating in plant cells. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Characterization of an ntrX mutant of Neisseria gonorrhoeae reveals a response regulator that controls expression of respiratory enzymes in oxidase-positive proteobacteria.

PubMed

Atack, John M; Srikhanta, Yogitha N; Djoko, Karrera Y; Welch, Jessica P; Hasri, Norain H M; Steichen, Christopher T; Vanden Hoven, Rachel N; Grimmond, Sean M; Othman, Dk Seti Maimonah Pg; Kappler, Ulrike; Apicella, Michael A; Jennings, Michael P; Edwards, Jennifer L; McEwan, Alastair G

2013-06-01

NtrYX is a sensor-histidine kinase/response regulator two-component system that has had limited characterization in a small number of Alphaproteobacteria. Phylogenetic analysis of the response regulator NtrX showed that this two-component system is extensively distributed across the bacterial domain, and it is present in a variety of Betaproteobacteria, including the human pathogen Neisseria gonorrhoeae. Microarray analysis revealed that the expression of several components of the respiratory chain was reduced in an N. gonorrhoeae ntrX mutant compared to that in the isogenic wild-type (WT) strain 1291. These included the cytochrome c oxidase subunit (ccoP), nitrite reductase (aniA), and nitric oxide reductase (norB). Enzyme activity assays showed decreased cytochrome oxidase and nitrite reductase activities in the ntrX mutant, consistent with microarray data. N. gonorrhoeae ntrX mutants had reduced capacity to survive inside primary cervical cells compared to the wild type, and although they retained the ability to form a biofilm, they exhibited reduced survival within the biofilm compared to wild-type cells, as indicated by LIVE/DEAD staining. Analyses of an ntrX mutant in a representative alphaproteobacterium, Rhodobacter capsulatus, showed that cytochrome oxidase activity was also reduced compared to that in the wild-type strain SB1003. Taken together, these data provide evidence that the NtrYX two-component system may be a key regulator in the expression of respiratory enzymes and, in particular, cytochrome c oxidase, across a wide range of proteobacteria, including a variety of bacterial pathogens.

Solar X-Ray Processes

NASA Astrophysics Data System (ADS)

Mallik, P. C. V.; Brown, J. C.; MacKinnon, A. L.

Past analyses of solar flares have ignored nonthermal recombination (NTR) emission as a means of producing Hard X-rays (HXRs) in the corona and chromosphere. However, Brown and Mallik (2008, A&A, 481, 507) have shown that NTR can be significant and even exceed nonthermal bremsstrahlung (NTB) emission for certain flare conditions that are quite common. For hot enough plasma (T > 10 MK), HXR emission of a few deka-keV has a large contribution from NTR onto highly ionized heavy elements, especially Fe. Consequently, including NTR has implications for the magnitude and the form of the inferred electron spectrum, F(E), and hence for fast-electron density and energy budgets and for the acceleration mechanisms. We show under what circumstances NTR dominates in deka-keV HXR emission. It is important to note that at high temperatures, HXR emission from thermal electrons (recombination and bremsstrahlung) becomes important. However, NTR dominates over NTB without being swamped by thermal emission in the photon energy (ɛ) regime of 20-30 keV and temperature range of 10-25MK (Fig. 1, left). By integrating the flux for all ɛ > 20keV, i.e., looking at the source luminosity function above 20 keV, we were able to show that by including NTR, the acceleration requirements are less demanding for every event, but to varying degrees based on temperature (T), spectral index (δ) and electron low-energy cut-off (Ec). Our key result is that, for T > 10MK and δ ≈ 5, including NTR reduces the demand for nonthermal electrons by up to 85%. Our paper with these results will be submitted to ApJ Letters.

Ehrlichia chaffeensis Proliferation Begins with NtrY/NtrX and PutA/GlnA Upregulation and CtrA Degradation Induced by Proline and Glutamine Uptake

PubMed Central

Cheng, Zhihui; Lin, Mingqun

2014-01-01

ABSTRACT How the obligatory intracellular bacterium Ehrlichia chaffeensis begins to replicate upon entry into human monocytes is poorly understood. Here, we examined the potential role of amino acids in initiating intracellular replication. PutA converts proline to glutamate, and GlnA converts glutamate to glutamine. E. chaffeensis PutA and GlnA complemented Escherichia coli putA and glnA mutants. Methionine sulfoximine, a glutamine synthetase inhibitor, inhibited E. chaffeensis GlnA activity and E. chaffeensis infection of human cells. Incubation of E. chaffeensis with human cells rapidly induced putA and glnA expression that peaked at 24 h postincubation. E. chaffeensis took up proline and glutamine but not glutamate. Pretreatment of E. chaffeensis with a proline transporter inhibitor (protamine), a glutamine transporter inhibitor (histidine), or proline analogs inhibited E. chaffeensis infection, whereas pretreatment with proline or glutamine enhanced infection and upregulated putA and glnA faster than no treatment or glutamate pretreatment. The temporal response of putA and glnA expression was similar to that of NtrY and NtrX, a two-component system, and electrophoretic mobility shift assays showed specific binding of recombinant E. chaffeensis NtrX (rNtrX) to the promoter regions of E. chaffeensis putA and glnA. Furthermore, rNtrX transactivated E. chaffeensis putA and glnA promoter-lacZ fusions in E. coli. Growth-promoting activities of proline and glutamine were also accompanied by rapid degradation of the DNA-binding protein CtrA. Our results suggest that proline and glutamine uptake regulates putA and glnA expression through NtrY/NtrX and facilitates degradation of CtrA to initiate a new cycle of E. chaffeensis growth. PMID:25425236

p75 neurotrophin receptor is involved in proliferation of undifferentiated mouse embryonic stem cells

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

Moscatelli, Ilana; Pierantozzi, Enrico; Camaioni, Antonella

2009-11-01

Neurotrophins and their receptors are known to play a role in the proliferation and survival of many different cell types of neuronal and non-neuronal lineages. In addition, there is much evidence in the literature showing that the p75 neurotrophin receptor (p75{sup NTR}), alone or in association with members of the family of Trk receptors, is expressed in a wide variety of stem cells, although its role in such cells has not been completely elucidated. In the present work we have investigated the expression of p75{sup NTR} and Trks in totipotent and pluripotent cells, the mouse pre-implantation embryo and embryonic stemmore » and germ cells (ES and EG cells). p75{sup NTR} and TrkA can be first detected in the blastocyst from which ES cell lines are derived. Mouse ES cells retain p75{sup NTR}/TrkA expression. Nerve growth factor is the only neurotrophin able to stimulate ES cell growth in culture, without affecting the expression of stem cell markers, alkaline phosphatase, Oct4 and Nanog. Such proliferation effect was blocked by antagonizing either p75{sup NTR} or TrkA. Interestingly, immunoreactivity to anti-p75{sup NTR} antibodies is lost upon ES cell differentiation. The expression pattern of neurotrophin receptors in murine ES cells differs from human ES cells, that only express TrkB and C, and do not respond to NGF. In this paper we also show that, while primordial germ cells (PGC) do not express p75{sup NTR}, when they are made to revert to an ES-like phenotype, becoming EG cells, expression of p75{sup NTR} is turned on.« less

A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75(NTR.).

PubMed

Tani, Hiroaki; Osbourn, Jane K; Walker, Edward H; Rush, Robert A; Ferguson, Ian A

2013-01-01

The neurotrophin receptor p75(NTR) is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75(NTR) antibody or phage scFv library pre-panned against p75(NTR) are internalized by neurons expressing p75(NTR); (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75(NTR) antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75(NTR) expression is upregulated in motor neurons in response to injury and in disease, the p75(NTR) antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier.

The Role of Neurotrophin Signaling in Gliomagenesis: A Focus on the p75 Neurotrophin Receptor (p75NTR/CD271).

PubMed

Alshehri, M M; Robbins, S M; Senger, D L

2017-01-01

The p75 neurotrophin receptor (p75 NTR , a.k.a. CD271), a transmembrane glycoprotein and a member of the tumor necrosis family (TNF) of receptors, was originally identified as a nerve growth factor receptor in the mid-1980s. While p75 NTR is recognized to have important roles during neural development, its presence in both neural and nonneural tissues clearly supports the potential to mediate a broad range of functions depending on cellular context. Using an unbiased in vivo selection paradigm for genes underlying the invasive behavior of glioma, a critical characteristic that contributes to poor clinical outcome for glioma patients, we identified p75 NTR as a central regulator of glioma invasion. Herein we review the expanding role that p75 NTR plays in glioma progression with an emphasis on how p75 NTR may contribute to the treatment refractory nature of glioma. Based on the observation that p75 NTR is expressed and functional in two critical glioma disease reservoirs, namely, the highly infiltrative cells that evade surgical resection, and the radiation- and chemotherapy-resistant brain tumor-initiating cells (also referred to as brain tumor stem cells), we propose that p75 NTR and its myriad of downstream signaling effectors represent rationale therapeutic targets for this devastating disease. Lastly, we provide the provocative hypothesis that, in addition to the well-documented cell autonomous signaling functions, the neurotrophins, and their respective receptors, contribute in a cell nonautonomous manner to drive the complex cellular and molecular composition of the brain tumor microenvironment, an environment that fuels tumorigenesis. © 2017 Elsevier Inc. All rights reserved.

A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75NTR

PubMed Central

Tani, Hiroaki; Osbourn, Jane K.; Walker, Edward H.; Rush, Robert A.; Ferguson, Ian A.

2013-01-01

The neurotrophin receptor p75NTR is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75NTR antibody or phage scFv library pre-panned against p75NTR are internalized by neurons expressing p75NTR; (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75NTR antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75NTR expression is upregulated in motor neurons in response to injury and in disease, the p75NTR antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier. PMID:23549155

Transcriptional and translational adaptation to aerobic nitrate anabolism in the denitrifier Paracoccus denitrificans

PubMed Central

Luque-Almagro, Victor M.; Manso, Isabel; Sullivan, Matthew J.; Rowley, Gary; Ferguson, Stuart J.; Moreno-Vivián, Conrado; Richardson, David J.; Gates, Andrew J.

2017-01-01

Transcriptional adaptation to nitrate-dependent anabolism by Paracoccus denitrificans PD1222 was studied. A total of 74 genes were induced in cells grown with nitrate as N-source compared with ammonium, including nasTSABGHC and ntrBC genes. The nasT and nasS genes were cotranscribed, although nasT was more strongly induced by nitrate than nasS. The nasABGHC genes constituted a transcriptional unit, which is preceded by a non-coding region containing hairpin structures involved in transcription termination. The nasTS and nasABGHC transcripts were detected at similar levels with nitrate or glutamate as N-source, but nasABGHC transcript was undetectable in ammonium-grown cells. The nitrite reductase NasG subunit was detected by two-dimensional polyacrylamide gel electrophoresis in cytoplasmic fractions from nitrate-grown cells, but it was not observed when either ammonium or glutamate was used as the N-source. The nasT mutant lacked both nasABGHC transcript and nicotinamide adenine dinucleotide (NADH)-dependent nitrate reductase activity. On the contrary, the nasS mutant showed similar levels of the nasABGHC transcript to the wild-type strain and displayed NasG protein and NADH–nitrate reductase activity with all N-sources tested, except with ammonium. Ammonium repression of nasABGHC was dependent on the Ntr system. The ntrBC and ntrYX genes were expressed at low levels regardless of the nitrogen source supporting growth. Mutational analysis of the ntrBCYX genes indicated that while ntrBC genes are required for nitrate assimilation, ntrYX genes can only partially restore growth on nitrate in the absence of ntrBC genes. The existence of a regulation mechanism for nitrate assimilation in P. denitrificans, by which nitrate induction operates at both transcriptional and translational levels, is proposed. PMID:28385879

Cryogenic Fluid Management Technology and Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Taylor, Brian D.; Caffrey, Jarvis; Hedayat, Ali; Stephens, Jonathan; Polsgrove, Robert

2016-01-01

Cryogenic fluid management (CFM) is critical to the success of future nuclear thermal propulsion powered vehicles. While this is an issue for any propulsion system utilizing cryogenic propellants, this is made more challenging by the radiation flux produced by the reactor in a nuclear thermal rocket (NTR). Managing the cryogenic fuel to prevent propellant loss to boil off and leakage is needed to limit the required quantity of propellant to a reasonable level. Analysis shows deposition of energy into liquid hydrogen fuel tanks in the vicinity of the nuclear thermal engine. This is on top of ambient environment sources of heat. Investments in cryogenic/thermal management systems (some of which are ongoing at various organizations) are needed in parallel to nuclear thermal engine development in order to one day see the successful operation of an entire stage. High durability, low thermal conductivity insulation is one developmental need. Light weight cryocoolers capable of removing heat from large fluid volumes at temperatures as low as approx. 20 K are needed to remove heat leak from the propellant of an NTR. Valve leakage is an additional CFM issue of great importance. Leakage rates of state of the art, launch vehicle size valves (which is approximately the size valves needed for a Mars transfer vehicle) are quite high and would result in large quantities of lost propellant over a long duration mission. Additionally, the liquid acquisition system inside the propellant tank must deliver properly conditioned propellant to the feed line for successful engine operation and avoid intake of warm or gaseous propellant. Analysis of the thermal environment and the CFM technology development are discussed in the accompanying presentation.

Genetically Engineered Theranostic Mesenchymal Stem Cells for the Evaluation of the Anticancer Efficacy of Enzyme/Prodrug Systems

PubMed Central

Nouri, Faranak Salman; Wang, Xing; Hatefi, Arash

2015-01-01

Over the past decade, various enzyme/prodrug systems such as thymidine kinase/ganciclovir (TK/GCV), yeast cytosine deaminase/5-fluorocytosine (yCD/5-FC) and nitroreductase/CB1954 (NTR/CB1954) have been used for stem cell mediated suicide gene therapy of cancer. Yet, no study has been conducted to compare and demonstrate the advantages and disadvantages of using one system over another. Knowing that each enzyme/prodrug system has its own strengths and weaknesses, we utilized mesenchymal stem cells (MSCs) as a medium to perform for the first time a comparative study that illustrated the impact of subtle differences among these systems on the therapeutic outcome. For therapeutic purposes, we first genetically modified MSCs to stably express a panel of four suicide genes including TK (TK007 and TKSR39 mutants), yeast cytosine deaminase: uracil phosphoribosyltransferase (yCD:UPRT) and nitroreductase (NTR). Then, we evaluated the anticancer efficacies of the genetically engineered MSCs in vitro and in vivo by using SKOV3 cell line which is sensitive to all four enzyme/prodrug systems. In addition, all MSCs were engineered to stably express luciferase gene making them suitable for quantitative imaging and dose-response relationship studies in animals. Considering the limitations imposed by the prodrugs’ bystander effects, our findings show that yCD:UPRT/5-FC is the most effective enzyme/prodrug system among the ones tested. Our findings also demonstrate that theranostic MSCs are a reliable medium for the side-by-side evaluation and screening of the enzyme/prodrug systems at the preclinical level. The results of this study could help scientists who utilize cell-based, non-viral or viral vectors for suicide gene therapy of cancer make more informed decisions when choosing enzyme/prodrug systems. PMID:25575867

Effects of age and insulin-like growth factor-1 on rat neurotrophin receptor expression after nerve injury.

PubMed

Luo, T David; Alton, Timothy B; Apel, Peter J; Cai, Jiaozhong; Barnwell, Jonathan C; Sonntag, William E; Smith, Thomas L; Li, Zhongyu

2016-10-01

Neurotrophin receptors, such as p75(NTR) , direct neuronal response to injury. Insulin-like growth factor-1 receptor (IGF-1R) mediates the increase in p75(NTR) during aging. The aim of this study was to examine the effect of aging and insulin-like growth factor-1 (IGF-1) treatment on recovery after peripheral nerve injury. Young and aged rats underwent tibial nerve transection with either local saline or IGF-1 treatment. Neurotrophin receptor mRNA and protein expression were quantified. Aged rats expressed elevated baseline IGF-1R (34% higher, P = 0.01) and p75(NTR) (68% higher, P < 0.01) compared with young rats. Post-injury, aged animals expressed significantly higher p75(NTR) levels (68.5% above baseline at 4 weeks). IGF-1 treatment suppressed p75(NTR) gene expression at 4 weeks (17.2% above baseline, P = 0.002) post-injury. Local IGF-1 treatment reverses age-related declines in recovery after peripheral nerve injuries by suppressing p75(NTR) upregulation and pro-apoptotic complexes. IGF-1 may be considered a viable adjuvant therapy to current treatment modalities. Muscle Nerve 54: 769-775, 2016. © 2016 Wiley Periodicals, Inc.

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.

Lunar NTR vehicle design and operations study

NASA Technical Reports Server (NTRS)

Hodge, John

1993-01-01

The results of a lunar nuclear thermal rocket (NTR) vehicle design and operations study are presented in text and graphic form. The objectives of the study were to evaluate the potential applications of a specific NTR design to past and current (First Lunar Outpost) mission profiles for piloted and cargo lunar missions, and to assess the applicability of utilizing lunar vehicle design concepts for Mars missions.

A measuring stand for a ducted fan aircraft propulsion unit

NASA Astrophysics Data System (ADS)

Hlaváček, David

2014-03-01

The UL-39 ultra-light aircraft which is being developed by the Department of Aerospace Engineering, Faculty of Mechanical Engineering, Czech Technical University in Prague, is equipped with an unconventional ducted fan propulsion unit. The unit consists of an axial fan driven by a piston engine and placed inside a duct ended with a nozzle. This article describes the arrangement of a modernised measuring stand for this highly specific propulsion unit which will be able to measure the fan pressure ratio and velocity field in front of and behind the fan and its characteristic curve.

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells.

PubMed

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders.

Neurotrophin Receptor p75NTR Regulates Immune Function of Plasmacytoid Dendritic Cells

PubMed Central

Bandoła, Joanna; Richter, Cornelia; Ryser, Martin; Jamal, Arshad; Ashton, Michelle P.; von Bonin, Malte; Kuhn, Matthias; Dorschner, Benjamin; Alexopoulou, Dimitra; Navratiel, Katrin; Roeder, Ingo; Dahl, Andreas; Hedrich, Christian M.; Bonifacio, Ezio; Brenner, Sebastian; Thieme, Sebastian

2017-01-01

Plasmacytoid dendritic cells (pDCs) regulate innate and adaptive immunity. Neurotrophins and their receptors control the function of neuronal tissue. In addition, they have been demonstrated to be part of the immune response but little is known about the effector immune cells involved. We report, for the first time, the expression and immune-regulatory function of the low affinity neurotrophin receptor p75 neurotrophin receptor (p75NTR) by the antigen-presenting pDCs, mediated by toll-like receptor (TLR) 9 activation and differential phosphorylation of interferon regulatory factor 3 and 7. The modulation of p75NTR on pDCs significantly influences disease progression of asthma in an ovalbumin-induced mouse model mediated by the TLR9 signaling pathway. p75NTR activation of pDCs from patients with asthma increased allergen-specific T cell proliferation and cytokine secretion in nerve growth factor concentration-dependent manner. Further, p75NTR activation of pDCs delayed the onset of autoimmune diabetes in RIP-CD80GP mice and aggravated graft-versus-host disease in a xenotransplantation model. Thus, p75NTR signaling on pDCs constitutes a new and critical mechanism connecting neurotrophin signaling and immune response regulation with great therapeutic potential for a variety of immune disorders. PMID:28861085

The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells.

PubMed

Sicard, Flavie; Contesse, Vincent; Lefebvre, Hervé; Ait-Ali, Djida; Gras, Marjorie; Cartier, Dorthe; Decker, Annick; Chartrel, Nicolas; Anouar, Youssef; Vaudry, Hubert; Delarue, Catherine

2006-08-01

Neurotensin (NT) modulates corticosteroid secretion from the mammalian adrenal gland. The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland. In vitro studies were conducted on cultured human adrenocortical cells. This study was conducted in a university research laboratory. Adrenal explants from patients undergoing expanded nephrectomy for kidney cancer were studied. Cortisol secretion from cultured adrenocortical cells was measured. NT1-11, the N-terminal fragment of NT, dose-dependently inhibited basal and ACTH-stimulated cortisol production by human adrenocortical cells in primary culture. In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m. HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts. Molecular and pharmacological studies were performed to determine the type of NT receptor involved in the corticostatic effect of NT1-11. RT-PCR analysis revealed the expression of NT receptor type (NTR) 3 mRNA but not NTR1 and NTR2 mRNAs in the human adrenal tissue. However, the pharmacological profile of the adrenal NT1-11 receptor was different from that of NTR3, indicating that this receptor type is not involved in the action of NT1-11 on corticosteroidogenesis. Our results indicate that NT1-11 may act as an endocrine factor to inhibit cortisol secretion through activation of a receptor distinct from the classical NTR1, NTR2, and NTR3.

The Nuclear Thermal Propulsion Stage (NTPS): A Key Space Asset for Human Exploration and Commercial Missions to the Moon

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; McCurdy, David R.; Burke, Laura M.

2014-01-01

The nuclear thermal rocket (NTR) has frequently been discussed as a key space asset that can bridge the gap between a sustained human presence on the Moon and the eventual human exploration of Mars. Recently, a human mission to a near Earth asteroid (NEA) has also been included as a "deep space precursor" to an orbital mission of Mars before a landing is attempted. In his "post-Apollo" Integrated Space Program Plan (1970 to 1990), Wernher von Braun, proposed a reusable Nuclear Thermal Propulsion Stage (NTPS) to deliver cargo and crew to the Moon to establish a lunar base initially before sending human missions to Mars. The NTR was selected because it was a proven technology capable of generating both high thrust and high specific impulse (Isp approx. 900 s)-twice that of today's best chemical rockets. During the Rover and NERVA programs, 20 rocket reactors were designed, built and successfully ground tested. These tests demonstrated the (1) thrust levels; (2) high fuel temperatures; (3) sustained operation; (4) accumulated lifetime; and (5) restart capability needed for an affordable in-space transportation system. In NASA's Mars Design Reference Architecture (DRA) 5.0 study, the "Copernicus" crewed NTR Mars transfer vehicle used three 25 klbf "Pewee" engines-the smallest and highest performing engine tested in the Rover program. Smaller lunar transfer vehicles-consisting of a NTPS with three approx. 16.7 klbf "SNRE-class" engines, an in-line propellant tank, plus the payload-can be delivered to LEO using a 70 t to LEO upgraded SLS, and can support reusable cargo delivery and crewed lunar landing missions. The NTPS can play an important role in returning humans to the Moon to stay by providing an affordable in-space transportation system that can allow initial lunar outposts to evolve into settlements capable of supporting commercial activities. Over the next decade collaborative efforts between NASA and private industry could open up new exploration and commercial opportunities for both organizations. With efficient NTP, commercial habitation and crew delivery systems, a "mobile cislunar research station" can transport crews to small NEAs delivered to the E-ML2 point. Also possible are week-long "lunar tourism" missions that can carry passengers into lunar orbit for sightseeing (and plenty of picture taking), then return them to Earth orbit where they would re-enter and land using a small reusable lifting body based on NASA's HL-20 design. Mission descriptions, key vehicle features and operational characteristics are described and presented.

Transcriptional and translational adaptation to aerobic nitrate anabolism in the denitrifier Paracoccus denitrificans.

PubMed

Luque-Almagro, Victor M; Manso, Isabel; Sullivan, Matthew J; Rowley, Gary; Ferguson, Stuart J; Moreno-Vivián, Conrado; Richardson, David J; Gates, Andrew J; Roldán, M Dolores

2017-05-10

Transcriptional adaptation to nitrate-dependent anabolism by Paracoccus denitrificans PD1222 was studied. A total of 74 genes were induced in cells grown with nitrate as N-source compared with ammonium, including nasTSABGHC and ntrBC genes. The nasT and nasS genes were cotranscribed, although nasT was more strongly induced by nitrate than nasS The nasABGHC genes constituted a transcriptional unit, which is preceded by a non-coding region containing hairpin structures involved in transcription termination. The nasTS and nasABGHC transcripts were detected at similar levels with nitrate or glutamate as N-source, but nasABGHC transcript was undetectable in ammonium-grown cells. The nitrite reductase NasG subunit was detected by two-dimensional polyacrylamide gel electrophoresis in cytoplasmic fractions from nitrate-grown cells, but it was not observed when either ammonium or glutamate was used as the N-source. The nasT mutant lacked both nasABGHC transcript and nicotinamide adenine dinucleotide (NADH)-dependent nitrate reductase activity. On the contrary, the nasS mutant showed similar levels of the nasABGHC transcript to the wild-type strain and displayed NasG protein and NADH-nitrate reductase activity with all N-sources tested, except with ammonium. Ammonium repression of nasABGHC was dependent on the Ntr system. The ntrBC and ntrYX genes were expressed at low levels regardless of the nitrogen source supporting growth. Mutational analysis of the ntrBCYX genes indicated that while ntrBC genes are required for nitrate assimilation, ntrYX genes can only partially restore growth on nitrate in the absence of ntrBC genes. The existence of a regulation mechanism for nitrate assimilation in P. denitrificans , by which nitrate induction operates at both transcriptional and translational levels, is proposed. © 2017 The Author(s).

Small Molecule p75NTR Ligands Reduce Pathological Phosphorylation and Misfolding of Tau, Inflammatory Changes, Cholinergic Degeneration, and Cognitive Deficits in AβPPL/S Transgenic Mice

PubMed Central

Nguyen, Thuy-Vi V.; Shen, Lin; Griend, Lilith Vander; Quach, Lisa N.; Belichenko, Nadia P.; Saw, Nay; Yang, Tao; Shamloo, Mehrdad; Wyss-Coray, Tony; Massa, Stephen M.; Longo, Frank M.

2014-01-01

The p75 neurotrophin receptor (p75NTR ) is involved in degenerative mechanisms related to Alzheimer’s disease (AD). In addition, p75NTR levels are increased in AD and the receptor is expressed by neurons that are particularly vulnerable in the disease. Therefore, modulating p75NTR function may be a significant disease-modifying treatment approach. Prior studies indicated that the non-peptide, small molecule p75NTR ligands LM11A-31, and chemically unrelated LM11A-24, could block amyloid-β-induced deleterious signaling and neurodegeneration in vitro, and LM11A-31 was found to mitigate neuritic degeneration and behavioral deficits in a mouse model of AD. In this study, we determined whether these in vivo findings represent class effects of p75NTR ligands by examining LM11A-24 effects. In addition, the range of compound effects was further examined by evaluating tau pathology and neuroinflammation. Following oral administration, both ligands reached brain concentrations known to provide neuroprotection in vitro. Compound induction of p75NTR cleavage provided evidence for CNS target engagement. LM11A-31 and LM11A-24 reduced excessive phosphorylation of tau, and LM11A-31 also inhibited its aberrant folding. Both ligands decreased activation of microglia, while LM11A-31 attenuated reactive astrocytes. Along with decreased inflammatory responses, both ligands reduced cholinergic neurite degeneration. In addition to the amelioration of neuropathology in AD model mice, LM11A-31, but not LM11A-24, prevented impairments in water maze performance, while both ligands prevented deficits in fear conditioning. These findings support a role for p75NTR ligands in preventing fundamental tau-related pathologic mechanisms in AD, and further validate the development of these small molecules as a new class of therapeutic compounds. PMID:24898660

Nitrate assimilation pathway (NAP): role of structural (nit) and transporter (ntr1) genes in Fusarium oxysporum f.sp. lycopersici growth and pathogenicity.

PubMed

Gomez-Gil, Lucia; Camara Almiron, Jesus; Rodriguez Carrillo, Patricia Lizett; Olivares Medina, Cindy Nayely; Bravo Ruiz, Gustavo; Romo Rodriguez, Pamela; Corrales Escobosa, Alma Rosa; Gutierrez Corona, Felix; Roncero, M Isabel

2018-04-01

The tomato pathogen Fusarium oxysporum f.sp. lycopersici possesses the capability to use nitrate as the only nitrogen source under aerobic and anaerobic conditions and to activate virulence-related functions when cultivated in the presence of nitrate, but not in ammonium. The genome of F. oxysporum f.sp. lycopersici encodes three paralogs nitrate reductase (NR) genes (nit1, nit2 and nit3) and one predicted ortholog of the Aspergillus nidulans high-affinity nitrate/nitrite transporters NtrA and NtrB, named ntr1. We set out to clarify the role of nit1, nit2, nit3 and ntr1 genes in nitrate assimilation and in the virulence of F. oxysporum f.sp. lycopersici. Quantitative RT-PCR analysis revealed that only nit1, nit2 and ntr1 are expressed at significant levels during growth in nitrate as the only nitrogen source. Targeted deletion of nit1 and ntr1, but not of nit2 or nit3, severely impaired growth of F. oxysporum on nitrate as nitrogen source, indicating that Nit1 and Ntr1 proteins are involved in nitrate assimilation by the fungus; biochemical analysis of nit mutants indicated that Nit1 and Nit2 enzymes contribute to about 50 and 30% of the total NR activity, respectively. In addition, a spontaneous chlorate-resistant mutant derived from F. oxysporum 4287, denoted NitFG, was characterized, showing inability to grow in nitrate under aerobic and anaerobic conditions and low levels of NR activity, in spite of its increased transcription levels of nit1 and nit2 genes. Tomato plant infection assays showed that NitFG and ∆ntr1 mutants induced an earlier death in tomato plants, whereas the single mutants ∆nit1, ∆nit2 and ∆nit1∆nit2 double mutant showed a mortality rate similar to the wild-type strain. Taken together, these results indicate that the Nit1 and Ntr1 proteins are important for nitrate assimilation of F. oxysporum f.sp. lycopersici incubated under aerobic and anaerobic conditions and that this metabolic process is not essential for the virulence of the fungus. These observations open new questions about the role of Nit1, Nit2, and Nit3 proteins in other routes of nitrate metabolism in this pathogenic fungus and in the possible regulatory role that can be exerted by the AreA protein in these routes.

Advanced supersonic propulsion study, phases 3 and 4. [variable cycle engines

NASA Technical Reports Server (NTRS)

Allan, R. D.; Joy, W.

1977-01-01

An evaluation of various advanced propulsion concepts for supersonic cruise aircraft resulted in the identification of the double-bypass variable cycle engine as the most promising concept. This engine design utilizes special variable geometry components and an annular exhaust nozzle to provide high take-off thrust and low jet noise. The engine also provides good performance at both supersonic cruise and subsonic cruise. Emission characteristics are excellent. The advanced technology double-bypass variable cycle engine offers an improvement in aircraft range performance relative to earlier supersonic jet engine designs and yet at a lower level of engine noise. Research and technology programs required in certain design areas for this engine concept to realize its potential benefits include refined parametric analysis of selected variable cycle engines, screening of additional unconventional concepts, and engine preliminary design studies. Required critical technology programs are summarized.

Adaptations and Analysis of the AFIT Noise Radar Network for Indoor Navigation

DTIC Science & Technology

2013-03-01

capable of producing bistatic/multistatic radar images. NTR is unique because it utilizes amplified random thermal noise as its transmission waveform...structure and operation of NTR is described. A minutia of the EM theory describing the various phenomenon found when operating RF devices in indoor...construction of NTR is simple in comparison to other CW radars. The system begins with a commercial thermal noise source, which produces a uniform

A generalized sizing method for revolutionary concepts under probabilistic design constraints

NASA Astrophysics Data System (ADS)

Nam, Taewoo

Internal combustion (IC) engines that consume hydrocarbon fuels have dominated the propulsion systems of air-vehicles for the first century of aviation. In recent years, however, growing concern over rapid climate changes and national energy security has galvanized the aerospace community into delving into new alternatives that could challenge the dominance of the IC engine. Nevertheless, traditional aircraft sizing methods have significant shortcomings for the design of such unconventionally powered aircraft. First, the methods are specialized for aircraft powered by IC engines, and thus are not flexible enough to assess revolutionary propulsion concepts that produce propulsive thrust through a completely different energy conversion process. Another deficiency associated with the traditional methods is that a user of these methods must rely heavily on experts' experience and advice for determining appropriate design margins. However, the introduction of revolutionary propulsion systems and energy sources is very likely to entail an unconventional aircraft configuration, which inexorably disqualifies the conjecture of such "connoisseurs" as a means of risk management. Motivated by such deficiencies, this dissertation aims at advancing two aspects of aircraft sizing: (1) to develop a generalized aircraft sizing formulation applicable to a wide range of unconventionally powered aircraft concepts and (2) to formulate a probabilistic optimization technique that is able to quantify appropriate design margins that are tailored towards the level of risk deemed acceptable to a decision maker. A more generalized aircraft sizing formulation, named the Architecture Independent Aircraft Sizing Method (AIASM), was developed for sizing revolutionary aircraft powered by alternative energy sources by modifying several assumptions of the traditional aircraft sizing method. Along with advances in deterministic aircraft sizing, a non-deterministic sizing technique, named the Probabilistic Aircraft Sizing Method (PASM), was developed. The method allows one to quantify adequate design margins to account for the various sources of uncertainty via the application of the chance-constrained programming (CCP) strategy to AIASM. In this way, PASM can also provide insights into a good compromise between cost and safety.

Rotorcraft convertible engine study

NASA Technical Reports Server (NTRS)

Gill, J. C.; Earle, R. V.; Mar, H. M.

1982-01-01

The objective of the Rotorcraft Convertible Engine Study was to define future research and technology effort required for commercial development by 1988 of convertible fan/shaft gas turbine engines for unconventional rotorcraft transports. Two rotorcraft and their respective missions were defined: a Fold Tilt Rotor aircraft and an Advancing Blade Concept (ABC) rotorcraft. Sensitivity studies were conducted with these rotorcraft to determine parametrically the influence of propulsion characteristics on aircraft size, mission fuel requirements, and direct operating costs (DOC). The two rotorcraft were flown with conventional propulsion systems (separate lift/cruise engines) and with convertible propulsion systems to determine the benefits to be derived from convertible engines. Trade-off studies were conducted to determine the optimum engine cycle and staging arrangement for a convertible engine. Advanced technology options applicable to convertible engines were studied. Research and technology programs were identified which would ensure technology readiness for commercial development of convertible engines by 1988.

Structure of Hordeum vulgare NADPH-dependent thioredoxin reductase 2. Unwinding the reaction mechanism

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

Kirkensgaard, Kristine G.; Enzyme and Protein Chemistry, Department of Systems BioIogy, Technical University of Denmark; Hägglund, Per

2009-09-01

The first crystal structure of a cereal NTR, a protein involved in seed development and germination, has been determined. The structure is in a conformation that excludes NADPH binding and indicates that a domain reorientation facilitated by Trx binding precedes NADPH binding in the reaction mechanism. Thioredoxins (Trxs) are protein disulfide reductases that regulate the intracellular redox environment and are important for seed germination in plants. Trxs are in turn regulated by NADPH-dependent thioredoxin reductases (NTRs), which provide reducing equivalents to Trx using NADPH to recycle Trxs to the active form. Here, the first crystal structure of a cereal NTR,more » HvNTR2 from Hordeum vulgare (barley), is presented, which is also the first structure of a monocot plant NTR. The structure was determined at 2.6 Å resolution and refined to an R{sub cryst} of 19.0% and an R{sub free} of 23.8%. The dimeric protein is structurally similar to the structures of AtNTR-B from Arabidopsis thaliana and other known low-molecular-weight NTRs. However, the relative position of the two NTR cofactor-binding domains, the FAD and the NADPH domains, is not the same. The NADPH domain is rotated by 25° and bent by a 38% closure relative to the FAD domain in comparison with AtNTR-B. The structure may represent an intermediate between the two conformations described previously: the flavin-oxidizing (FO) and the flavin-reducing (FR) conformations. Here, analysis of interdomain contacts as well as phylogenetic studies lead to the proposal of a new reaction scheme in which NTR–Trx interactions mediate the FO to FR transformation.« less

Proneurotrophin-3 may induce Sortilin dependent death in inner ear neurons

PubMed Central

Tauris, Jacob; Gustafsen, Camilla; Christensen, Erik Ilsø; Jansen, Pernille; Nykjaer, Anders; Nyengaard, Jens R.; Teng, Kenneth K.; Schwarz, Elisabeth; Ovesen, Therese; Madsen, Peder; Petersen, Claus Munck

2010-01-01

The precursor of the neurotrophin NGF (proNGF) serves physiological functions distinct from its mature counterpart as it induces neuronal apoptosis through activation of a p75 neurotrophin receptor (p75NTR) and Sortilin death-signalling complex. The neurotrophins BDNF and NT3 provide essential trophic support to auditory neurons. Injury to the neurotrophin secreting cells in the inner ear is followed by irreversible degeneration of spiral ganglion neurons with consequences such as impaired hearing or deafness. Lack of mature neurotrophins may explain the degeneration of spiral ganglion neurons, but another mechanism is possible since unprocessed proNTs released from the injured cells may contribute to the degeneration by induction of apoptosis. Recent studies demonstrate that proBDNF, like proNGF, is a potent inducer of Sortilin:p75NTR mediated apoptosis. In addition, a coincident upregulation of proBDNF and p75NTR has been observed in degenerating spiral ganglion neurons, but the Sortilin expression in the inner ear is unresolved. Here we demonstrate that Sortilin and p75NTR are coexpressed in neurons of the neonatal inner ear. Furthermore, we establish that proNT3 exhibits high affinity binding to Sortilin and has the capacity to enhance cell surface Sortilin:p75NTR complex formation as well as to mediate apoptosis in neurons coexpressing p75NTR and Sortilin. Based on examination of wt and Sortilin deficient mouse embryos, Sortilin does not significantly influence the developmental selection of spiral ganglion neurons. However, our results suggest that proNT3 and proBDNF may play important roles in the response to noise-induced injuries or ototoxic damage via the Sortilin:p75NTR death-signalling complex. PMID:21261755

Towards the PET radiotracer for p75 neurotrophin receptor: [(11)C]LM11A-24 shows biological activity in vitro, but unfavorable ex vivo and in vivo profile.

PubMed

Gibon, Julien; Kang, Min Su; Aliaga, Arturo; Sharif, Behrang; Rosa-Neto, Pedro; Séguéla, Philippe; Barker, Philip A; Kostikov, Alexey

2016-10-01

Mature neurotrophins as well as their pro forms are critically involved in the regulation of neuronal functions. They are signaling through three distinct types of receptors: tropomyosin receptor kinase family (TrkA/B/C), p75 neurotrophin receptor (p75(NTR)) and sortilin. Aberrant expression of p75(NTR) in the CNS is implicated in a variety of neurodegenerative diseases, including Alzheimer's disease. The goal of this work was to evaluate one of the very few reported p75(NTR) small molecule ligands as a lead compound for development of novel PET radiotracers for in vivo p75(NTR) imaging. Here we report that previously described ligand LM11A-24 shows significant inhibition of carbachol-induced persistent firing (PF) of entorhinal cortex (EC) pyramidal neurons in wild-type mice via selective interaction with p75(NTR). Based on this electrophysiological assay, the compound has very high potency with an EC50<10nM. We optimized the radiosynthesis of [(11)C]LM11A-24 as the first attempt to develop PET radioligand for in vivo imaging of p75(NTR). Despite some weak interaction with CNS tissues, the radiolabeled compound showed unfavorable in vivo profile presumably due to high hydrophilicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail

PubMed Central

Ludwigsen, Johanna; Pfennig, Sabrina; Singh, Ashish K; Schindler, Christina; Harrer, Nadine; Forné, Ignasi; Zacharias, Martin; Mueller-Planitz, Felix

2017-01-01

ISWI-family nucleosome remodeling enzymes need the histone H4 N-terminal tail to mobilize nucleosomes. Here we mapped the H4-tail binding pocket of ISWI. Surprisingly the binding site was adjacent to but not overlapping with the docking site of an auto-regulatory motif, AutoN, in the N-terminal region (NTR) of ISWI, indicating that AutoN does not act as a simple pseudosubstrate as suggested previously. Rather, AutoN cooperated with a hitherto uncharacterized motif, termed AcidicN, to confer H4-tail sensitivity and discriminate between DNA and nucleosomes. A third motif in the NTR, ppHSA, was functionally required in vivo and provided structural stability by clamping the NTR to Lobe 2 of the ATPase domain. This configuration is reminiscent of Chd1 even though Chd1 contains an unrelated NTR. Our results shed light on the intricate structural and functional regulation of ISWI by the NTR and uncover surprising parallels with Chd1. DOI: http://dx.doi.org/10.7554/eLife.21477.001 PMID:28109157

Regulation of glutamine synthetase II activity in Rhizobium meliloti 104A14.

PubMed Central

Shatters, R G; Somerville, J E; Kahn, M L

1989-01-01

Most rhizobia contain two glutamine synthetase (GS) enzymes: GSI, encoded by glnA, and GSII, encoded by glnII. We have found that WSU414, a Rhizobium meliloti 104A14 glutamine auxotroph derived from a glnA parental strain, is an ntrA mutant. The R. meliloti glnII promoter region contains DNA sequences similar to those found in front of other genes that require ntrA for their transcription. No GSII was found in the glnA ntrA mutant, and when a translational fusion of glnII to the Escherichia coli lacZ gene was introduced into WSU414, no beta-galactosidase was expressed. These results indicate that ntrA is required for glnII expression. The ntrA mutation did not prevent the expression of GSI. In free-living culture, the level of GSII and of the glnII-lacZ fusion protein was regulated by altering transcription in response to available nitrogen. No GSII protein was detected in alfalfa, pea, or soybean nodules when anti-GSII-specific antiserum was used. Images PMID:2570059

Isolation of ntrA-like mutants of Azotobacter vinelandii.

PubMed Central

Santero, E; Luque, F; Medina, J R; Tortolero, M

1986-01-01

A number of chlorate-resistant mutants of Azotobacter vinelandii affected in a general control of nitrogen metabolism were isolated. These mutants could not utilize dinitrogen, nitrate, or nitrite as a nitrogen source. The reason for this inability is that they were simultaneously deficient in nitrogenase and nitrate and nitrite reductase activities. They were complemented by a cosmid carrying a DNA fragment of A. vinelandii able to complement ntrA mutants of Escherichia coli, so they seemed to be ntrA-like mutants. PMID:3009406

Nuclear Thermal Rocket Simulation in NPSS

NASA Technical Reports Server (NTRS)

Belair, Michael L.; Sarmiento, Charles J.; Lavelle, Thomas M.

2013-01-01

Four nuclear thermal rocket (NTR) models have been created in the Numerical Propulsion System Simulation (NPSS) framework. The models are divided into two categories. One set is based upon the ZrC-graphite composite fuel element and tie tube-style reactor developed during the Nuclear Engine for Rocket Vehicle Application (NERVA) project in the late 1960s and early 1970s. The other reactor set is based upon a W-UO2 ceramic-metallic (CERMET) fuel element. Within each category, a small and a large thrust engine are modeled. The small engine models utilize RL-10 turbomachinery performance maps and have a thrust of approximately 33.4 kN (7,500 lbf ). The large engine models utilize scaled RL-60 turbomachinery performance maps and have a thrust of approximately 111.2 kN (25,000 lbf ). Power deposition profiles for each reactor were obtained from a detailed Monte Carlo N-Particle (MCNP5) model of the reactor cores. Performance factors such as thermodynamic state points, thrust, specific impulse, reactor power level, and maximum fuel temperature are analyzed for each engine design.

Nuclear Thermal Rocket Simulation in NPSS

NASA Technical Reports Server (NTRS)

Belair, Michael L.; Sarmiento, Charles J.; Lavelle, Thomas L.

2013-01-01

Four nuclear thermal rocket (NTR) models have been created in the Numerical Propulsion System Simulation (NPSS) framework. The models are divided into two categories. One set is based upon the ZrC-graphite composite fuel element and tie tube-style reactor developed during the Nuclear Engine for Rocket Vehicle Application (NERVA) project in the late 1960s and early 1970s. The other reactor set is based upon a W-UO2 ceramic- metallic (CERMET) fuel element. Within each category, a small and a large thrust engine are modeled. The small engine models utilize RL-10 turbomachinery performance maps and have a thrust of approximately 33.4 kN (7,500 lbf ). The large engine models utilize scaled RL-60 turbomachinery performance maps and have a thrust of approximately 111.2 kN (25,000 lbf ). Power deposition profiles for each reactor were obtained from a detailed Monte Carlo N-Particle (MCNP5) model of the reactor cores. Performance factors such as thermodynamic state points, thrust, specific impulse, reactor power level, and maximum fuel temperature are analyzed for each engine design.

Performance improvements of single-engine business airplanes by the integration of advanced technologies

NASA Technical Reports Server (NTRS)

Kohlman, D. L.

1982-01-01

An assessment is presented of the performance gains and economic impact of the integration in general aviation aircraft of advanced technologies, relating to such aspects of design as propulsion, natural laminar flow, lift augmentation, unconventional configurations, and advanced aluminum and composite structures. All considerations are with reference to a baseline mission of 1300 nm range and 300-knot cruise speed with a 1300-lb payload, and a baseline aircraft with a 40 lb/sq ft wing loading and an aspect ratio of 8. Extensive analytical results are presented from the NASA-sponsored General Aviation Synthesis Program. Attention is given to the relative performance gains to be expected from the single-engined baseline aircraft's use of a low cost general aviation turbine engine, a spark-ignited reciprocating engine, a diesel engine, and a Wankel rotary engine.

Next generation system modeling of NTR systems

NASA Technical Reports Server (NTRS)

Buksa, John J.; Rider, William J.

1993-01-01

The topics are presented in viewgraph form and include the following: nuclear thermal rocket (NTR) modeling challenges; current approaches; shortcomings of current analysis method; future needs; and present steps to these goals.

A review on risk assessment techniques for hydraulic fracturing water and produced water management implemented in onshore unconventional oil and gas production.

PubMed

Torres, Luisa; Yadav, Om Prakash; Khan, Eakalak

2016-01-01

The objective of this paper is to review different risk assessment techniques applicable to onshore unconventional oil and gas production to determine the risks to water quantity and quality associated with hydraulic fracturing and produced water management. Water resources could be at risk without proper management of water, chemicals, and produced water. Previous risk assessments in the oil and gas industry were performed from an engineering perspective leaving aside important social factors. Different risk assessment methods and techniques are reviewed and summarized to select the most appropriate one to perform a holistic and integrated analysis of risks at every stage of the water life cycle. Constraints to performing risk assessment are identified including gaps in databases, which require more advanced techniques such as modeling. Discussions on each risk associated with water and produced water management, mitigation strategies, and future research direction are presented. Further research on risks in onshore unconventional oil and gas will benefit not only the U.S. but also other countries with shale oil and gas resources. Copyright © 2015 Elsevier B.V. All rights reserved.

Neurotensin-induced proinflammatory signaling in human colonocytes is regulated by β-arrestins and endothelin-converting enzyme-1-dependent endocytosis and resensitization of neurotensin receptor 1.

PubMed

Law, Ivy Ka Man; Murphy, Jane E; Bakirtzi, Kyriaki; Bunnett, Nigel W; Pothoulakis, Charalabos

2012-04-27

The neuropeptide/hormone neurotensin (NT) mediates intestinal inflammation and cell proliferation by binding of its high affinity receptor, neurotensin receptor-1 (NTR1). NT stimulates IL-8 expression in NCM460 human colonic epithelial cells by both MAP kinase- and NF-κB-dependent pathways. Although the mechanism of NTR1 endocytosis has been studied, the relationship between NTR1 intracellular trafficking and inflammatory signaling remains to be elucidated. In the present study, we show that in NCM460 cells exposed to NT, β-arrestin-1 (βARR1), and β-arrestin-2 (βARR2) translocate to early endosomes together with NTR1. Endothelin-converting enzyme-1 (ECE-1) degrades NT in acidic conditions, and its activity is crucial for NTR1 recycling. Pretreatment of NCM460 cells with the ECE-1 inhibitor SM19712 or gene silencing of βARR1 or βARR2 inhibits NT-stimulated ERK1/2 and JNK phosphorylation, NF-κB p65 nuclear translocation and phosphorylation, and IL-8 secretion. Furthermore, NT-induced cell proliferation, but not IL-8 transcription, is attenuated by the JNK inhibitor, JNK(AII). Thus, NTR1 internalization and recycling in human colonic epithelial cells involves βARRs and ECE-1, respectively. Our results also indicate that βARRs and ECE-1-dependent recycling regulate MAP kinase and NF-κB signaling as well as cell proliferation in human colonocytes in response to NT.

The coat protein of prunus necrotic ringspot virus specifically binds to and regulates the conformation of its genomic RNA.

PubMed

Aparicio, Frederic; Vilar, Marçal; Perez-Payá, Enrique; Pallás, Vicente

2003-08-15

Binding of coat protein (CP) to the 3' nontranslated region (3'-NTR) of viral RNAs is a crucial requirement to establish the infection of Alfamo- and Ilarviruses. In vitro binding properties of the Prunus necrotic ringspot ilarvirus (PNRSV) CP to the 3'-NTR of its genomic RNA using purified E. coli- expressed CP and different synthetic peptides corresponding to a 26-residue sequence near the N-terminus were investigated by electrophoretic mobility shift assays. PNRSV CP bound to, at least, three different sites existing on the 3'-NTR. Moreover, the N-terminal region between amino acid residues 25 to 50 of the protein could function as an independent RNA-binding domain. Single exchange of some arginine residues by alanine eliminated the RNA-interaction capacity of the synthetic peptides, consistent with a crucial role for Arg residues common to many RNA-binding proteins possessing Arg-rich domains. Circular dichroism spectroscopy revealed that the RNA conformation is altered when amino-terminal CP peptides bind to the viral RNA. Finally, mutational analysis of the 3'-NTR suggested the presence of a pseudoknotted structure at this region on the PNRSV RNA that, when stabilized by the presence of Mg(2+), lost its capability to bind the coat protein. The existence of two mutually exclusive conformations for the 3'-NTR of PNRSV strongly suggests a similar regulatory mechanism at the 3'-NTR level in Alfamo- and Ilarvirus genera.

Subconjunctival Delivery of p75NTR Antagonists Reduces the Inflammatory, Vascular, and Neurodegenerative Pathologies of Diabetic Retinopathy.

PubMed

Galan, Alba; Barcelona, Pablo F; Nedev, Hinyu; Sarunic, Marinko V; Jian, Yifan; Saragovi, H Uri

2017-06-01

The p75NTR is a novel therapeutic target validated in a streptozotocin mouse model of diabetic retinopathy. Intravitreal (IVT) injection of small molecule p75NTR antagonist THX-B was therapeutic and resolved the inflammatory, vascular, and neurodegenerative phases of the retinal pathology. To simplify clinical translation, we sought a superior drug delivery method that circumvents risks associated with IVT injections. We compared the pharmacokinetics of a single 40 μg subconjunctival (SCJ) depot to the reported effective 5 μg IVT injections of THX-B. We quantified therapeutic efficacy, with endpoints of inflammation, edema, and neuronal death. The subconjunctival depot affords retinal exposure equal to IVT injection, without resulting in detectable drug in circulation. At week 2 of diabetic retinopathy, the SCJ depot provided therapeutic efficacy similar to IVT injections, with reduced inflammation, reduced edema, reduced neuronal death, and a long-lasting protection of the retinal structure. Subconjunctival injections are a safe and effective route for retinal delivery of p75NTR antagonists. The subconjunctival route offers an advantageous, less-invasive, more compliant, and nonsystemic method to deliver p75NTR antagonists for the treatment of retinal diseases.

The Importance of Field Demonstration Sites: The View from the Unconventional Resource Region of the Appalachian Basin

NASA Astrophysics Data System (ADS)

Carr, T.

2017-12-01

The Appalachian basin with the Marcellus and Utica shale units is one of the most active unconventional resource plays in North America. Unconventional resource plays are critical and rapidly-growing areas of energy, where research lags behind exploration and production activity. There remains a poor overall understanding of physical, chemical and biological factors that control shale gas production efficiency and possible environmental impacts associated with shale gas development. We have developed an approach that works with local industrial partners and communities and across research organizations. The Marcellus Shale Energy and Environment Laboratory (MSEEL) consists of a multidisciplinary and multi-institutional team undertaking integrated geoscience, engineering and environmental studies in cooperation with the Department of Energy. This approach is being expanded to other sites and to the international arena. MSEEL consists of four horizontal production wells, which are instrumented, a cored and logged vertical pilot bore-hole, and a microseismic observation well. MSEEL has integrated geophysical observations (microseismic and surface), fiber-optic monitoring for distributed acoustic (DAS) and temperature sensing (DTS), well logs, core data and production logging and continued monitoring, to characterize subsurface rock properties, and the propagation pattern of induced fractures in the stimulated reservoir volume. Significant geologic heterogeneity along the lateral affects fracture stimulation efficiency - both completion efficiency (clusters that receive effective stimulation), and production efficiency (clusters effectively contributing to production). MSEEL works to develop new knowledge of subsurface geology and engineering, and surface environmental impact to identify best practices that can optimize hydraulic fracture stimulation to increase flow rates, estimated ultimate recovery in order to reduce the number of wells and environmental impact.

Contribution of p75NTR to Schwannoma Growth and Therapeutic Responses

DTIC Science & Technology

2015-05-01

This depends on the phosphorylation state of merlin. We also find that activation of p75NTR fails to induce apoptosis in SCs and schwannoma cells that...cells from apoptosis induced by inhibition of JNK. This prosurvival effect is due, at least in part, to the ability of p75NTR to activate NF-κB...Thus, JNK activity appears to be required for basal levels of NF-jB activity but not for proNGF- induced NF-jB activity. To confirm that the increase in

Power processing

NASA Technical Reports Server (NTRS)

Schwarz, F. C.

1971-01-01

Processing of electric power has been presented as a discipline that draws on almost every field of electrical engineering, including system and control theory, communications theory, electronic network design, and power component technology. The cost of power processing equipment, which often equals that of expensive, sophisticated, and unconventional sources of electrical energy, such as solar batteries, is a significant consideration in the choice of electric power systems.

Statement Testimony of Mr. Alan Shaffer, Principal Deputy, Defense Research and Engineering, Before the United States House of Representatives Committee on Armed Services, Subcommittee on Terrorism, Unconventional Threats and Capabilities

DTIC Science & Technology

2008-03-13

neuroscience , biotechnology, immersive technology, quantum information science, nanotechnology, and autonomous systems. The Army has also increased...already occurred within the intelligence community. These include (but were not limited to) a 10 Gigabit/second encryption to NSA , delivering a

Genetically engineered theranostic mesenchymal stem cells for the evaluation of the anticancer efficacy of enzyme/prodrug systems.

PubMed

Nouri, Faranak Salman; Wang, Xing; Hatefi, Arash

2015-02-28

Over the past decade, various enzyme/prodrug systems such as thymidine kinase/ganciclovir (TK/GCV), yeast cytosine deaminase/5-fluorocytosine (yCD/5-FC) and nitroreductase/CB1954 (NTR/CB1954) have been used for stem cell mediated suicide gene therapy of cancer. Yet, no study has been conducted to compare and demonstrate the advantages and disadvantages of using one system over another. Knowing that each enzyme/prodrug system has its own strengths and weaknesses, we utilized mesenchymal stem cells (MSCs) as a medium to perform for the first time a comparative study that illustrated the impact of subtle differences among these systems on the therapeutic outcome. For therapeutic purposes, we first genetically modified MSCs to stably express a panel of four suicide genes including TK (TK007 and TK(SR39) mutants), yeast cytosine deaminase:uracil phosphoribosyltransferase (yCD:UPRT) and nitroreductase (NTR). Then, we evaluated the anticancer efficacies of the genetically engineered MSCs in vitro and in vivo by using SKOV3 cell line which is sensitive to all four enzyme/prodrug systems. In addition, all MSCs were engineered to stably express luciferase gene making them suitable for quantitative imaging and dose-response relationship studies in animals. Considering the limitations imposed by the prodrugs' bystander effects, our findings show that yCD:UPRT/5-FC is the most effective enzyme/prodrug system among the ones tested. Our findings also demonstrate that theranostic MSCs are a reliable medium for the side-by-side evaluation and screening of the enzyme/prodrug systems at the preclinical level. The results of this study could help scientists who utilize cell-based, non-viral or viral vectors for suicide gene therapy of cancer make more informed decisions when choosing enzyme/prodrug systems. Copyright © 2015 Elsevier B.V. All rights reserved.

Circadian control of p75 neurotrophin receptor leads to alternate activation of Nrf2 and c-Rel to reset energy metabolism in astrocytes via brain-derived neurotrophic factor.

PubMed

Ishii, Tetsuro; Warabi, Eiji; Mann, Giovanni E

2018-05-01

Circadian clock genes regulate energy metabolism partly through neurotrophins in the body. The low affinity neurotrophin receptor p75 NTR is a clock component directly regulated by the transcriptional factor Clock:Bmal1 complex. Brain-derived neurotrophic factor (BDNF) is expressed in the brain and plays a key role in coordinating metabolic interactions between neurons and astrocytes. BDNF transduces signals through TrkB and p75 NTR receptors. This review highlights a novel molecular mechanism by which BDNF via circadian control of p75 NTR leads to daily resetting of glucose and glycogen metabolism in brain astrocytes to accommodate their functional interaction with neurons. Astrocytes store glycogen as an energy reservoir to provide active neurons with the glycolytic metabolite lactate. Astrocytes predominantly express the truncated receptor TrkB.T1 which lacks an intracellular receptor tyrosine kinase domain. TrkB.T1 retains the capacity to regulate cell morphology through regulation of Rho GTPases. In contrast, p75 NTR mediates generation of the bioactive lipid ceramide upon stimulation with BDNF and inhibits PKA activation. As ceramide directly activates PKCζ, we discuss the importance of the TrkB.T1-p75 NTR -ceramide-PKCζ signaling axis in the stimulation of glycogen and lipid synthesis and activation of RhoA. Ceramide-PKCζ-casein kinase 2 signaling activates Nrf2 to support oxidative phosphorylation via upregulation of antioxidant enzymes. In the absence of p75 NTR , TrkB.T1 functionally interacts with adenosine A 2A R and dopamine D1R receptors to enhance cAMP-PKA signaling and activate Rac1 and NF-κB c-Rel, favoring glycogen hydrolysis, gluconeogenesis and aerobic glycolysis. Thus, diurnal changes in p75 NTR levels in astrocytes resets energy metabolism via BDNF to accommodate their metabolic interaction with neurons. Copyright © 2018 Elsevier Inc. All rights reserved.

Ablation study of tungsten-based nuclear thermal rocket fuel

NASA Astrophysics Data System (ADS)

Smith, Tabitha Elizabeth Rose

The research described in this thesis has been performed in order to support the materials research and development efforts of NASA Marshall Space Flight Center (MSFC), of Tungsten-based Nuclear Thermal Rocket (NTR) fuel. The NTR was developed to a point of flight readiness nearly six decades ago and has been undergoing gradual modification and upgrading since then. Due to the simplicity in design of the NTR, and also in the modernization of the materials fabrication processes of nuclear fuel since the 1960's, the fuel of the NTR has been upgraded continuously. Tungsten-based fuel is of great interest to the NTR community, seeking to determine its advantages over the Carbide-based fuel of the previous NTR programs. The materials development and fabrication process contains failure testing, which is currently being conducted at MSFC in the form of heating the material externally and internally to replicate operation within the nuclear reactor of the NTR, such as with hot gas and RF coils. In order to expand on these efforts, experiments and computational studies of Tungsten and a Tungsten Zirconium Oxide sample provided by NASA have been conducted for this dissertation within a plasma arc-jet, meant to induce ablation on the material. Mathematical analysis was also conducted, for purposes of verifying experiments and making predictions. The computational method utilizes Anisimov's kinetic method of plasma ablation, including a thermal conduction parameter from the Chapman Enskog expansion of the Maxwell Boltzmann equations, and has been modified to include a tangential velocity component. Experimental data matches that of the computational data, in which plasma ablation at an angle shows nearly half the ablation of plasma ablation at no angle. Fuel failure analysis of two NASA samples post-testing was conducted, and suggestions have been made for future materials fabrication processes. These studies, including the computational kinetic model at an angle and the ablation of the NASA sample, could be applied to an atmospheric reentry body, reentering at a ballistic trajectory at hypersonic velocities.

Understanding Chemistry-Specific Fuel Differences at a Constant RON in a Boosted SI Engine

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

Szybist, James P.; Splitter, Derek A.

The goal of the US Department of Energy Co-Optimization of Fuels and Engines (Co-Optima) initiative is to accelerate the development of advanced fuels and engines for higher efficiency and lower emissions. A guiding principle of this initiative is the central fuel properties hypothesis (CFPH), which states that fuel properties provide an indication of a fuel’s performance, regardless of its chemical composition. This is an important consideration for Co-Optima because many of the fuels under consideration are from bio-derived sources with chemical compositions that are unconventional relative to petroleum-derived gasoline or ethanol. In this study, we investigated a total of sevenmore » fuels in a spark ignition engine under boosted operating conditions to determine whether knock propensity is predicted by fuel antiknock metrics: antiknock index (AKI), research octane number (RON), and octane index (OI). Six of these fuels have a constant RON value but otherwise represent a wide range of fuel properties and chemistry. Consistent with previous studies, we found that OI was a much better predictor of knock propensity that either AKI or RON. However, we also found that there were significant fuel-specific deviations from the OI predictions. Combustion analysis provided insight that fuel kinetic complexities, including the presence of pre-spark heat release, likely limits the ability of standardized tests and metrics to accurately predict knocking tendency at all operating conditions. While limitations of OI were revealed in this study, we found that fuels with unconventional chemistry, in particular esters and ethers, behaved in accordance with CFPH as well as petroleum-derived fuels.« less

Application of Optimization Techniques to Design of Unconventional Rocket Nozzle Configurations

NASA Technical Reports Server (NTRS)

Follett, W.; Ketchum, A.; Darian, A.; Hsu, Y.

1996-01-01

Several current rocket engine concepts such as the bell-annular tri-propellant engine, and the linear aerospike being proposed for the X-33 require unconventional three dimensional rocket nozzles which must conform to rectangular or sector shaped envelopes to meet integration constraints. These types of nozzles exist outside the current experience database, therefore, the application of efficient design methods for these propulsion concepts is critical to the success of launch vehicle programs. The objective of this work is to optimize several different nozzle configurations, including two- and three-dimensional geometries. Methodology includes coupling computational fluid dynamic (CFD) analysis to genetic algorithms and Taguchi methods as well as implementation of a streamline tracing technique. Results of applications are shown for several geometeries including: three dimensional thruster nozzles with round or super elliptic throats and rectangualar exits, two- and three-dimensional thrusters installed within a bell nozzle, and three dimensional thrusters with round throats and sector shaped exits. Due to the novel designs considered for this study, there is little experience which can be used to guide the effort and limit the design space. With a nearly infinite parameter space to explore, simple parametric design studies cannot possibly search the entire design space within the time frame required to impact the design cycle. For this reason, robust and efficient optimization methods are required to explore and exploit the design space to achieve high performance engine designs. Five case studies which examine the application of various techniques in the engineering environment are presented in this paper.

Understanding Chemistry-Specific Fuel Differences at a Constant RON in a Boosted SI Engine

DOE PAGES

Szybist, James P.; Splitter, Derek A.

2018-01-02

The goal of the US Department of Energy Co-Optimization of Fuels and Engines (Co-Optima) initiative is to accelerate the development of advanced fuels and engines for higher efficiency and lower emissions. A guiding principle of this initiative is the central fuel properties hypothesis (CFPH), which states that fuel properties provide an indication of a fuel’s performance, regardless of its chemical composition. This is an important consideration for Co-Optima because many of the fuels under consideration are from bio-derived sources with chemical compositions that are unconventional relative to petroleum-derived gasoline or ethanol. In this study, we investigated a total of sevenmore » fuels in a spark ignition engine under boosted operating conditions to determine whether knock propensity is predicted by fuel antiknock metrics: antiknock index (AKI), research octane number (RON), and octane index (OI). Six of these fuels have a constant RON value but otherwise represent a wide range of fuel properties and chemistry. Consistent with previous studies, we found that OI was a much better predictor of knock propensity that either AKI or RON. However, we also found that there were significant fuel-specific deviations from the OI predictions. Combustion analysis provided insight that fuel kinetic complexities, including the presence of pre-spark heat release, likely limits the ability of standardized tests and metrics to accurately predict knocking tendency at all operating conditions. While limitations of OI were revealed in this study, we found that fuels with unconventional chemistry, in particular esters and ethers, behaved in accordance with CFPH as well as petroleum-derived fuels.« less

Localization of brain-derived neurotrophic factor, neurotrophin-4, tropomyosin-related kinase b receptor, and p75 NTR receptor by high-resolution immunohistochemistry on the adult mouse neuromuscular junction.

PubMed

Garcia, Neus; Tomàs, Marta; Santafe, Manel M; Lanuza, M Angel; Besalduch, Nuria; Tomàs, Josep

2010-03-01

Neurotrophins and their receptors, the trk receptor tyrosine kinases (trks) and p75(NTR), are differentially expressed among the cell types that make up synapses. It is important to determine the precise location of these molecules involved in neurotransmission. Here we use immunostaining and Western blotting to study the localization and expression of neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4) and the receptors tropomyosin-related kinase b (trkB) and p75(NTR) at the adult neuromuscular junction. Our confocal immunofluorescence results on the whole mounts of the mouse Levator auris longus muscle and on semithin cross-sections showed that BDNF, NT-4, trkB, and p75(NTR) were localized on the three cells in the neuromuscular synapse (motor axons, post-synaptic muscle and Schwann cells).

On the operation of machines powered by quantum non-thermal baths

DOE PAGES

Niedenzu, Wolfgang; Gelbwaser-Klimovsky, David; Kofman, Abraham G.; ...

2016-08-02

Diverse models of engines energised by quantum-coherent, hence non-thermal, baths allow the engine efficiency to transgress the standard thermodynamic Carnot bound. These transgressions call for an elucidation of the underlying mechanisms. Here we show that non-thermal baths may impart not only heat, but also mechanical work to a machine. The Carnot bound is inapplicable to such a hybrid machine. Intriguingly, it may exhibit dual action, concurrently as engine and refrigerator, with up to 100% efficiency. Here, we conclude that even though a machine powered by a quantum bath may exhibit an unconventional performance, it still abides by the traditional principlesmore » of thermodynamics.« less

Dependence of Relative Expression of NTR1 and EGFR on Cell Density and Extracellular pH in Human Pancreatic Cancer Cell Lines

PubMed Central

Olszewski-Hamilton, Ulrike; Hamilton, Gerhard

2011-01-01

Pancreatic adenocarcinoma is a devastating disease characterized by early dissemination and poor prognosis. These solid tumors express receptors for neuropeptides like neurotensin (NT) or epidermal growth factor (EGF) and exhibit acidic regions when grown beyond a certain size. We previously demonstrated increases in intracellular Ca2+ levels, intracellular pH and interleukin-8 (IL-8) secretion in BxPC-3 and PANC-1 pancreatic cancer cells in response to a stable NT analog. The present study aimed at investigation of the dependence of the relative expression of NT receptor 1 (NTR1) and EGFR in BxPC-3 and MIA PaCa-2 cells on cell density and extracellular pH (pHe). MTT assays revealed the NTR1 inhibitor SR 142948-sensitive Lys8-ψ-Lys9NT (8–13)-induced proliferation in BxPC-3 and PANC-1 cells. Confluent cultures of BxPC3 and HT-29 lines exhibited highest expression of NTR1 and lowest of EGFR and expression of NTR1 was maximal at slightly acidic pHe. IL-8 production was stimulated by Lys8-ψ-Lys9NT (8–13) and even enhanced at both acidic and alkaline pHe in BxPC-3 and PANC-1 cells. In conclusion, our in vitro study suggests that one contributing factor to the minor responses obtained with EGFR-directed therapy may be downregulation of this receptor in tumor cell aggregates, possibly resulting in acquisition of a more aggressive phenotype via other growth factor receptors like NTR1. PMID:24212612

Identification of an NADP/thioredoxin system in Chlamydomonas reinhardtii

NASA Technical Reports Server (NTRS)

Huppe, H. C.; Picaud, A.; Buchanan, B. B.; Miginiac-Maslow, M.

1991-01-01

The protein components of the NADP/thioredoxin system, NADP-thioredoxin reductase (NTR) and thioredoxin h, have been purified and characterized from the green alga, Chlamydomonas reinhardtii. The analysis of this system confirms that photoautotrophic Chlamydomonas cells resemble leaves in having both an NADP- and ferrodoxin-linked thioredoxin redox system. Chlamydomonas thioredoxin h, which is smaller on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than thioredoxin m from the same source, cross-reacted with antisera to thioredoxin h from spinach (Spinacia oleracea L.) and wheat germ (Triticum vulgaris L.) but not with antisera to m or f thioredoxins. In these properties, the thioredoxin h resembled a thioredoxin from Chlamydomonas, designated Ch1, whose sequence was reported recently (P. Decottignies et al., 1991, Eur. J. Biochem. 198, 505-512). The differential reactivity of thioredoxin h with antisera was used to demonstrate that thioredoxin h is enriched outside the chloroplast. The NTR was purified from Chlamydomonas using thioredoxin h from the same source. Similar to its counterpart from other organisms, Chlamydomonas NTR had a subunit size of approx. 36 kDa and was specific for NADPH. Chlamydomonas NTR effectively reduced thioredoxin h from the same source but showed little activity with the other thioredoxins tested, including spinach thioredoxin h and Escherichia coli thioredoxin. Comparison of the reduction of Chlamydomonas thioredoxins m and h by each of the endogenous thioredoxin reductases, NTR and ferredoxin-thioredoxin reductase, revealed a differential specificity of each enzyme for thioredoxin. Thus, NTR showed increased activity with thioredoxin h and ferredoxin-thioredoxin reductase with thioredoxins m and f.

Neurotensin-induced Proinflammatory Signaling in Human Colonocytes Is Regulated by β-Arrestins and Endothelin-converting Enzyme-1-dependent Endocytosis and Resensitization of Neurotensin Receptor 1*

PubMed Central

Law, Ivy Ka Man; Murphy, Jane E.; Bakirtzi, Kyriaki; Bunnett, Nigel W.; Pothoulakis, Charalabos

2012-01-01

The neuropeptide/hormone neurotensin (NT) mediates intestinal inflammation and cell proliferation by binding of its high affinity receptor, neurotensin receptor-1 (NTR1). NT stimulates IL-8 expression in NCM460 human colonic epithelial cells by both MAP kinase- and NF-κB-dependent pathways. Although the mechanism of NTR1 endocytosis has been studied, the relationship between NTR1 intracellular trafficking and inflammatory signaling remains to be elucidated. In the present study, we show that in NCM460 cells exposed to NT, β-arrestin-1 (βARR1), and β-arrestin-2 (βARR2) translocate to early endosomes together with NTR1. Endothelin-converting enzyme-1 (ECE-1) degrades NT in acidic conditions, and its activity is crucial for NTR1 recycling. Pretreatment of NCM460 cells with the ECE-1 inhibitor SM19712 or gene silencing of βARR1 or βARR2 inhibits NT-stimulated ERK1/2 and JNK phosphorylation, NF-κB p65 nuclear translocation and phosphorylation, and IL-8 secretion. Furthermore, NT-induced cell proliferation, but not IL-8 transcription, is attenuated by the JNK inhibitor, JNK(AII). Thus, NTR1 internalization and recycling in human colonic epithelial cells involves βARRs and ECE-1, respectively. Our results also indicate that βARRs and ECE-1-dependent recycling regulate MAP kinase and NF-κB signaling as well as cell proliferation in human colonocytes in response to NT. PMID:22416137

Contribution of p75NTR to Schwannoma Growth and Therapeutic Responses

DTIC Science & Technology

2017-05-01

13 6. Products …………………………………….……….….……………14 7. Participants & Other Collaborating Organizations……………15 8. Special Reporting...reducing schwannoma cell growth in culture and in animal models of human schwannoma disease. We find that the NF2 gene product , merlin, regulates p75NTR...treated with mTOR inhibitors, either singly or in combination with p75NTR inhibitory peptides. Given these results we focused our in vivo studies on

Effect of an ntrC mutation on amino acid or urea utilization and on nitrogenase switch-off in Herbaspirillum seropedicae.

PubMed

Gusso, Claudio L; de Souza, Emanuel M; Rigo, Liu Un; de Oliveira Pedrosa, Fábio; Yates, M G; de M Rego, Fabiane G; Klassen, Giseli

2008-03-01

Herbaspirillum seropedicae is a nitrogen-fixing bacterium that grows well with ammonium chloride or sodium nitrate as alternative single nitrogen sources but that grows more slowly with L-alanine, L-serine, L-proline, or urea. The ntrC mutant strain DCP286A was able to utilize only ammonium or urea of these nitrogen sources. The addition of 1 mmol.L-1 ammonium chloride to the nitrogen-fixing wild-type strain inhibited nitrogenase activity rapidly and completely. Urea was a less effective inhibitor; approximately 20% of nitrogenase activity remained 40 min after the addition of 1 mmol x L-1 urea. The effect of the ntrC mutation on nitrogenase inhibition (switch-off) was studied in strain DCP286A containing the constitutively expressed gene nifA of H. seropedicae. In this strain, nitrogenase inhibition by ammonium was completely abolished, but the addition of urea produced a reduction in nitrogenase activity similar to that of the wild-type strain. The results suggest that the NtrC protein is required for assimilation of nitrate and the tested amino acids by H. seropedicae. Furthermore, NtrC is also necessary for ammonium-induced switch-off of nitrogenase but is not involved in the mechanism of nitrogenase switch-off by urea.

Military Space Mission Design and Analysis in a Multi-Body Environment: An Investigation of High-Altitude Orbits as Alternative Transfer Paths, Parking Orbits for Reconstitution, and Unconventional Mission Orbits

DTIC Science & Technology

2017-03-23

Dynamical Astronomy , vol. 90, no. January 2004, pp. 165–178, 2004. [Online]. Available: https://www.researchgate.net/publication/ 225231299 On The...Celestial Mechanics and Dynamical Astronomy , vol. 32, no. 1, pp. 53–71, 1984. [Online]. Available: https://engineering.purdue.edu/people/kathleen.howell

Statement Testimony of The Honorable Zachary J. Lemnios Director, Defense Research and Engineering Before the United States House of Representatives Committee on Armed Services Subcommittee on Terrorism, Unconventional Threats and Capabilities

DTIC Science & Technology

2010-03-23

nationwide virtual science libary adapted for Afghanistan’s needs. Prepare for an Uncertain Future In preparing for an uncertain future, a...to assess the military implications of the ubiquitous availability of high performance analog, digital , electro-optical, radio frequency and signal

A Crewed Mission to Apophis Using a Hybrid Bimodal Nuclear Thermal Electric Propulsion (BNTEP) System

NASA Technical Reports Server (NTRS)

Mccurdy, David R.; Borowski, Stanley K.; Burke, Laura M.; Packard, Thomas W.

2014-01-01

A BNTEP system is a dual propellant, hybrid propulsion concept that utilizes Bimodal Nuclear Thermal Rocket (BNTR) propulsion during high thrust operations, providing 10's of kilo-Newtons of thrust per engine at a high specific impulse (Isp) of 900 s, and an Electric Propulsion (EP) system during low thrust operations at even higher Isp of around 3000 s. Electrical power for the EP system is provided by the BNTR engines in combination with a Brayton Power Conversion (BPC) closed loop system, which can provide electrical power on the order of 100's of kWe. High thrust BNTR operation uses liquid hydrogen (LH2) as reactor coolant propellant expelled out a nozzle, while low thrust EP uses high pressure xenon expelled by an electric grid. By utilizing an optimized combination of low and high thrust propulsion, significant mass savings over a conventional NTR vehicle can be realized. Low thrust mission events, such as midcourse corrections (MCC), tank settling burns, some reaction control system (RCS) burns, and even a small portion at the end of the departure burn can be performed with EP. Crewed and robotic deep space missions to a near Earth asteroid (NEA) are best suited for this hybrid propulsion approach. For these mission scenarios, the Earth return V is typically small enough that EP alone is sufficient. A crewed mission to the NEA Apophis in the year 2028 with an expendable BNTEP transfer vehicle is presented. Assembly operations, launch element masses, and other key characteristics of the vehicle are described. A comparison with a conventional NTR vehicle performing the same mission is also provided. Finally, reusability of the BNTEP transfer vehicle is explored.

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

Guan, Rongjin; Aiyer, Sriram; Cote, Marie L.

The retroviral integrase (IN) carries out the integration of a dsDNA copy of the viral genome into the host DNA, an essential step for viral replication. All IN proteins have three general domains, the N-terminal domain (NTD), the catalytic core domain, and the C-terminal domain. The NTD includes an HHCC zinc finger-like motif, which is conserved in all retroviral IN proteins. Two crystal structures of Moloney murine leukemia virus (M-MuLV) IN N-terminal region (NTR) constructs that both include an N-terminal extension domain (NED, residues 1–44) and an HHCC zinc-finger NTD (residues 45–105), in two crystal forms are reported. The structuresmore » of IN NTR constructs encoding residues 1–105 (NTR1–105) and 8–105 (NTR8–105) were determined at 2.7 and 2.15 Å resolution, respectively and belong to different space groups. While both crystal forms have similar protomer structures, NTR1–105 packs as a dimer and NTR8–105 packs as a tetramer in the asymmetric unit. The structure of the NED consists of three anti-parallel β-strands and an α-helix, similar to the NED of prototype foamy virus (PFV) IN. These three β-strands form an extended β-sheet with another β-strand in the HHCC Zn2+ binding domain, which is a unique structural feature for the M-MuLV IN. The HHCC Zn2+ binding domain structure is similar to that in HIV and PFV INs, with variations within the loop regions. Differences between the PFV and MLV IN NEDs localize at regions identified to interact with the PFV LTR and are compared with established biochemical and virological data for M-MuLV. Proteins 2017; 85:647–656.« less

Metalloproteinase-dependent transforming growth factor-alpha release mediates neurotensin-stimulated MAP kinase activation in human colonic epithelial cells.

PubMed

Zhao, Dezheng; Zhan, Yanai; Koon, Hon Wai; Zeng, Huiyan; Keates, Sarah; Moyer, Mary P; Pothoulakis, Charalabos

2004-10-15

Expression of the neuropeptide neurotensin (NT) and its high affinity receptor (NTR1) is increased during the course of Clostridium difficile toxin A-induced acute colitis, and NTR1 antagonism attenuates the severity of toxin A-induced inflammation. We recently demonstrated in non-transformed human colonic epithelial NCM460 cells that NT treatment caused activation of a Ras-mediated MAP kinase pathway that significantly contributes to NT-induced interleukin-8 (IL-8) secretion. Here we used NCM460 cells, which normally express low levels of NTR1, and NCM460 cells stably transfected with NTR1 to identify the upstream signaling molecules involved in NT-NTR1-mediated MAP kinase activation. We found that inhibition of the epidermal growth factor receptor (EGFR) by either an EGFR neutralizing antibody or by its specific inhibitor AG1478 (0.2 microm) blocked NT-induced MAP kinase activation. Moreover, NT stimulated tyrosine phosphorylation of the EGFR, and pretreatment with a broad spectrum metalloproteinase inhibitor batimastat reduced NT-induced MAP kinase activation. Using neutralizing antibodies against the EGFR ligands EGF, heparin-binding-EGF, transforming growth factor-alpha (TGFalpha), or amphiregulin we have shown that only the anti-TGFalpha antibody significantly decreases NT-induced phosphorylation of EGFR and MAP kinases. Furthermore, inhibition of the EGF receptor by AG1478 significantly reduced NT-induced IL-8 promoter activity and IL-8 secretion. This is the first report demonstrating that NT binding to NTR1 transactivates the EGFR and that this response is linked to NT-mediated proinflammatory signaling. Our findings indicate that matrix metalloproteinase-mediated release of TGFalpha and subsequent EGFR transactivation triggers a NT-mediated MAP kinase pathway that leads to IL-8 gene expression in human colonic epithelial cells.

The Theory of Unconventional Warfare: Win, Lose, and Draw

DTIC Science & Technology

2008-12-01

UNCONVENTIONAL WARFARE MODEL ...................................12 1. Planning Phase...Superiority over Time........................................................................11  Figure 3.  Unconventional Warfare Model ...superiority through the six principles of UW illustrated below in the UW model . . B. THE UNCONVENTIONAL WARFARE MODEL Figure 3. Unconventional

Affordable Development and Demonstration of a Small NTR engine and Stage: A Preliminary NASA, DOE, and Industry Assessment

NASA Technical Reports Server (NTRS)

Borowski, S. K.; Sefcik, R. J.; Fittje, J. E.; McCurdy, D. R.; Qualls, A. L.; Schnitzler, B. G; Werner, J.; Weitzberg, A.; Joyner, C. R.

2015-01-01

In FY'11, Nuclear Thermal Propulsion (NTP) was identified as a key propulsion option under the Advanced In-Space Propulsion (AISP) component of NASA's Exploration Technology Development and Demonstration (ETDD) program A strategy was outlined by GRC and NASA HQ that included 2 key elements -"Foundational Technology Development" followed by specific "Technology Demonstration" projects. The "Technology Demonstration "element proposed ground technology demonstration (GTD) testing in the early 2020's, followed by a flight technology demonstration (FTD) mission by approx. 2025. In order to reduce development costs, the demonstration projects would focus on developing a small, low thrust (approx. 7.5 -16.5 klb(f)) engine that utilizes a "common" fuel element design scalable to the higher thrust (approx. 25 klb(f)) engines used in NASA's Mars DRA 5.0 study(NASA-SP-2009-566). Besides reducing development costs and allowing utilization of existing, flight proven engine hard-ware (e.g., hydrogen pumps and nozzles), small, lower thrust ground and flight demonstration engines can validate the technology and offer improved capability -increased payloads and decreased transit times -valued for robotic science missions identified in NASA's Decadal Study.

The 5' non-translated region of Varroa destructor virus 1 (genus Iflavirus): structure prediction and IRES activity in Lymantria dispar cells.

PubMed

Ongus, Juliette R; Roode, Els C; Pleij, Cornelis W A; Vlak, Just M; van Oers, Monique M

2006-11-01

Structure prediction of the 5' non-translated region (NTR) of four iflavirus RNAs revealed two types of potential internal ribosome entry site (IRES), which are discriminated by size and level of complexity, in this group of viruses. In contrast to the intergenic IRES of dicistroviruses, the potential 5' IRES structures of iflaviruses do not have pseudoknots. To test the activity of one of these, a bicistronic construct was made in which the 5' NTR of Varroa destructor virus 1 (VDV-1) containing a putative IRES was cloned in between two reporter genes, enhanced green fluorescent protein and firefly luciferase (Fluc). The presence of the 5' NTR of VDV-1 greatly enhanced the expression levels of the second reporter gene (Fluc) in Lymantria dispar Ld652Y cells. The 5' NTR was active in a host-specific manner, as it showed lower activity in Spodoptera frugiperda Sf21 cells and no activity in Drosophila melanogaster S2 cells.

NTR-Enhanced Lunar-Base Supply using Existing Launch Fleet Capabilities

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

John D. Bess; Emily Colvin; Paul G. Cummings

During the summer of 2006, students at the Center for Space Nuclear Research sought to augment the current NASA lunar exploration architecture with a nuclear thermal rocket (NTR). An additional study investigated the possible use of an NTR with existing launch vehicles to provide 21 metric tons of supplies to the lunar surface in support of a lunar outpost. Current cost estimates show that the complete mission cost for an NTR-enhanced assembly of Delta-IV and Atlas V vehicles may cost 47-86% more than the estimated Ares V launch cost of $1.5B; however, development costs for the current NASA architecture havemore » not been assessed. The additional cost of coordinating the rendezvous of four to six launch vehicles with an in-orbit assembly facility also needs more thorough analysis and review. Future trends in launch vehicle use will also significantly impact the results from this comparison. The utility of multiple launch vehicles allows for the development of a more robust and lower risk exploration architecture.« less

Initial cloning and sequencing of hydHG, an operon homologous to ntrBC and regulating the labile hydrogenase activity in Escherichia coli K-12.

PubMed Central

Stoker, K; Reijnders, W N; Oltmann, L F; Stouthamer, A H

1989-01-01

To isolate genes from Escherichia coli which regulate the labile hydrogenase activity, a plasmid library was used to transform hydL mutants lacking the labile hydrogenase. A single type of gene, designated hydG, was isolated. This gene also partially restored the hydrogenase activity in hydF mutants (which are defective in all hydrogenase isoenzymes), although the low hydrogenase 1 and 2 levels were not induced. Therefore, hydG apparently regulates, specifically, the labile hydrogenase activity. Restoration of this latter activity in hydF mutants was accompanied by a proportional increase of the H2 uptake activity, suggesting a functional relationship. H2:fumarate oxidoreductase activity was not restored in complemented hydL mutants. These latter strains may therefore lack, in addition to the labile hydrogenase, a second component (provisionally designated component R), possibly an electron carrier coupling H2 oxidation to the anerobic respiratory chain. Sequence analysis showed an open reading frame of 1,314 base pairs for hydG. It was preceded by a ribosome-binding site but apparently lacked a promoter. Minicell experiments revealed a single polypeptide of approximately 50 kilodaltons. Comparison of the predicted amino acid sequence with a protein sequence data base revealed strong homology to NtrC from Klebsiella pneumoniae, a DNA-binding transcriptional activator. The 411 base pairs upstream from pHG40 contained a second open reading frame overlapping hydG by four bases. The deduced amino acid sequence showed considerable homology with the C-terminal part of NtrB. This sequence was therefore assumed to be part of a second gene, encoding the NtrB-like component, and was designated hydH. The labile hydrogenase activity in E. coli is apparently regulated by a multicomponent system analogous to the NtrB-NtrC system. This conclusion is in agreement with the results of Birkmann et al. (A. Birkmann, R. G. Sawers, and A. Böck, Mol. Gen. Genet. 210:535-542, 1987), who demonstrated ntrA dependence for the labile hydrogenase activity. Images PMID:2666400

Immunological recognition of different forms of the neurotensin receptor in transfected cells and rat brain.

PubMed Central

Boudin, H; Grauz-Guyon, A; Faure, M P; Forgez, P; Lhiaubet, A M; Dennis, M; Beaudet, A; Rostene, W; Pelaprat, D

1995-01-01

In this work, the molecular forms of the rat neurotensin receptor (NTR) expressed in transfected Chinese hamster ovary (CHO) cells, in infected Sf9 insect cells and in rat cerebral cortex were immunologically detected by means of an anti-peptide antibody raised against a fragment of the third intracellular loop of the receptor. Immunoblot experiments against a fusion protein indicated that the anti-peptide antibody recognized, under denaturing conditions, the corresponding amino acid sequence within the NTR. In immunoblot analysis of membranes from NTR-transfected CHO cells, high levels of immunoreactivity were observed between 60 and 72 kDa, while only a faint labelling was observed at 47 kDa, the molecular mass deduced for the rat NTR cDNA. The bands of high molecular mass were no longer observed after deglycosylation of membrane proteins by peptide N-glycosidase F, indicating that they represented glycosylated forms of the receptor. Extracts of membranes derived from baculovirus-infected Sf9 insect-cells expressing the NTR provided a quite different immunoblot pattern, since the major band detected in that case was at 47 kDa, the molecular size of the non-glycosylated receptor. Taken together, these data show that, while most of the NTR protein was glycosylated in CHO cells, it was unglycosylated in Sf9 insect-cells. In addition, molecular sizes of the receptor proteins observed in these two cell lines differed from those obtained for the NTR endogenously expressed in the rat cerebral cortex of 7 day-old rats, where bands at 56 and 54 kDa were detected. Binding experiments carried out on membrane preparations obtained from baculovirus-infected Sf9 cells demonstrated that the immunogenic sequence was still accessible to the antibody when the receptor was embedded in the cell membrane. Immunohistochemical studies carried out on both transfected CHO cells and infected Sf9 cells confirmed this interpretation and further indicated that the antibody could be applied in the visualization of the receptor. Images Figure 1 Figure 2 Figure 3 Figure 5 PMID:7826341

Choice of unconventional treatment by patients with cancer.

PubMed

Kimby, Charlotte Kira; Launsø, Laila; Henningsen, Inge; Langgaard, Henrik

2003-08-01

Previous studies conducted on the use of unconventional treatment by patients with cancer have focused on unconventional treatment as a joint group of therapies. The objective of this study is to gather preliminary information about the use of different modes of unconventional cancer treatment by patients with cancer and to describe user profiles of standardized and individualized treatments. Data originate from an ongoing explorative 5-year study of 441 consecutively registered cancer patients who have consulted medical doctors and alternative therapists practicing unconventional treatment in Denmark. This paper is based on data from the first and second of six questionnaires. The unconventional treatments included in this study are categorized into two forms of treatment: standardized and individualized treatment. Four hundred and forty-one (441) Danish patients with cancer who use unconventional cancer treatment. The analysis shows significant correlations between type of treatment and the following variables: gender, education, occupational status, type of cancer, purpose of seeking unconventional treatment, metastatic spread, opinion regarding appropriate unconventional treatment, and simultaneous use of unconventional treatment. The study shows that there are significant differences between patients with cancer choosing standardized and those choosing individualized unconventional treatment. The probability of choosing standardized unconventional treatment is greatest among male participants, patients having shorter school education, and for patients who have recovery as the goal of seeking unconventional treatment. The probability of choosing individualized unconventional treatment is greatest among women, for patients with longer school education, and for patients wanting relief from symptoms, information, and improvement of general condition as the purpose of seeking unconventional cancer treatment. Patients with breast and gynecologic cancer are more inclined to seek individualized treatment than patients with all other cancer diseases. The study points to the fact that it might be essential to differentiate between different forms of unconventional treatment to understand the use by patients with cancer and the outcomes of these treatments.

Characterization of p75{sup +} ectomesenchymal stem cells from rat embryonic facial process tissue

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

Wen, Xiujie; Liu, Luchuan; Deng, Manjing

2012-10-12

Highlights: Black-Right-Pointing-Pointer Ectomesenchymal stem cells (EMSCs) were found to migrate to rat facial processes at E11.5. Black-Right-Pointing-Pointer We successfully sorted p75NTR positive EMSCs (p75{sup +} EMSCs). Black-Right-Pointing-Pointer p75{sup +} EMSCs up to nine passages showed relative stable proliferative activity. Black-Right-Pointing-Pointer We examined the in vitro multilineage potential of p75{sup +} EMSCs. Black-Right-Pointing-Pointer p75{sup +}EMSCs provide an in vitro model for tooth morphogenesis. -- Abstract: Several populations of stem cells, including those from the dental pulp and periodontal ligament, have been isolated from different parts of the tooth and periodontium. The characteristics of such stem cells have been reported as well.more » However, as a common progenitor of these cells, ectomesenchymal stem cells (EMSCs), derived from the cranial neural crest have yet to be fully characterized. The aim of this study was to better understand the characteristics of EMSCs isolated from rat embryonic facial processes. Immunohistochemical staining showed that EMSCs had migrated to rat facial processes at E11.5, while the absence of epithelial invagination or tooth-like epithelium suggested that any epithelial-mesenchymal interactions were limited at this stage. The p75 neurotrophin receptor (p75NTR), a typical neural crest marker, was used to select p75NTR-positive EMSCs (p75{sup +} EMSCs), which were found to show a homogeneous fibroblast-like morphology and little change in the growth curve, proliferation capacity, and cell phenotype during cell passage. They also displayed the capacity to differentiate into diverse cell types under chemically defined conditions in vitro. p75{sup +} EMSCs proved to be homogeneous, stable in vitro and potentially capable of multiple lineages, suggesting their potential for application in dental or orofacial tissue engineering.« less

Cholinergic Degeneration and Alterations in the TrkA and p75NTR Balance as a Result of Pro-NGF Injection into Aged Rats

PubMed Central

Fortress, Ashley M.; Buhusi, Mona; Helke, Kris L.; Granholm, Ann-Charlotte E.

2011-01-01

Learning and memory impairments occurring with Alzheimer's disease (AD) are associated with degeneration of the basal forebrain cholinergic neurons (BFCNs). BFCNs extend their axons to the hippocampus where they bind nerve growth factor (NGF) which is retrogradely transported to the cell body. While NGF is necessary for BFCN survival and function via binding to the high-affinity receptor TrkA, its uncleaved precursor, pro-NGF has been proposed to induce neurodegeneration via binding to the p75NTR and its coreceptor sortilin. Basal forebrain TrkA and NGF are downregulated with aging while pro-NGF is increased. Given these data, the focus of this paper was to determine a mechanism for how pro-NGF accumulation may induce BFCN degeneration. Twenty-four hours after a single injection of pro-NGF into hippocampus, we found increased hippocampal p75NTR levels, decreased hippocampal TrkA levels, and cholinergic degeneration. The data suggest that the increase in p75NTR with AD may be mediated by elevated pro-NGF levels as a result of decreased cleavage, and that pro-NGF may be partially responsible for age-related degenerative changes observed in the basal forebrain. This paper is the first in vivo evidence that pro-NGF can affect BFCNs and may do so by regulating expression of p75NTR neurotrophin receptors. PMID:21785728

Purchasing unconventional fuels

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

Doyal, J.

1995-09-01

The reasons to seek unconventional fuels are to either insure a fuel supply or to reduce existing fuel costs. The keys to successfully utilizing unconventional fuel are: (1) build as much flexibility as possible in the variety, quality, quantity and deliverability of the unconventional fuel sources that you can utilize; (2) provide maximum pricing flexibility; (3) fully commit to work with unconventional fuel suppliers; and to (4) consider unconventional fuel operations as a market opportunity. Unconventional fuels operations are well suited to marginal existing operations and can also supplement new startups with uncertain fuel supplies. Unconventional fuel operations can alsomore » help existing facilities generate above market profits for those willing to accommodate the wide market swings inherent in this fledgling industry.« less

Involvement of TrkB- and p75NTR-signaling pathways in two contrasting forms of long-lasting synaptic plasticity

NASA Astrophysics Data System (ADS)

Sakuragi, Shigeo; Tominaga-Yoshino, Keiko; Ogura, Akihiko

2013-11-01

The repetition of experience is often necessary to establish long-lasting memory. However, the cellular mechanisms underlying this repetition-dependent consolidation of memory remain unclear. We previously observed in organotypic slice cultures of the rodent hippocampus that repeated inductions of long-term potentiation (LTP) led to a slowly developing long-lasting synaptic enhancement coupled with synaptogenesis. We also reported that repeated inductions of long-term depression (LTD) produced a long-lasting synaptic suppression coupled with synapse elimination. We proposed these phenomena as useful in vitro models for analyzing repetition-dependent consolidation. Here, we hypothesized that the enhancement and suppression are mediated by the brain-derived neurotrophic factor (BDNF)-TrkB signaling pathway and the proBDNF-p75NTR pathway, respectively. When we masked the respective pathways, reversals of the enhancement and suppression resulted. These results suggest the alternative activation of the p75NTR pathway by BDNF under TrkB-masking conditions and of the TrkB pathway by proBDNF under p75NTR-masking conditions, thus supporting the aforementioned hypothesis.

Expression of the nifA gene of Herbaspirillum seropedicae: role of the NtrC and NifA binding sites and of the -24/-12 promoter element.

PubMed

Souza, E M; Pedrosa, F O; Rigo, L U; Machado, H B; Yates, M G

2000-06-01

The nifA promoter of Herbaspirillum seropedicae contains potential NtrC, NifA and IHF binding sites together with a -12/-24 sigma(N)-dependent promoter. This region has now been investigated by deletion mutagenesis for the effect of NtrC and NifA on the expression of a nifA::lacZ fusion. A 5' end to the RNA was identified at position 641, 12 bp downstream from the -12/-24 promoter. Footprinting experiments showed that the G residues at positions -26 and -9 are hypermethylated, and that the region from -10 to +10 is partially melted under nitrogen-fixing conditions, confirming that this is the active nifA promoter. In H. seropedicae nifA expression from the sigma(N)-dependent promoter is repressed by fixed nitrogen but not by oxygen and is probably activated by the NtrC protein. NifA protein is apparently not essential for nifA expression but it can still bind the NifA upstream activating sequence.

Dissecting the role of NtrC and RpoN in the expression of assimilatory nitrate and nitrite reductases in Bradyrhizobium diazoefficiens.

PubMed

López, María F; Cabrera, Juan J; Salas, Ana; Delgado, María J; López-García, Silvina L

2017-04-01

Bradyrhizobium diazoefficiens, a nitrogen-fixing endosymbiont of soybeans, is a model strain for studying rhizobial denitrification. This bacterium can also use nitrate as the sole nitrogen (N) source during aerobic growth by inducing an assimilatory nitrate reductase encoded by nasC located within the narK-bjgb-flp-nasC operon along with a nitrite reductase encoded by nirA at a different chromosomal locus. The global nitrogen two-component regulatory system NtrBC has been reported to coordinate the expression of key enzymes in nitrogen metabolism in several bacteria. In this study, we demonstrate that disruption of ntrC caused a growth defect in B. diazoefficiens cells in the presence of nitrate or nitrite as the sole N source and a decreased activity of the nitrate and nitrite reductase enzymes. Furthermore, the expression of narK-lacZ or nirA-lacZ transcriptional fusions was significantly reduced in the ntrC mutant after incubation under nitrate assimilation conditions. A B. diazoefficiens rpoN 1/2 mutant, lacking both copies of the gene encoding the alternative sigma factor σ 54 , was also defective in aerobic growth with nitrate as the N source as well as in nitrate and nitrite reductase expression. These results demonstrate that the NtrC regulator is required for expression of the B. diazoefficiens nasC and nirA genes and that the sigma factor RpoN is also involved in this regulation.

Neurotrophin Receptors TrkA, p75NTR, and Sortilin Are Increased and Targetable in Thyroid Cancer.

PubMed

Faulkner, Sam; Jobling, Philip; Rowe, Christopher W; Rodrigues Oliveira, S M; Roselli, Severine; Thorne, Rick F; Oldmeadow, Christopher; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M; Hondermarck, Hubert

2018-01-01

Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75 NTR , and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75 NTR was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75 NTR , and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75 NTR , and sortilin as potential therapeutic targets in thyroid cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Changes in expression of BDNF and its receptors TrkB and p75NTR in the hippocampus of a dog model of chronic alcoholism and abstinence.

PubMed

Xu, R; Duan, S R; Zhao, J W; Wang, C Y

2015-08-01

Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.

Co-localization patterns of neurotensin receptor 1 and tyrosine hydroxylase in brain regions involved in motivation and social behavior in male European starlings.

PubMed

Merullo, Devin P; Spool, Jeremy A; Zhao, Changjiu; Riters, Lauren V

2018-04-01

Animals communicate in distinct social contexts to convey information specific to those contexts, such as sexual or agonistic motivation. In seasonally-breeding male songbirds, seasonal changes in day length and increases in testosterone stimulate sexually-motivated song directed at females for courtship and reproduction. Dopamine and testosterone may act in the same brain regions to stimulate sexually-motivated singing. The neuropeptide neurotensin, acting at the neurotensin receptor 1 (NTR1), can strongly influence dopamine transmission. The goal of this study was to gain insight into the degree to which seasonal changes in physiology modify interactions between neurotensin and dopamine to adjust context-appropriate communication. Male European starlings were examined in physiological conditions that stimulate season-typical forms of communication: late summer/early fall non-breeding condition (low testosterone; birds sing infrequently), late fall non-breeding condition (low testosterone; birds produce non-sexually motivated song), and spring breeding condition (high testosterone; males produce sexually-motivated song). Double fluorescent immunolabeling was performed to detect co-localization patterns between tyrosine hydroxylase (TH; the rate-limiting enzyme in dopamine synthesis) and NTR1 in brain regions implicated in motivation and song production (the ventral tegmental area, medial preoptic nucleus, periaqueductal gray, and lateral septum). Co-localization between TH and NTR1 was present in the ventral tegmental area for all physiological conditions, and the number of co-localized cells did not differ across conditions. Immunolabeling for TH and NTR1 was also present in the other examined regions, although no co-localization was seen. These results support the hypothesis that interactions between NTR1 and dopamine in the ventral tegmental area may modulate vocalizations, but suggest that testosterone- or photoperiod-induced changes in NTR1/TH co-localization do not underlie seasonally-appropriate adjustment of communication. Copyright © 2018 Elsevier B.V. All rights reserved.

To amend title 10, United States Code, to authorize the Secretary of Defense to make grants to recognized science and technology secondary schools to support research and development projects at such schools in science, mathematics, engineering, and technology to supplement the national security functions of the Department of Defense.

THOMAS, 111th Congress

Rep. Connolly, Gerald E. [D-VA-11

2009-07-24

House - 01/12/2010 Referred to the Subcommittee on Terrorism, Unconventional Threats and Capabilities. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Symposium on Naval Hydrodynamics (9th). Volume 1. Unconventional Ships; Ocean Engineering. Held at Paris (France) on August 20-25, 1972

DTIC Science & Technology

1972-01-01

DESIGN OF AN S3 SEMI-SUBMERGED SHIP 549 Thomas G. Lang, PhD, Naval Undersea Research and Development Center, San Diego, California... Undersea Research and Development Center, San Diego, California DISCUSSION 574 Nils Salvesen, Naval Ship Research and De- velopment Center...Bethesda, Maryland REPLY TO DISCUSSION 576 Thomas G. Lang, Naval Undersea Research and Development Center, San Diego, California

Unconventional medicine in dermatology outpatients in Turkey.

PubMed

Gönül, Müzeyyen; Gül, Ulker; Cakmak, Seray Külcü; Kiliç, Selim

2009-06-01

Many people use unconventional therapies for health problems, but the extent and pattern of this use in dermatology have not been studied in detail. This article reports the first investigation on the use of unconventional therapies in dermatology in Turkey. To determine the prevalence and characteristics of unconventional therapies used by dermatology outpatients in Turkey. A questionnaire was employed to determine the use of unconventional therapies in patients attending a dermatology clinic in Ankara, Turkey. The patients were questioned about the number of attendances at dermatology clinics, whether they had ever used unconventional therapies and/or drugs without the suggestion of a medical doctor for the current dermatologic disorder, and the forms of unconventional therapies employed. The data were compared statistically with the age, sex, and education status of the patients. The respondents included 443 men and 563 women, with a total of 1006 patients. The mean age of the patients was 36.62 +/- 17.55 years. Of the 1006 patients, 337 (33.5%) had used at least one form of unconventional therapy. The most common diagnoses of the patients using unconventional therapy were acne, psoriasis, contact dermatitis, and fungal infections. The most frequent forms of unconventional therapy used by the patients were humectants, cologne, spiritual healing, and herbs. Unconventional therapy use according to the sex, age, and education status of the patients did not show any significant difference. A significant relationship was found between some forms of unconventional therapy and some skin disorders, including: generalized pruritus and application of cologne; warts and spiritual healing; fungal infections and application of henna; psoriasis and herbal therapy or spiritual healing; alopecia areata and application of garlic; acne and application of lemon juice, clay, or cosmetics. Regardless of patient age, sex, and education status, dermatology outpatients use unconventional therapies for their health. Dermatologists should be aware of the tendency of patients to use unconventional therapies and should guide patients towards the use of harmless treatments.

77 FR 10485 - Unconventional Resources Technology Advisory Committee

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Demonstration of Subscale Cermet Fuel Specimen Fabrication Approach Using Spark Plasma Sintering and Diffusion Bonding

NASA Technical Reports Server (NTRS)

Barnes, Marvin W.; Tucker, Dennis S.; Benensky, Kelsa M.

2018-01-01

Nuclear thermal propulsion (NTP) has the potential to expand the limits of human space exploration by enabling crewed missions to Mars and beyond. The viability of NTP hinges on the development of a robust nuclear fuel material that can perform in the harsh operating environment (> or = 2500K, reactive hydrogen) of a nuclear thermal rocket (NTR) engine. Efforts are ongoing to develop fuel material and to assemble fuel elements that will be stable during the service life of an NTR. Ceramic-metal (cermet) fuels are being actively pursued by NASA Marshall Space Flight Center (MSFC) due to their demonstrated high-temperature stability and hydrogen compatibility. Building on past cermet fuel development research, experiments were conducted to investigate a modern fabrication approach for cermet fuel elements. The experiments used consolidated tungsten (W)-60vol%zirconia (ZrO2) compacts that were formed via spark plasma sintering (SPS). The consolidated compacts were stacked and diffusion bonded to assess the integrity of the bond lines and internal cooling channel cladding. The assessment included hot hydrogen testing of the manufactured surrogate fuel and pure W for 45 minutes at 2500 K in the compact fuel element environmental test (CFEET) system. Performance of bonded W-ZrO2 rods was compared to bonded pure W rods to access bond line integrity and composite stability. Bonded surrogate fuels retained structural integrity throughout testing and incurred minimal mass loss.

77 FR 23105 - Supporting Safe and Responsible Development of Unconventional Domestic Natural Gas Resources

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... Safe and Responsible Development of Unconventional Domestic Natural Gas Resources #0; #0; #0..., 2012 Supporting Safe and Responsible Development of Unconventional Domestic Natural Gas Resources By... and responsible development of unconventional domestic natural gas resources and associated...

Plug cluster engine concept for in-space missions

NASA Technical Reports Server (NTRS)

Obrien, C. J.; Aukerman, C. A.

1979-01-01

The development of a suitable orbital transfer vehicle (OTV) engine is discussed. The OTV's dimensions are limited by those of the Space Shuttle payload bay on which it will be carried. An approach to utilize the available diameter to achieve high area ratio and thus high engine performance, is presented. Unconventional nozzles, such as clusters of small thrusters around a large diameter contoured plug, are investigated to arrive at engine designs which feature lower chamber pressures, with attendant lower heat flux, lower wall temperature, longer fatigue life, and less critical turbomachinery. Attention is also given to plug nozzle technology, high area ratio module- and scarfed bell- Plug Cluster Engine (PCE) concepts, as well as PCE performance, weight, and assessment. A conceptual design of a PCE formed from a cluster of high area ratio, scarfed, bell nozzles proved to be competitive with bell and spike nozzle engines. PCE advantages cited include increased payload length due to shorter engine length, ability to increase or decrease the number of modules and thereby the thrust, and low cost due to utilization of off-the-shelf technology.

A Pro-Nerve Growth Factor (proNGF) and NGF Binding Protein, α2-Macroglobulin, Differentially Regulates p75 and TrkA Receptors and Is Relevant to Neurodegeneration Ex Vivo and In Vivo

PubMed Central

Barcelona, Pablo F.

2015-01-01

Nerve growth factor (NGF) is generated from a precursor, proNGF, that is proteolytically processed. NGF preferentially binds a trophic tyrosine kinase receptor, TrkA, while proNGF binds a neurotrophin receptor (NTR), p75NTR, that can have neurotoxic activity. Previously, we along with others showed that the soluble protein α2-macroglobulin (α2M) is neurotoxic. Toxicity is due in part to α2M binding to NGF and inhibiting trophic activity, presumably by preventing NGF binding to TrkA. However, the mechanisms remained unclear. Here, we show ex vivo and in vivo three mechanisms for α2M neurotoxicity. First, unexpectedly the α2M-NGF complexes do bind TrkA receptors but do not induce TrkA dimerization or activation, resulting in deficient trophic support. Second, α2M makes stable complexes with proNGF, conveying resistance to proteolysis that results in more proNGF and less NGF. Third, α2M-proNGF complexes bind p75NTR and are more potent agonists than free proNGF, inducing tumor necrosis factor alpha (TNF-α) production. Hence, α2M regulates proNGF/p75NTR positively and mature NGF/TrkA negatively, causing neuronal death ex vivo. These three mechanisms are operative in vivo, and α2M causes neurodegeneration in a p75NTR- and proNGF-dependent manner. α2M could be exploited as a therapeutic target, or as a modifier of neurotrophin signals. PMID:26217017

Structure, function, and tethering of DNA-binding domains in σ 54 transcriptional activators

DOE PAGES

Vidangos, Natasha; Maris, Ann E.; Young, Anisa; ...

2013-07-02

In this paper, we compare the structure, activity, and linkage of DNA-binding domains (DBDs) from σ 54 transcriptional activators and discuss how the properties of the DBDs and the linker to the neighboring domain are affected by the overall properties and requirements of the full proteins. These transcriptional activators bind upstream of specific promoters that utilize σ 54-polymerase. Upon receiving a signal the activators assemble into hexamers, which then, through adenosine triphosphate (ATP) hydrolysis, drive a conformational change in polymerase that enables transcription initiation. We present structures of the DBDs of activators nitrogen regulatory protein C 1 (NtrC1) and Nif-likemore » homolog 2 (Nlh2) from the thermophile Aquifex aeolicus. The structures of these domains and their relationship to other parts of the activators are discussed. These structures are compared with previously determined structures of the DBDs of NtrC4, NtrC, ZraR, and factor for inversion stimulation. The N-terminal linkers that connect the DBDs to the central domains in NtrC1 and Nlh2 were studied and found to be unstructured. Additionally, a crystal structure of full-length NtrC1 was solved, but density of the DBDs was extremely weak, further indicating that the linker between ATPase and DBDs functions as a flexible tether. Flexible linking of ATPase and DBDs is likely necessary to allow assembly of the active hexameric ATPase ring. Finally, the comparison of this set of activators also shows clearly that strong dimerization of the DBD only occurs when other domains do not dimerize strongly.« less

Sequences required for induction of neurotensin receptor gene expression during neuronal differentiation of N1E-115 neuroblastoma cells.

PubMed

Tavares, D; Tully, K; Dobner, P R

1999-10-15

The promoter region of the mouse high affinity neurotensin receptor (Ntr-1) gene was characterized, and sequences required for expression in neuroblastoma cell lines that express high affinity NT-binding sites were characterized. Me(2)SO-induced neuronal differentiation of N1E-115 neuroblastoma cells increased both the expression of the endogenous Ntr-1 gene and reporter genes driven by NTR-1 promoter sequences by 3-4-fold. Deletion analysis revealed that an 83-base pair promoter region containing the transcriptional start site is required for Me(2)SO activation. Detailed mutational analysis of this region revealed that a CACCC box and the central region of a large GC-rich palindrome are the crucial cis-regulatory elements required for Me(2)SO induction. The CACCC box is bound by at least one factor that is induced upon Me(2)SO treatment of N1E-115 cells. The Me(2)SO effect was found to be both selective and cell type-restricted. Basal expression in the neuroblastoma cell lines required a distinct set of sequences, including an Sp1-like sequence, and a sequence resembling an NGFI-A-binding site; however, a more distal 5' sequence was found to repress basal activity in N1E-115 cells. These results provide evidence that Ntr-1 gene regulation involves both positive and negative regulatory elements located in the 5'-flanking region and that Ntr-1 gene activation involves the coordinate activation or induction of several factors, including a CACCC box binding complex.

Field Testing of Environmentally Friendly Drilling System

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

David Burnett

2009-05-31

The Environmentally Friendly Drilling (EFD) program addresses new low-impact technology that reduces the footprint of drilling activities, integrates light weight drilling rigs with reduced emission engine packages, addresses on-site waste management, optimizes the systems to fit the needs of a specific development sites and provides stewardship of the environment. In addition, the program includes industry, the public, environmental organizations, and elected officials in a collaboration that addresses concerns on development of unconventional natural gas resources in environmentally sensitive areas. The EFD program provides the fundamentals to result in greater access, reasonable regulatory controls, lower development cost and reduction of themore » environmental footprint associated with operations for unconventional natural gas. Industry Sponsors have supported the program with significant financial and technical support. This final report compendium is organized into segments corresponding directly with the DOE approved scope of work for the term 2005-2009 (10 Sections). Each specific project is defined by (a) its goals, (b) its deliverable, and (c) its future direction. A web site has been established that contains all of these detailed engineering reports produced with their efforts. The goals of the project are to (1) identify critical enabling technologies for a prototype low-impact drilling system, (2) test the prototype systems in field laboratories, and (3) demonstrate the advanced technology to show how these practices would benefit the environment.« less

U.S./CIS eye joint nuclear rocket venture

NASA Technical Reports Server (NTRS)

Clark, John S.; Mcilwain, Melvin C.; Smetanikov, Vladimir; D'Yakov, Evgenij K.; Pavshuk, Vladimir A.

1993-01-01

An account is given of the significance for U.S. spacecraft development of a nuclear thermal rocket (NTR) reactor concept that has been developed in the (formerly Soviet) Commonwealth of Independent States (CIS). The CIS NTR reactor employs a hydrogen-cooled zirconium hydride moderator and ternary carbide fuels; the comparatively cool operating temperatures associated with this design promise overall robustness.

"Bimodal" Nuclear Thermal Rocket (BNTR) Propulsion for Future Human Mars Exploration Missions

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.

2004-01-01

The Nuclear Thermal Rocket (NTR) Propulsion program is discussed. The Rover/NERVA program from 1959-1972 is compared with the current program. A key technology description, bimodal vehicle design for Mars Cargo and the crew transfer vehicle with inflatable module and artificial gravity capability, including diagrams are included. The LOX-Augmented NTR concept/operational features and characteristics are discussed.

The Use of Nuclear Propulsion, Power and 'In-Situ' Resources for Routine Lunar Space Transportation and Commercial Base Development

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.

2003-01-01

This viewgraph presentation illustrates possible future strategies for solar system exploration supported by Nuclear Thermal Rocket (NTR) Propulsion. Topics addressed in the presentation include: lunar mining, Liquid Oxygen (LOX) augmented NTR (LANTR), 'Shuttle-Derived' Heavy Lift Vehicle (SDHLV) options for future human Lunar missions, and lunar-produced oxygen (LUNOX).

Observation of pendular butterfly Rydberg molecules

PubMed Central

Niederprüm, Thomas; Thomas, Oliver; Eichert, Tanita; Lippe, Carsten; Pérez-Ríos, Jesús; Greene, Chris H.; Ott, Herwig

2016-01-01

Engineering molecules with a tunable bond length and defined quantum states lies at the heart of quantum chemistry. The unconventional binding mechanism of Rydberg molecules makes them a promising candidate to implement such tunable molecules. A very peculiar type of Rydberg molecules are the so-called butterfly molecules, which are bound by a shape resonance in the electron–perturber scattering. Here we report the observation of these exotic molecules and employ their exceptional properties to engineer their bond length, vibrational state, angular momentum and orientation in a small electric field. Combining the variable bond length with their giant dipole moment of several hundred Debye, we observe counter-intuitive molecules which locate the average electron position beyond the internuclear distance. PMID:27703143

Live imaging of targeted cell ablation in Xenopus: a new model to study demyelination and repair

PubMed Central

Kaya, F.; Mannioui, A.; Chesneau, A.; Sekizar, S.; Maillard, E.; Ballagny, C.; Houel-Renault, L.; Du Pasquier, D.; Bronchain, O.; Holtzmann, I.; Desmazieres, A.; Thomas, J.-L.; Demeneix, B. A.; Brophy, P. J.; Zalc, B.; Mazabraud, A.

2012-01-01

Live imaging studies of the processes of demyelination and remyelination have so far been technically limited in mammals. We have thus generated a Xenopus laevis transgenic line allowing live imaging and conditional ablation of myelinating oligodendrocytes throughout the central nervous system (CNS). In these transgenic pMBP-eGFP-NTR tadpoles the myelin basic protein (MBP) regulatory sequences, specific to mature oligodendrocytes, are used to drive expression of an eGFP (enhanced green fluorescent protein) reporter fused to the E. coli nitroreductase (NTR) selection enzyme. This enzyme converts the innocuous pro-drug metronidazole (MTZ) to a cytotoxin. Using two-photon imaging in vivo, we show that pMBP-eGFP-NTR tadpoles display a graded oligodendrocyte ablation in response to MTZ, which depends on the exposure time to MTZ. MTZ-induced cell death was restricted to oligodendrocytes, without detectable axonal damage. After cessation of MTZ treatment, remyelination proceeded spontaneously, but was strongly accelerated by retinoic acid. Altogether, these features establish the Xenopus pMBP-eGFP-NTR line as a novel in vivo model for the study of demyelination/remyelination processes and for large-scale screens of therapeutic agents promoting myelin repair. PMID:22973012

The future of oil: unconventional fossil fuels.

PubMed

Chew, Kenneth J

2014-01-13

Unconventional fossil hydrocarbons fall into two categories: resource plays and conversion-sourced hydrocarbons. Resource plays involve the production of accumulations of solid, liquid or gaseous hydro-carbons that have been generated over geological time from organic matter in source rocks. The character of these hydrocarbons may have been modified subsequently, especially in the case of solids and extra-heavy liquids. These unconventional hydrocarbons therefore comprise accumulations of hydrocarbons that are trapped in an unconventional manner and/or whose economic exploitation requires complex and technically advanced production methods. This review focuses primarily on unconventional liquid hydro-carbons. The future potential of unconventional gas, especially shale gas, is also discussed, as it is revolutionizing the energy outlook in North America and elsewhere.

A dual-function fluorescent probe for monitoring the degrees of hypoxia in living cells via the imaging of nitroreductase and adenosine triphosphate.

PubMed

Fang, Yu; Shi, Wen; Hu, Yiming; Li, Xiaohua; Ma, Huimin

2018-05-24

A new dual-function fluorescent probe is developed for detecting nitroreductase (NTR) and adenosine triphosphate (ATP) with different responses. Imaging application of the probe reveals that intracellular NTR and ATP display an adverse changing trend during a hypoxic process and ATP can serve as a new sign for cell hypoxia.

N-terminal splicing extensions of the human MYO1C gene fine-tune the kinetics of the three full-length myosin IC isoforms.

PubMed

Zattelman, Lilach; Regev, Ronit; Ušaj, Marko; Reinke, Patrick Y A; Giese, Sven; Samson, Abraham O; Taft, Manuel H; Manstein, Dietmar J; Henn, Arnon

2017-10-27

The MYO1C gene produces three alternatively spliced isoforms, differing only in their N-terminal regions (NTRs). These isoforms, which exhibit both specific and overlapping nuclear and cytoplasmic functions, have different expression levels and nuclear-cytoplasmic partitioning. To investigate the effect of NTR extensions on the enzymatic behavior of individual isoforms, we overexpressed and purified the three full-length human isoforms from suspension-adapted HEK cells. MYO1C C favored the actomyosin closed state (AM C ), MYO1C 16 populated the actomyosin open state (AM O ) and AM C equally, and MYO1C 35 favored the AM O state. Moreover, the full-length constructs isomerized before ADP release, which has not been observed previously in truncated MYO1C C constructs. Furthermore, global numerical simulation analysis predicted that MYO1C 35 populated the actomyosin·ADP closed state (AMD C ) 5-fold more than the actomyosin·ADP open state (AMD O ) and to a greater degree than MYO1C C and MYO1C 16 (4- and 2-fold, respectively). On the basis of a homology model of the 35-amino acid NTR of MYO1C 35 (NTR 35 ) docked to the X-ray structure of MYO1C C , we predicted that MYO1C 35 NTR residue Arg-21 would engage in a specific interaction with post-relay helix residue Glu-469, which affects the mechanics of the myosin power stroke. In addition, we found that adding the NTR 35 peptide to MYO1C C yielded a protein that transiently mimics MYO1C 35 kinetic behavior. By contrast, NTR 35 , which harbors the R21G mutation, was unable to confer MYO1C 35 -like kinetic behavior. Thus, the NTRs affect the specific nucleotide-binding properties of MYO1C isoforms, adding to their kinetic diversity. We propose that this level of fine-tuning within MYO1C broadens its adaptability within cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Unconventional style reaps rewards for Ruckdeschel. Physician executive's career carries cancer center to the forefront. Interview by Patty Ryan.

PubMed

Ruckdeschel, J

2001-01-01

He didn't like math. Loved biology. So he ditched his plans to become an engineer and ended up pursuing a career in medicine and hospital administration. He led a sleepy cancer center to new heights of cutting-edge research and progressive types of treatment. And he did it all on his own terms--a mix of practicality and instinct that serves up some interesting perspectives for fellow physician executives to consider. Meet John Ruckdeschel, MD.

LANTR Engine Optimization for Lunar Missions

NASA Astrophysics Data System (ADS)

Bulman, M. J.; Poth, Greg; Borowski, Stan

2006-01-01

Propulsion requirements for sustainable Lunar missions are very demanding. The high Delta V for short transit times and/or reusable vehicles are best served with the High Isp of Nuclear Propulsion. High thrust is needed to reduce gravity losses during earth departure. The LOX-Augmented Nuclear Thermal Rocket (LANTR) is a concept whereby thrust from a nuclear thermal rocket can be doubled, or even quadrupled, by the injection and combustion of gaseous oxygen downstream of the throat. This has many advantages for the mission including a reduction in the size of the reactor(s) and propellant tank volume for a given payload delivered to Low Lunar Orbit. In this paper, we conduct mission studies to define the optimum basic (Unaugmented) engine thrust, Lox augmentation level and Lox loading for minimum initial mass in low earth orbit. 35% mass savings are seen for NTR powered LTVs with over twice the propellant Volume. The LANTR powered LTV has a similar mass savings with minimal volume penalties.

Unconventional Aqueous Humor Outflow: A Review

PubMed Central

Johnson, Mark; McLaren, Jay W.; Overby, Darryl R.

2016-01-01

Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or ‘unconventional’ route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans. PMID:26850315

Amended Results for Hard X-Ray Emission by Non-thermal Thick Target Recombination in Solar Flares

NASA Astrophysics Data System (ADS)

Reep, J. W.; Brown, J. C.

2016-06-01

Brown & Mallik and the corresponding corrigendum Brown et al. presented expressions for non-thermal recombination (NTR) in the collisionally thin- and thick-target regimes, claiming that the process could account for a substantial part of the hard X-ray continuum in solar flares usually attributed entirely to thermal and non-thermal bremsstrahlung (NTB). However, we have found the thick-target expression to become unphysical for low cut-offs in the injected electron energy spectrum. We trace this to an error in the derivation, derive a corrected version that is real-valued and continuous for all photon energies and cut-offs, and show that, for thick targets, Brown et al. overestimated NTR emission at small photon energies. The regime of small cut-offs and large spectral indices involve large (reducing) correction factors but in some other thick-target parameter regimes NTR/NTB can still be of the order of unity. We comment on the importance of these results to flare and microflare modeling and spectral fitting. An empirical fit to our results shows that the peak NTR contribution comprises over half of the hard X-ray signal if δ ≳ 6{≤ft(\\tfrac{{E}0c}{4{keV}}\\right)}0.4.

DNA Recognition by a σ 54 Transcriptional Activator from Aquifex aeolicus

DOE PAGES

Vidangos, Natasha K.; Heideker, Johanna; Lyubimov, Artem; ...

2014-08-23

Transcription initiation by bacterial σ 54-polymerase requires the action of a transcriptional activator protein. Activators bind sequence-specifically upstream of the transcription initiation site via a DNA-binding domain. The structurally characterized DNA-binding domains from activators all belong to the Factor for Inversion Stimulation (Fis) family of helix-turn-helix DNA-binding proteins. We report here structures of the free and DNA-bound forms of the DNA-binding domain of NtrC4 (4DBD) from Aquifex aeolicus, a member of the NtrC family of σ 54 activators. Two NtrC4 binding sites were identified upstream (-145 and -85 base pairs) from the start of the lpxC gene, which is responsiblemore » for the first committed step in Lipid A biosynthesis. This is the first experimental evidence for σ 54 regulation in lpxC expression. 4DBD was crystallized both without DNA and in complex with the -145 binding site. The structures, together with biochemical data, indicate that NtrC4 binds to DNA in a manner that is similar to that of its close homologue, Fis. Ultimately, the greater sequence specificity for the binding of 4DBD relative to Fis seems to arise from a larger number of base specific contacts contributing to affinity than for Fis.« less

Organic Rankine cycle - review and research directions in engine applications

NASA Astrophysics Data System (ADS)

Panesar, Angad

2017-11-01

Waste heat to power conversion using Organic Rankine Cycles (ORC) is expected to play an important role in CO2 reductions from diesel engines. Firstly, a review of automotive ORCs is presented focusing on the pure working fluids, thermal architectures and expanders. The discussion includes, but is not limited to: R245fa, ethanol and water as fluids; series, parallel and cascade as architectures; dry saturated, superheated and supercritical as expansion conditions; and scroll, radial turbine and piston as expansion machines. Secondly, research direction in versatile expander and holistic architecture (NOx + CO2) are proposed. Benefits of using the proposed unconventional approaches are quantified using Ricardo Wave and Aspen HYSYS for diesel engine and ORC modelling. Results indicate that, the implementation of versatile piston expander tolerant to two-phase and using cyclopentane can potentially increase the highway drive cycle power by 8%. Furthermore, holistic architecture offering complete utilisation of charge air and exhaust recirculation heat increased the performance noticeably to 5% of engine power at the design point condition.

Unconventional nozzle tradeoff study. [space tug propulsion

NASA Technical Reports Server (NTRS)

Obrien, C. J.

1979-01-01

Plug cluster engine design, performance, weight, envelope, operational characteristics, development cost, and payload capability, were evaluated and comparisons were made with other space tug engine candidates using oxygen/hydrogen propellants. Parametric performance data were generated for existing developed or high technology thrust chambers clustered around a plug nozzle of very large diameter. The uncertainties in the performance prediction of plug cluster engines with large gaps between the modules (thrust chambers) were evaluated. The major uncertainty involves, the aerodynamics of the flow from discrete nozzles, and the lack of this flow to achieve the pressure ratio corresponding to the defined area ratio for a plug cluster. This uncertainty was reduced through a cluster design that consists of a plug contour that is formed from the cluster of high area ratio bell nozzles that have been scarfed. Light-weight, high area ratio, bell nozzles were achieved through the use of AGCarb (carbon-carbon cloth) nozzle extensions.

Human outposts on Mars: engineering and scientific lessons learned from history

NASA Astrophysics Data System (ADS)

Gruenwald, J.

2014-06-01

There are several planned projects that aim to send humans to Mars which are currently developed by the ESA, the NASA or by initiatives from the private sector (e.g. The Mars One Project). Some of these projects include long-term stays or even permanent human outposts on the red planet. To achieve the necessary habitats on Mars, a vast amount of different engineering and scientific problems has to be solved. This paper identifies some of the most important issues by analyzing a similar endeavor from human history—the colonization of the American continent by the Europeans. This might seem to be an unconventional approach, but some valuable insights can be gathered by studying the significant dangers and drawbacks experienced by the early settlers in America. These historical records can help scientists and engineers to set up some guidelines for avoiding some of the risks for the first human beings on Mars.

Contribution of p75NTR to Schwannoma Growth and Therapeutic Responses

DTIC Science & Technology

2016-05-01

AWARD NUMBER: W81XWH-14-1-0096 TITLE: Contribution of p75NTR to schwannoma growth and therapeutic responses PRINCIPAL INVESTIGATOR: Marlan R...schwannoma growth and therapeutic responses Marlan R. Hansen Iram Ahmad J. Jason Clark Jed Rasmussen Charles Yates University of Iowa Iowa City, IA 52242...and schwannoma cells and to determine the efficacy of therapies that target these differences in reducing schwannoma cell growth in culture and in

The complete nucleotide sequence of the glnALG operon of Escherichia coli K12.

PubMed Central

Miranda-Ríos, J; Sánchez-Pescador, R; Urdea, M; Covarrubias, A A

1987-01-01

The nucleotide sequence of the E. coli glnALG operon has been determined. The glnL (ntrB) and glnG (ntrC) genes present a high homology, at the nucleotide and aminoacid levels, with the corresponding genes of Klebsiella pneumoniae. The predicted aminoacid sequence for glutamine synthetase allowed us to locate some of the enzyme domains. The structure of this operon is discussed. PMID:2882477

A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies.

PubMed

Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

2016-04-08

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior - a key element for the transport selectivity of the NPC - was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface.

Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

PubMed

Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

2016-07-19

Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

Nitrogen stress response and stringent response are coupled in Escherichia coli

PubMed Central

Brown, Daniel R.; Barton, Geraint; Pan, Zhensheng; Buck, Martin; Wigneshweraraj, Sivaramesh

2014-01-01

Assimilation of nitrogen is an essential process in bacteria. The nitrogen regulation stress response is an adaptive mechanism used by nitrogen-starved Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E. coli cells synthesize a signal molecule, guanosine tetraphosphate (ppGpp), which serves as an effector molecule of many processes including transcription to initiate global physiological changes, collectively termed the stringent response. The regulatory mechanisms leading to elevated ppGpp levels during nutritional stresses remain elusive. Here, we show that transcription of relA, a key gene responsible for the synthesis of ppGpp, is activated by NtrC during nitrogen starvation. The results reveal that NtrC couples these two major bacterial stress responses to manage conditions of nitrogen limitation, and provide novel mechanistic insights into how a specific nutritional stress leads to elevating ppGpp levels in bacteria. PMID:24947454

Adaptive Modeling, Engineering Analysis and Design of Advanced Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Mukhopadhyay, Vivek; Hsu, Su-Yuen; Mason, Brian H.; Hicks, Mike D.; Jones, William T.; Sleight, David W.; Chun, Julio; Spangler, Jan L.; Kamhawi, Hilmi; Dahl, Jorgen L.

2006-01-01

This paper describes initial progress towards the development and enhancement of a set of software tools for rapid adaptive modeling, and conceptual design of advanced aerospace vehicle concepts. With demanding structural and aerodynamic performance requirements, these high fidelity geometry based modeling tools are essential for rapid and accurate engineering analysis at the early concept development stage. This adaptive modeling tool was used for generating vehicle parametric geometry, outer mold line and detailed internal structural layout of wing, fuselage, skin, spars, ribs, control surfaces, frames, bulkheads, floors, etc., that facilitated rapid finite element analysis, sizing study and weight optimization. The high quality outer mold line enabled rapid aerodynamic analysis in order to provide reliable design data at critical flight conditions. Example application for structural design of a conventional aircraft and a high altitude long endurance vehicle configuration are presented. This work was performed under the Conceptual Design Shop sub-project within the Efficient Aerodynamic Shape and Integration project, under the former Vehicle Systems Program. The project objective was to design and assess unconventional atmospheric vehicle concepts efficiently and confidently. The implementation may also dramatically facilitate physics-based systems analysis for the NASA Fundamental Aeronautics Mission. In addition to providing technology for design and development of unconventional aircraft, the techniques for generation of accurate geometry and internal sub-structure and the automated interface with the high fidelity analysis codes could also be applied towards the design of vehicles for the NASA Exploration and Space Science Mission projects.

Unconventional Deterrence Strategy

DTIC Science & Technology

2005-06-01

200 words) This thesis examines a largely unexplored area of deterrence theory – unconventional deterrence. Unconventional deterrence is defined...hypothesis of deterrence theory which says that the balance of the opponents’ military capabilities is the basic determinant of successful deterrence...

Interfacial sciences in unconventional petroleum production: from fundamentals to applications.

PubMed

He, Lin; Lin, Feng; Li, Xingang; Sui, Hong; Xu, Zhenghe

2015-08-07

With the ever increasing demand for energy to meet the needs of growth in population and improvement in the living standards in particular in developing countries, the abundant unconventional oil reserves (about 70% of total world oil), such as heavy oil, oil/tar sands and shale oil, are playing an increasingly important role in securing global energy supply. Compared with the conventional reserves unconventional oil reserves are characterized by extremely high viscosity and density, combined with complex chemistry. As a result, petroleum production from unconventional oil reserves is much more difficult and costly with more serious environmental impacts. As a key underpinning science, understanding the interfacial phenomena involved in unconventional petroleum production, such as oil liberation from host rocks, oil-water emulsions and demulsification, is critical for developing novel processes to improve oil production while reducing GHG emission and other environmental impacts at a lower operating cost. In the past decade, significant efforts and advances have been made in applying the principles of interfacial sciences to better understand complex unconventional oil-systems, while many environmental and production challenges remain. In this critical review, the recent research findings and progress in the interfacial sciences related to unconventional petroleum production are critically reviewed. In particular, the chemistry of unconventional oils, liberation mechanisms of oil from host rocks and mechanisms of emulsion stability and destabilization in unconventional oil production systems are discussed in detail. This review also seeks to summarize the current state-of-the-art characterization techniques and brings forward the challenges and opportunities for future research in this important field of physical chemistry and petroleum.

Final Report - Assessment of Testing Options for the NTR at the INL

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

Howe, Steven D; McLing, Travis L; McCurry, Michael

One of the main technologies that can be developed to dramatically enhance the human exploration of space is the nuclear thermal rocket (NTR). Several studies over the past thirty years have shown that the NTR can reduce the cost of a lunar outpost, reduce the risk of a human mission to Mars, enable fast transits for most missions throughout the solar system, and reduce the cost and time for robotic probes to deep space. Three separate committees of the National Research Council of the National Academy of Sciences have recommended that NASA develop the NTR. One of the primary issuesmore » in development of the NTR is the ability to verify a flight ready unit. Three main methods can be used to validate safe operation of a NTR: 1) Full power, full duration test in an above ground facility that scrubs the rocket exhaust clean of any fission products; 2) Full power , full duration test using the Subsurface Active Filtering of Exhaust (SAFE) technique to capture the exhaust in subsurface strata; 3) Test of the reactor fuel at temperature and power density in a driver reactor with subsequent first test of the fully integrated NTR in space. The first method, the above ground facility, has been studied in the past. The second method, SAFE, has been examined for application at the Nevada Test Site. The third method relies on the fact that the Nuclear Furnace series of tests in 1971 showed that the radioactive exhaust coming from graphite based fuel for the NTR could be completely scrubbed of fission products and the clean hydrogen flared into the atmosphere. Under funding from the MSFC, the Center for Space Nuclear Research (CSNR) at the Idaho National laboratory (INL) has completed a reexamination of Methods 2 and 3 for implementation at the INL site. In short, the effort performed the following: 1) Assess the geology of the INL site and determine a location suitable SAFE testing; 2) Perform calculations of gas transport throughout the geology; 3) Produce a cost estimate of a non-nuclear , sub-scale test using gas injection to validate the computational models; 4) Produce a preliminary cost estimate to build a nuclear furnace equivalent facility to test NTR fuel on a green field location on the INL site. The results show that the INL geology is substantially better suited to the SAFE testing method than the NTS site. The existence of impermeable interbeds just above the sub-surface aquifer ensure that no material from the test, radioactive or not, can enter the water table. Similar beds located just below the surface will prevent any gaseous products from reaching the surface for dispersion. The extremely high permeability of the strata between the interbeds allows rapid dispersion of the rocket exhaust. In addition, the high permeability suggests that a lower back-pressure may develop in the hole against the rocket thrust, which increases safety of operations. Finally, the cost of performing a sub-scale, non-nuclear verification experiment was determined to be $3M. The third method was assessed through discussions with INL staff resident at the site. In essence, any new Category I facility on any DOE site will cost in excess of $250M. Based on the results of this study, a cost estimate for testing a nuclear rocket at the INL site appears to be warranted. Given the fact that a new nuclear fuel may be possible that does not release any fission products, the SAFE testing option appears to be the most affordable.« less

JPRS Report, Near East & South Asia

DTIC Science & Technology

1987-08-03

Range (NTR) at Baliapal in coas- tal Balasore district has assumed a new dimension with the disclo- sure by the defence ministry this week that the...ongoing Interim Test Range (ITR) project at Chandipur, near Balasore , is part of the NTR. The people of Baliapal got powerful support from the...peo- ple of Balasore town, which observed a total bandh on June 1 in protest against the location of the ITR at Chandipur, which is only 3 kms

Making sense of "alternative", "complementary", "unconventional" and "integrative" medicine: exploring the terms and meanings through a textual analysis.

PubMed

Ng, Jeremy Y; Boon, Heather S; Thompson, Alison K; Whitehead, Cynthia R

2016-05-20

Medical pluralism has flourished throughout the Western world in spite of efforts to legitimize Western biomedical healthcare as "conventional medicine" and thereby relegate all non-physician-related forms of healthcare to an "other" category. These "other" practitioners have been referred to as "unconventional", "alternative" and "complementary", among other terms throughout the past half century. This study investigates the discourses surrounding the changes in the terms, and their meanings, used to describe unconventional medicine in North America. Terms identified by the literature as synonymous to unconventional medicine were searched using the Scopus database. A textual analysis following the method described by Kripendorff 2013 was subsequently performed on the five most highly-cited unconventional medicine-related peer-reviewed literature published between 1970 and 2013. Five commonly-used, unconventional medicine-related terms were identified. Authors using "complementary and alternative", "complementary", "alternative", or "unconventional" tended to define them by what they are not (e.g., therapies not taught/used in conventional medicine, therapy demands not met by conventional medicine, and therapies that lack research on safety, efficacy and effectiveness). Authors defined "integrated/integrative" medicine by what it is (e.g., a new model of healthcare, the combining of both conventional and unconventional therapies, accounting for the whole person, and preventative maintenance of health). Authors who defined terms by "what is not" stressed that the purpose of conducting research in this area was solely to create knowledge. Comparatively, authors who defined terms by "what is" sought to advocate for the evidence-based combination of unconventional and conventional medicines. Both author groups used scientific rhetoric to define unconventional medical practices. This emergence of two groups of authors who used two different sets of terms to refer to the concept of "unconventional medicine" may explain why some journals, practitioner associations and research/practice centres may choose to use both "what is not" and "what is" terms in their discourse to attract interest from both groups. Since each of the two groups of terms (and authors who use them) has different meanings and goals, the evolution of this discourse will continue to be an interesting phenomenon to explore in the future.

Statement Testimony of Mr. Alan R. Shaffer, Principal Deputy, Defense Research and Engineering Before the United States House of Representatives Committee on Armed Services, Subcommittee on Terrorism, Unconventional Threats and Capabilities

DTIC Science & Technology

2009-05-20

Advanced Composite Cargo Aircraft ( ACCA ) platform to assess and validate the structural behavior and cost impact of using large out-of-autoclave...capabilities to fight the current and future wars 3. Improving our acquisition capabilities and accountability . The Department of Defense S&T budget...In fact, the S&T program fared well in comparison to many other discretionary accounts . For instance, the RDT&E budget categories of Advanced

Insights on unconventional natural gas development from shale: an interview with Anthony R. Ingraffea by Adam Law.

PubMed

Ingraffea, Anthony R

2013-01-01

Adam Law, M.D., interviewed Anthony R. Ingraffea, Ph.D., P.E., as part of a series of interviews funded by the Heinz Endowment. Dr. Ingraffea is the Dwight C. Baum Professor of Engineering at Cornell University, and has taught structural mechanics, finite element methods, and fracture mechanics at Cornell for 33 years. He discusses issues related to hydraulic fracturing, including inherent risks, spatial intensity, and the importance of a multi-disciplinary organization in establishing a chain of evidence.

The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment.

PubMed

Jiang, H; Chen, S; Li, C; Lu, N; Yue, Y; Yin, Y; Zhang, Y; Zhi, X; Zhang, D; Yuan, Y

2017-04-04

Evidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA-BDNF pathway in MDD. We examined serum protein concentrations in the tPA-BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA-BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.

Attenuation of exercise-induced heat shock protein 72 expression blunts improvements in whole-body insulin resistance in rats with type 2 diabetes.

PubMed

Tsuzuki, Takamasa; Kobayashi, Hiroyuki; Yoshihara, Toshinori; Kakigi, Ryo; Ichinoseki-Sekine, Noriko; Naito, Hisashi

2017-03-01

Heat shock proteins (HSPs) play an important role in insulin resistance and improve the cellular stress response via HSP induction by exercise to treat type 2 diabetes. In this study, the effects of exercise-induced HSP72 expression levels on whole-body insulin resistance in type 2 diabetic rats were investigated. Male 25-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into three groups: sedentary (Sed), trained in a thermal-neutral environment (NTr: 25 °C), and trained in a cold environment (CTr: 4 °C). Exercise training was conducted 5 days/week for 10 weeks. Rectal temperature was measured following each bout of exercise. An intraperitoneal glucose tolerance test (IPGTT) was performed after the training sessions. The serum, gastrocnemius muscle, and liver were sampled 48 h after the final exercise session. HSP72 and heat shock cognate protein 73 expression levels were analyzed by Western blot, and serum total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels were measured. NTr animals exhibited significantly higher body temperatures following exercise, whereas, CTr animals did not. Exercise training increased HSP72 levels in the gastrocnemius muscle and liver, whereas, HSP72 expression was significantly lower in the CTr group than that in the NTr group (p < 0.05). Glucose tolerance improved equally in both trained animals; however, insulin levels during the IPGTT were higher in CTr animals than those in NTr animals (p < 0.05). In addition, the TG and FFA levels decreased significantly only in NTr animals compared with those in Sed animals. These results suggest that attenuation of exercise-induced HSP72 expression partially blunts improvement in whole-body insulin resistance and lipid metabolism in type 2 diabetic rats.

Involvement of brain-derived neurotrophic factor (BDNF) in the functional elimination of synaptic contacts at polyinnervated neuromuscular synapses during development.

PubMed

Garcia, N; Santafe, M M; Tomàs, M; Lanuza, M A; Besalduch, N; Tomàs, J

2010-05-15

We use immunohistochemistry to describe the localization of brain-derived neurotrophic factor (BDNF) and its receptors trkB and p75(NTR) in the neuromuscular synapses of postnatal rats (P6-P7) during the synapse elimination period. The receptor protein p75(NTR) is present in the nerve terminal, muscle cell and glial Schwann cell whereas BDNF and trkB proteins can be detected mainly in the pre- and postsynaptic elements. Exogenously applied BDNF (10 nM for 3 hr or 50 nM for 1 hr) increases ACh release from singly and dually innervated synapses. This effect may be specific for BDNF because the neurotrophin NT-4 (2-8 nM) does not modulate release at P6-P7. Blocking the receptors trkB and p75(NTR) (with K-252a and anti-p75-192-IgG, respectively) completely abolishes the potentiating effect of exogenous BDNF. In addition, exogenous BDNF transiently recruits functionally depressed silent terminals, and this effect seems to be mediated by trkB. Calcium ions, the L-type voltage-dependent calcium channels and protein kinase C are involved in BDNF-mediated nerve ending recruitment. Blocking experiments suggest that endogenous BDNF could operate through p75(NTR) receptors coupled to potentiate ACh release in all nerve terminals because the anti-p75-192-IgG reduces release. However, blocking the trkB receptor (K-252a) or neutralizing endogenous BDNF with the trkB-IgG fusion protein reveals a trkB-mediated release inhibition on almost mature strong endings in dual junctions. Taken together these results suggest that a BDNF-induced p75(NTR)-mediated ACh release potentiating mechanism and a BDNF-induced trkB-mediated release inhibitory mechanism may contribute to developmental synapse disconnection. (c) 2009 Wiley-Liss, Inc.

Associations between smoking and caffeine consumption in two European cohorts

PubMed Central

Taylor, Amy E.; Ware, Jennifer J.; McMahon, George; Hottenga, Jouke‐Jan; Baselmans, Bart M. L.; Willemsen, Gonneke; Boomsma, Dorret I.; Munafò, Marcus R.; Vink, Jacqueline M.

2016-01-01

Abstract Aims To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption in two population‐based samples from the Netherlands and the United Kingdom. Design Observational study employing data on self‐reported smoking behaviour and caffeine consumption. Setting Adults from the general population in the Netherlands and the United Kingdom. Participants Participants from the Netherlands Twin Register [NTR: n = 21 939, mean age 40.8, standard deviation (SD) = 16.9, 62.6% female] and the Avon Longitudinal Study of Parents and Children (ALSPAC: n = 9086, mean age 33.2, SD = 4.7, 100% female). Measurements Smoking initiation (ever versus never smoking), smoking persistence (current versus former smoking), smoking heaviness (number of cigarettes smoked) and caffeine consumption in mg per day through coffee, tea, cola and energy drinks. Findings After correction for age, gender (NTR), education and social class (ALSPAC), smoking initiation was associated with consuming on average 52.8 [95% confidence interval (CI) = 45.6–60.0; NTR] and 59.5 (95% CI = 51.8–67.2; ALSPAC) mg more caffeine per day. Smoking persistence was also associated with consuming more caffeine [+57.9 (95% CI = 45.2–70.5) and +83.2 (95% CI = 70.2–96.3) mg, respectively]. Each additional cigarette smoked per day was associated with 3.7 (95% CI = 1.9–5.5; NTR) and 8.4 (95% CI = 6.9–10.0; ALSPAC) mg higher daily caffeine consumption in current smokers. Smoking was associated positively with coffee consumption and less strongly with cola and energy drinks. For tea, associations were positive in ALSPAC and negative in NTR. Conclusions There appears to be a positive association between smoking and caffeine consumption in the Netherlands and the United Kingdom. PMID:26750569

Optical system design, analysis, and production; Proceedings of the Meeting, Geneva, Switzerland, April 19-22, 1983

NASA Astrophysics Data System (ADS)

Rogers, P. J.; Fischer, R. E.

1983-01-01

Topics considered include: optical system requirements, analysis, and system engineering; optical system design using microcomputers and minicomputers; optical design theory and computer programs; optical design methods and computer programs; optical design methods and philosophy; unconventional optical design; diffractive and gradient index optical system design; optical production and system integration; and optical systems engineering. Particular attention is given to: stray light control as an integral part of optical design; current and future directions of lens design software; thin-film technology in the design and production of optical systems; aspherical lenses in optical scanning systems; the application of volume phase holograms to avionic displays; the effect of lens defects on thermal imager performance; and a wide angle zoom for the Space Shuttle.

Neutralizer Characterization of a NEXT Multi-Thruster Array With Electrostatic Probes

NASA Technical Reports Server (NTRS)

Foster, John E.; Patterson, Michael; Pencil, Eric; McEwen, Heather; Diaz, Esther

2006-01-01

Neutralizers in a multi-thruster array configuration were characterized using conventional diagnostics such as peak-to-peak keeper oscillation amplitude as well as unconventional methods which featured the application of electrostatic probes. The response of the array local plasma environment to neutralizer flow rate changes were documented using Langmuir probes and retarding potential analyzers. Such characterization is necessary for system efficiency and stability optimization. Because the local plasma environment was measured in conjunction with the neutralizer characterization, particle fluxes at the array and thus array lifetime impacts associated with neutralizer operating mode could also be investigated. Neutralizer operating condition was documented for a number of multithruster array configurations ranging from three-engines, three-neutralizers to a single engine, one-neutralizer all as a function of neutralizer flow rate.

Distributed nitrate transport and reaction routines (NTR) inside the mesoscale Hydrological Model (mHM) framework: Development and Application in the Selke catchment

NASA Astrophysics Data System (ADS)

Sinha, Sumit; Rode, Michael; Kumar, Rohini; Yang, Xiaoqiang; Samaniego, Luis; Borchardt, Dietrich

2016-04-01

Precise measurements of where, when and how much denitrification occurs on the basis of measurements alone persist to be vexing and intractable research problem at all spatial and temporal scales. As a result, models have become essential and vital tools for furthering our current understanding of the processes that control denitrification on catchment scale. Emplacement of Water Framework Directive (WFD) and continued efforts in improving water treatment facilities has resulted in alleviating the problems associated with point sources of pollution. However, the problem of eutrophication still persists and is primarily associated with the diffused sources of pollution originating from agricultural area. In this study, the nitrate transport and reaction (NTR) routines are developed inside the distributed mesoscale Hydrological Model (mHM www.ufz.de/mhm) which is a fully distributed hydrological model with a novel parameter regionalization scheme (Samaniego et al. 2010; Kumar et al. 2013) and has been applied to whole Europe (Rakovec et al. 2016) and numerous catchments worldwide. The aforementioned NTR model is applied to a mesoscale river basin, Selke (463 km2) located in central Germany. The NTR model takes in account the critical and pertinent processes like transformation in vadose zone, atmospheric deposition, plant uptake, instream denitrification and also simulates the process of manure and fertilizer application. Both streamflow routines and the NTR model are run on daily time steps. The split-sample approach was used for model calibration (1994-1999) and validation (2000-2004). Flow dynamics at three gauging stations located inside this catchment are successfully captured by the model with consistently high Nash-Sutcliffe Efficiency (NSE) of at least 0.8. Regarding nitrate estimates, the NSE values are greater than 0.7 for both validation and calibration periods. Finally, the NTR model is used for identifying the critical source areas (CSAs) that contribute significantly to nutrient pollution due to different local hydrological and topographical conditions. Postulations for a comprehensive sensitivity analysis and further regionalization of key parameters of the NTR model are also investigated. References: Kumar, R., L. Samaniego, and S. Attinger (2013a), Implications of distributed hydrologic model parameterization on water fluxes at multiple scales and locations, Water Resour. Res., 49, 360-379, doi:10.1029/2012WR012195. Samaniego, L., R. Kumar, and S. Attinger (2010), Multiscale parameter regionalization of a grid-based hydrologic model at the mesoscale, Water Resour. Res., 46, W05523, doi:10.1029/2008WR007327. Rakovec, O., Kumar, R., Mai, J., Cuntz, M., Thober, S., Zink, M., Attinger, S., Schäfer, D., Schrön, M., Samaniego, L. (2016): Multiscale and multivariate evaluation of water fluxes and states over European river basins, J. Hydrometeorol., 17, 287-307, doi: 10.1175/JHM-D-15-0054.1.

Large number limit of multifield inflation

NASA Astrophysics Data System (ADS)

Guo, Zhong-Kai

2017-12-01

We compute the tensor and scalar spectral index nt, ns, the tensor-to-scalar ratio r , and the consistency relation nt/r in the general monomial multifield slow-roll inflation models with potentials V ˜∑iλi|ϕi| pi . The general models give a novel relation that nt, ns and nt/r are all proportional to the logarithm of the number of fields Nf when Nf is getting extremely large with the order of magnitude around O (1040). An upper bound Nf≲N*eZ N* is given by requiring the slow variation parameter small enough where N* is the e -folding number and Z is a function of distributions of λi and pi. Besides, nt/r differs from the single-field result -1 /8 with substantial probability except for a few very special cases. Finally, we derive theoretical bounds r >2 /N* (r ≳0.03 ) and for nt, which can be tested by observation in the near future.

A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies

PubMed Central

Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

2016-01-01

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior – a key element for the transport selectivity of the NPC – was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface. DOI: http://dx.doi.org/10.7554/eLife.14119.001 PMID:27058170

Unconventional Word Segmentation in Emerging Bilingual Students' Writing: A Longitudinal Analysis

ERIC Educational Resources Information Center

Sparrow, Wendy

2014-01-01

This study explores cross-language and longitudinal patterns in unconventional word segmentation in 25 emerging bilingual students' (Spanish/English) writing from first through third grade. Spanish and English writing samples were collected annually and analyzed for two basic types of unconventional word segmentation: hyposegmentation, in…

Unconventionality and Originality: Does Self-Assessed Unconventionality Increase Original Achievement?

ERIC Educational Resources Information Center

Andreas, Stuart F. K.; Zech, Stefan; Coyle, Thomas R.; Rindermann, Heiner

2016-01-01

Creativity is negatively associated with certain personality traits (e.g., conformity) and social influences (e.g., group pressure). In this study, creativity was examined in relation to unconventionality, which was expected to correlate positively with creativity, especially originality. This hypothesis was based on the theory that unconventional…

Geology and assessment of unconventional oil and gas resources of northeastern Mexico

USGS Publications Warehouse

,

2015-01-01

The U.S. Geological Survey, in cooperation with the U.S. Department of State, quantitatively assessed the potential for unconventional oil and gas resources within the onshore portions of the Tampico-Misantla Basin, Burgos Basin, and Sabinas Basin provinces of northeastern Mexico. Unconventional resources of the Veracruz Basin were not quantitatively assessed because of a current lack of required geological information. Unconventional resources include shale gas, shale oil, tight gas, tight oil, and coalbed gas. Undiscovered conventional oil and gas resources were assessed in Mexico in 2012.

Assessment of surface water chloride and conductivity trends in areas of unconventional oil and gas development-Why existing national data sets cannot tell us what we would like to know

USGS Publications Warehouse

Bowen, Zachary H.; Oelsner, Gretchen P.; Cade, Brian S.; Gallegos, Tanya J.; Farag, Aïda M.; Mott, David N.; Potter, Christopher J.; Cinotto, Peter J.; Clark, Melanie L.; Kappel, William M.; Kresse, Timothy M.; Melcher, Cynthia P.; Paschke, Suzanne; Susong, David D.; Varela, Brian A.

2015-01-01

Heightened concern regarding the potential effects of unconventional oil and gas development on regional water quality has emerged, but the few studies on this topic are limited in geographic scope. Here we evaluate the potential utility of national and publicly available water-quality data sets for addressing questions regarding unconventional oil and gas development. We used existing U.S. Geological Survey and U.S. Environmental Protection Agency data sets to increase understanding of the spatial distribution of unconventional oil and gas development in the U.S. and broadly assess surface water quality trends in these areas. Based on sample size limitations, we were able to estimate trends in specific conductance (SC) and chloride (Cl-) from 1970 to 2010 in 16% (n=155) of the watersheds with unconventional oil and gas resources. We assessed these trends relative to spatiotemporal distributions of hydraulically fractured wells. Results from this limited analysis suggest no consistent and widespread trends in surface water quality for SC and Cl- in areas with increasing unconventional oil and gas development and highlight limitations of existing national databases for addressing questions regarding unconventional oil and gas development and water quality.

Neurotrophins regulate ApoER2 proteolysis through activation of the Trk signaling pathway.

PubMed

Larios, Jorge A; Jausoro, Ignacio; Benitez, Maria-Luisa; Bronfman, Francisca C; Marzolo, Maria-Paz

2014-09-19

ApoER2 and the neurotrophin receptors Trk and p75(NTR) are expressed in the CNS and regulate key functional aspects of neurons, including development, survival, and neuronal function. It is known that both ApoER2 and p75(NTR) are processed by metalloproteinases, followed by regulated intramembrane proteolysis. TrkA activation by nerve growth factor (NGF) increases the proteolytic processing of p75(NTR) mediated by ADAM17. Reelin induces the sheeding of ApoER2 ectodomain depending on metalloproteinase activity. However, it is not known if there is a common regulation mechanism for processing these receptors. We found that TrkA activation by NGF in PC12 cells induced ApoER2 processing, which was dependent on TrkA activation and metalloproteinases. NGF-induced ApoER2 proteolysis was independent of mitogen activated protein kinase activity and of phosphatidylinositol-3 kinase activity. In contrast, the basal proteolysis of ApoER2 increased when both kinases were pharmacologically inhibited. The ApoER2 ligand reelin regulated the proteolytic processing of its own receptor but not of p75(NTR). Finally, in primary cortical neurons, which express both ApoER2 and TrkB, we found that the proteolysis of ApoER2 was also regulated by brain-derived growth factor (BDNF). Our results highlight a novel relationship between neurotrophins and the reelin-ApoER2 system, suggesting that these two pathways might be linked to regulate brain development, neuronal survival, and some pathological conditions.

Deciphering the Principles of Bacterial Nitrogen Dietary Preferences: a Strategy for Nutrient Containment

PubMed Central

Wang, Jilong; Yan, Dalai

2016-01-01

ABSTRACT A fundamental question in microbial physiology concerns why organisms prefer certain nutrients to others. For example, among different nitrogen sources, ammonium is the preferred nitrogen source, supporting fast growth, whereas alternative nitrogen sources, such as certain amino acids, are considered to be poor nitrogen sources, supporting much slower exponential growth. However, the physiological/regulatory logic behind such nitrogen dietary choices remains elusive. In this study, by engineering Escherichia coli, we switched the dietary preferences toward amino acids, with growth rates equivalent to that of the wild-type strain grown on ammonia. However, when the engineered strain was cultured together with wild-type E. coli, this growth advantage was diminished as a consequence of ammonium leakage from the transport-and-catabolism (TC)-enhanced (TCE) cells, which are preferentially utilized by wild-type bacteria. Our results reveal that the nitrogen regulatory (Ntr) system fine tunes the expression of amino acid transport and catabolism components to match the flux through the ammonia assimilation pathway such that essential nutrients are retained, but, as a consequence, the fast growth rate on amino acids is sacrificed. PMID:27435461

The Design of a Primary Flight Trainer using Concurrent Engineering Concepts

NASA Technical Reports Server (NTRS)

Ladesic, James G.; Eastlake, Charles N.; Kietzmann, Nicholas H.

1993-01-01

Concurrent Engineering (CE) concepts seek to coordinate the expertise of various disciplines from initial design configuration selection through product disposal so that cost efficient design solutions may be achieve. Integrating this methodology into an undergraduate design course sequence may provide a needed enhancement to engineering education. The Advanced Design Program (ADP) project at Embry-Riddle Aeronautical University (EMU) is focused on developing recommendations for the general aviation Primary Flight Trainer (PFT) of the twenty first century using methods of CE. This project, over the next two years, will continue synthesizing the collective knowledge of teams composed of engineering students along with students from other degree programs, their faculty, and key industry representatives. During the past year (Phase I). conventional trainer configurations that comply with current regulations and existing technologies have been evaluated. Phase I efforts have resulted in two baseline concepts, a high-wing, conventional design named Triton and a low-wing, mid-engine configuration called Viper. In the second and third years (Phases II and III). applications of advanced propulsion, advanced materials, and unconventional airplane configurations along with military and commercial technologies which are anticipated to be within the economic range of general aviation by the year 2000, will be considered.

Assessment of unconventional oil and gas resources in Northeast Mexico, 2014

USGS Publications Warehouse

Schenk, Christopher J.; Charpentier, Ronald R.; Klett, Timothy R.; Tennyson, Marilyn E.; Gaswirth, Stephanie B.; Brownfield, Michael E.; Pawlewicz, Mark J.; Weaver, Jean Noe

2014-01-01

Using a geology-based assessment methodology, the U.S. Geological Survey estimated means of 0.78 billion barrels of unconventional oil, 23.5 trillion cubic feet of unconventional gas, and 0.88 billion barrels of natural gas liquids in the Sabinas Basin, Burgos Basin, and Tampico-Misantla Basin provinces of northeast Mexico.

Unconventional superconductivity in heavy-fermion compounds

DOE PAGES

White, B. D.; Thompson, J. D.; Maple, M. B.

2015-02-27

Over the past 35 years, research on unconventional superconductivity in heavy-fermion systems has evolved from the surprising observations of unprecedented superconducting properties in compounds that convention dictated should not superconduct at all to performing explorations of rich phase spaces in which the delicate interplay between competing ground states appears to support emergent superconducting states. In this article, we review the current understanding of superconductivity in heavy-fermion com- pounds and identify a set of characteristics that is common to their unconventional superconducting states. These core properties are compared with those of other classes of unconventional superconductors such as the cuprates andmore » iron-based superconductors. Lastly, we conclude by speculating on the prospects for future research in this field and how new advances might contribute towards resolving the long-standing mystery of how unconventional superconductivity works.« less

Emerging Methane Sources: A Bang or Whimper? (Invited)

NASA Astrophysics Data System (ADS)

Harriss, R. C.

2013-12-01

In this presentation we examine two emerging methane emission sources that may further accelerate climate change in the 21st century: 1) Will fugitive methane emissions associated with the development of unconventional natural gas resources pose a significant threat of accelerating climate change? 2) Will continued warming of Arctic regions destabilize permafrost and methane hydrates rapidly increasing global atmospheric methane that results in a catastrophic climate change emergency? These risks are currently described in two different guises, with unconventional gas as persistent and gradually unfolding threat and Arctic rapid warming and release of methane as a low-probability event that could in an instant change everything. Current research is far from answering the question of whether these emerging methane sources will lead to a climate change bang or whimper. Both issues reflect the need to understand complex environmental and engineered systems as they interact with social and economic forces. While the evolution of energy systems favors methane as a contemporary transition fuel, researchers and practitioners need to address the fugitive methane leakage, reliability, and safety of natural gas systems. The concept of a methane bridge as a viable direction to decarbonization is appealing; it's just not as big or fast a step as many scientists want.

Extending injury prevention methodology to chemical terrorism preparedness: the Haddon Matrix and sarin.

PubMed

Varney, Shawn; Hirshon, Jon Mark; Dischinger, Patricia; Mackenzie, Colin

2006-01-01

The Haddon Matrix offers a classic epidemiological model for studying injury prevention. This methodology places the public health concepts of agent, host, and environment within the three sequential phases of an injury-producing incident-pre-event, event, and postevent. This study uses this methodology to illustrate how it could be applied in systematically preparing for a mass casualty disaster such as an unconventional sarin attack in a major urban setting. Nineteen city, state, federal, and military agencies responded to the Haddon Matrix chemical terrorism preparedness exercise and offered feedback in the data review session. Four injury prevention strategies (education, engineering, enforcement, and economics) were applied to the individual factors and event phases of the Haddon Matrix. The majority of factors identified in all phases were modifiable, primarily through educational interventions focused on individual healthcare providers and first responders. The Haddon Matrix provides a viable means of studying an unconventional problem, allowing for the identification of modifiable factors to decrease the type and severity of injuries following a mass casualty disaster such as a sarin release. This strategy could be successfully incorporated into disaster planning for other weapons attacks that could potentially cause mass casualties.

Engineering frequency-dependent superfluidity in Bose-Fermi mixtures

NASA Astrophysics Data System (ADS)

Arzamasovs, Maksims; Liu, Bo

2018-04-01

Unconventional superconductivity and superfluidity are among the most exciting and fascinating quantum phenomena in condensed-matter physics. Usually such states are characterized by nontrivial spin or spatial symmetry of the pairing order parameter, such as "spin triplet" or "p wave." However, besides spin and spatial dependence the order parameter may have unconventional frequency dependence which is also permitted by Fermi-Dirac statistics. Odd-frequency fermionic pairing is an exciting paradigm when discussing exotic superfluidity or superconductivity and is yet to be realized in experiments. In this paper we propose a symmetry-based method of controlling frequency dependence of the pairing order parameter via manipulating the inversion symmetry of the system. First, a toy model is introduced to illustrate that frequency dependence of the order parameter can be achieved through our proposed approach. Second, by taking advantage of recent rapid developments in producing spin-orbit-coupled dispersions in ultracold gases, we propose a Bose-Fermi mixture to realize such frequency-dependent superfluid. The key idea is introducing the frequency-dependent attraction between fermions mediated by Bogoliubov phonons with asymmetric dispersion. Our proposal should pave an alternative way for exploring frequency-dependent superfluids with cold atoms.

Wavelength and energy dependent absorption of unconventional fuel mixtures

NASA Astrophysics Data System (ADS)

Khan, N.; Saleem, Z.; Mirza, A. A.

2005-11-01

Economic considerations of laser induced ignition over the normal electrical ignition of direct injected Compressed Natural Gas (CNG) engines has motivated automobile industry to go for extensive research on basic characteristics of leaner unconventional fuel mixtures to evaluate practical possibility of switching over to the emerging technologies. This paper briefly reviews the ongoing research activities on minimum ignition energy and power requirements of natural gas fuels and reports results of present laser air/CNG mixture absorption coefficient study. This study was arranged to determine the thermo-optical characteristics of high air/fuel ratio mixtures using laser techniques. We measured the absorption coefficient using four lasers of multiple wavelengths over a wide range of temperatures and pressures. The absorption coefficient of mixture was found to vary significantly over change of mixture temperature and probe laser wavelengths. The absorption coefficients of air/CNG mixtures were measured using 20 watts CW/pulsed CO2 laser at 10.6μm, Pulsed Nd:Yag laser at 1.06μm, 532 nm (2nd harmonic) and 4 mW CW HeNe laser at 645 nm and 580 nm for temperatures varying from 290 to 1000K using optical transmission loss technique.

Carbon dioxide storage in unconventional reservoirs workshop: summary of recommendations

USGS Publications Warehouse

Jones, Kevin B.; Blondes, Madalyn S.

2015-01-01

The storage capacity for all unconventional reservoirs may be modeled using a volumetric equation starting with the extent of the rock unit and adjusted using these key factors and reaction terms. The ideas that were developed during this workshop can be used by USGS scientists to develop a methodology to assess the CO2 storage resource in unconventional reservoirs. This methodology could then be released for public comment and peer review. After completing this development process, the USGS could then use the methodology to assess the CO2 storage resource in unconventional reservoirs.

Topological Acoustic Delay Line

NASA Astrophysics Data System (ADS)

Zhang, Zhiwang; Tian, Ye; Cheng, Ying; Wei, Qi; Liu, Xiaojun; Christensen, Johan

2018-03-01

Topological protected wave engineering in artificially structured media is at the frontier of ongoing metamaterials research that is inspired by quantum mechanics. Acoustic analogues of electronic topological insulators have recently led to a wealth of new opportunities in manipulating sound propagation with strikingly unconventional acoustic edge modes immune to backscattering. Earlier fabrications of topological insulators are characterized by an unreconfigurable geometry and a very narrow frequency response, which severely hinders the exploration and design of useful devices. Here we establish topologically protected sound in reconfigurable phononic crystals that can be switched on and off simply by rotating its three-legged "atoms" without altering the lattice structure. In particular, we engineer robust phase delay defects that take advantage of the ultrabroadband reflection-free sound propagation. Such topological delay lines serve as a paradigm in compact acoustic devices, interconnects, and electroacoustic integrated circuits.

Geology and assessment of unconventional resources of Phitsanulok Basin, Thailand

USGS Publications Warehouse

,

2014-01-01

The U.S. Geological Survey (USGS) quantitatively assessed the potential for unconventional oil and gas resources within the Phitsanulok Basin of Thailand. Unconventional resources for the USGS include shale gas, shale oil, tight gas, tight oil, and coalbed gas. In the Phitsanulok Basin, only potential shale-oil and shale-gas resources were quantitatively assessed.

Design of Heat Exchanger for Ericsson-Brayton Piston Engine

PubMed Central

Durcansky, Peter; Papucik, Stefan; Jandacka, Jozef

2014-01-01

Combined power generation or cogeneration is a highly effective technology that produces heat and electricity in one device more efficiently than separate production. Overall effectiveness is growing by use of combined technologies of energy extraction, taking heat from flue gases and coolants of machines. Another problem is the dependence of such devices on fossil fuels as fuel. For the combustion turbine is mostly used as fuel natural gas, kerosene and as fuel for heating power plants is mostly used coal. It is therefore necessary to seek for compensation today, which confirms the assumption in the future. At first glance, the obvious efforts are to restrict the use of largely oil and change the type of energy used in transport. Another significant change is the increase in renewable energy—energy that is produced from renewable sources. Among machines gaining energy by unconventional way belong mainly the steam engine, Stirling engine, and Ericsson engine. In these machines, the energy is obtained by external combustion and engine performs work in a medium that receives and transmits energy from combustion or flue gases indirectly. The paper deals with the principle of hot-air engines, and their use in combined heat and electricity production from biomass and with heat exchangers as primary energy transforming element. PMID:24977174

Design of heat exchanger for Ericsson-Brayton piston engine.

PubMed

Durcansky, Peter; Papucik, Stefan; Jandacka, Jozef; Holubcik, Michal; Nosek, Radovan

2014-01-01

Combined power generation or cogeneration is a highly effective technology that produces heat and electricity in one device more efficiently than separate production. Overall effectiveness is growing by use of combined technologies of energy extraction, taking heat from flue gases and coolants of machines. Another problem is the dependence of such devices on fossil fuels as fuel. For the combustion turbine is mostly used as fuel natural gas, kerosene and as fuel for heating power plants is mostly used coal. It is therefore necessary to seek for compensation today, which confirms the assumption in the future. At first glance, the obvious efforts are to restrict the use of largely oil and change the type of energy used in transport. Another significant change is the increase in renewable energy--energy that is produced from renewable sources. Among machines gaining energy by unconventional way belong mainly the steam engine, Stirling engine, and Ericsson engine. In these machines, the energy is obtained by external combustion and engine performs work in a medium that receives and transmits energy from combustion or flue gases indirectly. The paper deals with the principle of hot-air engines, and their use in combined heat and electricity production from biomass and with heat exchangers as primary energy transforming element.

NACA Research on Slurry Fuels

NASA Technical Reports Server (NTRS)

Pinns, M L; Olson, W T; Barnett, H C; Breitwieser, R

1958-01-01

An extensive program was conducted to investigate the use of concentrated slurries of boron and magnesium in liquid hydrocarbon as fuels for afterburners and ramjet engines. Analytical calculations indicated that magnesium fuel would give greater thrust and that boron fuel would give greater range than are obtainable from jet hydrocarbon fuel alone. It was hoped that the use of these solid elements in slurry form would permit the improvement to be obtained without requiring unconventional fuel systems or combustors. Small ramjet vehicles fueled with magnesium slurry were flown successfully, but the test flights indicated that further improvement of combustors and fuel systems was needed.

Marcellus Shale Drilling's Impact on the Dairy Industry in Pennsylvania: A Descriptive Report.

PubMed

Finkel, Madelon L; Selegean, Jane; Hays, Jake; Kondamudi, Nitin

2013-01-01

Unconventional natural gas drilling in Pennsylvania has accelerated over the past five years, and is unlikely to abate soon. Dairy farming is a large component of Pennsylvania's agricultural economy. This study compares milk production, number of cows, and production per cow in counties with significant unconventional drilling activity to that in neighboring counties with less unconventional drilling activity, from 1996 through 2011. Milk production and milk cows decreased in most counties since 1996, with larger decreases occurring from 2007 through 2011 (when unconventional drilling increased substantially) in five counties with the most wells drilled compared to six adjacent counties with fewer than 100 wells drilled. While this descriptive study cannot draw a causal association between well drilling and decline in cows or milk production, given the importance of Pennsylvania's dairy industry and the projected increase in unconventional natural gas drilling, further research to prevent unintended economic and public health consequences is imperative.

Establishment of a Transgenic Zebrafish Line for Superficial Skin Ablation and Functional Validation of Apoptosis Modulators In Vivo

PubMed Central

Chen, Chi-Fang; Chu, Che-Yu; Chen, Te-Hao; Lee, Shyh-Jye; Shen, Chia-Ning; Hsiao, Chung-Der

2011-01-01

Background Zebrafish skin is composed of enveloping and basal layers which form a first-line defense system against pathogens. Zebrafish epidermis contains ionocytes and mucous cells that aid secretion of acid/ions or mucous through skin. Previous studies demonstrated that fish skin is extremely sensitive to external stimuli. However, little is known about the molecular mechanisms that modulate skin cell apoptosis in zebrafish. Methodology/Principal Findings This study aimed to create a platform to conduct conditional skin ablation and determine if it is possible to attenuate apoptotic stimuli by overexpressing potential apoptosis modulating genes in the skin of live animals. A transgenic zebrafish line of Tg(krt4:NTR-hKikGR)cy17 (killer line), which can conditionally trigger apoptosis in superficial skin cells, was first established. When the killer line was incubated with the prodrug metrodinazole, the superficial skin displayed extensive apoptosis as judged by detection of massive TUNEL- and active caspase 3-positive signals. Great reductions in NTR-hKikGR+ fluorescent signals accompanied epidermal cell apoptosis. This indicated that NTR-hKikGR+ signal fluorescence can be utilized to evaluate apoptotic events in vivo. After removal of metrodinazole, the skin integrity progressively recovered and NTR-hKikGR+ fluorescent signals gradually restored. In contrast, either crossing the killer line with testing lines or transiently injecting the killer line with testing vectors that expressed human constitutive active Akt1, mouse constitutive active Stat3, or HPV16 E6 element displayed apoptosis-resistant phenotypes to cytotoxic metrodinazole as judged by the loss of reduction in NTR-hKikGR+ fluorescent signaling. Conclusion/Significance The killer/testing line binary system established in the current study demonstrates a nitroreductase/metrodinazole system that can be utilized to conditionally perform skin ablation in a real-time manner, and provides a valuable tool to visualize and quantify the anti-apoptotic potential of interesting target genes in vivo. The current work identifies a potential use for transgenic zebrafish as a high-throughput platform to validate potential apoptosis modulators in vivo. PMID:21655190

The p75 neurotrophin receptor: at the crossroad of neural repair and death

PubMed Central

Meeker, Rick B.; Williams, Kimberly S.

2015-01-01

The strong repair and pro-survival functions of neurotrophins at their primary receptors, TrkA, TrkB and TrkC, have made them attractive candidates for treatment of nervous system injury and disease. However, difficulties with the clinical implementation of neurotrophin therapies have prompted the search for treatments that are stable, easier to deliver and allow more precise regulation of neurotrophin actions. Recently, the p75 neurotrophin receptor (p75NTR) has emerged as a potential target for pharmacological control of neurotrophin activity, supported in part by studies demonstrating 1) regulation of neural plasticity in the mature nervous system, 2) promotion of adult neurogenesis and 3) increased expression in neurons, macrophages, microglia, astrocytes and/or Schwann cells in response to injury and neurodegenerative diseases. Although the receptor has no intrinsic catalytic activity it interacts with and modulates the function of TrkA, TrkB, and TrkC, as well as sortilin and the Nogo receptor. This provides substantial cellular and molecular diversity for regulation of neuron survival, neurogenesis, immune responses and processes that support neural function. Upregulation of the p75NTR under pathological conditions places the receptor in a key position to control numerous processes necessary for nervous system recovery. Support for this possibility has come from recent studies showing that small, non-peptide p75NTR ligands can selectively modify pro-survival and repair functions. While a great deal remains to be discovered about the wide ranging functions of the p75NTR, studies summarized in this review highlight the immense potential for development of novel neuroprotective and neurorestorative therapies. PMID:26109945

Framework for comparing ecosystem impacts of developing unconventional energy resources on western US rangelands

Treesearch

Urs P. Kreuter; William E. Fox; John A. Tanaka; Kristie A. Maczko; Daniel W. McCollum; John E. Mitchell; Clifford S. Duke; Lori Hidinger

2012-01-01

More diverse sources of energy are needed for countries to progress toward energy independence and to meet future food production needs. The US Task Force on Strategic Unconventional Fuels concluded that to achieve this objective it is essential to develop a domestic unconventional fuels industry. Rangelands, which cover 50% to 70% of the earth's terrestrial...

Interim Report on Interagency National Personnel Recovery Architecture

DTIC Science & Technology

2003-07-01

adversaries are smart , however, and rather than face our forces on open battlefields, they will seek to use any asymmetric advantage open to them. If...Liaison Officer SARNEG Search and Rescue Numeric Encryption Grid SARPO Search and Rescue Planning Officer SARREQ Search and Rescue Request SARSAT...Unconventional Assisted Recovery UARCC Unconventional Assisted Recovery Coordination Center UARM Unconventional Assisted Recovery Mechanism UART

Structural basis of death domain signaling in the p75 neurotrophin receptor

PubMed Central

Lin, Zhi; Tann, Jason Y; Goh, Eddy TH; Kelly, Claire; Lim, Kim Buay; Gao, Jian Fang; Ibanez, Carlos F

2015-01-01

Death domains (DDs) mediate assembly of oligomeric complexes for activation of downstream signaling pathways through incompletely understood mechanisms. Here we report structures of complexes formed by the DD of p75 neurotrophin receptor (p75NTR) with RhoGDI, for activation of the RhoA pathway, with caspase recruitment domain (CARD) of RIP2 kinase, for activation of the NF-kB pathway, and with itself, revealing how DD dimerization controls access of intracellular effectors to the receptor. RIP2 CARD and RhoGDI bind to p75NTR DD at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding. The p75NTR DD forms non-covalent, low-affinity symmetric dimers in solution. The dimer interface overlaps with RIP2 CARD but not RhoGDI binding sites, supporting a model of receptor activation triggered by separation of DDs. These structures reveal how competitive protein-protein interactions orchestrate the hierarchical activation of downstream pathways in non-catalytic receptors. DOI: http://dx.doi.org/10.7554/eLife.11692.001 PMID:26646181

Engagement of Arginine Finger to ATP Triggers Large Conformational Changes in NtrC1 AAA+ ATPase for Remodeling Bacterial RNA Polymerase

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

Chen, Baoyu; Sysoeva, Tatyana A.; Chowdhury, Saikat

The NtrC-like AAA+ ATPases control virulence and other important bacterial activities through delivering mechanical work to {sigma}54-RNA polymerase to activate transcription from {sigma}54-dependent genes. We report the first crystal structure for such an ATPase, NtrC1 of Aquifex aeolicus, in which the catalytic arginine engages the {gamma}-phosphate of ATP. Comparing the new structure with those previously known for apo and ADP-bound states supports a rigid-body displacement model that is consistent with large-scale conformational changes observed by low-resolution methods. First, the arginine finger induces rigid-body roll, extending surface loops above the plane of the ATPase ring to bind {sigma}54. Second, ATP hydrolysismore » permits Pi release and retraction of the arginine with a reversed roll, remodeling {sigma}54-RNAP. This model provides a fresh perspective on how ATPase subunits interact within the ring-ensemble to promote transcription, directing attention to structural changes on the arginine-finger side of an ATP-bound interface.« less

Construction of an efficient two-photon fluorescent probe for imaging nitroreductase in live cells and tissues

NASA Astrophysics Data System (ADS)

Zhou, Liyi; Gong, Liang; Hu, Shunqin

2018-06-01

Compared with traditional confocal microscopy, two-photon fluorescence microscopy (TPFM), which excites a two-photon (TP) fluorophore by near-infrared light, provides improved three-dimensional image resolution with increased tissue-image depth (>500 μm) and an extended observation time. Therefore, the development of novel functional TP fluorophores has attracted great attention in recent years. Herein, a novel TP fluorophore CM-NH2, which have the donor-π-acceptor (D-π-A)-structure, was designed and synthesized. We further used this dye developed a new type of TP fluorescent probe CM-NO2 for detecting nitroreductase (NTR). Upon incubated with NTR for 15 min, CM-NO2 displayed a 90-fold fluorescence enhancement at 505 nm and the maximal TP action cross-section value after reaction was detected and calculated to be 200 GM at 760 nm. The probe exhibited excellent properties such as high sensitivity, high selectivity, low cytotoxicity, and high photostability. Moreover, the probe was utilized to image the tumor hypoxia in live HeLa cells. Finally, using the CM-NO2 to image NTR in tissues was demonstrated.

Subtotal resection of vestibular schwannoma: Evaluation with Ki-67 measurement, magnetic resonance imaging, and long-term observation

PubMed Central

Iannella, Giannicola; de Vincentiis, Marco; Di Gioia, Cira; Carletti, Raffaella; Pasquariello, Benedetta; Manno, Alessandra; Angeletti, Diletta; Savastano, Ersilia; Magliulo, Giuseppe

2017-01-01

Purpose The aim of this study was to compare the postoperative clinical and radiological data of patients with vestibular schwannomas who were initially managed by near total resection (NTR) or subtotal resection (STR). The Ki-67 analysis results were compared with tumor regrowth to determine the presence of a correlation between this proliferative index and postoperative tumor regrowth. Study Design Seventeen adult patients (7 male, 10 female) were retrospectively reviewed. Nine (52.9%) and eight (47.1%) patients underwent NTR and STR, respectively. Postoperative clinical and radiological data associated with vestibular schwannoma growth were compared with the Ki-67 immunohistochemical analysis results. Results Evidence of clinically significant regrowth was observed in four (23.5%) patients. Patients who underwent NTR had a lower rate/incidence of tumor regrowth than did patients who underwent STR. Patients with a higher Ki-67 index had the highest tumor regrowth rates. Conclusions Our study indicates that assessment of the Ki-67 index may be useful for determining the probability of regrowth of vestibular schwannomas when only partial removal is accomplished. PMID:28447494

An emerging case for membrane pore formation as a common mechanism for the unconventional secretion of FGF2 and IL-1β.

PubMed

Brough, David; Pelegrin, Pablo; Nickel, Walter

2017-10-01

Extracellular proteins with important signalling roles in processes, such as inflammation and angiogenesis, are known to employ unconventional routes of protein secretion. Although mechanisms of unconventional protein secretion are beginning to emerge, the precise molecular details have remained elusive for the majority of cargo proteins secreted by unconventional means. Recent findings suggest that for two examples of unconventionally secreted proteins, interleukin 1β (IL-1β) and fibroblast growth factor 2 (FGF2), the common molecular principle of pore formation may be shared. Under specific experimental conditions, secretion of IL-1β and FGF2 is triggered by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P 2 ]-dependent formation of pores across the plasma membrane. However, the underlying mechanisms are different, with FGF2 known to directly interact with PI(4,5)P 2 , whereas in the case of IL-1β secretion, it is proposed that the N-terminal fragment of gasdermin D interacts with PI(4,5)P 2 to form the pore. Thus, although implemented in different ways, these findings suggest that pore formation may be shared by the unconventional secretion mechanisms for FGF2 and IL-1β in at least some cases. In this Opinion article, we discuss the unconventional mechanisms of FGF2 and IL-1β release with a particular emphasis on recent discoveries suggesting the importance of pore formation on the plasma membrane. © 2017. Published by The Company of Biologists Ltd.

Nuclear Thermal Rocket/Vehicle Characteristics And Sensitivity Trades For NASA's Mars Design Reference Architecture (DRA) 5.0 Study

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

2009-01-01

This paper summarizes Phase I and II analysis results from NASA's recent Mars DRA 5.0 study which re-examined mission, payload and transportation system requirements for a human Mars landing mission in the post-2030 timeframe. Nuclear thermal rocket (NTR) propulsion was again identified as the preferred in-space transportation system over chemical/aerobrake because of its higher specific impulse (I(sub sp)) capability, increased tolerance to payload mass growth and architecture changes, and lower total initial mass in low Earth orbit (IMLEO) which is important for reducing the number of Ares-V heavy lift launches and overall mission cost. DRA 5.0 features a long surface stay (approximately 500 days) split mission using separate cargo and crewed Mars transfer vehicles (MTVs). All vehicles utilize a common core propulsion stage with three 25 klbf composite fuel NERVA-derived NTR engines (T(sub ex) approximately 2650 - 2700 K, p(sub ch) approximately 1000 psia, epsilon approximately 300:1, I(sub sp) approximately 900 - 910 s, engine thrust-toweight ratio approximately 3.43) to perform all primary mission maneuvers. Two cargo flights, utilizing 1-way minimum energy trajectories, pre-deploy a cargo lander to the surface and a habitat lander into a 24-hour elliptical Mars parking orbit where it remains until the arrival of the crewed MTV during the next mission opportunity (approximately 26 months later). The cargo payload elements aerocapture (AC) into Mars orbit and are enclosed within a large triconicshaped aeroshell which functions as payload shroud during launch, then as an aerobrake and thermal protection system during Mars orbit capture and subsequent entry, descent and landing (EDL) on Mars. The all propulsive crewed MTV is a 0-gE vehicle design that utilizes a fast conjunction trajectory that allows approximately 6-7 month 1-way transit times to and from Mars. Four 12.5 kW(sub e) per 125 square meter rectangular photovoltaic arrays provide the crewed MTV with approximately 50 kW(sub e) of electrical power in Mars orbit for crew life support and spacecraft subsystem needs. Vehicle assembly involves autonomous Earth orbit rendezvous and docking between the propulsion stages, in-line propellant tanks and payload elements. Nine Ares-V launches -- five for the two cargo MTVs and four for the crewed MTV -- deliver the key components for the three MTVs. Details on mission, payload, engine and vehicle characteristics and requirements are presented and the results of key trade studies are discussed.

An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-15-1-0138 TITLE: An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury PRINCIPAL...2015 - 30 Jun 2017 4. TITLE AND SUBTITLE An Unconventional Approach to Reducing Retinal Degeneration After Traumatic Ocular Injury 5 a . CONTRACT...optic confocal microscope system , test it, and establish protocols for the first successful in vivo retinal microvessel and pericyte advanced

Pulsed Magnetic Field Driven Gas Core Reactors for Space Power & Propulsion Applications

NASA Technical Reports Server (NTRS)

Anghaie, Samim; Smith, Blair; Knight, Travis; Butler, Carey

2003-01-01

The present results indicated that: 1. A pulsed magnetic driven fission power concept, PMD-GCR is developed for closed (NER) and semi-open (NTR) operations. 2. In power mode, power is generated at alpha less than 1 for power levels of hundreds of KW or higher 3. IN semi open NTR mode, PMD-GCR generates thrust at I(sub sp) approx. 5,000 s and jet power approx. 5KW/Kg. 4. PMD-GCR is highly subcritical and is actively driven to critically. 5. Parallel path with fusion R&D needs in many areas including magnet and plasma.

Space transfer concepts and analysis for exploration missions. Implementation plan and element description document (draft final). Volume 3: Nuclear thermal rocket vehicle

NASA Technical Reports Server (NTRS)

1991-01-01

This document presents the nuclear thermal rocket (NTR) concept design developed in support of the Space Transfer Concepts and Analysis for Exploration Missions (STCAEM) study. The evolution of the NTR concept is described along with the requirements, guidelines and assumptions for the design. Operating modes and options are defined and a systems description of the vehicle is presented. Artificial gravity configuration options and space and ground support systems are discussed. Finally, an implementation plan is presented which addresses technology needs, schedules, facilities and costs.

Evaluation of Short and Long Term Cold Stress Challenge of Nerve Grow Factor, Brain-Derived Neurotrophic Factor, Osteocalcin and Oxytocin mRNA Expression in BAT, Brain, Bone and Reproductive Tissue of Male Mice Using Real-Time PCR and Linear Correlation Analysis.

PubMed

Camerino, Claudia; Conte, Elena; Caloiero, Roberta; Fonzino, Adriano; Carratù, Mariarosaria; Lograno, Marcello D; Tricarico, Domenico

2017-01-01

The correlation between the Ngf/p75ntr-Ntrk1 and Bdnf , Osteocalcin- Ost / Gprc6a and Oxytocin- Oxt/Oxtr genes, was challenged investigating their mRNA levels in 3 months-old mice after cold-stress (CS). Uncoupling protein-1 ( Ucp-1) was used as positive control. Control mice were maintained at room temperature T = 25°C, CS mice were maintained at T = 4°C for 6 h and 5-days ( N = 15 mice). RT-PCR experiments showed that Ucp-1 and Ngf genes were up-regulated after 6 h CS in brown adipose tissues (BAT), respectively, by 2 and 1.5-folds; Ucp-1 was upregulated also after 5-days, while Ngfr (p75ntr) and Ntrk1 genes were downregulated after 6 h and 5-days CS in BAT. NGF and P75NTR were upregulated in bone and testis following 5-days, and P75NTR in testis after 6 h CS. Bdnf was instead up-regulated in bone following 5-days CS and down-regulated in testis. OST was upregulated by 16 and 3-fold in bone and BAT, respectively, following 5-days CS. Gprc6a was upregulated after 6 h in brain, while Bglap ( Ost) gene was downregulated. Oxt gene was upregulated by 5-fold following 5-days CS in bone. Oxtr was upregulated by 0.5 and 0.3-fold, respectively, following 6 h and 5-days CS in brain. Oxtr and Oxt were downregulated in testis and in BAT. The changes in the expression levels of control genes vs. genes following 6 h and 5-days CS were correlated in all tissues, but not in BAT. Correlation in BAT was improved eliminating Ngfr (p75ntr) data. The correlation in brain was lost eliminating Oxtr data. In sum, Ucp-1 potentiation in BAT after cold stress is associated with early Ngf -response in the same tissue and trophic action in bone and testis. In contrast, BDNF exerts bone and neuroprotective effects. Similarly to Ucp-1, Bglap ( Ost) signaling is enhanced in bone and BAT while it may exert local neuroprotective effects thought its receptor. Ngfr (p75ntr) regulates the adaptation to CS through a feed-back loop in BAT. Oxtr regulates the gene-response to CS through a feed-forward loop in brain. Overall these results expand the understanding of the physiology of these molecules under metabolic thermogenesis.

Varieties of healing. 2: a taxonomy of unconventional healing practices.

PubMed

Kaptchuk, T J; Eisenberg, D M

2001-08-07

The first of two essays in this issue demonstrated that the United States has had a rich history of medical pluralism. This essay seeks to present an overview of contemporary unconventional medical practices in the United States. No clear definition of "alternative medicine" is offered because it is a residual category composed of heterogeneous healing methods. A descriptive taxonomy of contemporary unconventional healing could be more helpful. Two broad categories of unconventional medicine are described here: a more prominent, "mainstream" complementary and alternative medicine (CAM) and a more culture-bound, "parochial" unconventional medicine. The CAM component can be divided into professional groups, layperson-initiated popular health reform movements, New Age healing, alternative psychological therapies, and non-normative scientific enterprises. The parochial category can be divided into ethno-medicine, religious healing, and folk medicine. A topologic examination of U.S. health care can provide an important conceptual framework through which health care providers can understand the current situation in U.S. medical pluralism.

Evaluation of an Aircraft Concept With Over-Wing, Hydrogen-Fueled Engines for Reduced Noise and Emissions

NASA Technical Reports Server (NTRS)

Guynn, Mark D.; Olson, Erik D.

2002-01-01

This report describes the analytical modeling and evaluation of an unconventional commercial transport aircraft concept designed to address aircraft noise and emission issues. A strut-braced wing configuration with overwing, ultra-high bypass ratio, hydrogen fueled turbofan engines is considered. Estimated noise and emission characteristics are compared to a conventional configuration designed for the same mission and significant benefits are identified. The design challenges and technology issues which would have to be addressed to make the concept a viable alternative to current aircraft designs are discussed. This concept is one of the "Quiet Green Transport" aircraft concepts studied as part of NASA's Revolutionary Aerospace Systems Concepts (RASC) Program. The RASC Program seeks to develop revolutionary concepts that address strategic objectives of the NASA Enterprises, such as reducing aircraft noise and emissions, and to identify enabling advanced technology requirements for the concepts.

NASA's Quiet Aircraft Technology Project

NASA Technical Reports Server (NTRS)

Whitfield, Charlotte E.

2004-01-01

NASA's Quiet Aircraft Technology Project is developing physics-based understanding, models and concepts to discover and realize technology that will, when implemented, achieve the goals of a reduction of one-half in perceived community noise (relative to 1997) by 2007 and a further one-half in the far term. Noise sources generated by both the engine and the airframe are considered, and the effects of engine/airframe integration are accounted for through the propulsion airframe aeroacoustics element. Assessments of the contribution of individual source noise reductions to the reduction in community noise are developed to guide the work and the development of new tools for evaluation of unconventional aircraft is underway. Life in the real world is taken into account with the development of more accurate airport noise models and flight guidance methodology, and in addition, technology is being developed that will further reduce interior noise at current weight levels or enable the use of lighter-weight structures at current noise levels.

[NRH2 induces cell apoptosis of cerebral tissues around hematomas after intracerebral hemorrhage through up-regulating proNGF, sortilin and p75NTR expressions].

PubMed

Zeng, Zhiqing; Liu, Hong; Jiang, Di

2015-04-01

To observe the expressions of neurotrophin receptor homolog 2 (NRH2), nerve growth factor precursor (proNGF), sortilin and neurotrophin receptor p75 (p75NTR) in cerebral tissues around hematomas in the different periods after intracerebral hemorrhage, and explore their relationships to cell apoptosis. The specimens of cerebral tissues around hematomas were collected from the patients undergoing hematoma removal operation after intracerebral hemorrhage. These specimens were divided into four groups, namely ≤ 6 hours, 6-24 hours(including 24 hours), 24-72 hours (including 72 hours) and over 72 hours according to the time from intracerebral hemorrhage to specimen collection. At the same time, 10 brain tissues distant to hemorrhage that dropped in the operative process were collected as a control group. Apoptosis index (AI) was examined in brain cells by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL). The expressions of NRH2, proNGF, sortilin and p75NTR mRNAs and proteins in brain tissues were detected through real-time quantitative PCR and Western blotting, respectively. Also, the expressions of Bcl-2 and Bax in brain tissues were analyzed using Western blotting. In vitro cultured astrocytes of rat cortex were transfected by NRH2 siRNA or scramble siRNA. The expressions of proNGF, sortilin and p75NTR proteins were detected using Western blotting. AI was higher in all groups of hemorrhage for 6 hours or longer than that in control and ≤ 6 hours groups, and AI in the group of 24-72 hours after intracerebral hemorrhage was the highest. However, there was no significant difference in AI between ≤ 6 hours group and control group. With the extension of intracerebral hemorrhage time, the expression levels of proNGF and p75NTR mRNAs and proteins were gradually elevated, reached the peak in 24-72 hours, and maintained a higher level after 72 hours, whereas there were no significant differences in the above indicators between ≤ 6 hours group and control group. In comparison with control group and ≤ 6 hours group, the expression levels of NRH2 and sortilin mRNAs and proteins and Bax expression started to increase in 6-24 hours, reached the peak in 24-72 hours, and then stayed a higher level after 72 hours, whereas there were no significant differences in the above indicators between ≤ 6 hours group and control group. There was no obvious change in Bcl-2 expression level between ≤ 6 hours group and control group. The level of Bcl-2 decreased in all groups of intracerebral hemorrhage for over 6 hours, and reached the nadir in 24-72 hours. Astrocytes transfected with NRH2 siRNA displayed a significant decrease in proNGF, sortilin and p75NTR protein levels as compared with scramble siRNA or blank control groups. The expression of NRH2 would increase in the cerebral tissues around hematomas after intracerebral hemorrhage. NRH2 might enhance the ratio of Bax/Bcl-2 by promoting the expressions of proNGF, sortilin and p75NTR, thereby inducing brain cell apoptosis.

Unconventional gas development and its effect on forested ecosystems in the Northern Appalachians, USA

NASA Astrophysics Data System (ADS)

Drohan, Patrick; Brittingham, Margaret; Mortensen, David; Barlow, Kathryn; Langlois, Lillie

2017-04-01

Worldwide unconventional shale-gas development has the potential to cause substantial landscape disturbance. The northeastern U.S.A. Appalachian Mountains across the states of Pennsylvania, West Virginia, Ohio, and Kentucky, are experiencing rapid landscape change as unconventional gas development occurs. We highlight several years of our research from this region in order to demonstrate the unique effect unconventional development has had on forested ecosystems. Infrastructure development has had a wide-reaching and varied effect on forested ecosystems and their services, which has resulted in temporary disturbances and long-lasting ones altering habitats and their viability. Corridor disturbances, such as pipelines, are the most spatially extensive disturbance and have substantially fragmented forest cover. Core forest disturbance, especially, in upper watershed positions, has resulted in disproportionate disturbances to forested ecosystems and their wildlife, and suggests a need for adaptive land management strategies to minimize and mitigate the effects of gas development. Soil and water resources are most affected by surface disturbances; however, soil protection and restoration strategies are evolving as the gas play changes economically. Dynamic soil properties related to soil organic matter and water availability respond uniquely to unconventional gas development and new, flexible restoration strategies are required to support long-term ecosystem stability. While the focus of management and research to date has been on acute disturbances to forested ecosystems, unconventional gas development is clearly a greater chronic, long-term disturbance factor in the Appalachian Mountains. Effectively managing ecosystems where unconventional gas development is occurring is a complicated interplay between public, private and corporate interests.

Unconventional natural gas development and birth outcomes in Pennsylvania, USA

PubMed Central

Casey, Joan A.; Savitz, David A.; Rasmussen, Sara G.; Ogburn, Elizabeth L.; Pollak, Jonathan; Mercer, Dione G.; Schwartz, Brian S.

2015-01-01

Background Unconventional natural gas development has expanded rapidly. In Pennsylvania the number of producing wells increased from zero in 2005 to 3689 in 2013. To our knowledge, no prior publications have focused on unconventional natural gas development and birth outcomes. Methods We performed a retrospective cohort study using electronic health record data on 9384 mothers linked to 10946 neonates in the Geisinger Health System from January 2009-January 2013. We estimated cumulative exposure to unconventional natural gas development activity with an inverse-distance squared model that incorporated distance to the mother’s home; dates and durations of well pad development, drilling, and hydraulic fracturing; and production volume during the pregnancy. We used multilevel linear and logistic regression models to examine associations between activity index quartile and term birth weight, preterm birth, low 5 minute Apgar score and small size for gestational age, while controlling for potential confounding variables. Results In adjusted models, there was an association between unconventional natural gas development activity and preterm birth that increased across quartiles, with a fourth quartile odds ratio of 1.4 (95% CI: 1.0-1.9). There were no associations of activity with Apgar score, small for gestational age, or term birth weight (after adjustment for year). In a post-hoc analysis, there was an association with physician-recorded high-risk pregnancy identified from the problem list (fourth vs. first quartile, 1.3 [95% CI: 1.1-1.7]). Conclusion Prenatal residential exposure to unconventional natural gas development activity was associated with two pregnancy outcomes, adding to evidence that unconventional natural gas development may impact health. PMID:26426945

Characteristics Study of In-Situ Capacitive Sensor for Monitoring Lubrication Oil Debris.

PubMed

Han, Zhibin; Wang, Yishou; Qing, Xinlin

2017-12-08

As an essential part of engine health monitoring (EHM), online lubrication oil debris monitoring has recently received great attention for the assessment of rotating and reciprocating parts in aero-engines, due to its high integration, low cost and safe characteristics. However, it is be a challenge to find a suitable sensor operating in such a complex environment. We present an unconventional novel approach, in which a cylinder capacitive sensor is designed and integrated with the pipeline of an engine lubrication system, so that the capacitive sensor can effectively detect changes in the lubrication oil condition. In this paper, an attempt to illustrate the performance characteristics of the developed cylinder capacitive sensor is made, through an experiment system that simulates a real scenario of a lubrication oil system. The main aim of the research was to qualitatively describe the relationship between the sensor parameter and the lubrication oil debris. In addition, the effect of the temperature and flow rate of the lubrication oil on capacitance change was performed by several experiments and we figured out a compensation method. The experimental results demonstrated that the cylinder capacitive sensor can potentially be used for lubrication oil debris monitoring of the health condition of an aero-engine.

Upregulation of blood proBDNF and its receptors in major depression.

PubMed

Zhou, Li; Xiong, Jing; Lim, Yoon; Ruan, Ye; Huang, Chaohong; Zhu, Yuhong; Zhong, Jin-hua; Xiao, Zhicheng; Zhou, Xin-Fu

2013-09-25

In recent decades, the role of brain-derived neurotrophic factor (BDNF) in depression has received intensive attention. However, the relationship between proBDNF and depression has not been clearly elucidated. Forty drug-free women patients diagnosed with major depression and 50 healthy female controls were enrolled in our study. Peripheral blood was sampled from all the subjects. With the blood samples, we assessed the relationship between BDNF and major depression from following aspects: the levels of BDNF, proBDNF and their receptors in the sera and lymphocytes. The mRNA levels of these factors in lymphocytes were also examined. Furthermore, the correlations between each factor and the severity of major depression were tested. It was found that: (a) the protein and serum levels of proBDNF, sortilin and p75NTR were higher in major depressive patients than in healthy controls while mature BDNF and TrkB levels were lower; (b) the BDNF, TrkB, sortilin and p75NTR mRNA levels changed in line with their protein levels; (c) The levels of mature BDNF and TrkB had negative correlations with the major depression severity, and the levels of proBDNF, p75NTR and sortilin were positively correlated with the scores of HRSD-21; (d) the ratio of proBDNF and mBDNF was imbalanced in major depressive patients. The balance between the proBDNF/p75NTR/sortilin and mBDNF/TrkB signaling pathways appears dysregulated in major depression and both pathways should be considered as biomarkers for the major depression More cases on both genders should be enrolled in our study. And further works on the mechanisms of how BDNF and its receptors are regulated in depression should also be carried out. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Immunization Against Specific Fragments of Neurotrophin p75 Receptor Protects Forebrain Cholinergic Neurons in the Olfactory Bulbectomized Mice

PubMed Central

Bobkova, Natalia; Vorobyov, Vasily; Medvinskaya, Natalia; Nesterova, Inna; Tatarnikova, Olga; Nekrasov, Pavel; Samokhin, Alexander; Deev, Alexander; Sengpiel, Frank; Koroev, Dmitry; Volpina, Olga

2016-01-01

Alzheimer’s disease (AD) is characterized by progressive cognitive impairment associated with marked cholinergic neuron loss and amyloid-β (Aβ) peptide accumulation in the brain. The cytotoxicity in AD is mediated, at least in part, by Aβ binding with the extracellular domain of the p75 neurotrophin receptor (p75NTR), localized predominantly in the membranes of acetylcholine-producing neurons in the basal forebrain. Hypothesizing that an open unstructured loop of p75NTR might be the effective site for Aβ binding, we have immunized both olfactory bulbectomized (OBX) and sham-operated (SO) mice (n = 82 and 49, respectively) with synthetic peptides, structurally similar to different parts of the loops, aiming to block them by specific antibodies. OBX-mice have been shown in previous studies, and confirmed in the present one, to be characterized by typical behavioral, morphological, and biochemical AD hallmarks, including cholinergic deficits in forebrain neurons. Immunization of OBX- or SO-mice with KLH conjugated fragments of p75NTR induced high titers of specific serum antibodies for each of nine chosen fragments. However, maximal protective effects on spatial memory, evaluated in a Morris water maze, and on activity of choline acetyltransferase in forebrain neurons, detected by immunoreactivity to specific antibodies, were revealed only for peptides with amino acid residue sequences of 155–164 and 167–176. We conclude that the approach based on immunological blockade of specific p75NTR sites, linked with the cytotoxicity, is a useful and effective tool for study of AD-associated mechanisms and for development of highly selective therapy of cholinergic malfunctioning in AD patients. PMID:27163825

Synthesis and Evaluation of 64Cu-DOTA-NT-Cy5.5 as a Dual-Modality PET/Fluorescence Probe to Image Neurotensin Receptor-Positive Tumor.

PubMed

Deng, Huaifu; Wang, Hui; Wang, Mengzhe; Li, Zibo; Wu, Zhanhong

2015-08-03

Overexpression of neurotensin receptors (NTRs) has been suggested to play important roles in the growth and survival of a variety of tumor types. The aim of this study is to develop a dual-modality probe (64Cu -DOTA-NT-Cy5.5) for imaging NTR1 expression in vivo with both positron emission tomography (PET) and fluorescence. In this approach, the thiol group and N terminal amino group of neurotensin analogue (Cys-NT) were chemically modified with Cy5.5 dye and DOTA chelator, respectively. After radiolabeling with 64Cu, the resulting probe (64Cu-DOTA-NT-Cy5.5) was evaluated in NTR1 positive HT-29 tumor model. Small animal PET quantification analysis demonstrated that the tumor uptake was 1.91±0.22 and 1.79±0.16%ID/g at 1 and 4 h postinjection (p.i.), respectively. The tumor-to-muscle ratio was 17.44±3.25 at 4 h p.i. based on biodistribution. Receptor specificity was confirmed by the successful blocking experiment at 4 h p.i. (0.42±0.05%ID/g). In parallel with PET experiment, fluorescence imaging was also performed, which demonstrated prominent tumor uptake in HT-29 model. As a proof of concept, an imaging guided surgery was performed to the fluorescent moiety of this probe and could provide potential surgery guidance for NTR positive patients. In summary, our results clearly indicated that the dual-modality probe, 64Cu-DOTA-NT-Cy5.5, could serve as a promising agent to image NTR positive tumors in vivo.

Conditional ablation of osteoblasts in medaka.

PubMed

Willems, Bernd; Büttner, Anita; Huysseune, Ann; Renn, Joerg; Witten, P Eckhard; Winkler, Christoph

2012-04-15

Different from tetrapods, teleost vertebral centra form without prior establishment of a cartilaginous scaffold, in two steps: First, mineralization of the notochord sheath establishes the vertebral centra. Second, sclerotome derived mesenchymal cells migrate around the notochord sheath. These cells differentiate into osteoblasts and deposit bone onto the mineralized notochord sheath in a process of intramembranous bone formation. In contrast, most skeletal elements of the cranial skeleton arise by chondral bone formation, with remarkably similar mechanisms in fish and tetrapods. To further investigate the role of osteoblasts during formation of the cranial and axial skeleton, we generated a transgenic osx:CFP-NTR medaka line which enables conditional ablation of osterix expressing osteoblasts. By expressing a bacterial nitroreductase (NTR) fused to Cyan Fluorescent Protein (CFP) under control of the osterix promoter these cells become sensitive towards Metronidazole (Mtz). Mtz treatment of stable osx:CFP-NTR transgenic medaka for several consecutive days led to significant loss of osteoblasts by apoptosis. Live staining of mineralized bone matrix revealed reduced ossification in head skeletal elements such as cleithrum and operculum, as well as in the vertebral arches. Interestingly in Mtz treated larvae, intervertebral spaces were missing and the notochord sheath was often continuously mineralized resulting in the fusion of centra. We therefore propose a dual role for osx-positive osteoblasts in fish. Besides a role in bone deposition, we suggest an additional border function during mineralization of the chordal centra. After termination of Mtz treatment, osteoblasts gradually reappeared, indicating regenerative properties in this cell lineage. Taken together, the osx:CFP-NTR medaka line represents a valuable tool to study osteoblast function and regeneration at different stages of development in whole vertebrate specimens in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

CcpA-Dependent Carbon Catabolite Repression in Bacteria

PubMed Central

Warner, Jessica B.; Lolkema, Juke S.

2003-01-01

Carbon catabolite repression (CCR) by transcriptional regulators follows different mechanisms in gram-positive and gram-negative bacteria. In gram-positive bacteria, CcpA-dependent CCR is mediated by phosphorylation of the phosphoenolpyruvate:sugar phosphotransferase system intermediate HPr at a serine residue at the expense of ATP. The reaction is catalyzed by HPr kinase, which is activated by glycolytic intermediates. In this review, the distribution of CcpA-dependent CCR among bacteria is investigated by searching the public databases for homologues of HPr kinase and HPr-like proteins throughout the bacterial kingdom and by analyzing their properties. Homologues of HPr kinase are commonly observed in the phylum Firmicutes but are also found in the phyla Proteobacteria, Fusobacteria, Spirochaetes, and Chlorobi, suggesting that CcpA-dependent CCR is not restricted to gram-positive bacteria. In the α and β subdivisions of the Proteobacteria, the presence of HPr kinase appears to be common, while in the γ subdivision it is more of an exception. The genes coding for the HPr kinase homologues of the Proteobacteria are in a gene cluster together with an HPr-like protein, termed XPr, suggesting a functional relationship. Moreover, the XPr proteins contain the serine phosphorylation sequence motif. Remarkably, the analysis suggests a possible relation between CcpA-dependent gene regulation and the nitrogen regulation system (Ntr) found in the γ subdivision of the Proteobacteria. The relation is suggested by the clustering of CCR and Ntr components on the genome of members of the Proteobacteria and by the close phylogenetic relationship between XPr and NPr, the HPr-like protein in the Ntr system. In bacteria in the phylum Proteobacteria that contain HPr kinase and XPr, the latter may be at the center of a complex regulatory network involving both CCR and the Ntr system. PMID:14665673

Spatial correlations of population and ecological factors with distribution of visceral leishmaniasis cases in southwestern Iran.

PubMed

Ghatee, Mohammad Amin; Sharifi, Iraj; Haghdoost, Ali Akbar; Kanannejad, Zahra; Taabody, Zahra; Hatam, Gholamreza; Abdollahipanah, Abbas

2013-09-01

Leishmaniasis as a dynamic disease may be markedly influenced by demographic and ecological factors. A geospatial information system study was developed to determine the distribution of visceral leishmaniasis (VL) cases in relation to population, climatic and environmental factors in Fars province, southwest of Iran. The dwelling addresses of 217 VL patients were obtained from hospital files. A hazard map produced by unifying buffers (5 km) around nomads travel routes (NTR) was developed to survey the effect of close proximity to NTR on the distribution of VL. Mean annual rainfall (MAR), mean annual temperature (MAT), four months temperature mean (T4), elevation, slope and landcover were climatic and environmental factors that have been analysed. Finally, data of dwelling foci were extracted from maps and analysed using logistic regression models. Close proximity to NTR was the most important factor influenced on the disease distribution. Climatic factors were in second rank. Among them, temperature especially T4 is the most effective variable and rainfall was also shown to be another effective climatic agent. Most cases of VL were reported from temperate and semiarid areas in western and central regions while arid condition was a confined factor. The environmental factor of landcovers including urban, dry farm and thin forest regions was revealed as the third rank effective factor. Altitude importance was only shown when its effect was studied independently from other factors. These findings present the distribution of VL in Fars province is influenced by combination of ecological and nomads demographical variables although closeness to NTR and nomads role in distribution and continuance of kala-azar are the most important factors.

Neurotensin expression and release in human colon cancers.

PubMed Central

Evers, B M; Ishizuka, J; Chung, D H; Townsend, C M; Thompson, J C

1992-01-01

Neurotensin (NT), a distal gut peptide released by intraluminal fats, is trophic for normal small bowel and colonic mucosa. In addition, NT stimulates growth of certain colon cancers; the mechanism for this effect is not known. The purpose of this study was to determine whether human colon cancers (HCC) (1) express the mRNA for NT/neuromedin N (N), (2) produce NT peptide, and (3) express the mRNA for a functional NT receptor (NTR). RNA was extracted from four HCC cell lines in culture, nine HCC lines established in athymic nude mice, and from six HCC and adjacent normal mucosa from freshly resected operative specimens; the RNA was analyzed for NT/N mRNA by Northern hybridization with a complementary DNA probe. Neurotensin peptide content, NTR expression, and intracellular Ca++ ([Ca++]i) mobilization in response to NT were evaluated in three HCC cell lines (LoVo, HT29, HCT116). Neurotensin/N mRNA transcripts were identified in all four of the HCC cell lines and in one of nine HCC in nude mice. Neurotensin expression was found in two of six freshly resected HCC and in none of the six corresponding samples of normal mucosa. Neurotensin peptide was identified by RIA in LoVo, HT29, and HCT116. In addition, NTR mRNA was found in HT29 and HCT116. Neurotensin stimulated [Ca++]i mobilization in HCT116 (without serum) and in LoVo (with 0.25% serum). These findings demonstrate the presence of NT/N mRNA and NT peptide and the presence of a functional NTR in certain HCC. Neurotensin, a potent trophic factor for normal gut mucosa, may function as an autocrine growth factor in certain human colon cancers. Images FIG. 1. FIG. 4. PMID:1329682

ENGage: The use of space and pixel art for increasing primary school children's interest in science, technology, engineering and mathematics

NASA Astrophysics Data System (ADS)

Roberts, Simon J.

2014-01-01

The Faculty of Engineering at The University of Nottingham, UK, has developed interdisciplinary, hands-on workshops for primary schools that introduce space technology, its relevance to everyday life and the importance of science, technology, engineering and maths. The workshop activities for 7-11 year olds highlight the roles that space and satellite technology play in observing and monitoring the Earth's biosphere as well as being vital to communications in the modern digital world. The programme also provides links to 'how science works', the environment and citizenship and uses pixel art through the medium of digital photography to demonstrate the importance of maths in a novel and unconventional manner. The interactive programme of activities provides learners with an opportunity to meet 'real' scientists and engineers, with one of the key messages from the day being that anyone can become involved in science and engineering whatever their ability or subject of interest. The methodology introduces the role of scientists and engineers using space technology themes, but it could easily be adapted for use with any inspirational topic. Analysis of learners' perceptions of science, technology, engineering and maths before and after participating in ENGage showed very positive and significant changes in their attitudes to these subjects and an increase in the number of children thinking they would be interested and capable in pursuing a career in science and engineering. This paper provides an overview of the activities, the methodology, the evaluation process and results.

Deterrence in the Human Domain: A COIN Framework to Deterring Unconventional Warfare in Shaping Operations

DTIC Science & Technology

2017-05-25

Wilkinson US Army School of Advanced Military Studies United States Army Command and General Staff College Fort Leavenworth, Kansas 2017 Approved for...SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) Advanced Military Studies Program 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S...adversary’s unconventional threat. To test this framework, this monograph analyzes a case study of how Russia will likely use unconventional forces and

East-West paths to unconventional computing.

PubMed

Adamatzky, Andrew; Akl, Selim; Burgin, Mark; Calude, Cristian S; Costa, José Félix; Dehshibi, Mohammad Mahdi; Gunji, Yukio-Pegio; Konkoli, Zoran; MacLennan, Bruce; Marchal, Bruno; Margenstern, Maurice; Martínez, Genaro J; Mayne, Richard; Morita, Kenichi; Schumann, Andrew; Sergeyev, Yaroslav D; Sirakoulis, Georgios Ch; Stepney, Susan; Svozil, Karl; Zenil, Hector

2017-12-01

Unconventional computing is about breaking boundaries in thinking, acting and computing. Typical topics of this non-typical field include, but are not limited to physics of computation, non-classical logics, new complexity measures, novel hardware, mechanical, chemical and quantum computing. Unconventional computing encourages a new style of thinking while practical applications are obtained from uncovering and exploiting principles and mechanisms of information processing in and functional properties of, physical, chemical and living systems; in particular, efficient algorithms are developed, (almost) optimal architectures are designed and working prototypes of future computing devices are manufactured. This article includes idiosyncratic accounts of 'unconventional computing' scientists reflecting on their personal experiences, what attracted them to the field, their inspirations and discoveries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Spiral-like multi-beam emission via transformation electromagnetics

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

Tichit, Paul-Henri, E-mail: paul-henri.tichit@u-psud.fr; Burokur, Shah Nawaz, E-mail: shah-nawaz.burokur@u-psud.fr; Lustrac, André de, E-mail: andre.de-lustrac@u-psud.fr

Transformation electromagnetics offers an unconventional approach for the design of novel radiating devices. Here, we propose an electromagnetic metamaterial able to split an isotropic radiation into multiple directive beams. By applying transformations that modify distance and angles, we show how the multiple directive beams can be steered at will. We describe transformation of the metric space and the calculation of the material parameters. Different transformations are proposed for a possible physical realization through the use of engineered artificial metamaterials. Full wave simulations are performed to validate the proposed approach. The idea paves the way to interesting applications in various domainsmore » in microwave and optical regimes.« less

NADE (p75NTR-associated cell death executor) suppresses cellular growth in vivo.

PubMed

Tong, Xiangjun; Xie, Dong; Roth, Wilfried; Reed, John; Koeffler, H Phillip

2003-06-01

NADE, a p75NTR (low-affinity neurotrophin receptor p75) -associated cell death executor, was initially cloned from a human ovarian granulosa cell cDNA library, as an unknown protein with the name, pHGR74. It was reported to mediate nerve growth factor-induced apoptosis. We independently isolated human NADE (pHGR74) from breast cancer cell lines. Expression of NADE in various human cancer cell lines, and human and murine tissues was examined. NADE was highly expressed in human endocrine-related organs and embryotic murine tissues. Forced expression of NADE in CHO (Chinese hamster ovary) cells and MDA-MB-231 human breast cancer cells had little effect on the growth of the cells in vitro, while it dramatically suppressed cellular growth in vivo. We used the yeast two-hybrid system to search for NADE binding protein. Dynactin was identified as a candidate. The p75NTR was not found in this assay and did not co-immunoprecipitate with human NADE. Furthermore, the cells stably transfected with NADE did not respond to NGF or TNF. Thus, human and murine NADE appear to have different functions.

Study on Alternative Cargo Launch Options from the Lunar Surface

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

Cheryl A. Blomberg; Zamir A. Zulkefli; Spencer W. Rich

In the future, there will be a need for constant cargo launches from Earth to Mars in order to build, and then sustain, a Martian base. Currently, chemical rockets are used for space launches. These are expensive and heavy due to the amount of necessary propellant. Nuclear thermal rockets (NTRs) are the next step in rocket design. Another alternative is to create a launcher on the lunar surface that uses magnetic levitation to launch cargo to Mars in order to minimize the amount of necessary propellant per mission. This paper investigates using nuclear power for six different cargo launching alternatives,more » as well as the orbital mechanics involved in launching cargo to a Martian base from the moon. Each alternative is compared to the other alternative launchers, as well as compared to using an NTR instead. This comparison is done on the basis of mass that must be shipped from Earth, the amount of necessary propellant, and the number of equivalent NTR launches. Of the options, a lunar coil launcher had a ship mass that is 12.7% less than the next best option and 17 NTR equivalent launches, making it the best of the presented six options.« less

Construction of an efficient two-photon fluorescent probe for imaging nitroreductase in live cells and tissues.

PubMed

Zhou, Liyi; Gong, Liang; Hu, Shunqin

2018-06-15

Compared with traditional confocal microscopy, two-photon fluorescence microscopy (TPFM), which excites a two-photon (TP) fluorophore by near-infrared light, provides improved three-dimensional image resolution with increased tissue-image depth (>500μm) and an extended observation time. Therefore, the development of novel functional TP fluorophores has attracted great attention in recent years. Herein, a novel TP fluorophore CM-NH 2 , which have the donor-π-acceptor (D-π-A)-structure, was designed and synthesized. We further used this dye developed a new type of TP fluorescent probe CM-NO 2 for detecting nitroreductase (NTR). Upon incubated with NTR for 15min, CM-NO 2 displayed a ~90-fold fluorescence enhancement at 505nm and the maximal TP action cross-section value after reaction was detected and calculated to be 200 GM at 760nm. The probe exhibited excellent properties such as high sensitivity, high selectivity, low cytotoxicity, and high photostability. Moreover, the probe was utilized to image the tumor hypoxia in live HeLa cells. Finally, using the CM-NO 2 to image NTR in tissues was demonstrated. Copyright © 2018 Elsevier B.V. All rights reserved.

177Lu-3BP-227 for Neurotensin Receptor 1-Targeted Therapy of Metastatic Pancreatic Adenocarcinoma: First Clinical Results.

PubMed

Baum, Richard P; Singh, Aviral; Schuchardt, Christiane; Kulkarni, Harshad R; Klette, Ingo; Wiessalla, Stefan; Osterkamp, Frank; Reineke, Ulrich; Smerling, Christiane

2018-05-01

Neurotensin receptor 1 (NTR1) is overexpressed in ductal pancreatic adenocarcinoma, which is still one of the deadliest cancers, with a very poor prognosis. Eligible patients were offered salvage radiopharmaceutical therapy with the novel NTR1 antagonist 177 Lu-3BP-227. Methods: Six patients with confirmed ductal pancreatic adenocarcinoma who had exhausted all other treatment options received 177 Lu-3BP-227 for evaluation of NTR1 expression in vivo. Three patients received treatment activities of 5.1-7.5 GBq. Results: Administration of 177 Lu-3BP-227 was well tolerated by all patients. The kidneys were identified as the dose-limiting organ. The most severe adverse event was reversible grade 2 anemia. One patient achieved a partial response and experienced significant improvement of symptoms and quality of life. This patient survived 13 mo from diagnosis and 11 mo from the start of 177 Lu-3BP-227 therapy. Conclusion: This initial report provides clinical evidence of the feasibility of treatment of ductal pancreatic adenocarcinoma using 177 Lu-3BP-227. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Neural differentiation promoted by truncated trkC receptors in collaboration with p75(NTR).

PubMed

Hapner, S J; Boeshore, K L; Large, T H; Lefcort, F

1998-09-01

trkC receptors, which serve critical functions during the development of the nervous system, are alternatively spliced to yield isoforms containing the catalytic tyrosine kinase domain (TK+) and truncated isoforms which lack this domain (TK-). To test for potential differences in their roles during early stages of neural development, TK+ and TK- isoforms were ectopically expressed in cultures of neural crest, the stem cell population that gives rise to the vast majority of the peripheral nervous system. NT-3 activation of ectopically expressed trkC TK+ receptors promoted both proliferation of neural crest cells and neuronal differentiation. Strikingly, the trkC TK- isoform was significantly more effective at promoting neuronal differentiation, but had no effect on proliferation. Furthermore, the trkC TK- response was dependent on a conserved receptor cytoplasmic domain and required the participation of the p75(NTR) neurotrophin receptor. Antibody-mediated receptor dimerization of TK+ receptors, but not TK- receptors, was sufficient to stimulate differentiation. These data identify a phenotypic response to activation of the trkC TK- receptor and demonstrate a functional interaction with p75(NTR), indicating there may be multiple trkC receptor-mediated systems guiding neuronal differentiation. Copyright 1998 Academic Press.

Non-thermal recombination - a neglected source of flare hard X-rays and fast electron diagnostics (Corrigendum)

NASA Astrophysics Data System (ADS)

Brown, J. C.; Mallik, P. C. V.; Badnell, N. R.

2010-06-01

Brown and Mallik (BM) recently claimed that non-thermal recombination (NTR) can be a dominant source of flare hard X-rays (HXRs) from hot coronal and chromospheric sources. However, major discrepancies between the thermal continua predicted by BM and by the Chianti database as well as RHESSI flare data, led us to discover substantial errors in the heuristic expression used by BM to extend the Kramers expressions beyond the hydrogenic case. Here we present the relevant corrected expressions and show the key modified results. We conclude that, in most cases, NTR emission was overestimated by a factor of 1-8 by BM but is typically still large enough (as much as 20-30% of the total emission) to be very important for electron spectral inference and detection of electron spectral features such as low energy cut-offs since the recombination spectra contain sharp edges. For extreme temperature regimes and/or if the Fe abundance were as high as some values claimed, NTR could even be the dominant source of flare HXRs, reducing the electron number and energy budget, problems such as in the extreme coronal HXR source cases reported by e.g. Krucker et al.

Unconventional Natural Gas Development and Birth Outcomes in Pennsylvania, USA.

PubMed

Casey, Joan A; Savitz, David A; Rasmussen, Sara G; Ogburn, Elizabeth L; Pollak, Jonathan; Mercer, Dione G; Schwartz, Brian S

2016-03-01

Unconventional natural gas development has expanded rapidly. In Pennsylvania, the number of producing wells increased from 0 in 2005 to 3,689 in 2013. Few publications have focused on unconventional natural gas development and birth outcomes. We performed a retrospective cohort study using electronic health record data on 9,384 mothers linked to 10,946 neonates in the Geisinger Health System from January 2009 to January 2013. We estimated cumulative exposure to unconventional natural gas development activity with an inverse-distance squared model that incorporated distance to the mother's home; dates and durations of well pad development, drilling, and hydraulic fracturing; and production volume during the pregnancy. We used multilevel linear and logistic regression models to examine associations between activity index quartile and term birth weight, preterm birth, low 5-minute Apgar score and small size for gestational age birth, while controlling for potential confounding variables. In adjusted models, there was an association between unconventional natural gas development activity and preterm birth that increased across quartiles, with a fourth quartile odds ratio of 1.4 (95% confidence interval = 1.0, 1.9). There were no associations of activity with Apgar score, small for gestational age birth, or term birth weight (after adjustment for year). In a posthoc analysis, there was an association with physician-recorded high-risk pregnancy identified from the problem list (fourth vs. first quartile, 1.3 [95% confidence interval = 1.1, 1.7]). Prenatal residential exposure to unconventional natural gas development activity was associated with two pregnancy outcomes, adding to evidence that unconventional natural gas development may impact health.See Video Abstract at http://links.lww.com/EDE/B14.

GaN-based light-emitting diodes on various substrates: a critical review.

PubMed

Li, Guoqiang; Wang, Wenliang; Yang, Weijia; Lin, Yunhao; Wang, Haiyan; Lin, Zhiting; Zhou, Shizhong

2016-05-01

GaN and related III-nitrides have attracted considerable attention as promising materials for application in optoelectronic devices, in particular, light-emitting diodes (LEDs). At present, sapphire is still the most popular commercial substrate for epitaxial growth of GaN-based LEDs. However, due to its relatively large lattice mismatch with GaN and low thermal conductivity, sapphire is not the most ideal substrate for GaN-based LEDs. Therefore, in order to obtain high-performance and high-power LEDs with relatively low cost, unconventional substrates, which are of low lattice mismatch with GaN, high thermal conductivity and low cost, have been tried as substitutes for sapphire. As a matter of fact, it is not easy to obtain high-quality III-nitride films on those substrates for various reasons. However, by developing a variety of techniques, distincts progress has been made during the past decade, with high-performance LEDs being successfully achieved on these unconventional substrates. This review focuses on state-of-the-art high-performance GaN-based LED materials and devices on unconventional substrates. The issues involved in the growth of GaN-based LED structures on each type of unconventional substrate are outlined, and the fundamental physics behind these issues is detailed. The corresponding solutions for III-nitride growth, defect control, and chip processing for each type of unconventional substrate are discussed in depth, together with a brief introduction to some newly developed techniques in order to realize LED structures on unconventional substrates. This is very useful for understanding the progress in this field of physics. In this review, we also speculate on the prospects for LEDs on unconventional substrates.

ON A GENERALIZED SELF-SIMILARITY IN THE p-ADIC FIELD

NASA Astrophysics Data System (ADS)

Mukhamedov, Farrukh; Khakimov, Otabek

2016-08-01

In the present paper, we introduce a new set which defines a generalized self-similar set for contractive functions {fi}i=1N on the unit ball ℤp of p-adic numbers. This set is called unconventional limit set. We prove that the unconventional limit set is compact, perfect and uniformly disconnected. Moreover, we provide an example of two contractions for which the corresponding unconventional limiting set is quasi-symmetrically equivalent to the symbolic Cantor set.

U.S. Joint Special Operations Forces: Two Few, Overworked, Young, Homogenous & Macho to Fulfill the Unconventional Demands of the Long War?

DTIC Science & Technology

2008-05-28

OVERWORKED , YOUNG, HOMOGENOUS, & MACHO TO FULFILL THE UNCONVENTIONAL DEMANDS OF THE LONG WAR? SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR...U.S. Joint Special Operations Forces: Two Few, Overworked , Young, Homogenous & Macho to Fulfill the Unconventional Demands of the Long War? 5a...to be the targets of nearly daily mortar, improvised explosive devices (IEDs), and occasional suicide vehicle-borne IED (SVBIED) attacks. It

Design and life-cycle considerations for unconventional-reservoir wells

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

Miskimins, J.L.

2009-05-15

This paper provides an overview of design and life-cycle considerations for certain unconventional-reservoir wells. An overview of unconventional-reservoir definitions is provided. Well design and life-cycle considerations are addressed from three aspects: upfront reservoir development, initial well completion, and well-life and long-term considerations. Upfront-reservoir-development issues discussed include well spacing, well orientation, reservoir stress orientations, and tubular metallurgy. Initial-well-completion issues include maximum treatment pressures and rates, treatment diversion, treatment staging, flowback and cleanup, and dewatering needs. Well-life and long-term discussions include liquid loading, corrosion, refracturing and associated fracture reorientation, and the cost of abandonment. These design considerations are evaluated with case studiesmore » for five unconventional-reservoir types: shale gas (Barnett shale), tight gas (Jonah feld), tight oil (Bakken play), coalbed methane (CBM) (San Juan basin), and tight heavy oil (Lost Hills field). In evaluating the life cycle and design of unconventional-reservoir wells, 'one size' does not fit all and valuable knowledge and a shortening of the learning curve can be achieved for new developments by studying similar, more-mature fields.« less

The health implications of unconventional natural gas development in Pennsylvania.

PubMed

Peng, Lizhong; Meyerhoefer, Chad; Chou, Shin-Yi

2018-06-01

We investigate the health impacts of unconventional natural gas development of Marcellus shale in Pennsylvania between 2001 and 2013 by merging well permit data from the Pennsylvania Department of Environmental Protection with a database of all inpatient hospital admissions. After comparing changes in hospitalization rates over time for air pollution-sensitive diseases in counties with unconventional gas wells to changes in hospitalization rates in nonwell counties, we find a significant association between shale gas development and hospitalizations for pneumonia among the elderly, which is consistent with higher levels of air pollution resulting from unconventional natural gas development. We note that the lack of any detectable impact of shale gas development on younger populations may be due to unobserved factors contemporaneous with drilling, such as migration. Copyright © 2018 John Wiley & Sons, Ltd.

Affordable Development and Demonstration of a Small NTR Engine and Stage: How Small is Big Enough?

NASA Technical Reports Server (NTRS)

Borowski, S. K.; Sefcik, R. J.; Fittje, J. E.; McCurdy, D. R.; Qualls, A. L.; Schnitzler, B. G.; Werner, J.; Weitzberg, A.; Joyner, C. R.

2015-01-01

In FY11, NASA formulated a plan for Nuclear Thermal Propulsion (NTP) development that included Foundational Technology Development followed by system-level Technology Demonstrations The ongoing NTP project, funded by NASAs Advanced Exploration Systems (AES) program, is focused on Foundational Technology Development and includes 5 key task activities:(1) Fuel element fabrication and non-nuclear validation testing of heritage fuel options;(2) Engine conceptual design;(3) Mission analysis and engine requirements definition;(4) Identification of affordable options for ground testing; and(5) Formulation of an affordable and sustainable NTP development program Performance parameters for Point of Departure designs for a small criticality-limited and full size 25 klbf-class engine were developed during FYs 13-14 using heritage fuel element designs for both RoverNERVA Graphite Composite (GC) and Ceramic Metal (Cermet) fuel forms To focus the fuel development effort and maximize use of its resources, the AES program decided, in FY14, that a leader-follower down selection between GC and cermet fuel was required An Independent Review Panel (IRP) was convened by NASA and tasked with reviewing the available fuel data and making a recommendation to NASA. In February 2015, the IRP recommended and the AES program endorsed GC as the leader fuel In FY14, a preliminary development schedule DDTE plan was produced by GRC, DOE industry for the AES program. Assumptions, considerations and key task activities are presented here Two small (7.5 and 16.5 klbf) engine sizes were considered for ground and flight technology demonstration within a 10-year timeframe; their ability to support future human exploration missions was also examined and a recommendation on a preferred size is provided.

Theory of disordered unconventional superconductors

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

Keles, A.; Andreev, A. V.; Spivak, B. Z., E-mail: spivak@uw.edu

In contrast to conventional s-wave superconductivity, unconventional (e.g., p- or d-wave) superconductivity is strongly suppressed even by relatively weak disorder. Upon approaching the superconductormetal transition, the order parameter amplitude becomes increasingly inhomogeneous, leading to effective granularity and a phase ordering transition described by the Mattis model of spin glasses. One consequence of this is that at sufficiently low temperatures, between the clean unconventional superconducting and the diffusive metallic phases, there is necessarily an intermediate superconducting phase that exhibits s-wave symmetry on macroscopic scales.

PerSEUS: Ultra-Low-Power High Performance Computing for Plasma Simulations

NASA Astrophysics Data System (ADS)

Doxas, I.; Andreou, A.; Lyon, J.; Angelopoulos, V.; Lu, S.; Pritchett, P. L.

2017-12-01

Peta-op SupErcomputing Unconventional System (PerSEUS) aims to explore the use for High Performance Scientific Computing (HPC) of ultra-low-power mixed signal unconventional computational elements developed by Johns Hopkins University (JHU), and demonstrate that capability on both fluid and particle Plasma codes. We will describe the JHU Mixed-signal Unconventional Supercomputing Elements (MUSE), and report initial results for the Lyon-Fedder-Mobarry (LFM) global magnetospheric MHD code, and a UCLA general purpose relativistic Particle-In-Cell (PIC) code.

Investigating operation at geometrically unconventional intersections.

DOT National Transportation Integrated Search

2014-08-01

This report documents the development of decision assistance curves (DAC) for unconventional intersections, particularly : median U-turns (MUT), continuous flow intersections (CFI), and jughandles. The operational measure of effectiveness : such as d...

Unconventional Oil and Gas Extraction Effluent Guidelines

EPA Pesticide Factsheets

Overview and documents for the Unconventional Oil and Gas Extraction Pretreatment Standards final rule (6/28/2016), direct final rule (Sept. 2016) and proposed rule (Sept. 2016). 40 CFR Part 435, Subpart C.

Quantity of flowback and produced waters from unconventional oil and gas exploration.

PubMed

Kondash, Andrew J; Albright, Elizabeth; Vengosh, Avner

2017-01-01

The management and disposal of flowback and produced waters (FP water) is one of the greatest challenges associated with unconventional oil and gas development. The development and production of unconventional natural gas and oil is projected to increase in the coming years, and a better understanding of the volume and quality of FP water is crucial for the safe management of the associated wastewater. We analyzed production data using multiple statistical methods to estimate the total FP water generated per well from six of the major unconventional oil and gas formations in the United States. The estimated median volume ranges from 1.7 to 14.3millionL (0.5 to 3.8milliongal) of FP per well over the first 5-10years of production. Using temporal volume production and water quality data, we show a rapid increase of the salinity associated with a decrease of FP production rates during the first months of unconventional oil and gas production. Based on mass-balance calculations, we estimate that only 4-8% of FP water is composed of returned hydraulic fracturing fluids, while the remaining 92-96% of FP water is derived from naturally occurring formation brines that is extracted together with oil and gas. The salinity and chemical composition of the formation brines are therefore the main limiting factors for beneficial reuse of unconventional oil and gas wastewater. Copyright © 2016 Elsevier B.V. All rights reserved.

A Comparison of the Impacts of Wind Energy and Unconventional Gas Development on Land-use and Ecosystem Services: An Example from the Anadarko Basin of Oklahoma, USA.

PubMed

Davis, Kendall M; Nguyen, Michael N; McClung, Maureen R; Moran, Matthew D

2018-05-01

The United States energy industry is transforming with the rapid development of alternative energy sources and technological advancements in fossil fuels. Two major changes include the growth of wind turbines and unconventional oil and gas. We measured land-use impacts and associated ecosystem services costs of unconventional gas and wind energy development within the Anadarko Basin of the Oklahoma Woodford Shale, an area that has experienced large increases in both energy sectors. Unconventional gas wells developed three times as much land compared to wind turbines (on a per unit basis), resulting in higher ecosystem services costs for gas. Gas wells had higher impacts on intensive agricultural lands (i.e., row crops) compared to wind turbines that had higher impacts on natural grasslands/pastures. Because wind turbines produced on average less energy compared to gas wells, the average land-use-related ecosystem cost per gigajoule of energy produced was almost the same. Our results demonstrate that both unconventional gas and wind energy have substantial impacts on land use, which likely affect wildlife populations and land-use-related ecosystem services. Although wind energy does not have the associated greenhouse gas emissions, we suggest that the direct impacts on ecosystems in terms of land use are similar to unconventional fossil fuels. Considering the expected rapid global expansion of these two forms of energy production, many ecosystems are likely to be at risk.

Hidden magnetism and quantum criticality in the heavy fermion superconductor CeRhIn5.

PubMed

Park, Tuson; Ronning, F; Yuan, H Q; Salamon, M B; Movshovich, R; Sarrao, J L; Thompson, J D

2006-03-02

With only a few exceptions that are well understood, conventional superconductivity does not coexist with long-range magnetic order (for example, ref. 1). Unconventional superconductivity, on the other hand, develops near a phase boundary separating magnetically ordered and magnetically disordered phases. A maximum in the superconducting transition temperature T(c) develops where this boundary extrapolates to zero Kelvin, suggesting that fluctuations associated with this magnetic quantum-critical point are essential for unconventional superconductivity. Invariably, though, unconventional superconductivity masks the magnetic phase boundary when T < T(c), preventing proof of a magnetic quantum-critical point. Here we report specific-heat measurements of the pressure-tuned unconventional superconductor CeRhIn5 in which we find a line of quantum-phase transitions induced inside the superconducting state by an applied magnetic field. This quantum-critical line separates a phase of coexisting antiferromagnetism and superconductivity from a purely unconventional superconducting phase, and terminates at a quantum tetracritical point where the magnetic field completely suppresses superconductivity. The T --> 0 K magnetic field-pressure phase diagram of CeRhIn5 is well described with a theoretical model developed to explain field-induced magnetism in the high-T(c) copper oxides, but in which a clear delineation of quantum-phase boundaries has not been possible. These experiments establish a common relationship among hidden magnetism, quantum criticality and unconventional superconductivity in copper oxides and heavy-electron systems such as CeRhIn5.

A network of molecular switches controls the activation of the two-component response regulator NtrC

NASA Astrophysics Data System (ADS)

Vanatta, Dan K.; Shukla, Diwakar; Lawrenz, Morgan; Pande, Vijay S.

2015-06-01

Recent successes in simulating protein structure and folding dynamics have demonstrated the power of molecular dynamics to predict the long timescale behaviour of proteins. Here, we extend and improve these methods to predict molecular switches that characterize conformational change pathways between the active and inactive state of nitrogen regulatory protein C (NtrC). By employing unbiased Markov state model-based molecular dynamics simulations, we construct a dynamic picture of the activation pathways of this key bacterial signalling protein that is consistent with experimental observations and predicts new mutants that could be used for validation of the mechanism. Moreover, these results suggest a novel mechanistic paradigm for conformational switching.

Unconventional Transport Routes of Soluble and Membrane Proteins and Their Role in Developmental Biology

PubMed Central

Pompa, Andrea; De Marchis, Francesca; Pallotta, Maria Teresa; Benitez-Alfonso, Yoselin; Jones, Alexandra; Schipper, Kerstin; Moreau, Kevin; Žárský, Viktor; Di Sansebastiano, Gian Pietro; Bellucci, Michele

2017-01-01

Many proteins and cargoes in eukaryotic cells are secreted through the conventional secretory pathway that brings proteins and membranes from the endoplasmic reticulum to the plasma membrane, passing through various cell compartments, and then the extracellular space. The recent identification of an increasing number of leaderless secreted proteins bypassing the Golgi apparatus unveiled the existence of alternative protein secretion pathways. Moreover, other unconventional routes for secretion of soluble or transmembrane proteins with initial endoplasmic reticulum localization were identified. Furthermore, other proteins normally functioning in conventional membrane traffic or in the biogenesis of unique plant/fungi organelles or in plasmodesmata transport seem to be involved in unconventional secretory pathways. These alternative pathways are functionally related to biotic stress and development, and are becoming more and more important in cell biology studies in yeast, mammalian cells and in plants. The city of Lecce hosted specialists working on mammals, plants and microorganisms for the inaugural meeting on “Unconventional Protein and Membrane Traffic” (UPMT) during 4–7 October 2016. The main aim of the meeting was to include the highest number of topics, summarized in this report, related to the unconventional transport routes of protein and membranes. PMID:28346345

Impact of Unconventional Gas Technology in the Annual Energy Outlook 2000

EIA Publications

2000-01-01

This paper describes the methodology used in the National Energy Modeling System (NEMS) to represent unconventional gas technologies and their impacts on projections in the Annual Energy Outlook 2000 (AEO2000).

Silicon solar cell process development, fabrication and analysis

NASA Technical Reports Server (NTRS)

Minahan, J. A.

1981-01-01

The fabrication of solar cells from several unconventional silicon materials is described, and cell performance measured and analyzed. Unconventional materials evaluated are edge defined film fed grown (EFG), heat exchanger method (HEM), dendritic web grown, and continuous CZ silicons. Resistivity, current voltage, and spectral sensitivity of the cells were measured. Current voltage was measured under AM0 and AM1 conditions. Maximum conversion efficiencies of cells fabricated from these and other unconventional silicons were compared and test results analyzed. The HEM and continuous CZ silicon were found to be superior to silicon materials considered previously.

REVIEW ARTICLE: Unconventional isotope effects in the high-temperature cuprate superconductors

NASA Astrophysics Data System (ADS)

Zhao, Guo-meng; Keller, H.; Conder, K.

2001-07-01

We review various isotope effects in the high-Tc cuprate superconductors to assess the role of the electron-phonon interaction in the basic physics of these materials. Of particular interest are the unconventional isotope effects on the supercarrier mass, on the charge-stripe formation temperature, on the pseudogap formation temperature, on the electron paramagnetic resonance (EPR) linewidth, on the spin-glass freezing temperature and on the antiferromagnetic ordering temperature. The observed unconventional isotope effects strongly suggest that lattice vibrations play an important role in the microscopic pairing mechanism of high-temperature superconductivity.

Radon in unconventional natural gas from gulf coast geopressured-geothermal reservoirs

USGS Publications Warehouse

Kraemer, T.F.

1986-01-01

Radon-222 has been measured in natural gas produced from experimental geopressured-geothermal test wells. Comparison with published data suggests that while radon activity of this unconventional natural gas resource is higher than conventional gas produced in the gulf coast, it is within the range found for conventional gas produced throughout the U.S. A method of predicting the likely radon activity of this unconventional gas is described on the basis of the data presented, methane solubility, and known or assumed reservoir conditions of temperature, fluid pressure, and formation water salinity.

Characteristics Study of In-Situ Capacitive Sensor for Monitoring Lubrication Oil Debris

PubMed Central

Han, Zhibin; Wang, Yishou; Qing, Xinlin

2017-01-01

As an essential part of engine health monitoring (EHM), online lubrication oil debris monitoring has recently received great attention for the assessment of rotating and reciprocating parts in aero-engines, due to its high integration, low cost and safe characteristics. However, it is be a challenge to find a suitable sensor operating in such a complex environment. We present an unconventional novel approach, in which a cylinder capacitive sensor is designed and integrated with the pipeline of an engine lubrication system, so that the capacitive sensor can effectively detect changes in the lubrication oil condition. In this paper, an attempt to illustrate the performance characteristics of the developed cylinder capacitive sensor is made, through an experiment system that simulates a real scenario of a lubrication oil system. The main aim of the research was to qualitatively describe the relationship between the sensor parameter and the lubrication oil debris. In addition, the effect of the temperature and flow rate of the lubrication oil on capacitance change was performed by several experiments and we figured out a compensation method. The experimental results demonstrated that the cylinder capacitive sensor can potentially be used for lubrication oil debris monitoring of the health condition of an aero-engine. PMID:29292748

Direct Quantification of Methane Emissions Across the Supply Chain: Identification of Mitigation Targets

NASA Astrophysics Data System (ADS)

Darzi, M.; Johnson, D.; Heltzel, R.; Clark, N.

2017-12-01

Researchers at West Virginia University's Center for Alternative Fuels, Engines, and Emissions have recently participated in a variety of studies targeted at direction quantification of methane emissions from across the natural gas supply chain. These studies included assessing methane emissions from heavy-duty vehicles and their fuel stations, active unconventional well sites - during both development and production, natural gas compression and storage facilities, natural gas engines - both large and small, two- and four-stroke, and low-throughput equipment associated with coal bed methane wells. Engine emissions were sampled using conventional instruments such as Fourier transform infrared spectrometers and heated flame ionization detection analyzers. However, to accurately quantify a wide range of other sources beyond the tailpipe (both leaks and losses), a full flow sampling system was developed, which included an integrated cavity-enhanced absorption spectrometer. Through these direct quantification efforts and analysis major sources of methane emissions were identified. Technological solutions and best practices exist or could be developed to reduce methane emissions by focusing on the "lowest-hanging fruit." For example, engine crankcases from across the supply chain should employ vent mitigation systems to reduce methane and other emissions. An overview of the direct quantification system and various campaign measurements results will be presented along with the identification of other targets for additional mitigation.

Genetic variation in N- and C-terminal regions of bovine DNAJA1 heat shock protein gene in African, Asian and American cattle.

PubMed

Ajayi, Oyeyemi O; Peters, Sunday O; De Donato, Marcos; Mujibi, F Denis; Khan, Waqas A; Hussain, Tanveer; Babar, Masroor E; Imumorin, Ikhide G; Thomas, Bolaji N

2018-01-01

DNAJA1 or heat shock protein 40 (Hsp40) is associated with heat adaptation in various organisms. We amplified and sequenced a total of 1,142 bp of bovine Hsp40 gene representing the critical N-terminal (NTR) and C-terminal (CTR) regions in representative samples of African, Asian and American cattle breeds. Eleven and 9 different haplotypes were observed in the NTR in Asian and African breeds respectively while in American Brangus, only two mutations were observed resulting in two haplotypes. The CTR appears to be highly conserved between cattle and yak. In-silico functional analysis with PANTHER predicted putative deleterious functional impact of c.161 T>A; p. V54Q while alignment of bovine and human NTR-J domains revealed that p.Q19H, p.E20Q and p. E21X mutations occurred in helix 2 and p.V54Q missense mutation occurred in helix 3 respectively. The 124 bp insertion found in the yak DNAJA1 ortholog may have significant functional relevance warranting further investigation. Our results suggest that these genetic differences may be concomitant with population genetic history and possible functional consequences for climate adaptation in bovidae.

cis-acting RNA elements required for replication of bovine viral diarrhea virus-hepatitis C virus 5' nontranslated region chimeras.

PubMed Central

Frolov, I; McBride, M S; Rice, C M

1998-01-01

Pestiviruses, such as bovine viral diarrhea virus (BVDV), share many similarities with hepatitis C virus (HCV) yet are more amenable to virologic and genetic analysis. For both BVDV and HCV, translation is initiated via an internal ribosome entry site (IRES). Besides IRES function, the viral 5' nontranslated regions (NTRs) may also contain cis-acting RNA elements important for viral replication. A series of chimeric RNAs were used to examine the function of the BVDV 5' NTR. Our results show that: (1) the HCV and the encephalomyocarditis virus (EMCV) IRES element can functionally replace that of BVDV; (2) two 5' terminal hairpins in BVDV genomic RNA are important for efficient replication; (3) replacement of the entire BVDV 5' NTR with those of HCV or EMCV leads to severely impaired replication; (4) such replacement chimeras are unstable and efficiently replicating pseudorevertants arise; (5) pseudorevertant mutations involve deletion of 5' sequences and/or acquisition of novel 5' sequences such that the 5' terminal 3-4 bases of BVDV genome RNA are restored. Besides providing new insight into functional elements in the BVDV 5' NTR, these chimeras may prove useful as pestivirus vaccines and for screening and evaluation of anti-HCV IRES antivirals. PMID:9814762

ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75NTR-dependent mechanism

PubMed Central

Howard, Laura; Wyatt, Sean; Nagappan, Guhan; Davies, Alun M.

2013-01-01

The somatosensory and sympathetic innervation of the vertebrate head is derived principally from the neurons of trigeminal and superior cervical ganglia (SCG), respectively. During development, the survival of both populations of neurons and the terminal growth and branching of their axons in the tissues they innervate is regulated by the supply of nerve growth factor (NGF) produced by these tissues. NGF is derived by proteolytic cleavage of a large precursor protein, proNGF, which is recognised to possess distinctive biological functions. Here, we show that proNGF promotes profuse neurite growth and branching from cultured postnatal mouse SCG neurons. In marked contrast, proNGF does not promote the growth of trigeminal neurites. Studies using compartment cultures demonstrated that proNGF acts locally on SCG neurites to promote growth. The neurite growth-promoting effect of proNGF is not observed in SCG neurons cultured from p75NTR-deficient mice, and proNGF does not phosphorylate the NGF receptor tyrosine kinase TrkA. These findings suggest that proNGF selectively promotes the growth of neurites from a subset of NGF-responsive neurons by a p75NTR-dependent mechanism during postnatal development when the axons of these neurons are ramifying within their targets in vivo. PMID:23633509

Blocking p75 (NTR) receptors alters polyinnervationz of neuromuscular synapses during development.

PubMed

Garcia, Neus; Tomàs, Marta; Santafe, Manel M; Lanuza, Maria A; Besalduch, Nuria; Tomàs, Josep

2011-09-01

High-resolution immunohistochemistry shows that the receptor protein p75(NTR) is present in the nerve terminal, muscle cell, and glial Schwann cell at the neuromuscular junction (NMJ) of postnatal rats (P4-P6) during the synapse elimination period. Blocking the receptor with the antibody anti-p75-192-IgG (1-5 μg/ml, 1 hr) results in reduced endplate potentials (EPPs) in mono- and polyinnervated synapses ex vivo, but the mean number of functional inputs per NMJ does not change for as long as 3 hr. Incubation with exogenous brain-derived neurotrophic factor (BDNF) for 1 hr (50 nM) resulted in a significant increase in the size of the EPPs in all nerve terminals, and preincubation with anti-p75-192-IgG prevented this potentiation. Long exposure (24 hr) in vivo of the NMJs to the antibody anti-p75-192-IgG (1-2 μg/ml) results in a delay of postnatal synapse elimination and even some regrowth of previously withdrawn axons, but also in some acceleration of the morphologic maturation of the postsynaptic nicotinic acetylcholine receptor (nAChR) clusters. The results indicate that p75(NTR) is involved in both ACh release and axonal retraction during postnatal axonal competition and synapse elimination. Copyright © 2011 Wiley-Liss, Inc.

Coalbed methane: Clean energy for the world

USGS Publications Warehouse

Ahmed, A.-J.; Johnston, S.; Boyer, C.; Lambert, S.W.; Bustos, O.A.; Pashin, J.C.; Wray, A.

2009-01-01

Coalbed methane (CBM) has the potential to emerge as a significant clean energy resource. It also has the potential to replace other diminishing hydrocarbon reserves. The latest developments in technologies and methodologies are playing a key role in harnessing this unconventional resource. Some of these developments include adaptations of existing technologies used in conventional oil and gas generations, while others include new applications designed specifically to address coal's unique properties. Completion techniques have been developed that cause less damage to the production mechanisms of coal seams, such as those occurring during cementing operations. Stimulation fluids have also been engineered specifically to enhance CBM production. Deep coal deposits that remain inaccessible by conventional mining operations offer CBM development opportunities.

Propulsion Noise Reduction Research in the NASA Advanced Air Transport Technology Project

NASA Technical Reports Server (NTRS)

Van Zante, Dale; Nark, Douglas; Fernandez, Hamilton

2017-01-01

The Aircraft Noise Reduction (ANR) sub-project is focused on the generation, development, and testing of component noise reduction technologies progressing toward the NASA far term noise goals while providing associated near and mid-term benefits. The ANR sub-project has efforts in airframe noise reduction, propulsion (including fan and core) noise reduction, acoustic liner technology, and propulsion airframe aeroacoustics for candidate conventional and unconventional aircraft configurations. The current suite of propulsion specific noise research areas is reviewed along with emerging facility and measurement capabilities. In the longer term, the changes in engine and aircraft configuration will influence the suite of technologies necessary to reduce noise in next generation systems.

Just fracking: a distributive environmental justice analysis of unconventional gas development in Pennsylvania, USA

NASA Astrophysics Data System (ADS)

Clough, Emily; Bell, Derek

2016-02-01

This letter presents a distributive environmental justice analysis of unconventional gas development in the area of Pennsylvania lying over the Marcellus Shale, the largest shale gas formation in play in the United States. The extraction of shale gas using unconventional wells, which are hydraulically fractured (fracking), has increased dramatically since 2005. As the number of wells has grown, so have concerns about the potential public health effects on nearby communities. These concerns make shale gas development an environmental justice issue. This letter examines whether the hazards associated with proximity to wells and the economic benefits of shale gas production are fairly distributed. We distinguish two types of distributive environmental justice: traditional and benefit sharing. We ask the traditional question: are there a disproportionate number of minority or low-income residents in areas near to unconventional wells in Pennsylvania? However, we extend this analysis in two ways: we examine income distribution and level of education; and we compare before and after shale gas development. This contributes to discussions of benefit sharing by showing how the income distribution of the population has changed. We use a binary dasymetric technique to remap the data from the 2000 US Census and the 2009-2013 American Communities Survey and combine that data with a buffer containment analysis of unconventional wells to compare the characteristics of the population living nearer to unconventional wells with those further away before and after shale gas development. Our analysis indicates that there is no evidence of traditional distributive environmental injustice: there is not a disproportionate number of minority or low-income residents in areas near to unconventional wells. However, our analysis is consistent with the claim that there is benefit sharing distributive environmental injustice: the income distribution of the population nearer to shale gas wells has not been transformed since shale gas development.

Fatty acid profile of unconventional oilseeds.

PubMed

Sabikhi, Latha; Sathish Kumar, M H

2012-01-01

The continued increase in human population has resulted in the rise in the demand as well as the price of edible oils, leading to the search for alternative unconventional sources of oils, particularly in the developing countries. There are hundreds of un- or underexplored plant seeds rich in oil suitable for edible or industrial purposes. Many of them are rich in polyunsaturated essential fatty acids, which establish their utility as "healthy oils." Some agrowaste products such as rice bran have gained importance as a potential source of edible oil. Genetic modification has paved the way for increasing the oil yields and improving the fatty acid profiles of traditional as well as unconventional oilseeds. Single cell oils are also novel sources of edible oil. Some of these unconventional oils may have excellent potential for medicinal and therapeutic uses, even if their low oil contents do not promote commercial production as edible oils. Copyright © 2012 Elsevier Inc. All rights reserved.

Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75 NTR in malignancy.

PubMed

Dalley, Andrew J; AbdulMajeed, Ahmad A; Upton, Zee; Farah, Camile S

2013-01-01

Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75(NTR), CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75(NTR) was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75(NTR), CD24 antigens and ALDH activity (ALDEFLUOR(®) assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells. © 2012 John Wiley & Sons A/S.

Molecular characterization of hepatitis A virus strains in a tertiary care health set up in north western India.

PubMed

Singh, Mini Pritam; Majumdar, Manasi; Thapa, Babu Ram; Gupta, Puneet Kumar; Khurana, Jasmine; Budhathoki, Bimal; Ratho, Radha Kanta

2015-02-01

Hepatitis A virus usually causes acute viral hepatitis (AVH) in the paediatric age group with a recent shift in age distribution and disease manifestations like acute liver failure (ALF). This has been attributed to mutations in 5'non-translated region (5'NTR) which affects the viral multiplication. The present study was aimed to carry out the molecular detection and phylogenetic analysis of hepatitis A virus strains circulating in north western India. Serum samples from in patients and those attending out patient department of Pediatric Gastroenterology in a tertiary care hospital in north India during 2007-2011 with clinically suspected AVH were tested for anti-hepatitis A virus (HAV) IgM antibodies. Acute phase serum samples were subjected to nested PCR targeting the 5'NTR region followed by sequencing of the representative strains. A total of 1334 samples were tested, 290 (21.7%) were positive for anti-HAV IgM antibody. Of these, 78 serum samples (< 7 days old) were subjected to PCR and 47.4% (37/78) samples showed the presence of HAV RNA. Children < 15 yr of age accounted for majority (94%) of cases with highest seropositivity during rainy season. Sequencing of 15 representative strains was carried out and the circulating genotype was found to be III A. The nucleotide sequences showed high homology among the strains with a variation ranging from 0.1-1 per cent over the years. An important substitution of G to A at 324 position was shown by both AVH and ALF strains. The cumulative substitution in AVH strains Vs ALF strains as compared to GBM, Indian and prototype strain in the 200-500 region of 5' NTR was comparable. Our results showed hepatitis A still a disease of children with III A as a circulating genotype in this region. The mutations at 5'NTR region warrant further analysis as these affect the structure of internal ribosomal entry site which is important for viral replication.

Initial Operation of the Nuclear Thermal Rocket Element Environmental Simulator

NASA Technical Reports Server (NTRS)

Emrich, William J., Jr.; Pearson, J. Boise; Schoenfeld, Michael P.

2015-01-01

The Nuclear Thermal Rocket Element Environmental Simulator (NTREES) facility is designed to perform realistic non-nuclear testing of nuclear thermal rocket (NTR) fuel elements and fuel materials. Although the NTREES facility cannot mimic the neutron and gamma environment of an operating NTR, it can simulate the thermal hydraulic environment within an NTR fuel element to provide critical information on material performance and compatibility. The NTREES facility has recently been upgraded such that the power capabilities of the facility have been increased significantly. At its present 1.2 MW power level, more prototypical fuel element temperatures nay now be reached. The new 1.2 MW induction heater consists of three physical units consisting of a transformer, rectifier, and inverter. This multiunit arrangement facilitated increasing the flexibility of the induction heater by more easily allowing variable frequency operation. Frequency ranges between 20 and 60 kHz can accommodated in the new induction heater allowing more representative power distributions to be generated within the test elements. The water cooling system was also upgraded to so as to be capable of removing 100% of the heat generated during testing In this new higher power configuration, NTREES will be capable of testing fuel elements and fuel materials at near-prototypic power densities. As checkout testing progressed and as higher power levels were achieved, several design deficiencies were discovered and fixed. Most of these design deficiencies were related to stray RF energy causing various components to encounter unexpected heating. Copper shielding around these components largely eliminated these problems. Other problems encountered involved unexpected movement in the coil due to electromagnetic forces and electrical arcing between the coil and a dummy test article. The coil movement and arcing which were encountered during the checkout testing effectively destroyed the induction coil in use at the time and resulted in NTREES being out of commission for a couple of months while a new stronger coil was procured. The new coil includes several additional pieces of support structure to prevent coil movement in the future. In addition, new insulating test article support components have been fabricated to prevent unexpected arcing to the test articles. Additional activities are also now underway to address ways in which the radial temperature profiles across test articles may be controlled such that they are more prototypical of what they would encounter in an operating nuclear engine. The causes of the temperature distribution problem are twofold. First, the fuel element test article is isolated in NTREES as opposed to being in the midst of many other mostly identical fuel elements in a nuclear engine. As a result, the fuel element heat flux boundary conditions in NTREES are far from adiabatic as would normally be the case in a reactor. Second, induction heating skews the power distribution such that power is preferentially deposited near the outside of the fuel element. Nuclear heating, conversely, deposits its power much more uniformly throughout the fuel element. Current studies are now looking at various schemes to adjust the amount of thermal radiation emitted from the fuel element surface so as to essentially vary the thermal boundary conditions on the test article. It is hoped that by properly adjusting the thermal boundary conditions on the fuel element test article, it may be possible to substantially correct for the inappropriate radial power distributions resulting from the induction heating so as to yield a more nearly correct temperature distribution throughout the fuel element.

Nanowires Bending over Backward from Strain Partitioning in Asymmetric Core-Shell Heterostructures.

PubMed

Lewis, Ryan B; Corfdir, Pierre; Küpers, Hanno; Flissikowski, Timur; Brandt, Oliver; Geelhaar, Lutz

2018-04-11

The flexibility and quasi-one-dimensional nature of nanowires offer wide-ranging possibilities for novel heterostructure design and strain engineering. In this work, we realize arrays of extremely and controllably bent nanowires comprising lattice-mismatched and highly asymmetric core-shell heterostructures. Strain sharing across the nanowire heterostructures is sufficient to bend vertical nanowires over backward to contact either neighboring nanowires or the substrate itself, presenting new possibilities for designing nanowire networks and interconnects. Photoluminescence spectroscopy on bent-nanowire heterostructures reveals that spatially varying strain fields induce charge carrier drift toward the tensile-strained outside of the nanowires, and that the polarization response of absorbed and emitted light is controlled by the bending direction. This unconventional strain field is employed for light emission by placing an active region of quantum dots at the outer side of a bent nanowire to exploit the carrier drift and tensile strain. These results demonstrate how bending in nanoheterostructures opens up new degrees of freedom for strain and device engineering.

Unconventional Treatments for Vitiligo: Are They (Un) Satisfactory?

PubMed

Gianfaldoni, Serena; Tchernev, Georgi; Lotti, Jacopo; Wollina, Uwe; Satolli, Francesca; Rovesti, Miriam; França, Katlein; Lotti, Torello

2018-01-25

The authors show a brief overview of the vitiligo's unconventional therapies. A part for well-documented effectiveness of L-phenylalanine, PGE2 and antioxidant agents in the treatment of vitiligo, for the other therapeutical approaches more investigations are needed.

Machinability of nickel based alloys using electrical discharge machining process

NASA Astrophysics Data System (ADS)

Khan, M. Adam; Gokul, A. K.; Bharani Dharan, M. P.; Jeevakarthikeyan, R. V. S.; Uthayakumar, M.; Thirumalai Kumaran, S.; Duraiselvam, M.

2018-04-01

The high temperature materials such as nickel based alloys and austenitic steel are frequently used for manufacturing critical aero engine turbine components. Literature on conventional and unconventional machining of steel materials is abundant over the past three decades. However the machining studies on superalloy is still a challenging task due to its inherent property and quality. Thus this material is difficult to be cut in conventional processes. Study on unconventional machining process for nickel alloys is focused in this proposed research. Inconel718 and Monel 400 are the two different candidate materials used for electrical discharge machining (EDM) process. Investigation is to prepare a blind hole using copper electrode of 6mm diameter. Electrical parameters are varied to produce plasma spark for diffusion process and machining time is made constant to calculate the experimental results of both the material. Influence of process parameters on tool wear mechanism and material removal are considered from the proposed experimental design. While machining the tool has prone to discharge more materials due to production of high energy plasma spark and eddy current effect. The surface morphology of the machined surface were observed with high resolution FE SEM. Fused electrode found to be a spherical structure over the machined surface as clumps. Surface roughness were also measured with surface profile using profilometer. It is confirmed that there is no deviation and precise roundness of drilling is maintained.

'Unconventional' coordination chemistry by metal chelating fragments in a metalloprotein active site.

PubMed

Martin, David P; Blachly, Patrick G; Marts, Amy R; Woodruff, Tessa M; de Oliveira, César A F; McCammon, J Andrew; Tierney, David L; Cohen, Seth M

2014-04-09

The binding of three closely related chelators: 5-hydroxy-2-methyl-4H-pyran-4-thione (allothiomaltol, ATM), 3-hydroxy-2-methyl-4H-pyran-4-thione (thiomaltol, TM), and 3-hydroxy-4H-pyran-4-thione (thiopyromeconic acid, TPMA) to the active site of human carbonic anhydrase II (hCAII) has been investigated. Two of these ligands display a monodentate mode of coordination to the active site Zn(2+) ion in hCAII that is not recapitulated in model complexes of the enzyme active site. This unprecedented binding mode in the hCAII-thiomaltol complex has been characterized by both X-ray crystallography and X-ray spectroscopy. In addition, the steric restrictions of the active site force the ligands into a 'flattened' mode of coordination compared with inorganic model complexes. This change in geometry has been shown by density functional computations to significantly decrease the strength of the metal-ligand binding. Collectively, these data demonstrate that the mode of binding by small metal-binding groups can be significantly influenced by the protein active site. Diminishing the strength of the metal-ligand bond results in unconventional modes of metal coordination not found in typical coordination compounds or even carefully engineered active site models, and understanding these effects is critical to the rational design of inhibitors that target clinically relevant metalloproteins.

Beryllofluoride mimics phosphorylation of NtrC and other bacterial response regulators

PubMed Central

Yan, Dalai; Cho, Ho S.; Hastings, Curtis A.; Igo, Michele M.; Lee, Seok-Yong; Pelton, Jeffrey G.; Stewart, Valley; Wemmer, David E.; Kustu, Sydney

1999-01-01

Two-component systems, sensor kinase-response regulator pairs, dominate bacterial signal transduction. Regulation is exerted by phosphorylation of an Asp in receiver domains of response regulators. Lability of the acyl phosphate linkage has limited structure determination for the active, phosphorylated forms of receiver domains. As assessed by both functional and structural criteria, beryllofluoride yields an excellent analogue of aspartyl phosphate in response regulator NtrC, a bacterial enhancer-binding protein. Beryllofluoride also appears to activate the chemotaxis, sporulation, osmosensing, and nitrate/nitrite response regulators CheY, Spo0F, OmpR, and NarL, respectively. NMR spectroscopic studies indicate that beryllofluoride will facilitate both biochemical and structural characterization of the active forms of receiver domains. PMID:10611291

An integrated computer system for analysis, selection, and evaluation of unconventional intersections.

DOT National Transportation Integrated Search

2011-03-01

The emergence of unconventional intersections in the traffic community has been motivated by the notion : of improving service quality with innovative control strategies, such as rerouting the turning movements : or flipping the paths of two traffic ...

Unconventional microfluidics: expanding the discipline.

PubMed

Nawaz, Ahmad Ahsan; Mao, Xiaole; Stratton, Zackary S; Huang, Tony Jun

2013-04-21

Since its inception, the discipline of microfluidics has been harnessed for innovations in the biomedicine/chemistry fields-and to great effect. This success has had the natural side-effect of stereotyping microfluidics as a platform for medical diagnostics and miniaturized lab processes. But microfluidics has more to offer. And very recently, some researchers have successfully applied microfluidics to fields outside its traditional domains. In this Focus article, we highlight notable examples of such "unconventional" microfluidics applications (e.g., robotics, electronics). It is our hope that these early successes in unconventional microfluidics prompt further creativity, and inspire readers to expand the microfluidics discipline.

Water Issues Related to Transitioning from Conventional to Unconventional Oil Production in the Permian Basin.

PubMed

Scanlon, Bridget R; Reedy, Robert C; Male, Frank; Walsh, Mark

2017-09-19

The Permian Basin is being transformed by the "shale revolution" from a major conventional play to the world's largest unconventional play, but water management is critical in this semiarid region. Here we explore evolving issues associated with produced water (PW) management and hydraulic fracturing water demands based on detailed well-by-well analyses. Our results show that although conventional wells produce ∼13 times more water than oil (PW to oil ratio, PWOR = 13), this produced water has been mostly injected back into pressure-depleted oil-producing reservoirs for enhanced oil recovery. Unconventional horizontal wells use large volumes of water for hydraulic fracturing that increased by a factor of ∼10-16 per well and ∼7-10 if normalized by lateral well length (2008-2015). Although unconventional wells have a much lower PWOR of 3 versus 13 from conventional wells, this PW cannot be reinjected into the shale reservoirs but is disposed into nonproducing geologic intervals that could result in overpressuring and induced seismicity. The potential for PW reuse from unconventional wells is high because PW volumes can support hydraulic fracturing water demand based on 2014 data. Reuse of PW with minimal treatment (clean brine) can partially mitigate PW injection concerns while reducing water demand for hydraulic fracturing.

Assessment of unconventional tight-gas resources of the Magallanes Basin Province, Chile, 2015

USGS Publications Warehouse

Schenk, Christopher J.; Charpentier, Ronald R.; Pitman, Janet K.; Tennyson, Marilyn E.; Brownfield, Michael E.; Gaswirth, Stephanie B.; Le, Phuong A.; Leathers-Miller, Heidi M.; Marra, Kristen R.

2016-01-20

Using a geology-based assessment methodology, the U.S. Geological Survey assessed a technically recoverable mean resource of 8.3 trillion cubic feet of unconventional tight gas in the Zona Glauconitica of the Magallanes Basin Province, Chile.

Unconventional eating practices and their health implications.

PubMed

Hanning, R M; Zlotkin, S H

1985-04-01

The authors discuss a number of unconventional or faddist foods and eating practices and their health implications. Among the topics included are vegetarianism, Zen macrobiotic diets, fast foods, junk foods, megavitamins and their toxicity, health foods, fad diets in infancy, and elimination diets.

Effective Control of Chronic γ-Herpesvirus Infection by Unconventional MHC Class Ia–Independent CD8 T Cells

PubMed Central

Tibbetts, Scott A; McClellan, Kelly B

2006-01-01

Control of virus infection is mediated in part by major histocompatibility complex (MHC) Class Ia presentation of viral peptides to conventional CD8 T cells. Although important, the absolute requirement for MHC Class Ia–dependent CD8 T cells for control of chronic virus infection has not been formally demonstrated. We show here that mice lacking MHC Class Ia molecules (Kb−/−xDb−/− mice) effectively control chronic γ-herpesvirus 68 (γHV68) infection via a robust expansion of β2-microglobulin (β2-m)-dependent, but CD1d-independent, unconventional CD8 T cells. These unconventional CD8 T cells expressed: (1) CD8αβ and CD3, (2) cell surface molecules associated with conventional effector/memory CD8 T cells, (3) TCRαβ with a significant Vβ4, Vβ3, and Vβ10 bias, and (4) the key effector cytokine interferon-γ (IFNγ). Unconventional CD8 T cells utilized a diverse TCR repertoire, and CDR3 analysis suggests that some of that repertoire may be utilized even in the presence of conventional CD8 T cells. This is the first demonstration to our knowledge that β2-m–dependent, but Class Ia–independent, unconventional CD8 T cells can efficiently control chronic virus infection, implicating a role for β2-n–dependent non-classical MHC molecules in control of chronic viral infection. We speculate that similar unconventional CD8 T cells may be able to control of other chronic viral infections, especially when viruses evade immunity by inhibiting generation of Class Ia–restricted T cells. PMID:16733540

In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75{sup +} stem cells with dental follicle cell conditioned medium

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

Wen, Xiujie; Liu, Luchuan; Deng, Manjing

Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75{sup +}) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75{sup +} CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features tomore » cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75{sup +} cells, suggesting their differentiation along cementoblast-like lineage. p75{sup +} stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75{sup +}) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75{sup +} CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75{sup +} cells express cementoblast specific mineralization markers. • p75{sup +} cells are pure stem cells and able to differentiate to neuronal cells.« less

Unconventional oil and gas: The role of politics and proximity

NASA Astrophysics Data System (ADS)

Schelly, Chelsea

2016-10-01

Political divisions are important in understanding public perceptions of unconventional oil and natural gas development, but so is proximity to drilling activities. New research highlights that, as geographical distance from development areas increases, political ideology becomes more influential in explaining diverging perceptions.

Energy-Water Modeling and Analysis | Energy Analysis | NREL

Science.gov Websites

future electricity scenarios under cases of limited water availability and electricity sector impacts of Manufacturing Water Use The Water Intensity and Resource Impacts of Unconventional Hydrocarbon Development Impacts of Unconventional Hydrocarbon Development Life Cycle Harmonization Project (Water) Sample

Induced unconventional superconductivity on the surface states of Bi2Te3 topological insulator.

PubMed

Charpentier, Sophie; Galletti, Luca; Kunakova, Gunta; Arpaia, Riccardo; Song, Yuxin; Baghdadi, Reza; Wang, Shu Min; Kalaboukhov, Alexei; Olsson, Eva; Tafuri, Francesco; Golubev, Dmitry; Linder, Jacob; Bauch, Thilo; Lombardi, Floriana

2017-12-08

Topological superconductivity is central to a variety of novel phenomena involving the interplay between topologically ordered phases and broken-symmetry states. The key ingredient is an unconventional order parameter, with an orbital component containing a chiral p x  + ip y wave term. Here we present phase-sensitive measurements, based on the quantum interference in nanoscale Josephson junctions, realized by using Bi 2 Te 3 topological insulator. We demonstrate that the induced superconductivity is unconventional and consistent with a sign-changing order parameter, such as a chiral p x  + ip y component. The magnetic field pattern of the junctions shows a dip at zero externally applied magnetic field, which is an incontrovertible signature of the simultaneous existence of 0 and π coupling within the junction, inherent to a non trivial order parameter phase. The nano-textured morphology of the Bi 2 Te 3 flakes, and the dramatic role played by thermal strain are the surprising key factors for the display of an unconventional induced order parameter.

Material requirements for the adoption of unconventional silicon crystal and wafer growth techniques for high-efficiency solar cells

DOE PAGES

Hofstetter, Jasmin; del Cañizo, Carlos; Wagner, Hannes; ...

2015-10-15

Silicon wafers comprise approximately 40% of crystalline silicon module cost and represent an area of great technological innovation potential. Paradoxically, unconventional wafer-growth techniques have thus far failed to displace multicrystalline and Czochralski silicon, despite four decades of innovation. One of the shortcomings of most unconventional materials has been a persistent carrier lifetime deficit in comparison to established wafer technologies, which limits the device efficiency potential. In this perspective article, we review a defect-management framework that has proven successful in enabling millisecond lifetimes in kerfless and cast materials. Control of dislocations and slowly diffusing metal point defects during growth, coupled tomore » effective control of fast-diffusing species during cell processing, is critical to enable high cell efficiencies. As a result, to accelerate the pace of novel wafer development, we discuss approaches to rapidly evaluate the device efficiency potential of unconventional wafers from injection-dependent lifetime measurements.« less

Unconventional Consumption Methods and Enjoying Things Consumed: Recapturing the "First-Time" Experience.

PubMed

O'Brien, Ed; Smith, Robert W

2018-06-01

People commonly lament the inability to re-experience familiar things as they were first experienced. Four experiments suggest that consuming familiar things in new ways can disrupt adaptation and revitalize enjoyment. Participants better enjoyed the same familiar food (Experiment 1), drink (Experiment 2), and video (Experiments 3a-3b) simply when re-experiencing the entity via unusual means (e.g., eating popcorn using chopsticks vs. hands). This occurs because unconventional methods invite an immersive "first-time" perspective on the consumption object: boosts in enjoyment were mediated by revitalized immersion into the consumption experience and were moderated by time such that they were strongest when using unconventional methods for the first time (Experiments 1-2); likewise, unconventional methods that actively disrupted immersion did not elicit the boost, despite being novel (Experiments 3a-3b). Before abandoning once-enjoyable entities, knowing to consume old things in new ways (vs. attaining new things altogether) might temporarily restore enjoyment and postpone wasteful replacement.

Enhanced recovery of unconventional gas. Volume II. The program. [Tight gas basins; Devonian shale; coal seams; geopressured aquifers

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

Kuuskraa, V.A.; Brashear, J.P.; Doscher, T.M.

1978-10-01

This study was conducted to assist public decision-makers in selecting among many choices to obtain new gas supplies by addressing 2 questions: 1) how severe is the need for additional future supplies of natural gas, and what is the economic potential of providing part of future supply through enhanced recovery from unconventional natural gas resources. The study also serves to assist the DOE in designing a cost-effective R and D program to stimulate industry to recover this unconventional gas and to produce it sooner. Tight gas basins, Devonian shale, methane from coal seams, and methane from geopressured aquifers are considered.more » It is concluded that unconventional sources, already providing about 1 Tcf per year, could provide from 3 to 4 Tcf in 1985 and from 6 to 8 Tcf in 1990 (at $1.75 and $3.00 per Mcf, respectively). However, even with these additions to supply, gas supply is projected to remain below 1977 usage levels. (DLC)« less

Material requirements for the adoption of unconventional silicon crystal and wafer growth techniques for high-efficiency solar cells

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

Hofstetter, Jasmin; del Cañizo, Carlos; Wagner, Hannes

Silicon wafers comprise approximately 40% of crystalline silicon module cost and represent an area of great technological innovation potential. Paradoxically, unconventional wafer-growth techniques have thus far failed to displace multicrystalline and Czochralski silicon, despite four decades of innovation. One of the shortcomings of most unconventional materials has been a persistent carrier lifetime deficit in comparison to established wafer technologies, which limits the device efficiency potential. In this perspective article, we review a defect-management framework that has proven successful in enabling millisecond lifetimes in kerfless and cast materials. Control of dislocations and slowly diffusing metal point defects during growth, coupled tomore » effective control of fast-diffusing species during cell processing, is critical to enable high cell efficiencies. As a result, to accelerate the pace of novel wafer development, we discuss approaches to rapidly evaluate the device efficiency potential of unconventional wafers from injection-dependent lifetime measurements.« less

Subclinical hypothyroidism in pregnant rats impaired learning and memory of their offspring by promoting the p75NTR signal pathway.

PubMed

Zhang, Fan; Chen, Jian; Lin, Xinyue; Peng, Shiqiao; Yu, Xiaohui; Shan, Zhongyan; Teng, Weiping

2018-05-01

Maternal hypothyroidism during pregnancy can affect the neurodevelopment of their offspring. This study aimed to investigate the effects of maternal subclinical hypothyroidism (SCH) on spatial learning and memory, and its relationship with the apoptotic factors in cerebral cortex of the offspring. Female adult Wistar rats were randomly divided into three groups ( n  = 15 per group): control (CON) group, SCH group and overt hypothyroidism (OH) group. Spatial learning and memory in the offspring were evaluated by long-term potentiation (LTP) and Morris water-maze (MWM) test. The protein expression of the p75 neurotrophin receptor (p75 NTR ), phospho-c-Jun N-terminal kinase (p-JNK), the pro-apoptotic protein p53 and Bax were detected by Western blotting. The Pups in the SCH and OH groups showed longer escape latencies in the MWM and decreased field-excitatory post synaptic potentials in LTP tests compared with those in the CON group. p75 NTR , p-JNK, p53 and Bax expression levels in the cerebral cortex increased in pups in the SCH and OH groups compared with those in the CON group. Maternal SCH during pregnancy may impair spatial learning and memory in the offspring and may be associated with the increased apoptosis in the cerebral cortex. © 2018 The authors.

Essential role for zinc-triggered p75NTR activation in preconditioning neuroprotection.

PubMed

Lee, Jin-Yeon; Kim, Yu-Jin; Kim, Tae-Youn; Koh, Jae-Young; Kim, Yang-Hee

2008-10-22

Ischemic preconditioning (PC) of the brain is a phenomenon by which mild ischemic insults render neurons resistant to subsequent strong insults. Key steps in ischemic PC of the brain include caspase-3 activation and poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, but upstream events have not been clearly elucidated. We have tested whether endogenous zinc is required for ischemic PC of the brain in rats. Mild, transient zinc accumulation was observed in certain neurons after ischemic PC. Moreover, intraventricular administration of CaEDTA during ischemic PC abrogated both zinc accumulation and the protective effect against subsequent full ischemia. To elucidate the mechanism of the zinc-triggered PC (Zn PC) effect, cortical cultures were exposed to sublethal levels of zinc, and 18 h later to lethal levels of zinc or NMDA. Zn PC exhibited the characteristic features of ischemic PC, including caspase-3 activation, PARP-1 cleavage, and HSP70 induction, all of which are crucial for subsequent neuroprotection against NMDA or zinc toxicity. HSP70 induction was necessary for protection, as it halted caspase-3 activation before apoptosis. Interestingly, in both Zn PC in vitro and ischemic PC in vivo, p75(NTR) was necessary for neuroprotection. These results suggest that caspase-3 activation during ischemic PC, a necessary event for subsequent neuroprotection, may result from mild zinc accumulation and the consequent p75(NTR) activation in neurons.

Creating unconventional geometric beams with large depth of field using double freeform-surface optics.

PubMed

Feng, Zexin; Froese, Brittany D; Huang, Chih-Yu; Ma, Donglin; Liang, Rongguang

2015-07-10

We consider here creation of an unconventional flattop beam with a large depth of field by employing double freeform optical surfaces. The output beam is designed with continuous variations from the flattop to almost zero near the edges to resist the influence of diffraction on its propagation. We solve this challenging problem by naturally incorporating an optimal transport map computation scheme for unconventional boundary conditions with a simultaneous point-by-point double surface construction procedure. We demonstrate experimentally the generation of a long-range propagated triangular beam through a plano-freeform lens pair fabricated by a diamond-tuning machine.

Unconventional cancer remedies.

PubMed Central

Danielson, K J; Stewart, D E; Lippert, G P

1988-01-01

Unproven and disproven remedies continue to abound for illnesses for which conventional treatment is only partially effective. This is particularly true with cancer, for which up to 50% of patients may be receiving unorthodox therapy. This article examines unconventional cancer remedies, their adverse effects, their common factors and the basis for their appeal, as well as what motivates and characterizes patients who choose these treatments. Also discussed is an approach that may be used by the conventional physician for patients who are likely to seek unorthodox treatment. This approach will help patients make the best decision about their treatment and protect them from the hazards of unconventional remedies. PMID:3285984

Test Methodology to Evaluate the Safety of Materials Using Spark Incendivity

NASA Technical Reports Server (NTRS)

Buhler, Charles; Calle, Carlos; Clements, Sid; Ritz, Mindy; Starnes, Jeff

2007-01-01

For many years scientists and engineers have been searching for the proper test method to evaluate an electrostatic risk for materials used in hazardous environments. A new test standard created by the International Electrotechnical Commission is a promising addition to conventional test methods used throughout industry. The purpose of this paper is to incorporate this test into a proposed new methodology for the evaluation of materials exposed to flammable environments. However, initial testing using this new standard has uncovered some unconventional behavior in materials that conventional test methods were thought to have reconciled. For example some materials tested at higher humidities were more susceptible to incendive discharges than at lower humidity even though the surface resistivity was lower.

A Review on Ubiquitination of Neurotrophin Receptors: Facts and Perspectives

PubMed Central

Sánchez-Sánchez, Julia; Arévalo, Juan Carlos

2017-01-01

Ubiquitination is a reversible post-translational modification involved in a plethora of different physiological functions. Among the substrates that are ubiquitinated, neurotrophin receptors (TrkA, TrkB, TrkC, and p75NTR) have been studied recently. TrkA is the most studied receptor in terms of its ubiquitination, and different E3 ubiquitin ligases and deubiquitinases have been implicated in its ubiquitination, whereas not much is known about the other neurotrophin receptors aside from their ubiquitination. Additional studies are needed that focus on the ubiquitination of TrkB, TrkC, and p75NTR in order to further understand the role of ubiquitination in their physiological and pathological functions. Here we review what is currently known regarding the ubiquitination of neurotrophin receptors and its physiological and pathological relevance. PMID:28335430

Recent advances in understanding neurotrophin signaling

PubMed Central

Bothwell, Mark

2016-01-01

The nerve growth factor family of growth factors, collectively known as neurotrophins, are evolutionarily ancient regulators with an enormous range of biological functions. Reflecting this long history and functional diversity, mechanisms for cellular responses to neurotrophins are exceptionally complex. Neurotrophins signal through p75 NTR, a member of the TNF receptor superfamily member, and through receptor tyrosine kinases (TrkA, TrkB, TrkC), often with opposite functional outcomes. The two classes of receptors are activated preferentially by proneurotrophins and mature processed neurotrophins, respectively. However, both receptor classes also possess neurotrophin-independent signaling functions. Signaling functions of p75 NTR and Trk receptors are each influenced by the other class of receptors. This review focuses on the mechanisms responsible for the functional interplay between the two neurotrophin receptor signaling systems. PMID:27540475

Recent advances in understanding neurotrophin signaling.

PubMed

Bothwell, Mark

2016-01-01

The nerve growth factor family of growth factors, collectively known as neurotrophins, are evolutionarily ancient regulators with an enormous range of biological functions. Reflecting this long history and functional diversity, mechanisms for cellular responses to neurotrophins are exceptionally complex. Neurotrophins signal through p75 (NTR), a member of the TNF receptor superfamily member, and through receptor tyrosine kinases (TrkA, TrkB, TrkC), often with opposite functional outcomes. The two classes of receptors are activated preferentially by proneurotrophins and mature processed neurotrophins, respectively. However, both receptor classes also possess neurotrophin-independent signaling functions. Signaling functions of p75 (NTR) and Trk receptors are each influenced by the other class of receptors. This review focuses on the mechanisms responsible for the functional interplay between the two neurotrophin receptor signaling systems.

Adapting Unconventional Warfare Doctrine to Cyberspace Operations: An Examination of Hacktivist Based Insurgencies

DTIC Science & Technology

2015-06-12

Unconventional Warfare, Cyberspace Operations, Cyber Warfare , Hacktivism, China, Russia, Georgia, Estonia, Umbrella Revolution, UW, Cyber, Guerilla, Hacktivist...6 Cyber Warfare ............................................................................................................. 7...Internet, and cyber warfare , the nature of the human element in cyberspace exhibits only a scientific advancement in the evolution of warfare, not a

Assessment of potential unconventional Carboniferous-Permian gas resources of the Liaohe Basin eastern uplift, Liaoning Province, China, 2011

USGS Publications Warehouse

Pollastro, Richard M.; Potter, Christopher J.; Schenk, Christopher J.; Charpentier, Ronald R.; Cook, Troy A.; Klett, Timothy R.; Kirschbaum, Mark A.

2012-01-01

The U.S. Geological Survey estimated a mean of 448 billion cubic feet of potential technically recoverable unconventional natural gas in Carboniferous and Permian coal-bearing strata in the eastern uplift of the Liaohe Basin, Liaoning Province, China.

Conquest from Within: A Comparative Analysis between Soviet Active Measures and United States Unconventional Warfare Doctrine

DTIC Science & Technology

2015-05-27

irregular threats. Unconventional Warfare (UW), traditionally a Special Operations Forces core activity, has served U.S. strategic interests in a variety...Special Operations Forces core activity, has served U.S. strategic interests in a variety of operational environments. Throughout the Cold War, the

Retrospective Case Study in Wise County, Texas, Study of the Potential Impacts of Hydraulic Fracturing on Drinking Water Resources

EPA Science Inventory

This report describes the retrospective case study in north central Texas, conducted at three locations in Wise County where both conventional and unconventional gas production occurred in the past. Currently unconventional gas production occurs from the Mississippian-aged Barne...

Adolescents' Response to Unconventional War Threat Prior to the Gulf War.

ERIC Educational Resources Information Center

Klingman, Avigdor; Goldstein, Zehava

1994-01-01

Examined Israeli adolescents' responses to impending unconventional warfare by administering Nuclear Threat Index to 269 junior high school students 2 months prior to Persian Gulf War. Younger adolescents and females reported more activity, pessimistic thoughts, and concerns than older adolescents and males, respectively; and "internal"…

Nuclear Thermal Rocket (NTR) Development Risk Communication

NASA Technical Reports Server (NTRS)

Kim, Tony

2014-01-01

There are clear advantages of development of a Nuclear Thermal Rocket (NTR) for a crewed mission to Mars. NTR for in-space propulsion enables more ambitious space missions by providing high thrust at high specific impulse (approximately 900 sec) that is 2 times the best theoretical performance possible for chemical rockets. Missions can be optimized for maximum payload capability to take more payload with reduced total mass to orbit; saving cost on reduction of the number of launch vehicles needed. Or missions can be optimized to minimize trip time significantly to reduce the deep space radiation exposure to the crew. NTR propulsion technology is a game changer for space exploration. However, "NUCLEAR" is a word that is feared and vilified by some groups and the hostility towards development of any nuclear systems can meet great opposition by the public as well as from national leaders and people in authority. Communication of nuclear safety will be critical to the success of the development of the NTR. Why is there a fear of nuclear? A bomb that can level a city is a scary weapon. The first and only times the Nuclear Bomb was used in a war was on Hiroshima and Nagasaki during World War 2. The "Little Boy" atomic bomb was dropped on Hiroshima on August 6, 1945 and the "Fat Man" on Nagasaki 3 days later on August 9th. Within the first 4 months of bombings, 90- 166 thousand people died in Hiroshima and 60-80 thousand died in Nagasaki. It is important to note for comparison that over 500 thousand people died and 5 million made homeless due to strategic bombing (approximately 150 thousand tons) of Japanese cities and war assets with conventional non-nuclear weapons between 1942- 1945. A major bombing campaign of "firebombing" of Tokyo called "Operation Meetinghouse" on March 9 and 10 consisting of 334 B-29's dropped approximately1,700 tons of bombs around 16 square mile area and over 100 thousand people have been estimated to have died. The declaration of death is very clear for conventional weapons and then the declaration of death due to radiation becomes vague and unclear. This may have been due to people mis-understanding the dangers and effects of radiation when assessing the damage and harm to people initially, but it is also become insidious when expressing opposition to nuclear energy. A nuclear radiation accident can be scary due to the power involved and the fear of radiation release. The International Atomic Energy Agency defines a nuclear and radiation accident a "an event that has led to significant consequences to people, the environment or the facility." There have been 3 commercial nuclear reactor accidents (Chernobyl, Three Mile Island, and Fukushima) that stand out to the public and much of the information about the result and impact to workers, environment, and public can be misleading. Often information is presented without clear correlation with radiation and other pertinent information is left out presenting a very scary situation to affect the emotions of the reader. A very boring but "critically acclaimed" movie was made in 1979 called "The China Syndrome" starring Jane Fonda and Jack Lemmon. The film was released on March 16, 1979, 12 days before the 3-Mile Island nuclear accident in Pennsylvania. The basis from the movie was from a few nuclear plant incidents and in particular, the Brown's Ferry Alabama Power Plant fire. In one scene from the movie, a physicist Dr. Elliott Lowell played by Donald Hotton states that a China Syndrome event would make "an area the size of Pennsylvania" permanently uninhabitable. Real serious nuclear incidents like Chernobyl and Fukushima are often sited to make people fear the consequences of using nuclear power. However, the consequences are at best poorly communicated and at worst fictitiously inflated to instigate social unrest against nuclear power. There is an article being circulated on Facebook with a title "28 Signs that the (US) West Coast is being absolutely fried with nuclear radiation from Fukushima" which focus on mis-information and fear mongering. Nuclear power and NTR are powerful resources that can open many doors for future prosperity and capability. With great power comes great responsibility. Radiation and its effects need to be better understood, quantified, and communicated. A human mission to mars has its own risks of deep space radiation and is considered a considerable risk at 400 milli-Sieverts per year in deep space and 245 milli-Sieverts per year on the surface of Mars as measured by the Mars Curiosity mission. Although these quantities of ionizing radiation are within the astronaut career limit, it exceeds the yearly average amounts of ionizing radiation. Astronaut crews have experienced these levels of radiation before, but for durations shorter than a year, and a mission to Mars could possibly be 3 years in length. There is also evidence that people can comfortably handle higher levels of ionizing radiation where the radiation occurs naturally like Ramsar, Iran when people can experience 270 milli-Sieverts per year. A risk posture that the development, test, and flight of an NTR will meet opposition from groups who oppose nuclear energy must be likely and the impact can be sever to the effort. Active risk mitigation must be taken for an NTR full-scale development project. The NTR design must take into account safety for transport and off nominal conditions. Nuclear fuel element must consider containment of fission products and Low Enriched Uranium (LEU) that may meet less opposition should be considered for safety and security reasons. Even though testing was conducted on Rover/NERVA safely and successfully in the 60's with exhaust sent heavenward in to open air, modern testing of NTR must consider full containment and no release of ionizing radiation to the public and must meet the current requirement of no more than 0.1 milli-Sieverts per year to the public. 0.1 milli-Sieverts is equivalent to eating one banana or a 20 hour plane flight. Good communication with the public and regulatory agencies will be essential to show that all effort is applied toward protection to the public and astronauts. The inspiring endeavor to put humans on Mars to study the planet, search for life, and learn more about this Solar System will be full of risks but it will be worth it. NTR will be worth the development effort if it allows humans to explore our Solar System.

The Unconventional Revolution in Exploration Geophysics

NASA Astrophysics Data System (ADS)

House, N. J.

2014-12-01

During the last 25 years, 3D seismic imaging has revolutionized hydrocarbon exploration by delivering an accurate 3 dimensional picture of the subsurface. The image is capable of detecting fluids within the reservoir, and has significantly reduced the risk of locating and developing hydrocarbon deposits. In late 1990s, deregulation of natural gas prices allowed long recognized deposits of natural gas locked in tight rocks be economic. It sparked factory drilling (repeatable high density evenly spaced) wells and hydraulic fracturing that would help unlock the reservoirs. All that was needed was a geologist to determine depths and limits of the reservoir and engineers to drill and complete the wells. If 3D seismic data was available, it might have been used to define both the limits of the field and drilling hazards. Generally the cost and time required to process and interpret 3D Seismic was considered too high to affect the perceived geologic risk of the Factory approach. Completion costs in unconventional reservoirs account for over 50% of the well costs. It's therefore critical to understand the geometry of how the rock is fracturing and determine optimum well spacing to balance the cost of development with the value of the gas or oil being produced. By extending AVO to the pre-stack domain, it's possible to simultaneously invert for Vp, Vs and density. Armed with these three fundamental rock properties that dictate elastic and inelastic rock response, researchers were able to combine those properties to tie directly to how well a rock will respond to hydraulic fracturing, or which rocks contain a higher TOC, or other rock properties that control how a rock responds to seismic waves or hydraulic fracturing. Combining these results allows interpreters to map areas of higher productivity, and identify bypassed reserves. Currently hundreds of different seismic attributes that are generated from 3D seismic data are used to identify the highest productive areas and how to develop them. MicroSeismic mapping has made completion more efficient and safe. While the geophysics involved in unconventional resource development may not be the first thought in the board room, thier data has become an accepted early development tool of successful oil and gas companies.

H2 Control of Natural T Regulatory Cell Frequency in the Lymph Node Correlates with Susceptibility to Day Three Thymectomy Induced Autoimmune Disease

PubMed Central

Rio, Roxana del; Sun, Yuefang; Alard, Pascale; Tung, Kenneth S.K.; Teuscher, Cory

2010-01-01

Day 3 thymectomy (D3Tx) results in a loss of peripheral tolerance mediated by natural T regulatory cells (nTR) and development of autoimmune ovarian dysgenesis (AOD) and dacryoadenitis (ADA) in A/J and (C57BL/6J × A/J) F1 hybrids (B6A) but not in C57BL/6J (B6) mice. Previously, using quantitative trait locus (QTL) linkage analysis, we showed that D3Tx-AOD is controlled by five unlinked QTL (Aod1-Aod5) and H2. In the present study, using D3Tx B6-ChrA/J/NaJ chromosome substitution strains, we confirm that QTL on chromosome (Chr) 16 (Aod1a/Aod1b), Chr3 (Aod2), Chr1 (Aod3), Chr2 (Aod4), Chr7 (Aod5), and Chr17 (H2) control D3Tx-AOD susceptibility. Additionally, we present the first data mapping QTL controlling D3Tx-ADA to Chr17 (Ada1/H2), Chr1 (Ada2), and Chr3 (Ada3). Importantly, B6-ChrXA/J mice were as resistant to D3Tx-AOD and D3Tx-ADA as B6 mice thereby excluding Foxp3 as a susceptibility gene in these models. Moreover, we report quantitative differences in the frequency of nTR cells in the lymph nodes (LNs), but not spleen or thymus, of AOD/ADA-resistant B6 and AOD/ADA-susceptible A/J, B6A, and B6-Chr17A/J mice. Similar results correlating with experimental allergic encephalomyelitis and orchitis susceptibility were seen with B10.S and SJL/J mice. Using H2-congenic mice we show that the observed difference in frequency of LN nTR cells is controlled by H2. These data support the existence of a LN-specific, H2-controlled mechanism regulating the prevalence of nTR cells in autoimmune disease susceptibility. PMID:21135167

Protein and cell wall polysaccharide carbonyl determination by a neutral pH 2,4-dinitrophenylhydrazine-based photometric assay.

PubMed

Georgiou, Christos D; Zisimopoulos, Dimitrios; Argyropoulou, Vasiliki; Kalaitzopoulou, Electra; Salachas, George; Grune, Tilman

2018-04-10

A new 2,4-dinitrophenylhydrazine (DNPH)-based photometric assay is developed for the quantification of carbonyls in protein samples from any biological source by protein carbonyl-DNPH hydrazone formation at acidic pH in the presence of denaturing urea, and subsequent hydrazone solubilization in the presence of SDS and stabilization from acid hydrolysis at pH 7.0. At this neutral (ntr) pH, interfering unreacted DNPH is uncharged and its thus increased hydrophobicity permits its 100% effective removal from the solubilizate with ethyl acetate/hexane wash. The ntrDNPH assay is more reliable and sensitive than the standard (std) DNPH photometric assay because it eliminates its main limitations: (i) interfering unreacted DNPH (pKa 1.55) that is nonspecifically bound to the TCA (pKa 0.7)-protein pellet is not effectively removed after wash with EtOH: ethyl acetate because it is positively charged, (ii) acid (TCA-induced) hydrolysis of the protein carbonyl-DNPH hydrazone, (iii) sample protein concentration re-determination, (iv) loss of sample acid (TCA)-soluble proteins, (v) DNA interference, and (vi) requires high protein quantity samples (≥ 1 mg). Considering ntrDNPH assay's very low protein limit (1 µg), its cumulative and functional sensitivities are 2600- and 2000-fold higher than those of the stdDNPH assay, respectively. The present study elucidates the DNA interference mechanism on the stdDNPH assay, and also develops a standardized protocol for sample protein treatment and fractionation (into cytoplasmic/aqueous, membrane/lipid-bound, and histone/DNA-bound proteins; see Supplement section V) in order to ensure reproducible carbonyl determination on defined cell protein fractions, and to eliminate assay interference from protein samples containing (i) Cys sulfenic acid groups (via their neutralization with dithiothreitol), and (ii) DNA (via its removal by streptomycin sulfate precipitation). Lastly, the ntrDNPH assay determines carbonyl groups on cell wall polysaccharides, thus paving the way on studies to investigate cell walls acting as antioxidant defense in plants, fungi, bacteria and lichens. Copyright © 2018. Published by Elsevier B.V.

Molecular characterization of hepatitis A virus strains in a tertiary care health set up in north western India

PubMed Central

Singh, Mini Pritam; Majumdar, Manasi; Thapa, Babu Ram; Gupta, Puneet Kumar; Khurana, Jasmine; Budhathoki, Bimal; Ratho, Radha Kanta

2015-01-01

Background & objectives: Hepatitis A virus usually causes acute viral hepatitis (AVH) in the paediatric age group with a recent shift in age distribution and disease manifestations like acute liver failure (ALF). This has been attributed to mutations in 5’non-translated region (5’NTR) which affects the viral multiplication. The present study was aimed to carry out the molecular detection and phylogenetic analysis of hepatitis A virus strains circulating in north western India. Methods: Serum samples from in patients and those attending out patient department of Pediatric Gastroenterology in a tertiary care hospital in north India during 2007-2011 with clinically suspected AVH were tested for anti-hepatitis A virus (HAV) IgM antibodies. Acute phase serum samples were subjected to nested PCR targeting the 5’NTR region followed by sequencing of the representative strains. Results: A total of 1334 samples were tested, 290 (21.7%) were positive for anti-HAV IgM antibody. Of these, 78 serum samples (< 7 days old) were subjected to PCR and 47.4% (37/78) samples showed the presence of HAV RNA. Children < 15 yr of age accounted for majority (94%) of cases with highest seropositivity during rainy season. Sequencing of 15 representative strains was carried out and the circulating genotype was found to be III A. The nucleotide sequences showed high homology among the strains with a variation ranging from 0.1-1 per cent over the years. An important substitution of G to A at 324 position was shown by both AVH and ALF strains. The cumulative substitution in AVH strains Vs ALF strains as compared to GBM, Indian and prototype strain in the 200-500 region of 5’ NTR was comparable. Interpretation & conclusion: Our results showed hepatitis A still a disease of children with III A as a circulating genotype in this region. The mutations at 5’NTR region warrant further analysis as these affect the structure of internal ribosomal entry site which is important for viral replication. PMID:25900957

Radiosynoviorthesis of acromioclavicular joint using 169Er-citrate: prospective evaluation of efficacy.

PubMed

Vereb, Marika; Liepe, Knut; Fischer, Manfred; Kaliska, Lucia; Noskovicova, Lucia; Balogova, Sona

2018-01-01

There is a clinical need for therapeutic alternative in patients with persisting painful arthritis of AC-joint and failure of previous treatments. However, no radiopharmaceutical is currently explicitly approved for radiosynoviorthesis of acromioclavicular joint. The aim of our study was to prospectively assess the efficacy and safety of radiosynoviorthesis of acromioclavicular joint using erbium-169 citrate. Radiosynoviorthesis of acromioclavicular joint was performed in 51 consecutive patients (18 males, 33 females) mean age 64.3 (range 43.8-82.6, median 63.6) years with clinically confirmed arthritis of 85 acromioclavicular joints. The efficacy of RSO was reported by patients according to 10-step visual analogue scale of pain (VAS) (0 = no pain, 10 = most severe pain) at 6 months after radiosynoviorthesis and by ranking the global therapeutic effect of RSO in 4 categories (1 = the best effect, 4 = no change). To assess the variation of blood perfusion in treated joints, the efficacy of RSO was also evaluated by variation of target (acromioclavicular joint)/non-target (soft tissue) uptake ratio (T/NTR) of metylendiphosphonate (99mTc) measured as number of counts over region of interest on blood pool phase of two-phase bone scintigraphy performed before and 6 months after RSO. Radiosynoviorthesis was followed by significant decrease in VAS, mean - 3.1 (-47%). Excellent, good, moderate and bad response was observed in 57 (67%), 25 (29%), 1 (1%) and in 2 (2%) of acromioclavicular joints respectively. A significant correlation between decrease of T/NTR and variation of VAS in % (ρ = 0.532, p < 0.0001) and between T/NTR and subjective evaluation of therapeutic effect in scale 1-4 (ρ = 0.388, p = 0.0002) was observed. However, it was not possible to identify the cut-off value of relative decrease in T/NTR showing sufficient sensitivity and specificity to detect the therapeutic response. Results of this prospective study permit to conclude a good efficacy and safety of radiosynoviorthesis using erbium-169 citrate in a series of patients with arthritis of acromioclavicular joint in whom previous line(s) of treatment did not lead to satisfactory pain relief.

Mechanics and Activation of Unconventional Myosins.

PubMed

Batters, Christopher; Veigel, Claudia

2016-08-01

Many types of cellular motility are based on the myosin family of motor proteins ranging from muscle contraction to exo- and endocytosis, cytokinesis, cell locomotion or signal transduction in hearing. At the center of this wide range of motile processes lies the adaptation of the myosins for each specific mechanical task and the ability to coordinate the timing of motor protein mobilization and targeting. In recent years, great progress has been made in developing single molecule technology to characterize the diverse mechanical properties of the unconventional myosins. Here, we discuss the basic mechanisms and mechanical adaptations of unconventional myosins, and emerging principles regulating motor mobilization and targeting. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Microbial Biotechnology 2020; microbiology of fossil fuel resources.

PubMed

Head, Ian M; Gray, Neil D

2016-09-01

This roadmap examines the future of microbiology research and technology in fossil fuel energy recovery. Globally, the human population will be reliant on fossil fuels for energy and chemical feedstocks for at least the medium term. Microbiology is already important in many areas relevant to both upstream and downstream activities in the oil industry. However, the discipline has struggled for recognition in a world dominated by geophysicists and engineers despite widely known but still poorly understood microbially mediated processes e.g. reservoir biodegradation, reservoir souring and control, microbial enhanced oil recovery. The role of microbiology is even less understood in developing industries such as shale gas recovery by fracking or carbon capture by geological storage. In the future, innovative biotechnologies may offer new routes to reduced emissions pathways especially when applied to the vast unconventional heavy oil resources formed, paradoxically, from microbial activities in the geological past. However, despite this potential, recent low oil prices may make industry funding hard to come by and recruitment of microbiologists by the oil and gas industry may not be a high priority. With regards to public funded research and the imperative for cheap secure energy for economic growth in a growing world population, there are signs of inherent conflicts between policies aimed at a low carbon future using renewable technologies and policies which encourage technologies which maximize recovery from our conventional and unconventional fossil fuel assets. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

78 FR 15377 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Requests To...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-11

... for OMB Review; Comment Request; Requests To Approve Conformed Wage Classifications and Unconventional... Classifications and Unconventional Fringe Benefit Plans Under the Davis-Bacon and Related Acts and Contract Work... collection consist of: (A) Reports of conformed classifications and wage rates and (B) requests for approval...

Assessment of undiscovered oil and gas resources of the Paris Basin, France, 2015

USGS Publications Warehouse

Schenk, Christopher J.; Charpentier, Ronald R.; Klett, Timothy R.; Tennyson, Marilyn E.; Mercier, Tracey J.; Le, Phoung A.; Brownfield, Michael E.; Pitman, Janet K.; Gaswirth, Stephanie B.; Marra, Kristen R.; Leathers, Heidi M.

2015-01-01

Using a geology-based assessment methodology, the U.S. Geological Survey estimated means of 222 million barrels of unconventional oil; 2,092 billion cubic feet of unconventional gas; 18 million barrels of conventional oil; and 47 billion cubic feet of conventional gas resources in the Paris Basin of France.

Aspects of a Neoteric Approach to Advance Students' Ability to Conjecture, Prove, or Disprove

ERIC Educational Resources Information Center

McLoughlin, M. Padraig M. M.

2010-01-01

The author of this paper suggests several neoteric, unconventional, idiosyncratic, or unique approaches to beginning Set Theory that he found seems to work well in building students' introductory understanding of the Foundations of Mathematics. This paper offers some ideas on how the author uses certain "unconventional" definitions and…

Unconventional topological Hall effect in skyrmion crystals caused by the topology of the lattice

NASA Astrophysics Data System (ADS)

Göbel, Börge; Mook, Alexander; Henk, Jürgen; Mertig, Ingrid

2017-03-01

The hallmark of a skyrmion crystal (SkX) is the topological Hall effect (THE). In this article we predict and explain an unconventional behavior of the topological Hall conductivity in SkXs. In simple terms, the spin texture of the skyrmions causes an inhomogeneous emergent magnetic field whose associated Lorentz force acts on the electrons. By making the emergent field homogeneous, the THE is mapped onto the quantum Hall effect (QHE). Consequently, each electronic band of the SkX is assigned to a Landau level. This correspondence of THE and QHE allows us to explain the unconventional behavior of the THE of electrons in SkXs. For example, a skyrmion crystal on a triangular lattice exhibits a quantized topological Hall conductivity with steps of 2 .e2/h below and with steps of 1 .e2/h above the van Hove singularity. On top of this, the conductivity shows a prominent sign change at the van Hove singularity. These unconventional features are deeply connected to the topology of the structural lattice.

Associations Between Positive Body Image, Sexual Liberalism, and Unconventional Sexual Practices in U.S. Adults.

PubMed

Swami, Viren; Weis, Laura; Barron, David; Furnham, Adrian

2017-11-01

While studies have documented robust relationships between body image and sexual health outcomes, few studies have looked beyond sexual functioning in women. Here, we hypothesized that more positive body image would be associated with greater sexual liberalism and more positive attitudes toward unconventional sexual practices. An online sample of 151 women and 164 men from the U.S. completed measures of sexual liberalism, attitudes toward unconventional sexual practices, and indices of positive body image (i.e., body appreciation, body acceptance by others, body image flexibility, and body pride), and provided their demographic details. Regression analyses indicated that, once the effects of sexual orientation, relationship status, age, and body mass index had been accounted for, higher body appreciation was significantly associated with greater sexual liberalism in women and men. Furthermore, higher body appreciation and body image flexibility were significantly associated with more positive attitudes toward unconventional sexual practices in women and men. These results may have implications for scholars working from a sex-positive perspective, particularly in terms of understanding the role body image plays in sexual attitudes and behaviors.

Modeling the Relative GHG Emissions of Conventional and Shale Gas Production

PubMed Central

2011-01-01

Recent reports show growing reserves of unconventional gas are available and that there is an appetite from policy makers, industry, and others to better understand the GHG impact of exploiting reserves such as shale gas. There is little publicly available data comparing unconventional and conventional gas production. Existing studies rely on national inventories, but it is not generally possible to separate emissions from unconventional and conventional sources within these totals. Even if unconventional and conventional sites had been listed separately, it would not be possible to eliminate site-specific factors to compare gas production methods on an equal footing. To address this difficulty, the emissions of gas production have instead been modeled. In this way, parameters common to both methods of production can be held constant, while allowing those parameters which differentiate unconventional gas and conventional gas production to vary. The results are placed into the context of power generation, to give a ″well-to-wire″ (WtW) intensity. It was estimated that shale gas typically has a WtW emissions intensity about 1.8–2.4% higher than conventional gas, arising mainly from higher methane releases in well completion. Even using extreme assumptions, it was found that WtW emissions from shale gas need be no more than 15% higher than conventional gas if flaring or recovery measures are used. In all cases considered, the WtW emissions of shale gas powergen are significantly lower than those of coal. PMID:22085088

Modeling the relative GHG emissions of conventional and shale gas production.

PubMed

Stephenson, Trevor; Valle, Jose Eduardo; Riera-Palou, Xavier

2011-12-15

Recent reports show growing reserves of unconventional gas are available and that there is an appetite from policy makers, industry, and others to better understand the GHG impact of exploiting reserves such as shale gas. There is little publicly available data comparing unconventional and conventional gas production. Existing studies rely on national inventories, but it is not generally possible to separate emissions from unconventional and conventional sources within these totals. Even if unconventional and conventional sites had been listed separately, it would not be possible to eliminate site-specific factors to compare gas production methods on an equal footing. To address this difficulty, the emissions of gas production have instead been modeled. In this way, parameters common to both methods of production can be held constant, while allowing those parameters which differentiate unconventional gas and conventional gas production to vary. The results are placed into the context of power generation, to give a ″well-to-wire″ (WtW) intensity. It was estimated that shale gas typically has a WtW emissions intensity about 1.8-2.4% higher than conventional gas, arising mainly from higher methane releases in well completion. Even using extreme assumptions, it was found that WtW emissions from shale gas need be no more than 15% higher than conventional gas if flaring or recovery measures are used. In all cases considered, the WtW emissions of shale gas powergen are significantly lower than those of coal.

Heavy fermions, quantum criticality, and unconventional superconductivity in filled skutterudites and related materials

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

Andraka, Bohdan

2015-05-14

The main goal of this program was to explore the possibility of novel states and behaviors in Pr-based system exhibiting quantum critical behavior, PrOs₄Sb₁₂. Upon small changes of external parameter, such as magnetic field, physical properties of PrOs₄Sb₁₂ are drastically altered from those corresponding to a superconductor, to heavy fermion, to field-induced ordered phase with primary quadrupolar order parameter. All these states are highly unconventional and not understood in terms of current theories thus offer an opportunity to expand our knowledge and understanding of condensed matter. At the same time, these novel states and behaviors are subjects to intense internationalmore » controversies. In particular, two superconducting phases with different transition temperatures were observed in some samples and not observed in others leading to speculations that sample defects might be partially responsible for these exotic behaviors. This work clearly established that crystal disorder is important consideration, but contrary to current consensus this disorder suppresses exotic behavior. Superconducting properties imply unconventional inhomogeneous state that emerges from unconventional homogeneous normal state. Comprehensive structural investigations demonstrated that upper superconducting transition is intrinsic, bulk, and unconventional. The high quality of in-house synthesized single crystals was indirectly confirmed by de Haas-van Alphen quantum oscillation measurements. These measurements, for the first time ever reported, spanned several different phases, offering unprecedented possibility of studying quantum oscillations across phase boundaries.« less

Unconventional therapies for cancer: 1. Essiac

PubMed Central

Kaegi, E

1998-01-01

Physicians and patients have been frustrated by the lack of reliable information on unconventional therapies. To help fill this gap in the area of breast cancer therapy, the Canadian Breast Cancer Research Initiative formed a task force to advise it on how best to promote research into unconventional therapies. As part of the work of the task force, a review of the available literature was carried out for each of the following products: Essiac, green tea, Iscador, hydrazine sulfate, vitamins A, C and E, and 714-X. The first article in this series on unconventional therapies for cancer describes the methodology used to obtain and evaluate the information and provides a summary of the findings on Essiac. Subsequent articles will cover the other products. For most of the products reviewed, there has been some indication of possible benefit but no definitive evidence. Innovative and collaborative research needed to meet the information needs of growing numbers of patients and their physicians is now being sponsored by the Canadian Breast Cancer Research Initiative. Open communication between patients and physicians is also necessary for the maintenance of an appropriate therapeutic partnership and for the identification and control of side effects. The Ontario Division of the Canadian Cancer Society, a partner in the Canadian Breast Cancer Research Initiative, supported the preparation of a patient-information piece on unconventional therapies to accompany the series. This item will assist patients who are considering such therapies and will promote open communication between patients and their physicians. PMID:9559016

Unconventional oil and gas spills: Materials, volumes, and risks to surface waters in four states of the U.S.

PubMed

Maloney, Kelly O; Baruch-Mordo, Sharon; Patterson, Lauren A; Nicot, Jean-Philippe; Entrekin, Sally A; Fargione, Joseph E; Kiesecker, Joseph M; Konschnik, Kate E; Ryan, Joseph N; Trainor, Anne M; Saiers, James E; Wiseman, Hannah J

2017-03-01

Extraction of oil and gas from unconventional sources, such as shale, has dramatically increased over the past ten years, raising the potential for spills or releases of chemicals, waste materials, and oil and gas. We analyzed spill data associated with unconventional wells from Colorado, New Mexico, North Dakota and Pennsylvania from 2005 to 2014, where we defined unconventional wells as horizontally drilled into an unconventional formation. We identified materials spilled by state and for each material we summarized frequency, volumes and spill rates. We evaluated the environmental risk of spills by calculating distance to the nearest stream and compared these distances to existing setback regulations. Finally, we summarized relative importance to drinking water in watersheds where spills occurred. Across all four states, we identified 21,300 unconventional wells and 6622 reported spills. The number of horizontal well bores increased sharply beginning in the late 2000s; spill rates also increased for all states except PA where the rate initially increased, reached a maximum in 2009 and then decreased. Wastewater, crude oil, drilling waste, and hydraulic fracturing fluid were the materials most often spilled; spilled volumes of these materials largely ranged from 100 to 10,000L. Across all states, the average distance of spills to a stream was highest in New Mexico (1379m), followed by Colorado (747m), North Dakota (598m) and then Pennsylvania (268m), and 7.0, 13.3, and 20.4% of spills occurred within existing surface water setback regulations of 30.5, 61.0, and 91.4m, respectively. Pennsylvania spills occurred in watersheds with a higher relative importance to drinking water than the other three states. Results from this study can inform risk assessments by providing improved input parameters on volume and rates of materials spilled, and guide regulations and the management policy of spills. Published by Elsevier B.V.

Unconventional oil and gas spills: Materials, volumes, and risks to surface waters in four states of the U.S.

USGS Publications Warehouse

Maloney, Kelly O.; Baruch-Mordo, Sharon; Patterson, Lauren A.; Nicot, Jean-Philippe; Entrekin, Sally; Fargione, Joe E.; Kiesecker, Joseph M.; Konschnik, Kate E.; Ryan, Joseph N.; Trainor, Anne M.; Saiers, James E.; Wiseman, Hannah J.

2017-01-01

Extraction of oil and gas from unconventional sources, such as shale, has dramatically increased over the past ten years, raising the potential for spills or releases of chemicals, waste materials, and oil and gas. We analyzed spill data associated with unconventional wells from Colorado, New Mexico, North Dakota and Pennsylvania from 2005 to 2014, where we defined unconventional wells as horizontally drilled into an unconventional formation. We identified materials spilled by state and for each material we summarized frequency, volumes and spill rates. We evaluated the environmental risk of spills by calculating distance to the nearest stream and compared these distances to existing setback regulations. Finally, we summarized relative importance to drinking water in watersheds where spills occurred. Across all four states, we identified 21,300 unconventional wells and 6622 reported spills. The number of horizontal well bores increased sharply beginning in the late 2000s; spill rates also increased for all states except PA where the rate initially increased, reached a maximum in 2009 and then decreased. Wastewater, crude oil, drilling waste, and hydraulic fracturing fluid were the materials most often spilled; spilled volumes of these materials largely ranged from 100 to 10,000 L. Across all states, the average distance of spills to a stream was highest in New Mexico (1379 m), followed by Colorado (747 m), North Dakota (598 m) and then Pennsylvania (268 m), and 7.0, 13.3, and 20.4% of spills occurred within existing surface water setback regulations of 30.5, 61.0, and 91.4 m, respectively. Pennsylvania spills occurred in watersheds with a higher relative importance to drinking water than the other three states. Results from this study can inform risk assessments by providing improved input parameters on volume and rates of materials spilled, and guide regulations and the management policy of spills.

Neurotrophin signalling pathways regulating neuronal apoptosis.

PubMed

Miller, F D; Kaplan, D R

2001-07-01

Recent evidence indicates that naturally occurring neuronal death in mammals is regulated by the interplay between receptor-mediated prosurvival and proapoptotic signals. The neurotrophins, a family of growth factors best known for their positive effects on neuronal biology, have now been shown to mediate both positive and negative survival signals, by signalling through the Trk and p75 neurotrophin receptors, respectively. The mechanisms whereby these two neurotrophin receptors interact to determine neuronal survival have been difficult to decipher, largely because both can signal independently or coincidentally, depending upon the cell or developmental context. Nonetheless, the past several years have seen significant advances in our understanding of this receptor signalling system. In this review, we focus on the proapoptotic actions of the p75 neurotrophin receptor (p75NTR), and on the interplay between Trk and p75NTR that determines neuronal survival.

Nuclear electric propulsion

NASA Technical Reports Server (NTRS)

Keaton, Paul W.; Tubb, David J.

1986-01-01

The feasibility is investigated of using nuclear electric propulsion (NEP) for slow freighter ships traveling from a 500 km low Earth orbit (LEO) to the Moon's orbit about the Earth, and on to Mars. NEP is also shown to be feasible for transporting people to Mars on long conjunction-class missions lasting about nine months one way, and on short sprint missions lasting four months one way. Generally, it was not attempted to optimize ion exhaust velocities, but rather suitable parameters to demonstrate NEP feasibility were chosen. Various combinations of missions are compared with chemical and nuclear thermal propulsion (NTR) systems. Typically, NEP and NTR can accomplish the same lifting task with similar mass in LEO. When compared to chemical propulsion, NEP was found to accomplish the same missions with 40% less mass in LEO. These findings are sufficiently encouraging as to merit further studies with optimum systems.

Comparison of N-terminal modifications on neurotensin(8-13) analogues correlates peptide stability but not binding affinity with in vivo efficacy.

PubMed

Orwig, Kevin S; Lassetter, McKensie R; Hadden, M Kyle; Dix, Thomas A

2009-04-09

Neurotensin(8-13) and two related analogues were used as model systems to directly compare various N-terminal peptide modifications representing both commonly used and novel capping groups. Each N-terminal modification prevented aminopeptidase cleavage but surprisingly differed in its ability to inhibit cleavage at other sites, a phenomenon attributed to long-range conformational effects. None of the capping groups were inherently detrimental to human neurotensin receptor 1 (hNTR1) binding affinity or receptor agonism. Although the most stable peptides exhibited the lowest binding affinities and were the least potent receptor agonists, they produced the largest in vivo effects. Of the parameters studied only stability significantly correlated with in vivo efficacy, demonstrating that a reduction in binding affinity at NTR1 can be countered by increased in vivo stability.

Short communication: identification of the conformational requirement for the specificities of coreceptors for human and simian immunodeficiency viruses.

PubMed

Shimizu, Nobuaki; Tanaka, Atsushi; Jinno-Oue, Atsushi; Mori, Takahisa; Ohtsuki, Takahiro; Hoshino, Hiroo

2010-03-01

More than 10 G protein-coupled receptors (GPCRs) work as coreceptors for human and simian immunodeficiency viruses (HIVs/SIVs); however, structural features critical for coreceptor activity have not been identified. Our objective was to elucidate the structural requirement of coreceptor activities. Amino-terminal regions (NTRs), extracellular loops (ECLs), and the undecapeptidyl arch (UPA) in the second ECL have been shown to be important for coreceptor function. We made chimeric coreceptors for these regions between CCR5 and GPR1, which is genetically distant from CCR5, and analyzed their activities. The coreceptor activity and specificity of CCR5 were maintained when its NTR or UPA was replaced with GPR1. In contrast, the GPR1 chimera with CCR5 NTR was used by HIV-1 strains that can use only CCR5, but not both CCR5 and CXCR4, or GPR1. GPR1 chimera with CCR5 UPA almost lost activity. All ECL chimeras could hardly maintain activity. Thus, CCR5 is more flexibly acceptable to heterologous NTR and UPA than GPR1, suggesting the existence of conformational differences made by the integration of multiple extracellular regions. This conformation may specifically interact with HIV-1 in a strain-dependent manner. Identification of a factor that is critical to make this conformation will contribute to understanding the mechanism of coreceptor function of GPCRs. For this, the coreceptor activity of GPR1, which is genetically distant from CCR5, will be a useful tool.

Neurotrophin/receptor expression in urinary bladder of mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Malley, Susan E; Vizzard, Margaret A

2011-02-01

Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency, and results in increased referred somatic hypersensitivity. Additional NGF-mediated pleiotropic changes might contribute to the increased voiding frequency and pelvic hypersensitivity observed in these transgenic mice, such as modulation of other growth factor/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific uroplakin II promoter. In the present study, we examined NGF, brain-derived neurotrophic factor (BDNF), and associated receptor [p75(NTR), tyrosine kinase (Trk)A, TrkB] transcript and protein expression in urothelium and detrusor smooth muscle of NGF-overexpressing (OE) and littermate wild-type mice, using real-time quantitative reverse transcription-polymerase chain reaction, ELISAs, and semiquantitation of immunohistochemistry. We focused on these growth factor/receptors given the established roles of NGF/TrkA, NGF/p75(NTR), and BDNF/TrkB systems in bladder function. Increased voiding frequency in NGF-OE mice was confirmed by examining urination patterns. BDNF, TrkA, and TrkB protein expression was significantly (P ≤ 0.01) reduced and p75(NTR) protein expression was significantly (P ≤ 0.01) increased in urinary bladder of NGF-OE mice. The NGF-OE-induced changes in neurotrophic factor/receptor expression in urinary bladder may represent compensatory changes to reduce voiding frequency in the NGF-OE mouse.

Conformational switching upon phosphorylation: a predictive framework based on energy landscape principles.

PubMed

Lätzer, Joachim; Shen, Tongye; Wolynes, Peter G

2008-02-19

We investigate how post-translational phosphorylation modifies the global conformation of a protein by changing its free energy landscape using two test proteins, cystatin and NtrC. We first examine the changes in a free energy landscape caused by phosphorylation using a model containing information about both structural forms. For cystatin the free energy cost is fairly large indicating a low probability of sampling the phosphorylated conformation in a perfectly funneled landscape. The predicted barrier for NtrC conformational transition is several times larger than the barrier for cystatin, indicating that the switch protein NtrC most probably follows a partial unfolding mechanism to move from one basin to the other. Principal component analysis and linear response theory show how the naturally occurring conformational changes in unmodified proteins are captured and stabilized by the change of interaction potential. We also develop a partially guided structure prediction Hamiltonian which is capable of predicting the global structure of a phosphorylated protein using only knowledge of the structure of the unphosphorylated protein or vice versa. This algorithm makes use of a generic transferable long-range residue contact potential along with details of structure short range in sequence. By comparing the results obtained with this guided transferable potential to those from the native-only, perfectly funneled Hamiltonians, we show that the transferable Hamiltonian correctly captures the nature of the global conformational changes induced by phosphorylation and can sample substantially correct structures for the modified protein with high probability.

SorCS2 is required for BDNF-dependent plasticity in the hippocampus.

PubMed

Glerup, S; Bolcho, U; Mølgaard, S; Bøggild, S; Vaegter, C B; Smith, A H; Nieto-Gonzalez, J L; Ovesen, P L; Pedersen, L F; Fjorback, A N; Kjolby, M; Login, H; Holm, M M; Andersen, O M; Nyengaard, J R; Willnow, T E; Jensen, K; Nykjaer, A

2016-12-01

SorCS2 is a member of the Vps10p-domain receptor gene family receptors with critical roles in the control of neuronal viability and function. Several genetic studies have suggested SORCS2 to confer risk of bipolar disorder, schizophrenia and attention deficit-hyperactivity disorder. Here we report that hippocampal N-methyl-d-aspartate receptor-dependent synaptic plasticity is eliminated in SorCS2-deficient mice. This defect was traced to the ability of SorCS2 to form complexes with the neurotrophin receptor p75 NTR , required for pro-brain-derived neurotrophic factor (BDNF) to induce long-term depression, and with the BDNF receptor tyrosine kinase TrkB to elicit long-term potentiation. Although the interaction with p75 NTR was static, SorCS2 bound to TrkB in an activity-dependent manner to facilitate its translocation to postsynaptic densities for synaptic tagging and maintenance of synaptic potentiation. Neurons lacking SorCS2 failed to respond to BDNF by TrkB autophosphorylation, and activation of downstream signaling cascades, impacting neurite outgrowth and spine formation. Accordingly, Sorcs2 -/- mice displayed impaired formation of long-term memory, increased risk taking and stimulus seeking behavior, enhanced susceptibility to stress and impaired prepulse inhibition. Our results identify SorCS2 as an indispensable coreceptor for p75 NTR and TrkB in hippocampal neurons and suggest SORCS2 as the link between proBDNF/BDNF signaling and mental disorders.

p75 neurotrophin receptor positive dental pulp stem cells: new hope for patients with neurodegenerative disease and neural injury.

PubMed

Dai, Jie-wen; Yuan, Hao; Shen, Shun-yao; Lu, Jing-ting; Zhu, Xiao-fang; Yang, Tong; Zhang, Jiang-fei; Shen, Guo-fang

2013-08-01

Neurodegenerative diseases and neural injury are 2 of the most feared disorders that afflict humankind by leading to permanent paralysis and loss of sensation. Cell based treatment for these diseases had gained special interest in recent years. Previous studies showed that dental pulp stem cells (DPSCs) could differentiate toward functionally active neurons both in vitro and in vivo, and could promote neuranagenesis through both cell-autonomous and paracrine neuroregenerative activities. Some of these neuroregenerative activities were unique to tooth-derived stem cells and superior to bone marrow stromal cells. However, DPSCs used in most of these studies were mixed and unfractionated dental pulp cells that contain several types of cells, and most were fibroblast cells while just contain a small portion of DPSCs. Thus, there might be weaker ability of neuranagenesis and more side effects from the fibroblast cells that cannot differentiate into neural cells. p75 neurotrophin receptor (p75NTR) positive DPSCs subpopulation was derived from migrating cranial neural crest cells and had been isolated from DPSCs, which had capacity of differentiation into neurons and repairing neural system. In this article, we hypothesize that p75NTR positive DPSCs simultaneously have greater propensity for neuronal differentiation and fewer side effects from fibroblast, and in vivo transptantation of autologous p75NTR positive DPSCs is a novel method for neuranagenesis. This will bring great hope to patients with neurodegenerative disease and neural injury.

Anomalous Refraction of Acoustic Guided Waves in Solids with Geometrically Tapered Metasurfaces.

PubMed

Zhu, Hongfei; Semperlotti, Fabio

2016-07-15

The concept of a metasurface opens new exciting directions to engineer the refraction properties in both optical and acoustic media. Metasurfaces are typically designed by assembling arrays of subwavelength anisotropic scatterers able to mold incoming wave fronts in rather unconventional ways. The concept of a metasurface was pioneered in photonics and later extended to acoustics while its application to the propagation of elastic waves in solids is still relatively unexplored. We investigate the design of acoustic metasurfaces to control elastic guided waves in thin-walled structural elements. These engineered discontinuities enable the anomalous refraction of guided wave modes according to the generalized Snell's law. The metasurfaces are made out of locally resonant toruslike tapers enabling an accurate phase shift of the incoming wave, which ultimately affects the refraction properties. We show that anomalous refraction can be achieved on transmitted antisymmetric modes (A_{0}) either when using a symmetric (S_{0}) or antisymmetric (A_{0}) incident wave, the former clearly involving mode conversion. The same metasurface design also allows achieving structure embedded planar focal lenses and phase masks for nonparaxial propagation.

"Total Physical Response": Un apprentissage non conventionnel ("Total Physical Response": An Unconventional Way to Learn).

ERIC Educational Resources Information Center

Lafayette, R. C.

1991-01-01

A discussion of the Total Physical Response method of second language instruction places the concept within the context of other unconventional language learning methods, reviews the rationale behind the approach, and outlines the classroom procedures used. A sampling of useful commands for classroom use is included. (19 references) (MSE)

An unconventional approach to ecosystem unit classification in western North Carolina, USA

Treesearch

W. Henry McNab; Sara A. Browning; Steven A. Simon; Penelope E. Fouts

1999-01-01

The authors used an unconventional combination of data transformation and multivariate analyses to reduce subjectivity in identification of ecosystem units in a mountainous region of western North Carolina, USA. Vegetative cover and environmental variables were measured on 79 stratified, randomly located, 0.1 ha sample plots in a 4000 ha watershed. Binary...

Introduction

USGS Publications Warehouse

Warwick, Peter D.

2011-01-01

The Energy Minerals Division (EMD) of the American Association of Petroleum Geologists (AAPG) is a membership-based, technical interest group having the primary goal of advancing the science of geology, especially as it relates to exploration, discovery, and production of unconventional energy resources. Current research on unconventional energy resources is rapidly changing and exploration and development efforts for these resources are constantly expanding. Nine summaries derived from 2011 committee reports presented at the EMD Annual Meeting in Houston, Texas in April, 2011, are contained in this review. The complete set of committee reports is available to AAPG members at http://emd.aapg.org/members_only/ annual2011/index.cfm. This report updates the 2006 and 2009 EMD unconventional energy review published in this journal (American Association of Petroleum Geologists, Energy Minerals Division 2007, 2009).

From Cytosol to the Apoplast: The Hygromycin Phosphotransferase (HYG(R)) Model in Arabidopsis.

PubMed

Zhang, Haiyan; Li, Jinjin

2016-01-01

The process by which proteins are secreted via endoplasmic reticulum (ER)/Golgi-independent mechanism is conveniently called unconventional protein secretion. Recent studies have revealed that unconventional protein secretion operates in plants, but little is known about its underlying mechanism and function. This chapter provides methods we have used to analyze unconventional character of hygromycin phosphotransferase (HYG(R)) secretion in plant cells. Following isolation of protoplasts from HYG (R) -GFP-transgenic plants and incubation with brefeldin A (BFA), an inhibitor of conventional secretory pathway, we easily obtain protein extracts from protoplasts and culture medium separately. These proteins are separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), followed by Western blot analysis with anti-GFP antibodies.

Geckoprinting: assembly of microelectronic devices on unconventional surfaces by transfer printing with isolated gecko setal arrays

PubMed Central

Jeong, Jaeyoung; Kim, Juho; Song, Kwangsun; Autumn, Kellar; Lee, Jongho

2014-01-01

Developing electronics in unconventional forms provides opportunities to expand the use of electronics in diverse applications including bio-integrated or implanted electronics. One of the key challenges lies in integrating semiconductor microdevices onto unconventional substrates without glue, high pressure or temperature that may cause damage to microdevices, substrates or interfaces. This paper describes a solution based on natural gecko setal arrays that switch adhesion mechanically on and off, enabling pick and place manipulation of thin microscale semiconductor materials onto diverse surfaces including plants and insects whose surfaces are usually rough and irregular. A demonstration of functional ‘geckoprinted’ microelectronic devices provides a proof of concept of our results in practical applications. PMID:25056216

Unconventional aspects of electronic transport in delafossite oxides

NASA Astrophysics Data System (ADS)

Daou, Ramzy; Frésard, Raymond; Eyert, Volker; Hébert, Sylvie; Maignan, Antoine

2017-12-01

The electronic transport properties of the delafossite oxides ? are usually understood in terms of two well-separated entities, namely the triangular ? and (? layers. Here, we review several cases among this extensive family of materials where the transport depends on the interlayer coupling and displays unconventional properties. We review the doped thermoelectrics based on ? and ?, which show a high-temperature recovery of Fermi-liquid transport exponents, as well as the highly anisotropic metals ?, ?, and ?, where the sheer simplicity of the Fermi surface leads to unconventional transport. We present some of the theoretical tools that have been used to investigate these transport properties and review what can and cannot be learned from the extensive set of electronic structure calculations that have been performed.

Systems Engineering Capstone Marketplace

DTIC Science & Technology

2017-06-05

well. There have been unconventional teams in previous CM  projects  that operated  outside  of  the  typical  capstone  design  format  and  managed   great... projects  do not need the full $10,000 delegated, and the  lack of charging  the expected personnel  to help  manage   the Capstone Marketplace  impacted  the...University Affiliated  Research  Center  managed  by Stevens Institute of Technology.      This material  is based upon work  supported,  in whole or  in part

Ultraviolet laser-induced voltage in anisotropic shale

NASA Astrophysics Data System (ADS)

Miao, Xinyang; Zhu, Jing; Li, Yizhang; Zhao, Kun; Zhan, Honglei; Yue, Wenzheng

2018-01-01

The anisotropy of shales plays a significant role in oil and gas exploration and engineering. Owing to various problems and limitations, anisotropic properties were seldom investigated by direct current resistivity methods. Here in this work, a 248 nm ultraviolet laser was employed to assess the anisotropic electrical response of a dielectric shale. Angular dependence of laser-induced voltages (V p) were obtained, with a data symmetry at the location of 180° and a ~62.2% V p anisotropy of the sample. The double-exponential functions have provided an explanation for the electrical field controlled carrier transportation process in horizontal and vertical directions. The results demonstrate that the combination of optics and electrical logging analysis (Opti-electrical Logging) is a promising technology for the investigation of unconventional reservoirs.

Development of an Object-Oriented Turbomachinery Analysis Code within the NPSS Framework

NASA Technical Reports Server (NTRS)

Jones, Scott M.

2014-01-01

During the preliminary or conceptual design phase of an aircraft engine, the turbomachinery designer has a need to estimate the effects of a large number of design parameters such as flow size, stage count, blade count, radial position, etc. on the weight and efficiency of a turbomachine. Computer codes are invariably used to perform this task however, such codes are often very old, written in outdated languages with arcane input files, and rarely adaptable to new architectures or unconventional layouts. Given the need to perform these kinds of preliminary design trades, a modern 2-D turbomachinery design and analysis code has been written using the Numerical Propulsion System Simulation (NPSS) framework. This paper discusses the development of the governing equations and the structure of the primary objects used in OTAC.

Hotol and Saenger are good political trump cards

NASA Astrophysics Data System (ADS)

Ruppe, Harry O.

Political and technological aspects of proposals for ESA reusable and/or SSTO launch vehicles (LVs) are examined in a critical review. The lack of reliable performance and cost estimates for such unconventional LV designs as Hotol, Saenger II, LART, ADV, and EARL is pointed out, and it is argued that progress toward the ESA goal of greater European space autonomy could be seriously endangered by abandoning or underfunding the current Ariane/Hermes LV program. The cost and reliability of expendable and reusable LV systems are discussed; two-stage and hybrid air-breathing engine concepts are compared; and the need for fundamental in-depth planning studies based on presently available technology or realistic projections is stressed. Long-term funding of such research at about 5 percent of present Ariane/Hermes levels is recommended.

A Noise and Emissions Assessment of the N3-X Transport

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.; Haller, William J.

2014-01-01

Analytical predictions of certification noise and exhaust emissions for NASA's N3-X - a notional, hybrid wingbody airplane - are presented in this paper. The N3-X is a 300-passenger concept transport propelled by an array of fans distributed spanwise near the trailing edge of the wingbody. These fans are driven by electric motors deriving power from twin generators driven by turboshaft engines. Turboelectric distributed hybrid propulsion has the potential to dramatically increase the propulsive efficiency of aircraft. The noise and exhaust emission estimates presented here are generated using NASA's conceptual design systems analysis tools with several key modifications to accommodate this unconventional architecture. These tools predict certification noise and the emissions of oxides of nitrogen by leveraging data generated from a recent analysis of the N3-X propulsion system.

Modeling the Impact of Deformation on Unstable Miscible Displacements in Porous Media

NASA Astrophysics Data System (ADS)

Santillán, D.; Cueto-Felgueroso, L.

2014-12-01

Coupled flow and geomechanics is a critical research challenge in engineering and the geosciences. The simultaneous flow of two or more fluids with different densities or viscosities through deformable media is ubiquitous in environmental, industrial, and biological processes, including the removal of non-aqueous phase liquids from underground water bodies, the geological storage of CO2, and current challenges in energy technologies, such as enhanced geothermal systems, unconventional hydrocarbon resources or enhanced oil recovery techniques. Using numerical simulation, we study the interplay between viscous-driven flow instabilities (viscous fingering) and rock mechanics, and elucidate the structure of the displacement patterns as a function of viscosity contrast, injection rate and rock mechanical properties. Finally, we discuss the role of medium deformation on transport and mixing processes in porous media.

Modeling the Impact of Fracture Growth on Fluid Displacements in Deformable Porous Media

NASA Astrophysics Data System (ADS)

Santillán, D.; Cueto-Felgueroso, L.; Juanes, R.

2015-12-01

Coupled flow and geomechanics is a critical research challenge in engineering and the geosciences. The flow of a fluid through a deformable porous media is present in manyenvironmental, industrial, and biological processes,such as the removal of pollutants from underground water bodies, enhanced geothermal systems, unconventional hydrocarbon resources or enhanced oil recovery techniques. However, the injection of a fluid can generate or propagate fractures, which are preferential flow paths. Using numerical simulation, we study the interplay between injection and rock mechanics, and elucidate fracture propagation as a function of injection rate, initial crack topology and mechanical rock properties. Finally, we discuss the role of fracture growth on fluid displacements in porous media. Figure: An example of fracture (in red) propagated in a porous media (in blue)

Optimizing Water Management for Collocated Conventional and Unconventional Reservoirs

NASA Astrophysics Data System (ADS)

Reedy, R. C.; Scanlon, B. R.; Walsh, M.

2016-12-01

With the U.S. producing much more water than oil from oil and gas reservoirs, managing produced water is becoming a critical issue. Here we quantify water production from collocated conventional and unconventional reservoirs using well by well analysis and evaluate various water management strategies using the U.S. Permian Basin as a case study. Water production during the past 15 years in the Permian Basin totaled 55×109 barrels (bbl), 95% from wells in conventional reservoirs resulting in an average water to oil ratio of 12 compared to ratios of 2-3 in wells in unconventional reservoirs. Some of this water ( 25%) is returned to the reservoir for secondary oil recovery (water flooding) while the remaining water is injected into an average of 18,000 salt water disposal wells. Total water production over the past 15 yr (2000 - 2015) exceeds water used for hydraulic fracturing by almost 40 times. Analyzing water injection into salt water disposal wells relative to water requirements for hydraulic fracturing at a 5 square mile grid scale based on 2014 data indicates that water disposal exceeds water requirements for hydraulic fracturing throughout most of the play. Reusing/recycling of produced water for hydraulic fracturing would reduce sourcing and disposal issues related to hydraulic fracturing. Because shales (unconventional reservoirs) provide the source rocks for many conventional reservoirs, coordinating water management from both conventional and unconventional reservoirs can help resolve issues related to sourcing of water for hydraulic fracturing and disposing of produced water. Reusing/recycling produced water can also help reduce water scarcity concerns in some regions.

Can Unconventional Exercise be Helpful in the Treatment, Management and Prevention of Osteosarcopenic Obesity?

PubMed

Kelly, Owen J; Gilman, Jennifer C

2017-01-01

Body composition changes occur with aging; bone and muscle mass decrease while fat mass increases. The collective term for these changes is osteosarcopenic obesity. It is known that conventional resistance exercise programs build/maintain lean mass and reduce fat mass. However, unconventional (to Western society/medicine) forms of exercise may be viable for the treatment/prevention of osteosarcopenic obesity. The purpose of this review is to assess relatively unconventional exercises for their efficacy in maintaining/improving bone and muscle mass and reducing fat mass. A literature search for unconventional exercise showed Tai Chi, yoga, Pilates, whole body vibration, electrical stimulation of muscle, and the Alexander Technique were considered alternative/ unconventional. A PubMed and Medline search for human data using combinations and synonyms of osteoporosis, sarcopenia and obesity, and each exercise was then conducted. Tai Chi, yoga, and Pilates, in addition to whole body vibration, electrical stimulation of muscle, and the Alexander Technique are all considered low impact. Tai Chi, yoga, and Pilates not only physically support the body, but also increase balance and quality of life. The devices showed promise in reducing or preventing muscle atrophy in older people that are unable to perform conventional exercises. Any exercise, conventional or otherwise, especially in sedentary older people, at risk of, or diagnosed with osteosarcopenic obesity may be better than none. Exercise prescriptions should suit the patient and the desired outcomes; the patient should not be forced to fit an exercise prescription, so all potential forms of exercise should be considered. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Conventional and Bimodal Nuclear Thermal Rocket (NTR) Artificial Gravity Mars Transfer Vehicle Concepts

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

2016-01-01

A variety of countermeasures have been developed to address the debilitating physiological effects of zero-gravity (0-g) experienced by cosmonauts and astronauts during their approximately 0.5 to 1.2 year long stays in low Earth orbit (LEO). Longer interplanetary flights, combined with possible prolonged stays in Mars orbit, could subject crewmembers to up to approximately 2.5 years of weightlessness. In view of known and recently diagnosed problems associated with 0-g, an artificial gravity (AG) spacecraft offers many advantages and may indeed be an enabling technology for human flights to Mars. A number of important human factors must be taken into account in selecting the rotation radius, rotation rate, and orientation of the habitation module or modules. These factors include the gravity gradient effect, radial and tangential Coriolis forces, along with cross-coupled acceleration effects. Artificial gravity Mars transfer vehicle (MTV) concepts are presented that utilize both conventional NTR, as well as, enhanced bimodal nuclear thermal rocket (BNTR) propulsion. The NTR is a proven technology that generates high thrust and has a specific impulse (Isp) capability of approximately 900 s-twice that of today's best chemical rockets. The AG/MTV concepts using conventional Nuclear Thermal Propulsion (NTP) carry twin cylindrical International Space Station (ISS)- type habitation modules with their long axes oriented either perpendicular or parallel to the longitudinal spin axis of the MTV and utilize photovoltaic arrays (PVAs) for spacecraft power. The twin habitat modules are connected to a central operations hub located at the front of the MTV via two pressurized tunnels that provide the rotation radius for the habitat modules. For the BNTR AG/MTV option, each engine has its own closed secondary helium(He)-xenon (Xe) gas loop and Brayton Rotating Unit (BRU) that can generate 10s of kilowatts (kWe) of spacecraft electrical power during the mission coast phase eliminating the need for large PVAs. A single inflatable TransHab-type habitation module is also used with multiple vertical floors oriented radial to the MTV spin axis. The BNTR MTV's geometry-long and linear-is naturally compatible with AG operation. By rotating the vehicle about its center-of-mass (CM) and perpendicular to its flight vector at approximately 3.0 to 5.2 rpm, a centrifugal force and AG environment corresponding to approximately 0.38 to 1.0 g can be established to help maintain crew fitness out to Mars and back. Vehicles using NTP/ Bimodal Nuclear Thermal Propulsion (BNTP) can more readily accommodate the heavier payload mass and increased RCS propellant loading associated with AG operation, and can travel faster to and from Mars thereby reducing the crew's exposure to galactic cosmic radiation and solar flares. Mission scenario descriptions, key vehicle features and operational characteristics for each propulsion option are presented using the lift capability and payload volumes estimated for the Space Launch System (SLS)-1B and followon Heavy Lift Vehicle (HLV).

Conventional and Bimodal Nuclear Thermal Rocket (NTR) Artificial Gravity Mars Transfer Vehicle Concepts

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

2014-01-01

A variety of countermeasures have been developed to address the debilitating physiological effects of "zero-gravity" (0-g) experienced by cosmonauts and astronauts during their approximately 0.5-1.2 year long stays in LEO (Low Earth Orbit). Longer interplanetary flights, combined with possible prolonged stays in Mars orbit, could subject crewmembers to up to approximately 2.5 years of weightlessness. In view of known and recently diagnosed problems associated with 0-g, an artificial gravity spacecraft offers many advantages and may indeed be an enabling technology for human flights to Mars. A number of important human factors must be taken into account in selecting the rotation radius, rotation rate, and orientation of the habitation module or modules. These factors include the gravity gradient effect, radial and tangential Coriolis forces, along with cross-coupled acceleration effects. Artificial gravity (AG) Mars transfer vehicle (MTV) concepts are presented that utilize both conventional NTR, as well as, enhanced "bimodal" nuclear thermal rocket (BNTR) propulsion. The NTR is a proven technology that generates high thrust and has a specific impulse (I (sub sp)) capability of approximately 900 s - twice that of today's best chemical rockets. The AG/MTV concepts using conventional NTP carry twin cylindrical "ISS-type" habitation modules with their long axes oriented either perpendicular or parallel to the longitudinal spin axis of the MTV and utilize photovoltaic arrays (PVAs) for spacecraft power. The twin habitat modules are connected to a central operations hub located at the front of the MTV via two pressurized tunnels that provide the rotation radius for the habitat modules. For the BNTR AG/MTV option, each engine has its own "closed" secondary helium-xenon gas loop and Brayton rotating unit that can generate tens of kilowatts (kW (sub e)) of spacecraft electrical power during the mission coast phase eliminating the need for large PVAs. A single inflatable "TransHab-type" habitation module is also used with multiple vertical floors oriented radial to the MTV spin axis. The BNTR MTV's geometry - long and linear - is naturally compatible with AG operation. By rotating the vehicle about its center-of-mass and perpendicular to its flight vector at approximately 3.0 - 5.2 rpm, a centrifugal force and AG environment corresponding to approximately 0.38 - 1.0 g can be established to help maintain crew fitness out to Mars and back. Vehicles using NTP/BNTP can more readily accommodate the heavier payload mass and increased RCS propellant loading associated with AG operation, and can travel faster to and from Mars thereby reducing the crew's exposure to galactic cosmic radiation and solar flares. Mission scenario descriptions, key vehicle features and operational characteristics for each propulsion options are presented using the lift capability and payload volumes estimated for the SLS-1A and HLV.

Novel gradient-diameter magnetic nanowire arrays with unconventional magnetic anisotropy behaviors.

PubMed

Wang, Jing; Zuo, Zhili; Huang, Liang; Warsi, Muhammad Asif; Xiao, John Q; Hu, Jun

2018-06-21

Fe-Co-Ni gradient-diameter magnetic nanowire arrays were fabricated via direct-current electrodeposition into a tapered anodic aluminium oxide template. In contrast to the magnetic behaviors of uniform-diameter nanowire arrays, these arrays exhibited tailorable magnetic anisotropy that can be used to switch magnetic nanowires easily and unconventional temperature-dependent coercivity with much better thermal stability.

Unconventional Dentistry in India – An Insight into the Traditional Methods

PubMed Central

Boloor, Vinita Ashutosh; Hosadurga, Rajesh; Rao, Anupama; Jenifer, Haziel; Pratap, Sruthy

2014-01-01

Unconventional medicine (UM) has been known and practised since the recorded history of civilization. Some unconventional practices may be viewed as “the continuity of traditions, religious beliefs, and even quackery that non-specialists practice.” These practices have been associated with religious beliefs and the spiritual domain as well as with the physical domain. In ancient Old World civilizations, UM was performed by skilled experts or wise men; in today's Western civilization, practitioners may or may not be licensed, and some are charlatans. Dentistry, like medicine, is a traditional, science-based, highly regulated healthcare profession that serves increasingly sophisticated and demanding clients. Today, traditional dental practice is dealing with an array of challenges to the established professional system; these challenges are generally termed “alternative” (or complementary, unconventional, or integrative). Genuine alternatives are comparable methods of equal value that have met scientific and regulatory criteria for safety and effectiveness. Because “alternative care” has become politicized and is often a misnomer – referring to practices that are not alternative to, complementary to, or integrating with conventional health care – the more accurate term “unconventional” is used. PMID:25161919

Monitoring radionuclides in subsurface drinking water sources near unconventional drilling operations: a pilot study.

PubMed

Nelson, Andrew W; Knight, Andrew W; Eitrheim, Eric S; Schultz, Michael K

2015-04-01

Unconventional drilling (the combination of hydraulic fracturing and horizontal drilling) to extract oil and natural gas is expanding rapidly around the world. The rate of expansion challenges scientists and regulators to assess the risks of the new technologies on drinking water resources. One concern is the potential for subsurface drinking water resource contamination by naturally occurring radioactive materials co-extracted during unconventional drilling activities. Given the rate of expansion, opportunities to test drinking water resources in the pre- and post-fracturing setting are rare. This pilot study investigated the levels of natural uranium, lead-210, and polonium-210 in private drinking wells within 2000 m of a large-volume hydraulic fracturing operation--before and approximately one-year following the fracturing activities. Observed radionuclide concentrations in well waters tested did not exceed maximum contaminant levels recommended by state and federal agencies. No statistically-significant differences in radionuclide concentrations were observed in well-water samples collected before and after the hydraulic fracturing activities. Expanded monitoring of private drinking wells before and after hydraulic fracturing activities is needed to develop understanding of the potential for drinking water resource contamination from unconventional drilling and gas extraction activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microfluidics: Science and Engineering at the Edge of the Continuum

NASA Astrophysics Data System (ADS)

Breuer, Kenny

2002-11-01

The widespread growth of microengineering and the development of a new generation of micron- and nanometer scale diagnostic techniques has focussed much recent attention on the mechanics of fluids at the micron and sub-micron scale. Challenges with both scientific and engineering relevance have been raised by this activity, ranging from the prediction of viscous damping and lubrication effects in MEMS to the design of microengines to the understanding of bacterial propulsion. Identifying and addressing these challenges form the basis of this talk. >From a scientific perspective, a question that refuses to die is that of the applicability of the continuum hypothesis, and the possible existence of new physical phenomena only observable in small systems. To be brief, the reports of the demise of the Navier-Stokes equations are greatly exaggerated and to illustrate this we will review the more recent work on near-continuum fluid mechanics in micron and sub-micron scale devices with an emphasis on our own experiments on the breakdown of the continuum description in both gaseous and liquid flows. From an engineering perspective, the tight coupling between fluids, structures and manufacturing result in flows characterized by unfamiliar parameter regimes and unconventional geometries. We will look at several examples of such microfluidic engineering, drawn from MEMS (inertial instruments, microengines) and biology (bacterial propulsion) that illustrate the the unique design challenges that we encounter in microfluidic devices and the solutions (and lack of solutions) to these problems.

Two unconventional risk factors for major adverse cardiovascular events in subjects with sexual dysfunction: low education and reported partner's hypoactive sexual desire in comparison with conventional risk factors.

PubMed

Rastrelli, Giulia; Corona, Giovanni; Fisher, Alessandra D; Silverii, Antonio; Mannucci, Edoardo; Maggi, Mario

2012-12-01

The classification of subjects as low or high cardiovascular (CV) risk is usually performed by risk engines, based upon multivariate prediction algorithms. However, their accuracy in predicting major adverse CV events (MACEs) is lower in high-risk populations as they take into account only conventional risk factors. To evaluate the accuracy of Progetto Cuore risk engine in predicting MACE in subjects with erectile dysfunction (ED) and to test the role of unconventional CV risk factors, specifically identified for ED. A consecutive series of 1,233 men (mean age 53.33 ± 9.08 years) attending our outpatient clinic for sexual dysfunction was longitudinally studied for a mean period of 4.4 ± 2.6 years. Several clinical, biochemical, and instrumental parameters were evaluated. Subjects were classified as high or low risk, according to previously reported ED-specific risk factors. In the overall population, Progetto Cuore-predicted population survival was not significantly different from the observed one (P = 0.545). Accordingly, receiver operating characteristic (ROC) analysis shows that Progetto Cuore has an accuracy of 0.697 ± 0.037 (P < 0.001) in predicting MACE. Considering subjects at high risk according to ED-specific risk factors, the observed incidence of MACE was significantly higher than the expected for both low educated and patients reporting partner's hypoactive sexual desire (HSD, both <0.05), but not for other described factors. The area under ROC curves of Progetto Cuore for MACE in subjects with low education and reported partner's HSD were 0.659 ± 0.053 (P = 0.008) and 0.550 ± 0.076 (P = 0.570), respectively. Overall, Progetto Cuore is a proper instrument for evaluating CV risk in ED subjects. However, in ED, other factors such as low education and partner's HSD concur to risk profile. At variance with low education, Progetto Cuore is not accurate enough to predict MACE in subjects with partner's HSD, suggesting that the latter effect is not mediated by conventional risk factors included in the algorithm. © 2012 International Society for Sexual Medicine.

Evaluation of Potential Damage to Unconventional Structures by Sonic Booms

DTIC Science & Technology

1990-05-01

plaster and gypsum board caused by sonic boom is broken...on wood lath 3.3 5.6 2. Plaster on gyplath 7.5 16 3. Plaster on expanded metal lath 16 16 4. Plaster on concrete block 16 16 5. Gypsum board (new) 16... wallboard (also called plasterboard or drywall), it is assumed that interior walls of unconventional historic wood frame buildings used plaster instead.

How to Survive and Prosper in the Real World after Graduation: An Unconventional Approach to Achieving Your Success.

ERIC Educational Resources Information Center

Connors, Shawn M.

Unconventional advice to help college graduates be successful is offered. Ways to find sources of money (i.e., jobs) are described, including: using services or products offered through the mail, making phone calls to build a network of contacts in a particular industry, attending seminars to further one's knowledge of a field, learning about…

Unconventional Cyber Warfare: Cyber Opportunities in Unconventional Warfare

DTIC Science & Technology

2014-06-01

thanks to Tunisia’s modern communications infrastructure , pervasive Internet, and mobile phone network.”151 Although the use of information and...and physical space. Tunisia had a well-developed mobile phone and Internet infrastructure with nearly nine out of 10 Tunisians owning a mobile phone...OF TABLES Table 1. Top 20 countries of mobile phones per 100 people .........................................60 Table 2. Top 20 countries by number

Design of a trial-based economic evaluation on the cost-effectiveness of employability interventions among work disabled employees or employees at risk of work disability: The CASE-study

PubMed Central

2012-01-01

Background In the Netherlands, absenteeism and reduced productivity due to work disability lead to high yearly costs reaching almost 5% of the gross national product. To reduce the economic burden of sick leave and reduced productivity, different employability interventions for work-disabled employees or employees at risk of work disability have been developed. Within this study, called 'CASE-study' (Cost-effectiveness Analysis of Sustainable Employability), five different employability interventions directed at work disabled employees with divergent health complaints will be analysed on their effectiveness and cost-effectiveness. This paper describes a consistent and transparent methodological design to do so. Methods/design Per employability intervention 142 participants are needed whereof approximately 66 participants receiving the intervention will be compared with 66 participants receiving usual care. Based on the intervention-specific characteristics, a randomized control trial or a quasi-experiment with match-criteria will be conducted. Notwithstanding the study design, eligible participants will be employees aged 18 to 63, working at least 12 h per week, and at risk of work disability, or already work-disabled due to medical restrictions. The primary outcome will be the duration of sick leave. Secondary outcomes are health status and quality of life. Outcomes will be assessed at baseline and then 6, 12 and 18 months later. Economic costs will consist of healthcare costs and cost of lost production due to work disability, and will be evaluated from a societal perspective. Discussion The CASE-study is the first to conduct economic evaluations of multiple different employability interventions based on a similar methodological framework. The cost-effectiveness results for every employability intervention will be published in 2014, but the methods, strengths and weaknesses of the study protocol are discussed in this paper. To contribute to treatment options in occupational health practice and enable the development of guidelines on how to conduct economic evaluation better suited to this field; this paper provides an important first step. Trial registration Four trials involved in the CASE-study are registered with the Netherlands Trial Registry: Care for Work (NTR2886), Health and Motion (NTR3111), Guidance to Excel in Return to Work (NTR3151), Care for Companies/Second Care (NTR3136). PMID:22257557

Unconventional signal detection techniques with Gaussian probability mixtures adaptation in non-AWGN channels: full resolution receiver

NASA Astrophysics Data System (ADS)

Chabdarov, Shamil M.; Nadeev, Adel F.; Chickrin, Dmitry E.; Faizullin, Rashid R.

2011-04-01

In this paper we discuss unconventional detection technique also known as «full resolution receiver». This receiver uses Gaussian probability mixtures for interference structure adaptation. Full resolution receiver is alternative to conventional matched filter receivers in the case of non-Gaussian interferences. For the DS-CDMA forward channel with presence of complex interferences sufficient performance increasing was shown.

Unconventional Warfare in the American Civil War

DTIC Science & Technology

2004-06-18

Miller Thesis Title: Unconventional Warfare in the American Civil War Approved by: , Thesis Committee Chair LTC ( R ) Gregory T. Beck...M.A. , Member LTC ( R ) Richard Barbuto, Ph.D. , Consulting Faculty LTC ( R ) James B. Martin, Ph.D. Accepted this 18th day of...troops and supplies to forward areas. In official correspondence dated 26 May 1864 from Captain A. V. Barringer , Chief Quartermaster, Department of West

Transcription factor-based biosensors enlightened by the analyte

PubMed Central

Fernandez-López, Raul; Ruiz, Raul; de la Cruz, Fernando; Moncalián, Gabriel

2015-01-01

Whole cell biosensors (WCBs) have multiple applications for environmental monitoring, detecting a wide range of pollutants. WCBs depend critically on the sensitivity and specificity of the transcription factor (TF) used to detect the analyte. We describe the mechanism of regulation and the structural and biochemical properties of TF families that are used, or could be used, for the development of environmental WCBs. Focusing on the chemical nature of the analyte, we review TFs that respond to aromatic compounds (XylS-AraC, XylR-NtrC, and LysR), metal ions (MerR, ArsR, DtxR, Fur, and NikR) or antibiotics (TetR and MarR). Analyzing the structural domains involved in DNA recognition, we highlight the similitudes in the DNA binding domains (DBDs) of these TF families. Opposite to DBDs, the wide range of analytes detected by TFs results in a diversity of structures at the effector binding domain. The modular architecture of TFs opens the possibility of engineering TFs with hybrid DNA and effector specificities. Yet, the lack of a crisp correlation between structural domains and specific functions makes this a challenging task. PMID:26191047

Transcription factor-based biosensors enlightened by the analyte.

PubMed

Fernandez-López, Raul; Ruiz, Raul; de la Cruz, Fernando; Moncalián, Gabriel

2015-01-01

Whole cell biosensors (WCBs) have multiple applications for environmental monitoring, detecting a wide range of pollutants. WCBs depend critically on the sensitivity and specificity of the transcription factor (TF) used to detect the analyte. We describe the mechanism of regulation and the structural and biochemical properties of TF families that are used, or could be used, for the development of environmental WCBs. Focusing on the chemical nature of the analyte, we review TFs that respond to aromatic compounds (XylS-AraC, XylR-NtrC, and LysR), metal ions (MerR, ArsR, DtxR, Fur, and NikR) or antibiotics (TetR and MarR). Analyzing the structural domains involved in DNA recognition, we highlight the similitudes in the DNA binding domains (DBDs) of these TF families. Opposite to DBDs, the wide range of analytes detected by TFs results in a diversity of structures at the effector binding domain. The modular architecture of TFs opens the possibility of engineering TFs with hybrid DNA and effector specificities. Yet, the lack of a crisp correlation between structural domains and specific functions makes this a challenging task.

Unconventional gas development facilitates plant invasions.

PubMed

Barlow, Kathryn M; Mortensen, David A; Drohan, Patrick J; Averill, Kristine M

2017-11-01

Vegetation removal and soil disturbance from natural resource development, combined with invasive plant propagule pressure, can increase vulnerability to plant invasions. Unconventional oil and gas development produces surface disturbance by way of well pad, road, and pipeline construction, and increased traffic. Little is known about the resulting impacts on plant community assembly, including the spread of invasive plants. Our work was conducted in Pennsylvania forests that overlay the Marcellus and Utica shale formations to determine if invasive plants have spread to edge habitat created by unconventional gas development and to investigate factors associated with their presence. A piecewise structural equation model was used to determine the direct and indirect factors associated with invasive plant establishment on well pads. The model included the following measured or calculated variables: current propagule pressure on local access roads, the spatial extent of the pre-development road network (potential source of invasive propagules), the number of wells per pad (indicator of traffic density), and pad age. Sixty-one percent of the 127 well pads surveyed had at least one invasive plant species present. Invasive plant presence on well pads was positively correlated with local propagule pressure on access roads and indirectly with road density pre-development, the number of wells, and age of the well pad. The vast reserves of unconventional oil and gas are in the early stages of development in the US. Continued development of this underground resource must be paired with careful monitoring and management of surface ecological impacts, including the spread of invasive plants. Prioritizing invasive plant monitoring in unconventional oil and gas development areas with existing roads and multi-well pads could improve early detection and control of invasive plants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal pathways from unconventional personal attributes in the late 20s to cannabis use prior to sexual intercourse in the late 30s.

PubMed

Lee, Jung Yeon; Brook, Judith S; Pahl, Kerstin; Brook, David W

2017-11-01

A quarter of people living with human immunodeficiency virus (HIV) infection in the United States are women. Furthermore, African American and Hispanic/Latina women continue to be disproportionately affected by HIV, compared with women of other races/ethnicities. Cannabis use prior to intercourse may be associated with increased risky sexual behaviors which are highly related to HIV. The ultimate goal of this research is to better understand the relationships between unconventional personal attributes (e.g., risk-taking behaviors) in the late 20s, substance use (e.g., alcohol) in the mid 30s, and cannabis use prior to intercourse in the late 30s using a community sample; such an understanding may inform interventions. This study employing data from the Harlem Longitudinal Development Study includes 343 female participants (50% African Americans, 50% Puerto Ricans). Structural equation modeling indicated that unconventional personal attributes in the late 20s were associated with substance use in the mid 30s (β=0.32, p<0.001), which in turn, was associated with cannabis use prior to sexual intercourse in the late 30s (β=0.64, p<0.001). Unconventional personal attributes in the late 20s were also directly related to cannabis use prior to sexual intercourse in the late 30s (β=0.39, p<0.01). The findings of this study suggest that interventions focused on decreasing unconventional personal attributes as well as substance use may reduce sexual risk behaviors among urban African American and Puerto Rican women. Also, the implications of this study for health care providers and researchers working in HIV prevention are that these precursors may be useful as patient screening tools. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pig Feeding under the Potato-green Forage Base System with or without Addition of Herbs versus a Concentrate Based System: Effect on Post-slaughter Performance and Pork Characteristics

PubMed Central

Turyk, Zofia; Osek, Maria; Olkowski, Bogusław; Janocha, Alina

2014-01-01

This study examined carcass and meat quality parameters in growing/finishing pigs fed unconventionally versus the concentrate-based system. Ninety-six, 12 wk old pigs (34±SD 0.3 kg) were randomly divided into three groups, assigned to one of the three dietary treatments: standard complete concentrate mixture, conventional (C diet); unconventional, steamed potato-green forage-concentrate based diet (U diet), and unconventional basal diet+herbage mix (UH diet). Pigs fed U diet showed lower dressing percentage, meatiness, loin eye area, and weight of pork neck (p≤0.05), but their carcasses were significantly (p≤0.05) longer and had increased backfat depth (p≤0.05). There was no impact of the diet on the meat content of dry matter, crude ash, acidity, and colour parameters of m. longissimus. Unconventional feeding significantly (p≤0.05) elevated water the holding capacity of m. longissimus and slightly improved the sensory attributes analysis of meat. The addition of herbs resulted in increased loin eye area (p≤0.05), decreased fat content (p≤0.05) in m. longissimus, and tended to improve some sensory attributes of meat. There were significant gender differences in response to all diets. There were significant diet×sex interactions for some measured variables, but there were no clearly identifiable trends with regard to any specific carcass or meat parameters. Feeding unconventional diet to pigs may offer better culinary attributes of the meat, and improve some technologically important characteristics of pig carcass, but may negatively affect some carcass or meat parameters. PMID:25050003

Sarcomeric Myosin Expression in the Tongue Body of Humans, Macaques and Rats

PubMed Central

Rahnert, Jill A.; Sokoloff, Alan J.; Burkholder, Thomas J.

2010-01-01

Expression of developmental and unconventional myosin heavy chain (MHC) isoforms in some adult head and neck muscles is thought to reflect specific contractile demands of muscle fibers active during kinematically complex movements. Mammalian tongue muscles are active during oromotor behaviors that encompass a wide range of tongue movement speeds and tongue shape changes (e.g. respiration, oral transport, swallowing, rejection), but the extent to which tongue muscles express developmental and unconventional MHC is not known. Quantitative PCR was used to determine the mRNA content of conventional MHC-beta, MHC-2a, MHC-2b and MHC-2x, the developmental isoforms embryonic MHC and neonatal MHC and the unconventional isoforms atrial/cardiac-α MHC (MHC-alpha), extraocular MHC, masseter MHC and slow tonic MHC in tongue body muscles of the rat, macaque and human. In all species, conventional MHC isoforms predominate. MHC-2b and MHC-2x account for 98% of total MHC mRNA in the rat. MHC-2a, MHC-2x and MHC-beta account for 94% of total MHC mRNA in humans and 96% of total MHC mRNA in macaque. With the exception of MHC-alpha in humans (5%), developmental and unconventional MHC mRNA represents less than 0.3% of total MHC mRNA. We conclude that in these species, there is limited expression of developmental and unconventional MHC and that diversity of tongue body muscle fiber contractile properties is achieved primarily by MHC-beta, MHC-2a, MHC-2x and MHC-2b. Whether expression of MHC-alpha mRNA in tongue is unique to humans or present in other hominoids awaits further investigation. PMID:19907142

Water Issues Associated with Increasing Unconventional Oil Production in the Permian Basin

NASA Astrophysics Data System (ADS)

Reedy, R. C.; Scanlon, B. R.; Male, F.; Walsh, M.

2017-12-01

The Permian Basin is being transformed from a major conventional oil play to the world's largest unconventional play; however, managing water for this transition is critical in this semiarid region. The study included quantifying produced water volumes with oil and gas production along with water demands for hydraulic fracturing using a detailed well-by-well analysis. Our results show that oil wells in conventional reservoirs generate large volumes of produced water relative to oil production with produced water to oil ratios of 13 (i.e. 13 barrels [bbl] of water relative to a bbl of oil). However, produced water from conventional reservoirs has been mostly injected back into the pressure-depleted oil-producing reservoirs for enhanced oil recovery using water flooding. Unconventional horizontal wells use large volumes of water for hydraulic fracturing that has been markedly increasing by factors of 10 - 16 per well and by factors of 7-10 after dividing by lateral well length (2008-2015). Although unconventional wells generate less produced water relative to oil ( 3 bbl of water relative to oil) than conventional wells, the main difference is that this produced water cannot be reinjected into the low permeability shale reservoirs. Instead, the produced water is disposed into non-producing geologic zones that could result in overpressuring and induced seismicity. There is a high potential for reusing produced water from unconventional wells in the Permian Basin because the produced water volumes can support the hydraulic fracturing water demand based on 2014 data. Reusing produced water with minimal water treatment (clean brine) could partially mitigate produced water injection concerns while reducing water demand for hydraulic fracturing.

An Escherichia coli nitrogen starvation response is important for mutualistic coexistence with Rhodopseudomonas palustris.

PubMed

McCully, Alexandra L; Behringer, Megan G; Gliessman, Jennifer R; Pilipenko, Evgeny V; Mazny, Jeffrey L; Lynch, Michael; Drummond, D Allan; McKinlay, James B

2018-05-04

Microbial mutualistic cross-feeding interactions are ubiquitous and can drive important community functions. Engaging in cross-feeding undoubtedly affects the physiology and metabolism of individual species involved. However, the nature in which an individual's physiology is influenced by cross-feeding and the importance of those physiological changes for the mutualism have received little attention. We previously developed a genetically tractable coculture to study bacterial mutualisms. The coculture consists of fermentative Escherichia coli and phototrophic Rhodopseudomonas palustris In this coculture, E. coli anaerobically ferments sugars into excreted organic acids as a carbon source for R. palustris In return, a genetically-engineered R. palustris constitutively converts N 2 into NH 4 + , providing E. coli with essential nitrogen. Using RNA-seq and proteomics, we identified transcript and protein levels that differ in each partner when grown in coculture versus monoculture. When in coculture with R. palustris , E. coli gene-expression changes resembled a nitrogen starvation response under the control of the transcriptional regulator NtrC. By genetically disrupting E. coli NtrC, we determined that a nitrogen starvation response is important for a stable coexistence, especially at low R. palustris NH 4 + excretion levels. Destabilization of the nitrogen starvation regulatory network resulted in variable growth trends and in some cases, extinction. Our results highlight that alternative physiological states can be important for survival within cooperative cross-feeding relationships. Importance Mutualistic cross-feeding between microbes within multispecies communities is widespread. Studying how mutualistic interactions influence the physiology of each species involved is important for understanding how mutualisms function and persist in both natural and applied settings. Using a bacterial mutualism consisting of Rhodopseudomonas palustris and Escherichia coli growing cooperatively through bidirectional nutrient exchange, we determined that an E. coli nitrogen starvation response is important for maintaining a stable coexistence. The lack of an E. coli nitrogen starvation response ultimately destabilized the mutualism and, in some cases, led to community collapse after serial transfers. Our findings thus inform on the potential necessity of an alternative physiological state for mutualistic coexistence with another species compared to the physiology of species grown in isolation. Copyright © 2018 American Society for Microbiology.

Unconventional energy resources: 2007-2008 review

USGS Publications Warehouse

Warwick, Peter D.; ,

2009-01-01

This paper summarizes five 2007–2008 resource commodity committee reports prepared by the Energy Minerals Division (EMD) of the American Association of Petroleum Geologists. Current United States and global research and development activities related to gas hydrates, gas shales, geothermal resources, oil sands, and uranium resources are included in this review. These commodity reports were written to advise EMD leadership and membership of the current status of research and development of unconventional energy resources. Unconventional energy resources are defined as those resources other than conventional oil and natural gas that typically occur in sandstone and carbonate rocks. Gas hydrate resources are potentially enormous; however, production technologies are still under development. Gas shale, geothermal, oil sand, and uranium resources are now increasing targets of exploration and development, and are rapidly becoming important energy resources that will continue to be developed in the future.

Magnetic Field Enhanced Superconductivity in Epitaxial Thin Film WTe2.

PubMed

Asaba, Tomoya; Wang, Yongjie; Li, Gang; Xiang, Ziji; Tinsman, Colin; Chen, Lu; Zhou, Shangnan; Zhao, Songrui; Laleyan, David; Li, Yi; Mi, Zetian; Li, Lu

2018-04-25

In conventional superconductors an external magnetic field generally suppresses superconductivity. This results from a simple thermodynamic competition of the superconducting and magnetic free energies. In this study, we report the unconventional features in the superconducting epitaxial thin film tungsten telluride (WTe 2 ). Measuring the electrical transport properties of Molecular Beam Epitaxy (MBE) grown WTe 2 thin films with a high precision rotation stage, we map the upper critical field H c2 at different temperatures T. We observe the superconducting transition temperature T c is enhanced by in-plane magnetic fields. The upper critical field H c2 is observed to establish an unconventional non-monotonic dependence on temperature. We suggest that this unconventional feature is due to the lifting of inversion symmetry, which leads to the enhancement of H c2 in Ising superconductors.

Pseudospin Dependent One-Way Transmission in Graphene-Based Topological Plasmonic Crystals

NASA Astrophysics Data System (ADS)

Qiu, Pingping; Qiu, Weibin; Ren, Junbo; Lin, Zhili; Wang, Zeyu; Wang, Jia-Xian; Kan, Qiang; Pan, Jiao-Qing

2018-04-01

Originating from the investigation of condensed matter states, the concept of quantum Hall effect and quantum spin Hall effect (QSHE) has recently been expanded to other field of physics and engineering, e.g., photonics and phononics, giving rise to strikingly unconventional edge modes immune to scattering. Here, we present the plasmonic analog of QSHE in graphene plasmonic crystal (GPC) in mid-infrared frequencies. The band inversion occurs when deforming the honeycomb lattice GPCs, which further leads to the topological band gaps and pseudospin features of the edge states. By overlapping the band gaps with different topologies, we numerically simulated the pseudospin-dependent one-way propagation of edge states. The designed GPC may find potential applications in the fields of topological plasmonics and trigger the exploration of the technique of the pseudospin multiplexing in high-density nanophotonic integrated circuits.

Generalization and transfer of advanced Ukrainian expertise in dynamic aerospace design to students

NASA Astrophysics Data System (ADS)

Konyukhov, Stanislav; Igdalov, Iosif; Polyakov, Nikolai; Sheptun, Yuory

2009-01-01

The presentation of the textbooks, A launch Vehicle as a Control Object (2004) and Launch Vehicles and Space Stages as Control Objects (2007, an updated and structured edition of the first book in Ukrainian), is discussed here. The textbooks are edited by Academician S.N. Konyukhov and the authors are I.M. Igdalov, L.D. Kuchma, N.V. Polyakov, and Yu.D. Sheptun. The textbooks are devoted to the problems of the theory and practice of dynamic design of long-range ballistic missiles (LRBM) and launch vehicles designed using "unconventional" approaches or original engineering solutions by a team of specialized companies lead by the Dniepropetrovsk Aerospace Center at Yuzhnoye SDO and Yuzhmash, with the participation of scientists of the Dniepropetrovsk National University (DNU) and the Institute of Technical Mechanics (ITM) at the National Academy of Science of Ukraine.

Droplets As Liquid Robots.

PubMed

Čejková, Jitka; Banno, Taisuke; Hanczyc, Martin M; Štěpánek, František

2017-01-01

Liquid droplets are very simple objects present in our everyday life. They are extremely important for many natural phenomena as well as for a broad variety of industrial processes. The conventional research areas in which the droplets are studied include physical chemistry, fluid mechanics, chemical engineering, materials science, and micro- and nanotechnology. Typical studies include phenomena such as condensation and droplet formation, evaporation of droplets, or wetting of surfaces. The present article reviews the recent literature that employs droplets as animated soft matter. It is argued that droplets can be considered as liquid robots possessing some characteristics of living systems, and such properties can be applied to unconventional computing through maze solving or operation in logic gates. In particular, the lifelike properties and behavior of liquid robots, namely (i) movement, (ii) self-division, and (iii) group dynamics, will be discussed.

Multifunctional materials for bone cancer treatment

PubMed Central

Marques, Catarina; Ferreira, José MF; Andronescu, Ecaterina; Ficai, Denisa; Sonmez, Maria; Ficai, Anton

2014-01-01

The purpose of this review is to present the most recent findings in bone tissue engineering. Special attention is given to multifunctional materials based on collagen and collagen–hydroxyapatite composites used for skin and bone cancer treatments. The multi-functionality of these materials was obtained by adding to the base regenerative grafts proper components, such as ferrites (magnetite being the most important representative), cytostatics (cisplatin, carboplatin, vincristine, methotrexate, paclitaxel, doxorubicin), silver nanoparticles, antibiotics (anthracyclines, geldanamycin), and/or analgesics (ibuprofen, fentanyl). The suitability of complex systems for the intended applications was systematically analyzed. The developmental possibilities of multifunctional materials with regenerative and curative roles (antitumoral as well as pain management) in the field of skin and bone cancer treatment are discussed. It is worth mentioning that better materials are likely to be developed by combining conventional and unconventional experimental strategies. PMID:24920907

Bio-inspired Ni2+-polyphenol hydrophilic network to achieve unconventional high-flux nanofiltration membranes for environmental remediation.

PubMed

You, Fangjie; Xu, Yanchao; Yang, Xiaobin; Zhang, Yanqiu; Shao, Lu

2017-06-01

A novel Ni 2+ -polyphenol network was designed as an excellent bio-coating by a one-step strategy to obtain nanofiltration membranes, possessing unconventional high water flux up to 56.1 L m -2 h -1 bar -1 with rose bengal (RB) rejection above 95%. This study provides a facile approach to prepare highly-efficient nanofiltration membranes for wastewater remediation.

Sub state Unconventional Warfare: Expanding United States Military Political Options

DTIC Science & Technology

2016-05-26

phases due to competing incumbent efforts. Giap was influenced in his understanding of revolutionary war phasing by Sun Tzu who Giap called one of his...Challenge of Unconventional Warfare. London: Routledge, 2012. Ames, Roger T. Sun - Tzu The Art of Warfare. New York: Ballantine Books, 1993. Amin, Samir...Guerrilla: Insurgents, Patriots, and Terrorists from Sun Tzu to Bin Laden. London: Brassey’s Inc., 2004. Rosenau, William, Subversion and Insurgency

Unconventional high-Tc superconductivity in fullerides.

PubMed

Takabayashi, Yasuhiro; Prassides, Kosmas

2016-09-13

A3C60 molecular superconductors share a common electronic phase diagram with unconventional high-temperature superconductors such as the cuprates: superconductivity emerges from an antiferromagnetic strongly correlated Mott-insulating state upon tuning a parameter such as pressure (bandwidth control) accompanied by a dome-shaped dependence of the critical temperature, Tc However, unlike atom-based superconductors, the parent state from which superconductivity emerges solely by changing an electronic parameter-the overlap between the outer wave functions of the constituent molecules-is controlled by the C60 (3-) molecular electronic structure via the on-molecule Jahn-Teller effect influence of molecular geometry and spin state. Destruction of the parent Mott-Jahn-Teller state through chemical or physical pressurization yields an unconventional Jahn-Teller metal, where quasi-localized and itinerant electron behaviours coexist. Localized features gradually disappear with lattice contraction and conventional Fermi liquid behaviour is recovered. The nature of the underlying (correlated versus weak-coupling Bardeen-Cooper-Schrieffer theory) s-wave superconducting states mirrors the unconventional/conventional metal dichotomy: the highest superconducting critical temperature occurs at the crossover between Jahn-Teller and Fermi liquid metal when the Jahn-Teller distortion melts.This article is part of the themed issue 'Fullerenes: past, present and future, celebrating the 30th anniversary of Buckminster Fullerene'. © 2016 The Author(s).

Unconventional high-Tc superconductivity in fullerides

PubMed Central

Takabayashi, Yasuhiro; Prassides, Kosmas

2016-01-01

A3C60 molecular superconductors share a common electronic phase diagram with unconventional high-temperature superconductors such as the cuprates: superconductivity emerges from an antiferromagnetic strongly correlated Mott-insulating state upon tuning a parameter such as pressure (bandwidth control) accompanied by a dome-shaped dependence of the critical temperature, Tc. However, unlike atom-based superconductors, the parent state from which superconductivity emerges solely by changing an electronic parameter—the overlap between the outer wave functions of the constituent molecules—is controlled by the C603− molecular electronic structure via the on-molecule Jahn–Teller effect influence of molecular geometry and spin state. Destruction of the parent Mott–Jahn–Teller state through chemical or physical pressurization yields an unconventional Jahn–Teller metal, where quasi-localized and itinerant electron behaviours coexist. Localized features gradually disappear with lattice contraction and conventional Fermi liquid behaviour is recovered. The nature of the underlying (correlated versus weak-coupling Bardeen–Cooper–Schrieffer theory) s-wave superconducting states mirrors the unconventional/conventional metal dichotomy: the highest superconducting critical temperature occurs at the crossover between Jahn–Teller and Fermi liquid metal when the Jahn–Teller distortion melts. This article is part of the themed issue ‘Fullerenes: past, present and future, celebrating the 30th anniversary of Buckminster Fullerene’. PMID:27501971

Quantitative mass spectrometry of unconventional human biological matrices

NASA Astrophysics Data System (ADS)

Dutkiewicz, Ewelina P.; Urban, Pawel L.

2016-10-01

The development of sensitive and versatile mass spectrometric methodology has fuelled interest in the analysis of metabolites and drugs in unconventional biological specimens. Here, we discuss the analysis of eight human matrices-hair, nail, breath, saliva, tears, meibum, nasal mucus and skin excretions (including sweat)-by mass spectrometry (MS). The use of such specimens brings a number of advantages, the most important being non-invasive sampling, the limited risk of adulteration and the ability to obtain information that complements blood and urine tests. The most often studied matrices are hair, breath and saliva. This review primarily focuses on endogenous (e.g. potential biomarkers, hormones) and exogenous (e.g. drugs, environmental contaminants) small molecules. The majority of analytical methods used chromatographic separation prior to MS; however, such a hyphenated methodology greatly limits analytical throughput. On the other hand, the mass spectrometric methods that exclude chromatographic separation are fast but suffer from matrix interferences. To enable development of quantitative assays for unconventional matrices, it is desirable to standardize the protocols for the analysis of each specimen and create appropriate certified reference materials. Overcoming these challenges will make analysis of unconventional human biological matrices more common in a clinical setting. This article is part of the themed issue 'Quantitative mass spectrometry'.

Microbial production of lactic acid: the latest development.

PubMed

Juturu, Veeresh; Wu, Jin Chuan

2016-12-01

Lactic acid is an important platform chemical for producing polylactic acid (PLA) and other value-added products. It is naturally produced by a wide spectrum of microbes including bacteria, yeast and filamentous fungi. In general, bacteria ferment C5 and C6 sugars to lactic acid by either homo- or hetero-fermentative mode. Xylose isomerase, phosphoketolase, transaldolase, l- and d-lactate dehydrogenases are the key enzymes that affect the ways of lactic acid production. Metabolic engineering of microbial strains are usually needed to produce lactic acid from unconventional carbon sources. Production of d-LA has attracted much attention due to the demand for producing thermostable PLA, but large scale production of d-LA has not yet been commercialized. Thermophilic Bacillus coagulans strains are able to produce l-lactic acid from lignocellulose sugars homo-fermentatively under non-sterilized conditions, but the lack of genetic tools for metabolically engineering them severely affects their development for industrial applications. Pre-treatment of agriculture biomass to obtain fermentable sugars is a pre-requisite for utilization of the huge amounts of agricultural biomass to produce lactic acid. The major challenge is to obtain quality sugars of high concentrations in a cost effective-way. To avoid or minimize the use of neutralizing agents during fermentation, genetically engineering the strains to make them resist acidic environment and produce lactic acid at low pH would be very helpful for reducing the production cost of lactic acid.

The effects of size and surface modification of amorphous silica particles on biodistribution and liver metabolism in mice

NASA Astrophysics Data System (ADS)

Lu, Xiaoyan; Ji, Cai; Jin, Tingting; Fan, Xiaohui

2015-05-01

Engineered nanoparticles, with unconventional properties, are promising platforms for biomedical applications. Since they may interact with a wide variety of biomolecules, it is critical to understand the impact of the physicochemical properties of engineered nanoparticles on biological systems. In this study, the effects of particle size and surface modification alone or in combination of amorphous silica particles (SPs) on biological responses were determined using a suite of general toxicological assessments and metabonomics analysis in mice model. Our results suggested that amino or carboxyl surface modification mitigated the liver toxicity of plain-surface SPs. 30 nm SPs with amino surface modification were found to be the most toxic SPs among all the surface-modified SP treatments at the same dosage. When treatment dose was increased, submicro-sized SPs with amino or carboxyl surface modification also induced liver toxicity. Biodistribution studies suggested that 70 nm SPs were mainly accumulated in liver and spleen regardless of surface modifications. Interestingly, these two organs exhibited different uptake trends. Furthermore, metabonomics studies indicated that surface modification plays a more dominant role to affect the liver metabolism than particle size.

Polyhydroxybutyrate production from marine source and its application.

PubMed

Kavitha, Ganapathy; Rengasamy, Ramasamy; Inbakandan, Dhinakarasamy

2018-05-01

The increasing significance of non-degradable plastic wastes is an emerging concern. As a substitute, researches are being endeavoured from existing reserve to yield bioplastics based on their properties of biodegradability. Owing to their cost, now the experts are quest for a substitute source like bacteria, microalgae, actinomycetes, cyanobacteria and plants. PHB is biodegradable, environmental friendly and biocompatible thermoplastics. Varying in toughness and flexibility, depending on their formulation, they are used in various ways similar to many non-biodegradable petrochemical plastics currently in use. Promising strategies contain genetic engineering of microorganisms to introduce production pathways examined for the past two decades. Such kind of researches focusing on the use of unconventional substrates, novel extraction methods, and genetically enhanced species with assessment to make PHB from marine microbes are commercially attractive field. Hence, this biopolymer synthesis may displayed as one of the survival mechanisms of endosymbiotic, macroalgae, or sponge-associated bacteria, which exist in a highly competitive and stressful marine microenvironment. This review throws light on the promising and growing awareness of using marine microbes as PHB source, along with their applications in different fields of aquaculture, medicine, antifouling and tissue engineering. Copyright © 2018 Elsevier B.V. All rights reserved.

High-Fidelity Multidisciplinary Design Optimization of Aircraft Configurations

NASA Technical Reports Server (NTRS)

Martins, Joaquim R. R. A.; Kenway, Gaetan K. W.; Burdette, David; Jonsson, Eirikur; Kennedy, Graeme J.

2017-01-01

To evaluate new airframe technologies we need design tools based on high-fidelity models that consider multidisciplinary interactions early in the design process. The overarching goal of this NRA is to develop tools that enable high-fidelity multidisciplinary design optimization of aircraft configurations, and to apply these tools to the design of high aspect ratio flexible wings. We develop a geometry engine that is capable of quickly generating conventional and unconventional aircraft configurations including the internal structure. This geometry engine features adjoint derivative computation for efficient gradient-based optimization. We also added overset capability to a computational fluid dynamics solver, complete with an adjoint implementation and semiautomatic mesh generation. We also developed an approach to constraining buffet and started the development of an approach for constraining utter. On the applications side, we developed a new common high-fidelity model for aeroelastic studies of high aspect ratio wings. We performed optimal design trade-o s between fuel burn and aircraft weight for metal, conventional composite, and carbon nanotube composite wings. We also assessed a continuous morphing trailing edge technology applied to high aspect ratio wings. This research resulted in the publication of 26 manuscripts so far, and the developed methodologies were used in two other NRAs. 1

Engineering the Charge Transport of Ag Nanocrystals for Highly Accurate, Wearable Temperature Sensors through All-Solution Processes.

PubMed

Joh, Hyungmok; Lee, Seung-Wook; Seong, Mingi; Lee, Woo Seok; Oh, Soong Ju

2017-06-01

All-nanocrystal (NC)-based and all-solution-processed wearable resistance temperature detectors (RTDs) are introduced. The charge transport mechanisms of Ag NC thin films are engineered through various ligand treatments to design high performance RTDs. Highly conductive Ag NC thin films exhibiting metallic transport behavior with high positive temperature coefficients of resistance (TCRs) are achieved through tetrabutylammonium bromide treatment. Ag NC thin films showing hopping transport with high negative TCRs are created through organic ligand treatment. All-solution-based, one-step photolithography techniques that integrate two distinct opposite-sign TCR Ag NC thin films into an ultrathin single device are developed to decouple the mechanical effects such as human motion. The unconventional materials design and strategy enables highly accurate, sensitive, wearable and motion-free RTDs, demonstrated by experiments on moving or curved objects such as human skin, and simulation results based on charge transport analysis. This strategy provides a low cost and simple method to design wearable multifunctional sensors with high sensitivity which could be utilized in various fields such as biointegrated sensors or electronic skin. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of ART-27, a Novel Androgen Receptor Coactivator, in Normal Prostate and Prostate Cancer

DTIC Science & Technology

2005-04-01

associates with pro- teins that include RBP5, a subunit shared by RNA polymerases I, II , and Ill, an RBP5 binding protein called unconventional prefoldin ...of a large multiprotein complex that contains RNA polymerase II subunit 5, a subunit shared by all three RNA polymerases; unconventional prefoldin ...dithiothreitol; GRIP, glucocorticoid re- ceptor Interacting p rotein; HA, hemagglutinin; MMTV, mouse mamm ary tumor virus ; PAIS, partial AIS; SDS

Psychological and Unconventional Warfare, 1941-1952: Origins of a Special Warfare Capability for the United States Army

DTIC Science & Technology

1979-11-01

nic -,L-dant orer unconventional wsr:fare? In shnrt, wfiat were-the pre-1952 roots of tbe’ P9ych𔃺rg1.ca1 WArfArPg Contme" artx], cMocom~tant y, the...General Robert A. McClure, 30 March 1948, from Co’.onel William S. Biddle , Assistant Chief, Plans and Policy Group, 1, 319, Plans and Operations Division

Breakdown of Landau Fermi liquid theory: Restrictions on the degrees of freedom of quantum electrons

NASA Astrophysics Data System (ADS)

Su, Yue-Hua; Lu, Han-Tao

2018-04-01

One challenge in contemporary condensed matter physics is to understand unconventional electronic physics beyond the paradigm of Landau Fermi-liquid theory. Here, we present a perspective that posits that most such examples of unconventional electronic physics stem from restrictions on the degrees of freedom of quantum electrons in Landau Fermi liquids. Since the degrees of freedom are deeply connected to the system's symmetries and topology, these restrictions can thus be realized by external constraints or by interaction-driven processes via the following mechanisms: (i) symmetry breaking, (ii) new emergent symmetries, and (iii) nontrivial topology. Various examples of unconventional electronic physics beyond the reach of traditional Landau Fermi liquid theory are extensively investigated from this point of view. Our perspective yields basic pathways to study the breakdown of Landau Fermi liquids and also provides a guiding principle in the search for novel electronic systems and devices.

Unconventional treatments for chronic inflammatory demyelinating polyneuropathy.

PubMed

Rajabally, Yusuf A

2017-10-01

This article focuses on the unconventional treatments used in chronic inflammatory demyelinating polyneuropathy (CIDP). First line, evidence-based treatments for CIDP include corticosteroids, immunoglobulins and plasma exchanges. Several unproven treatments are however given in treatment-refractory disease or to reduce requirements in validated therapies for reasons of side effects/practical delivery/cost. Despite methodological issues, IFN-α, azathioprine and methotrexate have not been shown to be useful in randomized controlled trials. Cyclophosphamide, rituximab and, as final resort in highly selected cases, hematopoietic stem cell transplant may be options considered in severely disabled refractory patients. Debatably, azathioprine, methotrexate, cyclosporine and mycophenolate mofetil are still occasionally used, among others, in milder disease. Physical therapy may be of benefit in CIDP but is not systematically considered as an integral part of management strategies. Current literature relating to unconventional therapies in CIDP is reviewed here and the possible avenues that require consideration in severe refractory disease and less disabling forms are discussed.

Unconventional Superconductivity in the BiS_{2}-Based Layered Superconductor NdO_{0.71}F_{0.29}BiS_{2}.

PubMed

Ota, Yuichi; Okazaki, Kozo; Yamamoto, Haruyoshi Q; Yamamoto, Takashi; Watanabe, Shuntaro; Chen, Chuangtian; Nagao, Masanori; Watauchi, Satoshi; Tanaka, Isao; Takano, Yoshihiko; Shin, Shik

2017-04-21

We investigate the superconducting-gap anisotropy in one of the recently discovered BiS_{2}-based superconductors, NdO_{0.71}F_{0.29}BiS_{2} (T_{c}∼5  K), using laser-based angle-resolved photoemission spectroscopy. Whereas the previously discovered high-T_{c} superconductors such as copper oxides and iron-based superconductors, which are believed to have unconventional superconducting mechanisms, have 3d electrons in their conduction bands, the conduction band of BiS_{2}-based superconductors mainly consists of Bi 6p electrons, and, hence, the conventional superconducting mechanism might be expected. Contrary to this expectation, we observe a strongly anisotropic superconducting gap. This result strongly suggests that the pairing mechanism for NdO_{0.71}F_{0.29}BiS_{2} is an unconventional one and we attribute the observed anisotropy to competitive or cooperative multiple paring interactions.

Superconductivity and Competing Ordered Phase in RuPn (Pn = As, P)

NASA Astrophysics Data System (ADS)

Hirai, Daigorou; Takayama, Tomohiro; Hashizume, Daisuke; Yamamoto, Ayako; Takagi, Hidenori

2011-03-01

Unconventional superconductivity likely manifests itself when some competing electronic phases are suppressed down to zero temperature such as cuprates and iron-pnictide superconductors. Therefore, the correlated metallic state neighboring a competing electronic ordering can be a promising playground for unconventional superconductivity. Here we report superconductivity emerging adjacent to electronically ordered phases of RuPn (Pn = As, P). We found that RuAs(P) exhibits phase transitions at 240 (265) K, which is discerned as a drop of magnetic susceptibility or a resistivity upturn. Such anomalies can be suppressed by substituting Rh to the Ru site. Accompanied by the disappearance of the electronic order, superconductivity was found to emerge below 1.8 K and 3.8 K for RuAs and RuP, respectively. The superconductivity in Rh substituted RuPn, which neighbors a competing electronic order, might exhibit an exotic pairing state as seen in the unconventional superconductors known to date.

H2S and polysulfide metabolism: Conventional and unconventional pathways.

PubMed

Olson, Kenneth R

2018-03-01

It is now well established that hydrogen sulfide (H 2 S) is an effector of a wide variety of physiological processes. It is also clear that many of the effects of H 2 S are mediated through reactions with cysteine sulfur on regulatory proteins and most of these are not mediated directly by H 2 S but require prior oxidation of H 2 S and the formation of per- and polysulfides (H 2 S n , n = 2-8). Attendant with understanding the regulatory functions of H 2 S and H 2 S n is an appreciation of the mechanisms that control, i.e., both increase and decrease, their production and catabolism. Although a number of standard "conventional" pathways have been described and well characterized, novel "unconventional" pathways are continuously being identified. This review summarizes our current knowledge of both the conventional and unconventional. Copyright © 2017 Elsevier Inc. All rights reserved.

Index theorem for the flat Andreev bound states at a dirty surface of a nodal superconductor

NASA Astrophysics Data System (ADS)

Ikegaya, Satoshi; Asano, Yasuhiro

2018-03-01

We discuss the stability of at-band Andreev bound states appearing at a surface of a nodal unconventional superconductor. In the clean limit, the existence of the surface bound states is topologically characterized by a momentum-dependent topological invariant: one-dimensional winding number de ned in the restricted Brillouin zone. Thus, such topological invariant is ill-defined in the presence of potential disorder which is inevitable in experiments. By paying attention to chiral symmetry of the Hamiltonian, we provide an alternative topological index N ZES that predicts the number of Andreev bound states at a dirty surface of an unconventional superconductor. Moreover, we demonstrate that the zero-bias differential conductance in a normal metal/unconventional superconductor junction is quantized at (4e 2 /h)|N ZES | in the limit of strong impurity scattering in the normal metal.

Unconventional energy resources: 2015 review. Shale gas and liquids

USGS Publications Warehouse

Fishman, Neil S.; Bowker, Kent; Cander, Harris; Cardott, Brian; Charette, Marc; Chew, Kenneth; Chidsey, Thomas; Dubiel, Russell F.; Egenhoff, Sven O.; Enomoto, Catherine B.; Hammes, Ursula; Harrison, William; Jiang, Shu; LeFever, Julie A.; McCracken, Jock; Nordeng, Stephen; Nyahay, Richard; Sonnenberg, Stephen; Vanden Berg, Michael; ,

2015-01-01

Introduction As the source rocks from which petroleum is generated, organic-rich shales have always been considered an important component of petroleum systems. Over the last few years, it has been realized that in some mudrocks, sufficient hydrocarbons remain in place to allow for commercial development, although advanced drilling and completion technology is typically required to access hydrocarbons from these reservoirs. Tight oil reservoirs (also referred to as continuous oil accumulations) contain hydrocarbons migrated from source rocks that are geologically/stratigraphically interbedded with or occur immediately overlying/underlying them. Migration is minimal in charging these tight oil accumulations (Gaswirth and Marra 2014). Companies around the world are now successfully exploiting organic-rich shales and tight rocks for contained hydrocarbons, and the search for these types of unconventional petroleum reservoirs is growing. Unconventional reservoirs range in geologic age from Ordovician to Tertiary (Silverman et al. 2005; EIA 2013a). 

Unconventional oil and gas extraction and animal health.

PubMed

Bamberger, M; Oswald, R E

2014-08-01

The extraction of hydrocarbons from shale formations using horizontal drilling with high volume hydraulic fracturing (unconventional shale gas and tight oil extraction), while derived from methods that have been used for decades, is a relatively new innovation that was introduced first in the United States and has more recently spread worldwide. Although this has led to the availability of new sources of fossil fuels for domestic consumption and export, important issues have been raised concerning the safety of the process relative to public health, animal health, and our food supply. Because of the multiple toxicants used and generated, and because of the complexity of the drilling, hydraulic fracturing, and completion processes including associated infrastructure such as pipelines, compressor stations and processing plants, impacts on the health of humans and animals are difficult to assess definitively. We discuss here findings concerning the safety of unconventional oil and gas extraction from the perspectives of public health, veterinary medicine, and food safety.

Epigenome-Wide Association Study of Tic Disorders.

PubMed

Zilhão, Nuno R; Padmanabhuni, Shanmukha S; Pagliaroli, Luca; Barta, Csaba; Smit, Dirk J A; Cath, Danielle; Nivard, Michel G; Baselmans, Bart M L; van Dongen, Jenny; Paschou, Peristera; Boomsma, Dorret I

2015-12-01

Tic disorders are moderately heritable common psychiatric disorders that can be highly troubling, both in childhood and in adulthood. In this study, we report results obtained in the first epigenome-wide association study (EWAS) of tic disorders. The subjects are participants in surveys at the Netherlands Twin Register (NTR) and the NTR biobank project. Tic disorders were measured with a self-report version of the Yale Global Tic Severity Scale Abbreviated version (YGTSS-ABBR), included in the 8th wave NTR data collection (2008). DNA methylation data consisted of 411,169 autosomal methylation sites assessed by the Illumina Infinium HumanMethylation450 BeadChip Kit (HM450k array). Phenotype and DNA methylation data were available in 1,678 subjects (mean age = 41.5). No probes reached genome-wide significance (p < 1.2 × 10(-7)). The strongest associated probe was cg15583738, located in an intergenic region on chromosome 8 (p = 1.98 × 10(-6)). Several of the top ranking probes (p < 1 × 10(-4)) were in or nearby genes previously associated with neurological disorders (e.g., GABBRI, BLM, and ADAM10), warranting their further investigation in relation to tic disorders. The top significantly enriched gene ontology (GO) terms among higher ranking methylation sites included anatomical structure morphogenesis (GO:0009653, p = 4.6 × 10-(15)) developmental process (GO:0032502, p = 2.96 × 10(-12)), and cellular developmental process (GO:0048869, p = 1.96 × 10(-12)). Overall, these results provide a first insight into the epigenetic mechanisms of tic disorders. This first study assesses the role of DNA methylation in tic disorders, and it lays the foundations for future work aiming to unravel the biological mechanisms underlying the architecture of this disorder.

Neurotensin stimulates sortilin and mTOR in human microglia inhibitable by methoxyluteolin, a potential therapeutic target for autism.

PubMed

Patel, Arti B; Tsilioni, Irene; Leeman, Susan E; Theoharides, Theoharis C

2016-09-23

We had reported elevated serum levels of the peptide neurotensin (NT) in children with autism spectrum disorders (ASD). Here, we show that NT stimulates primary human microglia, the resident immune cells of the brain, and the immortalized cell line of human microglia-SV40. NT (10 nM) increases the gene expression and release (P < 0.001) of the proinflammatory cytokine IL-1β and chemokine (C-X-C motif) ligand 8 (CXCL8), chemokine (C-C motif) ligand 2 (CCL2), and CCL5 from human microglia. NT also stimulates proliferation (P < 0.05) of microglia-SV40. Microglia express only the receptor 3 (NTR3)/sortilin and not the NTR1 or NTR2. The use of siRNA to target sortilin reduces (P < 0.001) the NT-stimulated cytokine and chemokine gene expression and release from human microglia. Stimulation with NT (10 nM) increases the gene expression of sortilin (P < 0.0001) and causes the receptor to be translocated from the cytoplasm to the cell surface, and to be secreted extracellularly. Our findings also show increased levels of sortilin (P < 0.0001) in the serum from children with ASD (n = 36), compared with healthy controls (n = 20). NT stimulation of microglia-SV40 causes activation of the mammalian target of rapamycin (mTOR) signaling kinase, as shown by phosphorylation of its substrates and inhibition of these responses by drugs that prevent mTOR activation. NT-stimulated responses are inhibited by the flavonoid methoxyluteolin (0.1-1 μM). The data provide a link between sortilin and the pathological findings of microglia and inflammation of the brain in ASD. Thus, inhibition of this pathway using methoxyluteolin could provide an effective treatment of ASD.

Role of the σ 54 Activator Interacting Domain in Bacterial Transcription Initiation

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

Siegel, Alexander R.; Wemmer, David E.

Bacterial sigma factors are subunits of RNA polymerase that direct the holoenzyme to specific sets of promoters in the genome and are a central element of regulating transcription. Most polymerase holoenzymes open the promoter and initiate transcription rapidly after binding. However, polymerase containing the members of the σ 54 family must be acted on by a transcriptional activator before DNA opening and initiation occur. A key domain in these transcriptional activators forms a hexameric AAA + ATPase that acts through conformational changes brought on by ATP hydrolysis. Contacts between the transcriptional activator and σ 54 are primarily made through anmore » N-terminal σ 54 activator interacting domain (AID). To better understand this mechanism of bacterial transcription initiation, we characterized the σ 54 AID by NMR spectroscopy and other biophysical methods and show that it is an intrinsically disordered domain in σ 54 alone. In this paper, we identified a minimal construct of the Aquifex aeolicus σ 54 AID that consists of two predicted helices and retains native-like binding affinity for the transcriptional activator NtrC1. Using the NtrC1 ATPase domain, bound with the non-hydrolyzable ATP analog ADP-beryllium fluoride, we studied the NtrC1–σ 54 AID complex using NMR spectroscopy. We show that the σ 54 AID becomes structured after associating with the core loops of the transcriptional activators in their ATP state and that the primary site of the interaction is the first predicted helix. Finally, understanding this complex, formed as the first step toward initiation, will help unravel the mechanism of σ 54 bacterial transcription initiation.« less

Presence of Functional Neurotrophin TrkB Receptors in the Rat Superior Cervical Ganglion

PubMed Central

Valle-Leija, Pablo; Cancino-Rodezno, Angeles; Sánchez-Tafolla, Berardo M.; Arias, Erwin; Elinos, Diana; Feria, Jessica; Zetina, María E.; Morales, Miguel A.; Cifuentes, Fredy

2017-01-01

Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non-functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) modulate synaptic transmission and synaptic plasticity in neurons of the superior cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in sympathetic ganglia and contributes to the effects of BDNF upon sympathetic function, we characterized the presence and activity of the neurotrophin receptors expressed in the adult SCG compared with their presence in neonatal and cultured sympathetic neurons. Here, we expand our previous study regarding the immunodetection of neurotrophin receptors. Immunohistochemical analysis revealed that 19% of adult ganglionic neurons expressed TrkB-Fl immunoreactivity (IR), 82% expressed TrkA-IR, and 51% expressed p75NTR-IR; TrkB-Tc would be expressed in 36% of neurons. In addition, using Western-blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses, we confirmed the expression of TrkB-Fl and TrkB-Tc protein and mRNA transcripts in adult SCG. Neonatal neurons expressed significantly more TrkA-IR and TrkB-Fl-IR than p75NTR-IR. Finally, the application of neurotrophin, and high frequency stimulation, induced the activation of Trk receptors and the downstream PI3-kinase (phosphatidyl inositol-3-kinase) signaling pathway, thus evoking the phosphorylation of Trk and Akt. These results demonstrate that SCG neurons express functional TrkA and TrkB-Fl receptors, which may contribute to the differential modulation of synaptic transmission and long-term synaptic plasticity. PMID:28744222

Radiation Therapy Dose Escalation for Glioblastoma Multiforme in the Era of Temozolomide

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

Badiyan, Shahed N.; Markovina, Stephanie; Simpson, Joseph R.

Purpose: To review clinical outcomes of moderate dose escalation using high-dose radiation therapy (HDRT) in the setting of concurrent temozolomide (TMZ) in patients with newly diagnosed glioblastoma multiforme (GBM), compared with standard-dose radiation therapy (SDRT). Methods and Materials: Adult patients aged <70 years with biopsy-proven GBM were treated with SDRT (60 Gy at 2 Gy per fraction) or with HDRT (>60 Gy) and TMZ from 2000 to 2012. Biological equivalent dose at 2-Gy fractions was calculated for the HDRT assuming an α/β ratio of 5.6 for GBM. Results: Eighty-one patients received SDRT, and 128 patients received HDRT with a median (range) biological equivalent dosemore » at 2-Gy fractions of 64 Gy (61-76 Gy). Overall median follow-up time was 1.10 years, and for living patients it was 2.97 years. Actuarial 5-year overall survival (OS) and progression-free survival (PFS) rates for patients that received HDRT versus SDRT were 12.4% versus 13.2% (P=.71), and 5.6% versus 4.1% (P=.54), respectively. Age (P=.001) and gross total/near-total resection (GTR/NTR) (P=.001) were significantly associated with PFS on multivariate analysis. Younger age (P<.0001), GTR/NTR (P<.0001), and Karnofsky performance status ≥80 (P=.001) were associated with improved OS. On subset analyses, HDRT failed to improve PFS or OS for those aged <50 years or those who had GTR/NTR. Conclusion: Moderate radiation therapy dose escalation above 60 Gy with concurrent TMZ does not seem to improve clinical outcomes for patients with GBM.« less

Does calcium influx regulate melatonin production through the circadian pacemaker in chick pineal cells? Effects of nitrendipine, Bay K 8644, Co2+, Mn2+, and low external Ca2+.

PubMed

Zatz, M; Mullen, D A

1988-11-01

We have recently described a system, using dispersed chick pineal cells in static culture, which displays a persistent, photosensitive, circadian rhythm of melatonin production and release. Here, we describe the effects of nitrendipine (NTR) (a dihydropyridine 'antagonist' of L-type calcium channels), Bay K 8644 (BK) (a dihydropyridine calcium channel 'agonist'), cobalt and manganese ions (both inorganic calcium channel blockers), and low external calcium concentrations, on the melatonin rhythm. NTR inhibited and BK stimulated melatonin output; they were potent and effective. Co2+, Mn2+, and low external Ca2+ markedly inhibited melatonin output. These results support a role for calcium influx through voltage-dependent calcium channels (L-type) in the regulation of melatonin production. Four or 8 h pulses of white light or darkness, in otherwise constant red light, cause, in addition to acute effects, phase-dependent phase shifts of the melatonin rhythm in subsequent cycles. Such phase shifts indicate an effect on (proximal to) the pacemaker generating the rhythm. Four or 8 h pulses of NTR, BK, Co2+, or low Ca2+, however, did not appreciably alter the phase of subsequent melatonin cycles. Neither did BK interfere with phase shifts induced by light pulses. Mn2+ pulses did induce phase-dependent phase shifts, but, unlike those evoked by light or dark pulses, these were all delays. Such effects of Mn2+ in other systems have been attributed to, and are characteristic of, 'metabolic inhibitors'. On balance, the results fail to support a prominent role for calcium influx in regulating the pacemaker underlying the circadian rhythm in chick pineal cells. Rather, calcium influx appears to regulate melatonin production primarily by acting on the melatonin-synthesizing apparatus, distal to the pacemaker.

Sevoflurane-induced memory impairment in the postnatal developing mouse brain.

PubMed

Lu, Zhijun; Sun, Jihui; Xin, Yichun; Chen, Ken; Ding, Wen; Wang, Yujia

2018-05-01

The aim of the present study was to confirm that sevoflurane induces memory impairment in the postnatal developing mouse brain and determine its mechanism of action. C57BL/6 mice 7 days old were randomly assigned into a 2.6% sevoflurane (n=68), a 1.3% sevoflurane (n=68) and a control (n=38) group. Blood gas analysis was performed to evaluate hypoxia and respiratory depression during anesthesia in 78 mice. Measurements for expression of caspase-3 by immunohistochemistry, cleavage of poly adenosine diphosphate-ribose polymerase (PARP) by western blotting, as well as levels of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor type 2 (Ntrk2), pro-BDNF, p75 neurotrophin receptor (p75NTR) and protein kinase B (PKB/Akt) by enzyme-linked immunosorbent assay were performed in the hippocampus of 12 mice from each group. A total of 60 mice underwent the Morris water maze (MWM) test. Results from the MWM test indicated that the time spent in the northwest quadrant and platform site crossovers by mice in the 2.6 and 1.3% sevoflurane groups was significantly lower than that of the control group. Meanwhile, levels of caspase-3 and cleaved PARP in the 2.6 and 1.3% sevoflurane groups were significantly higher than that in the control group. Levels of pro-BDNF and p75NTR were significantly increased and the level of PKB/Akt was significantly decreased following exposure to 2.6% sevoflurane. Finally, the memory of postnatal mice was impaired by sevoflurane, this was determined using a MWM test. Therefore, the results of the current study suggest that caspase-3 induced cleavage of PARP, as well as pro-BDNF, p75NTR and PKB/Akt may be important in sevoflurane-induced memory impairment in the postnatal developing mouse brain.

Robust Exploration and Commercial Missions to the Moon Using NTR LANTR Propulsion and Lunar-Derived Propellants

NASA Technical Reports Server (NTRS)

Borowski, Stanley K.; Ryan, Stephen W.; Burke, Laura M.; McCurdy, David R.; Fittje, James E.; Joyner, Claude R.

2017-01-01

NASAs current focus is on the Journey to Mars sometime around the mid-to-late 2030s. However, it is also supporting the development of commercial cargo and crew delivery to the ISS (e.g., SpaceX, Orbital Sciences, SNC, Boeing) where inflatable habitation technology (e.g., Bigelow Aerospaces BEAM) is currently being tested Significant private sector interest in commercial lunar activities has also been expressed by Bigelow Aerospace, Golden Spike Company, Shackleton Energy Company (SEC), and most recently by United Launch Alliance (ULA) in their Cislunar-1000 plan Lunar-derived propellant (LDP) production specifically LLO2 and LLH2 offers significant mission leverage and are central themes of both SECs and ULAs plans for commercial lunar development. An efficient, proven propulsion technology with reuse capability like NTP offers the potential for affordable access through space essential to realizing commercial lunar missions.This presentation examines the performance potential of an evolutionary lunar transportation system (LTS) architecture using NTR initially, then transitioning to LANTR as LDPs(e.g., LLO2 from regolith or volcanic glass, LLO2 and LLH2 from lunar polar ice deposits) become available in lunar orbit (LO) Mission applications range from cargo delivery, to crewed landing, to routine commuter flights to and from transportation system nodes located in both lunar equatorial and lunar polar orbits. This presentation examines the performance potential of an evolutionary lunar transportation system (LTS) architecture using NTR initially, then transitioning to LANTR as LDPs (e.g., LLO2 from regolith or volcanic glass, LLO2 and LLH2 from lunar polar ice deposits) become available in lunar orbit (LO) Mission applications range from cargo delivery, to crewed landing, to routine commuter flights to and from transportation system nodes located in both lunar equatorial and lunar polar orbits.

Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model.

PubMed

Arita, Minetaro; Ami, Yasushi; Wakita, Takaji; Shimizu, Hiroyuki

2008-02-01

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

Peroxiredoxins and NADPH-dependent thioredoxin systems in the model legume Lotus japonicus.

PubMed

Tovar-Méndez, Alejandro; Matamoros, Manuel A; Bustos-Sanmamed, Pilar; Dietz, Karl-Josef; Cejudo, Francisco Javier; Rouhier, Nicolas; Sato, Shusei; Tabata, Satoshi; Becana, Manuel

2011-07-01

Peroxiredoxins (Prxs), thioredoxins (Trxs), and NADPH-thioredoxin reductases (NTRs) constitute central elements of the thiol-disulfide redox regulatory network of plant cells. This study provides a comprehensive survey of this network in the model legume Lotus japonicus. The aims were to identify and characterize these gene families and to assess whether the NTR-Trx systems are operative in nodules. Quantitative reverse transcription-polymerase chain reaction and immunological and proteomic approaches were used for expression profiling. We identified seven Prx, 14 Trx, and three NTR functional genes. The PrxQ1 gene was found to be transcribed in two alternative spliced variants and to be expressed at high levels in leaves, stems, petals, pods, and seeds and at low levels in roots and nodules. The 1CPrx gene showed very high expression in the seed embryos and low expression in vegetative tissues and was induced by nitric oxide and cytokinins. In sharp contrast, cytokinins down-regulated all other Prx genes, except PrxQ1, in roots and nodules, but only 2CPrxA and PrxQ1 in leaves. Gene-specific changes in Prx expression were also observed in response to ethylene, abscisic acid, and auxins. Nodules contain significant mRNA and protein amounts of cytosolic PrxIIB, Trxh1, and NTRA and of plastidic NTRC. Likewise, they express cytosolic Trxh3, Trxh4, Trxh8, and Trxh9, mitochondrial PrxIIF and Trxo, and plastidic Trxm2, Trxm4, and ferredoxin-Trx reductase. These findings reveal a complex regulation of Prxs that is dependent on the isoform, tissue, and signaling molecule and support that redox NTR-Trx systems are functional in the cytosol, mitochondria, and plastids of nodules.

Presence of Functional Neurotrophin TrkB Receptors in the Rat Superior Cervical Ganglion.

PubMed

Valle-Leija, Pablo; Cancino-Rodezno, Angeles; Sánchez-Tafolla, Berardo M; Arias, Erwin; Elinos, Diana; Feria, Jessica; Zetina, María E; Morales, Miguel A; Cifuentes, Fredy

2017-01-01

Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non-functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) modulate synaptic transmission and synaptic plasticity in neurons of the superior cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in sympathetic ganglia and contributes to the effects of BDNF upon sympathetic function, we characterized the presence and activity of the neurotrophin receptors expressed in the adult SCG compared with their presence in neonatal and cultured sympathetic neurons. Here, we expand our previous study regarding the immunodetection of neurotrophin receptors. Immunohistochemical analysis revealed that 19% of adult ganglionic neurons expressed TrkB-Fl immunoreactivity (IR), 82% expressed TrkA-IR, and 51% expressed p75NTR-IR; TrkB-Tc would be expressed in 36% of neurons. In addition, using Western-blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses, we confirmed the expression of TrkB-Fl and TrkB-Tc protein and mRNA transcripts in adult SCG. Neonatal neurons expressed significantly more TrkA-IR and TrkB-Fl-IR than p75NTR-IR. Finally, the application of neurotrophin, and high frequency stimulation, induced the activation of Trk receptors and the downstream PI3-kinase (phosphatidyl inositol-3-kinase) signaling pathway, thus evoking the phosphorylation of Trk and Akt. These results demonstrate that SCG neurons express functional TrkA and TrkB-Fl receptors, which may contribute to the differential modulation of synaptic transmission and long-term synaptic plasticity.

Granulocyte colony-stimulating factor (G-CSF) positive effects on muscle fiber degeneration and gait recovery after nerve lesion in MDX mice

PubMed Central

Simões, Gustavo F; Benitez, Suzana U; Oliveira, Alexandre L R

2014-01-01

Background G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. Aims The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. Methods Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75NTR and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. Results Both groups treated with G-CSF showed increased p75NTR and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. Conclusions The reduction in p75NTR and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF. PMID:25328849

Effect of diagnosis and treatment of clinical endometritis based on vaginal discharge score grading system in postpartum Holstein cows

PubMed Central

OKAWA, Hiroaki; FUJIKURA, Atsushi; WIJAYAGUNAWARDANE, Missaka M.P.; VOS, Peter L.A.M.; TANIGUCHI, Masayasu; TAKAGI, Mitsuhiro

2017-01-01

In this study, the prevalence, effectiveness of diagnosis, and treatment based on vaginal discharge score (VDS) of clinical endometritis in cattle were evaluated. To detect clinical endometritis and classify its severity, vaginoscopy was performed during 21 to 60 days postpartum in 164 Holstein cows consisting of 229 lactations. Groups were defined using the 4-point VDS scale. Study groups included the following: non-endometritis (VDS=0; no/clear mucus; NEM group; n=168); mild endometritis, no treatment (VDS=1; mucus containing flecks of white/off-white pus; NTR group; n=30); and severe endometritis, treated with PGF2α (VDS≥2; discharge containing <50% pus; and VDS=3; discharge containing >50% pus, and fluid or uterine horn asymmetry; TEM group; n=31). Cows treated with PGF2α that did not recover (VDS≥1, n=5) received intrauterine procaine penicillin and streptomycin. Prevalence of clinical endometritis (VDS≥1) was 26.6%. The NTR group required significantly more artificial inseminations per pregnancy than NEM and TEM groups (2.8 ± 1.8 vs 2.0 ± 1.3, 1.9 ± 0.8, P<0.05). In survival analysis, the proportion of non-pregnant cows was higher in the NTR group compared to the NEM (P=0.012) and TEM (P=0.076) groups. In the TEM group, calving to first artificial insemination interval tended to be higher in cows treated 41 to 60 days postpartum than cows treated 29 to 40 days postpartum (97.2 ± 27.1 vs 74.4 ± 19.7, P=0.084). Our study suggests that cows with VDS=1 may require treatment to recover fertility. Diagnosis and treatment of clinical endometritis based on a VDS grading system may improve dairy herd reproductive performance. PMID:28740032

Biodistribution and catabolism of (18)F-labeled neurotensin(8-13) analogs.

PubMed

Bergmann, Ralf; Scheunemann, Matthias; Heichert, Christoph; Mäding, Peter; Wittrisch, Holm; Kretzschmar, Marion; Rodig, Heike; Tourwé, Dirk; Iterbeke, Koen; Chavatte, Kris; Zips, Daniel; Reubi, Jean Claude; Johannsen, Bernd

2002-01-01

4-([(18)F]fluoro)benzoyl-neurotensin(8-13) ((18)FB-Arg(8)-Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 1) and two analogs stabilized in one and two positions ((18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)- Ile(12)-Leu(13)-OH, 2, (18)FB-Arg(8)psi(CH(2)NH)Arg(9)-Pro(10)-Tyr(11)-Tle(12)-Leu(13)-OH, 3) were synthesized in a radiochemical yield of 25-36% and a specific activity of 5-15 GBq/mmol. The peptides were evaluated in vitro and in vivo for their potential to image tumors overexpressing neurotensin receptor 1 (NTR1) by positron emission tomography (PET). All analogs exhibited in vitro binding affinity in the low nanomolar range to NTR1-expressing human tumors, measured by quantitative receptor autoradiography, HT-29 and WiDr cells, and to sections of tumors derived from these cell lines in mice. The radiotracers were internalized in the cells in vitro, and the fluorinated peptides were able to mobilize intracellular Ca(2+) of WiDr cells. In in vivo studies in rats and in mice bearing HT-29 cell tumors, only a moderate uptake of the radioligands into the studied tumors was observed, presumed to be due to degradation in vivo and fast elimination by the kidneys. In comparison with the other analogs, the specific tumor uptake expressed as tumor-to-muscle relation was highest for the radioligand 3. The blood clearance of 3 was reduced by co-injection of peptidase inhibitors. The catabolic pathways of the radiofluorinated peptides were elucidated. The results suggest that the high binding affinity to NTR1 and the stabilization against proteolytic degradation are not yet sufficient for tumor imaging by PET.

Effect of diagnosis and treatment of clinical endometritis based on vaginal discharge score grading system in postpartum Holstein cows.

PubMed

Okawa, Hiroaki; Fujikura, Atsushi; Wijayagunawardane, Missaka M P; Vos, Peter L A M; Taniguchi, Masayasu; Takagi, Mitsuhiro

2017-09-12

In this study, the prevalence, effectiveness of diagnosis, and treatment based on vaginal discharge score (VDS) of clinical endometritis in cattle were evaluated. To detect clinical endometritis and classify its severity, vaginoscopy was performed during 21 to 60 days postpartum in 164 Holstein cows consisting of 229 lactations. Groups were defined using the 4-point VDS scale. Study groups included the following: non-endometritis (VDS=0; no/clear mucus; NEM group; n=168); mild endometritis, no treatment (VDS=1; mucus containing flecks of white/off-white pus; NTR group; n=30); and severe endometritis, treated with PGF2α (VDS≥2; discharge containing <50% pus; and VDS=3; discharge containing >50% pus, and fluid or uterine horn asymmetry; TEM group; n=31). Cows treated with PGF2α that did not recover (VDS≥1, n=5) received intrauterine procaine penicillin and streptomycin. Prevalence of clinical endometritis (VDS≥1) was 26.6%. The NTR group required significantly more artificial inseminations per pregnancy than NEM and TEM groups (2.8 ± 1.8 vs 2.0 ± 1.3, 1.9 ± 0.8, P<0.05). In survival analysis, the proportion of non-pregnant cows was higher in the NTR group compared to the NEM (P=0.012) and TEM (P=0.076) groups. In the TEM group, calving to first artificial insemination interval tended to be higher in cows treated 41 to 60 days postpartum than cows treated 29 to 40 days postpartum (97.2 ± 27.1 vs 74.4 ± 19.7, P=0.084). Our study suggests that cows with VDS=1 may require treatment to recover fertility. Diagnosis and treatment of clinical endometritis based on a VDS grading system may improve dairy herd reproductive performance.

Peroxiredoxins and NADPH-Dependent Thioredoxin Systems in the Model Legume Lotus japonicus1[W][OA

PubMed Central

Tovar-Méndez, Alejandro; Matamoros, Manuel A.; Bustos-Sanmamed, Pilar; Dietz, Karl-Josef; Cejudo, Francisco Javier; Rouhier, Nicolas; Sato, Shusei; Tabata, Satoshi; Becana, Manuel

2011-01-01

Peroxiredoxins (Prxs), thioredoxins (Trxs), and NADPH-thioredoxin reductases (NTRs) constitute central elements of the thiol-disulfide redox regulatory network of plant cells. This study provides a comprehensive survey of this network in the model legume Lotus japonicus. The aims were to identify and characterize these gene families and to assess whether the NTR-Trx systems are operative in nodules. Quantitative reverse transcription-polymerase chain reaction and immunological and proteomic approaches were used for expression profiling. We identified seven Prx, 14 Trx, and three NTR functional genes. The PrxQ1 gene was found to be transcribed in two alternative spliced variants and to be expressed at high levels in leaves, stems, petals, pods, and seeds and at low levels in roots and nodules. The 1CPrx gene showed very high expression in the seed embryos and low expression in vegetative tissues and was induced by nitric oxide and cytokinins. In sharp contrast, cytokinins down-regulated all other Prx genes, except PrxQ1, in roots and nodules, but only 2CPrxA and PrxQ1 in leaves. Gene-specific changes in Prx expression were also observed in response to ethylene, abscisic acid, and auxins. Nodules contain significant mRNA and protein amounts of cytosolic PrxIIB, Trxh1, and NTRA and of plastidic NTRC. Likewise, they express cytosolic Trxh3, Trxh4, Trxh8, and Trxh9, mitochondrial PrxIIF and Trxo, and plastidic Trxm2, Trxm4, and ferredoxin-Trx reductase. These findings reveal a complex regulation of Prxs that is dependent on the isoform, tissue, and signaling molecule and support that redox NTR-Trx systems are functional in the cytosol, mitochondria, and plastids of nodules. PMID:21562331

Mutations that alter a repeated ACCA element located at the 5' end of the Potato virus X genome affect RNA accumulation.

PubMed

Park, Mi-Ri; Kwon, Sun-Jung; Choi, Hong-Soo; Hemenway, Cynthia L; Kim, Kook-Hyung

2008-08-15

The repeated ACCA or AC-rich sequence and structural (SL1) elements in the 5' non-translated region (NTR) of the Potato virus X (PVX) RNA play vital roles in the PVX life cycle by controlling translation, RNA replication, movement, and assembly. It has already been shown that the repeated ACCA or AC-rich sequence affect both gRNA and sgRNA accumulation, while not affecting minus-strand RNA accumulation, and are also required for host protein binding. The functional significance of the repeated ACCA sequence elements in the 5' NTR region was investigated by analyzing the effects of deletion and site-directed mutations on PVX replication in Nicotiana benthamiana plants and NT1 protoplasts. Substitution (ACCA into AAAA or UUUU) mutations introduced in the first (nt 10-13) element in the 5' NTR of the PVX RNA significantly affected viral replication, while mutations introduced in the second (nt 17-20) and third (nt 20-23) elements did not. The fourth (nt 29-32) ACCA element weakly affected virus replication, whereas mutations in the fifth (nt 38-41) significantly reduced virus replication due to the structure disruption of SL1 by AAAA and/or UUUU substitutions. Further characterization of the first ACCA element indicated that duplication of ACCA at nt 10-13 (nt 10-17, ACCAACCA) caused severe symptom development as compared to that of wild type, while deletion of the single element (nt 10-13), DeltaACCA) or tripling of this element caused reduced symptom development. Single- and double-nucleotide substitutions introduced into the first ACCA element revealed the importance of CC located at nt positions 11 and 12. Altogether, these results indicate that the first ACCA element is important for PVX replication.

(Methyl)ammonium Transport in the Nitrogen-Fixing Bacterium Azospirillum brasilense

PubMed Central

Van Dommelen, Anne; Keijers, Veerle; Vanderleyden, Jos; de Zamaroczy, Miklos

1998-01-01

An ammonium transporter of Azospirillum brasilense was characterized. In contrast to most previously reported putative prokaryotic NH4+ transporter genes, A. brasilense amtB is not part of an operon with glnB or glnZ which, in A. brasilense, encode nitrogen regulatory proteins PII and PZ, respectively. Sequence analysis predicts the presence of 12 transmembrane domains in the deduced AmtB protein and classifies AmtB as an integral membrane protein. Nitrogen regulates the transcription of the amtB gene in A. brasilense by the Ntr system. amtB is the first gene identified in A. brasilense whose expression is regulated by NtrC. The observation that ammonium uptake is still possible in mutants lacking the AmtB protein suggests the presence of a second NH4+ transport mechanism. Growth of amtB mutants at low ammonium concentrations is reduced compared to that of the wild type. This suggests that AmtB has a role in scavenging ammonium at low concentrations. PMID:9573149

ProBDNF and mature BDNF as punishment and reward signals for synapse elimination at mouse neuromuscular junctions.

PubMed

Je, H Shawn; Yang, Feng; Ji, Yuanyuan; Potluri, Srilatha; Fu, Xiu-Qing; Luo, Zhen-Ge; Nagappan, Guhan; Chan, Jia Pei; Hempstead, Barbara; Son, Young-Jin; Lu, Bai

2013-06-12

During development, mammalian neuromuscular junctions (NMJs) transit from multiple-innervation to single-innervation through axonal competition via unknown molecular mechanisms. Previously, using an in vitro model system, we demonstrated that the postsynaptic secretion of pro-brain-derived neurotrophic factor (proBDNF) stabilizes or eliminates presynaptic axon terminals, depending on its proteolytic conversion at synapses. Here, using developing mouse NMJs, we obtained in vivo evidence that proBDNF and mature BDNF (mBDNF) play roles in synapse elimination. We observed that exogenous proBDNF promoted synapse elimination, whereas mBDNF infusion substantially delayed synapse elimination. In addition, pharmacological inhibition of the proteolytic conversion of proBDNF to mBDNF accelerated synapse elimination via activation of p75 neurotrophin receptor (p75(NTR)). Furthermore, the inhibition of both p75(NTR) and sortilin signaling attenuated synapse elimination. We propose a model in which proBDNF and mBDNF serve as potential "punishment" and "reward" signals for inactive and active terminals, respectively, in vivo.

Prostate Cell Specific Regulation of Androgen Receptor Phosphorylation in Vivo

DTIC Science & Technology

2009-11-01

includes both Rpb5, a subunit shared by RNA polymerase (Pol) I, II , and III, and the corepressor, Unconventional prefoldin Rpb5-Interactor (URI/C19orf2...complex that contains RNA polymerase II subunit 5, a subunit shared by all three RNA polymerases; unconventional prefoldin RPB5-in- teractor (URI), which...sequence of ART-27 is conserved throughout evolution from worms to humans and its predicted protein structure is homologous to the prefoldin -a family of

Ending the Debate: Unconventional Warfare, Foreign Internal Defense, and Why Words Matter

DTIC Science & Technology

2006-06-01

JCS] apparently was fearful of what it perceived to be the stigma of having the military accused of engaging in subrosa [sic], cloak -and­ dagger ...was fearful of what it perceived to be the stigma of having the military accused of engaging in sub-rosa, cloak - and- dagger activities in the event of...disrupted by the terrorist attacks of 11 September. Less than two years later, Special Forces had successfully prosecuted two unconventional warfare

U.S. Geological Survey assessments of continuous (unconventional) oil and gas resources, 2000 to 2011

USGS Publications Warehouse

,

2015-10-20

From 2000 to 2011, the U.S. Geological Survey conducted 139 quantitative assessments of continuous (unconventional) oil and gas accumulations within the United States. This report documents those assessments more fully than previously done by providing detailed documentation of both the assessment input and output. This report also compiles the data into spreadsheet tables that can be more readily used to provide analogs for future assessments, especially for hypothetical continuous accumulations.

The endoplasmic reticulum is a hub to sort proteins toward unconventional traffic pathways and endosymbiotic organelles.

PubMed

Bellucci, Michele; De Marchis, Francesca; Pompa, Andrea

2017-12-18

The discovery that much of the extracellular proteome in eukaryotic cells consists of proteins lacking a signal peptide, which cannot therefore enter the secretory pathway, has led to the identification of alternative protein secretion routes bypassing the Golgi apparatus. However, proteins harboring a signal peptide for translocation into the endoplasmic reticulum can also be transported along these alternative routes, which are still far from being well elucidated in terms of the molecular machineries and subcellular/intermediate compartments involved. In this review, we first try to provide a definition of all the unconventional protein secretion pathways in eukaryotic cells, as those pathways followed by proteins directed to an 'external space' bypassing the Golgi, where 'external space' refers to the extracellular space plus the lumen of the secretory route compartments and the inner space of mitochondria and plastids. Then, we discuss the role of the endoplasmic reticulum in sorting proteins toward unconventional traffic pathways in plants. In this regard, various unconventional pathways exporting proteins from the endoplasmic reticulum to the vacuole, plasma membrane, apoplast, mitochondria, and plastids are described, including the short routes followed by the proteins resident in the endoplasmic reticulum. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Unconventional spin distributions in thick Ni{sub 80}Fe{sub 20} nanodisks

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

Kumar, D.; Lupo, P.; Haldar, A.

2016-05-09

We study the spin distributions in permalloy (Py: Ni{sub 80}Fe{sub 20}) nanodisks as a function of diameter D (300 nm ≤ D ≤ 1 μm) and thickness L (30 nm ≤ L ≤ 100 nm). We observed that beyond a certain thickness, for a fixed disk diameter, an unconventional spin topology precipitates which is marked by the presence of a divergence field within the magnetic vortex curl. The strength of this divergence changes anti-symmetrically from negative to positive—depending on the core polarity—along the axis of the cylindrical nanodisk. This is also accompanied by a skyrmion-like out-of-plane bending of the spin vectors farther away from the disk center. Additionally, the vortex core dilatesmore » significantly when compared to its typical size. This has been directly observed using magnetic force microscopy. We determined from the ferromagnetic resonance spectroscopy measurements that the unconventional topology in the thicker nanodisks gyrated at a frequency, which is significantly lower than what is predicted by a magnetic vortex based analytical model. Micromagnetic simulations involving dipolar and exchange interactions appear to satisfactorily reproduce the experimentally observed static and dynamic behaviors. Besides providing a physical example of an unconventional topology, these results can also aid the design of topologically protected memory elements.« less

Landscape disturbance from unconventional and conventional oil and gas development in the Marcellus Shale region of Pennsylvania, USA

USGS Publications Warehouse

Slonecker, Terry E.; Milheim, Lesley E.

2015-01-01

The spatial footprint of unconventional (hydraulic fracturing) and conventional oil and gas development in the Marcellus Shale region of the State of Pennsylvania was digitized from high-resolution, ortho-rectified, digital aerial photography, from 2004 to 2010. We used these data to measure the spatial extent of oil and gas development and to assess the exposure of the extant natural resources across the landscape of the watersheds in the study area. We found that either form of development: (1) occurred in ~50% of the 930 watersheds that defined the study area; (2) was closer to streams than the recommended safe distance in ~50% of the watersheds; (3) was in some places closer to impaired streams and state-defined wildland trout streams than the recommended safe distance; (4) was within 10 upstream kilometers of surface drinking water intakes in ~45% of the watersheds that had surface drinking water intakes; (5) occurred in ~10% of state-defined exceptional value watersheds; (6) occurred in ~30% of the watersheds with resident populations defined as disproportionately exposed to pollutants; (7) tended to occur at interior forest locations; and (8) had >100 residents within 3 km for ~30% of the unconventional oil and gas development sites. Further, we found that exposure to the potential effects of landscape disturbance attributable to conventional oil and gas development was more prevalent than its unconventional counterpart.

An overview on exploration and environmental impact of unconventional gas sources and treatment options for produced water.

PubMed

Silva, Tânia L S; Morales-Torres, Sergio; Castro-Silva, Sérgio; Figueiredo, José L; Silva, Adrián M T

2017-09-15

Rising global energy demands associated to unbalanced allocation of water resources highlight the importance of water management solutions for the gas industry. Advanced drilling, completion and stimulation techniques for gas extraction, allow more economical access to unconventional gas reserves. This stimulated a shale gas revolution, besides tight gas and coalbed methane, also causing escalating water handling challenges in order to avoid a major impact on the environment. Hydraulic fracturing allied to horizontal drilling is gaining higher relevance in the exploration of unconventional gas reserves, but a large amount of wastewater (known as "produced water") is generated. Its variable chemical composition and flow rates, together with more severe regulations and public concern, have promoted the development of solutions for the treatment and reuse of such produced water. This work intends to provide an overview on the exploration and subsequent environmental implications of unconventional gas sources, as well as the technologies for treatment of produced water, describing the main results and drawbacks, together with some cost estimates. In particular, the growing volumes of produced water from shale gas plays are creating an interesting market opportunity for water technology and service providers. Membrane-based technologies (membrane distillation, forward osmosis, membrane bioreactors and pervaporation) and advanced oxidation processes (ozonation, Fenton, photocatalysis) are claimed to be adequate treatment solutions. Copyright © 2017 Elsevier Ltd. All rights reserved.

The postman always rings twice: two cases of shotgun deaths associated with an unconventional home security alarm system.

PubMed

Asirdizer, Mahmut; Turkmen, Nursel; Akan, Okan; Yavuz, Mehmet Sunay

2014-06-01

Injury and death cases caused by booby traps are not common in forensic medicine practice. Besides, installation of booby traps including firearms is generally for suicidal and rarely for homicidal purposes. Although few patents were described about home security alarm system that were created by firearms in the United States, 1 sample of injury with a similar unconventional mechanism of home safety system was reported by Asirdizer and Yavuz in 2009. In the published case report, the story of an electrical technician who was invited to a summer house by the homeowner to check the home security alarm system was reported. In the so-called report, he was stated to be injured by the shotgun attached to the unconventional home security alarm system while checking the system. As a result, the homeowner was convicted of a possible intent to cause a life-threatening injury to the technician.The so-called homeowner and his wife died by the same shotgun attached to the same unconventional home security alarm system 4 years on from the first event. In the present case report, we have aimed to present the findings of the crime scene and the autopsies of these unusual 2 deaths and to discuss individual and legal factors in paving the way for the deaths of 2 people.

Shale Gas Geomechanics for Development and Performance of Unconventional Reservoirs

NASA Astrophysics Data System (ADS)

Domonik, Andrzej; Łukaszewski, Paweł; Wilczyński, Przemysław; Dziedzic, Artur; Łukasiak, Dominik; Bobrowska, Alicja

2017-04-01

Mechanical properties of individual shale formations are predominantly determined by their lithology, which reflects sedimentary facies distribution, and subsequent diagenetic and tectonic alterations. Shale rocks may exhibit complex elasto-viscoplastic deformation mechanisms depending on the rate of deformation and the amount of clay minerals, also bearing implications for subcritical crack growth and heterogeneous fracture network development. Thus, geomechanics for unconventional resources differs from conventional reservoirs due to inelastic matrix behavior, stress sensitivity, rock anisotropy and low matrix permeability. Effective horizontal drilling and hydraulic fracturing technologies are required to obtain and maintain high performance. Success of these techniques strongly depends on the geomechanical investigations of shales. An inelastic behavior of shales draws increasing attention of investigators [1], due to its role in stress relaxation between fracturing phases. A strong mechanical anisotropy in the vertical plane and a lower and more variable one in the horizontal plane are characteristic for shale rocks. The horizontal anisotropy plays an important role in determining the direction and effectiveness of propagation of technological hydraulic fractures. Non-standard rock mechanics laboratory experiments are being applied in order to obtain the mechanical properties of shales that have not been previously studied in Poland. Novel laboratory investigations were carried out to assess the creep parameters and to determine time-dependent viscoplastic deformation of shale samples, which can provide a limiting factor to tectonic stresses and control stress change caused by hydraulic fracturing. The study was supported by grant no.: 13-03-00-501-90-472946 "An integrated geomechanical investigation to enhance gas extraction from the Pomeranian shale formations", funded by the National Centre for Research and Development (NCBiR). References: Ch. Chang M. D. Zoback. 2009. Viscous creep in room-dried unconsolidated Gulf of Mexico shale (I): Experimental results. Journal of Petroleum Science and Engineering 69: 239-246.

Assessment of the Performance Potential of Advanced Subsonic Transport Concepts for NASA's Environmentally Responsible Aviation Project

NASA Technical Reports Server (NTRS)

Nickol, Craig L.; Haller, William J.

2016-01-01

NASA's Environmentally Responsible Aviation (ERA) project has matured technologies to enable simultaneous reductions in fuel burn, noise, and nitrogen oxide (NOx) emissions for future subsonic commercial transport aircraft. The fuel burn reduction target was a 50% reduction in block fuel burn (relative to a 2005 best-in-class baseline aircraft), utilizing technologies with an estimated Technology Readiness Level (TRL) of 4-6 by 2020. Progress towards this fuel burn reduction target was measured through the conceptual design and analysis of advanced subsonic commercial transport concepts spanning vehicle size classes from regional jet (98 passengers) to very large twin aisle size (400 passengers). Both conventional tube-and-wing (T+W) concepts and unconventional (over-wing-nacelle (OWN), hybrid wing body (HWB), mid-fuselage nacelle (MFN)) concepts were developed. A set of propulsion and airframe technologies were defined and integrated onto these advanced concepts which were then sized to meet the baseline mission requirements. Block fuel burn performance was then estimated, resulting in reductions relative to the 2005 best-in-class baseline performance ranging from 39% to 49%. The advanced single-aisle and large twin aisle T+W concepts had reductions of 43% and 41%, respectively, relative to the 737-800 and 777-200LR aircraft. The single-aisle OWN concept and the large twin aisle class HWB concept had reductions of 45% and 47%, respectively. In addition to their estimated fuel burn reduction performance, these unconventional concepts have the potential to provide significant noise reductions due, in part, to engine shielding provided by the airframe. Finally, all of the advanced concepts also have the potential for significant NOx emissions reductions due to the use of advanced combustor technology. Noise and NOx emissions reduction estimates were also generated for these concepts as part of the ERA project.

Prediction of Ablation Rates from Solid Surfaces Exposed to High Temperature Gas Flow

NASA Technical Reports Server (NTRS)

Akyuzlu, Kazim M.; Coote, David

2013-01-01

A mathematical model and a solution algorithm is developed to study the physics of high temperature heat transfer and material ablation and identify the problems associated with the flow of hydrogen gas at very high temperatures and velocities through pipes and various components of Nuclear Thermal Rocket (NTR) motors. Ablation and melting can be experienced when the inner solid surface of the cooling channels and the diverging-converging nozzle of a Nuclear Thermal Rocket (NTR) motor is exposed to hydrogen gas flow at temperatures around 2500 degrees Kelvin and pressures around 3.4 MPa. In the experiments conducted on typical NTR motors developed in 1960s, degradation of the cooling channel material (cracking in the nuclear fuel element cladding) and in some instances melting of the core was observed. This paper presents the results of a preliminary study based on two types of physics based mathematical models that were developed to simulate the thermal-hydrodynamic conditions that lead to ablation of the solid surface of a stainless steel pipe exposed to high temperature hydrogen gas near sonic velocities. One of the proposed models is one-dimensional and assumes the gas flow to be unsteady, compressible and viscous. An in-house computer code was developed to solve the conservations equations of this model using a second-order accurate finite-difference technique. The second model assumes the flow to be three-dimensional, unsteady, compressible and viscous. A commercial CFD code (Fluent) was used to solve the later model equations. Both models assume the thermodynamic and transport properties of the hydrogen gas to be temperature dependent. In the solution algorithm developed for this study, the unsteady temperature of the pipe is determined from the heat equation for the solid. The solid-gas interface temperature is determined from an energy balance at the interface which includes heat transfer from or to the interface by conduction, convection, radiation, and ablation. Two different ablation models are proposed to determine the heat loss from the solid surface due to the ablation of the solid material. Both of them are physics based. Various numerical simulations were carried out using both models to predict the temperature distribution in the solid and in the gas flow, and then predict the ablation rates at a typical NTR motor hydrogen gas temperature and pressure. Solid mass loss rate per foot of a pipe was also calculated from these predictions. The results are presented for fully developed turbulent flow conditions in a sample SS pipe with a 6 inch diameter.

Some unconventional approaches to the exploration of Mars

NASA Astrophysics Data System (ADS)

French, J. R.

1991-02-01

The topics of space transport to Mars, and surface transport and surface operations on Mars are discussed in detail and new options for accomplishing these activities are presented. The question of maximizing the return on the investment in a Mars mission is addressed. One way to accomplish this is through reduction of propellant requirements by increasing the performance of the rocket engine, while another option is to make use of nuclear fuel. A technique discussed in detail would provide a means to manufacture fuel from Martian resources for both the return trip and for Mars surface exploration. Options for Mars surface transport include battery and nuclear powered rovers, solar powered automobiles, and either battery, nuclear or Mars-generated-propellant-powered aircraft specially designed to explore the Martian surface. The advantages and disadvantages of each of these options are considered, and the usefulness of a manned aircraft for both exploration and surface operational functions is discussed.

Topological valley transport of plate-mode waves in a homogenous thin plate with periodic stubbed surface

NASA Astrophysics Data System (ADS)

Chen, Jiu-Jiu; Huo, Shao-Yong; Geng, Zhi-Guo; Huang, Hong-Bo; Zhu, Xue-Feng

2017-11-01

The study for exotic topological effects of sound has attracted uprising interests in fundamental physics and practical applications. Based on the concept of valley pseudospin, we demonstrate the topological valley transport of plate-mode waves in a homogenous thin plate with periodic stubbed surface, where a deterministic two-fold Dirac degeneracy is form by two plate modes. We show that the topological property can be controlled by the height of stubs deposited on the plate. By adjusting the relative heights of adjacent stubs, the valley vortex chirality and band inversion are induced, giving rise to a phononic analog of valley Hall phase transition. We further numerically demonstrate the valley states of plate-mode waves with robust topological protection. Our results provide a new route to design unconventional elastic topological insulators and will significantly broaden its practical application in the engineering field.

Luminescent hyperbolic metasurfaces

NASA Astrophysics Data System (ADS)

Smalley, J. S. T.; Vallini, F.; Montoya, S. A.; Ferrari, L.; Shahin, S.; Riley, C. T.; Kanté, B.; Fullerton, E. E.; Liu, Z.; Fainman, Y.

2017-01-01

When engineered on scales much smaller than the operating wavelength, metal-semiconductor nanostructures exhibit properties unobtainable in nature. Namely, a uniaxial optical metamaterial described by a hyperbolic dispersion relation can simultaneously behave as a reflective metal and an absorptive or emissive semiconductor for electromagnetic waves with orthogonal linear polarization states. Using an unconventional multilayer architecture, we demonstrate luminescent hyperbolic metasurfaces, wherein distributed semiconducting quantum wells display extreme absorption and emission polarization anisotropy. Through normally incident micro-photoluminescence measurements, we observe absorption anisotropies greater than a factor of 10 and degree-of-linear polarization of emission >0.9. We observe the modification of emission spectra and, by incorporating wavelength-scale gratings, show a controlled reduction of polarization anisotropy. We verify hyperbolic dispersion with numerical simulations that model the metasurface as a composite nanoscale structure and according to the effective medium approximation. Finally, we experimentally demonstrate >350% emission intensity enhancement relative to the bare semiconducting quantum wells.